ISSN 2313-8254 (English ed.

Online)
ISSN 0042-8817 (Russian ed. Print)
ISSN 2309-1681 (Russian ed. Online)
Burdenko Neurosurgical Institute, Moscow,
Russia

PROBLEMS
Official journal of the Association
of Neurosurgeons of Russia

«Zhurnal voprosy neirokhirurgii imeni

N N Burdenko» (Problems of
OF NEUROSURGERY
Neurosurgery named after N.N. Burdenko)
is a bimonthly
named after N.N. Burdenko
peer-reviewed medical journal published
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Founded in 1937. Vol. 80 6'2016
FUNDAMENTAL AND PRACTICAL JOURNAL

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 CONTENTS

ORIGINAL ARTICLES

Absalyamova O.V., Kobyakov G.L., Ryzhova M.V., Poddubskiy A.A., Inozemtseva M.V., Lodygina K.S.
Outcomes of Application of Modern First-Line Chemotherapy Regimens in the Multimodality Therapy of Patients with Glioblastoma . . . . . . 4
Gushcha A.O., Arestov S.O., Vershinin A.V.
The First Experience with a New Technique of Portal Endoscopic Discectomy for Herniated Cervical Discs . . . . . . . . . . . . . . . . . . . . . . . . . . 13
Astaf’eva L.I., Kadashev B.A., Shishkina L.V., Kalinin P.L., Fomichev D.V., Kutin M.A., Aref’eva I.A., Dzeranova L.K., Sidneva Yu.G.,
Klochkova I.S., Rotin D.L.
Clinical and Morphological Characteristics, Diagnostic Criteria, and Outcomes of Surgical Treatment
of TSH-secreting Pituitary Adenomas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
Khabarova E.A., Denisova N.P., Rogov D.Yu., Dmitriev A.B.
The Preliminary Results of Subthalamic Nucleus Stimulation after Destructive Surgery in Parkinson’s Disease . . . . . . . . . . . . . . . . . . . . . . . . 32
Kondrakhov S.V., Zakharova N.E., Fadeeva L.M., Tanyashin S.V.
Phase Contrast MRI-based Evaluation of Cerebrospinal Fluid Circulation Parameters in Patients with Foramen Magnum Meningiomas. . . 37
Kushel’ Yu.V., Belova Yu.D., Tekoev A.R.
Application of Resorbable Plates for Fixation of a Laminotomy Flap . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
Dzhindzhikhadze R.S., Dreval’ O.N., Lazarev V.A., Kambiev R.L.
Minipterional Craniotomy in Surgery for Anterior Circle of Willis Aneurysms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52

CASE REPORTS

Savateev A.N., Konovalov A.N., Gorelyshev S.K., Satanin L.A., Khukhlaeva E.A., Shishkina L.V., Ozerova V.I., Valiakhmetova E.F.,
Medvedeva O.A.
A Giant Hyperostotic Parasagittal Meningioma in a Child with Neurofibromatosis Type II. A Case Report and Literature Review . . . . . . . . 59
Martynova M.A., Konovalov N.A., Lubnin A.Yu., Shmigel’skiy A.V., Savin I.A., Tabasaranskiy T.F., Akhvlediani K.N., Sinbukhova E.V.,
Onoprienko R.A.
Spinal Stroke in a Pregnant Female with an Endodermal Cyst of the Cervical Spinal Cord (a Case Report and Literature Review). . . . . . . . . 67
Goroshchenko S.A., Ivanov A.Yu., Rozhchenko L.V., Ivanova N.E., Zabrodskaya Yu.M., Razmologova O.Yu., Kondrat’ev A.N., Potemkina E.G.,
Dmitrievskaya A.Yu., Blagorazumova G.P., Radzhabov S.D., Petrov A.E., Ivanov A.A., Sinitsyn P.S., Bobinov V.V.
Extrapontine Myelinolysis Developed After Aneurysmal Subarachnoid Hemorrhage (a Case Report and Literature Review) . . . . . . . . . . . . . 74
Konovalov N.A., Shishkina L.V., Asyutin D.S., Onoprienko R.A., Korolishin V.A., Zakirov B.A., Martynova M.A., Cherkiev I.U., Pogosyan A.L.,
Timonin S.Yu.
Extradural Spinal Cord Hemangioblastoma (a Case Report and Literature Review) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79
Vasin R.A., Krasnikov M.A., Vasina S.V.
Infant Form of Alexander Disease (Clinical Case and Literature Review) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84

GUIDELINES FOR THE PRACTITIONER

Shimanskiy V.N., Karnaukhov V.V., Tanyashin S.V., Poshataev V.K., Shevchenko K.V., Odamanov D.A., Kondrakhov S.V.
Use of Surgical Approaches to the Posterior Cranial Fossa in Patients in a Lying Position. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90

REVIEWS

Shurkhay V.A., Goryaynov S.A., Aleksandrova E.V., Spallone A., Potapov A.A.
Navigation Systems in Neurosurgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98

Zav’yalov D.M., Peretechikov A.V.

Prevention and Treatment of Postoperative Epidural Scar Adhesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105

2 © Media Sphera, 2016

 Topics to be covered in our next issue:

● The current status of neurosurgical services in the Russian Federation

● Anatomy of the neural pathways of the brain

● Clinical recommendations for management of acoustic neuromas

In accordance with the resolution of the Higher Attestation Commission of the Ministry of Education and Science of the
Russian Federation, the Problems of Neurosurgery named after N.N. Burdenko was included in the List of Leading
PeerReviewed Journals and Periodicals issued in the Russian Federation where the main results of Candidate and Doctor
Theses are recommended to be published.

3
 ORIGINAL ARTICLES

doi: 10.17116/engneiro20168064-12

Outcomes of Application of Modern First-Line Chemotherapy Regimens in the

Multimodality Therapy of Patients with Glioblastoma
O.V. ABSALYAMOVA, G.L. KOBYAKOV, M.V. RYZHOVA, A.A. PODDUBSKIY, M.V. INOZEMTSEVA, K.S. LODYGINA

Burdenko Neurosurgical Institute, Moscow, Russia

Objective. The objective of this study is to describe the procedure and outcomes of comprehensive first-line treatment in
glioblastoma patients.
Material and methods. We analyzed 107 glioblastoma patients who were operated on in 2010—2011. Seventy five patients
underwent combined chemoradiotherapy (CRT) with simultaneous administration of 75 mg/m2 temozolomide (TMZ) followed by
chemotherapy with 200 mg/m2 TMZ for 5 days, every 28 days. Separately, we examined 32 patients with large tumors, who
received alternative treatments.
Results. The median time to progression was 11.7 months in the study group and 7.2 and 8.1 months in the groups of alternative
therapy. The one-year progression-free survival rate was 37%. Overall survival was 29.2 months.
Conclusion. The chemoradiotherapy regimen involving TMZ followed by one-year TMZ monotherapy is an appropriate treatment
for patients who underwent glioblastoma resection. With this approach, no tumor progression occurs in one third of patients
during the first year. Thorough study of clinical and radiological findings in the course of treatment makes it possible to achieve
maximum efficacy, avoid unreasonably early switch to second-line therapy, and timely detect tumor recurrence signs. The
Response Assessment in Neuro-Oncology (RANO) criteria should be used to assess MRI-detected changes in the tumor size. The
rates of overall and recurrence-free survival were significantly lower in patients with inoperable or partially resected tumors. The
applied approaches provide only a slight advantage in tumor growth control, which necessitates the search for more effective
treatment options for these patients. Inclusion of bevacizumab to the first-line therapy regimen may be a possible approach.
Keywords: glioblastoma, chemotherapy, evaluation criteria, tumor pseudoprogression.

Glioblastoma (GB) is the most common primary
malignant tumor of the central nervous system in adults,
whose incidence is 20%. GB is characterized by an
extremely unfavorable prognosis: in most patients,
progression of the disease is detected within the first year
after surgery; overall survival (OS) did not exceed 1 year
for a long time [1]. Currently, a comprehensive approach
is used to treat GB patients, including surgery,
radiotherapy (RT), and chemotherapy (CT) and life
expectancy is up to 2 years.
Maximum possible tumor resection followed by a
combination of chemoradiotherapy (CRT) with
temozolomide (TMZ) and subsequent adjuvant
chemotherapy (TMZ) is the “gold standard” of the first-
line treatment of patients with GB. RT is applied on the
tumor area (including about 2―3 cm around it) at a total
dose of 60 Gy and single dose of 2 Gy along with
administration of TMZ (75 mg/m2). Chemotherapy with
TMZ at a unit dose of 200 mg/m2 is started 28 days after
completion of this treatment (during 5 days followed by
23-day break). This regimen was first described by R.
Stupp et al. [2], who have shown that inclusion of TMZ
in this treatment regimen increases the median time to
progression (MTTP) from 5 to 6.9 months, and OS from
12.1 to 14.6 months as compared to the group of patients
treated with radiation therapy alone. According to the
study by M. Gilbert et al. [3], which was completed in
2013, MTTP was 8.8 months, and OS was 18.9 months,
when using this regimen.
This study was aimed at evaluating the overall and
disease-free survival of 107 patients with morphologically
verified glioblastoma, who were treated at the Burdenko
Neurosurgical Institute in 2010—2011.
Materials and methods
We analysed treatment outcomes of 107 patients
with morphologically verified GBs, who were operated
on in 2010—2011 and followed on a regular basis at the
Burdenko Neurosurgical Institute. We retrospectively
analyzed the results of everyday work, when the decision
was made in each case in accordance with modern
standards of GB treatment with allowance for individual
characteristics, such as tumor size, general status, and
presence of intracranial hypertension.
A total of 75 patients underwent a combined CRT
with simultaneous administration of TMZ at a dose of 75
mg/m2 followed by CT with TMZ at a dose of 200 mg/
m2 for 5 days and then a 23-day break. Patients, who
postoperatively had large residual tumors, received the
combined chemoradiotherapy followed by CT with TMZ
at a dose of 150 mg/m2 from the 1st to 5th day of treatment
session + Carboplatin 300 mg/m2 on the first day of the
course; treatment courses repeated every 28 days
(treatment regimen with TMZ and Carboplatin, TC).
There were a total of 20 such patients. The average
number of CT courses in both groups was 6.2, from 0 (7
patients) to 21 (2 patients) courses. Twelve patients did
not receive RT. This decision was taken in patients, who
postoperatively had persisting signs of intracranial
hypertension in the fundus and/or very large tumor
(tumor remnants) accompanied by shift of midline

© Group of authors, 2016 e-mail: 5732493oks@gmail.com

4 PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016

structures. These patients underwent CT in TC mode; in
the case of regression of intracranial hypertension signs
and decrease in tumor signs, RT was performed in
combination with CT. Postoperative treatment was
carried out at the Burdenko Neurosurgical Institute and
Oncology Centers in Moscow and other regions of
Russian Federation.
General information about the patient is shown in
Table 1.
Tumor size dynamics was assessed based on the
archival data of contrast-enhanced MRI of the brain
performed before CRT, 1 month after completion of the
CRT, and then after every 3 CT courses. Upon
completion of treatment, MRI was performed every 3—5
months and in the case of clinical signs of tumor
progression and evaluated according to RANO (Response
Assessment in Neuro-Oncology International Group)
criteria.
Results
At the time of data analysis, progression of the disease
was observed in 91 (85%) of 107 patients. Progression-
free survival for more than 1 year was observed in 37%
(40 patients). Progression-free survival for 12—18
months was observed in 17 (15.8%) patients, PFS for
18—24 months was observed in another 12 (11.2%)
patients, more than 24 months — 11 patients (10 — up to
3 years and 1 — more than 3 years). Regardless of
treatments, MTTP was 10.3 months, OS — 29.2 months.
In treatment groups, MTTP was as follows: combined
CRT with TMZ followed by therapy with TMZ — 11.7
months; combined CRT with TMZ followed by TC
treatment — 7.2 months; patients who started CT
possibly followed by RT — 8.1 months (p=0.008) (Fig. 1).
Overall survival was 33.3, 26.3, and 18 months,
respectively (p=0,007).
Discussion
Objective of the study was to assess treatment
outcomes of patients with glioblastoma, using high-level
surgical techniques, modern RT techniques, and
sufficient number of modern CT courses.
Table 1. General information about 107 patients with glioblastoma
CRT + TMZ, abs.
Combination therapy
(%)
Number of patients 75 (70)
Males 37 (49,4)
Females 38 (50,6)
Average age, years 49
Local lesion 74 (98)
Multiple lesions 1 (2)
Tumor resection 75 (100)
Biopsy 0 1 (5)
PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
The number of followed patients
We describe treatment outcomes of only 107 patients,
which accounts for 31.4% of all patients, who were for
the first time operated on for GB at the Burdenko
Neurosurgical Institute in 2010—2011. Relatively small
number of patients included in the analysis was due to
both loss of medical history and failure to comply with
GB treatment standards [4]. Our findings are consistent
with data of A.V. Smolin et al., who conducted the
Russian multi-centered study on the epidemiology of
malignant gliomas from 01.01.2012 to 31.12.2013. This
study included 325 patients from 29 medical centers in
Russia. It has been shown that only every fourth patient
received combined CRT and 1/3 of patients received no
first-line CT. Among the patients who received first-line
CT, some patients received medications other than
TMZ [5].
Thus, higher numbers of MTTP obtained in this
study were due to the use of modern glioblastoma
treatment regimens. Furthermore, patients who did not
receive treatment, did not request re-consultation, those
who were unavailable for history taking and possibly died
in the early postoperative period, were not included in
our study.
Combined chemoradiation therapy with temozolomide
followed by adjuvant therapy with temozolomide
In the study group, MTTP was 11.7 months. In
patients, who were treated at the Burdenko Neurosurgical
Institute using an identical regimen in 2006—2007,
MTTP was 9.7 months [6].
In world practice, the standard CRT mode with
TMZ followed by treatment with TMZ includes only 6
CT courses.
However, some clinicians are inclined to the opinion
that larger number of courses are advisable, especially in
patients with contrasted tumor remnants. There were no
comparative randomized trials assessing the effectiveness
of this approach. When comparing suitable groups from
various studies, the following results were obtained. In
the study by M. Stupp et al. [2], MTTP was 6.9 months in
the group of patients, who received CRT + 6 courses of
TMZ; in the study by Chinot O. et al. [7], MTTP was 6.2
months in the group of CRT + 6 courses of TMZ; in the
study by M. Gilbert et al. [4], MTTP was 8.8 months in
CRT + TC, abs.
TC +/- RT, abs. (%) Total, abs. (%)
(%)
20 (18,7) 12 (11,3) 107
8 (40) 7 (58,4) 52 (49)
12 (60) 5 (41,6) 55 (51)
47 48 —
19 (95) 8 (66,6) 101 (94)
1 (5) 4 (33,4) 6 (6)
19 (95) 9 (75) 103 (96,2)
3 (25) 4 (3,8)
5
 ORIGINAL ARTICLES
the group of patients who received CRT + 12 courses of
TMZ. It should be noted that in the study of R. Stupp et
al., 16—17% of patients underwent only tumor biopsy, in
the study of Chinot O. et al., the proportion of biopsies
was 9.5—13.1%, M. Gilbert — 3%. Thus, it is still unclear
what exactly has determined increase in MTTP, either
longer CT or radical tumor resection.
In our series, 3.8% of patients underwent only tumor
biopsy. When prescribing more than 6 CT courses, we
were primarily guided by tolerability of therapy and the
presence of residual tumor. If therapy was tolerated
satisfactorily (blood parameters), we continued treatment
up to 10 courses. Retrospective analysis has shown that
51 patients had no progression after CRT and 6 CT
courses. In the cases, where CT was stopped or continued,
MTTP was 17.7 and 17.3 months, respectively, the
differences are not significant (p=0.512) (Fig. 2). When
extending CT for more than 10 courses, we were guided
by the presence of contrasted tumor remnants, absence
of progression signs during continued treatment, as well
as increased metabolic activity in a tumor as shown by
positron emission tomography (PET) of the brain with
C11 methionine. In 20 patients without progression after
10 CT courses, MTTP was 26.4 months in the cases when
CT was termination, and 19.2 months when it was
continued over 10 courses (p=0.015) (Fig. 3). The
differences were not significant. This results lead to
conclusion that these patients require continued
antitumor therapy, by probably in other regimens.
Fig. 1. Median time to tumor progression in patients with glioblastoma who received various types of post-operative treatment.
6 PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
Bevacizumab in the first-line therapy for GB
The study of Cloughesy was one of the first researches
that provided the basis for the use of bevacizumab (Bev)
in patients with GB progression. The study described 167
patients with GB relapse, who were treated with Bev or
Bev in combination with irinotecan. Partial response
(tumor reduction by 50% or more) was achieved in 28.3%
of patients who received Bev and 37.8% of patients who
received Bev + irinotecan; in several patients, complete
response was achieved. We obtained similar results in 36
patients with GB relapse, who received combinations of
various cytostatics with Bev (in Russian Federation, Bev
was approved for the treatment of GB since November
2009). Partial response was achieved in 13 patients,
complete response – 3 patients [9].
According to the results of Avaglio and RTOG 0825
studies, application of Bev in the first-line treatment in
addition to R. Stupp’s regimen increases the MTTP, but
does not affect the OS. For example, MTTP was 6.2
months in patients, who were included in Avaglio and
used CRT regimen with TMZ. When this regimen was
supplemented with Bev at a dose of 10 mg/kg every 2
weeks starting from the first day of the CRT and further
until progression, MTTP was 10.8 months. OS was 16.7
and 16.8 months, respectively [7]. Such a difference in
the effect of Bev on the MTTP and OS was due to the fact
that patients, who did not receive Bev in the first line
treatment, received it in the second-line treatment and
for this reason OS was similar in both groups of patients.
Fig. 2. Median time to tumor progression in GB patients, who received 6 cycles of TMZ and more.
Currently, Bev is not recommended as the first-line
therapy for GB.
Criteria to assess the efficacy of treatment of central
nervous system tumors
When speaking of tumor progression, the criteria for
determining progression signs should be mentioned.
Since 1990, criteria suggested by D. Macdonald et al. [10]
were used in neuro-oncology for tumor evaluation. They
take into account tumor size, the presence of new lesions,
the dynamics of neurological symptoms, and the use of
steroid therapy. However, these criteria can not be used
to assess non-contrasted tumors, which is a drawback.
Another serious problem lies in the fact that Macdonald’s
criteria are used for the tumors subjected to therapy with
anti-angiogenic drugs (e.g., Bev), which change the
permeability of the capillaries and thereby inhibit tumor
contrasting. In this situation, the true spread of the tumor
can only be determined in the T2/FLAIR-mode. For this
reason, RANO [11] criteria are used since 2010. RANO
criteria assess tumor size over time using T1 contrast-
enhanced MRI and hyperintensive signal area using T2
and FLAIR modes and also take into account neurological
status and the use of dexamethazone (Table 2).
Case report
Here we provide a case report to illustrate our
treatment strategy.
Patient C., 40 years old. Since May 2012, the patient
experienced progressive headaches, there was an episode
of generalized seizure. MRI of the brain with intravenous
contrast performed on 26 May 2012 detected a mass
lesion of the right temporal lobe, actively accumulating
PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
contrast and accompanied by a pronounced perifocal
edema (Fig. 4a). Tumor was resected on 02.07.12.
Histological examination identified GB. In July —
August 2012, the patient underwent CRT: RT single dose
of 2—3 Gy, total dose of 48 Gy (unfortunately, in some
institutions in the Russian Federation, non-standard
single-dose radiation therapy is used in the treatment of
patients with brain tumors) with simultaneous oral intake
of TMZ at a dose of 140 mg daily. MRI in September
2012 detected no contrasted tumor remnants (see
Fig. 4b). During the period from September 2012 to July
2013, the patient underwent 11 courses of chemotherapy
with oral intake of TMZ at a dose of 400 mg for 5 days
every 28 days. MRI in July 2013 detected no contrasted
tumor remnants (see Fig. 4c). In July 2013, PET of the
brain with C11 methionine detected the area with
enhanced accumulation of radiopharmaceutical,
accumulation index (AI) 1.62, tumor remnants with
moderate metabolic activity. Due to this fact, CT with
TMZ was continued and a total of 17 courses were
conducted by February 2014. Patient's condition was
satisfactory, steroid therapy was not carried out, seizures
did not recur, and the patient returned to work. During
the period from February 2014 to September 2015 (20
months), chemotherapy was not carried out. Scheduled
MRI in September 2015 (38 months after surgery)
detected increased area of hyperintensive signal in
FLAIR mode at the surgical area and in the right pole of
the temporal lobe. There was no worsening of neurological
symptoms. On 28.09.15, PET detected hypermetabolic
area with AI of 2.05 at the pole of the temporal lobe in
accordance with the changes detected by MRI, continued
tumor growth (see Fig. 4c). During the period from
7
 ORIGINAL ARTICLES
Fig. 3. Median time to tumor progression in GB patients, who received 10 courses of TMZ and more.
19.10.15 to 21.10.15, the patient underwent stereotactic
radiotherapy using hypofractionation regimen at the area
of tumor recurrence in the right temporal lobe, including
3 mm margin around this area (GTV/CTV 2.969/5.612
cm3), a total of 3 fractions, 8 Gy per fraction until average
total dose of =24.82/24.1 Gy using multiple beams
method (A=145), until total dose of 21.5 Gy prescribed
at the isodose of 81%. TMZ chemotherapy was resumed
from October 2015 to March 2016, a total of 6 courses
were carried out. In February 2016 (44 months after
surgery), MRI showed decrease in the hyperintensive
signal area in FLAIR mode at the pole of the right
temporal lobe and stable pattern at the surgical area. PET
of the brain with C11 methionine: decreased
accumulation of the radiopharmaceutical, AI 1.23 (see
Fig. 5d). There was no worsening of neurological status.
Headache and seizures did not recur since the surgery. At
the time of writing of this article, 48 months have elapsed,
there is no signs of disease progression.
Pseudoprogression
“Pseudoprogression” term was first suggested in
2007. Pseudoprogression (PsP) is a name for subacute
changes, developing within 12 weeks after RT and
characterized by X-ray picture of increase in contrasted
area by more than 25%. It is believed that combined CRT
with TMZ increases the incidence of PsP phenomenon.
Despite the MR-signs of disease progression, spontaneous
regression of both clinical symptoms and contrasted area
(MRI) is subsequently observed in some of these patients.
The incidence of PsP averages 20—30%. It was shown
that development of PsP correlates with methylated
MGMT gene in the tumor and may be a predictor of high
efficacy of the therapy [12]. Therefore, the use of the
aforementioned evaluation criteria is relevant no earlier
8 PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
than 12 weeks after completion of RT. Before that time,
appearance of new lesions outside the irradiated area is
the main symptom of tumor progression.
For clinicians, pseudoprogression phenomenon
causes doubts in the choice of further treatment strategy.
On the one hand, when ignoring the PsP phenomenon
and changing treatment schedule, we deprive a patient of
the possibility to continue effective and convenient
therapy with TMZ. On the other hand, true progression
is much more common, and in this case, continuation of
previous therapy is inadvisable. A number of
investigators [13] “modify” pseudoprogression criteria,
considering as PsP only those cases, where increase is
contrasted area is not associated with worsening of
symptoms and the time acceptable for PsP diagnosis does
not exceed 1 month after chemoradiotherapy.
It is highly important to distinguish between true
progression and pseudoprogression, when planning a
second-line therapy of GB. False-high effectiveness
values can be obtained when including PsP patients in
the study.
In our series, we observed increase in contrasted area
by more than 25% within the period of 160 days after
diagnosis, i.e. about 12 week after completion of CRT, in
17 patients (10 of these patients continued treatment).
Seven (41%) of 17 patients survived for more than 1 year
after detection of progression. At the time of writing of
this article, 6 patients died and 1 patient is alive; overall
survival in this group is 22 to 66 months (average survival
is 33 months). Most likely, these 7 patients had
pseudoprogression phenomenon.
Metabolic, perfusion, diffusion, and X-ray studies
can be used to distinguish between progression and
pseudoprogression. Further studies are required to
investigate reliability and procedure of their use [12].
Table 2. Criteria to assess the dynamics of central nervous system tumors
Complete response Partial response Stabilization Progression
*M **R M R M R M R
Contrasted foci No No Decrease Decrease Any other Any other Increase by Increase by
in T1 mode by 50% and by 50% and situation situation 25% and 25% and
more more more more
compared compared compared compared to
to the to the to the the baseline
baseline baseline baseline
T2/FLAIR Not Stable or Not Stable or Not Stable or Not Increase
considered decrease considered decrease considered decrease considered significantly
New foci No No No No No No Yes Yes
Corticosteroids No No Stable or Stable or Stable or Stable or Any Any
decrease decrease decrease decrease
Clinical status Stable or Stable or Stable or Stable or Stable or Stable or Worsened Worsened
improved improved improved improved improved improved
Considered in All All All Any of the above
evaluation
Note: *Macdonald’s criteria; **RANO criteria.

Patients with large and inoperable GBs
In 2009, the study “Chemotherapy in the treatment
of patients with inoperable malignant supratentorial
astrocytic gliomas” was completed at the Burdenko
Neurosurgical Institute. In this study, 37 patients with
inoperable large GBs, who underwent only STB followed
by CT, were treated using three regimens: PCV was used
in 15 (40.5%) patients, TMZ — 5 (13.5%), TMZ +
cisplatin — 17 (54%) patients. MTTP was 5, 4, and 8
months, median OS — 8.5, 6.0, and 10.5 months,
respectively. In the cases, where only CT was applied, the
highest direct effectiveness was obtained when using the
TMZ + cisplatin regimen: complete response was
observed in 2 patients, partial response — 10,
stabilization — 7, and progression — 7. When using
monotherapy with TMZ, stabilization was the maximum
effect [14].
The study of combination of TMZ + cisplatin was
preceded by a series of studies performed in patients with
recurrent GB. The study by A. Brandes et al. [15] was the
first and the largest series of cases that showed the efficacy
of the combination of TMZ + cisplatin in patients with
recurrent GB, who were not previously treated with CT.
The investigation was based on in vitro study, showing
that cisplatin is capable of not only reducing activity of
MGMT, but also enhancing the efficacy of TMZ in this
direction. Additionally, the efficacy of combination
TMZ + cisplatin as the first-line treatment was shown in
patients, who already received TMZ and thereafter had
PROP [16]. S. Balana et al. [17] have shown the
effectiveness of the use of TMZ + cisplatin as the first-
line treatment in patients with verified inoperable GB.
We used carboplatin instead of cisplatin in
combination with TMZ in this group of GB patients.
Carboplatin is less nephrotoxic and significantly less
emetogenic.
In 792 patients with advanced ovarian cancer,
combination carboplatin + paclitaxel was no less effective
than combination cisplatin + paclitaxel, had fewer side
effects and more convenient administration regimen
[18]. When comparing the effectiveness of combinations
bleomycin + etoposide + carboplatin or cisplatin (BEC/
BEP), it was shown that BEP is essentially superior to
BEC in terms of relapse-free and overall survival [19].
Previous treatment of 618 patients with disseminated
non-small cell lung cancer using carboplatin + paclitaxel
or cisplatin + paclitaxel modes showed that, while the
number of responses to treatment was similar, OS of
patients was higher in the case of the combination
cisplatin + paclitaxel, and carboplatin + paclitaxel
combination is a reasonable alternative, with the same
response rate, good safety profile, acceptable toxicity,
and ease of application [20]. No comparative evaluation
of the efficacy of the combinations cisplatin + paclitaxel
and TMZ + carboplatin was carried out in patients with
inoperable gliomas.
In our series, 12 patients received only CT as a first-
line therapy. Multifocal GBs were detected in 4 patients,
STB was performed in one of them and the rest underwent
resection of one tumor node. Disseminated diffuse GB
was observed in 8 patients. STB was done in 2 cases,
partial tumor resection — 6. In all cases, the size of the
original tumor or tumor remnants after resection
excluded the possibility of RT. These 12 patients received
CT in the TC mode. Six patients underwent RT after
tumor size reduction. MTTP was 8.1 months in the entire
group.
Based on the available data on the effectiveness of
TMZ in combination with platinum preparations in
patients with large GBs, we administered TC after
completion of CRT in patients with partially resected
GBs, a total of 20 patients. Of these, tumor progression
before completion of 6 CT courses was observed in 16
patients. Four patients continued treatment for more
than 6 courses, including 3 patients who had progression
after 8, 9 and 12 courses, respectively. The treatment was

PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016 9

 ORIGINAL ARTICLES
Fig. 4. Example of treatment of a patient with glioblastoma of the right temporal lobe.
Explanation in the text.
1, a — preoperative MRI; 1,b — MRI 2 months after surgery; 2 — MRI one year after surgery; 3 — PET and MRI 38 months after surgery, tumor progression; 4 — PET
and MRI 44 months after surgery, positive dynamics.
stopped after 10 courses in 1 patient. The median time to
progression in this group was 7.2 months.
Historical data show that patients with inoperable
GBs who receive only symptomatic therapy survive for
about 3 months, while those who receive radiotherapy
survive for 6—7 months [21]. Therefore, temozolomide +
cisplatin and TMZ + carboplatin regimens can be
recommended for the use in patients with disseminated
diffuse glioblastoma. However, in spite of the improved
OS, the results of treatment of patients with large GBs
remain unsatisfactory.
Early tumor progression in these patients is indicative
of relatively low efficacy of therapy and the need for more
effective medications, for example, Bev.
As mentioned above, the results of randomized phase
III studies show that Bev is not indicated in the first-line
treatment of GB. However, data analysis by O. Chinot
have shown that the use of Bev in the first-line treatment
has different effects on survival of patients with various
subtypes of GB. Thus, in patients with proneural GB and
10
no mutations of IDH1 gene, who received Bev in the
first-line treatment, OS was 17.1 months, while in the
placebo group it was 12.8 months (p = 0.002) [22]. It was
also shown that the use of Bev resulted in significantly
longer time to worsening of overall health status, physical
and social functioning, communication, and motor
deficits. It was reported that Bev can effectively reduce
the cerebral edema [23].
It should also be noted that the criteria for inclusion
of patients to Avaglio and RTOG 0825 implied that they
have Karnofsky score of 70 or higher, while the majority
of patients in our series who received TC had a lower
score. Thus, taking into account high direct efficacy of
Bev, which was detected both clinically and in MRI
studies, it is reasonable to examine its efficacy in the first-
line treatment of patients with diffuse disseminated GB.
The factors, predicting beneficial effect of Bev, such as
GB subtype, serum level of matrix metalloproteinase,
and methylation status of the MGMT gene, should be
studied.
PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
 Conclusion
Chemoradiation therapy with temozolomide
followed by a year-long temozolomide monotherapy is
an optimal treatment regimen for patients who underwent
resection of GB. A third of patients treated using this
approach have no signs of tumor progression during the
first year. Thorough study of clinical and radiological
findings in the course of treatment makes it possible to
achieve maximum efficacy, avoid unreasonably early
switch to second-line therapy, and timely detect tumor
recurrence signs. The Response Assessment in Neuro-
Oncology (RANO) criteria should be used to assess
MRI-detected changes in the tumor size. The rates of
overall and recurrence-free survival were significantly
lower in patients with inoperable or partially resected
tumors. The applied approaches provide only a slight
advantage in control of tumor growth, which necessitates
the search for more effective treatment options for these
patients. Inclusion of bevacizumab to the first-line
therapy regimen may be a possible approach.
Commentary
This work focuses on an obviously important issue,
the treatment of patients with brain glioblastomas.
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doi: 10.17116/engneiro201680613-20

The First Experience with a New Technique of Portal Endoscopic Discectomy for
Herniated Cervical Discs
A.O. GUSHCHA, S.O. ARESTOV, A.V. VERSHININ

Research Center of Neurology, Moscow, Russia

Selection of the most appropriate tactics for surgical treatment of herniated cervical discs is a topical issue to be discussed. The
idea of herniated disc removal using an endoscopic technique is not new. This is a routine surgery for the lumbar spine. However,
application of endoscopic techniques in the cervical spine surgery was first reported only in 2014 (J. Yang, et al.).
Objective. This study was aimed at mastering the methodology of a new technique, portal endoscopic discectomy, determining
the indications for this surgery for herniated cervical discs, and comparing outcomes of this surgery with outcomes of anterior
microsurgical discectomy. Material and methods. The study included 25 patients, who underwent portal endoscopic cervical
discectomy. A comparison group consisted of 25 patients, who underwent anterior microsurgical discectomy and placement of
an interbody cage.
Results. Comparison of surgical outcomes showed no significant difference (p>0.05) in the severity of postoperative local and
radicular pain syndrome. According to the Neck Disability Index (NDI), significant improvement occurred in patients with
endoscopic surgery. According to the Odom criterion, significant advantage in the number of excellent and good outcomes was
observed in study group patients. There were significant differences between the groups in the duration of postoperative hospital
stay. The average duration was 3 days in the study group and 5 days in the control group.
Conclusion. Portal endoscopic discectomy is a highly effective treatment for herniated cervical discs, which provides clinical
outcomes associated with much less surgical trauma. The study demonstrates not only the efficacy of the suggested technique, but
also its safety compared to conventional anterior microsurgical techniques, which usually involve interbody fusion. This surgery
is superior to other interventions in terms of the rate of rehabilitation and social adaptation of patients and reduces postoperative
hospital stay.
Keywords: portal endoscopic discectomy, cervical disc herniation, endoscopic spinal surgery.

The incidence of cervical discogenic compression
syndromes is extremely high. According to J. Lawrence [1],
despite the relatively small proportion of detectable
lesions of the cervical intervertebral disc among the total
number of degenerative spinal diseases, about 10% of the
population experience periodic compression-related pain
in the cervical spine or in the hand.
Assessment of cervical hernia is based on conventional
staging classification of intervertebral disc herniation
(protrusion, prolapse, and sequester) proposed by
A. Decoulx [2], which is important in evaluation of the
clinical course of the process and selection of treatment
strategy, as well as classification of herniated intervertebral
discs in terms of their axial arrangement and relationship
with the bony structures of the spinal canal. The latter
distinguish between median, paramedian (laterally shifted
with respect to the sagittal plane), lateral, and foraminal
hernia.
Based on the analysis of a large number of cases,
J. Bland et al. [3] determined characteristic clinical
symptoms associated with cervical radicular compression,
having practical value to assess the severity of impairment
and axial arrangement of hernia. Along with the
characteristic radicular irradiation of pain, sensory
disturbances, loss of tendon reflexes corresponding to
innervated myosclerotome, and paresthesia, which are
indicative of root compression in the intervertebral
foramen, are often detected. In the case of questionable
data, Spurling’s test is recommended (axial load on the
neck along with side-to-side shaking), which leads to
worsening of paresthesia [4].
J. Knightly [5] conveniently distinguish two
pathoanatomical type of compression substrate formation
at the level of intervertebral disc: soft disc (or fragments of
prolapsing disc as the acute phase of the disease) and hard
disc (uncovertebral osteophytes as the chronic phase of
the disease). In our opinion, the structural state of the
compressing factor, as well as its axial arrangement is the
key factor in in the choice of surgical treatment. In
patients with “soft disc”, clinical presentation is
dominated by symptoms of brachialgia that often occur
after physical activity, sudden movement of the head, or
neck injury. Irradiation of acute radicular pain
corresponds to dermatomes and often depends on the
position of the head and limbs. “Helmet”-like or
homolateral hemicrania-like irradiation of the pain is
very typical for this group of patients. Hypesthesia,
accompanying this kind of compression, always involve
individual dermatomes and may be accompanied by an
isolated reduction of tendon reflexes in adjacent muscles.
Decrease in strength (paresis) of the proximal parts of the
upper limbs, which is often unilateral and transient.
The symptoms associated with the development of
“hard disc” are characterized by headache and armache,
which are often symmetrical and accompanied by
transient localized palpatory tenderness at the level of

© Group of authors, 2016 e-mail: sarestov@gmail.com

PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016 13

 ORIGINAL ARTICLES
a complementary information in the diagnosis of the
b radicular syndrome.
c
Fig. 1. Neurodiagnostic studies in patients with right-sided
osteophyte at C5—C6 level on the right and “soft” disc hernia at
C6—C7 level on the right. The use of CT (a) in combination with
MRI (b, c) enabled determining the morphological character of root
compression. The arrow shows the bone-density disc herniation.
14 PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
hernia, which has a certain diagnostic value. This variant
of the disease is characterized by multiple areas of
desensitization up to conduction anesthesia, originating
at the level of the lesion and accompanied by impaired
muscle strength below the segment concerned, sometimes
up to deep paresis. Clinical presentation of calcified
compressing structures in the cervical spinal canal is
characterized by normoreflexia or hyperreflexia, which is
most likely due to chronic circulatory disturbances in the
anterior spinal artery system.
In patients with “hard disc”, development of clinical
symptoms takes much more time compared to those in
with “soft” hernias.
Conventional CT and MPT-studies provide
disease. The former method is preferable to identify
compression factors (hernia, osteophytes), and the latter
is preferable to detect the results of compression
(compression of the spinal cord and roots). Bischoff
(2003) investigated sensitivity, specificity, and accuracy
of CT, MRI, and myelography when establishing the
“herniated disc” and “spinal stenosis” diagnoses. The
accuracy and sensitivity of CT is slightly higher compared
to MRI. CT remains the best method to assess central
stenosis. MRI provides images of the whole cervical spine
and enables detecting stenosis in frontal and sagittal
projections (Fig. 1).
The studies of J. Wilmink [6] showed the following
clinical and radiographic correlations of CT results.
1. Complete occlusion of the intervertebral
foramen by laterally migrated masses of the degenerated
intervertebral disc (“soft disc”) is always accompanied by
2. Narrowing of the intervertebral foramen due to
osteophyte (“hard disc”) results in the root swelling and
less pronounced radicular syndrome compared to the first
variant.
3. Paramedian disc protrusion that does not result
in complete occlusion of the intervertebral foramen and
pronounced compression of the spinal cord often causes
the development of radicular symptoms on the
contralateral (with respect to hernia) side.
Treatment of compression syndromes caused by
degenerative changes in the cervical spine has a 50-year-
long history, and, despite this fact, there is currently no
common viewpoint on the criteria for selection of certain
surgical procedures. This can be explained, on the one
hand, by continuous improvement of the techniques of
cervical spine surgery and development of “spinal design”
operations, and, on the other hand, deepening of
understanding of the pathogenesis and biomechanics of
these changes. Both anterior and posterior approaches in
the cervical spine surgery have been developing in parallel
over 50 years. Many surgeons developed the anterior
approach through the interfascial space, using the
transverse or oblique incision along the anterior margin of
the sternocleidomastoid muscle [7, 8]. The history of
posterior approaches begins in 1955, when
D. Northfield [9] proposed bilateral laminectomy,
extended by one segment above and below the pathological
level. In 1961, W. Scoville [10] performed the limited
bilateral laminectomy supplemented with bilateral facet
resection. The development of the posterior approached
was aimed at decompression of neural structures by means
of resection of the posterior supporting complex of the
arch and spinous process. These approaches did not
always enables removal of compressing masses located on
the ventral surface of the spinal canal, although several
cases of removal of disc hernia and vertebral body
osteophytes have been reported [11]. Posterolateral
approaches include posterior foraminotomy or
facetectomy. This surgical technique was developed in
1944 by R. Spurling [4] and later on, in more detail, by
Frykholm, W. Scoville [12] (“keyhole” technique). This
posterior approach enabled foraminotomy and herniated
disc resection through a small incision. However, most
neurosurgeons still prefer to use a more safe anterior
approach due to the probability of neurological deficit
and the need for segment stabilization [13]. Existing
endoscopic methods belong to intradisc interventions,
which are not capable of sufficient decompression of the
spinal structures.
During the last 10 years, portal endoscopic
discectomy, which was proved to be effective and safe,
has been widely used in our department to treat herniated
lumbar intervertebral discs [14]. Since 2014, this
technique has been successfully used to treat herniated
cervical intervertebral discs. In this paper, we provide a
detailed description of the portal endoscopic discectomy
for herniated cervical intervertebral discs and the most
important technical features of this method based on our
own experience.
It should be noted that this is the first ever detailed
report on application of this method in cervical surgery
both in Russian and international literature. When
analyzing published data, we found a large number of
research dealing only with application of full endoscopic
technique (i.e., cervical surgery through percutaneous
approach, both anterior and posterior, including only
foraminotomy) [15—17]. It should be taken into account
that both lumbar and cervical portal endoscopic methods
are technically similar to microsurgical interventions, but
differ from the latter in the degree of soft tissue
traumatization associated with these approaches and
visualization quality, which in this case enables “peeking
behind the root”.
The study was aimed at mastering the methodology of
the new technique, portal endoscopic discectomy,
determining the indications for this operation in patients
with herniated cervical disc, and comparing the results of
this operation with the results of the anterior microsurgical
discectomy.
PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
Material and Methods
We compared surgical outcomes in 25 patients with
C5—C6 [9] and C6—C7 lateral disc herniation [16], who
underwent endoscopic portal cervical discectomy.
Retrospective evaluation of surgical outcomes in 25
patients, who were also operated on by the first author and
underwent a microsurgical single-level anterior cervical
discectomy with interbody fusion at C5—C6 or C6—C7,
was used as a comparison group. The operation performed
in the control group patients is described in detail in
relevant guidelines [14, 15].
In both groups, early postoperative outcomes were
assessed as follows: VAS (visual analogue scale) — timing
and extent of radicular pain regression; decrease in pain
based on NDI (Neck Disability Index) — social adaptation
of patients; Odom criteria — overall postoperative
recovery. NDI provides a measure of patient's social
adaptation based on summation of points characterizing
the possibility of usual activities (walking, sleeping,
reading, recreation, etc.). Odom characterizes the effect
of the surgery in general, from good to unsatisfactory.
Evaluation of NDI and Odom criteria was carried out
immediately before the discharge. In addition, the time of
postoperative hospital stay was evaluated.
Mann-Whitney test was used in statistical processing
to assess the validity of the results.
The technique of portal endoscopic cervical
discectomy
Patient’s positioning on the operating table
The patient is laid on the operating table in prone
position with hands placed along the body. The head is
placed on the soft headrest or fixed in Mayfield head
clamp. The cervical spine is placed in neutral position.
Planning the incision
Electron-optical converter (EOC) is typically used
for incision planning, images of the cervical spine are
taken in the lateral projection. A sterile needle is placed in
the plane of the target intervertebral disc. Incision is
planned 1—2 cm lateral to the midline, depending on
patient’s physique (Fig. 2).
Operative approach
Skin incision is followed by incision of fascia and
EOC-controlled punctural placement of surgical cone at
the projection of the desired interval (Fig. 3). The base of
the lower articular process of the overlying vertebra is and
optimal point to place a port. Surgical port installation is
followed by preserving resection of adjacent vertebral
arches and flaval ligament is released. When the port is
properly installed, no significant resection of the
intervertebral joint is required. It should be remembered
that, according to various authors [16—18], resection of
15
 ORIGINAL ARTICLES

a b

Fig. 2. Positioning of incision, frontal (a) and lateral (b) projection (EOC display view).

25 to 50% of the intervertebral joint results in segmental
instability. Soft tissue removal from the intralaminar
space is followed by opening of the flaval ligament,
preferably as medial as possible and by blunt
dissection [19].
The main stage of the surgery
Opening of the flaval ligament usually results in
visualization of dural sac, whose separation provides the
approach to the gaine radiculaire. There is usually venous
plexus along the latter (see Fig. 3a), which is coagulated
and intersected. After that, the root becomes more mobile
despite the compression. Root displacement enables
visualization of disc hernia and its removal (see. Fig. 3b).
Surgical wound closure
The wound is closed layer by layer. Particular
attention is paid to restoration of the integrity of the
muscle aponeuroses in the surgical area.
Rigid cervical collar should be used for 3 weeks in the
early postoperative period to reduce axial loads on the
operated spinal motion segment.
Results
There was no worsening of neurological deficit in
both the study and control groups. In 2 (8%) patients in
the group of endoscopic removal of disc hernia, transient
numbness in the region of innervated dermatome was
observed followed by full regression by the time of
discharge. Preoperatively, median intensity of pain in the
shoulder and forearm as assessed by VAS score was 6 (3;
8) in the endoscopic discectomy group and 6 (4; 8) in the
microsurgical anterior discectomy group. After surgery,
this value decreased to 1 (0, 6) in the posterior endoscopic
discectomy group and 2 (1; 6) in the microsurgical
anterior discectomy group. In both groups, there was
significant decrease in pain (p=0.016 and p=0.034,
respectively). Immediately before discharge from the

a b

Fig. 3. The main stage of the operation.

a — separation of the gaine radiculaire; b — removal of disc herniation.

16 PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016

 Table 1. The intensity of pain in the neck, shoulder, and forearm on the visual analogue scale (VAS) before and after surgery
Patients with endoscopic posterior discectomy Patients with microsurgical anterior discectomy
Criterion
(n=25), study group (n=25), control group
Pain in the shoulder and forearm (median and range)
Preoperative score 6 (3; 8) 6 (4; 8)
Score before discharge 1 (0; 4) 2 (1; 6)
Whitney-Mann test, р 0,016 0,034
Pain in the neck (median and range)
Preoperative score 5 (2; 6) 6 (3; 7)
Score before discharge 1 (0; 3) 3 (1; 5)
Whitney-Mann test, р 0,024 0,034

hospital, the level of pain in the shoulder and forearm did
not differ significantly in these two groups (p>0.05). When
assessing pain in the neck, two groups were comparable in
the preoperative period (p>0.05) and significant decrease
in the severity of pain was observed in the postoperative
period (p=0.024 in the study group and p=0.034 in the
control group) (Table 1).
All study group patients noted complete or nearly
complete regression of pain syndrome immediately after
the operation.
Significant improvement of the score was observed in
patients who underwent endoscopic surgery. In both
groups, patients were subjectively satisfied with the
outcome. As for Odom criteria, there were significantly
more excellent and good outcomes in study group patients
(Table. 2).
Significant differences were found, when comparing
the time of postoperative hospital stay: it was 3 (2; 5) days
in the study group and 5 (4; 6) days in the control group.
In the study group, 1 (4%) patient reported the recurrence
of radicular pain one week after surgery. Preoperative and
postoperative MPT of this patient are shown in Fig. 4
and 5. Control MRI showed that disс hernia was
completely removed and the pain was not associated with
its recurrence. Antineuritic therapy for 2 weeks resulted in
complete regression of pain syndrome.
Thus, these studies demonstrate safety and efficacy of
the posterior portal endoscopic discectomy. When the
anatomy of the compressing factor is quite clearly
understood, this type of intervention is superior to other
operations in terms of the rate of rehabilitation and social
adaptation of patients and shortens postoperative hospital
stay.
Our results provided the basis for formulation of
indications and contraindications for the portal cervical
endoscopic discectomy.
Surgery is indicated in the following cases:
— clinical presentation of radiculopathy
corresponds to the side and level of the lesion detected by
MRI/CT;
— CT/MRI studies confirm the correspondence
between the “soft” compression of the root, which is
located in the lateral third of the width of the spinal canal,
and the clinical presentation of the disease;
— there is no effect of conservative treatment
during 3 weeks.
The operation is contraindicated in the following cases:
— There are signs of segmental instability;
— There is kyphotic deformity of the spine at the
level of disc herniation.
Discussion
The choice of surgical approaches in the treatment of
compression syndromes presenting with neurological and
vascular disorders is associated with a number of
controversial issues [20, 21], although these interventions
have been existing for rather long period [15]. The main
problem is, which decompression option should be
selected, either anterior or posterior one. Both methods
enable quite adequate solution of this problem. Selection
of decompression direction is determined by localization

Table 2. Surgical outcomes according to NDI index and Odom criterion

Patients with endoscopic posterior Patients with microsurgical anterior discectomy
Criterion (criterion)
discectomy (n=25), study group (n=25), control group
NDI (median and range)
Preoperative score 24 (8; 32) 23 (6; 39)
Score before discharge 13 (5; 25) 13 (5; 19)
Whitney-Mann test, р 0,056 0,026
Odom criterion (median and range)
Very good/good 21 17
Satisfactory/unsatisfactory 4 8

PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016 17

 ORIGINAL ARTICLES

a b

Fig. 4. Preoperative MRI.

a — sagittal projection; b — axial projection (explanation in the text).

a
b
Fig. 5. Postoperative MRI.
a — sagittal projection; b — axial projection (explanation in the text).

Fig. 6. The algorithm of selection of surgical approach in patients with cervical spondylogenic compression.
18 PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
 of compressing factor as proved for single-level
procedures.
According to opinion of H. Jho expressed in a private
conversation, posterior cervical foraminotomy has
limitations in the case of frontal compression with
osteophyte, posterior compression with uncovertebral
joint, and pronounced cicatricial process. The cardinal
clinical syndrome of cervical radiculopathy requires more
thorough examination of the patient, since it is often not
accompanied by unequivocal x-ray data about the cause
of the compression, and almost never has pathognomonic
changes in neurovascular structures. The highest accuracy
of detection of muscular atrophy in corresponding
muscles was proved to be the main criterion of the level of
radiculopathy. Modern neurovisualization methods
enable identification of the compressing factor: “soft”
(herniated disc) or “hard” (osteophyte or bone spike),
which is a decisive factor in the choice of surgical
approach. In the case of lateral “soft” disc, posterior
portal endoscopic resection is indicated, whereas more
radical removal of osteophyte in this area can be achieved
through the ventral approach. The nature of the
compressing factor in patients with the cervical
radiculopathy syndrome should also be considered in the
context of neurological symptoms. In the case of
osteophyte, the severity of radicular symptoms (especially
pain) is substantially lower than in the case of “soft”
hernia.
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PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
To our knowledge, inefficiency of surgical treatment
of patients with radiculopathy is primarily due to
underestimation of neurological symptoms and
interpretation of neurovisualization data. In particular,
the paramedian location of disc hernia is often
accompanied by radicular symptoms in the contralateral
hand. The ignorance of this fact may cause inadequate
choice of the side of surgical approach and therefore the
lack of clinical effect of the surgery.
Confirmed spine deformity and detected segmental
instability are significant factors in choosing the direction
of surgical approach. Cervical spine kyphosis associated
with degenerative processes in the vertebrae always
suggests the use of ventral approach accompanied by
appropriate stabilizing measures.
Based on these data and surgical outcomes, we
developed the algorithm for selection of surgical approach
in patients with cervical spondylogenic compression
(Fig. 6).
The use of endoscopic microdiscectomy in the
treatment of herniated cervical intervertebral discs is
highly effective and provides clinical results with
considerably less surgical trauma. We discovered technical
features and proposed recommendations, which will
contribute to widespread use of this promising minimally
invasive technique in neurosurgical practice.
There is no conflict of interest.
11. Shen FH, Samartzis D, Khanna BS, Goldberg EJ, An H. Comparison of
clinical and radiographic outcome in instrumented anterior cervical discec-
tomy and fusion with or without direct uncovertebral joint decompression.
Spine J. 2004;4:629-635.
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Denisenko EI, Stepanenko VV. Differencirovannaja taktika hirurgicheskogo
lechenija bol'nyh s vertebral'nymi kompressionnymi sindromami na
shejnom urovne. Voprosy nejrohirurgii im. N.N. Burdenko. 2003;3:28 (In
Russ.).
14. Arestov SO, Vershinin AV, Gushha AO. Sravnenie jeffektivnosti i
vozmozhnostej jendoskopicheskogo i mikrohirurgicheskogo metodov
udalenija gryzh mezhpozvonkovyh diskov pojasnichno-krestcovogo otdela
pozvonochnika. Voprosy nejrohirurgii im. N.N. Burdenko. 2014;78:6:9-14
(In Russ.).
15. Goushcha AO, Arestov SO. Endoskopicheskaya spinal'naya khirurgiya.
Monography. 2010. (In Russ.).
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19. Goushcha AO, Arestov SO. Torakoskopicheskaya khirurgiya v lechenii
novoobrazovanii pozvonochnika i paraspinal'nykh neirogennykh
opukholei. Russian traumotology and orthopedy. 2010;2(56):129-131.
(In Russ.).
20. Yang JS, Chu L Chen L, Chen F, Ke ZY, Deng ZL. Anterior or posterior
approach of full-endoscopic cervical discectomy for cervical intervertebral
Commentary
The article provides a detailed description and comparative
analysis of the use of innovative technique of portal endoscopic
discectomy in treatment of herniated cervical discs. The study
included 25 patients, who were operated on in 2014—2016. The
control group included 25 patients, who were operated on using
anterior cervical discectomy with installation of a single-level
interbody implant. The authors suggested indications for the
use of portal endoscopic discectomy: paramedian or lateral
herniation of the cervical disc with monoradicular symptoms
and no calcification of disc herniation as evidenced by CT. The
signs of segmental instability and spinal deformity, which is
usually indicative of segment stabilization, are considered as
contraindication. The technique of surgical intervention from
patient positioning on the operating table to surgical wound
suturing is described in detail.
Treatment outcomes were assessed on VAS scale (visual
analog scale), preoperative and postoperative values were
compared. Preoperative comparison of the groups showed no
statistically significant difference between the groups of
patients. Social adaptation and quality of life have been assessed
using NDI (Neck Disability Index). Additionally, overall
recovery of patients was compared using Odom criterion and
time of patients’ hospital stay was evaluated. High level
statistical processing of the results was performed using modern
statistical processing tools, which proves the validity of the
results of the study.
In my opinion, this article is a valuable and relevant
scientific work. The provided information can be used to
develop methods of portal cervical endoscopic discectomy. The
presented data demonstrate the efficacy and safety of the
method.
20 PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
disc herniation? A comparative cohort study. Spine (Phila Pa 1976). 2014
Oct 1;39(21):1743-1750.
PMID: 25010095
doi: 10.1097/BRS.0000000000000508
21. Li XC, Zhong CF, Deng GB, Liang RW, Huang CM. Full-Endoscopic
Procedures Versus Traditional Discectomy Surgery for Discectomy: A Sys-
tematic Review and Meta-analysis of Current Global Clinical Trials. Pain
Physician. 2016 Mar;19(3):103-118.
PMID: 27008284
The bulk of the article focuses on describing the techniques
and nuances of the operation. In our clinic, we use portal
endoscopic discectomy to treat lumbosacral intervertebral disc
herniation, but the use of this technique in the cervical spine is
associated with a number of difficulties. The correct positioning
of the endoscopic port is the most challenging problem. The
authors carefully describe this issue and note the nuances, so
that it is, in fact, guidelines to master this method.
Selection of patients for this operation is a disputable
question. Indeed, the posterior approach is only suitable for
resection of lateral and paramedian disc hernia, since even a
small traction of the compressed spinal cord can cause severe
postoperative neurological disorders. This fact was the main
argument to switch from the posterior microsurgical approach
to anterior approaches in the late 1900s. The authors
supplemented the standard preoperative examination complex
with CT of the cervical spine to measure preoperative density of
disc hernia. This is due to the fact that significant traction of
nerve structures and the use of bulky microsurgical instruments
is required for removal of ossified herniation of intervertebral
discs, which in turn eliminates the advantages of endoscopic
approach. In our view, this additional preoperative examination
is reasonable and improves safety of the technique.
Therefore, this material is relevant and highly informative.
The detailed description of the procedures and techniques of
the portal endoscopic discectomy makes this work a valuable
guideline for the operation. This technique is a new promising
trend in neurosurgery. The authors fully proved the effectiveness
and safety of the method.
N.L. Konovalov (Moscow)
doi: 10.17116/engneiro201680621-31

Clinical and Morphological Characteristics, Diagnostic Criteria, and Outcomes of

Surgical Treatment of TSH-secreting Pituitary Adenomas
L.I. ASTAF’EVA1, B.A. KADASHEV1, L.V. SHISHKINA1, P.L. KALININ1, D.V. FOMICHEV1, M.A. KUTIN1, I.A. AREF’EVA1,
L.K. DZERANOVA2, YU.G. SIDNEVA1, I.S. KLOCHKOVA1, D.L. ROTIN3

1
Burdenko Neurosurgical Institute, Moscow, Russia; 2Endocrinology Research Center, Moscow, Russia; 3Moscow Scientific Clinical Center,
Moscow, Russia

Thyrotropinomas (TSH-secreting tumors) are a rare type of pituitary adenomas, which account for about 0.5—2.0% of all pituitary
tumors. The criterion of thyrotropinoma includes visualization of the tumor along with normal or elevated blood level of the
thyroid-stimulating hormone (TSH) and high level of free T4 (fT4) and free T3 (fT3).
Objective. The study was aimed at investigating clinical, diagnostic, and morphological characteristics and treatment outcomes
of TSH-secreting pituitary tumors.
Material and methods. The study included 21 patients aged 15 to 67 years with pituitary adenoma and normal or elevated blood
level of TSH in combination with elevated levels of fT4 and fT3, who were operated on at the Burdenko Neurosurgical Institute in
the period between 2002 and 2015. The patients were tested for the levels of TSH, fT4, fT3, prolactin, cortisol, luteinizing
hormone (LH), follicle-stimulating hormone (FSH), estradiol/testosterone, and insulin-like growth factor (IGF-1) before surgery, in
the early postoperative period, and 6 months after surgery. The thyroid status was evaluated using the following reference values:
TSH, 0.4—4.0 mIU/L; fT4, 11.5—22.7 pmol/L; fT3, 3.5—6.5 pmol/L. An immunohistochemical study of material was performed
with antibodies to TSH, PRL, GH, ACTH, LH, FSH, and Ki-67 (MiB-1 clone); in 13 cases, we used tests with antibodies to type 2
and 5 somatostatin receptors and D2 subtype dopamine receptors.
Results. Thyrotropinomas were detected in patients aged 15 to 67 years (median, 39 years) with an equal rate in males (48%) and
females (52%). Before admission to the Neurosurgical Institute, 11 (52%) patients were misdiagnosed with primary hyperthyroidism;
based on the diagnosis, 7 of these patients underwent thyroid surgery and/or received thyrostatics (4 cases). Hyperthyroidism
symptoms were observed in 16 (76%) patients. The blood level of TSH was 2.47—38.4 mIU/L (median, 6.56); fT4, 22.8—54.8
nmol/L (median, 36); fT3, 4.24—12.9 pmol/L (median, 9.66). Tumors were endosellar in 4 (19%) cases and the endo-extrasellar
in 17 (91%) cases. Total tumor resection was performed in 7 (33%) patients. All these tumors were either endosellar or endo-
suprasellar. No total resection was performed in patients with infiltrative growth of adenoma (invading the skull base structures).
An immunohistochemical study of resected tumor specimens detected only TSH expression in 3 (14%) cases; 18 (86%) tumors
were plurihormonal and secreted TSH and GH and/or PRL. Of 13 tumors, expression of the type 2 dopamine receptor was
detected in 9 (69%) cases; expression of type 5 and type 2 somatostatin receptors was found in 6 (46%) and 2 (15%) cases,
respectively.
Conclusion. Postoperative decrease in the TSH level to 0.1 mIU/L or less was the criterion of total tumor resection. Total resection
was performed in 33% of patients, having only endosellar and endo-suprasellar tumors. In most cases, tumors were plurihormonal
and secreted TSH and GH and/or PRL.
Keywords: thyrotropinoma, TSH-secreting pituitary adenoma, central hyperthyroidism, acromegaly, somatostatin analogues.

Abbreviations:
ACTH — adrenocorticotrophic hormone
AB — antibodies
IMH — immunohistochemical study
IGF-1 — insulin-like growth factor-1
LH — luteinizing hormone
OGTT — oral glucose tolerance test
PRL — prolactin
fT3 — free T3
fT4 — free T4
STH — somatotropic hormone
TRH — thyrotropin-releasing hormone
TSH — thyroid stimulating hormone, thyrotropic hormone
TSH-PA — TSH-secreting pituitary adenoma
FSH — follicle stimulating hormone
CAIT — chronic autoimmune thyroiditis
D2DR — D2 subtype dopamine receptors
L-T4 — levothyroxine
SSt2 — type 2 somatostatin receptors
SSt5 — type 5 somatostatin receptors

© Group of authors, 2016 e-mail: Last@nsi.ru

PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016 21

 ORIGINAL ARTICLES
Thyrotropinomas (TSH-secreting tumors) are a rare
type of pituitary adenomas, which account for about
0.5—2.0% of all pituitary tumors. The criterion of
thyrotropinoma includes visualization of the tumor along
with normal or elevated blood level of the thyroid-
stimulating hormone (TSH) and high level of free T4
(fT4) and free T3 (fT3). Overproduction of TSH by these
tumors leads to hyperstimulation of the thyroid gland
and clinical presentation of so-called central
hyperthyroidism. This TSH production is autonomous
due to impaired down-regulation of thyroid hormones,
which affects the hypothalamic-pituitary-thyroidal
system. Low incidence of these tumors as well as
sometimes insufficient doctors’ awareness of clinical
features and diagnosis of central hyperthyroidism can
lead to hyperdiagnosis of Basedow's disease or other
thyroid diseases involving hyperthyroidism, which can
result in unreasonable thyroid surgery and/or therapy
with radioactive iodine.
Material and methods
The study included patients with pituitary adenoma
and normal or elevated blood level of TSH in combination
with elevated levels of fT3 and fT4, who were operated on
at the Burdenko Neurosurgical Institute during the
period from 2002 to 2015. The group included 21 patients
aged 15 to 67 years (median 39 years), 11 females (52%)
aged 15 to 63 years (median 30 years) and 10 males (48%)
aged 15 to 67 years (median 49 years).
All patients underwent MRI of the brain. All
identified tumors were macroadenomas sized 16 to 64
mm in diameter (median 26 mm). We classifies them
according to their growth pattern and location (see
Table). Thus, endo-sellar and endo-suprasellar adenomas
not invading skull base structures (10 cases) were
considered as non-infiltrative. Endo-extrasellar tumors
invading the skull base structures, including cavernous
sinus, were considered as infiltrative (11 cases).
The patients were tested for the levels of TSH, fT4,
fT3, prolactin, cortisol, LH, FSH, estradiol/testosterone,
and, in 13 cases, IGF-1 before surgery and in the early
postoperative period. In the case of high level of IGF-1,
growth hormone level was additionally studies during
oral glucose tolerance test. Thyroid status was evaluated
using the following reference values: TSH, 0.4—4.0
mIU/L; fT4, 11.5—22.7 pmol/L; fT3, 3.5—6.5 pmol/L.
At admission to the Burdenko Neurosurgical Institute,
thyroid status of patients who had a history of
thyroidectomy and patients treated with somatostatin
analogues or thyrostatics was assessed prior to the
thyroidectomy or beginning of medication. In patients
with thyrotropinoma and primary hypothyroidism,
evaluation was carried out during therapy with
levothyroxine; high levels of free thyroid hormone
fractions and high levels of TSH were the criteria for
inclusion in the study.
22 PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
The patients were operated on through the
transsphenoidal approach in 18 cases, including 14 cases
of endoscopic endonasal approach and 3cases of
transcranial approach (cases 2, 8, and 9). One patient
(case 9) was reoperated at the Burdenko Neurosurgical
Institute for continued tumor growth after non-radical
transcranial tumor resection 6 years before reoperation.
Another patient (case 19) was previously operated on in
other clinic and was admitted with tumor recurrence 18
months after surgery. In both cases, hormone level before
the first operation is unknown.
Operating material was stained with hematoxylin
and eosin using the standard procedure followed by
thorough histological examination.
Immunohistochemical study of the material was carried
out using antibodies (ABs) to TSH, PRL, STH, ACTH,
LH, FSH, and Ki-67 proliferation marker (MiB-1
clone). Tumors with Ki-67 MI expression of less than 3%
were considered as non-aggressive, 3% or more —
aggressive. In 13 cases, AT tests were carried out with
type 2 and 5 somatostatin receptors and D2 subtypes
dopamine receptors (D2DR).
Follow-up study was carried out in 12 patients.
Follow-up time was 1 month to 7 years (median, 6
months).
Results
Clinical presentation of the disease included mainly
symptoms of hyperthyroidism in 16 (76%) of patients,
whose history was 1 to 13 years (median 4 years).
Furthermore, we detected symptoms of mass effect of the
tumor: visual impairment in 8 (38%) patients and
cephalgic syndrome in 7 (33%). Two patients were
admitted in grave condition with large tumors
accompanied by occlusive symptoms due to compression
of the third ventricle (case 2, 8).
Four of eight reproductive-age females had
amenorrhea (in two of them it was primary); 4 female
patients had normal menstrual function. Lactorrhea was
observed in 3 females. Androgen deficiency was
diagnosed in 3 males.
Psychopathology usually fit into the presentation of
anxiety and phobic disorders in the form of neurotic
syndrome (12 patients) and panic attacks (11). Emotional
disturbances in the form of depression were observed
only in 3 patients. Eight patients complained of fatigue
and weakness, 8 — palpitations, 5 — anxiety, 11 — mood
lability, 3 — sleep disorder, 3 — sweating, 3 — tremor, 2
— subfebrile temperature, 2 — weight loss. The patients
often had a combination of the aforementioned
complaints. Psychiatric symptoms were most often
moderate (13 patients).
Seven patients (see Table) had a history of thyroid
surgery (6 — hemithyroidectomy, one of these patients
had been operated on twice; 1 — thyroidectomy).
 Four patients received thyreostatic therapy; at the
time of admission, 2 of them (cases 9 and 10) still received
thyrostatics. In these patients, fT4 levels before treatment
with thyrostatics were 27.4 and 54.8 nmol/L and TSH
levels were 5.59 and 6.52 mIU/L, respectively. At the
time of admission to the Burdenko Neurosurgical
Institute, normalization of fT4 level to 17.5 and 22.0
nmol/L was accompanied by increase in TSH levels to
9.72 and 10.2 mIU/L, respectively.
Thyroid ultrasound was performed in 13 patients:
diffuse goiter was detected in 4 patients, nodular goiter —
3, diffuse nodular goiter — 1, and thyroid hypoplasia was
observed in 1 patient with secondary TSH-PA.
At admission, three patients received levothyroxine:
one of them previously underwent thyroidectomy (case
8), two patients with chronic autoimmune thyroiditis
(CAIT) had primary hypothyroidism. Despite the high
dose of levothyroxine (200 and 175 μg) and high level of
free fractions of the thyroid hormones, TSH level was
high (cases 16 and 19). We regarded these tumors as
secondary thyrotropinomas. One of them had previously
been operated on at the other hospital and was admitted
to the Burdenko Neurosurgical Institute with recurrent
pituitary adenoma.
Three patients had symptoms of acromegaly (change
in appearance, growth of extremities, etc), confirmed by
the results of hormonal blood test (high levels of IGF-1
and absence of STH suppression below 1.0 ng/ml during
the oral glucose tolerance test, OGTT).
In patients with TSH-PA, blood level of TSH was
2.47—38.4 mIU/L (median, 6.56), fT4 level — 22.8—
54.8 nmol/L (median, 36), fT4 level — 4.24—12.9
pmol/L (median, 9.66).
We found no correlation between the levels of TSH
and fT4 (Fig. 1), between the level of TSH and fT3, as
well as fT4 and fT3.
IGF-1 was tested in 10 patients with no clinical
symptoms of acromegaly, 2 of them had elevated levels of
IGF-1. They were tested for STH during OGTT,
suppression of STH below 1.0 ng/ml was found. Five
(24%) patients had hyperprolactinemia from 528 to 2678
mIU/L (median, 758).
Two patients (one with TSH-PA and the other with
mixed TSH-STH-secreting adenoma) were
preoperatively treated with prolonged somatostatin
analogues, which resulted in normalization of TSH,
STH, and IGF-1 levels (cases 12 and 14).
All 21 patients had macroadenomas: 4 cases —
endosellar, 6 cases — endo-suprasellar, not invading the
skull base structures (non-infiltrative). In 11 patients,
tumors invaded the skull base structures, including the
cavernous sinus (infiltrative). When comparing the
growth pattern of tumors in 7 patients having a history of
thyroid surgery, we found that, in this group, infiltrative
growth occurred in 5 (71%) cases, whereas in 14 patients,
who had no previous thyroid surgery, infiltrative growth
occurred in 6 (43%) cases. However, there were no
PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
statistical differences, when comparing tumor growth
pattern in the groups of patients with and without history
of thyroid surgery, as well as in various age and gender
groups.
Postoperative TSH level was elevated in only 1 out of
21 patients. It decreased in 20 patients; in 10 cases, it was
even lower than normal (0.01 ± 0.19 mIU/L), and in 10
patients it reached the normal range (0.68—2.9 mIU/L).
Maximal reduction occurred on day 1 after operation.
The rate of decrease in fT4 levels were significantly lower.
Thus, fT4 level tested on day 1—3 after surgery remained
high in all patients. However, subsequent measurements
on day 5—7 days after surgery showed its normalization
or reduction in most of the cases.
The tumor was totally resected only in patients with
endosellar (3 cases) and endo-suprasellar (4) tumors. In
the case of infiltrative tumor, there were no cases of total
resection. We studies protocols of operations and
concluded that thyrotropinomas were in most cases
similar to other typical adenomas, they were rarely dense
and well perfused. Intense venous bleeding occurred only
in 2 cases during tumor resection from the cavernous
sinus. Close adherence of the tumor with vessels and
nerves was observed in 2 cases during transcranial
operations. One patient had a large hemorrhagic cyst
within the tumor.
We compared postoperative TSH levels in patients
with radical and non-radical tumor resection. In the first
case, TSH level measured in the early postoperative
period was not detectable or no more than 0.1 mIU/L.
Normalization of TSH or its reduction to 0.1 mIU/L,
as well as transient postoperative hypothyroidism, are
not the criteria of completeness of tumor resection. Thus,
normalization or reduction of serum level of TSH, fT4,
and fT3 was observed in all patients even in the case of
subtotal resection. However, further follow up of 5
patients with postoperative euthyroidism and tumors
remnants showed that 4 patients had elevated levels of
TSH and/or fT4 6—12 months after surgery; one patient
with mixed STH-TSH-secreting tumor maintained
euthyroidism, but the levels of STH and IGF-1 remained
high. These patients underwent stereotactic radiotherapy
of residual tumor tissue.
Fig. 2 shows the dynamics of TSH and fT4 in
patient A., 21 years old, with non-radical tumor resection,
Fig. 3 shows changes in the level of TSH and fT4 in
patient B., 38 years old, with radical tumor resection.
As can be seen from Fig. 2, subtotal tumor resection
in patient A. led to decrease in TSH level to 0.52 mIU/L
on day 1 after the operation and development of transient
hypothyroidism. However, euthyroid state was diagnosed
in 1 month, and recurrence of hyperthyroidism occurred
in 1 year. The patient underwent a course of stereotactic
radiation therapy followed by remission of the disease.
TSH level below 0.1 mIU/L was considered as the
criterion of radical tumor resection.
23
 Summary table of the main data of 21 patients with thyrotropinoma

24
Prior to adenomectomy and treatment with thyrostatics and/or SA in the early After pituitary adenomectomy
IMG characteristics of resected tumors*
postoperative period and in 6—18 months

Tumor MRI signs of Ki-

Age, History of Thyroid TSH, fТ4, PRL, TSH, fТ4, Thyroid
S/N Sex growth tumor Treatment TSH PRL STH DR-D2 Sst2 Sst5 67,
years treatment status mIU/L pmol/L mIU/L pattern
mIU/L pmol/l status %
remnants
ORIGINAL ARTICLES

1 F 25 - HyperT 2,71 43,17 266 Inf 0,19 20,60 ND ND + + + + – + 0—1

2 F 15 - HyperT 3,15 37,00 147 Inf 2,35 30,40 Yes HyperT RT + – – + – – 0—1

3 F 26 - HyperT 4,05 31,70 850 Non- <0,01 11,70 No HypoT L-Т4 + + + ND ND ND 2

inf
4 M 38 - HyperT 4,28 23,60 420 Non- 0,06 28,30 No HypoT L-Т4 + + + ND ND ND 3
inf
5 M 67 - HyperT 4,75 39,50 133 Non- 0,09 17,30 No HypoT L-Т4 + + + ND ND ND 3
inf
6 M 45 HME HyperT 5,01 39,20 134 Non- 0,92 22,30 ND ND + + + ND ND ND 5
+ACRO inf
7 F 30 - HyperT 5,21 40,50 273 Non- <0,01 10,40 No HypoT L-Т4 + + + ND ND ND 5
inf
8 M 39 - HyperT 5,59 20,56 420 Inf 2,90 21,50 ND ND + − − + – – 0—1

9 F 56 HME, HyperT 5,59 27,40 2678 Inf 2,40 21,30 Yes ND + + + + – – 0—1
TS
10 M 21 TS HyperT 6,52 54,80 237 Inf 0,52 33,11 Yes HyperT RT + − − – – – 0—1

11 M 34 - HyperT 6,56 36,40 528 Inf 2,13 21,50 ND ND + − + – – – 0—1

12 M 65 HME, HyperT 7,50 26,90 280 Inf 1,12 11,80 ND ND + + + ND ND ND 0—1

SA
13 M 59 HME HyperT 7,70 36,10 148 Inf 0,14 10,50 Yes EuT+ SA,RT + + + ND ND ND 5
+ACRO ACRO
14 M 53 SA HyperT 7,96 28,86 151 Non- 0,10 15,10 No EuT No + + + + – + 2
inf
15 F 33 - HyperT 10,87 39,73 1909 Inf 0,16 16,90 ND ND + + + + – + 0—1

16 F 39 - HypoT 13,50 22,80 705 Non- 0,10 13,00 No HypoT L-Т4 + + + ND ND ND 3

inf
17 F 15 - HyperT 13,96 23,70 540 Non- 0,01 10,90 No HypoT L-Т4 + − + + – + 5
inf
18 F 63 TE HypoT 22,93 28,30 758 Non- 1,44 9,80 ND ND + + − – – + 0—1
inf
19 F 21 - HypoT 27,90 24,50 288 Non- 2,47 27,20 No EuT L-Т4 + + − + – + 5
inf
20 F 56 HME, HyperT 28,10 36,20 483 Inf 4,20 24,90 Yes HyperT RT + − + + + – 0—1
TS
21 F 60 HME, HyperT 38,40 52,80 499 Inf 1,60 24,50 ND ND + − + – + – 0—1

PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016

TS +ACRO
Note. HME — hemithyroidectomy; TE — thyroidectomy; TS — thyrostatics; HyperT — hyperthyroidism; HypoT — hypothyroidism; EuT euthyroid; ACRO — acromegaly, the active phase; Inf — infiltrative tumor; Non-inf — non-
infiltrative tumor; ND — no data; L-T4 — levothyroxine; SA — somatostatin analogues; RT — radiotherapy. * no cases of expression of LH, FSH, ACTH were detected.
 As can be seen from Fig. 3, radical tumor resection in
patient B. was accompanied by decrease in TSH level to
0.06 mIU/L on day 1 after surgery and persistent
hypothyrosis. Disease remission was observed throughout
the whole follow-up period (2 years). The patient was
administered with levothyroxine 1 month after surgery.
Four patients with radical tumor resection developed
panhypopituitarism, which persisted 6—18 months after
surgery (secondary hypothyroidism, hypocorticism,
hypogonadism, STH-deficiency); in 3 of them, it
occurred in combination with diabetes insipidus.
IMH-study of resected tumor samples showed that
all tumor were stained with AB to TSH; expression of
only TSH was detected in 3 (14%) cases (“pure” TSH-
secreting tumors), in 18 (86%) cases, tumors were
plurihormonal: 2 cases demonstrated expression of TSH
and PRL, 4 cases — TSH and STH, 12 cases — TSH,
STH, and PRL (Fig. 4).
In 4 (29%) out of 14 cases with expression of PRL,
there was increased blood level of PRL before surgery
(758 mIU/L, 850 mIU/L, 1909 mIU/L, 2678 mIU/L);
the remaining 10 (71%) tumors were accompanied by
normoprolactinemia (133—288 mIU/L). Tree (19%) out
of 16 patients with STH expression in tumor tissue were
diagnosed with acromegaly (see Table).
Expression of type 2 dopamine receptors (D2DR)
was detected in 9 (69%) of the 13 tumors, type 5
somatostatin receptor (SSt5) — 6 (46%), type 2
somatostatin receptor (SSt2) — 2 (15%) (see Table).
In 5 of 9 cases, D2DR expression occurred in
combination with expression of PRL. In 4 of 6 cases,
SSt5 expression was accompanied by STH expression.
Two tumors with SSt2 expression were also associated
with expression of STH, however, there were no cases of
adenoma with concomitant expression of SSt5 and SSt2.
The patients, who preoperatively received somatostatin
60 Levels of TSH, mIU/L
and fT4, pmol/L
50
40
30
20
10
0
1 2 3 4 5 6 7 8
Fig. 1. Preoperative blood level of TSH and fT4 in patients with thyrotropinoma.
Dotted lines show the upper limits of reference values for both parameters. No correlation between blood levels of TSH and fT4 were found.
PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
analogues with a positive effect in the form of
normalization of TSH and fT4 levels, demonstrated
expression of TSH and STH (case 12) and SSt5 (case 14)
in tumors.
There was no relationship between expression of
PRL and dopamine receptors, as well as STH and
somatostatin receptors in tumor cells.
The group average Ki-67 MI was 0—5% (median
1%), it was less than 3% in 13 cases, 3% or more in 8
cases. No statistical difference was found when analyzing
the proliferative activity of the pituitary tumor (Ki-67
MI) in patients who previously underwent thyroid
surgery and not operated patients (see Table).
Discussion
TSH-PA accounts for 0.5—2% of all pituitary
tumors [1]. The first case of hyperthyroidism and increase
in sella dimensions was described in 1960. [2]. In 1970, S.
Hamilton et al. [3] described TSH-PA with proved TSH
measurement using radioimmunoassay. Previously,
these tumors were considered casuistic and were detected
at the stage of large invasive pituitary macroadenomas.
However, the discovery of supersensitive hormonal
methods and high-resolution neuroimaging techniques
facilitated detection of TSH-PA at the stage of small
tumors. Recently published data show that the incidence
of TSH-PA in European countries may be 0.28 cases per
1 million population [4]. The incidence of TSH-PA is
equal in males and females, in contrast to the
predominance of females among the patients with thyroid
diseases [5]. Familial cases of TSH-PA were described
within MEN-1 [6] and in FIPA-families (familial
isolated pituitary adenoma associated with AIP gene
mutation) [7].
TSH
fT4
Case
9 10 11 12 13 14 15 16 17 18 19 20 21 numbers
25
 ORIGINAL ARTICLES

6,52

4,0 TSH
2,48
2,94 2,17 3,16 1,73
2,79
1,56
0,4
0,52 0,68
0,1

Preoperave 1 5 14 1 6 1 year 2 years 3 years 4 years

day days days month months
a

fT4, pmol/L
54,8

33,1 27,3
22,7 fT4
19,4
22 14,2 12,4
18,9
11,5
10,1 7,18

Preoperave 1 5 14 1 6 1 year 2 years 3 years 4 years

b day days days month months

Fig. 2. Patient A., 21 years old, with non-radical tumor resection (case 10).
a — dynamics of TSH level; b — dynamics of fT4 level (yellow dotted line show upper and lower limits of reference values of blood level of TSH and fT4, respectively;
red dotted line shows the threshold, below which TSH values correspond to completeness of surgery).

TSH-PA occurs in various age groups of patients
from 8 to 84 years [8—10]. However, most of the cases
described in the literature occurred in patients aged 50—
60 years [1]. In our study, the average age of males was 49
years, females were younger, their average age was 30
years.
The criteria of TSH-secreting pituitary tumors
include its visualization and normal or elevated blood
levels of TSH along with elevated levels of fT4 and fT3.
The symptoms of hyperthyroidism in combination with
these hormonal values exclude Graves disease [11]. In
difficult diagnostic cases, when there is no obvious
clinical hyperthyroidism and TSH-PA cannot be reliably
diagnosed based on the analysis of basal levels of
hormones, functional tests are used (test with thyrotropin-
releasing hormone, TSH), triiodothyronine suppression
assay, assessment of the molar ratio of α-subunit/TSH).
Differential diagnosis with the syndrome of thyroid
hormone resistance, which is also characterized by high
levels of fT4 and fT3 in combination with high or normal
level of TSH is the most challenging problem. This
syndrome is characterized by reduced sensitivity of
peripheral tissues to thyroid hormones; it is an autosomal
dominant hereditary disease caused by mutation in the
gene encoding β-type receptor to thyroid hormones [1,
12]. Pituitary adenoma detected by MPT-study in most
cases confirms TSH-PA. However, there are reported
cases of combination of the syndrome of thyroid hormone
resistance with TSH-secreting pituitary microadenomas
and pituitary incidentaloma [13].
According to the literature [14], normal level of TSH
is detected in approximately 30% of cases of TSH-PA.
Despite the TSH-dependent genesis of hyperthyroidism,
we found no direct correlation between the level of fT4
and TSH in our study. Similar data are reported in the
review by R. Beck-Peccoz [1].
Normal level TSH along with high levels of fT3 and
fT4 can be explained by increase in biological activity of
TSH molecule [15]. TSH molecules secreted by pituitary
tumors are heterogeneous and may have normal,
reduced, or increased ratio between their biological and
immunological activity, which that can be associated
with post-translation changes in the tumor cell [16, 17].
Normal blood level of TSH in some TSH-PA patients
justifies the need for testing both TSH and free fractions
of thyroid hormones in all patients with pituitary
adenoma.

26 PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016

 TSH, mIU/L
4,28

4,0

0,68 0,7
0,27 TSH
0,4 0,16
0,1
0,06 0,01 0,01

Preoperave 1 day 5 days 1 month 2 months 6 months 1 year 2 years

а
L-Т4

fT4, pmol/L

28,3
23,6
22,7
16,9 12,6 12,6 13,2 13,5
fT4
11,5
7,00

Preoperave 1 day 5 days 1 month 2 months 6 months 1 year 2 years

б
L-T4

Fig. 3. Patient B., 38 years old, who underwent radical tumor resection (case 4).
a — dynamics of TSH level; b — dynamics of fT4 level (yellow dotted line show upper and lower limits of the reference values of blood level of TSH and fT4,
respectively, red dotted line shows the threshold, below which TSH values correspond to completeness of surgery).

Cases of TSH-secreting tumors associated with
chronic autoimmune thyroiditis have been reposted in
the literature [18—20]. Normal or elevated level of TSH
along with high level of fT4 and fT3 [18] is also considered
a diagnosis criterion of TSH-PA in patients with primary
hypothyroidism resulting from CAIT or thyroidectomy,
who receive replacement therapy with levothyroxine. We
reported 2 cases of TSH-PA in CAIT patients. Despite
the high dosed of levothyroxine and elevated level of fT4,
TSH level remained high. MRI study detected decrease
in tumor size in one case, and relapse after previous
pituitary adenomectomy in the other. Histological
examination confirmed the presence of mixed pituitary
adenoma with expression of TSH, PRL, and STH in
both cases. The role of long-lasting increase in TSH level
and pituitary hyperplasia in CAIT patients in the
pathogenesis of TSH-PA was discussed in the literature
[19, 20].
Clinical presentation of TSH-PA consists of
symptoms of hyperthyroidism and mass-tumor effect.
Symptoms of hyperthyroidism were detected in most
(76%) patients and were similar to manifestation of
PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
primary hyperthyroidism, but they were characterized by
milder course and absence of other autoimmune
syndromes, which are common in diffuse toxic goiter
(endocrine ophthalmopathy, pretibial myxedema, and
acropathy). Prevalence of circulating antibodies to
thyreoglobulin and thyroid peroxidase in TSH-PA
patients is similar to that in the general population.
However, the literature [21, 22] described the patients
who developed Graves' disease after resection of pituitary
adenoma; bilateral exophthalmos in combination with
autoimmune thyroiditis. In most patients,
hyperstimulation of thyroid with TSH results in diffuse
increase in thyroid size, in 72% of cases — to formation
of single or multiple nodules [1]. Goiter is usually
detected even in patients who previously underwent
partial thyroidectomy due to growth of residual thyroid
tissue. Differentiated thyroid cancer was reported in
several patients with TSH-PA [23—26]. In patients with
thyroid nodules, monitoring of thyroid nodules and thin-
needle aspiration biopsy are required.
In most cases of TSH-PA reported in the literature,
where patients were first misdiagnosed with primary
27
 ORIGINAL ARTICLES
TSH-posive tumors (21)
“pure” TSH-3
TSH-STH-4
Fig. 4. Immunohistochemical expression of hormones by TSH-secreting pituitary adenomas.
hyperthyroidism (Graves' disease), they often had a
history of thyroid surgery and/or radioactive iodine
therapy. In these cases, tumors often become more
aggressive and demonstrate infiltrative growth pattern.
Decrease in blood levels of circulating thyroid hormones
resulting from this treatment leads to activation of tumor
growth by a mechanism similar to development Nelson
syndrome after bilateral adrenalectomy during treatment
of Cushing's disease [1].
Likewise, more than half (52%) of patients in our
study were misdiagnosed with primary hyperthyroidism.
For this reason, most of them underwent thyroid surgery
and/or received thyreostatic therapy. In our study, we
found no clear statistical differences in the infiltrative
growth pattern depending on the previous thyroid
surgery. This is probably due to the general late diagnosis
of TSH-PA, when they are detected at the stage of large
tumor. Nevertheless, 7 patients were operated on at our
institution over the last 2 years (2014—2015), and only 3
(43%) of them had endosellar adenomas and
hyperthyroidism without symptoms of tumor mass effect,
whereas during the period from 2002 to 2013, most
patients, 13 (93%) of 14, had large tumors and were
diagnosed at the stage of tumor mass effect with
pronounced visual or other neurological disorders. It is
likely that in the future, given the use of ultra-sensitive
hormonal methods, as well as better doctors’ awareness
of these rare tumors, the rate of early detection of TSH-
PA at the stage of small-size tumor will increase.
Most of TSH-PA secret not only TSH, but also other
pituitary hormones, mainly STH and PRL. This may be
due to the fact that somatotropic, lactotropic, and
thyrotropic cells have a common progenitor cell. A rare
type of mixed TSH/gonadotropin secreting adenoma is
described in the literature without hypersecretion of
ACTH in the blood; the mechanism of occurrence of
these tumors have not been studied, because thyrotropic
and gonadotropic cells have different progenitor cells [1].
Clinically silent thyrotropinomas with TSH expression
but without increase in blood level of TSH and clinical
presentation of hyperthyroidism have been reported [27].
In our study, most tumors, 18 (86%), were
plurihormonal with preferential secretion of TSH, STH,
and/or PRL. None of the tumors secreted gonadotropin
28 PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
Plurihormonal-18
TSH-PRL-2 TSH-STH-PRL-12
and ACTH. “Pure” TSH-secreting tumors were found
only in 3 (14%) cases. Tumors with concomitant
expression of PRL or STH were associated with increased
blood level of RLP and clinical presentation of
acromegaly only in 4 (29%) and 3 (19%) cases,
respectively. The absence of clinical presentation of
hyperprolactinemia and/or acromegaly in other patients
with expression of PRL and/or STH was probably due to
secretion of biologically inactive forms of PRL and/or
STH.
According to the literature [1], most TSH-PAs
demonstrate expression of various receptors, including
receptors to TRH, dopamine, and somatostatin.
Expression of somatostatin receptors is often detected in
TSH-PA, especially in mixed STH-TSH-secreting
tumors. This explains the effective ability of somatostatin
analogs to lower TSH levels in patients with these tumors
[28, 29]. In our study, SSt5 expression was detected in
46% of cases and in most cases, it was accompanied by
STH expression in the tumor, while SSt5 expression was
rarely detected.
Surgery followed by radiotherapy is the basic method
of treatment for TSH-PA in the case of non-radical
resection [30, 31]. The literature provides no strict
criteria for remission after surgical treatment of
thyrotropinomas. However, clinical remission of
hyperthyroidism, normalization of thyroid hormone
levels, and regression of neurological symptoms are
considered as remission criteria. At the same time, these
biochemical and clinical criteria can be transitory and
are not considered as indicators of complete resection
[1]. Normalization of blood level of TSH also cannot be
an indicator of completeness, especially in patients with
normal preoperative level of TSH. Normalization of
α-subunit and/or the molar ratio of α-subunit and TSH
may be used to assess the effectiveness of therapy [32,
33]. Nevertheless, these two parameters are of low
sensitivity and are not applicable in patients with normal
preoperative levels. Triiodothyronine suppression test
and TRH stimulation test, which have optimal sensitivity
and specificity, were suggested as the most valid tests for
completeness of tumor resection [32, 33].
Undetectable blood level of TSH may be a good
indicator of radical resection. It is important to clarify
that virtually undetectable TSH level should be
understood as its level below the functional sensitivity
threshold of detection method (<0.01 mIU/L). Indeed,
in our series of observations, postoperative decrease in
TSH levels below 0.01 mIU/L was characteristic of
completely resected tumors. However, all these cases
were accompanied by the development of
panhypopituitarism, including hypothyroidism, which
required administration of levothyroxine. Patients with
postoperative TSH levels of 0.01-0.1 mIU/L remained
euthyroid during the follow-up period (6—18 months).
Therefore, we arbitrarily defined TSH level of 0.1 mIU/L
and below as a marker of radical tumor removal.
However, these patients should be followed in the future
since delayed relapse of hyperthyroidism can occur.
Although adenomectomy is currently the treatment
of choice, treatment with somatostatin analogues is
believed to be effective in reducing TSH level,
normalization of fT4 and fT3 levels, and restoring
euthyrosis in 90% of cases [30, 34, 35]. In our study,
preoperative therapy with somatostatin analogues in 2
patients successfully normalized euthyrosis and the levels
of TSH and fT4.
The literature provides no data on the incidence of
TSH-PA recurrence. We observed 2 cases of continued
tumor growth in previously operated patients, which
required reoperation. In our series of observations, none
of the patients operated on at the Burdenko Neurosurgical
Institute had continued tumor growth during the
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BD. Thyrotropin-secreting pituitary tumors. Endocr Rev. 1996;17:610-638.
http://dx.doi.org/10.1210/edrv-17-6-610
6. Taylor TJ, Donlon SS, Bale AE, Smallridge RC, Francis TB, Christensen
RS, Burma KD. Treatment of a thyrotropinoma with octreotide-LAR in a
patient with multiple endocrine neoplasia-1. Thyroid. 2000;10:1001-1007.
http://dx.doi.org/10.1089/thy.2000.10.1001
7. Daly AF, Tichomirowa MA, Petrossians P, Heliövaara E, Jaffrain-Rea ML,
Barlier A, Naves LA, Ebeling T, Karhu A, Raappana A, Cazabat L, De
Menis E. Clinical characteristics and therapeutic responses in patients with
germ-line AIP mutations and pituitary adenomas: an international collab-
orative study. J Clin Endocrinol Metab. 2010 Nov;95(11):E373-E383.
http://dx.doi.org/10.1210/jc.2009-2556
PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
aforementioned follow-up period. Given the possibility
of delayed recurrence of hyperthyroidism in patients with
non-radical tumor resection, the possibility of stereotactic
irradiation of residual tumor tissue should be considered
even in the cases of euthyroid state. In the case of
complete resection of the tumor and the development of
hypothyroidism, tumor recurrence is unlikely at least
during the first years after the surgery.
Conclusion
In summary, TSH-secreting tumors are rare
representatives of pituitary adenomas. Early diagnosis of
these tumors and differential diagnosis, which rule out
other conditions accompanied by hyperthyroidism, are
of key importance. Surgical treatment is currently the
main method of treatment, however radical removal of
infiltrative tumors is impossible. Postoperative TSH level
of no more than 0.1 mIU/L can be considered as the
criterion of radical removal. It should be noted that
transient euthyrosis often occurs in patients with non-
radical tumor resection. However, the likelihood of
recurrence of hyperthyroidism nessessitates considering
the question of stereotactic irradiation of residual tumor
tissue. Therapy with somatostatin analogs can be effective
to achieve euthyrosis.
There is no conflict of interest.
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9. Nakayama Y, Jinguji S, Kumakura S, Nagasaki K, Natsumeda M, Yoneo-
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10. Mazerkina N, Trunin Y, Gorelyshev S, Golanov A, Kadashev B, Shishki-
na L, Rotin D, Karmanov M, Orlova E. J Pediatr Thyrotropin-secreting
pituitary adenoma in an 11-year-old boy with type 1 autoimmune polyglan-
dular syndrome. Endocrinol Metab. 2016 Feb 1;29(2):237-240.
doi: 10.1515/jpem-2015-0018
11. Kadashev BA, Astaf'eva LI. Adenomy gipofiza (klinika, diagnostika, leche-
nie). Tver'. 2007;31-46. (In Russ.).
12. Prgijalkovskaja EG, Gasisova DO, Grigoriev AYu, Voronkova IA,
Tyulpakov AN, Rochinskaja LYa. Thyrotropin-producing adenoma:
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sio G, Spada A, Nissim M, Weintraub BD, Faglia G. Endocrine, biochem-
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with increased bioactivity. J Clin Endocrinol Metab. 1986;62:704-711.
http://dx.doi.org/10.1210/jcem-62-4-704
29
 ORIGINAL ARTICLES
15. Gesundheit N, Petrick P, Nissim M, Dahlberg PA, Doppman L,
Emerson CH, Braverman LE, Oldfield EH, Weintraub BD. Thyrotropin-
secreting pituitary adenomas: clinical and biochemical heterogeneity. Ann
Intern Med. 1989;111:827-835.
http://dx.doi.org/10.7326/0003-4819-111-10-827
16. Magner JA, Klibanski A, Fein H, et al. Ricin and lentil lectin affinity
chromatography reveals oligosaccharide heterogeneity of thyrotropin
secreted by 12 human pituitary tumors. Metabolism. 1992;41:1009-1015.
http://dx.doi.org/10.1016/0026-0495(92)90129-x
17. Beck-Peccoz P, Persani L. Variable biological activity of thyroid-
stimulating hormone. Eur J Endocrinol. 1994;131:331-340.
http://dx.doi.org/10.1530/eje.0.1310331
18. Losa M, Mortini P, Minelli R, Giovanelli M. Coexistence of TSH-secreting
pituitary adenoma and autoimmune hypothyroidism. J Endocrinol Invest.
2006 Jun;29(6):555-559.
http://dx.doi.org/10.1007/bf03344147
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pituitary tumor and Hashimoto’s disease: a novel association. South Med J.
2003;96:933-936.
http://dx.doi.org/10.1097/01.smj.0000054784.64420.8b
20. Ma W, Ikeda H, Watabe N, Kanno M, Yoshimoto T. A plurihormonal
TSH-producing pituitary tumor of monoclonal origin in a patient with
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http://dx.doi.org/10.1159/000070227
21. Lee MT, Wang CY. Concomitant Graves hyperthyroidism with
thyrotrophin-secreting pituitary adenoma. South Med J. 2010
Apr;103(4):347-349.
http://dx.doi.org/10.1097/smj.0b013e3181d3ce93
22. Azukizawa M, Morimoto S, Miyai K, Miki T, Yabu Y, Amino N, Kuma
K, Kumahara Y. TSH-producing pituitary adenoma associated with
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1980;8:645-648.
23. Nguyen HD, Galitz MS, Mai VQ, Clyde PW, Glister BC, Shakir MK.
Management of coexisting thyrotropin/growth-hormone-secreting
pituitary adenoma and papillary thyroid carcinoma: a therapeutic challenge.
Thyroid. 2010 Jan;(1):99-103.
http://dx.doi.org/10.1089/thy.2009.0160
24. Gasparoni P, Rubello D, Persani L, Beck-Peccoz P. Unusual association
between a thyrotropin-secreting pituitary adenoma and a papillary thyroid
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http://dx.doi.org/10.1089/thy.1998.8.181
25. Poggi M, Monti S, Pascucci C, Toscano V. A rare case of follicular thyroid
carcinoma in a patient with thyrotropin-secreting pituitary adenoma. Am J
Med Sci. 2009 Jun;337(6):462-465.
http://dx.doi.org/10.1097/maj.0b013e3181949948
Commentary
The article analyzes clinical cases of TSH-secreting tumor,
which is an extremely rare endocrine disease. Measurement of
TSH level is among the most commonly prescribed hormonal
tests. Increased TSH requires an accurate differential diagnosis,
because it can be caused by various endocrine disorders and
therefore it can require fundamentally different approaches to
the choice of treatment. In typical cases, thyrotropinoma is
accompanied by development of thyrotoxicosis with normal or
elevated TSH levels. Long-lasting untreated thyrotoxicosis
(including cases of misinterpretation of hormonal disorders)
leads to severe changes in many body systems (cardiovascular,
nervous, digestive, reproductive, etc.).
The authors provide very important guidelines for
practicing endocrinologists and neurosurgeons, characterizing
clinical cases of thyrotropinomas. They pay attention to the
very high percentage of misdiagnosis at the stage of outpatient
examination before admission to the Burdenko Neurosurgical
30 PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
26. Perticone F, Pigliaru F, Mariotti S, Deiana L, Furlani L, Mortini P, Losa
M. Is the incidence of differentiated thyroid cancer increased in patients
with thyrotropin-secreting adenomas? Report of three cases from a large
consecutive series. Thyroid. 2015 Apr;25(4):417-424.
27. Lim EM, Bhagat CI, Walsh J. Asymptomatic thyrotropin-secreting
pituitary microadenoma. Intern Med J. 2001;31:428-429.
http://dx.doi.org/10.1046/j.1445-5994.2001.00083.x
28. Gatto F, Grasso LF, Nazzari E, Cuny T, Anania P, Di Somma C, Colao A,
Zona G, Weryha G, Pivonello R, Ferone D. Clinical outcome and evidence
of high rate post-surgical anterior hypopituitarism in a cohort of TSH-
secreting adenoma patients: Might somatostatin analogs have a role as first-
line therapy? Pituitary. 2015 Oct;18(5):583-591.
doi: 10.1007/s11102-014-0611-8
29. Rimareix F, Grunenwald S, Vezzosi D, Rivière LD, Bennet A, Caron P.
Primary Medical Treatment of Thyrotropin-Secreting Pituitary Adenomas
by First-Generation Somatostatin Analogs: A Case Study of Seven Patients.
Thyroid. 2015 Aug;25(8):877-882.
doi: 10.1089/thy.2015.0041
30. Beck-Peccoz P, Lania A, Beckers A, Chatterjee K, Wemeau JL. European
thyroid association guidelines for the diagnosis and treatment of
thyrotropin-secreting pituitary tumors. Eur Thyroid J. 2013 Jun;2(2):76-82.
http://dx.doi.org/10.1159/000351007
31. Mouslech Z, Somali M, Sakali AK, Savopoulos C, Mastorakos G,
Hatzitolios AI. TSH-secreting pituitary adenomas treated by gamma knife
radiosurgery: our case experience and a review of the literature. Hormones
(Athens). 2016 Jan 6.
doi: 10.14310/horm.2002.1640
32. Brucker-Davis F, Oldfield EH, Skarulis MC, Doppman JL, Weintraub BD.
Thyrotropin-secreting pituitary tumors: diagnostic criteria, thyroid
hormone sensitivity, and treatment outcome in 25 patients followed at the
National Institutes of Health. J Clin Endocrinol Metab. 1999;84:476-486.
http://dx.doi.org/10.1210/jcem.84.2.5505
33. Losa M, Giovanelli M, Persani L, Mortini P, Faglia G, Beck-Peccoz P.
Criteria of cure and follow-up of central hyperthyroidism due to
thyrotropin-secreting pituitary adenomas. J Clin Endocrinol Metab.
1996;81:3086-3090.
http://dx.doi.org/10.1210/jcem.81.8.8768879
34. Atkinson JL, Abboud CF, Lane JI. Dramatic volume reduction of a large
GH/TSH secreting pituitary tumor with short term Octreotide therapy.
Pituitary. 2005;8(2):89-91.
http://dx.doi.org/10.1007/s11102-005-3279-2
35. Beck-Peccoz P, Persani L. Medical management of thyrotropin-secreting
pituitary adenomas. Pituitary. 2002;5:83-88.
http://dx.doi.org/10.1007/978-1-4615-1115-1_8
Institute; in some cases, patients with thyrotropinomas even
underwent thyroid resection.
All reported tumors were macroadenomas, in 91% of cases
they were endo-extrasellar. Most patients (76%) had clinical
signs of hyperthyroidism. Along with clinical signs of
hyperthyroidism, these patients also had various neurological
symptoms, including visual disturbances and cephalgic
syndrome. According to US study of the thyroid gland, 13
patients had various structural changes (diffuse goiter, nodular
goiter, diffusely nodular goiter). When combined with
thyrotoxicosis, this could contribute to inadequate differential
diagnosis of primary, rather than central thyrotoxicosis. When
comparing tumor growth patterns in 7 (71%) patients with a
history of thyroid surgery, most of them were diagnosed with
infiltrative growth. However, no statistical differences were
found, when comparing tumor growth patterns in the groups of
patients with and without history of thyroid surgery. In any
case, erroneous management of these patients may have
irreversible consequences.
Concomitant primary hypothyroidism, either
postoperative or resulting from chronic autoimmune thyroiditis,
with thyrotropinoma is one of the most disputable and
challenging problems. The authors regard these tumors as
secondary thyrotropinomas.
Complex hormonal examination of some patients also
detected other hormonal disorders. Tumors polymorphism was
further confirmed by immunohistochemical studies, where
isolated TSH expression was detected in only 14% of cases,
while the majority of tumors showed expression of TSH and
STH and/or PRL.
The paper points out that radical resection was possible in
33% of patients, having only endosellar and endo-suprasellar
tumor. There were no cases of complete resection of infiltrative
tumors. It would be proper to specify the tactics of management
of these patient, when radical adenomectomy is impossible.
It was found that normal postoperative level of TSH or its
decrease to 0.1 mIU/L, as well as transient postoperative
PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
hypothyroidism are not the criteria of the effectiveness of tumor
removal. This proves once again that the verification of the
diagnosis and radical treatment pose significant problems. The
literature provides evidence of high efficacy of the use of
somatostatin analogues for thyrotropinomas, as also shown in
this work.
In this regard, the study of expression of dopamine and
somatostatin receptors in the resected tissue of pituitary
adenoma becomes highly important. The paper demonstrated
high incidence of expression of type 2 dopamine receptors and
type 5 somatostatin receptors.
In conclusion, the authors once again emphasize diagnostic
criteria of TSH-secreting pituitary tumor and differential
diagnosis of various types of thyrotoxicosis.
The article is extremely important, since it covers very
challenging issues of diagnostic criteria and management of
pituitary adenomas.
F.M. Abdulhabirova (Moscow, Russia)
31
 ORIGINAL ARTICLES

doi: 10.17116/engneiro201680632-36

The Preliminary Results of Subthalamic Nucleus Stimulation after Destructive

Surgery in Parkinson’s Disease
E.A. KHABAROVA, N.P. DENISOVA, D.YU. ROGOV, A.B. DMITRIEV

Federal Center of Neurosurgery, Novosibirsk, Russia

Objective. The study was aimed at evaluating the efficacy of bilateral electrical stimulation (ES) of the subthalamic nucleus (STN)
in patients with Parkinson's disease (PD) after prior pallidotomy or ventrolateral (VL) thalamotomy.
Material and methods. The study included 9 patients with bilateral STN ES, who previously underwent unilateral destructive
surgery on the subcortical structures: pallidotomy (5 patients) and VL thalamotomy (4). Control group consisted of 9 patients with
STN ES and without prior destructive surgery.
Clinical and neurological examination included quantitative assessment of motor disturbances using the Hoehn—Yahr scale and
Unified Parkinson's Disease Rating Scale (UPDRS). UPDRS was used to evaluate the motor activity (part III of the scale) and
severity of drug-induced dyskinesia and motor fluctuations (part IV of the scale).
Results. In the group of STN ES with preceding destruction of the subcortical structures, an improvement in motor functions in the
early period (6 months) was 45%, and severity of drug-induced complications decreased by 75%. In a group of STN DBS without
destruction, motor disturbances were improved by 61%, and drug-induced complications were decreased by 77%. Improvement
in motor functions amounted to 51.9% in patients with preceding pallidotomy (GPi destruction) and 37.5% in a group with
preceding VL thalamotomy.
The equivalent dose of levodopa was reduced by 51.39%, from 1,008±346 to 490±194, in the study group and by 55.04%, from
963±96 to 433±160, in the control group.
Conclusion. Bilateral STN neurostimulation is effective after unilateral stereotaxic destruction of the subcortical structures in PD
patients.
Keywords: Parkinson’s disease, bilateral subthalamic nucleus neurostimulation, pallidotomy, VL thalamotomy.

Parkinson's disease (PD) or idiopathic parkinsonism Complications of VL thalamotomy in the form of

is the second most common (after Alzheimer's disease)
neurodegenerative disease [1]. Detectability of PD
among individuals older than 65 years is about 1%. Most
cases occur at the ages of 60—70 years, but in 15% of
cases, PD first occurs at the age of 45 years [1], i.e. in
workable and socially active population.
Despite the fact that the replacement dopaminergic
therapy is effective, more than 50% of patients develop
motor fluctuations within 2—5 years of therapy with
levodopa and the risk of dyskinesias increases by 10%
every year [2].
In this regard, development of complications or
resistance to dopaminergic therapy raises the question of
application of more effective non-drug methods to
correct parkinsonism symptoms. Neurostimulation of
subthalamic nucleus and ventrolateral thalamotomy and
pallidotomy are most commonly used for this purpose.
Surgical treatment of PD is effective at all stages of
the disease, but the modern trend is toward earlier
surgical treatment of patients, which prevents them from
losing social activity and enables returning to work [3, 4].
The moment when it is advisable to change from
pharmacotherapy to surgery still remains the main
disputable issue [4]. It is also being discussed, which
method should be offered to the patient: stimulation or
destructive interventions in the subcortical brain
structures. The unilateral thalamotomy and pallidotomy
effectively reduce the severity of tremor and rigidity on
the contralateral side, but this treatment has limitations.
hemiparesis, lateropulsion upon walking, dysarthria, and
dysphagia (in the case of operation on the dominant
hemisphere) occur within the first few days after surgery
in almost 1% of operated patients and usually mostly
regress within the first weeks after the operation [5, 6].
The incidence and severity of perioperative complications
increase considerably after the second operation on the
opposite side. According to D. Louw [7], dysarthria and
severe mental disorders after bilateral VL thalamotomy
developed in 30—60% of cases. In 5—14% of cases,
pallidotomy can cause intraoperative and postoperative
complications in the form of partial or complete
hemianopsia, transient aphasia, and central facial palsy
[7—10]. In the case of bilateral symptoms, pallidotomy
on the contralateral side is associated with quite high (up
to 17%) risk of mental and speech disorders without
significant improvement of the results of the first
pallidotomy [7, 11].
Bilateral chronic electrical stimulation (ES) of the
subthalamic nucleus (STN) reduces the severity of
tremor and rigidity on both sides, as well as intensity of
hypokinesia, reduces the overall severity of movement
disorders and increases daily activity of PD patients,
which improves the quality of life of these patients [6, 12,
13].
Thus, pharmacotherapy often cannot solve the
problem of multiple PD symptoms and the use of
functional neurosurgery methods based on modulation
of hyperactivity of the subthalamic nucleus and medial

© Group of authors, 2016 e-mail: e_khabarova@neuronsk.ru

32 PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016

segment of the globus pallidus has been acknowledged as
the effective treatment of PD patients [12, 13].
At the same time, it is poorly understood how
effective is bilateral STN ES after destructive
interventions. Additionally, there is no reliable
information, whether the result of this procedure in
patients after destructive operations is comparable to that
in patients, who did not undergo destructive surgery on
the subcortical structures, and whether destructive
operation provides the patient with any long-term
advantages.
The objective of this research was to demonstrate our
own experience with bilateral neurostimulation of the
subthalamic nucleus in PD patients after previous
pallidotomy and VL thalamotomy and evaluate the
effectiveness of this method in the early follow-up period.
Material and methods
The study included PD patients with bilateral STN
ES after prior destructive surgery. The patients were
operated on at the department of functional neurosurgery
of the Federal Neurosurgical Center in Novosibirsk from
2013 to 2014.
The study included 9 patients (5 males, 4 females)
with STN ES, who previously underwent unilateral
destructive operations on the subcortical structures
(study group). Of these, pallidotomy was performed in 5
patients, VL thalamotomy was performed in 4 patients.
At the time of destructive surgery, average age of patients
was 54.9 years (47—64 years), at the time of STN ES —
55.9 years (47—65 years). Disease duration ranged from
5 to 20 years (mean duration, 12 years). The average
period between operations was 14 months (5 — 26
months).
Bilateral neurostimulation was carried out in the case
of progression of motor disorders.
The control group consisted of 9 patients (5 males, 4
females) with STN ES, which did not undergo destructive
surgery. The average age in the group was 54.9 years
(48—61 years). The disease duration was 7—16 years
(mean duration, 12 years).
Indications for surgery and selection criteria for STN
ES were identical in both groups. In patients with bilateral
neurostimulation, minimum follow-up time was 12
months, maximum — 30 months (average, 21 months).
Motor disorders were quantified in the clinical
neurological study before and after operations on the
following scale:
Hoehn-Yahr Scale (M. Hoehn, M. Yahr, 1967)
modified by Lindvall, Tetrud, and Langston (O. Lindvall
et al, 1987; J. Tetmd, J. Langston, 1987), which includes
both the conventional 5-point classification of severity of
parkinsonism and 1.5 and 2.5-point severity gradations.
The third edition of the unified PD evaluation scale
(Unified Parkinson's Disease Rating Scale, UPDRS),
(S. Fahn, R.Elton, 1987) contains 42 criteria. It estimates
PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
motor activity (part III) and severity of drug-induced
dyskinesias and motor fluctuations (part IV). Each
criterion may score 0 to 4 points. The decrease in the
total score resulting from treatment was considered as a
positive dynamics.
There were no significant differences between study
and control group patients in age and duration of history.
In both groups, patients underwent a bilateral STN
ES. Neurostimulator programming was carried out
1 month after surgery. Neurostimulation parameters
were selected based on better clinical response of motor
manifestations and absence of side effects (dysarthria,
levodopa-dependent dyskinesia). No surgical
complications were observed in patients in the early
postoperative period.
Daily dose of dopaminergic preparations was
assessed based on determining the equivalent doses of
levodopa, which were calculated according to the
formula: 100 mg of levodopa = 130 mg of levodopa with
controlled drug release = 70 mg of levodopa + catechol-
O-methyltransferase inhibitor = 1 mg of pramipexole =
5 mg of ropinirole = 50 mg of piribedil [14]. Calculation
was made in the study and control groups before and 12
months after STN neurostimulation.
Results
In the study group, improvement of motor functions
after 12 months averaged 45% (22 to 50 UPDRS points)
(Table 1). Notably, 66.6% of patients in this group had a
dextral destruction (Table 2).
The number of UPDRS points (part III) 6 months
after the destructive intervention in this group decreased
by an average of 17% (33—65 points) (see Table 2). This
time interval for estimation was determined by the fact
that some of patients underwent STN ES in 6 months.
In the control group, improvement of motor
disorders in 12 months averaged 61%.
In 12 months, the severity of treatment complications
(medicinal dyskinesias and motor fluctuations) decreased
by an average of 75% in the main group and by 77% in the
control group (see Table 1).
Study group patients with bilateral STN ES had
various degrees of improvement depending on the
location of destruction. In patients with unilateral
pallidotomy, improvement of motor disorders was
51.9%, in the group with preceding VL thalamotomy —
37.5% (Table 3).
According to UPDRS (part III), clinical presentation
before ES was more severe in the control group patients
compared to that in the study group. This is due to
preserved clinical effect of unilateral stereotaxic
destruction in the study group, which occurred in the
form of milder rigidity, tremor, and dyskinesias on the
contralateral side.
The results of tests were similar in both groups 12
months after connection of neurostimulator (see
33
 ORIGINAL ARTICLES

Table 1). Prior to STN ES, study group scored 51 UPDRS
points (35—65), control group — 74 points (63—82).
During STN ES, study and control groups scored 28
(22—50) and 29 points (20—42), respectively (see
Table 1). After bilateral neurostimulation, equivalent
dose of levodopa decreased by 51.39%, from 1008±346
to 490±194, in the study group, and by 55.04%, from
963±96 to 433±160, in the control group.
Discussion
Stereotactic thermal destruction of the deep
structures of the brain is a technique that enabled safe
and effective suppression of PD symptoms at certain
stage of the disease [6].
Unilateral pallidotomy (destruction of the internal
segment of the globus pallidus, GPI) effectively treats
medicamentous dyskinesia in the contralateral limbs,
and, to a lesser extent, in the ipsilateral limbs, and also
reduces fluctuations of daily motor activity [9].
For many years, ventrolateral thalamotomy was used
to treat pharmacoresistant tremor in PD patients [9, 15,
16]. In this case, the incidence and severity of
perioperative complications significantly increase after
the second operation on the contralateral side [7].
Despite the excellent initial clinical effect in the case
of optimal positioning of destruction point, 10—15% of
patients resume preoperative symptoms within 1—2
years after the operation, often in the ipsilateral
extremities and axial muscles, which is associated with
progression of the disease [15]. Therefore, further surgery
is required in the future. Bilateral destructive interventions
are associated with high risk of complications. According
to J. Siegfried and B. Lippitz [17], chronic ES of
subcortical structures is the method of choice in PD
patients, who previously underwent stereotactic
destruction. This method uses autonomous implantable
systems, which enable chronic neurostimulation [18].
The main advantages of ES include minimal injury
to the brain tissue, which occurs during implantation of
the electrode, and reversibility of neurostimulation
effects. Modern neurostimulators enable noninvasive
correction of many parameters of stimulation program
(the use of monopolar or bipolar stimulation, various
intensity of electrical stimulation) [19]. Minimal
invasiveness of this techniques prevent from persistent
neurological complications characteristic of destructive
methods [12, 20].
Minimal invasiveness of this technique enables
single-stage bilateral surgery even in elderly patients [4,
20, 21]. The results of postmortem studies of operated
patients, who died of intercurrent diseases, have shown
that prolonged exposure to electrical stimulation does
not cause damage to the structures around the active
electrode [22]. The possibility of noninvasive correction
of neurostimulation parameters enables selecting an
individual effective and comfortable treatment program,
and eliminates side effects of neurostimulation [4].
The literature provides scarce information on the
effectiveness of STN ES in patients with previous
destructive interventions. The study of G. Kleiner-
Fisman et al. [23] showed that prior unilateral pallidotomy
does not impair the effectiveness of the subsequent
bilateral STN ES. In this study, electrophysiological
parameters also did not change significantly in the study
and control groups.
Our study showed that decrease in the severity of
motor disorders as assesses on the UPDRS scale was
lower in the group of patients with bilateral STN EN
preceded by unilateral pallidotomy and VL thalamotomy
as compared to the control group. This is due to preserved
clinical effect of previous unilateral stereotaxic
destruction, which occurs in the form of milder rigidity,
tremor and/or drug-induced dyskinesias on the side
contralateral to destruction area. Similar results were
obtained in the work of W. Ondo et al. [14]. In our study,
improvement in motor disturbances resulting from STN
ES were less pronounced in the group with prior VL
thalamotomy compared to the group with prior
destruction of GPi.
Assessment of the dynamics of drug-induced
complications showed that improvement was similar in
the study and control groups, which is consistent with the
aforementioned studies [14, 23]. Decrease in the
equivalent dose of levodopa in the study and control

Table 1. Characteristics of STN ES group patients, who previously underwent destruction, and STN EN group without prior destruction

Study group with previous destruction Control group without destruction

Parameter
(n=9) (n=9)
Age at the time of stimulation, years 55,58 (47—65) 54,88 (48—61)
Sex:
M 5 (56%) 5 (56%)
UPDRS part III prior to STN neurostimulation
(off) 51 (35—65) 74 (63—82)
UPDRS part III after STN neurostimulation in
12 months (off) 28 (22—50), 45% 29 (20—42), 61%
UPDRS part IV prior to STN neurostimulation 8 (5—11) 9 (5—12)
UPDRS part III after STN neurostimulation in
12 months 2 (1—3), 75% 2 (1—4), 77%

34 PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016

Table 2. Characteristics of patients with ES, who previously underwent stereotactic destruction (study group)
Preceding destruction Following STN ES
Motor
Motor Motor
Age at the disturbances Age at the Motor disturbances
Location disturbances Location disturbances
time of Destruction after time of after
Sex (R, right; before (B, before
destruction, nucleus destruction stimulation, neurostimulation
L, left) destruction bilateral) neurostimulation
years in 6 months years in 6 months (off)
(off) (off)
(off)
M 54 Gpi R 55 45 55 B 55 25
F 62 Vim L 59 54 63 B 54 25
M 53 Gpi L 67 62 53 B 62 31
M 47 Vim R 65 65 47 B 65 50
M 59 Vim R 57 33 60 B 35 22
F 64 Gpi L 52 40 65 B 50 28
F 47 Gpi R 57 46 50 B 54 22
M 51 Vim R 56 39 53 B 37 22
F 57 Gpi R 53 49 57 B 50 23
54,88 58 (52—67) 48 (33— 55,88 51 (35—65) 28 (22—50)
(47—64) 65) (47—65)

Table 3. Study group with preceding stereotactic destruction

GPI VIM

Motor Motor
Age at the Duration Motor Age at the Duration Motor
disturbances disturbances
time of of disease disturbances after time of of disease disturbances after
Sex before Sex before
stimulation, history, neurostimulation stimulation, history, neurostimulation
neurostimulation neurostimulation
years years in 6 months (off) years years in 6 months (off)
(off) (off)

M 55 15 55 25 F 63 11 54 25
M 53 13 62 31 M 47 5 65 50
F 65 12 50 28 M 60 11 35 22
F 50 15 54 22 M 53 20 37 22
F 57 10 50 23 3m/ 55,75 12 (5— 48 (35—65) 30 (22—50)
1f (47—63) 20)
2 56 (50— 13 (10— 54 (50—62) 26 (22—31)
m/3 65) 15)
f
51,85%

groups before STN EN and after 12 months of ES also
did not differ significantly.
W. Ondo et al. [14] believe that unilateral VL
thalamotomy may cause insufficiently accurate
positioning of STN EN electrode on the side of prior
destruction. A. Zaidel et al. [24] reported change and
decrease in neuronal activity of the subthalamic nucleus
after previous pallidotomy. In this regard, in patients
with preserved good clinical effect of destructive
operations or extensive destruction area, an option of
unilateral STN ES on the side contralateral to the
destruction area may be considered in the case of further
progression of the disease and emergence of indications
to STN ES.
Conflicting results of analyzed studies may be due to
a small number of patients with prior destruction of
subcortical structures in all these studies.
Methods of functional neurosurgery are currently an
integral part of the treatment of PD patients [25, 26].
Modern trends are towards earlier surgical treatment of
patients [3, 4]. In some patients, motor disorders can be
significantly reduced by unilateral stereotactic
interventions [14, 23]. However, disease progression is
accompanied by depletion of reserves of pharmacotherapy,
and some patients, who previously underwent destructive
operations, may require repeated surgery [27, 28].
Conclusion
The literature data and the results of our study show
that bilateral STN electrostimulation is effective and can
be used in patients with Parkinson's disease, who
previously underwent unilateral stereotactic destructive
operations on subcortical structures.
There is no conflict of interest.

PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016 35

 ORIGINAL ARTICLES
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12. Tomsky AA, Bril EV, Shabalov VA, Fedorova NB. Electrical stimulation of
the subthalamic nucleus in Parkinson's disease. Voprosy neirokhirurgii imeni
NN Burdenko. 2006;3:14-17. (In Russ.).
13. Walker HC, Watts RL, Schrandt CJ, Huang He, Guthrie CL, Guthrie BL,
Montgomery EB. J Activation of subthalamic neurons by contralateral sub-
thalamic deep brain stimulation in Parkinson disease. J Neurophysiol. 2011
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Stimulation in Patients With a Previous pallidotomy. Movement Disorders.
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Commentary
The article focuses on electrical stimulation (ES) of the
subthalamic nucleus (STN) in patients with Parkinson's
disease, who previously underwent destructive operation on the
deep structures of the brain. Modern literature provides
numerous publications dealing with ES of STN and the internal
segment of the globus pallidus. The effectiveness of this method
of treatment during short follow-up period was proved by a
number of randomized trials; there are also publications
reporting long-term results. A large number of studies cover the
issues of the effect of neurostimulation on various manifestations
of Parkinson's disease: motor symptoms, cognitive impairment,
balance and gait disorders, impulsive-compulsive disorders.
In recent years, destructive operations were abandoned in
favor of neurostimulation all over the world, which is very
promising due to the adjustability of its effect. However,
destructive operations still can be used in some cases with
36 PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
16. Tronnier V, Fogel W, Kronenbuerger M, Steinvorth S. Pallidal stimulation:
an alternative to pallidotomy? Neurosurgical Focus. 1997;2:3:E12.
17. Siegfried J, Lippitz B. Chronic electrical stimulation of the VL-VPL com-
plex and of the pallidum in the treatment of movement disorders: personal
experience since 1982. Stereotact. Funct Neurosurg. 1994;62:71-75.
18. Haris M. Complications of deep brain stimulation surgery. Mov Disord.
2002;17(3):S162−S166.
19. Paul S. Larson Deep Brain Stimulation for Movement Disorders. Neuro-
therapeutics. 2014 July;11(3):465-474.
20. Bril EV, Tomsky AA, Gamaleya AA, Shabalov VA. Comparative study of
efficiency of neurosurgical treatment (electrostimulation of a subthalamic
nucleus) and pharmacotherapy in patients with developed stage of Parkin-
son's disease. Zhurnal nevrologii i psikhiatrii im SS Korsakova. 2014;6:55-61.
(In Russ.).
21. Deuschl G, Volkmann J, Krack P. Deep brain stimulation for movement
disorders. Mov Disord. 2002;17:S1.
22. Haberler C, Alesch F, Mazal PR, Pilz P, Jellinger K, Pinter MM, Hainfell-
ner JA, Budka H. No tissue damage by chronic deep brain stimulation in
Parkinson’s disease. Ann Neurol. 2000 Sep;48(3):372-376.
23. Kleiner-Fisman G, Fisman D, Zamir O, et al. Subthalamic nucleus deep
brain stimulation for Parkinson’s disease after successful pallidotomy: clini-
cal and electrophysiological observations. Mov Disord. 2004;19:1209-1214.
24. Zaidel A, Moran A, Marjan G. Prior pallidotomy reduces and modifies neu-
ronal activity in the subthalamic nucleus of Parkinson’s disease patients. Jour-
nal Compilation a Federation of European Neuroscience Societies and Black-
well Publishing Ltd. European Journal of Neuroscience. 2008;27:483-491.
25. Castrioto A, Lozano AM, Poon YY, et al. Ten-year outcome of subthalam-
ic stimulation in Parkinson disease: a blinded evaluation. Arch Neurol.
2011;68:1550-1556.
26. Zibetti M, Merola A, Rizzi L. Beyond Nine Years of Continuous Subtha-
lamic Nucleus Deep Brain Stimulation in Parkinson’s Disease. Mov Disord.
2011;26:13.
27. Esselink RA, de Bie RM, de Haan RJ, Lenders MW, Nijssen PC, Staal MJ,
Smeding HM, Schuurman PR, Bosch DA, Speelman JD. Unilateral palli-
dotomy versus bilateral subthalamic nucleus stimulation in Parkinson’ s
disease: one year follow-up of a randomized observer — blind multicentre
trial. Acta Neurochir (Wien). 2006;148(12):1247-1255.
28. Heo JH, Lee KM, Paek SH, Kim MJ, Lee JY, Kim JY, Cho SY, Lim YH,
Kim MR, Jeong SY, Jeon BS. The effects of bilateral subthalamic nucleus
deep brain stimulation (STN DBS) on cognition in Parkinson disease. J
Neurol Sci. 2008 Oct 15;273(1-2):19-24. Epub 2008 Jul 21
predominance of unilateral manifestations of Parkinson's
disease. At the same time, patients who underwent destructive
operations can be sent for neurostimulation in the case of
disease progression.
In recent studies dealing with neurostimulation, previous
destructive operation was considered as an exclusion criterion.
However, there are several studies containing information on
the use of STN ES in small groups of patients, who previously
underwent destruction, and its effectiveness.
In general, this study is highly relevant and the results are
interesting and important for functional neurosurgery of
Parkinson's disease. Further studies will provide valuable data
to develop the optimal strategy of neurosurgical treatment of
Parkinson’s disease.
A.A. Tomskiy (Moscow, Russia)
doi: 10.17116/engneiro201680637-48

Phase Contrast MRI-based Evaluation of Cerebrospinal Fluid Circulation

Parameters in Patients with Foramen Magnum Meningiomas
S.V. KONDRAKHOV, N.E. ZAKHAROVA, L.M. FADEEVA, S.V. TANYASHIN

Burdenko Neurosurgical Institute, Moscow, Russia

Background. Meningiomas of the foramen magnum (FM) region account for 1.8 to 3.2% of all meningiomas. The international
literature provides insufficient data describing the state of cerebrospinal fluid (CSF) circulation in these patients.
Material and methods. We studied 38 patients with FM meningiomas aged 35 to 79 years (mean age, 56.7 years). Meningioma
size averaged 30 mm (10—60 mm). Anterolateral meningiomas were observed in 29 patients, ventral — in 5 patients, and
dorsal — in 4 patients. Twenty nine patients underwent surgery. All operated patients were examined before and after surgery. CSF
circulation was studied using phase contrast MRI (PC-MRI).
Results. The size and localization of FM meningiomas do not significantly affect CFS circulation parameters. Pyramidal symptoms,
sensory disorders, and XIth cranial nerve dysfunction correlate with CFS circulation parameters. According to preoperative PC-MRI
data, CFS circulation parameters were significantly higher in all patients with FM meningioma compared to normal values. Surgery
was followed by decrease in the peak positive velocity, peak negative velocity, and range of maximum linear velocity amplitude.
Positive and negative volumes and stroke volume did not change. Recovery dynamics of CFS circulation parameters was similar,
regardless of surgery completeness. According to PC-MRI data, CFS circulation parameters did not reach normal values in all
groups of operated patients.
Conclusion. The results of investigation of CFS circulation in patients with FM meningiomas support the use of palliative surgery
(partial resection, dural plasty, craniovertebral junction decompression) in the case of inoperable meningiomas.
Keywords: foramen magnum meningioma, surgery, cerebrospinal fluid circulation, phase contrast magnetic resonance imaging.

Meningiomas of the foramen magnum (FM) region
account for 1.8 to 3.2% of all meningiomas [1,2].
FM meningiomas are among the most challenging
pathologies in neurosurgery in connection with the fact
that the main arteries, cranial nerves, and medulla
oblongata are located in this area. Growing tumor
displaces and, in many cases, involves vertebral arteries
in its stroma.
Completeness of resection of meningiomas located
in this area depends on the location of the original
growth, density, and size of the tumor, arachnoid
membrane integrity, tumor invasion of vertebrobasilar
system vessels and caudal group of cranial nerves, applied
approach, and many other factors [3—7]. According to
different authors, total resection of FM meningiomas
was achieved in 70—96% of cases [8—11]. Therefore, the
rate of non-radical removal of meningiomas located in
his region is high.
Most publications dealing with craniovertebral
meningiomas describe the degree of completeness of
tumor resection. Available literature provides no reports
demonstrating the effect of tumor size and location on
the state of CSF circulation, severity and dynamics of its
impairment in patients with FM meningiomas and after
resection of these meningiomas.
The issues of the effect of the extent of meningioma
resection or decompressive surgery on the passability of
the subarachnoid cisterns of the craniovertebral junction
and the role of impairment and recovery of the CSF
circulation in the development of clinical manifestations
of this pathology and their changes were almost not
covered so far.
According to available preliminary data, the
effectiveness of tumor resection characterized by various
extent can be assessed based on both clinical signs and
reliable quantitative values of CSF circulation.
Phase-contrast MR is the main non-invasive imaging
method for CSF spaces. As opposed to MR and CT
cisternography, this technique can be used to assess not
only anatomical characteristics of the CSF system and
geometry of CSF spaces with slow CSF motion, but also
to visualize fast CSF motion [12—16]. Thus, phase
contrast MRI provides the most adequate assessment of
CSF dynamics without limitation to the craniovertebral
junction [17—22]. The literature [23] provides data on
the evaluation of CSF circulation using phase contrast
MRI in patients with syringomyelic and arachnoid cysts.
Elucidation of the mechanisms of CSF circulation
disorders in patients with FM meningiomas will clarify
the pathogenesis of clinical manifestations of the disease
caused by direct tumor action on the neural structures
and impaired CSF circulation.
The research was aimed at studying the characteristics
of the CSF circulation in patients with meningiomas of
the craniovertebral junction and changes in the CSF
circulation parameters depending on the extent of the
surgery.
The study was aimed at:
— Evaluating CSF circulation disturbances
depending on the size of FM meningiomas;
— Assessing CSF circulation disturbances
depending on the location of meningiomas (anterior,
anterolateral, posterior);

© Group of authors, 2016 e-mail: skondrahov@nsi.ru

PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016 37

 ORIGINAL ARTICLES
— Assessing the impact of CSF circulation
disorders on the severity and dynamics of clinical
symptoms in patients with FMR meningiomas;
— Assessing the severity of CSF circulation
disorders before and after surgery and the nature of
changes in CSF circulation parameters, depending on
the extent of surgical intervention.
Materials and methods
The study was based on the results of examination of
38 patients with FM meningiomas aged 35 to 79 years
(mean age, 56.7 years). In our series, most patients were
45—50 and 60 —65 years old (Fig. 1).
Maximum tumor size was calculated based on
contrast enhanced T1-weighed MRI anatomical slices in
three projections. Maximum size of meningiomas ranged
10 to 60 mm, median 30 mm. Distribution of the
maximum size of meningiomas is shown in Fig. 2.
Most patients in our series had anterolateral FM
meningiomas, a total of 29 cases. Ventral meningiomas
were detected in 5 patients, dorsal — 4 (Fig. 3).
Surgery was conducted in 28 patients. The extend of
the surgery varied from total resection to biopsy
accompanied by dural plasty with aponeurosis. One
patient underwent ventriculoperitoneal shunting due to
occlusive hydrocephalus. Nine patients had not been
operated on. Five of them underwent radiotherapy. In 1
6
Case No
0
30 35 40 45 50
Fig. 1. Patients’ age distribution.
38 PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
patient, operation was canceled due to the burdened
somatic status. In 3 cases, surgery was not proposed due
to small tumor size and minimal symptoms. These
patients were followed. We used the classification
proposed by K. Amautovic [24, 25] to assess the
completeness of tumor resection:
— total resection (gross-total resection) — complete
tumor resection, including the involved DM fragments.
It corresponds to grade I tumor resection according to
Simpson's classification (Simpson I);
— almost total resection (near-total resection) — in
the case of preservation and coagulation of the tumor at
the DM matrix. It corresponds to grade II tumor resection
according to Simpson's classification (Simpson II);
— subtotal resection — resection of more than 60%
of tumor volume It corresponds to grade III tumor
resection according to Simpson's classification (Simpson
III);
— partial resection — resection of less than 60% of
the tumor, including biopsies and simple decompression.
It corresponds to grade IV—V tumor resection according
to Simpson's classification (Simpson IV—V).
The examples of total and subtotal resection of
meningiomas are shown in Fig. 4 and 5.
Distribution of patients according to the extent of
tumor resection is shown in Fig. 6.
All operated patients underwent preoperative and
postoperative (in 3—6 months) examination. Nine
55 60 65 70 75 80 85
Age, years
 9
6
Case No
0
0 5 10 15 20
Maximum size, mm
Fig. 2. Distribution of the maximum size of meningiomas.
patients, who had not been operated on, were examined
once.
The studies were carried out on Signa HDxt MR
tomograph (General Electric Medical Systems) using the
magnetic field strength of 1.5 T.
All patients underwent MRI in the following modes:
– standard T1 and T2-weighted MRI in the axial and
sagittal planes; they were obtained using spin echo pulse
sequence, SE (600/20) and FastSE (4500/84);
— 3D T2-weighed MRI modes (3D-CUBE mode,
which provides a clear view of the outline of the
subarachnoid spaces, and FIESTA mode, showing
pulsatile CSF movement);
— phase contrast MRI (PC-MRI) with reference to
the cardiac cycle based on the PC-MRI pulse sequence
with parameters TR 26/TE 11/FA 20 gy, 256/160 image
matrix, in two replicates. The slice (4 mm thick) was
selected at C2—C3 level, perpendicular to the vertebral
canal, with FOV = 200 mm. The average scan time was
3—4 min.
Heart contraction curve was recorded using
peripheral plethysmograph. A total of 16 images per
cardiac cycle were recorded, corresponding to the
different phases of the cardiac cycle. Spin velocity
encoding (VENC-Velocity encoding) averaged 15 cm/s.
In the case of artifacts, VENC could be changed in the
range from 0 to 20 cm/s. Data were processed in offline
mode based of the Report Card software package. Region
PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
25 30 35 40 45 50 55 60 65
of interest in the intradural space was selected based on
PC-MRI (Fig. 7), stroke volume, linear and volumetric
velocity of CSF circulation were calculated as a function
of the cardiac cycle phase (Fig. 8).
Data processing using Report Card software provided
the following characteristics of the CSF circulation:
positive peak velocity, negative peak velocity, positive
volume, negative volume, amplitude range of the
maximum linear velocity, and stroke volume. The
physical meaning of CSF circulation parameters obtained
by PC-MRI is as follows:
— positive peak velocity — maximum linear
velocity of CSF in the craniocaudal direction;
— negative peak velocity — maximum linear
velocity of the CSF in the caudocranial direction;
— amplitude range of the peak velocity — the range
of maximum linear velocity variation in one cardiac
cycle.
These three parameters represent velocity
characteristics of CSF circulation, wherein the latter one
is derived from the positive and negative velocities.
Positive volume — the amount of CSF passing
through the axial slice at C2—C3 during systole.
Negative volume — the amount of CSF passing
through the axial slice at C2—C3 during diastole.
Stroke volume — the amount of CSF passing through
the axial slice at C2—C3 during one cardiac cycle.
39
 ORIGINAL ARTICLES

Dorsal
which was previously performed at the Burdenko
11% Neurosurgical Institute (Table 1) [26].
Statistical processing of the material used Descriptive
Statistics methods (scattering diagram, distribution of
Ventral
13% variables, mean and standard deviation) and
nonparametric statistics methods describing the ordinal
values (linear relationship between the Spearman’s
parameters, group analysis with calculation of confidence
probability of intergroup differences using Mann Whitney
Anterolateral test, medians, and percentiles). The data were processed
76% using Statistica v.10 software.

Fig. 3. Location of FM meningiomas in the analyzed series.
Positive and negative volume and stroke volume are
volumetric characteristics of CSF circulation. As in the
case of linear velocity, stroke volume is derived from the
positive and negative volume.
Normal values of the main indices at C2—C3 were
obtained based the study including healthy volunteers,
Results
Preoperative characteristics of CSF circulation in
patients with FMR meningiomas.
We used MRI to visualize CSF movement through
the third ventricle, cerebral aqueduct, large cistern, and
spinal canal. Fig. 9 shows an example of the preoperative
examination of patient S., 46 years old, who was
diagnosed with FM meningioma.
Table 2 shows the average and median values of CSF
circulation parameters in 38 patients.

Fig. 4. Total resection of FM meningioma.

a, b — preoperative contrast enhanced T1-weighed MRI of the brain (sagittal and axial projections); d, e — contrast enhanced T1-weighed MRI of the brain after total
resection (gross-total resection, sagittal and axial projection); c —overall view of the tumor after opening of the dura mater and arachnoid membranes; f — after total
removal of the tumor node (1 — cerebellum, 2 — arachnoid, 3 — tumor, 4 — caudal group of cranial nerves, 5 — resected tumor bed, 6 — medulla oblongata, 7 — loop
of the posterior inferior cerebellar artery).

40 PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016

Fig. 5. Subtotal resection of FM meningioma.
a, b — preoperative contrast enhanced T1-weighed MRI of the brain (sagittal and axial projections); d, e — contrast enhanced T1-weighed MRI of the brain after
subtotal resection (subtotal resection, sagittal and axial projections); c —overall view of the tumor after opening of the dura mater and arachnoid membranes; f —
intraoperative view after subtotal removal of the tumor (1 — cerebellum, 2 — arachnoid, 3 — meningioma, 4 — caudal group of cranial nerves, 5 — medulla oblongata,
6 — meningioma remnants tightly adherent to the vertebral artery, 7 — loop of the posterior inferior cerebellar artery).

significant increase in all investigated parameters

Partial Near-total (p<0.05) in patients with meningioma.
25% 21%

The relationship between meningioma size and CSF

circulation parameters
We found no correlation between meningioma size
and CSF circulation parameters.
Examples of various relationships between tumor
Gross-total size and CSF circulation parameters are shown in Fig. 10
Subtotal
25%
29% and 11.

The relationship between CSF circulation and location

Fig. 6. The completeness of meningioma resection in 28 patients.
Comparative analysis of quantitative characteristics
of СSF circulation at C2—C3 in apparently healthy
individuals and patients with CSF meningiomas showed
СSF circulation disorders in the form of statistically
of meningiomas
CSF circulation parameters were compared in three
groups of patients depending on tumor location (ventral,
anterolateral, and dorsal) based on Mann-Whitney test.
The analysis found that tumor location, as well as FM
meningioma size, has no significant effect of CSF
circulation parameters.

PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016 41

 ORIGINAL ARTICLES
Fig. 7. Axial slice at C2—C3.
a — the spinal cord; b — “area of interest” in the intradural space.
Clinical manifestations and their correlation with CSF
circulation parameters
Clinical presentation of FM meningiomas consists of
various symptoms. We combined these symptoms into
several characteristic syndromes:
1) cerebellar syndrome — dizziness, cerebellar
ataxia, impaired statics, gait, and coordination;
2) cerebral symptoms are caused by increased
intracranial pressure. They manifest in the forms of
headache, dizziness, nausea, and vomiting;
3) bulbar syndrome — hoarseness, nasal voice,
decreased palatal and pharyngeal reflexes, choking when
swallowing, tongue deviation toward the affected muscle,
atrophy and fibrillar twitching of a half of the tongue.
This syndrome is associated with a direct effect of the
tumor on the medulla oblongata and exiting roots of the
IX, X, and XII pairs of cranial nerves;
4) pyramidal disorders — symptom resulting from
tumor compression of the pyramidal pathways at the
level of medulla oblongata and spinal cord and
manifesting in the form of various severity of conduction
motor disorders;
5) sensitivity disorders. These disorders are mainly
caused by direct effect of meningiomas on the afferent
pathways of the medulla oblongata and superior cervical
spinal cord;
6) cervical syndrome — presents with restricted
neck mobility, pain in the cervico-occipital area, head
tilt;
7) dysfunction of the XIth pair of cranial nerves
presents with paresis, plegia, atrophy of
sternocleidomastoid and trapezius muscles.
42
Fig. 8. PC-MRI study protocol.
Preoperative and postoperative distribution of the
incidence of the aforementioned syndromes and their
relationship to the CSF circulation parameters, as well as
the significance of differences in the subgroups are
summarized in Tables 3 and 4.
Preoperative positive and negative volume and stroke
volume significantly differ (p<0.05) in the subgroups of
patients with/without pyramidal symptoms. In the
subgroup of patients having pyramidal symptoms, these
values are significantly lower compared to patients
without pyramidal disturbances. In our opinion, this may
be due to the characteristics of the tumor node
configuration. Local effect on the anterolateral surface of
the medulla oblongata is characterized by more
pronounced clinical manifestations in the case of smaller
tumor compared to larger tumor volume, having no
direct contact with the anterolateral surface of the
medulla oblongata. Positive and negative peak velocity
and range of maximum velocity amplitude do not depend
on the neurological symptoms (p> 0.05).
Postoperative values (29 patients) of the positive and
negative peak velocity and range of the maximum velocity
amplitude are significantly higher (p<0.05) in patients
having sensory disorders and dysfunction of the XIth pair
of cranial nerves. No statistically significant correlation
Table 1. Quantitative characteristics of CSF circulation at C2—C3
in healthy volunteers
CSF circulation parameter according to
Values
PC-MRI
Amplitude range of the maximum linear 7,2±0,68
velocity, cm/s
Stroke volume, ml 1,04±0,37
PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
Table 2. Preoperative quantitative characteristics of CSF circulation at C2—C3 in patients with FM meningiomas
CSF circulation parameter Median Std. Dev. Median 25,000 th 75,000 th
Positive peak velocity, cm/s 10,97 4,7 12,2 6,67 14,8
Negative peak velocity, cm/s 9,89 4,59 9,77 5,33 14
Positive volume, ml 0,99 0,48 0,93 0,75 1,39
Negative volume, ml 0,84 0,49 0,92 0,38 1,16
Amplitude range of the maximum linear velocity, cm/s 20,86 8,61 21,38 16,23 29
Stroke volume, ml 1,83 0,83 1,83 1,43 2,41

Рис. 9. a — FIESTA MRI: CSF circulation unit is visualized on the anterior surface of the brain stem (at the FM); b — axial peak PC image
at C2—C3 during systole. A narrow high-signal band in the intradural space (shown by arrow) corresponds to CSF movement in the
craniocaudal direction during systole; c — axial peak PC image at C2—C3 during diastole. A narrow high-signal band in the intradural space
(shown by arrow) corresponds to CSF movement in the caudocranial direction during diastole.

of other CSF circulation parameters with clinical
presentation was found (p>0.05). In some cases, this is
due to the small number of observations. For example,
only one patient was initially diagnosed with hypertensive-
hydrocephalic syndrome, which regressed after surgery,
and therefore this parameter could not be reliably
evaluated.
Postoperative dynamics of CSF circulation in patients
with FM meningiomas
Examination of 28 patients before and 3—6 months
after tumor resection resulted in the following quantitative
values of the main CSF circulation parameters at C2—
C3 (Tables 5 and 6).
Comparative analysis of preoperative and
postoperative medians of the main CSF circulation
parameters showed that positive peak velocity, negative
peak velocity, and amplitude range of the maximum
linear velocity are significantly lower after surgery. There
is no significant differenced in the positive and negative
volume and stroke volume (p>0.05). Therefore, CSF
circulation improves after surgery in terms of velocity
characteristics and remains unchanged in terms of
volumetric characteristics (Table 7).
The effect of the extent of surgical intervention on the
recovery of CSF circulation
We compared the medians of all significantly varying
parameters of CSF circulation (peak positive velocity,
peak negative velocity, amplitude range of maximum
linear velocity) between the four groups of patient
according to completeness of tumor resection (Table 8,
Fig. 12).
The resulting values demonstrate that significant
improvement of CSF circulation parameters was
achieved in the case of total resection; they were better
than postoperative values after almost total and subtotal
tumor resection. The group with partial resection was the
second best in terms of recovery of CSF circulation
parameters.
Comparative analysis of the medians of the main
parameters of preoperative and postoperative CSF
circulation has shown that surgery results in significantly
reduced positive peak velocity, negative peak velocity,
amplitude range of the maximum linear velocity. There
was no significant changes in the positive and negative
volume and stroke volume (p>0.05). Therefore, CSF
circulation improves after surgery in terms of velocity

PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016 43

 ORIGINAL ARTICLES

Fig. 10. Anterolateral FM meningioma sized 24 mm. All CSF circulation characteristics are 2—3-fold higher than normal.
a — contrast-enhanced T1-weighed MRI, sagittal view; B — contrast-enhanced T1 MRI, axial view.

Fig. 11. Anterolateral FM meningioma sized 38 mm. All CSF circulation characteristics are within the normal range.
a — T1-weighed MRI, sagittal view; b — T2-weighted MRI, axial view.

characteristics and remains unchanged in terms of
volumetric characteristics (Table 7).
It should be noted that postoperative velocity
characteristics of CSF circulation improve according to
PC-MRI, but does not reach normal values, regardless of
the completeness of resection.
Discussion
Publications dealing with investigation of CSF
circulation based on PC-MRI studies are dominated by
studies in patients with Chiari malformation [13—16]
and hydrocephalus [22, 27]. Available literature provides
no studies of CSF circulation in patients with FM
meningioma.
Chiari malformation is the most similar to FM
tumors in terms of the pathogenetic basis of CSF
circulation changes. Analysis of the literature
demonstrates conflicting data on CSF circulation
parameters at the superior cervical level in both healthy
volunteers and patients with type I Chiari malformation
before and after the operation [13—16, 28, 29]. This may
be caused by the following reasons: different specifications
of MR imager; measurements at different levels;
heterogenous age composition of the patients under
study; the study did not take into account the
degenerative-dystrophic changes affecting CSF
circulation processes; many authors provide not all CSF
circulation parameters, which makes it difficult to
compare the results.

44 PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016

 Table 3. Preoperative neurological symptoms in 38 patients with FM meningiomas. Medians of CSF circulation parameters at C2—C3 depending on the presence/absence of a certain symptom
complex, as well as the significance of differences between the subgroups.
Peak positive velocity Peak negative velocity Positive volume Negative volume Amplitude range, max. Stroke volume
Symptom
complex Medi- Medi- Medi- Medi- Medi- Medi- Medi- Medi- Medi- Medi- Medi- Medi-
n % p p p p p
an+ an– an+ an– an+ an– an+ an– an+ an– an+ an–
Cerebellar 26 68,4 10,20 14,65 0,25 9,64 10,84 0,95 1,86 1,78 0,64 0,96 0,85 0,72 20,60 23,70 0,51 1,86 1,78
syndrome
Cerebral 16 42,1 10,74 13,45 0,99 10,94 9,62 0,48 0,99 0,87 0,37 1,06 0,79 0,37 21,38 20,93 0,70 1,96 1,71
syndrome
Bulbar 6 15,8 11,77 12,20 0,78 10,71 9,77 0,83 0,63 0,97 0,36 0,90 0,92 0,95 23,48 21,38 0,96 1,54 1,87
syndrome
Pyramidal 10 26,3 11,65 12,54 0,84 11,90 9,62 0,62 0,79 1,00 0,04 0,49 1,00 0,03 23,55 20,64 0,87 1,47 1,91
disorders
Sensory disorders 11 28,9 14,70 10,20 0,41 13,60 9,56 0,15 0,84 0,99 0,26 0,84 0,93 0,84 28,00 19,889 0,22 1,81 1,91
Cervical 10 26,3 11,63 12,19 0,45 8,09 9,87 0,49 1,07 0,92 0,52 0,87 0,92 0,83 20,60 21,30 0,43 1,71 1,87
syndrome
Dysfunction of 5 13,2 12,99 11,29 0,60 13,30 9,60 0,35 0,95 0,90 0,86 1,06 0,90 0,52 28,00 20,13 0,43 2,02 1,81
XI
Note. In Tables 3 and 4: n — the number of patients, % — syndrome occurrence rate; median+ — median of respective indices in patients having the complex of symptoms; median– — median of respective indices in patients without
symptom complex; p<0.05.

PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016

Table 4. Postoperative neurological symptoms in 29 patients with FM meningiomas. Medians of CSF circulation parameters at C2—C3 depending on the presence/absence of a certain symptom
complex, as well as the significance of differences between the subgroups

Symptom Peak positive velocity Peak negative velocity Positive volume Negative volume Amplitude range, max.. Stroke volume
complex n % Median+ Median– p Median+ Median– p Median+ Median– p Median+ Median– p Median+ Median– p Median+ Median–
Cerebellar 11 37,9 8,21 9,7 0,6 8,5 9,68 0,67 0,56 0,8 0,76 0,7 0,6 0,59 17,86 19,31 0,62 1,2 1,47
syndrome
Cerebral 7 24,1 9,8 9,63 0,85 9,65 9,65 0,85 0,62 0,8 0,7 0,88 0,6 0,45 17,3 19,31 0,99 1,31 1,2
syndrome
Bulbar syndrome 9 31 8,21 9,7 0,6 8,5 9,68 0,68 0,8 0,62 0,82 0,87 0,52 0,28 17,86 19,31 0,63 1,52 1,2
Pyramidal 4 13,8 11,85 8,88 0,1 10,25 8,92 0,36 0,3 0,77 0,17 0,52 0,61 0,7 21,3 17,52 0,19 0,82 1,21
disorders
Sensory 8 27,6 11,55 7,46 0,03 11,65 8,35 0,02 0,75 0,73 0,83 0,65 0,61 0,55 24 17,03 0,02 1,14 1,26
disorders
Cervical 3 10,3 13,6 9,63 0,34 12,9 9,65 0,43 1,42 0,73 0,23 0,48 0,61 0,98 26,5 17,86 0,37 1,47 1,2
syndrome
Dysfunction of 14 48,3 10,79 6,19 0,01 10,15 8,34 0,08 0,86 0,57 0,19 0,86 0,5 0,09 20,69 14,54 0,03 1,57 1,15
XI

45
 ORIGINAL ARTICLES

25 23,4
20,53
20 19,31

15 13,53
10,63 11,7 10,2
9,3 9,63 9,68
10 7,15 6,36
5

0
Gross-total Near-total Subtotal Partial

Positive peak velocity, cm/s

Peak negative velocity, cm/s
Amplitude range of maximum linear velocity, cm/s

Fig. 12. CSF circulation recovery as a function of the extent of tumor resection according to PC-MRI.

We used the technique that was previously developed
at the Burdenko Neurosurgical Institute and
demonstrated in the article of N.V. Arutyunov reporting
the study of CSF circulation in patients with type I Chiari
malformation [26]. According to the findings of N.V.
Arutyunov et al. (2009), all preoperative CSF circulation
parameters in patients with type I Chiari malformation
were significantly lower than normal values. After
surgery, all CSF circulation characteristics significantly
increase and reach normal level. In our study, the reverse
trend was observed in patients with FM meningiomas
before surgery: all CSF circulation parameters were
above normal. Our data, demonstrating increase in
velocity values of CSF circulation, are in agreement with
hydrodynamic continuity law (Castelli’s law), whereby
the flow rate of the fluid in pipes is inversely proportional
to their cross-section. In our opinion, increase in
volumetric characteristics of CSF circulation is due to
turbulent motion of the CSF below meningiomas (C2―
C3). After surgery, velocity characteristics of CSF
circulation (peak positive and negative velocity,
amplitude range of the maximum linear velocity) in
patients with FM meningiomas significantly decreased,
but did not reach normal values; volumetric parameters
(positive and negative volume, stroke volume) did not
changed. Since the follow-up study was conducted 3—6
months after the operation, these CSF circulation
characteristics can be attributed to the development of
postoperative cicatrical changes.
Conclusion
According to PC-MRI, all preoperative CSF
circulation parameters in patients with FMR
meningiomas exceed normal values. The relationship
between these parameters and tumor size and location
was not established. We found only correlations between
some parameters and clinical manifestations of the
disease, which can indirectly indicate the role of tumor
configuration in CSF circulation disorders. After the
operation, velocity characteristics of CSF circulation
decrease, volumetric characteristics remain unchanged.

Table 5. Quantitative characteristics of CSF circulation at C2—C3 in 28 patients with FM meningiomas before tumor resection
CSF circulation parameter Median Std.Dev. Median 25,000 th 75,000 th
Positive peak velocity, cm/s 12,12 4,35 14,20 10,05 15,05
Peak negative velocity, cm/s 10,85 4,47 11,90 6,46 14,52
Positive volume, ml 1,06 0,47 1,01 0,82 1,44
Negative volume, ml 0,85 0,51 0,97 0,46 1,16
Amplitude range of maximum linear velocity, cm/s 22,97 8,16 23,70 17,27 29,26
Stroke volume, ml 1,92 0,80 1,91 1,56 2,28

Table 6. Quantitative characteristics of CSF circulation at C2—C3 in 28 patients with FM meningiomas after tumor resection
CSF circulation parameter Median Std.Dev. Median 25,000 th 75,000 th
Positive peak velocity, cm/s 8,96 3,95 9,75 4,66 12,45
Peak negative velocity, cm/s 8,88 3,87 9,67 4,96 11,40
Positive volume, ml 0,80 0,48 0,78 0,42 1,18
Negative volume, ml 0,70 0,51 0,66 0,21 1,14
Amplitude range of maximum linear velocity, cm/s 17,84 7,65 19,56 9,71 24,05
Stroke volume, ml 1,50 0,90 1,27 1,04 2,15

46 PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016

Table 7. Median of preoperative and postoperative quantitative characteristics of the CSF circulation at C2 —C3 and probability values in
patients with FM meningiomas

CSF circulation parameter Median 25,000 th 75,000 th Median 25,000 th 75,000 th p-value
Positive peak velocity, cm/s 14,20 10,05 15,05 9,75 4,66 12,45 0,0058
Peak negative velocity, cm/s 11,90 6,46 14,52 9,67 4,96 11,40 0,039
Positive volume, ml 1,01 0,82 1,44 0,78 0,42 1,18 0,096
Negative volume, ml 0,97 0,46 1,16 0,66 0,21 1,14 0,29
Amplitude range of maximum linear
velocity, cm/s 23,70 17,27 29,26 19,56 9,71 24,05 0,0072
Stroke volume, ml 1,91 1,56 2,28 1,27 1,04 2,15 0,12

Table 8. Quantitative characteristics of CSF circulation (median and percentiles) at C2—C3 as a function of the extent of surgical
intervention

Extent of tumor resection

Parameter
Total Near-total Subtotal Partial
Positive peak velocity, cm/s 7,15 (4,39—11,7) 10,63 (5,15—12,6) 11,7 (6,71—13,2) 9,63 (3,93—9,88)
Peak negative velocity, cm/s 6,36 (4,77−10,56) 9,3 (4,9—10,1) 10,2 (9,65—14,30) 9,68 (3,25—10,4)
Amplitude range of maximum linear velocity,
cm/s 13,53 (9,25—22,13) 20,53 (9,88—21,5) 23,4 (16,36—27,4) 19,31 (7,27—20,28)

Decrease in these values does not depend on the
completeness of tumor resection.
The small number of patients and differently directed
changes in the velocity and volumetric parameters
complicate interpretation of the results and indicate that
routine use of PC-MRI in the treatment of FM
meningiomas is inappropriate at this stage.
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Commentary
In this article, the authors focus on a rare pathology,
namely meningioma of the foramen magnum (FM) region,
which accounts for 3.2% of all meningiomas, and CSF
circulation status after surgical treatment, which is scarcely
described in the literature.
The Materials and Methods summarizes the experience in
38 patients with anterolateral (29 patients), ventral (5), and
dorsal (4) FM meningiomas. A total of 29 patients were
operated on. All operated patients were examined before and
after surgery. CSF circulation was studies using phase contrast
MRI (PC-MRI).
The study demonstrated that the size and location of FM
meningiomas did not significantly affect the characteristics of
CSF circulation. Neurologic deficit correlated with CSF
circulation parameters. Most importantly, the dynamics of
recovery of CSF circulation parameters is the same regardless
48 PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
23. Battal B, Kocaoglu M, Bulakbasi N, Husmen G, Tuba Sanal H, Tayfun C.
Cerebrospinal fluid flow imaging by using phase-contrast MR technique. Br
J Radiol. 2011;84(1004):758-765.
doi: 10.1259/bjr/66206791
24. Gupta SK, Khosla VK, Chhabra R, Mukherjee KK. Posterior midline ap-
proach for large anterior/anterolateral foramen magnum tumours. Br J
Neurosurg. 2004;18:164-167.
doi: 10.1080/02688690410001681028
25. Arnautović KI, Al-Mefty O, Husain M. Ventral foramen magnum menini-
giomas. J Neurosurg. 2000;92:71-80.
doi: 10.3171/spi.2000.92.1.0071
26. Arutyunov NV, Korniyenko VN, Reutov AA, Fadeyeva LM. Cerebrospinal
fluid flow at the upper cervical spinal level in health and Chiari I
malformation. Vestnik Rentgenplogii i radiologii. 2009;4-6:37-42. (In
Russ.).
27. Henry-Feugeas M, Idy-Peretti I, Baledent O, Cornu P, Lejay H, Bittoun J,
Schouman-Claeys AE. Cerebrospinal fluid flow waveforms: MR analysis in
chronic adult hydrocephalus. Invest Radiol. 2001;36:146-154.
doi: 10.1097/00004424-200103000-00003
28. Hofman E, Warmuth-Metz M, Bendszus M, Solymosi L. Phase-contrast
MR imaging of the cervical CSF and spinal cord volumetric motion analysis
in patients with Chiari I Malformation. AJNR. 2000;21:151-158.
29. Meadows J, Kraut M, Guarnieri M, Haroun RI, Carson BS. Asymptom-
atic Chiari type I malformations identified on magnetic resonance imaging.
J Neurosurg. 2000;92:920-926.
doi: 10.3171/jns.2000.92.6.0920
of the completeness of surgery. In all groups of operated
patients, CSF circulation characteristics do not reach normal
values as evidenced by PC-MRI, which pathogenetically
justifies the use of palliative surgery (partial resection, dural
plasty, decompression of the craniovertebral junction) in the
case of inoperable meningiomas.
The article as a whole, references, and summary provide
detailed presentation of the matter under investigation. This
study included a sufficient number of patients, which makes it
statistically significant, summarizes the experience with PC-
MRI and the influence of radical surgery on the CSF
circulation parameters in patients with FM meningiomas, and
proves the possibility of palliative surgery.
L.M. Zaytsev (Moscow, Russia)
doi: 10.17116/engneiro201680649-51
Application of Resorbable Plates for Fixation of a Laminotomy Flap
YU.V. KUSHEL’, YU.D. BELOVA, A.R. TEKOEV
Burdenko Neurosurgical Institute, Moscow, Russia
The paper describes a new technology ― application of resorbable plates and pins for securing a laminotomy flap in children’s
neurosurgery. Four patients were operated on at our clinic. We describe in detail a surgical technique and compare it with a
traditional fixation technique using ligatures.
Keywords: fixation, resorbable plates and pins, ultrasonic tip, laminotomy.
Laminotomy is widely used for surgical access to
pathologies of the spinal canal [1]. The duration of
laminotomy, especially in case of multilevel access, is
rather short (much shorter than standard laminectomy).
However, the process of fixing the laminotomy flap can
take a lot of time, often as much as the time required for
all previous stages of the surgery. The technology used for
fixing the laminated flap is either ligatures through each
arch or titanium mini-plates [1, 2]. We deliberately did
not use titanium mini-plates in our practice for several
reasons: difficulty of achieving good fixation of screws in
children’s thin and soft vertebrae arches and issues with
relaminotomy in the event of relapse of the disease.
Therefore, until recently our main method of fixation
was ligatures [1, 3].
Resorbable plates and pins (biodegradable plates and
special screws for them) are made of amorphous polymer
consisting of D-lactide and L-lactide in equal proportions
[4, 5]. Biodegradation requires about 90 days and occurs
by hydrolysis. The screws used for this method differ
from the “true” ones by the absence of threads and
therefore there is no need use a screwdriver. In essence,
they are pins that can be softened using a special
ultrasonic nozzle and subsequently “flow into” the
bone’s diploque, which allows them to become fixated in
it once the ultrasonic action is stopped and they solidify.
The technology is simple and convenient. In addition,
the plate itself is also softened by heating at a temperature
of 60 °C and can be modeled “in situ”. The manufacturer
positions these products for cranial and maxillofacial
surgery [5, 6]. Our experience with the use of resorbable
plates and screws in the surgery of craniosynostosis and
complex skull defects in children led to the idea of using
the same fixation technology for laminotomy.
Material and Methods
Resorbable plates and screws were used to fix
laminotomy flaps in 4 patients aged 4 to 11 years (at 3, 4,
5, and 9 levels). In total, the fixation was performed at 21
levels. The operations were performed for intradural
tumors and cysts of the spinal cord. The average time of
© Group of authors, 2016
PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
fixation was 15 minutes (which is approximately 2.5
times shorter than the duration of traditional fixation by
ligatures). There were no complications, flap
displacements or tissue reactions. The minimal follow up
period was 3 months.
Operation technique
In all cases laminotomy was performed after
subperiosteal dissection, following the procedure
described previously by the first author [1]. The intradural
stage of the surgery was performed using microsurgical
techniques and depended on a specific pathology. The
stage of fixing the flap began after tight sealing of the dura
mater. We used 1-mm thick plates with 4 holes in all
cases (the length and arrangement of holes was always
sufficient for our purpose) and pins with a diameter of 2.4
mm and a length of 5 mm. Plates were bent “in situ” to
produce the required configuration, just before they were
fixed. The fixation of all plates to the flap was carried out
immediately afterwards (Fig. 1).
Further, the flap was put in place and, if necessary,
the plates were additionally bent to ensure their optimal
contact with the base of the arches. Then most cranial
and caudal arches were fixed, which ensured correct
position of the flap in the wound. Finally, all the other
plates were fixed (Fig. 2). The wound was sutured layer
by layer in accordance with general surgical principles.
A schematic depiction of the method for fixing a
laminated bone flap is shown in Fig. 3.
Discussion
Literature search for use of resorbable plates and
screws in neurosurgery produced only results related to
cranial application [4, 6—8]. Therefore, it was not
possible to compare our experience with the literature
data. Nevertheless, it should be noted that resorbable
materials are gradually getting traction in traumatology,
orthopedics and spinal surgery and there are already
relevant publications. However, the main issues that are
discussed in these papers are mechanical strength and
e-mail: ubelova@nsi.ru
49
 ORIGINAL ARTICLES

reliability of fixation in comparison with metallic

analogs [5].
In our clinical study, this comparison is not
determinative. It is well known that the purpose of
laminotomy and fixation of the flap is not so much
immediate “stabilization” as restoration of the place of
fixation of the paraspinal musculature and prevention of
gross epidural fibrosis. In this situation, the main goal of
fixation is to position the flap “in situ”, where the
mechanical load on it is minimal, so even ligature fixation
is sufficient. We have been successfully using ligatures to
fix the laminotomy flaps since 2003 (more than 270
laminotomies were performed), and we have never noted
any issues related to insufficient rigidity of fixation or flap Fig. 1. Laminotomy flap with fixed plates.
displacement. The only significant drawback of this
technique is that it is labor-intense and time-consuming,
especially in case of laminotomies of more than 3 levels.
For example, the process of fixing a 5-level flap in the
thoracic spine can take up to 40 minutes. This procedure
becomes even more time-consuming in case of narrow
canal and thick arches. In addition, the process of drilling
holes in the roots of the arches often leads to additional
venous bleeding from the epidural veins, which also leads
to unnecessary waste of time and resources. The use of
resorbable plates is more promising in this situation. The
use of standard titanium plates in children is less desirable
for reasons we have already mentioned above: difficulty
in achieving good fixation of screws in thin and soft
arches of children’s vertebrae and issues with
relaminotomy in the event of relapse of the disease. In
addition, the classical technology of drilling holes and Fig. 2. Laminotomy flap fixed in place.
tightening the screws does not provide any benefits in
terms of technology or convenience (in a narrow and
deep wound it is even more difficult) than imposing
ligatures.
Therefore, we became interested in resorbable plates
with ultrasonic “welding” of “screws”. Our preliminary
experience with the use of resorbable plates and pins was
positive. This technology provides reliable and fast
fixation for fixing a laminotomy flap. In addition, by
bending the plates in a specific manner, one can slightly
increase the transverse dimension of the spinal canal to
ensure decompression. The biggest drawback and the
main obstacle to the wide application of the described
technology, are the price of implantable products and
special equipment required for their installation. Fig. 3. Scheme of the flap fixation.
a — sagittal projection; b — frontal projection; c — general view in three
Conclusion projections. 1 — laminotomy flap, fixed in its place; 2 — resorbable pins (screws);
3 — resorbable plates.

The paper presents the initial experience of using

resorbable plates and pins (screws) for fixing a laminotomy
No 06/2016) approved the publication of this paper in a
flap. We describe the surgical technique and provide
specialized medical journal.
comparative evaluation of the proposed technology with
those already commonly used in practice.
There is no conflict of interest.
The local ethical committee of the Burdenko
Neurosurgical Institute of the Ministry of Health of the
Russian Federation at the meeting of 09.06.16 (protocol

50 PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016

REFERENCES
1. Kuschel YV. The role of laminotomy and laminoplasty in reducing the
frequency of post-operative kyphoscoliosis in children operated on for
intramedullary tumors. Problems of neurosurgery named after N.N. Burdenko.
2007;20-24..
2. Ruggeri A, Pichierri A, Marotta N, Tarantino R, Delfini R. Laminotomy in
adults: technique and results. Eur Spine J. 2012;21:364-372.
doi: 10.1007/s00586-011-1826-2
3. Kuschel YV. «Open-door» laminoplasty to remove common intramedullary
tumors in children — a new approach to intradural spinal pathology.
Problems of neurosurgery named after N.N. Burdenko. 2007;45-46.
4. Acosta HL, Stelnicki EJ, Rodriguez L, Slingbaum LA. Use of absorbable
poly (d,l) lactic acid plates in cranial-vault remodeling: presentation of the
first case and lessons learned about its use. Cleft Palate Craniofac J.
2005;42:333-339.
Commentary
This work is devoted to the use of resorbable plates and
pins for laminoplasty in children. The process described by the
authors was previously used only for cranioplasty, so its
application in spinal surgery is off-label.
The laminoplasty is widely used in treatment of cervical
spondylogenic myelopathy in Japan (Hirobayashi, Kurokava),
and in Russia (A.O. Guscha, O.A. Dreval). At present, there are
titanium plates of special shape for fixing the arches available
for carrying out this operation. Of course, the use of resorbable
PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
5. Vaccaro AR, Madigan L. Spinal applications of bioabsorbable implants. J
Neurosurg. 2002;97:407-412.
6. Freudlsperger C, Castrillon-Oberndorfer G, Baechli H, Hoffmann J,
Mertens C, Engel M. The value of ultrasound-assisted pinned resorbable
osteosynthesis for cranial vault remodelling in craniosynostosis. J Cranio-
maxillofac Surg. 2014;42:503-507.
7. Salokorpi N, Sinikumpu JJ, Iber T, Zibo HN, Areda T, Ylikontiola L, San-
dor GK, Serio W. Frontal cranial modeling using endocranial resorbable
plate fixation in 27 consecutive plagiocephaly and trigonocephaly patients.
Childs Nerv Syst. 2015;31:1121-1128.
8. Stendel R, Krischek B, Pietila TA. Biodegradable implants in neurosurgery.
Acta Neurochir (Wien). 2001;143:237-243.
products is an attractive alternative to metal ones, especially
when ultrasonic “welding” is used for fixing pins in place.
It remains unclear whether it is possible to use these
products in the elderly, given the frequency of laminoplasty in
the stenosis of the spinal canal at the cervical level and the
frequent sclerosis and fragility of the arches in this category of
patients.
A.O. Guscha (Moscow, Russia)
51
 ORIGINAL ARTICLES

doi: 10.17116/engneiro201680652-58

Minipterional Craniotomy in Surgery for Anterior Circle of Willis Aneurysms

R.S. DZHINDZHIKHADZE, O.N. DREVAL’, V.A. LAZAREV, R.L. KAMBIEV

Russian Medical Academy of Postgraduate Education, Moscow, Russia; Inozemtsev City Clinical Hospital, Moscow, Russia

One of the significant events in aneurysm surgery was promotion of a microneurosurgical technique by G. Yasargil. Despite its
versatility, pterional craniotomy is associated with extensive osteotomy and a significant incision of the skin and temporal muscle,
which may lead to the adverse cosmetic effects, risk of temporomandibular joint dysfunction, injury to the frontal branch of the
facial nerve, and facial and scalp numbness. We present our experience with minipterional craniotomy in surgery for anterior
circle of Willis aneurysms in 40 patients. There were no serious complications or deaths. Also, there were no intraoperative
aneurysm ruptures. All patients experienced expected transient hypesthesia in the temporal region, which was not considered as
a complication. In this case, hypesthesia was significantly milder compared to that in the classical pterional craniotomy. Patients
assessed the postoperative cosmetic outcome as excellent.
Keywords: minipterional craniotomy, keyhole, minimally invasive surgery, aneurysms.

The traditional pterional approach in surgery of
cerebral aneurysms was proposed by G. Yasargil. The
approach includes an arcuate incision of the skin from
the tragus to the midline along the hairline, followed by
an extensive dissection of the temporal muscle and
craniotomy of the frontotemporal region [1, 2].
This classical extensive approach is often associated
with various postoperative complications, unsatisfactory
cosmetic results, prolonged stay of patients in a hospital,
and prolonged postoperative recovery at the outpatient
stage, which entails great economic costs. Later,
J. Hernesniemi et al. [3] modified pterional craniotomy
(PC) and proposed a lateral supraorbital approach that
differed (in the authors’ opinion) from PC by the
subfrontal trajectory facilitating an approach to the
parasellar space and causing less damage.
The modern concept of keyhole surgery involves
reducing the aggressiveness of surgery by minimizing a
surgical approach. Modified keyhole approaches were
initially proposed in surgery of anterior circulation
aneurysm and parasellar space-occupying lesions
[4―23]. We have used a differentiated approach for
surgical accesses and the concept of keyhole surgery for
anterior circulation aneurysms and anterior and middle
cranial fossa tumors since 2014.
In this work, we present the experience of using the
minipterional craniotomy (MPC) in surgery of anterior
circle of Willis aneurysms.
Material and methods
In the period between March 2014 and December
2015, 40 aneurysms were clipped using the minipterional
craniotomy. The aneurysm location was as follows: 30
middle cerebral artery (MCA) aneurysms, 7 internal
carotid artery (ICA) aneurysms in the area of the posterior
communicating artery orifice, and 3 ophthalmic
aneurysms. The male:female ratio was 1:2.5. The mean
age of patients was 53.7 years. Thirty patients had
unruptured aneurysms. Ten patients had subarachnoid
hemorrhage (SAH): 7 of these were operated on in the
acute period. The condition of these patients was assessed
using the Hunt―Hess scale, and the amount of SAH was
assessed using the Fisher scale. Four patients underwent
surgery in the early period. Three patients underwent
clipping in the long-term period. All patients had a
Hunt―Hess grade of I or II and Fisher grade 1 or 2 SAH.
Preoperatively, all patients underwent two-
dimensional and 3D-CT angiography. The surgical
approach was chosen after a thorough evaluation of the
anatomy of intracranial structures and aneurysms. All
aneurysms clipped using MPC were of small or medium
size, no more than 15 mm in diameter. In the case of
complex large and giant aneurysms, the method of choice
involved more extended approaches ranging from the
classical pterional craniotomy to the orbitozygomatic
approach and its different modifications. Also, we did
not consider MPC as an acceptable technique in patients
in a decompensated state (Hunt―Hess grade IV―V) as
well as in the case of massive subarachnoid hemorrhages
and large parenchymal hematomas accompanied by
brain edema and intracranial hypertension. Along with
clipping, most of the patients underwent extensive
decompressive trepanation.
Surgical technique
Surgery is performed under general anesthesia, with
the patient in a supine position with the head turned in
the opposite direction at an angle of 30―60°, depending
on the lesion location. The neck is maximally extended
to provide gravitational retraction of the frontal lobe
from the skull base and adequate venous drainage. A
4―5 cm arcuate incision of the skin and soft tissues is
performed in the temporal region, starting from the

© Group of authors, 2016 e-mail: brainsurg77@gmail.com

52 PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016

zygomatic process, 1 cm anterior to the superficial and/or after pharmacological exposures, there is no need
temporal artery, and to the hairline or not reaching the for significant retraction of the parenchyma. In the case
superior temporal line (Fig. 1). of hemorrhage, the brain may be edematous. In these
Next, the classical interfascial temporal muscle cases, the carotid cistern is first opened for adequate
dissection is performed, with the frontal branch of the relaxation, which then enables more comfortable and
facial nerve being preserved. An incision of the temporal less traumatic dissection of the Sylvian fissure. Early
fascia is performed by monopolar coagulation with placement of a lumbar drain may be an alternative in
preservation of the myofascial cuff. After a subperiosteal SAH patients.
dissection, the temporal muscle is expanded by a small After clipping the aneurysm and verifying its
retractor or reduced by hook tensioners. This enables full complete exclusion (it is optimal to use intraoperative
exposure of the pterion area. A burr hole is placed indocyanine green (ICG) angiography, followed by
superior to the frontozygomatic suture. A craniotomy, opening of the aneurysm), hemostasis is performed. The
2―3 cm in size, includes the lateral sphenoid bone, a DM is tightly closed. A bone flap is fixed with craniofixes
portion of the frontal bone below the superior temporal or miniplates. The temporal fascia/muscle, subcutaneous
line, and a minimum portion of the temporal bone. Like tissue, and skin are sutured in layers (Fig. 4). Given a
in the classical PC, the sphenoid crest is resected until small wound size, wound drainage is not performed,
the meningo-orbital artery in the superior orbital fissure which is also an undoubted advantage of minimally
is visualized (Fig. 2). invasive surgery.
The dura mater (DM) is opened by a semi-oval Below, we provide an example of surgery in a female
incision, with its base directed towards the pterion. The patient with a carotid-ophthalmic ICA aneurysm. The
intradural stage of surgery is performed under a microsurgical stage of surgery was performed without
microscope (Fig. 3). retractors (Fig. 5).
The subsequent technique depends on the aneurysm
location. In the case of MCA aneurysms, the Sylvian Results and discussion
fissure is dissected anteriorly to the superficial Sylvian
veins that should be preserved from damage. The Sylvian All aneurysms were completely excluded from the
fissure is sharply dissected. Usually, small bridging veins cerebral circulation, which was confirmed by
coming from the temporal lobe to the frontal lobe can be
coagulated without consequences. Of great importance is
a dissection in the subarachnoid space area to preserve
the cortex and minimize its damage. However, this is not
always possible in patients after massive subarachnoid
hemorrhage accompanied by brain edema and
obliteration of the Sylvian fissure. In the case of MCA
M1 bifurcation aneurysms, the transsylvian approach,
without dissection of the parasellar cisterns, may be
sufficient. In this situation, identification of the M1
segment to provide proximal control is the priority, and
then, the MCA branches (M2 segment) and aneurysms
are identified. After dissection, the aneurysm is clipped
with temporary clipping or without it. In the case of ICA a
aneurysms, the classical microsurgical technique with
early brain relaxation by opening of the optic nerve and
carotid artery cisterns is used. Further, a limited
dissection of the medial Sylvian fissure is performed to
provide moderate traction of the frontal lobe and
visualization of the ICA bifurcation. The posterior
communicating artery is visualized through the optic-
carotid triangle. Arachnoid adhesions of the ICA are
sharply dissected, and then the anterior choroid artery is
identified. The microsurgical technique is dictated by the
aneurysm location. In the case of carotid-ophthalmic
aneurysms, intradural resection of the anterior clinoid
b
process may be necessary to provide proximal control
and visualization of the ophthalmic artery.
In the case of adequate brain relaxation after draining Fig. 1. A skin incision (solid line) for minipterional craniotomy. The
dotted line indicates an incision for classical pterional craniotomy.
the cerebrospinal fluid from the subarachnoid cisterns

PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016 53

 ORIGINAL ARTICLES

a b

Fig. 2. Minimal pterional craniotomy.

a ― an intraoperative view: a skin-aponeurotic flap is moved anteriorly, and the temporal muscle is spread by a retractor; b ― the size of a bone flap.

Fig. 3. Stages of microsurgical treatment of a left MCA aneurysm.

a ― SCT-angiography: a saccular aneurysm of the left MCA M1 segment is seen; b ― an intraoperative view after minipterional craniotomy and opening of the DM;
the center of craniotomy is situated over the Sylvian fissure; c, d ― stages of Sylvian fissure dissection; e ― the saccular aneurysm of the MCA M1 segment; f ―
clipping of the aneurysm; g, h ― intraoperative indocyanine green angiography: the aneurysm is excluded from blood flow, the MCA branches, not stenotic, are
visualized; i ― a view after clipping of the aneurysm and opening of the aneurysmal sac.

intraoperative opening of aneurysms and subsequent
monitoring using intraoperative indocyanine green
angiography and control 3D-SCT angiography in the
postoperative period. There were no serious complications
or lethal cases in patients. Also, there were no
intraoperative aneurysm ruptures. All patients
experienced transient hypesthesia in the temporal region,
which was expected and, therefore, was not regarded as a
complication. It should be noted, that the hypesthesia
area was significantly smaller when compared to the
outcomes of classical pterional craniotomy.

54 PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016

Fig. 4. The wound closure stage.
a ― a bone flap is put in place and fixed; b ― sutures on the skin; c, d, e ― control craniography and CT.
Patients assessed the postoperative cosmetic result as
excellent. In 2 patients, a follow-up examination at up to
10 months revealed minimal dysfunction in the
temporomandibular joint area and symptoms of temporal
muscle atrophy in the craniotomy area.
The traditional approach in surgery for intracranial
aneurysms of the anterior circulation is the pterional
craniotomy proposed by M. Yasargil in 1975 [1, 2].
Pterional craniotomy is associated with a quite extensive
osteotomy and a significant incision of the skin and
temporal muscle, which may lead to the following side
effects: temporal muscle atrophy, scar formation, facial
asymmetry, risk of temporomandibular joint dysfunction,
chewing pain, discomfort when wearing glasses, damage
to the frontal branch of the facial nerve, scalp numbness,
and scar alopecia. Exposure of the cortex at the intradural
stage, more significant in size, may be accompanied
by damage to the cortex due to the influence
of the non-physiological environment, retractor
trauma, etc [21―25].
The concept of keyhole is not new. Since its
introduction by A. Perneczky et al. [10, 11, 21―25],
considerable experience in surgery of aneurysms and
intracranial tumors has been accumulated. Keyhole
surgery is a modern concept that significantly reduces
PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
injury caused by surgery. The size of keyhole craniotomy
is 2―3 cm, on average. However, this is not just a
reduction in the trephination window size. Keyhole
means the creation of an optimal surgical corridor in
each particular case to access a certain lesion with
minimal injury to both soft tissues, including the temporal
muscle, and brain tissue. This goal is achieved through
the use of small incisions of soft tissues, minimal DM
opening, and exposure of the cortex with minimal
retraction of the brain. This enables achieving the main
goals of minimally invasive neurosurgery: minimization
of surgical invasion, improvement of the cosmetic effect
compared to that of classical surgery, shorter surgery
time, reduction in blood loss, postoperative pain, and
postoperative complications, and shorter total hospital
stay, which reduces financial and economic costs for
treatment of patients. It is also important to assess the
outcomes of minimally invasive microsurgery of
aneurysms in terms of patient satisfaction with surgery.
The keyhole approaches used for anterior circulation
aneurysms are primarily supraorbital and minipterional
ones. B. Chehrazi [6] was one of the first researchers who
described a temporal transsylvian approach to aneurysms
as an alternative to the classical pterional craniotomy,
which was accompanied by a decrease in the trephination
55
 ORIGINAL ARTICLES

Fig. 5. Stages of microsurgical treatment of a carotid-ophthalmic ICA aneurysm.

a ― SCT-angiography: a carotid-ophthalmic aneurysm on the right is visualized; b ― an intraoperative image after minipterional craniotomy and opening of the
DM; the Sylvian fissure is indicated by the arrow; c ― intradural resection of the anterior clinoid process by a 2 mm diamond burr; d, e ― stages of aneurysm
isolation; f ― aneurysm clipping; g ― a view of the surgical wound at the end of surgery.

window. Later, many authors [5―16] used the mini-
invasive approach in aneurysm surgery, calling it a
modified pterional craniotomy. E. Figueiredo et al. [10,
11] compared the minipterional approach and the
pterional craniotomy in two groups of patients. Despite
the similar treatment outcomes, the authors noted that
the minipterional approach was associated with less
damage to soft tissues and less craniotomy, which
reduced the time of surgery and recovery period and
improved cosmetic results. A necessary support in
keyhole surgery of aneurysms is the use of an additional
imaging technique, intraoperative indocyanine green
fluorescence angiography [4, 26―28].
Keyhole surgery is based on a thorough preoperative
assessment to determine the trephination window
position depending on the pathological process and
individual patho-anatomic picture. We associate the
good results of surgical treatment in our group with
careful preoperative selection of candidates for minimally
invasive surgery and exclusion of patients being at the
decompensated stage (Hunt―Hess grade IV―V).
Patients with unruptured aneurysms are ideal candidates
for keyhole surgery, except for patients with large and
giant aneurysms. Among patients with the clinical
presentation of SAH, the most favorable candidates for
minimally invasive surgery are patients with Hunt―Hess
grade I―II aneurysms. For subcompensated and
decompensated patients, we consider the classical
pterional approach with its modifications (orbitopterional
or orbitozygomatic craniotomy) as the method of choice.

56 PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016

 Conclusion
The minipterional craniotomy is the method of
choice for most MCA and some ICA aneurysms. The
main goal of keyhole surgery is not only to reduce the
trephination window but also to decrease traction brain
injury. An important support in minimally invasive
surgery of aneurysms is the use of ICG-angiography and
endoscopic assistance, which greatly enhances
visualization and control in a narrow deep wound.
.
There is no conflict of interest.

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 ORIGINAL ARTICLES
Commentary
Pterional craniotomy with transsylvian dissection provides
a wide viewing angle for manipulations with intracranial
structures and is used as a standard approach for clipping of
anterior circulation and upper basilar artery aneurysms. A
modification of the pterional craniotomy in terms of mini-
invasive surgery, called minipterional craniotomy, is
characterized by reduced iatrogenic trauma. High safety of
surgery is achieved by reducing the length of a skin incision,
length of temporal muscle dissection, size of a bone flap, and
time spent on performing the approach and closing the wound.
Any desire to minimize a surgical approach to intracranial
structures requires a comparative evaluation of the safety of the
new technique, degree of its versatility (applicability), duration
of surgery, cosmetic results, etc. In the presented work, R.S.
Dzhindzhikhadze and co-authors analyze the experience of
using minipterional craniotomy in treatment of 40 saccular
aneurysms of the carotid territory, with 30 of them being middle
cerebral artery aneurysms.
In the discussion of minimally invasive approaches in
surgery of aneurysms, the authors refer to studies devoted to a
supraciliary approach. The supraciliary approach is a variant of
the supraorbital subfrontal approach and, being significantly
different, provides significantly less freedom of surgical
manipilations in the Sylvian fissure compared to the
minipterional approach.
The indications for minimally invasive surgery, including
minipterional craniotomy, in treatment of arterial aneurysms
are determined not only by the aneurysm size but also by the
aneurysm neck configuration. The use of a relatively narrow
intracranial corridor reduces visualization and hampers
arachnoid dissection of the vascular structures as well as limits
the use of complex configuration clips and clip holders with
large swing flexible heads.
58 PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
The minipterional approach is most appropriate for
clipping of middle cerebral artery and supraclinoid internal
carotid artery aneurysms with a simple neck configuration
directed perpendicular to the axis of a planned approach.
Exposure of the Sylvian fissure within a relatively small
trephination window enables its safe dissection in the
lateromedial (distal-proximal) direction, which is usually
sufficient for clipping of middle cerebral artery aneurysms. In
my opinion, this approach can not be used for complex middle
cerebral artery and anterior communicating artery aneurysms
and, if necessary, for contralateral dissection in multiple
aneurysms. All similar cases require extensive arachnoid
dissection with retraction of the frontal lobe and the standard
pterional craniotomy, the size of which enables insertion of
instruments and clips into the depth of the wound at different
angles.
The presented good results of minipterional craniotomy in
surgical treatment of aneurysms of the carotid territory are
associated with careful analysis of the relationship among the
aneurysm location, the direction and shape of the aneurysm
neck, the presence of hemorrhages and edema of brain tissue
that have been considered by the authors at the preoperative
planning stage. Experience of R.S. Dzhindzhikhadze and co-
authors emphasizes the important point about the need for
selecting not only a surgical approach but also its minimally
invasive modification to ensure both the primary goal of surgical
intervention (safe clipping of the aneurysm) and reduce the
total injury rate and duration of surgery.
Yu.A. Grigoryan (Moscow, Russia)
 CASE REPORTS

doi: 10.17116/engneiro201680659-66

A Giant Hyperostotic Parasagittal Meningioma in a Child with Neurofibromatosis

Type II. A Case Report and Literature Review
A.N. SAVATEEV, A.N. KONOVALOV, S.K. GORELYSHEV, L.A. SATANIN, E.A. KHUKHLAEVA, L.V. SHISHKINA,
V.I. OZEROVA, E.F. VALIAKHMETOVA, O.A. MEDVEDEVA

Burdenko Neurosurgical Institute, Moscow, Russia

Large parasagittal meningiomas, in particular hyperostotic ones, in children are rare and problematic in the differential diagnosis.
The literature reports only single clinical cases related to this issue; opinions about the indications, surgical treatment options, and
prognosis are contradictory. This paper presents a clinical case of a hyperostotic parasagittal meningioma with intra- and
extracranial growth in a 10-year-old boy with neurofibromatosis type II, which significantly worsened the prognosis. We discuss
the epidemiological and clinical features of childhood meningiomas and issues of their diagnosis, treatment, and prognosis.
Keywords: parasagittal, meningioma, hyperostosis, children, neurofibromatosis.

Abbreviations
VEGF ― vascular endothelial growth factor
DFS ― disease-free survival
ICA ― internal carotid artery
SSS ― superior sagittal sinus
Gr ― Gray
MRI ― magnetic resonance imaging
ECA ― external carotid artery
NF-2 ― neurofibromatosis type II
SCT ― spiral computed tomography
DМ ― dura mater

Meningiomas diagnosed in children under the age of
15 years form a special group and have a number of
principal differences from meningiomas in adults.
Parasagittal meningiomas are less common in children
than in adults and account for only 4% of all brain tumors
[1]. Hyperostosis can occur in association with convexity
and parasagittal meningiomas [2]. In childhood,
25―49% of meningiomas are associated with
hyperostosis [3―6], while in adults, this figure amounts
to 4.5% [2]. In children, 33―40% of meningiomas are
associated with neurofibromatosis type II (NF-2) [3,
6―8], which is a factor worsening the disease prognosis
[1, 3, 9].
In this article, we present a rare clinical case of
hyperostosis associated with a giant parasagittal
meningioma with intra- and extracranial growth in a
child with NF-2.
Clinical case
A 10-year-old boy L. applied to the Neurosurgical
Institute (August 31, 2015) with complaints of a bulging
in the parietal region. Eleven days before hospitalization,
the patient had acutely developed right-sided hemiparesis
and hemihypesthesia that completely regressed within 8
days of conservative treatment, including osmodiuretics
and glucocorticoids. Careful taking of a family history
revealed that the child’s grandmother had bilateral
neurinomas of the vestibulocochlear nerve (absolute
diagnostic criterion for NF-2 [10]), and his mother died
of an unspecified brain tumor (she refused surgery, so
there was no histological verification). MRI of the brain
detected a large parasagittal tumor with intra- and
extracranial growth, perifocal edema, and involvement
of the parietal bones, which invaded the middle third of
the superior sagittal sinus (Fig. 1).
At admission, there were no focal neurological and
intracranial hypertension symptoms. The Karnofsky
scale score was 100. On examination, a tight elastic
bulging in the temporal parasagittal region, mostly on the
left, was found. The time of its emergence was unknown.
No subcutaneous neurofibromas were found. SCT of the
brain revealed a parasagittal contrast enhanced tumor as
well as a hyperostotic lesion of both parietal bones,
11×8.5 cm in size, with a marked periosteal reaction
(Fig. 2). According to total selective cerebral angiography,
the afferents feeding the tumor were multiple small
branches of the ICA and ECA; the superior sagittal sinus
was not enhanced at the tumor site (Fig. 3).
Given the history, examination, and radiographic
findings, including intra- and extracranial components
of the tumor and the bone lesion, the diagnosis was

© Group of authors, 2016 e-mail: asavateev@nsi.ru

PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016 59

 CASE REPORTS
differentiated between primary Ewing’s sarcoma of the
parietal bone and hyperostotic parasagittal meningioma.
To determine the tactics of treatment, an open
biopsy of the extracranial portion of the tumor was
performed (03.09.15). The biopsy revealed
meningotheliomatous meningioma, WHO Grade I, with
a Ki-67 labeling index of 5―7%. An attempt to resect the
tumor was made (10.09.15). Resection of the extracranial
tumor component and resection trepanation of the skull
with removal of hyperostosis were performed through a
horseshoe-shaped skin incision in the projection of the
affected calvarial area. This procedure exposed the
intracranial tumor portion, but surgery was terminated
due to a high blood loss and a high risk of further massive
bleeding. At the second stage, 8 days later, the intracranial
tumor portion was removed. The superior sagittal sinus
walls occurred to be the initial site of tumor growth.
Because of marked venous bleeding from the sagittal
sinus, a drop in arterial pressure, and the risk of
impairment of venous outflow from large vessels of the
parietal region, total removal with resection of the ICA
was not performed. The ICA wall was strengthened with
tachocomb and artificial DM. The extent of tumor
resection was Simpson grade 4 [11]. According to the
pathology report, the resected intracranial meningioma
portion was identified as atypical meningioma, WHO
Grade II. On September 23, 2015, the patient underwent
duraplasty (artificial sheath) and bone defect
reconstruction using Palakos (Fig. 4). The patient was
discharged home 2 weeks after surgery. By that time, the
child was active, walked around the department, played,
communicated with others, and was capable of self care.
The Karnofsky scale score was 100.
One month later, control MRI of the brain revealed
small residuals of the meningioma in the superior sagittal
Fig. 1. Preoperative MRI scans of the 10-year-old patient L. Extra- and intracranial components of a space-occupying lesion and a parietal
bone lesion are seen.
60 PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
sinus region (Fig. 5). Given the family history, MRI of all
parts of the spinal cord was also performed, which
revealed a space-occupying lesion at the C6―C7 space
level on the left, most likely neurinoma, which did not
clinically manifest itself (Fig. 5, 6). Thus, the child had a
combination of the intracranial meningioma, neurinoma
of the C6―C7 spinal nerve, and family history (a direct
relative with NF-2), which was the basis to diagnose
neurofibromatosis type II.
Three months after tumor resection, the patient
underwent a course of stereotactic radiation therapy at a
dose of 60 Gy in 30 fractions for the residual meningioma.
Control MRI of the brain at 6 and 12 months after surgery
did not detect continued growth. Further radiation
treatment for the neurinoma at the C6―C7 level was
under discussion.
Discussion
The annual incidence rate of meningiomas increases
with age and peaks at 8.4 per 100,000 population by the
eighth decade of life [12]. Meningiomas account for
13―25% of all adult intracranial tumors [13]. At the
same time, the occurrence of these tumors in children is
much lower and is only 0.4―4.6% [1, 3, 14]. Adult
meningiomas are more common in females [9, 12]; on
the contrary, pediatric meningiomas are more common
in boys [1]. However, according to some studies [4], the
primary incidence of meningiomas is approximately the
same in children of both genders. Pediatric meningiomas
are associated with hyperostosis in 25―49% of cases
[3―6], while this parameter is 4.5% for adult tumors [2].
The topography of pediatric and adult meningiomas
is also different. Convexity meningiomas account for
41% of pediatric meningiomas [1] and only 19% of adult
Fig. 2. Preoperative SCT images of the 10-year-old patient L. Periosteal hyperostosis of both parietal bones and an irregular surface of the
affected bone are presented.
Fig. 3. Angiography of the 10-year-old patient L. The afferents are small branches of the ICA and ECA. The superior sagittal sinus is not
enhanced in the tumor area.
meningiomas [15]. Parasagittal pediatric meningiomas
are rare (about 4% of cases [1]) in contrast to adult tumors
(25% of cases [15]). In addition, pediatric meningiomas
are often (about 15% of cases) found in the ventricle
cavity [1, 4].
Y. Liu et al. [1] (2008) analyzed a large number of
pediatric meningiomas and concluded that the prognosis
was primarily affected by the following factors: the extent
of initial resection (total resection is associated with a
better prognosis), location of the tumor (affects the
completeness of resection and, indirectly, the prognosis),
presence of NF-2, and previous radiation treatment for
other tumors (worsens the prognosis). In 33―40% of
cases, pediatric meningiomas are associated with
neurofibromatosis type II [3, 6―8]. Neurofibromatosis
type II is believed to increase the risk of recurrence and
PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
death in meningiomas [1, 3, 9, 16]. At the same time, the
degree of anaplasia is a less significant factor [1].
Bilateral neurinomas of the VIIIth nerve are the
absolute diagnostic criteria for NF-2 [10, 17]. Also, the
diagnosis of NF-2 is established if there is a direct relative
having this disease in a combination with either unilateral
neurinoma of the VIIIth nerve or two or more of the
following signs: neurofibroma, meningioma (one or
more), glioma (one or more), schwannomas (including
one or more spinal schwannomas), and juvenile posterior
subcapsular lenticular cataract [10, 17]. Cafe-au-lait
spots occur in approximately 80% of NF-2 patients but
have no diagnostic significance [10].
The main method to diagnose meningiomas is MRI.
Meningiomas sometimes invade vital vascular structures,
so direct selective cerebral angiography is an important
61
 CASE REPORTS
Fig. 4. A CT image of the 10-year-old patient L. after duraplasty and
bone defect reconstruction.
adjunctive diagnostic technique in the preoperative
period. In addition, in the presence of large feeding
vessels, the vessels can be embolized to reduce blood loss
at the main stage of treatment [3, 18].
As early as 1987, K. Kim et al. [19] emphasized the
importance of spiral computed tomography for the
diagnosis of tumors associated with hyperostosis. The
authors noted that hyperostosis associated with convexity
or sphenoid wing meningiomas may often be confused
with bone changes associated with other pathological
processes, such as fibrous dysplasia, osteoma, or sarcoma.
All 9 cases presented in the study had one or more CT
features typical of hyperostosing meningiomas, namely:
a pronounced periosteal reaction, inward bulging of the
bone in the lesion area, an irregular eroded surface of the
Fig. 5. Postoperative MRI scans of the 10-year-old patient L. Tumor residuals in the sagittal sinus area are indicated by arrows.
62
affected bone, and intracranial changes. The authors [19]
argue that high-resolution computed tomography is the
method of choice for evaluation of hyperostosis and
differential diagnosis of hyperostosing meningiomas and
other diseases. The literature [18, 20, 21] reports only
single cases of meningiomas associated with hyperostosis
in children. The presented clinical case is rare and of
great interest because of the medical history features and
the complexity of differential diagnosis. Before the tumor
biopsy, one of the presumptive diagnoses was a
meningioma in the setting of neurofibromatosis type II.
However, the patient did not fully meet the diagnostic
criteria: having a direct relative with bilateral neurinomas
of the VIIIth nerve, the patient himself had a single tumor
and no neurinomas by the time of hospitalization. A giant
meningioma in the child without neurofibromatosis was
unlikely. MRI and CT findings might equally indicate
hyperostosing meningioma and Ewing’s sarcoma.
Therefore, the second potential diagnosis was primary
Ewing’s sarcoma of the cranial vault. This diagnosis was
favored by a short history of just 11 days after the onset of
symptoms and location of the tumor ― the parietal and
frontal regions that are typical primary sites of Ewing’s
sarcoma growth [22]. In addition, bone changes
associated with this tumor can be characterized either by
lysis of the inner and outer bone plates or by sclerosis of
bone tissue with a periosteal reaction in the form of
spicules, which is hardly distinguishable from hyperostosis
in meningioma on CT images.
In the world practice, both tumor resection and
neoadjuvant chemotherapy are used as the primary
treatment for Ewing’s sarcoma [22―25]. Chemotherapy
can be selected as primary treatment in the absence of
symptoms of intracranial hypertension [25]; in our case,
there was no intracranial hypertension. If treatment starts
with chemotherapy, the 5-, 10-, 15-, and 20-year overall
PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
Fig. 6. MRI scans of all parts of the spinal cord of the 10-year-old patient L. A neurinoma at the C6―C7 level on the left is indicated by
arrows.

survival of patients with Ewing’s sarcoma is 57.2, 49.3,
44.9, and 38.4%, respectively [26].
The standard of treatment for meningiomas is
surgical resection. However, total resection is achieved
PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
only in 80―90% of patients [3]. The surgeon should
strive for total resection of convexity and olfactory
meningiomas as well as meningiomas of the anterior
third of the cerebral falx and the superior sagittal sinus.
63
 CASE REPORTS
At the same time, if the tumor is located in the medial
sphenoid wings, posterior superior sagittal sinus, clivus,
or orbit, subtotal resection is safer treatment [18, 27].
Based on these factors and the diagnosis, a treatment
approach is chosen. After an open biopsy and receiving
the results of a histological study, the diagnosis and the
need in maximally radical surgery became apparent.
According to the literature [28], adjuvant radiation
therapy significantly improves local tumor control in
atypical and malignant meningiomas, especially in cases
of subtotal resection. Despite the fact that the difference
in disease-free survival after surgical and combined
treatment of meningiomas was not statistically significant
in most studies [28], some authors have still found a
significant difference confirming the positive effect of
radiotherapy on disease-free survival [29]. For example,
I. Piscevic et al. [29] (2015) reported the following results:
out of 88 meningioma patients, 58 patients had recurrence
within a mean follow-up period of 5.6 years. Five-year
disease-free survival (DFS) in patients who underwent
tumor resection followed by radiotherapy at a dose of
55/60 Gy (n=34) was 65%, and that in patients who
underwent surgery alone (n=24) was 13%. The differences
were statistically significant (Log rank=31.9; p=0.001).
For atypical meningiomas, the DFS difference was even
more significant (Log rank=34.1; p=0.001): the 5-year
DFS in combined and surgical treatment groups was 75
and 12%, respectively. It should be noted that the
literature lacks studies devoted to the efficacy and safety
of radiation therapy in pediatric meningiomas, and
patients with neurofibromatosis have been excluded from
most similar studies.
Unlike patients with sporadic tumors, patients with
NF-2 often have multiple or extensive tumors and a high
risk of recurrence [1, 3, 9, 16], which in some cases limits
the capabilities of surgery and radiotherapy.
Pharmacological therapy with proven efficacy in
meningiomas is currently not available. However, a
better understanding of the molecular mechanisms of
NF-2 pathogenesis opens the opportunity for application
of targeted therapy.
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Tumor growth is often accompanied by
neovascularization, therefore tumors produce angiogenic
factors, such as the vascular endothelial growth factor
(VEGF) [30]. A VEGF inhibitor is the medication
bevacizumab [30]. This is a humanized monoclonal
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Despite the fact that bevacizumab is effective only in
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Conclusion
In the presented case, the cause to use staged surgery
was poorly controlled bleeding at all stages of soft tissue
manipulations and tumor resection, which may lead to a
significant blood loss and serious complications. The
staged surgical treatment enabled resection of the extra-
and intracranial tumor portions, followed by
reconstructive closure of the bone defect without negative
somatic and neurological effects, as well as good and
rapid functional recovery of the patient.
In conclusion, it is necessary to emphasize the
importance of a careful taking of family and hereditary
history as well as MRI of not only the head but all parts of
the spinal cord in children operated on for meningiomas.
In the presented case, this facilitated identification of an
asymptomatic neurinoma at the cervical level,
establishment of the diagnosis of NF-2 (negatively
affecting the prognosis), and adjustment of the treatment.
There is no conflict of interest.
7. Greenberg MS. Handbook of neurosurgery. 3rd ed. Lakeland (Florida):
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demiology of primary intracranial tumors in the Valle d’Aosta (Italy) during
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RS. Pediatric meningiomas: a single-center experience with 15 consecutive
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Commentary
The paper describes and discusses a rare clinical case that is
also of great theoretical importance. The work is easy to read
and well illustrated. The discussion of the case and comparison
with the literature data provide the reader with an adequate
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24. Moschovi M, Alexiou GA, Tourkantoni N, Balafouta ME, Antypas C,
Tsiotra M, Sfakianos G, Prodromou N. Cranial Ewing’s sarcoma in chil-
dren. Neurol Sci. 2011;32(4):691-694.
25. Salunke PS, Gupta K, Malik V, Kumar N, Henke LE, Cai C, Chen WS,
Pfeifer JD. Primary Ewing’s sarcoma of cranial bones: analysis of ten pa-
tients. Acta Neurochir (Wien). 2011;153(7):1477-1485.
26. Bacci G, Forni C, Longhi A, Ferrari S, Donati D, De Paolis M, Barbieri E,
Pignotti E, Rosito P, Versari M. Long-term outcome for patients with non-
metastatic Ewing’s sarcoma treated with adjuvant and neoadjuvant chemo-
therapies. 402 patients treated at Rizzoli between 1972 and 1992. Eur J Can-
cer. 2004;40(1):73-83.
27. Bonnal J, Thibaut A, Brotchi J, Born J. Invading meningiomas of the sphe-
noid ridge. J Neurosurg. 1980;53(5):587-599.
28. Kaur G, Sayegh ET, Larson A, Bloch O, Madden M, Sun MZ, Barani IJ,
James CD, Parsa AT. Adjuvant radiotherapy for atypical and malignant me-
ningiomas: a systematic review. Neuro Oncol. 2014;16(5):628-636.
29. Pisćević I, Villa A, Milićević M, Ilić R, Nikitović M, Cavallo LM, Grujičić
D. The Influence of Adjuvant Radiotherapy in Atypical and Anaplastic Me-
ningiomas: A Series of 88 Patients in a Single Institution. World Neurosurg.
2015;83(6):987-995.
30. Kholodov BV, Abdullaev RT, Tarasova EM, Gorelyshev SK, Shishkina LV,
Zheludkova OG, Klimchuk OV, Shcherbenko OI, Prityko AG. The use of
the monoclonal antibody Bevacizumab (Avastin) in combination therapy of
low-grade glial tumors of the CNS in children (a literature review and au-
thors’ experience). Farmateka. 2010; 17: 61-66. (In Russ.).
31. Nunes FP, Merker VL, Jennings D, Caruso PA, di Tomaso E, Muzikansky
A, Barker FG. 2nd, Stemmer-Rachamimov A, Plotkin SR. Bevacizumab
treatment for meningiomas in NF2: a retrospective analysis of 15 patients.
PLoS One. 2013;8(3):e59941.
view of the issue and the current state of the problem. The
article is of great interest to a wide range of neurooncologists
and neuropediatricians.
V.A. Khachatryan (Saint Petersburg, Russia)
65
 CASE REPORTS
Commentary
The presented observation is a rare case of neurofibromatosis
type II combined with parasagittal meningioma in a child and is
devoted to solving topical issues of neurosurgery, in particular,
modern treatment options for primary brain tumors. This
problem is important for several reasons related to improvement
of diagnostic methods, new capabilities of the modern
microneurosurgical complex, and an increase in the resectability
of this complex group of patients. Undoubtedly, surgery is
believed to be the main modern technique in complex treatment
is surgical, but the tactics of surgical treatment, choice of an
operative approach and methods that increase the radicalness
of tumor resection still remain controversial, which causes
increased interest in this clinical case and confirms the topicality
of the problem.
The tumor nature of hyperostosis in meningiomas is now
generally recognized. However, invasion of the dura mater and
bone by the tumor and formation of hyperostosis are not
considered as signs of biological aggressiveness, and hyperostosis
associated with parasagittal meningiomas has no effect on
recurrence. Only an increased number of recurrences in the
case of bone destruction or hyperostosis combined with
destruction have been observed. Head soft tissue invasion by
66 PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
meningioma is considered as an indicator of biological
aggressiveness of the tumor.
The literature emphasizes a high recurrence rate of
parasagittal meningiomas, which is associated with anatomic
limitations of surgical radicalness in this area. Parasagittal
meningiomas affect the superior sagittal sinus in 15―50% of
cases, which sometimes objectively complicates one-stage
resection of the tumor. In these cases, surgery should be broken
up into several stages. Anatomical data should be considered
when planning and evaluating outcomes of surgical treatment.
The presented work provides a detailed, critical, and
chronological analysis of the literature data on neurofibromatosis
type II associated with meningiomas. The authors rightly put
emphasis on insufficiently resolved issues of this complex
pathology.
This clinical case is of considerable scientific and practical
interest and is devoted to the solution of topical issues of
neurosurgery and neurooncology. The work is well illustrated
and written in a good literary language and may serve as a guide
for both novice neurosurgeons and experienced specialists.
V.V. Timirgaz (Chisinau, Moldova)
doi: 10.17116/engneiro201680667-73

Spinal Stroke in a Pregnant Female with an Endodermal Cyst of the Cervical Spinal
Cord (a Case Report and Literature Review)
M.A. MARTYNOVA1, N.A. KONOVALOV1, A.YU. LUBNIN1, A.V. SHMIGEL’SKIY1, I.A. SAVIN1, T.F. TABASARANSKIY1,
K.N. AKHVLEDIANI2, E.V. SINBUKHOVA1, R.A. ONOPRIENKO1

1
Burdenko Neurosurgical Institute, Moscow, Russia; 2Moscow Regional Research Institute of obstetriics and Gynecology, Moscow, Russia

Objective. The study purpose was to present a clinical case of spinal stroke in a pregnant female, which was caused by
an endodermal cyst of the cervical spinal cord, and to analyze treatment tactics.
Results. A 20 week pregnant female presented with acute transverse spinal cord injury at the of C3―C5 spinal segment level. CT
revealed an extramedullary space-occupying lesion in the ventrolateral position, with compression of the spinal cord at this level.
The patient in the state of progressive deterioration with respiratory failure was transferred to the Neurosurgical Institute on the 5th
day after disease onset. The patient underwent surgery on the 7th day after disease onset. Doctors of various specialties participated
in preparation for surgery. During surgery, total resection of the space-occupying lesion and spinal cord decompression were
performed. An obstetrician-gynecologist conducted intraoperative fetal monitoring by ultrasound. The histological diagnosis was an
endodermal cyst. There was no improvement of neurological symptoms in the early postoperative period. After stabilization of the
condition, the patient was discharged for follow-up care at the place of residence. According to the follow-up report, the patient
underwent the cesarean section because of exacerbation of lung infection and a significant delay in the fetal development. After a
few days, the patient died due to multiple organ failure. The child was alive, in serious condition, under mechanical ventilation.
Conclusion. In the case of spinal stroke, the decision on treatment tactics should be made no later than 12 hours after its onset;
otherwise, the outcome is usually unfavorable, and a neurological deficit is irreversible. The decision about continuing pregnancy
should be made individually in each case, and an approach to the choice of appropriate treatment tactics should be multi-disciplinary.
Keywords: spinal stroke, extramedullary tumor, spinal cord tumor, endodermal cyst, pregnancy.

Spinal stroke, especially at the cervical level, poses a
serious danger to the patient’s life and health. In our
practice, we were faced with a similar situation where the
patient was a female with incomplete pregnancy. This
article discusses the experience in treatment of the patient
and associated problems.
Clinical case
A 24-year-old female patient M. was transferred
from a regional hospital at the place of residence to the
Burdenko Neurosurgical Institute (BNI). The patient
was at 20 weeks gestation.
According to a medical history, the patient suffered
from neck pain since the end of August 2015 and received
pain relievers. In the evening of September 05, 2015, she
noted numbness and growing weakness in the upper and
lower extremities. In the morning, she could not move
the extremities. The patient was transported by an
ambulance team to a regional hospital; after examination
by a neurologist and neurosurgeon, she was immediately
transferred to the Critical Care Department. The
patient’s condition at admission was evaluated as serious.
The patient was clearly conscious and complained of
neck pain, especially during head movements. Breathing
was spontaneous and adequate. Bilateral anesthesia of all
kinds of sensitivity, starting at the C3―C5 level of the
spinal cord, and flaccid tetraplegia were present. Reflexes
in the upper and lower extremities were absent. There
was acute urinary retention.
Within 1 day of hospitalization, the patient’s
condition began to deteriorate rapidly: respiratory failure
© Group of authors 2016
worsened, which required intubation of the trachea and
ventilation. On the second day of stay at the hospital,
after stabilization of the vital functions, the patient
underwent spiral computed tomography (SCT) of the
cervical spine, which revealed a space-occupying lesion
in the vertebral canal at the C3―C5 level, which was
located extramedullary and markedly compressed the
spinal cord (Fig. 1). Blood test indicators were without
significant abnormalities, except for hypokalemia
(3.0 mmol/L).
Ultrasound of the uterine cavity confirmed a
normally developing pregnancy at 20 weeks. There were
no obstetric indications for abortion.
On the 3rd day after the development of focal
symptoms, the patient was transferred to the BNI for
surgical treatment. The patient’s condition at admission
was serious: she was in the supine position in a passive
pose. Ventilation was performed through an orotracheal
tube. The patient followed simple instructions (she
answered simple questions by nodding of the head,
articulated, and closed the eyes on command) but quickly
exhausted; there were no movements in all the
extremities; there was a loss of all types of sensation,
starting at the C5―C6 level of the spinal cord and below.
The patient had hyperthermia of up to 38.7 °C and
arterial hypotension that required intravenous infusion of
vasopressors (norepinephrine), and worsening respiratory
failure (acceptable SpO2 figures were reached only at
FiO2=0.8). X-ray of the lungs revealed bilateral infiltrative
shadows in the lower lobes and perihilar portions. The
patient underwent therapeutic fibrobronchoscopy
e-mail: martynova_mariya@mail.ru

PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016 67

 CASE REPORTS
Fig. 1. SCT scans of the cervical spine. A large extramedullary space-occupying lesion is located anterolaterally at the C3―C5 level on the
right and compresses the spinal cord.
accompanied by removal of a small amount of viscous
purulent sputum. Given the episodes of desaturation and
desynchronization with the respirator, elevation of the
CRP level, fever, pulmonary radiographic findings,
nature of the underlying disease, and expected need for
prolonged ventilation, a puncture tracheostomy was
performed on the second day of stay at the Critical Care
Department of the BNI. On ventilation with positive end
expiratory pressure of 10 cm and FiO2=0.6 as well as
norepinephrine infusion, the patient’s condition was
stabilized, after which (on the 5th day of stay at the BNI),
she underwent magnetic resonance imaging (MRI) of
the cervical spinal cord (Fig. 2) and brain. MRI revealed
an extramedullary space-occupying lesion at the C3―
C5 level, which was located in the vertebral canal on the
right anteriorly, compressing the spinal cord and
displacing it to the left posteriorly. The lesion had a high
T2 signal (Fig. 2a, c), differing from that of free CSF, and
relatively clear smooth contours. T1-weighted MRI
revealed signs of parietal hemorrhage in the lesion
(Fig. 2b). The spinal cord at the pathology level and I or
II vertebra below it, as well as the medulla oblongata, had
signs of vasogenic edema. Series of T1 and T2-weighted
axial MRI scans of the brain revealed no pathological
changes.
The patient repeatedly consulted an obstetrician-
gynecologist and underwent daily ultrasound of the
uterine cavity, which revealed signs of threatened
miscarriage. There were no obstetric indications for
abortion. The patient was offered surgery for removal of
the space-occupying lesion at the C3―C5 level with
preserving pregnancy; the patient and her mother gave a
written consent.
68 PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
On the 7th day of stay at the BNI, the patient
underwent surgery: microsurgical resection of the
extramedullary space-occupying lesion at the C3―C5
level using ultrasound monitoring of the fetus.
Anesthesia included intravenous propofol (infusion
under control of anesthesia depth) + intravenous bolus of
fentanyl and rocuronium during surgery. Arterial pressure
was monitored directly through a catheter placed in the
left radial artery. Continuous intravenous infusion of
norepinephrine was performed throughout surgery due
to the tendency to arterial hypotension.
The patient was placed in the left lateral position that
was considered as the most physiological one, given the
gestational age and the need for intraoperative ultrasound
monitoring of the fetus. The patient’s head was fixed with
a Mayfield clamp; the patient underwent a laminectomy
at the C3―C5 level. The dural sac was stretched, not
pulsed, and prolapsed into the wound. After opening of
the dura mater, about 3 mL of fluid discharge released
into the wound, which was collected for testing. The
spinal cord was pale and ischemic. After excision of
arachnoid adhesions, a pale-gray space-occupying lesion
located anterolaterally on the right was found; it grossly
compressed and displaced the spinal cord. After
identifying poles of the lesion, its capsule was opened.
The space-occupying lesion contained viscous yellowish
liquid. The space-occupying lesion and its capsule were
resected en bloc (Fig. 3).
An urgent biopsy revealed that the resected lesion
had an endodermal origin.
Surgery was performed in the presence of an
obstetrician-gynecologist, with continuous ultrasound
monitoring of the fetal condition (Fig. 4).
Fig. 2. T1- and T2-weighted MRI scans of the cervical spinal cord.
a, b ― sagittal views; c ― an axial view; d ― 3D-MRI. (See the explanation in the text).
The duration of surgery was 1.5 h. The total time of
anesthesia, including positioning of the patient, was
about 4 h. The amount of intraoperative blood loss was
less than 150 mL.
After surgery, the patient was transferred to the
Critical Care Department where she continued receiving
intensive therapy. No changes in the neurological status
occurred.
Postoperatively, the patient’s condition remained
unstable: she was conscious; episodes of fever, up to 39
°C, persisted, without any effect of administration of
antipyretics; artificial ventilation through the
tracheostomy was continued. There was marked
production of viscous sputum, requiring sanitation
bronchoscopy; the tendency to arterial hypotension
persisted, which required continuation of intravenous
infusion of norepinephrine; salt-wasting syndrome
typical of patients with a high level of spinal cord injury
developed [1].
A control MRI study of the cervical spinal cord
confirmed complete resection of the space-occupying
lesion (Fig. 5).
A histological examination of the lesion capsule
revealed the presence of cell-free masses with
hemorrhages as well as fibrous tissue with cylindrical
epithelium, the morphological structure of which was
typical of an endodermal cyst (Fig. 6).
A histological examination of the discharge collected
after opening of the dura mater revealed necrotized tissue
with hemorrhages (cerebral detritus).
On intensive therapy, the patient’s general condition
gradually stabilized: fever, hypoalbuminemia, and
anemia regressed. There was no improvement in the
neurologic status. According to an examination by an
obstetrician-gynecologist, the fetus continued to develop
normally; there were no indications for abortion.
Given expected prolonged subsequent treatment and
rehabilitation and upon agreement with relatives, the
patient was transferred to the Critical Care Department
of a regional hospital at the place of residence.
PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
Further information on the fate of the patient and
the child was obtained from the doctors of appropriate
clinics by phone. The patient’s condition remained
relatively stable within a month after surgery; then, an
infectious process in the lungs worsened. This fact and
the need for antibacterial therapy with high doses of
potentially fetotoxic antibiotics, as well as significant
intrauterine fetal growth retardation, served as the basis
for the decision to terminate the pregnancy. Preterm
labor surgery (cesarean section) was performed at 29
weeks gestation, and a premature baby (boy) with a body
weight of 780 g, with an Apgar score of 6, was born. The
child was intubated and transferred to a specialized
perinatal center for artificial ventilation. According to
the available information, the child’s condition remained
severe by the time of manuscript preparation; the child
had several intracranial hemorrhages and was on artificial
ventilation. The mother’s condition after cesarean
section rapidly deteriorated. In the setting of bilateral
pneumonia, sepsis, and progressive multiple organ
failure, she died.
Discussion
Spinal pathology is the second most common disease
after traumatic brain injury among neurosurgical diseases
in Russia. Degenerative spine diseases are the most
common spinal pathologies. Primary tumors of the spinal
cord are relatively rare and account for only 10―15% of
all CNS tumors, or 1―2 cases per 100,000 people per
year [2]. Manifestations of spinal cord tumors during
pregnancy refer to casuistic cases. For example, A. Moles
et al. in their recent work on symptomatic vertebral
hemangiomas [3] (ones of the most common spinal
tumors) in pregnant females note that only 27 similar
cases have been reported in the literature since 1948.
Spinal cord tumors in pregnant females are even rarer.
Our patient had an extremely rare pathology ― an
endodermal cyst.
69
 CASE REPORTS

Fig. 3. Intraoperative images.

a ― after dissection of the dura mater; b ― after excision of arachnoid adhesions, a space-occupying lesion of a pale gray color is seen; c ― opening of the capsule
during resection of the lesion; d ― the space-occupying lesion and capsule resected en bloc; e, f ― the spinal cord after resection of the space-occupying lesion.

An endodermal cyst is a cystic lesion resulting from
endogenous dysgenesis; it is often combined with other
developmental anomalies [4]. The endodermal cyst wall
consists of columnar epithelium with cylindrical,
cuboidal, or goblet cells that usually produce mucin.
Inside, the endodermal cyst is lined with the ciliated
epithelium. Depending on the location, there are
intraspinal (intradural extramedullary) cysts, which are
most common, and intracranial cysts that are usually
located in the posterior cranial fossa, anteriorly to the
brainstem. Intraspinal cysts often occur in the lower
cervical and upper thoracic spine. The cysts typically
have an intradural extramedullary (mainly anterior)
location [5]. Endodermal cysts usually have an isointense

70 PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016


Fig. 4. Intraoperative ultrasound examination of the fetus.
or hypointense signal on T1-weighted MR images and a
hyperintense signal on T2-weighted MR images and are
not contrast-enhanced. The lack of tracer uptake in the
cyst wall distinguishes endodermal cysts from other cystic
lesions, such as cystic schwannomas, cystic meningiomas,
cystic ependymomas, and cysticercosis [6]. Differential
diagnosis with arachnoid, epidermal, and dermoid cysts
should be performed. Despite the benign nature,
endodermal cysts can recur, therefore the main surgical
treatment option is total cyst resection [5, 6].
The symptoms of spinal cord space-occupying
lesions usually develop slowly and can be represented by
pain as well as motor and sensation disorders [7]. An
acute onset occurs extremely rare and usually is a
consequence of concomitant spinal stroke, as it obviously
occurred in the presented case. This is confirmed by the
rapid development of a neurological deficit and the
presence of hemorrhages in histological specimens. It is
Fig. 5. Postoperative T1- and T2-weighted MR images of the cervical spinal cord in the sagittal (a) and axial (b) projections; there is no residual
cyst; the area of vasogenic edema and ischemia at the cervical level is decreased in size.
PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
important that the rate of deterioration and the severity
of clinical symptoms should be considered and profoundly
influence the management of these patients.
Examination and, if necessary, surgical intervention
should be performed as soon as possible, no later than the
“golden” day, and preferably earlier [8―10]. In the
presented case, surgery should be performed immediately,
even at the place of residence, to provide at least
decompression of the spinal cord. Transfer to the BNI
and stabilization of the patient’s general condition took
some time. The delay in surgery resulted in irreversible
changes in the tissues of the spinal cord, as evidenced by
the morphological picture of the fluid discharge released
after dissection of the dura mater, represented by a
necrotic tissue with hemorrhages.
In general, the management of pregnant females
with spinal pathology, especially in cases of severe
neurological symptoms, is extremely complex, and
information on this topic is quite limited [11―14].
Usually, one or two clinical cases with almost full-term
pregnancy or in the postpartum period are reported. In
this regard, the most interesting is a paper by I. Han et al.
[11], which summarizes the experience of managing 10
pregnant patients with different spinal pathologies at one
clinic for 13 years, and an article by K. Vijay et al. [14],
which describes 10 patients with vertebral hemangiomas.
Summarizing the data provided by the authors of these
two papers, we believe that two points are of crucial
importance: 1) neurological status of the pregnant female
and its dynamics and 2) gestational age of the fetus. In
the case of life-threatening neurological symptoms, full-
term or almost full-term pregnancy (32 weeks or more)
almost uniquely necessitates the following approach:
cesarean section and subsequent surgical treatment of the
mother. In the case of life-threatening neurological
71
 CASE REPORTS
Fig. 6 (a, b). A morphological picture of the endodermal cyst wall consisting of the columnar epithelium with cylindrical, cuboidal, or goblet
cells. Inside, the endodermal cyst is lined with the ciliated epithelium.
symptoms and early pregnancy, the authors of both works
suggest abortion because of the risk of fetal exposure to
X-rays and potentially fetotoxic drugs during diagnosis
and surgery in the first trimester of pregnancy.
We consider this recommendation as not quite
reasonable, especially given the recommendations of the
American Society of Radiologists, which contain the
only limitations related to the use of gadolinium as an
MRI tracer and a moderate risk of newborn
hypothyroidism associated with the use of iodine-
containing contrast agents [15].
Parturition in the case of incomplete pregnancy is an
approach that always requires serious argumentation.
A complication in premature newborns, such as
intracranial hemorrhage, is a well-known phenomenon
with the rate of occurrence, according to various
authors [16], ranging from 35 to 90%. The cause for this
high rate of the severe complication is now known: a
highly vascularized embryonic matrix is a substrate of the
developing brain. It is located in the subependymal space
of the lateral ventricles and undergoes a reverse
development at the 32―34th week of pregnancy.
Capillaries of this embryonic matrix are immature and
fragile and lack autoregulation mechanisms, which sets
the ground for hemorrhage in the case of even a slight
increase in cerebral blood flow [16]. In our opinion, the
only solution in our situation was an attempt to preserve
pregnancy by all means. Obviously, our colleagues had
solid indications for operative delivery in the case of
incomplete pregnancy. However, the consequences of
prematurity in the form of typical complications affected
the further fate of the baby.
72
Conclusion
The presented clinical case is a rare coincidence of
unfavorable circumstances: the presence of an
extramedullary space-occupying lesion in the patient,
lesion-induced spinal stroke, and incomplete pregnancy.
All these factors influenced the unsatisfactory outcome
of the disease. An endodermal cyst is a rare cystic lesion
of the intradural space, which we encountered for the
first time in our practice. Spinal stroke caused by an
anterior endodermal cyst at the cervical spinal cord level
in a pregnant female had not been reported in the
literature before, so we tried to present in detail this case
and the features of microsurgery, anesthesia, and critical
care. Regarding the management of the patient, we
believe that the decision of surgery should have been
made within the first 12 h after the disease onset. The
outcome of later interventions is unfavorable in most
cases, and the neurological deficit is irreversible.
Treatment of patients with combined pathology requires
participation of various specialists. In our case, the fetus
condition was controlled by obstetrician-gynecologists.
Unfortunately, prolongation of pregnancy up to 37―38
weeks was excluded in the presented situation. Was it
possible to avoid this treatment outcome? In our view,
under these circumstances, unfortunately not.
There is no conflict of interest.
PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
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neurenteric Cyst in association with Klippel-Feil syndrome: case report and
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6. Ito K, Aoyama T, Kiuchi T, Okada M, Kanaya K, Muraoka H, Horiuchi T,
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7. Shevelev IN, Konovalov NA, Kushel’ YuV, Zelenkov PV, Nazarenko AG.
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8. Fehlings MG, Perrin RG. The role and timing of early decompression for
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Commentary
The article describes a rare clinical case of intensive therapy
and surgical treatment of a 24-year-old patient who was
admitted to the Neurosurgical Institute at 20 weeks gestation
with spinal stroke associated with a space-occupying lesion of
the cervical spinal cord ― an endodermal cyst.
Undoubtedly, the presented clinical case is of great
practical importance and real interest. Pregnancy combined
with spinal pathology is rarely encountered by the neurosurgeon
and neurointensivist in their practical work and is always
associated with considerable difficulties in choosing the
treatment strategy and tactics. In the present case, the authors
encountered a combination of unusual and, unfortunately,
extremely unfavorable factors that occurred simultaneously in
the patient. These factors included a very rapid development of
the clinical and radiographic picture of the tumor in the form of
spinal stroke, a rare histological type of the space-occupying
lesion, and delayed radical surgery (because the patient had no
surgery at a hospital where she was initially admitted).
Of great interest is the surgical approach used by the
operating team, including the surgical stage with the patient in
a lateral position due to pregnancy, which is a non-standard
solution for modern interventions in the cervical spine,
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9. Fehlings MG, Perrin RG. The timing of surgical intervention in the treat-
ment of spinal cord indjury: a systematic review of recent clinical evidence.
Spine. 2006;31:S28-S36.
doi: 10.1097/01.brs.0000217973.11402.7f
10. La Rosa G, Conti A, Cardali S, Cacciola F, Tomasello F. Does early de-
compression improve neurological outcome of spinal cord injured patients?
Appraisal of the literature using a metaanalytical approach. Spinal Cord.
2004;42:503-512.
doi: 10.1038/sj.sc.3101627
11. Han IH, Kuh SU, Kim JH, Chin DK, Kim KS, Yoon YS, Jin BH, Cho YE.
Clinical approach and surgical strategy for spinal diseases in pregnant wom-
en. Spine. 2008;33:E614-E619.
doi: 10.1097/brs.0b013e31817c6c7d
12. Pikis S, Cohen JE, Rosenthal G, Barzilay Y, Kaplan L, Shoshan Y, Itshayek
E. Spinal meningeoma becoming symptomatic in the third trimester of
pregnancy. J Clin Neurosci. 2013;20:1797-1799.
doi: 10.1016/j.jocn.2013.08.001
13. Shinozaki M, Morita A, Kamijo K, Seichi A, Saito N, Kirino T. Symptom-
atic T2 vertebral hemangioma in a pregnant woman treated by one stage
combination surgery: Posterior stabilization and anterior subtotal tumor
resection. Neurol Med Chir. 2010;50:674-677.
doi: 10.2176/nmc.50.674
14. Vijay K, Shetty AP, Rajasekaran S. Symptomatic vertebral hemangioma in
pregnancy treated antepartum: a case report with review of literature. Eur
Spine J. 2008;17(Suppl. 2):S299-S303.
doi: 10.1007/s00586-008-0592-2
15. Chen MM, Coakley FV, Kaimal A, Laros RK. Guidelines for computed
tomography and magnetic resonance imaging use during pregnancy and
lactation. Obstet Gynecol. 2008;112:333-340.
doi: 10.1097/aog.0b013e318180a505
16. Greenberg MS. Intracerebral hemorrhages in newborns. In: Neurosurgery.
Мoscow: MEDpress-inform. 2010; 891-895. In Russian (translated from
English).
especially with intraoperative ultrasound monitoring of the
fetus condition. Also, of interest is the successful treatment at
the Neurocritical Care Department, which included reversal of
life-threatening conditions, such as salt-losing syndrome and
hyperthermia.
The perioperative period was complicated by not quite
ordinary phenomena, the genesis of which as well as initial
severity of the patient’s condition are not clear because of
limited world experience. Preserving pregnancy in this situation
is also debatable.
Undoubtedly, only joint efforts of doctors of different
specialties in a well-equipped hospital are able to solve the
problems of treatment of spinal cord space-occupying lesions
in the pregnant patient with severe and rapidly worsening
neurological symptoms. Unfortunately, surgical care, at least
decompression of the spinal canal, was not provided in the first
hours after admission of the patient to a local hospital. Despite
the fatal outcome of the disease for the mother and dubious
prospects for the newborn, this clinical case demonstrates high
skills of the authors and the coherence of their work.
A.O. Gushcha, A.A. Kashcheev (Moscow, Russia)
73
 CASE REPORTS

doi: 10.17116/engneiro201680674-78

Extrapontine Myelinolysis Developed After Aneurysmal Subarachnoid Hemorrhage

(a Case Report and Literature Review)
S.A. GOROSHCHENKO, A.YU. IVANOV, L.V. ROZHCHENKO, N.E. IVANOVA, YU.M. ZABRODSKAYA,
O.YU. RAZMOLOGOVA, A.N. KONDRAT’EV, E.G. POTEMKINA, A.YU. DMITRIEVSKAYA, G.P. BLAGORAZUMOVA,
S.D. RADZHABOV, A.E. PETROV, A.A. IVANOV, P.S. SINITSYN, V.V. BOBINOV

Polenov Russian Scientific Research Institute of Neurosurgery, the Branch of the Almazov Federal North-West Medical Research Centre,
St. Petersburg, Russia

Topicality. Central pontine and extrapontine myelinolysis is a rare and dangerous form of the demyelinating process of unknown
origin, the development of which is associated with abrupt changes in the serum sodium level (hypernatremia).
Objective — to describe a rare case of extrapontine myelinolysis complicating the hemorrhagic period of anterior communicating
artery aneurysm rupture as well as to demonstrate the ability to intravitally diagnose this condition.
Conclusions. Clinical vigilance of extrapontine myelinolysis may promote the timely diagnosis and treatment of this disease that
is a potential cause of death. Pulse-therapy with glucocorticoids alleviates neurological symptoms and stabilizes the patient’s
condition.
Keywords: hypernatremia, subarachnoid hemorrhage, extrapontine myelinolysis, glucocorticoids.

The paper is published to describe the development,
diagnostic capabilities, and treatment of a rare life-
threatening complication of subarachnoid hemorrhage.
Clinical case
A 58-year-old female patient was transferred to the
Department of Cerebral Vascular Surgery of the Polenov
Russian Scientific Research Institute of Neurosurgery
(PRSRIN) from a city hospital on the 15th day after
subarachnoid hemorrhage (SAH) from an anterior
communicating artery (AComA) aneurysm. The patient
was admitted with a WFNS grade 1 SAH. Neurological
status: the patient had clear consciousness and cerebral
symptoms with signs of intracranial hypertension and
focal lesions of the frontal lobes. Spiral computed
tomography (SCT) of the head revealed narrowing of the
subarachnoid spaces in the right cerebral hemisphere.
There was no hydrocepalus and deformity of the ventricles.
The patient had a concomitant disease, rheumatoid
polyarthritis, and constantly received 20 mg of
methotrexate per week. Spiral computed tomographic
angiography of the brain revealed a saccular aneurysm
and diverticula of the AComA (Fig. 1).
The patient underwent urgent osteoplastic craniotomy
and microsurgical clipping of the AComA aneurysm. In
the postoperative period, there was no worsening of
cerebral and focal symptoms. The patient received
antibacterial, anti-edematous, and cerebroprotective
therapy (medocef, nimotop, cytoflavin, mexidol). In a
blood chemistry panel, the sodium level changed between
144―152 mmol/L; there were no other changes. On the
14th postoperative day, the patient’s condition sharply
deteriorated: the consciousness level worsened to
profound obtundation with development of spastic
tetraparesis of up to 1 point. A CT examination revealed
signs of right hemisphere edema with a brain displacement
© Group of authors, 2016
of 7 mm to the left. Magnetic resonance imaging (MRI)
of the brain detected multiple areas of a hyperintense T2-
weighted image (T2-WI) signal, having clear contours in
the area of the corpora quadrigemina, both cerebral
peduncles, and oral pons (Fig. 2). A blood chemistry
panel revealed hypernatremia of up to 170 mmol/L as
well as elevated AST (58.5 U/L) and ALT (103 U/L)
levels.
The patient’s condition was assessed as the
development of pontine and extrapontine myelinolysis.
Pulse-therapy with glucocorticoids (solu-medrol for 3
days according to the schedule) provided a pronounced
positive effect: recovery of the consciousness, partial
restoration of limb movements (up to 4 points), and
normalization of natremia. However, a week later (on day
28 of the postoperative period), negative changes again
occurred in the patient’s condition: bulbar symptoms,
tetraplegia, and locked-in syndrome. An EEG
examination revealed gross diffuse changes clearly
predominating in the diencephalic brainstem structures.
A blood test again detected hypernatremia (172 mmol/L).
A cerebrospinal fluid test demonstrated a significant
increase in the myelin basic protein level (460 ng/mL,
with the normal level being less than 1 ng/mL) as well as a
sharp increase in the anti-myelin-associated glycoprotein
level (4,850 U/mL, with the normal level being
1000 U/mL); the S100 protein and neuron-specific
enolase levels were not significantly increased. Repeated
pulse-therapy with glucocorticoids had no significant
effect. The patient’s condition progressively worsened,
multiple organ failure (bilateral pneumonia and renal,
hepatic, and cardiovascular failure) deteriorated, which
led to death of the patient.
Autopsy findings: the white matter of the brain was of
a pale color, soft elastic in its texture, with bulging over
e-mail: goroschenkos@gmail.com

74 PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016

the cut surface in the subcortical nuclei area and in the
pons; the grey matter of the subcortical nuclei and thalami
was of a heterogeneous color, with small yellowish foci
(Fig. 3).
A histological examination of fragments of the
subcortical nuclei, thalami, and white matter of the
hemispheres as well as a cross-section of the pons, staining
with hematoxylin and eosin, and Nissl (for detection of
the Nissl substance in neurons) and Spielmeyer (for
myelin) staining were performed. In all the examined
fragments, diffuse foci of complete demyelination were
detected; edema in the form of a spongy transformation of
the white matter was present in the perifocal area of the
foci (Fig. 4).
In the demyelination foci, there was destruction of
the brain tissue, disintegration of neuropils, neuronal
shrinkage, the presence of eosinophilic bodies, moderate
gliosis with the microglial response, and swollen
oligodendrocytes (Fig. 5).
Neurons in these foci had dystrophic changes:
pericellular edema, moderate neuronophagia, foci of
neuronal dropout, and granular disintegration of the Nissl
substance (Fig. 6).
Therefore, the patient had diffuse microfocal
demyelination in the white matter of the hemispheres and
brainstem.
Discussion
Central pontine myelinolysis (CPM) was first
described by R. Adams et al. [1] (1959) in a patient with
chronic alcoholism, which was defined as osmotic
demyelination syndrome. Later, CPM was detected in
patients with diabetes mellitus, systemic lupus
erythematosus, renal failure, pituitary adenoma, and
cerebellar astrocytoma [2, 3]. The development of CPM
after liver transplantation was reported. As it was
Fig. 1. SCT angiography of the brain.
a, b ― a ruptured saccular aneurysm of the AComA (indicated by arrows).
PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
demonstrated in an experimental model of CPM in rats,
rapid administration of hypertonic saline (rapid
hypernatremia) resulted in extracellular edema of the
brain, provoking swelling of oligodendrocytes and
destruction of the myelin sheath [4]. Damage to the
myelin sheath can develop not only in the pons but also in
other brain structures, both in combination with CPM
and alone [5]. These disorders were called extrapontine
myelinolysis (EPM); in this case, demyelination foci can
occur in the brain peduncles, thalamus, corpus callosum,
geniculate bodies, and other brain structures [5]. Pontine
and extrapontine myelinolysis may be caused by other
hyperosmolar states [6].
The pathogenesis of this rare demyelinating process
has not been sufficiently studied. Currently, its
development is believed to be associated with a sharp
disturbance of the electrolyte (sodium) balance and blood
osmolarity [3, 6].
The major regulator of electrolyte metabolism in the
body is the hypothalamus. Studies of researchers guided
by Prof. M.V. Ugryumov (neurohistological,
neurohistochemical, and ultrastructural studies) at the
PRSRIN proved involvement of the hypothalamus in the
genesis of the degenerative-dystrophic process in the
nervous system and internal organs [7, 8]. The
development of the pathological process may involve
decreased functional activity of the hypothalamic
neurosecretory centers, which leads to deficiency of
viscerotropic peptide neurohormones in the general
circulation. The hormones maintain homeostasis, change
permeability of biological membranes, and affect various
aspects of metabolism, which, in turn, may cause gross
disturbances of electrolyte metabolism (hypo- and
hypernatremia).
The clinical picture of myelinolysis includes spastic
tetraparesis, pseudobulbar palsy and mental disorders [9],
75
 CASE REPORTS
Fig. 2 (a―d). T2-WI and FLAIR MRI of the brain.
Arrows indicate changes in the brainstem and subcortical nuclei.
epileptic seizures [10], Parkinson’s syndrome, and
locked-in syndrome [12―14].
CPM and EPM are primarily diagnosed based on
neuroimaging data. Myelinolysis appears as a high H2O
content area on the X-ray film and can resemble infarction
on the SCT scan. The method of differential diagnosis of
myelinolysis is MRI. Brain lesion areas are characterized
by a homogeneous high signal on T2-WI MR images and
by a low signal, the absence of perifocal edema, and mass-
effect signs on T1-WI MR images. A characteristic feature
of this pathology is non-involvement of the pontine
tegmentum and anterolateral pontine structures. The
affected area can involve the midbrain, periventricular
white matter, internal and external capsules, and corpora
callosa. MRI findings of bilateral symmetric lesions of the
thalami and basal nuclei in combination with brainstem
76
lesions facilitate the correct clinical interpretation of
myelinolysis [15].
A significant contribution to the differential diagnosis
in the present case was made by the data of chemistry
blood and cerebrospinal fluid panels that revealed elevated
levels of the demyelination markers ― the myelin basic
protein (its level was increased hundreds-fold) and
antimyelin-associated glycoprotein, with no increase in
the S100 protein (a marker of damage and inflammation
of the brain) and neuron-specific enolase (a marker of
ischemia) levels. This indicates the demyelinating process
in the brain, developing without signs of ischemia and
inflammation.
In the literature, there are separate reports on the use
of high doses of corticosteroid hormones [16] and
plasmapheresis for the treatment of EPM [17―19]. The
PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
Fig. 3. A gross specimen.
A cross section of the pons: 1 ― developing microcysts; 2 ― bulging of the white
matter.
Fig. 4. A microspecimen of the white matter from the subcortical
nuclei area.
1 ― demyelination area; 2 ― edema in the perifocal area with spongy
transformation; 3 ― area of positive staining of myelin fibers. Spielmeyer
staining, ×200.
use of pulse-therapy with glucocorticoids enabled us to
slow down the process in the presented case as well as to
achieve pronounced regression of the neurological
symptoms. However, the intravital diagnosis of this rare
complication did not help stop the development of severe
REFERENCES
1. Adams RD, Victor M, Mancall EL. Central pontine myelinolysis: a hither
to undescribed disease occurring in alcoholic and malnourished patients.
AMA Arch Neurol Psychiatry. 1959 Feb;81(2):154-172.
doi: 1959.02340140020004
2. Atkin JJ, Coady AM, White MC, Mathew B. Hyponatraemia secondary to
cerebral salt wasting syndrome following routine pituitary surgery. Eur J
Endocrinol. 1996;135:245-247.
doi 10.1530/eje.0.1350245
3. Stakhovskaya LV, Erokhina LG, Leskova NN, Gubskiy LV. Central pontine
and extrapontine myelinolysis. Zhurnal nevrologii i psikhiatrii. 2000; 100: 2:
55-58. (In Russ.).
PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
Fig. 5. A microspecimen of the white matter from the subcortical
nuclei area.
1 ― neuronal death; 2 ― neuronal shrinkage; 3 ― eosinophilic bodies. Staining
with hematoxylin and eosin, ×400.
Fig. 6. A microspecimen of the white matter from the subcortical
nuclei area.
1 ― a dead neuron; 2 ― granular disintegration of the Nissl substance, initial
neuronal karyolysis; 3 ― a deformed neuron with chromatolysis. Nissl staining,
×400.
neurodystrophic lesions of internal organs, which led to
multiple organ failure that caused patient’s death.
There is no conflict of interest.
4. Norenberg MD, Papendick RE. Chronicity of hyponatremia as a factoir in
experimental myelinolysis. Ann Neurol. 1984;15:544-547.
doi 10.1002/ana.410150606
5. Hadfield MG, Kubal WS. Extrapontine myelinolysis of the basal ganglia with-
out central pontine myelinolysis. Clin Neuropathol. 1996 Mar-Apr;15(2):96-100.
doi 10.1007/3-540-27660-2_89
6. Bourgouin PM, Chalk С, Richardson J, Duang H, Vezina JL. Subcortical
white matter lesions in osmotic demyelination syndrome. Am J Neuroradiol.
1995;16:1495-1497.
77
 CASE REPORTS
7. Polenov AL. The problem of central neurodystrophies of internal organs.
Leningrad: Meditsina. 1972. (In Russ.).
8. Tayushev KG. Hypothalamogenic degenerative-dystrophic process. Saint
Petersburg: Eskulap. 2002; 202. (In Russ.).
9. Laureno R, Karp BI. Myelinolysis after correction of hyponatremia. Ann
Intern Med. 1997;126:1:57-62.
doi 10.7326/0003-4819-126-1-199701010-00008
10. Girmenia F, Colasimo Di Biasi C, Faroni J, Pozzilli C. Central pontine my-
elinolysis: report of an asymptomatic case. Ann Ital Med Int. 1995;10(1):53-54.
11. Greenberg WM, Shah PJ. CPM in polydipsic psychiatric patients. Am J
Psychiat. 1993;150:842-843.
doi 10.1176/ajp.150.5.842-b
12. Go M, Amino A, Shindo K, Tsunoda S, Shiozawa Z. A case of central pon-
tine myelinolysis and extrapontine myelinolysis during rapid correction of
hypernatremia. Kinsho Shinkeigaku. 1994;34:11:1130-1135.
13. Morlan L, Rodriguex E, Gonzalez J, Jimene-Ortiz C, Escartin P, Liano H.
Central pontine myelinolysis following correction of hyponatremia: MRI
diagnosis. Eur Neurol. 1990;30:1:149-152.
doi 10.1159/000117333
14. Ardizzone G, Arrigo A, Schellino MM, Stratta C, Valzan S, Skurzak S,
Andruetto P, Panio A, Ballaris MA, Lavezzo B, Salizzoni M, Cerutti E.
Neurological complications of liver cirrhosis and orthotopic liver trans-
plant. Transplant Proc. 2006;38(3):789-792.
doi: 10.1016/j.transproceed.2006.01.039
Commentary
The article presents a case of surgical treatment of a patient
during the subacute stage of subarachnoid hemorrhage from an
anterior cerebral (communicating) artery aneurysm, which was
complicated by the development of pontine and extrapantine
myelinolysis in the late postoperative period, discusses this rare
complication, and reviews the literature. The article describes
the clinical course of the disease, data of CT and MRT
examinations in the postoperative period, results of chemistry
blood and cerebrospinal fluid panels (including tests for markers
of demyelination, inflammation, and ischemia), as well as
results of pathomorphological and histological examinations of
the brain after the patient’s death. On the basis of these data,
the authors conclude that the patient had the demyelinating
process in the brainstem and basal ganglia caused by osmotic
disorders.
Acute pontine and extrapontine myelinolysis is a rare
condition; however, the international and domestic literature
reports a sufficient number of clinical cases of this condition as
well as studies of its pathogenesis. In most studies, this condition
is considered to result from hyponatremia or rapid and abrupt
electrolyte changes during correction of hyponatremia that, in
turn, is often caused by various somatic pathologies.
In the presented case, it is difficult to reliably conclude on
the causes of demyelination because the data on electrolyte
78 PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
15. Ho VB, Fitz CR, Yoder CC, Geyer CA. Resolving MR features in osmotic
myelinolysis (central pontine and extrapontine myelinolysis). Am J Neuro-
radiol. 1993;14(1):163-167.
16. Kallakatta RN, Radhakrishnan A, Fayaz RK, Unnikrishnan JP, Kesa-
vadas C, Sarma SP. Clinical and functional outcome and factors predicting
prognosis in osmotic demyelination syndrome (central pontine and/or ex-
trapontine myelinolysis) in 25 patients. J Neurol Neurosurg Psychiatry.
2011;82(3):326-331.
doi: 10.1136/jnnp.2009.201764
17. Ludwig KP, Thiesset HF, Gayowski TJ, Schwartz JJ. Plasmapheresis and
Intravenous Immune Globulin Improve Neurologic Outcome of Central
Pontine Myelinolysis Occurring Post Orthotopic Liver Transplant. Ann
Pharmacother. 2011;45(2):e10.
doi: 10.1345/aph.1P371
18. Saner FH, Koeppen S, Meyer M, Kohnle M, Hergel-Rosenthal S, Soti-
ropoulos GC, Paul A, Radtke A, Malago M, Broelsch CE. Treatment of
central pontine myelinolysis with plasmapheresis and immunoglobulins in
liver transplant patient. Transpl Int. 2008;21(4):390-391.
doi: 10.1111/j.1432-2277.2007.00608.x
19. Dzyadz’ko AM, Katin ML, Rummo OO, Shcherba AE, Santotskiy EO,
Minov AF, Gurova MYu, Chugunova OA, Slobodin YuV, Zubritskiy SМ,
Avdey LL. Central pontine myelinolysis after orthotopic liver transplantation
(two case reports). Vestnik transplantologii i iskustvennykh organov. 2013; 15
(1): 89-95. (In Russ.).
doi 10.15825/1995-1191-2013-1-89-95
disturbances and infusion therapy are fragmentary. There is
also no information about the presence and severity of
angiospasm in the preoperative and, particularly, postoperative
periods, which may also be a cause of diencephalic disorders,
especially given postoperative edema of the right hemisphere
and postoperative hypernatremia. It is not entirely clear what
led to the patient’s death because it is not indicated on what day
after surgery she died, and the cause of death is not cerebral
disorders but multiple organ failure typical of patients being in
a serious condition for a long time. There is no discussion of a
relationship between the revealed changes and the patient’s
autoimmune disease as well as long-term therapy with
immunosuppressors. There are questions about quality of the
morphological study and its description that does not provide
an unambiguous confirmation of demyelination and may also
indicate ischemia.
However, the article is of undoubted interest, drawing
attention to the problem of pathogenesis of various
complications in neurosurgical patients and their differential
diagnosis. In this regard, of great interest are chemistry blood
and cerebrospinal fluid panels for demyelination markers,
which are rarely used in neurosurgical practice.
O.B. Belousova, I.A. Savin, O.A. Gadzhieva, L.V. Shishkina
(Moscow, Russia)
doi: 10.17116/engneiro201680679-83

Extradural Spinal Cord Hemangioblastoma (a Case Report and Literature Review)

N.A. KONOVALOV, L.V. SHISHKINA, D.S. ASYUTIN, R.A. ONOPRIENKO, V.A. KOROLISHIN, B.A. ZAKIROV,
M.A. MARTYNOVA, I.U. CHERKIEV, A.L. POGOSYAN, S.YU. TIMONIN

Burdenko Neurosurgical Institute, Moscow, Russia

Hemangioblastoma is a rare CNS vascular tumor that develops sporadically and can also be associated with von Hippel—Lindau
disease. Hemangioblastomas account for 2—6% of all spinal cord tumors and rank third in the structure of intramedullary space-
occupying lesions of the spinal cord. For the first time in our practice, we observed a dumbbell paravertebral hemangioblastoma.
The international literature reports only 3 cases of the tumor with this growth type.
Keywords: hemangioblastoma, von Hippel—Lindau disease, extradural dumbbell tumor.

Case report
Patient N., 56 years old, was admitted to the
Burdenko Neurosurgical Institute on 03.09.14 with
complaints of pain in the lumbosacral region irradiating
to the left leg, as well as sensory disorders in the form of
hypesthesia along the posterior surface of the left femur
and tibia. The history showed that the patient suffered
from back pain for a long time, pain gradually increased
over time and became permanent. The patient repeatedly
received drug therapy aimed at treatment of degenerative
disc disease, which did not result in improvement. Since
2006, the pain intensified and occurred in the rest, sitting,
and lying positions. In August 2013, the pain became
very intense and conservative therapy still was ineffective.
In this regard, MRI of the lumbosacral spine was carried
out, which revealed extradural mass lesion having
paravertebral spread at L4 —L5 into the intervertebral
foramen on the left. The mass was oval-shaped, sized
16x25x10 mm. Spinal angiography with contrasting of
tumor’s own vascular network at the level of L4 vertebra
was carried out (images are not shown). The patient was
admitted to neurosurgical department at the place of
residence for surgical treatment. The attempt of tumor
resection was unsuccessful. Histological examination of
resected fragment led to conclusion that it was
ganglioneuroma.
Control MRI 12 months after surgery showed the
same MR pattern as preoperative one (Fig. 1).
Resection of extradural paravertebral dumbbell
tumor on the left at L4—L5 was carried out at the
Burdenko Neurosurgical Institute on 11.09.14.
Operation
Patient’s position on the operating table: prone
position under a combination anesthesia with
endotracheal ventilation. Tumor level was localized
using O-arm intraoperative CT tomograph, images were
taken in the lateral and frontal planes in 2D-mode.
Paramedian skin incision was performed a few
centimeters to the left from the scar resulting from the
previous surgery. Caspar surgical microscope and
retractor system were used to approach the tumors. The
use of this expander minimized trauma to surrounding
tissues. Hemilaminectomy on the left at the level of L4
vertebral arch was carried out using microsurgical
instruments and Zimmer high-speed bur. Orange
elongated tumor sized 3x2 cm was observed. The tumor
was located in the L4—L5 intervertebral foramen and
was shaped similar to neurinoma. Extradural portion of
the L4 root on the left was determined to be the growth
origin. Major arterial vessel supplying the tumor was
detected during tumor separation along its perimeter. It
was coagulated and transected. Proximal part of the
tumor and root were ligated and then the tumor and
nerve root were coagulated and removed en bloc.
Hemostatic material was placed to the bed of resected
tumor (Fig. 2). The wound was closed using the standard
scheme.
In the postoperative period, pain regression was
observed. The patient was aroused on day 1 after the
operation. After 7 days, the patient was discharged home
in satisfactory condition. Histological diagnosis:
hemangioblastoma. Follow-up MRI study was carried
out 3 months after the operation (Fig. 3).
The histological characteristics of the tumor
Histological examination (Fig. 4) confirmed the
microscopic diagnosis of hemangioblastoma. Tumor
consisted of two types of cells: stromal cells with optically
empty cytoplasm and a large number of vascular cells.
The tumor was surrounded by a thin layer of fibrous
tissue closely bordered by nervous tissue fragments and
clusters of ganglion cells (Fig. 5).
During the study, adjacent nerve stem was discovered
(Fig. 6); the same finding was reported by R. Pluta et
al. [2].
Comparative analysis of the results of surgical
treatment of hemangioblastomas
Spinal hemangioblastomas belong to the group of
highly vascularized tumors, which are often characterized
by intramedullary localization. Hemangioblastoma

© Group of authors 2016 e-mail: nkonovalov@nsi.ru

PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016 79

 CASE REPORTS

account for 2—6% of all spinal cord neoplasms and rank
third in the structure of intramedullary space-occupying
lesions of the spinal cord [1]. In our case, the tumor was
paravertebral, dumbbell-shaped, and was not connected
to the dura mater. In the international literature [2—4],
we found three case reports describing patients with
similar localization of a space-occupying mass. The
Table shows some information about these patients, in
particular, clinical status and results of surgical treatment
(cases 1—3) and compares these data to the case descried
in our study (case 4).
When evaluating data shown in the Table, it is clear
that there were certain differences in the clinical
presentation of the disease. Thus, case 3 was characterized
by acute onset of the disease, where strong pain evolved
within 2 weeks, followed by admission of the patient to
neurosurgical hospital. In two other cases, (cases 1
and 2), as well as in our patient (case 4), there was a 2—20
years-long history. The tumor mainly manifested in the
form of radiculopathy characterized by pain in the
lumbosacral spine radiating to the leg, and also radicular
sensory disorders. Dysfunction of pelvic organs (urinary
incontinence) was observed in the case 3, possibly due to
compression of the roots of “cauda equina”.
The Table shows that preoperative clinical and X-ray
examination suggested correct histological diagnosis

Fig. 1. Hemangioblastoma of L4 root.

The series of T2-weighed MRI scans in the sagittal, frontal and axial projections (a, b, c) shows extradural hypointense space-occupying mass at L4—L5 vertebrae
characterized by hyperintense foci and dumbbell-shaped paravertebral growth to the left (the tumor is shown by white arrows). The sagittal and frontal views (a, b) show
pronounced vasculature (indicated by red arrows), which corresponds to multiple areas of hypointense signal in T2-weighed mode.

Fig. 2. Operation stages.

a, b — exposure and mobilization of the solid part of the tumor; c — ligation of the neck of the tumor of the L4 root; d — tumor resection along with the root. 1 — solid
portion, 2 — L4 root, 3 — gaine radiculaire, 4 — tumor bed.

80 PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016

Fig. 3. T2-weighed MRI, sagittal and axial views (a, b, c, d) after resection of hemangioblastoma.

Fig. 4. Hemangioblastoma. Stromal cells with optically empty Fig. 5. Hemangioblastoma (shown by red arrow) and clusters of
cytoplasm (shown by red arrow) and vascular cells (shown by blue ganglion cells (shown by green arrow).
arrow). H & E stain, magnification x100.
H & E stain, magnification x200.

only in one case (case 1) owing to the fact that this patient
with von Hippel—Lindau disease was diagnosed with
multiple CNS hemangioblastoma. In 2 cases (cases 2
and 3) preoperative MRI study led to a presumable
diagnosis of radicular neurogenic tumor, neuroma
(schwannoma). In our case (case 4), the tumor was
considered as paravertebral ganglioneuroma of the L4
root, corresponding histological diagnosis was made after
the first operation at the place of residence.
Our analysis of X-ray data led to the following
conclusions. Firstly, the studies should be contrast-
enhanced. Second, detection of pathologically dilated
tortuous vessels within the spinal canal around the
neoplasm is a pathognomonic sign of hemangioblastoma. Fig. 6. Hemangioblastoma and adjacent nerve stem (arrow).
The vessels are best visualized in T2-weighted mode. H & E stain, magnification x 50.
Thirdly, the solid component of the tumor has hypo-
intensive or iso-intensive T1-weighed MR signal, and
cystic cavities have T1- and T2-weighed signal similar to all four cases (see Table). This was accompanied by
that of the CSF or brighter T2-weighed signal. At least regression of pain syndrome. Possible occurrence of
one of the above MRI features suggests a vascular tumor, minor neurological deficit should be considered as an
and in this connection selective angiography can be inevitable consequence of the operation rather than a
recommended [4, 5]. complication, since the tumor is most often removed
When evaluating the outcomes of surgical treatment, together with the root, where it originates from.
we should note that tumors were completely resected in

PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016 81

 CASE REPORTS

!!! Обзор публикаций о хирургическом лечении корешковых гемангиобластом спинного мозга

Author and Anamnesis HL (Von Presumable AG with

Case Age Clinical History, Treatment
year of Sex morbi, Location Hippel– preoperative emboli–
No (years) presentation months outcome
publication months Lindau) diagnosis zation
Ryszard M. 1 F 38 120 EL S1-S2 + Hemangio- + RPS at S1— 12 Regression
Pluta, 2003 left blastoma S2, SD RPS

Masaaki 2 F 48 24 EL-DS — Neurogenous − MD, SD 12 Regression

chazo NO, L5 left tumor (Neuro- MD
1999 fibroma,
schwannoma)
María 3 M 48 1 EL-DS — Neuri- + PS, RPS, 36 Regression PS,
Román-de L4 right noma SD, DPO RPS, SD,
Aragón, DPO
2014
N.A. 4 F 56 240 EL-DS — Para- — PS, RPS 3 Regression PS,
Konovalov, L4 left ganglioma RPS
2016
Footnotes. EL — extradural location, DS — dumbbell-shaped tumor, PS — pain syndrome, RPS — radicular pain syndrome, SD — sensory disorders, MD — motor
disorders, DPO — dysfunction of pelvic organs.

Discussion transection of the root, no negative symptoms in the

Extramedullary hemangioblastomas are a fairly rare
pathology and there are no standards for their resection.
Since the aforementioned case was the first case of
extradural hemangioblastoma in our practice, we applied
microsurgical resection technique similar to that used for
resection of dumbbell tumors. Unfortunately, we did not
embolized the vessel supplying the tumor, which resulted
in bleeding from that vessel, the radicular artery, during
separation of the paravertebral portion of the tumor,
going beyond the intervertebral foramen. The bleeding
was successfully stopped using bipolar coagulation.
As the second stage, we exposed tumor poles, while
maintaining the dilated tumor draining veins, since we
believe that it is a string requirement. Hemangioblastomas
are well encapsulated and can be easily separated from
the surrounding tissue. Manipulations inside the tumor
capsule are dangerous since pronounced bleeding is
possible, which is usually difficult to control and can
completely obscure the entire field of view. Next, we
exposed the part of the tumor adjacent to the dura; the
root entering the tumor was ligated to prevent liquorrhea
from the gaine radiculaire. In our case, hemangioblastoma
could not be separated from the root because they were
adhered to each other. Therefore, hemangioblastoma has
been removed together with the L4 root. Despite the
form of increasing muscle weakness were observed in
patient’s left foot in the postoperative period. Tumor
resection resulted in formation of a deep bed. We carefully
examined the bed and suppressed hemorrhage from small
blood vessels. In this situation, hemostasis should be
carried out with hemostatic material without the use of
bipolar coagulation.
Conclusions
Extradural hemangioblastoma is a very rare disease.
However, in the cases, where MRI signs of a vascular
tumor are detected, further examination in required,
which may include CT perfusion study, as well as selective
angiography, when necessary. In the case of
hemangioblastoma with clearly differentiated supplying
vessels, embolization is advisable to reduce the risk of
intraoperative hemorrhage.
In our view, resection technique for extradural
hemangioblastomas is similar to operations carried out
for other tumors characterized by mostly paravertebral
dumbbell growth.
There is no conflict of interest.

82 PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016

REFERENCES
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Functional outcome after resection of spinal cord hemangioblastomas as-
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rosurgery Spine. 2010;12(3):233-242.
2. Pluta RM, Wait SD, Butman JA, Leppig KA, Vortmeyer AO, Oldfield EH,
Lonser RR. Sacral hemangioblastoma in a patient with von Hippel—Lindau
disease: case report and review of the literature. Neurosurgical focus.
2003;15(2):1-4.
Commentary
Hemangioblastoma is a highly vascularized benign tumor,
consisting of clustered thin-walled vessels of various calibers,
whose interstitial cells contain lipid-rich cytoplasm. In most
cases, spinal hemangioblastomas are intramedullary and
account for 2 to 8% of all intramedullary neoplasms, being
exceeded in incidence only by ependymomas and astrocytomas.
Spinal hemangioblastoma account for up to 20% of all CNS
hemangioblastomas. In rare cases, these tumors can be
extramedullary, and, in exceptional cases, even extradural.
Despite the preferential location of the tumor within the central
nervous system, no histological relationship between this tumor
and glial tissue was found. This explains the fact that the disease
occurs not only in the boundary zone between the central and
peripheral part of the nervous system (intradural extramedullary
hemangioblastomas are usually connected with the dorsal
surface of the spinal cord or intradural portion of the posterior
PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
3. Chazono M, Shiba R, Funasaki H, Soshi S, Hattori A, Fujii K. Hemangio-
blastoma of the L-5 nerve root: Case illustration. Journal of Neurosurgery
Spine. 1999;90(1):160-160.
4. Román-de Aragón M, Márquez T, Isla A, Gómez-de la Riva Á. Hemangio-
blastoma radicular extraforaminal de la raíz L4 derecha. Neurocirugía.
2014;25(6):286-289.
5. Kornienko VN, Pronin IN. Diagnosticheskaya neiroradiologiya. T 5;307-
314.
root), but also in the distant areas. The literature describes
hemangioblastomas of radial and sciatic nerves.
Cases of extramedullary tumors are extremely rare, which
complicates the choice of correct diagnosis and surgical
treatment of this pathology.
In the present article, the authors describe the clinical
presentation, diagnostic algorithm, and preoperative
preparation of patients with extradural hemangioblastomas,
taking into account available literature. Special attention is paid
to the surgical techniques of tumor node resection.
The article is of great interest to a wide range of
neurosurgeons.
G.Yu. Evzikov (Moscow, Russia)
83
 CASE REPORTS
doi: 10.17116/engneiro201680684-89
Infant Form of Alexander Disease (Clinical Case and Literature Review)
R.A. VASIN, M.A. KRASNIKOV, S.V. VASINA
Regional Children’s Hospital, Lipetsk, Russia
We present a case of the infant form of Alexander disease. The case is unique because the patient’s examination was started at the
preclinical stage and continued during the manifestation and fastigium of the disease. We present rare images obtained during
neurosonography at the preclinical stage of the disease as well as the unique findings of MRI studies. The MRI findings at disease
onset and 3 years later indicate that the infant form of Alexander disease is characterized by clinical stages.
Keywords: Alexander disease, leukodystrophy, hydrocephalus.
Alexander’s disease is a rare hereditary disease,
characterized by progressive degeneration of white
matter of the brain. The disease is caused by mutation in
a gene, which encodes GFAP (glial fibrillar acidic
protein) protein. Russo et al. (1976) distinguish three
forms of the disease based on the time of its manifestation:
infant form, which manifests at the age from 0 to 2 years,
adolescent form, from 2 to 12 years, and adult form, after
12 years of age [1]. Some authors [2—4] also describe
neonatal form. The infant form accounts for 63 to 80% of
all cases [3, 5, 6].
Recently, another classification scheme has been
gaining traction which is based on the localization of the
lesion and clinical presentation. Prust et al. (2011)
identify types I and II of the disease. Type I includes early
forms with predominantly frontal leukodystrophy, while
type II includes mainly cerebellar lesions and lesions of
stem structures. The median survival for type I is 14
years, for type II, 25 years [1]. It is believed that the
earlier the disease manifests, the more malignant is its
course. This is especially true of the neonatal form [2, 3].
At the same time, some experts note unpredictable course
of the disease at any age and do not consider age-based
classification to be relevant [2].
S. Marjo van der Knaap et al. [7] offer five MRI
criteria for establishing the diagnosis of Alexander's
disease:
- extensive changes in the white matter of the cerebral
hemispheres, mainly in the frontal lobes;
- periventricular rim with high intensity T1 signal
and low level of T2 signal;
- changes in basal ganglia and thalamus;
- damage to the brainstem;
- increase the contrast of gray and white matter.
Four of the five criteria are sufficient for the
diagnosis [7].
Some patients develop hydrocephalus due to
compression of the Sylvian aqueduct; therefore these
patients require neurosurgical intervention [1—3, 8].
© Group of authors, 2016
84 PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
Clinical observation
We present the clinical case of the girl T., who first
came to the attention of neurologists and neurosurgeons
at the age of 2 months.
The child was from the first pregnancy, with urgent
delivery at 42 weeks, which proceeded on its own, without
complications. Body weight at birth, 3310 g, height,
53 cm. No anomalies were observed before the age of 2
months, the child grew and developed normally. At the
age of 2 months, preventive neurosonography (NSG)
was prescribed. At the time of the examination, the
mother had no complaints, noting only minor episodes
of the child's anxiety.
The results of the NSG are shown in Fig. 1. Frontal
standard projection. The arrows indicate cloudy
hyperechoic zones in the periventricular sections of the
anterior horns of the lateral ventricles. The ventricular
system is not enlarged. There is a narrowing of the
anterior horns of the lateral ventricles at the point of
contact with areas of increased echogenicity due to mass
effect of pathological foci.
Given the unusual nature of the NSG findings, were
in-hospital examination to clarify the diagnosis was
proposed to the parents. On June 28, 2011 the baby was
admitted to the nursing department. The NSG data were
regarded as possible ischemic lesion of the natal period or
expansive process. The child’s state drastically
deteriorated in the hospital: she lost ability to hold her
head, there were choreoid movements in the facial
musculature and athetoid movements in the distal parts
of the limbs, she suffered from expressed anxiety attacks.
On July 07, 2011 magnetic resonance imaging (MRI) of
the brain without contrast and with contrast enhancement
by Magnevist was performed. The results are shown in
Fig. 2 and 3.
In general, focal changes identified by MRI coincided
with those identified by NSG. A focus in the quadrigeminal
plate area is clearly visible. The beginning of
e-mail: vasinlodb@yandex.ru

Fig.1 Patient T. NSG at the age of 2 months.
ventriculomegaly can already be clearly seen from these
pictures. The mass effect of pathological foci on the
Fig. 2. Patient T., age 2.5 months. MRI of the head without contrast enhancement in T1 and T2-modes. The primary lesion of the white
matter of the frontal lobes with the involvement of the subcortical ganglia is visible. There is a moderate expansion of the lateral ventricles.
PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
anterior horns of the lateral ventricles is observed and its
lumen is practically invisible.
From July 26, 2011 there was further worsening of
the condition in the form of increase in anxiety, vomiting
and fits of “fading”. According to the NSG, there is a
progressive expansion of the ventricular system. On July
27, 2011, ventriculoperitoneostomy was performed. The
surgery had certain features dictated by the disease: due
to the narrowing of the anterior horns of the lateral
ventricles, caused by mass effect of the pathological foci,
it was decided to perform ventriculostomy not from the
Kocher point but through the horn (Dandy point) by
moving a catheter beyond the vascular plexus using
ultrasound control. Improvement was noted in the
postoperative period. General cerebral symptoms
regressed, hyperkinesis decreased. Genetic analysis
(genetic laboratory of the Russian Children's Clinical
Hospital, Moscow) revealed a mutation
85
 CASE REPORTS
Fig. 3. Patient T., age 2.5 months. MRI of the head with contrast enhancement. Symmetrical accumulation of contrast in the frontal lobes,
visual cusps and quadrigeminal plate.
c1117C>a(pClu373Lys) in the gene GFAP (Alexander's
disease), which is described in the mutation database
(cm023075) in the heterozygous state.
Later the child was observed by a neurologist and
received anticonvulsant therapy. A repeated in-depth
examination was conducted at the age of 3 years. The
general condition of the child was regarded as satisfactory.
There was marked delay in psychomotor development.
The child experienced epileptic seizures 1—2 times a
week in the form of a short-term “fading”. At the time of
the examination the child was sane, had speech at the
level of babbling, reacted to the examination positively,
could ‘fixate’ the eyesight, was interested in toys, took
them in hands and examined them for long time, sat
without support, did not walk. Exotropia. Choreoid-like
movements in the extremities. Pronounced muscular
hypotension.
86
MRI without contrast and with contrast enhancement
was performed. The results are shown in Fig. 4.
Discussion
This case is interesting in several aspects. Since the
first description of the disease back in 1949 and until
2011, there were less than 100 described cases, and only
ca. 50 of them were described with the use of modern
neuroimaging. In 2011, S.V. Serkov et al. [8] described
two cases of juvenile form of the disease for the first time
in Russia. Our case, perhaps, is the third case identified
in the Russian Federation.
We had a rare opportunity to obtain neuroimaging of
Alexander disease using NSG at the preclinical stage. It
should be noted that such NSG findings are difficult to
interpret, but they can point the clinician in the right
PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
 a

Fig. 4. Patient T., age 3 years 2 months. MRI of the head. The condition after ventriculo-peritoneal bypass (VPS).
a — MRI without contrast. The affected zones retain the former localization, but are less extensive. There are no indications of mass effect of pathological foci. The
luminaire of the anterior horns is visible together with the cavity of the transparent septum; b — MRI of the brain with contrast. There are not foci of contrast
accumulation.

PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016 87

 CASE REPORTS
direction. Localization of foci in the frontal lobes with
spreading into the visual cups and their mass effect is
probably pathognomonic for Alexander's disease. We
have not found similar neurosonographic findings in the
literature.
The second important observation is the data
obtained with MRI with contrast enhancement. The
nature of the accumulation of contrast and the period of
the disease in which this accumulation occurs are
important. Intense accumulation of the contrast was
recorded in the lesions at the onset of clinical symptoms.
In addition to the intensity of contrast accumulation, the
symmetry of the foci is also notable. Another feature is
the lack of accumulation 3 years after the manifestation
of the disease during the stabilization period. It can be
assumed that the accumulation of contrast in the
leukodystrophy foci is typical for onset and height of the
disease, and that the period of remission can be
characterized by the absence of such accumulation. In
case of juvenile form of the disease described by S.V.
Serkov et al. [8], the intensity of contrast accumulation
was constant. The change in contrast accumulation
observed in our case has not been described in the
literature and may be characteristic of the infant form of
the disease.
During the manifestation of the disease, MRI
presentation fully complied with the criteria proposed by
Marjo S. van der Knaap et al. [7], however, during the
stabilization of clinical symptoms, no more than 3 out of
the 5 described criteria were present.
The third important fact concerns the course of the
infant form of the disease. The disease can last from
88 PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
several months to 8 years. The average duration of the
disease is 2—3 years [8]. Our case demonstrates long
period of stabilization. It can be assumed that timely
shunt surgery in other cases can contribute to the
stabilization of the patient's condition and the
prolongation of his or her life.
Analysis of the described observations allows
proposal that there are distinct stages of the infant form
of Alexander's disease.
Conclusions
Focal changes detected in neurosonography in the
form of hyperechoic cloud-like foci that spread from the
periventricular sections of the anterior horn of the lateral
ventricles to the basal ganglia can be specific for the
infant form of Alexander's disease. Leukodystrophy foci
in the period of onset and height of the disease present as
mass process. Leukodystrophy foci identified during
MRI examination can intensively accumulate contrast
during the onset of the disease, and, on the contrary, do
not accumulate contrast during the period of the absence
of clinical manifestations, which may indicate the
presence of at least two distinct stages of the disease.
The infant form of the disease does not always lead to
a fatal outcome. At the same time, the severity of white
matter lesions inevitably leads to disability of the patient.
A timely shunt surgery is likely to prolong the life of these
patients.
There is no conflict of interest.
REFERENCES
1. Messing A, Brenner M, Feany MB, Nedergaard M, Goldman JE. Alexan-
der Disease. The Journal of Neuroscience. 2012 11 April;32(15):5017-5023.
doi: 10.1523/JNEUROSCI.5384-11.2012
2. Springer S, Erlewein R, Naegele T, Becker I, Auer D, Grodd W, Krägeloh-
Mann I. Alexander disease — classification revisited and isolation of a neo-
natal form. Neuropediatrics. 2000;31(2):86-92.
doi:10.1055/s-2000-7479
3. Vazquez A, Macaya N, Mayolas S, Arevalo MA, Enrıquez PG. Alexander
Disease: MR Imaging Prenatal Diagnosis. Case reporte. AJNR Am J Neuro-
radiol. 2008 Nov;29(10):1973-1975.
doi: 10.3174/ajnr.A1215. Epub 2008 Jul 24
4. Ashrafi MR, Tavasoli A, Aryani O, Alizadeh H, Houshmand M. Alexander
Disease: Report of Two Unrelated Infantile Form Cases, Identified by
GFAP Mutation Analysis and Review of Literature; The First Report from
Iran. Iran J Pediatr. 2013 Aug;23(4):481-484.
PMID:24427505 [PubMed]
Commentary
The work is devoted to a rare genetic disease. The
observations are unique due to good neuroimaging of various
stages of the development of the disease and rare data of
neurosonography with the observed pathology. The literature
review cited by the authors in the discussion is also interesting.
Undoubtedly, the work is worthy of publication in the
neurosurgical journal, as it broadens the horizons of
PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
5. Kumar KJ, Suryaprakash H, Manjunath VG, Harsha S. Infantile Alexander
disease: a rare leukodystrophy. J Pediatr Neurosci. 2012 May;7(2):117-119.
doi: 10.4103/1817-1745.102573
6. Ozkaya H, Akcan AB, Aydemir G, Kul M, Aydinoz S, Karademir F, Suley-
manoglu S. Juvenile Alexander disease: a case report. Eurasian J Med.
2012;44:46-50.
doi: 10.5152/eajm.2012.10
7. Marjo S. van der Knaap, Sakkubai Naidu, Breiter SN, Blaser S, Stroink H,
Springer S, Begeer JC, van Coster R, Barth PG, Thomas NH, Valk J,
Powers JM. Alexander Disease: Diagnosis with MR Imaging. AJNR Am J
Neuroradiol. 2001 Mar;22(3):541-552.
PMID:11237983
8. Serkov S.V., Pronin I.N., Bembeeva R.S., Kornienko V.N. Alexander’s Dis-
ease. Literature Review and Personal Observations. Luchevaya diagnostika
and terapiya. 2011;4(2):17-32 (in Russ.).
neurosurgeons in terms of differential diagnosis. In addition, as
the authors have shown, the presented disease sometimes
requires neurosurgical interventions to alleviate the patient's
condition.
Yu.V. Kushel (Moscow, Russia)
89
 GUIDELINES FOR THE PRACTITIONER

doi: 10.17116/engneiro201680690-97

Use of Surgical Approaches to the Posterior Cranial Fossa in Patients in a Lying

Position
V.N. SHIMANSKIY1, V.V. KARNAUKHOV1, S.V. TANYASHIN1, V.K. POSHATAEV1,2, K.V. SHEVCHENKO1,
D.A. ODAMANOV1, S.V. KONDRAKHOV2

1
Burdenko Neurosurgical Institute, Moscow, Russia; 2Clinical Hospital №1 (Volynskaya) of the Presidential Administration of the Russian
Federation, Moscow, Russia

Background. Various suboccipital approaches are extensively used in modern neurosurgery for treatment of posterior cranial fossa
disorders. The main patient’s positions on the operating table during surgery are the half-sitting and lying ones.
Material and Methods. The article provides a detailed description and the methodology of the suboccipital retrosigmoid and
median suboccipital approaches in the lying position.
Conclusion. The suboccipital retrosigmoid and median suboccipital approaches in the lying position, when used correctly,
provide a good view of the operating field with the minimal risk of complications associated with the patient’s position on the
operating table.
Keywords: suboccipital retrosigmoid approach, median suboccipital approach, posterior cranial fossa tumors, skull base surgery,
skull base tumors.

Various suboccipital approaches are extensively used
in modern neurosurgery to treat posterior cranial fossa
(PCF) pathologies, such as skull base, cerebellar, and
brainstem tumors, cranial nerve compression syndromes,
and vascular disorders of the vertebrobasilar basin [1—8].
The main patient's positions on the operating table during
surgery are the half-sitting and lying ones. Each of them
has its own advantages and drawbacks. The half-sitting
position ensures more adequate ventilation and provides
good visualization of the anatomical structures of the
posterior cranial fossa due to the natural passage of fluid
from the surgical wound under gravity. Meanwhile, this
position is associated with a high risk of air embolism and
hemodynamic disorders caused by shifting patient's
positioning (orthostatic hypotension), as well as results in
pneumocephalus and other complications. Air embolism
is the key life-threatening complication associated with
the semi-sitting position. It can result in severe
cardiovascular disorders, ischemic injury to cardiac muscle
and brain. These complications can be almost entirely
prevented if using the horizontal position [9]. This
circumstance makes many surgeons avoid using the semi-
sitting position for posterior cranial fossa surgeries. We
provide a detailed description and illustration to the
methodology of the main surgical approaches to the PCF
structures in the lying position.
Materials and Methods
More than 450 surgeries for PCF pathologies are
performed annually at the Department of Peri-brainstem
Tumors (Burdenko Neurosurgical Institute). The main
approaches used are the suboccipital retrosigmoid and the
median suboccipital approaches.
The suboccipital retrosigmoid approach (SRSA) has
been used by neurosurgeons for more than 100 years [1].
It is currently employed in surgeries of the following
PCF pathologies:
— tumors of the base of the PCF: neurinomas of
cranial nerves (auditory, germinal, and facial nerves and
the nerves passing in the jugular foramen area),
meningiomas, chordomas, etc.
— epidermoid cysts (cholesteatomas) of the
posterior fossa cisterns;
— syndromes of cranial nerve hyperfunction:
trigeminal and glossopharyngeal neuralgia, hemifacial
spasm, positional vertigo (the neurovascular conflict of the
vestibulocochlear nerve);
— tumors of the brainstem and cerebellar
hemispheres;
— vascular disorders of the vertebrobasilar basin.
For the lying position, a patient is placed in either
supine or lateral position.
Positioning the patient on the operating table in the
supine position. A surgeon, a surgeon's assistant, and an
anesthetist are engaged in positioning the patient. The
anesthetized and intubated patient is lying in the supine
position, with his/her head secured with a head rest. While
the anesthetist slightly raises the patient off his/her
position, the surgeon's assistant places a roll under the
patient's ipsilateral shoulder, trunk, and the gluteal region,
thus ensuring a 30° angle. The surgeon rotates the patient's
head towards the trunk bending (Fig. 1a, b). The assistant
places a support into the ipsilateral shoulder to prevent the
patient from sliding as his/her position may be corrected
during the surgery by tilting the operating table (see Fig. 1a).
The anesthetist simultaneously bends the ipsilateral leg at
knee and hip joints to an angle of 30° and rotates it inward.

© Group of authors, 2016 e-mail: shimava@nsi.ru

90 PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016

This ensures the required position of the body axis by
compensating for spine rotation around its axis as a roll is
placed. A foam pad is placed between the legs to prevent
soft tissue atrophy. The arm is placed on the patient's chest
ipsilaterally to the approach side. The surgeon and
surgeon's assistant perform head fixation using the
Mayfield skull clamp: while one of them holds the patient's
head raised, the other one places the pins. Pin positioning
is performed as follows: a single pin is ipsilaterally placed
onto the frontal protuberance, while the paired ones are
contralaterally positioned into the superior temporal line
and the occipital bone above the asterion (see Fig. 1a, b).
The pins are tightly secured in the outer table of skull; one
should avoid placing the pins above thin regions of calvarial
bones (above the frontal sinuses, mastoid air cells, and
along the anterior margin of the temporal muscle). Pin
position must provide an unencumbered view of the
operative field and leave a possibility for bone
skeletonization to a required extent.
The surgeon then rotates the patient's head secured
with the Mayfield–Kees skull clamp 30 degrees towards
the side contralateral to the pathological process and
maximally bends it forward , leaving no less than the
thickness of two transverse fingers between the patient's
chin and chest. One needs to make sure that the sagittal
suture is parallel to the floor (see Fig. 1a, b). This position
of the head ensures the best view of the structures of the
cerebellopontine angle. When rotating or bending the
head, it is also important to maintain the longitudinal body
Fig. 1. Suboccipital retrosigmoid approach in the supine position with a roller placed under the ipsilateral shoulder.
a, b — positions of rigid fixation pins. The sagittal sinus is parallel to the operating room floor: 1 — the coronal suture; 2 — the sagittal suture; c — lateral view of the
positions of the patient and the rigid fixation system. Landmarks for skin incision (d): 1 — mastoid notch, 2 — incision running parallel to the auricular concha.
PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
axis (the line running through the external occipital
protuberance and the apices of spinous processes of cervical
vertebrae must be straight). Allowance should be made for
the risk of compression of jugular veins associated with
excessive head flexion, which is particularly topical in
hypersthenic overweight patients having a short thick
neck.
Description of the surgical approach. The SRSA is
performed in the cervico-occipital region below the
superior nuchal line. Blood is supplied to this region from
the occipital and posterior auricular arteries. Blood
outflows from the soft tissues of the occipital region via the
veins accompanying the aforementioned arteries and
draining into the external jugular vein. Soft tissues of the
occipital region are innervated by the greater occipital
nerve accompanying the occipital artery [1].
The mastoid notch and the line of transition of the
occipital squama into the horizontal part are the landmarks
for incision of the soft tissues. In SRSA, skin incision is
often made parallel to the auricular concha, 1.5–2.5 cm
posterior to the mastoid notch (see Fig. 1d). The upper
one-third of the skin incision is made above the transverse
sinus projection line. The border between the middle and
the lower one-thirds of the incision runs at the level of the
mastoid notch (see Fig. 1d).
Once skin and subcutaneous fat were dissected,
muscles are transected at a point where they are attached
to the superior nuchal line and the occipital plane. It is
reasonable to perform the musclectomy stage using
91
 GUIDELINES FOR THE PRACTITIONER
monopolar coagulation, which allows one to significantly
reduce capillary hemorrhage. The portion of the occipital
bone, from the mastoid process to the median line in a
medial direction (tentatively until the anticipated midpoint
of the cerebellar hemisphere is reached) and from the
superior nuchal line down to the foramen magnum, needs
to be skeletonized.
When dissecting the soft tissues, one should not forget
about the occipital artery whose injury causes profound
bleeding. It is reasonable to begin with identifying the
occipital artery in the soft tissues and to transect it only
after precoagulation. Skeletonization of the occipital
squama is typically accompanied by opening the emissaria
located lateral and superior to the mastoid notch and, in
the inferior regions, in the foramen magnum area. The
opened emissaria need to be sealed with wax.
Asterion, the point where the lambdoid, the
occipitomastoid, and the parietomastoid sutures meet, is a
landmark for making the burr hole. Transition between
the sigmoid sinus and the transverse sinus is located in the
projection of this point (Fig. 2a). The asterion most
typically lies 3—4 cm above the mastoid notch. The burr
hole is made 5 mm below the asterion. After dura mater is
separated from the bone around the burr hole, osteoplastic
trepanation is performed using a pneumatic trephine (see
Fig. 2b). In some cases, when there is significant coherence
between the dura mater and the bone (which is often
observed in patients older than 60 years), resection
trepanation using bone-cutting forceps followed by closing
the bone defect with a graft is performed.
Special care is needed when cutting the bone above or
near the transverse and sigmoid sinuses, since injury to
these structures causes profound venous bleeding. The
Fig. 2. Right-sided suboccipital retrosigmoid approach.
a — schematic view of the main landmarks in the occipital region: 1 — coronal suture, 2 —superior sagittal sinus, 3 — confluence of sinuses, 4 — transverse sinus,
5 — lambdoid suture, 6 — occipitomastoid suture, 7 — asterion, 8 — mastoid notch, 9 — sigmoid sinus, and 10 — parietomastoid suture; b — general right-side view
of the craniotomy: 1 — transition from the transverse to the sigmoid sinus, 2 — projection of the sigmoid sinus (with a hemostatic sponge placed on it), and 3 — the
inferior margin of the transverse sinus.
92
injured sinus should be sealed with a hemostatic sponge or
the TachoComb material by placing them on the surface
of the injured sinus wall. By no way should the hemostatic
agents be placed into the cavity of an opened sinus, since
this may result in sinus thrombosis and severe neurological
deficit or even death.
In order to prevent injury to venous sinuses, the bone
should be cut 5 mm away from the tentative inferior border
of the transverse sinus and 5 mm medial to the sigmoid
sinus. The craniotomy is usually followed by additional
lateral resection of the bone to expose the margin of the
sigmoid sinus. Mastoid air cells often become opened as a
result of additional resection of the lateral margin of the
trepanation window. The disruption of their continuity
may cause nasal liquorrhea during the postoperative
period, which, in its turn, is associated with the risk of
meningitis. Therefore, they need to be sealed with
autotissue at the final stage of surgery. Adipose tissue
harvested from the patient's hip or fragments of muscle
tissue from the surgical wound on the neck can be used for
this purpose. TachoComb material or fibrin sealant can be
additionally used.
Most often, a trepanation window up to 4 cm in
diameter is sufficient for managing cerebellopontine angle
tumors. The borders of the trepanation window correspond
to the following structures: the upper border, to the inferior
margin of the transverse sinus; the lower border, to the line
of transition from the vertical portion of the occipital bone
to its horizontal portion; the lateral border, to the medial
margin of the sigmoid sinus; and the medial border, to the
midline of the cerebellar hemisphere [1]. Craniotomy size
varies depending on the type of the pathological process;
PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
however, visualization of the site of transition of the
sigmoid sinus to the transverse sinus is a prerequisite.
Lateral positioning on the operating table. The key
indication for this positioning is the hypersthenic body
habitus of a patient, namely, the short neck and broad
shoulders.
After the patient had been intubated, a surgeon and
surgeon's assistant roll him/her laterally onto one side
contralateral to the surgery side; the anesthetist is
simultaneously controlling the head position. Patient's
arms are secured using specialized holders (Fig. 3b, c); the
ipsilateral leg is bent at knee and hip joints to an angle of
30° and rotated inward. The surgeon's assistant places a
support under the lumbar region. Soft pads are placed
between the patient's legs and underarms to prevent soft
tissue atrophy. Maximum head flexion is achieved similar
to the position described previously; the distance between
the chest and chin is supposed to be equal to at least two
thicknesses of fingers in the transverse direction. The head
is then secured by the surgeon using a Mayfield skull clamp
(see Fig. 3a).
If needed, patient's shoulders can be stabilized using
adhesive tape (Fig. 4b). One should not forget about the
risk of stretch injury to the brachial plexus.
One should also bear in mind that the sagittal suture
must be parallel to the floor (see Fig. 3a). This head
position ensures the optimal approach angle for
manipulations within the cerebellopontine angle during
surgical intervention.
Description of the surgical approach
The landmarks for incision and the principles of
performing craniotomy are similar to those used for supine
positioning (see Fig. 2).
The median suboccipital approach. The key
indications for using the median suboccipital approach are
as follows:
— PCF neoplasms of median and craniovertebral
localization, including tumors of the fourth ventricle and
the brainstem;
— decompression of the craniovertebral junction in
patients with Chiari malformation and acute circulatory
failure in the brainstem; and
— vascular disorders of the vertebrobasilar basin.
Different positions on the operating table are used to
perform the median suboccipital approach in lying patients
are used: the prone and the three-quarter prone positions.
First, let us discuss the prone position, patient's
position on the operating table that is used most frequently
when performing this surgical approach.
Patient's position on the operating table. The patient is
intubated and anesthetized while lying on a patient
transport cart. Next, the surgeon and the surgeon's assistant
rotate the patient into the prone position onto the operating
table (the anesthetist is simultaneously controlling the
head position).
The patient is usually placed by rolling onto a
specialized foam frame, with its position controlled by a
PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
nurse anesthetist (see Fig. 4a). The foam frame ensures
proper chest excursion during mechanical ventilation (see
Fig. 4a, 1). Additional corrugated foam rollers or underpads
are placed under the sites where the patient's body and
limbs may be subjected to positional compression (see
Fig. 4a, 2). An additional roller can be placed under
patient's chest to ensure physiologically adjusted neck
flexion. The head is then secured with a Mayfield skull
clamp, with the longitudinal body axis strictly maintained.
The skull clamp pins need to be positioned in such a
manner as to ensure unencumbered view of the operating
field and leave a possibility for skeletonizing the occipital
bone to a required extent.
There are two modifications of the median suboccipital
approach: the inferior and the superior median approaches
(see Fig. 4c, d). The key difference is that both transverse
sinuses and the confluence of sinuses are exposed when the
superior median approach is performed (see Fig. 4d). The
foramen magnum and the arch of the C1 vertebra are not
affected by craniotomy performed through this
modification of the approach. In the case of the inferior
median approach, the upper border of trepanation runs
along the inferior margin of both transverse sinuses and the
confluence of sinuses until the foramen magnum, and is
accompanied by laminotomy of the posterior semi-ring of
C1 vertebra if necessary (see Fig. 4c).
The inferior median suboccipital approach is used
most frequently.
Description of the surgical approach. Skin incision is
made along the median line. It provides a minimally
invasive access to the target PCF structures.
The upper border of the incision lies 1—2 cm above
the external occipital protuberance (the inion); the lower
border lies in the projected point of the spinous process of
C3 vertebra (Fig. 5, a).
First, an incision of skin and subcutaneous fat is made.
A wound retractor device is placed, with its handle facing
upward. Dissection must be conducted along the cervical
white line in the avascular zone. The occipital arteries and
greater occipital nerves remain intact.
Once the soft tissues were prepared, the occipital bone
squama, the posterior arch of C1 vertebra, and the spinous
process of C2 vertebra are skeletonized. Deep cervical and
occipital muscles are separated from the nuchal line using
monopolar coagulation or a bone scraper and moved
downward and sideways.
Venous bleeding from the hypertrophied emissaria
may take place as the occipital bone squama is skeletonized.
In this case, they need to be closed with bone wax. When
skeletonizing the posterior semi-ring of C1 vertebra, one
should keep in mind the close proximity of vertebral
arteries that run in the posterior portion of the occipital
membrane. Bleeding from the venous plexuses of vertebral
arteries is stopped using hemostatic sponge.
Two burr holes are made below the inion, on both
sides from the external occipital crest (see Fig. 4c). "Pear-
shaped" craniotomy is then performed with a craniotome
93
 GUIDELINES FOR THE PRACTITIONER
Fig. 3. Suboccipital retrosigmoid approach in the lateral position.
a — positioning of rigid fixation pins; b, c — patient's position on the operating table.
(see Fig. 4c). If needed, the trepanation window can be
made wider: sideways to the maximum extent allowed by
the operating field and to the required extent, and
downward until the foramen magnum is reached.
Sometimes craniotome cannot pass through thickening in
the occipital bone near the margin of the foramen
magnum. This bone portion can be ground with a burr or
continue trepanation downwards and sideways using
bone-cutting forceps.
This approach can be either combined with
laminotomy of the posterior semi-ring of C1 vertebra
(see Fig. 5b) or performed individually. Indications for
laminotomy of the arch of C1 vertebra are determined by
pathology location, the degree of descent of the cerebellar
tonsils and, therefore, by the need to decompress the
craniovertebral junction and CPF structures. If
decompression of the craniovertebral junction is not
required, the posterior semi-ring of C1 vertebra is returned
to its original place and tightly secured with silk sutures.
The borders of laminotomy of the C1 cervical vertebra lie
no further than 1.5 cm sideways from the median line; i.e.,
its full absolute size is no more than 3 mm (see Fig. 5b) due
to the close proximity of vertebral arteries and the risk of
damaging them upon bone manipulation.
When performing the median suboccipital surgical
approach to a patient in the three-quarter prone position,
he/she is rolled sideways into the lateral position; the
patient's body is inclined by approximately 45 degrees.
Supports preventing trunk shifting with respect to the
94
operating table are placed at the level of the chest and
lumbar area. Patient's arms are secured with special
supports; the ipsilateral leg is bent at knee and hip joints to
an angle of 30° and rotated inward. Soft pads are placed
between the legs and in the underarm area to prevent the
development of soft tissue atrophy. The head is bent to a
maximum possible extent and then secured using a
Mayfield skull clamp (see Fig. 4b). Taking into account
the manipulation angle required to access the anatomical
structures of the fourth ventricular area and the
craniovertebral junction, no additional rotation of the
patient's head is required (see Fig. 4b).
Discussion
When choosing patient's position on the operating
table and performing the suboccipital approaches, a
number of questions may arise pertaining to the risks for a
patient, which are related only to his/her position rather
than to the existing neurosurgical pathology. Having
evaluated the experience of performing suboccipital
approaches to the patient in the lying and semi-sitting
positions that has been gained over the many years, we
have arrived at conclusion that performing these
approaches to the patient in the lying position is the most
safe procedure, since it allows one to avoid such life-
threatening complication as air embolism. An analysis of
200 vascular decompression procedures performed in
patients in different positions demonstrates that the semi-
PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
Fig. 4. The lying position for performing the suboccipital median approach.
a — prone position (Concorde position); b — three-quarter prone position; c, d — the modified median suboccipital approach; c — the inferior median suboccipital
approach. The arrows show the craniotomy borders: 1 — the sagittal sinus, 2 — the confluence of sinuses, 3 — the sigmoid sinus, 4 — C1 vertebral arch, d — superior
median suboccipital approach. The arrows show the craniotomy borders. The remaining notation is identical to that in Fig. 4c.

sitting position increases the risk of air embolism
25-fold [9]. Nevertheless, it is reasonable to use the
suboccipital approaches in some patients in the semi-
sitting position using intraoperative transesophageal
Doppler to control possible development of air embolism.
This category includes obese patients (in whom the lying
position blocks chest excursion), patients with giant-size
tumors and cervical osteochondrosis that prevents
adequate head rotation and/or flexion.
The use of the "lying" position makes it necessary to
accurately follow the landmarks when making a skin
incision and osteoplastic trepanation, since a deviation
from the trepanation performing standards narrow the
operating field and make the main surgical stage infeasible.
In its turn, this fact discredits the idea of using the lying
position that is safe if performed properly. Hence, when
using the suboccipital retrosigmoid approach, proper
mapping of the operating field ensures patient's safety.
The methods for sealing sinuses if damaged during a
surgery are often of concern. If a sinus was injured in the
"semi-sitting position", one should prevent the contact
between the sinus defect and air by all means, since the
sinus defect will become a source of air embolism in this
case. In this situation, a surgeon's assistant or a nurse must
continuously irrigate the sinus defect with normal saline
and subsequently seal its wall using a hemostatic sponge or
TachoComb.
Furthermore, a frequent question often is "what type
of trepanation should be performed, the resection or the
osteoplastic one?" When using the suboccipital
retrosigmoid approach, one should always prefer the
osteoplastic craniotomy. However, if pronounced
cohesion between the dura mater and the bone (especially
in elderly patients) is detected when a burr hole is drilled,
resection trepanation can be performed to avoid the
emergence of defects in the dura mater and sinuses; the
bone defect can be subsequently closed with a graft.
Osteoplastic trepanation should be preferred when using
the median suboccipital approach, excluding the cases
when decompression of the PCF structures are needed,
e.g., in surgeries for Chiari malformation [10].

PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016 95

 GUIDELINES FOR THE PRACTITIONER

Fig. 5. The inferior median approach.

a — the landmarks for skin incision: 1 — the external occipital protuberance, 2 — the inferior incision line (the level of the spinous process of the C3 cervical vertebra);
b — the final view of the inferior median suboccipital approach: 1 — the occipital bone and the C1 vertebral arch were resected, 2 — additional lateral resection of the
occipital bone near the foramen magnum was performed using bone cutting forceps, and 3 — the anlantooccipital membrane is visualized.

Conclusion approaches. The proper use of the approaches ensures a

When used properly, the suboccipital retrosigmoid
and median suboccipital surgical approaches in the patient
in a lying position provide a good view of the operating
field, while leaving the risks of complications associated
with the patient's position on the operating table minimal.
A neurosurgeon must have a perfect command of these
broad view of the cerebellopontine angle and the
craniovertebral junction area, while the traction of the
cerebral tissue is minimal and usually causes no
complications associated with their application.
Authors declare no conflict of interest.

REFERENCES
1. Makhmudov UB, Shimanskiy VN, Tanyashin SV, Murusidze NA.
Suboccipital retrosigmoid approach. Voprosy neirokhirurgii
im. NN Burdenko. 2001;3:25-28. (In Russ.).
2. Ribas GC, Rhoton ALJr, Cruz OR, Peace D. Suboccipital burr holes and
craniectomies. Neurosurgical Focus. 2005;19(2):1-12.
doi:10.3171/foc.2005.19.2.2
3. Rhoton ALJr. Cranial Anatomy and Surgical Approaches. Baltimore, MD:
Lippincott Williams & Wilkins. 2003;525-587.
4. Sekhar LN, Fessler RG. Atlas of neurosurgical techniques: brain. New York—
Sruttgart: Thieme Medical Publishing. 2006;860-870.
5. Shimanskiy VN, Karnaukhov VV, Odamanov DA, Kolycheva MV. Surgical
treatment of trigeminal neuralgia in patients with multiple sclerosis. Zhurnal
nevrologii i psikhiatrii im. SS Korsakova. 2015;2:66-70. (In Russ.).
6. Poshataev VK, Shimanskiy VN, Tanyashin SV, Karnaukhov VV. The use of
endoscopic assistance in surgery of cerebellopontine angle tumors. Voprosy
neirokhirurgii im. NN Burdenko. 2014;4:42-49. (In Russ.).
7. Shimanskiy VN, Karnaukhov VV, Sergienko TA, Poshataev VK,
Semenov MS. Endoscopic assistance in vascular decompression of cranial
nerves. Voprosy neirokhirurii im. NN Burdenko. 2012;2:3-10. (In Russ.).
8. Shimanskiy VN, Karnaukhov VV, Sergienko TA, Poshataev VK,
Semenov MS. Endoscopic assistance in single-stage resection of posterior
cranial fossa meningioma and vascular decompression of trigeminal nerve
root. Voprosy neirokhirurii im. NN Burdenko. 2011;4:70-74. (In Russ.).
9. Israelyan LA, Shimanskiy VN, Otamanov DA, Poshataev VK, Lubnin AYu.
Patient's position on the operating table in neurosurgery: the sitting or lying
position. Anesteziologiya i reanimatologiya. 2013;4:18-26. (In Russ.).
10. Reutov AA. Principles of diagnosis and tactics of surgical management of
patients with type I Chiari malformation [dissertation]. Moscow; 2012. (In
Russ.). Accessed July 20, 2016.
http://medical-diss.com/medicina/printsipy-diagnostiki-i-taktika-
hirurgicheskogo-lecheniya-bolnyh-s-malformatsiey-kiari-i-
tipa#ixzz4EvyZpoGT

96 PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016

 Commentary
The article by V.N. Shimanskiy et al. is highly relevant,
since the approaches being analyzed (the suboccipital
retrosigmoid and the median suboccipital approaches) are most
commonly used in surgical treatment of subtentorial
pathological neoplasms. While being rather simple, these
approaches ensure direct and the most convenient access to all
the posterior cranial fossa structures. However, only the
meticulous adherence to all the procedure nuances, starting
from proper patient positioning, allows one to achieve the
objectives of surgical management. It is the analysis of all
miniscule details of the aforementioned approaches that makes
this paper a thorough manual for using them in a patient in the
lying position. The criteria for selecting the patients for whom
these approaches are recommended were properly justified and
PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
clearly stated. The authors placed special focus on prevention
of complications, in particular, postoperative liquorrhea.
Numerous schemes and figures that meticulously demonstrate
proper patient's position on the operating table as well as the
features of skin incision and skull trepanation are provided in
addition to description of the sequence of actions of an
operating surgeon.
This work is important, especially for young neurosurgeons,
since it teaches them how to perform a proper surgical approach,
which, along with good microsurgical skills, is a prerequisite of
successful surgery.
V.I. Smolanka (Uzhgorod, Russia)
97
 REVIEWS

doi: 10.17116/engneiro201680698-104

Navigation Systems in Neurosurgery

V.A. SHURKHAY1,2, S.A. GORYAYNOV1, E.V. ALEKSANDROVA1, A. SPALLONE2, A.A. POTAPOV1

1
Burdenko Neurosurgical Institute, Moscow, Russia; 2Moscow Institute of Physics and Technology, Moscow, Russia; 3NCL-Neuromed,
Department of Biomedical Sciences University di Roma Tor Vergata, Via Orazio Raimondo, Rome, Italy

When preparing the review, we analyzed publications available in the Medline database; a total of 1,083 publications related to
the review's subject were analyzed. After more careful analysis, we selected 117 publications devoted to the development of
neuronavigation in craniocerebral surgery, its historical background, current trends, and future prospects of the technique.
Keywords: neurosurgery, neuronavigation, stereotaxis, computer-assisted neurosurgery.

At the initial stage, the development of neurosurgery was
limited by technical level of that time. The lack of accurate and
objective anatomical assessment of the relationship between
paraplasm and surrounding structures in each individual
patient [1—3] was another major limitation. Fundamental
studies on the functional brain mapping, which were started as
early as in the XIX century by Broca, Wernicke, Exner, and
Dejerine, provided data on the architectonics of the key
functional systems and their topical representation in the
cerebral cortex [4, 5]. W. Penfield significantly contributed to
this work [6]. Nevertheless, it was difficult to assess the
individual characteristic features of the anatomy and
neurophysiology of each individual patient. There was an
urgent need to integrate these data and present them to
neurosurgeons. This problem could not be solved until 1970s
due to the absence of direct brain imaging methods, possibility
of mathematical processing and alignment of various data.
The instruments for frame-based stereotactic navigation
laid the basis for the development of neuronavigation systems.
In 1873, H. Dittmar et al. [7] used the instrument, which
provided approach to the neoplasms in the medulla oblongata
of laboratory animals for the first time in a neurophysiological
laboratory. The pioneering work of D.N. Zernov 1889 [8]
marked the beginning of stereotactic surgery on the human
brain. Further development of the method was associated with
the studies of Clarke and Horsley, who developed the device to
study the brain of monkeys of in 1906—1908. Ranson and
Ingram obtained basic information about the functions of the
reticular formation, hypothalamus, and midbrain, using
frame-based stereotaxis and modified Horsley-Clarke
apparatus [10]. Kirshner has overcome the difficulties of the
use of stereotaxis in humans associated with variability of the
relationship between the skull bones and brain structures,
which enabled thermal ablation of the trigeminal ganglion in a
patient with trigeminal neuralgia for the first time, using
originally designed stereotactic device [11]. In the second half
of the 1940s, E. Spiegel and H. Wycis [12] used the stereotaxic
atlas, which they previously developed, in combination with
the data of contrast ventriculography and position of the pineal
gland to localize intracranial anatomical structures and
describe the use of frame-based stereotaxis during neurosurgery.
L. Leksell significantly contributed to the development of
these techniques [13]. In 1949, he developed his own
construction of stereotaxic apparatus. Later on, J. Talairach,
E. Monnier, T. Riechertand, and F. Mundinger [14—16]
developed original stereotaxic devices for functional
interventions. The articles of Russian authors E.I. Kandel and
V.V. Peresedov [17—19] reported the results of the use of the
original stereotaxic apparatus in the cryosurgery of the
subcortical structures, as well as clipping of cerebral arterial
aneurysms.
The development of X-ray diagnostic technique
significantly expanded the possibilities of neurosurgical
pathology diagnosis. In 1908, F. Krause et al. [20] devoted a
separate chapter of their multi-volume neurosurgery guide to
radiodiagnosis of neurosurgical diseases and identified
characteristic features of some of them. The development of
pneumoventriculography was the next milestone [21]. The
capabilities of the contrast cerebral angiography proposed by
E. Moniz [22, 23] greatly improved neurosurgeon’s knowledge
about the individual anatomy and pathological anatomy of
patient’s cerebral structures.
The use of metabolic navigation was based on the discovery
of the phototoxicity phenomenon in the early XX century and
was associated with the studies of Raab and von Tappeiner
[24]. In 1924, Policard showed that some malignant human
tumors fluoresce in the orange-red spectral range when
irradiated with ultraviolet light [25]. This effect is due to the
formation of endogenous porphyrins in tumors, which have
been confirmed by fluorescence of experimental tumors in the
red spectral region in animals pre-administered with
hematoporphyrin [26]. The first study on the use of fluorescein
dye during neurosurgical operations in patients with brain
tumors was published by G. Moore in 1947 [27]. Fluorescein is
not widely used in neurosurgical practice due to its toxicity and
low specificity of the method. The paper of B.A. Samotokin et
al. [28] reported the use of organic dyes for intraoperative
imaging of brain tumors. F.A. Serbinenko et al. [29] used the
technique of superselective intravascular injection of dyes in
tumor-supplying vessels. However, this method cannot be
used in routine practice due to insufficient specificity and
reproducibility of the results and toxicity of preparations.
Since the mid-1990s, idocyanin green dye, which is
fluorescent in the infrared range, is used for intraoperative
visualization of blood vessels (both in normal brain tissue and
in tumors). The possibilities of modern surgical microscopes
(e.g., Zeiss OPMIpentero) enable color mapping, determining
the direction of blood flow [30, 31].
Pioneering studies of the metabolism of porphyrins and
visualization of leukemic cells using 5-aminolevulinic acid
were reported by Z. Malik et al. [32] in 1979. It was shown that
5- aminolevulinic acid is metabolized by enzyme systems that

© Group of authors, 2016 e-mail: vash.nsi@gmail.com

98 PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016

are active only in tumor cells to produce protoporphyrin IX,
which is fluorescent under external light source having certain
wavelength [33]. In the late 1990s, the first reports on the
possibility of using 5-aminolevulinic acid in neurosurgery were
published [34]. Later studies showed that the use of metabolic
navigation improves the extent of tumor resection and
increases disease-free and overall survival of patients with
malignant gliomas [35]. The studies of A.A. Potapov et al.,
S.A. Goryaynov et al. [36, 37] have shown that metabolic
navigation using 5-aminolevulinic acid can be applied not only
in gliomas, but also in meningiomas. Currently, the ways to
improve sensitivity of fluorescence diagnosis in the surgery of
low-grade gliomas and metastases are being investigated [36,
38]. In the absence of visible fluorescence, the authors
suggested laser spectroscopy method to estimate the
concentration of amino-levulinic acid in the tumor tissue and
thus differentiate it from the healthy brain [24, 37, 38].
Along with fluorescence, high resolution mass
spectroscopy is another promising method for ultrafast real-
time intraoperative identification of tissues. The method
provides molecular “fingerprints” based on the analysis of
lipids and proteins produced in the ionization mass spectra,
which enables characterizing various brain tumor [39].
Radioisotope-based diagnostic techniques are being used
since the mid 1950s — early 1960s [40]. Various isotopes were
used, such as iodine(111I,123I,125I), bismuth, mercury, gold,
technetium, copper, and labeled serum albumin [41]. In 1964,
the article of E.V. Kotlyarov [42] reported the results of the use
of radioactive phosphorus for intraoperative localization of
brain tumors. The study of M. Fischer et al. [43] published in
1977 showed that radioangiography is more sensitive than
scintigraphy, when determining the histological structure of
the tumor. At the same time, the latter enables more reliable
assessment of tumor vascularization. The study of A.N.
Konovalov [44] published in 1980 notes very high sensitivity of
perioperative beta-radiometry, which enabled tumor
localization in 98% of cases. Later studies showed that positron
emission tomography with 11C-methionine involved in the
metabolic pathways in tumor cells is more specific for glial
tumors. The data on the accumulation of methionine enable
determining the degree of anaplasia, selecting the target for
stereotactic biopsy, differentiating between radiation necrosis
and continued tumor growth, developing a predictive model
for the patient [45, 46]. F.M. Lyass and E.Ya. Shcherbakov
[47—49] investigated the role of radionuclide studies in the
diagnosis of CSF system diseases, intracranial inflammation,
and the consequences of traumatic brain injury. Currently,
single-photon and positron emission tomography are mainly
used for differential and topical diagnosis of various
pathological processes; these methods have significant
limitations [46] in intraoperative navigation.
X-ray computed tomography (CT) is based on the studies
of Oldendorf, Hounsfield, and Cormack. The first ever in vivo
image of patient's brain was obtained in 1972 [50, 51]. In 1976,
L. Jacobs et al. [52] compared the results of computed
tomography and 79 autopsies, the accuracy of intracranial
pathology diagnosis was 86.2%. Today, CT with intravenous
contrast and perfusion techniques enable assessing the
condition of the blood flow in the mass lesion and perifocal
zone in different parts of the brain, including its deep structures
and brainstem [53—57]. The study of J. Maroon et al. [58]
focusing on the use of CT to navigate the puncture emptying of
tumor cysts and brain abscesses was an important milestone in
neurosurgery. In 1979, R. Brown [59] presented the results of
PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
successful use of CT and three-dimensional computer graphics
for stereotactic localization of targets in a phantom with
installed special stereotactic frame. Later on, the results of
clinical application of CT to calculate stereotactic surgery
(functional neurosurgery and tumor biopsy) were reported in
the articles of J. Boethius, B. Czerniak, and Z. Krzystolik
[60—62].
Intraoperative CT was developed in various fields of
neurosurgery to specify the completeness of tumor resection,
eliminate intraoperative complications, intraoperatively
correct navigation information, and provide more accurate
implantation of stabilization system elements in spinal
neurosurgery [63—66].
The studies of F. Cope and R. Damadian [67], who used
magnetic resonance to determine the concentration of
potassium ions in a bacterial cell in 1970, provided the basis for
magnetic resonance imaging (MRI). Obtaining information
about tumors in vivo was made possible through the use of a
field-focusing nuclear magnetic resonance, FONAR [68]. The
first magnetic resonance image of the human chest was
obtained in 1977 [69]. The first commercially available
magnetic resonance imager (MRI) was produced in 1980 [70].
When comparing CT and MRI for stereotactic interventions,
W. Birg et al. [71] noted high accuracy of the latter, better
visualization of brain structures located close to the bone
tissue, as well as the absence of necessity for contrast
ventriculography during functional operations.
Intraoperative MRI also enables intraoperative correction
of navigation data and improves the completeness of surgery.
However, it requires special equipment in the operating room,
non-magnetic devices and instruments [72]. Low-field
portable MR scanners require longer scan time due to low
resolution, which lengthens the operation time and does not
enable perfusion or spectroscopic studies during the operation.
High-field MRI scanner, providing better image quality and
wider visualization capabilities due to larger number of
sequences, are difficult to integrate into existing operating
rooms, requiring either major modernization of the operating
unit or its reconstruction with allowance for MRI placement.
In addition, the use of high-field scanners is associated with
image artifacts and requires long-term personnel training.
Furthermore, intraoperative use of CT and MRI is very
expensive and it is not available in all hospitals.
Intraoperative use of ultrasound (US) is the most available
and simple method for navigation and localization of
neoplasms and correction for brain displacement [73].
Application of three-dimensional US-navigation, such as
Sonowand Invite system, improved surgeon's orientation,
provided adequate assessment of the completeness of
paraplasm resection and identification of intraoperative
complications, including those in ventriculoendoscopic
surgery [74—76]. Along with Sonowand system, a combination
of a separate expert-level ultrasonic scanner, control computer,
and neuronavigation system were used for intraoperative
three-dimensional US-scanning and navigation [77, 78].
The effect of brain displacement reduces the accuracy of
intraoperative navigation [79, 80]. Reliable prediction of the
magnitude and direction of brain displacement is not possible
[81]. Correction for brain displacement can be achieved using
intraoperative computed tomography or MR imaging, as well
as ultrasound study.
The development of neuronavigation systems, which
made all of the above methods as much applicable as possible
from the neurosurgeon’s viewpoint, was the logical
99
 REVIEWS
continuation of the studies of intraoperative visualization of
paraplasms and other brain lesions. Currently, the most
accurate and sparing approach to the pathological lesion is
possible in each particular patient.
Since the inception of neuronavigation systems, they
developed along two parallel lines determined by the used
monitoring techniques, optical (active or passive) or
electromagnetic.
In the first report of A. Kato et al. [82] on the frameless
electromagnetic navigation, the system which enables
monitoring of inclination and spatial arrangement of the
surgical instrument equipped with electromagnetic sensor to
within 4 mm was described. ISG Magic Wand system produced
in 1992 was the first commercially available neuronavigation
system. It was a manipulator consisting of six segments, where
a special pointer, rigid endoscope, or biopsy needle can be
installed. This system was used for navigation in brain tumors,
epilepsy surgery, ventriculoscopic operations, stereotactic
biopsies, pathology of the skull base, posterior fossa, clivus,
and superior cervical vertebrae [83—85]. This system could not
be used for functional neurosurgery due to inability of rigid
fixation of navigation manipulator and relatively high
error (>2.2 mm) [86].
The operation principle of electromagnetic navigation
systems is based on the fact that a special generator (running on
DC or AC) creates an electromagnetic field around the
patient's head, which is the coordinate system where the
reference and surgical instrument equipped with a built-in
electromagnetic sensor or special adapter are positioned.
Spatial movement of the sensor changes the characteristics of
the field at this point, which allows the navigation system to
determine the coordinates of the instrument. The dimensions
and placement of the sensor on the instrument may vary,
affecting the functionality of the system: for example,
Medtronic Stealth Station 7 navigation system (Medtronic,
USA) incorporates a separate external electromagnetic
navigation module and DC electromagnetic field generator;
sensors in disposable instruments are located in the handle,
which prohibits changing the length of the instrument during
the operation or its bending. At the same time, Fiagon
navigation system (Fiagon GmbH, Germany) include
electromagnetic field generator operating on alternating
current, and instruments contain two sensors: one of them is
located on the working end of the instrument and the other is
located on the handle, which allows the surgeon to model
(bend) the instrument depending on the operating situation,
while preserving navigation accuracy. Application of direct
current to generate electromagnetic field is an earlier
technology. It requires the use of larger sensors and the
resulting field is more vulnerable to various factors that can
change its shape, such as the presence of large quantities of
metal or a source of electromagnetic interference near the
patient's head [87]. Using AC overcomes these limitations
[88]. Electromagnetic field generator can be fixed to the
operating table using a special bracket (Stealth Station 7,
Fiagon), as well as integrated into the universal head support
for an operating table (Fiagon). A separate module for
electromagnetic navigation that requires connection to the
main system increases the overall size and floor space occupied
by the system. The advantages of the last generation
electromagnetic navigation system include their portability
and compactness, the possibility of integration into existing
operating room system, very small sensor, which enables its
integration into an instrument without increasing its size and,
100 PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
more importantly, changing tool geometry during operation
without loss of navigation accuracy. According to C. Hayhurst
et al. [89], the use of electromagnetic navigation in most cases
enables avoiding rigid fixation of patient's head, for example,
during neuroendoscopic interventions, bypass surgery, awake
craniotomy. Compatibility with intraoperative
neurophysiological monitoring is an important factor.
The use of the most portable and mobile electromagnetic
navigation systems, which are not only a module in the basic
optical navigation system, but rather can be effectively
integrated into the workspace of the operating room, do not
require any special infrastructure owing to full compatibility
with existing equipment and instruments, and are easy to
master for the staff, is the most promising direction.
Most neuronavigation systems developed in the 1990—
2000s were based on optical monitoring technique. Historically,
its earlier version involves the use of diodes emitting light in
the IR range, which is detected by the receiving camera of the
system. The LEDs are located on the reference, which is
placed as close to the patient's head as possible. They form the
basis of the coordinate system and can also be placed on the
instruments using special adapter or directly integrated into
the instruments. Passive techniques involve the installation of
reflective spheres, which are located in the field of view of the
camera equipped with an infrared light source, on the
reference, instruments, and adapters. The article of K. Roessler
et al. [90] describes the results of clinical application of this
system in spinal and cranial neurosurgery. System accuracy
averaged 3.4 mm in 36 craniotomies and 11.3 mm in 4 cases of
spinal operations. The large error during spinal operations was
associated with difficulties in the registration of images and the
use of cutaneous registration markers. The development of
computer graphics and new data processing capabilities have
led to the use of “augmented reality” concept in neurosurgery,
which enabled direct real-time alignment of paraplasm
modeling results, functional areas, and anatomical landmarks
(based on CT or MRI data) with the surgical field [91].
New features of intraoperative neuronavigation were
associated with combining different modalities of
neuroimaging: CT, conventional MRI, diffusion-tensor and
functional MRI, as well as magnetoencephalography and
electrophysiological mapping of speech, sensory, and motor
areas of the cerebral cortex [92]. This improved the results of
surgical procedures for pathological processes at the functional
areas, hydrocephalus, ventriculoendoscopic interventions,
and epilepsy [93, 94]. Many authors noted a positive effect of
intraoperative navigation on completeness of paraplasm
resection, duration of hospital stay, overall survival, and
functional outcome [95—97].
The use of data provided by diffusion-tensor MRI,
magnetoencephalography, functional MRI in a navigation
system with simultaneous recording of cortical somatosensory
evoked potentials enabled successful reconstruction of
conductive paths of the brain at different levels and assessing
the impact of the pathological process on these pathways [98,
99]. Computer modeling facilitated understanding of the
anatomical relationships between the paraplasms and intact
structures of the brain [100]. The use of neuronavigation
significantly improved the resolution of transcranial magnetic
stimulation [101].
Comparative analysis of various neuronavigation system
(ISG Magic Wand, Cygnys PFS, SMN) by E. Benradette et al.
[102] in the laboratory showed that, regardless of the used
technique (mechanical manipulator, electromagnetic or
optical monitoring, respectively), the average precision of the
systems did not differ significantly and ranged 1.67 to 2.6 mm.
According to the authors, selection of navigation system was
mainly determined by portability, ease of use, and compatibility
with the operating microscope. The study of M. Cartellieri et
al. [103] comparing six different navigation systems also
showed no fundamental difference between the systems, since
their precision was comparable (error ranged 0 to 6.7 mm). For
a long time, precision of neuronavigation systems compared to
conventional frame-based stereotactic devices was the subject
for discussion. R. Steinmeier et al. [104] analysed the factors
(technical precision of the system, registration process, voxel
size and/or the presence of images distortions, intraoperative
situation) that have a direct impact on navigation precision. It
has been shown that imaging modality has minimal effect on
the accuracy of navigation. The number of registration markers
and the nature of their placement are the most important
factors. The authors concluded that the accuracy of
neuronavigation systems (as exemplified by a robotic
microscope MKM Carl Zeiss and optical system Stealth
Station Sofamor-Danek) is comparable to that of conventional
stereotactic frame-based devices. Particular attention was paid
to the fact that registration error calculated by each navigation
system does not reflect the real error. U. Spetzger et al. [105]
analyzed 10 years of experience in the application of
neuronavigation and came to conclusion that system accuracy
is mainly affected by the human factor. At the same time, S.
Poggi et al. [106] concluded that the parameters of CT or MRI
images also have an impact on the accuracy of neuronavigation.
The accuracy of target localization based of CT data was higher
than when using MRI data; the presence of image distortions
was an important parameter that reduces the accuracy of MRI
navigation. At the same time, Y. Enchev et al. [107] found no
statistically significant differences in accuracy of
neuronavigation with CT and MRI. There was also no
significant differences in the navigation accuracy when using
registration based on anatomical landmarks or fiducial
markers. For this reason, W. Pfisterer et al. [108] recommended
to use registration based on anatomical markers as more
economic and less costly.
Comparative analysis of systems with active (Stryker) and
passive (BrainLab Vector Vision) tracking technology
conducted by D. Paraskevopoulos et al. [109] at the
anthropomorphic model of the head showed that the accuracy
was similar for both systems (<1.5 mm), and accuracy data
calculated by the systems do not always fit the actual values
and always require rechecking by surgeon. In all options,
optical technique is characterised by following limitations: a)
the need for placing the camera at a distance of at least 1 meter
from the spheres or diodes; b) placing the camera on a separate
bracket or stand, increasing the size of the system and reducing
its portability and mobility; c) dependence of navigation
accuracy on the state of reflecting spheres or diodes; d) “visions
line” problem of the camera, leading to cessation of navigation
when closing diodes or spheres with some object; e) bulky
adapters for reflective spheres or diodes to be mounted on
surgical instruments; e) inability to provide navigation of
instrument with variable length, curvature, or made of soft
materials (silicone catheters); f) the need for rigid fixation of
patient's head, which limits the use of navigation in children
[110]. It was also shown that infrared radiation from the optical
navigation system tracker camera can substantially affect the
performance of pulse oximeters, causing errors in the quality of
signal and assessment of saturation level [111]. In 2001,
PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
M. Zaaroor et al. [110] published the paper, where the
experience with electromagnetic navigation system Magellan
(Biosense Webster) was analyzed. The electromagnetic sensor
was located at the working end of the instrument, which
enabled using the system for installation of flexible catheters,
navigation of endoscopes and other instruments.
The advantages of the use include high operation speed,
high precision, small size, the possibility to navigate flexible
instruments, greater freedom of movement of the surgeon,
which does not depend on the viewing field of the recording
camera, no need for rigid fixation of the head, which enables
operating children from the second week of life [110, 112,
113]. At the same time, T. Rodt et al. [114] noted that the
interference of the magnetic field might affect the performance
of the navigation system.
Comparative analysis of the accuracy of optical and
electromagnetic navigation systems conducted by J. Rosenow
et al. [115] revealed no significant differences (the target point
location error ranged 0.71 to 3.51 mm). A. Sieskiewicz et al.
[116] also compared optical and electromagnetic navigation
systems (Medtronic Stealth Station and Digipointeur,
respectively) and concluded that electromagnetic navigation is
faster and easier to configure, provides greater freedom of
surgeon’s hands, and its accuracy is similar to that of the
optical system; the small number of instrument supported for
navigation was the imitation of that specific electromagnetic
system.
Recently, intraoperative robot assistance became one of
the main trends in surgery, improving safety and accuracy of
surgery due to high-precision intraoperative navigation. In
neurosurgery, such systems have been tested in preserving
craniotomy, precise approach to deep brain structures for the
purpose of biopsy of tumors, inflammatory and other lesions,
implantation of shunt systems, electrodes and others. [117,
118]. Robotic systems are essentially a further option of the
development of navigation systems.
Conclusion
The analysis of the literature over the past 100 years
revealed preconditions for the development of neuronavigation
and traced the evolution of this trend from both technical and
clinical point of view. The advantages of using navigation
systems in modern neurosurgery are obvious. Neuronavigation
is one of the most popular high-tech methods, which enables
combining various studies to evaluate the anatomical and
functional situation in the preoperative and intraoperative
periods. All this enables conducting highly accurate and safe
surgical procedures much faster than conventional methods.
Application of neuronavigation systems is highly valuable from
both clinical and scientific viewpoint. Integrative nature of
neuronavigation enables combining different modalities of
data, including anatomical, neuroimaging, molecular, and
neurophysiological, which improves the efficiency,
effectiveness, and conclusiveness of clinical studies carried out
using this technique. Furthermore, it is undoubtedly highly
promising as an educational method. Currently,
neuronavigation should not be a luxury for neurosurgical
clinics; its application should be as widespread and routine as
possible. We believe that, although neuronavigation does not
replace the expertise and clinical thinking of neurosurgeon, it
is a necessary complement, which enables neurosurgeons to
maximize the use of their skills.
101
 REVIEWS

There is no conflict of interest. tumor tissues using multidimensional molecular profiles

database as the main element of data processing system of the
The article was supported by the grant of the Russian intelligent neurosurgical scalpel”.
Scientific Foundation 16-1510431 “The development of
methods and approaches for automated identification of brain

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doi: 10.17116/engneiro2016806105-107
Prevention and Treatment of Postoperative Epidural Scar Adhesions
D.M. ZAV’YALOV, A.V. PERETECHIKOV
Navy Clinical Hospital 1469, Severomorsk, Russia
Postoperative epidural scar adhesions remain one of the most common late complications of microdiscectomy, which worsens the
overall outcome in treatment of herniated lumbosacral discs. Despite a large number of conservative and surgical treatment
options for epidural scar adhesions, the treatment outcome not always satisfies patients and doctors. The review was aimed at
systematizing the available data on this complication and facilitating the choice of appropriate treatment strategy.
Keywords: epidural scar adhesion, epidural fibrosis, microdiscectomy, disc herniation, degenerative disc disease.
Despite the development of new techniques and
achievements in the surgical treatment of herniated discs, the
number of poor postoperative outcomes in the form of persistent
radicular pain syndrome still remains high and accounts for
5—20% according to different authors [1—4].
The development of adhesive process known as epidural
scar adhesions or epidural fibrosis is the most common cause of
persistent radicular pain syndrome. The incidence of epidural
scar adhesions among the other reasons of so-called “failed
back surgery syndrome” is up to 8—70% [3, 5—9].
The causes of excessive formation of connective tissue in
the epidural space after surgery are still not fully understood. It
is still not clear, why the pronounced epidural fibrosis develops
in the postoperative period in some cases, while it is less
pronounced or absent in other cases under identical conditions.
The relationship between the severity of epidural fibrosis
and discectomy technique still remains a debatable issue.
Several authors suggest that the incidence of this postoperative
complication is lower in the case of minimally invasive
interventions, application of gel materials and insulating
membranes, various surgical techniques preserving ligamenta
flava, and intraoperative irrigation of nerve structures with
steroidal and non-steroidal anti-inflammatory drugs. In the last
few years, there were publications describing the prevention of
scar-adhesions in the following way: the affected root and dural
sac at the area of surgical trauma are enveloped with fat injected
with methylprednisolone solution. The experimental studies
showed that this method reduces the activity of prostaglandins
E1 and E2 and leukotriene B, which are the triggering factor in
the development of peridural fibrosis. There are significantly
different opinions on the effectiveness of this method. Some
authors [3, 5, 10—15] believe that it is useful; on the contrary,
others believe that it increases scarring.
Many authors [16—21] believe that immuno-infiltrative
aseptic inflammation form the basis for discogenic epidural scar
adhesions, others note the important role of preoperative values
of fibrinolytic activity of the blood in the development of
epidural fibrosis, since decrease in fibrinolysis and anticoagulant
mechanisms and increase in blood coagulation in the
preoperative period increase the risk of epidural scar adhesions
[6, 22, 23].
Pain syndrome caused by the development of epidural
fibrosis is not characteristic of the early postoperative period,
© D.M. Zav'yalov, A.V. Peretechikov
PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
and patient’s quality of life worsens due to persistent pain
caused by fibrotic changes in the epidural space only 2—18
months after discectomy [6, 24, 25].
Clinical and neurological examination, including medical
history, local status, and neuroimaging techniques is the main
diagnostic method to verify the postoperative epidural scar
adhesions. Magnetic resonance imaging (MRI), whose
effectiveness is improved when using contrast enhancement
(Magnevist, Gd-DTPA), is the most popular and informative
imaging technique [26—32]. Electrophysiological methods of
investigation (somatosensory evoked potentials,
electroneuromyography) are no less informative [33].
Despite the fairly large number of treatment methods for
epidural fibrosis after microdiscectomy, most authors [34—37]
note that all of them lack clinical effectiveness. General
treatment regimen should be based of general principles of
vertebral pathology treatment, including pathogenetically
oriented complex and stage-by-stage sparing therapeutic
modalities with allowance for the individual characteristics of
patients [28].
Medicinal treatment with nonsteroidal anti-inflammatory
drugs was suggested as a conservative treatment, limiting the
development of fibrous tissue in the postoperative period [38—
40]. According to some researchers [41], the use of
corticosteroids for the purpose of anti-inflammatory therapy in
the treatment of epidural fibrosis is well founded. In the case of
persisting long-term intractable pain syndrome caused by
epidural fibrosis, epidural block is effective [42, 43].
Physiotherapy (amplipuls, magnetotherapy, electrophoresis
with caripazim) is widely used as the non-drug treatments for
pain [44]. Outcomes of reoperations carried out due to
ineffective conservative therapy do not always satisfy patients
and surgeons [45, 46].
Epidural scar adhesions are still quite common in today’s
neurosurgical practice. It is highly significant medical and
social problem: recurrence of radicular pain in the postoperative
period makes patients to feel desperate, destroying their social
adaptation. The need for timely treatment and prevention of
epidural scar adhesions is undoubted and dissatisfaction with
clinical outcomes makes it a pressing problem.
There is no conflict of interests
e-mail: dezav@yandex.ru
105
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Commentary
Literature review “Prevention and treatment of
postoperative epidural scar adhesions” focuses on the topical
problem: scarring processes, developing after neurosurgical
interventions for spinal pathology, in particular after
microsurgical discectomy. It is well known that these processes
to some extent develop in all the operated patients and can
significantly reduce patient’s quality of life and even destroy the
results of formally successful surgery. The authors present data
on the importance of epidural scar adhesions in the development
of neurological symptoms, summarize the data obtained from
Russian and international literature on the diagnosis and
possible methods to prevent these processes.
Given the complexity and multidimensionality of these
problems, it would be interesting to determine risk factors for
PROBLEMS OF NEUROSURGERY NAMED AFTER N.N. BURDENKO 6, 2016
44. Sholomov I, Beidik O, Grishina T, Lihacheva E, Sholomova E, Lukina E,
Konopleva O. Conservative management of patients with the disease of the
operated disc. Polenovskie chteniya. SPb. 2005;156 (In Russ.).
45. Mirazimov D, Saburenko Yu, Golubyants A, Ishmuhamedov S. The results
of reoperation when hernias lumbar intervertebral discs. Sb. mater. III S"ezda
neirokhirurgov Rossii. SPb. 2002;267. (In Russ.).
46. Anderson SR. A rationale for the treatment algorithm of failed back surgery
syndrome. Curr Rev Pain. 2000;4:5:395-406.
doi: 10.1007/s11916-000-0024-4
adhesive processes in the case of decompressive and stabilysing
interventions, including their relationships with the type and
extent of stabilizing structure. The authors rightly pay attention
to MRI and contrast-enhanced MRI in the diagnosis; it would
be useful to mention the role of other techniques, such as
percutaneous minimally invasive diagnostics, in particular
flexible endoscopy (epiduroscopy and thecaloscopy). Among
possible prevention methods, the use of type 3 collagen, and,
more importantly, limited aggressiveness of discectomy, in
particular by applying portal endoscopic techniques, are worth
noticing.
A.O. Gushcha (Moscow, Russia)
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