See the corresponding editorial in this issue, pp 230–231.

J Neurosurg 115:232–239, 2011

Awake surgery for WHO Grade II gliomas within

“noneloquent” areas in the left dominant hemisphere:
toward a “supratotal” resection
Clinical article
Yordanka N. Yordanova, M.D.,1 Sylvie Moritz-Gasser, S.T.,1,2
and Hugues Duffau, M.D., Ph.D.1,2

Department of Neurosurgery, Hôpital Gui de Chauliac, CHU Montpellier; 2Team “Plasticity of Central
1

Nervous System, Stem Cells and Glial Tumors,” INSERM U1051, Institut of Neurosciences of Montpellier,
Hôpital Saint Eloi, Montpellier, France

Object. It has been demonstrated that an extensive resection (total or subtotal) may significantly increase the
overall survival in patients with WHO Grade II gliomas (low-grade gliomas [LGGs]). Yet, recent data have shown
that conventional MR imaging underestimates the spatial extent of LGG, since tumor cells were found up to 20 mm
around MR imaging abnormalities. Thus, it was hypothesized that an extended resection with a margin beyond MR
imaging–defined abnormalities—a “supratotal” resection—might improve the outcome of LGG. However, because
of the frequent location of LGG within “eloquent” brain areas, it is often difficult to achieve such a supratotal re-
section. This could nevertheless be possible when LGGs involve “noneloquent” areas, even in the left dominant
hemisphere. The authors report on their use of awake electrical mapping to tailor the resection according to func-
tional boundaries, that is, to pursue the resection beyond MR imaging–defined abnormalities, until corticosubcortical
eloquent structures are encountered. Their aim was to apply this reliable surgical technique to LGGs located not
within eloquent areas but distant from eloquent areas, to take a margin around the LGG visible on MR imaging while
preserving brain function.
Methods. Fifteen right-handed patients with a total of 17 tumors underwent resection of WHO Grade II gliomas
involving nonfunctional areas within the left dominant hemisphere. In all patients, seizures were the initial manifes-
tation of the tumors. Awake surgery with intraoperative electrostimulation was performed in all cases. The resection
was continued until the surgeon reached cortical and subcortical areas crucial for brain function, especially language,
as defined by the intrasurgical electrical mapping. The extent of resection was evaluated on postoperative FLAIR-
weighted MR images.
Results. Despite transient neurological worsening in 60% of cases, all patients recovered and returned to a nor-
mal life. Seizure control was obtained in all patients with a decrease of antiepileptic drug therapy. Postoperative MR
imaging showed that total resection was achieved in all 17 tumors and supratotal resection in 15. The average volume
of the postoperative cavity (36.8 cm3) was significantly larger than the mean preoperative tumor volume (26.6 cm3)
(p = 0.009). Neuropathological examination confirmed the diagnosis of WHO Grade II glioma in all cases. The mean
duration of postoperative follow-up was 35.7 months (range 6–135 months). Only 4 of 15 patients experienced recur-
rence (without anaplastic transformation); the average time to recurrence in these cases was 38 months; radiotherapy
was performed 6 years after the relapse in 1 case; no other patients received any adjuvant treatment. This series was
compared with a control group of 29 patients who had “only” complete resection: anaplastic transformation was
observed in 7 cases in the control group but not in any case in the series of patients who underwent supracomplete
resection (p = 0.037). Furthermore, adjuvant treatment was administered in 10 patients in the control group compared
with 1 patient who underwent supracomplete resection (p = 0.043).
Conclusions. These findings support the usefulness of awake surgery with intraoperative functional (language)
mapping with the attempt to perform supratotal resection of LGGs involving noneloquent areas in the left hemi-
sphere. Indeed, the extent of resection was significantly increased in all cases but 2, with no additional permanent
deficit and with control of seizures in all patients. The goal of supracomplete resection is currently to delay the ana-
plastic transformation, even if it does not (yet) enable a cure. (DOI: 10.3171/2011.3.JNS101333)

Key Words      •      WHO Grade II glioma      •      noneloquent areas      •

S
language mapping      •      supratotal resection      •      awake surgery      •      oncology
upratentorial diffuse WHO Grade II gliomas unavoidable anaplastic transformation.21,28,30 Recently, a
(the so-called “low-grade gliomas” [LGGs]) are large number of surgical studies based on objective eval-
primitive brain tumors characterized by continu- uation of the extent of resection by postoperative MR im-
ous growth, migration along the white matter tracts, and aging found that an extensive (total or at least subtotal)
This article contains some figures that are displayed in color
Abbreviations used in this paper: KPS = Karnofsky Performance on­line but in black and white in the print edition.
Scale; LGG = low-grade glioma.

232 J Neurosurg / Volume 115 / August 2011

Supratotal resection of low-grade gliomas
resection was significantly associated with an increase
in overall survival by delaying malignant transforma-
tion.1,4,13,24,33,35,36 Thus, maximal resection with preserva-
tion of eloquent brain areas is currently the first therapeu-
tic option to consider in LGG.8 However, a recent study
using biopsy samples within and beyond MR imaging–
defined abnormalities demonstrated that conventional
MR imaging underestimated the actual spatial extent of
LGGs, since tumor cells were present beyond the area of
MR imaging signal abnormalities, up to 20 mm—even
when gliomas were well defined on MR images.29 Inter-
estingly, it was suggested that an extended resection of a
margin beyond these MR imaging–defined abnormalities
might improve the outcome of LGG.29 Although an ex-
tensive resection is often difficult because of the frequent
location of LGGs within eloquent brain areas,9 a “supra-
total” resection—that is, resection extending beyond the
area of MR imaging signal abnormalities—could never-
theless be considered in “noneloquent” structures. On the
other hand, preoperative determination of the boundary
between noneloquent and eloquent brain areas in individ-
uals remains difficult, especially for language areas, due
to substantial interindividual anatomo-functional vari-
ability26,40 and the lack of reliability in functional neuro-
imaging methods.15
We recently showed that it is possible to use awake
surgery with intraoperative mapping to remove invasive
LGGs within language areas according to functional
boundaries—that is, to continue the resection until func-
tional boundaries have been encountered with no mar-
gin—without increasing the rate of permanent deficit.11,14
Here, for the first time, we apply this concept to diffuse
LGGs located in presumed noneloquent areas within the
left dominant hemisphere. Indeed, we performed awake
cra­ni­ot­omy with intrasurgical functional mapping (par-
ticularly language mapping) to remove the parenchyma
beyond the area of MR imaging signal abnormalities,
known to be invaded by tumoral cells, until eloquent
structures were detected by both cortical and subcortical
direct electrostimulation. Our objective was to achieve a
supratotal resection while preserving the patient’s quality
of life.
Methods
Selection of Patients
We analyzed a consecutive series of right-handed
adult patients (older than 18 years at the time of diag-
nosis), who underwent awake surgery for an LGG lo-
cated in a presumed nonfunctional area—that is, at least
5 mm from functional areas—within the dominant left
hemisphere. In all cases, surgery was performed by the
senior author (H.D.) between December 1998 and Febru-
ary 2010.
Definition of Noneloquent Areas
A functional area was defined according to the recent
UCSF (University of California, San Francisco) classifi-
cation, including the sensorimotor areas (precentral and
postcentral gyri), perisylvian language areas in the domi-
J Neurosurg / Volume 115 / August 2011
nant hemisphere (superior temporal, inferior frontal, and
inferior parietal gyri), basal ganglia, internal capsule,
thalamus, and visual cortex around the calcarine sulcus.3
The presumed noneloquent areas were defined as all
brain structures not belonging to the regions mentioned
above. They were therefore determined on the basis of
preoperative anatomical MR imaging.
Evaluation Methods
Information concerning the following parameters
was obtained for all patients: sex, age at diagnosis, first
symptom, tumor location, preoperative tumor volume and
surgically resected volume (evaluated on pre- and post-
operative MR imaging, respectively), neuropathology, ad-
ministration of radiotherapy and/or chemotherapy, time
to progression, and survival.
In addition, the patients’ neurological status and lan-
guage functions were evaluated pre- and postoperatively
(at 3 months after surgery and every 6 months thereaf-
ter). Handedness was assessed using the Edinburgh in-
ventory.27 Language evaluation was performed using the
Boston Diagnostic Aphasia Examination16 and a test of
picture naming (DO80 test).25 Finally, each patient’s sta-
tus was systematically evaluated by means of the KPS18
before and after the surgery.
Magnetic Resonance Imaging Evaluation
Preoperatively, the tumor volume was calculated on
the basis of the 3 largest diameters (D1, D2, and D3) of
areas of signal abnormality on FLAIR or T2-weighted
MR images according to the 3 orthogonal planes (axial,
sagittal, and coronal). An estimation of tumor volume
was calculated by the ellipsoid approximation ([D1 × D2
× D3]/2), as already reported.22 Postoperatively, the vol-
ume of the residual tumor (if any) was calculated using
the same method on the FLAIR-weighted MR images
obtained 3 months after surgery. According to the Berg-
er classification, resection was defined as “total” when
no residual signal abnormalities were present.2 In these
cases, to quantify the extent of the “supratotal” resection,
the volume of the surgical cavity was calculated with the
same technique, and compared with the preoperative tu-
mor volume. In patients who underwent total or suprato-
tal resection, a relapse was defined as the occurrence of
any FLAIR-weighted MR imaging abnormality.
Surgical Procedure
In all cases intraoperative functional electrostimula-
tion mapping was performed using the “asleep-awake-
asleep” protocol, as already reported.11,12 In the first
stage, the tumor and cerebral sulci and gyri were iden-
tified using ultrasonography. Cortical mapping was then
performed to detect the eloquent areas, using a bipolar
electrode with a 5-mm space between the tips (Nimbus,
Newmedic) and delivering a biphasic current (pulse fre-
quency 60 Hz, single-pulse phase duration 1 msec, ampli-
tude 1.5–4 mA). In all cases in which the central region
was exposed, sensorimotor mapping was first performed
to confirm a positive response (movement and/or pares-
thesias). The current intensity used for individual patients
233
 Y. N. Yordanova, S. Moritz-Gasser, and H. Duffau
was determined by progressively increasing the ampli-
tude in 1-mA increments (from a baseline of 2 mA) until
a functional response was elicited. Then the patient was
asked to perform counting (in a regular rhythm from 1 to
10, over and over) and picture-naming tasks, with the goal
to identify the essential cortical language sites known to
be inhibited by stimulation.11,12,26 Before naming each pic-
ture, the patient was asked to read a short phrase, namely
the French translation of “this is a …,” to check that there
were no seizures generating complete speech arrest if the
patient was not able to name the picture. For the picture-
naming task, we used the DO80 test pre- and postopera-
tively. Mapping of spatial cognition was also performed
in parietal lesions, using a line-bisection task.6,38
The patient was never informed when the brain was
stimulated. The duration of each stimulation was about
4 seconds. At least 1 picture presentation without stimu-
lation separated each stimulation, and in order to avoid
seizures, no site was stimulated twice in succession. Each
cortical site of the entire cortex exposed by the bone flap
was tested 3 times and all areas where a response was
obtained were stimulated at least 3 times for confirma-
tion. In all cases, a speech therapist was present in the
operating room during the stimulation and classified
the type of language disturbance using a system previ-
ously developed for the classification of language distur-
bances.12 Specifically, the disturbances were classified as
speech arrest, anomia, phonetic paraphasia, phonemic
paraphasia, semantic paraphasia, slowness with initiation
disturbances, and perseverations. Each eloquent area was
marked by a sterile number tag on the brain surface and
its location was correlated with the anatomical landmarks
previously identified by ultrasonography. An intraopera-
tive photograph of the cortical map was routinely made
before resection.
During a second surgical stage, the glioma was re-
moved by alternating resection and subcortical stimula-
tions. Using the same parameters of stimulation, the func-
tional pathways were followed progressively from the
cortical eloquent sites already mapped to the depth of the
resection. The patient had to continue the naming and/or
line-bisection (movement) task when the resection came
close to the subcortical eloquent structures, which were
also identified by functional inhibition during stimulation
as at the cortical level. Thus, the white matter tracts in-
volved in language, motor, somatosensory, and/or visual
functions could be detected in the deeper brain paren-
chyma. Again, the type of functional disturbance was
detailed by a speech therapist throughout the resection.
To optimize the tumor removal, with preservation of
function, all resections were pursued until eloquent struc-
tures were encountered around the surgical cavity. Thus,
resection was performed according to functional cortical
and subcortical boundaries. This means that there was
no margin left around the eloquent areas, both within
the gray and the white matter.14 As a consequence, when
possible, the resection was extended beyond the tumor’s
limits visible on preoperative MR imaging (and on intra-
operative ultrasonography).
Comparison With a Control Group
A control group of patients who underwent a com-
234
plete (not supracomplete) resection under local anesthe-
sia, using the same operative technique of awake map-
ping, for an LGG involving eloquent areas in the left
dominant hemisphere was compared with the patients
who underwent supracomplete resection regarding the
following parameters: sex, age, first symptom, preopera-
tive neurological examination, median duration of follow-
up, rate of recurrence, rate of anaplastic transformation,
and adjuvant treatments.
Statistical Analysis
A Kolmogorov-Smirnov test was used to study the
distribution of the variables, and P-P and Q-Q charts were
used to confirm it. The variables did not follow a nor-
mal distribution, and nonparametric tests were used for
comparisons. An intrasubject Wilcoxon signed-rank test
was used to determine if there were differences between
the pre- and postoperative tumor volumes. A significance
level of 5% (p < 0.05) was accepted in all cases. SPSS
software version 15.0 was used for the statistical analysis.
Results
Clinical and Radiological Presentation
Patient characteristics are summarized in Table 1.
Our series consisted of 15 right-handed patients (8
men and 7 women) with a mean age of 36.4 years (range
24–59 years). The first clinical symptom was seizure in
all patients. The average time between the onset of symp-
toms and the surgical treatment by our team was 28.5
months (range 1–222 months). Three patients had under-
gone previous surgery with partial resection performed
by another team using general anesthesia. One of these
patients had also been treated with adjuvant chemothera-
py. In these 3 cases, the average time between the 2 sur-
geries was 14 months (range 6–24 months).
Preoperatively, no patient had sensorimotor deficit or
intracranial hypertension. Mild language and/or cogni-
tive disorders were found in 12 patients (80%). The pre-
operative KPS score was 90 or greater in all patients but
one, who had a KPS score of 80 due to verbal working
memory disorders.
All gliomas were located in noneloquent areas with-
in the left dominant hemisphere (for details, see Table 1)
(Fig. 1). It is worth noting that a bifocal multicentric glio-
ma39 was present in 2 patients. These lesions also involved
noneloquent areas in both cases (left presupplementary
motor area and posterior part of the superior parietal
lobule in the first case; left prefrontal and temporopolar
lobes in the second case).
The average presurgical volume was 26.6 cm3 (range
1–68.8 cm3).
In summary, 17 lesions were removed, including 11
in the frontal lobe, 4 in the temporal lobe, and 2 in the
parietal lobe.
In all patients, the cortical and subcortical functional
areas were detected by intraoperative stimulation. These
cortical and subcortical functional structures represented
the limits of resection (Fig. 2).
J Neurosurg / Volume 115 / August 2011
Supratotal resection of low-grade gliomas
TABLE 1: Clinical and radiological characteristics of 15 patients*

Time Btwn
Case Age (yrs),† Preop Sx Onset
No. Sex Deficit & Op (mos) Tumor Location
1 26, M none 9 pre-SMA
2 32, F MLD 12 pre-SMA, SPL
3 30, M MLD 9 temporal pole
4 59, M MLD 1 frontal pole
5 47, M MLD 28 pre-SMA
6 26, F MLD 2 SMA
7 27, M MLD 40 frontal pole Fig. 1.  Case 7. Preoperative axial FLAIR-weighted (left) and sagit-
8 39, F MLD 9 SPL tal T2-weighted (right) MR images showing a WHO Grade II glioma
located in a “nonfunctional” area (the left frontal pole) in a patient with
9 54, M MLD 42 temporal pole no neurological deficit except for very mild disturbances of the verbal
10 39, F MLD 24 frontal pole episodic memory detected by an extensive neuropsychological assess-
11 27, M MLD 2 temporobasal area ment. Note that the tumor is far from the ventricle.
12 24, M MLD 7 temporal pole, frontal pole
13 42, F MLD 6.5 frontal pole volume for all but 2 lesions (despite the absence of re-
sidual signal abnormalities). Therefore, the resection can
14 29, F none 14 frontal pole
be considered supratotal for 15 lesions (Figs. 3 and 4).
15 45, F none 222 pre-SMA Neuropathological examination confirmed the diag-
nosis of WHO Grade II glioma in all 17 tumors. Exami-
*  MLD = mild language disorder (on Boston Diagnosis Aphasia Ex-
nation of the margin of the resected brain tissue showed
amination); SMA = supplementary motor area; SPL = superior parietal
tumoral cells in all but 1 case. The exception involved 1
lobule.
of the patients with 2 lesions (temporal and frontal); the
†  Patient age at time of surgery.
periphery around the frontal tumor showed normal brain
tissue.
Postoperative Results No adjuvant treatment was administered after sur-
In the immediate postsurgical period, a transient gery.
worsening was noted in 9 patients (60%). There were 2 The mean duration of postoperative follow-up was
supplementary motor area syndromes and 7 mild lan- 35.7 months (range 6–135 months). A relapse was noted in
guage disorders, which improved after rehabilitation in 4 patients after a mean period of 38 months (range 18–72
all cases. Three months after surgery, there was no severe months). One of these 4 patients underwent radiotherapy
permanent deficit. A slight somatosensory deficit and a 6 years after the recurrence. No treatment was adminis-
quadrantanopia persisted in 2 patients with parietal and tered to the other 3 patients, due to a slow rate of tumor
posterior basal temporal lesions, respectively, but with growth with no clinical impact. There was no anaplastic
no consequence on the quality of life. All 15 patients re- transformation (that is, no occurrence of enhancement on
turned to a normal life. follow-up MR images), and none of the patients died.
Relief of seizures was obtained in all 15 patients
Comparison With the Control Group
postoperatively. The doses of the antiepileptic drugs have
been reduced in all cases in which the follow-up period The control group of patients who underwent a com-
was longer than 9 months. In 4 cases, the antiepileptic plete (not supracomplete) resection for an LGG involving
treatment has been stopped. eloquent areas in the left dominant hemisphere consisted
All 15 patients have resumed their social activities. of 29 patients (19 men and 10 women) with a mean age
Professional activities have also been resumed by all pa- of 37 years (range 17–61 years). The first symptom was
tients but one, who had a preoperative working memory seizure in all patients, with no neurological deficit. The
disorder, which persisted following surgery. mean postoperative follow-up duration was 36 months
The KPS score was 90 or greater in all cases but one (range 6–132 months). Thus, there was no significant
(in which it was 80). difference with respect to these parameters between the
The resection was total in all cases—that is, with no control group and the series of 15 patients who had a su-
signal abnormalities on postoperative FLAIR-weighted pracomplete resection.
MR imaging 3 months after surgery. The control group had a higher rate of recurrence,
The average volume of the postoperative cavity was 41% versus 26% in the series of patients who underwent
36.8 cm3 (range 2.7–83.9 cm3). This mean volume was supracomplete resection, although the difference was not
significantly larger than the mean preoperative tumor statistically significant. In addition, anaplastic transfor-
volume calculated at 26.6 cm3 (range 1–68.8 cm3) (p = mation was observed in 7 cases in the control group but
0.009). not in any case in the series of patients who underwent su-
For individual lesions, the postoperative volume of pracomplete resection (p = 0.037). Furthermore, adjuvant
the cavity was also greater than the preoperative tumor treatment was administered in 10 patients in the control

J Neurosurg / Volume 115 / August 2011 235

 Y. N. Yordanova, S. Moritz-Gasser, and H. Duffau

Fig. 3.  Case 7. Postoperative axial FLAIR-weighted (left) and sagit-

tal T2-weighted (right) MR images showing a supratotal resection of
the glioma. Note the large opening of the ventricle, demonstrating that a
margin was taken around the MR imaging–defined abnormalities. The
patient returned to a normal social and professional life, with no deficit
Fig. 2.  Case 7. Intraoperative photograph obtained after resection, and no seizures.
which was performed under local anesthesia. The resection was per-
formed according to functional boundaries, which were identified by
using electrostimulation both at the cortical (ventral premotor cortex surgery in LGG, on the condition that the resection is total
inducing speech arrest when stimulated [1]; and primary motor cortex or at least subtotal on postoperative FLAIR-weighted MR
of the face [2]) and subcortical levels (46: phonemic paraphasia due to images.1,4,13,24,33,35,36 Therefore, by reducing the number of
stimulation of the anterior part of the superior longitudinal fasciculus; 47: peripheral tumor cells, a supratotal resection might have a
perseveration during stimulation of the head of the caudate nucleus; 48: greater impact on tumor growth and transformation.
fibers coming from the ventral premotor cortex, eliciting speech arrest
during stimulation).
Low-Grade Glioma Surgery and Functional Areas
group compared with 1 patient who underwent supracom- Patients with LGG are most often young, with a
plete resection (p = 0.043). nor­mal social and professional life. Thus, preservation
of function is essential during the resection of these le-
sions. Because of the common location of LGGs in elo-
Discussion quent sites, total (and a fortiori supratotal) resection is
often difficult. Indeed, even if we previously observed
Low-Grade Glioma Surgery and the Concept of Supratotal mechanisms of brain plasticity allowing functional re-
Resection mapping, and sometimes leading to a multistage surgi-
Several decades ago, it was demonstrated, using mul- cal approach,7,10,14,23 it is nevertheless most of the time not
tiple stereotactic biopsies in high-grade gliomas, that tu- possible to achieve a truly complete LGG removal.
mor cells invaded most of the hemisphere (or even the In parallel, the development of intraoperative stimula-
contralateral side through the corpus callosum), far be-
yond the tumor visible on imaging studies (CT scanning
and then MR imaging).19 These results explained why it
was impossible to cure glioblastoma, even with extensive
resection.
Recently, it was also shown using multiple biopsy
samples that LGG invaded the brain beyond the abnor-
malities visible on conventional MR images. This study
demonstrated that tumor cells were present at a distance
of 10–20 mm from the tumor boundaries defined by MR
imaging, but that their number was significantly less be-
yond 20 mm.29 In our series, examination of the resected
brain tissue showed tumor cells in the tissue obtained
from the tumor margins of all lesions but one. Thus, our
results confirm that conventional MR imaging underes-
timates the actual spatial extent of WHO Grade II glio-
ma. Thus, in LGG, in contrast to glioblastoma, Pallud et
al.29 hypothesized that a large resection, ideally with 2
cm of margin around the lesion visible on MR imaging,
could dramatically change the natural history of this tu-
mor (even if not cure it), especially by delaying anaplastic Fig. 4.  Comparison between the preoperative tumor volume (Series
transformation. Such a hypothesis is in agreement with 1) and the postoperative volume (Series 2) of the surgical cavity. The x
the recent literature, which strongly supports the role of axis indicates tumors (1–17) and the y axis volume in cm3.

236 J Neurosurg / Volume 115 / August 2011

Supratotal resection of low-grade gliomas
tion in awake patients has been extensively demonstrated
to allow a dramatic decrease in permanent deficits, with a
rate of sequelae currently lower than 1.5%.8,11,34 Interest-
ingly, awake surgery also enabled a significant increase of
the extent of resection while operating in eloquent areas,
as shown in patients who underwent 2 consecutive sur-
geries, the first under general anesthesia and the second
under local anesthesia with an optimization of the LGG
removal.5
As a consequence, our goal in this series of cases was
to apply this reliable surgical technique to LGGs located
not within eloquent areas but distant from eloquent areas,
to take a margin around the LGG visible on MR imag-
ing while preserving brain functions (that is, resection
according to functional and not anatomical boundaries).
Surgery for Low-Grade Gliomas at a Distance From
Functional Areas
To our knowledge, the role of brain stimulation un-
der local anesthesia in LGG within noneloquent areas
in the left dominant hemisphere has never been studied
in the literature. Indeed, in patients with LGGs in pre-
sumed noneloquent areas, resection is traditionally per-
formed under general anesthesia, thus with no language
mapping, despite the involvement of the left hemisphere.
Interestingly, 3 of our patients who underwent a previous
resection under general anesthesia in another institution
had only partial resection, while it has been possible to
perform not just a total but a supratotal resection during a
second surgery with these patients awake—with no neu-
rological worsening. These data confirm the limits of the
conventional surgery, in which the neurosurgeon stops
the resection prematurely to avoid language disorders
in the dominant hemisphere. Indeed, it has been clearly
demonstrated that without functional mapping the ana-
tomical landmarks are not reliable enough to identify the
cortical and subcortical structures crucial for language.31
Therefore, these results in noneloquent areas support the
findings already reported in eloquent areas, that is, the
significant increase of the extent of resection thanks to
the use of awake mapping.5,13
In addition to the fact that a complete resection was
obtained in all cases, intraoperative electrostimulation
under local anesthesia enabled us to perform a supratotal
resection in 15 (88%) of the 17 lesions, as demonstrated by
comparing the preoperative tumor volume and the post-
surgical cavity volume (p = 0.009). Indeed, the volume of
the postoperative cavity reflects the volume of the brain
tissue that was removed, tissue that was invaded by tumor
cells even if this infiltration was not visible on presurgical
MR imaging. In 2 patients, the volume of the cavity was
nevertheless smaller than the presurgical tumor volume,
despite the absence of signal abnormalities on the postop-
erative FLAIR-weighted MR imaging. This postoperative
volume may be underestimated because of parenchymal
retraction. Even with this underestimation of the extent
of resection, the mean postoperative volume has been
enlarged by 10.8 cm3 (38%), due to the awake mapping,
which allowed resection until functional boundaries were
reached. It means that we increased the resection by more
than 10 cm3 in comparison with a “classic” surgery con-
J Neurosurg / Volume 115 / August 2011
ducted according to oncological limits—that is, based on
neuronavigation or even on intraoperative MR imaging—
since the goal, according to this principle, in essence is
to remove only the MR imaging–defined abnormalities.
From a functional point of view, a transient clinical
worsening occurred in 60% of cases after surgery, es-
pecially with respect to language function. Such results
are not surprising due to the absence of margin between
functional cortico-subcortical structures and the edge of
the surgical cavity, even if the (visible) glioma was a pri-
ori located in noneloquent areas. It must be emphasized
that according to classic recommendations, a margin of
security of about 5–10 mm around the area detected by
functional brain stimulation is generally preserved in
the surgical series reported in the literature. However,
we recently demonstrated in a series with 162 patients
who underwent surgery for an LGG in the left dominant
hemisphere that resection to the point of contact with elo-
quent areas was possible without increasing the rate of
postoperative definitive deficits (less than 2%), despite a
transitory impairment in the immediate postoperative pe-
riod.14 Here, we confirm that all patients recovered their
preoperative neurological status within a few weeks of
surgery, with specific functional rehabilitation, and that
they returned to a normal social and professional life (ex-
cept for 1 patient who did not work preoperatively due to
cognitive disorders). Moreover, seizures were controlled
in all cases with decrease or cessation of antiepileptic
drug therapy.
Limitations and Perspectives
The main limitations of our study are the small num-
ber of patients and a short duration of postoperative fol-
low-up for some of them. Indeed, the mean duration of
follow-up is only 3 years, due to the inclusion of 5 patients
with only 6 months of follow-up. However, it is worth not-
ing that 8 patients have been followed up for 2–11 years,
without any case of death or anaplastic transformation
(without adjuvant treatment in all cases but one), support-
ing a possible impact of the supracomplete resection on
the long-term course of the disease. Indeed, comparison
with the control group of patients who had “only” a com-
plete resection (no supracomplete resection due to the fact
that the LGG involved eloquent areas) showed a higher
rate of recurrence in the control group (41% versus 26%
in the patients who underwent supracomplete resection),
although the difference was not statistically significant.
Interestingly, anaplastic transformation was observed in 7
cases in the control group, compared with no cases in the
series of patients who underwent supracomplete resection
(p = 0.037). Furthermore, adjuvant treatment was given in
10 patients in the control group, but only in 1 patient who
underwent supracomplete resection (p = 0.043). Thus,
these results support the hypothesis that a supracomplete
resection may significantly delay anaplastic transforma-
tion with no adjuvant chemotherapy or radiotherapy, even
if it does not prevent LGG recurrence.
Indeed, we must also emphasize that a relapse oc-
curred in 4 of the 15 patients, indicating that the primary
goal of the supratotal resection remains to delay ma-
lignant transformation and thus to increase the median
237
 Y. N. Yordanova, S. Moritz-Gasser, and H. Duffau
survival while preserving (or improving) brain function.
Although the quality of life was not evaluated using vali-
dated instruments (except the KPS) in the present series,
no patient suffered additional permanent neurological
deficit, and seizures have been controlled in all patients.
Of course, we do not claim to be able to cure patients
with LGG, even when performing supracomplete resec-
tion. Indeed, these recurrences might mean that it was
not possible to take at least 20 mm of margin all around
the tumor in all patients, due to the functional structures
(even if distant from the glioma). Interestingly, although
the ages of the 4 patients with recurrence and their tu-
mor volumes were not significantly different from those
of the 11 other patients with no recurrence, it is nonethe-
less worth noting that this subgroup includes the 2 pa-
tients with a postoperative cavity volume smaller than the
preoperative tumor volume. As a consequence, we can
suggest that the margin around the FLAIR signal abnor-
mality was less than in the other patients, likely explain-
ing a quicker relapse. The relapses might also mean that
the technique used in the study by Pallud et al.29 (MIB-1
immunostaining based on the detection of proliferating
cells) might not be sensitive enough in LGG. It is possible
that tumor cells not identified by MIB-1 immunostaining
exist in the perilesional parenchyma beyond a margin of 2
cm around the MR imaging–defined abnormalities.
On the other hand, it is interesting to note that some
patients in our series had a relapse after 18 months while
others had no recurrence with 135 months of follow-up
after the sole surgery. This could be explained by the
fact that some LGGs are more “invasive” whereas other
LGGs are more “proliferative.” It is likely that surgery,
especially supratotal resection, by definition has a better
chance of controlling the latter than the former. In the
future, advances in MR imaging might allow for better
selection with respect to indications for supracomplete
resection. Indeed, it has been suggested that MR spec-
troscopy and perfusion MR imaging could be more ef-
fective than conventional MR imaging for evaluating ac-
tual LGG infiltration. Metabolic imaging might be more
sensitive than morphological MR imaging based on T2/
FLAIR signal abnormalities, and could be closer to the
neuropathological tumor infiltration.20,37,41 However, these
techniques still lack reliability and need to be validated.
Another method could be to use the new biomathematical
models of proliferation and diffusion, based on at least 2
sets of MR images acquired 3–6 months apart, before any
treatment.17,22,32
Conclusions
Our findings support the usefulness of awake surgery
with intraoperative functional (language) mapping with
the attempt to achieve a supratotal resection of LGG in-
volving noneloquent areas in the left hemisphere. Indeed,
the extent of resection was significantly increased in all
but 2 cases, with no additional permanent neurological
deficit and with seizure control despite a decrease of an-
tiepileptic drugs in the 15 patients. The goal would be to
delay the anaplastic transformation and to delay the use of
adjuvant therapy, without claiming to cure patients. These
preliminary results need to be validated by increasing the
238
number of patients and the follow-up period, using pro-
spective multicenter studies.
Disclosure
The authors report no conflict of interest concerning the mate-
rials or methods used in this study or the findings specified in this
paper.
Author contributions to the study and manuscript preparation
include the following. Conception and design: Duffau. Acquisition
of data: Duffau, Moritz-Gasser. Analysis and interpretation of data:
all authors. Drafting the article: Duffau, Yordanova. Critically revis-
ing the article: Duffau, Yordanova. Approved the final version of
the paper on behalf of all authors: Duffau. Administrative/technical/
material support: Duffau, Moritz-Gasser. Study supervision: Duffau.
Acknowledgments
The authors thank Juan Martino, M.D., (Department of Neuro-
surgery, Hospital Universitario Marqués de Valdecilla, Santander,
Cantabria, Spain) for his help with the statistics.
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Manuscript submitted August 5, 2010.
Accepted March 29, 2011.
Please include this information when citing this paper: published
online May 6, 2011; DOI: 10.3171/2011.3.JNS101333.
Address correspondence to: Hugues Duffau, M.D., Ph.D., Depart-
ment of Neurosurgery, Hôpital Gui de Chauliac, CHU Montpel-
lier, 80 Avenue Augustin Fliche, 34295 Montpellier, France. email:
h-duffau@chu-montpellier.fr.
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