Case Report
Corpus Callosotomy for Refractory Epilepsy in Aicardi Syndrome: Case Report and
Focused Review of the Literature
Joshua D. Bernstock1,2, Hannah E. Olsen4, David Segar1,2, Kevin Huang1,2, Ari D. Kappel1,2, Walid Ibn Essayed1,2,
Phillip L. Pearl3, Joseph R. Madsen2
Key words
- Aicardi syndrome
- Corpus callosotomy
- Epilepsy
Abbreviations and Acronyms
EEG: Electroencephalogram
VNS: Vagus nerve stimulation
From the Departments of 1Neurosurgery, Brigham and
Women’s Hospital, Harvard Medical School, and
2
Neurosurgery and 3Neurology, Boston Children’s Hospital,
Harvard Medical School; and 4Harvard Medical School,
Boston, Massachusetts, USA
To whom correspondence should be addressed:
Joshua D. Bernstock, M.D., Ph.D.
[E-mail: Jbernstock@partners.org]
Joshua D. Bernstock and Hannah E. Olsen contributed
equally to this work.
Citation: World Neurosurg. (2020) 142:450-455.
https://doi.org/10.1016/j.wneu.2020.06.230
Journal homepage: www.journals.elsevier.com/world-
neurosurgery
Available online: www.sciencedirect.com
1878-8750/$ - see front matter ª 2020 Elsevier Inc. All
rights reserved.
INTRODUCTION
Aicardi syndrome is a rare neuro-
developmental disorder characterized by
the classic triad of complete or partial
agenesis of the corpus collosum, chorior-
etinal lacunae, and infantile spasms, with
polymicrogyria, intracranial cysts, and
periventricular heterotopias also
commonly observed.1-4 Though the pre-
cise genetic etiology remains unknown,
Aicardi syndrome is an X-linked dominant
disorder that primarily affects females
with an estimated incidence of 1 in
100,000 live births.5-8 Given the severity of
brain dysgenesis, children with Aicardi
syndrome generally have profound psy-
chomotor retardation and experience poor
functional outcomes.2,9-11 Current
mainstays of clinical management
include antiseizure agents and physical
therapy with neurosurgical intervention
reserved for patients with medically
450 www.SCIENCEDIRECT.com
- BACKGROUND: Aicardi syndrome is a severe neurodevelopmental disorder
that occurs primarily in females and is characterized by seizures, agenesis of the
corpus callosum, and chorioretinal lacunae, which occur together in the ma-
jority of affected individuals. Seizures begin in infancy and tend to progress in
intensity and are often refractory to standard multimodal medication treatments.
- CASE DESCRIPTION: We present here a unique case of a 12-year-old girl
with partial agenesis of the corpus callosum who underwent a corpus callos-
otomy for treatment of medically refractory epilepsy. In so doing, we also review
the literature with regard to the neurosurgical management of these unique
patients.
- CONCLUSIONS: For the subset of children who present with partial, rather
than complete, agenesis of the corpus callosum, corpus callosotomy should be
considered as a treatment option to reduce seizure burden.
refractory epilepsy.12-14 Here, we present spontaneous discharges over the right
the case of a 12-year-old girl with Aicardi hemisphere without evidence of frank
syndrome who underwent a corpus cal- epileptiform activity; valproate was initi-
losotomy for intractable epilepsy. ated and levetiracetam dosing was
increased. Given our concern over new
seizure activity, the family was referred for
CASE evaluation at Boston Children’s Hospital.
The patient was a 12-year-old, right- Medical history at this time was also
handed, full-term female, who first notable for right eye coloboma and pre-
developed myoclonic seizures with asso- cocious puberty, treated for a period of
ciated left lower extremity spasms at 5 time with gonadotropin-releasing hor-
months of age. At that time, electroen- mone. Family history was notable for a
cephalogram (EEG) showed multifocal maternal second cousin with cleft lip and
spikes, predominantly over the right tem- palate, agenesis of the corpus callosum,
poral region. Following initiation of leve- and developmental delay.
tiracetam, symptoms improved and she Magnetic resonance imaging done on
required no further treatment for several presentation demonstrated findings char-
years. During that time, the patient acteristic of Aicardi syndrome including
demonstrated evidence of moderate polymicrogyria involving the right frontal
learning disabilities, demonstrating lobe, bilateral cingulate gyri, and right
particular difficulty with social interaction posterior insula, as well as bilateral peri-
and abstract thought. At age 10, the pa- ventricular subependymal nodular hetero-
tient began to experience frequent yet topia, a 4.8-mm round lesion in the
brief events again, concerning for seizure atrium of the right lateral ventricle, most
activity, in which she would become likely representing a choroid plexus pap-
briefly unaware of her environment and illoma and bilateral colobomas.
exhibit brief myoclonic right hemibody The patient was admitted for contin-
movements, often triggered by sound and uous EEG monitoring and monitored for a
associated with urinary incontinence. total of 5 days while on her home dose of
Video EEG at age 11 demonstrated levetiracetam and valproate. During the
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2020.06.230
 CASE REPORT
JOSHUA D. BERNSTOCK ET AL. CORPUS CALLOSOTOMY IN AICARDI SYNDROME

hospitalization, there were frequent inter-
ictal right frontal sleep potentiated spikes,
as well as right anterior temporal rhythmic
sharp waves and occasional fast spikes.
Fourteen seizures—1 electrographic and 13
with electroclinical correlates—were
recorded, manifest by high-amplitude,
broadly distributed delta activity with
superimposed beta and attenuated back-
ground, better developed over the right
hemisphere. Each electrical event lasted
between 2 and 4 seconds, with clusters up
to 10 seconds, and was clinically associ-
ated with bilateral upper extremity tonic
stiffening, head drop, whole body
myoclonic jerking, and hip abduction.
Each time, events were preceded by audi-
tory stimuli. Positron emission tomogra-
phy computed tomography demonstrated
right inferior frontal, right insular, and
right lateral temporal and bilateral cingu-
late hypometabolism. Given the nonle-
sional, generalized nature of her seizure
semiology and ictal EEG signature
(Figure 1), a corpus callosotomy
addressing the residual callosal fibers
was recommended by our
multidisciplinary team. After discussion
with the family and informed consent,
the patient was scheduled for open
corpus callosotomy.
Our operative technique was in line with
our standard approach for corpus callos-
otomies. The patient was positioned su-
pine with the head slightly flexed. A
bicoronal incision was made anterior to
the coronal suture and behind the hair-
line, with stereotactic navigation
employed to optimize the subsequent
approach to the atrophic corpus callosum.
After the scalp was reflected, 2 burr holes
were placed on the contralateral (left) side
of the sagittal sinus approximately 5 cm
apart in the sagittal orientation and used
to dissect the sinus and dura free from the
underside of the bone. The dura was
opened from lateral to medial and flapped
toward the superior sagittal sinus, with
care taken to preserve any bridging veins.
Eventually, a 3-cm window was identified
for interhemispheric dissection.
As the interhemispheric dissection was
performed, the corpus callosum was
rapidly encountered. Notably, the arach-
noid tissue dorsal to the callosum was
thickened and formed a cystic structure
(Figure 2). Moreover, both the extreme
anterior and posterior border of the
corpus callosum could be visualized with
different angulations of the operating
microscope from our approach. The
callosotomy was then performed using a
blunt nerve hook. The ventral surface
was also found to be invested with a
thick layer of arachnoid rather than any
ependymal lining. An intraoperative MRI
was performed and confirmed a
complete callosotomy (Figure 3).
Postoperatively, the patient recovered
rapidly, without evidence of postoperative
interhemispheric disconnection syn-
drome, presumed to be related to the
reduced baseline connectivity through the
shortened and dysgenic corpus callosum.
She was discharged home on post-
operative day 3 on her baseline antiseizure
medications, without clinical evidence of
seizure activity during her hospitalized
postoperative course. Subsequent follow-
up 4 months postoperatively revealed a
seizure reduction rate of >50%, consistent
with Engel IIIA (worthwhile improvement)
and ILAE 4 (of 6) outcome scores.
DISCUSSION
Children with Aicardi syndrome are
neurologically complex and present within
the first several months of life with sei-
zures that nearly invariably become re-
fractory to multiagent pharmacotherapy.
Infantile spasms are present in the vast
majority of patients, with clonic,

Figure 1. Ictal electroencephalogram (EEG). Head drop associated with marks onset of clinical seizure and “e” marks end. EEG shows an 8-second
shoulder myoclonus associated with a high voltage generalized delta epoch using bipolar longitudinal montage, HFF 70 Hz, LFF 1 Hz, sensitivity 7
transient with overriding low voltage fast activity that evolves into mcV/mm, and time base 30 mm/sec.
polyspikes having right hemispheric predominance. The designation “o”

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 CASE REPORT
JOSHUA D. BERNSTOCK ET AL. CORPUS CALLOSOTOMY IN AICARDI SYNDROME

poor candidates for resective surgery due

to bihemispheric multifocal
epileptogenicity. Multiple reports have
demonstrated both amelioration and
complete cessation of seizures with
minimal morbidity after corpus
callosotomy in children with bilateral
brain malformations.14,22-29 To our
knowledge, this is the sixth report of a
corpus callosotomy performed in a child
with Aicardi syndrome for palliation of
drug-resistant epilepsy. A summary of
the following cases can be found in
Table 1.
Reports on the use of epilepsy surgery
in patients with Aicardi syndrome are
scarce. Rosser et al9 reviewed data from
the Aicardi Syndrome Foundation’s
family-based, self-reported survey of 77
children with Aicardi Syndrome and found
6 patients had undergone surgery for re-
fractory epilepsy. Five patients had a VNS
device implanted, 2 of whom reported
improved seizure control and alertness
postoperatively. One patient underwent a
hemispherectomy and subsequently
became seizure-free on a significantly
reduced drug regimen. Her parents also
reported substantial developmental
improvement. In a multidecade nation-
wide survey in Sweden, Palmer et al21,30
identified 18 patients with Aicardi
syndrome, 1 of whom underwent
resection of a parietal epileptogenic zone
at age 11, resulting in a seizure-free
period of 4 years. In a retrospective study
Figure 2. Intraoperative views of the interhemispheric approach. (A) An examining methods of epilepsy treatment
approximately 3-cm-long working angle could be identified between 2 in children with bilateral cortical malfor-
bridging veins to perform the dissection. (B) A thick arachnoid layer was
mations, Saito et al14 describe a 3-year-old
found to be investing the corpus callosum upon initial approach. (C) After the
callosotomy was performed, the ventral border of the callosum was found to patient with Aicardi syndrome and partial
end in a thickened layer of arachnoid as well. agenesis of the corpus callosum who un-
derwent total callosotomy, which resulted
in partial alleviation of the severity of her
tonic-clonic seizures. An additional left
functional hemispherectomy performed 5
myoclonic, and focal seizures also neurosurgical intervention may be months later produced a seizure-free
commonly seen with increasing age. considered.18-20 period of 7 months at time of study
Classic EEG findings include asynchro- Optimal surgical management of pa- publication.
nous multifocal epileptiform abnormal- tients with Aicardi syndrome has yet to be In a case series of 4 patients with
ities with burst-suppression and definitively established, due in large part Aicardi syndrome who underwent surgical
hemispheric dissociation.1,2,15-17 to the rarity of the condition. Vagus nerve management of refractory epilepsy,
Hypsarrhythmia has been reported in a stimulation (VNS) and various forms of Kasasbeh et al12 identified 3 children with
minority of patients.11,16 As children age resective surgery have been performed in VNS implantation and 2 who had a corpus
and seizure control becomes patients with variable efficacy in seizure callosotomy. Outcomes were remarkably
progressively more difficult to manage reduction and developmental out- variable, ranging from near-complete
their risk for secondary complications,1-35 comes.12-14,21 Corpus callosotomy has reduction in seizure burden to a wors-
such as injuries from falls and worsening been used as a palliative surgery in ening of seizure frequency and severity
neuropsychologic deficits, increases and patients with intractable epilepsy who are postoperatively irrespective of surgical

452 www.SCIENCEDIRECT.com WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2020.06.230

 CASE REPORT
JOSHUA D. BERNSTOCK ET AL. CORPUS CALLOSOTOMY IN AICARDI SYNDROME

Figure 3. T1-weighted images from the preoperative magnetic T1-sequences after the callosotomy demonstrate complete
resonance imaging demonstrated a small corpus callosum in (A) sectioning of the corpus callosum, as well as the operative
axial, (B) sagittal, and (C) coronal views. Intraoperative corridor in (D) axial, (E) sagittal, and (F) coronal views.

method or degree of corpus callosum
agenesis.12 Podkorytova et al13 identified 8
patients with Aicardi syndrome from the
Cleveland Clinic epilepsy database, 2 of
whom underwent resective epilepsy
surgery. They describe a 6-year-old pa-
tient who had a left functional hemi-
spherectomy and was seizure free for 6
months after surgery. She then experi-
enced a recurrence of asymmetric epileptic
spasms, which have remained amenable
to medical therapy for 42 months as of the
time of study publication. They also
describe a patient with global develop-
mental delay, left hemiparesis, and right
microphthalmia who had a right fronto-
parietal lobectomy at 1 year of age. After a
complicated postoperative course
involving 1 week of status epilepticus, she
ultimately saw a 50% reduction in seizures
and marginal developmental
improvement.
Data guiding the neurosurgical man-
agement of patients with refractory
epilepsy due to Aicardi syndrome are
scant, with fewer than 10 published re-
ports. Though it is difficult to draw con-
clusions regarding best clinical practice
from such a limited number of cases, it
does appear that a subset of patients with
intractable epilepsy due to Aicardi syn-
drome who are not candidates for resec-
tive surgery given the bilateral nature of
their cortical dysgenesis and diffuse epi-
leptogenicity stand to derive significant
benefit from corpus callosotomy when
there is partial callosal agenesis. Of the 5
previously reported cases, 4 of the patients
with Aicardi syndrome who underwent
corpus callosotomy experienced a partial
or complete reduction in seizures after
surgery with 1 patient also reporting sub-
stantial developmental improvement. In
this case report, we describe a 12-year-old
girl with Aicardi syndrome who developed
infantile spasms at 5 months of age, which
were initially well controlled with medi-
cation. At age 10 she began to experience a
recurrence of myoclonic seizures that did
not respond to intensified dosing or
addition of new antiseizure medications.
She underwent a corpus callosotomy and
has had a reduced seizure burden on
baseline drug regimen for 4 months as of
the time of this study publication.
Our findings in conjunction with the
previous literature underscore the utility of
corpus callosotomy as an effective, well-
tolerated method of controlling seizures
that have become refractory to medical
management, particularly for patients with
partial, rather than complete, agenesis of
the corpus callosum. Though corpus cal-
losotomy is unlikely to result in complete
seizure cessation in all patients, there is
also evidence to suggest that in the event
of recurrence after surgery, seizures are
more easily amenable to management
with antiseizure medication. Moreover,
even a temporary seizure-free period may
allow for significant developmental pro-
gression. However, larger cohort studies

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 CASE REPORT
JOSHUA D. BERNSTOCK ET AL. CORPUS CALLOSOTOMY IN AICARDI SYNDROME

Table 1. Summary of Cases

Age Surgery Seizure Outcome Developmental Outcome

Paper
Rosser et al., 20029 Unknown Hemispherectomy Seizure free on 1 AED Improved from a 2-month to a
9-month level
Palmer et al., 200730 11 years Right parietal resection Seizure free for 4 years High motor function (walks
and runs); functional age of 7
years at 15 years of age
Saito et al., 200914 3 years Corpus callosotomy with left Seizure free for 7 months Unknown
functional hemispherectomy 5
months afterwards
Kasasbeh et al., 201312 7 years Corpus callosotomy 90% reduction in partial and tonic Behavioral and communication
seizures; cessation of drop attacks improvements
8 years VNS followed by corpus Reduced seizure burden at 6 months Unknown
callosotomy postoperative,
followed by an increase in seizure
frequency beginning at 1 year
postoperative
Podkorytova et al., 201713 6 years Left functional hemispherectomy Seizure free 6 months after surgery Improved alertness, affect,
behavior and growth; able to
sit and stand
1 year Right fronto-parietal lobectomy 50% seizure reduction Improved alertness and
recognition of caregivers;
head and trunk control
improved
Bernstock et al., 2020 12 years Corpus callosotomy Reduced seizure burden Pending clinical follow-up

will be critical in furthering our under-
standing of the indications for and long-
term outcomes of palliative epilepsy sur-
gery in children with Aicardi syndrome.
It is prudent to note that less invasive
approaches to corpus callosotomy have
recently been described within literature,
including endoscopically assisted versus
purely endoscopic callosotomy.31-33 These
approaches have indeed been proven to be
safe surgical options in select cases.32,33
Such approaches are most valuable in
decreasing the invasiveness of a total
callosotomy; however, given the short
dysgenic corpus callosum in our patient,
the pertinence of such techniques was
less evident. A growing body of literature
is also beginning to emerge with regard
to laser interstitial thermal therapy as a
safe and relatively effective option for
corpus callosotomy.34,35 Initial seizure
control results are encouraging, but more
prospective and comparative data will be
required to establish this technique as a
standard of care.34 Nonetheless, it has
become clear that laser ablation will be
an invaluable tool in subsets of medical
fragile patients were open surgical
callosotomy is associated with higher
morbidity.35
CONCLUSION
Aicardi syndrome is an extremely rare
neurologic disorder characterized by sei-
zures, agenesis of the corpus callosum,
and chorioretinal lacunae. For the subset
of children who present with partial,
rather than complete, agenesis of the
corpus callosum, corpus callosotomy
should be considered as an option to
reduce seizure burden in patients that
have become refractory to medical
management.
CRediT AUTHORSHIP CONTRIBUTION
STATEMENT
Joshua D. Bernstock: Writing - original
draft, Writing - review & editing. Hannah
E. Olsen: Writing - original draft, Writing
- review & editing. David Segar: Writing -
original draft, Writing - review & editing.
Kevin Huang: Writing - original draft,
Writing - review & editing. Ari D. Kappel:
Writing - original draft, Writing - review &
editing. Walid Ibn Essayed: Writing -
original draft, Writing - review & editing.
Phillip L. Pearl: Writing - original draft,
Writing - review & editing. Joseph R.
Madsen: Writing - original draft, Writing -
review & editing.
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Conflict of interest statement: J. D. B. has positions and
equity in CITC Ltd, Treovir LLC, and Avidea Technologies and
is on the scientific board of advisors for POCKiT Diagnostics.
Received 9 May 2020; accepted 30 June 2020
Citation: World Neurosurg. (2020) 142:450-455.
https://doi.org/10.1016/j.wneu.2020.06.230
Journal homepage: www.journals.elsevier.com/world-
neurosurgery
Available online: www.sciencedirect.com
1878-8750/$ - see front matter ª 2020 Elsevier Inc. All
rights reserved.
455