early hemispherotomy in a patient with multilobar cortical dysplasia with intractable seizure:...
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Official Journal of the European Paediatric Neurology Society
Case study
Early hemispherotomy in a patient with multilobarcortical dysplasia with intractable seizure:Clinical–neurophysiological study
Masaya Kubotaa,d,�, Keiji Goishia, Sachiko Takemuraa, Kensuke Kawaib, Nobutaka Araic
aDepartment of Pediatrics, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, JapanbDepartment of Neurosurgery, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, JapancDepartment of Clinical Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo, JapandDepartment of Pediatrics, Metropolitan Hachioji Children’s Hospital, 4-33-13, Dai-machi, Hachioji, Tokyo 193-0931, Japan
a r t i c l e i n f o
Article history:
Received 13 May 2006
Received in revised form
17 December 2007
Accepted 23 December 2007
Keywords:
Hemispherotomy
Multilobar cortical dysplasia
Hemimegalencephaly
Somatosensory evoked potentials
nt matter & 2008 Europe07.12.006
uthor at: Department of.: +81 42 624 2255x391; fax
a b s t r a c t
We present a patient with multilobar cortical dysplasia who underwent hemispherotomy, a
modified functional hemispherectomy, at the age of 2 months because of intractable
seizures and report the clinical–neurophysiological findings including EEG and somato-
sensory evoked potentials (SEP). After hemispherotomy, the seizures and EEG abnormality
disappeared completely and postoperative SEP showed an ipsilateral cortical response at
the unaffected hemisphere, suggesting a reorganization process, which was possibly
facilitated more intensively after surgery. Furthermore, developmental catch-up was
observed. Our patient’s clinical course and neurophysiological data suggested that very
early hemispherotomy resulted in not only the control of seizures but also a better
developmental outcome.
& 2008 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
1. Introduction
Hemimegalencephaly is a rare migration or hamartomatous
disorder characterized by overgrowth of part or all of a
cerebral hemisphere. Patients with this disorder show psy-
chomotor retardation, hemiparesis, and medically intractable
seizures. In children with hemimegalencephaly, early func-
tional hemispherectomy may result in remarkable seizure
reduction and also steady developmental progress.1 However,
Jonas et al.2 showed that patients with hemimegalencephaly
had the poorest prognosis for postoperative language and
motor status compared with other pathologic groups.
Holthausen et al.3 stated that age at surgery may play a
an Paediatric Neurology
Pediatrics, Metropolitan: +81 42 622 3048.
.jp (M. Kubota).
substantial role as long as myelination is incomplete in
patients, whose reorganization has not occurred due to the
underlying etiology. Because the report of very early hemi-
spherectomy under 2 months of age is scarce, there are
uncertainties in postoperative neurological functions in such
cases.
We herein present a patient with multilobar cortical
dysplasia that resembled hemimegalencephaly who under-
went hemispherotomy,4,5 a modified functional hemispher-
ectomy, at the age of 2 months because of intractable seizure
and report clinical–neurophysiological findings suggesting
CNS (central nervous system) reorganization during the
follow-up period.
Society. Published by Elsevier Ltd. All rights reserved.
Hachioji Children’s Hospital, 4-33-13, Dai-machi, Hachioji, Tokyo
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Fp1-F7
F7-T3
T3-O1
Fp1-C3
C3-P3
P3-O1
Fp2-C4
C4-P4
P4-O2
Fp2-F8
F8-T4
T4-O2
Preoperative EEG
1 sec
Fig. 2 – EEG before hemispherotomy showing left-sided
polyspikes and poor right-sided activity.
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2. Case report
The patient was born to non-consanguineous parents as a
dizygotic twin at 37 weeks of gestation by Cesarean section
without asphyxia. Her body weight was 2.3 kg at birth. The
family history was unremarkable and her sibling was healthy.
She was found to have hypoplasia of the left eyeball and cleft
lip and cleft palate. She had no skin lesions. Soon after birth,
she developed intractable myoclonic and tonic seizures of the
face and bilateral limbs with apnea that required intubation
and continuous infusion of midazolum (MDZ) or pentobarbi-
tal for the control.
Brain MRI (Fig. 1) showed a thick cortex and abnormal white
matter intensity with left frontal predominance, poor sulcal
formation of the left hemisphere, agenesis of the corpus
callosum and left ventricular dilatation. The third ventricle
also showed downward dilatation. In the right hemisphere,
the cortical and sulcal structures appeared to be normal.
As shown in Fig. 2, EEG showed a left-sided polyspike burst
and poor right-sided activity. In a long-term video EEG, almost
continuous high-voltage spikes and occasional seizure activ-
ity with rhythmical fast waves were observed exclusively
from the left hemisphere. The right hemisphere showed
neither independent spike discharges nor propagation spikes
from the left side. Based on the intractable seizures and
hemispheric anomaly on MRI, she was diagnosed as multi-
lobar cortical dysplasia and hydrocephalus. Because her
seizures were quite resistant to any medication including
Fig. 1 – MRIs before hemispherotomy showing left-sided
ventriculomegaly and a thick cortex in the left frontal area at
the age of 1 month (upper column), and CTs after
hemispherotomy and ventriculoperitoneal shunting at 10
months of age.
phenobarbital, valproate (VPA), MDZ and pentobarbital,
hemispherotomy 4,5 (a modified functional hemispherect-
omy) was performed at the age of 81 days. Preoperative
neurological examinations showed relatively hypotonic state
of extremities, weak tendon reflexes, minimal extremities
movement without laterality and no pathological reflexes.
The surgical procedure used in this case was a modification
of Delalande’s vertical hemispherotomy.4,5 It is ordinarily
composed of transventricular callosotomy and vertical dis-
connection of the projection fibers via a parasagittal corti-
cectomy but the callosal disconnection was not necessary in
this case because of her callosal agenesis. Through a small
frontal corticectomy, from which the pathological specimen
was sampled, the lateral ventricle was opened. Then the
projection fibers from the cortices to the diencephalon were
completely severed by starting the disconnection with
aspirating the posterolateral border of the thalamus, then
vertically disconnecting the lateral border of the thalamus by
following the choroid plexus anteriorly in the inferior horn,
and finally disconnecting the anterior border of the thalamus
by aspirating between the Monro’s foramen and the most
posterior point of the hippocampal head (anterior choroidal
point). The fornix was severed at the trigone of the lateral
ventricle. Thus, the anomalous left cortices had been
completely disconnected from the contralateral hemisphere
and the diencephalon.
Since the existence of hydrocephalus was strongly sug-
gested by the progressive increase in her head circumference
preoperatively (34 cm at birth and 41 cm at 1 month), we
placed an Ommaya reservoir from the left lateral ventricle
simultaneously with hemispherotomy. At this point, ventri-
culo-peritoneal shunt was not of choice because obstruction
of the system was highly probable after the surgical
procedures involving the ventricle. Follow-up imaging studies
revealed a gradually progressive enlargement of the left
lateral ventricle, which could not be explained only by the
postoperative atrophy of the left hemisphere because of the
mass effect to the contralateral hemisphere. Four months
after hemispherotomy, the Ommaya reservoir was exchanged
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postoperative SEP (somatosensory evoked potentials)
C4-Fz
C3-Fz
Lt Med. N. Stim.
Rt Med. N. Stim.
C4-Fz
C3-Fz
10ms
N20
iN20: ipsilateral N20
iN20
0 10 20 30 40
Latency (ms)
Fig. 4 – Postoperative (4 months after hemispherotomy)
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to a ventiriculo-peritoneal shunt. The variable pressure valve
of the system was set at 12 cm H2O. Although the size of the
left lateral ventricle was reduced and the mass effect
disappeared after this procedure, she became less active
and fed poorly. The follow-up CTs showed a progressive
enlargement of the right lateral and the third ventricles. Two
months after the placement of ventriculo-peritoneal shunt,
we placed the catheter into the right lateral ventricle
and connected it with the left ventricular catheter using a
Y-shaped connector. This time, postoperative course was
uneventful and she regained her activity. Postoperative EEG
showed no spike discharges at both hemispheres.
As shown in Fig. 3, a neuropathological study of the brain
specimen resected at surgery revealed clusters of small
dysplastic neurons and relatively large dysplastic neurons in
the intermediate to deep cortical layers. Loss of cortical
lamination and the heterotopic neurons in the white matter
was also observed. These findings were compatible with
histological features of multilobar cortical dysplasia including
hemimegalencephaly.6,7
As previously reported,8 the sequential analysis of diffusion
tensor imagings of our patient’s brain before and after surgery
showed that myelination gradually progressed on the un-
affected side of the posterior limb of the internal capsule,
whereas centrifugal degeneration of the tract occurred on the
affected side after surgery due to amputation of the neuro-
fibers.
At present (1 year of age), her developmental status
corresponds to 7–8 months of age in gross and fine motor
function and 5–6 months in mentality. She shows right-sided
mild spastic hemiplegia with mild palmar and planter grasp,
and good facial expression. She can reach each hand toward
an object almost equally. She can sit without help quite
steadily, but cannot crawl. Deep tendon reflexes are normally
induced without laterality. Ankle clonus and the Babinski
Fig. 3 – Neuropathology of the surgically resected brain specime
large dysplastic neurons (b, arrows) in the intermediate to deep
matter (c).
reflex are observed at the right foot. Sensory and autonomic
functions seem to be normal. Her seizures have completely
disappeared and no involuntary movement was currently
observed.
2.1. Postoperative somatosensory evoked potentials (SEP)recorded 4 months after hemispherotomy
The median nerve at the wrist was stimulated with a
constant-current pulse of 0.2 ms duration at a strength above
the motor threshold. The analysis time was 20 ms before and
60 ms after the stimuli. Two hundred trials were averaged.
As shown in Fig. 4, a clear N20 was observed in the
right hemisphere (unaffected side) by left median nerve
n showing clusters of small dysplastic neurons (a), relatively
cortical layers and the heterotopic neurons in the white
somatosensory evoked potentials elicited by median nerve
stimulation.
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stimulation, whereas only an ipsilateral response (iN20) was
observed in the right hemisphere by right median nerve
stimulation. The latency of N20 and iN20 was 19.2 and
21.7 ms, respectively. No reproducible responses were found
in the left hemisphere (affected side) by each median nerve
stimulation.
3. Discussion
MRI findings, intractable seizures after birth and neuropatho-
logy of the brain in our patient were compatible with
multilobar cortical dysplasia. Because of atypical features
such as thin cortex and the absence of corpus callosum in
our patient, we diagnosed our patient as not hemimegalen-
cephaly but multilobar cortical dysplasia. Multilobar cortical
dysplasia includes hemimegalencephaly and the treat-
ment for intractable seizures in both conditions might not
be so different. Following hemispherotomy, the seizures
completely disappeared and developmental catch-up was
observed. It seems beneficial for not only the control of
seizures but also the developmental outcome to perform
hemispherotomy for patients with hemimegalencephaly at
an early stage.1,9,10 The same story might be true for multi-
lobar cortical dysplasia.
Surprisingly, in postoperative SEP, ipsilateral N20 (at the
unaffected hemisphere) was elicited by right median nerve
stimulation, in addition to N20 by left median nerve stimula-
tion. The N20 of the SEP, the first cortical response, is
considered to be generated in the posterior bank of the
central sulcus (area 3b of the hand sensory cortex).
Usually, in the normal human brain, ipsilateral N20 is not
observed in median nerve stimulated SEP.11 In the case of
ipsilateral N20 appearance, it is believed to be volume-
conducted from the contralateral hemisphere, rather than
originating in the ipsilateral hemisphere.11 In our patient,
however, ipsilateral N20 appearance due to volume-conduc-
tion was excluded, because no definite N20 response was
elicited at the contralateral hemisphere (affected hemi-
sphere) by right median nerve stimulation. Because of
agenesis of the corpus callosum, ipsilateral N20 appearance
through transcallosal connections was also unlikely.11 Thus,
we consider that the ipsilateral N20 (at the unaffected
hemisphere) to right median nerve stimulation originated
through uncrossed ascending pathways. The ipsilateral N20
was longer in latency and smaller in amplitude than the N20
to right median nerve stimulation. These findings are
corresponding to the previous research.12 Although we could
not perform the SEP before surgery, the ipsilateral N20 reflects
the reorganization process, which was possibly facilitated
more intensively after surgery. Holloway et al.12 demon-
strated that median nerve stimulation study of the hemi-
plegic hand in children after hemispherectomy showed
reproducible early-latency ipsilateral SEP components in the
remaining sensorimotor cortex.
In addition to the uncrossed somatosensory pathway, an
uncrossed motor pathway from the right hemisphere func-
tions in the present patient, because she can reach both
hands toward an object almost equally. Investigation of
sensorimotor function in hemispherectomized patients pro-
vides an excellent opportunity to study responses through a
direct ipsilateral pathway. There are several possible reasons
why direct ipsilateral pathways may have become more
active in our patient: (1) strengthening of ipsilateral pathways
already present due to functional demand, (2) axonal sprout-
ing to allow a novel functional connection and (3) the absence
of transcallosal inhibitory influence. Because of agenesis of
the corpus callosum in our patient, the first or second
possibility seems to be plausible. In addition, another reason
for good outcome in our patient may be that abnormal
epileptogenic discharges originated from the affected hemi-
sphere had no harmful influence on the unaffected hemi-
sphere due to agenesis of the corpus callosum from
intrauterine stage.
The present case showed catch-up of psychomotor devel-
opment after surgery, and swelling of the unaffected hemi-
sphere was observed, though generally hemimegalencephaly
is known to have a poor long-term prognosis even after
successful surgery. This is the first report that reveals the
efficacy of very early hemispherotomy using SEP as well as
clinical improvement in a patient with multilobar cortical
dysplasia.
4. Conclusion
In this case with multilobar cortical dysplasia, very early
hemispherotomy (a modified functional hemispherectomy)
resulted in not only the control of seizures but also a
better developmental outcome. It might be possible that very
early hemispherotomy prevents the progress of epileptic
encephalopathy involving the bilateral hemisphere. A reorga-
nization process at the unaffected hemisphere was specu-
lated.
R E F E R E N C E S
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3. Holthausen H, Strobl K. Modes of reorganization of thesensorimotor system in children with infantile hemiplegiaand after hemispherectomy. Adv Neurol 1999;81:201–20.
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