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 multilobar cortical dysplasia with intractable seizure: Clinical–neurophysiological study Masaya Kubota a,d, , Keiji Goishi a , Sachiko Takemura a , Kensuke Kawai b , Nobutaka Arai c a Department of Pediatrics, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, Japan b Department of Neurosurgery, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, Japan c Department of Clinical Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo, Japan d Department of Pediatrics, Metropolitan Hachioji Children’s Hospital, 4-33-13, Dai-machi, Hachioji, Tokyo 193-0931, Japan article info 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 abstract 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 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. ARTICLE IN PRESS 1090-3798/$ - see front matter & 2008 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.ejpn.2007.12.006 Corresponding author at: Department of Pediatrics, Metropolitan Hachioji Children’s Hospital, 4-33-13, Dai-machi, Hachioji, Tokyo 193-0931, Japan. Tel.: +81 42 624 2255x391; fax: +81 42 622 3048. E-mail address: [email protected] (M. Kubota). EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY 12 (2008) 516– 520

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ARTICLE IN PRESS

E U R O P E A N J O U R N A L O F PA E D I A T R I C N E U R O L O G Y 1 2 ( 2 0 0 8 ) 5 1 6 – 5 2 0

1090-3798/$ - see frodoi:10.1016/j.ejpn.20

�Corresponding a193-0931, Japan. Tel

E-mail address: m

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

[email protected]

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

ARTICLE IN PRESS

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.

E U R O P E A N J O U R N A L O F PA E D I AT R I C N E U R O L O G Y 1 2 ( 2 0 0 8 ) 5 1 6 – 5 2 0 517

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

ARTICLE IN PRESS

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)

E U R O P E A N J O U R N A L O F PA E D I A T R I C N E U R O L O G Y 1 2 ( 2 0 0 8 ) 5 1 6 – 5 2 0518

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

1. Sasaki M, Hashimoto T, Furushima W, Okada M, Kinoshita S,Fujikawa Y, et al. Clinical aspects of hemimegalencephaly bymeans of a nationwide survey. J Child Neurol 2005;20:337–41.

2. Jonas R, Nguyen S, Hu B, Asarnow RF, LoPresti C, Curtiss S,et al. Cerebral hemispherectomy: hospital course, seizure,developmental, language, and motor outcomes. Neurology2004;62:1712–21.

3. Holthausen H, Strobl K. Modes of reorganization of thesensorimotor system in children with infantile hemiplegiaand after hemispherectomy. Adv Neurol 1999;81:201–20.

4. Delalande O, Fohlen M, Jalin C, Pinard J-M. From hemispher-ectomy to hemispherotomy. In: Luders HO, Comair YG,editors. Epilepsy surgery. 2nd ed. Philadelphia: LippincottWilliams & Wilkins; 2001. p. 741–6.

5. Kawai K, Shimizu H, Delalande O. Comparison of varioussurgical procedures in hemispherotomy and a new modifica-tion. Epilepsia 2005;46(Suppl. 2):22.

6. De Rosa MJ, Secor DL, Barsom M, Fisher RS, Vinters HV.Neuropathologic findings in surgically treated hemimegalen-cephaly: immunohistochemical, morphometric, and ultra-structural study. Acta Neuropathol 1992;84:250–60.

7. Yasha TC, Santosh V, Das S, Shankar SK. Hemimegalence-phaly—morphological and immunocytochemical study. ClinNeuropathol 1997;16:17–22.

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E U R O P E A N J O U R N A L O F PA E D I A T R I C N E U R O L O G Y 1 2 ( 2 0 0 8 ) 5 1 6 – 5 2 0520

8. Mori H, Aoki S, Abe O, Hayashi N, Masutani Y, Ohtomo K, et al.Diffusion property following functional hemispherectomy inhemimegalencephaly. Acta Radiol 2004;45:778–81.

9. Maehara T, Shimizu H, Kawai K, Shigetomo R, Tamagawa K,Yamada T, et al. Postoperative development of children afterhemispherotomy. Brain Dev 2002;24:155–60.

10. Maehara T, Shimizu H, Shigetomo R, Tamagawa K. Functionalhemispherectomy for children aged 2 years or less for thetreatment of intractable epilepsy caused by cortical dysgen-esis. No To Hattatsu 2000;32:395–400.

11. Kakigi R. Ipsilateral and contralateral SEP componentsfollowing median nerve stimulation: effects of interferingstimuli applied to the contralateral hand. ElectroencephalogrClin Neurophysiol 1986;64:246–59.

12. Holloway V, Gadian DG, Vargha-Khadem F, Porter DA, Boyd SG,Connelly A. The reorganization of sensorimotor function inchildren after hemispherectomy. A functional MRI andsomatosensory evoked potential study. Brain2000;123:2432–44.