Seizure 22 (2013) 320–323

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Case report

Early total corpus callosotomy in a patient with cryptogenic West syndrome

a, b b b c c

Yuka Suzuki *, Hiroshi Baba , Keisuke Toda , Tomonori Ono , Mika Kawabe , Mitsumasa Fukuda

Graduate School of Medicine Ehime University, Community Emergency Medicine, Japan

National Hospital Organization Nagasaki Medicine Center, Neurosurgery Department, Japan

Graduate School of Medicine Ehime University, Pediatrics Department, Japan

A R T I C L E I N F O

2. Case

Article history:

Received 26 September 2012

An 8 month-old boy was referred to our hospital following the

Received in revised form 9 January 2013

appearance of repetitive spastic movements. He was born

Accepted 11 January 2013

naturally at 38 weeks of gestation with no complications and

Keywords: reached all developmental milestones until 7 months-old. About

Cryptogenic West syndrome one week before referral he started having clusters of 5–7 sudden,

Corpus callosotomy

brief spastic movements, during which he dropped his head and

Epilepsy surgery

raised both arms. He became unable to sit and lost his smile. His

interictal waking and sleep EEG showed typical hypsarrhythmia

consisting of random high-voltage slow waves and spikes. His ictal

1. Introduction EEG showed voltage attenuation superimposed with bursts of low

voltage, fast activity that was often contaminated with movements

West syndrome is a generalized epileptic syndrome of infancy, artifacts (Fig. 1A). MRI showed no abnormalities and other tests

that is characterized by clinical spasms and hypsarrhythmia and were also within normal limits.

usually has an onset age before two years old. Children affected by The patient was diagnosed with cryptogenic West syndrome.

West syndrome have a high risk of severe psychomotor After VitB6 administration (40 mg/kg/day), adrenocorticotrophic

developmental delay. Infants with West syndrome without hormone (ACTH) (0.0125 mg/kg/day = 0.5 IU/kg/day) was started.

identiﬁcation of underlying neurological disorder after adequate Because of several series of epileptic spasms, ACTH dosage was

investigations are classiﬁed as ‘‘cryptogenic’’ and usually have increased to 0.025 mg/kg/day and valproic acid (VPA) (40 mg/kg/

better prognoses than children with ‘‘symptomatic’’ West syn- day; serum concentration 80 mg/dl) was added. Seizures ceased

drome. Early seizure cessation, particularly among cryptogenic completely after ﬁve days and an EEG showed age-appropriate

cases, may cure the disease and allow a good neurodevelopmental background activity without any epileptiform discharges. At one

outcome. year old, the patient started having a series of similar epileptic

Corpus callosotomy was ﬁrst introduced as a palliative spasms and he again showed developmental regression. His EEG

treatment for epilepsy in 1940 and is performed in patients showed typical hypsarrhythmia, but MRI and interictal and ictal

whose seizures are not amenable to surgical focal resection. West ECD-single photon emission computed tomography (SPECT)ﬁnd-

syndrome is often medically intractable and has features of ings were unremarkable (Fig. 2A-1). Increasing the VPA dose

‘‘generalized’’ epilepsy, but corpus callosotomy has not been (serum concentration 120 mg/dl), nitrazepam, zonisamide, and

discussed widely as a treatment strategy. Given the catastrophic lamotrigine were all tried with no response.

nature of West syndrome, an early indication for total corpus At the age of 14 months, total callosotomy was performed at the

callosotomy may be appropriate. Here, we describe a case that was National Hospital Organization Nagasaki Medical Center. After

diagnosed as cryptogenic West syndrome, in which the epilepto- corpus callosotomy all spasms lateralized to the left side of the

genic focus was deﬁned after total corpus callosotomy. body. During seizures, he suddenly looked up and raised his left

arm. Ictal EEG showed polyspikes and waves followed by brief

voltage attenuation predominantly over the right hemisphere

(Fig. 1B). Interictally, polyspike-wave discharges were expressed in

the right fronto-central region. An ictal ECD-SPECT study

demonstrated hyperperfusion in the right frontal lobe (Fig. 2A-

2). Interictal FDG-positron emission tomography (PET) showed

* Corresponding author at: Graduate School of Medicine Ehime University,

hypometabolism in the right hemisphere (Fig. 2B). Based on these

Community Emergency Medicine, 454 Shitsukawa, Toon, Ehime 7910295, Japan.

localized ﬁndings, right frontal resection was performed two

Tel.: +81 89 9605930; fax: +81 89 9605485.

E-mail address: [email protected] (Y. Suzuki). months after corpus callosotomy. The resected lesion was

Y. Suzuki et al. / Seizure 22 (2013) 320–323 321

Fig. 1. (A) Example of an ictal EEG recorded during preoperative EEG-video monitoring. The ictal pattern is characterized by diffuse voltage suppression superimposed with

bursts of low voltage beta range activities. The EEG was recorded by 21 electrodes using the 10–20 system and is represented in monopolar reference. (B) Example of an ictal

EEG recorded during routine EEG-video monitoring after corpus callosotomy. The ictal pattern is characterized by high voltage polyspike wave discharges followed by brief

voltage attenuation over the right hemisphere. The EEG was recorded by 19 electrodes using the 10–20 system and is represented in monopolar reference. Arrowheads

indicate times at which an ictal event was noted by observers.

determined by intraoperative electrocorticography. Surgical speci- syndrome, and led to successful surgical lesional resection.

mens showed preserved cortical lamination and prominent gliosis Surgical treatment for symptomatic West syndrome is effective

in the subcortical areas. Subsequently, he has been seizure-free for for controlling seizures and cessation of spasms, and early surgery

three years. for catastrophic epilepsy such as West syndrome has been shown

Before corpus callosotomy at 16 months old his developmental to have positive effects on developmental outcomes. Structural

age was 10 months, he had no language, showed autistic behavior, abnormalities also strongly inﬂuence the prognosis in patients

1,3

and his developmental quotient (DQ) was 62.5 on the Kinder Infant with West syndrome. Therefore, the importance of evaluation to

Development Scale. Six months after surgery, his behavior clearly determine resectable epileptogenic lesions in medically intracta-

changed and he was able to sit still for 30 min watching TV, speak ble West syndrome cannot be stressed enough.

several words, and follow simple verbal commands, although the Corpus callosotomy is most effective in patients with atonic

DQ was only 66.7. Post surgically, he showed ‘‘catch-up’’ seizures with drop attacks, and has not been established as a

developmental progress, and his DQ improved to 72.7, 80.4, and standard surgical strategy for cryptogenic West syndrome. Clear

81.8 yearly over three years. At his current age of 4 years 7 month improvements with corpus callosotomy also occur for other types

old, 3 years after surgery, his language is beyond the telegraphic of seizures, such as tonic seizures and secondarily generalized

4 5

stage with some Japanese grammatical errors. seizures. Pinard et al. ﬁrst reported seizure reductions and

developmental improvements in patients with post-West syn-

3. Discussion drome after corpus callosotomy. Baba and colleagues performed

early total corpus callosotomy in patients with West syndrome

Total corpus callosotomy revealed previously unperceivable without a clear resectable region, of whom 75% showed signiﬁcant

seizure foci in our patient diagnosed with cryptogenic West developmental improvement during three-year follow-up.

322 Y. Suzuki et al. / Seizure 22 (2013) 320–323

Fig. 2. (A-1) Interictal ECD-single photon emission computed tomography (SPECT) performed prior to corpus callosotomy. Perfusion is symmetrically distributed without

localizing ﬁndings. (A-2) Ictal and interictal ECD-SPECT after corpus callosotomy. Ictal ECD-SPECT showed hyperperfusion in the right frontal region (arrowheads) and

interictal ECD-SPECT showed hypoperfusion in a similar region (small arrows). (B) Interictal FDG-positron emission tomography (PET). Interictal FDG PET showed cortical

hypometabolism (large arrows) in right frontotemporal regions.

Patients with generalized epilepsy persisting after West syndrome Prior to corpus callosotomy, neither interictal and ictal EEG nor

can also beneﬁt from complete callosotmy. These ﬁndings suggest neuroimaging indicated a localized epileptic focus in our patient. It

that corpus callosotomy may ameliorate frequent generalized or was only after disconnecting the corpus callosum that a conﬁned

rapidly secondarily generalized seizures in West syndrome. epileptic focus was deﬁned. Prior to corpus callosotomy, clinical

Traditionally, anterior two-thirds or total corpus callosotomy presentation, EEG, interictal SPECT, and MRI all pointed to

have been performed. Comparing these methods, total callosotomy cryptogenic West syndrome. We did not perform ictal SPECT or

showed better seizure reduction in patients after West syndrome, PET and it is possible that these studies might have deﬁned a

whereas only one of 13 patients after West syndrome beneﬁted localized focus without corpus callosotomy, and that lesionectomy

from anterior callosotomy and 12 required additional second stage itself would have been sufﬁcient to control the seizures. Surgical

surgery. Spencer reported that seizure types including tonic, specimens revealed prominent white matter gliosis and preserved

atonic, and generalized tonic–clonic are markedly decreased or cortical structures, and MRI may not detect this kind of dysplastic

totally eliminated in 80–90% of patients after total corpus callosum area. Pinard et al. found that bilateral hypsarrhythmia in West

disconnection, but in 50% or less after partial resection. Thus, syndrome patients altered after total corpus callosotomy to

patients with post-West syndrome showed better seizure control become unilateral hypsarrhythmia with asymmetrical spasms.

and behavioral improvement without disconnection syndrome Three patients with medically intractable frequent generalized

after total and two-staged total corpus callosotomy, compared seizures were shown to have a regional ictal zone after corpus

5,8 5

with anterior resection. callosotomy. Thus, an absence of localized ﬁndings in EEG and

Our patient showed a good ﬁrst response to the standard dose of neuroimaging does not imply the absence of epileptic foci in some

ACTH. Therefore, he was a good candidate for a second course of patients, and we recommend though preoperative work-up

ACTH therapy. However, patients who relapse after the ﬁrst course including interictal SPECT or PET.

9,10

of ACTH therapy often show re-relapse after a second course. The pathophysiology of developmental comorbidities in West

Seizure recurrence with as short an interval as that in our patient syndrome has not been well established. It is also unclear whether

strongly suggested medically intractable seizures and the early intervention and seizure cessation can prevent developmen-

effective treatment window for West syndrome is limited because tal regression. Several studies have shown that a short treatment

of its age dependency. Furthermore, a second course of ACTH can lag is correlated with a more favorable developmental outcome in

be given after surgery, if necessary. For all of these reasons, we patients with both symptomatic and cryptogenic West syn-

1,12

selected one-step total corpus callosotomy for treatment of drome. Some recommend early surgery before development

1,6,12

relapsed spams, so as not to lose the treatment window. Total of severe psychomotor delay. Our patient showed dramatic

corpus callosotomy was performed without major sequelae or behavioral changes and began to speak some words several

neurological deﬁcits. months after surgery. This observation supports the view that early

Y. Suzuki et al. / Seizure 22 (2013) 320–323 323

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