Susumu Miyake

A screening test for the prediction of Dravet syndrome before one year of age.

Purpose: Our aim was to develop a screening test to predict Dravet syndrome before the first birthday based on the clinical characteristics of infants and the SCN1A mutation analysis.

Treatment of the Lennox syndrome with ACTH: a clinical and electroencephalographic study.

In 45 cases of Lennox syndrome treated with ACTH, the immediate and long-term effects and the various factors affecting them were investigated by a follow-up study. 1) Regarding the immediate effect, 23 (51.1%) of the 45 cases became seizure free for over 10 days. 2) As to the long-term prognosis of these 23 cases, 10 cases relapsed into Lennox syndrome within 6 months and in the remaining 13 cases, seizures were suppressed for over 6 months; out of these 13, seizure relapse was observed in eight cases from 9 months to 7 years later, and the other five cases followed a very favorable course without relapse. 3) The favorable factors related to the effect of ACTH for Lennox syndrome are: a) age at ACTH treatment: up to 4 years old, b) time lag between onset of Lennox syndrome and initiation of ACTH treatment: the shorter the better; at least within 1 year, preferably within 3 months, c) presumptive causes and underlying diseases: idiopathic cases are best, d) mental defects before treatment: the slighter the better, e) seizure patterns: without tonic seizures, and f) EEG findings: disorganized diffuse slow spike-waves without asymmetry. 4) It is desirable to continue the ACTH treatment as long as possible, with the goal of the disappearance of seizure discharges, or at least the disappearance of diffuse seizure discharges.

Follow‐Up Study of Children with a History of a Febrile Convulsion.

Although adrenocorticotropic hormone (ACTH) has long been the therapy of choice in infantile spasms, frequent side effects occur during ACTH therapy. In addition, previous studies have shown a disappointing outcome in mental development in patients with symptomatic infantile spasms treated with ACTH. Therefore an improved treatment is required. We report the results of a new treatment for infantile spasms. Twenty-one patients (14 boys and seven girls, aged 4-31 months; mean, 9.8 months) who had symptomatic infantile spasms between November 1986 and October 1992 were enrolled in this study. The etiologic factors were perinatal asphyxia in four, neonatal intracranial hemorrhage in three, brain atrophy in three, brain infarction in one, purulent meningitis in one, encephalomeningocele in one, ectopic gray matter in one, phacomatosis in one, and unknown in six (patients with developmental delay before onset and no significant history). Initially, all of the patients were administered pyridoxal phosphate orally at a dosage of 20-30 mglkglday followed by an increase to 40-50 mglkglday. When seizures did not disappear completely, ACTH (zinc hydroxide suspension of tetracosactide) was then combined with pyridoxal phosphate. ACTH was administered at a dosage of 0.01 mglkg (0.4 IUIkg of natural ACTH) in daily injections for the first 2 weeks. The frequency of the injections was then gradually reduced over a 3to 6-week period. An excellent response was defined as total cessation of seizures at 1 month after discontinuation of ACTH. Pyridoxal phosphate therapy was continued as long as a good, sustained effect with the first course of ACTH was seen. If the infantile spasms recurred or the EEG returned to a hypsarrhythmic pattern (or both), a short course of ACTH therapy (0.01 mg/kg/day for 1 week) was added to the treatment regimen. If other antiepileptic drugs (AEDs) were required because of poor control or the occurrence of other types of seizures, follow-up was ended, and the final evaluation of developmental outcome was performed. Pyridoxal phosphate alone produced excellent seizure control in two of the 21 patients. ACTH was added to the regimen in 19 patients, excluding the two patients who had an excellent response to pyridoxal phosphate alone. At 1 month after discontinuation of ACTH, 15 (79%) of the 19 patients had excellent seizure responses. The mean interval until achievement of seizure control was 4.4 days. Outcomes have been monitored in 15 patients, excluding the two responders to pyridoxal phosphate alone and the four nonresponders to combination therapy. The mean follow-up time was 32.7 months (range, 2-104 months). Infantile spasms relapsed after a seizure-free period in six (40%) of the 15 patients. Normal development was observed in five (33%) of the 15 patients. Combination therapy seemed to provide a better outcome in mental development than has been observed in previous studies, in which development was normal in only 5-7% of patients with symptomatic infantile spasms. Moreover, our combination therapy stopped the spasms more rapidly than did other ACTH regimens. In view of these findings, vitamin B, may have played an important role in controlling seizures by as yet to be clarified mechanisms. In addition, it has been shown that ACTH itself may have an adverse effect on the developing brain. Thus it is reasonable to recommend that the dose of ACTH be minimized to avoid potential risk to the developing brain. At present, in view of its therapeutic efficacy and low total ACTH dose, combination therapy with high-dose pyridoxal phosphate and low-dose ACTH should be regarded as the best available method of treating infantile spasms.

A Case with Absence Seizures After Neuroimaging Changes of Rasmussen Syndrome

Case Report The patient was a 5 year and 5 month‐old boy. A brother had a history of febrile convulsions. The patient was born after 38 weeks of pregnancy, birth weight 3,260 g. The neonatal period was uneventful. His development was normal until 1 year and 3 months of age, after which he suffered generalized tonic seizures 2–3 times per year. Episodes of unconsciousness as often as ten times per day began at 5 years of age. Brain MRI, performed at 2 years of age, was normal. EEG revealed spikes from the right mid‐temporel and right central regions and diffuse irregular spike and waves at 4 years of age. Cryptogenic localization‐related epilepsy was diagnosed and treated with phenobarbital, carhamazepine, valproic acid, and acetazolamide without control of his convulsions. After 5 years of age, he began losing consciousness approximately 10 times per day. At 5 years and 5 months of age, he had fever, cough, rhinorrhea, and 2 generalized tonic‐clonic convulsions for about 2 minutes and subsequently generalized tonicclonic convulsive status epilepticus for 30 minutes. He was admitted to Kagawa Prefectural Central Hospital. At admission, his consciousness score was 200 points (JCS) and he had intermittent clonic convulsions of the right hand and face. He also exhibited right hemiplegia. Partial seizures continued for about 2 weeks, Blood examination revealed CRP of 1.4 mg/dl, with negative antibody titers for herpes simplex and EB virus. CSF findings were normal. At 6 days of admission, T2‐weighted brain MRI studies revealed high density i n the gray matter in the left hemisphere. After 2 months of hospitalization, MRI revealed remarkable left hemispheric atrophy. Two SPECT studies done at an interval of 2 months disclosed hyperperfusion of the left hemisphere. These findings were considered compatible with Rasmussen syndrome. At admission, the EEG revealed left high‐voltage slow wave activity and frequent spikes in the left anterior temporal region. After 4 months of hospitalization, tonic‐clonic convulsions occurred once per month. After 8 months of hospitalization, episodes of unconsciousness occurred 10 times per day. The ictal EEG revealed diffuse right hemisphere dominant 3isecond spike and wave bursts, which were induced by hyperventilation. Ethosuximide completely controlled these episodes and also improved EEG findings.