Kaoru Imai

Clinical spectrum of early onset epileptic encephalopathies caused by KCNQ2 mutation.

KCNQ2 mutations have been found in patients with benign familial neonatal seizures, myokymia, or early onset epileptic encephalopathy (EOEE). In this study, we aimed to delineate the clinical spectrum of EOEE associated with KCNQ2 mutation.

Study on the Early-Onset Variant of Benign Childhood Epilepsy with Occipital Paroxysms Otherwise Described as Early-Onset Benign Occipital Seizure Susceptibility Syndrome

Summary: Purpose: We studied the early‐onset variant of benign childhood epilepsy with occipital paroxysms (EVBCEOP) proposed by Panayiotopoulos, to confirm whether his five criteria are sufficient to delineate EVBCEOP as a new epileptic syndrome, as well as to predict a good outcome prospectively at the time of the first examination.

STXBP1 mutations cause not only Ohtahara syndrome but also West syndrome—Result of Japanese cohort study

We performed STXBP1 mutation analyses in 86 patients with various types of epilepsies, including 10 patients with OS, 43 with West syndrome, 2 with Lennox‐Gastaut syndrome, 12 with symptomatic generalized epilepsy, 14 with symptomatic partial epilepsy, and 5 with other undetermined types of epilepsy. In all patients, the etiology was unknown, but ARX and CDKL5 mutations were negative in all cases. All coding exons of STXBP1 were analyzed by direct‐sequencing. Two de novo nucleotide alterations of STXBP1 were identified in two patients with Ohtahara and West syndrome, respectively. No de novo or deleterious mutations in STXBP1 were found in the remaining 84 patients with various types of symptomatic epilepsies. This is the first case report showing that STXBP1 mutations caused West syndrome from the onset of epilepsy. STXBP1 analysis should be considered as an etiology of symptomatic West syndrome without explainable cause.

A comparative study of high-dose and low-dose ACTH therapy for West syndrome

PURPOSE A prospective randomized controlled study was conducted for the purpose of identifying the lowest effective ACTH dose, with the fewest adverse effects, for the treatment of West syndrome (WS). SUBJECTS AND METHODS Twenty-five subjects with cryptogenic (CWS, n = 9) or symptomatic (SWS, n = 16) WS were enrolled in this study. They were randomly assigned to receive either low-dose (0.005 mg/kg per day = 0.2 IU/kg per day) or high-dose (0.025 mg/kg per day = 1 IU/kg per day) synthetic ACTH therapy. ACTH was administered every morning for 2 weeks and tapered to zero over the subsequent 2 weeks. Both effectiveness and adverse effects were compared between the two treatment regimens in each type of WS. RESULT After completion of the treatment protocol in the CWS group, spasms and hypsarrhythmia were completely suppressed in 3/4 (75%) given the low-dose and 5/5 (100%) given the high-dose treatment. In the SWS group, the spasms and hypsarrhythmia disappeared in 6/8 (75%) in each dose group. There were no significant differences in initial responses between the low-dose and high-dose treatments for either type of WS (P > 0.05). Long-term seizure and developmental outcomes, assessed in the 17 responders who were followed up for longer than 1 year after the completion of ACTH therapy, were also essentially the same. We did not recognize differences in side effect profiles between the two treatment regimens with the exceptions of sleepiness and brain shrinkage estimated by CT scan, both of which were significantly milder in the low-dose than in the high-dose group (P < 0.05). CONCLUSION Unexpectedly, this prospective randomized controlled study demonstrated the dose of ACTH required for spasm cessation and disappearance of the hypsarrhythmic EEG pattern to be lower than previously believed. A low-dose regimen should thus be considered for CWS, and for SWS associated with significant cerebral atrophy.

EEG in Children with Early‐onset Benign Occipital Seizure Susceptibility Syndrome: Panayiotopoulos Syndrome

Summary:  Purpose: We analyzed sequential changes in the localization of EEG foci along with age to identify a specific EEG pattern, and the relation between the clinical manifestations and the EEG pattern in patients with Panayiotopoulos syndrome (PS).

CDKL5 alterations lead to early epileptic encephalopathy in both genders

Purpose:  Genetic mutations of the cyclin‐dependent kinase‐like 5 gene (CDKL5) have been reported in patients with epileptic encephalopathy, which is characterized by intractable seizures and severe‐to‐profound developmental delay. We investigated the clinical relevance of CDKL5 alterations in both genders.

Rasmussen Syndrome: Multifocal Spread of Inflammation Suggested from MRI and PET Findings

Summary:  Background: A 6‐year‐old girl with Rasmussen syndrome (RS) showed multiple small high‐signal‐intensity areas independently in the right hemisphere by fluid‐attenuated inversion recovery (FLAIR) imaging on magnetic resonance imaging (MRI) 1 year after the onset of epilepsy.

Differentiation of myoclonic seizures in epileptic syndromes: a video-polygraphic study of 26 patients.

Objective:  We conducted a video‐polygraphic study of myoclonic seizures (MS) in different epileptic syndromes to clarify semiologic and electroencephalography (EEG) differences among them.

Extremely low-dose ACTH step-up protocol for West syndrome: Maximum therapeutic effect with minimal side effects

We studied the effectiveness of our new ACTH treatment strategy for West syndrome (WS), which was based on the results of our previous extremely low-dose ACTH study. The subjects were 31 infants with WS (cryptogenic WS in nine; symptomatic WS in 22). Synthetic ACTH-Z in a dose of 0.005 mg (= 0.2 IU)/kg/day was injected once every morning for at least 2 weeks, up to a maximum of 3 weeks. When this first treatment course achieved full seizure and EEG control, ACTH was tapered to zero over the subsequent 1 or 2 weeks. In the absence of a documented response, the dosage was increased to 0.025 mg (= 1.0 IU)/kg/day for the next 2 weeks (second treatment course). We analyzed the short-term as well as long-term effects, and the incidence of side effects. The first treatment course successfully controlled both spasms and hypsarrhythmia in 17 patients (55%), only spasms in one, and hypsarrhythmia in two. The second treatment course was then introduced in eight of the remaining 14 patients, providing complete suppression of WS in an additional two patients. Regarding the long-term effects, 13 patients (48%), with excellent short-term results and a longer than 1-year follow-up, remained seizure-free. Side effects of a mild degree were seen in 13 patients during ACTH treatment. Our new ACTH step-up method brought 61 and 48% of the patients into short-term and long-term remission, respectively, without significant side effects. The dose of ACTH required to control WS appears to be unexpectedly smaller than the dose we previously used.

Zonisamide for West syndrome: a comparison of clinical responses among different titration rate

We administered zonisamide (ZNS) to patients with West syndrome in different titration protocols and compared their short-term therapeutic effects. We designed three protocols to raise the serum ZNS concentration (SZC): (1) increase the dose in three steps, from 3 to 10 mg/kg every 3 days, (2) increase the dose from 5 to 10 mg/kg over 3-7 days, and (3) start with 10 mg/kg and maintain this dosage for 2 weeks. The subjects were 23 infants with West syndrome, 8 of whom comprised the 1st group, 5 the 2nd group, and the remaining 10, the 3rd group. As a result, excellent and good effects were obtained in a total of seven patients (30.4%) and one patient, respectively (1/8 in the 1st step-up group, 3/5 in the 2nd step-up group, and 4/10 in the 3rd group). The maximum SZC was higher in the excellent and good effect groups (n=8; 32.0+/-8.0 microg/ml) than in the ineffective group (n=15; 22.4+/-8.2 microg/ml) (P<0.05). The period of time required for cessation of spasms appeared shorter in the 3rd group (n=4; mean=5.7 days) than in the 1st and 2nd groups (n=4; mean=10.3 days). There were few side effects except for transient hyperthermia and gastrointestinal symptoms. Our new protocol of starting with 10 mg/kg of ZNS can be introduced safely and make a therapeutic judgment feasible within 2 weeks.