村松 一洋

OBJECTIVE: The early diagnosis of beta-propeller protein-associated neurodegeneration (BPAN) before distinct brain magnetic resonance imaging (MRI) findings of iron deposition occur remains challenging. This study examined whether children with BPAN have characteristic high-amplitude (>50 μV) fast activity (HAFA) on electroencephalography (EEG). METHODS: We conducted a retrospective analysis of EEG performed during childhood in five patients with BPAN. We also examined 143 EEGs from 59 patients with different etiologies, including epilepsy (n = 33), acute encephalopathy (n = 6), neurodevelopmental disorders (n = 5), non-epileptic events (n = 4), and others (n = 11). Trained electroencephalographers reviewed all of the EEGs. When excessive fast activity was observed, the amplitude, frequency, and locality were assessed. RESULTS: All five patients with BPAN underwent initial EEGs at 12-21 months old, and diffuse continuous HAFA (range 20-50 Hz) was observed on both awake and sleep EEGs. In the awake records, there was no clear posterior dominant rhythm in 4 of the 5 patients. Although 28% of the 143 EEGs had continuous excessive fast activity, mainly in the sleep records, only two (1.4%) exhibited HAFA when asleep, and their awake EEGs had clear posterior dominant rhythm. CONCLUSIONS: The EEGs of children with BPAN showed diffuse HAFA continuously when both awake and asleep, which is uncommon in children with other etiologies. SIGNIFICANCE: This study provides an important clue for the early diagnosis of BPAN.

Ring chromosome 20 syndrome is an epileptic and neurodevelopmental encephalopathy that occurs in children, characterised by a triad of refractory frontal lobe seizures, recurrent non-convulsive status epilepticus and frontal lobe-dominant paroxysmal discharges. However, details of other clinical features associated with ring chromosome 20 syndrome remain unknown. Here, we report two patients with ring chromosome 20 syndrome who had praxis-induced reflex seizures. Case 1 was an 11-year-old girl who presented with seizures triggered by specific activities such as mental and written calculations, writing, decision-making, recall, sudden changes in routine or ambient temperature and bathing. During calculations, left frontal lobe-dominant, 3-Hz slow-wave bursts were observed on EEG. Lacosamide effectively suppressed her tonic seizures. Case 2 was a six-year-old boy who presented with seizures triggered by specific activities such as calculations, recall and bathing. During calculations, frontal lobe-dominant, 3-Hz spike and slow-wave bursts were observed on EEG. Although his epilepsy was refractory, gabapentin reduced the frequency of focal seizures. In both cases, the hyperexcitability in the frontal lobe may have spread to the motor cortex and precipitated praxis-induced seizures. Therefore, in addition to the known characteristic triad, praxis-induced reflex seizures may also be a feature of ring chromosome 20 syndrome.

Lacosamide (LCM) is a novel class of anti-epileptic drug that selectively promotes slow inactivation of the sodium channel. Case studies, including pediatric cases, have not been described in Japan. We examined the efficacy and side effects of LCM in Japanese epilepsy patients, including those under 16 years old. Responders were defined when seizures were reduced by more than 50%. The responder rate for overall seizure was 40%. There were no significant differences in efficacy by seizure types or age (&lt 16 or ≥16 years old). Among epilepsy types, the efficacy in patients with focal epilepsy (17/39) was higher than in generalized epilepsy (0/8) (p=0.0045). Patients with ≤2 AEDs had significantly higher efficacy (16/27) than those with ≥3 AEDs (8/33) (p=0.0055). In patients with concomitant AEDs, LTG (2/16) and PER (0/10) were significantly less effective than other drugs (LTG: p=0.0055, PER: p=0.0007). Although adverse effects occurred in 23% of pa- tients, including somnolence 20%, dizziness 5%, agitation 2%, there was no significant difference by age (&lt 16 and ≥16 years). Our study suggests that LCM is effective focal-epilepsy patients especially those with ≤2 concomitant AEDs. Studies of more cases with long-term observation are needed to establish the role of LCM in childhood epilepsy treat- ment.

<title>Abstract</title> Idiopathic restless legs syndrome (RLS) has a genetic basis wherein <italic>BTBD9</italic> is associated with a higher risk of RLS. Hemodialysis patients also exhibit higher rates of RLS compared with the healthy population. However, little is known about the relationship of <italic>BTBD9</italic> and end-stage renal disease to RLS pathophysiology. Here we evaluated sleep and leg muscle activity of <italic>Btbd9</italic> mutant (MT) mice after administration of serum from patients with either idiopathic or RLS due to end-stage renal disease (renal RLS) and investigated the efficacy of treatment with the dopamine agonist rotigotine. At baseline, the amount of rapid eye movement (REM) sleep was decreased and leg muscle activity during non-REM (NREM) sleep was increased in MT mice compared to wild-type (WT) mice. Wake-promoting effects of rotigotine were attenuated by injection of serum from RLS patients in both WT and MT mice. Leg muscle activity during NREM sleep was increased only in MT mice injected with serum from RLS patients of ideiopatic and renal RLS. Subsequent treatment with rotigotine ameliorated this altered leg muscle activity. Together these results support previous reports showing a relationship between the Btbd9/dopamine system and RLS, and elucidate in part the pathophysiology of RLS.

INTRODUCTION: Neuronal ceroid lipofuscinoses (NCLs; CLN) are mainly autosomal recessive neurodegenerative disorders characterized by the accumulation of autofluorescent lipopigments in neuronal and other cells. Symptoms include visual disabilities, motor decline, and epilepsy. Causative genes are CLN1, CLN2, CLN3, CLN5, CLN6, CLN7, CLN8, CLN10, CLN11, CLN12, CLN13, and CLN14. We present the fourth Japanese case with a CLN6 mutation. CASE PRESENTATION: At 3 years of age, our patient became clumsy and fell down easily. He developed focal seizures with impaired consciousness and was started on carbamazepine. He showed ataxic walking and dysarthria with increased deep tendon reflexes. Interictal electroencephalogram revealed slow waves in the left temporal and occipital areas. Brain magnetic resonance imaging showed cerebellar atrophy and ventriculomegaly. In optical coherence tomography (OCT), the inner layer of the retina was thick and highly reflective. Exome sequencing revealed a known homozygous mutation, C.794_976del, p. (Ser265del) in CLN6. DISCUSSION: A total of 130 cases of NCL with CLN6 mutations have been reported globally, of which only four were from Japan including the current patient. The deletion of serine at position 265 has been reported in six cases. Ser265 is located in a region of short repeated sequences that is susceptible to mutation. Clinical trials of gene therapy using adeno-associated virus serotype 9 have started for NCL6, making early diagnosis crucial. OCT examination might be helpful in achieving a diagnosis.

Objective: Drug sedation for examination and treatment, as well as for magnetic resonance imaging, is commonly performed in pediatric patients, and “a Co-proposal on sedation at the time of MRI examination”has been published. The Medical Safety Committee of the Japan Pediatric Neurology Association aims to prepare guidelines for sedation during electroencephalography. As a preliminary step to preparing guidelines, a questionnaire survey was conducted to investigate the current status of sedation during electroencephalography. Methods: A web questionnaire was conducted among 1,118 full-time pediatric neurologists in FY 2015, and information on drug sedation for electroencephalography in children under 15 years old was obtained. We asked about drugs and dosages used for sedation, oral intake restriction, monitoring, criteria for discharge home, and adverse events. Results: We obtained responses from 179 physicians（16.0%）. A total of 28,390 cases underwent electroencephalography by 163 physicians. A total of 13,829 cases underwent electroencephalography with drug sedation by 157 physicians. Trichlorophos sodium was used by 151 physicians（96.2%）, and 125（79.6%）used chloral hydrate. Three cases（0.02%）of adverse events were reported, with 2 cases of trauma due to unstable gait and 1 case of respiratory arrest. Conclusions: We could not determine overall usage because of the low response rate, but this is the first report to evaluate the safety of sedation based on physiological examination. Although sedation for electroencephalography is safe compared with that for MRI, careful monitoring and preparation for emergencies is necessary.

Objective: This survey aimed to determine the current usage and adverse events associated with intravenous（IV）anticonvulsants, to better understand their safety profile. Methods: We issued web-based questionnaires to 1,118 pediatric neurologists in Japan to gather information on IV anticonvulsant usage at the time of convulsions and associated adverse events in children younger than 15 years in 2015. Results: Out of the 145 respondents（13.0% response rate）, 2,355 events associated with IV anticonvulsants were reported by 86 pediatric neurologists. The majority of the injections comprised midazolam（MDL）, diazepam（DZP）, and fosphenytoin（FOS）. For drugs administered for off-label use, DZP enema（22 cases）, intranasal MDL（50 cases）, MDL IV infusion for children younger than 45 weeks after correction for gestational age（26 cases）, FOS IV infusion for children younger than 2 years（72 cases）, and thiopental/thiamylal IV infusion （128 cases）were reported. There was one adverse event that led to respiratory arrest and 24 cases of other adverse events for which patients required intensive care and intervention. Conclusions: Including off-label usage, a large proportion of IV anticonvulsants was safely administered however, adverse events occurred in some cases. As most IV anticonvulsants are administered to patients with status epilepticus, not all the adverse events may be related to the anticonvulsants, and the rapid responses that occurred after the convulsions themselves may be included however, more attention should be paid to emergency treatment.

© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Genetic abnormalities in mitochondrial complex assembling factors are associated with leukoencephalopathy. We present a 1-year-old girl with consciousness disturbance after a respiratory infection. Brain MRI revealed leukoencephalopathy with bilaterally symmetrical hyperintensity in the substantia nigra, medial thalamic nuclei, and basal nuclei, as well as cavities in the cerebral white matter and corpus callosum. Lactate levels in the spinal fluid were high, while magnetic resonance spectroscopy of the cerebral white matter and basal nuclei showed high peak lactate levels, suggesting mitochondrial dysfunction. The respiratory enzyme activity of complex I was reduced to 17% to 21% in skeletal muscle. Whole exome sequencing identified compound heterozygous variations in NDUFAF3, involved in the assembly of mitochondrial complex I (c.342_343insGTG:p.117Valdup, c.505C > A:p.Pro169Thr). Two-dimensional, blue-native polyacrylamide gel electrophoresis (PAGE) and sodium dodecyl sulfate-PAGE revealed reductions in Q-module (NDUFS2, NDUFS3, and NDUFA9) and P-module (NDUFB10 and NDUFB11) subunits, indicating disruption of mitochondrial complex I assembly. Our report expands the spectrum of clinical phenotypes associated with pathogenic variants of NDUFAF3.

Herein we report the case of a 6-year-old girl with autism spectrum disorder (ASD) and weakness in the distal portion of the right upper limb. Although difficult to perform, nerve conduction studies indicated demyelinating neuropathy. Magnetic resonance imaging (MRI) showed swelling a nd high-intensity signals in the right brachial plexus and cervical spinal roots. The symptoms recovered after a single course of i.v. immunoglobulin. Electrophysiological indices and MRI findings also improved after treatment. This case demonstrates the utility of neuroimaging in addition to electrophysiological assessments for the diagnosis of demyelinating neuropathy, particularly in young patients with ASD.

Introduction: Levetiracetam has a high tolerability and is effective against various seizure types and epilepsy syndromes. However, no study has specifically evaluated the efficacy of levetiracetam in children with refractory epilepsy based on magnetic resonance imaging (MRI) findings and the presence of intellectual disability (ID). Methods: We retrospectively evaluated levetiracetam efficacy and safety in 49 pediatric patients who met the following inclusion criteria: (1) diagnosis of refractory epilepsy with first-line antiepileptic (AED) treatment &gt;= 2 years, (2) younger than 20 years old, and (3) received oral levetiracetam treatment for &gt;= 6 months. We assessed the relationships of these outcomes with MRI findings and ID status. Results: Eighteen (37%) patients achieved a &gt;= 50% reduction in seizure frequency, and the majority (78%) had no remarkable side effects. Twenty-two (45%) patients had previously been treated with more than seven antiepileptic drugs prior to levetiracetam. Among 18 patientg who achieved a 3 &gt;= 50% reduction in seizure frequency, 13 and 5 had negative and positive MRI findings, and 9 and 9 had and did not have ID, respectively. Conclusions: Our findings suggest that even for intractable pediatric cases with symptomatic etiology (i.e., MRI lesion and ID), levetiracetam has favorable efficacy for refractory epilepsy with tolerable adverse effects. (C) 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.