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Purpose: This study aimed to elucidate the distribution of intracranial gamma-aminobutyric acid (GABA) receptors in patients with infantile epileptic spasms syndrome (IESS) of normal brain MRI findings using 123 I-iomazenil single-photon emission computed tomography (IMZ-SPECT)., Methods: This retrospective study compared IMZ-SPECT images from 20 patients with IESS of unknown etiology with normal brain MRI (unknown IESS group) and 23 patients with developmentally normal epilepsy of the same age (developmentally normal group). A three-dimensional stereotactic region of interest (ROI) template was used to divide the brain into 24 segments (left and right callosomarginal, precentral, central, parietal, angular, temporal, posterior cerebral, pericallosal, lenticular nucleus, thalamus, hippocampus, and cerebellum), and the mean accumulation of 123 I-iomazenil in each ROI was calculated. The IMZ ratio for each ROI was calculated by dividing the ROI count by the mean cerebellar count of the left and right sides for the same patient. IMZ ratios for 22 ROIs, excluding the cerebellum, between the unknown IESS group and the developmentally normal group were compared., Results: No significant differences were observed between the background characteristics of the unknown and developmentally normal groups. Hypsarrhythmia were observed in 16 patients in the IESS group. The IMZ ratio showed no significant differences between the two groups across all 22 ROIs., Conclusion: The IMZ ratio of the unknown IESS group was not significantly different from that of the developmentally normal group across the 22 ROIs, suggesting that GABA receptor distribution has little effect on epileptic spasms and hypsarrhythmia, and vice versa., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: Infantile epileptic spasms syndrome (IESS) often has a severe neurodevelopmental prognosis. However, few studies have examined the aspect of elementary school enrollment. This study evaluated elementary school enrollment after adrenocorticotropic hormone (ACTH) therapy in patients with IESS., Methods: We retrospectively evaluated the elementary school enrollment of patients with IESS who were administered ACTH at the Saitama Children's Medical Center between January 1993 and August 2024. We evaluated elementary school enrollment, seizure outcomes, motor development, and intellectual development at the time of school enrollment in the ACTH responder and nonresponder groups. Response was defined as complete remission of epileptic spasms and no other seizure occurrence from ACTH administration initiation until the age of 6 years., Results: In total, 116 patients (62 male) were included in this study. The median age at IESS onset was 5 (range, 0-24) months. Twenty-seven patients (23.3 %) maintained complete remission of epileptic spasms from ACTH initiation to elementary school enrollment. The responder group had a significantly higher rate of regular class attendance (48.1 %) and exhibited normal intelligence or developmental quotient (33.3 %) compared with the nonresponder group (p < 0.01 and p < 0.01, respectively). Patients with an unknown etiology were more likely to attend regular classes (37.5 %). The median age of the last hospital visit was 13 (6.0-24.4) years. Lennox-Gastaut syndrome was diagnosed in 5.2 % (6/116) of patients at the last visit., Conclusion: Our findings can help pediatricians predict elementary school enrollment and neurodevelopmental outcomes in patients with IESS receiving ACTH therapy., Competing Interests: Declaration of competing interest Shin-ichiro Hamano received funds from Daiichi Sankyo Co. Ltd., UCB Japan Co. Ltd., and Eisai Co. Ltd. Kenjiro Kikuchi received research funding from Syneos Health Clinical Co. Ltd. and Janssen Pharmaceutical K.K. The other authors declare that they have no conflicts of interest., (Copyright © 2024 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: We aimed to assess the effectiveness of vigabatrin (VGB) in patients diagnosed with infantile epileptic spasm syndrome (IESS) and categorize these patients based on their etiologies., Methods: This retrospective study included patients diagnosed with IESS who exhibited epileptic spasms before the age of 2 years between January 1, 2015, and October 31, 2023 at Saitama Children's Medical Center. Patients with tuberous sclerosis as the identified etiology were excluded. The effectiveness of VGB was assessed based on the resolution of ES for three months with the absence of hypsarrhythmia on interictal electroencephalogram., Results: This study analyzed 41 patients (26 boys). The etiologies included genetic, congenital structural, acquired structural, and unknown in 12, 11, 10, and 8 patients, respectively. Patient characteristics did not significantly differ among the four groups. The overall effectiveness of VGB for IESS was 39.0 % (16/41). Categorized based on etiology, VGB was effective in 41.7 % (5/12), 9.1 % (1/11), 50 % (5/10), and 75 % (6/8) in the genetic, congenital structural, acquired structural, and unknown groups, respectively. Statistical analysis revealed a significant difference in effectiveness among the four groups (p = 0.03). Categorized based on diseases, VGB was effective in 28.6 % (2/7) and 50 % (4/8) in trisomy 21 and perinatal brain injury, respectively., Conclusion: The effectiveness of VGB in patients with IESS varied with etiology. Further investigations into the effectiveness of VGB in etiological subtypes of IESS could facilitate the development of tailored treatment algorithms for each etiology, representing valuable guidelines for future medical practice., Competing Interests: Declaration of competing interest The authors have nothing to disclose., (Copyright © 2024. Published by Elsevier Ltd.)

Purpose: Epileptic spasms are the primary symptom of infantile epileptic spasms syndrome (IESS); however, their direct impact on blood-brain barrier (BBB) function is unknown. Matrix metallopeptidase-9 (MMP-9), degrades type IV collagen, a key component of the blood-brain barrier, while tissue inhibitor of metalloproteinase-1 (TIMP-1) suppresses its activity, protecting BBB integrity. This study aimed to assess serum MMP-9 and TIMP-1 levels in patients with IESS of unknown etiology., Methods: We prospectively assessed serum MMP-9 and TIMP-1 levels prior to administering vigabatrin or adrenocorticotropic hormone therapy in patients with IESS of unknown etiology at Saitama Children's Medical Center between February 2012 and December 2023. We compared these biomarkers between patients with epileptic spasms and age-matched controls and performed a curve regression analysis between the biomarkers and the frequency of epileptic spasms. Additionally, we assessed whether MMP-9 and TIMP-1 levels were diagnostic predictors of IESS., Results: This study included 22 patients with IESS (11 males) and 12 controls. Serum MMP-9 and MMP-9/TIMP-1 ratios were higher in patients with IESS than in controls (p < 0.001 and p = 0.002, respectively). A high frequency of epileptic spasms also led to higher serum MMP-9 levels (y = 0.0871x 2 + 0.195x + 195.15, R² = 0.77, p < 0.001). Using MMP >188 ng/mL as the cutoff level, the sensitivity for diagnosing IESS was 95.5 %, the specificity was 75.0 %, the positive likelihood ratio was 3.82 (95 % confidence interval (CI) 1.43-10.22), and the relative risk was 8.75 (95 % CI 1.36-56.5)., Conclusion: Patients with IESS had elevated serum MMP-9 levels, suggesting an association between epileptic spasms and blood-brain barrier dysfunction. MMP-9 level measurement may be useful for diagnosing suspected patients., Competing Interests: Declaration of Competing Interest Shin-ichiro Hamano received funding from Daiichi Sankyo Co. Ltd., UCB Japan Co. Ltd., and Eisai Co. Ltd. Kenjiro Kikuchi received research funding from Syneos Health Clinical Co. Ltd. and Janssen Pharmaceutical K.K. The other authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Infantile epileptic spasms syndrome (IESS) with epileptic spasms as the main seizure type, is treated with adrenocorticotropic hormone (ACTH). This study, for the first time, examines the effects of epileptic spasms and ACTH on blood-brain barrier (BBB) permeability in patients with IESS of unknown etiology., Methods: We prospectively evaluated the changes in BBB permeability in patients with IESS of unknown etiology at the Saitama Children's Medical Center between February 2012 and February 2024. We compared the levels of serum-albumin, cerebrospinal fluid (CSF)-albumin, Q-albumin, and CSF-neuron-specific enolase (NSE) before and after ACTH therapy. We also assessed the correlation between the frequency of epileptic spasms and these markers., Results: Overall, 16 patients with IESS (8 males) were included in the study. The median age at IESS onset was 5 (range, 2-9) months. The median duration between the epileptic spasms onset and the serum and CSF sample examination before ACTH therapy was 26 (range, 1-154) days. After ACTH therapy, CSF-albumin and Q-albumin levels significantly decreased (CSF-albumin: 13.5 (9.0-32.0) mg/dL vs 11.0 (7.0-19.0) mg/dL, p = 0.001. Q-albumin: 3.7× 10 -3 (2.2 × 10 -3 -7.3 × 10 -3 ) vs 2.8× 10 -3 (1.9 × 10 -3 -4.5 × 10 -3 ), p = 0.003). No correlation was observed between the epileptic spasms frequency and levels of serum-albumin, CSF-albumin, Q-albumin, and CSF-NSE (Spearman's coefficient: r = 0.291, r = 0.141, r = 0.094, and r = -0.471, respectively)., Conclusion: ACTH therapy is one of the factors that play a role in restoring BBB permeability in patients with IESS of unknown etiology. Our findings may be useful in elucidating the mechanism of ACTH action and IESS pathophysiology., Competing Interests: Declaration of competing interest Shin-ichiro Hamano has received funds for speaker honoraria and travel from Eisai Co. Ltd., Daiichi Sankyo Co. Ltd., and UCB Japan Co. Ltd. Akira Oka has received funds for speaker honoraria and travel from Eisai Co. Ltd. and Nippon Shinyaku Co. Ltd. Kenjiro Kikuchi has received research funding from Syneos health clinical Co. Ltd. for clinical trial of Zogenix. The other authors have nothing to disclose conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Few studies have investigated intravenous lacosamide use to treat cluster seizures in pediatric patients. Therefore, we aimed to investigate the efficacy and safety of intravenous lacosamide therapy in pediatric patients with cluster seizures., Methods: We retrospectively evaluated the efficacy and safety of intravenous lacosamide therapy in 25 pediatric patients with cluster seizures at Saitama Children's Medical Center between March 2019 and June 2023. Cluster seizures were defined as a single seizure of less than five minutes duration, repeated three or more times within 12 hours, with recovery of consciousness between seizures. Response was defined as seizure freedom for at least 12 hours after lacosamide infusion., Results: The median age at onset of epilepsy was 1.5 (0.0 to 9.8) years. The median seizure frequency was 5 (3 to 20) times per 12 hours. The etiologies were remote (n = 17), acute (n = 4), and progressive (n = 4). The median age at which intravenous lacosamide therapy was administered was 4.2 (0.0 to 11.3) years. The median lacosamide dose was 2.6 (1.3 to 5.2) mg/kg. In total, 12 of 25 patients (48.0%) responded. Among patients treated with intravenous lacosamide as first-line therapy, nine of 17 (52.9%) had complete seizure remission. The frequency of complete seizure remission in patients with remote etiologies was 58.8% (10 of 17); among them, seven of 12 (58.3%) patients with structural abnormalities showed complete seizure remission. No adverse events were observed., Conclusions: Intravenous lacosamide therapy is a potentially useful treatment option for cluster seizures in pediatric patients., Competing Interests: Declaration of competing interest Shin-ichiro Hamano has received funds for speaker honoraria and travel from Eisai Co Ltd, Daiichi Sankyo Co Ltd, and UCB Japan Co Ltd and has received research funding from Syneos Health Clinical Co Ltd for the clinical trial of Zogenix. Kenjiro Kikuchi has received research funding from Janssen Pharmaceutical K.K. and Syneos Health Clinical Co Ltd for clinical trial of Zogenix. The other authors have no conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Infantile epileptic spasms syndrome (IESS) with Down syndrome has good treatment response and good seizure outcomes with high-dose adrenocorticotrophic hormone (ACTH) therapy. We investigated the early treatment response of epileptic spasms (ES), long-term seizure outcome, and efficacy of very-low-dose ACTH therapy for IESS with Down syndrome., Methods: We retrospectively investigated patients with Down syndrome and IESS between April 1983 and January 2023. We defined response to treatment as clinical remission and electrographic resolution of hypsarrhythmia after treatment for more than one month and early treatment as any treatment for ES within three months of initiation of treatment. Long-term seizure outcomes were determined by the presence of any type of seizure within one year of the last visit. We investigated the dosage and efficacy of very-low-dose ACTH therapy., Results: Thirty patients were enrolled with a median follow-up period of 7.7 years (range: 1.3 to 19.1). The response and relapse rates in the early treatment were 83.3% and 16.0%, respectively. The seizure-free rate of long-term seizure outcomes was 80.0%. Long-term seizure outcomes correlated with early treatment response to ES. The response rate of very-low-dose ACTH therapy was 59.3%. The efficacy of ACTH therapy tended to be dose-dependent (P = 0.055)., Conclusions: Early treatment response to ES may be useful in predicting long-term seizure outcomes of IESS with Down syndrome. Very-low-dose ACTH therapy was the most effective treatment for ES and could exhibit dose-dependent efficacy. Depending on the IESS etiology, the ACTH dose could be reduced to minimize its side effects., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Wolf-Hirschhorn syndrome (WHS) is caused by deletion of the terminal region of chromosome 4 short arm and is frequently associated with intractable epilepsy. This article evaluates the clinical features of epileptic seizures in WHS and the therapeutic efficacy of oral antiseizure medications (ASMs). Patients with WHS who were treated for epilepsy at the Saitama Children's Medical Center under 5 years of age were included. WHS was diagnosed based on genetic tests and clinical symptoms. Medical records regarding the age of onset of epilepsy, seizure type, treatment of status epilepticus (SE), and effectiveness of ASMs were retrospectively reviewed. Oral ASMs were considered effective when seizures were reduced by at least 50% compared with the premedication level. Eleven patients were included in the study. The median age at the onset of epilepsy was 9 months (range: 5-32 months). Unknown-onset bilateral tonic-clonic seizure was the most common type of seizure, occurring in 10 patients. Focal clonic seizures occurred in four patients. Ten patients exhibited recurrent episodes of SE, and its frequency during infancy was monthly in eight patients and yearly in two. SE occurrence peaked at 1 year of age and decreased after 3 years of age. The most effective ASM was levetiracetam. Although WHS-associated epilepsy is intractable with frequent SE occurrence during infancy, improvement in seizure control is expected with age. Levetiracetam may be a novel ASM for WHS., Competing Interests: S.H. received funding for travel and speaker honoraria from UCB Japan Co. Ltd, Daiichi Sankyo Co. Ltd., and Eisai Co. Ltd., and received research funds from Syneos Health Clinical Co. Ltd for the clinical trial of Zogenix. K.K. received research funds from Syneos Health Clinical Co. Ltd. for the clinical trial of Zogenix. Atsuro Daida received grant funding to research abroad from SENSHIN Medical Research Foundation. The other authors have no conflicts of interest to declare., (Thieme. All rights reserved.)

By converting physical forces into electrical signals or triggering intracellular cascades, stretch-activated ion channels allow the cell to respond to osmotic and mechanical stress. Knowledge of the pathophysiological mechanisms underlying associations of stretch-activated ion channels with human disease is limited. Here, we describe 17 unrelated individuals with severe early-onset developmental and epileptic encephalopathy (DEE), intellectual disability, and severe motor and cortical visual impairment associated with progressive neurodegenerative brain changes carrying ten distinct heterozygous variants of TMEM63B, encoding for a highly conserved stretch-activated ion channel. The variants occurred de novo in 16/17 individuals for whom parental DNA was available and either missense, including the recurrent p.Val44Met in 7/17 individuals, or in-frame, all affecting conserved residues located in transmembrane regions of the protein. In 12 individuals, hematological abnormalities co-occurred, such as macrocytosis and hemolysis, requiring blood transfusions in some. We modeled six variants (p.Val44Met, p.Arg433His, p.Thr481Asn, p.Gly580Ser, p.Arg660Thr, and p.Phe697Leu), each affecting a distinct transmembrane domain of the channel, in transfected Neuro2a cells and demonstrated inward leak cation currents across the mutated channel even in isotonic conditions, while the response to hypo-osmotic challenge was impaired, as were the Ca 2+ transients generated under hypo-osmotic stimulation. Ectopic expression of the p.Val44Met and p.Gly580Cys variants in Drosophila resulted in early death. TMEM63B-associated DEE represents a recognizable clinicopathological entity in which altered cation conductivity results in a severe neurological phenotype with progressive brain damage and early-onset epilepsy associated with hematological abnormalities in most individuals., Competing Interests: Declaration of interests The authors have declared that no conflict of interest exists., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Infantile epileptic spasms syndrome (IESS) with periventricular leukomalacia (PVL) has a poor neurological prognosis. Adrenocorticotropic hormone (ACTH) and vigabatrin therapies are the recommended first-line treatments for IESS. However, ACTH monotherapy for IESS with PVL has not been studied in detail. We analysed long-term outcomes of ACTH monotherapy for IESS with PVL., Methods: We retrospectively examined 12 patients with IESS and PVL at Saitama Children's Medical Center between January 1993 and September 2022. We evaluated seizure outcomes 3 months post-ACTH therapy and at the last visit. We also assessed electroencephalography findings and developmental outcomes. A positive response was defined as complete remission of epileptic spasms, no other seizure types, and hypsarrhythmia resolution post-ACTH therapy., Results: The median onset age of epileptic spasms was 7 (range: 3-14) months. The median age at initiation of ACTH therapy was 9 (7-17) months. Seven of 12 patients (58.3%) showed a positive response. The median age at the last visit was 5 years and 6 months (1 year and 5 months-22 years and 2 months). At the last visit, only 2 of 7 initial responders remained seizure-free who demonstrated normal electroencephalography findings within 1-month post-ACTH therapy. Patients with epileptic discharge in the parieto-occipital region within 1-month post-ACTH therapy showed relapse of epileptic spasms or other seizure types., Conclusion: Patients having epileptic discharge in the parietal or occipital regions on electroencephalography within 1-month post-ACTH therapy may be at a high risk of epileptic spasm recurrence or other seizure types in the long term., Competing Interests: Declaration of Competing Interest Shin-ichiro Hamano has received research funding from Syneos Health Clinical Co. Ltd for the clinical trial of Zogenix and has received funds for speaker honoraria and travel from UCB Japan Co. Ltd., Daiichi Sankyo Co. Ltd., and Eisai Co. Ltd. Kenjiro Kikuchi has received research funding from Janssen Pharmaceutical K.K. and Syneos Health Clinical Co. Ltd. for clinical trial of Zogenix. The other authors have nothing to disclose in terms of conflict of interest., (Copyright © 2023 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: We aimed to evaluate choice and efficacy of intravenous antiepileptic drugs (AEDs) for status epilepticus (SE) in Dravet syndrome and to find predictable clinical features demonstrating the effectiveness of benzodiazepine (BZD) for SE., Methods: We retrospectively investigated the medical records in patients with Dravet syndrome and evaluated the effectiveness rate of intravenous AEDs and the rate of adverse effects. To find the clinical features of BZD-effective SE, we divided the SE episodes into the following two groups: BZD effective group and BZD non-effective group. The choice of treatment was dependent on physicians' discretion according to the protocol for SE in our institution., Results: Sixty-eight SE episodes in 10 patients were assessed. The median age at SE was 31 months. Of 68 episodes, 42 episodes (61.8%) were in the BZD effective group and 26 (38.2%) in the BZD non-effective group. There were no significant differences in clinical features. In the BZD non-effective group, the effective rates of continuous midazolam, phenobarbital, phenytoin/fosphenytoin were 9/9 episodes (100%), 14/17 (82.4%), and 2/5 (40.0%), respectively. Adverse effects were identified in 19/68 episodes (27.9%), including 11/42 episodes in the BZD effective group and 8/26 in the BZD non-effective group, which was no statistical difference between the two groups. Respiratory suppression was found in all 19 episodes and the incidence of endotracheal intubation in the BZD non-effective group (15.4%) was higher than that in the BZD effective group (2.4%) (p = 0.046)., Conclusion: BZD may be used as first choice, and phenobarbital prior to continuous midazolam as second choice for SE with Dravet syndrome. There might be no predictable clinical features showing that BZD will be effective., (Copyright © 2022 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate whether serum matrix metallopeptidase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels predict response to adrenocorticotropic hormone (ACTH) therapy in patients with infantile spasms., Methods: We prospectively evaluated patients with infantile spasms who were referred to Saitama Children's Medical Center from January 2011 to December 2020. We measured Q-albumin and serum MMP-9 and TIMP-1 levels before ACTH therapy. Patients were divided into three groups based on the etiology of their infantile spasms: those with an unknown etiology and normal development (unknown-normal group); those with a structural and acquired etiology (structural-acquired group); and those with a structural and congenital, genetic, metabolic, or unknown etiology with developmental delay (combined-congenital group). Responders were defined as those having complete cessation of spasms for more than 3 months with the resolution of hypsarrhythmia on electroencephalography during ACTH therapy., Results: We collected serum from 36 patients with West syndrome and five patients with infantile spasms without hypsarrhythmia before ACTH therapy. Twenty-three of 41 patients (56.1%) were responders, including 8/8 (100%) in the unknown-normal group, 6/9 (66.7%) in the structural-acquired group, and 9/24 (37.5%) in the combined-congenital group. The serum MMP-9 level and MMP-9/TIMP-1 ratio were significantly higher in responders than in nonresponders (P = 0.001 for both)., Conclusion: A therapeutic response to ACTH was associated with a higher serum MMP-9 level and higher MMP-9/TIMP-1 ratio in patients with infantile spasms. Therefore, these biomarkers may predict responses to ACTH therapy in this patient population., (Copyright © 2021 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background: Perampanel is an antiepileptic drug. Some studies have documented the efficacy of perampanel in epileptic spasms. We aimed to evaluate the efficacy and safety of adjunctive perampanel therapy (PT) in patients with epileptic spasms., Methods: We retrospectively surveyed the efficacy and safety of adjunctive PT in 14 patients with epileptic spasms at the Saitama Children's Medical Center between June 2016 and September 2021. Seizure outcomes and safety were evaluated 12 months after commencing PT. Response to perampanel was defined as complete remission of epileptic spasms for more than 3 months., Results: The median age at onset of epileptic spasms was 0.4 years (range, 0.1-1.3 years). The etiology was structural in 11 patients, genetic in two, and unknown in one. The median age at the commencement of PT was 3.2 years (1.5-10.3 years). The initial and maintenance doses of perampanel were administered at 0.04 (range, 0.02-0.05) mg/kg/day and 0.12 (range, 0.03-0.24) mg/kg/day, respectively. Five of the 14 patients (35.7%) showed remission of epileptic spasms for more than 3 months at 12 months after PT; these patients had a structural etiology. The median duration between commencement of perampanel and spasm remission was 2 months (range, 1-6 months). No serious adverse effects occurred., Conclusions: This is the first case series evaluating adjunctive PT for epileptic spasms. PT is worth investigating to treat epileptic spasms in patients with structural etiologies. As our study population primarily comprised children aged 2 years and older, PT may be useful for epileptic spasms beyond infancy., (© 2022 Japan Pediatric Society.)

Background: Telemedicine has spread rapidly during the coronavirus disease 2019 (COVID-19) pandemic and shown its usefulness, particularly for patients with epilepsy, compared to face-to-face visits. We sought to evaluate the clinical features of patients with childhood onset epilepsy associated with consultations by telephone call during the COVID-19 pandemic., Methods: We retrospectively investigated the medical records of patients with childhood onset epilepsy who visited an outpatient clinic in Saitama Children's Medical Center, Saitama, Japan, from 1 March 2020 to 30 September 2020. To find the clinical features of patients who utilized telemedicine consultation (by telephone call), we divided the patients into the telemedicine group and the face-to-face group. We then reviewed the clinical features. Telemedicine consultation was not implemented for new patients., Results: We enrolled 776 outpatients in total, and 294 patients (37.9%) utilized telemedicine consultations. The total number of visits was 2,299 and the total number of telemedicine consultations was 373 (16.2%). No clinical feature was associated with telemedicine consultations except for age at onset of epilepsy. The number of oral antiepileptic drugs prescriptions decreased in 23 of 776 (3.0%) of the patients who did not experience seizure deterioration, including status epilepticus, or who visited the emergency room., Conclusion: Telemedicine consultations were successfully utilized for epilepsy treatment at our outpatient clinic, regardless of epilepsy type, etiology, seizure frequency, comorbidities, and patients' residential areas. Thus, telemedicine by telephone call may be a useful resource in the management of patients with childhood onset epilepsy during the pandemic., (© 2021 Japan Pediatric Society.)

Purpose: We aimed to study the efficacy of adrenocorticotropic hormone (ACTH) treatment on infantile spasms with different aetiologies. In particular, we were interested in patients with structural-acquired aetiology., Methods: Patients with infantile spasms, who were treated with ACTH, were divided into three groups based on the aetiologies: unknown aetiology with normal development (unknown-normal), structural-acquired, and combined-congenital aetiologies that included genetic, metabolic, structural-congenital, or unknown aetiology with developmental delay., Results: Of the 107 patients included (58 males, 49 females), 25 patients had unknown-normal aetiology [median age at onset 5 months, standard deviation (SD) 3.12, range 2-16 months]; 20 patients had structural-acquired aetiology (median age at onset 6.5 months, SD 3.85 months, range 4-17 months); and 62 patients had combined-congenital aetiologies (median age at onset 5 months, SD 2.73 months, range 2-16 months). The efficacy of ACTH was 64.0 %, 65 %, and 30.6 % in the unknown-normal aetiology, structural-acquired aetiology, and combined-congenital aetiologies, respectively (p < 0.01). Multivariate analysis showed a statistically significant higher efficacy in the unknown-normal aetiology [Odds ratio (OR) 4.63, 95 % confidence interval (CI) 1.60-13.30] and structural-acquired aetiology (OR 3.41, 95 % CI 1.01-11.50) compared to that in the combined-congenital aetiologies., Conclusion: Infantile spasms with structural-acquired aetiology had greater response to ACTH treatment than those with combined-congenital aetiologies. The efficacy of standard therapy of infantile spasms should be considered based on aetiology., (Copyright © 2020 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Background: Nonketotic hyperglycinemia is a severe form of early onset epileptic encephalopathy caused by disturbances in the glycine cleavage system; the neurological damage is mainly attributed to overstimulation of the N -methyl-D-aspartate receptor., Case: The patient presented with a severe form of nonketotic hyperglycinemia and experienced frequent epileptic spasms and focal seizures, which were resistant to vigabatrin, adrenocorticotropic hormone therapy, and combined dextromethorphan and sodium benzoate treatments. By 9 months of age, perampanel reduced epileptic spasms by >50%. At 14 months of age, the ketogenic diet markedly reduced focal seizures and glycine levels in the cerebrospinal fluid., Conclusion: Perampanel reduced fast excitatory neuronal activity, which was induced by an α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor, followed by prolonged electrical depolarizations due to an N -methyl-D-aspartate receptor. Furthermore, the ketogenic diet may have modulated the excessive neurotoxic cascade through the N -methyl-D-aspartate receptor. Perampanel and ketogenic diet were effective for seizure control in our patient., Competing Interests: None., (Thieme. All rights reserved.)

Background: We evaluated zonisamide therapy in patients with paroxysmal kinesigenic dyskinesia (PKD)., Methods: We analyzed zonisamide therapy in 17 patients with PKD at Saitama Children's Medical Center between November 1994 and April 2020. We collected information regarding family history, previous history, age at onset, age at zonisamide commencement, dyskinesia characteristics, brain magnetic resonance imaging, interictal electroencephalography, treatment lag, zonisamide efficacy, zonisamide dose, serum zonisamide concentration, and adverse effects. We evaluated PKD frequency at six months after zonisamide therapy commencement., Results: Fourteen patients met the inclusion criteria. The median age at zonisamide therapy commencement was 12.8 (9.4 to 16.3) years. Zonisamide therapy was effective in 13 of 14 (92.9%) patients: complete remission for more than three months after zonisamide therapy (n = 7), decreased dyskinesia frequency by more than 90% (n = 4), dyskinesia frequency by 75% to 90% (n = 2), and no change of dyskinesia frequency (n = 1). The initial and maintenance zonisamide doses were 2.0 (1.4 to 3.8) and 2.0 (1.5 to 5.9) mg/kg/day, respectively. The median duration between zonisamide therapy commencement and dyskinesia decrease or cessation was 4 (1 to 60) days: 10 of 14 (71.4%) patients responded to zonisamide within one week after zonisamide therapy commencement. Regarding adverse effects, two patients experienced somnolence and one developed reduced perspiration., Conclusions: We suggest that zonisamide monotherapy is effective for patients with PKD as a first-line treatment. We can evaluate the efficacy of zonisamide therapy within one week. Because zonisamide lacks the enzyme-inducing effects of carbamazepine and phenytoin, it may be useful for PKD treatment., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Hypomyelinating leukodystrophies (HLDs) are genetically heterogeneous syndromes, presenting abnormalities in myelin development in the central nervous system. Recently, a recurrent de novo mutation in TMEM106B was identified to be responsible for five cases of HLD. We report the first Japanese case of TMEM106B gene mutation., Case Study: A 3-year-old patient presented with nystagmus and muscle hypotonia in his neonatal period, followed by delayed psychomotor development. Brain magnetic resonance images showed delayed myelination. Wave III and subsequent components were not presented by his auditory brainstem response. These features were similar to those observed in Pelizaeus-Merzbacher disease (PMD)., Methods: Proteolipid protein 1 (PLP1) gene screening, Mendelian disease panel exome, and whole-exome sequencing (WES) were sequentially performed., Results: After excluding mutations in either PLP1 or other known HLD genes, WES identified a mutation c.754G > A, p.(Asp252Asn) in TMEM106B, which appeared to occur de novo, as shown by Sanger sequencing and SalI restriction enzyme digestion of PCR products., Discussion: This is the sixth case of HLD with a TMEM106B mutation. All six cases harbored the same variant. This specific TMEM106B mutation should be investigated when a patient shows PMD-like features without PLP1 mutation. Our PCR-SalI digestion assay may serve as a tool for rapid HLD diagnosis., (Copyright © 2020 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Objective: Absence status epilepticus (ASE) is a form of non-convulsive status epilepticus characterized by ongoing or intermittent epileptic activity accompanied by behavioral and cognitive changes. Herein, we assessed high-frequency oscillations in the ripple band in patients with ASE and typical absence seizures., Methods: We enrolled five patients with ASE, 26 patients with childhood absence epilepsy (CAE), and 15 patients with juvenile absence epilepsy (JAE). We performed time-frequency analysis of electroencephalogram data for ictal absence seizures at each electrode to assess the high frequency activity (HFA) rate, peak frequency, and peak power., Results: The average HFA rates were 60.7%, 20.8%, and 12.9% in ASE, CAE, and JAE patients, respectively. The average peak frequencies were 126.4 Hz, 120.9 Hz, and 126.1 Hz in ASE, CAE, and JAE patients, respectively. The average peak power values were 2,388.8 μV 2 , 120.9 μV 2 , and 126.1 μV 2 in ASE, CAE, and JAE patients, respectively, and all epilepsy groups exhibited frontal-dominant ripple distribution., Conclusion: ASE patients presented higher power and frontal dominant ripples of absence seizure, compared to CAE and JAE patients., Significance: Future studies should utilize scalp-recorded ripples as a biomarker of absence epilepsy. This may aid in the development of novel treatment strategies for ASE., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: Some pediatric patients with autoimmune encephalitis (AE) experience sequelae in spite of immunotherapy. In this study, we aimed to evaluate the association of serum matrix metallopeptidase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels with the neurological prognosis of AE., Methods: We retrospectively included 13 patients with AE who had been referred to Saitama Children's Medical Center from February 2011 to May 2019. We compared serum MMP-9 levels, TIMP-1 levels, and MMP-9/TIMP-1 ratio in the acute period (within 30 days from the onset of AE) and subacute period (30-day period following the acute period). We also compared these biomarker levels between patients with (group A) and without sequelae (group B). Sequelae were evaluated at discharge or the last visit., Results: Group A (median age, 7.8 years; range, 5.3-10.7 years) and group B (median age, 13.3 years; range, 11.1-15.4 years) had 6 patients each; 1 patient was excluded because the time of AE onset was unknown. In the acute period, there were no significant differences in MMP-9 levels, TIMP-1 levels, and MMP-9/TIMP-1 ratio between groups A and B. In the subacute period, serum MMP-9/TIMP-1 ratio was higher in group A than in group B (p < 0.01). There were no significant differences in MMP-9 and TIMP-1 levels between groups A and B., Conclusions: Patients with sequelae of AE showed a high MMP-9/TIMP-1 ratio in the subacute period. Our study demonstrates that elevation of serum MMP-9/TIMP-1 ratio in the subacute period may be a predictive factor of sequelae of AE., (Copyright © 2019 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

This study aimed to investigate the general presentation of epileptic spasms without hypsarrhythmia (ESwoH) and retrospectively determine whether there are differences in treatment effects related to ACTH therapy, long-term seizure outcome, and evolution of EEG features according to pre-treatment EEG patterns. According to the pattern of background activity, we divided our cohort into two groups: Group 1: normal background activity or with localized intermittent slow waves; Group 2: intermittent slow waves appearing generalized or in two or more lobes. Subjects included 22 children (Group 1: n=10; Group 2: n=12) diagnosed with ESwoH who received treatment from 2007 to 2017. The median age at onset of epileptic spasms was 5.5 months and the follow-up period lasted for 40.5 months. ACTH therapy was performed for seven patients from Group 1 and eight patients from Group 2. Only one patient from Group 2 responded to ACTH. Patients receiving effective treatments at early stages had excellent seizure outcome. Refractory cases included six patients in Group 1 and eight patients in Group 2; subsequent follow-up EEGs indicated hypsarrhythmia in one patient in Group 1 (17%) and six patients (75%) in Group 2, including one patient whose EEG pattern indicated progression to Lennox-Gastaut syndrome. Overall, ACTH is ineffective for patients with epileptic spasms without hypsarrhythmia. The EEG may indicate possible future development of hypsarrhythmia if epileptic spasms are resistant to treatment, especially in patients with diffuse slow waves on pre-treatment EEG. The efficacy of treatment introduced at early stages from onset may predict long-term seizure outcome.

Purpose: Perampanel (PER) is a selective, non-competitive antagonist of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor. In Japan, PER is approved for patients with epilepsy who are at least 12 years old for the adjunctive treatment of primary generalised tonic-clonic seizures and partial-onset seizures (with or without secondary generalization). We surveyed the efficacy, adverse effects, and serum concentrations of PER, focusing especially on patients younger than 12 years of age., Methods: We retrospectively surveyed the clinical information of patients treated with PER and assessed the efficacy at 6 months after treatment initiation. We compared efficacy, adverse effects, and serum concentration in patients younger or older than 12 years of age. Responders were defined as those who experienced a ≥50% seizure reduction., Results: Eighty-four patients were enrolled. The average age of the younger group was 7.1 ± 3.3 (standard deviation) years compared to 16.4 ± 3.7 years in the older group. The responder rate was 42.9% (36/84). The responder rate did not differ between the two age groups (<12 years, 20/44, 45.4%; >12 years, 16/40, 40.0%; p = 0.78). The younger age group had a significantly lower concentration-to-dose (CD) ratio than the older age group (<12 years, 1849.8 ± 2209.3; >12 years, 3076.3 ± 3352.2, p = 0.02). Treatment-emergent adverse events (TEAEs) were observed in 22.6% (19/84) of patients, with the most common being somnolence (8/84, 9.5%)., Conclusion: PER may be an alternative to treat seizures in paediatric drug-resistant epilepsy. Serum concentrations of PER might be lower in patients younger than 12 years than in older patients., (Copyright © 2019 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objective: To evaluate the efficacy and safety of pyridoxal for treating West syndrome., Methods: We retrospectively investigated pyridoxal's efficacy and safety in 117 patients with West syndrome at Saitama Children's Medical Center from July 1993 to May 2016. Pyridoxal was administered at doses of 10-50 mg/kg/day. We evaluated seizure outcomes and electroencephalographic findings at 4 weeks after pyridoxal therapy. The responders were those with complete cessation of spasms for more than 4 weeks and those with resolution of hypsarrhythmia on EEG at 1-4 weeks after pyridoxal therapy., Results: Five of the 117 patients (4.3%) were responders. The median duration between pyridoxal therapy to spasm cessation was 6 (5-13) days. Among the responders, four had hypsarrhythmia resolution, no spasm relapse, and no other seizure types more than 2 years after pyridoxal therapy. One responder had partial seizures and spasm relapse. No serious adverse effects occurred. There were no significant differences in sex, etiologies, complication, other seizure types preceding the spasms, onset age of spasms, age of pyridoxal therapy, treatment lag, initial and maintenance doses of pyridoxal, and adverse effects between pyridoxal responders and non-responders., Conclusions: The efficacy rate of pyridoxal monotherapy as first-line treatment for West syndrome was low. However, pyridoxal therapy showed a rapid response within 1 week and was safe. We consider pyridoxal therapy as a kind of challenge therapy during the evaluation period concerning differential diagnosis and etiologies of West syndrome and immunological risks before adrenocorticotrophic hormone therapy or vigabatrin therapy., (Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Objective: To determine whether the characteristics of scalp-recorded high frequency oscillations, especially ripples, can predict the "atypical forms" of benign epilepsy of childhood with centrotemporal spikes (ABECTS), in BECTS., Methods: Seven patients with ABECTS and eighteen patients with BECTS underwent electroencephalography (EEG) in the secondary bilateral synchrony (SBS) and non-SBS periods for ABECTS patients. SBS period is that when more than 50% of the interictal epileptiform discharges (IEDs) are bilaterally synchronized. We determined the IED-ripple co-occurrence rate, performed time frequency analysis, and calculated the asymmetry index (AI)., Results: The IEDs-ripple co-occurrence rate increased in the SBS compared to the non-SBS period. Time frequency analysis showed higher high-frequency activity rate and peak power in the SBS than in the non-SBS period. The AI was lower in ABECTS than BECTS, both in the non-SBS and SBS periods., Conclusions: Ripples were enhanced in the SBS period of ABECTS, and bilaterally synchronized both in the non-SBS and SBS periods, whereas ripples in BECTS were localized unilaterally., Significance: Bilaterally synchronized ripples in the non-SBS period of ABECTS may distinguish ABECTS from BECTS in the non-SBS period of IEDs, and may be helpful for early detection of progressive neurophysiological regression leading to early intervention., (Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: Mutations in Lysine-Specific Histone Methyltransferase 2B gene (KMT2B) have been reported to be associated with complex early-onset dystonia. Almost all reported KMT2B mutations occurred de novo in the paternal germline or in the early development of the patient. We describe clinico-genetic features on four Japanese patients with novel de novo mutations and demonstrate the phenotypic spectrum of KMT2B mutations., Methods: We performed genetic studies, including trio-based whole exome sequencing (WES), in a cohort of Japanese patients with a seemingly sporadic early-onset generalized combined dystonia. Potential effects by the identified nucleotide variations were evaluated biologically. Genotype-phenotype correlations were also investigated., Results: Four patients had de novo heterozygous mutations in KMT2B, c.309delG, c.1656dupC, c.3325&#95;3326insC, and c.5636delG. Biological analysis of KMT2B mRNA levels showed a reduced expression of mutant transcript frame. All patients presented with motor milestone delay, microcephaly, mild psychomotor impairment, childhood-onset generalized dystonia and superimposed choreoathetosis or myoclonus. One patient cannot stand due to axial hypotonia associated with cerebellar dysfunction. Three patients had bilateral globus pallidal deep brain stimulation (DBS) with excellent or partial response., Conclusions: We further demonstrate the allelic heterogeneity and phenotypic variations of KMT2B-associated disease. Haploinsufficiency is one of molecular pathomechanisms underlying the disease. Cardinal clinical features include combined dystonia accompanying mild psychomotor disability. Cerebellum would be affected in KMT2B-associated disease., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: To elucidate the pathophysiology of West syndrome and mechanism of immunoglobulin therapy for this syndrome, we investigated serum and cerebrospinal fluid (CSF) cytokine levels before and after high-dose intravenous immunoglobulin (IVIG) therapy in patients with West syndrome. Methods: We measured serum and CSF cytokine levels of 11 patients with West syndrome who was referred to Saitama Children’s Medical Center from April 2010 to May 2014. All patients received IVIG, ranging from 200 to 500 mg/kg/day for 3 consecutive days (initial IVIG treatment), before adrenocorticotrophic hormone therapy. When spasms disappeared within 2 weeks after initial IVIG treatment, maintenance IVIG treatment was commenced. We measured cytokines level in patients before and after initial IVIG treatment. We compared the levels of cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-17, Interferon γ, Granulocyte macrophage colony stimulating factor, IL-18, Tumor necrosis factor-α〔TNF-α〕) in serum and CSF, and between the seizure-free group and seizure-persisting group. Seizure free was defined as remission of spasms within 2 weeks after initial IVIG treatment and no relapse for at least 1 week after remission. Results: After IVIG therapy, 5 of 11 patients were in the seizure-free group (4 males, 1 cryptogenic) while 6 were in the seizure-persisting group (2 males, 1 cryptogenic). Levels of IL-1β, IL-10, IL-18, and TNF-α in serum were significantly higher than those in CSF before initiation of IVIG. Before IVIG treatment, the level of IL-8 in CSF was significantly higher than that in serum, while the serum IL-18 level in the seizure-free group was significantly lower than that in the seizure-persisting group. Alterations of serum IL-18 level and CSF IL-8 level were different between the seizure-free and seizure-persisting groups. Conclusions: Serum IL-18 and CSF IL-8 may be important factors for elucidating the pathophysiology of West syndrome and mechanism of IVIG therapy.

A 6-year-old boy with normal development experienced tonic-clonic seizures and myoclonus. His electroencephalogram showed epileptic discharge and he was administered antiepileptic drugs ; however, they were ineffective. Antiepileptic drugs were discontinued temporarily because of no ictal recordings. He could not walk unaided and his speech reduced gradually. He was admitted to our hospital at the age of seven years and eight months. He experienced daily tonic-clonic seizures and myoclonus. Epileptic encephalopathy related to autoimmunity was suspected as he had psychomotor regression and his cerebrospinal and serum anti-glutamate receptor antibody (anti-GluR) levels were elevated. After being administered immunoglobulins, his motor and cognitive functions improved and his seizures almost stopped. After one year, he could walk unaided and speak fluently. We strongly suspect an autoimmune reaction to be the pathological cause because of the effectiveness of immunoglobulin treatment. Immunoglobulin interventions should be considered in patients with unknown-cause, sub-acute onset, and destructively progressive epileptic encephalopathy.

An 11-year-old boy presented with progressive walking disturbances. He exhibited severe equinovarus feet that together presented with hyperreflexia of the patellar tendon and extensor plantar, resembling spastic paraplegia or upper neuron disease. He showed mild distal muscle atrophy, as well. We did not observe signs of cognitive impairment, cerebellar signs, or brain magnetic resonance imaging abnormalities. Nerve biopsy showed giant axon swellings filled with neurofilaments. Gene analysis revealed novel compound heterozygous missense mutations in the gigaxonin gene, c.808G>A (p.G270S) and c.1727C>A (p.A576E). He was diagnosed with mild giant axonal neuropathy (GAN) without apparent central nervous system involvement. Patients with classical GAN manifest their symptoms during early childhood. Mild GAN, particularly in early stages, can be misdiagnosed because of lack of typical hair features and incomplete or indistinct peripheral and central nervous system symptoms. This case is important since it can aid to identify atypical and milder clinical courses of GAN. This report widens the mild GAN clinical spectrum, alerting physicians for correct diagnosis., (Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Distal arthrogryposis (DA) encompasses a heterogeneous group of hereditary disorders with multiple congenital contractures predominant in the distal extremities. A total of 10 subtypes are proposed based on the pattern of contractures and association with extraarticular symptoms. DA5 is defined as a subtype with ptosis/oculomotor limitation. However, affected individuals have a variety of non-ocular features as well. We report on a two-generation family, including four affected individuals who all had congenital contractures of the distal joints, ptosis, restricted ocular movements, distinct facial appearance with deep-set eyes, and shortening of the 1st and 5th toes. The proband and her affected mother had restrictive lung disease, a recently recognized syndromic component of DA5, while younger patients did not. The proband had metacarpal and metatarsal synostosis, and the mother showed excavation of the optic disk. Whole-exome sequencing revealed a novel heterozygous mutation c.4456G>C (p.A1486P) of PIEZO2. PIEZO2 encodes a mechanosensitive ion channel, malfunction of which provides pleiotropic effects on joints, ocular muscles, lung function, and bone development., (© 2015 Wiley Periodicals, Inc.)

A 15-year-old girl developed severe pain in her right upper limb within a few days after she experienced an astatic epileptic seizure accompanied by falling on her right side. She was treated with fluid infusion through a cannula into her right hand. Swelling, mild flaring, and muscle weakness of the right arm subsequently appeared. Pharmacotherapy and stellate ganglion block were ineffective, and continuous epidural anesthesia was commenced 14 days after the falling event. The pain and accompanying symptoms completely disappeared within 5 days. Early treatment with continuous epidural anesthesia may be a promising option for the management of complex regional pain syndrome during childhood., (Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

High-dose phenobarbital (PB) therapy is effective for refractory status epilepticus. We reviewed medical records of patients with intractable partial epilepsies on whom performed non-intravenous high-dose PB therapy. Thirteen patients received PB rectally or orally at a dosage of 20-30mg/kg/day initially, and the PB dosage was gradually reduced to a maintenance dosage of 5-10mg/kg/day orally. We evaluated the effectiveness and safety of this procedure after 14days at the maintenance dosage level. Twelve patients had partial seizures and one had secondary generalized seizures. In six of 13 patients (46%), seizure frequencies decreased more than 50%, and two of 13 patients (15%) became seizure free. In five of seven patients who were treated by continuous midazolam infusion therapy, we were able to discontinue the midazolam therapy. Adverse effects were found in seven of 13 patients. We were able to continue high-dose PB therapy in six patients because their adverse effects were transient and improved after a decrease in PB concentration, but we discontinued this therapy in the patient who developed Stevens-Johnson syndrome. Respiratory depression and hypotension were not found in our study. We conclude that high-dose PB therapy is effective and may be considered as an additional treatment for intractable partial epilepsy in childhood., (Copyright © 2010 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

A retrospective analysis of the clinical and MRI features in 20 Japanese children diagnosed with central nervous system inflammatory demyelinating disorders was performed. Using the new criteria proposed by International Pediatric MS Study Group, half of children were reclassified into clinical isolated demyelinating syndrome (CIS). Presence of seizures and a pattern of diffuse bilateral lesions on brain MRIs are more frequent in children with ADEM than in CIS. However we suggest these features and encephalopathy may be associated with the age of patients. Furthermore, though persistence of abnormal MRI lesions is significantly more likely in the group of CIS, none of these patients had a subsequent recurrence or developed MS during the follow-up period. The prediction of patient prognosis seems to be difficult even based on the new criteria, and the nationwide multicenter analysis may be necessary in Japan for acquiring the definite conclusion.

Purpose: To elucidate the abnormality of interictal regional cerebral blood flow (rCBF) of West syndrome at the onset., Methods: Quantitative measurement of rCBF with an autoradiography method using N-isopropyl-((123)I) p-iodoamphetamine single photon emission computed tomography (SPECT) was performed on 14 infants with cryptogenic West syndrome. Regions of interest (ROIs) for rCBF were placed automatically using an automated ROI analysis software (three-dimensional stereotactic ROI template), and were grouped into 12 segments: callosomarginal, precentral, central, parietal, angular, temporal, posterior cerebral, pericallosal, lenticular nucleus, thalamus, hippocampus, and cerebellum. We compared rCBF between the patients and seven age-matched infants with cryptogenic focal epilepsy as a control group. The patients were divided into two groups according to the duration from onset to SPECT, to compare rCBF., Results: Quantitative analysis revealed cerebral hypoperfusion in cryptogenic West syndrome with normal SPECT images under visual inspection. In bilateral central, posterior cerebral, pericallosal, lenticular nucleus, and hippocampus, and in the left parietal, temporal, and cerebellum, and in the right angular and thalamus segments there were statistical differences (p < 0.05). Compared with the duration from onset to SPECT, there were no significant differences of rCBF in all segments., Discussion: Broad cerebral hypoperfusion with posterior predominance involving the hippocampus and lenticular nucleus implies that even cryptogenic West syndrome has a widespread cerebral dysfunction at least transiently, which would correspond to clinical manifestations of hypsarrhythmia and epileptic spasms. Hippocampal hypoperfusion suggests the dysfunction of hippocampal circuitry in the brain adrenal axis, and may contribute to subsequent cognitive impairment of cryptogenic West syndrome.

We reported the clinical and neuroradiological findings of 8 patients (4 males; 4 females; age range; 3 - 14 years) with posterior leukoencephalopathy syndrome (PLES). Previous case reports suggested that one of the major factors leading to PLES was severe hypertension. We divided the patients into two groups with or without severe hypertension, and each group was divided furthermore into two corresponding to the reversibility of brain lesions. The four cases of PLES with severe hypertension were all due to renal hypertension, and half of them resulted in irreversible outcomes, which were considered to be associated with inappropriate treatment. On the other hand, the four cases of PLES without severe hypertension showed reversible change, suggesting intravascular endothelial dysfuncton in respect of their causing factors. We consider that PLES could be caused without sever hypertension, particularly in children. Those with severe hypertension must be treated immediately to prevent irreversible brain damage.

A 14-year-old girl with Guillain-Barré syndrome manifested headaches during the administration of intravenous immunoglobulin. Magnetic resonance imaging revealed posterior reversible encephalopathy syndrome. Several reports described posterior reversible encephalopathy syndrome associated with intravenous immunoglobulin, but only in adults. We suggest that this syndrome should be considered in children as a neurologic complication.

A 30-year-old man complained of polyarthralgia and fatigue. The clinical findings and laboratory data included myositis, polyarthritis, interstitial pneumonia, Raynaud's phenomenon, mechanic's hand, and anti PL-7 antibody (threonyl-tRNA synthetase antibody). All of these signs were consistent with antisynthetase syndrome. His chest radiograph revealed bilateral hilar lymphadenopathy. Biopsy specimens from his mediastinal lymph node and muscle showed noncaseating epithelioid cell granulomas. Lung histology revealed nonspecific interstitial pneumonia. Antisynthetase syndrome associated with sarcoidosis was diagnosed. Interstitial pneumonia in this patient responded well to high-dose corticosteroid therapy.