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Epilepsy, a recurrent neurological disorder involving abnormal neurotransmitter kinetics in the brain, has emerged as a global health concern. The mechanism of epileptic seizures is thought to involve a relative imbalance between excitatory and inhibitory neurotransmitters. Despite the recent advances in clinical and basic research on the pathogenesis of epilepsy, the complex relationship between the neurotransmitter changes and behavior with and without antiepileptic drugs (AEDs) during seizures remains unclear. To investigate the effects of AEDs such as levetiracetam (LEV), carbamazepine (CBZ), and fenfluramine (FFR) on key neurotransmitters in the pentylenetetrazol (PTZ)-induced seizures in adult zebrafish, we examined the changes in glutamic acid, gamma-aminobutyric acid (GABA), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), choline, acetylcholine, norepinephrine, dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and adenosine. In this study, we observed that 5-HT and DA levels in the brain increased immediately after PTZ-induced seizures. Behavioral tests clearly showed that all of these AEDs suppressed the PTZ-induced seizures. Upon treatment of PTZ-induced seizures with these AEDs, CBZ decreased the glutamic acid and FFR increased the GABA levels; however, no neurotransmitter changes were observed in the brain after LEV administration. Thus, we demonstrated a series of neurotransmitter changes linked to behavioral changes during PTZ-induced epileptic seizures when LEV, CBZ, or FFR were administered. These findings will lead to a more detailed understanding of the pathogenesis of epilepsy associated with behavioral and neurotransmitter changes under AED treatment., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Objectives: To clarify whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection cause acute encephalopathy in children and which are the most common syndromes that cause them and what are the outcomes., Methods: A nationwide web-based survey among all members of the Japanese Society of Child Neurology to identify pediatric patients aged < 18 years who developed acute encephalopathy in Japan between 1 January 2020 and 31 May 2022 associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection confirmed by polymerase chain reaction or antigen tests using pharyngeal swabs. Acute encephalopathy was defined as acute onset of impaired consciousness lasting > 24 h or an altered mental state; neurological symptoms arising within 2 weeks of onset of COVID-19 or multisystem inflammatory syndrome in children (MIS-C)/pediatric inflammatory multisystem syndrome (PIMS); evidence of SARS-CoV-2 infection; and reasonable exclusion of other diseases. Patients were divided into the known clinico-radiological acute encephalopathy syndrome group and unexplained or unclassifiable acute encephalopathy group. Outcomes were assessed by pediatric cerebral performance category (PCPC) score at hospital discharge., Results: Of the 3,802 society members, 217 representing institutions responded, and 39 patients with suspected acute encephalopathy were reported, of which 31 met inclusion criteria. Of these patients, 14 were diagnosed with known clinico-radiological acute encephalopathy syndromes, with acute encephalopathy with biphasic seizures and late reduced diffusion (five patients) being the most common. Five developed acute encephalopathy associated with MIS-C/PIMS. Among 31 patients, 9 (29.0%) had severe sequelae or died (PCPC ≥ 4). Two of three patients with encephalopathy with acute fulminant cerebral edema and two with hemorrhagic shock and encephalopathy syndrome died. The PCPC scores were higher in the known clinico-radiological acute encephalopathy syndrome group than in the unexplained or unclassifiable acute encephalopathy group ( P < 0.01)., Discussion: Acute encephalopathy related to SARS-CoV-2 infection was demonstrated to be more severe than that caused by other viruses in Japan. Acute encephalopathy syndromes characterized by specific neuroradiological findings was associated with poor clinical outcomes., Competing Interests: HS received a University–Industry Joint Research Fund from Meiji Co., Ltd. KK received research funds from Syneos Health Clinical Co., Ltd. for the clinical trial of Zogenix. The funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sakuma, Takanashi, Muramatsu, Kondo, Shiihara, Suzuki, Okanari, Kasai, Mitani, Nakazawa, Omata, Shimoda, Abe, Maegaki, Murayama, Murofushi, Nagase, Okumura, Sakai, Tada and Mizuguchi.)

Objective: This study evaluated the feasibility of a matching-pair test using eye-tracking technology to assess nusinersen effectiveness in patients with advanced spinal muscular atrophy (SMA) type I., Methods: This prospective, observational study enrolled patients with 5q-SMA type I who had lost gross motor function. Three different levels of matching-pair tests were conducted using the eye-gaze system (My Tobii; TobiiDynavox Inc.) at baseline, and after 9 and 24 weeks of nusinersen treatment. The primary endpoint was the change from baseline in matching-pair test scores and response times (i.e., the time to answer matching-pair test) at 24 weeks from baseline. Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), Pediatric Quality of Life inventory for patients with Neuromuscular Disease (PedsQL-NM) and Numerical Rating Scale (NRS) scores were also assessed as secondary endpoints. Analysis of ocular fixation was performed as an additional analysis. This study was registered at https://www.umin.ac.jp/ctr/ (UMIN000033935)., Results: Seven patients (one male, six female) aged 5-21 years (median 11 years) were enrolled; all patients were bedridden and six patients were ventilated. All seven patients were able to conduct level 1 matching-pair tests at each assessment; five patients were also able to conduct levels 2 and 3. Two patients (those with the highest CHOP-INTEND scores) were able to complete all tests correctly within 60 s. There was a non-significant trend toward improvement in CHOP-INTEND, PedsQL-NM, and NRS scores over the 6-month period. There were no significant differences in the number of actions, errors, correct answers, or response times between baseline and Week 9 or 24 at any level. However, the result of an additional analysis suggests that detection of eye movement would be useful to evaluate for advanced SMA., Conclusions: Eye-tracking systems are possibly feasible for the assessment of treatment efficacy in patients with advanced SMA type I., Competing Interests: This study received funding from Biogen Japan Ltd (Tokyo, Japan). The funder had the following involvement with the study: design, analysis and interpretation, writing and the decision to submit this article for publication. All named authors have contributed significantly to the intellectual content of the manuscript, and have critically reviewed all drafts and approved the final version for submission. Author KY has received speaker honoraria from Biogen Japan, Novartis Japan, and Chugai Pharmaceutical for activities unrelated to the present work. Author OK has received honoraria from Biogen Japan and UCB Japan for activities unrelated to the present work. Authors SM and TF have attended a Biogen Japan advisory board unrelated to the present work. Author YYu has received honoraria from Shionogi, Novartis, Takeda, Daiichi Sankyo, Novel Pharma and Janssen for activities unrelated to the present work. Author MC is an employee of Biogen Japan Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yae, Yuge, Maeda, Ichinose, Matsuo, Kobayashi, Okanari, Baba, Yonee, Maruyama, Shibata, Fujii, Chinen and Yamashita.)

Objective: We aimed to clarify the patterns of ictal power and phase lag among bilateral hemispheres on scalp electroencephalography (EEG) recorded pre-operatively during epileptic spasms (ESs) and the correlation with the outcomes following corpus callosotomy. Methods: We enrolled 17 patients who underwent corpus callosotomy for ESs before 20 years of age. After corpus callosotomy, seven patients did not experience further ESs (favorable outcome group), and the remaining 10 patients had ongoing ESs (unfavorable outcome group). We used pre-operative scalp EEG data from monopolar montages using the average reference. The relative power spectrum (PS), ictal power laterality (IPL) among the hemispheres, and phase lag, calculated by the cross-power spectrum (CPS) among symmetrical electrodes (i.e., F3 and F4), were analyzed in the EEG data of ESs from 143 pre-operative scalp video-EEG records. Analyses were conducted separately in each frequency band from the delta, theta, alpha, beta, and gamma range. We compared the means of those data in each patient between favorable and unfavorable outcome groups. Results: Among all frequency bands, no significant differences were seen in the individual mean relative PSs in the favorable and unfavorable outcome group. Although the mean IPLs in each patient tended to be high in the unfavorable outcome group, no significant differences were found. The mean CPSs in the delta, theta, and gamma frequency bands were significantly higher in the unfavorable than in the favorable outcome group. Using the Youden index, the optimal cutoff points of those mean CPS values for unfavorable outcomes were 64.00 in the delta band (sensitivity: 100%, specificity: 80%), 74.20 in the theta band (100, 80%), and 82.05 in the gamma band (100, 80%). Subanalyses indicated that those CPS differences originated from pairs of symmetrical electrodes in the bilateral frontal and temporal areas. Significance: Ictal power and laterality of the ictal power in each frequency band were not associated with the outcomes of CC; however, the phase lags seen in the delta, theta, and gamma frequency bands were larger in the unfavorable than in the favorable outcome group. The phase lags may predict outcomes of CC for ESs on pre-surgical scalp-ictal EEGs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Oguri, Okanishi, Kanai, Baba, Nishimura, Ogo, Himoto, Okanari, Maegaki, Enoki and Fujimoto.)

Myelin oligodendrocyte glycoprotein is a major target of the humoral immune response in children affected by inflammatory demyelinating diseases of the central nervous system. Although myelin oligodendrocyte glycoprotein causes autoimmune encephalitis in different animal models, the relevance of this mechanism in human autoimmune diseases of the central nervous system is unclear. We herein report a child with acute disseminated encephalomyelitis possibly triggered by central nervous system infection of primary herpes simplex virus in the presence of antimyelin oligodendrocyte glycoprotein antibody. A healthy 5-year-old Japanese boy suffered from acute disseminated encephalomyelitis. He was positive for antimyelin oligodendrocyte glycoprotein antibody in both the serum and the cerebrospinal fluid, and herpes simplex virus-1 DNA on polymerase chain reaction of the cerebrospinal fluid. We speculated that the central nervous system infection of primary herpes simplex virus disrupted the blood-brain barrier, and antimyelin oligodendrocyte glycoprotein antibody already present in serum was transferred to the cerebrospinal fluid, resulting in the onset of acute disseminated encephalomyelitis. This might be the mechanism underlying postinfectious acute disseminated encephalomyelitis associated with myelin oligodendrocyte glycoprotein antibody., Competing Interests: Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Although spinal meningiomas are uncommon in children, clear cell meningioma has been described as the most common variant of spinal meningiomas in the pediatric age group. 24 cases of pediatric spinal clear call meningioma have been reported in the literature. We report one case and review the literature regarding pediatric spinal clear cell meningioma.

Objective: We aimed to clarify the association between magnetic resonance imaging (MRI)-lesion patterns, including cortices and white matters, and the development, occurrence, and intractableness of West syndrome in patients with tuberous sclerosis complex (TSC), using visual analysis., Methods: We collected data for 44 patients with TSC who had undergone brain MRI and developmental evaluation after the ages of 2 and 3 years, respectively. Fluid-attenuated inversion recovery (FLAIR) and T1-weighted images were used to analyze the number of cyst-like tubers, the number of cyst-like subcortical lesions, and the presence of diffuse lesions involving the cortices and white matter., Results: Developmental delays were observed in 28 patients. Nineteen patients had a history of West syndrome. Cyst-like tubers (range: 1-10), cyst-like subcortical lesions (range: 1-4), and diffuse lesions (range: 1-6 areas) were observed in 15, 9, and 14 patients, respectively. In the univariate analyses, all MRI findings were associated with development and/or history of West syndrome. However, in the multivariate analyses, only the diffuse lesion was associated with severe development (p = 0.003) and history of West syndrome (p = 0.012). In the subanalysis of patients with West syndrome, the diffuse lesions were also associated with pharmacological intractableness. Patients with diffuse lesions had a history of West syndrome with sensitivity of 68% and specificity of 96%. Patients with two or more areas of diffuse lesions had history of pharmacologically intractable West syndrome with sensitivity of 89% and specificity of 91%., Conclusions: Diffuse lesions may help to predict the poor neurological outcomes in patients with TSC., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: Postictal generalized electroencephalographic suppression (PGES) has been associated with sudden unexpected death in epilepsy (SUDEP) in adults. Decreased heart rate variability (HRV) is one clinical marker of SUDEP in adults with epilepsy. The objective of this study was to analyze the characteristics of HRV associated with generalized convulsive seizures (GCS) ± PGES in children., Methods: Nine hundred and seventy-seven consecutive children who underwent prolonged scalp video-EEG (vEEG) and 1-lead electrocardiogram (ECG) monitoring at the Hospital for Sick Children, Toronto, Ontario, Canada were reviewed retrospectively from 2009 to 2011. Thirty-five children had GCS captured during their vEEG with or without PGES and met inclusion criteria. Children were subdivided into three age groups and compared with age-matched controls: 3-6 years; 7-12 years; and 13-18 years. Interictal HRV was measured at 5 min during N2 sleep. Preictal HRV was measured at 1 h prior to GCS onset, and postictal HRV was measured at 3 min post-GCS cessation. Low frequency (LF: ms 2 , 0.04-0.15 Hz) and high frequency (HF: ms 2 , 0.15-0.4 Hz) bands of heart rate oscillations were analyzed during the interictal and preictal periods. The root mean square of successive differences (RMSSDs) was analyzed during the following time points: interictal; preictal; and postictal., Results: Thirty-five children had GCS: 18 children with PGES [3-6 years (n = 2); 7-12 years (n = 6); 13-18 years (n = 10)] and 17 children without PGES [3-6 years (n = 6); 7-12 years (n = 5); 13-18 years (n = 6)]. Seventeen additional age-matched controls were identified [3-6 years (n = 3); 7-12 years (n = 5); 13-18 years (n = 9)]. Seventy-four GCS were captured consisting of 36 GCS + PGES and 38 GCS - PGES. There was no difference of interictal HRV among children with GCS ± PGES and controls. The preictal LF and HF in 36 GCS + PGES were significantly higher compared with 38 GCS - PGES (p < 0.01). The postictal RMSSD in 36 GCS + PGES was significantly higher compared with 38 GCS - PGES (p < 0.01). The pre- to postictal RMSSD change was significantly lower in children with GCS + PGES than in those with GCS - PGES (p = 0.035)., Conclusions: In summary, the preictal HRV in GCS + PGES was significantly higher than in children with GCS - PGES. The higher remaining postictal RMSSD in children with GCS + PGES is a potential indicator of autonomic dysregulation. In certain children with epilepsy, autonomic dysregulation may contribute to poor recovery from a GCS with subsequent PGES, thereby contributing to SUDEP. Heart rate variability and autonomic regulation in children with epilepsy should be further studied prospectively in order to better understand the mechanism by which PGES may lead to SUDEP., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Corpus callosotomy (CC) has recently been adopted for the treatment of drug-resistant epileptic spasms and tonic spasms. In the present study, we investigated CC outcomes among patients with drug-resistant epileptic spasms or tonic spasms associated with tuberous sclerosis complex (TSC)., Methods: We retrospectively collected data from seven patients (3 women, 4 men) with diagnosed TSC and who were treated using CC at Seirei Hamamatsu General Hospital in Japan. All patients had experienced drug-resistant epileptic spasms (<3 s of muscular contraction) or tonic spasms (>3 s) prior to CC, which were confirmed via video-electroencephalogram monitoring., Results: All patients exhibited multiple bilateral cortical tubers on brain magnetic resonance imaging. The main seizure types were epileptic spasms in four, tonic spasms in one, and both seizure types in two patients. Patients underwent total CC between the ages of 25 months and 21.5 years. Additional resection or disconnection was performed in two patients. The follow-up period after CC ranged between 9 months and 3.5 years. Three patients achieved remission from spasms following CC alone. Two other patients became free from spasms several months after CC but required an additional focus disconnection or medical treatment. The remaining two patients continued to show spasms or asymmetrical tonic seizures., Conclusion: Total CC resulted in freedom from drug-resistant epileptic or tonic spasms in several patients with TSC. Stepwise progression from CC to additional resection or disconnection surgery may aid in the treatment of spasms secondary to TSC., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: Sudden death in the bathtub occurs relatively frequently in Japan, particularly among elderly people. We hypothesize that sudden death in epilepsy occurring in the bathtub (SDEPB) can be distinguished from sudden death in nonepilepsy occurring in the bathtub (SDnonEPB), but is identical to sudden unexpected death in epilepsy (SUDEP)., Methods: Tokyo Medical Examiner's Office conducts postmortem examinations for all sudden and unexpected deaths in Tokyo. Clinical, social, and autopsy findings of 43 SDEPB were compared with 76 SDnonEPB, 50 SUDEP outside the bathtub, and Japanese forensic autopsy data as controls., Results: Extension of the leg(s) outside the bathtub was seen in 33% of SDEPB, but none of SDnonEPB. Sitting position was seen less frequently in SDEPB (37%) than in SDnonEPB (64%). Lung weight and pleural effusion volume were significantly lower in SDEPB than in SDnonEPB. Age at death in SDEPB was significantly younger than that in SDnonEPB. Sudden death in epilepsy occurring in the bathtub showed no differences in lung weight and pleural effusion volume from SUDEP. Living with family was more frequent in SDEPB (73%) than in SUDEP (48%). Few antiepileptic drugs, infrequent seizures, and low rate of mental retardation were identical between SDEPB and SUDEP. Lung weight was significantly heavier in all three groups than in age- and sex- matched autopsy controls., Conclusions: Leg extension outside the bathtub, lower lung weight, and absence of pleural effusion distinguish SDEPB from SDnonEPB in elderly people. Sudden death in epilepsy occurring in the bathtub may represent a form of SUDEP occurring in the bathtub, rather than drowning despite submergence in the bathtub at discovery. Conditions for bathing require careful attention from physicians and relatives, even for patients with epilepsy with few medications and infrequent seizures, and without mental retardation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Everolimus is a mammalian target of rapamycin (mTOR) inhibitor that has cytoreductive effects on subependymal giant cell astrocytoma and renal angiomyolipoma in tuberous sclerosis complex (TSC). Recent studies have also shown its efficacy against refractory seizures in TSC. We investigated the efficacy of everolimus in nine patients with TSC, who were admitted to the TSC clinic in Seirei Hamamatsu General Hospital and who suffered from refractory seizures. At the start of treatment, patients ranged from 1 month to 23 years of age, and were refractory to a mean of 5.4 antiepileptic agents. Main seizures were focal in six patients and generalized in three patients. After 0.5 to 4.0 years (mean=2.4 years), three patients (33%) were seizure-free and two patients (22%) experienced >90% reduction in seizures. Everolimus may therefore be effective in the treatment of refractory seizures in TSC. (Received February 20, 2019; Accepted April 2, 2019; Published June 1, 2019).

Background: The purpose of this study was to elucidate whether H1 antihistamine administration increases susceptibility to febrile convulsions in children., Methods: A single-center, retrospective observational study was conducted in Japan. The study included 380 children with febrile convulsions between the ages of six months and five years transported via ambulance from 2011 through 2016. They were divided into the preseizure H1 antagonist "use group" and the "nonuse group." The former consisted of children who took H1 antagonists within 24 hours before the seizure onset. The primary outcome (seizure duration) and the secondary outcome (interval from fever to seizure onset) were compared between the two groups., Results: Of the 380 study patients, 70 (18%) were identified as the use group. None of the patients was taking excessive doses of H1 antagonists. The prevalence of seizures lasting 15 minutes or longer was not different between the use group and the nonuse group (11% versus 8%, prevalence ratio 1.47 [95% confidence interval, 0.63 to 3.42], P = 0.37). The prevalence of fever to seizure onset less than six hours was significantly lower in the use group (26% versus 52%, prevalence ratio 0.33 [95% confidence interval 0.19 to 0.60], P < 0.001). Similar results were obtained when analyses were conducted separately by different generations (first and second) of H1 antagonists., Conclusions: Prolonged seizure duration and shortened interval from fever to seizure were not observed in children who received H1 antagonists. This study provides evidence that H1 antagonists at optimal doses could be safely used in febrile children with allergic symptoms., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The identification of a biomarker for sudden unexpected death in epilepsy (SUDEP) has the potential to save lives. Generalized convulsive seizures and postictal generalized suppression on electroencephalography (EEG) most often precede sudden unexpected death in epilepsy (SUDEP) and are potential biomarkers. We identify the EEG and seizure characteristics associated with postictal generalized EEG suppression in children with epilepsy., Methods: Video EEGs were reviewed for seizure type, duration and semiology, and electrographic features. To identify predictors of postictal generalized EEG suppression, we identified 40 children with generalized convulsive seizures from a group of 399 patients who experienced an electroclinical seizure during video-EEG. Seventy-seven generalized convulsive seizures with and without postictal generalized EEG suppression were anayzed., Results: Age of seizure onset was older in 19 children with postictal generalized EEG suppression (mean 6.8 years old, 95% CI [4.7-8.9]) than in 21 without postictal generalized EEG suppression (3.0 years old, [1.1-4.1], P = 0.041). Postictal generalized EEG suppression occurred significantly more often from sleep than awake (point of estimate 16.67; 95% CI [0.97-32.36], P < 0.038). Shorter duration of the clonic phase (-0.76; [-1.338, -0.133], P = 0.018) was significantly associated with postictal generalized EEG suppression. Ictal symmetric tonic extension posturing significantly increased the odds of postictal generalized EEG suppression (42.94; [18.77, 67.12], P = 0.001). All 15 generalized convulsive seizures with a terminal burst-suppression pattern were followed by postictal generalized EEG suppression in contrast to 19 of 62 generalized convulsive seizures without burst-suppression (15.32, P < 0.001)., Conclusions: Ictal decerebrate-like symmetric tonic extension posturing with shorter clonic phase and a terminal burst-suppression pattern identify malignant generalized convulsive seizures, associated with postictal generalized EEG suppression and a potentially increased risk of sudden unexpected death in epilepsy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: Although many surgical treatment strategies for Chiari malformation type I (CM-I) have been reported, the most appropriate surgical technique remains controversial. It is wholly ascribable to the complicacy of pathological condition in CM-I. Recently, intraoperative neurophysiologic monitoring (INM) is becoming prevalent in spinal surgery. Indeed, motor-evoked potentials (MEPs) monitoring and somatosensory-evoked potentials (SSEPs) monitoring are standard tools to minimize the risk of neurologic injury and postoperative deficits. The most recent study suggested that multimodality INM can be beneficial in foramen magnum decompression surgery for CM-I patients for surgical positioning and planning. Various authors have investigated the consistency of intraoperative evoked potential changes that might aid the surgeon to determine the appropriate extent of decompression required for an individual patient., Patient Description: The authors report the case of a 7-year-old boy who had the signs of medullary and cerebellar dysfunction, clumsy hands, and ataxic gait. He underwent a surgery of foramen magnum decompression with tonsillectomy and duraplasty for CM-I with cervicomedullary compression. His intraoperative MEPs improved (indicated increased-amplitude and shortened-latency) both after craniotomy and durotomy, whereas SSEPs improved only after durotomy. Those results were correlated well with a functional improvement that was apparent in the immediate postoperative hospitalization., Conclusions: The authors' data provides 1 possible interpretation of INM for safety aspect, but also which degree of decompression in each patient will require. The improvement in MEPs and SSEPs observed during decompression procedure may be a good indicator for the prediction of the clinical improvement seen postoperatively.

Patients with COL4A1 mutation-related disorders demonstrate a variety of disease phenotypes, which caused by small-vessel dysfunction in the brain, eyes, kidney, muscle, or heart. The involvement of organs mainly depends on the expression of the COL4A1 gene. Complication or dysfunction of the alveolar tissue has not been reported in the literature on COL4A1 mutation-related disorders. We herein report the case of a boy with schizencephaly, renovascular hypertension, and retinal arteriosclerosis of unknown origin, who suffered from severe and repetitive alveolar hemorrhage at 9 years of age. A novel COL4A1 mutation was finally identified as the genetic cause. The pulmonary complication in the present case represents an important pathophysiological mechanism COL4A1 mutation-related disorders; lung tissue with COL4A1 gene mutations may be vulnerable and environmental substances and microorganisms in the air could accumulate to cause chronic damage in the alveolar tissues, especially in patients with tracheostoma and renovascular hypertension., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Objective: Cortical resections in epilepsy surgery tend to involve multiple lobes in children, compared to adults, partly due to underlying pathology. Oligodendroglia-like cells (OLCs) have been observed in surgical specimens from children with pharmacoresistant epilepsy. We hypothesize that OLCs recruit multiple-lobe epileptogenic zones in pediatric pharmacoresistant focal epilepsy., Methods: We examined the surgical specimens from 30 children who underwent epilepsy surgery (1.8- to 16.9-years-old; mean age 9.7 years). Immunohistochemical assays of OLCs were performed using Olig2, which is a marker of OLC. OLC populations in three sites (gray matter, gray-white matter junction, and white matter) were counted. We also performed immunohistochemical staining with neuronal nuclear antigen (NeuN) and glial fibrillary acidic protein (GFAP) for neuronal and astroglial markers, respectively. NeuN- and GFAP-positive cells were distinguished from OLCs. OLC results were compared with seizure types, scalp and intracranial video-electroencephalography (EEG), magnetic resonance imaging (MRI), surgical resection area, histopathologic diagnosis, and seizure outcome., Results: Histopathologic diagnosis consisted of 14 cases of focal cortical dysplasia (FCD; type I; 4, type II; 9, type III; one); 6 cases of oligodendrogliosis; 6 cases of astrocytic gliosis; 2 cases of hyaline protoplasmic astrocytopathy; and 2 cases of tuberous sclerosis. Fifteen children (50%) underwent multiple-lobe resections after intracranial video-EEG. There was a positive correlation between the number of resected electrodes and the OLC population in the white matter (correlation coefficient 0.581, p = 0.001) and at the gray-white matter junction- (correlation coefficient 0.426, p = 0.027). OLC populations in both areas were increased significantly in nine children with epileptic spasms (ES) (gray-white matter junction [p = 0.021] and white matter [p = 0.025]), and nine nonfocal ictal scalp EEG findings (gray-white matter junction [p = 0.04] and white matter [p = 0.042]). The OLC population in white matter was significantly increased in children with 11 nonfocal interictal scalp EEG findings (p = 0.01), with 15 multiple-lobe resections (p = 0.028)., Significance: Pharmacoresistant epilepsy in children with increased OLCs presented with nonfocal epileptiform discharges on scalp EEG and ES, and they required multiple-lobe resections. We found increased populations of subcortical OLCs in the extensive epileptogenic zone., (Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.)

We report a pediatric case of reversible cerebral vasoconstriction syndrome with focal seizures without a thunderclap headache. A 7-year-old girl had a mild acute headache with nausea after swimming. She subsequently developed hemi-convulsions followed by right hemiplegia. Brain magnetic resonance angiography revealed generalized vasoconstriction of the main cerebral peripheral arteries. Her hemiplegia was spontaneously resolved within 6h. Over the next 24h she suffered from recurrent and transient headaches, which recurred on days 3 and 5. Follow-up magnetic resonance angiography on day 3 documented the multifocal narrowing of the main cerebral arteries, which was observed to have diminished at 12weeks after her initial presentation. She did not have any headaches or neurological deficits after day 5. This case indicates that reversible cerebral vasoconstriction syndrome should be considered in children with focal seizures even when they do not present with thunderclap headaches. The timely and appropriate evaluation by magnetic resonance angiography and imaging is essential for diagnosing reversible cerebral vasoconstriction syndrome., (Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Objective: Epilepsy surgery can be successful in children with extensive congenital or early acquired focal or hemispheric brain lesion on magnetic resonance imaging (MRI) despite generalized interictal epileptiform discharges (IEDs). The aim of this study was to assess if rapid eye movement (REM) sleep reduced generalized IEDs and revealed lateralized IEDs to identify the epileptogenic hemisphere in children with generalized IEDs and normal/subtle changes on MRI., Methods: We studied 20 children with generalized IEDs on scalp electroencephalography (EEG) and normal/subtle changes on MRI who underwent intracranial video-EEG for epilepsy surgery. We assessed a minimum of 100 IEDs during REM, non-REM, and wakefulness, and assigned the distribution (generalized, left, or right hemisphere) to each IED. The number of lobes in the resected areas and seizure outcome were compared between 20 children with generalized IEDs and a comparison group of 28 children without generalized IEDs., Results: The mean occurrence rate of generalized IEDs during REM (37%) was significantly lower than that during non-REM (67%, p < 0.001) and wakefulness (54%, p = 0.003). The number of children whose largest number of IEDs was lateralized in REM was significantly higher than that in non-REM (15 vs. 3 children, 75% vs. 15%, p < 0.001). The hemisphere with lateralized IEDs among three states corresponded with the surgical side in 16 children with generalized IEDs. Seventeen children (85%) with generalized IEDs and 27 (96%) without generalized IEDs underwent resective surgery. Multilobar resection was required for 16 children (94%) with generalized IEDs more frequently than 7 children (26%) without generalized IEDs (p < 0.001). Thirteen children (77%) with generalized IEDs and 19 (73%) without generalized IEDs were seizure-free with a mean of 3.3 years of follow-up., Significance: Our study demonstrates the importance of assessing REM in children with generalized IEDs as it reveals lateralized epileptogenic spikes. Seizure freedom may be achieved with multilobar resection in these children with generalized IEDs and normal/subtle changes on MRI. Generalized IEDs in children with normal/subtle changes on MRI should not preclude surgical resection., (Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.)

Infants with Sturge-Weber syndrome (SWS) are considered for surgery if they develop seizures and the seizures prove medically refractory. The authors report on 2 infants (15 and 19 months old) with SWS who underwent scalp video electroencephalography (EEG) and subsequent functional hemispherotomy for intractable partial motor seizures due to extensive left hemispheric angiomatosis. They presented with similar interictal and ictal EEG findings. Ictal EEG showed abrupt high-amplitude delta slow waves, without evolution on the contralateral hemisphere before the build-up of ictal EEG changes on the lesional hemisphere. The patients became seizure free after hemispherotomy. The ictal contralateral slow waves were not a sign of an ictal hemisphere and may indicate prominent ischemic changes resulting from a steal phenomenon of hemispheric angiomatosis during seizure.

Background: Generalized paroxysmal fast activity (GPFA) consists of burst of generalized rhythmic discharges; 100-200 μV; 1-9s; 8-26 Hz; with frontal predominance; appearing during NREM sleep. GPFA was originally described as an electrographic feature of Lennox-Gastaut Syndrome (LGS). We analyzed GPFA on scalp video EEG (VEEG) in children to evaluate that GPFA presents in patients with intractable localization-related epilepsy., Methods: We collected cases with GPFA with intractable localization-related epilepsy who underwent scalp VEEG, MRI, and magnetoencephalography (MEG) prior to intracranial video EEG (IVEEG) and surgical resection. We collected 50 epochs of GPFA per patient during the first night during scalp VEEG. We analyzed amplitude, duration and frequency of GPFA over the bilateral frontal region between surgical resection side with grid placement and non-resection side., Results: We identified 14 (14%) patients with GPFA on scalp VEEG. The mean amplitude ranged from 145 to 589 μV (mean 293 μV). The mean duration ranged from 1.18 to 2.31s (mean 1.6s). The mean frequencies ranged from 9.3 to 14.7 Hz (mean 11.1 Hz). The amplitude (307 ± 156 μV) and duration (1.62 ± 0.8s) of GPFAs in all the patients over the resection side were significantly higher than those (279 ± 141 μV, 1.58 ± 0.8s) of the non-resection side (p<0.001). All nine patients who showed significant duration differences between two hemispheres (p<0.05) had longer duration of GPFA over the resection side. Eight of 12 patients who showed significant amplitude differences between two hemispheres (p<0.05) had higher amplitude of GPFA over the resection side. Four of six patients who showed significant frequency differences between two hemispheres (p<0.05) had higher frequency of GPFA over the resection side. Nine (64%) patients became seizure free after surgical resection including multilobar resections in eight patients., Conclusions: GPFA can exist in localization-related epilepsy with secondary bilateral synchrony. Although EEG shows GPFA on scalp VEEG, the precise localization of the epileptogenic zone using IVEEG could achieve the successful surgical resection., (Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Background: Xeroderma pigmentosum group A (XPA) is a rare autosomal-recessive disorder caused by a defect in nucleotide excision repair. Progressive dysautonomia in patients with XPA is rarely described., Patients: Two juvenile male patients with XPA suffered from dysphagia, sleep interruption, and dysuria from the age of 10 to 19 years, successively. These autonomic symptoms might have been caused by progressive descending degeneration of cranial nerves IX and X and the sacral parasympathetic nerve, including Onuf's nucleus. One patient died from sudden cardiopulmonary arrest during postural change and tracheal suction., Results: Heart rate variability analyses of these patients revealed parasympathetic dysautonomia, based on decreased high-frequency values., Conclusions: The insidiously progressive dysautonomia in these two patients with XPA suggested progressive descending degeneration extending from the medulla oblongata to the sacral spinal cord, which is an ominous sign of end-stage disease and a risk factor of sudden death attributable to XPA., (Copyright © 2014 Elsevier Inc. All rights reserved.)

A male infant with trisomy 21 simultaneously showed clinical features of hypomelanosis of Ito and hemimegalencephaly, with related intractable epileptic seizures. The epileptic seizures were refractory to conventional antiepileptic drugs and persisted until the patient underwent functional hemispherotomy. It is well known that patients with hypomelanosis of Ito may also have cortical dysplasia and hemimegalencephaly and that approximately half of these patients have chromosomal abnormalities. However, to our knowledge, there is no previous report of a patient with trisomy 21 associated with hemimegalencephaly. Here, we describe a rare case of coexisting trisomy 21 and hypomelanosis of Ito, associated with hemimegalencephaly.

A 1-year and 11-month-old female infant with bilateral lesions of the thalamus, basal ganglia, cerebellar and brainstem disease died from heart failure 9 days after being administered a measles vaccination. She had a high fever, hypocarnitinemic and non-ketotic hypoglycemia, serum levels of total carnitine 7.4 micromol/L, free carnitine 5.6 micromol/L, acylcarnitine 1.8 micromol/L and glucose 13 mg/dL. Due to feeding difficulty, the patient, however, had been administered parenteral elementary nutrition through a feeding tube since early infancy. The commercially available parenteral nutrition solutions do not contain carnitine. A secondary carnitine deficiency followed by non-ketotic hypoglycemia-related heart failure may readily develop even in a patient without valproic acid, during high fever.