Publications by authors named "Kenji Sugai"

166 Publications

Improvement of brain function after surgery in infants with posterior quadrant cortical dysplasia.

Clin Neurophysiol 2021 Feb 3;132(2):332-337. Epub 2020 Dec 3.

Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi-cho, Kodaira, Tokyo 187-8551, Japan. Electronic address:

Objective: To reveal whether neurodevelopmental outcome of infants after epilepsy surgery can be quantitatively assessed by electroencephalography (EEG) functional connectivity analysis.

Methods: We enrolled 13 infants with posterior quadrant dysplasia aged <2 years who were treated using posterior quadrantectomy and 21 age-matched infants. EEG was performed both before and one year after surgery. Developmental quotient (DQ) was assessed both before and 3 years after surgery. The phase lag index (PLI) of three different pairs of electrodes in the nonsurgical hemisphere, i.e., the anterior short distance (ASD), posterior short distance (PSD), and long distance (LD) pairs, were calculated as indices of brain connectivity. The relationship between the PLI and DQ was evaluated.

Results: Overall, 77% infants experienced seizure freedom after surgery. The beta- and gamma- range PLI of PSD pairs increased preoperatively. All these pairs normalized postoperatively. Simple linear regression analysis revealed a significant relationship between the postoperative DQ and the postoperative beta-band PLI of ASD pairs.

Conclusion: Preoperative abnormal hyper-connectivity was normalized to the control level after surgery. The postoperative hyperconnectivity was associated with long-term neurodevelopmental improvement.

Significance: PLI quantifies neurodevelopmental improvements after posterior quadrantectomy.
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http://dx.doi.org/10.1016/j.clinph.2020.11.020DOI Listing
February 2021

Association between lack of functional connectivity of the frontal brain region and poor response inhibition in children with frontal lobe epilepsy.

Epilepsy Behav 2020 12 21;113:107561. Epub 2020 Nov 21.

Department of Developmental Disorders, National Institute of Mental Health, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi-cho, Kodaira, Tokyo 187-8553, Japan. Electronic address:

Purpose: We investigated the relationship between electroencephalographic (EEG) functional connectivity and executive function in children with frontal lobe epilepsy (FLE).

Methods: We enrolled 24 children with FLE (mean age, 11.0 years; 13 boys) and 22 sex-, age-, and intelligence-matched typically developing children (TDC) to undergo 19-channel EEG during light sleep. We estimated functional connectivity using the phase lag index (PLI) that captures the synchronization of EEG. We also performed continuous performance tests (CPTs) on the children and obtained questionnaire responses on attention deficit hyperactivity disorder and oppositional defiant disorder (ODD).

Results: The average gamma PLI was lower in the FLE group than in the TDC group, especially between long-distance frontoparietal pairs, between interhemispheric frontal pairs, and between interhemispheric parietotemporal pairs. Gamma PLIs with long-distance frontoparietal and interhemispheric frontal pairs were positively associated with inattention, ODD scores, omission error, and reaction time in the FLE group but not in the TDC group. Conversely, they were negatively associated with age, hyperactivity score, and commission error.

Conclusions: A lack of functional connectivity of the frontal brain regions in children with FLE was associated with poor response inhibition.
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http://dx.doi.org/10.1016/j.yebeh.2020.107561DOI Listing
December 2020

Postoperative improvement of executive function and adaptive behavior in children with intractable epilepsy.

Brain Dev 2021 Feb 29;43(2):280-287. Epub 2020 Aug 29.

Department of Developmental Disorders, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan.

Introduction: An alteration in postoperative cognitive function varies according to the patients' background characteristics, such as etiology, focus, and seizure duration. Accurate prediction and assessment of postoperative cognitive function is difficult in each patient. Adaptive behavior could describe the typical performance of daily activities and represents the ability to translate cognitive potential into real-world skills. We examined the relationship between alterations of executive function (EF) and adaptive behavior in school children undergoing surgery for intractable epilepsy.

Methodology: We enrolled 31 children with focal resection or corpus callosotomy for intractable epilepsy [mean age at surgery, 12.5 years; 16 boys; mean intellectual quotient, 73.3]. We surveyed answered questionnaires on attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and adaptive behavior using the Vineland Adaptive Behavior Scale, 2nd edition (VABS-II), and performed continuous performance tests (CPTs) on children pre- and postoperatively.

Result: ADHD and ASD symptoms improved after epilepsy surgery. The omission error (OE) in the CPT variable improved after epilepsy surgery, especially in children with a shorter preoperative period. Improved ASD symptoms led to an increased score of the coping skills subdomain. The reduced OE observed after surgery also increased the score of the community skills subdomain.

Conclusion: Improvement in EF and ASD symptoms resulted in better adaptive behavior postoperatively. These results were important for the pre- and postoperative evaluation and re-evaluation of children with epilepsy requiring special education and related services.
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http://dx.doi.org/10.1016/j.braindev.2020.08.005DOI Listing
February 2021

Cognitive and developmental outcomes after pediatric insular epilepsy surgery for focal cortical dysplasia.

J Neurosurg Pediatr 2020 Aug 7:1-9. Epub 2020 Aug 7.

Departments of1Neurosurgery and.

Objective: Cognitive risk associated with insular cortex resection is not well understood. The authors reviewed cognitive and developmental outcomes in pediatric patients who underwent resection of the epileptogenic zone involving the insula.

Methods: A review was conducted of 15 patients who underwent resective epilepsy surgery involving the insular cortex for focal cortical dysplasia, with a minimum follow-up of 12 months. The median age at surgery was 5.6 years (range 0.3-13.6 years). Developmental/intelligence quotient (DQ/IQ) scores were evaluated before surgery, within 4 months after surgery, and at 12 months or more after surgery. Repeated measures multivariate ANOVA was used to evaluate the effects on outcomes of the within-subject factor (time) and between-subject factors (resection side, anterior insular resection, seizure control, and antiepileptic drug [AED] reduction).

Results: The mean preoperative DQ/IQ score was 60.7 ± 22.8. Left-side resection and anterior insular resection were performed in 9 patients each. Favorable seizure control (International League Against Epilepsy class 1-3) was achieved in 8 patients. Postoperative motor deficits were observed in 9 patients (permanent in 6, transient in 3). Within-subject changes in DQ/IQ were not significantly affected by insular resection (p = 0.13). Postoperative changes in DQ/IQ were not significantly affected by surgical side, anterior insular resection, AED reduction, or seizure outcome. Only verbal function showed no significant changes before and after surgery and no significant effects of within-subject factors.

Conclusions: Resection involving the insula in children with impaired development or intelligence can be performed without significant reduction in DQ/IQ, but carries the risk of postoperative motor deficits.
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http://dx.doi.org/10.3171/2020.5.PEDS2058DOI Listing
August 2020

KCNT1-positive epilepsy of infancy with migrating focal seizures successfully treated with nonnarcotic antitussive drugs after treatment failure with quinidine: A case report.

Brain Dev 2020 Sep 3;42(8):607-611. Epub 2020 Jun 3.

College of Nursing and Nutrition, Shukutoku University, Tokyo, Japan.

Background: Epilepsy of infancy with migrating focal seizures (EIMFS) is one of the early-onset epileptic encephalopathies resistant to antiepileptic drugs, therefore carrying an extremely poor neurodevelopmental outcome. KCNT1, encoding for a sodium-activated potassium channel (K4.1 channel), has recently been reported as the major gene responsible for EIMFS. Since gain of function is the only type of mutation identified in patients with EIMFS, quinidine, a partial antagonist of K4.1 channel, is considered as a potential candidate for targeted treatment of EIMFS. However, treatment results reported so far vary from seizure-free state to no response, and cardiac side effect remains a challenge for dose titration and long-term treatment.

Case Report: Our case was an infant diagnosed with EIMFS with confirmed mutation in KCNT1 gene. Quinidine therapy was started as early as 9 months old. Within the first month of treatment, the number of seizures reduced to about one third. However, seizure-free state was not obtained and his neuropsychological development remained severely delayed. After 16 months of treatment, quinidine had to be discontinued because of cardiac side effects. At 27 months of age, however, his seizures suddenly stopped and he remained seizure-free for five days. This coincided with the prescription of tipepidine, a commonly used antitussive, administered for his persistent cough. Reduction in seizure frequency was also observed with dextromethorphan, another conventional antitussive drug. Although the relation between these treatments and his symptom improvement is a matter of elucidation, there is a possibility that these nonnarcotic antitussive drugs might play a role in the treatment of EIFMS.
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http://dx.doi.org/10.1016/j.braindev.2020.05.002DOI Listing
September 2020

Variant in the neuronal vesicular SNARE VAMP2 (synaptobrevin-2): First report in Japan.

Brain Dev 2020 Aug 23;42(7):529-533. Epub 2020 Apr 23.

Department of Pediatrics, JCHO Gunma Central Hospital, Gunma, Japan.

Background: A report presenting five heterozygous de novo variants in VAMP2 in unrelated individuals with a neurodevelopmental disorder characterized by axial hypotonia, intellectual disability, and autistic features was first published in April 4, 2019.

Case Report: We report the case of a male child with VAMP2 variant who was delivered at 38 weeks and 4 days without neonatal asphyxia. At 4 months of age he showed hypotonia and no visual pursuit and fixation. He presented with infantile spasms at 6 months, and electroencephalography (EEG) showed hypsarrhythmia. His infantile spasms completely disappeared by adrenocorticotropic hormone therapy, but his EEG findings continued to show high voltage slow-waves with multi-focal spikes. At 2 years of age he was non-verbal, had an absence of purposeful hand movements, and no visual fixation. He had somnolence tendency in the daytime. Biochemical and extensive genetic examinations were unrevealed. Magnetic resonance imaging showed slight brain atrophy. At 2 years and 7 months of age, he suffered from myoclonic seizures of the eyelid and tongue, which propagated to unilateral fingers, and sometimes to the bilateral legs. At 8 years of age hyperkinetic movement occurred. At age 13, whole-exome sequence identified a heterozygous missense variant, NM_014232.2:c.199G>C,[p.(Ala67Pro)] in exon 3 of VAMP2 which was a de novo non-synonymous variant.

Conclusion: This is the first case report of VAMP2 variant in Japan. Hypotonia at early infancy, poor visual fixation, and absence of purposeful hand movements may be indicative of the diagnosis for VAMP2 variant.
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http://dx.doi.org/10.1016/j.braindev.2020.04.001DOI Listing
August 2020

Adaptive behavior and its related factors in children with focal epilepsy.

Epilepsy Behav 2020 07 19;108:107092. Epub 2020 Apr 19.

Department of Developmental Disorders, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan.

Objective: We aimed to clarify the strengths and weaknesses in adaptive behavior in children with focal epilepsy and show children-associated factors related to adaptive behavior.

Materials And Methods: Sixty-three children with focal epilepsy aged 5-18 years with intellectual quotient (IQ) ranging from 67 to 135 were enrolled in this study. Adaptive behavior was evaluated using the Vineland Adaptive Behavior Scale, 2nd edition (VABS-II). The children performed continuous performance test and tests of reading, writing, and IQ; parents answered questionnaires regarding attention-deficit hyperactivity disorder and autism spectrum disorder (ASD). Participants were categorized into four groups based on IQ and adaptive behavior scores for statistical comparisons.

Results And Discussion: Children with low adaptive behavior were more likely to show a reduction in daily living skills, and those with both low adaptive behavior and IQ were more likely to show a reduction in daily living skills and communication. Lower adaptive behavior was related to more severe autistic symptoms, lower academic achievement in children with IQ > 85, and lower executive function in children with IQ ≤ 85. There was a qualitative difference of cognitive dysfunction in adaptive behavior between both groups.

Conclusions: There were differences in VABS-II domain and subdomain characteristics between children with focal epilepsy and those with ASD; however, it was more difficult for children with more severe ASD and coexisting focal epilepsy to show age-equivalent adaptive behavior.
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http://dx.doi.org/10.1016/j.yebeh.2020.107092DOI Listing
July 2020

Transient water-electrolyte disturbance after hemispherotomy in young infants with epileptic encephalopathy.

Childs Nerv Syst 2020 05 16;36(5):1043-1048. Epub 2019 Dec 16.

Department of Neurosurgery, National Center of Neurology and Psychiatry, Tokyo, Japan.

Purpose: This study aimed to elucidate the clinical features of water-electrolyte disturbance (WED) as a sequela of hemispherotomy.

Methods: We performed a retrospective chart review to identify the clinical features of diabetes insipidus (DI) as a complication in < 12-month-old patients who underwent hemispherectomy or hemispherotomy for severe epilepsy between 2007 and 2018. Central DI was diagnosed if a patient developed polyuria (urine output > 5 mL/kg/h), abnormally high serum osmolality (> 300 mOsm/kg), high serum sodium level (> 150 mEq/L), either abnormally low urine specific gravity (< 1.005) or low urine osmolality (< 300 mOsm/kg) or both, and effective control of polyuria with arginine vasopressin (AVP). The clinical course of post-hemispherotomy WED, complications other than WED, and seizure outcomes were analyzed.

Results: The review identified that 3 of 23 infants developed WED. All patients developed polyuria within 2 days after surgery, with high serum osmolality and hypotonic urine; AVP was effective in treating these symptoms. The clinical course was compatible with central DI. Two patients subsequently developed hyponatremia in a biphasic or triphasic manner. All patients had multiple seizures that were probably related to WED. Two patients developed asymptomatic cerebral sinovenous thrombosis, possibly because of the surgical procedure and dehydration; anticoagulant treatment was provided. All patients were treated for WED for up to 2 months and had no residual pituitary dysfunction.

Conclusion: Systemic complications other than intracranial ones can occur in patients who have undergone hemispherotomy. Perioperative systemic management of young infants undergoing this procedure should include careful water and electrolyte balance monitoring.
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http://dx.doi.org/10.1007/s00381-019-04452-1DOI Listing
May 2020

Alteration of the anatomical covariance network after corpus callosotomy in pediatric intractable epilepsy.

PLoS One 2019 5;14(12):e0222876. Epub 2019 Dec 5.

Department of Developmental Disorders, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan.

Purpose: This study aimed to use graph theoretical analysis of anatomical covariance derived from structural MRI to reveal how the gray matter connectivity pattern is altered after corpus callosotomy (CC).

Materials And Methods: We recruited 21 patients with epilepsy who had undergone CC. Enrollment criteria were applied: (1) no lesion identified on brain MRI; (2) no history of other brain surgery; and (3) age not younger than 3 years and not older than 18 years at preoperative MRI evaluation. The most common epilepsy syndrome was Lennox-Gastaut syndrome (11 patients). For voxel-based morphometry, the normalized gray matter images of pre-CC and post-CC patients were analyzed with SPM12 (voxel-level threshold of p<0.05 [familywise error-corrected]). Secondly, the images of both groups were subjected to graph theoretical analysis using the Graph Analysis Toolbox with SPM8. Each group was also compared with 32 age- and sex-matched control patients without brain diseases.

Results: Comparisons between the pre- and post-CC groups revealed a significant reduction in seizure frequency with no change in mean intelligence quotient/developmental quotient levels. There was no relationship among the three groups in global network metrics or in targeted attack. A regional comparison of betweenness centrality revealed decreased connectivity to and from the right middle cingulate gyri and medial side of the right superior frontal gyrus and a partial shift in the distribution of betweenness centrality hubs to the normal location. Significantly lower resilience to random failure was found after versus before CC and versus controls (p = 0.0450 and p = 0.0200, respectively).

Conclusion: Graph theoretical analysis of anatomical covariance derived from structural imaging revealed two neural network effects of resection associated with seizure reduction: the reappearance of a structural network comparable to that in healthy children and reduced connectivity along the median line, including the middle cingulate gyrus.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0222876PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6894802PMC
March 2020

The effect of the guidelines for management of febrile seizures 2015 on clinical practices: Nationwide survey in Japan.

Brain Dev 2020 Jan 8;42(1):28-34. Epub 2019 Oct 8.

Working Group for Guidelines for Management of Febrile Seizures, Japanese Society of Child Neurology, Nagoya, Japan; Faculty of Health and Medical Sciences, Tokoha University Hamamatsu Campus, Hamamatsu, Japan.

Objective: To investigate the effect of guidelines for management of febrile seizures on the clinical practice, we conducted a nationwide survey in Japan.

Methods: The Japanese guidelines for management of febrile seizures 2015 (GL2015) was released in 2015. In 2016, a questionnaire was sent to all 512 certified hospitals (3 pediatricians each) of the Japan Pediatric Society and all 47 prefecture Pediatric Associations (10 private pediatricians each) in Japan asking about management policies for febrile seizures (FSs) during 2013-2014 and 2016. The questionnaires were about the following procedures: (1) lumbar punctures, blood examinations, and diazepam suppositories for children after a first simple FS at emergency departments; and (2) prophylactic diazepam during febrile illnesses in children with two or three past simple FSs, with no known predictors of recurrence.

Results: A total of 1327 pediatricians (66.2%) answered the questionnaire. Numbers of pediatricians performing lumbar punctures and blood examinations, and giving diazepam suppositories after a first simple FS were less in 2016 than in 2013-2014 (1.2% and 2.0%, 53.1% and 61.3%, and 36.7% and 51.9%, respectively). Pediatricians recommending prophylactic diazepam for children with two and three FSs decreased from 45.7% and 82.4% in 2013-2014 to 31.0% and 65.0% in 2016, respectively.

Conclusion: GL2015 had an effect on the clinical practices of pediatricians. On the other hand, 65% recommended prophylactic diazepam to children with three simple FSs even though GL2015 did not recommend use of diazepam based on number of previous FS. Anxiety about frequent seizures may affect pediatricians' clinical practice.
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http://dx.doi.org/10.1016/j.braindev.2019.08.009DOI Listing
January 2020

Static Leukoencephalopathy Associated with 17p13.3 Microdeletion Syndrome: A Case Report.

Neuropediatrics 2019 12 1;50(6):387-390. Epub 2019 Aug 1.

Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan.

Background: Leukoencephalopathy associated with dysmorphic features may be attributed to chromosomal abnormalities such as 17p13.3 microdeletion syndrome.

Case: A 19-year-old female patient was referred to our hospital for diagnostic evaluation of her leukoencephalopathy. She demonstrated moderate intellectual disability, minor dysmorphic features, and short stature. Serial brain magnetic resonance images obtained within a 16-year interval revealed prolonged T2 signals in the deep cerebral white matter with enlarged Virchow-Robin spaces. A nonsymptomatic atlas anomaly was also noted. Using microarray-based comparative genomic hybridization, we identified a 2.2-Mb terminal deletion at 17p13.3, encompassing , , and but not .

Conclusion: Except for atlas anomaly, the patient's clinical and imaging findings were compatible with the diagnosis of 17p13.3 microdeletion syndrome. The white matter abnormality was static and nonprogressive. The association between the atlas abnormality and this deletion remains elusive. We note the importance of exploring submicroscopic chromosomal imbalance when patients show prominent but static white matter abnormalities with discrepantly mild and stable neurological signs.
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http://dx.doi.org/10.1055/s-0039-1693972DOI Listing
December 2019

Altered Expression of Astrocyte-Related Receptors and Channels Correlates With Epileptogenesis in Hippocampal Sclerosis.

Pediatr Dev Pathol 2019 Nov-Dec;22(6):532-539. Epub 2019 Jun 5.

Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Japan.

Background: Hippocampal sclerosis (HS) is one of the major causes of intractable epilepsy. Astrogliosis in epileptic brain is a peculiar condition showing epileptogenesis and is thought to be different from the other pathological conditions. The aim of this study is to investigate the altered expression of astrocytic receptors, which contribute to neurotransmission in the synapse, and channels in HS lesions.

Methods: We performed immunohistochemical and immunoblotting analyses of the P2RY1, P2RY2, P2RY4, Kir4.1, Kv4.2, mGluR1, and mGluR5 receptors and channels with the brain samples of 20 HS patients and 4 controls and evaluated the ratio of immunopositive cells and those expression levels.

Results: The ratio of each immunopositive cell per glial fibrillary acidic protein-positive astrocytes and the expression levels of all 7 astrocytic receptors and channels in HS lesions were significantly increased. We previously described unique astrogliosis in epileptic lesions similar to what was observed in this study.

Conclusion: This phenomenon is considered to trigger activation of the related signaling pathways and then contribute to epileptogenesis. Thus, astrocytes in epileptic lesion may show self-hyperexcitability and contribute to epileptogenesis through the endogenous astrocytic receptors and channels. These findings may suggest novel astrocytic receptor-related targets for the pharmacological treatment of epilepsy.
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http://dx.doi.org/10.1177/1093526619855488DOI Listing
April 2020

Ictal deafness in drug-resistant MRI-negative epilepsy.

Epileptic Disord 2019 Apr;21(2):215-220

Department of Neurosurgery.

Ictal clinical semiology indicates where the patient's seizure arises from and how it progresses. A patient's description of a focal sensory seizure may support a surgical decision even when MRI and PET abnormalities are absent. Ictal deafness is a focal auditory seizure characterized by suppression of hearing, presumably originating from the auditory cortex in the temporal lobe. However, the precise localization has not been confirmed with surgical cases. We present a case in which the region from where ictal deafness arose was confirmed by intracranial electroencephalography, with successful epilepsy surgery and review other published cases.
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http://dx.doi.org/10.1684/epd.2019.1042DOI Listing
April 2019

Genetic landscape of Rett syndrome-like phenotypes revealed by whole exome sequencing.

J Med Genet 2019 06 6;56(6):396-407. Epub 2019 Mar 6.

Division of Pediatrics, Tokyo Metropolitan Tobu Medical Center for Persons with Developmental and Multiple Disabilities, Tokyo, Japan.

Background: Rett syndrome (RTT) is a characteristic neurological disease presenting with regressive loss of neurodevelopmental milestones. Typical RTT is generally caused by abnormality of methyl-CpG binding protein 2 (). Our objective to investigate the genetic landscape of -negative typical/atypical RTT and RTT-like phenotypes using whole exome sequencing (WES).

Methods: We performed WES on 77 -negative patients either with typical RTT (n=11), atypical RTT (n=22) or RTT-like phenotypes (n=44) incompatible with the RTT criteria.

Results: Pathogenic or likely pathogenic single-nucleotide variants in 28 known genes were found in 39 of 77 (50.6%) patients. WES-based CNV analysis revealed pathogenic deletions involving six known genes (including ) in 8 of 77 (10.4%) patients. Overall, diagnostic yield was 47 of 77 (61.0 %). Furthermore, strong candidate variants were found in four novel genes: a de novo variant in each of ATPase H transporting V0 subunit A1 (), ubiquitin-specific peptidase 8 () and microtubule-associated serine/threonine kinase 3 (), as well as biallelic variants in nuclear receptor corepressor 2 ().

Conclusions: Our study provides a new landscape including additional genetic variants contributing to RTT-like phenotypes, highlighting the importance of comprehensive genetic analysis.
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http://dx.doi.org/10.1136/jmedgenet-2018-105775DOI Listing
June 2019

Disrupted cortico-ponto-cerebellar pathway in patients with hemimegalencephaly.

Brain Dev 2019 Jun 18;41(6):507-515. Epub 2019 Jan 18.

Integrative Brain Imaging Center, National Center Hospital of Neurology and Psychiatry, Tokyo, Japan.

Objective: Cerebellar dysmaturation and injury is associated with a wide range of neuromotor, neurocognitive and behavioral disorders as well as with preterm birth. We used diffusion tensor MR imaging to investigate a disruption in structural cortico-ponto-cerebellar (CPC) connectivity in children with infantile-onset severe epilepsy.

Methods: We performed CPC tract reconstructions in 24 hemimegalencephaly (HME) patients, 28 West syndrome (WS) of unknown etiology patients, and 25 pediatric disease control subjects without a history of epilepsy nor brain abnormality on MRI. To identify the CPC tract, we placed a seeding ROI separately in each right and left cerebral peduncle. We evaluated the distribution patterns of the CPC tracts to the cerebellum and their correlation with clinical findings.

Results: In control and WS of unknown etiology groups, both sides' CPC tracts descended to bilateral hemispheres in 20 (80.0%) and 21 (75.0%); mixed (bilateral on one side and unilateral on the other side) in five (20.0%) and five (17.9%); and unilateral in zero (0.0%) and two (7.1%), respectively. However, in the HME, both sides' CPC tracts descended to bilateral hemispheres in four (16.7%); mixed in 13 (54.1%); and unilateral in seven (29.2%). These CPC patterns differed significantly between the HME and other groups (p < 0.001). Among HME patients, those with a unilateral cerebellar distribution on both sides had significantly earlier seizure onset (p = 0.049) and more frequent seizures (p = 0.052) at a trend level compared to those with bilateral and mixed distributions.

Conclusion: Disrupted CPC tracts were observed more frequently in HME patients than in WS of unknown etiology patients and controls, and they may be correlated with earlier seizure onset and more frequent seizures in HME patients. DTI is a useful and non-invasive method for speculating the pathology in the developing brain.
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http://dx.doi.org/10.1016/j.braindev.2019.01.002DOI Listing
June 2019

Efficacy, safety, and pharmacokinetics of intravenous midazolam in Japanese children with status epilepticus.

J Neurol Sci 2019 01 4;396:150-158. Epub 2018 Oct 4.

Department of Pediatrics, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. Electronic address:

Background: No dosing regimen has been established for the initial treatment of pediatric status epilepticus with intravenous midazolam. We therefore evaluated the efficacy, safety, and pharmacokinetics of bolus and continuous midazolam infusion.

Methods: This open-label, prospective, multicenter study involved 34 Japanese children with status epilepticus unresponsive to diazepam. An initial bolus of 0.15 mg/kg midazolam was given, with additional doses of 0.1-0.3 mg/kg up to a cumulative dose of 0.6 mg/kg. A continuous infusion was initiated at 0.1 mg/kg/h (maximum 0.4 mg/kg/h) for patients at high risk of recurrence or in whom seizure reduction was achieved, and continued for 24 h after seizure cessation. Seizure cessation was assessed based on clinical observation (disappearance of motor symptoms regardless of recovery of consciousness), rather than the disappearance of electroencephalography abnormalities.

Results: The seizure cessation rate with bolus midazolam was 88%. The cumulative dose was ≤0.3 mg/kg in 90% of patients who responded to bolus administration. Adverse events were observed in three patients; one had mild respiratory depression that required supplemental oxygen and bag-valve-mask ventilation. Elimination half-life was 0.999 ± 0.241 h in seven patients. Total body clearance ranged from 423 to 1220 mL/h/kg in older children but was notably higher in a 10-month-old infant (2010 mL/h/kg).

Conclusions: The efficacy and safety of midazolam were demonstrated in children with status epilepticus, suggesting that intravenous midazolam is suitable as first-line treatment.
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http://dx.doi.org/10.1016/j.jns.2018.09.035DOI Listing
January 2019

Urinary prostaglandin metabolites as Duchenne muscular dystrophy progression markers.

Brain Dev 2018 Nov 10;40(10):918-925. Epub 2018 Jul 10.

Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan.

Background: Patients with Duchenne muscular dystrophy (DMD) exhibit increased prostaglandin D (PGD) expression in necrotic muscle and increased PGD metabolites in their urine. In mouse models, inhibiting PGD production suppresses muscle necrosis, suggesting a possible intervention through PGD-mediated activities.

Objective: We investigated the involvement of PGD and its potential use as a marker of pathological progression in DMD.

Methods: Sixty-one male children with DMD and thirty-five age-matched controls were enrolled in the study. DMD patients were divided into "ambulant" and "non-ambulant" groups, which were further subdivided into "steroid" and "non-steroid" therapy groups. Levels of the PGD metabolite tetranor-PGDM (t-PGDM) and creatinine were measured in both spot and 24-hour urine samples, with comparisons between groups made according to geometric mean values.

Results: DMD patients had significantly higher levels of creatinine-corrected t-PGDM in spot urine samples as compared with the control group. Additionally, both ambulant and non-ambulant DMD groups had significantly higher levels of t-PGDM as compared with controls, with no significant difference in t-PGDM levels observed between steroid and non-steroid groups. Moreover, total creatinine excretion in 24-hour urine samples was significantly lower in DMD patients as compared with controls, and although DMD patients had lower muscle mass than controls, their overall levels of t-PGDM did not differ significantly from those in the non-ambulant and control groups.

Conclusion: PGD might help explain the progression and symptomatic presentations (e.g., ambulatory difficulty) associated with DMD, suggesting it as a useful pathological marker and use of a selective PGD inhibitor as a potential treatment modality.
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http://dx.doi.org/10.1016/j.braindev.2018.06.012DOI Listing
November 2018

Seizure imitators monitored using video-EEG in children with intellectual disabilities.

Epilepsy Behav 2018 07 20;84:122-126. Epub 2018 May 20.

Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan.

Diagnosis of seizure imitators in children is often challenging, and individuals with intellectual disability (ID) could be at additional risk of seizure imitator misdiagnosis. We aimed to elucidate distinct features of clinical semiology among children of different intellectual levels, which may help in distinguishing seizure imitators from epilepsy in such individuals. We retrospectively compared semiological features of seizure imitators in children with and without ID captured using video-electroencephalography (video-EEG). Seizure imitators were classified based on the definition of the International League Against Epilepsy (ILAE). A total of 67 individuals (mean age: 8.4 years, SD: 4.2 years) with seizure imitators documented using long-term video-EEG were identified, in which 27 patients had normal IQ/DQ, 20 had moderate ID, and 20 had severe ID. There was no statistically significant difference in the semiological features of seizure imitators between individuals with ID and those without ID; similarly, no difference was found between those with moderate ID and severe ID compared with individuals with normal IQ/DQ. Among all the patients, altered responsiveness mimicking cognitive or absence seizures was most frequently observed (36%), followed by jerks mimicking myoclonic seizures (22%). The most common seizure imitators among all the patients were unclassifiable nonepileptic seizures per the ILAE definition (28 cases, 42%), followed by day dreaming (24 cases, 36%) and physiological myoclonus (14 cases, 21%). In summary, the present study found no marked difference in semiological features of seizure imitators between patients with ID and those without ID regardless of ID severity, suggesting the necessity of early video-EEG for correct diagnosis.
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http://dx.doi.org/10.1016/j.yebeh.2018.05.006DOI Listing
July 2018

Two Japanese cases of epileptic encephalopathy associated with an FGF12 mutation.

Brain Dev 2018 Sep 23;40(8):728-732. Epub 2018 Apr 23.

Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan.

A heterozygous mutation in the fibroblast growth factor 12 (FGF12) gene, which elevates the voltage dependence of neuronal sodium channel fast inactivation, was recently identified in some patients with epileptic encephalopathy. Here we report 1 Japanese patient diagnosed with early infantile epileptic encephalopathy (EIEE) and another diagnosed with epilepsy of infancy with migrating focal seizures (EIMFS). These 2 patients had an identical heterozygous missense mutation [c.341G>A:p.(Arg114His)] in FGF12 , which was identified with whole-exome sequencing. This mutation is identical to previously reported mutations in cases with early onset epileptic encephalopathy. One of our cases exhibited EIMFS, and this case responded to phenytoin and high-dose phenobarbital (PB). FGF12-related epileptic encephalopathy may exhibit diverse phenotypes and may respond to sodium channel blockers or high-dose PB.
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http://dx.doi.org/10.1016/j.braindev.2018.04.002DOI Listing
September 2018

Intractable epilepsy due to a rosette-forming glioneuronal tumor with a dysembryoplastic neuroepithelial background.

Neuropathology 2018 Jun 18;38(3):300-304. Epub 2017 Dec 18.

Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan.

A rosette-forming glioneuronal tumor (RGNT) was initially reported as an infratentorial tumor that comprised both small neurocytic rosettes and astrocytic components. However, a few studies have reported supratentorial RGNTs arising in the cerebral hemispheres. Here, we report an unusual case involving a 9-year-old boy with a supratentorial RGNT who presented with intractable epilepsy and behavioral changes. Brain MRI revealed a well-circumscribed space-occupying lesion with septae in the right inferomedial parietal lobe. Electroencephalography showed multifocal spikes over the right frontal, temporal and parietal regions. The seizure frequency decreased dramatically after tumorectomy. Histopathological examination revealed prominent neurocytic rosette formation appearing with the specific glioneuronal element of a dysembryoplastic neuroepithelial tumor (DNT). Although the pathogenesis has not been elucidated, a supratentorial RGNT presenting with epilepsy may exhibit a rosette component, which is the major feature of this tumor, against the background of a specific glioneuronal element mimicking DNT. However, RGNT arising in regions other than the fourth ventricle is rare, and the pathogenesis of epilepsy due to RGNT has not been fully elucidated. Further clinical and histological studies are required to understand the pathology underlying epilepsy caused by RGNT.
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http://dx.doi.org/10.1111/neup.12450DOI Listing
June 2018

mutations abrogate iron-sulfur cluster assembly leading to cavitating leukoencephalopathy.

Neurol Genet 2017 Oct 8;3(5):e184. Epub 2017 Sep 8.

Department of Child Neurology (A.I., Y.S., E.N., H.K, K.S., M.S.), National Center Hospital; Department of Neuromuscular Research (A.I., S.N., S.M., Y.E., Y.K.H., I. Nonaka, I. Nishino.), National Institute of Neuroscience; Department of Mental Retardation and Birth Defect Research (C.S., Y.M., Y.-i.G.), National Institute of Neuroscience; Department of Radiology (N.S.), National Center Hospital, National Center of Neurology and Psychiatry, Tokyo; Department of Pharmacology (A.I.), Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi; and Department of Pathophysiology (Y.K.H), Tokyo Medical University, Japan.

Objective: To determine the molecular factors contributing to progressive cavitating leukoencephalopathy (PCL) to help resolve the underlying genotype-phenotype associations in the mitochondrial iron-sulfur cluster (ISC) assembly system.

Methods: The subjects were 3 patients from 2 families who showed no inconsistencies in either clinical or brain MRI findings as PCL. We used exome sequencing, immunoblotting, and enzyme activity assays to establish a molecular diagnosis and determine the roles of ISC-associated factors in PCL.

Results: We performed genetic analyses on these 3 patients and identified compound heterozygosity for the gene, which encodes the mitochondrial iron-sulfur protein assembly factor. Protein expression analysis revealed substantial decreases in IBA57 protein expression in myoblasts and fibroblasts. Immunoblotting revealed substantially reduced expression of SDHB, a subunit of complex II, and lipoic acid synthetase (LIAS). Levels of pyruvate dehydrogenase complex-E2 and α-ketoglutarate dehydrogenase-E2, which use lipoic acid as a cofactor, were also reduced. In activity staining, SDH activity was clearly reduced, but it was ameliorated in mitochondrial fractions from rescued myoblasts. In addition, NFU1 protein expression was also decreased, which is required for the assembly of a subset of iron-sulfur proteins to SDH and LIAS in the mitochondrial ISC assembly system.

Conclusions: Defects in IBA57 essentially regulate NFU1 expression, and aberrant NFU1 ultimately affects SDH activity and LIAS expression in the ISC biogenesis pathway. This study provides new insights into the role of the iron-sulfur protein assembly system in disorders related to mitochondrial energy metabolism associated with leukoencephalopathy with cavities.
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http://dx.doi.org/10.1212/NXG.0000000000000184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5591399PMC
October 2017

Epileptic apnea in a patient with inherited glycosylphosphatidylinositol anchor deficiency and PIGT mutations.

Brain Dev 2018 Jan 17;40(1):53-57. Epub 2017 Jul 17.

Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan.

We report an 11-month-old boy with acetazolamide-responsive epileptic apnea and inherited glycosylphosphatidylinositol (GPI)-anchor deficiency who presented with decreased serum alkaline phosphatase associated with compound PIGT mutations. The patient exhibited congenital anomalies, severe intellectual disability, and seizures, including epileptic apnea with epileptiform discharges from bilateral temporal areas. Brain magnetic resonance imaging revealed delayed myelination and progressive atrophy of the brainstem, cerebellum, and cerebrum. Whole-exome sequencing revealed compound heterozygous mutations in PIGT (c.250G>T, p.Glu84X and c.1096G>T, p.Gly366Trp), which encodes a subunit of the GPI transamidase complex. Flow cytometry revealed decreased expression of CD16 (a GPI anchor protein) on granulocytes, supporting the putative pathogenicity of the mutations. Phenobarbital, clonazepam, and potassium bromide decreased the frequency of tonic seizure and acetazolamide decreased epileptic apnea. To our knowledge, this is the first reported case of intractable seizures accompanied by epileptic apnea associated with GPI anchor deficiency and a compound PIGT mutation.
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http://dx.doi.org/10.1016/j.braindev.2017.06.005DOI Listing
January 2018

Pathologic Active mTOR Mutation in Brain Malformation with Intractable Epilepsy Leads to Cell-Autonomous Migration Delay.

Am J Pathol 2017 May;187(5):1177-1185

Epilepsy Center, National Center of Neurology and Psychiatry, National Institute of Neuroscience, Kodaira, Japan; Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, Kodaira, Japan. Electronic address:

The activation of phosphatidylinositol 3-kinase-AKTs-mammalian target of rapamycin cell signaling pathway leads to cell overgrowth and abnormal migration and results in various types of cortical malformations, such as hemimegalencephaly (HME), focal cortical dysplasia, and tuberous sclerosis complex. However, the pathomechanism underlying abnormal cell migration remains unknown. With the use of fetal mouse brain, we performed causative gene analysis of the resected brain tissues from a patient with HME and investigated the pathogenesis. We obtained a novel somatic mutation of the MTOR gene, having approximately 11% and 7% mutation frequency in the resected brain tissues. Moreover, we revealed that the MTOR mutation resulted in hyperphosphorylation of its downstream molecules, S6 and 4E-binding protein 1, and delayed cell migration on the radial glial fiber and did not affect other cells. We suspect cell-autonomous migration arrest on the radial glial foot by the active MTOR mutation and offer potential explanations for why this may lead to cortical malformations such as HME.
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http://dx.doi.org/10.1016/j.ajpath.2017.01.015DOI Listing
May 2017

Behavioral disorder in people with an intellectual disability and epilepsy: A report of the Intellectual Disability Task Force of the Neuropsychiatric Commission of ILAE.

Epilepsia Open 2016 12 15;1(3-4):102-111. Epub 2016 Sep 15.

Melbourne School of Psychological Sciences the University of Melbourne Melbourne Victoria Australia.

The management and needs of people with intellectual disability (ID) and epilepsy are well evidenced; less so, the comorbidity of behavioral disorder in this population. "Behavioral disorder" is defined as behaviors that are difficult or disruptive, including stereotypes, difficult or disruptive behavior, aggressive behavior toward other people, behaviors that lead to injury to self or others, and destruction of property. These have an important link to emotional disturbance. This report, produced by the Intellectual Disability Task Force of the Neuropsychiatric Commission of the ILAE, aims to provide a brief review of some key areas of concern regarding behavioral disorder among this population and proposes a range of research and clinical practice recommendations generated by task force members. The areas covered in this report were identified by experts in the field as being of specific relevance to the broad epilepsy community when considering behavioral disorder in persons with epilepsy and ID; they are not intended to be exhaustive. The practice recommendations are based on the authors' review of the limited research in this field combined with their experience supporting this population. These points are not graded but can be seen as expert opinion guiding future research and clinical practice.
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http://dx.doi.org/10.1002/epi4.12018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5719831PMC
December 2016

New guidelines for management of febrile seizures in Japan.

Brain Dev 2017 Jan 6;39(1):2-9. Epub 2016 Sep 6.

Faculty of Health and Medical Sciences, Tokoha University Hamamatsu Campus, Hamamatsu, Japan.

In 2015, the Japanese Society of Child Neurology released new guidelines for the management of febrile seizures, the first update of such guidelines since 1996. In 1988, the Conference on Febrile Convulsions in Japan published "Guidelines for the Treatment of Febrile Seizures." The Task Committee of the Conference proposed a revised version of the guidelines in 1996; that version released in 1996 was used for the next 19years in Japan for the clinical management of children with febrile seizures. Although the guidelines were very helpful for many clinicians, new guidelines were needed to reflect changes in public health and the dissemination of new medical evidence. The Japanese Society of Child Neurology formed a working group in 2012, and published the new guidelines in March 2015. The guidelines include emergency care, application of electroencephalography, neuroimaging, prophylactic diazepam, antipyretics, drugs needing special attention, and vaccines. While the new guidelines contain updated clinical recommendations, many unsolved questions remain. These questions should be clarified by future clinical research.
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http://dx.doi.org/10.1016/j.braindev.2016.06.003DOI Listing
January 2017

Impaired neuronal KCC2 function by biallelic SLC12A5 mutations in migrating focal seizures and severe developmental delay.

Sci Rep 2016 07 20;6:30072. Epub 2016 Jul 20.

Department of Human Genetics, Graduate School of Medicine, Yokohama City University, 3-9 Fukuura, Yokohama 236-0004, Japan.

Epilepsy of infancy with migrating focal seizures (EIMFS) is one of the early-onset epileptic syndromes characterized by migrating polymorphous focal seizures. Whole exome sequencing (WES) in ten sporadic and one familial case of EIMFS revealed compound heterozygous SLC12A5 (encoding the neuronal K(+)-Cl(-) co-transporter KCC2) mutations in two families: c.279 + 1G > C causing skipping of exon 3 in the transcript (p.E50_Q93del) and c.572 C >T (p.A191V) in individuals 1 and 2, and c.967T > C (p.S323P) and c.1243 A > G (p.M415V) in individual 3. Another patient (individual 4) with migrating multifocal seizures and compound heterozygous mutations [c.953G > C (p.W318S) and c.2242_2244del (p.S748del)] was identified by searching WES data from 526 patients and SLC12A5-targeted resequencing data from 141 patients with infantile epilepsy. Gramicidin-perforated patch-clamp analysis demonstrated strongly suppressed Cl(-) extrusion function of E50_Q93del and M415V mutants, with mildly impaired function of A191V and S323P mutants. Cell surface expression levels of these KCC2 mutants were similar to wildtype KCC2. Heterologous expression of two KCC2 mutants, mimicking the patient status, produced a significantly greater intracellular Cl(-) level than with wildtype KCC2, but less than without KCC2. These data clearly demonstrated that partially disrupted neuronal Cl(-) extrusion, mediated by two types of differentially impaired KCC2 mutant in an individual, causes EIMFS.
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http://dx.doi.org/10.1038/srep30072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4951812PMC
July 2016

Successful immunoglobulin treatment in a case of epileptic encephalopathy.

No To Hattatsu 2016 Jul;48(4):277-81

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.
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July 2016

Long-term outcomes of steroid therapy for Duchenne muscular dystrophy in Japan.

Brain Dev 2016 Oct 21;38(9):785-91. Epub 2016 Apr 21.

Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.

Introduction: Corticosteroids are effective for improving motor function in patients with Duchenne muscular dystrophy (DMD), but there is no consensus on a regimen that balances efficacy and side effects.

Methods: Data from three groups of DMD patients were retrospectively analyzed: those treated with 0.75mg/kg/day prednisolone every day (daily group, n=51); those treated with 1mg/kg/day prednisolone on alternate days (intermittent group, n=36), and those not treated with steroids (nontreatment group, n=42).

Results: Although the age of ambulation loss did not differ significantly among the groups, the hazard ratios for ambulation loss relative to the nontreatment group were 0.24 (95% confidence interval [CI]: 0.11-0.54) in the daily group and 0.34 (95% CI: 0.19-0.62) in the intermittent group. The percentage of predicted forced vital capacity increased until 9.6years of age (to 94.1%) in the daily group, until 8.8years of age (to 96.9%) in the intermittent group, and until 7.2years of age (to 87.6%) in the nontreatment group. Weight gain was the most frequently observed side effect in the treated groups. Height was significantly lower in the daily than in the nontreatment group. Other side effects were observed, but no patient discontinued therapy. There were no marked differences in benefits and side effects between the two treated groups.

Discussion: This is the first assessment of long-term outcomes of different steroid therapy regimens in Japanese DMD patients. Benefits and side effects, except height, did not differ significantly between steroid regimens.
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http://dx.doi.org/10.1016/j.braindev.2016.04.001DOI Listing
October 2016

Surgical versus medical treatment for children with epileptic encephalopathy in infancy and early childhood: Results of an international multicenter cohort study in Far-East Asia (the FACE study).

Brain Dev 2016 May 10;38(5):449-60. Epub 2015 Dec 10.

Epilepsy Center, National Center of Neurology and Psychiatry, Tokyo, Japan.

Objective: To compare the seizure and developmental outcomes in infants and young children with epileptic encephalopathy who have undergone surgical and medical treatments.

Methods: An international, multicenter, observational cohort study was undertaken. A total of 317 children aged <6 years, who had frequent disabling seizures despite intensive medical treatments, were registered. Among the enrolled children, 250 were treated medically (medical group), 31 underwent resective surgery (resective group), and 36 underwent palliative surgery [callosotomy (n=30) or vagal nerve stimulation (n=6); palliative group] on admission. Seizure and developmental outcomes were obtained for 230 children during the 3-year follow-up period. Cox proportional hazard model was used to adjust for clinical backgrounds among treatment groups when comparing the seizure-free survival rates.

Results: At the 3-year follow-up, seizure-free survival was 15.7%, 32.1%, and 52.4% in the medical, palliative, and resective groups, respectively. The adjusted hazard ratios for seizure recurrence in the resective and palliative groups versus the medical group were 0.43 (95% CI, 0.21-0.87, P=0.019) and 0.82 (95% CI, 0.46-1.46, P=0.50), respectively; the former was statistically significant. Regarding the developmental outcome, the mean DQs in the resective group increased significantly compared to those in the medical group during the follow-up (P<0.01). As for subgroup analysis, better seizure and development outcomes were demonstrated in the resective group compared to the medical group in children with nonsyndromic epilepsies (those to which no known epilepsy syndromes were applicable).

Significance: These results suggest that surgical treatments, particularly resective surgeries, are associated with better seizure and developmental outcomes compared with successive medical treatment. The present observations may facilitate the identification of infants and young children with epileptic encephalopathy who could benefit from surgery.
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http://dx.doi.org/10.1016/j.braindev.2015.11.004DOI Listing
May 2016

Characterization of ictal slow waves in epileptic spasms.

Epileptic Disord 2015 Dec;17(4):425-35

Department of Child Neurology, National Center of Neurology and Psychiatry, Tokyo.

We characterized the clinico-neurophysiological features of epileptic spasms, particularly focusing on high-voltage slow waves during ictal EEG. We studied 22 patients with epileptic spasms recorded during digital video-scalp EEG, including five individuals who still had persistent spasms after callosotomy. We analysed the duration, amplitude, latency to onset of electromyographic bursts, and distribution of the highest positive and negative peaks of slow waves in 352 spasms. High-voltage positive slow waves preceded the identifiable muscle contractions of spasms. The mean duration of these positive waves was 569±228 m, and the mean latency to electromyographic onset was 182±127 m. These parameters varied markedly even within a patient. The highest peak of the positive component was distributed in variable regions, which was not consistent with the location of lesions on MRI. The peak of the negative component following the positivity was distributed in the neighbouring or opposite areas of the positive peak distribution. No changes were evident in the pre- or post-surgical distributions of the positive peak, or in the interhemispheric delay between both hemispheres, in individuals with callosotomy. Our data imply that ictal positive slow waves are the most common EEG changes during spasms associated with a massive motor component. Plausible explanations for these widespread positive slow waves include the notion that EEG changes possibly reflect involvement of both cortical and subcortical structures.
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http://dx.doi.org/10.1684/epd.2015.0783DOI Listing
December 2015