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Background Wolf–Hirschhorn syndrome (WHS) is caused by deletion of the terminal region of chromosome 4 short arm and is frequently associated with intractable epilepsy. Objective This article evaluates the clinical features of epileptic seizures in WHS and the therapeutic efficacy of oral antiseizure medications (ASMs) Methods Patients with WHS who were treated for epilepsy at the Saitama Children's Medical Center under 5 years of age were included. WHS was diagnosed based on genetic tests and clinical symptoms. Medical records regarding the age of onset of epilepsy, seizure type, treatment of status epilepticus (SE), and effectiveness of ASMs were retrospectively reviewed. Oral ASMs were considered effective when seizures were reduced by at least 50% compared with the premedication level. Results Eleven patients were included in the study. The median age at the onset of epilepsy was 9 months (range: 5–32 months). Unknown-onset bilateral tonic-clonic seizure was the most common type of seizure, occurring in 10 patients. Focal clonic seizures occurred in four patients. Ten patients exhibited recurrent episodes of SE, and its frequency during infancy was monthly in eight patients and yearly in two. SE occurrence peaked at 1 year of age and decreased after 3 years of age. The most effective ASM was levetiracetam. Conclusion Although WHS-associated epilepsy is intractable with frequent SE occurrence during infancy, improvement in seizure control is expected with age. Levetiracetam may be a novel ASM for WHS.

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

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

スパズムと他の焦点性発作を同時期に有する症例におけるVigabatrin（VGB）の有効性を検討した。当センターでスパズムに対しVGBを投与した症例のうち結節性硬化症を除き、同時期に焦点性発作を有した11例を対象とした。後方視的に各発作型へのVGBの有効性、VGB中止による発作変化、最終診察時の発作転帰について評価した。経過観察は1年～6年9カ月でVGB継続期間は2週間～1年3カ月、全例で焦点性発作がスパズムに先行発症した。VGBの発作型別の有効性は、スパズムは消失例がなく、焦点性発作は消失の5例を含め半減以上が9例だった。10例でVGBを中止し、VGB投与中焦点性発作が半減以上だった8例全例で再発又は増加した。発作転帰は、両発作型消失と焦点性発作のみ消失が各々1例、スパズムのみ消失が2例、両発作型残存が7例だった。両発作型を同時期に有する症例において、VGBはスパズムには無効でも焦点性発作に有効性を認めた。VGBは、スパズムと共に焦点性発作への有効性も考慮し、VGB継続ならびに再開を検討すべきである。また、難治性てんかんにおけるスパズム以外の発作型に対するVGBの適応拡大が望まれる。

Objective Absence status epilepticus (ASE) is a form of non-convulsive status epilepticus characterized by ongoing or intermittent epileptic activity accompanied by behavioral and cognitive changes. Herein, we assessed high-frequency oscillations in the ripple band in patients with ASE and typical absence seizures. Methods We enrolled five patients with ASE, 26 patients with childhood absence epilepsy (CAE), and 15 patients with juvenile absence epilepsy (JAE). We performed time–frequency analysis of electroencephalogram data for ictal absence seizures at each electrode to assess the high frequency activity (HFA) rate, peak frequency, and peak power. Results The average HFA rates were 60.7%, 20.8%, and 12.9% in ASE, CAE, and JAE patients, respectively. The average peak frequencies were 126.4 Hz, 120.9 Hz, and 126.1 Hz in ASE, CAE, and JAE patients, respectively. The average peak power values were 2,388.8 μV2, 120.9 μV2, and 126.1 μV2 in ASE, CAE, and JAE patients, respectively, and all epilepsy groups exhibited frontal-dominant ripple distribution. Conclusion ASE patients presented higher power and frontal dominant ripples of absence seizure, compared to CAE and JAE patients. Significance Future studies should utilize scalp-recorded ripples as a biomarker of absence epilepsy. This may aid in the development of novel treatment strategies for ASE.

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

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

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

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

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

Background Nonketotic hyperglycinemia is a severe form of early onset epileptic encephalopathy caused by disturbances in the glycine cleavage system; the neurological damage is mainly attributed to overstimulation of the N-methyl-D-aspartate receptor. Case The patient presented with a severe form of nonketotic hyperglycinemia and experienced frequent epileptic spasms and focal seizures, which were resistant to vigabatrin, adrenocorticotropic hormone therapy, and combined dextromethorphan and sodium benzoate treatments. By 9 months of age, perampanel reduced epileptic spasms by >50%. At 14 months of age, the ketogenic diet markedly reduced focal seizures and glycine levels in the cerebrospinal fluid. Conclusion Perampanel reduced fast excitatory neuronal activity, which was induced by an α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor, followed by prolonged electrical depolarizations due to an N-methyl-D-aspartate receptor. Furthermore, the ketogenic diet may have modulated the excessive neurotoxic cascade through the N-methyl-D-aspartate receptor. Perampanel and ketogenic diet were effective for seizure control in our patient.

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

We retrospectively investigated whether perampanel (PER) could serve as an alternative for treating drug-resistant seizures in lissencephaly. We investigated the following data: age at onset of epilepsy, age at start of PER, etiology, brain MRI findings, seizure type, seizure frequency, adverse effects, and concomitant anti-epileptic drugs. There were 5 patients with lissencephaly, including 2 with Miller–Dieker syndrome. Four out of five patients exhibited ≥ 50% seizure reduction. Myoclonic seizures disappeared in 1 patient. PER was an effective adjunctive anti-seizure drug in our series of patients with lissencephaly., Highlights • PER could treat drug-resistant seizures of patients with lissencephaly. • PER could be effective against epileptic myoclonus in lissencephaly. • AMPA receptor phenotype in neuronal migration disorder may explain effects of PER.

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

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

Introduction: We investigated serum matrix metalloprotease-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels in patients with acute phase hemiplegic migraine and migrainous infarction. Background: Migraine is a common disorder that is characterized by episodic headaches. Hemiplegic migraine and migrainous infarction are rare migraine-related conditions with unknown pathophysiology. Methods and Findings: We evaluated serum MMP-9, TIMP-1, and the MMP-9/TIMP-1 ratio in patients with migrainous infarction (patient 1), hemiplegic migraine (patient 2), cerebral infarction with other causes (group 3, n=4), and non-organic disease (group 4, n=5). Serum MMP-9 levels were significantly higher in patients 1 and 2 than in groups 3 and 4. The serum TIMP-1 level was significantly lower in patient 1 than in groups 3 and 4. MMP-9/TIMP-1 ratios were higher in patients 1 and 2 than in groups 3 and 4. Conclusion: MMP-9 levels and the MMP/TIMP-1 ratio may aid in the diagnosis of migraine, and therefore may provide a clue to the etiology of cerebral infarction.

Background Mutations in Lysine-Specific Histone Methyltransferase 2B gene (KMT2B) have been reported to be associated with complex early-onset dystonia. Almost all reported KMT2B mutations occurred de novo in the paternal germline or in the early development of the patient. We describe clinico-genetic features on four Japanese patients with novel de novo mutations and demonstrate the phenotypic spectrum of KMT2B mutations. Methods We performed genetic studies, including trio-based whole exome sequencing (WES), in a cohort of Japanese patients with a seemingly sporadic early-onset generalized combined dystonia. Potential effects by the identified nucleotide variations were evaluated biologically. Genotype-phenotype correlations were also investigated. Results Four patients had de novo heterozygous mutations in KMT2B, c.309delG, c.1656dupC, c.3325_3326insC, and c.5636delG. Biological analysis of KMT2B mRNA levels showed a reduced expression of mutant transcript frame. All patients presented with motor milestone delay, microcephaly, mild psychomotor impairment, childhood-onset generalized dystonia and superimposed choreoathetosis or myoclonus. One patient cannot stand due to axial hypotonia associated with cerebellar dysfunction. Three patients had bilateral globus pallidal deep brain stimulation (DBS) with excellent or partial response. Conclusions We further demonstrate the allelic heterogeneity and phenotypic variations of KMT2B-associated disease. Haploinsufficiency is one of molecular pathomechanisms underlying the disease. Cardinal clinical features include combined dystonia accompanying mild psychomotor disability. Cerebellum would be affected in KMT2B-associated disease.

Summary Purpose: To elucidate the abnormality of interictal regional cerebral blood flow (rCBF) of West syndrome at the onset. Methods: Quantitative measurement of rCBF with an autoradiography method using N-isopropyl-(123I) p-iodoamphetamine single photon emission computed tomography (SPECT) was performed on 14 infants with cryptogenic West syndrome. Regions of interest (ROIs) for rCBF were placed automatically using an automated ROI analysis software (three-dimensional stereotactic ROI template), and were grouped into 12 segments: callosomarginal, precentral, central, parietal, angular, temporal, posterior cerebral, pericallosal, lenticular nucleus, thalamus, hippocampus, and cerebellum. We compared rCBF between the patients and seven age-matched infants with cryptogenic focal epilepsy as a control group. The patients were divided into two groups according to the duration from onset to SPECT, to compare rCBF. Results: Quantitative analysis revealed cerebral hypoperfusion in cryptogenic West syndrome with normal SPECT images under visual inspection. In bilateral central, posterior cerebral, pericallosal, lenticular nucleus, and hippocampus, and in the left parietal, temporal, and cerebellum, and in the right angular and thalamus segments there were statistical differences (p

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

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

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

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

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

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

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

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