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We describe herein a girl who has had startle-induced seizures since she was 3 years old. These seizures were refractory to antiepileptic medications and worsened when the patient was 9 years old, following termination of phenytoin administration because of adverse effects. During this period she could walk only a few steps with support, and sudden drop attacks inevitably occurred. Interictal electroencephalography (EEG) revealed abundant spike–wave activity at the centroparietal midline areas, and ictal EEG of poststartle and gait-induced seizures revealed initial voltage attenuation followed by recruitment of vertex activity, which preceded a tonic or myoclonic–atonic phase. Magnetic resonance imaging (MRI) results were unremarkable, but magnetoencephalography (MEG) and positron emission tomography (PET) suggested the presence of an extensive epileptogenic zone in the bilateral pericentral gyri, and the bilateral paracentral and left precuneus lobules, including the primary motor, supplementary motor, and supplementary sensory areas. The pathophysiologic significance of these structures is discussed. [ABSTRACT FROM AUTHOR]

Summary: In order to find an effective treatment option for status epilepticus in progressive myoclonus epilepsy (PME), we reviewed the clinical course of 9 patients with PME. Initially, epilepsy was successfully treated with antiepileptics. However, it gradually became refractory to medication, and status epilepticus emerged 3–19 years after the onset of epilepsy. In these patients, status epilepticus in PME was classified into (1) myoclonic status epilepticus (MSE), (2) myoclonic-generalized status epilepticus (MGSE), and (3) generalized status epilepticus (GSE). MSE was common in patients with neuronal ceroid lipofuscinosis, and GSE was common in those with dentatorubral–pallidoluysian atrophy. MGSE was characterized by the mixture of escalating myoclonus and generalized seizures, and was observed in patients with Gaucher disease or unspecified PME. All patients were often refractory to infusion of benzodiazepines and barbiturates but phenytoin was able to terminate status epilepticus in 7 patients. Oral phenytoin administration as preventive therapy was effective in 6 patients. Aggravation of myoclonus was not provoked by these treatments. We propose that phenytoin should be considered as a treatment choice for PME patients at late stages to prevent the detrimental effects of prolonged or repeated status epilepticus on the brain tissues. [Copyright &y& Elsevier]

• Seventy-seven percent of infants with posterior quadrant dysplasia experienced seizure freedom after posterior quadrantectomy. • The preoperative hyperconnectivity on the nonsurgical side improved postoperatively to the same level as that in normal infants. • A better long-term neurodevelopment entailed a stronger postoperative connectivity on the nonsurgical side. To reveal whether neurodevelopmental outcome of infants after epilepsy surgery can be quantitatively assessed by electroencephalography (EEG) functional connectivity analysis. 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. 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. Preoperative abnormal hyper-connectivity was normalized to the control level after surgery. The postoperative hyperconnectivity was associated with long-term neurodevelopmental improvement. PLI quantifies neurodevelopmental improvements after posterior quadrantectomy. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Abstract: We report the case of a 5-year-old boy with multiple congenital anomalies, including ptosis, polydactyly, ventricular septal defect, epilepsy, and intellectual deficits. The patient presented with synkinetic eyelid movements accompanying jaw and ocular movements, including Marcus–Gunn phenomenon (eyelid elevation at mouth opening) in the right eye, inverse Marcus–Gunn phenomenon (aggravation of ptosis at mouth opening) in the left eye, and unilateral eyelid elevation on each side during ipsilateral abduction. This suggests that the different types of synkinesia may represent a common etiology of aberrant innervations and/or reflex phenomena of the cranial nerves caused by a specific genetic defect. [Copyright &y& Elsevier]

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 (K Ca 4.1 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 K Ca 4.1 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. 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. [ABSTRACT FROM AUTHOR]

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. 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. 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. [ABSTRACT FROM AUTHOR]

To investigate the effect of guidelines for management of febrile seizures on the clinical practice, we conducted a nationwide survey in Japan. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 YWHAE , CRK , and RTN4RL1 but not PAFAH1B1. 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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Abstract Background Patients with Duchenne muscular dystrophy (DMD) exhibit increased prostaglandin D 2 (PGD 2) expression in necrotic muscle and increased PGD 2 metabolites in their urine. In mouse models, inhibiting PGD 2 production suppresses muscle necrosis, suggesting a possible intervention through PGD 2 -mediated activities. Objective We investigated the involvement of PGD 2 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 2 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 2 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 2 inhibitor as a potential treatment modality. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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.250 G > T, p.Glu84X and c.1096 G > 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. [ABSTRACT FROM AUTHOR]

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 19 years 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. [ABSTRACT FROM AUTHOR]

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 0.75 mg/kg/day prednisolone every day (daily group, n = 51); those treated with 1 mg/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 9.6 years of age (to 94.1%) in the daily group, until 8.8 years of age (to 96.9%) in the intermittent group, and until 7.2 years 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. [ABSTRACT FROM AUTHOR]

Summary 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. [ABSTRACT FROM AUTHOR]

Aim The aim of the study was to understand the long-term health issues and potential predictors of cardiopulmonary arrest (CPA) in patients with severe childhood-onset psychomotor impairments. Method In this single-center, retrospective observational study, the medical records of 140 patients with severe childhood-onset psychomotor impairments were reviewed. The medical interventions and functional status of patients with a history of CPA ( n = 22: 14 M/8F; mean ± SD age: 26.6 ± 12.4 years) were compared with age- and sex-matched patients without a history of CPA ( n = 44: 28 M/16F; mean ± SD age: 26.5 ± 12.3 years). Results The prevalence of CPA was 15.7%. The most frequent cause was respiratory issues, and CPA occurred most frequently between 0 and 5 years old. The patients who had a history of CPA were more likely to have required a feeding tube ( p = 0.0007), tracheostomy ( p < 0.0001), and ventilator ( p = 0.002) compared to the non-CPA patients, while the prevalence of tracheostomy or ventilator treatment during early infancy was comparable between both groups. Although statistically non-significant, patients who used antiepileptics or feeding tubes during the neonatal period had higher odds of a future CPA. Interpretation This single-center study indicated that the prevalence of CPA could be high among individuals with severe childhood-onset psychomotor impairments, and patients who experience CPA have more health issues. The potential predictors for a future CPA are young age (0–5 years), respiratory issues, and antiepileptic or feeding tube usage during the neonatal period. These patients may require extra attention in medical managements. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim To delineate the clinical and neuroimaging characteristics of localized megalencephaly involving the right frontal lobe. Method Data from three patients aged 14–16 years at the last follow-up were retrospectively reviewed. Results All the patients were normal on neurological examination with no signs of hemiparesis. Enlargement of the right frontal lobe with increased volume of subcortical and deep white matter, as well as thickening of the ipsilateral genu of the corpus callosum was common. The onset of epilepsy was 4–7 years of age, with seizure types of massive myoclonus in two and generalized tonic-clonic in two, which could be eventually controlled by antiepileptics. Interictal electroencephalography showed frontal alpha-like activity in one, and abundant spike–wave complexes resulting in diffuse continuous spike–wave activity during sleep in two patients even after suppression of clinical seizures. Psychomotor development appeared unaffected or slightly delayed before the onset of epilepsy, but became mildly disturbed during follow-up period of 7–11 years. Conclusion Certain patients with right frontal megalencephaly can present with a milder epileptic and intellectual phenotype among those with localized megalencephaly and holohemispheric hemimegalencephaly, whose characteristic as epileptic encephalopathy was assumed from this study. [ABSTRACT FROM AUTHOR]

Duchenne muscular dystrophy (DMD) is a progressive muscular disorder in which respiratory and heart failures are the main causes of death. Intensive intervention in respiratory and cardiac function has dramatically improved the prognosis; however, dysfunction in other multiple organs may emerge in the later stages of the disease. We report the case of four non-ambulatory DMD patients who presented with renal failure. Common findings included decreased fluid intake, use of diuretics, and presence of chronic heart failure. The levels of serum cystatin C (CysC), a marker of kidney function unaffected by reduced muscle mass, were elevated in all four patients. In two patients, renal failure improved by increasing fluid intake, and discontinuing or reducing the dose of diuretics. The findings suggest that non-ambulatory DMD patients are at a risk of reduced kidney perfusion, which potentially leads to prerenal failure. Therefore, in DMD patients, dehydration signs and CysC levels should be monitored. [ABSTRACT FROM AUTHOR]

The older of two siblings began to have spasms and partial seizures at 1 month of age. Head magnetic resonance imaging showed an abnormal area in the left temporo-parieto-occipital region. Interictal electroencephalogram ( EEG) showed a suppression-burst pattern. Adrenocorticotropic hormone stopped the spasms, but the seizures continued. Clonazepam, carbamazepine, zonisamide, and clobazam were ineffective. She underwent focal resection at age 8 months. Postoperatively, the seizures disappeared. Histopathologically, the lesion appeared to be focal cortical dysplasia type IIa. The younger sibling had spasms from birth. Head magnetic resonance imaging showed left hemi-megalencephaly. Interictal EEG showed a suppression-burst pattern. Phenobarbital, valproic acid, and zonisamide were ineffective. He underwent hemispherotomy at age 2 months and became seizure free. The histopathological features were consistent with those of hemi-megalencephaly. The siblings' EEG and clinical courses had some similarities. These siblings' conditions may have the same genetic background. [ABSTRACT FROM AUTHOR]

Objective Neurological manifestations including psychomotor developmental delay and epilepsy in patients with Angelman syndrome caused by ubiquitin protein ligase E3A ( UBE3A ) mutations has been considered similar but is relatively milder than that in patients with deletion-type Angelman syndrome. This makes the diagnosis of the former subgroup often difficult. We here characterized epilepsy, specifically the types of tremulous movement, in 4 patients (age, 3–38 years) with Angelman syndrome caused by UBE3A mutations. Methods Ictal electroencephalography was used to record episodic tremors in all study patients. Jerk-locked averaging was performed using digital electroencephalography and surface electromyogram data from patients who were monitored for 24 h. Results All patients had tremors in the limbs, head, and trunk, which resulted in 2 patients falling backward. These tremors lasted several seconds, and could emerge in clusters for hours in older patients. In addition, the tremors coincided with 7–8 Hz rhythmic activity with a frontocentral predominance, diffuse spike-wave bursts, or no apparent change on electroencephalography. In 2 patients, these tremors were confirmed as cortical myoclonus using jerk-locked averaging. The other seizure types were isolated generalized myoclonus and tonic seizures. None of the patients experienced atypical absence seizures. Levetiracetam therapy was effective in controlling the myoclonic events in 2 of the 3 patients. Conclusion Semirhythmic myoclonus is common in patients with Angelman syndrome caused by UBE3A mutations, and such myoclonic events are often life disabling. The preserved expression of gamma-aminobutyric acid type A receptor subunit genes located proximal to UBE3A might explain the low prevalence of absence seizures in this population. [ABSTRACT FROM AUTHOR]

Aim: To clarify the evolution of an augmented startle reflex in Tay–Sachs disease and compare the temporal relationship between this reflex and brainstem evoked potentials. Subjects and methods: Clinical and electrophysiological data from 3 patients with Tay–Sachs disease were retrospectively collected. Results: The augmented startle reflex appeared between the age of 3 and 17 months and disappeared between the age of 4 and 6 years. Analysis of brainstem auditory evoked potentials revealed that poor segregation of peak I, but not peak III, coincided with the disappearance of the augmented startle reflex. A blink reflex with markedly high amplitude was observed in a patient with an augmented startle reflex. Conclusion: The correlation between the augmented startle reflex and the preservation of peak I but not peak III supports the theory that the superior olivary nucleus is dispensable for this reflex. The blink reflex with high amplitudes may represent augmented excitability of reticular formation at the pontine tegmentum in Tay–Sachs disease, where the pattern generators for the augmented startle and blink reflexes may functionally overlap. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: To describe the characteristics of hypophosphatemia in severely disabled individuals with neurological disorders and to identify its causative factors. Method: We retrospectively reviewed clinical data from 82 individuals with motor skills classified as sitting, rollover or bedridden. Age, gender and body mass index were compared in individuals with ( n = 19) and without ( n = 63) a history of hypophosphatemia (serum phosphate levels <2.0 mg/dl). The clinical course of each patient with hypophosphatemia was reviewed and the cause identified. Laboratory data during hypophosphatemia was compared with that after recovery. Results: The age, gender and body mass index did not differ significantly between the individuals with and without hypophosphatemia. Nineteen patients experienced 25 episodes of hypophosphatemia. The causes included febrile illnesses ( n = 17), refeeding syndrome ( n = 4) and Fanconi syndrome ( n = 3), but was unidentifiable in one episode. Significant elevations in C-reactive protein levels and reductions in sodium levels were observed during hypophosphatemia episodes. Interpretation: Hypophosphatemia is a common complication in severely disabled individuals with frequent bacterial infections, refeeding following malnutrition and valproate administration for epilepsy treatment. Because severe hypophosphatemia is life threatening, serum phosphate levels should be closely monitored in this population. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The purpose of this retrospective study was to clarify the cellular activities of ectopic neurons in subcortical bands and to evaluate the imaging features of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and 99mTc ethyl cysteinate dimer (ECD) single-photon emission computed tomography (SPECT) in a series of patients with subcortical band heterotopia (SBH). Materials and methods: The cases of 12 patients with SBH (3 men and 9 women; age range, 2–51years) were evaluated on the basis of their MRI findings. Eight 18F-FDG PET and 12 99mTc-ECD SPECT images were obtained. The uptakes of these images were compared with electroencephalography (EEG) or MRI findings such as band thickness. In all patients, easy Z-score Imaging System (eZIS) software was used to statistically analyze the SPECT images. Results: Of the eight 18F-FDG PET images, five showed higher uptake in the thick subcortical bands than in the overlying cortex. Of the 12 99mTc-ECD SPECT examinations with eZIS images, nine indicated increased regional cerebral blood flow (rCBF) areas corresponding to the band locations. Of the eight 18F-FDG PET examination findings, six were congruent with the rCBF distributions on the eZIS images. Eight of the 12 patients showed correspondence to the increased rCBF on the eZIS images, the band locations on MRI, and abnormal discharge sites on EEG. Conclusions: Ectopic neurons in subcortical bands may have higher glucose metabolism and/or increased rCBF compared to the overlying cortex. 18F-FDG PET and 99mTc-ECD SPECT using eZIS can be helpful to clearly detect the cellular activities of ectopic neurons in patients with SBH. [Copyright &y& Elsevier]

Abstract: An 8-year-old boy underwent a resection for focal cortical dysplasia at the left supplementary motor area (SMA) for the treatment of intractable epilepsy. The manifestations of SMA syndrome, such as transient mutism and right hemiparesis, resolved within a few weeks. Verbal disfluency and impaired executive function, accompanied by impulsivity and distractibility, persisted for more than 12months. The verbal and behavioral problems caused serious difficulties in the school life of the patient, until they became less evident at 18months after surgery. Tractography performed 18months after surgery revealed a defect in the subportion of fronto-parietal association fibers within the left superior longitudinal fascicles. Verbal influency can persist with unusually long duration after resection of SMA during childhood. Although not discernible on the routine neuroimaging, white matter damage beneath the SMA region could result in serious disabilities in executive function. These complications should be recognized for the prediction and assessment of deficits in children after surgical intervention involving this region. [Copyright &y& Elsevier]

Abstract: Purpose: To describe operative procedures, seizure control and complications of surgery for cortical dysplasia (CD) causing intractable epilepsy in infancy and early childhood. Methods: Fifty-six consecutive children (less than 6years old) underwent resective epilepsy surgery for CD from December 2000 to August 2011. Age at surgery ranged from 2 to 69months (mean 23months) and the follow-up was from 1 to 11years (mean 4years 4months). Results: Half of the children underwent surgery during infancy at an age less than 10months, and the majority (80%) of these infants needed extensive surgical procedures, such as hemispherotomy and multi-lobar disconnection. Seizure free (ILAE class 1) outcome was obtained in 66% of the cases (class 1a; 55%): 85% with focal resection (n =13), 50% with lobar resection (n =18), 71% with multilobar disconnection (n =7) and 67% with hemispherotomy (n =18). Peri-ventricular and insular structures were resected in 23% of focal and 61% of lobar resections. Repeated surgery was performed in 9 children and 5 (56%) became seizure free. Histological subtypes included hemimegalencephaly (16 patients), polymicrogyria (5 patients), and FCD type I (6 patients), type IIA (19 patients), type IIB (10 patients). Polymicrogyria had the worst seizure outcome compared to other pathologies. Surgical complications included 1 post-operative hydrocephalus, 1 chronic subdural hematoma, 2 intracranial cysts, and 1 case of meningitis. No mortality or severe morbidities occurred. Conclusions: Early surgical intervention in children with CD and intractable seizures in infancy and early childhood can yield favorable seizure outcome without mortality or severe morbidities although younger children often need extensive surgical procedures. [Copyright &y& Elsevier]

Abstract: Purpose: We studied children younger than 6years old who developed catastrophic epilepsy and were registered in the FACE study group to clarify their clinical characteristics and prevalence of seizure as well as epilepsy types. Subjects: Subjects were prospectively recruited from children with epilepsy who satisfied the following criteria and underwent intensive examination between 2009 and 2012 in 14 collaborative centers: (1) younger than 6years old and (2) more than 10 seizures/month refractory to all available medical treatments including ACTH therapy, leading to significant psychosocial morbidity. Methods: We analyzed epilepsy onset age, predominant seizure type, etiology, neuropsychological findings, and syndromic classification according to the pre-determined registration format. Results: A total of 314 children were enrolled in this study. Epilepsy onset age in 239 cases (80%) was younger than 12months. The most frequent seizure type was epileptic spasms (ES), followed by generalized tonic seizures (GTS), which accounted for 42% and 20%, respectively. West syndrome (WS) was the most frequent epileptic syndrome and accounted for 37%, followed by unclassified epilepsy at 21%, neocortical epilepsy at 19%, Lennox–Gastaut syndrome at 12%, Dravet syndrome at 4%, Rasmussen syndrome at 2%, and others. The two most frequent causes of epilepsy were cortical dysplasia and chromosomal anomalies, as shown in 16% and 6%, respectively. However, the etiology of nearly one half of all patients remained unknown. Psychomotor development was already worse than a moderate degree in 62% of subjects at the first examination. Conclusion: The highest proportion of catastrophic epilepsy was WS and its related syndromes featuring ES and GTS, followed by neocortical epilepsy, whose psychomotor development was significantly retarded at examinations. [Copyright &y& Elsevier]

Abstract: We examined seizure, cognitive, and motor outcomes in patients with Rasmussen syndrome or Rasmussen encephalitis (RS), after recent initiation of immunomodulatory therapies. Among 53 patients with a diagnosis of RS referred from all over Japan, 49 patients (male 22, female 27) with symptoms and findings characteristic of RS were evaluated. Regular intravenous immunoglobulin (IVIg) therapy was administered at a dose of 100mg/kg/day, etc. Regular steroid pulse therapy was conducted with methylprednisolone at a dose of 30mg/kg/day (children) or 1000mg/day (adults) for 3days. Tacrolimus was given at an initial dose of 0.1mg/kg/day (children). Mean onset age was 8.7±10.5years. Seizure-free rate was 71% after treatment by functional hemispherectomy (FH), and response rate for seizures was 81% by regular steroid pulse therapy, 42% by tacrolimus therapy, and 23% by regular IVIg therapy. Rate of patients with IQ higher than 80 (R80) was 50% by regular steroid pulse therapy, 43% by regular IVIg therapy, 29% by tacrolimus therapy, and 0% by FH. R80 after regular steroid pulse therapy was 100% in patients without MRI lesions, and 37% in those with advanced MRI lesions. Improvement of motor function (paresis) was observed only by immunomodulatory therapy. Motor function was aggravated in 100% of patients treated by FH, 62% by regular IVIg, and 10% by regular steroid pulse therapy. We suggest a new treatment strategy for RS using early immunomodulatory therapy: initiation of regular steroid pulse therapy after early diagnosis indicated by biomarkers, then switching to tacrolimus therapy after several months. [Copyright &y& Elsevier]

Abstract: No association between mitochondrial disease and pancreatitis has yet been established, although diabetes mellitus and diseases caused by exocrine insufficiency, such as Pearson syndrome, are the commonest pancreatic complications of mitochondrial diseases. Here, we report 2 cases of mitochondrial disease complicated by pancreatitis as an unusual pancreatic exocrine manifestation. One patient was a 10-year-old girl with mild retardation of psychomotor development who had experienced recurrent pancreatitis since the age of 4years. Chronic progressive external ophthalmoplegia (CPEO) due to m.8344A>G mutation was diagnosed when the patient was 10years old. The other patient was a 28-year-old woman who was diagnosed with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) due to m.3243A>G mutation at 10years of age. She had experienced regular recurrent vomiting since the age of 16 and suffered an episode of critical pancreatitis at 23years. In both cases, no possible etiological, morphological, or genetic factors for pancreatitis were identified, including anomalous pancreaticobiliary duct. A combination therapy of the standard treatment for chronic pancreatitis and supportive therapy for mitochondrial energy production may be beneficial to prevent the recurrence of acute pancreatitis complicating mitochondrial diseases. The pathophysiological mechanism of pancreatitis in mitochondrial disease has not been adequately established; however, our observations suggest that pancreatitis should be included in the list of pancreatic complications of mitochondrial disease. [Copyright &y& Elsevier]

Purpose KCNQ2 mutations have been found in patients with benign familial neonatal seizures, myokymia, or early onset epileptic encephalopathy ( EOEE). In this study, we aimed to delineate the clinical spectrum of EOEE associated with KCNQ2 mutation. Methods A total of 239 patients with EOEE, including 51 cases with Ohtahara syndrome and 104 cases with West syndrome, were analyzed by high-resolution melting ( HRM) analysis or whole-exome sequencing. Detailed clinical information including electroencephalography ( EEG) and brain magnetic resonance imaging ( MRI) were collected from patients with KCNQ2 mutation. Key Findings A total of nine de novo and one inherited mutations were identified (two mutations occurred recurrently). The initial seizures, which were mainly tonic seizures, occurred in the early neonatal period in all 12 patients. A suppression-burst pattern on EEG was found in most. Only three patients showed hypsarrhythmia on EEG; eight patients became seizure free when treated with carbamazepine, zonisamide, phenytoin, topiramate, or valproic acid. Although the seizures were relatively well controlled, moderate-to-profound intellectual disability was found in all except one patient who died at 3 months. Significance De novo KCNQ2 mutations are involved in EOEE, most of which cases were diagnosed as Ohtahara syndrome. These cases showed distinct features with early neonatal onset, tonic seizures, a suppression-burst EEG pattern, infrequent evolution to West syndrome, and good response to sodium channel blockers, but poor developmental prognosis. Genetic testing for KCNQ2 should be considered for patients with EOEE. [ABSTRACT FROM AUTHOR]

We delineate a complication of hypoalbuminemia in dentatorubral−pallidoluysian atrophy (DRPLA), which we have found to be common in this disorder. In addition, we explored the pathogenesis of this phenomenon through clinical and histological examinations. Clinical course and laboratory findings of nine patients with childhood-onset DRPLA (aged 6-49 years; CAG repeat length 62-93) were retrospectively reviewed. Autopsied specimens from three patients were examined by histopathological and immunohistochemical analyses. Eight DRPLA patients showed hypoalbuminemia <3.5 g/dl in the initial stages of the disease (age, 2-32 years), which correlated with the CAG repeat length in each patient. Disease worsened in six patients, often triggered by febrile infections and accompanied by increased urinary protein excretion. One patient showed increased fecal α1-antitripsin while another showed accumulation of radioactive albumin in the urinary and gastrointestinal tracts after intravenous infusion. Immunohistochemistry revealed albumin-containing monocytes and astrocytes in the perivascular areas of the cerebral white matter. Fluid collection in the glomerular capillaries was noted. Immunolabeling using antibodies against the expanded polyglutamine (polyQ) polypeptide was positive in cerebral cortical neurons, hepatocytes, renal collecting ducts, and glomerular podocytes, which act as filtration barrier against serum proteins. Serum albumin appears to easily leak from blood vessels in certain visceral organs in DRPLA during later stages of the illness, particularly in the kidneys of patients with largely expanded CAG repeats. We hypothesize that the accumulation of the DRPLA gene product with expanded polyQ sequences in the podocytes results in the dysfunction of the glomerular filtration barrier. [ABSTRACT FROM AUTHOR]

Abstract: We examined the specific nerve conduction deficits distinguishing spinal muscular atrophy (SMA) subtypes I and II. Five SMA I patients (age, 0.2–1.1years) and 10 SMA II patients (age, 1.0–2.8years) were examined. Patients were compared to age-matched controls for motor and sensory conduction velocity (MCV and SCV) changes, compound muscle and sensory nerve action potential amplitudes (CMAP and SNAP), and F-wave occurrence (FO). Slower MCVs were found in three of five SMA I patients; all five exhibited markedly decreased CMAP amplitudes. Tibial nerve CMAP amplitudes significantly reduced in SMA II patients (p <0.01). Slower SCVs and decreased SNAP amplitudes were observed in three of five SMA I patients but not in SMA II patients. Although FOs were reduced in both extremities of SMA I patients, the reduction was prominent in the tibial nerve of SMA II patients (p =0.031). Loss of motor units may be widespread in the early stage of SMA I, while specific to the legs in young SMA II patients. SMA I showed sensory nerve degeneration, especially of large myelinated fibers. SMA II showed no sensory nerve abnormalities. [Copyright &y& Elsevier]

To elucidate a relationship between CAG repeat expansion length and disease progression history in patients with childhood-onset dentatorubral-pallidoluysian atrophy (DRPLA). We retrospectively evaluated information from nine Japanese patients with disease onset reported as between 6 months and 12 years of age. CAG repeat length in these patients ranged from 62 to 93. A strong correlation was confirmed for the age of disease onset, with the onset of epilepsy and involuntary movements, emergence of regression, and autonomic symptoms. The age at becoming wheelchair-bound and initiation of tube feeding also showed a significant correlation with CAG repeat length. This is the first report detailing this aspect of DRPLA focusing on the childhood-onset population. Earlier disease milestones were revealed compared to the expected age based upon a previous report that contained data from the entire patient population, including adult-onset cases (Hasegawa et al. in Mov Disord 25:1694-1700, ). These results provide a basis for predicting the outcome of patients in this particular age group, as well as for assessing the results of future clinical therapeutic trials. [ABSTRACT FROM AUTHOR]

Abstract: A 2-year-old girl presented with brief episodes of left hemifacial twitching. On ictal electroencephalography, repetitive focal spike discharges appeared at the right fronto-centro-temporal regions; these discharges preceded the onset of each twitch by 12ms. Magnetic resonance imaging showed a linear abnormal signal intensity in the subcortical white matter at the right postcentral gyrus, where a cluster of dipole sources was detected by magnetoencephalography. These findings suggested that the patient had focal cortical myoclonus due to rolandic focal cortical dysplasia. [Copyright &y& Elsevier]

Abstract: We report the case of a 15-year-old Japanese girl with myopathy associated with antibodies to a signal recognition particle (anti-SRP myopathy). The patient presented with progressive symmetrical proximal muscle weakness that caused difficulty in walking within 3months, and marked elevation of the serum creatine kinase levels. A skeletal muscle biopsy revealed active necrotic and regenerating processes, with mild inflammatory changes. Based on the above findings, the patient was diagnosed as having anti-SRP myopathy. Only a limited number of pediatric patients with anti-SRP myopathy has been reported previously, with usually a poor prognosis. Early diagnosis is important for obtaining a better prognosis in patients with anti-SRP myopathy. [Copyright &y& Elsevier]

Abstract: In this study, we present the case of a 2-year-old boy who exhibited facial and bulbar paralysis since birth, severe dysphagia, signs of oculomotor disturbance, jaw jerks, pyramidal signs on both toes, intellectual disability, and severe gastroesophageal reflux. His blink reflex and auditory/somatosensory evoked potentials suggested abnormalities in the lower brainstem, and magnetic resonance imaging showed a T2 hyperintense area in the pontine tegmentum. These findings combined with the patient’s symptoms suggested “dorsal brainstem syndrome” and indicated a possibility of prenatal asphyxia in this patient. Nosologic issues regarding this subgroup of cerebral palsy are discussed here. [Copyright &y& Elsevier]

Abstract: Focal cortical dysplasia (FCD) and hemimegalencephaly (HME) are major causes of intractable epilepsy in children. The probable pathogenesis of FCD and HMG is the abnormal migration and differentiation of neurons. The aim of the present study was to clarify the abnormal cytoarchitecture, based on neuronal immaturation. Tissue samples were obtained from 16 FCD and seven HME patients, aged between 2 months and 12 years, who had been diagnosed as typical FCD and HME, following surgical treatment for intractable epilepsy. Paraffin-embedded sections were stained with the antibodies of three layer-markers that are usually present only during the fetal period, namely SATB2 (expressed in the upper layer of the normal fetal neocortex), FOXP1 (expressed in the 5th layer), and TBR1 (expressed in the 6th layer). In FCD, SATB2-positive (+) cells located in the middle and deep regions of FCD Ia and Ib, but only in the superficial region of FCD IIa and IIb. FOXP1+ cells diffusely located in the neocortex, especially the upper layer of FCD IIa and IIb. TBR1+ cells mainly located in the middle and deep regions, and also white matter. In FCD IIb, TBR1+ cells were in the superficial region. In HME, SATB2+ and FOXP1+ cells were found diffusely. TBR1+ cells were in the middle and deep regions. On the basis of continued expression of fetal cortical layer-specific markers in FCD and HME brains, the abnormal neocortical formation in both is likely to be the result of disrupted neuronal migration and dysmaturation. The expression pattern is different between FCD and HME. [Copyright &y& Elsevier]

This article reports the case of a female with late infantile neuronal ceroid lipofuscinosis who developed right and left anterior bundle branch blocks and episodic bradycardia at 23 years of age. Several episodes of supraventricular tachycardia manifested at 23 and 27 years of age. In addition, a transient second-degree atrioventricular conduction block also emerged at 27 years of age. Atrial fibrillation and aggravation of the atrioventricular conduction block resulted in progressive bradycardia and cardiac death at the age of 28 years. Cardiac involvement and accumulation of lipopigments in the myocardium and cardiac conduction system have been recognized in juvenile neuronal ceroid lipofuscinosis, but this is the first report to describe progressive conduction defects in a case of late infantile neuronal ceroid lipofuscinosis. [ABSTRACT FROM AUTHOR]

Abstract: Background: Skeletal muscle metabolism is a major determinant of resting energy expenditure (REE). Although the severe muscle loss that characterizes Duchenne muscular dystrophy (DMD) may alter REE, this has not been extensively investigated. Methods: We studied REE in 77 patients with DMD ranging in age from 10 to 37years using a portable indirect calorimeter, together with several clinical parameters (age, height, body weight (BW), body mass index (BMI), vital capacity (VC), creatine kinase, creatinine, albumin, cholinesterase, prealbumin), and assessed their influence on REE. In addition, in 12 patients maintaining a stable body weight, the ratio of energy intake to REE was calculated and defined as an alternative index for the physical activity level (aPAL). Results: REE (kcal/day, mean±SD) in DMD patients was 1123 (10–11years), 1186±188 (12–14years), 1146±214 (15–17years), 1006±136 (18–29years) and 1023±97 (⩾30years), each of these values being significantly lower than the corresponding control (p <0.0001). VC (p <0.001) was the parameter most strongly associated with REE, followed by BMI (p <0.01) and BW (p <0.05). The calculated aPAL values were 1.61 (10–11years), 1.19 (12–14years), 1.16 (15–17years), and 1.57 (18–29years). Conclusion: The REE in DMD patients was significantly lower than the normal value in every age group, and strongly associated with VC. Both the low REE and PAL values during the early teens, resulting in a low energy requirement, might be related to the obesity that frequently occurs in this age group. In contrast, the high PAL value in the late stage of the disease, possibly due to the presence of respiratory failure, may lead to a high energy requirement, and thus become one of the risk factors for development of malnutrition. [Copyright &y& Elsevier]

Abstract: Muscle glycogen storage disease 0 (GSD0) is caused by glycogen depletion in skeletal and cardiac muscles due to deficiency of glycogen synthase 1 (GYS1), which is encoded by the GYS1 gene. Only two families with this disease have been identified. We report a new muscle GSD0 patient, a Japanese girl, who had been suffering from recurrent attacks of exertional syncope accompanied by muscle weakness and pain since age 5years until she died of cardiac arrest at age 12. Muscle biopsy at age 11years showed glycogen depletion in all muscle fibers. Her loss of consciousness was gradual and lasted for hours, suggesting that the syncope may not be simply caused by cardiac event but probably also contributed by metabolic distress. [Copyright &y& Elsevier]

Abstract: To evaluate the effect of corpus callosotomy (CC) on attention deficit and behavioral problems in pediatric patients with intractable epilepsy, we retrospectively investigated sequential patients who had undergone CC to control seizures. Between August 2005 and April 2010, a total of 15 patients aged between 3.1 and 17.9 years underwent CC at our institute. All the patients experienced either drop attacks or head nodding, which were considered to be therapeutic targets of CC. A standardized instrument, the Child Behavior Checklist (CBCL), was used to assess behavioral and emotional problems before and after surgery. On postoperative EEGs, 8 (53%) showed improvement and 7 (47%) showed no change in epileptiform discharges. The Attention Problems scale and total score on the CBCL significantly improved in patients whose postoperative EEGs showed improvement. In addition to amelioration of target seizures, CC can improve attention impairments in association with improvement in the postoperative EEG. [Copyright &y& Elsevier]

Abstract: A 26-year-old woman with psychomotor developmental delay since late infancy showed rapid deterioration of her psychomotor abilities at the 11years of age. She had gained the ability to verbally express herself and perform motor activities such as running and dancing in early childhood, but she lost the ability to verbally communicate and was unable to walk independently after this period. She also presented with dystonia in the right extremities, which markedly fluctuated with a periodicity of hours to months. Sleep disturbance and epileptic seizures also emerged during adolescence. Frontal lobe atrophy and hypoperfusion of the left cerebral hemisphere were noted on neuroimaging examinations. Analysis of the MECP2 gene revealed a late truncating mutation of c.1196_1200delCCACC (p.P399QfsX4) near the 3′-terminal of the coding region. The phenotype of this patient corresponds to the rare, unestablished variant of “late childhood deterioration” in MECP2-related disorders. For the first time, MECP2 mutation was confirmed to be the genetic basis of this condition. [Copyright &y& Elsevier]

Abstract: Mutations in LMNA cause wide variety of disorders including Emery–Dreifuss muscular dystrophy, limb girdle muscular dystrophy, and congenital muscular dystrophy. We recently found a LMNA mutation in a patient who was previously diagnosed as infantile onset inflammatory myopathy. In this study, we screened for LMNA mutations in 20 patients suspected to have inflammatory myopathy with onset at 2years or younger. The diagnosis of inflammatory myopathy was based on muscle pathology with presence of perivascular cuffing and/or endomysial/perimysial lymphocyte infiltration. We identified heterozygous LMNA mutations in 11 patients (55%), who eventually developed joint contractures and/or cardiac involvement after the infantile period. Our findings suggest that LMNA mutation should be considered in myopathy patients with inflammatory changes during infancy, and that this may help avoid life-threatening events associated with laminopathy. [Copyright &y& Elsevier]

Abstract: A 3-months-old boy presented with partial seizures that soon evolved into infantile spasms. Magnetic resonance imaging revealed bilateral perisylvian polymicrogyria with right-sided predominance. ACTH therapy successfully controlled epilepsy and electroencephalograms were normalized. Conventional G-banded chromosomal analysis was performed due to his distinctive features and a derivative chromosome 1 derived from parental balanced translocation with a karyoptype of 46,XY,der(1)t(1;4)(p36.23;q35) was detected. Fluorescent in situ hybridization analysis confirmed the deleted region of 1p36 as large as 8.6Mb. This is the first delineation of concurrent complications of infantile spasms and polymicrogyria in patient with 1p36 deletion. 1p36 deletion syndrome should be broadly recognized as a differential diagnosis of regional polymicrogyria and/or infantile spasms. [Copyright &y& Elsevier]

Abstract: To clarify the effects of hydrochlorothiazide (HCT) on calcium metabolism in subjects with severe motor and intellectual disabilities (SMID), we examined four patients (16–48years old) with a history of urolithiasis and/or bone fracture and increased urinary calcium/creatinine ratio (U-Ca/Cr). U-Ca/Cr, blood markers of bone turnover, and bone-mineral density (BMD) were measured before and after administration of low-dose HCT (0.25–0.5mg/kg/day). Three months after the initiation of HCT, U-Ca/Cr decreased in all patients, but this effect was less evident at 9–18months. Bone-turnover marker of bone-specific alkaline phosphatase also showed a tendency to decrease, but BMD remained unchanged during the follow-up period. In SMID patients, HCT is beneficial for the treatment of hypercalciuria but its effects can be transient in certain cases. HCT may also ameliorate the increase in bone turnover, but its effects on the prevention of bone fractures remain uncertain. Hyponatremia is the most frequent and significant adverse effect of HCT, for which a close observation is mandatory in HCT application for patients with SMID. [Copyright &y& Elsevier]

Abstract: We report a 3-year-old boy with opsoclonus-myoclonus syndrome (OMS) who presented with exaggerated startle responses to unexpected auditory stimuli during an episode of myoclonic status. An augmented blink reflex was also observed clinically and electrophysiologically. Based on the assumption that hyperexcitability in the lower pontine tegmentum may be responsible for the acoustic startle and blink reflex in OMS, we considered that increased excitability of independent but neighboring structures, including the pontine paramedian reticular formation, may cause OMS symptoms. [Copyright &y& Elsevier]