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Background Hemispherotomy, which involves disconnecting hemispherical fibers, is a treatment option for medically intractable epilepsy. As various neurological disorders can cause strabismus, we hypothesized that hemispherotomy can cause post-operative strabismus in patients with medically intractable epilepsy. Methods Nineteen patients underwent the Hirschberg test before and after hemispherical disconnection surgery. Among the 19 patients, 16 patients (six females and 10 males; mean age, 12.2 years; range, 0.17–43 years) who underwent hemispherotomy were included in this study. Results The difference in the angle between the left and right eyes was significantly widened (p = 0.025). Nine (56%) of 16 patients exhibited post-operative chronic strabismus as evaluated with the Hirschberg test. Intermittent strabismus was noticed by family members or caregivers in 10 (63%) of 16 patients. Patients older than 12 years did not show post-operative strabismus as evaluated by the Hirschberg test. Conclusion Hemispherotomy can cause or worsen post-operative strabismus in pediatric patients.

Background Patients with MECP2 duplication syndrome present with distinct facial anomalies and clinical features such as global developmental delay, recurrent respiratory infections, and epileptic seizures. Approximately half of all patients develop epileptic seizures which are refractory in most cases despite active medical management. Furthermore, no previous reports have discussed the efficacy of surgical treatment for seizures in patients with MECP2 duplication syndrome. Case report In the present report, we describe a case of MECP2 duplication syndrome in a 15-year-old boy who developed epileptic seizures following influenza-associated acute encephalitis. His frequent epileptic spasms, tonic, atonic, and partial seizures were refractory to multiple antiepileptic medications. Electroencephalography revealed continuous diffuse epileptic discharge, resulting in regression. A total corpus callosotomy (CC) was performed at the age of 14 years and 7 months. His seizures markedly decreased following CC, although he continued to experience brief partial seizures approximately once per month. Post-operative examination revealed that his epileptic discharges had disappeared, and that his developmental state had returned to pre-encephalopathy levels. Conclusion Our findings indicate that CC may represent a valuable surgical option for children with medically refractory generalized seizures following acute encephalopathy, irrespective of genetic disorders such as MECP2 duplication syndrome.

Panayiotopoulos syndrome (PS) is a self-limited focal epilepsy appearing in childhood. Seizures in PS are self-limiting and do not usually continue into adulthood. Juvenile myoclonic epilepsy (JME) is the most common type of idiopathic generalized epilepsy, developing around puberty and continuing throughout adulthood. We describe four cases of PS in childhood in which JME developed in adolescence. Age at onset ranged from 4 to 8 years for PS, and 11 to 14 years for JME. JME developed after PS subsided, with the interval between last PS seizure and first JME seizure ranging from 1 to 10 years. No link between the two conditions has previously been described. Since PS is considered to show good prognosis and to be self-limiting, long-term observation has been considered unnecessary. No definitive factors were found to predict future evolution to JME in our series, so longer-term follow-up may be warranted for all PS patients.

Objectives Long‐term adrenocorticotropic therapy (LT‐ACTH), which consisted of 2‐4 weeks of daily injections of adrenocorticotropic hormone (ACTH) and subsequent months of weekly injections, was tried for relapsed West syndrome (WS) or other intractable epilepsies in small case reports. Our aim was to explore the efficacy of LT‐ACTH for preventing WS relapse, as well as the prevalence of its adverse events. Methods This is a retrospective, nationwide, multicenter case series of patients with WS who underwent LT‐ACTH. Clinical information of the patients and protocol of LT‐ACTH were collected from participating institutes in this study. We defined clinical response to ACTH as achievement of hypsarrhythmia and epileptic spasms resolution. Patients who responded to daily ACTH injections were identified and assessed whether they experienced WS relapse during/after the weekly ACTH injection period. The outcome was measured by the nonrelapse rate at 24 months after daily ACTH injections using the Kaplan‐Meier method. Results Clinical information of 16 children with WS was analyzed. The median age at LT‐ACTH initiation was 14.5 months (range: 7‐68 months). Thirteen (81%) patients had previously undergone conventional ACTH treatment. The LT‐ACTH regimens comprised a median of 16 days of daily injections (range: 11‐28 days) and 10 months of weekly injections (range: 3‐22 months). Seven patients experienced WS relapse during/after subsequent weekly ACTH period, and the nonrelapse rate at 24 months after daily injections was estimated at 60.6% (95% confidence interval: 32.3%‐80.0%). Height stagnation, hypertension, and irritability were observed; lethal adverse events were not reported. Significance Our study firstly explored the efficacy of LT‐ACTH for preventing WS relapse. LT‐ACTH might be a treatment option for patients with relapsed or intractable WS; however, we note that our study is limited by its small sample size and the lack of an appropriate control group.

Ayataka Fujimoto,1 Tohru Okanishi,1 Yosuke Masuda,1 Keishiro Sato,1 Mitsuyo Nishimura,1 Shimpei Baba,1 Shinji Itamura,1 Yoichiro Homma,2 Hideo Enoki1 1Comprehensive Epilepsy Center, Seirei Hamamatsu General Hospital, Hamamatsu, Shizuoka, Japan; 2Department of General Internal Medicine, Seirei Hamamatsu General Hospital, Hamamatsu, Shizuoka, Japan Purpose: Diagnosing epilepsy in the elderly population can be difficult due to mimicking symptoms. Furthermore, epileptic symptoms can also be masked by various symptoms. We hypothesized that elderly patients with epilepsy exhibit specific clinical features among the various symptoms.Patients and methods: From 2009 to 2017, 177 patients who were older than 65 years were referred to our epilepsy center. Out of this group, the onset of symptoms occurred after reaching the age of 50 years in 152 of the patients, who were additionally being treated at our clinic. We divided their symptoms in accordance with their consciousness levels, which were defined as follows: full wakefulness level I, impaired awareness level II, and loss of consciousness level III. We also classified the duration of the symptoms as

We aimed to analyse the ictal electrographic changes on scalp electroencephalography (EEG), focusing on high-voltage slow waves (HVSs) in children with epileptic spasms (ES) and tonic spasms (TS) and then identified factors associated with corpus callosotomy (CC) outcomes. We enrolled 17 patients with ES/TS who underwent CC before 20 years of age. Post-CC Engel’s classification was as follows: I in 7 patients, II in 2, III in 4, and IV in 4. Welch’s t-test was used to analyse the correlation between ictal HVSs and CC outcomes based on the following three symmetrical indices: (1) negative peak delay: interhemispheric delay between negative peaks; (2) amplitude ratio: interhemispheric ratio of amplitude values for the highest positive peaks; and (3) duration ratio: interhemispheric ratio of slow wave duration. Ages at CC ranged from 17–237 months. Four to 15 ictal EEGs were analysed for each patient. The negative peak delay, amplitude ratio and duration ratio ranged from 0–530 ms, 1.00–7.40 and 1.00–2.74, respectively. The negative peak delay, amplitude ratio and duration ratio were significantly higher in the seizure residual group (p = 0.017

Hemiconvulsion-hemiplegia-epilepsy syndrome (HHES) is a subset of acute encephalopathy characterized by infantile-onset with acute hemiconvulsive febrile status and subsequent unilateral cerebral atrophy and hemiparesis. In the chronic phase, patients with HHES develop epilepsy, typically displayed as intractable focal seizures. The patients are often intractable with antiepileptic drugs and need surgical treatment. Although viral encephalitis and genetic abnormalities are presumed to be the underlying etiology, the pathogenesis remains mostly unknown. We describe three cases of successful functional hemispherotomy for intractable epilepsy in HHES. Patients developed acute asymmetrical convulsive status following viral infections during the ages of 17–30 months. Their seizures were intractable with antiepileptic drugs and required hemispherotomy. On the basis of the pathological findings, all cases were diagnosed as focal cortical dysplasia (FCD) type IIId. The epileptogenic mild cortical malformations may be the cause of HHES.

When the results of electroencephalography (EEG), magnetic resonance imaging (MRI), and seizure semiology are discordant or no structural lesion is evident on MRI, single-photon emission computed tomography (SPECT) and positron emission tomography (PET) are important examinations for lateralization or localization of epileptic regions. We hypothesized that the concordance between interictal 2-[18F]fluoro-2-deoxy-D-glucose (18FDG)-PET and iomazenil (IMZ)-SPECT could suggest the epileptogenic lobe in patients with non-lesional findings on MRI. Fifty-nine patients (31 females, 28 males; mean age, 29 years; median age, 27 years; range, 7–56 years) underwent subdural electrode implantation followed by focus resection. All patients underwent 18FDG-PET, IMZ-SPECT, and focus resection surgery. Follow-up was continued for ≥ 2 years. We evaluated surgical outcomes as seizure-free or not and analyzed correlations between outcomes and concordances of low-uptake lobes on PET, SPECT, or both PET and SPECT to the resection lobes. We used uni- and multivariate logistic regression analyses. In univariate analyses, all three concordances correlated significantly with seizure-free outcomes (PET, p = 0.017; SPECT, p = 0.030; both PET and SPECT, p = 0.006). In multivariate analysis, concordance between resection and low-uptake lobes in both PET and SPECT correlated significantly with seizure-free outcomes (p = 0.004). The odds ratio was 6.0. Concordance between interictal 18FDG-PET and IMZ-SPECT suggested that the epileptogenic lobe is six times better than each examination alone among patients with non-lesional findings on MRI. IMZ-SPECT and 18FDG-PET are complementary examinations in the assessment of localization-related epilepsy.

Niemann-Pick disease type C (NPC) is a rare, progressive autosomal recessive disease. It is caused by mutations in either the NPC1 or NPC2 genes, resulting in defective regulation of intracellular lipid trafficking. Miglustat, which reversibly inhibits glucosylceramide synthase, reportedly has beneficial effects on the progressive neurological symptoms of NPC and was approved in Japan in 2012. Some reports suggested that miglustat therapy delayed the onset or progression of NPC when treatment was initiated before the onset of neurological manifestation or at an early stage. We report here a patient with the early-infantile form of NPC who started on miglustat at 4months of ages. To our knowledge, this patient is the youngest reported patient with NPC in which miglustat therapy was initiated. Our patient, who had hypotonia and developmental delay before treatment, remained stable and showed no new neurological symptoms. In addition, pulmonary involvement was improved during miglustat therapy. Our case and previous reports underscore the importance of early initiation of miglustat therapy for NPC.

Background Risk factors for infection after vagus nerve stimulation (VNS) device implantation represent an important issue but remain unclear. We hypothesized that specific risk factors for infection would be associated with VNS device implantation. This study reviewed patients with epilepsy who underwent VNS device implantation and undertook a statistical analysis of risk factors for surgical site infection (SSI). Methods We reviewed all medical records for patients who underwent VNS therapy in our facility between August 2011 and May 2018. Age, sex, height, body weight, body mass index (BMI), intelligence quotient (IQ), surgical incision opening time, blood loss, epilepsy classification, activities of daily living, and generator replacement were statistically compared between cases with and without SSI. Results We performed 208 VNS device implantation surgeries at our facility during the study period. Among these, 150 patients underwent initial implantation, 56 patients underwent first generator replacement, and 2 patients underwent second replacement. Six patients (2.7%) with initial implantation and 3 patients (5.4%) with first replacement showed SSI. Low BMI was a risk factor for infection at initial implantation (P Conclusions This study identified low BMI and low IQ at initial implantation as risk factors for infection.

Although central nervous system complications occasionally accompany during the acute phase of Kawasaki disease, clinically problematic arrhythmia is quite rare. We report a case accompanied by encephalitis and several kinds of problematic arrhythmia. Following the diagnosis of Taussig–Bing anomaly and coarctation of the aorta, the patient underwent aortic arch reconstruction, an arterial switch operation, and ventricular septal defect closure. No significant arrhythmias were observed. At the age of 5 years, the patient presented with a fever, rash, conjunctival hyperemia, and redness of the lips and fingertips. He was subsequently diagnosed with Kawasaki disease. The patient also presented with disorientation, and electroencephalography revealed overall slow-wave activity, indicating encephalitis. The patient received high-dose immunoglobulin and steroid pulse therapy. Sinus arrest was detected on day 10, and an atrial flutter with a 2 : 1 to 4 : 1 atrioventricular conduction block occurred on day 20. Although cardioversion succeeded in alleviating the atrial flatter, the patient experienced significant sinus arrest. The sinus arrest was alleviated 3 days later. Kawasaki disease-induced vasculitis and the arterial switch operation may both have influenced the sinus node dysfunction. Although sinus node function recovered, the possibility of progression into the sinus node dysfunction in the future should be considered.

Objective Gaucher disease (GD) is a lysosomal storage disease characterized by a deficiency of glucocerebrosidase. Although enzyme-replacement and substrate-reduction therapies are available, their efficacies in treating the neurological manifestations of GD are negligible. Pharmacological chaperone therapy is hypothesized to offer a new strategy for treating the neurological manifestations of this disease. Specifically, ambroxol, a commonly used expectorant, has been proposed as a candidate pharmacological chaperone. The purpose of this study was to evaluate the safety, tolerability, and neurological efficacy of ambroxol in patients with neuronopathic GD. Methods This open-label pilot study included five patients who received high-dose oral ambroxol in combination with enzyme replacement therapy. Safety was assessed by adverse event query, physical examination, electrocardiography, laboratory studies, and drug concentration. Biochemical efficacy was assessed through evidence of glucocerebrosidase activity in the lymphocytes and glucosylsphingosine levels in the cerebrospinal fluid. Neurological efficacy was evaluated using the Unified Myoclonus Rating Scale, Gross Motor Function Measure, Functional Independence Measure, seizure frequency, pupillary light reflex, horizontal saccadic latency, and electrophysiologic studies. Results High-dose oral ambroxol had good safety and tolerability, significantly increased lymphocyte glucocerebrosidase activity, permeated the blood–brain barrier, and decreased glucosylsphingosine levels in the cerebrospinal fluid. Myoclonus, seizures, and pupillary light reflex dysfunction markedly improved in all patients. Relief from myoclonus led to impressive recovery of gross motor function in two patients, allowing them to walk again. Interpretation Pharmacological chaperone therapy with high-dose oral ambroxol shows promise in treating neuronopathic GD, necessitating further clinical trials.

Background This retrospective study is designed to determine whether the thickness of the corpus callosum can predict corpus callosotomy outcome in pediatric patients with epileptic or tonic spasms. Methods We retrospectively studied 25 patients (18 boys) with intractable childhood-onset epileptic or tonic spasms who underwent corpus callosotomy between March 2008 and January 2017. Seizure outcomes were classified as favorable (class I and II of Engel's outcome classification) or unfavorable (class III and IV of Engel's outcome classification) at 12 months postoperatively. We measured the corpus callosum area on the midline and maximum cerebral area on the para-midline in sagittal magnetic resonance images just before surgery. We statistically analyzed the associations between surgical outcomes and corpus callosum area, corpus callosum area/maximum cerebral area (corpus callosum/cerebrum ratio), or age at magnetic resonance imaging just before surgery, using univariate and multivariate logistic regression analyses. Results Age at surgery ranged from six to 237 months (mean: 119). Main seizure types were epileptic spasms in 17 patients and tonic spasms in eight. Favorable outcomes occurred in 10 (40%) patients and unfavorable outcomes in 15 (60%). Both corpus callosum area and corpus callosum/cerebrum ratio did not show significant associations with the outcomes in the univariate and multivariate analyses. The 95% confidence intervals of corpus callosum/cerebrum ratio strongly overlapped between the favorable and unfavorable outcome groups. Conclusions Our data failed to support that corpus callosum thickness on the sagittal image is associated with corpus callosotomy outcomes in pediatric patients with epileptic spasms or tonic spasms.

Purpose Polymicrogyria, a malformation of the cerebral cortex, frequently causes epilepsy. Diffuse bilateral polymicrogyria (DBP) is related to poor epilepsy prognosis, but most patients with DBP are not good candidates for resective epilepsy surgery and effectiveness of corpus callosotomy (CC), a palliative surgery, for patients without resective epileptogenic cortices, has not been established in DBP. Because CC might be effective against DBP-related epilepsy, we conducted total CC in three pediatric DBP cases. Methods Case 1. A girl developed epilepsy at 3 months of age, with focal versive seizures and epileptic spasms. The electroencephalogram (EEG) showed a suppression-burst pattern. Total CC was performed at 6 months of age. Case 2. A female infant developed epilepsy on the day of birth, exhibiting epileptic spasms, generalized tonic-clonic seizures, and eye-deviating seizures. She had a history of clusters of tonic seizures. Total CC was performed at 1 year and 2 months of age. After CC, the epileptic focus of the tonic seizures was identified; a secondary resective surgery was conducted. Case 3. A girl developed multiple types of seizures at 3 years of age. Frequent atypical absence status was refractory to antiepileptic drugs. Total CC was conducted at 8 years of age. Results Case 1: Frequencies of both seizure types decreased. The background EEG changed to continuous high-voltage slow waves. Case 2: Clusters of tonic seizures were well-controlled. Case 3: Atypical absence seizures completely disappeared. Conclusion CC could be effective for patients with DBP, whose habitual seizures include epileptic spasms and absence seizures.

A 2-year-old boy had glaucoma, bilateral facial haemangioma and widespread blue nevi on the trunk and extremities since birth. Dilated medullary veins were detected in the left cerebral periventricular white matter on magnetic resonance imaging (MRI). Macrocephaly and delayed psychomotor development were observed during late infancy, and susceptibility-weighted angiography revealed an extensive developmental venous anomaly with multiple caput medusae throughout bilateral hemispheres, accompanied by periventricular hyperintense alterations on MRI and progressive diffuse atrophy of the cerebral mantle with left-sided predominance. Hypoperfusion in the left cerebral and cerebellar hemisphere was also uncovered. No meningeal haemangioma was observed. This patient may represent a novel subgroup of phakomatosis cases that can be regarded as a variant of Sturge-Weber syndrome.

Aim To determine the use of high b value diffusion-weighted imaging (DWI) in the diagnosis and assessment of acute febrile encephalopathy/encephalitis in childhood. Subjects and methods We enrolled 22 children, for whom we examined DWI with b = 1000 s/mm2, DWI with b = 3000 s/mm2, and apparent diffusion coefficient (ADC) map with b = 1000 during the acute phase of febrile encephalopathy/encephalitis. Clinical diagnoses included acute encephalopathy with biphasic seizures and late reduced diffusion (AESD; n = 6), clinically mild encephalopathy/encephalitis with a reversible splenial lesion (MERS; n = 6), and herpes simplex virus encephalitis (HSE; n = 3), unclassified acute encephalopathy/acute encephalitis (n = 2); acute encephalitis with refractory, repetitive partial seizures (AERRPS; n = 1); other encephalopathy (n = 1); infarction (n = 1); head injury (n = 1); or mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (n = 1). The diagnostic quality of brain lesions was compared between b = 1000 and b = 3000 DWI images by visual inspection. In addition, we attempted a quantitative assessment using apparent diffusion coefficient (ADC) value and an index of signal intensity (SI) ratio, defined as the mean SI at the affected lesion divided by the mean SI at the pons. Results High intensity lesions were either visible only on b = 3000 DWI (n = 5; 2 AESD, 1 MERS, 1 HSE, and 1 unclassifiable encephalopathy) or more effectively identified on b = 3000 DWI than on b = 1000 DWI (n = 17). The outcome of the former five subjects was favorable, without motor or intellectual sequelae. The mean SI ratio of b = 3000 was significantly greater than that of b = 1000 in AESD and MERS subgroups as well as in all 22 subjects. Mean ADC values were lower in the AESD and MERS than that in the HSE subgroups. Conclusion We concluded that b = 3000 DWI was superior to b = 1000 DWI in detecting abnormal lesions in acute encephalopathy/encephalitis during childhood.

Background: Recurrent persistent cough and wheezing often begin in early childhood; however, not all episodes of them are caused by asthma and/or an allergic reaction, they are exacerbated with several respiratory infections. Previous research suggests that the best treatment for toddlers and preschool-age children with persistent cough and/or wheeze is a difficult clinical challenge. Methods: In this single-center prospective clinical trial, HIROSIMA study, we observed the clinical effect of oral leukotriene receptor antagonists (LTRAs: montelukast, pranlukast) with carbocystein and lysozyme chloride or ambroxol for over a year and assessed the relationship between infantile wheeze, chronic cough and rhinosinusitis. The patients were allocated to the intervention with their consent. Results: Eighty patients, who were admitted to hospital for persistent cough and dyspnea episodes, completed the study for a year and showed significantly fewer asthma exacerbation episodes (clinical asthma scores/week; 16.1 ± 3.1 vs 7.9 ± 2.7) during the first eight weeks (p < 0.01), comparing to the use of LTRA alone (n = 40).; and the improvement of conditions persisted for over the twelve-month period. None of the subjects was admitted to the hospital for asthma exacerbation, and had any corticosteroid treatment during the study. Conclusion: Our strategy for chronic cough including the management of allergic rhinitis and sinusitis significantly evaded persistent cough and wheeze of children age from 1 to 5 years, and reduced the frequency of recurrent otitis media. Note: HIROSIMA study provides promising data for the control of persistent cough and wheeze of children age from 1 to 5 years without the use of corticosteroids for over a year with a good adherence to the treatment.

We present the case of a 5-year-old-boy who developed a fever and cellulitis-like groin rash 5 days before developing conjunctivitis and 6 to 7 days before other typical signs of Kawasaki disease (KD) appeared. The cellulitis failed to respond to antibiotics and no pathogens were isolated. His fever and clinical signs resolved with intravenous immunoglobulin and high-dose aspirin after discontinuation of antibiotics. Nonbacterial cellulitis is a rare presenting sign of KD, but in the appropriate clinical setting and population, a diagnosis of KD should be considered when cellulitis and fever fail to respond to an appropriate antibiotic regimen and no pathogen can be isolated.

Kawasaki disease, a systemic vasculitis of unknown etiology, develops frequently in infants and demonstrates a variety of clinical symptoms during the disease course. The most important complication, coronary artery lesions, is found in 15-25% of untreated patients. Meanwhile, acute myocarditis, another complication that can occur during the acute phase of severe systemic vasculitis, has been found in more than 50% of affected individuals when asymptomatic cases are included. However, cases that require treatment are rare as reported by Yoshikawa et al. (Circ J 70:202-205, 2006). As for neural complications, aseptic meningitis is well known, but it is extremely rare for these patients to develop encephalitis or encephalopathy as reported by Imai et al. (Jpn Soc Emerg Pediatr 8:50-55, 2009). Recently reported magnetic resonance images (MRIs) have shown reversible lesions in the median splenium of patients complicated with encephalitis or encephalopathy. Reversible lesions have also been observed after the administration of an antiepileptic agent, drastic weight loss, and development of metabolic abnormalities as reported by Massimo et al. (Neuroradiology 49:541-544, 2007) and Tada et al. (Neurology 63:1854-1858, 2004). Aggressive therapy for such lesions is not considered necessary because most disappear without neurologic aftereffects. However, the clinical significance and pathogenesis of the condition remain largely unknown. We present the first known report of a Kawasaki disease case complicated with acute myocarditis and mild encephalitis/encephalopathy with a reversible splenial lesion (MERS). These findings may be valuable for the diagnosis and treatment of affected patients.

This report describes 3 year old girl with the unusual presentation of polyarticular juvenile idiopathic arthritis (JIA) with anti-cyclic citrullinated peptide (anti-CCP) antibodies and a positive rheumatoid factor (RF). She was initially treated with a nonsteroidal anti-inflammatory drug (NSAID; ibuprofen) followed by methotrexate (MTX, 10 mg/m2/week) and prednisolone (0.25 mg/kg/day), but these treatments were ineffective. Administration of tocilizumab, a humanized antihuman interleukin-6 receptor monoclonal antibody, promptly improved her clinical manifestations, and she has been in complete remission (DAS28