[A case of anti-MOG antibody-positive multiphasic disseminated encephalomyelitis co-occurring with unilateral cerebral cortical encephalitis].

A 20-year-old woman first developed acute disseminated encephalomyelitis (ADEM) at 11 years of age. At 17 years of age, she was hospitalized due to generalized seizure and diagnosed with encephalitis. Brain MRI revealed a FLAIR-hyperintense lesion in the unilateral cerebral cortex. At 18 years of age, serum anti-myelin oligodendrocyte glycoprotein (MOG) antibody was detected. At 20 years of age, she was admitted to our hospital, diagnosed with multifocal disseminated encephalomyelitis (MDEM). MDEM has been observed in patients that are seropositive for the anti-MOG antibody. More recently, unilateral cerebral cortex encephalitis with epilepsy has also been reported in such patients. The co-occurrence of MDEM and cortical encephalitis in the same patient has important implications for the pathogenesis of anti-MOG antibody-associated autoimmune diseases.

WU polyomavirus detected in respiratory tract specimens from young children in Japan.

Polyomaviruses (PyV) WU and KI are reportedly associated with respiratory tract disease (RTD) worldwide but their incidence is unclear in Japan. In a 2 year prospective study, WU/KIPyV were detected in 48 (13.9%) and in five (1.4%) of 345 children hospitalized with lower RTD, respectively. The seasonal distribution was observed in spring and early summer. Other respiratory viruses were co-detected in 51% of PyV-positive patients, but eight (2.3%) of the WUPyV-positive patients were negative for other known pathogens.

Early induction of interleukin-5 and peripheral eosinophilia in acute pneumonia in Japanese children infected by pandemic 2009 influenza A in the Tokyo area.

A novel influenza A (2009 H1N1) virus has led to a worldwide pandemic. A significant number of patients with pneumonia have been reported, although its pathogenesis remains to be elucidated. To determine its pathogenesis, we evaluated serum interleukin (IL)-5 and peripheral eosinophil counts in patients with acute pneumonia caused by the 2009 H1N1 virus. During the period from October to December 2009, 40 patients with laboratory-confirmed 2009 H1N1 pneumonia were under investigation. Their mean age at presentation was 6.8 years. The most characteristic finding was the early development of hypoxemic respiratory distress in the first 24 hr after the onset of fever. Bronchial mucous plugs included eosinophils in addition to neutrophils, even in patients without allergies. Serum IL-5 levels were elevated in 20 out of 24 patients (83%) whose samples were obtained in the first 24 hr after the onset of fever (26.5 ± 20.1 pg/mL), independent of the presence of underlying allergies. In contrast, induction of IL-5 was not documented in sera from eight patients with laboratory-confirmed 2009 H1N1 virus who developed neurological complications, but without lower respiratory infection (2.1 ± 0.7 pg/mL, P < 0.001 vs acute pneumonia). Peripheral eosinophilia was characteristic in acute pneumonia, but not in patients without a lower respiratory infection. There was a marked difference in the induction of IL-5 in 2009 H1N1 patients who developed acute pneumonia, compared with those without a lower respiratory infection. IL-5 may play a role in the early phase of acute pneumonia caused by the 2009 H1N1 virus in Japanese children.

Distinctive clinical features of human bocavirus in children younger than 2 years.

BACKGROUND AND OBJECTIVE: Clinical characteristics of human bocavirus (HBoV) infection have been studied worldwide, but their importance of those characteristics remains unknown. We investigated distinctive clinical features of HBoV-positive children with lower respiratory tract infection (LRTI). METHODS AND RESULTS: During April 2007-July 2009, for 402 hospitalized children younger than 2 years with LRTI, we prospectively examined virus genomes in nasopharyngeal swabs for HBoV, respiratory syncytial virus (RSV), rhinovirus, metapneumovirus, parainfluenzavirus, and adenovirus. The HBoV genomes were identified in 34 patients (8.5%). Clinical and laboratory data of HBoV-positive and other virus/bacteria-negative patients (n = 18) were analyzed and compared with data of RSV-single positive patients (n = 99). The seasonal distribution of HBoV exhibits a concentration of cases during March-September, with most RSV cases occurring during winter in Japan. The minimum age of HBoV-positive patients was 5 months, although 44 patients (44%) with RSV were younger than 6 months. The main clinical features were respiratory distress and hypoxia. Hypoxia advances within 3 days after onset. The mean oxygen saturation on arrival was 92.8%, which was significantly lower than that in patients with RSV (p < 0.001). White blood cell counts were similar among groups. However, the percentage of neutrophils in white blood cells were significantly higher in HBoV-positive patients (62 vs. 45%, p < 0.001). Their prognoses were good. Their hospital stays were 6.6 days. CONCLUSIONS: HBoV-single positive patients show several clinical characteristics, such as seasonality, age, hypoxia, and neutrophilia, which differ from those with RSV infection.

Effectiveness of lidocaine infusion for status epilepticus in childhood: a retrospective multi-institutional study in Japan.

We evaluated the usefulness of intravenous lidocaine therapy for managing of status epilepticus (SE) during childhood in a retrospective multi-institutional study. Questionnaires were sent to 28 hospitals concerning patients admitted for SE who were managed with lidocaine, assessing patient characteristics, treatment protocols and efficacy. In 279 treated patients, 261 SE occurrences at ages between 1 month and 15 years were analyzed. SE was classified as showing continuous, clustered, or frequently repeated seizures. Considering efficacy and side effects in combination, the usefulness of lidocaine was classified into six categories: extremely useful, useful, slightly useful, not useful, associated with deterioration, or unevaluated. In 148 SE cases (56.7%), lidocaine was rated as useful or extremely useful. Multivariate analysis indicated lidocaine was to be useful in SE with clustered and frequently repeated seizures, and SE attributable to certain acute illnesses, such as convulsions with mild gastroenteritis. Efficacy was poor when SE caused by central nervous system (CNS) infectious disease. Standard doses (approximately 2mg/kg as a bolus, 2mg/kg/h as maintenance) produced better outcomes than lower or higher doses. Poor responders to the initial bolus injection of lidocaine were less likely to respond to subsequent continuous infusion than good initial responders. We recommend lidocaine for use in SE with clustered or frequently repeated seizures, and in SE associated with benign infantile convulsion and convulsions with mild gastroenteritis. Lidocaine should be initiated with a bolus of 2mg/kg. If SE is arrested by the bolus, continuous maintenance infusion should follow; treatment should proceed to different measures when SE shows a poor response to the initial bolus of lidocaine.

Efficacy of intravenous midazolam for status epilepticus in childhood.

A retrospective multicenter study was conducted, designed to evaluate the efficacy and safety of midazolam for the treatment of status epilepticus. The subjects were 358 inpatients who received intravenous midazolam therapy for status epilepticus. The mean age was 48.6 +/- 46.5 months. The underlying disorder was epilepsy in 195 cases, and acute symptomatic diseases in 163 (encephalitis or encephalopathy in 88 cases). Midazolam was administered as a bolus dose (0.25 +/- 0.21 mg/kg), followed if necessary by continuous infusion (0.26 +/- 0.25 mg/kg/hr). The bolus injection was effective in 162 (56.6%) of the 286 cases. In the end, seizure suppression was obtained in 231 cases (64.5% of the total). The effectiveness of midazolam was lower in patients in whom midazolam was initiated more than 3 hours after seizure onset, and this tendency was particularly marked in the epilepsy group. During the treatment period, 10 patients died, but none of these deaths were associated with midazolam therapy. The incidence and types of adverse events were consistent with previously reported data. The present results indicate that midazolam is highly effective for the management of status epilepticus, if used sufficiently early after seizure onset.

[Acute non-herpetic encephalitis with severe refractory status epilepticus --its overwhelming ictogenicity, epileptogenicity, long-term prognosis and review of the literature].

In 1980s, the authors experienced 5 patients with "a peculiar form of acute encephalitis/encephalopathy "which is characterized by three features: 1. Complex partial seizures with secondary generalization recur incessantly or continue persistently without regaining consciousness for many days in spite of intensive diazepam (DZP) therapy; usually general anesthesia at ICU setting for 2-3 weeks becomes mandatory. 2. After weaning from long-run anesthesia, seizures of the same type still persist, though much less frequent, during the convalescent and chronic phases of the disease throughout. There is no seizure-free interval between the acute and chronic stages. 3. Etiology is totally unknown;extensive laboratory examinations mostly remain within normal ranges, though clinical features such as acute onset, frequent accompaniment of fever, etc., mimic those of acute encephalitis/encephalopathy. The synopsis of our 5 patients were; age ranged from 2 to 5 years old, no antecedent history of seizures, fever of moderate degree preceded seizures a few days and persisted in the acute stage; complex partial seizures with secondary generalization recurred several times every hour. Circulatory/respiratory compromise necessitated a drastic intervention with barbiturate coma at ICU. Etiology was unknown. Follow-up for 19 years in average revealed mental retardation and chronic epilepsies in all patients. Since our first report in 1987, 49 similar cases with ours have been sporadically reported. The majority of the reported cases had been submitted to longstanding general anesthesia and placed in barbiturate coma for weeks to 2 months. The death occurred in 7 patients. In all reported cases, the first line drugs such as DZP iv, phenytoin iv, etc did not work, and it was highly recommended to place the patient under barbiturate coma as early as possible.

Extremely low-dose ACTH step-up protocol for West syndrome: maximum therapeutic effect with minimal side effects.

We studied the effectiveness of our new ACTH treatment strategy for West syndrome (WS), which was based on the results of our previous extremely low-dose ACTH study. The subjects were 31 infants with WS (cryptogenic WS in nine; symptomatic WS in 22). Synthetic ACTH-Z in a dose of 0.005 mg (= 0.2 IU)/kg/day was injected once every morning for at least 2 weeks, up to a maximum of 3 weeks. When this first treatment course achieved full seizure and EEG control, ACTH was tapered to zero over the subsequent 1 or 2 weeks. In the absence of a documented response, the dosage was increased to 0.025 mg (= 1.0 IU)/kg/day for the next 2 weeks (second treatment course). We analyzed the short-term as well as long-term effects, and the incidence of side effects. The first treatment course successfully controlled both spasms and hypsarrhythmia in 17 patients (55%), only spasms in one, and hypsarrhythmia in two. The second treatment course was then introduced in eight of the remaining 14 patients, providing complete suppression of WS in an additional two patients. Regarding the long-term effects, 13 patients (48%), with excellent short-term results and a longer than 1-year follow-up, remained seizure-free. Side effects of a mild degree were seen in 13 patients during ACTH treatment. Our new ACTH step-up method brought 61 and 48% of the patients into short-term and long-term remission, respectively, without significant side effects. The dose of ACTH required to control WS appears to be unexpectedly smaller than the dose we previously used.

[Clinical and electroencephalogram study of 5 children with hypothalamic hamartoma].

We retrospectively studied 5 children with hypothalamic hamartoma (HH) to elucidate the clinical, neuroimaging and electroencephalogram (EEG) characteristics of this disorder. In all cases, high resolution MRI scans demonstrated an intrahypothalamic mass protruding into the 3rd ventricle. An initial symptom was epileptic attack in 4 cases and precocious puberty in the remaining one. Gelastic seizures developed in 4 of 5 patients at ranging from 2 days to 11 years of age. The ictal EEGs during the gelastic seizures showed diffuse attenuation of background activity, followed by rhythmic slow discharges either diffusely or in the central area. Gamma-knife radiosurgery was performed on 2 cases whose seizures were resistant to available antiepileptic drugs. One of the 2 patients was responded significantly to this treatment, showing the disappearance of combined attacks and a marked reduction of the generalized spike-waves discharges. A more aggressive therapy, including gamma-knife radiosurgery and surgical treatment, should be considered for patients whose seizures are resistant to the medical treatment and causing deterioration of intelligence and behavioral problem.

Zonisamide for West syndrome: a comparison of clinical responses among different titration rate.

We administered zonisamide (ZNS) to patients with West syndrome in different titration protocols and compared their short-term therapeutic effects. We designed three protocols to raise the serum ZNS concentration (SZC): (1) increase the dose in three steps, from 3 to 10 mg/kg every 3 days, (2) increase the dose from 5 to 10 mg/kg over 3-7 days, and (3) start with 10 mg/kg and maintain this dosage for 2 weeks. The subjects were 23 infants with West syndrome, 8 of whom comprised the 1st group, 5 the 2nd group, and the remaining 10, the 3rd group. As a result, excellent and good effects were obtained in a total of seven patients (30.4%) and one patient, respectively (1/8 in the 1st step-up group, 3/5 in the 2nd step-up group, and 4/10 in the 3rd group). The maximum SZC was higher in the excellent and good effect groups (n=8; 32.0+/-8.0 microg/ml) than in the ineffective group (n=15; 22.4+/-8.2 microg/ml) (P<0.05). The period of time required for cessation of spasms appeared shorter in the 3rd group (n=4; mean=5.7 days) than in the 1st and 2nd groups (n=4; mean=10.3 days). There were few side effects except for transient hyperthermia and gastrointestinal symptoms. Our new protocol of starting with 10 mg/kg of ZNS can be introduced safely and make a therapeutic judgment feasible within 2 weeks.

A 1-year-old infant with McArdle disease associated with hyper-creatine kinase-emia during febrile episodes.

A 14-month-old girl was hospitalized due to repeated hyper-creatine kinase (CK)-emia during pyrexia. Mild hypotonia was observed, but other physical and neurological findings were unremarkable. The serum CK level was normal at rest or normothermia. Open muscle biopsy was performed on the rectus femoris, and showed glycogen storage and complete lack of phosphorylase activity histochemically and biochemically, establishing the diagnosis of McArdle disease. The diagnosis of McArdle disease in early infancy is uncommon. Until this study there have been no reports of clinical symptoms or muscle biopsy findings for McArdle disease in early childhood. This disease must be considered when transient hyper-CKemia is observed in infants, even if glycogen storage is unremarkable as compared with adult cases.

Aberrant neuronal migration in the brainstem of fukuyama-type congenital muscular dystrophy.

We examined the brainstem of 10 patients with Fukuyama-type congenital muscular dystrophy (FCMD). In the midbrain we noted leptomeningeal glioneuronal heterotopia (LGH) (n = 9) and intramural "micropolygyria" (n = 1) in the tectum, as well as tyrosine hydroxylase-positive ectopic neurons/fibers ventral to the cerebral peduncle (n = 3). In the pontomedullary region, glial fibrillary acidic protein-positive subpial tissue intermingled with neurons and myelinated fibers was present in the ventrolateral pontine surface in all cases and extended over the lateral surface of the upper medulla oblongata. This subpial gliotic band was often contiguous with the extra-pial LGH tissues. The gliotic band protruded from the ventrolateral pontine surface in 3 cases and appeared to include ectopic neurons of the pontine nucleus. Disarrangement of the arcuate nuclei (n = 3) was also noted in the medulla oblongata. We hypothesize that both the radial and tangential neuronal migration systems are disrupted in the FCMD brainstem in addition to altered neuronal migration in the cerebral and cerebellar cortex. Fukutin protein may play a part in the morphogenesis of certain neuronal structures in the brainstem and the dysplastic structure termed "aberrant pyramidal tract" in previous reports may essentially result from an ectopic migration of pontine nucleus neurons.

EEG in children with early-onset benign occipital seizure susceptibility syndrome: Panayiotopoulos syndrome.

PURPOSE: We analyzed sequential changes in the localization of EEG foci along with age to identify a specific EEG pattern, and the relation between the clinical manifestations and the EEG pattern in patients with Panayiotopoulos syndrome (PS). METHODS: The subjects were 76 children, who had been followed up >2 years with repeated EEG examinations at 6-month intervals. Analysis of EEG findings included the determination of localization of spike foci, as a function of age, by using cross-sectional data, and the identification of subgroups with homogeneous EEG patterns. Then we compared certain clinical features among these subgroups. RESULTS: In the cross-sectional EEG study, the occipital EEG spike focus was most frequently seen between ages 2 and 5 years. Independent and synchronous frontopolar and occipital spikes (Fp-O spikes) and centroparietotemporal (CPT) EEG spike foci had increased incidences between ages 4 and 7 years, and between ages 6 and 10 years, respectively. We subclassified the 76 patients into the following five subgroups based on the evolutional changes in epileptic EEG foci, which frequently showed shifting, multiplications, and generalization: (a) persistent occipital focus group (O group), (b) Fp-O spikes group (Fp-O pattern group), (c) generalized EEG pattern group, (d) CPT foci group (CPT group), and (e) no epileptic EEG focus group. The Fp-O group showed the latest age at onset of epilepsy. The generalized EEG pattern group had the highest frequency of seizures as well as recurrences of status epilepticus (SE), as well as the longest active seizure period among the five groups. CONCLUSIONS: These results indicated that the EEG foci in most of patients with PS are frequently shifting location, multiplying, and propagating diffusely with age, rather than persistently localizing in the occipital region. In addition, the EEG patterns showed a certain trend and roughly corresponded to certain clinical characteristics. However, the prognosis of the seizures appeared to be favorable regardless of the EEG pattern.

Clinical study of catastrophic infantile epilepsy with focal seizures.

This study investigated clinico-electrical and etiologic characteristics of catastrophic infantile epilepsy with focal seizures developed in early infancy. The patients included 15 children who fulfilled the following criteria: seizure onset before 12 months of age, presence of daily focal or secondarily generalized seizures resistant to antiepileptic drugs for at least 3 months, and exclusion of Ohtahara and West syndromes. Patients were classified into three subgroups. Three patients demonstrated progressively deteriorating neurologic symptoms associated with progressive cerebral atrophy and multifocal seizure onset. Three other children were characterized by hemiparesis and exclusively lateralized seizure onset because of focal cortical dysplasia in the contralateral hemisphere. The remaining nine children did not demonstrate any rapidly progressive neurologic deterioration or increasing cerebral atrophy and exhibited multifocal seizure onset. At the last examinations, all except one patient demonstrated moderate to severe psychomotor retardation. Catastrophic infantile epilepsy with focal seizures tended to demonstrate multifocal seizure onset and a deleterious clinical course with numerous focal seizures regardless of etiology. Because migratory focal seizures appear to be common in these infants, we have to search for the underlying etiopathogenesis of these patients, including not only metabolic errors but also localized or lateralized structural abnormality.

[Urolithiasis induced by combined ACTH and zonisamide treatment in a patient with startle induced epilepsy].

A 5-year-old boy had periodic spasms and startle-induced drop attacks. Zonisamide (ZNS) was partially effective for the former seizures, and propranolol for the latter. An add-on therapy with ACTH resulted in a transient disappearance of seizures and an improvement of EEG. However, the patient developed urolithiasis with resultant hematuria and pyelectasis during ACTH therapy. ZNS can induce urolithiasis by increasing urinary pH and calcium (Ca) excretion, and ACTH may facilitate this rare adverse effect of ZNS by further increasing the urinary Ca. Hydrochlorothiazide could resolve the urolithiasis by decreasing the urinary Ca excretion.

[A case of idiopathic torsion dystonia showing blepharospasm at the onset].

We report a 12-year-old boy with idiopathic torsion dystonia. Blepharospasm appeared at the age of 10, followed by truncal hypertonia and progressive scoliosis after 1 year. He had bizarre involuntary movement of his limbs upon waking, which was initially misinterpreted as a psychogenic reaction. Routine neurological examinations revealed no abnormality. Treatment with diazepam, bacrophen, 1-dopa, and clonazepam, led to only short time improvement of symptoms. At the age of 14, his symptoms gradually improved in natural course. At present he is 15 years old, and capable of normal daily activities. His clinical course was not typical of idiopathic torsion dystonia and very rare in children.