Takuya Tanabe

Outcome of acute necrotizing encephalopathy in relation to treatment with corticosteroids and gammaglobulin

OBJECTIVE To examine the relation between outcome and treatment with steroids and gammaglobulin in children with acute necrotizing encephalopathy. METHODS We retrospectively evaluated the clinical course and outcome of 34 children with acute necrotizing encephalopathy. They were divided into two groups; 17 patients with brainstem lesion and 17 patients without brainstem lesion. Early steroid use was defined as when steroids were administered within 24h after the onset. The outcome was judged as good when a patient had no or mild cognitive impairment and poor when a patient had more severe sequelae, or died. RESULTS Among patients without brainstem lesions, the outcome was good in 7 of 12 with early steroid, whereas it was poor in all 5 patients without early steroid. There was no significant difference in sex, age, and laboratory data between patients with and without early steroid. The outcome was not correlated with gammaglobulin treatment. As to patients without brainstem lesions, the outcome was not correlated with early steroid or gammaglobulin treatment. CONCLUSIONS Steroid within 24 h after the onset was related to better outcome of children with acute necrotizing encephalopathy without brainstem lesions. Early steroid treatment will be an important option of the treatment for acute necrotizing encephalopathy.

Management of and prophylaxis against status epilepticus in children with severe myoclonic epilepsy in infancy (SMEI; Dravet syndrome) – A nationwide questionnaire survey in Japan

UNLABELLED The aim of this study was to establish strategies for prophylaxis against status epilepticus (SE) associated with high fever and for management of ongoing SE in children with severe myoclonic epilepsy in infancy (SMEI). METHODS The investigation was performed retrospectively using a questionnaire, asking about medications, which was distributed to epilepsy specialists throughout Japan. All respondents were members of the Japan Epilepsy Society (JES) and/or the Japanese Society of Child Neurology (JSCN). Data from 109 SMEI patients (51 males and 58 females), 1-37 (M+/-SD, 10.7+/-6.53) years old, were used for this study. Of these 109 patients, 10 were excluded because they had not experienced SE, such that data from 99 patients were analyzed. RESULTS Among the anti-epileptic drugs (AEDs) used daily, excellent efficacy against SE evolution was obtained with the following: potassium bromide (KBr) (41.7%), zonisamide (ZNS) (13.5%), clobazam (CLB) (10.0%), valproate (VPA) (8.0%), phenobarbital (PB) (6.7%), and phenytoin (PHT) (2.6%). Excellent efficacy was not obtained with either clonazepam (CZP) or carbamazepine (CBZ). The diazepam (DZP) suppository was the most frequently given drug for prophylaxis against SE triggered by fever, but only 2 (2.4%) cases showed excellent results. Excellent efficacy in terminating ongoing SE was obtained with the following medications; intravenous barbiturates (75-100%), intravenous midazolam (MDZ) (68.8%), intravenous DZP (54.3%), intravenous lidocaine (Lid) (21.4%), and intravenous PHT (15.4%). CONCLUSIONS Daily KBr was most efficacious for controlling seizures in SMEI patients. Early use of intravenous barbiturates is the most effective strategy in stopping SE in a subset of patients. Reliable efficacy in SE was not obtained with prophylactic DZP, intravenous benzodiazepines (BZPs), PHT and Lid.

Neopterin, biopterin, and nitric oxide concentrations in the cerebrospinal fluid of children with central nervous system infections.

We measured neopterin, biopterin and nitric oxide (NO) concentrations in the cerebrospinal fluid of pediatric patients with central nervous system (CNS) infectious diseases. The nitric oxide and neopterin concentrations were significantly elevated in encephalitis patients, especially in two cases with serious neurological sequelae, while the biopterin levels were not elevated. The bacterial meningitis patients, on the contrary, had high cerebrospinal fluid concentrations of neopterin and biopterin, but not of NO. Although these findings are preliminary, it may suggest that cerebrospinal fluids nitric oxide would be a useful marker to prospect neurological prognoses in the CNS infections.

Cerebrospinal fluid and Serum neuron-specific enolase levels after febrile seizures

Summary:  Purpose: Neuron‐specific enolase (NSE) has been established as a reliable marker of neuronal damage in various neurologic disorders. The aim of this study was to evaluate whether febrile seizures (FS) cause brain damage, based on the serum and cerebrospinal fluid (CSF) levels of NSE.

Pelizaeus-Merzbacher disease caused by a duplication-inverted triplication-duplication in chromosomal segments including the PLP1 region.

Pelizaeus-Merzbacher disease (PMD; MIM#312080) is a rare X-linked leukodystrophy presenting with motor developmental delay associated with spasticity and nystagmus. PMD is mainly caused by abnormalities in the proteolipid protein 1 gene (PLP1), most frequently due to duplications of chromosomal segments including PLP1. In this study, a 9-year-old male patient manifesting severe developmental delay and spasticity was analyzed for PLP1 alteration, and triplication of PLP1 was identified. Further examination revealed an underlying genomic organization, duplication-inverted triplication-duplication (DUP-TRP/INV-DUP), in which a triplicated segment was nested between 2 junctions. One of the 2 junctions was caused by inverted homologous regions, and the other was caused by non-homologous end-joining. PMD patients with PLP1 duplications usually show milder-classical forms of the disease compared with patients with PLP1 missense mutations manifesting severe connatal forms. The present patient showed severe phenotypic features that represent an intermediate form of PMD between classical and connatal forms. This is the first report of a patient with PLP1 triplication caused by a DUP-TRP/INV-DUP structure. This study adds additional evidence about the consequences of PLP1 triplication.

Febrile seizures associated with influenza A

To clarify the clinical impact of influenza A on the development of febrile seizures (FS), consecutive FS patients brought to our hospital between October 2003 and September 2004 were prospectively surveyed. Patients infected with influenza A (influenza A patients) and those uninfected with influenza (non-influenza patients) were compared with regard to clinical characteristics of FS. Influenza infection was determined by rapid antigen test and/or serologically. Associations of influenza A with atypical findings of FS, including partial seizures, prolonged seizures, multiple seizures during the same illness, and 30-min or longer prolonged postictal impairment of consciousness (PPIC), were analyzed by multiple logistic regression. A total of 215 patients (47 influenza A and 168 non-influenza patients) were enrolled in the study. Age was significantly higher in the influenza A group (39.85+/-22.16 months vs. 27.51+/-17.14 months, P<0.001). Of 42 patients aged 48 months or older, which corresponded to the 80th percentile for age, 15 (35.7%) were influenza A patients, with a significantly higher incidence of such patients than in the subgroup of patients aged 47 months or younger (32/173, 18.5%) (P=0.015). On multiple logistic regression analysis, influenza A was independently associated with PPIC (odds ratio: 4.44, 95% confidence interval: 1.52-12.95, P=0.006), but not with other atypical findings. The positive association of influenza A with PPIC suggests that influenza may affect state of consciousness at the same time that it induces seizures with fever.

PRRT2 mutation in Japanese children with benign infantile epilepsy

Mutations in PRRT2 genes have been identified as a major cause of benign infantile epilepsy and/or paroxysmal kinesigenic dyskinesia. We explored mutations in PRRT2 in Japanese patients with BIE as well as its related conditions including convulsion with mild gastroenteritis and benign early infantile epilepsy. We explored PRRT2 mutations in Japanese children who had had unprovoked infantile seizures or convulsion with mild gastroenteritis. The probands included 16 children with benign infantile epilepsy, 6 children with convulsions with mild gastroenteritis, and 2 siblings with benign early infantile epilepsy. In addition, we recruited samples from family members when PRRT2 mutation was identified in the proband. Statistical analyses were performed to identify differences in probands with benign infantile epilepsy according to the presence or absence of PRRT2 mutation. Among a total of 24 probands, PRRT2 mutations was identified only in 6 probands with benign infantile epilepsy. A common insertion mutation, c.649_650insC, was found in 5 families and a novel missense mutation, c.981C>G (I327M), in one. The family history of paroxysmal kinesigenic dyskinesia was more common in probands with PRRT2 mutations than in those without mutations. Our study revealed that PRRT2 mutations are common in Japanese patients with benign infantile epilepsy, especially in patients with a family history of paroxysmal kinesigenic dyskinesia.

Classification of benign infantile afebrile seizures

PURPOSE The aim of this study is to classify infantile cases with benign seizures into known epileptic syndromes, thereby facilitating discussion of clinical factors that could play an important role in diagnosis. SUBJECTS Fifty-seven patients with afebrile seizures fulfilling all of the following criteria were enrolled: (1) normal development prior to the onset, (2) no underlying disorders nor neurological abnormalities, (3) onset before the age of four and (4) normal interictal EEG and neuroimaging findings. RESULTS Thirty-nine cases (Group A) were characterized by an association of mild gastroenteritis. The remaining 18 cases were divided into two groups according to the seizure type. One group had partial seizures (Group B, 13 cases) while the other was suspected to have generalized seizures (Group C, 5 cases). Age at onset was significantly higher for Group A (19.5 +/- 5.5 months) than Groups B (5.3 +/- 1.8 months) (p<0.001) and C (5.8 +/- 3.5 months) (p=0.038). Positive family history of seizure disorder, seizure cluster tendency, and the efficacy of lidocaine against seizure clusters were common in the three groups. CONCLUSIONS Features in Group A were consistent with benign convulsions with mild gastroenteritis (proposed by Morooka) [Morooka, K., 1982. Mild diarrhea and convulsions. Shonika 23, 134-137 (in Japanese)], those of Group B with benign partial epilepsy in infancy [Watanabe, K., Yamamoto, N., Negoro, T., Takaesu, E., Aso, K., Furune, S., Takahashi, I., 1987. Benign complex partial epilepsies in infancy. Pediatr. Neurol. 3, 208-211], and those of Group C with benign infantile convulsions [Fukuyama, Y., 1963. Borderland of epilepsy with special reference to febrile convulsions and so-called infantile convulsions. Seishin Igaku 5, 211-223 (in Japanese)]. The distinction between these syndromes depends upon age at onset, association with gastroenteritis, and ictal symptomatology. In our experience, however, it was not easy to catch seizure type accurately in clinical situations. As far as the results of ictal video-EEG monitoring ever carried out concern, focal initiation of parxysmal discharges was demonstrated in all cases, not only of BPEI but also of apparent generalized seizures examined without exception. These observations led the authors to conclude that the identity of BIC is dubious, most probably it will represent a subtype of BPEI.

Oseltamivir treatment for children showing abnormal behavior during influenza virus infection

UNLABELLED We investigated the clinical courses of children with influenza infection, who showed abnormal behavior, who were treated with oseltamivir (Tamiflu). SUBJECTS The subjects were 22 children, 2-15 (mean+/-SD, 6.6+/-3.2) years old, admitted to our hospital during the 2004-2005, 2005-2006, and 2006-2007 influenza seasons. Abnormal behavior appeared before treatment with oseltamivir in 13 children (pre-Tami group), and after administration of the medication in 9 (post-Tami group). All patients continued to receive oseltamivir for 3-5 days after admission. RESULTS Meaningless speech and movements without a specific purpose were the most frequent abnormal behavior (16 children), while illusions, delusions, and misidentifying awareness were the second most common (14 children). Sensations of marked fear and excitement were recognized in 6 children. One child rushed up and down the stairs unconsciously, raising concern that a serious accident might occur. All patients showed a favorable clinical course, without worsening of neurological symptoms or the development of encephalopathy, and outcomes were good. The clinical course, number of recurrences of abnormal behavior, and outcome were similar in the pre-Tami and post-Tami groups. CONCLUSIONS Our observations suggest that oseltamivir is not a prerequisite for the development of abnormal behavior and does not worsen the clinical manifestations of abnormal behaviors, although further investigations are needed to determine whether oseltamivir is necessary, or even useful, for patients with influenza virus encephalopathy.

Hippocampal damage after prolonged febrile seizure: One case in a consecutive prospective series

The factors that contribute to hippocampal damage as a sequela, and its frequency, in patients experiencing febrile status epilepticus, remain unknown. Of the 472 patients with febrile seizures admitted to our hospital between February 2004 and August 2008, 77 had prolonged seizures. Among them, 59 underwent magnetic resonance imaging (MRI). A 21‐month‐old girl showed hippocampal changes after her first episode of febrile status epilepticus. The seizure lasted about 35 min, with eye deviation to the right and ictal rhythmic discharges in the left hemisphere. MRI at 72 h after the seizure revealed high‐signal intensities in T2 and fluid‐attenuated inversion recovery (FLAIR) images of the left hippocampus. Left hippocampal volume diminished over the next several months suggesting the occurrence of neuronal cell death. In no other cases, not even those with longer seizure durations, did significant hippocampal changes develop. The frequency of hippocampal damage was 1.7% in this case series. The involvement of factors other than seizure duration merits further study.