An outbreak investigation of parechovirus-A3 in a newborn nursery.

OBJECTIVE: To investigate parechovirus-A3 (PeV-A3) transmission in a newborn nursery, after encountering 3 neonates with fever and rash. DESIGN: An observational study. SETTING: At a newborn nursery at the general hospital in Hyogo, Japan. PARTICIPANTS: Symptomatic neonates and their family members, and asymptomatic neonates born during the same period. METHODS: PCR assays for PeV-A and genotyping were used for the investigation of PeV-A3. Preserved umbilical cords were used to identify the route of transmission. RESULTS: PeV-A3 infection was confirmed in the three symptomatic neonates. The index case had fever and rash, and the 2 neonates treated later became symptomatic and had serum, cerebrospinal fluid, and stool specimens that were positive for PeV-A3 on PCR. The umbilical cord of the index case was positive for PeV-A3 on PCR. The family members of the index case, including the mother, were asymptomatic before delivery. The older sister and cousin of the PeV-A3-infected neonate had positive PCR results. The sequence analysis suggested 2 possible transmission routes: vertical and horizontal transmission in a newborn nursery and/or a family outside the hospital. The incubation period of PeV-A3 infection was estimated to be 1-3 days (maximum, 7 days). CONCLUSION: Horizontal transmission of PeV-A3 was confirmed in a newborn nursery. Vertical transmission was suggested by the detection of RNA in an umbilical cord sample from the index case. These observations indicate that PeV-A3 can be horizontally transmitted in a newborn nursery and that special caution is required to prevent healthcare-associated transmission of PeV-A3.

Clinical prediction rule for neurological sequelae due to acute encephalopathy: a medical community-based validation study in Harima, Japan.

OBJECTIVES: This study aimed to verify the screening performance of our clinical prediction rule for neurological sequelae due to acute encephalopathy (NSAE-CPR), which previously identified the following three variables as predictive of poor outcomes: (1) refractory status epilepticus; (2) consciousness disturbance and/or hemiplegia at 6 hours from onset and (3) aspartate aminotransferase >90 IU/L within 6 hours of onset. DESIGN: Medical community-based multicentre retrospective cohort study. SETTING: Six regional hospitals in Harima and one tertiary centre in Kobe, Japan, from 2008 to 2012. PARTICIPANTS: We enrolled a total of 1612 patients aged <16 years who met the diagnostic criteria for an initial diagnosis of complex febrile seizure. Patients with a history of neurological disease and those included in the derivation cohort were excluded. PRIMARY OUTCOME MEASURES: Univariate and multivariate analyses were performed to determine the association between each of the three predictor variables and poor AE outcome (Pediatric Cerebral Performance Category score ≥2). Receiver operating characteristic curve (ROC) analysis was also performed to assess the screening performance of the NSAE-CPR. RESULTS: The ROC analysis identified at least one of the three predictive variables as an optimal cut-off point, with an area under the curve of 0.915 (95% CI 0.825 to 1.000). The sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios and Matthews correlation coefficient were 0.867, 0.954, 0.149, 0.999, 18.704, 0.140 and 0.349, respectively. CONCLUSIONS: Our findings indicate that the NSAE-CPR can be used for the screening and identification of patients with poor outcomes due to acute encephalopathy within 6 hours of onset.

Clinical features in very early-onset demyelinating disease with anti-MOG antibody.

BACKGROUND: The clinical features of patients with very early-onset acquired demyelinating syndrome (ADS) with the anti-myelin oligodendrocyte glycoprotein (MOG) antibody are unknown. We investigated the clinical characteristics and described detailed treatment of weekly intramuscular interferon ß-1a (IFNß-1a) in children aged <4years with ADS and the anti-MOG antibody. METHODS: We conducted a retrospective chart review of patients with anti-MOG positivity who were diagnosed as having multiple sclerosis (MS) at <4years of age. RESULTS: Subjects comprised 2 boys and 2 girls. Initial symptoms included ataxia, facial paresis, status epilepticus, and encephalopathy. Abnormal lesions on magnetic resonance imaging scans were often detected in the brainstem and cerebellum as well as the cerebrum. All patients started receiving IFNß-1a at age 3.1-3.5years. The initial doses ranged from 3 to 6µg, which were 1/10-1/5 doses, respectively, for adults. During 0.6-4.3years of IFNß-1a administration, all patients had flu-like symptoms, and 1 patient had an increased liver enzyme level. Although 1 patient discontinued IFNß-1a therapy because of frequent relapses, no patient discontinued therapy due to severe adverse events. CONCLUSIONS: This case series adds novel information regarding the clinical features of children <4years old with ADS and the anti-MOG antibody.

Thiamine-deficient encephalopathy due to excessive intake of isotonic drink or overstrict diet therapy in Japanese children.

AIM: To report on two children with encephalopathy caused by dietary thiamine deficiency due to newly developing nutritional problems in contemporary Japan. SUBJECTS: A 1-year-old boy who had consumed 1l of isotonic drinks per day for 4 months after an episode of diarrhea, and presented with ocular movement disorder, dystonia, and unconsciousness. The other subject was an 11-month-old boy who suffered from vomiting and somnolence; he and his mother had atopic dermatitis, and he had been on a low-allergen diet that strictly restricted intake of eggs, dairy products, meat, and fish since his early infancy. RESULTS: Both patients showed decreased blood thiamine levels and magnetic resonance imaging revealed striatal and thalamic lesions. Thiamine administration yielded prompt improvement of symptoms, but cavitiform lesions in the bilateral putamen persisted in the first patient, accompanied by residual generalized dystonia. Marked elevation of blood/cerebrospinal lactate levels and severe hyponatremia were present in this patient. CONCLUSION: Thiamine-deficient encephalopathy in Japanese children due to excessive intake of sports drink or overstrict diet therapy for atopic dermatitis has been increasingly reported during the last decade, but is still not broadly recognized. These children may visit hospitals due to persistent vomiting as a symptom of thiamine deficiency, but glucose infusion without thiamine supplementation can aggravate their condition. Knowledge of these facts in medical and public settings is necessary to correct the erroneous impression that nutritional options given to ill children are necessarily beneficial for health, and promote awareness that they can be harmful when consumed in excess.

Startle epilepsy associated with gait-induced seizures: Pathomechanism analysis using EEG, MEG, and PET studies.

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.

Genotyping of Mycobacterium leprae on the basis of the polymorphism of TTC repeats for analysis of leprosy transmission.

The polymorphism of TTC repeats in Mycobacterium leprae was examined using the bacilli obtained from residents in villages at North Maluku where M. leprae infections are highly endemic (as well as from patients at North Sulawesi of Indonesia) to elucidate the possible mode of leprosy transmission. TTC genotypes are stable for several generations of passages in nude mice footpads and, hence, are feasible for the genotyping of isolates and epidemiological analysis of leprosy transmission. It was found that bacilli with different TTC genotypes were distributed among residents at the same dwelling in villages in which leprosy is endemic and that some household contacts harbored bacilli with a different genotype from that harbored by the patient. Investigations of a father-and-son pair of patients indicated that infections of bacilli with 10 and 18 copies, respectively, had occurred. Genotypes of TTC repeats were found to differ between a son under treatment and two brothers. These results reveal the possibility that in addition to exposure via the presence of a leprosy patient with a multibacillary infection who was living with family members, there might have been some infectious sources to which the residents had been commonly exposed outside the dwellings. A limited discriminative capacity of the TTC polymorphism in the epidemiological analysis implies the need of searching other useful polymorphic loci for detailed subdivision of clinical isolates.