Nationwide survey of childhood Guillain-Barré syndrome, Fisher syndrome, and Bickerstaff brainstem encephalitis in Japan.

OBJECTIVE: Guillain-Barré syndrome (GBS), Fisher syndrome (FS), and Bickerstaff brainstem encephalitis (BBE) are immune-mediated neuropathies presenting with symptoms such as weakness, ophthalmoplegia, ataxia, and consciousness disturbances. Although the epidemiology of GBS and BBE in patients of all ages has been reported, childhood data have not been well-investigated. We aimed to determine the clinical features, therapeutics, and prognoses of childhood GBS, FS, and BBE in Japan. METHODS: We sent questionnaires to 1068 pediatric neurologists in Japan from 2014 to 2016 to determine the number of children less than 15 years old with GBS, FS, or BBE and their age and sex. We subsequently performed a secondary survey to investigate the clinical features, laboratory data, treatment, and prognosis. RESULTS: Five-hundred thirty-eight pediatric neurology specialists (50.4%) responded to the first survey. The total number of children with GBS, FS, and BBE in Japan from 2014 to 2016 were 87, 10, and 6, respectively. GBS was classified as acute inflammatory demyelinating neuropathy (35.6%), acute motor axonal neuropathy (20.7%), or acute motor-sensory axonal neuropathy (10.3%), with a male-to-female ratio of 1.29:1.0 and a wide distribution of onset ages. The disease severities of GBS, FS, and BBE were variable, but all children could walk within one year. CONCLUSION: The prognoses of childhood GBS, FS, and BBE were generally favorable, as long as the patient was promptly treated with either intravenous immunoglobulin or plasma exchange.

Inflammatory features in sporadic late-onset nemaline myopathy are independent from monoclonal gammopathy.

Sporadic late-onset nemaline myopathy (SLONM) is a rare adult-onset non-hereditary disease with subacute proximal muscle and often axial muscle weakness, characterized by the presence of nemaline bodies in skeletal muscle biopsies. Considering its association with concurrent monoclonal gammopathy of undetermined significance (MGUS), the disease is classified into two major subtypes (1) SLONM without MGUS (SLONM-noMGUS) and (2) with MGUS (SLONM-MGUS) association. SLONM associated with HIV infection (SLONM-HIV) is also reported. SLONM-MGUS has been shown to be associated with poorer prognosis and required aggressive treatment including high-dose melphalan and autologous stem cell transplantation. The approach is currently debatable as recent reports suggested effectiveness of intravenous immunoglobulin as initial treatment with indifference of overall survival despite the presence of MGUS. Our study aimed to find an underlying basis by review of pathological features in 49 muscle biopsy proven-SLONM from two large tertiary centers in Japan and Germany (n = 49: SLONM-noMGUS = 34, SLONM-MGUS = 13, SLONM-HIV = 2). We compared pathological findings in SLONM-noMGUS and SLONM-MGUS and focused on the presence of any detectable inflammatory features by immunohistochemistry. The clinical and histological features in SLONM-noMGUS and SLONM-MGUS were not distinctively different except for more common regenerating fibers (>5% of myofibers) present in SLONM-MGUS (p < 0.01). HLA-ABC expression and fine granular p62 were observed in 66.7% and 78.3% of SLONM, respectively. The predominant inflammatory cells were CD68+ cells. The inflammatory cells showed positive correlations with the percentage of nemaline-containing fibers (p < 0.001). In conclusion, inflammatory features are present although rather mild in SLONM. This finding contributes to the hypothesis of an acquired inflammatory disease pathogenesis and opens the possibility to offer immunotherapy in SLONM with inflammatory features regardless of the monoclonal gammopathy status.

Longitudinal magnetic resonance imaging changes in Japanese encephalitis.

BACKGROUND: Japanese encephalitis is a flavivirus that can cause pandemic encephalitis, and is prevalent in Southeast Asia and Australia. Brain images of patients with Japanese encephalitis are characterized by thalamic lesions, distinct from those seen in viral encephalopathies caused by the herpes simplex virus and West Nile virus. AIM: Herein, we describe for the first time a time-dependent magnetic resonance imaging pattern in Japanese encephalitis in a 10-month-old Japanese boy. CASE: The patient was a previously healthy 10-month-old Japanese boy, who exhibited acute-onset flaccid tetraplegia and loss of tendon reflexes. RESULTS: Brain MRI showed characteristic thalamic changes on diffusion weighted images from spotty to uniform and from the left to the right side, associated with low apparent diffusion coefficient maps. These images suggest that the Japanese encephalitis virus may first affect the unilateral thalamus, possibly expanding to the other side, with characteristic patterns changing from spotty to uniform in a manner consistent with the presentation of cytotoxic edema. CONCLUSION: This report first showed longitudinal magnetic resonance changes in Japanese encephalitis, which may help in accurate diagnosis and in discrimination from other etiologies.

A Nationwide Survey of Pediatric-onset Japanese Encephalitis in Japan.

BACKGROUND: Japanese encephalitis (JE) is the leading cause of viral encephalitis with high mortality and morbidity in Asia. In Japan, however, the active recommendation of JE vaccine was retracted in 2005 because of the potential risk of acute disseminated encephalomyelitis. We aimed to determine the recent incidence of childhood-onset JE after the domestic change of vaccination policy in Japan, and to analyze the clinical features of affected children. METHODS: A retrospective nationwide survey was conducted for pediatric patients with JE in Japan from 1995 to 2015. The national surveillance system was used to identify the pediatric patients with JE. Follow-up questionnaires were sent to analyze their clinical and neuroimaging profiles. RESULTS: Among a total of 109 patients registered to the national surveillance, 10 (9%) were less than age 15 years. The annual incidence rate of childhood-onset JE was higher during 2005-15 than that during 1995-2004 (4.3 × 10-3 vs 1.1 × 10-3 per 100000, respectively; P = .04). Endemic regions overlapped with prefectures that farmed pigs harboring antibodies against JE virus with high prevalence. Detailed clinical data were collected from 9 patients. None of them died, but 5 of 9 patients (56%) had neurological sequelae after recovery. One patient who was partially vaccinated with 2 doses of JE vaccine fully recovered from a coma. The age of 3 years or less was associated with unfavorable neurological prognosis. CONCLUSIONS: Our data provide evidence for the importance and prophylactic effect of the JE vaccine in young children in the endemic area.

Clinical features of children with nontyphoidal Salmonella bacteremia: A single institution survey in rural Japan.

Nontyphoidal Salmonella (NTS) can cause bacterial enterocolitis. Although some children with NTS infection develop bacteremia, its clinical manifestations have not been discussed adequately. Therefore, we examined children with NTS bacteremia. We retrospectively examined the medical records of 15 patients aged less than 15 years. Salmonella spp. were detected in the blood cultures of these patients between 1991 and 2014. We divided an additional sample group of 34 patients diagnosed with an NTS infection between 2005 and 2014, into 2 groups. Group bacteremia (B) included patients in whose blood cultures Salmonella spp. were detected, and group non-bacteremia (NB) included patients in whom Salmonella infection was not detected. We compared each group using Wilcoxon test and Fisher's exact test. The number of patients with fever, diarrhea, or abdominal pain was 15 (100%), 13 (87%), and 9 (60%), respectively, in the first sample of patients. However, vomiting and bloody stool were observed in only 5 patients (33%). More than 70% of patients exhibited a reduced white blood cell count, while C-reactive protein levels were variable in the patients. Salmonella spp. were detected via stool culture in 10 patients (67%). Diarrhea persisted for more than 4 days more frequently in group B than group NB (p = 0.004). The number of patients whose fever persisted for more than 4 days was significantly higher in group B than group NB (p = 0.030). Therefore, if NTS bacteremia is suspected, blood cultures should be collected and antibiotics should be initiated in cases with diarrhea or fever for more than 4 days. Furthermore, a negative stool culture result does not preclude the possibility of NTS bacteremia.

[Group B streptococcal bacteremia in a 10-year-old girl undergoing corticosteroid therapy].

Group B streptococcus (GBS), a major cause of neonate and pediatric sepsis and meningitis, rarely causes invasive infection beyond infancy. We report the case of a 10-year-old girl developing GBS bacteremia during corticosteroid therapy for chronic idiopathic thrombocytopenic purpura. Brought to the emergency room due to sudden high fever and abdominal pain, she was in compensated shock. White blood cell count was 19,600/mm3 and C-reactive protein 0.18 mg/dL. She was diagnosed with sepsis and admitted for evaluation. Cefotaxime (100 mg/kg/day) administration and fluid replacement were begun immediately after blood culture. Her condition improved over the next 6 hours and she was afebrile by the next day. GBS isolated from blood had a serotype of Ib. Based on routine susceptibility testing, this strain was susceptible to penicillin, cephem, carbapenem, erythromycin, clindamycin, and vancomycin, but resistant to quinolone, including levofloxacin (MIC > or = 8.0 microg/mL) and gatifloxacin (MIC > or = 4.0 microg/mL). She was discharged on hospital day 8. This is, to our knowledge, the first report of pediatric meningitis-free GBS bacteremia in Japan. Physicians should therefore be aware of the possibility of invasive GBS infection such as bacteremia in this age group, especially during immunosuppressive therapy, because epidemiological studies in the US have showed significant mortality in those aged 1 to 14 years old with invasive GBS.