Breastfeeding and risk of febrile seizures in the first 3 years of life: The Japan Environment and Children's Study.

OBJECTIVE: Our study was conducted to examine the association between breastfeeding and febrile seizures (FS) in the first 3 years of life. METHODS: We analyzed the dataset of the Japan Environment and Children's Study (JECS), which is a birth cohort study undertaken to elucidate the influence of environmental factors on children's health during the fetal period and early childhood. Information on feeding duration and feeding pattern, as well as information on febrile seizures, were obtained from questionnaires sent to mothers/caregivers. We categorized a child as having experienced FS if the child was reported as having been diagnosed with FS in the first 3 years. Modified Poisson regression with a robust error variance was used to estimate the effect of duration of breastfeeding and the risk of FS. RESULTS: Of the 84,321 children included in the analysis, 6264 (7.4%) were reported to have experienced FS at least once in the first 3 years of life. Multivariate analyses showed that the risk of FS during the first 3 years of life tended to decrease as the duration of breastfeeding increased. Male sex and frequent fever episodes were also associated with an increased risk of FS. CONCLUSIONS: Continued breastfeeding until 2 years of age, the most susceptible age for FS, had a small but protective effect on FS.

[A case of persistent cerebellar ataxia complicated by conversion disorder--confirmed by positive cerebrospinal fluid glutamate receptor delta2 and epsilon2 antibodies].

We recently encountered a 13-year-old girl who developed persistent cerebellar symptoms one month after mixed measles/rubella vaccination, making it difficult to distinguish this condition from conversion disorders. Severe truncal ataxia was the initial manifestation in this case. The patient had no abnormalities in objective tests but began to show extraordinary circadian variations in certain parameters. Her cerebellar symptoms were thus considered to possibly be associated with conversion disorders. Later, she tested positive for cerebrospinal fluid anti-glutamic acid receptor (GluR) delta2 antibody. The lymphocyte stimulation test yielded a positive reaction to GluRdelta2 antigen. In addition, in the chronic stage SPECT revealed reduced cerebellar blood flow. She was thus diagnosed as having persistent cerebellar ataxia due to autoimmune mechanisms and modification of cerebellar symptoms due to secondary conversion disorders. Our experience with this case suggests that checking cerebrospinal fluid for anti-GluRdelta2 antibody is possibly useful for distinguishing between conversion disorders and cerebellar ataxia due to autoimmune mechanisms.

Breastfeeding and risk of febrile seizures in infants: The Japan Environment and Children's Study.

OBJECTIVE: Our study was conducted to examine the association between breastfeeding and febrile seizures (FS) in the first year of life. METHODS: We used data from a birth cohort study, the Japan Environment and Children's Study (JECS). In a self-administered questionnaire, we asked participants the duration of breastfeeding and whether their children were diagnosed as having FS during their first 12 months. We estimated the association of duration and exclusiveness of breastfeeding with the FS by using multiple logistic regression analysis. RESULTS: Of 84,082 children, 995 (1.2%) were diagnosed as having FS by the age of 12 months. The prevalence of FS was higher in children who were breastfed for shorter duration. Multiple logistic regression analysis showed that, compared with children breastfed for less than 1 month, those breastfed for 4-6 months and 7-12 months had lower risks of FS (adjusted odds ratio [aOR], 0.65 [95% confidence interval {CI}, 0.42-0.99]; aOR, 0.66 [95% CI: 0.45-0.96], respectively). Moreover, compared with infants who received both breast milk and formula milk for 6 months, infants who were breastfed exclusively for 6 months had lower risk of FS (aOR: 0.78 [95% CI: 0.64-0.95]). CONCLUSIONS: Our results suggest that breastfeeding has a protective effect against FS in the first year of life.

Incidence of infantile spinal muscular atrophy on Shikoku Island of Japan.

BACKGROUND: Spinal muscular atrophy (SMA) is an autosomal recessive disorder caused by homozygous mutations in the SMN1 gene. SMA has long been known to be the most common genetic cause of infant mortality. However, there have been no reports on the epidemiology of infantile SMA (types 1 and 2) based on genetic testing in Japan. In this study, we estimated the incidence of infantile SMA on Shikoku Island, which is a main island of Japan and consists of four prefectures: Ehime, Kagawa, Tokushima and Kochi. METHODS: A questionnaire was sent to 91 hospitals on Shikoku Island to investigate the number of SMA infants born from 2011 to 2015. A second questionnaire was then sent to confirm the diagnoses of SMA based on clinical and genetic features. RESULTS: Responses were received from all of the hospitals, and four patients were diagnosed with infantile SMA among 147,950 live births. We estimated the incidence of infantile SMA patients as 2.7 per 100,000 live births (95% confidence interval, 0.1-5.4). A comparison of the four prefectures indicated that the incidence of infantile SMA was significantly higher in Ehime Prefecture than in the other three prefectures; 5.6 per 100,000 live births (95% confidence interval, -0.7 to 11.9) in Ehime Prefecture and 1.1 per 100,000 live births (95% confidence interval, -1.0 to 3.1) in the other prefectures. CONCLUSION: We estimated the incidence of infantile SMA in an isolated area of Japan. For more precise determination of the incidence of infantile SMA, further studies that include neonatal screening will be needed.

Long-Term Evaluation of Low-Dose Betamethasone for Ataxia Telangiectasia.

BACKGROUND: Ataxia telangiectasia is an autosomal recessive disorder characterized by cerebellar ataxia, telangiectases, immune defects, and a predisposition to malignancy. Quality of life is severely impaired by neurological symptoms. However, curative options for the neurological symptoms are limited. Recent studies have demonstrated short-term improvement in neurological symptoms with betamethasone therapy. However, the long-term and adverse effects of betamethasone are unclear. The aim of this study was to evaluate the long-term effects, benefits, and adverse effects of low-dose betamethasone in ataxia telangiectasia. METHODS: Six patients with ataxia telangiectasia received betamethasone at 0.02 mg/kg/day for two years. After cessation of betamethasone, the patients were observed for two additional years. Neurological assessments were performed, and adverse effects were monitored every three months throughout the four-year study period. RESULTS: Transient improvement of neurological symptom was observed in five of the six patients. However, after two years betamethasone treatment, only one of the six patients showed a slight improvement in the neurological score, one patient showed no change, and the neurological scores of the remaining four patients deteriorated. After the cessation of betamethasone treatment, neurological symptoms worsened in all patients. As an adverse effect of betamethasone, transient adrenal dysfunction was observed in all cases. CONCLUSIONS: Although these findings are in agreement with previous studies suggesting that short-term betamethasone treatment transiently benefits patients with ataxia telangiectasia, the long-term benefits and risks should be carefully considered.

Diffusion-weighted MRI for early diagnosis of neonatal herpes simplex encephalitis.

AIM: To determine the early changes and evolutions of brain diffusion-weighted imaging (DWI), and analyze prognostic factors of the early changes among patients with neonatal herpes simplex encephalitis (NHSE). METHOD: We selected patients who developed encephalitis by 28 d after birth; had herpes simplex infection; and who underwent magnetic resonance imaging, including DWI, ⩽7 d of symptom onset. Thirty-two DWI scans between 0 and 28 d after onset in 13 patients and the clinical data were recruited. The distribution, evolution of the lesions, and neurological outcome were analyzed. RESULTS: DWI frequently showed multiple cortical lesions in both hemispheres in the early period and both hemispheres on DWI (8/9 scans at ⩽48 h, 7/7 patients). As time from onset increased, the cortical lesions tended to coincide with subcortical white matter lesions beneath the initial cortical lesions (p<0.01). Lesions from the cortex extended to the subcortical white matter in 7 patients. Deep cerebral lesions, involving basal ganglia, internal capsules, thalamus, were also found in 9 patients ⩽7 d of onset. The distributions of deep cerebral lesions (none/unilateral/bilateral) ⩽7 d of onset showed significant correlations with neurological prognoses (gross motor functions: p<0.01; developmental or intellectual quotient scores: p<0.01). INTERPRETATION: Cortical lesions were main findings of DWI in NHSE in the early period. Bilateral deep cerebral lesions ⩽7 d were highly indicative of poor motor and cognitive outcomes.

Neutrophil infiltration and oxidant-production in human atherosclerotic carotid plaques.

To clarify the clinical implications of neutrophils in vulnerable plaques we evaluated the function and activity of infiltrated neutrophils in an atherosclerotic plaque, focusing on oxidant production. A histopathological investigation was performed using carotid arterial samples obtained from seven patients. The atherosclerotic plaques were examined cytochemically for naphthol-ASD-chloroacetate esterase activity and oxidant-production, and immunohistochemically using N-formyl peptide receptor-like 1 (fPRL1)-, CD66b-, CD68- or p22phox-specific antibodies. The cytoplasmic fPRL1 intensity value of the neutrophils in the plaque was estimated using an activity index. Naphthol-ASD-chloroacetate esterase activity was found in cells located in the atherosclerotic plaque, indicating that the cells were neutrophils. The cytoplasmic fPRL1 intensity value of the neutrophils in the plaque decreased to approximately 60% of the intensity observed in the capillary vessels. Oxidant-production was also detected in the plaques, and both neutrophils and macrophages were observed at the corresponding oxidant-production sites. p22phox expression was also located in the same areas in which oxidant-production was observed in these plaques. We could not directly evaluate how much ROS generated from the infiltrated neutrophils contributed the plaque vulnerability followed by its rupture. However, the infiltrated neutrophils in the atherosclerotic plaques morphologically appeared activated and were actively generating oxidant, implying that neutrophils, together with macrophages, infiltrate into atherosclerotic plaques and contribute to plaque vulnerability.

Pediatric Hirayama disease.

We report on a 16-year-old girl with muscular atrophy of a distal upper extremity (Hirayama disease). The disease progressed insidiously, and during our first examination, she exhibited weakness and wasting in the right hand, accompanied by cold paresis. No sensory disturbance was evident. A nerve conduction test revealed reduced compound muscle action potential of the ulnar and median nerves of the affected hand. However, conduction velocities were normal. An F-wave test of the right ulnar nerve indicated reduced frequency and prolonged minimum latency. Magnetic resonance imaging of the cervical spinal cord demonstrated abnormal signal intensity in the anterior horn, atrophy in the lower cervical cord, a forward shift of the lower cervical cord upon neck flexion, and flow voids in the epidural space. These clinical findings are typical of Hirayama disease. The use of a cervical collar did improve the patient's hand strength after 2 years. Pediatric neurologists should be aware of this disease, particularly in its early course, to diagnose it early, and to introduce a neck cervical collar as soon as possible after diagnosis.