I will introduce the key points to dispatch good clinical evidence. In the randomized trial, a clinical question should be transformed into P (patients), I (intervention), C (comparison), and O (outcome). You should decide parallel or crossover design and calculate its sample size. Then you should evaluate the effectiveness focusing the main outcome. To establish the clinical prediction model, you should form P (patients), E (exposure), M (mode), and O (outcome). After carrying out a cohort study or a case-control study, you should elucidate the dose-response relationship. Then, you should establish a prediction model selecting some variables. Finally, you should evaluate its performance and validity.

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[in Japanese]

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[in Japanese]

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[in Japanese]

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  Objective: We evaluated the effectiveness of synthetic adrenocorticotropic hormone (ACTH) therapy without tapering in treating patients with West syndrome. Methods: Forty-four patients with cryptogenic (n=7) or symptomatic (n=37) West syndrome were treated with synthetic ACTH therapy between 2003 and 2012. The synthetic ACTH dosage was 0.0125 mg/kg/day administered daily for 2 weeks and then stopped without a tapering period. The initial effectiveness, long-term seizure outcome, and adverse effects were examined. Results: During synthetic ACTH therapy, epileptic spasms disappeared in 37 of 44 patients (84.1%) and hypsarrhythmia on electroencephalography disappeared in 42 of 44 patients (95.5%). The average number of synthetic ACTH injections needed to achieve spasm control in these 37 patients was 5.8. Long-term seizure outcomes were assessed in 31 patients followed up for longer than half a year after synthetic ACTH therapy. Nine (29.0%) of these patients experienced recurrence of epileptic spasms, with a mean interval to recurrence of 2.4 months. Overall, 12 patients (38.7%) experienced various types of seizures other than spasms with a mean interval to recurrence of 8.0 months. Although adverse effects such as hypertension, infection, and mild brain shrinkage were noted in 13 patients (29.5%), no severe adverse effects were observed. Conclusions: These results are comparable to those of other reports on the initial effectiveness and long-term seizure control following synthetic ACTH therapy, and suggest that administration without tapering is reasonable to treat patients with West syndrome.

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  A 10-year-old boy developed bilateral optic neuritis and myelitis after a suspected viral infection and appendicitis. Magnetic resonance imaging (MRI) showed multiple lesions in both optic nerves, the optic chiasm, and the spinal cord. Several small lesions were also observed in the cerebellum and cerebral white matter. The serum tested negative for anti-aquaporin (AQP) -4 antibody and positive for anti-myelin oligodendrocyte glycoprotein (MOG) antibody. The diagnosis was neuromyelitis optica spectrum disorder (NMOSD). Two courses of high-dose methylprednisolone were administered ; however, only a small improvement in his visual acuity was achieved. He underwent 3 courses of plasma exchange to achieve sufficient visual acuity. After the serum anti-MOG antibody titer decreased to the cut-off level, oral prednisolone and azathioprine administration were also stopped, 10 months after onset. Recently, NMO and NMOSD cases positive for anti-MOG antibodies have been reported, which showed clinical features different from those of NMO cases positive for anti-AQP4 antibody. Although most of the reported cases responded to steroid therapy, plasma exchange was required in our case. Further analysis on larger numbers of cases is needed to establish treatments for anti-MOG antibody-positive NMO and NMOSD.

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  Enlarged parietal foramina (EPF) are rare congenital skull defects. These round or oval defects are situated on each parietal bone approximately 1 cm from the midline. Most patients with EPF have a positive family history. The condition is inherited as an autosomal dominant trait with relatively high, but not full, penetrance. Mutation in either MSX2 or ALX4 genes is associated with enlarged parietal foramina. Case 1 is a boy who was noticed to have a large anterior fontanelle, large posterior fontanelle, and widely opened sagittal suture at 2 months. During development, the anterior fontanelle and sagittal suture closed at 3 years and the posterior fontanelle subsequently divided into two foramina with ossification of the midline bridge by 4 years. The foramina were about 2.5×2.5 cm in diameter at 8 years. Case 2 is the 34-year-old mother of Case 1. She showed similar bone defects in her cranium, again about 2.5×2.5 cm in diameter. Neither patient showed any neurological symptoms. Genetic analysis revealed a mutation in the ALX4 gene in both patients, and magnetic resonance imaging showed a persistent falcine sinus and a hypoplastic straight sinus. Further evaluation revealed that the mother of Case 2 also had a mutation in the ALX4 gene, but no enlarged parietal foramina. Although high penetrance of this condition has been reported, this family suggests incomplete penetrance of this disorder.

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  Beta-propeller protein-associated neurodegeneration (BPAN) is one of the neurodegenerative disorders characterized by iron deposition in the brain and is the only known disease in humans to be caused by an aberration in autophagocytosis. Here, we present the case of a 42-year-old woman with BPAN identified by the WDR45 mutation. From early childhood, she was recognized as having global developmental delay, and she frequently sucked her hand, which was considered to be a stereotypical movement. She had a febrile convulsion at 6 months of age but there was no history of epilepsy. The delay in language development was more severe than the delay in motor development ; she was able to dress herself, walk unaided, and follow simple instructions until adolescence. After the age of 20, her movement ability rapidly declined. By the time she was 42 years old, she was bedridden and unable to communicate. Brain magnetic resonance imaging (MRI) at 21 years revealed no abnormality except non-specific cerebral atrophy. However, MRI at 39 years revealed abnormalities in the globus pallidus and substantia nigra, with neurodegeneration and iron accumulation in the brain. Genetic analysis for WDR45 revealed that she had a splice site mutation (NM_007075.3 : c.830+2T>C) which was previously reported, and a diagnosis of BPAN was confirmed. For specific therapies to be developed for BPAN in the future, it is necessary to establish early diagnosis, including genetic analysis.

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  The ability to visualize brain perfusion is important for identifying epileptic foci. We present three pediatric cases showing asymmetrical cerebral blood flow (CBF) distributions during the post-ictal phase of febrile status epilepticus measured by arterial spin labeling (ASL) perfusion MRI. During the acute phase, regional CBF measurements in the areas considered including epileptic foci were higher than in the corresponding area of the contralateral hemisphere, though the exact quantitative value varied between cases. We could not identify the correct epileptogenic foci, because those ASL images were taken after the prolonged and extraordinary activation of neurons in the affected area. During the recovery phase, the differences reduced and the average regional CBF measurement was 54.6±6.1 ml/100 g per minute, which was a little less than the number of previous ASL studies. ASL perfusion MRI imaging provides a method for evaluating regional CBF by using magnetically labeled arterial blood water as an endogenous tracer. With this technique, we can repeatedly evaluate both the brain structure and the level of perfusion at the same time. ASL is noninvasive and easily accessible, and therefore it could become a routine tool for assessment of perfusion in daily practice of pediatric neurology.

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