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Febrile infection-related epilepsy syndrome (FIRES), or acute encephalitis with refractory, repetitive partial seizures (AERRPS), is an epileptic encephalopathy beginning with fever-mediated seizures. The etiology remains unclear. To elucidate the genetic background of FIRES/AERRPS (hereafter FIRES), we recruited 19 Japanese patients, genotyped polymorphisms of the IL1B , IL6 , IL10 , TNFA , IL1RN , SCN1A and SCN2A genes, and compared their frequency between the patients and controls. For IL1RN , the frequency of a variable number of tandem repeat (VNTR) allele, RN2, was significantly higher in the patients than in controls ( p =0.0067), and A allele at rs4251981 in 5′ upstream of IL1RN with borderline significance (p =0.015). Haplotype containing RN2 was associated with an increased risk of FIRES (OR 3.88, 95%CI 1.40–10.8, p =0.0057). For SCN1A , no polymorphisms showed a significant association, whereas a missense mutation, R1575C, was found in two patients. For SCN2A , the minor allele frequency of G allele at rs1864885 was higher in patients with borderline significance ( p =0.011). We demonstrated the association of IL1RN haplotype containing RN2 with FIRES, and showed a possible association of IL1RN rs4251981 G>A and SCN2A rs1864885 A>G, in Japanese patients. These preliminary findings suggest the involvement of multiple genetic factors in FIRES, which needs to be confirmed by future studies in a larger number of FIRES cases.

Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) at onset manifests an early seizure (ES) usually lasting more than 30 min. Following ES, some patients exhibit almost clear consciousness with no neurological symptoms, and no MRI abnormality for a few days, which may lead to an initial misdiagnosis of prolonged febrile seizures (PFS). To allow an early diagnosis of AESD, we retrospectively analyzed clinical manifestations, laboratory data, and radiologic and EEG findings in patients with AESD (n=62) having ES of over 30 min, and ones with PFS (n=54), using logistic regression analyses. Multivariate logistic regression analysis revealed that an age below 1.5 years and a Glasgow Coma Scale score of 14 or less than 14 (Japan Coma Scale score of 1 or higher) were high risk factors of developing AESD. We proposed an AESD prediction score system consisting of consciousness level, age, duration of convulsions, enforcement of mechanical intubation, and aspartate aminotransferase, blood glucose and creatinine levels (full score: 9), the mean scores in AESD and PFS being 5.9 and 1.8, which were significantly different (p

We retrospectively collected three patients with clinically mild encephalitis with a reversible splenial lesion (MERS) after mumps vaccination, and reviewed five patients, including two patients previously reported. The five patients (all males, aged 1 to 9) presented with fever, vomiting, or headache as the initial symptoms (day 0), suggesting meningitis, at 13 to 21 days after mumps vaccination. Consciousness disturbance, delirious behavior, seizures, or dysarthria was observed on days 1 to 3, which had completely resolved before day 11. Hyponatremia was observed in all patients. A cerebrospinal fluid study showed pleocytosis, and confirmed the vaccine strain genome. MRI revealed reduced diffusion in the splenium of the corpus callosum on days 2 to 4, which had completely disappeared on the follow-up studies performed on days 7-15. EEG showed high voltage slow wave in three patients, which later normalized. These findings led to a diagnosis of MERS after mumps vaccination. MERS after mumps vaccination may be more common than previously considered. MERS is suspected when a male patient after mumps vaccination presents with neurological symptoms with hyponatremia, following symptoms of aseptic meningitis, and MRI would be performed to examine the splenium of the corpus callosum.

We describe a 12-year-old girl, who had been medicated with theophylline for bronchial asthma and developed acute encephalopathy with refractory status epilepticus, showing bilateral mesial temporal and claustral lesions, which were evident on fluid-attenuated inversion recovery images, obtained with 1.5 T magnetic resonance imaging. To date, oxidative stress has been implicated in aging or various disorders, including inflammatory or degenerative neurological disorders. One of the oxidative stress markers, 8-hydroxydeoxyguanosine, was increased in our patient's cerebro-spinal fluid, plasma and urine. We speculate that augmented oxidative stress was associated with refractory status epilepticus in our patient, accompanying bilateral mesial temporal, claustral lesions and severe neuronal damage. Serial measurements of oxidative stress markers in acute encephalitis, encephalopathy, or status epilepticus could clarify the relationships between acute brain damage and free radicals.

We report on a family with dominantly inherited asymptomatic Alexander's disease due to a novel Glial fibrillary acidic protein (GFAP) mutation. The proband, a 16-month-old boy, presented with megalocephaly and brain magnetic resonance imaging (MRI) showing the typical findings of Alexander's disease. Molecular analysis showed that he was a heterozygote of the L331P mutation of GFAP. His mother and sister, without megalocephaly or other neurological abnormalities, were also heterozygotes of the mutation and their brain magnetic resonance imaging showed mild changes in the caudates and deep frontal white matters. These results suggest the existence of a forme fruste of Alexander's disease. The L331P mutation may be associated with the mild phenotype of Alexander's disease. To elucidate the genotype-phenotype correlation in Alexander's disease, molecular diagnosis and MRI examination are required for many patients and their families.