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Objective The current study aimed to identify and compare the clinical characteristics of human parechovirus type 3 (HPeV3)-associated acute encephalitis/encephalopathy (HPeV3E/E) between infants with abnormal brain magnetic resonance imaging (MRI) findings (typical, or MRI-positive HPeV3E/E) and those with MRI-negative findings (MRI-negative HPeV3E/E). Methods This is a retrospective study on patients with HPeV3 infection, and a two-step questionnaire survey performed on 837 hospitals in Japan between 2014 and 2016. Results We identified 240 infants with HPeV3 infection, of which 34 had been clinically-diagnosed HPeV3E/E (cHPeV3E/E). However, detailed clinical data were provided by 32 of the 34 patients. Among these 32, 23 had undergone MRI and were categorized into two groups, MRI-positive (n = 17) and -negative (n = 6). There were no significant intergroup differences in clinical lab results or symptoms, except for gastrointestinal symptoms that were only present in the MRI-negative patients. The MRI-positive group showed white matter involvement on brain MRI during the acute phase, and 8 patients presented with lesions on follow-up MRI. Furthermore, 4 (50%) of the 8 patients had neurological sequelae. Conclusion Clinical characteristics of cHPeV3E/E patients with and without lesions on brain MRI showed no significant differences. Therefore, considering the difficulty in distinguishing febrile infants with cHPeV3E/E from those with a sepsis-like illness, during an HPeV3 infection epidemic, it is imperative to frequently perform brain MRI in febrile infants presenting with severe disease for the early diagnosis of HPeV3E/E presenting with brain lesions.

Epileptic encephalopathy, which commences during early infancy, is a severe epileptic syndrome that manifests as age-dependent seizures and severe developmental delay. The syntaxin-binding protein 1 gene (STXBP1) is one of the genes responsible for epileptic encephalopathy. We conducted a cohort study to analyze STXBP1 in 42 patients with epileptic encephalopathy. We identified four novel mutations: two splicing mutations, a frameshift mutation, and a nonsense mutation. All of these mutations were predicted to cause loss-of-function. This result suggests loss-of-function is a common mechanism underlying STXBP1-related epileptic encephalopathy. The four patients showed epileptic features consistent with STXBP1-related epileptic encephalopathy, but showed variable radiological findings, including brain volume loss and myelination delay.

Patients with epilepsy after encephalitis/encephalopathy (EAE) often have refractory seizures, resulting in polytherapy with the risk of adverse reactions due to anti-epileptic drugs (AEDs). We focused on the characteristics of cutaneous adverse reaction (CAR). In this retrospective study, the medical records of 67 patients who were diagnosed as having EAE in our hospital were reviewed and the clinical characteristics were analyzed. Immunological biomarkers including cytokines, chemokines, granzyme B, soluble tumor necrosis factor receptor 1 (s-TNFR 1), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were measured in 22 patients. CARs attributed to AEDs were observed in 16 of 67 EAE patients (23.9%) (CAR group). High CAR rates were observed with phenytoin, lamotrigine, phenobarbital, and carbamazepine. Severe CARs were found in three of 67 patients (4.5%). The frequencies of CARs were significantly higher in patients with encephalitis onset older than five years of age. CAR occurred only in patients who had onset of EAE within 6 months after encephalitis. The durations from acute encephalitis to CARs were within one year for almost all AEDs, except lamotrigine. The proportion of patients with serumregulated on activation normal T cell expressed and secreted (RANTES) levels higher than the upper limit of normal range was significantly higher in CAR group than in non-CAR group. Patients in the early stage of EAE and patients with encephalitis onset older than five years of age may be at higher risk of CARs to AEDs, especially to phenytoin, lamotrigine, phenobarbital, and carbamazepine. RANTES may be a biomarker for susceptibility to CARs in EAE patients.