Clinical characteristics and outcome of 29 children (19 male; 10 female) with acute encephalitis with refractory, repetitive partial seizures (AERRPS) were analyzed in a retrospective, multicenter nationwide questionnaire-based study in Japan. Age of disease onset ranged from 1 to 14 years (6.8 +/- 4.0). Four had a history of febrile seizures but none had preceding neurologic abnormalities. The acute phase characterized by persistent fever (>39C) and persistent seizures ranged from 15 to 312 days. Seizures were partial and repetitive, and consisted of eye deviation or facial twitching. They were refractory to conventional anticonvulsants and were suppressed by high-dose IV barbiturate. Impairment of consciousness was common. Pre-treatment EEGs in the first 14 days of illness showed high voltage slowing and in later stages, interictal epileptiform discharges. Ictal discharges were periodically repeated every 5-10 min. Early MRI, within 7 days of onset, showed mild brain edema in 2 of 14 cases, and later, 6 showed hippocampal or amygdaloid hyperintensities on FLAIR, without development of epileptic foci. Serial MRI revealed diffuse brain atrophy after a month or more. Laboratory studies showed high serum ferritin (221-2370 mg/dl) in 4/4 and positive anti-GluRe2 antibodies in 6/9 blood and CSF specimens. Other CSF abnormalities included pleocytosis in 19/29, high protein in 5/29, and high neopterin in 4/4. IV methylprednisolone in 12 was effective only in 2; IV immunoglobulin was ineffective in all 13 patients treated. Follow-up ranged from 8-194 months (mean 60.9 months), and outcome was uniformly poor. All had residual epilepsy without a latent period, and the majority had cognitive impairment. WISC scores were <70 in 16 and <20 in 10 patients. All with GluRe2 antibodies were cognitively impaired. Other neurologic deficits included memory impairment, autistic tendency, hyperkinesis, learning disability, and emotional instability, each occurring in 15-22% cases. One patient died of unknown cause at 9 year after onset. 
COMMENT. AERRPS differs from most types of childhood encephalitis with post-encephalitic epilepsy in that intractable partial seizures develop without a latent period between the acute febrile phase and the onset of epilepsy. Awaya Y and Fukuyama Y (1986) first described this unusual form of encephalitis and post-encephalitic epilepsy in 5 cases. More than 30 cases have now been reported in Japan (Awaya et al. 2007). Similar cases have also been reported worldwide. The cause is unknown but an autoimmune process related to anti-GluRe2 antibodies may be contributory.