The clinical, radiologic, and laboratory findings of 17 Asian patients with encephalopathy following a prolonged febrile seizure were reviewed retrospectively at Kameda Medical Center, and other centers in Japan and San Francisco, USA. Ages ranged from 10 months to 4 years (16 were 2 years or less). All patients presented with a febrile seizure lasting longer than 30 min, and longer than 1 hour in 12 patients. Twelve patients had continuous impaired consciousness, while 5 recovered consciousness completely and had no neurologic symptoms on the next day. Second seizures, clusters of complex partial seizures associated with impaired consciousness, occurred at 4 to 6 days after the initial seizure in 16 patients. Outcome was almost normal in 1 child, mild mental retardation (MR) in 3, and severe MR with paralysis and/or epilepsy in 11. Of 5 with rapid post-ictal recovery of consciousness, 3 had good outcomes, and 2 had moderate or severe MR.

Infectious agents identified in 10 patients were influenza A and B in 4, human herpes virus (HHV) 6 and 7 in 4, varicella zoster virus (1), and adenovirus (1). Analyses of CSF showed no pleocytosis and normal protein levels in the 17 patients, consistent with a diagnosis of encephalopathy. EEG showed slowing or epileptic discharges in 15 of 16 patients examined in the acute stage. MRIs obtained between 3 and 9 days after the initial prolonged seizure showed subcortical white matter lesions in all 17 patients, especially on diffusion-weighted MRI. Lesions were predominantly frontal or frontoparietal in location with sparing of the perirolandic region. Diffusion abnormalities disappeared between days 9 and 25, leaving cerebral atrophy after 2 weeks. Three patients with only frontal lesions had good outcomes. [1]

COMMENT. The authors describe an encephalopathy associated with a prolonged febrile seizure and generally resulting in a poor outcome. In 10 of 17 patients, the infectious agent was isolated from the throat, but neither viral PCR analysis of the CSF nor cytokine levels were recorded. The encephalopathy was similar to that described with influenza A [2, 3]. Some viruses (eg influenza A, HHV-6) particularly prone to cause encephalopathy or complex febrile seizures result in excessive systemic immune and cytokine reponses [4]. In febrile seizure patients CSF viral invasion is unusual, and the height of the fever has a more essential role in the febrile seizure mechanism than a specific viral neurotropism. Influenza-associated febrile seizure patients have significantly higher serum levels of pro-inflammatory cytokines than febrile patients without seizures [5]. Cytokine levels are useful indicators of the severity of the infection and the associated encephalopathy [6], and may help to distinguish the complex febrile seizure from an encephalopathy. Future research concerning the mechanism of encephalopathy complicating prolonged febrile seizures should include CSF viral PCR analysis, cytokine levels, and immune responses.