The clinical and radiologic features of nine infants with acute encephalopathy involving the frontal lobes are reported from Dokkyo University School of Medicine and Jichi Medical School, Tochigi; and University of Tokyo, Japan. The prenatal and perinatal histories were uneventful, and milestones of development were normal. Symptoms presented at 7 months to 3 years of age with 1) convulsive status epilepticus with hyperpyrexia and prolonged impairment of consciousness, 2) mental and motor regression after recovery of consciousness, 3) CSF leukocyte count of 8 cells/mm3, 4) MRI showing atrophy of both frontal lobes. The infection was influenza type A in 3 patients, exanthem subitum in 2, measles in 1, and upper respiratory viral illness nonspecified in 3. Regression of behavior on recovery of consciousness involved verbal function and language, stereotypic movements in 4, and cataplexy in 1. On 12-month follow-up, motor function recovered while speech remained retarded. Laboratory tests revealed increased lactate dehydrogenase and creatine kinase, normal CSF protein in all except one patient, and elevated interleukin-6 in 2 of 3 tested. EEG at time of onset showed high-amplitude delta predominantly in both frontal areas, and at 1 year, focal spikes or spike-and-wave discharge in 3 patients. One patient developed localization-related epilepsy. On serial MRI performed between the 20th and 42nd day from onset, atrophic changes were revealed in both frontal lobes of all patients. PET studies in the same period showed decreased perfusion in both frontal lobes, with normalized perfusion at the 7th to 38th month after onset. [1]

COMMENT. The differentiation of acute encephalopathy and complex febrile seizure (CFS) is often difficult, and the clinical presentation of all 9 infants with prolonged seizures and high fever highlights this controversy. Factors in favor of the diagnosis of CFS in the above series of patients include the type of infection causing the fever and seizure (influenza A, exanthem subitum, and nonspecific viral URI, all commonly associated with FS); and the elevation of interleukin-6 cytokines, previously reported in children with FS and with influenza encephalopathy [2, 3]. The role of the cytokine response to infection in relation to the mechanism of febrile seizures is discussed in subsequent correspondence [4]. A previous study negating an association of elevated cytokines and FS [5], cited by the authors of the current report, is now discounted.

The prolonged impairment of consciousness after the convulsions, and the behavioral sequelae are consistent with an encephalopathy. These cases are unique in the predilection for frontal lobe involvement, a finding that differentiates them from other acute encephalopathies of childhood, such as Reye syndrome and acute disseminated encephalomyelitis, but does not exclude a postictal pathology.

A rare case of acute necrotizing encephalopathy (ANE) associated with human herpesvirus-6 infection is reported from Sapporo, Japan [6]. A 14-month-old infant presented with high fever and generalized tonic convulsion followed by persistent coma, rash of exanthem subitum on the 4th day, brain swelling and herniation, the patient dying on the 12th day of the illness. CSF protein was 73 mg/dL, cell count 2, glucose 155 mg/dL. The MRI on the 3rd day revealed symmetric lesions in the thalamus, cerebellum, and brainstem, typical of ANE.

Cortical liquefaction is reported in a 9-month-old infant with severe HHV-6 encephalopathy [7]. MRI showing high signal intensity on T2-weighted images and low signal intensity on T1-weighted and FLAIR images in the cortex was consistent with liquefaction. Consciousness gradually improved, but the infant had severe retardation and quadriplegia.