Clinical, laboratory, and radiographic findings in 14 cases (median age 10 years; range 4-14 yrs) of nonparaneoplastic limbic encephalitis were analyzed by researchers at the National Center of Neurology and Psychiatry, Kodaira, Japan. Infectious febrile illness preceded onset by 0-9 days in 12 patients. Seizure (n=10) was the most common initial symptom, consciousness was impaired in 5, and 3 presented with psychiatric symptoms. All patients developed impaired consciousness, short-term memory loss occurred in 12, and psychiatric symptoms were common (emotional lability (n=7), irritability (7), hallucinations (4), aggression (4)). Ten patients had all 3 signs of limbic encephalitis (short-term memory deficit, limbic seizures, and psychiatric symptoms). Other symptoms included movement disorders (4), and dysarthria (2). CSF showed mild to moderate pleocytosis in 8 patients, and elevated protein in 4. EEG showed slowing. MRI revealed signal abnormalities in hippocampal or amygdaloid formations in 9. Herpes simplex virus antibody or PCR was negative in all. Anti-voltage-gated potassium channel antibody was negative in one patient. Other autoantibodies associated with limbic encephalitis were not examined. Ten patients received immunomodulatory treatment (corticosteroids, iv immunoglobulin, and plasmapharesis), and 12 were given prophylactic acyclovir. Overall prognosis was favorable: 10 recovered with normal IQ; only one had severe cognitive impairment. Neurological sequelae included epilepsy in 5, psychiatric disorder (3), and memory impairment (3). [1]

COMMENT. The authors conclude that childhood limbic encephalitis differs from that in adults. Whereas initial symptoms in children are principally acute seizures and impaired consciousness, adults present with subacute memory impairment or psychiatric symptoms, and most cases of limbic encephalitis in adults are associated with neoplasm. Antecedent infection may cause limbic encephalitis in children through a secondary autoimmune response. This study was limited by the lack of autoantibody tests. Age related differences in symptoms of limbic encephalitis in children and adults will require investigation through immunological, including humeral and cellular immunity.

Temporal progression of non-paraneoplastic NMDA antibody encephalitis in adults, studied in 35 European patients, found 10 (8 female) aged 17-44 years (median 25.5 yrs) had two to four relapses within 3 months and 6 years following improvement after the initial episode. These patients had received minimal or no immunotherapy for the initial illness. Good clinical outcome correlated with decreased NMDA receptor antibody levels and were associated with early immunotherapies. Progression in relapse cases was in two stages, initial neuropsychiatric symptoms and seizures, followed later by onset of movement disorders, impaired consciousness and dysautonomia. Early features are associated with CSF lymphocytosis, and later features with appearance of oligoclonal bands. [2]