The clinical, biological, and radiological features of 8 episodes of herpes simplex encephalitis (HSE) relapse are reviewed from the Hopital Saint Vincent de Paul, Paris. Of 42 children diagnosed with HSE between 1990 and 1997, 6 (7 months to 13 years of age) were referred for relapse and were followed for at least 5 years. Relapses occurred from 5 days to 26 months after acyclovir treatment (30-60 mg/kg/day, initiated at 0-3days after onset and continued for 9-21 days). Two patients had 2 relapses. Clinical presentation of the relapses were of 2 types: bilateral choreoathetoid movements and fever in 2 presenting within one month following the initial HSE; and other neurologic symptoms with fever in 6. The cases of movement disorder had no CT evidence of basal ganglia disease, they failed to respond to acyclovir, and symptoms persisted for 1.5 to 3 months. The 6 with no athetosis showed new lesions on CT and MRI, and a marked clinical improvement occurred with acyclovir. CSF showed increased leukocytes in all relapses, protein was elevated (>0.4 g/L) in 4, and HSV PCR was negative in all samples. Cases with extrapyramidal symptoms most likely represent a postinfectious immuno-inflammatory mechanism, and no virus is isolated in those with reported brain biopsy. In cases without extrapyramidal symptoms, resumption of viral replication is suspected based on new MRI lesions, detection of CSF interferon and HSV antibody synthesis, and marked response to acyclovir. Relapse is related to initial acyclovir treatment for too-short duration and too-low a dose. A minimum of 15 days course of acyclovir in a dose of 45 mg/kg/day is recommended to prevent relapse. Some cases of relapse may be due to a familial HSV-specific immune deficiency and inherited susceptibility to HSV disease. [1]

COMMENT. These authors have recently reported on the limitations of early diagnosis of HS encephalitis in children (see Ped Neur Briefs June 2003;17:44-46) [2]. A negative HSV PCR when testing CSF samples at 0-3 days after onset of symptoms should not delay initiation of acyclovir therapy in suspected cases of HSE. A repeat lumbar puncture is advised after a few days, without interruption of therapy. The EEG may be superior to CT in early diagnosis of neonatal HSE. A normal CT or MRI and absence of fever may sometimes lead to misdiagnosis.

A case of atypical herpes type 2 encephalitis with normal MRI is reported in an immuno-compromised adult [3]. Treatment with acyclovir was started after a positive PCR for HSV type 2 was obtained on CSF. Recovery followed prolonged valaciclovir for several relapses.