Records of 38 patients, 23 boys and 15 girls (ages 3 months to 16 years [42% ages 3-12 months]), seen between 1990 and 1997 with proven herpes simplex encephalitis (HSE), were reviewed retrospectively to determine the diagnostic reliability of polymerase chain reaction (PCR) results, in a study at the Neuropediatric Service, Hopital Saint Vincent de Paul, Paris, France. Neonatal and adult cases were excluded. The delay between the onset of symptoms and the initiation of treatment and the dose and duration of antiviral treatment were recorded. Patients were divided in 2 groups, according to their PCR results. Nasopharyngeal infections were recorded 1-10 days before the onset of encephalitis in 18 cases (47%). Clinical symptoms of HSE varied with age: Of 24 patients aged <3 years, 19 (79%) had partial febrile seizures, and 1 had a generalized febrile seizure; in 14 patients aged >5 years, febrile seizures occurred at onset in only 5 (36%). Seizures were associated with an altered state of consciousness in approximately 60%, and the others had meningeal irritation, altered behavior, or speech disorders. IV acyclovir was administered for 10-30 days, in a dosage of 30-70 mg/kg/day. The mean delay between the start of acyclovir and the first reported neurological symptoms was 1.5 days.
EEGs recorded in 29 children (76%) were obtained between days 0 and 1 in 80% of cases. EEG abnormalities present in 100% consisted of diffuse slow waves in 9 (31%) and focal slow waves in 20 (69%), of whom 11 were focal temporal and 7 had periodic discharges. Necrotic hemorrhagic brain lesions on CT scan or MRI, observed in 26 (84%) of 31 patients examined, were temporal in location in 12, parietal in 6, and temporoparietal in 4.
HSV PCR performed on CSF (mean, 2.2 samples per patient) obtained between day 0 and 3 in 33 patients was positive in at least 1 CSF sample in 28 (85%). HSV was detected in the first CSF specimen from only 25 (76%) of 33 patients. Initial negative PCR results observed in 8 patients drawn before day 3 were significantly associated with a low level of protein and <10 leucocytes/mm3 in CSF. PCR performed after day 3 in 9 of 33 patients was positive in 5 samples drawn on days 4-21 and negative in 4 drawn on days 8-25. The CSF protein was elevated (>0.50 g/L) in 13 (40%) of 33 patients, reaching 0.71 g/L in 20 PCR-positive samples; it was significantly lower (P=.0007) when PCR was negative. WBC in the CSF was elevated (>5 cells/mm3) in 28 (88%) patients, with a mean count of 229/mm3 in 24 PCR-positive samples; it was significantly lower (P=.0011) when PCR was negative. A diagnosis of primary HSE based on seroconversion was established in 6 of 32 patients tested. HSE secondary to reactivation or reinfection was diagnosed in 16 cases with HSV-specific IgG found at onset of symptoms.
A negative PCR in a child with clinical, EEG, and/or radiological findings suggestive of encephalitis should not delay administration of acyclovir and should not lead to interruption of therapy. Antiviral therapy should be administered as long as the diagnosis has not been excluded. 
COMMENT. Herpes simplex virus encephalitis (HSE) results from primary or recurrent infection and in infants beyond the neonatal period and children, HSE is manifested by fever, alterations in consciousness, and seizures (AAP Red Book 2000, 25th ed). Unusual CNS manifestations of HSV include Bell’s palsy, trigeminal neuralgia, myelitis, and postinfectious encephalomyelitis. The prognosis of HSE is significantly improved by IV acyclovir treatment, provided that therapy is begun early. Since its development in 1991, PCR for HSV DNA performed on CSF is widely accepted for the early diagnosis of HSE . Antiviral acyclovir is recommended immediately after CSF sampling when a diagnosis of HSE is suspected. A negative HSV PCR in 25% of cases when testing CSF at 0-3 days after onset of symptoms has lead to misdiagnosis of HSE. In these cases of suspected HSE, a repeat lumbar puncture is advised after a few days, without interruption of acyclovir therapy. Histological examination and viral culture of brain biopsy tissue may be necessary to confirm the diagnosis in PCR-negative cases. The AAP recommends treatment for 21 days with IV acyclovir.
The absence of fever and normal CT lead to difficulty in diagnosis in 4 of 6 children with proven HSE, presenting with focal seizures and altered consciousness . All cases had abnormal EEG findings. The EEG is a sensitive test that may be superior to CT and ultrasound in the early diagnosis of neonatal HSE ; the multifocal periodic EEG pattern with CSF pleocytosis is highly suggestive of the diagnosis. Early diagnosis is also facilitated by MRI with T2 weighted images showing multiple small disseminated lesions . A rare presentation of HSE in children is a relapsing biphasic illness manifested by fever and seizures and accompanied by generalized or hemi-chorea . Autism is another unusual sequel to HSE.