Children with herpes simplex encephalitis (HSE) admitted to the Hospital for Sick Children, Toronto, Canada, between Jan 1994 and Dec 2005, were studied prospectively. Sixteen (5%) of 322 patients with acute encephalitis fulfilled criteria for HSE (encephalopathy, defined as depressed or altered level of consciousness >24 hours, plus additional specific criteria). Median age was 4 years (range, 2 months to 14 years); neonatal cases were excluded. Exposure to HSV was known in 8 (50%). All 16 presented with fever, 11 (69%) with focal seizures, 5 (31%) with hemiparesis, and 2 (13%) with dysphasia. CSF showed pleocytosis (>5 x 106 cells per L) in 15 (94%), 50 to 100 x 106 RBCs per L in 3 (19%), and elevated protein levels in 8 (50%). CSF PCR evidence of HSV was present in 12 (75%) patients, and 4 with negative CSF PCR had -/> fourfold increase in complement fixation titers in convalescent cf acute serum. In 2 patients, PCR was negative on day 1 and positive on day 3 or 7. HSV-1 was detected in 10 (83%) and HSV-2 in 2 (17%). Other identified pathogens included mycoplasma pneumoniae in 4 patients, and 1 case each with HHV-6, enterovirus, Epstein-Barr virus, influenza A, and parainfluenza 3. EEG showed generalized slowing in 13 (81%), and periodic lateralizing epileptiform discharges (PLEDS) in 2 (13%). CT or MRI abnormalities consistent with HSE (localized edema, mass effect, or hemorrhage) were present in 14 (88%). Four (25%) had infarction and hemorrhage. Of 6 cases with negative CTs, 4 had abnormal MRIs. Despite treatment with acyclovir within the first 3 days and for 14 to 21 days, 10 (63%) patients had adverse neurologic outcomes. Sequelae included seizures in 7 (44%), global developmental delay in 4 (25%), and hemiplegia in 2 (13%). No patient died. Outcome was not correlated with age, clinical features, CSF, EEG or neuroimaging abnormalities. 
COMMENT. HSV accounts for 5% of all cases of acute encephalitis in children. The classic clinical presentation of HSE, with fever, altered level of consciousness, focal motor seizures, dysphasia, and hemiparesis, occurs in 75% of cases. Other presentations include ataxia, decreased visual acuity, tremor, or generalized tonic-clonic seizures. A single negative CSF PCR does not exclude a diagnosis of HSV as the cause of acute encephalitis, In patients with typical clinical presentation and consistent MRI findings, a second lumbar puncture is recommended after 3 days. The absence of CSF pleocytosis, elevated protein, and elevated RBC counts does not rule out the diagnosis. The frequent finding of additional viruses suggests a reactivation of HSV as the mechanism. Typical EEG findings helpful in diagnosis of HSE are less prevalent in children than adults. MRI is more sensitive than CT, showing localization to the limbic system in one half and bilateral disease in one third of cases. Adverse outcomes in two thirds are not predicted by clinical features or by diagnostic test abnormalities. Patients who receive a 21-day course of acyclovir, compared with a 14-day course, have a lower incidence of abnormal neurologic sequelae and tendency to relapse.
Coincidental occurrence of additional viruses may point to a reactivation of HSV as the cause of encephalitis, or alternatively, the additional virus may be the primary pathogen, as suggested in a letter to the editor . M pneurmoniae is an important cause of acute encephalitis in children, accounting for an estimated 6.9% of all cases . These authors doubt the significance of serologic teats as the only evidence of M pneumoniae infection, and emphasize the difficulties in determining the etiology of acute encephalitis in some cases.