Of 145 patients admitted to our hospital because of encephalitis-like illness, 50 patients hospitalized for > or =72 hours underwent standardized microbiological investigations. A confirmed or probable etiologic agent was identified in 20 cases (40%), including Mycoplasma pneumoniae (9 cases). M. pneumoniae and enterovirus (2), herpes simplex virus (4), Epstein-Barr virus (1), human herpes-virus 6 (HHV-6) (1), HHV-6 and influenza virus type A (1), influenza virus type A (1), and Powassan virus (1). In 13 cases (26%), a possible pathogen was identified, including M. pneumoniae in nine cases. Presenting features included fever (80% of patients), seizures (78%), focal neurological findings (78%), and decreased consciousness (47%). The frequency of findings at the time of admission vs. later in hospitalization was as follows: pleocytosis, 59% vs. 63%; electroencephalogram abnormalities, 87% vs. 96%; and neuroimaging abnormalities, 37% vs. 69%, respectively. The outcomes at the time of discharge were as follows: normal results of physical examination, 32% (16) of the patients; death, 2% (1); motor difficulties, 26% (13); global neurological deficits, 16% (severe, 6; mild, 2); mental status changes, 14% (7); visual defects, 8% (4); and hearing impairment, 2% (1).

Herpes simplex encephalitis continues to be associated with poor long-term neurologic outcomes despite appropriate therapy. Cerebrospinal fluid polymerase chain reaction results may be negative early in the course of herpes simplex encephalitis; therefore, repeat cerebrospinal fluid analysis should be considered if herpes simplex encephalitis is suspected. Atypical forms of herpes simplex virus central nervous system disease may occur in children.