Pitfalls associated with the diagnosis of herpes simplex encephalitis.

Herpes simplex encephalitis (HSE) still remains a serious illness with high morbidity and mortality. The characteristic presentation of HSE usually consists of fever, headache, and altered mental function. We present three patients with atypical features of HSE. First, a 48-year-old man with symptomatic posttraumatic epilepsy, who developed a gastrointestinal infection, seizures, and fever. After significant clinical improvement, the patient had fever again and developed a status epilepticus, which led to the diagnosis of HSE. Second, an 84-year-old woman with hyperactive delirium after levofloxacin intake. Cranial computed tomography (CCT) revealed hypodense temporal changes, prompting lumbar puncture and diagnosis of HSE. Third, a 51-year-old diabetic woman presented with fever and acute confusion. As CCT and cell count of cerebrospinal fluid (CSF) were normal, infection and hyperglycemia as initial diagnoses were postulated. Due to aphasic symptoms, the differential diagnosis of a stroke was taken into account. Thus a second lumbar puncture led to the correct diagnosis of HSE. These atypical presentations need a high grade of suspicion and a high willingness to reconsider the initial working diagnosis, in order to prevent a diagnostic delay.