Next-generation sequencing of cerebrospinal fluid for diagnosis of atypical herpes simplex encephalitis

Herpes simplex encephalitis (HSE) is one of the most common causes of severe viral encephalitis. The characteristic manifestations of HSE include cerebrospinal fluid with mild cytopenia, dominated by lymphocytes, elevated protein, and normal blood glucose values (3.9-6.1 mmol/L). Although it is not difficult to diagnose classical HSE, diagnosing clinically atypical cases is more difficult.

We reviewed the results of next-generation sequencing (NGS) of CSF in a series of patients diagnosed with atypical HSE.

Four patients lacking classical clinical manifestations of HSE, including no fever, headache, or other typical neurological deficit symptoms, 1-2 × 10⁶ cells/L CSF leucocyte count, and no typical imaging features, were diagnosed with atypical HSE by NGS of CSF. The NGS reads corresponding to herpes simplex virus type 1 ranged from 2 to 13,174.

Mild HSE may not present with classic frontotemporal lobe syndrome and fever may not be an inevitable symptom in patients with immunosuppression. However, the possibility of HSE should be considered in patients with atypical intracranial infection, and these patients should be tested by NGS.