Unveiling the clinical spectrum of herpes simplex virus CNS infections in adults: a systematic review.

Background: Herpes simplex virus (HSV) infections of the central nervous system (CNS) are associated with high morbidity and mortality. Prompt recognition and antiviral treatment are critical to improve patient outcomes. This systematic review of the literature aimed to aggregate the symptoms described with HSV infections of the CNS which may provide a framework to aid in early diagnosis.

Methods: This review was registered (PROSPERO; CRD42022366036) and adheres to PRISMA guidelines. MEDLINE, Embase, and Cochrane databases were systematically screened for studies including adult patients with HSV infections confirmed by histopathology or polymerase chain reaction. Demographics, clinical characteristics, diagnostics, and outcomes were assessed.

Results: Of 21 studies from 18 countries describing 1605 patients, the most frequently reported symptoms were fever (75%), headache (65%), neck stiffness (55%), and language/speech abnormalities (41%). Other common symptoms included seizures (36%) and gastrointestinal issues (35%). Information regarding a combination of symptoms was not provided. Diagnostics often included lumbar puncture and magnetic resonance imaging, revealing temporal lobe abnormalities in 88%. While mortality was 13%, 72% of survivors had good neurological outcomes. The risk of bias was high in most studies.

Conclusions: Fever, headache, neck stiffness, and language/speech abnormalities were frequently reported clinical findings in patients with proven HSV infection of the CNS. Despite limited evidence, these symptoms warrant a high index of suspicion, prompting early empiric antiviral therapy, especially when alternative diagnoses lack strong support. The predictive value of these symptoms and their combination for diagnosing HSV infection of the CNS should be further investigated, as they could accelerate diagnostics and treatment.