Herpes Simplex Virus (HSV) has become a common etiology of viral encephalitis in both immunocompromised as well as immunocompetent hosts. Prompt recognition of HSV encephalitis is crucial as a delay in treatment is associated with significant morbidity and mortality. Biopsy of the brain was previously the gold standard for the diagnosis of this condition, though has since fallen out of favor with the advent of the less invasive CSF polymerase chain reaction (PCR) – shown to have both high sensitivity as well as specificity in this diagnosis. Previous studies have suggested that patients are at low risk of HSV encephalitis when CSF wbc <5, CSF protein <50, the patient is older than 2 years old, and is immunocompetent – these are known are the “Reller Criteria,” and these thresholds have been shown to be extremely sensitive. A recently published multicenter, retrospective study examined 4,404 CSF samples in making a diagnosis of HSV encephalitis. In this cohort, 91 patients (2.1%) tested positive for HSV, 9 of whom were noted to have normal CSF WBC and protein (thereby not meeting the Reller criteria). These patients were noted to have clinical syndromes suggestive of encephalitis or meningoencephalitis, whereas clinical symptoms of meningitis were much more common in patients meeting the Reller criteria. Though this study has a number of limitations, including the use of different PCR assays between centers, it suggests that normal CSF cell and protein levels do not entirely rule out the possibility of a herpes simplex virus CNS infection. Therefore, we must maintain a high level of clinical suspicion in deciding whom to both test and treat for this potentially fatal condition.
References: Missing cases of HSV encephalitis
