From the Guidelines
Herpes Simplex Virus (HSV) encephalitis is characterized by cerebrospinal fluid (CSF) findings that typically include a moderately elevated opening pressure, moderate CSF pleocytosis with tens to hundreds of cells, mildly elevated CSF protein, and a normal CSF:plasma glucose ratio, as noted in the 2012 guidelines by the Association of British Neurologists and British Infection Association 1.
Key CSF Findings
- Moderately elevated CSF opening pressure
- Moderate CSF pleocytosis (tens to hundreds of cells)
- Mildly elevated CSF protein
- Normal CSF:plasma glucose ratio
- Presence of red blood cells in approximately 50% of cases due to the hemorrhagic nature of the disease
Diagnostic Considerations
- PCR testing for HSV DNA in CSF is crucial for diagnosis, with high sensitivity and specificity 1
- Early lumbar puncture is essential, but initial CSF findings may be normal in approximately 5-10% of adults with proven HSV encephalitis, especially early in the illness or in immunocompromised patients 1
- A second CSF examination 24-48 hours later may be necessary if the first CSF is normal but clinical suspicion remains high 1
Differential Diagnosis
- Bacterial infections, such as tuberculosis, listeriosis, and partially treated acute bacterial meningitis, can present with similar CSF findings, but usually have a lower glucose ratio and higher protein levels 1
- CSF lactate levels may help distinguish bacterial meningitis from viral CNS infections, with a CSF lactate <2 mmol/l suggesting viral etiology 1
From the Research
Cerebrospinal Fluid (CSF) Findings in Herpes Simplex Virus (HSV) Encephalitis
The CSF findings in HSV encephalitis can vary, but some common features include:
- Lymphoid pleocytosis, which is a prominent feature in the CSF of patients with HSV encephalitis 2
- Increased total protein level and concentrations of IgG, IgM, and IgA in the early phase of the disease 2
- Presence of red blood cells in CSF, which is associated with severe disability and death due to HSV 3
- Normocellular CSF, which can be present in some cases of HSV encephalitis, making diagnosis more challenging 4
- Increased local IgG production in the central nervous system during HSV encephalitis, which can be detected by measuring the ratio of HSV antibody in serum to that in CSF 2
Atypical CSF Findings
Some studies have reported atypical CSF findings in HSV encephalitis, including:
- Normocellular CSF, which was present in 22.2% of patients with PCR-proven HSV encephalitis 4
- Absence of significant CSF alterations, which can make diagnosis more difficult 2
- Presence of polymorphonuclear cells, which can dominate initially in some cases 2
Diagnostic Challenges
The diagnosis of HSV encephalitis can be challenging due to the variability of CSF findings and the presence of atypical presentations. Therefore, a high level of clinical suspicion and a low threshold to initiate life-saving acyclovir therapy are essential in suspected cases 4. The use of PCR to detect HSV DNA in CSF is a valuable tool for diagnosis, and clinical signs such as alteration in the level of consciousness and lateralization sign can guide the performance of HSV-PCR 5.