Treatment of Lymphocytic Meningitis with Normal Glucose, Elevated Protein, and Mildly Elevated Lactate
For first-episode HSV-2 meningitis presenting with this CSF profile, initiate acyclovir 10 mg/kg IV every 8 hours until resolution of fever and headache, followed by valacyclovir 1 g three times daily to complete a 14-day course. 1
Diagnostic Considerations
The CSF profile described—lymphocytic pleocytosis with normal glucose, elevated protein, and mildly elevated lactate—is most consistent with viral meningitis, particularly HSV-2 meningitis. 1, 2
Key Differentiating Features:
Normal CSF glucose strongly argues against bacterial or tuberculous meningitis: Both bacterial and TB meningitis typically present with very low CSF glucose (CSF/plasma glucose ratio <0.5 for TB, <0.36 for bacterial). 2, 3, 4
Mildly elevated lactate is consistent with viral etiology: CSF lactate <2 mmol/L effectively rules out bacterial disease and supports viral etiology. 2 While lactate can be elevated in bacterial meningitis (>4.2 mmol/L with 96% sensitivity), mildly elevated levels are more consistent with viral causes. 1
Lymphocytic predominance with elevated protein fits HSV-2 meningitis: HSV-2 meningitis characteristically shows lymphocytic pleocytosis with mildly elevated protein and normal glucose. 1, 5
Immediate Diagnostic Steps
Obtain HSV PCR from CSF immediately in all suspected cases, as this will identify the causative pathogen in the majority of viral meningitis cases. 1, 2
Additional testing should include:
- Enterovirus PCR: Enteroviruses are the most common cause of viral meningitis, though they typically present with completely normal glucose and less protein elevation. 2, 6
- VZV PCR: Especially if there is any vesicular rash or dermatomal distribution. 7
- Consider serum procalcitonin: Levels >10.2 ng/mL have 100% sensitivity and specificity for bacterial meningitis in adults; normal levels support viral etiology. 1
Treatment Algorithm
For First Episode:
Start empiric IV acyclovir 10 mg/kg every 8 hours immediately while awaiting PCR results, as HSV-2 is a leading cause of lymphocytic meningitis and early treatment may provide clinical benefit. 1, 6
Continue IV acyclovir until resolution of fever and headache, then transition to valacyclovir 1 g three times daily to complete a 14-day total course. 1
If HSV PCR is negative and enterovirus PCR is positive, acyclovir can be discontinued as there is no effective antiviral therapy for enterovirus, and the condition is self-limited. 6
For Recurrent Episodes:
Oral therapy may be used for the entire course in patients with established recurrent HSV-2 meningitis. 1
Critical Pitfalls to Avoid
Do NOT use valacyclovir 500 mg twice daily for suppression:
A randomized trial demonstrated that this dose failed to prevent recurrent HSV-2 meningitis episodes and was associated with increased risk of rebound meningitis after discontinuation. 1 The dose is insufficient for CNS penetration.
Distinguish HSV meningitis from HSV encephalitis:
HSV encephalitis requires 14-21 days of IV acyclovir due to high neurologic morbidity and mortality. 1 Encephalitis presents with altered mental status, focal neurologic deficits, and often hemorrhagic changes on imaging or elevated red blood cells in CSF. 2
Do not assume TB meningitis is ruled out by normal glucose alone:
While normal CSF glucose strongly suggests against TB meningitis (which typically has CSF/plasma glucose ratio <0.5), calculate the actual CSF/plasma glucose ratio as absolute values can be misleading when serum glucose is abnormal. 3, 4
Expected Clinical Course
- Hospitalization typically ranges from 16-31 days for viral meningitis cases. 6
- Outcome is generally good to fair (91% combined) with no seizures, neurological disability, or death expected in extended follow-up for HSV-2 meningitis. 6, 5
- Recurrence is possible but not universal with HSV-2 meningitis. 5
Special Populations
In immunocompromised patients with acyclovir-resistant HSV, pritelivir (helicase-primase inhibitor) is being studied in clinical trials and may be available through early-access programs. 1