What is the workup for diagnosing lymphocytic meningitis with normal glucose, elevated protein, and mildly elevated lactate levels in cerebrospinal fluid (CSF)?

Workup for Lymphocytic Meningitis with Normal Glucose, Elevated Protein, and Mildly Elevated Lactate

The diagnostic workup should prioritize HSV PCR on CSF immediately, as this CSF profile—lymphocytic pleocytosis with normal glucose, elevated protein, and mildly elevated lactate—is most consistent with viral meningitis, particularly HSV-2 meningitis. 1

Initial CSF Analysis Interpretation

The CSF findings described effectively rule out bacterial meningitis and strongly support viral etiology:

• Normal CSF glucose strongly argues against bacterial or tuberculous meningitis, as both typically present with very low CSF glucose (bacterial: <2.2 mmol/L; tuberculous: CSF/plasma ratio <0.5) 1, 2
• **Mildly elevated lactate (<2.4 mmol/L) effectively rules out bacterial disease**, as CSF lactate >4.2 mmol/L has 96% sensitivity and 100% specificity for bacterial meningitis 3, 4
• Lymphocytic predominance with normal glucose is the hallmark of viral meningitis, distinguishing it from bacterial meningitis which shows neutrophil predominance (80-95%) and very low glucose 3, 1

Essential Diagnostic Tests to Order Immediately

Highest Priority CSF Studies

• HSV-1 and HSV-2 PCR on CSF must be obtained immediately, as HSV (particularly HSV-2) is the leading cause of lymphocytic meningitis and PCR has 86-100% sensitivity 3, 1
• Enterovirus PCR on CSF, as enteroviruses are the most common cause of viral meningitis with sensitivity of 86-100% and specificity of 92-100% 3
• VZV PCR on CSF, particularly if any vesicular rash is present or suspected, as VZV meningitis can occur without rash 3, 5

Additional CSF Studies

• CSF opening pressure, cell count with differential, protein, and glucose to confirm lymphocytic predominance and quantify abnormalities 3
• Gram stain and bacterial culture to definitively exclude bacterial pathogens, even though clinical picture argues against this 3
• Cytology for malignant cells to rule out leptomeningeal metastases, particularly in patients with cancer history 3
• Parechovirus PCR in appropriate clinical contexts, as this is an emerging recognized cause of viral meningitis 3

Serum Studies

• Serum procalcitonin, as levels >10.2 ng/mL have 100% sensitivity and specificity for bacterial meningitis in adults; normal levels strongly support viral etiology 3, 1
• Serum CRP, as normal CRP has 99% negative predictive value for bacterial meningitis 3
• Simultaneous serum glucose to calculate CSF/plasma glucose ratio if there is any diagnostic uncertainty 2, 6

Neuroimaging Requirements

• MRI brain with and without contrast should be performed to evaluate for:
  • Meningeal enhancement suggesting inflammatory or infectious process 3
  • T2/FLAIR changes that may indicate encephalitis component 3
  • Exclusion of mass lesions or leptomeningeal disease 3
• Neuroimaging is most often normal (83%) in HSV-2 meningitis, though some cases show nonspecific (14%) or meningeal changes (3%) 7

Critical Diagnostic Pitfalls to Avoid

Do Not Delay Treatment While Awaiting Results

• Start empiric IV acyclovir 10 mg/kg every 8 hours immediately while awaiting PCR results, as HSV-2 is a leading cause and early treatment may provide clinical benefit 1, 5
• Consider empiric antibacterial therapy until CSF Gram stain and culture results are negative, particularly if patient appears toxic or has any atypical features 3

Do Not Misinterpret Mildly Elevated Lactate

• CSF lactate <2.4 mmol/L effectively excludes bacterial meningitis with high negative predictive value 4
• Lactate levels of 2.5-2.7 mmol/L can occur in aseptic meningitis and do not indicate bacterial disease when other parameters are consistent with viral etiology 4

Do Not Overlook Tuberculous Meningitis in High-Risk Patients

If the patient has risk factors for TB (immunosuppression, endemic exposure, subacute presentation):

• Calculate CSF/plasma glucose ratio, as ratio <0.5 has 90% sensitivity for tuberculous meningitis 2, 6
• Check for markedly elevated CSF protein (>1 g/L), which has 78% sensitivity and 94% specificity for TB meningitis 2, 6
• Consider AFB smear and culture, TB PCR if clinical suspicion exists 3

Expected Timeline for Diagnosis

• HSV PCR results typically available within 24-48 hours, allowing for targeted therapy decisions 7
• Enterovirus PCR significantly faster than viral culture (hours to 1 day vs. days to weeks) 3
• Bacterial culture results preliminary at 24-48 hours, final at 48-72 hours 3

Consultation Requirements

• Neurology consultation should be obtained for all cases to guide management and monitor for complications 3
• Infectious diseases consultation is valuable for complex cases or when etiology remains unclear after initial workup 3