Management of Meningitis with Normal Protein, Slightly Low Glucose, and Lymphocytic Predominance
Start empiric acyclovir immediately while awaiting confirmatory testing, as this CSF profile is most consistent with viral meningitis (particularly HSV-2), though tuberculous meningitis must also be considered based on the glucose findings. 1, 2, 3
Initial Diagnostic Interpretation
The CSF findings of lymphocytic predominance with slightly low glucose create a diagnostic challenge that requires immediate empiric treatment:
Lymphocytic predominance with normal protein strongly suggests viral meningitis rather than bacterial meningitis, which typically shows neutrophil predominance (80-95%) and markedly elevated protein (>2.2 g/L). 1, 3, 4
The slightly low glucose is the critical confounding factor - viral meningitis typically maintains normal or only slightly decreased CSF glucose with CSF/plasma glucose ratio >0.36, while bacterial meningitis shows ratio <0.36. 1, 3, 5
If the CSF/plasma glucose ratio is <0.5, tuberculous meningitis becomes highly likely despite the lymphocytic predominance, as TB meningitis characteristically presents with lymphocytes, low glucose (<2.2 mmol/L), and markedly elevated protein (>1 g/L). 2, 5
Immediate Management Algorithm
First-Line Empiric Therapy
Initiate IV acyclovir immediately as empiric antiviral therapy until viral PCR results (HSV-1, HSV-2, VZV, enteroviruses) are obtained and confirmed negative. 1, 6, 7
HSV-2 is the most likely viral cause in this clinical scenario, as it commonly presents with lymphocytic meningitis and can show slightly low glucose levels in 7 of 13 cases in immunocompromised patients. 7, 8
Early recognition and acyclovir treatment significantly improves outcomes - delayed treatment in HSV meningitis has resulted in progression to encephalitis and death in immunocompromised patients. 7
Critical Decision Points
Antibiotics (ceftriaxone/meropenem) should NOT be the primary therapy given the lymphocytic predominance and normal protein, which essentially exclude bacterial meningitis (CSF protein <0.6 g/L makes bacterial meningitis unlikely). 1, 5
However, if the absolute CSF glucose is <2.6 mmol/L or CSF/plasma ratio is <0.36, add empiric anti-tuberculous therapy (isoniazid, rifampin, pyrazinamide, ethambutol) immediately without waiting for microbiological confirmation. 2, 5
Corticosteroids are NOT indicated as first-line therapy in this presentation - they are reserved for confirmed bacterial meningitis or specific immune-mediated conditions after infectious causes are excluded. 1
Common Clinical Pitfalls
Early viral meningitis can show neutrophil predominance (especially enteroviral infections), but the total CSF white cell count rarely exceeds 2000 cells/μL, unlike bacterial meningitis. 1, 3
The absolute CSF glucose value can be misleading when serum glucose is abnormal - always calculate the CSF/plasma glucose ratio for accurate interpretation. 2, 5
Normal protein does not exclude serious pathology - HSV-2 meningitis can present with relatively normal CSF protein but still cause severe disease requiring urgent antiviral therapy. 7, 9
Monitoring and Reassessment
Repeat lumbar puncture in 12-24 hours if diagnosis remains uncertain - a shift from polymorphonuclear to mononuclear cells confirms viral etiology and allows safe discontinuation of antibiotics if they were started. 3, 8
CSF PCR for HSV, VZV, and enteroviruses identifies approximately 90% of viral causes and should be sent immediately on the initial CSF sample. 3, 6
If clinical deterioration occurs despite acyclovir, consider HSV encephalitis progression or alternative diagnoses including tuberculous meningitis, and escalate imaging and treatment accordingly. 7, 9