Management of CSF with Mild Pleocytosis, Elevated Protein, and Normal-Low Glucose
This CSF profile (sugar 69 mg/dL, protein 45 mg/dL, WBC 5 cells/μL with all lymphocytes, RBC 0) shows minimal pleocytosis with lymphocytic predominance and mildly elevated protein, requiring immediate viral PCR testing and empiric acyclovir while awaiting results, as HSV encephalitis can present with minimal CSF abnormalities in 5-10% of cases. 1
Immediate Diagnostic Workup
Essential CSF Studies to Send Immediately
Send CSF PCR for HSV-1, HSV-2, VZV, and enteroviruses immediately, as these account for 90% of viral CNS infections and must be identified rapidly. 1, 2
Obtain CSF bacterial culture and Gram stain to exclude partially treated bacterial meningitis, which can present with lymphocytic pleocytosis and minimal symptoms. 2
Measure CSF lactate, as levels <2 mmol/L effectively rule out bacterial disease (your profile suggests viral or non-infectious etiology). 1
Check CSF opening pressure if not already documented, as this guides management of potential complications. 1
Critical Additional Testing Based on Risk Factors
Send CSF for tuberculosis studies (culture, AFB smear, TB PCR) if the patient has immunocompromise, endemic exposure, or risk factors, as TB meningitis classically presents with low glucose, elevated protein, and lymphocytic pleocytosis. 2, 3
Obtain CSF fungal studies (cryptococcal antigen, fungal culture) in immunocompromised patients or those with appropriate exposures. 2
Send CSF oligoclonal bands and IgG index to evaluate for autoimmune/inflammatory conditions like ADEM or multiple sclerosis, which can present with mild pleocytosis. 1, 2
Perform CSF cytology and flow cytometry if there is any concern for malignancy (leptomeningeal disease, CNS lymphoma), especially in older patients or those with known cancer. 2
Empiric Treatment Decision
Start Acyclovir Immediately If:
Any neurological symptoms are present (altered mental status, focal deficits, seizures), as 5-10% of HSV encephalitis cases have normal or minimally abnormal initial CSF. 1
The patient cannot be closely monitored for clinical deterioration while awaiting PCR results (typically 24-48 hours). 1
Consider Withholding Acyclovir Only If:
The patient is completely asymptomatic with CSF obtained for another indication (e.g., headache workup, routine evaluation). 2
Close neurological monitoring is available and PCR results will return within 24 hours. 1
Risk Stratification Using the CHANCE Score
Calculate the CHANCE score to assess likelihood of bacterial meningitis (though your profile suggests low risk): 2, 4
- CSF cell count >100 cells/μL (absent in your case)
- CSF protein >100 mg/dL (absent in your case)
- CRP >5 mg/dL
- Elevated peripheral WBC count
- Abnormal mental status
- Nuchal rigidity
Your patient's CHANCE score appears low (WBC 5, protein 45), with sensitivity 92.1% and specificity 90.9% for identifying bacterial meningitis. 4
Neuroimaging Requirements
Obtain brain MRI with and without contrast (and consider spine MRI) to identify: 2
- Temporal lobe enhancement suggesting HSV encephalitis
- Basilar meningeal enhancement suggesting TB or fungal meningitis
- Demyelinating lesions suggesting autoimmune disease
- Leptomeningeal enhancement suggesting malignancy
Consider EEG if any concern for subclinical seizures or to identify focal abnormalities suggesting HSV encephalitis. 2
Follow-Up Strategy
Repeat lumbar puncture in 24-48 hours if initial CSF is non-diagnostic and clinical suspicion remains high, as HSV PCR can be negative early in disease course. 1
Monitor for clinical deterioration with serial neurological examinations every 4-6 hours until diagnosis is established. 1
Critical Pitfalls to Avoid
Do not assume viral meningitis is benign - HSV-2 is the leading identified pathogen in asymptomatic pleocytosis cases and can progress rapidly. 2
Do not miss Lyme disease with cranial nerve palsy, which often presents with CSF pleocytosis even without meningeal symptoms; treat with appropriate antibiotics to prevent sequelae. 2
Do not delay TB treatment if risk factors are present, as outcome depends on speed of therapy initiation; TB meningitis classically shows low glucose (though yours is normal-low at 69), elevated protein, and lymphocytic pleocytosis. 3
Recognize that normal CSF glucose does not exclude serious pathology - your glucose of 69 mg/dL is at the lower end of normal and warrants comparison with simultaneous plasma glucose. 1