What is the management for a patient with hyperproteinorrachia, leukocytosis, and normal CSF glucose in the context of suspected CNS infection?

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Management of Hyperproteinorrachia with Leukocytosis and Normal CSF Glucose

Start empiric intravenous acyclovir immediately (10 mg/kg every 8 hours) along with broad-spectrum antibiotics (ceftriaxone and vancomycin) until bacterial meningitis and HSV encephalitis are definitively excluded by culture and PCR results. 1, 2

Immediate Interpretation of CSF Values

Your CSF shows:

  • Glucose 117 mg/dL: Normal to elevated (rules out most bacterial, TB, and fungal infections) 3, 4
  • WBC 2,070 cells/µL: Moderate pleocytosis (bacterial meningitis typically shows >2,000 cells/µL but with much higher protein) 3
  • Protein 101 mg/dL: Mildly elevated (bacterial meningitis typically shows >220 mg/dL) 3, 4

This pattern strongly suggests viral meningoencephalitis, but partially treated bacterial meningitis and atypical infections cannot be excluded based on CSF alone. 1, 2

Critical Diagnostic Workup Required Immediately

Essential CSF Studies to Send Now:

  • CSF PCR for HSV-1, HSV-2, VZV, and enteroviruses (accounts for 90% of viral CNS infections) 1, 2
  • CSF bacterial culture and Gram stain (to exclude partially treated bacterial meningitis) 1, 2
  • CSF lactate level (if <2 mmol/L, effectively rules out bacterial disease) 1, 2, 4
  • CSF cell differential (lymphocytic vs neutrophilic predominance guides diagnosis) 3, 5

Additional Testing Based on Risk Factors:

  • TB studies (AFB smear, culture, TB PCR) if immunocompromised, endemic exposure, or risk factors present 3, 2
  • Cryptococcal antigen and fungal culture if immunocompromised (note: cryptococcal meningitis can present with completely normal CSF studies) 3, 6
  • CSF oligoclonal bands and IgG index if autoimmune/inflammatory conditions suspected 2, 4

Obtain Simultaneous Plasma Glucose:

  • Calculate CSF:plasma glucose ratio (normal >0.66) - this is far more informative than absolute CSF glucose alone 4

Empiric Treatment Protocol

Start Immediately (Do Not Wait for PCR Results):

Acyclovir 10 mg/kg IV every 8 hours 3, 1, 7

  • HSV encephalitis presents with normal/minimally abnormal CSF in 5-10% of cases 1, 2
  • Delays beyond 48 hours significantly worsen outcomes (mortality 70% untreated vs 20-30% with treatment) 1
  • Continue for 14-21 days if HSV confirmed 1

Ceftriaxone + Vancomycin (standard meningitis dosing) 1

  • Lymphocytic pleocytosis with normal glucose does NOT exclude bacterial meningitis 1
  • Partially treated bacterial meningitis, TB meningitis, and listeriosis can present identically 1
  • Discontinue once bacterial cultures negative and clinical course supports viral etiology 1

Neuroimaging Requirements

Obtain brain MRI with and without contrast urgently: 2

  • Temporal lobe enhancement suggests HSV encephalitis 1, 2
  • Basilar meningeal enhancement suggests TB or fungal meningitis 1, 2
  • Demyelinating lesions suggest autoimmune disease 2

Follow-Up Strategy

Repeat lumbar puncture in 24-48 hours if: 1, 2

  • Initial CSF HSV PCR is negative AND clinical suspicion remains high
  • HSV PCR can be negative early in disease course 1, 2

Monitor for acyclovir nephrotoxicity: 1

  • Ensure adequate hydration to prevent crystalluria 1

Serial neurological examinations every 4-6 hours until diagnosis established 2

Critical Pitfalls to Avoid

Never assume lymphocytic CSF with normal glucose means "just viral": 1, 4

  • TB meningitis, partially treated bacterial meningitis, and listeriosis all present with lymphocytic pleocytosis 1
  • Neurobrucellosis commonly shows mild pleocytosis (<50 cells/µL) with only mildly elevated protein and near-normal glucose 8

Never delay acyclovir waiting for HSV PCR results: 1, 2

  • If any neurological symptoms present (altered mental status, focal deficits, seizures), start immediately 2
  • 5-10% of HSV encephalitis cases have normal/minimally abnormal initial CSF 1, 2

Never rely on CSF glucose alone without plasma glucose: 4

  • The CSF:plasma ratio is the critical value, not absolute CSF glucose 4

Consider cryptococcal meningitis even with normal CSF: 6

  • C. neoformans can present with completely normal WBC, protein, and glucose 6
  • Opening pressure and cryptococcal antigen are critical diagnostic tools 6

References

Guideline

Management of Suspected Meningoencephalitis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Management of CSF with Mild Pleocytosis, Elevated Protein, and Normal-Low Glucose

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

CSF Analysis: Elevated Protein with Normal Glucose

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Neurobrucellosis: report of 54 cases.

Tropical medicine and health, 2022

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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