What does an elevated total protein level with normal sugar in CSF indicate?

CSF Analysis: Elevated Protein with Normal Glucose

This CSF profile showing mildly elevated protein (74 mg/dL or 0.74 g/L) with normal-to-high glucose (103 mg/dL or 5.7 mmol/L) most likely represents a viral CNS infection, Guillain-Barré syndrome, or a non-infectious inflammatory process, and effectively rules out bacterial meningitis.

Interpretation of These Specific Values

The protein level of 74 mg/dL (0.74 g/L) is mildly elevated (normal <40-45 mg/dL or <0.4 g/L), while the glucose of 103 mg/dL (5.7 mmol/L) is normal-to-elevated (normal CSF glucose 2.6-4.5 mmol/L or 47-81 mg/dL). 1

What This Pattern Rules Out

• Bacterial meningitis is highly unlikely because:

  • CSF protein in bacterial meningitis is typically >220 mg/dL (>2.2 g/L), and a level <60 mg/dL (<0.6 g/L) makes bacterial disease very unlikely 1
  • CSF glucose in bacterial meningitis is typically <35 mg/dL with a CSF:plasma ratio <0.36, and a CSF glucose >47 mg/dL (>2.6 mmol/L) is unlikely to be bacterial 1
  • Your patient's glucose of 103 mg/dL far exceeds this threshold

• Tuberculous meningitis is also unlikely because:

  • TB meningitis characteristically shows markedly elevated protein (often >1 g/L) and very low glucose 1
  • A CSF glucose <2.2 mmol/L (40 mg/dL) with protein >1 g/L has good specificity for TB meningitis 2

• Fungal meningitis is improbable given the normal glucose, as fungal infections typically present with low CSF glucose 1

Most Likely Diagnostic Considerations

Viral CNS Infection (Most Common)

Viral meningitis or encephalitis typically presents with mildly elevated protein and normal or slightly low glucose, exactly matching this profile. 1

• Send CSF PCR immediately for HSV-1, HSV-2, VZV, and enteroviruses, as these account for 90% of viral CNS infections 3
• In viral encephalitis, CSF protein is mildly elevated with normal CSF:plasma glucose ratio 1
• COVID-19 can also present with mild protein elevation (63% of cases) without pleocytosis 4

Guillain-Barré Syndrome

The classic finding in GBS is albumino-cytological dissociation: elevated CSF protein with normal cell count. 1

• However, protein levels are normal in 30-50% of patients in the first week and 10-30% in the second week, so timing matters 1
• Look for progressive bilateral limb weakness with absent/decreased reflexes 1
• This diagnosis requires clinical correlation with neurological examination findings

Non-Infectious Inflammatory Conditions

Consider autoimmune/demyelinating diseases such as multiple sclerosis, ADEM, or other inflammatory conditions. 3

• Send CSF oligoclonal bands and IgG index to evaluate for these conditions 3
• Brain and spine MRI with contrast may reveal characteristic lesions 3

Critical Missing Information

You must obtain a simultaneous plasma glucose to calculate the CSF:plasma glucose ratio, as this is far more informative than the absolute CSF glucose value alone. 1

• Normal CSF:plasma glucose ratio is >0.66 1
• If plasma glucose was significantly elevated (e.g., >200 mg/dL), the CSF glucose of 103 mg/dL could still represent a pathologically low ratio
• Without this ratio, interpretation is incomplete 1

The CSF white cell count and differential are absolutely essential and were not provided. 1

• Normal is <5 cells/μL 1
• Viral infections typically show 5-1000 cells/μL with lymphocytic predominance 1
• GBS shows normal cell count (albumino-cytological dissociation) 1
• Marked pleocytosis (>50 cells/μL) suggests infectious or inflammatory pathology other than GBS 1

Recommended Immediate Workup

Based on the UK Joint Specialist Societies and British Infection Association guidelines, the following tests should be performed: 1, 3

• CSF cell count with differential (if not already done)
• Simultaneous plasma glucose to calculate CSF:plasma ratio
• CSF PCR for HSV-1, HSV-2, VZV, and enteroviruses 3
• CSF bacterial culture and Gram stain (to exclude partially treated bacterial meningitis) 3
• CSF lactate: levels <2 mmol/L effectively rule out bacterial disease 1, 3
• CSF oligoclonal bands and IgG index if autoimmune etiology suspected 3

If risk factors present (immunocompromise, endemic exposure):

• CSF fungal studies and TB testing 3
• CSF cytology if malignancy suspected 3

Clinical Context Determines Next Steps

Correlate these findings with the clinical presentation:

• If headache with altered mental status or focal deficits: Consider viral encephalitis and start empiric acyclovir while awaiting HSV PCR 1
• If progressive ascending weakness with areflexia: Consider GBS and arrange electrodiagnostic studies 1
• If immunocompromised: Broader infectious workup including opportunistic pathogens 1
• If recent infection or vaccination: Increases likelihood of post-infectious processes like GBS 1

Common Pitfalls to Avoid

• Do not assume normal glucose excludes all serious pathology - viral encephalitis can be fatal and requires prompt antiviral therapy 1
• Do not delay treatment while awaiting test results if clinical suspicion for HSV encephalitis is high 1, 3
• Do not dismiss the diagnosis of GBS if protein is only mildly elevated - it can be normal early in the disease course 1
• Do not interpret CSF glucose in isolation - always obtain simultaneous plasma glucose 1

1, 3, 2, 4