How is a lumbar puncture (LP) interpreted?

Interpretation of Lumbar Puncture

Lumbar puncture interpretation requires systematic analysis of CSF appearance, cell counts, protein, glucose, and microbiological studies, with specific patterns distinguishing bacterial, viral, and other etiologies of CNS infection or disease. 1

Initial Visual Assessment

Examine the CSF immediately upon collection for:

• Clarity and color - Normal CSF is clear and colorless; turbidity suggests elevated white blood cells (>200 cells/μL) or protein; xanthochromia (yellow discoloration) indicates subarachnoid hemorrhage or elevated protein 1
• Red blood cells - Distinguish traumatic tap from true subarachnoid hemorrhage by observing if clearing occurs between tubes 1 and 4; approximately 50% of HSV encephalitis cases show elevated RBC count 2, 1

Cell Count Analysis

Normal CSF contains <5 white blood cells/μL 1

Pleocytosis Patterns:

• Neutrophilic predominance (>50% neutrophils) - Strongly suggests bacterial meningitis; requires immediate empiric antibiotics 1
• Lymphocytic predominance - Indicates viral infection, tuberculosis, fungal infection, or partially treated bacterial meningitis 1
• Correcting for traumatic tap: Subtract 1 WBC for every 700 RBCs/μL (some sources use 1:500-1000 ratio) 1, 3

Critical caveat: In approximately 5-10% of adults with proven HSV encephalitis, initial CSF findings may be completely normal, so negative findings do not rule out infection early in disease course 1

Biochemical Analysis

Protein Levels:

• Normal: 15-45 mg/dL
• Elevated protein - Seen in bacterial meningitis (typically >100 mg/dL), viral infections (mild elevation 50-100 mg/dL), and neurodegenerative diseases 2
• In traumatic taps: Expected protein increases by approximately 1 mg/dL for every 1,000 RBCs/μL 3

Glucose Levels:

• Normal CSF glucose: >60% of serum glucose (or >2/3 ratio)
• Low CSF glucose (<40 mg/dL or <50% of serum) - Highly suggestive of bacterial meningitis, tuberculosis, or fungal infection 2
• Glucose remains unchanged by blood contamination in traumatic taps 3

CSF Lactate:

• Values <2 mmol/L help rule out bacterial disease - The Infectious Diseases Society of America recommends this parameter to distinguish bacterial from viral meningitis 1

Microbiological Studies

Perform wet mount examination immediately for:

• Gram stain - Identifies bacterial pathogens in 60-90% of untreated bacterial meningitis cases 1
• Direct visualization - May reveal bacteria, fungi (India ink for Cryptococcus), or other pathogens 1
• Cultures - Bacterial, fungal, and mycobacterial cultures as clinically indicated 2
• PCR testing - Essential for HSV encephalitis diagnosis (sensitivity >95%); also available for enteroviruses, VZV, and other pathogens 2

Common pitfall: Delaying examination of the specimen reduces diagnostic yield; wet mount should be performed immediately 1

Alzheimer's Disease Biomarkers

When evaluating for neurodegenerative disease:

Interpretation Algorithm:

• Reduced Aβ1-42 with elevated tau and p-tau - Strongly supports AD diagnosis; proceed with AD-specific treatment 2
• Reduced Aβ1-42 alone (normal tau/p-tau) - AD possible but less likely; consider CSF reanalysis, check albumin quotient, or add imaging biomarker 2
• Elevated tau/p-tau with normal Aβ1-42 - Consider other neurodegenerative disorders; add Aβ1-40 or imaging biomarkers 2
• All biomarkers normal - AD unlikely as cause of dementia; pursue alternative diagnoses 2
• Values near cut-off points - Inherent 10% analytical variability creates gray zone; repeat analysis or add imaging biomarker 2

Opening Pressure

Normal opening pressure: 10-20 cm H₂O (measured in lateral recumbent position only) 4

• Elevated pressure (>25 cm H₂O) - Suggests increased intracranial pressure, meningitis, or venous sinus thrombosis 2
• Low pressure (<5 cm H₂O) - May indicate CSF leak or prior over-drainage 5

Critical error to avoid: Pressure measurements taken in sitting position are invalid and should not be documented as opening pressure 4

Special Considerations for CNS Infections

The Association of British Neurologists recommends additional testing based on clinical suspicion:

• Viral encephalitis workup - HSV PCR (most critical), enterovirus PCR, VZV serology, HIV testing 2
• Autoimmune encephalitis - Anti-NMDA receptor antibodies, voltage-gated potassium channel antibodies 2
• Fungal/TB meningitis - India ink, cryptococcal antigen, AFB smear and culture, TB PCR 2

Integration with Clinical Context

Interpret CSF findings alongside:

• Clinical presentation - Acute vs. subacute onset, fever, altered mental status, focal neurological signs 2, 1
• Imaging findings - CT/MRI abnormalities in 25-80% of HSV encephalitis cases; almost all with negative initial scan show abnormalities on repeat imaging 2
• Timing of LP - Early in disease course may show normal findings; consider repeat LP if clinical suspicion remains high 1

Most important principle: Begin empiric antimicrobial therapy immediately if bacterial meningitis is suspected; do not delay treatment waiting for CSF results 1