Lumbar Puncture Reference Guide¶
Purpose¶
This reference provides comprehensive CSF study recommendations organized by: 1. Core studies - Always order for any diagnostic LP 2. Diagnosis-specific panels - Tailored to clinical suspicion 3. Advanced testing - Newer molecular and genomic options 4. Special procedures - Therapeutic LPs (NPH, IIH)
CORE STUDIES (Always Order)¶
These studies should be sent with every diagnostic LP to maximize yield from a single procedure.
| Study | Tube | Volume | Rationale | Normal Values |
|---|---|---|---|---|
| Opening pressure | - | - | Elevated in IIH, meningitis, mass effect | 10-20 cm H2O |
| Cell count with differential | Tube 1 AND Tube 4 | 1-2 mL each | Tube 4 corrects for traumatic tap | WBC <5, RBC 0 |
| Protein | Tube 2 | 1 mL | Elevated in infection, GBS, tumor, inflammation | 15-45 mg/dL |
| Glucose | Tube 2 | 1 mL | Low in bacterial/fungal/carcinomatous meningitis | 50-80 mg/dL (>60% serum) |
| Gram stain | Tube 3 | 1 mL | Rapid bacterial identification | No organisms |
| Bacterial culture | Tube 3 | 2-3 mL | Gold standard for bacterial meningitis | No growth |
CRITICAL: Always send serum glucose at time of LP to calculate CSF:serum ratio.
Tube order matters: Tubes 1-4 should be collected and labeled sequentially. Cell count on both Tube 1 and Tube 4 helps distinguish traumatic tap (RBCs decrease tube 1→4) from true hemorrhage (RBCs stable).
DIAGNOSIS-SPECIFIC PANELS¶
Meningitis/Encephalitis Panel¶
| Study | Priority | Indication | Turnaround | Notes |
|---|---|---|---|---|
| BioFire FilmArray ME Panel | URGENT | Suspected bacterial/viral/fungal meningitis | ~1 hour | 14 pathogens; 94% sensitivity, 99.8% specificity |
| HSV-1/2 PCR | URGENT | Encephalitis, temporal lobe involvement | 24-48h | Most common treatable cause of encephalitis |
| VZV PCR | URGENT | Zoster history, dermatomal symptoms | 24-48h | Can cause vasculopathy |
| Enterovirus PCR | URGENT | Summer/fall, aseptic meningitis | 24-48h | Most common viral meningitis |
| Cryptococcal antigen | URGENT | Immunocompromised, HIV | 1-2h | More sensitive than India ink |
| AFB smear and culture | ROUTINE | TB risk factors, chronic meningitis | Smear 24h; culture 6-8 weeks | Low sensitivity; consider TB PCR |
| Fungal culture | ROUTINE | Immunocompromised, endemic areas | 4-6 weeks | Hold for extended incubation |
BioFire FilmArray ME Panel Targets (14 pathogens):
| Bacteria | Viruses | Yeast |
|---|---|---|
| E. coli K1 | HSV-1, HSV-2 | Cryptococcus neoformans/gattii |
| H. influenzae | VZV | |
| L. monocytogenes | CMV | |
| N. meningitidis | Enterovirus | |
| S. pneumoniae | HHV-6 | |
| S. agalactiae | Human parechovirus |
Multiple Sclerosis / Demyelinating Disease Panel¶
| Study | Priority | Indication | Target Finding |
|---|---|---|---|
| Oligoclonal bands (CSF + serum) | ROUTINE | MS diagnosis, CIS evaluation | ≥2 CSF-specific bands |
| IgG index | ROUTINE | Intrathecal antibody synthesis | >0.7 elevated |
| Myelin basic protein | ROUTINE | Acute demyelination | Elevated during relapse |
| CSF cytology | ROUTINE | Rule out lymphoma/carcinomatous | Negative |
| NMO-IgG (AQP4-Ab) | ROUTINE | Longitudinal myelitis, severe ON | Positive → NMOSD |
| MOG-IgG | ROUTINE | Atypical features, ADEM-like | Positive → MOGAD |
Autoimmune/Inflammatory Encephalitis Panel¶
| Study | Priority | Indication | Target Finding |
|---|---|---|---|
| Autoimmune encephalitis panel (Mayo/Quest) | ROUTINE | Limbic encephalitis, new-onset seizures, psychiatric symptoms | Anti-NMDAR, LGI1, CASPR2, GABA-B, AMPA |
| Paraneoplastic panel | ROUTINE | Subacute onset, smoking, weight loss | Anti-Hu, Yo, CV2, amphiphysin, etc. |
| Cytology | ROUTINE | Rule out carcinomatous meningitis | Negative |
Note: Send paired serum for autoimmune panels - some antibodies better detected in serum vs CSF.
Subarachnoid Hemorrhage Panel¶
| Study | Priority | Timing | Target Finding |
|---|---|---|---|
| Cell count Tube 1 vs Tube 4 | STAT | Immediate | Stable RBCs = true SAH; decreasing = traumatic |
| Xanthochromia (visual + spectrophotometry) | STAT | ≥6-12h from symptom onset | Yellow supernatant = prior hemorrhage |
| Bilirubin (CSF) | URGENT | ≥12h from symptom onset | Elevated = hemoglobin breakdown |
Timing critical: Xanthochromia may not be present if LP done <6 hours from symptom onset. If initial CT and LP negative but high clinical suspicion, consider repeat LP at 12h or CTA.
Guillain-Barré Syndrome Panel¶
| Study | Priority | Timing | Target Finding |
|---|---|---|---|
| Protein | URGENT | May be normal in first week | Elevated (albuminocytologic dissociation) |
| Cell count | URGENT | Diagnosis | WBC <10 (if >50, reconsider diagnosis) |
| Glucose | ROUTINE | Rule out infection | Normal |
| Cytology | ROUTINE | Rule out carcinomatous | Negative |
| GQ1b antibody (serum) | ROUTINE | Miller Fisher variant | Positive |
Note: CSF protein may be normal in first 1-2 weeks of GBS. Clinical diagnosis may precede CSF abnormalities.
Carcinomatous/Lymphomatous Meningitis Panel¶
| Study | Priority | Volume Needed | Target Finding |
|---|---|---|---|
| Cytology | URGENT | 10-20 mL (large volume) | Malignant cells |
| Flow cytometry | URGENT | 5-10 mL | Clonal B or T cells |
| Protein | ROUTINE | Standard | Often markedly elevated |
| Glucose | ROUTINE | Standard | Often low |
| LDH | ROUTINE | Standard | Elevated |
Volume matters: Sensitivity of cytology increases with CSF volume. If first cytology negative and high suspicion, repeat LP with large volume (10-20 mL) and rapid transport (<1 hour to lab).
Normal Pressure Hydrocephalus (Therapeutic LP)¶
| Parameter | Value | Notes |
|---|---|---|
| Volume to remove | 30-50 mL | Therapeutic trial |
| Opening pressure | <24 cm H2O (by definition) | Document precisely |
| Pre-LP gait assessment | Timed 10m walk, TUG test | Perform within 2h before LP |
| Post-LP gait assessment | Repeat at 1h, 2h, 24h, 72h | >20% improvement = positive |
| Core studies | Standard panel | Rule out other pathology |
Positive response: ≥20% improvement in gait speed or Timed Up-and-Go (TUG) suggests shunt-responsive NPH.
Idiopathic Intracranial Hypertension (IIH) - Therapeutic LP¶
| Parameter | Value | Notes |
|---|---|---|
| Opening pressure | >25 cm H2O | Diagnostic criterion |
| Volume to remove | Until OP <20 cm H2O | Therapeutic goal |
| CSF composition | Must be normal | Abnormal CSF excludes IIH |
| Patient position | Lateral decubitus, legs extended | Standardize measurement |
ADVANCED MOLECULAR TESTING¶
Metagenomic Next-Generation Sequencing (mNGS)¶
Delve Detect (CSF mNGS) - UCSF-developed, commercially available
| Feature | Details |
|---|---|
| Pathogens detected | >68,000 bacteria, viruses, fungi, parasites |
| Sample volume | 1-2 mL CSF |
| Turnaround time | 48 hours |
| Sensitivity | 63% (higher than all other direct tests combined) |
| Specificity | 99.6% |
| Best use case | Culture-negative meningitis/encephalitis, immunocompromised, prior antibiotics |
| Limitations | Expensive (~$2,000), may not be covered by insurance, interpretation requires expertise |
When to order mNGS: - Conventional workup negative but high clinical suspicion - Immunocompromised patient with CNS infection - Patient received antibiotics before LP - Suspected rare or unusual pathogen
When NOT to order mNGS: - Undifferentiated fever without CNS signs - Routine bacterial meningitis where conventional tests adequate - As first-line test (order alongside, not instead of, conventional studies)
CSF Cell-Free DNA for CNS Tumors¶
MSK-IMPACT, Foundation Medicine, institutional assays
| Feature | Details |
|---|---|
| Indication | Suspected CNS malignancy, leptomeningeal metastases |
| Detection rate | 53% of CNS tumors with clinically documented disease |
| Best yield | Disseminated/leptomeningeal disease, glioblastoma |
| Turnaround time | 2-3 weeks |
| Sample volume | 3-5 mL CSF |
CSF cfDNA provides: - Molecular diagnosis when biopsy not feasible - Identification of actionable mutations (EGFR, IDH, BRAF) - Monitoring treatment response - Detection of resistance mutations
When to consider: - Suspected CNS tumor in surgically inaccessible location - Monitoring known leptomeningeal disease - Suspected tumor progression on imaging - CSF cytology negative but high suspicion
SPECIAL HANDLING REQUIREMENTS¶
| Study | Temperature | Time Sensitivity | Special Instructions |
|---|---|---|---|
| Cell count | Room temp | <1 hour | Process immediately; cells lyse over time |
| Glucose | On ice | <1 hour | Glycolysis continues ex vivo |
| Gram stain/culture | Room temp | <2 hours | Never refrigerate |
| Viral PCR | 4°C or frozen | <24h if refrigerated | Can freeze at -70°C for later testing |
| Cytology | Room temp | <1 hour | Rapid transport critical for cell preservation |
| Oligoclonal bands | 4°C | Stable several days | Send paired serum |
| mNGS | Room temp <6h; 4°C <7d | Per lab protocol | Contact lab for frozen specimen requirements |
CONTRAINDICATIONS TO LP¶
Absolute Contraindications¶
| Contraindication | Rationale | Action |
|---|---|---|
| Infection at LP site | Risk of introducing infection | Choose alternate site or defer |
| Uncorrected coagulopathy (INR >1.5, platelets <50K) | Bleeding risk | Correct first; consider hematology consult |
Relative Contraindications (Require CT First)¶
| Clinical Feature | Concern | Management |
|---|---|---|
| Papilledema | Elevated ICP, risk of herniation | CT head before LP |
| Focal neurologic deficit | Mass lesion | CT head before LP |
| Altered consciousness | Mass lesion, elevated ICP | CT head before LP |
| Immunocompromised with new neuro symptoms | Opportunistic mass lesion | CT head before LP |
| History of CNS mass or shunt | Altered CSF dynamics | CT head before LP; neurosurgery consult |
QUICK REFERENCE: VOLUME REQUIREMENTS¶
| Clinical Scenario | Minimum Total Volume | Tube Distribution |
|---|---|---|
| Standard diagnostic LP | 10-15 mL | Tubes 1-4 (3-4 mL each) |
| Suspected infection (with BioFire/mNGS) | 15-20 mL | Extra for molecular testing |
| Suspected malignancy | 20-30 mL | Large volume for cytology |
| Therapeutic LP (NPH) | 30-50 mL | Serial collection until OP normalizes |
| Therapeutic LP (IIH) | Until OP <20 cm H2O | May require 20-40 mL |
CHANGE LOG¶
v1.0 (January 13, 2026) - Initial creation - Added BioFire FilmArray ME Panel (14 pathogens, ~1 hour turnaround) - Added Delve Detect mNGS (>68,000 pathogens, 48h turnaround) - Added CSF cfDNA for CNS tumor diagnosis - Added NPH and IIH therapeutic LP protocols - Comprehensive diagnosis-specific panels