CSF Test Reference Table
The clinical neurology CSF panel has expanded enormously beyond the classic four — opening pressure, cell count, glucose, protein. Modern CSF analysis includes microbiology, PCR multiplex panels, antibody panels for autoimmune and paraneoplastic syndromes, AD biomarkers (Aβ42/40, p-tau, t-tau), prion biomarkers (14-3-3, RT-QuIC), oligoclonal bands, IgG index, kappa free light chains, cytology, flow cytometry, neopterin, lactate, and many others. This page is the comprehensive reference table — every clinically useful CSF test, what it measures, normal range, when to order, and clinical interpretation — so you can match the right test to the right clinical question.
🔹 Bottom Line: Comprehensive CSF Testing
- Opening pressure normal range ≈ 6–25 cm H₂O in lateral decubitus — interpret with age, body habitus, and technique. IIH threshold >25 cm H₂O.
- Routine panel: cells (count + diff), glucose, protein, lactate. These four resolve most bedside questions.
- Inflammation / MS: oligoclonal bands + IgG index (or kappa free light chains) — supportive for MS but not diagnostic alone.
- Microbiology: Gram stain + culture + BioFire ME multiplex PCR + cryptococcal antigen + Xpert MTB/RIF Ultra for TB.
- Autoimmune encephalitis: send the antibody panel in both CSF and serum (cell-based assays); CSF more sensitive for anti-NMDAR.
- Neurodegeneration: AD biomarkers (Aβ42/40 ratio, p-tau, t-tau); RT-QuIC for prion disease; α-synuclein SAA for synucleinopathies.
- Use the search box below to filter the table by test name, disease, or finding.
Reference Table — Comprehensive CSF Tests
Showing all tests
| Test | What it measures | Normal value / threshold | When to order | Interpretation |
|---|---|---|---|---|
| Routine Panel | ||||
| Opening pressure | CSF hydrostatic pressure | ~6–25 cm H₂O (adult, lateral decubitus) | Every LP performed lateral decubitus | ↑↑ in IIH (>25 cm H₂O), meningitis, mass; ↓ in spontaneous intracranial hypotension / CSF leak. Interpret with age, body habitus, technique. |
| Appearance | Visual inspection | Clear, colorless | Every LP | Cloudy → ↑ WBC, RBC, protein, microbes. Xanthochromic → bilirubin (SAH 6+ hours) |
| WBC count | White cell count + differential | ≤5/µL; lymphocyte/monocyte predominance | Every LP | Pleocytosis (count + differential pattern) drives infectious vs inflammatory differential |
| RBC count | Red cell count tubes 1 and 4 | 0 (atraumatic tap) | Every LP | RBC drop tube 1→4 = traumatic tap; stable = true blood / SAH |
| Glucose | CSF glucose vs simultaneous serum | 50–80 mg/dL; CSF:serum ratio ≥0.6 | Every LP | Low in bacterial / TB / cryptococcal meningitis; low in leptomeningeal carcinomatosis; normal in viral / autoimmune / MS |
| Protein | Total CSF protein | 15–45 mg/dL; rises with age | Every LP | Markedly elevated in TB meningitis, GBS (albuminocytologic dissociation), CIDP, paraproteinemic neuropathy, carcinomatosis |
| Inflammation / Demyelination | ||||
| Oligoclonal bands (OCB) | Isoelectric focusing for unique CSF IgG bands | 0 unique CSF bands | Suspected MS, neurosyphilis, chronic CNS infection | ≥2 unique CSF bands not in serum supports MS (~95% sensitive); also positive in neurosyphilis, SSPE, autoimmune encephalitis |
| IgG index | (CSF IgG / serum IgG) / (CSF albumin / serum albumin) | ≤0.66 | Suspected intrathecal IgG synthesis | Elevated supports inflammatory CNS disease; not specific for MS |
| Kappa free light chains (kFLC) | Free kappa light chains in CSF | Lab-specific cutoff | MS workup, alternative to OCB | Elevated in MS; emerging marker; faster turnaround than OCB |
| Albumin (CSF and serum) | For Q-albumin (CSF/serum albumin ratio) | Q-albumin: lab and age-dependent (~5×10⁻³ in young adults) | BBB integrity assessment | ↑ Q-albumin = BBB dysfunction (inflammation, infection) |
| Lactate | CSF lactate concentration | <2.2 mmol/L | Suspected bacterial meningitis | ↑↑ in bacterial meningitis (often >3.5); normal in viral; useful when antibiotics started before LP |
| Neopterin | Pteridine — marker of cellular immune activation | Lab-specific | Suspected CNS inflammation, especially in immunocompromised | Elevated in viral / inflammatory / neoplastic CNS disease; not specific |
| Microbiology (Bacterial / Fungal) | ||||
| Gram stain | Microscopic bacterial identification | No organisms | Suspected meningitis | Sensitive ~60–90% in bacterial meningitis; lower if antibiotics started |
| Bacterial culture | Standard culture | No growth | Suspected meningitis | Gold standard but slow (24–72 hours) |
| Multiplex PCR panel (e.g., FilmArray ME) | PCR for common pathogens | Negative | Suspected meningitis / encephalitis | Rapid (~1 hour); covers Strep pneumo, N. meningitidis, H. flu, L. monocytogenes, HSV, VZV, CMV, EBV, enterovirus, HHV-6, parechovirus, Cryptococcus |
| AFB stain (Ziehl-Neelsen) | Acid-fast bacilli | Negative | Suspected TB meningitis | Low yield (~10–20%) |
| TB culture | Mycobacterial culture | No growth | Suspected TB meningitis | Gold standard but takes weeks; large volume CSF (5+ mL) improves yield |
| Xpert MTB/RIF (TB PCR) | Real-time PCR for M. tuberculosis + rifampin resistance | Negative | Suspected TB meningitis | Faster than culture; sensitivity moderate; rifampin resistance detection |
| Cryptococcal antigen (lateral flow) | Capsular polysaccharide | Negative | Suspected cryptococcal meningitis | Highly sensitive and specific; preferred over India ink |
| India ink | Negative stain for encapsulated yeast | Negative | Suspected cryptococcal meningitis | Less sensitive than antigen testing |
| Fungal cultures | Sabouraud agar etc. | No growth | Suspected fungal meningitis | Slow; large volume helps |
| ADA (adenosine deaminase) | Enzyme elevated in TB | <10 U/L | Adjunct in TB meningitis workup | Supportive; not specific |
| VDRL (CSF) | Non-treponemal antibody | Negative | Suspected neurosyphilis | Specific (positive diagnostic) but insensitive (~50%) |
| FTA-ABS (CSF) | Treponemal antibody | Negative | Suspected neurosyphilis | Sensitive; negative excludes; positive supports |
| Borrelia antibody index | Intrathecal Borrelia antibody production | <1.3 (lab-dependent) | Suspected Lyme neuroborreliosis | Elevated supports active CNS Lyme |
| Viral / Other Microbial PCR | ||||
| HSV-1/HSV-2 PCR | HSV DNA | Negative | Suspected HSV encephalitis | Highly sensitive after 24–48 hours; gold standard |
| VZV PCR | Varicella zoster DNA | Negative | Suspected VZV encephalitis / vasculopathy | Useful but sensitivity moderate; serum/CSF antibody index may help |
| EBV / CMV / HHV-6 PCR | Viral DNA | Negative | Immunocompromised patient with encephalitis | Quantitative results help interpretation; EBV positive in PCNSL but also reactivation |
| Enterovirus PCR | RNA detection | Negative | Suspected viral meningitis (especially summer/fall) | Most common cause of viral meningitis |
| JC virus PCR | JCV DNA | Negative | Suspected PML | Quantitative; clinical correlation with MRI essential |
| West Nile, EEE, La Crosse IgM | Virus-specific IgM in CSF | Negative | Suspected arboviral encephalitis | CSF IgM more useful than PCR (CSF viral load low) |
| HIV RNA / DNA | HIV in CSF | Negative or undetectable | HIV-related CNS disease workup | CSF/plasma viral load discordance can indicate CNS escape |
| Rabies (antigen, PCR, antibody) | Multiple modalities | Negative | Suspected rabies | Antemortem diagnosis difficult; consider in unexplained progressive encephalitis with exposure |
| Autoimmune Encephalitis / Paraneoplastic Antibody Panel | ||||
| Anti-NMDA receptor antibody | Cell-surface antibody | Negative | Suspected anti-NMDA encephalitis | CSF MORE sensitive than serum; sometimes serum negative |
| Anti-LGI1, anti-CASPR2 | Cell-surface antibodies (VGKC complex) | Negative | Limbic encephalitis, faciobrachial dystonic seizures | Serum testing often sufficient |
| Anti-GAD65 | Intracellular antigen, high titer in autoimmune cases | Negative or low titer | Limbic encephalitis, cerebellar ataxia, stiff-person spectrum | High titer (>100x normal) typically required for autoimmune attribution |
| Anti-Hu, Yo, Ri, Ma2, CV2, amphiphysin (paraneoplastic panel) | Intracellular antibodies | Negative | Subacute paraneoplastic syndromes | Onconeural antibodies → tumor screen; serum testing typically sufficient |
| Anti-AMPA receptor, GABA-B receptor, DPPX | Cell-surface antibodies | Negative | Autoimmune encephalitis | Comprehensive panel essential when clinical suspicion high |
| Anti-GFAP | Glial fibrillary acidic protein antibodies | Negative | Suspected autoimmune meningoencephalitis | Specific GFAP astrocytopathy syndrome |
| Neurodegenerative Disease Biomarkers | ||||
| Aβ42 | Amyloid-β 42 peptide | Lab-specific cutoff | AD biomarker confirmation | Reduced in AD (sequestered into plaques) |
| Aβ42/Aβ40 ratio | Ratio more reliable than Aβ42 alone | Lab-specific | AD biomarker confirmation (standard for anti-amyloid therapy eligibility) | Reduced ratio confirms amyloid pathology |
| Phospho-tau 181 (p-tau181) | Tau phosphorylated at threonine 181 | Lab-specific | AD biomarker | Elevated in AD; more specific than t-tau alone |
| Total tau (t-tau) | Total tau protein | Lab-specific | AD biomarker, CJD adjunct | Elevated in AD; markedly elevated (>1,200 pg/mL) in CJD |
| Neurofilament light chain (NfL) | Axonal damage marker | Lab-specific | Multiple neurodegenerative and inflammatory diseases | Elevated in ALS, FTD, MS, CIDP, AD; non-specific marker of axonal injury |
| 14-3-3 protein | Marker of rapid neuronal injury | Negative | Suspected CJD | Sensitive ~85% for CJD but non-specific (also HSV encephalitis, stroke, anoxia) |
| RT-QuIC (real-time quaking-induced conversion) | Detects misfolded prion protein | Negative | Suspected CJD | Specificity >98%, sensitivity ~90% for sporadic CJD; new diagnostic gold standard during life |
| α-synuclein SAA (RT-QuIC) | Detects misfolded α-synuclein via amplification | Negative | Suspected PD/DLB/MSA where biological confirmation would change management; expert centers | Available clinically in the US through CLIA labs (LDT); not equivalent to a routine FDA-cleared assay. FDA Letter of Support for trial enrichment. Distinct kinetic patterns help separate PD/DLB from MSA. |
| NSE (neuron-specific enolase) | Neuronal injury marker | Lab-specific | CJD, post-arrest prognostication (serum), neuroendocrine tumors | Supportive; non-specific |
| Hematologic / Neoplastic | ||||
| Cytology | Microscopic identification of malignant cells | No malignant cells | Suspected leptomeningeal carcinomatosis or CNS lymphoma | Specific but low single-sample sensitivity (~50%); repeat 2–3 LPs |
| Flow cytometry | Cell-surface marker analysis for lymphoma | No clonal population | Suspected CNS lymphoma | More sensitive than cytology for lymphoma; can identify clonal B/T cell populations |
| Cell block / immunohistochemistry | Histologic processing of CSF cells | No malignant cells | When cytology equivocal | Subspecialty hematopathology |
| β2-microglobulin | Marker of lymphocyte / lymphoma activity | Lab-specific | CNS lymphoma adjunct | Elevated in PCNSL, neuroinflammatory diseases; not specific |
| EBV PCR | EBV DNA in CSF | Negative | HIV-related PCNSL | Often positive in HIV-associated CNS lymphoma |
| Metabolic / Endocrine | ||||
| Lactate | CSF lactate | <2.2 mmol/L | Mitochondrial disease, ischemia, bacterial meningitis | Elevated in mitochondrial disease (MELAS); bacterial meningitis |
| Pyruvate | CSF pyruvate | Lab-specific | Mitochondrial disease | Lactate:pyruvate ratio in inborn errors of metabolism |
| Glycine | CSF glycine | Lab-specific | Non-ketotic hyperglycinemia | Markedly elevated in glycine encephalopathy |
| Neurotransmitter metabolites (HVA, 5-HIAA) | Dopamine and serotonin metabolites | Age-specific | Suspected neurotransmitter disorder | Diagnostic for AADC deficiency, BH4 deficiency, others; sample handling critical |
| Folate metabolites | 5-MTHF in CSF | Age-specific | Suspected cerebral folate deficiency | Reduced in cerebral folate deficiency syndromes |
| Tetrahydrobiopterin (BH4) | Cofactor for monoamine synthesis | Age-specific | Suspected BH4 deficiency | Reduced in cofactor disorders |
| Specialized Tests | ||||
| Hypocretin-1 (orexin) | Hypothalamic peptide | >200 pg/mL normal | Suspected narcolepsy type 1 | <110 pg/mL highly specific for narcolepsy type 1 |
| Anti-AQP4 / MOG (CSF) | NMOSD / MOGAD antibodies | Negative | Suspected NMOSD/MOGAD when serum negative | Serum testing standard; CSF rarely positive when serum negative |
| Galactocerebrosidase, etc. | Lysosomal enzymes | Age-specific | Suspected lysosomal storage disease | Now largely replaced by genetic testing |
| Pyridoxal phosphate | Active vitamin B6 form | Age-specific | Pyridoxine-dependent / pyridoxal phosphate-responsive epilepsy | Reduced in pyridoxine-dependent epilepsy variants |
| Spectrophotometry for xanthochromia | Quantitative bilirubin/oxyhemoglobin | Negative | Delayed SAH workup (>6 hours after onset) | More sensitive than visual xanthochromia assessment |
🔹 Clinical Relevance: α-Synuclein SAA — Emerging, Not Yet Standard
CSF α-synuclein seed amplification assays (SAA, sometimes called α-synuclein RT-QuIC) amplify a tiny misfolded-α-synuclein seed and have sensitivity ~87–96% and specificity >90% for Parkinson disease, with distinct kinetic patterns separating PD/DLB from MSA. They can be positive in prodromal disease (e.g., isolated RBD) before motor symptoms appear.
Regulatory reality: α-syn SAA is not FDA-cleared as a routine clinical IVD. It is clinically available in the US through specialized CLIA laboratory-developed tests (e.g., Mayo, Amprion), and the FDA has issued a Letter of Support for its use as a trial-enrichment biomarker. It is an emerging tool in expert centers — not a substitute for clinical diagnosis everywhere.
- Consider in atypical parkinsonism where the PD vs MSA vs DLB distinction would change management.
- Consider in isolated RBD if biomarker confirmation supports clinical-trial enrollment.
- Don’t frame as standard office testing in routine PD diagnosis.
Practical Notes on Ordering CSF Tests
- Volume needed: total ~10–20 mL safely removable in adults; specific tests may need 1–5 mL each — plan tube assignment with the lab.
- Send a saved aliquot: every LP should reserve a frozen aliquot for additional testing if the initial differential narrows. Repeat LPs are not always feasible.
- Process promptly: cell counts within 1 hour (cells deteriorate); cytology within several hours; many other tests are stable when refrigerated or frozen.
- Tube assignment: confirm with your lab — tube 1 vs tube 3 etc. matters for some assays.
- Specialty referral labs: many antibody panels and biomarker assays require send-out to reference laboratories (Mayo, Athena, Quest Brentwood, ARUP). Turnaround can be 1–4 weeks.
- Pretreatment with antibiotics: substantially reduces yield of Gram stain and culture but PCR (multiplex panels) often remain positive for 24–48 hours after antibiotic initiation.
- Order based on differential: don’t shotgun test everything; align tests with the leading clinical hypotheses.
Pitfalls and Pearls
- Plan tube assignments before LP: lab requirements vary; reserve a saved aliquot.
- Cell counts within 1 hour: cells lyse with delay.
- Match tests to differential: don’t shotgun; targeted testing better.
- Glucose: always interpret with simultaneous serum glucose; ratio more reliable than absolute value.
- OCB: ≥2 unique CSF bands not in serum; sensitive for MS but not specific.
- kFLC: emerging MS biomarker; faster turnaround.
- Multiplex PCR panels: rapid (~1 hour); cover most common causes; first-line for suspected meningitis/encephalitis.
- HSV PCR: highly sensitive after 24–48 hours; start empirical acyclovir, don’t wait.
- Autoimmune encephalitis: send both serum AND CSF; CSF more sensitive for anti-NMDA receptor.
- RT-QuIC: >98% specific for sporadic CJD; α-synuclein SAA emerging for synucleinopathies.
- AD CSF biomarkers: Aβ42/40 ratio + p-tau + t-tau; confirms amyloid before anti-amyloid therapy.
- Hypocretin-1 <110 pg/mL: highly specific for narcolepsy type 1.
- Lactate: useful for bacterial vs viral meningitis distinction; also mitochondrial disease.
- Cytology: low single-sample sensitivity; repeat LPs increase yield.
- Flow cytometry: more sensitive than cytology for lymphoma.
- Cryptococcal antigen: highly sensitive; preferred over India ink.
- TB workup: AFB + Xpert + culture + ADA + large-volume CSF.
- Antibiotics started before LP: Gram stain / culture yield reduced; PCR often still positive.
- NfL: non-specific axonal injury marker; useful for tracking ALS, MS, dementia progression.
References
- Engelborghs S, Niemantsverdriet E, Struyfs H, et al. Consensus guidelines for lumbar puncture in patients with neurological diseases. Alzheimers Dement (Amst). 2017;8:111-126.
- Graus F, Titulaer MJ, Balu R, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 2016;15(4):391-404.
- Hermann P, Appleby B, Brandel JP, et al. Biomarkers and diagnostic guidelines for sporadic Creutzfeldt-Jakob disease. Lancet Neurol. 2021;20(3):235-246.
- Jack CR Jr, Andrews JS, Beach TG, et al. Revised criteria for diagnosis and staging of Alzheimer’s disease. Nat Med. 2024;30(8):2121-2129.
- Siderowf A, Concha-Marambio L, Lafontant DE, et al. Assessment of heterogeneity among participants in the Parkinson’s Progression Markers Initiative cohort using α-synuclein seed amplification: a cross-sectional study. Lancet Neurol. 2023;22(5):407-417.
- Leitão MJ, Silva-Spínola A, Santana I, et al. Clinical validation of the Lumipulse G cerebrospinal fluid assays for routine diagnosis of Alzheimer’s disease. Alzheimers Res Ther. 2019;11(1):91.
- Mayo Clinic Laboratories. SAAmplify-alphaSYN (CSF) test notification — clarifies CLIA/LDT status and that the test has not been FDA-cleared or approved.