CSF analysis is among the most clinically informative tests in neurology because each disease leaves a recognizable fingerprint — bacterial meningitis with polymorphonuclear pleocytosis and low glucose; viral encephalitis with lymphocytic pleocytosis; tuberculous meningitis with lymphocytes, low glucose, and very high protein; MS with normal counts but oligoclonal bands; CJD with positive 14-3-3 and RT-QuIC; autoimmune encephalitis with antibody panels in CSF. This page is the unified clinical-pattern reference: the typical CSF findings, the supporting molecular and antibody studies, and the distinguishing features across the major neurologic diseases.
🔹 Bottom Line: CSF Findings Across Diseases
- Bacterial meningitis: PMN pleocytosis (often >1000), low glucose, very elevated protein, high lactate (>3.5 mmol/L). Gram stain + culture + BioFire ME panel.
- Viral / aseptic: lymphocytic pleocytosis (usually <500), normal glucose, mildly elevated protein, normal lactate. Enterovirus / HSV / VZV PCR.
- Tuberculous: lymphocytes, low glucose, very high protein (often >500), Xpert MTB/RIF Ultra + large-volume culture (≥6 mL).
- Cryptococcal: low-grade pleocytosis (may be normal in advanced HIV), low glucose; CSF cryptococcal antigen (CrAg) >95% sensitive.
- MS: normal cell count, oligoclonal bands + elevated IgG index (or kappa free light chains) — supports diagnosis, doesn’t make it alone.
- CJD: RT-QuIC (specificity >98%) is the modern bedside diagnostic; 14-3-3 is sensitive but non-specific (also positive in HSV encephalitis, anoxic injury, stroke).
- Autoimmune encephalitis: send antibody panels in both CSF and serum — CSF is more sensitive for anti-NMDAR.
Meningitis
Bacterial Meningitis
| Parameter |
Typical finding |
| Opening pressure |
Elevated (often >30 cm H₂O) |
| Appearance |
Cloudy / turbid |
| WBC |
Markedly elevated, often 1,000–10,000/µL |
| Differential |
Polymorphonuclear (neutrophil) predominance |
| Glucose |
Low (CSF:serum ratio <0.4) |
| Protein |
Markedly elevated (often >100 mg/dL, sometimes >500) |
| Lactate |
Elevated (>3.5 mmol/L typical) |
| Gram stain |
Positive in 60–90% |
| Culture |
Diagnostic gold standard |
| PCR / multiplex panel |
Increasingly used (FilmArray ME panel) |
Viral (Aseptic) Meningitis
| Parameter |
Typical finding |
| Opening pressure |
Normal to mildly elevated |
| WBC |
10–500/µL |
| Differential |
Lymphocytic predominance (neutrophils may dominate in first 24 hours) |
| Glucose |
Normal (CSF:serum >0.5) |
| Protein |
Normal to mildly elevated (50–100 mg/dL) |
| Lactate |
Normal |
| PCR |
Enterovirus, HSV, VZV, EBV, CMV, HIV, JC virus, West Nile |
Tuberculous Meningitis
| Parameter |
Typical finding |
| Opening pressure |
Often elevated |
| WBC |
50–500/µL |
| Differential |
Lymphocytic (early may be neutrophilic) |
| Glucose |
Low (CSF:serum <0.5) |
| Protein |
Very elevated (100–500+ mg/dL) |
| AFB smear |
Low yield (10–20%) |
| Culture |
Gold standard but slow (weeks) |
| PCR (Xpert MTB/RIF) |
Faster turnaround |
| ADA (adenosine deaminase) |
Often elevated; supportive |
Cryptococcal Meningitis
| Parameter |
Typical finding |
| Opening pressure |
Often markedly elevated |
| WBC |
Variable (often 20–500/µL); low in advanced HIV |
| Differential |
Lymphocytic |
| Glucose |
Low |
| Protein |
Elevated |
| Cryptococcal antigen |
Highly sensitive and specific (lateral flow assay) |
| India ink |
Classic but less sensitive than antigen testing |
| Culture |
Confirmatory |
Fungal Meningitis (Other)
- Coccidioides: serology + culture; eosinophilic pleocytosis common.
- Histoplasma: antigen testing in CSF and urine.
- Candida: usually with intracranial device or immunosuppression.
- Aspergillus: rare, immunocompromised.
Side-by-Side Comparison — Bacterial vs Viral vs Tuberculous vs Cryptococcal Meningitis
The four classic meningitis syndromes have overlapping clinical presentations (fever, headache, neck stiffness, altered mental status), and CSF analysis is the single most decisive test for differentiation. The pattern of opening pressure, cell count and predominance, glucose, protein, and the right confirmatory test usually identifies the cause within hours and drives empiric therapy. Memorize this table — it is one of the highest-yield reference points in clinical neurology.
| Parameter |
Bacterial |
Viral (Aseptic) |
Tuberculous |
Cryptococcal |
| Appearance |
Cloudy / turbid / purulent |
Clear |
Clear or slightly cloudy; fibrin web (“cobweb”) on standing |
Clear; occasionally cloudy |
| Opening pressure |
↑↑ (often 20–50 cm H₂O) |
Normal to mildly ↑ |
↑ (commonly 20–40 cm H₂O) |
↑↑↑ — frequently >25 cm H₂O; serial LPs often needed to manage |
| WBC count (cells/μL) |
1,000–10,000+ (often >500) |
10–500 (rarely >1,000) |
50–500 |
20–500; often low or normal in advanced HIV |
| Cell predominance |
Neutrophils (PMN, >80%) |
Lymphocytes (PMN possible in first 24–48 h) |
Lymphocytes (PMN possible early) |
Lymphocytes |
| Glucose (mg/dL) |
Low (<40), often very low |
Normal (40–80) |
Low (often <40) |
Low to normal |
| CSF / serum glucose ratio |
<0.4 (often <0.3) |
≥0.6 (normal) |
<0.5 |
Often <0.5 |
| Protein (mg/dL) |
↑↑ (often >100, can exceed 500) |
Normal to mildly ↑ (50–100) |
↑↑ (100–500+; very high suggests TB) |
Mildly to moderately ↑ |
| Lactate |
↑↑ (>3.5 mmol/L) — useful to distinguish bacterial from viral when WBC is mixed |
Normal |
Often mildly ↑ |
Variable |
| Confirmatory test |
Gram stain (60–90% sensitivity); culture; multiplex PCR (BioFire ME panel) |
Enterovirus, HSV, VZV, arbovirus PCR; serology |
AFB smear (low sensitivity); Xpert MTB/RIF Ultra (preferred); culture; ADA |
Cryptococcal antigen (CrAg) — >95% sensitive; India ink (~75%); culture |
| Other helpful clues |
Blood cultures often positive; procalcitonin ↑; petechial rash (meningococcus); CSF lactate >3.5 mmol/L |
Peripheral lymphocytosis; rash, mumps parotitis, hand-foot-mouth, encephalitic features may localize |
Subacute course; basal meningeal enhancement; cranial neuropathies (esp. CN VI, VII); hydrocephalus; hyponatremia (SIADH); known TB exposure / HIV |
Advanced HIV (CD4 <100) or other immunosuppression; subacute onset; raised ICP common; serum CrAg also positive |
| Empiric treatment |
IV ceftriaxone + vancomycin + dexamethasone; add ampicillin if >50 yr or immunocompromised (Listeria) |
Supportive; acyclovir if HSV/VZV suspected pending PCR |
RIPE (rifampin, isoniazid, pyrazinamide, ethambutol) + adjunctive corticosteroids |
Induction: liposomal amphotericin B + flucytosine; consolidation + maintenance fluconazole; serial therapeutic LPs for ↑ICP |
| Time course |
Hours to 1–2 days (acute) |
1–7 days (subacute) |
Weeks (subacute / chronic) |
Weeks (subacute / chronic) |
| Mortality / morbidity (untreated) |
Very high; medical emergency |
Generally low; mostly self-limited |
High; long-term neurologic deficits common |
High; raised ICP a major driver of mortality |
Key practical points:
- Bacterial vs viral when WBC is mixed: CSF lactate >3.5 mmol/L and very low CSF/serum glucose ratio (<0.4) strongly favor bacterial; procalcitonin ↑ supports bacterial.
- “Partially treated” bacterial meningitis (antibiotics before LP) may have lower WBC, shift toward lymphocytes, milder glucose drop, and negative Gram stain — but lactate often remains elevated and BioFire multiplex PCR can still identify the organism.
- TB meningitis is easy to miss: subacute course, lymphocytic predominance, basal meningitis on imaging; send Xpert MTB/RIF Ultra and large-volume CSF culture (≥6 mL ideal) when clinically suspected. Empiric RIPE while awaiting results is appropriate in high-suspicion cases.
- Cryptococcal meningitis: pleocytosis may be absent in advanced HIV, so a “normal” cell count does NOT rule it out. Send CrAg (CSF and serum) in any immunosuppressed patient with new headache or encephalopathy. Pressure-management with serial LPs is as important as antifungal therapy.
- The classical CSF profile may be incomplete or overlap: do not anchor on a single value. The full constellation — appearance, cell count and predominance, glucose, protein, lactate, opening pressure, clinical course — drives the diagnosis.
Encephalitis
Herpes Simplex Encephalitis (HSV-1)
| Parameter |
Typical finding |
| WBC |
Lymphocytic pleocytosis (10–500/µL) |
| RBC |
May be elevated (hemorrhagic encephalitis) |
| Glucose |
Normal |
| Protein |
Mildly to moderately elevated |
| HSV PCR |
Highly sensitive after 24–48 hours of symptoms; gold standard |
Empirical acyclovir should be started for any suspected HSV encephalitis; do not delay treatment waiting for PCR results.
Other Viral Encephalitides
- VZV, EBV, CMV, enterovirus: PCR testing.
- JC virus (PML): PCR; quantitative assays.
- West Nile, eastern equine, La Crosse: PCR + serology (IgM in CSF most useful).
- Rabies: brain biopsy / antigen detection.
Autoimmune Encephalitis
| Parameter |
Typical finding |
| WBC |
Lymphocytic pleocytosis (often mild, 5–100/µL); may be normal |
| Protein |
Normal to mildly elevated |
| Glucose |
Normal |
| Antibody panel |
Send both serum AND CSF; CSF more sensitive for anti-NMDA receptor encephalitis |
| OCB |
May be positive |
Specific antibodies covered in the dedicated Autoimmune Encephalitis Antibodies page; send a comprehensive panel including cell-surface (NMDA, LGI1, CASPR2, GAD65, DPPX, AMPA, GABA-B) and intracellular (anti-Hu, Yo, Ri, Ma2, CV2) targets when clinical suspicion is high.
Demyelinating and Inflammatory CNS Disease
Multiple Sclerosis
| Parameter |
Typical finding |
| WBC |
Normal or mild lymphocytic pleocytosis (typically <50/µL) |
| Protein |
Normal to mildly elevated |
| Glucose |
Normal |
| Oligoclonal bands (OCB) |
≥2 unique CSF bands not present in serum — supports MS diagnosis (positive in ~95% of MS); satisfies “dissemination in time” criterion in 2017 McDonald revision |
| IgG index |
Elevated (>0.66) |
| Kappa free light chains |
Elevated; emerging as an alternative or adjunct to OCB |
OCB are sensitive but not specific — also seen in neurosyphilis, SSPE, chronic CNS infections, autoimmune encephalitis, and other chronic inflammatory CNS conditions.
NMOSD (Neuromyelitis Optica Spectrum Disorder)
| Parameter |
Typical finding |
| WBC |
Often elevated during acute relapse (sometimes >100/µL with neutrophilic component — distinguishes from MS) |
| Protein |
Often markedly elevated |
| OCB |
Usually negative (<20%) — useful for distinguishing from MS |
| AQP4-IgG |
Serum-based testing is standard (cell-based assays); CSF testing sometimes useful when serum equivocal |
MOGAD (MOG Antibody-Associated Disease)
| Parameter |
Typical finding |
| WBC |
Variable, often lymphocytic |
| Protein |
Often elevated |
| OCB |
Variable |
| MOG-IgG |
Serum cell-based assay; titer matters (high-positive more specific); low-positive results need clinical context |
ADEM (Acute Disseminated Encephalomyelitis)
- Lymphocytic pleocytosis; protein often elevated; glucose normal.
- OCB usually negative or transient.
- Check MOG-IgG (subset is MOG-associated).
Neurosarcoidosis
- Lymphocytic pleocytosis; protein elevated; glucose may be low.
- ACE may be elevated in CSF (poor sensitivity/specificity alone).
- OCB may be present.
- Diagnosis usually requires biopsy of accessible non-CNS site + supportive imaging.
Subarachnoid Hemorrhage (SAH)
| Time after bleed |
CSF findings |
| 0–2 hours |
RBC present; xanthochromia not yet |
| 6–12 hours |
RBC stable across tubes; xanthochromia develops (oxyhemoglobin → bilirubin) |
| 1–2 weeks |
Xanthochromia persists; WBC may increase as inflammatory response develops |
| 2–4 weeks |
Xanthochromia clears; CSF returns to baseline |
Modern workflow: non-contrast CT within 6 hours of headache onset is nearly 100% sensitive for SAH — LP is reserved for delayed presentations or equivocal CT. Spectrophotometric xanthochromia is more sensitive than visual assessment.
Prion Disease (CJD)
| Test |
Role |
| Routine CSF (cells, protein, glucose) |
Usually normal (rules out other diseases) |
| 14-3-3 protein |
Sensitivity ~85%, specificity moderate; non-specific marker of rapid neuronal injury (also positive in HSV encephalitis, stroke, anoxia) |
| RT-QuIC (real-time quaking-induced conversion) |
Highly specific (>98%) and sensitive (~90%) for sporadic CJD; has become the diagnostic gold standard during life |
| Total tau |
Markedly elevated (often >1,200 pg/mL); supportive |
| Neuron-specific enolase (NSE) |
Elevated; supportive but non-specific |
🔹 Clinical Relevance: RT-QuIC Has Replaced 14-3-3 for Antemortem CJD Diagnosis
14-3-3 protein is sensitive but non-specific — also elevated in HSV encephalitis, anoxic brain injury, and acute stroke — and on its own can mislead. CSF RT-QuIC detects misfolded prion protein itself via amplification, with specificity >98% and sensitivity ~90% for sporadic CJD. A positive RT-QuIC in a patient with rapidly progressive dementia, myoclonus, and supportive EEG/MRI features (cortical ribboning on DWI, pulvinar sign in variant CJD) is essentially diagnostic during life — a result that used to require brain biopsy or autopsy.
- Send CSF RT-QuIC in any rapidly progressive dementia, especially with ataxia, myoclonus, or visual disturbance.
- Don’t anchor on isolated 14-3-3 positivity — interpret in clinical context and confirm with RT-QuIC.
- The same protein-amplification approach is now diagnostic for synucleinopathies (α-synuclein SAA) and is emerging for tau and Aβ.
Neurodegenerative Disease (AD Biomarkers)
| Marker |
Pattern in AD |
| Aβ42 (alone or as ratio) |
Reduced (sequestered into plaques) |
| Aβ42/Aβ40 ratio |
Reduced — more reliable than Aβ42 alone; standard biomarker confirmation under 2024 NIA-AA criteria |
| Total tau (t-tau) |
Elevated |
| Phospho-tau (p-tau181) |
Elevated |
| Combined profile |
Low Aβ42/40 + high p-tau confirms amyloid pathology + neurodegeneration — supports AD diagnosis under modern criteria |
CSF biomarkers are now used to confirm amyloid pathology before initiating anti-amyloid antibody therapy (lecanemab, donanemab) in early symptomatic AD.
Paraneoplastic Syndromes
- Variable CSF: lymphocytic pleocytosis often; protein normal to mildly elevated; glucose normal.
- OCB may be positive.
- Specific antibody testing in CSF + serum (see Paraneoplastic Antibodies page): anti-Hu, anti-Yo, anti-Ri, anti-Ma2, anti-CV2, anti-amphiphysin.
- Tumor workup parallel to antibody testing.
Neurosyphilis
| Parameter |
Typical finding |
| WBC |
Lymphocytic pleocytosis (5–500/µL) |
| Protein |
Elevated |
| Glucose |
Usually normal |
| CSF VDRL |
Specific but insensitive (~50%); positive CSF VDRL is diagnostic |
| CSF FTA-ABS |
Sensitive but not specific (negative excludes; positive supports but does not confirm) |
| OCB |
Often positive |
Lyme Neuroborreliosis
- Lymphocytic pleocytosis; protein elevated; glucose normal.
- Intrathecal Borrelia antibody production (CSF:serum antibody index) supports diagnosis.
- PCR less sensitive than serology.
CNS Leptomeningeal Carcinomatosis and Lymphoma
| Parameter |
Typical finding |
| Opening pressure |
Often elevated |
| WBC |
Variable; lymphocytic predominance |
| Glucose |
Often low |
| Protein |
Often very elevated |
| Cytology |
Diagnostic but low single-sample sensitivity (~50%); repeat LPs increase yield |
| Flow cytometry |
Highly sensitive for lymphoma (especially primary CNS lymphoma) |
Idiopathic Intracranial Hypertension (IIH)
- Opening pressure >25 cm H₂O in adults (or >28 cm H₂O in children >1 year).
- Otherwise normal CSF (cells, protein, glucose).
- Normal imaging (no mass, no hydrocephalus, slit ventricles, empty sella, optic nerve sheath distension).
- Therapeutic CSF removal can transiently improve symptoms.
Spontaneous Intracranial Hypotension
- Opening pressure low (often <6 cm H₂O; sometimes unrecordable).
- CSF composition usually normal.
- Image with MR brain (pachymeningeal enhancement, sagging brainstem) + spine to identify leak.
Quick Comparison Table — Common CSF Profiles
| Disease |
WBC (count, type) |
Glucose |
Protein |
Distinctive marker |
| Bacterial meningitis |
1,000–10,000, PMN |
Low |
>100 |
Gram stain, culture, lactate ↑↑ |
| Viral meningitis |
10–500, lymph |
Normal |
50–100 |
Enterovirus / HSV PCR |
| TB meningitis |
50–500, lymph |
Low |
100–500+ |
AFB / Xpert / ADA |
| Cryptococcal |
20–500, lymph (low in HIV) |
Low |
Elevated |
Cryptococcal antigen |
| HSV encephalitis |
10–500, lymph (± RBC) |
Normal |
Mild–mod elevated |
HSV PCR |
| MS |
0–50, lymph |
Normal |
Normal–mild ↑ |
OCB, IgG index, kFLC |
| NMOSD |
Often >50, mixed |
Normal |
Often ↑↑ |
AQP4-IgG (serum); OCB usually neg |
| Autoimmune encephalitis |
5–100, lymph |
Normal |
Mild ↑ |
Antibody panel (CSF + serum) |
| CJD |
Normal |
Normal |
Normal |
RT-QuIC, 14-3-3, t-tau ↑↑ |
| SAH (delayed) |
RBC stable across tubes |
Normal |
↑ from blood |
Xanthochromia |
| Leptomeningeal carcinomatosis |
Variable |
Low |
↑↑ |
Cytology, flow cytometry |
| Neurosyphilis |
5–500, lymph |
Normal |
Elevated |
CSF VDRL +, FTA-ABS |
| Lyme neuroborreliosis |
Lymph pleocytosis |
Normal |
Elevated |
Intrathecal Borrelia antibody index |
| IIH |
Normal |
Normal |
Normal |
Opening pressure >25 |
| SIH (CSF leak) |
Normal |
Normal |
Normal |
Opening pressure <6 |
Pitfalls and Pearls
- Bacterial meningitis: PMN pleocytosis + low glucose + elevated protein + elevated lactate; Gram stain + culture + multiplex PCR.
- Viral meningitis: lymphocytic pleocytosis + normal glucose; PCR for enterovirus, HSV, VZV, EBV, CMV.
- TB meningitis: lymphocytic + low glucose + very high protein; AFB / Xpert / ADA.
- Cryptococcal antigen: highly sensitive; lateral flow assay; more reliable than India ink.
- HSV encephalitis: HSV PCR after 24–48 hours; start empirical acyclovir, do not wait.
- Autoimmune encephalitis: send both serum AND CSF; CSF more sensitive for anti-NMDA receptor.
- MS: OCB ≥2 unique CSF bands + IgG index; kFLC emerging.
- OCB are sensitive but not specific: also in neurosyphilis, SSPE, chronic infection.
- NMOSD: AQP4-IgG serum testing; OCB usually negative (helps distinguish from MS).
- MOGAD: MOG-IgG serum; high-positive more specific than low-positive.
- CJD: RT-QuIC >98% specific; 14-3-3 less specific.
- AD biomarkers: Aβ42/40 ratio + p-tau181 + t-tau; confirms amyloid pathology before anti-amyloid therapy.
- Neurosyphilis: CSF VDRL specific (positive diagnostic) but insensitive (~50%); FTA-ABS sensitive.
- Leptomeningeal carcinomatosis: cytology low single-sample sensitivity; repeat LPs; flow cytometry for lymphoma.
- SAH: CT within 6 hours nearly 100% sensitive; LP for delayed presentations.
- Xanthochromia: appears 6–12 hours after SAH; spectrophotometry > visual.
- IIH vs SIH: opening pressure >25 vs <6; both with otherwise normal CSF.
- Always send a saved aliquot when LP is technically difficult — repeat LP may not be feasible.
References
- Bhatti MT, Tariq M. Cerebrospinal fluid analysis. Continuum (Minneap Minn). 2018;24(2):422-440.
- van de Beek D, Brouwer M, Hasbun R, et al. Community-acquired bacterial meningitis. Nat Rev Dis Primers. 2016;2:16074.
- Thompson AJ, Banwell BL, Barkhof F, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018;17(2):162-173.
- Wingerchuk DM, Banwell B, Bennett JL, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology. 2015;85(2):177-189.
- 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.
