CSF examination in CND infections This is a 10 marks shot answer in MUHS MD pathology exam. Give model answer
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CSF Examination in CNS Infections
MUHS MD Pathology - 10 Marks Model Answer
Introduction
Cerebrospinal fluid (CSF) examination via lumbar puncture is the most important laboratory investigation in diagnosing CNS infections. Normal CSF is clear, colourless, with opening pressure 70-180 mmH₂O, WBC <5 lymphocytes/μL, protein 15-45 mg/dL, and glucose 45-80 mg/dL (CSF:serum glucose ratio >0.6).
Classification of CNS Infections by CSF Pattern
CNS infections are broadly divided into:
- Acute Pyogenic (Bacterial) Meningitis
- Aseptic (Viral) Meningitis
- Chronic Meningitis - Tuberculous, Fungal, Spirochetal
1. Acute Pyogenic (Bacterial) Meningitis
Gross appearance: Turbid/purulent, opalescent, may clot on standing.
CSF Findings:
| Parameter | Finding |
|---|---|
| Opening pressure | Markedly elevated (>180 mmH₂O) in 90% |
| Appearance | Turbid, purulent |
| Cell count | >100-10,000 cells/μL; PMN (neutrophil) predominance |
| Protein | Elevated >45 mg/dL in 90% (often 100-500 mg/dL) |
| Glucose | Decreased <40 mg/dL; CSF:serum glucose ratio <0.4 in ~60% |
| Gram stain | Positive in >60% of untreated cases |
| Culture | Positive in >70% |
Common organisms: Neisseria meningitidis (young adults), S. pneumoniae (elderly), E. coli/Group B Streptococci (neonates), Listeria monocytogenes (immunocompromised/elderly).
Pathology: Neutrophils fill the subarachnoid space; gram stain shows organisms in leptomeningeal exudate. Secondary vasculitis, venous thrombosis, and leptomeningeal fibrosis may follow.
(Robbins & Kumar Basic Pathology, p. 833; Harrison's 22E, p. 1164)
2. Aseptic (Viral) Meningitis
Gross appearance: Clear, water-like ("gin-clear").
CSF Findings:
| Parameter | Finding |
|---|---|
| Opening pressure | Normal or mildly elevated (100-350 mmH₂O) |
| Appearance | Clear |
| Cell count | 25-500 cells/μL; lymphocytic pleocytosis |
| Protein | Normal or mildly elevated (<150 mg/dL) |
| Glucose | Normal (CSF:serum ratio >0.6) |
| Gram stain | Negative |
| Culture | Negative on routine culture |
Special notes:
- In the first 24-48 hours of enteroviral meningitis, PMN predominance (up to 90%) may be seen in ~50% of patients, which shifts to lymphocytes subsequently.
- West Nile Virus meningitis may show PMN predominance persisting >1 week.
- Low CSF glucose with lymphocytosis should raise suspicion for TB, fungal, or Listeria meningoencephalitis rather than viral cause.
- PCR (FilmArray ME panel) is the diagnostic procedure of choice - sensitivity 85-100% for enteroviruses and HSV.
Common organisms: Enteroviruses (80% of cases), HSV-2, mumps, LCMV, arboviruses.
(Harrison's 22E, p. 1170; Robbins & Kumar, p. 834)
3. Tuberculous (Chronic) Meningitis
Gross appearance: Clear or slightly turbid; a characteristic cobweb/pellicle clot may form on standing (due to high fibrinogen content).
CSF Findings:
| Parameter | Finding |
|---|---|
| Opening pressure | Elevated |
| Appearance | Clear/faintly turbid; pellicle/cobweb clot |
| Cell count | Lymphocytic pleocytosis (10-500 cells/μL); mixed early |
| Protein | Markedly elevated, 1-5 g/L (100-500 mg/dL) |
| Glucose | Decreased (20-40 mg/dL); mild-to-moderate reduction |
| AFB smear | Positive in only 10-40% of adults |
| Culture | Positive ~50%; gold standard; takes 4-8 weeks |
| Nucleic acid | Xpert MTB/RIF Ultra for rapid detection |
Pathology: Chronic meningitis leads to arachnoid fibrosis at the base of the brain and hydrocephalus. Tuberculomas (intraparenchymal granulomas) may coexist.
(Harrison's 22E, p. 1170; Robbins & Kumar, p. 833)
4. Fungal Meningitis
Gross appearance: Clear or slightly turbid.
CSF Findings:
| Parameter | Finding |
|---|---|
| Cell count | Mononuclear/lymphocytic pleocytosis |
| Protein | Elevated |
| Glucose | Decreased |
| India ink | Encapsulated budding yeast cells (Cryptococcus) |
| Cryptococcal antigen | Highly sensitive and specific - diagnostic |
| Eosinophils | May be present in Coccidioides immitis meningitis |
Key test: Cryptococcal polysaccharide antigen test in CSF (highly sensitive and specific) - a positive result establishes the diagnosis.
(Harrison's 22E, p. 1170; Medical Microbiology 9e)
5. Syphilitic (Spirochetal) Meningitis
CSF Findings:
- Lymphocytic or mononuclear pleocytosis
- Elevated protein
- CSF VDRL: highly specific (when positive), but low sensitivity (~30-70%)
- Diagnosis confirmed by reactive serum FTA-ABS or MHA-TP combined with CSF pleocytosis
Comparative Summary Table
| Parameter | Bacterial | Viral | TB | Fungal |
|---|---|---|---|---|
| Appearance | Turbid/Purulent | Clear | Clear ± pellicle | Clear |
| Pressure | ↑↑↑ | Normal/↑ | ↑ | ↑ |
| WBC type | PMNs | Lymphocytes | Lymphocytes | Lymphocytes |
| WBC count | 100-10,000 | 25-500 | 10-500 | 10-500 |
| Protein | ↑↑ (100-500 mg/dL) | Normal/mild ↑ | ↑↑ (100-500 mg/dL) | ↑ |
| Glucose | ↓↓ (CSF:serum <0.4) | Normal | ↓ (mild-mod) | ↓ |
| Gram stain | Positive >60% | Negative | Negative | Negative |
| Special test | Culture/PCR/Gram | PCR (BioFire) | AFB smear/culture/Xpert | India ink/Ag test |
Gross Appearance - Pyogenic Meningitis
The image below (Robbins & Kumar, Fig. 21.16) shows a thick suppurative exudate covering the brain stem and leptomeninges in acute pyogenic meningitis:
Additional Investigations on CSF
- Opening pressure measurement before fluid collection
- Cell count and differential - centrifuge and examine
- Biochemistry - glucose (with simultaneous blood glucose), protein, lactate
- Microbiology - Gram stain, AFB smear, India ink (for Cryptococcus), ZN stain
- Culture - aerobic, anaerobic, fungal, mycobacterial
- Serology/Antigen tests - Cryptococcal antigen, VDRL, Lyme serology
- Molecular - PCR (FilmArray ME panel for 14 pathogens; Xpert MTB/RIF Ultra)
- Cytology - to exclude malignant/neoplastic meningitis
Key Exam Points to Remember:
- Bacterial meningitis = PMN pleocytosis + low glucose + high protein + turbid CSF
- Viral meningitis = lymphocytic pleocytosis + normal glucose + clear CSF
- TB meningitis = lymphocytic + markedly elevated protein + mild-moderate glucose drop + pellicle + low AFB smear sensitivity (10-40%)
- Fungal meningitis = lymphocytic + low glucose + India ink / Cryptococcal antigen positive
- CSF:serum glucose ratio <0.4 is highly suggestive of bacterial but also seen in TB/fungal/carcinomatous meningitis
Sources: Robbins & Kumar Basic Pathology 10e; Harrison's Principles of Internal Medicine 22E; Medical Microbiology 9e
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