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PA34.1-3 | CNS Infections & Tumors — SDL Guide (Part 3)

Tubercular Meningitis — Histology and Sequelae

Microscopy (histology) of TBM:
• Granuloma — the hallmark histological lesion: central caseous necrosis surrounded by radially arranged epithelioid macrophages (modified histiocytes), Langhans giant cells (horseshoe/peripheral arrangement of nuclei), and outer rim of lymphocytes and plasma cells.
• Acid-fast bacilli (AFB) may be seen with Ziehl–Neelsen (ZN) stain — though yield is low in tissue sections (more reliable in CSF culture/PCR).
• Fibrinous exudate and lymphocytes in subarachnoid space.
• Endarteritis of basal vessels → fibrinoid necrosis → infarcts.

Sequelae and complications:
• Hydrocephalus (most common complication; can be communicating or obstructive from aqueductal stenosis)
• Cranial nerve palsies — CN III, IV, VI, VII, VIII from basal exudate compressing nerves
• Cerebral infarctions — particularly basal ganglia
• Spinal arachnoiditis → cord compression, paraplegia
• SIADH (syndrome of inappropriate ADH secretion) → hyponatraemia
• Paradoxical reaction on anti-TB therapy (IRIS — immune reconstitution inflammatory syndrome)

CSF AFB smear positive in only 10–40%; culture (gold standard) takes 4–8 weeks; PCR and adenosine deaminase (ADA) levels are useful adjuncts in Indian practice.

Histology of Tubercular Granuloma (High Power) — Langhans Giant Cell and Concentric Zones

Fungal Meningitis — Cryptococcal Meningitis

Cryptococcal meningitis is the most important fungal CNS infection and a leading opportunistic infection in HIV/AIDS (CD4 count <100 cells/µL) and other immunocompromised states (organ transplant, lymphoma, high-dose steroids).

Organism: Cryptococcus neoformans — an encapsulated yeast found in soil, bird droppings (especially pigeon). The polysaccharide capsule is its key virulence factor — it inhibits phagocytosis, impairs T-cell responses, and is the target of diagnostic tests (India ink, cryptococcal antigen/CrAg).

Pathogenesis:
• Inhalation → pulmonary infection → haematogenous spread → CNS.
• CNS disease particularly severe because cryptococcal capsule resists immune clearance in a space with limited immune surveillance.
• Soap-bubble lesions (gelatinous pseudocysts) in basal ganglia and grey matter — fungi expand locally with minimal inflammation (in immunosuppressed hosts).

Gross pathology: Brain surface may show minimal exudate (unlike pyogenic). Cut section reveals characteristic 'soap-bubble' or gelatinous pseudocysts in basal ganglia and cerebral cortex — filled with clusters of encapsulated yeasts, minimal host reaction.

Microscopy:
• India ink preparation of CSF — pathognomonic: dark background with clear halo of mucoid capsule around budding yeast cells. Single narrow-based budding distinguishes from Candida (which shows germ tubes/pseudohyphae).
• Mucicarmine stain — stains capsule red/magenta.
• Minimal inflammatory reaction in immunocompromised host.

Cryptococcus neoformans — India Ink CSF Preparation and Mucicarmine Tissue Stain

CSF Interpretation Framework — The Essential Comparison Table

This is the single most examined topic in meningitis pathology. Learn the table; understand the logic behind each parameter.

Logic of each parameter:
• Appearance: turbidity reflects cell count; xanthochromia (yellow) = prior haemorrhage or very high protein; pellicle/cobweb clot on standing = TBM (fibrin threads).
• Opening pressure: raised whenever inflammation is present (pyogenic > tubercular > viral; fungal can be very high).
• Cell count and predominant cell type: The key discriminator — neutrophils = bacteria (including early TB, before granuloma forms); lymphocytes = viral, TB, fungal, partially treated bacterial.
• Protein: elevated in all meningitis; very high in bacterial/TB (breakdown of BBB + exudate protein).
• Glucose: LOW in bacterial/TB/fungal (organisms + neutrophils/macrophages consume glucose); NORMAL in viral (viruses don't metabolise glucose in CSF; lymphocytes do not significantly consume glucose). Always compare with simultaneous blood glucose (CSF glucose <50% of blood glucose = hypoglycorrhachia = pathological).
• Gram stain: positive in ~80% of untreated bacterial meningitis.

Parameter	Normal	Bacterial (Pyogenic)	Viral (Aseptic)	Tubercular	Fungal (Crypto)
Appearance	Crystal clear	Turbid/purulent, cloudy	Clear / mildly turbid	Clear / turbid; cobweb clot	Clear / slightly turbid
Opening pressure	6–20 cm H₂O	Markedly raised	Normal/mildly raised	Moderately raised	Raised (often very high)
Total cells/µL	0–5	1,000–10,000+	10–500	100–500	10–200
Predominant cell	Lymphocytes	Neutrophils (>80%)	Lymphocytes (>80%)	Lymphocytes (mixed early)	Lymphocytes
Protein (mg/dL)	15–45	Very high (>100, up to 500)	Mildly raised (50–100)	High (100–500)	Mildly–moderately raised
Glucose (mg/dL)	50–80 (⅔ of blood)	Very low (<40)	Normal (>50% of blood)	Low (<45)	Low
Glucose ratio	>0.6	<0.4 (often <0.2)	>0.6	<0.5	Low
Special tests	—	Gram stain+; culture; CRP	PCR for virus	ZN/AFB smear; ADA; PCR	India ink; CrAg; culture

Memory hook: "Bacteria eat all the glucose and call all the neutrophils. Viruses are polite — they raise cells a little, never touch the glucose, and call only lymphocytes." TB is in between — lymphocytes, but it does consume glucose.

CSF Tube Appearance and Key Values in the Four Types of Meningitis