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Meningitis - Comprehensive Overview

Definition

• Goldman-Cecil Medicine, p. 3997
• Robbins & Kumar Basic Pathology, p. 833

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Classification

• Robbins & Kumar Basic Pathology

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Epidemiology

• Global incidence: ~1.2 million cases per year
• In the US, the leading causes of bacterial meningitis are: S. pneumoniae (58%), Group B Streptococcus (18.1%), N. meningitidis (13.9%), H. influenzae (6.7%), and L. monocytogenes (3.4%)
• Mortality is ~15% in developed countries, with rates unchanged despite antibiotic advances
• Vaccines against Hib, S. pneumoniae, and N. meningitidis have dramatically reduced incidence (now 0.5-1.5 cases/100,000 adults in developed countries)
• S. pneumoniae is now the most common cause, predominating in older adults
• Goldman-Cecil Medicine; Tintinalli's Emergency Medicine

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Pathogens by Age Group

• Bradley and Daroff's Neurology in Clinical Practice; Rosen's Emergency Medicine

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Pathophysiology

1. Bacteria invade bloodstream → cross the blood-brain barrier into the CSF
2. CSF lacks effective host defenses → rapid bacterial proliferation
3. Cytokine release triggers leukocyte infiltration into CSF
4. Inflammatory cascade → increased BBB permeability, cerebral vasculitis
5. Three types of cerebral edema develop:
   • Vasogenic (increased BBB permeability, protein/water entry)
   • Interstitial (hydrocephalus - reduced arachnoid granule absorption)
   • Cytotoxic (disrupted cell membrane homeostasis)
6. Elevated ICP → decreased cerebral blood flow → ischemia/thrombosis
7. Neurons injured by free radicals from granulocytes and endothelial cells

• Tintinalli's Emergency Medicine; Rosen's Emergency Medicine

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Gross Pathology

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Risk Factors

• Acute or chronic otitis media / sinusitis
• Immunosuppression / splenectomy
• Alcoholism
• Diabetes mellitus
• CSF leak (basal skull fracture)
• Endocarditis
• Neurosurgical procedures / head injury
• Close living quarters (N. meningitidis)
• Tintinalli's Emergency Medicine

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Clinical Features

Classic Triad (and Tetrad)

• Fever
• Severe headache (most common; >85% of patients)
• Nuchal rigidity (neck stiffness)
• Altered mental status (tetrad)

Meningeal Signs

Special Populations

• Immunocompromised / elderly: Altered mental status may be the ONLY finding
• Neonates: Bulging fontanelle, behavioral changes, decreased tone (subtle)
• Lower threshold for LP evaluation in these groups

Additional Findings

• Petechiae/purpura: Characteristic of meningococcemia (extremities, but anywhere) - indicates endotoxic shock risk
• Waterhouse-Friderichsen syndrome: Bilateral adrenal hemorrhage from meningococcemia + DIC + purpura
• Cerebral venous thrombosis: ~1% of meningitis cases - manifests as new seizures, focal deficits
• Signs of source infection (otitis media, sinusitis, endocarditis skin lesions)
• Rosen's Emergency Medicine; Bradley and Daroff's Neurology in Clinical Practice

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CSF Findings - Lumbar Puncture

• Hypoglycorrhachia (CSF glucose <40 mg/dL) is the hallmark of bacterial meningitis
• PMN count >1,180 cells/μL has 99% predictive value for bacterial meningitis
• Viral meningitis: lymphocytic pleocytosis, normal glucose - viral neutrophilia shifts to lymphocytic within 2-3 days
• Harrison's Principles of Internal Medicine 22E; Harriet Lane Handbook; Henry's Clinical Diagnosis

Gram Stain Findings by Organism

• Bradley and Daroff's Neurology

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Diagnostic Approach

Blood Tests

• Blood cultures (ideally before antibiotics - but do NOT delay antibiotics)
• CBC with differential, CMP (serum glucose to interpret CSF glucose)
• Procalcitonin: sensitivity ~90%, specificity ~98% for bacterial vs. viral (useful adjunct, not definitive)
• ESR, CRP: elevated but non-diagnostic
• Coagulation studies if anticoagulated

When to CT First (Before LP)?

• Papilledema or absent venous pulsations
• New-onset seizures
• Abnormal level of consciousness
• Focal neurologic deficits

Key principle: Neuroimaging and LP must NOT delay antibiotic administration. Start empiric antibiotics immediately if meningitis is strongly suspected.

MRI

• More sensitive than CT for complications
• Meningeal enhancement with gadolinium (non-specific - indicates increased BBB permeability)
• HSV encephalitis: T2/FLAIR high-signal in temporal lobes within 48h (not seen in bacterial meningitis)
• Rosen's Emergency Medicine

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Treatment

Empiric Antibiotic Therapy

• Vancomycin: 40-60 mg/kg/day q8-12h
• Ceftriaxone: 2g q12h
• Ampicillin: 2g q4h

Dexamethasone (Adjunctive Corticosteroid)

• Give 10 mg IV q6h x 4 days (adults)
• Administer before or with the first dose of antibiotics
• Benefits: reduces mortality and morbidity (especially in S. pneumoniae meningitis), reduces hearing loss and neurologic sequelae in children
• Landmark 2002 RCT (de Gans et al.): dexamethasone significantly improved outcomes; all mortality/morbidity benefits in pneumococcal subgroup
• Can be given up to 4 hours after antibiotic start if not given initially
• Note: Concurrent dexamethasone does NOT significantly reduce CSF vancomycin concentration - serum levels remain proportional to CSF levels
• Bradley and Daroff's Neurology; Tintinalli's Emergency Medicine

Narrowing Therapy

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Complications

• Rosen's Emergency Medicine; Adams and Victor's Neurology

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Viral Meningitis (Aseptic Meningitis)

• Now the most common type of meningitis (vaccines reduced bacterial incidence)
• Causes: Enteroviruses and Herpesviruses (most common); also mumps, HIV
• Clinical: similar symptoms but generally milder
• CSF: lymphocytic pleocytosis, normal glucose, mildly elevated protein
• Prognosis: excellent for the majority
• Treatment: supportive (antivirals for HSV/VZV)

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Tuberculous Meningitis (Chronic Meningitis)

• Subacute/chronic presentation (symptoms developing over weeks/months)
• Symptoms: fever, weight loss, night sweats, malaise ± headache
• Leading cause of chronic meningitis globally due to worldwide endemicity
• CSF: initially modest PMN pleocytosis → rapidly evolves to lymphocytic predominance
• Diagnosis: 20-30 mL CSF for AFB stain and culture; PCR
• 2026 Lancet Infectious Diseases [PMID: 40840485] published a new clinical practice guideline for tuberculous meningitis (Feb 2026)

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Fungal Meningitis

• Often subtle presentation even in healthy adults
• Common in immunocompromised (HIV/AIDS): Cryptococcus neoformans
• Symptoms: headache, low-grade fever, malaise, weight loss
• Diagnosis: India ink, cryptococcal antigen, CSF fungal culture
• Treatment: Amphotericin B + flucytosine (induction), then fluconazole (maintenance)

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Prevention / Vaccination

• Bradley and Daroff's Neurology in Clinical Practice

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Recent Evidence (2024-2026)

• A new clinical practice guideline for tuberculous meningitis was published in Lancet Infectious Diseases (Feb 2026) - [PMID: 40840485] - providing updated recommendations for a disease that remains a major global challenge.
• A systematic review on IgG4-related pachymeningitis (JAMA Neurology, Feb 2025, [PMID: 39556369]) characterized the clinical presentation, investigation findings, and outcomes of this rare autoimmune form.

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