Chronic and Recurrent Meningitis¶
Chapter 144 | Part 5: Infectious Diseases
KEY CLINICAL POINTS¶
- Chronic meningitis is defined by persistent neurologic symptoms (>4 weeks) with CSF inflammation (WBC >5/ µ L) and requires differentiation from acute or recurrent forms.
- Infectious causes include bacterial (e.g., TB, syphilis), fungal (e.g., Cryptococcus), viral (e.g., HSV), and parasitic agents, while non-infectious causes include malignancy, autoimmune disorders, and chemical meningitis.
- CSF analysis (cell count, glucose, protein, Gram stain, PCR) and imaging (MRI/CT) are critical for diagnosis, with meningeal enhancement patterns distinguishing leptomeningeal vs. pachymeningeal inflammation.
1. DEFINITION & OVERVIEW¶
Chronic meningitis refers to prolonged inflammation of the meninges (pia, arachnoid, dura) lasting >4 weeks, often with neurologic disability. Recurrent meningitis involves discrete episodes of inflammation. Key features include headache, cranial neuropathies, cognitive decline, and CSF pleocytosis.
Table 144-1: Symptoms and Signs of Chronic Meningitis¶
| SYMPTOM | SIGN |
|---|---|
| Chronic headache | ± Papilledema |
| Neck/back pain/stiffness | Brudzinski’s/Kernig’s sign |
| Change in personality | Altered mental status |
| Facial weakness | Peripheral seventh CN paresis |
| Double vision | Paresis of CNs III, IV, and/or VI |
| Diminished vision | Papilledema, CN II (optic atrophy/inflammation) |
| Hearing loss | Eighth CN paresis |
| Arm/leg weakness | Myelopathy/radiculopathy |
| Numbness in arms/legs | Myelopathy/radiculopathy |
| Urinary retention/incontinence | Frontal lobe dysfunction (hydrocephalus) |
| Clumsiness | Ataxia |
1.1 Clinical Manifestations¶
Persistent headache, hydrocephalus signs (papilledema, vomiting), cranial neuropathies (e.g., CN II-VI), myelopathy, and cognitive changes. Spinal meningitis may present with radiculopathy, incontinence, or arachnoiditis.
1.2 CSF Findings¶
Mononuclear pleocytosis (common), low glucose, high protein. Eosinophilia may suggest parasitic/fungal causes. PCR and cultures are essential for pathogen identification.
2. EPIDEMIOLOGY¶
Incidence varies by etiology: TB and cryptococcal meningitis are common in immunocompromised patients (e.g., HIV). Fungal infections (e.g., coccidioidomycosis, histoplasmosis) are endemic in specific regions. Recurrent meningitis may indicate autoinflammatory syndromes (e.g., CAPS, TRAPS).
2.1 Risk Factors¶
Immunosuppression (HIV, TB, cancer), travel to endemic regions (e.g., San Joaquin Valley for coccidioidomycosis), IV drug use, and exposure to ticks/arthropods (Lyme disease).
3. ETIOLOGY & PATHOPHYSIOLOGY¶
Infectious causes include bacterial (TB, syphilis), fungal (Cryptococcus, Histoplasma), viral (HSV, enteroviruses), and parasitic agents. Non-infectious causes include malignancy (lymphoma, sarcoma), autoimmune disorders (sarcoidosis, SLE), and chemical meningitis (epidermoid tumors).
Table 144-2: Infectious Causes of Chronic Meningitis¶
| CAUSATIVE AGENT | CSF FORMULA | HELPFUL DIAGNOSTIC TESTS | RISK FACTORS AND SYSTEMIC MANIFESTATIONS |
|---|---|---|---|
| Mycobacterium tuberculosis | Mononuclear cells (early: <500 WBC/mL); low glucose; high protein | Tuberculin skin test, PCR, AFB culture | Exposure history, immunosuppression, TB history |
| Syphilis (T. pallidum) | Mononuclear cells; elevated protein | CSF VDRL, FTA-ABS, RPR | HIV-seropositive, fever, lymphadenopathy, mucocutaneous rash |
| Cryptococcus neoformans | Mononuclear cells (not elevated in AIDS) | India ink stain, cryptococcal antigen | AIDS, pigeon exposure, disseminated infection |
| HSV-2 (Mollaret’s meningitis) | Large endothelial cells fi mononuclear cells | PCR, MRI/CT for epidermoid tumors | Recurrent episodes, rare HSV-1 cases |
| Lyme disease (Bannwarth’s syndrome) | Mononuclear cells; elevated protein | Serum Lyme antibody, western blot | Tick bite, arthritis, Bell’s palsy |
3.1 Pathogenic Mechanisms¶
Inflammatory exudate accumulates at the base of the brain, causing cranial neuropathies. Fungal/parasitic agents may form granulomas or abscesses. Autoimmune disorders involve vasculitis or lymphocytic infiltration.
4. CLINICAL FEATURES¶
Symptoms include persistent headache, cranial neuropathies (CN II-VI), cognitive decline, and myelopathy. Spinal meningitis may present with radiculopathy, incontinence, or arachyonditis. Systemic manifestations (e.g., fever, rash) may precede neurological symptoms.
4.1 Complications¶
Hydrocephalus, brain abscesses, myelopathy, and neurologic disability. Recurrent episodes may indicate autoinflammatory disorders or malignancy.
5. DIFFERENTIAL DIAGNOSIS¶
Infectious: TB, syphilis, fungal infections. Non-infectious: malignancy (lymphoma, sarcoma), autoimmune disorders (sarcoidosis, SLE), chemical meningitis (epidermoid tumors), and drug hypersensitivity.
5.1 Key Differentiators¶
Eosinophilia suggests parasitic/fungal causes. Mononuclear pleocytosis is common in TB, cryptococcal, or autoimmune diseases. Neutrophilic pleocytosis may indicate Nocardia, Actinomyces, or bacterial infections.
6. INVESTIGATIONS & DIAGNOSIS¶
CSF analysis (cell count, glucose, protein, Gram stain, PCR) and imaging (MRI/CT for meningeal enhancement). Diagnostic tests include VDRL for syphilis, cryptococcal antigen, and fungal cultures. Lumbar puncture is contraindicated in elevated ICP.
Table 144-3: Noninfectious Causes of Chronic Meningitis¶
| CAUSATIVE AGENTS | CSF FORMULA | HELPFUL DIAGNOSTIC TESTS | RISK FACTORS AND SYSTEMIC MANIFESTATIONS |
|---|---|---|---|
| CNS sarcoidosis | Mononuclear cells; elevated protein | Serum/CSF ACE, biopsy | CN palsies, diabetes insipidus, abnormal chest X-ray |
| Behçet’s syndrome | Mononuclear/PMNs; elevated protein | Anti-ANCA, PCR for HSV | Oral/genital ulcers, iridocyclitis, pathergic lesions |
| IgG4-related disease | Mild lymphocytic pleocytosis | Serum IgG4, ESR, MRI | Headache, dural involvement, orbital/brainstem lesions |
| Carcinomatous meningitis | Mononuclear cells | Cytology, flow cytometry | Metastatic cancer, lymphoma, leukemia |
| Drug hypersensitivity | PMNs/eosinophils | CBC, drug history | NSAIDs, sulfonamides, penicillin, carbamazepine |
6.1 Diagnostic Algorithms¶
- Measure CSF pressure and send for bacterial/fungal/mycobacterial cultures. 2. Perform PCR for HSV, TB, fungal species. 3. Use imaging to identify meningeal enhancement patterns (leptomeningeal vs. pachymeningeal). 4. Repeat CSF sampling if initial results are inconclusive.
7. MANAGEMENT & TREATMENT¶
Antimicrobial therapy (e.g., TB: rifampin, isoniazid; cryptococcal: amphotericin B, flucytosine). Corticosteroids for autoimmune/inflammatory causes. Surgical drainage for abscesses or shunts for hydrocephalus. Monitoring includes repeat CSF analysis and imaging.
8. PROGNOSIS & COMPLICATIONS¶
Prognosis varies by etiology: TB/cryptococcal meningitis may be fatal without treatment. Autoimmune disorders may respond to immunosuppression. Recurrent episodes suggest underlying malignancy or autoinflammatory syndromes.
9. SPECIAL CONSIDERATIONS¶
Pregnancy: Avoid certain antifungals (e.g., amphotericin B). Pediatrics: Suspect TB, fungal infections, or autoimmune disorders. Elderly: Higher risk of TB, fungal infections, and drug hypersensitivity. Immunocompromised: Prioritize TB, cryptococcal, and opportunistic infections.
10. KEY POINTS & CLINICAL PEARLS¶
- Chronic meningitis requires CSF analysis and imaging to differentiate infectious vs. non-infectious causes. 2. Eosinophilia suggests parasitic/fungal etiologies. 3. Recurrent episodes may indicate autoinflammatory syndromes or malignancy. 4. Lumbar puncture is contraindicated in elevated ICP. 5. PCR and metagenomic sequencing improve diagnostic accuracy.