Makindo Medical Notes

Introduction

Chronic and recurrent meningitis refers to inflammation of the meninges that persists for more than four weeks (chronic) or symptoms that recur after initial resolution (recurrent). Unlike acute meningitis, which develops rapidly over hours to days, chronic meningitis progresses more slowly and may present with intermittent symptoms. This condition poses diagnostic challenges and requires thorough investigation to identify the underlying cause. Immunocompromised patients are particularly at risk, but it can also occur in immunocompetent individuals.

Etiology: infectious and non-infectious etiologies.

• Infectious Causes:
  • Mycobacterial Infections: Mycobacterium tuberculosis is a leading cause worldwide.
  • Fungal Infections: Such as Cryptococcus neoformans, especially in immunocompromised patients (e.g., HIV/AIDS).
  • Spirochetes:
    • Treponema pallidum (Neurosyphilis).
    • Borrelia burgdorferi (Lyme disease).
  • Chronic Bacterial Infections:
    • Brucella species.
    • Nocardia species.
    • Chronic sinusitis or otitis leading to recurrent meningitis.
  • Viral Infections: Persistent infections like HIV, or reactivation of latent viruses.
  • Parasitic Infections: Such as cysticercosis caused by Taenia solium.
• Non-Infectious Causes:
  • Autoimmune and Inflammatory Diseases:
    • Sarcoidosis (neurosarcoidosis).
    • Systemic lupus erythematosus (SLE).
    • Vasculitis (e.g., primary angiitis of the CNS).
  • Neoplastic Causes:
    • Carcinomatous meningitis due to metastasis (e.g., breast, lung cancers).
    • Leukemia or lymphoma infiltration of the meninges.
  • Chemical Meningitis:
    • Response to intrathecal medications or substances.
    • Leakage of cerebrospinal fluid (CSF) due to trauma or surgery.
  • Congenital or Anatomical Defects:
    • Dermal sinuses or fistulas connecting skin to the subarachnoid space.
    • Cerebrospinal fluid leaks.

Clinical Presentation

• General Symptoms:
  • Persistent or intermittent headache.
  • Fever, often low-grade.
  • Malaise and fatigue.
  • Weight loss (especially in TB or neoplastic causes).
• Meningeal Signs:
  • Nuchal rigidity (neck stiffness).
  • Photophobia (sensitivity to light).
  • Phonophobia (sensitivity to sound).
• Neurological Symptoms:
  • Cranial nerve palsies (especially cranial nerves III, VI, and VII).
  • Seizures.
  • Altered mental status or encephalopathy.
  • Focal neurological deficits.
• Associated Conditions:
  • Signs of chronic sinusitis or otitis media.
  • History of skull fracture or neurosurgery.
  • Evidence of systemic diseases (e.g., skin lesions in sarcoidosis).
  • Immunosuppression (e.g., HIV infection, immunosuppressive therapy).

Investigations

• Laboratory Tests:
  • Blood Tests: Complete blood count (CBC), urea and electrolytes (U&E), liver function tests (LFTs), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR).
  • Inflammatory Markers: Elevated CRP and ESR may indicate ongoing inflammation.
  • Serological Tests:
    • HIV testing.
    • Syphilis serology (VDRL, FTA-ABS).
    • Lyme disease antibodies.
    • Autoimmune markers (ANA, ANCA, ACE levels for sarcoidosis).
  • Blood Cultures: To detect bacteremia or fungemia.
• Cerebrospinal Fluid (CSF) Analysis:
  • Obtain via lumbar puncture unless contraindicated.
  • Opening Pressure: May be elevated.
  • Cell Count: Elevated white cell count (pleocytosis), often lymphocytic.
  • Protein: Elevated CSF protein levels.
  • Glucose: Low or normal CSF glucose; CSF-to-blood glucose ratio decreased.
  • Microbiological Studies:
    • Gram stain and bacterial cultures.
    • Acid-fast bacilli (AFB) stain and culture for TB.
    • Fungal stains and cultures (e.g., India ink for Cryptococcus).
    • Viral PCR assays.
  • CSF Serology: VDRL, cryptococcal antigen testing.
  • CSF Cytology: To detect malignant cells in suspected neoplastic meningitis.
• Imaging Studies:
  • Magnetic Resonance Imaging (MRI):
    • Preferred over CT for better visualization of meningeal enhancement, hydrocephalus, infarcts.
    • May show leptomeningeal enhancement, tuberculomas, or neoplastic lesions.
  • Computed Tomography (CT) Scan:
    • Used when MRI is contraindicated.
    • CT of chest, abdomen, pelvis (CT CAP) to identify primary malignancies or tuberculosis foci.
  • Positron Emission Tomography (PET) Scan: May be useful in detecting systemic malignancies or inflammatory processes.
• Additional Tests:
  • Biopsy: Of lymph nodes, skin lesions, or meningeal tissue when indicated.
  • Electroencephalogram (EEG): If seizures are present.
  • Ophthalmologic Examination: To detect uveitis or optic neuritis associated with sarcoidosis or vasculitis.

Management: depends on cause

• Infectious Causes:
  • Tuberculous Meningitis: Prolonged antituberculous therapy (e.g., isoniazid, rifampicin, pyrazinamide, ethambutol) plus corticosteroids to reduce inflammation.
  • Fungal Infections: Antifungal agents such as amphotericin B, flucytosine, or fluconazole for cryptococcal meningitis.
  • Antibiotic Therapy: Tailored based on culture and sensitivity results for bacterial infections.
  • Antiviral Therapy: For viral etiologies if specific treatments are available (e.g., antiretroviral therapy for HIV).
• Non-Infectious Causes:
  • Autoimmune and Inflammatory Conditions:
    • Corticosteroids to reduce inflammation (e.g., prednisone).
    • Immunosuppressive agents such as methotrexate, azathioprine, or cyclophosphamide for refractory cases.
  • Neoplastic Meningitis:
    • Intrathecal chemotherapy (e.g., methotrexate, cytarabine).
    • Systemic chemotherapy or targeted therapy based on the primary malignancy.
    • Radiation therapy for localized control.
  • Symptomatic Management:
    • Analgesics for headache relief.
    • Anticonvulsants for seizure control.
    • Management of increased intracranial pressure (e.g., diuretics, ventricular shunting if hydrocephalus develops).
• Supportive Care:
  • Close monitoring in a hospital setting, especially if neurological deficits are present.
  • Multidisciplinary approach involving neurologists, infectious disease specialists, oncologists, and rheumatologists as appropriate.

Prognosis depends on the etiology, timely diagnosis, and initiation of appropriate therapy:

• Infectious Causes: Early treatment can lead to complete recovery, but delays may result in permanent neurological deficits or death.
• Autoimmune Conditions: May respond well to immunosuppressive therapy, but relapses can occur.
• Neoplastic Meningitis: Generally associated with poor prognosis; treatment focuses on symptom relief and prolonging survival.

Conclusion

Chronic and recurrent meningitis is a complex condition requiring comprehensive evaluation to identify the underlying cause. Early recognition and targeted therapy are crucial for improving outcomes. Collaboration among healthcare professionals and a high index of suspicion are essential in managing these patients effectively.

References

• Tunkel AR, et al. Practice Guidelines for the Management of Bacterial Meningitis. Clin Infect Dis. 2004;39(9):1267-1284.
• Gray LD, Fedorko DP. Laboratory diagnosis of bacterial meningitis. Clin Microbiol Rev. 1992;5(2):130-145.
• Schut ES, et al. Clinical, laboratory and radiological features of chronic meningitis. Ann Neurol. 2008;64(2):116-127.
• Rock RB, et al. Central nervous system tuberculosis: pathogenesis and clinical aspects. Clin Microbiol Rev. 2008;21(2):243-261.
• Marbaniang SP, Sharma N. Approach to a patient with chronic meningitis. Indian J Med Res. 2019;150(2):117-128.