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 tuberculosisis 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:
    • Brucellaspecies.
    • Nocardiaspecies.
    • 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.