Chronic and recurrent Meningitis

Related Subjects: | Meningococcal Meningitis | Pneumococcal Meningitis | Listerial Meningitis |Herpes Simplex Encephalitis (HSV) |Acute Encephalitis |Toxoplasmosis |Lumbar Puncture |CSF Interpretation |Tuberculosis |TB Meningitis |Chronic and recurrent Meningitis

🧠 Introduction

• Chronic meningitis is inflammation of the meninges causing symptoms that persist for ≥4 weeks.
• Recurrent meningitis describes ≥2 distinct episodes of meningitis, usually with CSF pleocytosis, separated by complete or near-complete clinical recovery.
• Unlike acute meningitis, chronic meningitis usually develops gradually over days to weeks and may follow a fluctuating course.
• Important causes include infection, malignancy and inflammatory/autoimmune disease.
• ⚠️ The diagnosis can be difficult: conventional investigations may fail to identify a cause, and repeated CSF sampling or tissue biopsy may occasionally be required.

💡 Think broadly: the major diagnostic groups are infectious, inflammatory/autoimmune and neoplastic. In recurrent bacterial meningitis, specifically look for a CSF leak, skull-base defect or immune deficiency.

🦠 Causes

• Infectious causes:
  • 🧫 Mycobacterial: Mycobacterium tuberculosis – one of the most important causes worldwide.
  • 🍄 Fungal: Cryptococcus neoformans and C. gattii; endemic fungi such as Histoplasma or Coccidioides depending on travel/geographical exposure.
  • 🌀 Spirochaetal: Treponema pallidum (neurosyphilis) and Borrelia burgdorferi (neuroborreliosis).
  • 🧪 Other bacteria: Brucella, Leptospira and occasionally other indolent bacterial infections.
  • 🦠 Viral: HIV itself may produce a chronic aseptic meningitis; HSV-2 is particularly associated with recurrent lymphocytic meningitis (Mollaret meningitis).
  • 🪱 Parasitic: selected parasitic infections may cause chronic or eosinophilic meningitis, depending on exposure and geography.
• Inflammatory / autoimmune causes:
  • 🔥 Neurosarcoidosis.
  • 🔥 Behçet disease.
  • 🔥 Systemic lupus erythematosus.
  • 🔥 ANCA-associated vasculitis and other CNS vasculitides.
  • 🔥 IgG4-related disease and other inflammatory pachymeningitides.
• Neoplastic causes:
  • 🎗️ Leptomeningeal metastases – particularly breast cancer, lung cancer and melanoma.
  • 🎗️ Lymphoma and leukaemia involving the meninges.
• Other causes:
  • 💊 Drug-induced aseptic meningitis – e.g. NSAIDs, IV immunoglobulin and some antimicrobials.
  • 🧠 Chemical meningitis – e.g. following neurosurgery or rupture of an epidermoid/dermoid cyst.

🔁 Recurrent Meningitis – Important Causes

• 🦠 HSV-2: the commonest recognised cause of recurrent aseptic meningitis (Mollaret meningitis).
• 👃 Skull-base or CSF leak: congenital or acquired defects may allow recurrent pneumococcal or other bacterial meningitis.
• 👂 Look for previous head trauma, neurosurgery, chronic ear disease or sinus disease.
• 🛡️ Consider immune deficiency, particularly complement deficiency, antibody deficiency or functional/anatomical asplenia in recurrent bacterial infection.

🧩 Clinical clue: recurrent pneumococcal meningitis should prompt a search for a CSF leak or skull-base defect. Recurrent meningococcal disease should raise suspicion of terminal complement deficiency.

🩺 Clinical Features

• 🤕 Headache – often persistent and progressive.
• 🌡️ Fever may be present, although it may be low-grade or absent.
• 😴 Malaise, lethargy, anorexia and weight loss may occur.
• 💡 Photophobia, neck stiffness and other classical meningeal signs may be mild or absent.
• 👁️ Cranial neuropathies are important, particularly with basal meningitis such as TB, cryptococcosis or malignancy.
• ⚡ Seizures, altered cognition or reduced consciousness may develop.
• 🦵 Focal neurological deficits may reflect vasculitis, infarction, hydrocephalus or focal lesions.
• 🔎 Look for systemic clues such as rash, lymphadenopathy, pulmonary disease, uveitis, arthritis or malignancy.

🧪 Investigations

⚠️ Before lumbar puncture: assess for contraindications and consider urgent neuroimaging when there are focal neurological signs, markedly impaired consciousness, papilloedema, seizures or concern about a mass lesion / obstructed CSF circulation.

• 🩸 Blood tests:
  • FBC, U&E, LFTs, CRP/ESR and blood cultures where infection is suspected.
  • HIV test should usually be included.
  • Syphilis serology ± Lyme serology according to clinical and epidemiological risk.
  • TB testing and investigation for extracranial TB where appropriate.
  • Autoimmune investigations should be guided by the clinical phenotype rather than indiscriminately screening with ANA/ANCA/ACE.
• 💉 Lumbar puncture / CSF:
  • 📏 Record the opening pressure.
  • Cell count and differential.
  • Protein and paired CSF/blood glucose.
  • Gram stain and bacterial culture.
  • Mycobacterial microscopy, culture and nucleic-acid testing where TB is suspected.
  • Fungal culture and cryptococcal antigen when appropriate.
  • HSV/VZV and other PCR tests according to the clinical presentation.
  • Syphilis testing and other targeted microbiology according to exposure.
  • 🔬 Cytology ± flow cytometry when leptomeningeal malignancy or lymphoma is suspected.
• 🧠 Imaging:
  • Contrast-enhanced MRI brain is generally the preferred imaging investigation.
  • Possible findings include basal or leptomeningeal enhancement, hydrocephalus, infarction, tuberculomas, cryptococcomas or neoplastic deposits.
  • Consider MRI spine if there are spinal symptoms or suspected leptomeningeal disease.
  • CT chest/abdomen/pelvis ± PET-CT may help identify occult malignancy, sarcoidosis or a focus of TB.
• 🔬 Further investigation:
  • Repeated large-volume CSF samples may increase diagnostic yield, particularly for malignancy or TB.
  • Biopsy of an accessible lymph node, skin lesion or other abnormal tissue is preferable to meningeal biopsy where possible.
  • Meningeal/brain biopsy may occasionally be required when extensive investigation remains non-diagnostic.

📊 Typical CSF Patterns

💡 Important: CSF findings overlap considerably. A lymphocytic CSF does not automatically mean viral meningitis. TB, fungal infection, malignancy and inflammatory disease may all produce a lymphocytic pleocytosis.

💊 Management

• 🧫 Tuberculous meningitis:
  • Do not wait for microbiological confirmation if the clinical picture strongly suggests TB meningitis.
  • UK NICE guidance recommends isoniazid + rifampicin + pyrazinamide + ethambutol for 2 months, followed by isoniazid + rifampicin for a further 10 months.
  • Give adjunctive dexamethasone or prednisolone, tapered gradually over approximately 4–8 weeks.
  • Manage complications such as hydrocephalus, cerebral infarction and tuberculomas with specialist input.
• 🍄 Cryptococcal meningitis:
  • Requires specialist infectious-disease/microbiology input.
  • Induction treatment usually contains liposomal amphotericin B + flucytosine, followed by fluconazole consolidation and maintenance therapy.
  • 📏 Raised intracranial pressure is common and must be actively sought.
  • Repeated therapeutic lumbar punctures are a key treatment when symptomatic intracranial pressure is elevated; CSF diversion may occasionally be required.
  • Routine acetazolamide, mannitol or corticosteroids are not substitutes for CSF pressure control.
• 🦠 Other infections:
  • Treat according to the identified pathogen and antimicrobial sensitivities.
  • Neurosyphilis, neuroborreliosis and other specific infections require targeted antimicrobial regimens.
  • HSV-associated meningitis may require antiviral treatment depending on severity and clinical circumstances.
• 🔥 Autoimmune / inflammatory meningitis:
  • Treatment depends on the underlying disorder and may involve corticosteroids and other immunosuppressive therapy.
  • ⚠️ Exclude important infectious causes, particularly TB and fungal infection, before substantial immunosuppression whenever possible.
• 🎗️ Leptomeningeal malignancy:
  • Treatment is individualised according to tumour type and may involve systemic therapy, targeted therapy, radiotherapy and occasionally intrathecal treatment.
  • Early oncology and neuro-oncology involvement is appropriate.
• 🧠 Complications:
  • Treat seizures appropriately.
  • Identify and manage hydrocephalus and raised intracranial pressure.
  • Provide rehabilitation for neurological disability.

⚠️ Red Flags

• 🚨 Reduced or deteriorating consciousness.
• 🚨 New focal neurological deficit.
• 🚨 Papilloedema or suspected markedly raised intracranial pressure.
• 🚨 New seizures.
• 🚨 Hydrocephalus on imaging.
• 🚨 Significant immunosuppression.
• 🚨 Suspected TB or cryptococcal meningitis.

📈 Prognosis

• Outcome depends strongly on the underlying cause and speed of diagnosis.
• 🧫 TB and fungal meningitis may cause death or permanent neurological disability if treatment is delayed.
• 🔥 Inflammatory disease may respond well to immunosuppression but can relapse.
• 🎗️ Leptomeningeal malignancy usually indicates advanced malignant disease and prognosis is often poor, although this varies considerably with tumour biology and available targeted treatments.

🧠 Key Learning Points

🧠 Chronic meningitis = symptoms ≥4 weeks.
🦠 Think particularly of TB, fungal infection, spirochaetal infection and HIV.
🔥 Do not forget neurosarcoidosis, vasculitis and other inflammatory disease.
🎗️ Consider leptomeningeal malignancy, especially with multiple cranial neuropathies.
💉 CSF should include opening pressure, cells, protein, glucose and targeted microbiology.
🔁 Recurrent bacterial meningitis → look for a CSF leak, anatomical defect or immune deficiency.
🍄 Cryptococcal meningitis → actively manage raised intracranial pressure.
⚠️ Avoid empirical immunosuppression until important chronic infections have been reasonably excluded.

📚 References

• NICE. Tuberculosis (NG33). Updated guidance.
• Chang CC, et al. Global guideline for the diagnosis and management of cryptococcosis. Lancet Infect Dis. 2024.
• Saylor D, et al. Chronic Meningitis: Diagnostic and Therapeutic Challenges. 2025.
• Baldwin KJ, et al. Chronic Meningitis. Continuum. 2018.