Makindo Medical Notes

Critical note: Take expert help. For study only, check all drugs and indications with experts and the British National Formulary (BNF).

🧠 About CNS Fungal Infections

• Central Nervous System (CNS) fungal infections are serious and potentially life-threatening conditions affecting the meninges, brain parenchyma, and surrounding structures.
• They are rare compared with bacterial or viral meningitis but carry a high mortality, especially in immunocompromised individuals.
• Prompt diagnosis and appropriate antifungal therapy are critical for improving outcomes.

CNS fungal infections arise from a variety of pathogens, each with distinct risk factors and clinical features. Recognising the likely organism is essential for targeted therapy.

🦠 Fungal Pathogens & Typical Profiles

• Cryptococcus neoformans: - Disease: cryptococcal meningitis - Risk factors: HIV/AIDS, immunocompromised states - Symptoms: headache, fever, neck stiffness, photophobia, altered mental status, nausea
• Aspergillus species: - Disease: cerebral aspergillosis (abscess, meningitis) - Risk factors: prolonged neutropenia, haematological malignancy, organ transplant - Symptoms: focal deficits, seizures, reduced consciousness, fever
• Candida species: - Disease: candidiasis (meningitis, abscess, encephalitis) - Risk factors: ICU patients, indwelling lines, broad-spectrum antibiotics - Symptoms: fever, headache, seizures, confusion
• Coccidioides immitis: - Disease: coccidioidomycosis (Valley fever with meningitis) - Risk factors: endemic to Southwestern USA, immunocompromised hosts - Symptoms: headache, fever, meningism, neurological deficits
• Histoplasma capsulatum: - Disease: chronic meningitis - Risk factors: exposure to bat/bird droppings, immunocompromised states - Symptoms: fever, headache, confusion, neck stiffness
• Mucorales species (Mucormycosis): - Disease: rhinocerebral disease with CNS invasion - Risk factors: uncontrolled diabetes, transplant recipients, long-term steroids - Symptoms: facial pain, cranial nerve palsies, headache, altered mental status

💊 Treatment by Pathogen

• Cryptococcus neoformans: Amphotericin B + Flucytosine (induction) → Fluconazole (maintenance, esp. HIV).
• Aspergillus: Voriconazole first-line; alternatives = liposomal Amphotericin B, isavuconazole. Surgical drainage may be needed.
• Candida: Liposomal Amphotericin B preferred; step-down to Fluconazole; echinocandins (e.g., caspofungin) in refractory disease.
• Coccidioides: Fluconazole or Itraconazole; Amphotericin B for severe disease; therapy often lifelong.
• Histoplasma: Amphotericin B (induction) → Itraconazole (maintenance).
• Mucorales: Liposomal Amphotericin B; alternatives = Posaconazole, Isavuconazole. Early surgical debridement often essential.

🩺 Clinical Presentation

• Neurological: headache, neck stiffness, confusion, photophobia, seizures.
• Systemic: fever, malaise, weight loss.
• Focal deficits: cranial nerve palsies, motor/sensory loss depending on site.
• Ocular: visual disturbances if optic pathways affected.

⚠️ Risk Factors

• HIV/AIDS and other immunocompromised states (transplants, chemotherapy).
• Prolonged corticosteroids or immunosuppressants.
• Diabetes mellitus (esp. with ketoacidosis).
• Endemic exposure (Coccidioides in Southwestern USA, Histoplasma in bat/bird habitats).
• IV drug use, contaminated lines/devices.

🔬 Diagnosis & Investigations

• Laboratory: CBC, U&E, LFTs, CRP, ESR.
• CSF analysis: lymphocytic pleocytosis, ↑ protein, ↓/normal glucose. - Cryptococcus: India ink stain, cryptococcal antigen. - Culture/PCR for specific fungi.
• Imaging: - MRI brain = best for abscesses, meningeal enhancement, perivascular spread. - CT useful if MRI contraindicated. - CT chest/abdomen/pelvis to look for primary focus.
• Microbiology/serology: fungal cultures, antigen/antibody tests, biopsy if needed.

⚕️ Management Principles

• Antifungal therapy: Amphotericin B (liposomal), flucytosine, azoles (fluconazole, voriconazole, posaconazole, isavuconazole), echinocandins for Candida.
• Surgical intervention: abscess drainage, sinus debridement, removal of infected devices.
• Underlying conditions: optimise HIV treatment, control diabetes, taper steroids if possible.
• Supportive care: ICP management, anticonvulsants for seizures, fluid/electrolyte balance, nutrition.
• Adjuncts: cautious corticosteroid use in selected cases; immunotherapy in research settings.

🛡️ Prevention

• Prophylactic antifungals in high-risk immunocompromised patients.
• Strict infection control in healthcare settings.
• Minimise environmental exposure (construction dust, soil, bird/bat droppings).
• Prompt treatment of systemic fungal infections before CNS spread.

📉 Prognosis

• Cryptococcus: better outcomes with ART and maintenance therapy, but mortality remains high.
• Aspergillus: poor prognosis even with treatment; immunosuppression worsens outcomes.
• Candida: high mortality with invasive CNS disease.
• Mucormycosis: very high mortality; early surgery + Amphotericin improves survival.
• Histoplasma & Coccidioides: better prognosis if diagnosed early and treated long-term.

✅ Conclusion

CNS fungal infections are rare but devastating. Early suspicion in immunocompromised patients, rapid diagnostics, and prompt antifungal therapy are essential. Multidisciplinary management with infectious disease, neurology, radiology, and surgery improves outcomes.

📚 References

• Perfect JR, et al. Clinical Practice Guidelines for the Management of Cryptococcal Disease. Clin Infect Dis. 2010.
• Denning DW, et al. Aspergillus fumigatus and aspergillosis. Clin Microbiol Rev. 2009.
• CDC: Histoplasmosis. https://www.cdc.gov/fungal/diseases/histoplasmosis
• Kuchta KJ, Perfect JR. Cryptococcal meningitis in non-HIV patients. Curr Opin Infect Dis. 2008.
• Kontoyiannis DP, et al. Aspergillus infections in transplant recipients. Clin Microbiol Rev. 2003.
• Mayer-Scholl A, et al. CNS aspergillosis. Expert Rev Anti Infect Ther. 2012.
• Kauffman CA. Invasive Candidiasis. N Engl J Med. 2016.
• Schwab C, et al. Mucormycosis. Lancet Infect Dis. 2013.