What is Aspergillus meningitis?

Aspergillus Meningitis: Clinical Features, Diagnosis, and Management

Aspergillus meningitis is a rare but devastating fungal infection of the central nervous system with mortality exceeding 90%, characterized by fungal invasion of the meninges and brain tissue by Aspergillus species, most commonly requiring aggressive combined medical and surgical intervention for optimal outcomes. 1

Definition and Pathophysiology

Aspergillus meningitis is a form of central nervous system (CNS) aspergillosis that specifically affects the meninges. It typically occurs through one of three mechanisms:

1. Hematogenous dissemination from a primary site (commonly lungs)
2. Direct extension from contiguous structures (paranasal sinuses, mastoid)
3. Direct inoculation (trauma, neurosurgical procedures, contaminated medical equipment) 1, 2

The CNS is the most common secondary site of invasive aspergillosis, with the fungus characterized by its rapid growth and tendency to invade blood vessels, leading to tissue infarction and hemorrhage 1.

Clinical Presentation

Patients with Aspergillus meningitis typically present with:

• Fever (often remittent despite broad-spectrum antibiotics)
• Headache
• Nuchal rigidity (neck stiffness)
• Altered mental status
• Focal neurological deficits

As the disease progresses, complications may include:

• Papilledema
• Cranial nerve palsies (particularly lateral rectus palsy)
• Cerebral infarction and hemorrhage
• Hydrocephalus 2, 3

Risk Factors

Aspergillus meningitis primarily affects:

• Immunocompromised patients (neutropenia, neutrophil/macrophage dysfunction)
• Recipients of cytotoxic chemotherapy
• Patients on long-term corticosteroid therapy
• Bone marrow or organ transplant recipients
• Patients with congenital or acquired immunodeficiency 1

However, cases have been reported in immunocompetent individuals, particularly those with:

• History of sinus disease 4
• Exposure to contaminated medical equipment during procedures (e.g., spinal anesthesia) 2

Diagnosis

Diagnosis of Aspergillus meningitis is challenging and requires:

1. CSF Analysis:

   • Pleocytosis (increased white blood cells)
   • Low glucose levels
   • Elevated protein
   • Gomori methenamine silver and Periodic acid-Schiff stains to detect septated hyphae 1

2. Microbiological Testing:

   • CSF culture (though blood, CSF, and bone marrow specimens rarely yield Aspergillus species)
   • Aspergillus galactomannan antigen detection in CSF
   • PCR for Aspergillus DNA 3

3. Neuroimaging:

   • CT and/or MRI to identify cerebral abscesses, infarction, or hemorrhage 1

4. Biopsy:

   • When feasible, to differentiate Aspergillus from other fungi (Pseudallescheria, dematiaceous fungi, Mucorales, Fusarium) 1

Treatment

Primary Therapy

Voriconazole is the preferred agent for treatment of Aspergillus meningitis due to its superior CNS penetration and demonstrated efficacy in CNS aspergillosis. 1, 5

Alternative options include:

• Liposomal amphotericin B (L-AMB) for patients who cannot tolerate voriconazole 1, 3
• Posaconazole as a salvage therapy option 1

Duration and Approach

• Treatment should be continued for a minimum of 6 weeks after surgical intervention 1
• For recurrent infections or high-risk cases, lifelong antifungal therapy with an oral triazole (voriconazole or posaconazole) should be considered 1

Surgical Intervention

Surgical approaches should be considered when feasible:

• Removal of nonviable tissue that may not be well-penetrated by antifungals
• Drainage of abscesses
• Biopsy for definitive diagnosis 1

Emerging Approaches

Recent evidence suggests potential benefit from adding corticosteroids to antifungal therapy in selected cases of Aspergillus meningitis, though this approach requires further study 6.

Prognosis

The prognosis for Aspergillus meningitis is generally poor:

• Mortality exceeds 90% in most published reports 1
• Early recognition and aggressive intervention are critical for survival
• Survivors may experience long-term sequelae including visual and hearing impairment 2

Prevention

Prevention strategies focus on:

• Controlling environmental exposure in high-risk patients
• Proper sterilization of medical equipment
• Appropriate storage of medical supplies to prevent fungal contamination 2

Key Pitfalls to Avoid

1. Delayed diagnosis - Consider Aspergillus meningitis in patients with persistent meningitis not responding to antibiotics
2. Inadequate treatment duration - Extended therapy is essential
3. Failure to identify and address the primary source - Particularly sinus disease or pulmonary aspergillosis
4. Relying solely on CSF cultures - Incorporate antigen testing and molecular methods
5. Overlooking surgical options - Combined medical-surgical approach often yields better outcomes