What is the treatment for fungal aspergillosis in the brain?

Treatment of Cerebral Aspergillosis

Voriconazole is the recommended first-line systemic antifungal therapy for confirmed cerebral aspergillosis, combined with surgical resection when feasible, as this approach achieves the highest survival rates (71% at 12 weeks) compared to amphotericin B (58%). 1

Initial Antifungal Therapy

When Aspergillus is Confirmed

• Initiate voriconazole immediately with a loading dose of 6 mg/kg IV every 12 hours for the first 24 hours, followed by 4 mg/kg IV every 12 hours for a minimum of 7 days 1, 2
• Transition to oral voriconazole 200 mg twice daily once clinically stable 2
• Voriconazole achieves superior CNS penetration with concentrations exceeding inhibitory levels for Aspergillus in cerebrospinal fluid and brain tissue, including abscess material 3
• Among patients receiving voriconazole combined with surgical intervention, favorable responses occurred in 35% with long-term survival in 31% 1

When Organism is Unknown or Pending

• Start amphotericin B formulation immediately if the causative organism is not yet identified, as voriconazole and itraconazole lack activity against zygomycosis, which can present identically 1
• This is critical because direct extension from paranasal sinuses may involve either Aspergillus or Zygomycetes, and distinguishing them requires histopathology 1

Alternative Agents

• Itraconazole, posaconazole, or lipid formulations of amphotericin B (L-AMB, ABLC, ABCD) are recommended for patients intolerant or refractory to voriconazole 1
• Caspofungin has demonstrated response in CNS aspergillosis refractory to amphotericin B, but limited data support echinocandins as monotherapy 1

Surgical Management

Indications for Surgery

• Surgical resection of accessible lesions is strongly recommended as an important adjunct to antifungal therapy, potentially serving as definitive treatment and preventing irreversible neurological sequelae 1
• Early surgical intervention prevents progression of focal neurological deficits, which may become irreversible once established 1
• Gross total or subtotal excision combined with antifungal therapy achieved 25% and 50% mortality respectively in immunocompetent patients, compared to 100% mortality with biopsy alone 4

Surgical Decision-Making

• Carefully weigh the patient's immune status, extent of surgery necessary, concomitant coagulopathy, and surgical morbidity before proceeding 1
• Resect lesions that would not result in worsening of neurological deficits 1
• Decompressive craniectomy with biopsy may be appropriate when complete resection is not feasible, with 25% mortality in one series 4

Management of Contiguous Infections

• Treatment of contiguous paranasal sinus or vertebral body infections is a necessary component of CNS aspergillosis management 1
• Surgical debridement of invasive sinus aspergillosis may be curative in some circumstances 1

Treatment Duration and Monitoring

• Continue antifungal therapy for a minimum of 6-12 weeks, throughout the period of immunosuppression, and until all lesions have resolved radiologically 5
• Duration should be determined by resolution of clinical and radiological findings, not solely by normalization of galactomannan antigenemia 5
• Serial galactomannan testing in CSF may enhance diagnostic certainty and monitor treatment response 1
• Regular CT or MRI scans are essential to assess lesion resolution 5

Critical Management Principles

Immune Reconstitution

• Reversal of underlying immune deficits is paramount for successful outcome 1
• Reduce or discontinue immunosuppressive medications when medically feasible 5
• Resolution of neutropenia and return of neutrophil function are critical determinants of treatment response 5

Interventions to Avoid

• Do not use corticosteroids - their role in CNS aspergillosis is deleterious and should be avoided despite any tendency to use them for progressive neurological deficits 1
• Do not administer intrathecal or intralesional antifungal therapy - intrathecal amphotericin B does not penetrate beyond the pia mater and may induce chemical arachnoiditis, seizures, severe headache, and altered mental status 1
• Instead, use high-dose systemic antifungal therapy to achieve adequate parenchymal concentrations 1

Prognosis and Clinical Context

• CNS aspergillosis remains the most lethal manifestation of Aspergillus infection, historically associated with mortality rates approaching 90-100% 1
• Focal neurological deficits or focal seizures are the most common clinical manifestations, distinguishing it from candidiasis or cryptococcosis 1
• The infection arises most commonly from hematogenous dissemination from pulmonary foci or direct extension from paranasal sinus infection 1
• Early recognition and aggressive therapeutic intervention are critical to limiting neurological injury and improving survival 1
• Even with optimal combined medical and surgical management, mortality remains 44.4% in immunocompetent patients 4
• Hydrocephalus is associated with particularly high mortality (83.3%) 4