CNS Aspergillosis

05 November 2004

2^nd most common fungal CNS infection in immunocompromised host

(Cryptococcus is commonest)

A disease of medical progress

Risk Factors

1.     Transplant recipients: renal >liver > heart

2.     1-4 months post transplant

3.     Recent transplant rejection +/- retransplantation

4.     Leukopenia

5.     Associated with CMV infection

6.     Reported nosocomial spread in some cases

7.     Lung is commonest source then sinuses

Neuropathology

Invasion of blood vessels causing hemorrhagic infarction usually subcortical

Meningeal infection usually focal & adjacent to infected cerebral region

Angular dichotomously branching septate hyphae infiltrates tissue in centrifugal pattern

Hyphae structure tend to be found on borders of large abscesses

Clinical

86%   altered mental status

41%   seizures

32%   focal neurological deficits

Meningeal signs uncommon

Investigations

Serology:     specific but not sensitive

CSF:  15% positive culture

          Slightly elevated protein

          Very low glucose

          PMN predominant

DSA: beading

          Mycotic aneurysms

MRI:  -multiple areas of T2 hyperintensity in cortex & subcortical white

matter consistent with multiple areas of infarction.

          -multiple ring enhancing lesions (irregular ring, low signal T2)

          -dural enhancement with enhancement in adjacent paranasal sinus

structure

Brain biopsy & culture

Prognosis

95% mortality

most diagnoses made postmortem; early recognition is essential

Treatment

Amphotericin B iv (liposomal form avoids nephrotoxicity)

          +/- 5 fluorocytosine

often combined with itraconazole

intrathecal amphotericin B available but rarely used (SE: headaches, delirium, vomiting, paresthesia, arachnoiditis, radiculopathy, myelopathy, nerve palsies, meningitis)