In most instances, this infection has presented as a chronic sinusitis (particularly sphenoidal), with osteomyelitis at the base of the skull or as a complication of otitis and mastoiditis. Cranial nerves adjacent to the infected bone or sinus may be involved. We have also observed brain abscesses and cranial and spinal dural granulomas. In one of our patients, the Aspergillus organisms had formed a granulomatous mass that compressed the cervical spinal cord. Aspergillosis does not present as meningitis but hyphal invasion of cerebral vessels may occur, with thrombosis, necrosis, and hemorrhage; that is, an infectious vasculitis. In some cases, the infection is acquired in the hospital, and in most it is preceded by a pulmonary infection that is unresponsive to antibiotics. Diagnosis can often be made by finding the organism in a biopsy specimen or by culturing it directly from a lesion. Also, specific antibodies and galactomannan are detectable in the blood.
Treatment Liposomal amphotericin in combination with voriconazole, and echinocandins in some cases, is the recommended treatment, but this regimen is not as effective for aspergillosis as it is for cryptococcal disease. The addition of itraconazole, 200 mg bid, in less-immunocompromised patients is recommended. If amphotericin B is given after surgical removal of the infected material, some patients recover.
Mucormycosis (Zygomycosis, Phycomycosis)
This is an aggressive infection of soft tissues or sinuses, spreading to cerebral vessels with one of the Mucorales family. It occurs as a rare complication in patients with diabetes, especially during diabetic acidosis, in drug addicts, and in those with leukemia and lymphoma, particularly those treated with corticosteroids and cytotoxic agents.
The cerebral infection begins in the nasal turbinates and paranasal sinuses and spreads from there along infected vessels to the retroorbital tissues and cavernous sinus (where it results in proptosis, ophthalmoplegia, and edema of the lids and retina) and then to the adjacent brain, causing hemorrhagic infarction. Numerous hyphae are present within the thrombi and vessel wall, often invading the surrounding parenchyma. The cerebral form of mucormycosis is usually fatal in short order. Rapid correction of hyperglycemia and acidosis and treatment with liposomal amphotericin or posaconazole have resulted in recovery in some patients. Debridement, even to the extent of enucleation may be necessary to control the local infection. The differential diagnosis is other forms of septic cavernous sinus thrombosis in a diabetic.
Coccidioidomycosis, Histoplasmosis, Blastomycosis, and Actinomycosis
Coccidioidomycosis is a common infection in the southwestern United States. It usually causes only a benign, influenza-like illness with pulmonary infiltrates that mimic those of nonbacterial pneumonia, but in a few individuals (0.05 to 0.2 percent), the disease takes a disseminated form, of which meningitis may be a part. The pathologic reactions in the meninges and CSF and the clinical features are very much like those of tuberculous meningitis. Coccidioides immitis is recovered with difficulty from the CSF but readily from the lungs, lymph nodes, and ulcerating skin lesions. Diagnosis is made from CSF serology.
Treatment consists of the intravenous administration of amphotericin B coupled with implantation of an Ommaya reservoir into the lateral ventricle, permitting injection of the drug for a period of years. Instillation of the drug by repeated lumbar punctures is an alternative, albeit cumbersome, procedure. Even with the most assiduous programs of treatment, only about half the patients with meningeal infections survive.