Molds are ubiquitous in soil, water, and decaying vegetation and can cause devastating infections that are difficult to treat. This review summarizes the epidemiologic profiles, clinical characteristics, and treatment of mold infections of the central nervous system.
Molds are ubiquitous organisms found in soil, water, and decaying vegetation. All have septate, angular, branching hyphae in tissue, with the exception of those in the order Mucorales, which have broad, ribbonlike, nonseptate or hyposeptate hyphae.
• What is the typical mechanism by which fungal infections reach the CNS?
The respiratory tract is usually the portal of entry, with subsequent hematogenous dissemination to the CNS. However, direct inoculation of CNS or paraspinal tissue as a result of surgery, trauma, intravenous drug use, or contaminated medical supplies may also occur in immunocompetent persons. Organisms may also spread to the CNS from adjacent structures, including the sinuses, mastoid, and orbit. Infection of the ethmoid sinuses may lead to cavernous sinus thrombosis as a result of invasion of the emissary veins that drain the sinuses. Hyphae can invade from the ethmoid sinuses through the lamina papyracea and into the periorbital space, thus threatening the eye, extraocular muscles, and posterior apical structures, including the optic nerve. Angioinvasion is common in immunocompromised patients and accounts for the hematogenous dissemination from the lungs that causes focal neurologic deficits.
• What are the characteristics of CNS aspergillosis?
The risk factors for CNS aspergillosis include neutropenia, systemic glucocorticoid treatment, mastoidectomy, spinal anesthesia, and paraspinal glucocorticoid injections. Focal neurologic deficits and seizures caused by stroke or mass effect are the most common clinical manifestations of CNS aspergillosis. Meningeal signs are uncommon, and their presence is indicative of a subarachnoid hemorrhage. CNS aspergillosis should be high on the list of disorders in the differential diagnosis for patients with immunosuppression and focal brain lesions, especially those with characteristic pulmonary infiltrates in whom focal neurologic deficits or focal seizures develop. Recovery of aspergillus from pulmonary lesions with the use of bronchoalveolar lavage or fine-needle aspiration should be pursued when possible. An enzyme immunoassay for detection of galactomannan in serum or bronchoalveolar lavage fluid should be performed when feasible. Galactomannan and 1,3-(beta)-d-glucan may be found in the serum or CSF of patients with CNS aspergillosis. Voriconazole is the first-line treatment for CNS aspergillosis.
Morning Report Questions
Q: What are typical features of cerebral mucormycosis?
A: Cerebral mucormycosis, which is perhaps the most aggressive mold infection of the CNS, constitutes a medical emergency. Diabetes mellitus and iron-overload conditions are distinctive risk factors for the development of mucormycosis. In patients with neutropenia or patients receiving glucocorticoid therapy, mold infections of the CNS develop as sino-orbital infections or through hematogenous dissemination of pulmonary mucormycosis. In contrast, patients with diabetes mellitus usually present with sino-orbital mucormycosis and seldom present with pulmonary or disseminated infection. Among intravenous drug users, CNS mucormycosis is a relatively common cause of intracerebral fungal abscesses. Perhaps more than any other infection, mucormycosis of the ethmoid sinuses may involve all structures along its invasive path, including the orbit and eye, bone, and brain tissue. Because venous drainage of the ethmoid sinuses extends into the cavernous sinuses, ethmoidal mucormycosis carries a high risk of cavernous sinus thrombosis. Successful management of rhinocerebral mucormycosis depends not only on early diagnosis but also on primary antifungal therapy with amphotericin B, reversal of host impairments and timely surgical intervention, when indicated.
Q: What are the features of CNS infection with fusarium species?
A: CNS fusariosis develops predominantly in patients with prolonged neutropenia. These organisms are highly angioinvasive and cause hemorrhagic infarction with strokelike events. Portals of entry include the lungs, sinuses, vascular catheters, and distinctively, periungual lesions (paronychia in patients with neutropenia). Fusarium species are also most frequently associated with fungemia, multiple erythematous nodular cutaneous lesions, and septic arthritis. A definitive mycologic diagnosis can be rapidly established by biopsy and culture of cutaneous lesions. As compared with other mold infections of the CNS, disseminated fusariosis is more commonly associated with bilateral endophthalmitis, which may lead to blindness. Fusarium species vary in their susceptibility to antifungal agents. Voriconazole is licensed for second-line therapy; however, amphotericin B also has been used successfully.