Mold infections of the central nervous system

Abstract

The recent outbreak of exserohilum rostratum meningitis linked to epidural injections of methylprednisolone acetate has brought renewed attention to mold infections of the central nervous system (CNS). Although uncommon, these infections are often devastating and difficult to treat. This focused review of the epidemiologic aspects, clinical characteristics, and treatment of mold infections of the CNS covers a group of common pathogens: aspergillus, fusarium, and scedosporium species, molds in the order Mucorales, and dematiaceous molds. Infections caused by these pathogen groups have distinctive epidemiologic profiles, clinical manifestations, microbiologic characteristics, and therapeutic implications, all of which clinicians should understand.

Figure 1. Comparative Features of Mold Infections of the Central Nervous System

The use of a polymerase-chain-reaction (PCR) assay of cerebrospinal fluid (CSF) remains investigational and has not been approved by the Food and Drug Administration. The host factors listed here are the most common; however, other hosts may be susceptible. LPCB denotes lacto-phenol cotton blue stain.

Figure 2. Characteristic Findings Associated with Mold Infections of the Central Nervous System

Patient 1, a 7-year-old girl with newly diagnosed, high-risk, pre–B-cell acute lymphocytic leukemia, presented with neutropenia and cough, paralysis of the left arm, and left homonymous hemianopsia. Computed tomography (CT) of the chest (Panel A) revealed nodular densities in the lower lobe of the right lung. Magnetic resonance imaging (MRI) of the head (Panel B) showed numerous cortical and subcortical infarcts with surrounding edema leading to mass effects; stereotactically guided brain biopsy yielded a specimen for culture that was positive for Aspergillus fumigatus. Patient 2, a 24-year-old woman with acute myeloid leukemia, was admitted for fever and neutropenia followed by rapid deterioration of mental status; CT of the chest (Panel C) showed nodular pneumonia. MRI of the head (Panel D) revealed multiple bilateral infarcts, the largest of which shown in the left parietal–occipital region. Examination of a brain-biopsy specimen (Panel E, Gomori methenamine silver stain) revealed numerous acutely branching septate hyphae. No organisms were grown in culture, because the biopsy specimen was obtained while the patient was receiving antifungal therapy. The histologically compatible organisms include aspergillus, fusarium, scedosporium, and other hyaline molds. The use of immunohistochemical and molecular diagnostic procedures, such as a PCR assay and in situ hybridization, may make it possible to further identify the causative organism.