ABSTRACT
Coccidiodal meningitis is a devastating complication of disseminated coccidioidomycosis. An animal model of this infection could enhance understanding of the pathogenesis of the disease and lead to improvements in therapy. A rabbit model of central nervous system infection simulating human disease was established using a blind cisternal tap technique to inoculate 4 x 10(3)-1 x 10(6) arthroconidia of Coccidioides immitis into the cisterna magna. Systemic, neurologic, and histopathologic findings of meningitis were observed in all rabbits, but an inoculum of 2 x 10(4) arthroconidia produced a chronic illness in which meningeal endarteritis obliterans was consistently observed. Serial sampling of cerebrospinal fluid demonstrated an inflammatory response. Growth of C. immitis was demonstrated by quantitative fungal culture from brains and proximal spinal cords.
Subject(s)
Central Nervous System/blood supply , Coccidioidomycosis/etiology , Disease Models, Animal , Endarteritis/etiology , Meningoencephalitis/etiology , Animals , Central Nervous System/microbiology , Central Nervous System/pathology , Coccidioidomycosis/cerebrospinal fluid , Coccidioidomycosis/pathology , Endarteritis/pathology , Male , Meningoencephalitis/pathology , RabbitsABSTRACT
A patient with high titers of the anti-Ri antibody died 3 years after a progressive course with ataxia, opsoclonus, dementia, and peripheral neuropathy. At autopsy, no tumor was found. The nervous system exhibited severe Purkinje cell loss and contained perivascular and interstitial inflammatory infiltrates, particularly involving the brainstem. B and CD4 cells predominated in the perivascular spaces and CD8 cells in the interstitial infiltrates. Complement reactivity and natural killer cells were present and predominated in areas with more intense inflammatory infiltrates. Deposits of IgG were detected in the cytoplasm and nuclei of some neurons, particularly those in the brainstem tegmentum. The proportion of anti-Ri IgG in the total IgG extracted from various areas of the brain, serum, and cerebrospinal fluid was determined by quantitative western blot analysis. Anti-Ri reactivity was identified in immunoblots of all regions of the brain, but it predominated in basis pontis and dorsal mesencephalon. Our findings support the hypothesis of an autoimmune basis for the disorder and suggest that an antibody-mediated mechanism may play a role in its pathogenesis.
Subject(s)
Autoantibodies/immunology , Brain Diseases/immunology , Aged , Blotting, Western , Brain/immunology , Brain/pathology , Brain Diseases/pathology , Female , Humans , Immunoenzyme Techniques , Immunoglobulin G/analysis , Ocular Motility Disorders/immunology , Ocular Motility Disorders/pathologyABSTRACT
Six cases of apparent and four cases of histopathologically confirmed vasculitis of the central nervous system (CNS), including one case of histopathologically documented vasculitis with encephalitis associated with coccidioidal meningitis (CM), are presented. Vasculitic complications included changes in mental status as well as stroke-like findings of aphasia, hemianopsia, and hemiparesis. Seven patients died. Vasculitic complications were unanticipated and often abrupt in onset, and delayed therapeutic intervention was characteristic. The diagnosis of vasculitis/encephalitis due to Coccidioides immitis infection must be based on clinical judgment, since serum antibody titers, cerebrospinal fluid findings, and initial radiological studies are not always helpful. Institution of both intravenous and intracisternal administration of amphotericin B and possibly concomitant intravenous administration of dexamethasone may be warranted in situations in which the association of C. immitis with CNS vasculitis or encephalitis appears likely before serologic or cultural confirmation of C. immitis infection involving the CNS is available.
