3A,B). A striking finding was degenerative Cytoskeletal Signaling inhibitor lesions in the cerebrum, cerebellum and pons. Notably, the degenerative lesions in the cerebrum were remarkable at the white matter and cortex adjacent to the leptomeninges, which were abundantly infiltrated by C. neoformans, especially near the frontal base, sylvian fissure and calcarine sulcus (Fig. 3C). In the affected deep white matter, perivascular infiltration of the lymphocytes was prominent (Fig. 3D), and reactive astrocytes and vascular proliferation were also evident. In contrast, vascular abnormalities and reactive astrocytes were not apparent in the subcortical

and cortical lesions. Basal ganglia and thalamus were partly necrotic with slight

infiltration of the lymphocytes. buy LEE011 In the cerebellum, the subcortical white matter was extensively degenerated, but the deep white matter was mostly preserved (Fig. 3E). There were no apparent vascular abnormalities in the cerebellum. C. neoformans was not present within the parenchyma of the brain or spinal cord. There was no abnormal oligodendroglia suggestive of progressive multifocal leukoencephalopathy (PML), and JC virus was not detected in the cerebrum, cerebellum or brainstem by immunohistochemistry using an antibody against SV40. IRIS is a condition observed mostly in immunocompromized patients, in which the immune system begins to recover and respond against a wide variety of pathogens with an overwhelming inflammatory response that paradoxically makes the symptoms worse.[4] C. neoformans is a major pathogen associated with the occurrence of buy CHIR-99021 IRIS. IRIS is well recognized in HIV-infected patients receiving highly active antiretroviral therapy,

but is also known as a complication of immunosuppressive treatment by corticosteroids.[5] In our case, the pathology in the cerebral deep white matter indicated the pathomechanism of lymphocytic inflammation. Cryptococcal meningitis often accompanies lymphocytic infiltration within the brain parenchyma in the absence of C. neoformans,[1] but the degenerative changes of the cerebral white matter in the early phase of cryptococcal meningitis are mostly unremarkable. In our case, cryptococcal meningitis and the MRI abnormalities predominantly in the cerebral deep white matter occurred after the cessation of strong immunosuppressive treatment by methylprednisolone along with the recovery of lymphocyte numbers, and thus, the degenerative lesions in the cerebral deep white matter could be recognized as a manifestation of IRIS against an opportunistic infection of C. neoformans at the leptomeninges. However, the degenerative lesions in the subcortical white matter and cortex were not accompanied by inflammation, and thus, the pathomechanism would be different from IRIS.