Infection with human immunodeficiency virus type 1 (HIV-1) is frequently complicated in its late stages by the AIDS dementia complex, a neurological syndrome characterized by abnormalities in cognition, motor performance, and behavior. This dementia is due partially or wholly to a direct effect of the virus on the brain rather than to opportunistic infection, but its pathogenesis is not well understood. Productive HIV-1 brain infection is detected only in a subset of patients and is confined largely or exclusively to macrophages, microglia, and derivative multinucleated cells that are formed by virus-induced cell fusion. Absence of cytolytic infection of neurons, oligodentrocytes, and astrocytes has focused attention on the possible role of indirect mechanisms of brain dysfunction related to either virus or cell-coded toxins. Delayed development of the AIDS dementia complex, despite both early exposure of the nervous system to HIV-1 and chronic leptomeningeal infection, indicates that although this virus is "neurotropic," it is relatively nonpathogenic for the brain in the absence of immunosuppression. Within the context of the permissive effect of immunosuppression, genetic changes in HIV-1 may underlie the neuropathological heterogeneity of the AIDS dementia complex and its relatively independent course in relation to the systemic manifestations of AIDS noted in some patients.

Background and Purpose Brain metastases from prostate cancer are uncommon and their imaging appearance has not been well defined. The main objectives of this study were to evaluate the incidence, MRI characteristics, and prognosis of parenchymal brain metastases originating in prostate cancer. Methods We retrospectively identified 21 patients with prostate cancer and evidence of brain metastases from 2000 to 2010. We reviewed the initial brain MRI scans and characterized the lesions according to location and appearance on MRI, while also determining patient demography, staging, and survival. Results The incidence of brain metastasis from prostate cancer was .16%. At the time of brain metastasis detection, 95% of the patients had concurrent osseous metastases, 86% lymph node metastases, and 76% liver and/or lung metastases. Brain metastases were multifocal in 71% of patients, hemorrhagic in 33%, diffusion restricted in 19%, and partially cystic/necrotic in 19%. The median overall survival after brain metastasis detection was 2.8 months. Conclusions Brain metastasis from prostate cancer remains a rare phenomenon that most frequently occurs in the setting of widely disseminated bone and soft tissue disease. Patients with nonadenocarcinoma pathology are more likely to develop brain metastases. The MRI appearance is highly variable and prognosis is poor.

Immune mediated demyelinating disease (IMDD) after allogeneic hemopoietic stem cell transplant (HSCT) is rare and its etiology unclear. In this retrospective study, we identified patients who underwent HSCT between January 1992 and December 2010 and had IMDD post transplant. A total of 1,484 patients received HSCT and 7 (0.5 %) suffered from IMDD; five were men, and the median age was 54 years (range, 29-64 years). HSCT treated acute myeloid leukemia (n = 5), myelodysplastic syndrome (n = 1), and Waldenström macroglobulinemia (n = 1). All received an HLA matched donor graft, related (6), unrelated (1); from the bone marrow (1), peripheral blood stem cell (6); and T-cell depleted, ex vivo (6) or in vivo (1). The median time from transplant to neurologic symptoms was 120 days (range, 60-390 days). Three had acute demyelinating encephalomyelitis (ADEM), three acute inflammatory demyelinating polyradiculopathy (AIDP) and one autonomic neuropathy. Four of six patients tested had hemopoietic mixed chimerism prior to neurologic symptoms and low CD4(+) T-cell counts, median 76 (15-500 cells/μL). Two patients had simultaneous systemic graft versus host disease (GVHD). Two patients with ADEM had a spinal cord or brain biopsy which revealed demyelination. No patients had a viral etiology identified in the cerebrospinal fluid. Patients were treated with IV immunoglobulin, high dose steroids and/or rituximab. Five patients had a significant recovery. Response to immune modulators suggests an immune-based etiology. The incidence of de novo autoimmune disease after HSCT for hematological diseases is rare and may be difficult to differentiate from GVHD.

The spectrum of West Nile virus (WNV) infection continues to be elucidated. Many cases of WNV are asymptomatic; however, in immunocompromised patients, symptoms are more likely to be severe. We describe fatal WNV central nervous system disease in lymphoma patients who received rituximab, blunting the inflammatory response and complicating diagnosis.

Anti-Hu is a polyclonal immunoglobulin G associated with a syndrome of paraneoplastic sensory neuropathy/encephalomyelitis that principally afflicts patients with small cell lung carcinoma. Anti-Hu antibodies, which identify a family of RNA-binding proteins that are normally neuron restricted and that appear to be integral to neuronal differentiation and maintenance, selectively label the nuclei (and, less strongly, the cytoplasm) of neurons throughout the human neuraxis. Small cell carcinomas of the lung and many neuroblastomas are also labeled. We screened 112 tumors of central neuroepithelial lineage for immunohistochemical evidence of Hu expression with anti-Hu immunoglobulin G that was purified from patient sera and with a recombinant Fab fragment (Fab GLN 495) selected from a patient-derived combinatorial antibody phage display library using a recombinant Hu protein (HuD). Both antibodies uniformly labeled, in addition to native neurons, the nuclei of central neurocytomas (6 of 6) and the neuronal components of "classic" (12 of 12) and desmoplastic infantile (2 of 2) gangliogliomas. Of 33 embryonal tumors, 29 were anti-Hu reactive, including 87% of medulloblastomas (26 of 30). Glial neoplasms (n = 59) were anti-Hu negative save for one "oligodendroglioma" (of 17 oligodendroglial/oligoastrocytic tumors) that may have been an extraventricular neurocytoma. Anti-Hu immunoglobulin G/Fab GLN 495 identifies neoplasms of differentiated neuronal type and embryonal tumors with neuronogenic potential.

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Background. Primary central nervous system lymphoma (PCNSL) still occurs mainly in patients who are immunosuppressed, but its incidence is rising dramatically among immunocompetent individuals. The Epstein‐Barr virus (EBV) has been detected by in situ hybridization in PCNSL tumor tissue from patients who are immunodeficient, but not from patients who are immunocompetent. Using the more sensitive polymerase chain reaction (PCR) technique, the authors analyzed PCNSL tissue from 13 patients with acquired immune deficiency syndrome (AIDS) and 13 patients who were immunocompetent for the presence of EBV genome. Methods. DNA was extracted from paraffin‐embedded biopsy or autopsy specimens. PCR was run using primers for EBV (from the first internal repeat segment of the EBV genome), and identical samples were run simultaneously with primers against actin or the p53 gene as controls to establish the presence of DNA in the sample. Reaction products were also Southern blotted to confirm EBV specificity. Results. EBV was detected in the tumor tissue of 11 of 13 patients (85%) with AIDS and of 7 of 13 patients (54%) who did not have AIDS. There was a history of illness that might suggest or predispose to immune compromise in 5 of 13 patients without AIDS; however, prior illness did not predict EBV‐positive tumors. Conclusions. Although mechanisms remain to be clarified, EBV was present in a high percentage of patients with AIDS‐related PCNSL and non‐AIDS‐related PCNSL.

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