HIV and spinal cord disease.

The epidemiology of spinal cord disease in human immunodeficiency virus (HIV) infection is largely unknown due to a paucity of data since combination antiretroviral therapy (cART). HIV mediates spinal cord injury indirectly, by immune modulation, degeneration, or associated infections and neoplasms. The pathologies vary and range from cytotoxic necrosis to demyelination and vasculitis. Control of HIV determines the differential for all neurologic presentations in infected individuals. Primary HIV-associated acute transverse myelitis, an acute inflammatory condition with pathologic similarities to HIV encephalitis, arises in early infection and at seroconversion. In contrast, HIV vacuolar myelopathy and opportunistic infections predominate in uncontrolled disease. There is systemic immune dysregulation as early as primary infection due to initial depletion of gut-associated lymphoid tissue CD4 cells and allowance of microbial translocation across the gut that never fully recovers throughout the course of HIV infection, regardless of how well controlled. The subsequent proinflammatory state may contribute to spinal cord diseases observed even after cART initiation. This chapter will highlight an array of spinal cord pathologies classified by stage of HIV infection and immune status.

Clinical pathologic case report: A 70-year-old man with inflammatory cerebral amyloid angiopathy causing headache, cognitive impairment, and aphasia.

A 70-year-old man presented with two months of worsening cognitive impairment, hallucinations, and difficulty speaking, with superimposed headaches. Cerebrospinal fluid analysis was notable for lymphocytic pleocytosis and elevated protein. Imaging studies revealed multiple acute and subacute infarcts with cortical microhemorrhages. The patient underwent a stereotactic brain biopsy. In this article, we discuss the patient's differential diagnosis, pathologic findings, ultimate diagnosis, and clinical outcome.

Stroke in HIV-infected African Americans: a retrospective cohort study.

The risk of having a first stroke is nearly twice as high among African Americans compared to Caucasians. HIV/AIDS is an independent risk factor for stroke. Our study aimed to report the risk factors and short-term clinical outcomes of African Americans with HIV infection and new-onset stroke admitted at the Johns Hopkins Hospitals (2000-2012). Multivariate linear regression was used to examine the association between potential predictors and odds of an unfavorable outcome, defined as a higher modified Rankin Scale (mRS) score on hospital discharge. African Americans comprised 105/125 (84%) of HIV-infected new-onset stroke inpatients (median age 50 years; 69% men; median CD4 140/mL; ischemic 77%; 39% taking highly active antiretroviral therapy). Vascular risk factors were common: hypertension (67%), cigarette smoking (66%), dyslipidemia (42%), hepatitis C (48%), intravenous drug abuse (32%), and prior myocardial infarction (29%). Prior aspirin and statin use were uncommon (18%, 9%). Unfavorable outcome (mRS score 4-6, n = 22 of 90 available records) was noted in 24% of patients, including seven in-hospital deaths. On multivariate analyses, higher CD4 count on hospital admission was associated with a lower mRS (-0.2 mRS points per 1 unit increase in CD4, 95% CI (-0.3, 0), p = 0.03). Intracerebral hemorrhage was also associated with a lower mRS (1.0 points lower, 95% CI (0.2, 1.8) compared to ischemic stroke, p = 0.01) after adjustment for other potential predictors. This underscores the importance of HIV infection on functional stroke outcomes beyond its recognized influence on stroke risk.

Neurologic complications in infective endocarditis: identification, management, and impact on cardiac surgery.

Neurologic complications of infective endocarditis (IE) are common and frequently life threatening. Neurologic events are not always obvious. The prediction and management of neurologic complications of IE are not easily approached algorithmically, and the impact they have on timing and ability to surgically repair or replace the affected valve often requires a painstaking evaluation and joint effort across multiple medical disciplines in order to achieve the best possible outcome. Although specific recommendations are always tailored to the individual patient, there are some guiding principles that can be used to help direct the decision-making process. Herein, we review the pathophysiology, epidemiology, manifestations, and diagnosis of neurological complications of IE and further consider the impact they have on clinical decision making.

Diffusion tensor imaging in brainstem tuberculoma.

Integrity of descending white matter tracts can be evaluated by diffusion tensor imaging. In rim-enhancing intraparenchymal lesions, this technique can assist in the differentiation of demyelinating disease from tumor or abscess. Diffusion tensor imaging characteristics of tuberculoma have not been previously reported to our knowledge. A patient with headaches, dizziness, and mild left-sided weakness underwent MRI with diffusion tensor imaging. A large, rim-enhancing lesion within the pons was discovered, which subsequently was diagnosed as tuberculoma. Tractography maps prepared from diffusion tensor imaging data revealed predominantly displaced descending fiber tracts in the region of the rim-enhancing lesion. A few tracts adjacent to the lesion appeared truncated, and this abnormal finding correlated to the patient's clinical deficit. The tractography characteristics of diffusion tensor imaging in this patient potentially are distinct from those seen with demyelinating lesions, which may show more extensive tract truncation. Together with the consonance of exam findings and tract truncation seen in this patient, tractography may prove useful in the diagnosis of suspected tuberculoma.

Selective cerebellar and basal ganglia injury in neuroleptic malignant syndrome.

BACKGROUND AND PURPOSE: High core body temperatures have been shown to selectively damage the cerebellum and basal ganglia in malignant hyperthermia, but involvement of both areas in neuroleptic malignant syndrome (NMS) has not been described. METHODS: Here, we report a case of acute cerebellar and basal ganglia injury by magnetic resonance imaging (MRI) in the setting of NMS. We discuss the pathophysiology, both of NMS and hyperthermic brain injury. RESULTS: MRI showed new restricted diffusion in cerebellar hemispheres bilaterally and right basal ganglia when compared with brain MRI obtained 1 month prior. T2 FLAIR hyperintensities corresponding to diffusion restriction were also seen in the cerebellum. CONCLUSIONS: Both the basal ganglia and cerebellum can be injured selectively in NMS.

HIV-2 encephalitis: case report and literature review.

We report the case of a 59-year-old man who moved from Cape Verde to Massachusetts at the age of 29. He had multiple sexual contacts with female partners in Cape Verde and with West African women in Massachusetts, as well as multiple past indeterminate HIV-1 antibody tests. He presented to our facility with 2-3 months of inappropriate behaviors, memory impairment, weight loss, and night sweats, at which time he was found to have an abnormal enhancing lesion of the corpus collosum on brain magnetic resonance imaging (MRI). Laboratory testing revealed a CD4 count of 63 cells/mm(3), positive HIV-2 Western blot, serum HIV-2 RNA polymerase chain reaction (PCR) of 1160 copies per milliliter and cerebrospinal fluid (CSF) HIV-2 RNA PCR of 2730 copies per milliliter. Brain biopsy demonstrated syncytial giant cells centered around small blood vessels and accompanied by microglia, which correlated with prior pathologic descriptions of HIV-2 encephalitis and with well-described findings of HIV-1 encephalitis. Based on genotype resistance assay results, treatment guidelines, and prior studies validating success with lopinavir-ritonavir, he was treated with tenofovir-emtricitabine and lopinavir-ritonavir, which has led to virologic suppression along with steady neurologic and radiologic improvement, although he continues to have deficits.

Monocyte activation markers in cerebrospinal fluid associated with impaired neurocognitive testing in advanced HIV infection.

BACKGROUND: Activated monocytes/macrophages play a role in severe forms of HIV-associated neurocognitive disorders (HAND), but little is known about the mechanisms driving milder forms that are prevalent despite combination antiretroviral therapy (cART). To examine relationships of monocyte activation markers to HAND of varying severity, we compared plasma and cerebrospinal fluid (CSF) biomarker levels with neurocognitive test scores in HIV+ subjects. METHODS: Plasma and CSF soluble CD14 (sCD14), CCL2, and interleukin (IL) 6 were measured by enzyme-linked immunosorbent assay in 67 HIV+ subjects with nadir CD4 <300, and CSF inflammatory biomarkers were measured by multiplex assay in 14 subjects on suppressive cART. RESULTS: Eighty-two percent were on cART, with 31% having undetectable plasma viral load (VL). CSF sCD14 was increased in subjects with impaired neurocognitive testing (P = 0.02), correlated inversely with global T scores in subjects with detectable but not undetectable plasma VL (P = 0.02), and yielded higher area under the receiver operating characteristic curve values for predicting impaired T scores (0.659) than plasma or CSF VL and current or nadir CD4 counts in single-marker and multivariate models. CSF sCD14, IL-6, IL-8, CCL2, CCL3, CXCL10, and interferon (IFN) gamma were increased in subjects on suppressive cART regardless of cognitive status and predicted patient class in unsupervised analyses, with IL-8, CCL2, and IFNγ explaining most of the variance. CONCLUSIONS: CSF sCD14 is associated with impaired neurocognitive testing in patients with HIV on nonsuppressive cART, suggesting potential utility as a biomarker to monitor HAND progression. CSF sCD14, IL-6, IL-8, CCL2, CCL3, CXCL10, and IFNγ remain elevated in patients on suppressive cART regardless of cognitive status, implying ongoing intrathecal inflammation even in the absence of clinical manifestations.