Plasma Oxidized Albumin in Acute Ischemic Stroke Is Associated With Better Outcomes.

Introduction: Plasma oxidized human serum albumin (OxHSA) is evidence of an active antioxidant mechanism as measured by oxidized species of HSA. CXCL-10 is a pro-inflammatory chemokine associated with ischemic conditions. Accordingly, we examined the relationship of admission OxHSA and CXCL-10 with discharge mRS in acute ischemic stroke (AIS). Methods: Plasma samples and clinical data were collected prospectively at a Comprehensive Stroke Center. Admission biomarkers of oxidative stress, CXCL-10 and %OxHSA, were measured. We examined if CXCL-10 or %OxHSA correlated with age, admission NIHSS score, and discharge mRS score using Spearman's Rank correlation. Logistic regression was performed to identify independent predictors of a favorable discharge mRS (≤2). Results: In 106 consecutive AIS patients, the median age was 73 (IQR 61-84), 47% were male, and the median admission NIHSS score was 11 (IQR 5-19). %OxHSA and CXCL-10 were significantly correlated (r = 0.23, p = 0.02). Both biomarkers were significantly correlated with age: %OxHSA (r = 0.44, p < 0.001) and CXCL-10 (r = 0.32, p = 0.001). Neither biomarker was correlated with admission NIHSS. There was a borderline significant correlation with discharge mRS and %OxHSA (r = -0.17, p = 0.08), where higher %OxHSA correlated with lower discharge mRS scores. For every 1% increase in %OxHSA, the odds of a favorable discharge mRS increased 11%. The odds of a favorable discharge mRS decreased 18% for every 1-point increase in the initial NIHSS. Conclusions: OxHSA, the result of an oxidative environment and evidence of the strong antioxidant buffering capacity of HSA, correlated with CXCL-10 and discharge mRS, implying that strong antioxidant activity of albumin may confer better outcomes.

White matter anisotropy and depression symptoms in patients with HIV.

HIV is associated with increased risk for depression. Normal appearing white matter (NAWM) fractional anisotropy in 15 HIV-seropositive (HIV+) adults with depressive symptoms was compared to 15 HIV+ adults without depressive symptoms. HIV+ adults with depressive symptoms showed increased NAWM fractional anisotropy within the left thalamus, the temporal, and frontal regions, as well as the right cingulate. Discrete components of depression were associated with distinct regional NAWM fractional anisotropy increases. These results demonstrate altered neural complexity in HIV+ adults with depressive symptoms and support the notion that depression is multifactorial with different morphological alterations contributing to discrete aspects of depression.

HIV-associated alterations in normal-appearing white matter: a voxel-wise diffusion tensor imaging study.

OBJECTIVE: There are conflicting reports of adverse HIV-associated alterations in white matter integrity as measured by diffusion tensor imaging (DTI). We sought to address these conflicting reports by assessing, on a voxel-by-voxel basis, HIV-associated regional changes in radiologically defined normal-appearing white matter (NAWM) integrity using high-resolution DTI. METHODS: 30 HIV-seropositive (SP) and 30 HIV-seronegative (SN) nondemented, community-dwelling participants underwent DTI to derive whole-brain measures of white matter integrity (fractional anisotropy [FA] and mean diffusivity [MD]). For each participant, the white matter T2 volume was thresholded to remove regions of abnormal signal, resulting in a NAWM mask, which was then applied to the FA and MD volumes to extract voxel-wise NAWM measures of white matter integrity. Voxel-wise group comparisons of FA and MD were conducted (P < 0.005, extent threshold 5 voxels) while controlling for age and substance-abuse history. RESULTS: There were no significant differences between the groups for demographic or cognitive performance variables. Summary whole-brain measures of FA and MD were equivalent between the SP and SN samples. Among the SP sample, history of substance abuse was associated with significantly increased whole-brain NAWM MD, and coinfection with hepatitis C virus (HCV) was associated with a trend for increased MD. Correlations between whole-brain NAWM FA and MD with cognitive performance measures were not significant. Regional analyses of DTI measures revealed variable differences in NAWM FA in the SP sample, with findings of both decreased and increased FA. Differences in NAWM MD were more consistent, with widespread increases noted in the SP sample compared to the SN sample. Eight of the 10 regions displaying significantly increased FA in the SP sample were also found to have significantly increased MD compared to the SN sample. CONCLUSIONS: Decreased white matter integrity is present even in radiologically defined NAWM in nondemented, community-dwelling patients with HIV. The decrease in NAWM integrity is best seen in increases in MD, a measure of generalized tissue breakdown. Indications of NAWM axonal integrity (FA) present a more complicated picture, with both decreased FA and increased FA in the SP sample. Our findings of variable HIV-associated FA changes in NAWM may account for previous conflicting reports of changes in DTI parameters in this population. The results of our study suggest that HIV infection contributes to variable changes in DTI values, reflecting both direct loss of axonal integrity and a loss of complexity to the underlying axonal matrix.

Multiple sclerosis, natalizumab therapy, and progressive multifocal leukoencephalopathy.

PURPOSE OF REVIEW: Multiple sclerosis affects many people, often in early adulthood, and causes significant disability. Natalizumab is a novel agent to be evaluated for multiple sclerosis and Crohn's disease that has demonstrated unique efficacy but has unfortunately been implicated in three cases of progressive multifocal leukoencephalopathy. This review covers the mechanism of action of natalizumab and efficacy for multiple sclerosis, the three cases of natalizumab-associated progressive multifocal leukoencephalopathy, our understanding of progressive multifocal leukoencephalopathy, and the mechanisms that may account for these events. RECENT FINDINGS: Natalizumab, an anti-alpha4-integrin antibody, binds to T-cell surface receptors to prevent migration from the circulation into the brain tissue. Phase II and III trials have been completed and demonstrate previously unseen efficacy in preventing relapses and disease progression. The cases of progressive multifocal leukoencephalopathy, two fatal and one disabling, resulted in the voluntary suspension of natalizumab and bring this entire class of agents into doubt. It is important to determine what led to the development of progressive multifocal leukoencephalopathy in the natalizumab-associated cases and to advance understanding and continue to develop therapies for the treatment of multiple sclerosis. SUMMARY: With ongoing safety evaluations, natalizumab is being reevaluated by the US Food and Drug Administration for possible reapproval and return to the market. If natalizumab is reapproved, challenging questions and issues will remain in treating patients with multiple sclerosis.

Statin-associated peripheral neuropathy: review of the literature.

Various pharmacologic agents are available for the treatment of hypercholesterolemia, including 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, commonly referred to as statins, which offer favorable lipid-lowering effects and reductions in morbidity and mortality. Statins are usually better tolerated than other lipid-lowering agents and therefore have become a mainstay of treatment for hypercholesterolemia. However, recent case reports of peripheral neuropathy in patients treated with statins may have gone unnoticed by health care professionals. To evaluate the possible link between statins and peripheral neuropathy, literature searches using MEDLINE (January 1993--November 2003) and International Pharmaceutical Abstracts (January 1970--June 2002) were performed. Key search terms were statin, neuropathy, and HMG-CoA reductase inhibitors. Based on epidemiologic studies as well as case reports, a risk of peripheral neuropathy associated with statin use may exist; however, the risk appears to be minimal. On the other hand, the benefits of statins are firmly established. These findings should alert prescribers to a potential risk of peripheral neuropathy in patients receiving any of the statins; that is, statins should be considered the cause of peripheral neuropathy when other etiologies have been excluded.

Leprosy (Hansen's Disease).

Leprosy (Hansen's disease) causes the most common treatable form of neuropathy in the world. Several endemic countries account for the majority of the world's cases and most of the cases seen in the US are amongst immigrants. However, endemic cases of leprosy occur in the US. The pathogen is Mycobacterium leprae, a slow-growing, obligate intracellular pathogen that consistently infects skin and peripheral nerves. The clinical appearance of the skin and neurologic deficits develop months to years after infection and are determined by the host's response to the infection. An individual's disease classification can change over time based on the immune status of the individual. Immune-mediated "reactional states" may also occur that require additional recognition and treatment. Varied in its manifestations, a successful treatment approach relies on proper recognition and classification of disease.