Effects of alcohol and HIV infection on the central nervous system.

Many people at risk for or infected with the human immunodeficiency virus (HIV) are heavy drinkers. Both HIV infection and heavy alcohol use adversely affect the immune system and central nervous system (CNS) function. However, little research has addressed the effects of heavy alcohol use on the severity and progression of HIV disease, including the development of HIV-associated CNS disease. Animal and in-vitro studies suggest that alcohol impairs various aspects of the immune system and increases the susceptibility to HIV infection, but may not accelerate progression of HIV disease. However, heavy alcohol use may interfere with the patient's adherence to antiretroviral treatment regimens. Neuropathological and neuropsychological studies have indicated that certain brain areas are affected by both HIV-infection and chronic alcohol abuse. Magnetic resonance spectroscopy studies of both HIV-positive and HIV-negative people who were either heavy or light drinkers found that chronic alcohol abuse exacerbates some metabolic injury in the brains of HIV-infected people, although this effect may be less pronounced in patients receiving effective antiretroviral therapy

Putamen volume and its clinical and neurological correlates in primary HIV infection

Objective: Little is known about the extent of cortical and subcortical volumetric alterations that may occur within the first year of HIV infection [primary HIV infection (PHI)]. Design: We used structural MRI in this prospective cross-sectional neuroimaging study to determine the extent of volumetric changes in early HIV infection. Methods: Cerebrospinal fluid, blood, neuropsychological testing, and structural T1 MRI scans were acquired from 18 HIV and 47 PHI age-matched antiretroviral-naïve male participants. Using FreeSurfer 5.1, volumetric measurements were obtained from the caudate, amygdala, corpus callosum, ventricles, putamen, thalamus, cortical white matter, and total gray matter. Regional volumes were compared groupwise and related to biomarkers in cerebrospinal fluid (viral load, neopterin, and neurofilament light chain), blood (viral load, CD4+, and CD8+ T-cell count), and neuropsychometric tests (digit-symbol, grooved pegboard, finger-tapping, and timed gait). Results: A trend-level moderate reduction of putamen volume (P = 0.076, adjusted Cohen's d = 0.5 after controlling for age) was observed for PHI compared with HIV-uninfected individuals. Within the PHI group, putamen volume associated with CD4+ cell count (P = 0.03), CD4+/CD8+ ratio (P = 0.045), infection duration (P = 0.009), and worsening psychomotor performance on the digit-symbol (P = 0.028), finger-tapping (P = 0.039), and timed gait (P = 0.009) tests. Conclusion: Our volumetric results suggest that the putamen is preferentially susceptible to early HIV-associated processes. Examining the natural course of early HIV infection longitudinally will allow for mapping of the trajectory of HIV-associated central nervous system changes, enabling creation of improved interventional strategies to potentially stabilize or reverse these observed structural changes

Experimental Design

AbstractThis chapter covers various issues related to the experimental design, a statistical technique at the core of a discrete choice experiment. Specifically, it focuses on the dimensionality of a choice experiment and the statistical techniques used to allocate attribute levels to choice tasks. Among others, the pros and cons of orthogonal designs, optimal orthogonal in the differences designs as well as efficient designs are addressed. The last section shows how a simulation exercise can help to test the appropriateness of the experimental design

Asymptomatic neurocognitive disorders in patients infected by HIV: fact or fiction?

Neurocognitive disorders are emerging as a possible complication in patients infected with HIV. Even if asymptomatic, neurocognitive abnormalities are frequently detected using a battery of tests. This supported the creation of asymptomatic neurocognitive impairment (ANI) as a new entity. In a recent article published in BMC Infectious Diseases, Magnus Gisslén and colleagues applied a statistical approach, concluding that there is an overestimation of the actual problem. In fact, about 20% of patients are classified as neurocognitively impaired without a clear impact on daily activities. In the present commentary, we discuss the clinical implications of their findings. Although a cautious approach would indicate a stricter follow-up of patients affected by this disorder, it is premature to consider it as a proper disease. Based on a review of the data in the current literature we conclude that it is urgent to conduct more studies to estimate the overall risk of progression of the asymptomatic neurocognitive impairment. Moreover, it is important to understand whether new biomarkers or neuroimaging tools can help to identify better the most at risk population

HIV infection and drugs of abuse: role of acute phase proteins

Background HIV infection and drugs of abuse such as methamphetamine (METH), cocaine, and alcohol use have been identified as risk factors for triggering inflammation. Acute phase proteins such as C-reactive protein (CRP) and serum amyloid A (SAA) are the biomarkers of inflammation. Hence, the interactive effect of drugs of abuse with acute phase proteins in HIV-positive subjects was investigated. Methods Plasma samples were utilized from 75 subjects with METH use, cocaine use, alcohol use, and HIV-positive alone and HIV-positive METH, cocaine, and alcohol users, and age-matched control subjects. The plasma CRP and SAA levels were measured by ELISA and western blot respectively and the CD4 counts were also measured. Results Observed results indicated that the CRP and SAA levels in HIV-positive subjects who are METH, cocaine and alcohol users were significantly higher when compared with either drugs of abuse or HIV-positive alone. The CD4 counts were also dramatically reduced in HIV-positive with drugs of abuse subjects compared with only HIV-positive subjects. Conclusions These results suggest that, in HIV-positive subjects, drugs of abuse increase the levels of CRP and SAA, which may impact on the HIV infection and disease progression

Alcohol Induces Sensitization to Gluten in Genetically Susceptible Individuals: A Case Control Study

Background: The mechanisms of cerebellar degeneration attributed to prolonged and excessive alcohol intake remain unclear. Additional or even alternative causes of cerebellar degeneration are often overlooked in suspected cases of alcohol-related ataxia. The objectives of this study were two fold: (1) to investigate the prevalence of gluten-related serological markers in patients with alcohol-related ataxia and; (2) to compare the pattern of brain involvement on magnetic resonance imaging between patients with alcohol and gluten ataxias. Materials & Methods: Patients diagnosed with alcohol and gluten ataxias were identified from a retrospective review of patients attending a tertiary clinic. HLA genotype and serological markers of gluten-related disorders were recorded. Cerebellar volumetry, MR spectroscopy and voxel-based morphometric analyses were performed on patients and compared with matched control data. Results: Of 904 registered patients, 104 had alcohol ataxia and 159 had gluten ataxia. 61% of the alcohol ataxia group and 70% of the gluten ataxia group had HLA DQ2/DQ8 genotype compared to 30% in healthy local blood donors. 44% of patients with alcohol ataxia had antigliadin antibodies compared to 12% in the healthy local population and 10% in patients with genetically confirmed ataxias. None of the patients with alcohol ataxia and antigliadin antibodies had celiac disease compared to 40% in patients with gluten ataxia. The pattern of structural brain abnormality in patients with alcohol ataxia who had antigliadin antibodies differed from gluten ataxia and was identical to that of alcohol ataxia. Conclusions: Alcohol related cerebellar degeneration may, in genetically susceptible individuals, induce sensitization to gluten. Such sensitization may result from a primary cerebellar insult, but a more systemic effect is also possible. The duration and amount of exposure to alcohol may not be the only factors responsible for the cerebellar insult

Proton Magnetic Resonance Spectroscopy Reveals Neuroprotection by Oral Minocycline in a Nonhuman Primate Model of Accelerated NeuroAIDS

Background: Despite the advent of highly active anti-retroviral therapy (HAART), HIV-associated neurocognitive disorders continue to be a significant problem. In efforts to understand and alleviate neurocognitive deficits associated with HIV, we used an accelerated simian immunodeficiency virus (SIV) macaque model of NeuroAIDS to test whether minocycline is neuroprotective against lentiviral-induced neuronal injury. Methodology/Principal Findings: Eleven rhesus macaques were infected with SIV, depleted of CD8+ lymphocytes, and studied until eight weeks post inoculation (wpi). Seven animals received daily minocycline orally beginning at 4 wpi. Neuronal integrity was monitored in vivo by proton magnetic resonance spectroscopy and post-mortem by immunohistochemistry for synaptophysin (SYN), microtubule-associated protein 2 (MAP2), and neuronal counts. Astrogliosis and microglial activation were quantified by measuring glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule 1 (IBA-1), respectively. SIV infection followed by CD8+ cell depletion induced a progressive decline in neuronal integrity evidenced by declining N-acetylaspartate/creatine (NAA/Cr), which was arrested with minocycline treatment. The recovery of this ratio was due to increases in NAA, indicating neuronal recovery, and decreases in Cr, likely reflecting downregulation of glial cell activation. SYN, MAP2, and neuronal counts were found to be higher in minocycline-treated animals compared to untreated animals while GFAP and IBA-1 expression were decreased compared to controls. CSF and plasma viral loads were lower in MN-treated animals. Conclusions/Significance: In conclusion, oral minocycline alleviates neuronal damage induced by the AIDS virus

Episodic Memory in Detoxified Alcoholics: Contribution of Grey Matter Microstructure Alteration

Even though uncomplicated alcoholics may likely have episodic memory deficits, discrepancies exist regarding to the integrity of brain regions that underlie this function in healthy subjects. Possible relationships between episodic memory and 1) brain microstructure assessed by magnetic resonance diffusion tensor imaging (DTI), 2) brain volumes assessed by voxel-based morphometry (VBM) were investigated in uncomplicated, detoxified alcoholics

Correlations between Diffusion Tensor Imaging (DTI) and Magnetic Resonance Spectroscopy (1H MRS) in schizophrenic patients and normal controls

<p>Abstract</p> <p>Background</p> <p>Evidence suggests that white matter integrity may play an underlying pathophysiological role in schizophrenia. N-acetylaspartate (NAA), as measured by Magnetic Resonance Spectroscopy (MRS), is a neuronal marker and is decreased in white matter lesions and regions of axonal loss. It has also been found to be reduced in the prefrontal and temporal regions in patients with schizophrenia. Diffusion Tensor Imaging (DTI) allows one to measure the orientations of axonal tracts as well as the coherence of axonal bundles. DTI is thus sensitive to demyelination and other structural abnormalities. DTI has also shown abnormalities in these regions.</p> <p>Methods</p> <p>MRS and DTI were obtained on 42 healthy subjects and 40 subjects with schizophrenia. The data was analyzed using regions of interests in the Dorso-Lateral Prefrontal white matter, Medial Temporal white matter and Occipital white matter using both imaging modalities.</p> <p>Results</p> <p>NAA was significantly reduced in the patient population in the Medial Temporal regions. DTI anisotropy indices were also reduced in the same Medial Temporal regions. NAA and DTI-anisotropy indices were also correlated in the left medial temporal region.</p> <p>Conclusion</p> <p>Our results implicate defects in the medial temporal white matter in patients with schizophrenia. Moreover, MRS and DTI are complementary modalities for the study of white matter disruptions in patients with schizophrenia.</p