Nutritional Contributions to the CNS Pathophysiology of HIV-1 Infection and Implications for Treatment

Nutritional deficiencies are commonplace in patients with human immunodeficiency virus type 1 (HIV-1) infection, and recent research has indicated that nutritional factors may play an important role in the pathogenesis of HIV-1 disease. Although nutritional deficiencies are unlikely to be the primary causative factor in disease progression, they may contribute to cognitive dysfunction, neurologic abnormalities, mood disturbance, and immune dysregulation associated with HIV-1 infection. Furthermore, deficiencies of specific micronutrients have been associated with increased risk of HIV-1-associated mortality. This article will briefly summarize the role of macronutrient deficiency, the interactions of specific micronutrient deficiencies with neuropsychiatric functioning, and the role of these factors in HIV-1 disease progression. Since recent research has shown that normalization of many nutritional deficits and supplementation beyond normal levels are associated with improvements in neuropsychiatric functioning, potential treatment implications will also be discussed.     

Cognitive Effects of HIV-1 Infection

The major neurological complication of human immunodeficiency virus type 1 (HIV-1) infection is cognitive impairment, which can range in severity from a mild subclinical cognitive inefficiency to a severe dementing illness. Mild to moderate cognitive impairment is identified primarily by neuropsychological tests. The prevalence and severity of cognitive impairment associated with HIV-1 infection increases as the disease progresses. Deficits in attention, information processing speed, memory, and motor abilities can occur early in the course of HIV-1 infection, with deficits in abstraction and executive functions observed in later stages of infection. The nature of the cognitive impairment observed is thought to reflect the effects of HIV-1 infection on the integrity of subcortical or frontostriatal brain systems. Issues related to the detection of subclinical to severe cognitive impairment are discussed, along with the clinical significance of mild cognitive impairment as a significant risk factor for mortality in HIV-1 infection. The need to control for possible confounding factors that can influence test performance is also reviewed.     

Dementia and the Neurovirulence of HIV-1

Infection with human immunodeficiency virus type 1 (HIV-1) leads rapidly to infection of the brain and subsequent neuropsychological impairment, including subclinical impairment, minor cognitive-motor disorder, and HIV-1-associated dementia (HAD). This article reviews HAD and the factors involved in its pathogenesis; the effectiveness of antiretroviral therapy; the prevalence of HIV-1 and subtypes; and the role of chemokines and cytokines as the capstones associated with neuropathology due to inflammation.     

HIV-1 infection and its impact on the HPA axis, cytokines, and cognition

Immediately after infection, Human immunodeficiency virus, type 1 (HIV-1) enters the central nervous system (CNS) and is localized in highest concentration in the hippocampus and basal ganglia. Since these areas are associated with HPA axis and autonomic activities as well as cognition, it has been hypothesized that these functions will be impacted adversely in HIV-1 infection. In the treatment of HIV infection, although the highly potent antiretroviral (HAART) drugs have been effective in reducing peripheral viral load and prolonging life expectancy, these drugs do not cross the blood-brain barrier in therapeutic concentrations. Therefore, it has been proposed that the beneficial effects of HAART on the CNS will be limited. Our investigations on seropositive individuals, showing hypo-reactivity of the autonomic system and HPA axis activity suggest that HIV-1 infection is a model of chronic stress. Furthermore, an elevated baseline TNF-alpha level as well as its increased reactivity to an alpha-adrenergic challenge among HIV-1+ individuals, may lead to additional neurodegeneration. It is proposed that the effects of HIV-1 infection on the brain will have implications for neurocognitive and mental health functioning in seropositive individuals even in patients undergoing HAART therapy. These outcomes may result in the need to develop facilities for long term "care-giving".     

Cynical Hostility: A Risk Factor in HIV-1 Infection?1

The aims of this study of HIV-1 positive and HIV-1 negative gay males without disease were (a) to determine whether cynical hostility in these groups (measured by the Cook-Medley Ho scale) is associated with psychosocial deficits that potentially could influence the course of HIV infection; and (b) to examine the construct validity of the sum of three Ho subsets in this sample. Correlational analyses on the full samples, and multivariate analyses of high- and low-hostility groups (formed using Ho scale cutoffs from previous research), examined person variables (traits, coping style), environmental variables (social support, stressors), and affect. In all domains other than stressors (traits, coping styles, social support, and affect), cynical hostility was associated with psychosocial deficits, with results generally stronger for the full Ho scale than for the subset sum. Results support previous research on psychosocial deficits of the cynically hostile, extend findings to HIV-infected gay males, and enlarge our understanding of the trait and coping style correlates of cynical hostility. Implications of these findings for HIV infection are discussed.     

Difficulties in interpersonal relationships associated with personality disorders and axis I disorders: a community-based longitudinal investigation

A longitudinal study was conducted to investigate the association between Axis I and Axis II psychiatric disorders, interpersonal relationships, and global functioning among men in the community. Structured clinical interviews assessing Axis I and Axis II psychiatric disorders, global assessments of functioning, and questionnaires assessing social support, social conflict, and loneliness were administered to a community sample of 95 HIV+ and 45 HIV- men. The questionnaires were readministered 1 year later. Results indicated that (a) Personality disorders (PDs) and unipolar depressive disorders were associated with loneliness, social conflict, and low levels of social support after HIV status was controlled statistically; (b) PDs were associated with interpersonal and global impairment after HIV status and co-occurring Axis I disorders were controlled statistically; (c) Axis I disorders were associated with global impairment, but were not associated with interpersonal difficulties after HIV status and PDs were controlled statistically; (d) PDs, but not Axis I disorders, predicted increases in social conflict and global impairment after HIV status was controlled statistically; (e) PDs continued to predict increases in global impairment after both Axis I disorders and HIV status were controlled statistically; and (f) HIV+ men reported more loneliness, less social support, and had a higher prevalence of substance use disorders than HIV- men. The present findings are of particular interest because they suggest that PDs are associated with loneliness, social conflict, and a lack of social support among men in the community, whether or not Axis I disorders are present.     

Central Nervous System Opportunistic Infections in HIV-1 Infection

Neurologic disease is commonly encountered in the population infected with human immunodeficiency virus type 1 (HIV-1). Although HIV-1 is responsible for many of these neurologic complications, other organisms will affect the nervous system as the immune deficiency state progresses. With the wide use of potent antiretroviral therapy, the mortality from and incidence of opportunistic infections (OIs) among persons with advanced HIV-1 infection has decreased. Nevertheless, these diseases are still seen frequently, especially among those with limited access to new antiretroviral therapies. Therefore, it remains important to recognize the most common OIs of the central nervous system (CNS) as well as primary CNS lymphoma, which will be the focus of this review.     

Psychosocial correlates of immune status and disease progression in HIV-1 infected homosexual men: Review of preliminary findings,and commentary

Abstract

Behavioral factors may have an effect on the course of infection in HIV-1 infected individuals. These effects can be mediated by the immune system of the host, which, based on psychoneuroimmunologic findings, can be affected by some psychosocial factors. We present a short review of some putative psychoneuroimmunologic pathways and their possible implications for HIV-1 infected individuals. We next summarize the findings of recent psychoimmunological work with HIV-1 seropositives and discuss the methodological problems in studying the psychoneuroimmunologic aspects of HIV-1 infection. Psychoneuroimmunologic research in HIV-1 seropositives is a rapidly developing field, yielding contradictory findings so far, but which in the long run could provide important knowledge for psychoimmunologic interventions, targeted at improving or preserving immune status and retarding disease progression, as well as optimizing psychosocial functioning.     

Computer tomography and electromyography studies in patients with traumatic neuropathy

Combined computerized tomography and neurophysiological techniques permit the simultaneous assessment of morphological and functional aspects associated with traumatic neuropathy. The simultaneous application of such techniques is one way of optimizing status analysis and prognosis .     

Neurobehavioral outcomes in diseases of childhood. Individual change models for pediatric human immunodeficiency viruses.

The growing incidence of human immunodeficiency virus-1 (HIV-1) and acquired immunodeficiency syndrome (AIDS) in children is a major public health problem. Current research emphasizes treatments for ameliorating deleterious effects on the child's neurological and behavioral development. This article outlines approaches to the assessment of individual change that may provide alternatives to more traditional approaches to the assessment of neurobehavioral outcomes in children with chronic diseases. These approaches provide more precise conceptualizations of changes that lead directly to statistical designs and measurement strategies for assessing effects of HIV-1 and AIDS on development. Such assessments can be superimposed on current clinical trial methodologies to evaluate the efficacy of pharmacological and behavioral interventions designed to improve quality of life in HIV-1 infected children.     

HIV-1 Infection, Neuroendocrine Abnormalities, and Clinical Outcomes

Different lines of evidence suggest that human immunodeficiency virus type 1 (HIV-1) infection is complicated by a variety of adverse effects on neuroendocrine systems. Soon after the discovery of HIV-1, reports began to appear suggesting that a number of neurotransmitter and neuroendocrine activities were negatively impacted by this infection. In 1987 it was observed that fine-needle aspiration of the lung in patients with acquired immunodeficiency syndrome resulted in syncopal reactions. Subsequently, an abnormality in the autonomic nervous system was reported in these patients. However, investigations in this area have remained limited due to the assumption that HIV-1-mediated activation of various endocrine systems was related to the major life stressor of living with a fatal disease. Evidence accumulated over the years has indicated, instead, that there are various other mechanisms in addition to life stressors that also play an important role in negatively impacting the neuroendocrine systems in this infection. This article examines various developments that have taken place in this area in order to provide avenues for future research.     

糖尿病周围神经病变的临床特征及诊断

对称性多发性神经病是糖尿病周围神经病变最常见的类型,根据受损神经纤维的不同,其临床特征亦有差别。目前已有多种方法用于糖尿病周围神经病变的诊断,包括简单的筛查方法,神经电生理检查,定量感觉检查及形态学检查等,但其标准的诊断定义还未达成一致。     

Coping and physical health during caregiving: the roles of positive and negative affect

The associations among coping, mood, and health variables were examined prospectively over 2 years in 86 HIV positive (HIV+) and 167 HIV negative (HIV-) gay men undergoing the stress of AIDS-related caregiving. Path models suggested that including both positive and negative mood and the men's associated coping strategies increases understanding of why some people suffer adverse health effects during times of stress. Among the HIV- caregivers, higher levels of social coping predicted increases in positive affect, which in turn resulted in lower levels of physical symptoms. In contrast, higher levels of cognitive avoidance predicted increases in negative affect, which in turn resulted in higher levels of physical symptoms. Self-injurious forms of avoidance coping predicted higher levels of physical symptoms independent of mood among the HIV+ caregivers.     

若干实验室指标对糖尿病神经病变的预测意义

近年来,人们发现了一些实验室指标对糖尿病神经病变有一定预测意义,包括糖化血红蛋白、维生素B12、甲基丙二酸、全反钴胺素、同型半胱氨酸、氧化型低密度脂蛋白、甘油三酯、超敏C反应蛋白、肿瘤坏死因子α(TNF-α)、可溶性肿瘤坏死因子受体1、可溶性肿瘤坏死因子受体2等。这些指标对糖尿病神经病变的早期防治提供了帮助。     

Left-handedness: a marker for decreased survival fitness

Life span studies have shown that the population percentage of left-handers diminishes steadily, so that they are drastically underrepresented in the oldest age groups. Data are reviewed that indicate that this population trend is due to the reduced longevity of left-handers. Some of the elevated risk for sinistrals is apparently due to environmental factors that elevate their accident susceptibility. Further evidence suggests that left-handedness may be a marker for birth stress related neuropathy, developmental delays and irregularities, and deficiencies in the immune system due to the intrauterine hormonal environment. Some statistical and physiological factors that may cause left-handedness to be selectively associated with earlier mortality are also presented.     

糖尿病周围神经病变临床研究进展

糖尿病周围神经病变(DPN)患者可无临床症状,通常结合症状、体症、10g单尼龙丝、128HZ音叉检查、神经电生理学、定量感觉检查、温度阈值、足底压力测定等检查判断。10g单尼龙丝、128HZ音叉检查、神经电生理学检查是最常用的临床检查。临床上经常应用一些简单的筛查性问卷调查来描述症状的严重性。近年来神经活检有创性检查,MRI、角膜共聚显微镜等无创性检查,以及对自主神经病变的早期诊断进展较快。由于流行病学研究中多不同程度采用上述检查方法,对于研究结果的一致性值得关注。     

A randomized controlled trial of a peer support intervention targeting antiretroviral medication adherence and depressive symptomatology in HIV-positive men and women.

OBJECTIVE: To determine the efficacy of a peer-led social support intervention involving support groups and telephone contacts compared with standard clinical care to enhance antiretroviral medication adherence. DESIGN: Randomized controlled trial with follow-up. Participants were 136 HIV-positive indigent mainly African American and Puerto Rican men and women recruited from an outpatient clinic in the Bronx, New York. The 3-month intervention was delivered by other HIV-positive clinic patients trained in addressing barriers to adherence and sensitively providing appraisal, spiritual, emotional, and informational adherence-related social support. MAIN OUTCOME MEASURES: Medical chart-abstracted HIV-1 RNA viral load, antiretroviral adherence according to electronic drug monitoring and participant self-report, and social support and depressive symptomatology. All assessments conducted at baseline, 3 months, and 6 months. RESULTS: Intent-to-treat and as-treated analyses indicated no between-conditions intervention effects on the primary outcome of HIV-1 RNA viral load or any of the secondary outcomes at immediate postintervention or follow-up. Post hoc analyses within the intervention condition indicated greater intervention exposure was associated with higher self-reported adherence, higher social support, and lower depressive symptomatology at follow-up, even after controlling for baseline adherence. CONCLUSION: Null findings, consistent with the limited literature on efficacious highly active antiretroviral therapy (HAART) adherence interventions, may be due to insufficient exposure to the intervention, its low intensity, or the nature of the sample-a heterogeneous HAART-experienced group of patients with high levels of substance use and multiple other competing stressors. Overall, findings highlight the need for more comprehensive and intensive efforts to battle nonadherence.     

Neuropsychological Assessment of HIV-Infected Populations in International Settings

Resource-limited regions of the world represent the areas most affected by the global HIV epidemic. Currently, there are insufficient data on the neurocognitive effects of HIV in these areas and neuropsychological studies that have been carried out thus far are marked by inconsistent methods, test batteries, and rating systems for levels of cognitive impairment. These differences in methods, along with genetic variability of both virus and host, differences in co-infections and other co-morbidities, differences in language and culture, and infrastructural deficiencies in many international settings create challenges to the assessment of neurocognitive functioning and interpretation of neuropsychological data. Identifying neurocognitive impairment directly attributable to HIV, exploring relationships between HIV-associated neurocognitive impairment, disease variables, and everyday functioning, evaluating differences in HIV-1 subtype associated neuropathology, and determining implications for treatment remain complicated and challenging goals. Endeavors to establish a more standardized approach to neurocognitive assessments across international studies in addition to accumulating appropriate normative data that will allow more accurate rating of neuropsychological test performance will be crucial to future efforts attempting to achieve these goals.     

A new approach to identifying the effect of diabetic peripheral neuropathy on the ability to drive safely

The purpose of this study was to estimate the potential for impaired driving performance in current drivers with diabetic peripheral neuropathy compared to healthy controls. We analysed, using a driving simulator, three important aspects of driving - use of the accelerator pedal, steering wheel and eye-steering coordination - to test for any differences, and then to integrate these findings to identify a unique pattern of changes in people driving with diabetic peripheral neuropathy. Patients with diabetic peripheral neuropathy displayed differences in use of the accelerator pedal compared to healthy control drivers (p < 0.05) which could be a direct consequence of their sensorimotor impairment due to diabetic peripheral neuropathy. Drivers with DPN used the more extreme high and low positions of the pedal to a greater extent than the Control group who exhibited a more graded use of the accelerator pedal over the mid-range. Eye-steering coordination was also different in drivers with diabetic peripheral neuropathy (p < 0.05) and, as it improved during the second drive, becoming closer to healthy drivers’ values, the occasional loss of control experienced during driving reduced. These insights demonstrate that diabetic peripheral neuropathy affects multiple aspects of driving performance suggesting the need for an integrated approach to evaluate the potential for driving safely in this population.