HIV-associated Distal Symmetrical Polyneuropathy Research Articles

Strength exercise for balance and gait in HIV-associated distal symmetrical polyneuropathy: A randomised controlled trial.

BackgroundHIV-associated peripheral neuropathy (PN) is a common neurological complication associated with HIV infection. Distal symmetrical polyneuropathy (DSPN) is the most commonly occurring type, which is associated with symptoms such as numbness, unsteady gait and, in some cases, muscle atrophy and weakness when myelinated nerve fibres are affected. If unmyelinated nerve fibres are affected, a painful neuropathy and autonomic symptoms may occur.ObjectivesThis research study assessed the effects of a strength exercise intervention on balance impairment and gait disturbance amongst individuals living with HIV-associated DSPN.MethodThe study was a single-blinded, randomised controlled trial (RCT) with participants sourced from four HIV centres in Kano metropolis, Nigeria. The intervention was supervised and included progressive resistance exercise (PRE) (three 40-min sessions per week for 12 weeks) using a quadriceps bench (n = 44). The control group (CG) included the non-exercise group (n = 47). The two groups continued to receive routine care. Data were summarised and analysed using inferential statistics (SPSS version 20 program) with the alpha level set at < 0.05.ResultsAt 12 weeks, the results revealed significant improvement with regard to balance performance (p = 0.001) and walking ability (p = 0.001) in the training group. In contrast, no significant differences in balance (P = 0.677) or gait (P = 0.578) were observed in the CG.ConclusionThe findings suggest that PRE is beneficial for balance impairment and gait disturbance caused by neuropathy in persons living with HIV and receiving antiretroviral drugs.

HIV neuropathy.

To present an overview of HIV-associated distal symmetric polyneuropathy (HIV-DSP) and other HIV-related peripheral neuropathies in the post-highly active retroviral therapy era. HIV-DSP has become the most common neurologic complication of HIV largely due to the prolonged survival of HIV-positive patients with the advent of highly active retroviral therapy. HIV-DSP can be attributed to the disease itself or to secondary effects of certain HAART agents, and often the two disease entities cannot be distinguished. HIV-DSP can lead to significant morbidity and interfere with daily activities. Diagnosis can be obtained from a detailed history and neurologic exam revealing absent ankle jerks and abnormal, vibratory perception or decreased pinprick or temperature. Supporting studies include nerve conduction studies and skin biopsy. Although there are no United States Food and Drug Administration-approved treatments for HIV-DSP, clinicians often use off-label medications, including antidepressants, anticonvulsants, topical agents and other analgesics. The prevalence of those affected by HIV-DSP will continue to grow with the aging population of HIV-infected individuals. Compared to the diabetic neuropathy drug trials, trials in both symptomatic and disease-modifying agents for HIV-DSP have had little success. Other forms of HIV-related peripheral neuropathies are discussed briefly, and include acute and chronic inflammatory demyelinating polyneuropathy, autonomic neuropathy, polyradiculopathy, mononeuropathies, mononeuritis multiplex, cranial neuropathies, and amyotrophic lateral sclerosis-like motor neuropathy.

Rates of autonomic dysfunction in HIV patients receiving antiretroviral therapy

We read the work by Robinson-Papp et al. with interest. The authors report that 61 % of participants had autonomic dysfunction (AD) as defined by a composite autonomic severity score (CASS) >3, with peripheral nerve dysfunction being the strongest predictor, affecting 90 % of participants who have HIV-associated distal symmetric polyneuropathy. Eighty-six percent of individuals with AD were symptomatic on survey of autonomic symptoms (SAS). The Composite Autonomic Scoring Scale (CASS) is a validated scale designed to quantify autonomic failure. CASS is derived from three areas of autonomic function: adrenergic, cardiovagal, and sudomotor (1996; Weimer 2010; Low et al. 2008). A CASS of 6 is indicative of severe autonomic failure (Low et al. 2008). CASS has been correlated with cardiovascular disease events and mortality (Gehrking et al. 2013). A CASS of 4–6 has been associated with orthostatic hypotension, abnormal sweating, and gastrointestinal abnormalities and is usually seen in autonomic failure (Low 1993). The authors report a median CASS of 3, suggesting that 50 % of subjects had a CASS of >3. The study reported on the CASS upper range of 6. A CASS this high would implicate major clinical outcomes and mortality which frankly have not been seen in large epidemiologic studies. The rates and severity of AD may have been overestimated in this study. In a convenience sample of 48 virologically suppressed HIV-infected individuals with and without polyneuropathy, we reported on a median CASS of 1 (IQR 1), and 40 % of subjects were symptomatic. We utilized the Composite Autonomic Symptom Scale to measure autonomic symptoms, a better instrument to detect and quantitate AD compared to the SAS used in the study. We wonder whether using the Q-sweat test for evaluating the sudomotor response used in the study may have overestimated AD. The qualitative sudomotor axon reflex test (QSART) has been a routine postganglionic sudomotor function test of the Mayo Clinic since 1983. The Q-sweat test is a commercial quantitative sweat measurement test modeled on QSART, but can overestimate sudomotor dysfunction (Sletten et al. 2010). In the era of combination antiretroviral therapy (cART), dramatic improvements in morbidity and mortality have been witnessed. However, autonomic symptoms such as light-headedness, dry mouth and eyes, cold feet, and constipation, as noted in the study and ours, have become common complaints among HIV-infected patients. AD has been correlated with HIV disease progression (Becker et al. 1997; Chow et al. 2011). Individuals with AIDS receiving cART have better measures of autonomic function compared to individuals that are not on cART (Correia et al. 2006). Forty-two percent of the study participants had a detectable viral load. Early and lifelong suppression of HIV infection and avoidance of medications that cause peripheral neuropathy and metabolic disorders needs to be considered for HIV-infected individuals (Askgaard et al. 2011). AD is a common condition. The rate and severity of autonomic dysfunction may not appear as elevated as suggested by the authors. Nonetheless, we commend Robinson-Papp et al. for bringing attention to AD which we agree is an underappreciated condition that is becoming increasingly common among our aging HIV-infected patients. Further investigation is needed to explain the prevalence and nature of AD, and its potential treatment.

Murine Immunodeficiency Virus-Induced Peripheral Neuropathy and the Associated Cytokine Responses

Distal symmetrical polyneuropathy is the most common form of HIV infection-associated peripheral neuropathy and is often associated with pain. C57BL/6 (B6) mice infected with LP-BM5, a murine retroviral isolate, develop a severe immunodeficiency syndrome similar to that in humans infected with HIV-1, hence the term murine AIDS. We investigated the induction of peripheral neuropathy after LP-BM5 infection in B6 mice. Infected B6 mice, like HIV-infected humans, exhibited behavioral (increased sensitivity to mechanical and heat stimuli) and pathological (transient loss of intraepidermal nerve fibers) signs of peripheral neuropathy. The levels of viral gag RNA were significantly increased in all tissues tested, including spleen, paw skin, lumbar dorsal root ganglia, and lumbar spinal cord, postinfection (p.i.). Correlated with the development of peripheral neuropathy, the tissue levels of several cytokines, including IFN-γ, IL-1β, IL-6, and IL-12, were significantly elevated p.i. These increases had cytokine-specific and tissue-specific profiles and kinetics. Further, treatment with the antiretroviral agent zidovudine either significantly reduced or completely reversed the aforementioned behavioral, pathologic, and cytokine changes p.i. These data suggest that LP-BM5 infection is a potential mouse model of HIV-associated distal symmetrical polyneuropathy that can be used for investigating the roles of various cytokines in infection-induced neuropathic pain. Further investigation of this model could give a better understanding of, and lead to more effective treatments for, HIV infection-associated painful peripheral neuropathy.

Infectious Neuropathies

The purpose of this review is to address bacterial, viral, and other infectious causes of neuropathy or neuronopathy, with an emphasis on clinical manifestations and treatment. Most infectious neuropathies have been well described for some time and treatments are well established. An exception is HIV-associated distal symmetric polyneuropathy, which is an area of active research. Current work in this area focuses on epidemiology, risk factors, and underlying mechanisms. Infectious diseases are an important part of the differential diagnosis of peripheral nerve disorders because they are among the most amenable to treatment. However, diagnosis of infectious peripheral neuropathy may be challenging because of variability in a number of factors, including the pattern of deficits, geographic distribution of pathogens, length of time from the onset of infection to the development of neuropathy, and mechanism of nerve injury.

Managing HIV peripheral neuropathy

Peripheral nerve disorders are frequent complications of HIV disease. Distal symmetrical polyneuropathy (DSP) is the most common peripheral nerve disorder associated with HIV and occurs in over one third of infected patients but may occur in up to 67% if asymptomatic patients are included. Risk factors for DSP include increased age, advanced HIV disease, and history of "d-drugs" or other neurotoxic drugs. The primary manifestations of polyneuropathy are slowly progressive numbness and paresthesias, with burning sensations in the feet usually in a symmetrical pattern. The etiology of HIV-associated DSP is unknown, although neurotoxic effects of cytokines, toxicity of HIV proteins, and mitochondrial damage have been implicated. The current treatment for HIV-associated DSP is symptomatic, with pain modifying medications, including anti-inflammatory agents, opioids, antidepressants, antiepileptics, topical anesthetics, and capsaicin. Sustained virologic control may improve DSP. Novel therapies such as -acetyl-l-carnitine or neurotrophic factors are being studied for treatment of DSP.

Ensure adequate and individualised symptomatic pain treatment of HIV-associated distal symmetrical polyneuropathy

Ensure adequate and individualised symptomatic pain treatment of HIV-associated distal symmetrical polyneuropathy

HIV-Associated Neuropathic Pain

Peripheral neuropathy is associated with numerous systemic illnesses including HIV infection. Neuropathic pain constitutes approximately 25-50% of all pain clinic visits. Distal symmetrical polyneuropathy (DSP) is the most common form of peripheral neuropathy in individuals with HIV infection. DSP is distinguished from other forms of neuropathy on the basis of history and neurological examination. The pain associated with DSP can be debilitating. Therefore, it is important to diagnose HIV-associated DSP properly and treat the neuropathic pain in order to improve quality of life. We review the clinical manifestations, epidemiology, pathophysiology and management strategies for HIV-associated DSP.

A Randomized Controlled Trial of 5% Lidocaine Gel for HIV-Associated Distal Symmetric Polyneuropathy

To investigate the analgesic efficacy and safety of 5% lidocaine gel in painful HIV-associated distal sensory polyneuropathy (DSP). Painful DSP, the most common neurologic complication in HIV infection, is difficult to treat. Lidocaine 5% gel was effective in alleviating neuropathic pain in an open-label study of HIV DSP. In a double-blind, placebo-controlled, crossover, multi-center study, 64 subjects were randomized to receive 5% lidocaine or vehicle gel for 2 weeks (phase A). A washout period of 2 weeks was followed by a crossover to the alternate agent for another 2 weeks (phase B). The primary outcome was difference in average pain scores (Gracely pain scale) between the 2 groups during the second week of each treatment period. Secondary outcomes included differential effect of the first treatment, difference in global pain relief, and pain response by neurotoxin exposure. The baseline pain scores of the 2 groups were similar. The average pain scores during the second week of each phase of the lidocaine gel group did not differ from those of the placebo group (phase A: lidocaine 1.09, placebo 1.15; phase B: lidocaine 1.16, placebo 1.10). There also was no difference noted in secondary outcomes. The pain responses of lidocaine gel-treated subjects with current exposure to neurotoxic antiretrovirals (1.18) did not differ compared with those without (1.10) (P = 0.358). There were no significant adverse effects. Lidocaine 5% gel is a safe but ineffective agent in the treatment of pain in HIV-associated DSP.

Severity of HIV-associated neuropathy is associated with plasma HIV-1 RNA levels,

Objective: To determine if there is an association between plasma HIV-1 RNA levels and severity of HIV-associated distal symmetrical polyneuropathy (DSP). Design: Substudy of AIDS Clinical Trials Group Protocol 291, a double-blind, placebo-controlled study of recombinant human nerve growth factor for the treatment of painful DSP. Methods: Two-hundred and thirty-six subjects had plasma HIV-1 RNA load assayed at baseline. Mean and maximum neuropathic pain was assessed once daily by the Gracely Pain Scale. Other measures included subjects’ global pain assessment and quantitative sensory tests (QST). These values were correlated with baseline HIV-1 RNA levels. Results: Among 168 subjects with detectable plasma HIV-1 RNA, there was a significant correlation between plasma HIV-1 RNA and the severity of maximum and global pain, and toe cooling thresholds. Maximum and global pain assessment correlated with plasma HIV-1 RNA in individuals with detectable viral load (r, 0.162 and 0.194; P = 0.04 and 0.01, respectively). Conclusions: There is an association between plasma HIV-1 RNA levels and the severity of pain and QST results in HIV-associated DSP. Further studies are needed to determine if aggressive use of antiretroviral drugs, including the use of dideoxynucleosides, may be of benefit to prevent or improve peripheral neuropathy.

Screening for HIV-associated distal-symmetric polyneuropathy in CDC-classification stages 1, 2, and 3.

A total of 670 patients were screened for distal symmetric HIV-associated polyneuropathy during CDC stages 1-3 and its correlation to immunological deterioration. Clinical examinations of 670 patients admitted to the neurological outpatient clinic at the Department of Neurology, University of Munster. Neurophysiological investigations were performed on the sural and peroneal nerve for detection of axonal and myelin lesion. Clinical examination proved progressive clinical signs and symptoms indicating distal symmetric polyneuropathy from CDC 1 (32%) to CDC 3 (55%). At least one neurophysiological result was impaired in CDC 1 in 25% and in CDC 3 in 45%. Significant correlation between neurophysiological changes and CDC4(+)-cells and beta-microglobuline were detected for stage CDC 3 C. Results show stage related prevalence of distal symmetric polyneuropathy already in early stages. In late stages of HIV-infection prevalence of distal symmetric polyneuropathy seems to be directly correlated to immunodeficiency syndrome. The pathogenesis of distal symmetric polyneuropathy during HIV-infection is up to now incompletely understood, but results indicate a clear dependency between progressive immunological dysfunction and neuropathy. High active antiretroviral therapy in patients suffering from distal symmetric polyneuropathy is a main topic of future studies.