Autonomic dysfunction is common in HIV and associated with distal symmetric polyneuropathy

Abstract

Neurologic complications of HIV are well characterized in the central and peripheral nervous systems but not in the autonomic nervous system, perhaps due to the complexities of measuring autonomic function in medically ill populations. We hypothesized that autonomic dysfunction is common in HIV, can be meaningfully measured with an autonomic reflex screen, and is associated with distal symmetric polyneuropathy (DSP) but not with signs of CNS disease. We also sought to characterize immuno-virologic and medical factors associated with autonomic dysfunction. We assessed 102 HIV-infected adults for autonomic dysfunction with a laboratory-based autonomic reflex screen summarized as the Composite Autonomic Severity Score (CASS). The Total Neuropathy Score (TNS) was used to quantify DSP based on neurologic interview/examination, quantitative sensory testing, and nerve conduction studies. Autonomic dysfunction was common, with a CASS ≥ 3 in 61% of participants, of whom 86% were symptomatic. Greater CASS abnormalities demonstrated univariate association with increasing TNS, age, viral load, hypertension, and use of medications (particularly anticholinergics), but not with antiretrovirals, current/nadir CD4+ count, HIV-duration, metabolic factors, or signs of CNS disease. The TNS was the only significant predictor of the CASS in multivariate analysis; anticholinergic medications were marginally significant. This study demonstrates that autonomic dysfunction is common and frequently symptomatic in HIV, and that an autonomic reflex screen, adjusted for anticholinergic medication, is useful in its assessment. Association of autonomic dysfunction with DSP suggests common factors in their pathogenesis, and autonomic neuropathy may be part of the spectrum of HIV-associated peripheral nerve pathologies.

Autonomic Neuropathy in HIV is Unrecognized and Associated with Medical Morbidity

“…1 In this study, we found that autonomic neuropathy is associated with a greater burden of illness and higher predicted mortality as measured by the VACS index, which includes age, CD4 + count, HIV-1 viral load, a NNRTI, non-nucleoside reverse transcriptase inhibitor; NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor; UD, undetectable ( < 20 copies/mL). hemoglobin, and markers of liver and kidney disease.…”

“…We previously reported that autonomic neuropathy was associated with HIV-associated distal symmetric polyneuropathy. 1 Thus a clinical phenotype of the HIV-patient likely to have autonomic neuropathy emerges: an older patient with peripheral neuropathy and one or more major co-morbid illnesses. Although this phenotype may be helpful in identifying patients at risk for autonomic neuropathy, arriving at a diagnosis is still complicated by the nonspecific nature of autonomic symptoms which makes them difficult to distinguish from the effects of end organ disease or medication toxicity.…”

“…1 Participants were recruited from the waiting room of an adult HIV clinic, in an academic medical center located in the East Harlem neighborhood of New York City. The clinic serves approximately 1500 predominantly minority, inner city patients.…”

“…The authors of the CASS suggest that a CASS < 2 is normal, and that a CASS of 2-3 represents mild autonomic neuropathy. 15 As we have done previously, 1 we chose a slightly more stringent cut-off of a CASS ‡ 3 to define autonomic neuropathy in acknowledgment of the medical complexity of our population.…”

“…1 Autonomic nerves are responsible for modulation of nearly all internal organ systems. Accordingly, symptoms of autonomic neuropathy are myriad and include: orthostatic dizziness or fainting, dry eyes or mouth, cold distal extremities, constipation and/or diarrhea, sexual dysfunction, nausea or vomiting especially with meals, urinary incontinence, and changes in sweating.…”