Simplification of the Research Diagnosis of HIV-Associated Sensory Neuropathy

Abstract

Peripheral neuropathy (PN) is the most common neurological complication of HIV infection, affecting over one third of patients. The research diagnosis of PN is complicated by the need for expensive, time-consuming, and noxious diagnostic tests. We investigated whether nerve conduction studies (NSC) and quantitative sensory tests (QST) provide added value for the diagnosis of PN for research purposes or whether the easily obtainable clinical measures (sensory and motor symptoms, sensitivity to pain and vibration, tendon reflexes, motor function) are sufficient. Keywords nerve conduction; peripheral neuropathy; quantitative tests; sensory neuropathyIn the HAART era, sensory neuropathies (SN) have increased in prevalence to become the most common neurological disorders associated with HIV infection. 1,2 The two most common types of SN in HIV-infected patients are HIV-associated distal sensory polyneuropathy (DSP) and antiretroviral toxic neuropathy (ATN), which together affect 30%-67% of subjects with advanced HIV disease. 3-5 Risk factors in the HAART era have been investigated. 6-10 The symptoms and signs of HIV-associated SN (HIV-SN) closely resemble some of the most common neuropathies encountered in clinical practice, including diabetic and alcohol associated neuropathy. Ellis et al. has reported the performance characteristics of a brief peripheral neuropathy screening instrument and Ebenezer et al. has investigated the use of epidermal nerve fiber density (ENFD) as a diagnostic tool. 11,12 A case definition of DSP for clinical research has been proposed, 13 although the definition was primarily based upon data obtained from studies of diabetic SN.The research diagnosis of SN may be complicated by the use of expensive, noxious, and timeconsuming diagnostic tests. To guide future research, we evaluated data from a clinical research study to identify an efficient battery of clinical measures and quantitative tests for use in Materials and Methods ACTG A5117AIDS Clinical Trials Group (ACTG) A5117 was a multicenter, prospective study of SN in HIV infection, performed at member sites of the Neurologic AIDS Research Consortium (NARC) and the ACTG with neurologic expertise. The methods and primary results have been previously reported. 5 A5117 enrolled HIV-infected subjects with and without SN, age ≥18 years old, advanced immunologic progression of HIV-infection (CD4+ lymphocyte cell count of <300 cells/mm 3 ), and prior antiretroviral (ARV) exposure of ≥15 weeks. Exclusion criteria included conditions, other than HIV or neurotoxic ARV therapy, which might confound the diagnosis of SN including diabetes mellitus, requiring oral hypoglycemic or insulin therapy; vitamin B12 level <200 pg/mL; alcoholism, defined by any alcohol-related medical complication within 6 months of study entry (a limited criterion for identifying the frequency of alcohol dependence); and treatment with neurotoxins other than ARV or potential neurotrophic agents, such as human growth hormone or acetyl carnitine derivatives.A5117 collec...

HIV Associated Sensory Neuropathy

“…In our study, axonal distal symmetrical sensory neuropathy was the commonest pattern noted in patients who were receiving ART and demyelinating type in HIV patients who were not on ART. HIV neuropathy preferably affects the myelinated fibres and ART the unmyelinated fibres [10][11][12]. In our study, subclinical involvement was noted even in five asymptomatic patients (all were on ART) as evidenced by abnormal NCSs.…”

“…In a patient with HIV infection, a diagnosis of HIV-SN is supported by symptoms and signs that are largely symmetrical and distal in nature, and by the absence of significant motor involvement. In a study by Evans et al, [10] absent tendon reflexes and pin sensitivity was 85% sensitive and 80% specific. In our study, impaired vibration (100%) and absent ankle jerks (75%) were common than reduced pin sensitivity (46.6%).…”

“…Some improvement in neuropathic symptoms may then be seen up to a year after discontinuation of the causative agent. Beyond this time, further improvement is unlikely [2][3][4][5]8,10].…”

Neurologic Presentations of AIDS

“…In most cases, an electromyogram (EMG) and nerve conduction studies (NCS) are not necessary to diagnose HIV DSPN {92}. If an electrodiagnostic study is performed, it will demonstrate findings similar to other degenerative, predominantly axonal neuropathies, such as reduced or absent action potentials.…”

HIV-associated sensory polyneuropathy and neuronal injury are associated with miRNA–455-3p induction

“…Clinical signs comprise reduced sensation that is more pronounced in the feet than the hands, absent or reduced deep tendon reflexes (especially at the ankles), and an antalgic gait necessitating, if sufficiently severe, the use of a wheelchair. Treatments for sDSP are limited to symptomatic relief using anticonvulsants (9), topical capsaicin (10), smoked cannabis (11), acupuncture (12), and opiates in select patients (13). In one study recombinant human nerve growth factor (NGF) delivered locally improved pain symptomatology but did not enhance nerve recovery (14).…”