Correlates of epidermal nerve fiber densities in HIV-associated distal sensory polyneuropathy

Zhou, Lan; Kitch, Douglas; Evans, Scott; Hauer, Peter; Raman, Sainath; Ebenezer, Gigi J.; Gerschenson, Mariana; Marra, Christina M.; Valcour, Victor; Diaz‐Arrastia, Ramon; Goodkin, Karl; Millar, Linda; Shriver, S.; Asmuth, David M.; Clifford, David B.; Simpson, David M.; McArthur, Justin C.

doi:10.1212/01.wnl.0000264888.87918.a1

Cited by 106 publications

(81 citation statements)

References 26 publications

(35 reference statements)

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“…16,17 A case definition of DSP for clinical research has been proposed, 18 however the definition was primarily based upon data obtained from studies of diabetic SN. These results provide an option of a simplified battery of clinical measures and quantitative tests for efficient use in clinical research of HIV-SN.…”

Section: Discussionmentioning

confidence: 99%

Simplification of the Research Diagnosis of HIV-Associated Sensory Neuropathy

Evans

Clifford

Kitch

et al. 2008

HIV Clinical Trials

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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...

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Section: Discussionmentioning

confidence: 99%

Simplification of the Research Diagnosis of HIV-Associated Sensory Neuropathy

Evans

Clifford

Kitch

et al. 2008

HIV Clinical Trials

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“…Intraepidermal nerve fiber density (IENFD) analysis was performed at the Cleveland Clinic's Cutaneous Nerve Laboratory using PGP 9.5 immunostaining of skin biopsy specimens, as previously described. [17][18][19] The number of epidermal nerve fibers, including fibers across the dermal-epidermal junction and nerve fragments within the epidermis, was counted using established counting rules. 18,20 IENFD was calculated and expressed as an average number of intraepidermal fibers per millimeter length of epidermis.…”

Section: Methodsmentioning

confidence: 99%

“…Normal IENFD was defined as 5 fibers/mm at the DL site, 7 fibers/mm at the DT site, and 8 fibers/mm at the PT site. [19][20][21] Those patients with reduced IENFD at DT and PT but not DL, or with more prominent reduction of IENFD at DT and/or PT than DL, were defined as having NLD-SFSN. Those patients who had reduced IENFD only at DL, or at DL and DT (more reduced at DT than DL), or at all three biopsy sites, with a distal-to-proximal gradient, were defined as having LD-SFSN.…”

Section: Methodsmentioning

confidence: 99%

Characterization of non–length‐dependent small‐fiber sensory neuropathy

2011

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“…These three models have distinct pain features that are different from each other (4,5), suggesting that mechanisms of neuropathic pain differ depending on the site and mode of nerve injury. In humans, persistent pain may be caused by trauma to distal nerve branches as well as nerve trunks, such as injury to distal nerve branches of the lower leg (6,7). Therefore, animal models of neuropathic pain produced by injury to the distal branch of the sciatic nerve are needed for investigating the mechanisms of neuropathic pain of distal nerve branches.…”

Section: Introductionmentioning

confidence: 99%

A Mouse Model of Sural Nerve Injury–Induced Neuropathy: Gabapentin Inhibits Pain-Related Behaviors and the Hyperactivity of Wide-Dynamic Range Neurons in the Dorsal Horn

et al. 2009

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Abstract. This study was conducted to make a new mouse model of neuropathic pain due to injury to a branch of the sciatic nerve. One of three branches (sural, tibial, and common peroneal nerves) of the sciatic nerve was tightly ligated, and mechanical and cool stimuli were applied to the medial part (tibial and common peroneal nerve territories) of the plantar skin. The three types of nerve injuries produced behavioral mechanical hypersensitivities, and the extent of the hypersensitivities after sural and tibial nerve ligation was larger than that of common peroneal nerve ligation. Sural nerve ligation did not affect motor function of the affected hind paw, but tibial and common peroneal nerve ligation produced motor dysfunction. These results suggest that the ligation of the sural nerve is the most suitable for behavioral study. Sural nerve ligation induced behavioral hypersensitivities to mechanical and cool stimuli, which were almost completely inhibited by gabapentin (30 mg/kg). Sural nerve ligation increased spontaneous activity and responses of the wide-dynamic range neurons in the lumbar dorsal horn, which were also almost completely inhibited by gabapentin (30 mg/kg). Sural nerve ligation provides a new mouse model of neuropathic pain, which is easy to prepare and sensitive to gabapentin.

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Correlates of epidermal nerve fiber densities in HIV-associated distal sensory polyneuropathy

Cited by 106 publications

References 26 publications

Simplification of the Research Diagnosis of HIV-Associated Sensory Neuropathy

Simplification of the Research Diagnosis of HIV-Associated Sensory Neuropathy

Characterization of non–length‐dependent small‐fiber sensory neuropathy

A Mouse Model of Sural Nerve Injury–Induced Neuropathy: Gabapentin Inhibits Pain-Related Behaviors and the Hyperactivity of Wide-Dynamic Range Neurons in the Dorsal Horn

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