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Published in: Journal of NeuroVirology 6/2012

01-12-2012

HIV neuropathy: an in vivo confocal microscopic study

Authors: Jorge L. Almodovar, Giovanni Schifitto, Michael P. McDermott, Michele Ferguson, David N. Herrmann

Published in: Journal of NeuroVirology | Issue 6/2012

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Abstract

Several approaches exist for quantitative assessment of human immunodeficiency virus (HIV)-associated distal sensory polyneuropathy (DSP). While useful, each has some limitations. This study evaluated non-invasive, in vivo reflectance confocal microscopy (RCM) of Meissner corpuscles (MCs) as a measure of HIV-DSP. Forty-eight adults (29 HIV-infected, 19 controls) underwent RCM of MC density (MCs/mm2) at the arch, fingertip, and thenar eminence (TE); ankle skin biopsy to measure epidermal nerve fiber density (ENFD); electrophysiologic studies; and tactile, vibration, and thermal threshold testing. HIV+ subjects were clinically categorized as having DSP signs or no signs. MC densities were lower in HIV+ subjects with DSP signs than in controls (arch, p = 0.0003; fingertip, p < 0.0001; TE, p = 0.0002). Tactile thresholds in the TE and foot were worse in HIV-DSP than in controls, but in this mild DSP cohort, sural amplitudes, ENFD, and vibration and thermal thresholds did not differ significantly from controls. Fingertip MC densities and tactile thresholds at the foot were also lower in HIV+ subjects without DSP signs than in controls. Other sensory measures were not significantly different in HIV+ subjects without DSP signs than in controls. MC density correlated inversely with tactile thresholds at each imaging location. The results suggest that RCM of MC density complements existing sensory DSP measures and discriminates mild HIV-DSP from controls at a stage when sural amplitudes do not. Further studies are required to determine whether RCM of MC density can establish quantitative changes in DSP, in response to treatment or disease progression.
Literature
go back to reference Almodovar J, Ferguson M, McDermott MP, Lewis RA, Shy ME, Herrmann DN (2011) In vivo confocal microscopy of Meissner corpuscles as a novel sensory measure in CMT1A. J Peripher Nerv Syst 16:169–174PubMedCrossRef Almodovar J, Ferguson M, McDermott MP, Lewis RA, Shy ME, Herrmann DN (2011) In vivo confocal microscopy of Meissner corpuscles as a novel sensory measure in CMT1A. J Peripher Nerv Syst 16:169–174PubMedCrossRef
go back to reference Baba M, Simonetti S, Krarup C (2001) Sensory potentials evoked by tactile stimulation of different indentation velocities at the finger and palm. Muscle Nerve 24:1213–1218PubMedCrossRef Baba M, Simonetti S, Krarup C (2001) Sensory potentials evoked by tactile stimulation of different indentation velocities at the finger and palm. Muscle Nerve 24:1213–1218PubMedCrossRef
go back to reference Berger AR, Arezzo JC, Schaumburg HH, Skowron G, Merigan T, Bozzette S, Richman D, Soo W (1993) 2′,3′-Dideoxycytidine (ddC) toxic neuropathy: a study of 52 patients. Neurology 43:358–362PubMedCrossRef Berger AR, Arezzo JC, Schaumburg HH, Skowron G, Merigan T, Bozzette S, Richman D, Soo W (1993) 2′,3′-Dideoxycytidine (ddC) toxic neuropathy: a study of 52 patients. Neurology 43:358–362PubMedCrossRef
go back to reference Bolton CF, Winkelmann RK, Dyck PJ (1996) A quantitative study of Meissner’s corpuscles in man. Neurology 16:1–9CrossRef Bolton CF, Winkelmann RK, Dyck PJ (1996) A quantitative study of Meissner’s corpuscles in man. Neurology 16:1–9CrossRef
go back to reference Cherry CL, Wesselingh SL, Lal L, McArthur JC (2005) Evaluation of a clinical screening tool for HIV-associated sensory neuropathies. Neurology 65:1778–1781PubMedCrossRef Cherry CL, Wesselingh SL, Lal L, McArthur JC (2005) Evaluation of a clinical screening tool for HIV-associated sensory neuropathies. Neurology 65:1778–1781PubMedCrossRef
go back to reference Conover WJ, Iman RL (1982) Analysis of covariance using the rank transformation. Biometrics 38:715–724PubMedCrossRef Conover WJ, Iman RL (1982) Analysis of covariance using the rank transformation. Biometrics 38:715–724PubMedCrossRef
go back to reference Cornblath DR, McArthur JC (1988) Predominantly sensory neuropathy in patients with AIDS and AIDS-related complex. Neurology 38:794–796PubMedCrossRef Cornblath DR, McArthur JC (1988) Predominantly sensory neuropathy in patients with AIDS and AIDS-related complex. Neurology 38:794–796PubMedCrossRef
go back to reference Dyck PJ, Winkelmann RK, Bolton CF (1966) Quantitation of Meissner’s corpuscles in hereditary neurologic disorders Charcot-Marie-Tooth Disease, Roussy-Levy syndrome, Dejerine-sottas, hereditary sensory neuropathy, spinocerebellar degenerations, and hereditary spastic paraplegia. Neurology 16:10–17PubMedCrossRef Dyck PJ, Winkelmann RK, Bolton CF (1966) Quantitation of Meissner’s corpuscles in hereditary neurologic disorders Charcot-Marie-Tooth Disease, Roussy-Levy syndrome, Dejerine-sottas, hereditary sensory neuropathy, spinocerebellar degenerations, and hereditary spastic paraplegia. Neurology 16:10–17PubMedCrossRef
go back to reference Dyck PJ, O’Brien PC, Kosanke JL, Gillen DA, Karnes JL (1993a) A 4, 2, and 1 stepping algorithm for quick and accurate estimation of cutaneous sensation threshold. Neurology 43:1508–1512PubMedCrossRef Dyck PJ, O’Brien PC, Kosanke JL, Gillen DA, Karnes JL (1993a) A 4, 2, and 1 stepping algorithm for quick and accurate estimation of cutaneous sensation threshold. Neurology 43:1508–1512PubMedCrossRef
go back to reference Dyck PJ, Zimmerman I, Gillen DA, Johnson D, Karnes JL, L’Brien PC (1993b) Cool, warm, and heat-pain detection thresholds: testing methods and inferences about anatomic distribution of receptors. Neurology 43:1500–1508PubMedCrossRef Dyck PJ, Zimmerman I, Gillen DA, Johnson D, Karnes JL, L’Brien PC (1993b) Cool, warm, and heat-pain detection thresholds: testing methods and inferences about anatomic distribution of receptors. Neurology 43:1500–1508PubMedCrossRef
go back to reference Ellis RJ, Rosario D, Clifford DB, McArthur JC, Simpson D, Alexander T, Gelman BB, Vaida F, Collier A, Marra CM, Ances B, Atkinson JH, Dworkin RH, Morgello S, Grant I, CHARTER Study Group (2010) Continued high prevalence and adverse clinical impact of human immunodeficiency virus-associated sensory neuropathy in the era of combination antiretroviral therapy: the CHARTER Study. Arch Neurol 67:552–558PubMedCrossRef Ellis RJ, Rosario D, Clifford DB, McArthur JC, Simpson D, Alexander T, Gelman BB, Vaida F, Collier A, Marra CM, Ances B, Atkinson JH, Dworkin RH, Morgello S, Grant I, CHARTER Study Group (2010) Continued high prevalence and adverse clinical impact of human immunodeficiency virus-associated sensory neuropathy in the era of combination antiretroviral therapy: the CHARTER Study. Arch Neurol 67:552–558PubMedCrossRef
go back to reference Herrmann DN, Griffin JW, Hauer P, Cornblath DR, McArthur JC (1999) Epidermal nerve fiber density and sural nerve morphometry in peripheral neuropathies. Neurology 53:1634–1640PubMedCrossRef Herrmann DN, Griffin JW, Hauer P, Cornblath DR, McArthur JC (1999) Epidermal nerve fiber density and sural nerve morphometry in peripheral neuropathies. Neurology 53:1634–1640PubMedCrossRef
go back to reference Herrmann DN, McDermott MP, Henderson D, Chen L, Akowuah K, Schifitto G, North East AIDS Dementia (NEAD) Consortium (2004) Epidermal nerve fiber density, axonal swellings and QST as predictors of HIV distal sensory neuropathy. Muscle Nerve 29:420–427PubMedCrossRef Herrmann DN, McDermott MP, Henderson D, Chen L, Akowuah K, Schifitto G, North East AIDS Dementia (NEAD) Consortium (2004) Epidermal nerve fiber density, axonal swellings and QST as predictors of HIV distal sensory neuropathy. Muscle Nerve 29:420–427PubMedCrossRef
go back to reference Herrmann DN, McDermott MP, Sowden JE, Henderson D, Messing S, Cruttenden K, Schifitto G (2006) Is skin biopsy a predictor of transition to symptomatic HIV neuropathy? A longitudinal study. Neurology 66:857–861PubMedCrossRef Herrmann DN, McDermott MP, Sowden JE, Henderson D, Messing S, Cruttenden K, Schifitto G (2006) Is skin biopsy a predictor of transition to symptomatic HIV neuropathy? A longitudinal study. Neurology 66:857–861PubMedCrossRef
go back to reference Herrmann DN, Boger JN, Jansen C, Alessi-Fox C (2007) In vivo confocal microscopy of Meissner corpuscles as a measure of sensory neuropathy. Neurology 69:2121–2127PubMedCrossRef Herrmann DN, Boger JN, Jansen C, Alessi-Fox C (2007) In vivo confocal microscopy of Meissner corpuscles as a measure of sensory neuropathy. Neurology 69:2121–2127PubMedCrossRef
go back to reference Holland NR, Stocks A, Hauer P, Cornblath DR, Griffin JW, McArthur JC (1997) Intraepidermal nerve fiber density in patients with painful sensory neuropathy. Neurology 48:708–711PubMedCrossRef Holland NR, Stocks A, Hauer P, Cornblath DR, Griffin JW, McArthur JC (1997) Intraepidermal nerve fiber density in patients with painful sensory neuropathy. Neurology 48:708–711PubMedCrossRef
go back to reference McArthur JC, Yiannoutsos C, Simpson DM, Adornato BT, Singer EJ, Hollander H, Marra C, Rubin M, Cohen BA, Tucker T, Navia BA, Schifitto G, Katzenstein D, Rask C, Zaborski L, Smith ME, Shriver S, Millar L, Clifford DB, Karalnik IJ (2000) A phase II trial of nerve growth factor for sensory neuropathy associated with HIV infection. Neurology 54:1080–1088PubMedCrossRef McArthur JC, Yiannoutsos C, Simpson DM, Adornato BT, Singer EJ, Hollander H, Marra C, Rubin M, Cohen BA, Tucker T, Navia BA, Schifitto G, Katzenstein D, Rask C, Zaborski L, Smith ME, Shriver S, Millar L, Clifford DB, Karalnik IJ (2000) A phase II trial of nerve growth factor for sensory neuropathy associated with HIV infection. Neurology 54:1080–1088PubMedCrossRef
go back to reference McCarthy BG, Hsieh ST, Stocks A, Hauer P, Macko C, Cornblath DR, Griffin JW, McArthur JC (1995) Cutaneous innervation in sensory neuropathies: evaluation by skin biopsy. Neurology 45:1848–1855PubMedCrossRef McCarthy BG, Hsieh ST, Stocks A, Hauer P, Macko C, Cornblath DR, Griffin JW, McArthur JC (1995) Cutaneous innervation in sensory neuropathies: evaluation by skin biopsy. Neurology 45:1848–1855PubMedCrossRef
go back to reference Polydefkis M, Yiannoutsos CT, Cohen BA, Hollander H, Schifitto G, Clifford DB, Simpson DM, Katzenstein D, Shriver S, Hauer P, Brown A, Haidich AB, Moo L, McArthur JC (2002) Reduced intraepidermal nerve fiber density in HIV-associated sensory neuropathy. Neurology 58:115–119PubMedCrossRef Polydefkis M, Yiannoutsos CT, Cohen BA, Hollander H, Schifitto G, Clifford DB, Simpson DM, Katzenstein D, Shriver S, Hauer P, Brown A, Haidich AB, Moo L, McArthur JC (2002) Reduced intraepidermal nerve fiber density in HIV-associated sensory neuropathy. Neurology 58:115–119PubMedCrossRef
go back to reference Rajadhyaksha M, Gonzalez S, Zavislan JM, Anderson RR, Webb RH (1999) In vivo confocal scanning laser microscopy of human skin II: advances in instrumentation and comparison with histology. J Invest Dermatol 113:293–303PubMedCrossRef Rajadhyaksha M, Gonzalez S, Zavislan JM, Anderson RR, Webb RH (1999) In vivo confocal scanning laser microscopy of human skin II: advances in instrumentation and comparison with histology. J Invest Dermatol 113:293–303PubMedCrossRef
go back to reference Schifitto G, McDermott MP, McArthur JC, Marder K, Sacktor N, Epstein L, Kieburtz K, Dana Consortium of the Therapy of HIV Dementia and Related Cognitive Disorders (2002) Incidence of and risk factors for HIV-associated distal sensory polyneuropathy. Neurology 58:1764–1768PubMedCrossRef Schifitto G, McDermott MP, McArthur JC, Marder K, Sacktor N, Epstein L, Kieburtz K, Dana Consortium of the Therapy of HIV Dementia and Related Cognitive Disorders (2002) Incidence of and risk factors for HIV-associated distal sensory polyneuropathy. Neurology 58:1764–1768PubMedCrossRef
go back to reference Selkin B, Rajadhyaksha M, Gonzalez S, Langley RG (2001) In vivo confocal microscopy in dermatology. Dermatol Clin 19:369–377PubMedCrossRef Selkin B, Rajadhyaksha M, Gonzalez S, Langley RG (2001) In vivo confocal microscopy in dermatology. Dermatol Clin 19:369–377PubMedCrossRef
go back to reference Shy ME, Frohman EM, So YT, Arezzo JC, Cornblath DR, Giulianai MJ, Kincaid JC, Ochoa JL, Parry GJ, Weimer LH, Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology (2003) Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Quantitative sensory testing: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 60:898–904PubMedCrossRef Shy ME, Frohman EM, So YT, Arezzo JC, Cornblath DR, Giulianai MJ, Kincaid JC, Ochoa JL, Parry GJ, Weimer LH, Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology (2003) Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Quantitative sensory testing: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 60:898–904PubMedCrossRef
go back to reference Simpson DM, Kitch D, Evans SR, McArthur JC, Asmuth DM, Cohen B, Goodkin K, Gerschenson M, So Y, Marra CM, Diaz-Arrastia R, Shriver S, Millar L, Clifford DB, the ACTG A5117 Study Group (2006) HIV neuropathy natural history cohort study: assessment measures and risk factors. Neurology 66:1679–1687PubMedCrossRef Simpson DM, Kitch D, Evans SR, McArthur JC, Asmuth DM, Cohen B, Goodkin K, Gerschenson M, So Y, Marra CM, Diaz-Arrastia R, Shriver S, Millar L, Clifford DB, the ACTG A5117 Study Group (2006) HIV neuropathy natural history cohort study: assessment measures and risk factors. Neurology 66:1679–1687PubMedCrossRef
go back to reference So YT, Holtzman DM, Abrams DI, Olney RK (1988) Peripheral neuropathy associated with acquired immunodeficiency syndrome. Prevalence and clinical features from a population-based survey. Arch Neurol 45:945–948PubMedCrossRef So YT, Holtzman DM, Abrams DI, Olney RK (1988) Peripheral neuropathy associated with acquired immunodeficiency syndrome. Prevalence and clinical features from a population-based survey. Arch Neurol 45:945–948PubMedCrossRef
go back to reference Tagliati M, Grinnell J, Godbold J, Simpson DM (1999) Peripheral nerve function in HIV infection: clinical, electrophysiologic and laboratory findings. Arch Neurol 56:84–89PubMedCrossRef Tagliati M, Grinnell J, Godbold J, Simpson DM (1999) Peripheral nerve function in HIV infection: clinical, electrophysiologic and laboratory findings. Arch Neurol 56:84–89PubMedCrossRef
go back to reference Tyor WR, Wesselingh SL, Griffin JW, McArthur JC, Griffin DE (1995) Unifying hypothesis for the pathogenesis of HIV-associated dementia complex, vacuolar myelopathy, and sensory neuropathy. J Acquir Immune Defic Syndr Hum Retrovirol 9:379–388PubMedCrossRef Tyor WR, Wesselingh SL, Griffin JW, McArthur JC, Griffin DE (1995) Unifying hypothesis for the pathogenesis of HIV-associated dementia complex, vacuolar myelopathy, and sensory neuropathy. J Acquir Immune Defic Syndr Hum Retrovirol 9:379–388PubMedCrossRef
go back to reference Zhou L, Kitch DW, Evans SR, Hauer P, Raman S, Ebenezer GJ, Gerschenson M, Marra CM, Valcour V, Diaz-Arrastia R, Goodkin K, Millar L, Shriver S, Asmuth DM, Clifford DB, Simpson DM, McArthur JC, NARC and ACTG A5117 Study Group (2007) Correlates of epidermal nerve fiber densities in HIV-associated distal sensory polyneuropathy. Neurology 68:2113–2119PubMedCrossRef Zhou L, Kitch DW, Evans SR, Hauer P, Raman S, Ebenezer GJ, Gerschenson M, Marra CM, Valcour V, Diaz-Arrastia R, Goodkin K, Millar L, Shriver S, Asmuth DM, Clifford DB, Simpson DM, McArthur JC, NARC and ACTG A5117 Study Group (2007) Correlates of epidermal nerve fiber densities in HIV-associated distal sensory polyneuropathy. Neurology 68:2113–2119PubMedCrossRef
Metadata
Title
HIV neuropathy: an in vivo confocal microscopic study
Authors
Jorge L. Almodovar
Giovanni Schifitto
Michael P. McDermott
Michele Ferguson
David N. Herrmann
Publication date
01-12-2012
Publisher
Springer US
Published in
Journal of NeuroVirology / Issue 6/2012
Print ISSN: 1355-0284
Electronic ISSN: 1538-2443
DOI
https://doi.org/10.1007/s13365-012-0130-1

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