Abstract
HIV affects many organs of the body, including the nervous system. As a result, a series of neurologic complications have created challenges for scientists and clinicians alike. Among these, HIV-associated neuropathy and myopathy may occur at all stages of the disease process. Of the neuropathies, distal symmetrical polyneuropathy is the most common form. The pathogenesis of primary HIV neuropathy is unknown. Other types of neuropathy seen in HIV-infected subjects include toxic neuropathy, inflammatory demyelinating polyneuropathy, progressive polyradiculopathy, and mononeuritis multiplex. In this review, we present the clinical manifestations, pathogenesis, diagnosis, and management of different types of neuropathy in HIV infection. Myopathy, another complication of HIV, is not associated with any particular stage of immunosuppression. Symptoms include symmetrical weakness of the proximal muscles in the extremities. Serum creatine kinase levels are often moderately elevated. Electromyography and muscle biopsy are helpful tests for diagnosis. Treatment of HIV myopathy includes corticosteroids, nonsteroidal antiinflammatory agents, and intravenous immunoglobulin.
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References and Recommended Reading
Simpson D, Tagliati M: Neuromuscular syndromes in human immunodeficiency virus disease. In AIDS and the Nervous System. Editd by Berger JL. Philadelphia: Lippincott-Raven; 1997:189–221.
Cornblath DR, McArthur JC: Predominantly sensory neuropathy in patients with AIDS and AIDS-related complex. Neurology 1988, 38:794–796.
de la Monte SM, Gabuzda DH, Ho DD, et al.: Peripheral neuropathy in the acquired immunodeficiency syndrome. Ann Neurol 1988, 23:485–492.
Williams D, Geraci A, Simpson D: AIDS and AIDS-treatment neuropathies. Curr Neurol Neurosci Rep 2001, 1:533–538.
Wulff EA, Wang AK, Simpson DM: HIV-associated peripheral neuropathy: epidemiology, pathophysiology and treatment. Drugs 2000, 59:1251–1260.
Wulff E, Simpson D: HIV-associated neuropathy: recent advances in management. HIV Adv Res Ther 1998, 8:23–29.
Brinley F, Pardo C, Verma A: Human immunodeficiency virus and the peripheral nervous system workshop. Arch Neurol 2001, 58:1561–1566.
Apostolski S, McAlarney T, Quattrini A, et al.: The gp120 glycoprotein of human immunodeficiency virus type 1 binds to sensory ganglion neurons. Ann Neurol 1993, 34:855–863.
Herzberg U, Sagen J: Peripheral nerve exposure to HIV viral envelope protein gp120 incudes neuropathic pain and spinal gliosis. J Neuroimmunol 2001, 116:29–39.
Griffin J, Grfiffin D: mRNA fingerprinting of cytokines and growth factors: a new means of characterizing nerve biopsies. Neurology 1993, 43(suppl 2):A232.
Wesselingh S, Glass J, McArthur J, et al.: Cytokine dysregulation in HIV-associated neurological disease. Adv Neuroimmunol 1994, 4:199–206.
Tyor WR, Wesselingh SL, Griffin JW, et al.: Unifying hypothesis for the pathogenesis of HIV-associated dementia complex, vacuolar myelopathy, and sensory neuropathy. J AIDS Hum Retrovirol 1995, 9:379–388.
Nagano I, Shapshak P, Yoshioka M, et al.: Increased NADPHdiaphorase reactivity and cytokine expression in dorsal root ganglia in acquired immunodeficiency syndrome. J Neurol Sci 1996, 136:117–128.
Rizzuto N, Cavallaro T, Monaco S, et al.: Role of HIV in the pathogenesis of distal symmetrical peripheral neuropathy. Acta Neuropathol 1995, 90:244–250.
Yoshioka M, Shapshak P, Srivastava AK, et al.: Expression of HIV-1 and interleukin-6 in lumbosacral dorsal root ganglia of patients with AIDS. Neurology 1994, 44:1120–1130.
Keswani S, Pardo C, Cherry C, et al.: HIV-associated sensory neuropathies. AIDS 2002, 16:2105–2117.
Petratos S, Turnbull V, Papadopoulos R, et al.: Antibodies against peripheral myelin glycolipids in people with HIV infection. Immunol Cell Biol 1998, 76:535–541.
Keilburtz K: Abnormal vitamin B12 metabolism in human immunodeficiency virus infection: association with neurologic dysfunction. Arch Neurol 1991, 48:312–315.
So YT, Holtzman DM, Abrams DI, Olney RK: Peripheral neuropathy associated with acquired immunodeficiency syndrome. Prevalence and clinical features from a populationbased survey. Arch Neurol 1988, 45:945–948.
Cornblath D, McArthur J: Predominantly sensory neuropathy in patients with AIDS and AIDS-related complex. Neurology 1988, 38:794–796.
Bacellar H, Munoz A, Miller EN, et al.: Temporal trends in the incidence of HIV-1-related neurologic diseases: Multicenter AIDS Cohort Study, 1985–1992. Neurology 1994, 44:1892–1900.
Schifitto G, McDermott M, McArthur J, et al.: Incidence of and risk factors for HIV-associated distal sensory polyneuropathy. Neurology 2002, 58:1764–1768. A prospective study to analyze risk factors and predictors of HIV DSP in addition to d-drugs, CD4 lymphocyte count, and viral load.
Mah V, Vartavarian LM, Akers MA, Vinters HV: Abnormalities of peripheral nerve in patients with human immunodeficiency virus infection. Ann Neurol 1988, 24:713–717.
Luciano C, Pardo J, McArthur J: Recent developments in HIV neuropathies. Curr Opin Neurol 2003, 16:403–409. This paper reviews the most recent developments in HIV neuropathy. Skin punch biopsy, as a reliable tool for evaluating the nerve fiber density and monitoring DSP, is described in this article.
Heseltine P, Goodkin K, Atkinson J, et al.: A randomized doubleblind placebo-controlled trial of Peptide T for HIV-associated cognitive impairment. Arch Neurol 1998, 55:41–51.
Simpson D, Dorfman D, Olney R, et al.: Peptide T in the treatment of painful distal neuropathy associated with AIDS; Results of a placebo-controlled trial. The Peptide T Neuropathy Study Group. Neurology 1996, 47:1254–1259.
Simpson D, Tagliati M: Nucleoside analogue-associated peripheral neuropathy in human immunodeficiency virus infection. J AIDS 1995, 9:153–161.
Blum A, Dal Pan G, Feinberg J, et al.: Low dose zalcitabinerelated toxic neuropathy: frequency, natural history, and risk factors. Neurology 1996, 46:999–1003.
Dalakas M: Peripheral neuropathy and antiretroviral drugs. J Periph Nervous System 2001, 16:14–20. An article on neuropathy associated with toxic antiretrovirals in HIV patients.
Pike IM, Nicaise C: The didanosine Expanded Access Program: safety analysis. Clin Infect Dis 1993, 16(suppl 1):S63-S68.
Rathburn R, Martin EI: Didanosine therapy in patients intolerant of or failing zidovudine therapy. Ann Pharmacother 1992, 2:1347–1351.
Moyle GJ, Sadler M: Peripheral neuropathy with nucleoside antiretrovirals: risk factors, incidence and management. Drug Safety 1998, 19:481–494.
Fichtenbaum C, Clifford D, Powderly W: Risk factors for dideoxynucleoside-induced toxic neuropathy in patients with the human immunodeficiency virus infection. J AIDS Hum Retrovir 1995, 10:169–174.
Chen C, Cheng Y: Delayed cytotoxicity and selective loss of mitochondrial DNA in cells treated with the anti-human immunodeficiency virus compound 2′3′-dideoxycytidine. J Biol Chem 1989, 264:11934–11937.
Anderson TD, Davidovich A, Arceo R, et al.: Peripheral neuropathy induced by 2′,3′-dideoxycytidine. A rabbit model of 2′,3′-dideoxycytidine neurotoxicity. Lab Invest 1992, 66:63–74.
Kailbaugh S, Prusoff W, Simson M: The PC 12 cell as a model for studies of the mechanism of induction of peripheral neuropathy by anti-HIV 1 dideoxynucleoside analogs. Biochem Pharmacol 1991, 42:R5-R8.
White A: Mitochondrial toxicity and HIV therapy. Sex Transm Infect 2001, 77:158–173.
Arezzo J: Dideoxycytidine and other nucleoside analogs. Exp Clin Neurotoxicol 2000, 2:486–489.
Brew B, Tisch S, Law M: Lactate concentrations distinguish between nucleoside neuropathy and HIV distal symmetrical sensory polyneuropathy (abstract 9). Presented at 8th Conference on Retroviruses and Opportunistic Infections. Chicago, IL, 2001.
Lonergan J, Behling C, Pfander H, et al.: Hyperlactatemia and hepatic abnormalities in 10 human immunodeficiency virus infected patients receiving nucleoside analogue combination regimens. Clin Infect Dis 2000, 31:162–166.
Simpson DM, Bender AN: Human immunodeficiency virusassociated myopathy: analysis of 11 patients. Ann Neurol 1988, 24:79–84.
Simpson DM, Citak KA, Godfrey E, et al.: Myopathies associated with human immunodeficiency virus and zidovudine: can their effects be distinguished? [see comments]. Neurology 1993, 43:971–976.
Miller RG, Carson PJ, Moussavi RS, et al.: Fatigue and myalgia in AIDS patients. Neurology 1991, 41:1603–1607.
Simpson DM, Slasor P, Dafni U, et al.: Analysis of myopathy in a placebo-controlled zidovudine trial. Muscle Nerve 1997, 20:382–385.
Chad D, Smith T, Blumenfield D, et al.: HIV-associated myopathy: Immunocytochemical identification of an HIV antigen (gp41) in muscle macrophages. Ann Neurol 1994, 36:752–758.
Dalakas MC, Illa I, Pezeshkpour GH, et al.: Mitochondrial myopathy caused by long-term zidovudine therapy. N Engl J Med 1990, 322:1098–1105.
Gerard Y, Maulin L, Yazdanpanah Y, et al.: Symptomatic hyperlactatemia: an emerging complication of antiretroviral therapy. AIDS 2000, 14:2723–2730.
Falco V, Rodriguez D, Ribera E, et al.: Severe nucleoside-associated lactic acidosis in HIV-infected patients: report of 12 cases and review of the literature. Clin Infect Dis 2002, 34:838–846.
May H, Laut F, Palmisano J, et al.: Lactic acidosis and antiretroviral therapy: a case report and literature review. Braz J Infect Dis 2000, 4:151–155.
Marcus K, Truffa M, Boxwell D, Toerner J: Recently identified adverse events secondary to NRTI therapy in HIV-infected individuals: cases from the FDA’s adverse event reporting system (AERS). Presented at 9th Conference on Retroviruses and Opportunistic Infections. Seattle, WA, 2002.
Galera C, Redondo C, Pozo G: Symptomatic hyperlactatemia and lactic acidosis syndrome in HIV patients treated with nucleoside analogue reverse transcriptase inhibitors. Presented at 1st Conference on HIV Pathogenesis and Treatment. Buenos Aires, Argentina, 2001.
Verma A, Roland M, Jayaweera D, Kett D: Fulminant neuropathy and lactic acidosis associated with nucleoside analog therapy. Neurology 1999, 53:1365–1369.
Miller KD, Cameron M, Wood LV, et al.: Lactic acidosis and hepatic steatosis associated with use of stavudine: report of four cases. Ann Intern Med 2000, 133:192–196.
Mokrzycki MH, Harris C, May H, et al.: Lactic acidosis associated with stavudine administration: a report of five cases. Clin Infect Dis 2000, 30:198–200.
Simpson D, Estanislao L, Marcus K, et al.: HIV-Associated neuromuscular weakness syndrome. Presented at 10th Conference on Retrovirus and Opportunistic Infections. Boston, MA; 2003.
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Verma, S., Micsa, E., Estanislao, L. et al. Neuromuscular complications in HIV. Curr Neurol Neurosci Rep 4, 62–67 (2004). https://doi.org/10.1007/s11910-004-0014-8
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DOI: https://doi.org/10.1007/s11910-004-0014-8