eMedicine Specialties > Neurology > Neurological Infections

HIV-1 Associated Neuromuscular Complications (Overview)

Florian P Thomas, MD, MA, PhD, Drmed, Director, Spinal Cord Injury Unit, St Louis Veterans Affairs Medical Center; Director, National MS Society Multiple Sclerosis Center; Professor, Department of Neurology and Psychiatry, Associate Professor, Institute for Molecular Virology, and Department of Molecular Microbiology and Immunology, St Louis University
Niranjan N Singh, MD, DNB, Assistant Professor of Neurology, University of Missouri Columbia

Updated: Jun 29, 2009

Introduction

Background

Patients may have more than one type of HIV-related neuromuscular disease. The type of neuromuscular problem is related to the stage of HIV disease. Patients also are susceptible to the same neuromuscular diseases as the general public (eg, carpal tunnel syndrome in an HIV-positive barber or computer operator). A wide spectrum of neuromuscular conditions is associated with HIV infection, including the following:

• Mononeuropathy multiplex
• Acute or chronic, inflammatory, demyelinating polyradiculoneuropathy
• Distal, symmetric, often painful, and predominantly sensory polyneuropathy
• Autonomic neuropathy (eg, erectile dysfunction)
• Antiretroviral-associated neuropathy
• Polyradiculopathy
• HIV myopathy
• Zidovudine myopathy
• HIV wasting syndrome
• Neuropathies associated with diffuse infiltrative lymphocytosis syndrome (DILS)
• Neurotoxin-associated peripheral neuropathy (typically a complication of treatment for associated conditions; antiretrovirals, infections, lymphoma, sarcoma, prophylaxis)
• Nonspecific myalgias occur as part of the flu-like illness during seroconversion

Pathophysiology

Relevant pathophysiologic mechanisms include the following:

• Nutritional deficits (eg, vitamin B₁₂) can be secondary to enteropathies and malabsorption caused by intestinal HIV, cytomegalovirus (CMV) infection, or herpes simplex virus infection.
• Drug toxicity: Zidovudine is associated with myopathy. Didanosine, zalcitabine, indinavir, ritonavir, saquinavir, and stavudine can cause polyneuropathy, possibly in part due to mitochondrial toxicity and in a dose-dependent fashion.¹
• Autoimmune mechanisms result in inflammatory demyelinating neuropathies, mononeuropathy multiplex, and polymyositis.
• Co-infection with CMV, herpes simplex virus, varicella zoster virus, Mycobacterium avium-intracellulare, Treponema pallidum, and other bacteria can cause neuromuscular complications.
• The likelihood of a particular syndrome correlates with viral load and CD4 lymphocyte counts. Acute inflammatory demyelinating polyradiculoneuropathy (Guillain-Barré syndrome) and isolated acute cranial nerve palsies are common at seroconversion. Distal symmetric, often painful sensorimotor polyneuropathy and CMV infection are more common in the late stages of AIDS.
• AIDP and CIDP may be the initial manifestation of disease, related to autoimmune dysfunction. AIDP has also been associated with immune reconstitution illnesses after initiation of highly active antiretroviral therapy (HAART).² CSF shows pleocytosis and increased protein. Nerve conduction studies (NCSs) and biopsy are compatible with demyelination.
• Mononeuropathy multiplex is an inflammatory response in the early stages of disease. Late MM is typically associated with CMV infection. May appear as IDP or PP. EMG and NCS show axonal degeneration and asymmetric involvement. CSF shows pleocytosis and elevated protein level.
• Progressive polyradiculopathy (PP) is typically associated with CMV and other herpes virus infections. HAART has reduced the incidence of PP. CSF shows pleocytosis and elevated protein level. It typically presents with a cauda equina–like picture, and EMG shows denervation of the lower extremities. NCSs are mildly slow.
• Autonomic neuropathy usually presents with sexual dysfunction, diarrhea, and bladder dysfunction. It can be related to medication effects.
• In association with peripheral CD8 lymphocytosis and infiltration by CD8 cells of organs such as the GI tract, kidneys, salivary glands, lungs, and nerves, patients may present with PNS manifestations including multifocal or symmetric, acute or subacute neuropathy. This is referred to as the diffuse infiltrative lymphocytosis syndrome (DILS).²
• Myopathy shows proximal weakness and is confirmed with EMG. Elevated CK may also be seen, and muscle biopsy can be helpful, demonstrating necrosis and inflammation. HIV-related myopathy must be differentiated from toxin-related (zidovudine)myopathies.

Frequency

United States

HIV-1 associated neuromuscular complications are still clinically apparent in more than 30% of patients, but certain complications of HIV, such as DSPN, have decreased since the advent of HAART.³ They can be clinically silent, and many additional neuromuscular abnormalities are detected by EMG/NCSs, biopsy, or autopsy.

• In one study, inflammatory changes, type II fiber atrophy, or denervation were detected in more than half of asymptomatic HIV-seropositive patients without weakness.
• In another report of untreated patients with mild muscle wasting, inflammation and fiber necrosis were found in one third, type II atrophy in more than one half, and denervation in more than three fourths of patients.

Mortality/Morbidity

Mortality and morbidity are related to the stage of HIV infection.

Age

Neuropathies are much more common in adults than in the pediatric HIV population.

Differential Diagnoses

Workup

Laboratory Studies

Laboratory studies depend on the type of neuromuscular complication that is suspected. A full neuropathy workup for suspected neuropathies, or myopathy workup for suspected myopathies, and can be found in eMedicine Neurology for each specific disorder. Typically, the workup includes serum laboratory testing, CSF examination, EMG/NCSs, and possible nerve and/or muscle biopsy.

See HIV-1 Associated Acute/Chronic Inflammatory Demyelinating Polyradiculoneuropathy, HIV-1 Associated Distal Painful Sensorimotor Polyneuropathy, HIV-1 Associated Multiple Mononeuropathies, HIV-1 Associated Myopathies, and HIV-1 Associated Progressive Polyradiculopathy.

Histologic Findings

HIV RNA and/or the virus have been detected in nerve and dorsal root ganglia. Infected cells include satellite and mononuclear cells and occasional dorsal root ganglion neurons. In the skin, epidermal nerve fiber densities are reduced in symptomatic and asymptomatic distal HIV polyneuropathy compared with controls.

Treatment

Medical Care

Treatment depends on the specific HIV-related neuromuscular condition encountered and is discussed in the individual topics found in eMedicine Neurology.

HIV-1 Associated Acute/Chronic Inflammatory Demyelinating Polyradiculoneuropathy

HIV-1 Associated Distal Painful Sensorimotor Polyneuropathy

HIV-1 Associated Multiple Mononeuropathies

HIV-1 Associated Myopathies

HIV-1 Associated Progressive Polyradiculopathy

Miscellaneous

Medicolegal Pitfalls

Some HIV-1 associated neuromuscular complications, for example, CMV polyradiculopathy, are often rapidly progressive and quickly lead to death unless expeditiously treated. While its clinical and cerebrospinal fluid patterns are fairly typical, the clinician must be careful not to ascribe progression of pain and weakness to a chronic painful distal neuropathy without evaluating other causes by electromyogram/nerve conduction study and cerebrospinal fluid analysis. Failure to do so may be seen as a deviation from standard medical care.

References

1. Dalakas MC, Semino-Mora C, Leon-Monzon M. Mitochondrial alterations with mitochondrial DNA depletion in the nerves of AIDS patients with peripheral neuropathy induced by 2'3'-dideoxycytidine (ddC). Lab Invest. 2001;81:1537-1544. [Medline].

2. Ferrari S, Vento S, Monaco S, Cavallaro T, Cainelli F, Rizzuto N, et al. Human immunodeficiency virus-associated peripheral neuropathies. Mayo Clin Proc. Feb 2006;81(2):213-9. [Medline].

3. Maschke M, Kastrup O, Esser S, et al. Incidence and prevalence of neurological disorders associated with HIV since the introduction of highly active antiretroviral therapy (HAART). J Neurol Neurosurg Psychiatry. Sep 2000;69(3):376-80. [Medline].

4. Chariot P, Gherardi R. Myopathy and HIV infection. Curr Opin Rheumatol. Nov 1995;7(6):497-502. [Medline].

5. Neuromuscular Disorders in HIV-1 Infection. In: Mancall E, ed. Continuum. 6 number 5 Part A. Lippincott Williams & Wilkins; 2000:73-79.

6. de Gans J, Portegies P. Neurological complications of infection with human immunodeficiency virus type 1. A review of literature and 241 cases. Clin Neurol Neurosurg. 1989;91(3):199-219. [Medline].

7. Gendelman HE, Lipton SA, Epstein L. The Neurology of AIDS. New York: Chapman & Hall; 1998.

8. Herrmann DN, McDermott MP, Henderson D. Epidermal nerve fiber density, axonal swellings and QST as predictors of HIV distal sensory neuropathy. Muscle & Nerve. 2004;29:420-427. [Medline].

9. Luciano CA, Pardo CA, McArthur JC. Recent developments in the HIV neuropathies. Curr Opin Neurol. Jun 2003;16(3):403-9. [Medline].

10. Said G, Saimont AG, Lacroix C. Neurological Complications of HIV and AIDS. Philadelphia, Pa: WB Saunders; 1998.

11. Simpson DM, Olney RK. Peripheral neuropathies associated with human immunodeficiency virus infection. Neurol Clin. Aug 1992;10(3):685-711. [Medline].

Keywords

acquired immunodeficiency syndrome, AIDS, HIV-related neuromuscular disease, mononeuropathy multiplex, acute inflammatory demyelinating polyradiculoneuropathy, chronic inflammatory demyelinating polyradiculoneuropathy, sensory polyneuropathy, autonomic neuropathy, polyradiculopathy, inflammatory myopathy, noninflammatory myopathy, drug toxicity, lymphoma, polymyositis, toxoplasmosis, bacterial infections, nonspecific myalgias, cytomegalovirus, CMV, herpes simplex virus infection, varicella zoster virus, Mycobacterium avium-intracellulare, Treponema pallidum, Guillain-Barré syndrome

Contributor Information and Disclosures

Author

Florian P Thomas, MD, MA, PhD, Drmed, Director, Spinal Cord Injury Unit, St Louis Veterans Affairs Medical Center; Director, National MS Society Multiple Sclerosis Center; Professor, Department of Neurology and Psychiatry, Associate Professor, Institute for Molecular Virology, and Department of Molecular Microbiology and Immunology, St Louis University
Florian P Thomas, MD, MA, PhD, Drmed is a member of the following medical societies: American Academy of Neurology, American Paraplegia Society, and National Multiple Sclerosis Society
Disclosure: Nothing to disclose.

Coauthor(s)

Niranjan N Singh, MD, DNB, Assistant Professor of Neurology, University of Missouri Columbia
Niranjan N Singh, MD, DNB is a member of the following medical societies: American Academy of Neurology
Disclosure: Nothing to disclose.

Medical Editor

Ronald A Greenfield, MD, Professor, Department of Internal Medicine, Section of Infectious Diseases, University of Oklahoma College of Medicine
Ronald A Greenfield, MD is a member of the following medical societies: American College of Physicians, American Federation for Medical Research, American Society for Microbiology, Central Society for Clinical Research, Infectious Diseases Society of America, Medical Mycology Society of the Americas, Phi Beta Kappa, Southern Society for Clinical Investigation, and Southwestern Association of Clinical Microbiology
Disclosure: Pfizer Honoraria Speaking and teaching; Gilead Honoraria Speaking and teaching; Ortho McNeil Honoraria Speaking and teaching; Wyeth Honoraria Speaking and teaching; Abbott Honoraria Speaking and teaching; Astellas Honoraria Speaking and teaching; Cubist  Speaking and teaching

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Glenn Lopate, MD, Associate Professor, Department of Neurology, Division of Neuromuscular Diseases, Washington University School of Medicine; Chief of Neurology, St Louis ConnectCare, Consulting Staff, Barnes Jewish Hospital
Glenn Lopate, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and Phi Beta Kappa
Disclosure: Nothing to disclose.

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Nicholas Y Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants
Nicholas Y Lorenzo, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Neurology
Disclosure: Nothing to disclose.

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