eMedicine Specialties > Neurology > Neurological Infections

HIV-1 Associated Neuromuscular Complications (Overview)

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
Coauthor(s): Niranjan N Singh, MD, DNB, Assistant Professor of Neurology, University of Missouri Columbia
Contributor Information and Disclosures

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.

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