Human Immunodeficiency Virus-Associated Peripheral Neuropathies

doi:10.4065/81.2.213

Mayo Clinic Proceedings

Volume 81, Issue 2, February 2006, Pages 213-219

https://doi.org/10.4065/81.2.213 Get rights and content

Peripheral neuropathy has emerged as the most common neurologic complication of human immunodeficiency virus (HIV) infection. It will continue to play an important role in HIV infection given the fact that HIV-infected individuals are living longer, are at risk of long-term metabolic complications, and face an increasing exposure to potentially neurotoxic antiretroviral drugs. We review the various types of peripheral neuropathy that have been associated with HIV infection, including distal symmetrical polyneuropathy, toxic neuropathy from antiretroviral drugs, diffuse infiltrative lymphocytosis syndrome, inflammatory demyelinating polyneuropathies, multifocal mononeuropathies, and progressive polyradiculopathy.

Section snippets

DISTAL SYMMETRICAL POLYNEUROPATHY

Distal symmetrical polyneuropathy is the most frequent form of neuropathy in HIV-1 infection. It is detected by clinical examination in 30% of infected patients⁴ and in almost 100% of cases at autopsy examination of individuals with acquired immunodeficiency syndrome (AIDS).⁵ In one study, DSP showed a significant decline in prevalence from 42.5% in 1995-1996 to 34.4% in 1997-1998.⁶ In contrast, the prevalence of suspected drug-induced polyneuropathy increased to 31% compared with 20% in

TOXIC NEUROPATHY FROM ANTIRETROVIRAL DRUGS

A clinical picture resembling DSP is frequently noted during antiretroviral therapy. With the advent of HAART, the incidence of DSP has increased largely from the use of the NRTIs didanosine, zalcitabine, and stavudine. The toxic effect of NRTIs is dose dependent and is estimated to occur in 15% to 30% of patients receiving each of these drugs.14, 23, 24 Recent preliminary data, reported at the 56th Annual Meeting of the American Academy of Neurology, show an increased risk of DSP in patients

DIFFUSE INFILTRATIVE LYMPHOCYTOSIS SYNDROME

Persistent CD8 lymphocytosis, named diffuse infiltrative lymphocytosis syndrome is characterized by a persistent peripheral blood polyclonal CD8 lymphocytosis and by visceral CD8 T-cell infiltration, including salivary glands, lungs, kidneys, gastrointestinal tract, and peripheral nerves.16, 28, 29 Infiltration of the salivary glands produces a Sjögren-like disorder. Patients with DILS tend to have higher CD4 cell counts, fewer opportunistic infections, and longer survival times than typical

INFLAMMATORY DEMYELINATING POLYNEUROPATHIES

Inflammatory demyelinating polyneuropathies are disorders with acute or chronic evolving weakness in arms and legs and minor sensory symptoms. Although data from large series or controlled trials are lacking, the clinical features and the disease course of patients with acute or chronic IDP appear to be similar in HIV-1-positive and HIV-1-negative patients. Although acute and chronic IDPs occur with increasing frequency in HIV-1-infected patients, they remain rare complications of HIV-1

MONONEURITIS MULTIPLEX

Mononeuritis multiplex is a rare complication that occurs in either early or late stages of HIV-1 infection.³⁸ When mononeuritis multiplex occurs early in HIV-1 infection, it is often the result of a self-limited dysimmune neuropathy or vasculitis. In patients with long-standing HIV-1 infection and CD4 cell counts less than 50/μL, an association with cytomegalovirus (CMV) infection has frequently been noted. Mononeuritis multiplex has also been associated with varicella zoster³⁹ and hepatitis C

PROGRESSIVE POLYRADICULOPATHY

Progressive polyradiculopathy is an uncommon but well-described complication of HIV infection. No accurate estimates exist of the incidence of progressive polyradiculopathy associated with HIV infection. Fuller et al⁴² identified 54 patients (approximately 4%) with peripheral nerve syndromes among a cohort of 1500 HIV-infected patients followed up for 15 months before the introduction of HAART. Only 2 patients (0.1%) had progressive polyradiculopathy. The incidence of HIV-associated progressive

PN ASSOCIATED WITH IMMUNE RECONSTITUTION

HAART has been associated with numerous immune reconstitution illnesses, which generally occur within 6 months after its introduction and are thought to constitute an aberrant immune response to opportunistic pathogens.64, 65, 66, 67 Makela et al⁶⁸ described the occurrence of a probable recurrent Guillain-Barré syndrome 6 weeks after initiation of HAART and after a striking increase in CD4 cell count in 1 HIV-infected individual. Piliero et al⁶⁹ described an HIV-infected patient with AIDS who

CONCLUSION

Peripheral neuropathy is the most frequent neurologic complication of HIV infection or its treatment. The spectrum and the frequency of this complication are expected to change with continued experience and introduction of new antiretroviral drugs, an aging HIV-infected population, and the emergence of other long-term complications of HIV and/or its treatment. There is a great need for an improved understanding of these complications and their pathogenetic mechanisms as well as for the

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Treatment and Management of Infectious, Granulomatous, and Toxic Neuromuscular Disorders
2021, Neuromuscular Disorders: Treatment and Management
The neuromuscular apparatus is susceptible to medications, toxins, granulomatous diseases, and infections by organisms like bacteria, parasites, and viruses. This chapter examines the most common and relevant neuromuscular disorders associated with these susceptibilities. The changes in the treatment of human immunodeficiency virus (HIV) infection have modified the profile of neuromuscular complications associated with HIV, but they continue to be an important cause of disability. Neurotropic viruses like West Nile virus represent the modern version of the old poliovirus-associated polymyelitis. Other viruses like human T-lymphotrophic virus type I can result in clinical phenotypes that resemble neurodegenerative conditions and must be excluded for accurate diagnosis. Neuroborreliosis must be considered in patients from endemic areas and will require a high degree of suspicion for proper diagnosis and treatment. Leprosy continues to be an important cause of neuropathy in developing nations, or in areas with high levels of poverty in more developed countries. A treatable cause of neuropathy, it requires early recognition and treatment to avoid incapacitating damage and deformities. The parasitic myositis from Trichinella and cysticercosis, although not as frequent in developed nations, must still be considered in areas with prevalent ingestion of wild game. Toxicities from heavy metals must still be considered in industrialized settings or suspicious circumstances. New medications and approaches in the fight against cancer have expanded the types of neuromuscular toxicities, from disruption of physiologic processes in neurons, axons, and muscles, to actual autoimmune responses against different neuromuscular components. These have resulted in an expanded profile of toxicities and clinical syndromes that clinicians must recognize.
Neuromuscular diseases associated with Human Immunodeficiency Virus infection
2018, Journal of the Neurological Sciences
From the most common distal symmetric polyneuropathy (Bilgrami and O'Keefe, 2014) to the rare motor neuron diseases, HIV infection is associated with pathology at all levels of the peripheral nervous system. HIV infection can cause these conditions due to viral exposure itself, the resulting immune dysregulation, opportunistic infections found in untreated patients, and from the therapy used in treatment of the virus. Before the advent of antiretroviral therapy, 5 neuromuscular diseases associated with HIV often resulted from opportunistic infections. With advances in antiretroviral therapy, the etiologies of neuromuscular complications more frequently become the result of prolonged HIV exposure, comorbid diseases, and side effects of medications. In this article we review the literature on HIV associated neuromuscular diseases, emphasizing the more recent studies in the post antiretroviral era, but also reviewing conditions more prevalent in the pre antiretroviral era which continue to be seen in developing countries and resource poor areas. This discussion includes the following conditions: distal symmetric polyneuropathy, autonomic neuropathy, inflammatory demyelinating polyneuropathy, mononeuropathy, mononeuropathy multiplex, polyradiculopathies, myelopathy, myopathy, motor neuron disease, and antiretroviral treatment related conditions.
CIDP in a HIV endemic population: A prospective case series from Johannesburg, South Africa
2016, Journal of the Neurological Sciences
Citation Excerpt :
Clinically, the CIDP in HIV infected patients has been reported to be similar to that in patients without HIV. In the few small patient series and case reports describing CIDP in HIV the main difference is a cerebrospinal fluid lymphocytic pleocytosis, which is found in the HIV positive patients [5,7–9]. We prospectively studied 23 CIDP patients in a tertiary referral center in Johannesburg, South Africa, a region of high HIV prevalence.
To describe patients with Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) in Johannesburg, South Africa, a setting of high HIV prevalence, and to determine the influence, if any, of HIV on CIDP.
Patients were recruited prospectively. The study design was a hospital based case series of unselected consecutive CIDP patients. CIDP was diagnosed according to the European Federation of Neurological Societies/Peripheral Nerve Society criteria for the diagnosis of CIDP (First Revision). Demographic, clinical, laboratory and electrophysiological data were documented.
Twenty three patients with CIDP were recruited over a two year period. Mean age was 38 years. The female to male ratio was 3.6:1. Less than half (43%) had a raised cerebrospinal fluid (CSF) protein. All patients had idiopathic CIDP, three had associated diabetes mellitus. Ten patients (43%) were HIV positive. Thirteen patients were HIV negative. Clinical and electrophysiological characteristics were identical in the two groups. In the HIV positive group all the patients were black females. The CD4 counts ranged from 87 to 747cells/mm³. HIV positive status was associated with a progressive disease course and significantly with a CSF lymphocytic pleocytosis (p = 0.007). Albuminocytological dissociation was associated with HIV negative status.
Testing for HIV in patients with CIDP in a region of high HIV prevalence is recommended.
CSF lymphocytic pleocytosis occurs in HIV associated CIDP.
The diffuse infiltrative lymphocytosis syndrome (DILS): A comprehensive review
2015, Journal of Autoimmunity
Citation Excerpt :
Peripheral nerve biopsy shows an angiocentric endoneurial and perineurial infiltration by CD8+ lymphocytes without fibrinoid necrosis. Neuritis or radiculitis due to other causes (infectious: HIV, VZV, CMV; drug-related: didanosine, zalcitabine, stavudine, isoniazide; tumoral: lymphoma; or immunological: Guillain-Barré syndrome, vasculitis, Immune Reconstitution Inflammatory Syndrome (IRIS)) have to be ruled out [21]. Renal involvement is described in only 6–8% of cases (Table 2).
The Diffuse Infiltrative Lymphocytosis Syndrome (DILS) is a rare multisystemic syndrome described in HIV-infected patients. It is characterised by CD8⁺ T-cell lymphocytosis associated with a CD8⁺ T-cell infiltration of multiple organs. DILS is usually seen in uncontrolled or untreated HIV infection but can also manifest itself independently of CD4⁺ T-cell counts. The syndrome may present as a Sjögren-like disease that generally associates sicca signs with bilateral parotiditis, lymphadenopathy, and extraglandular organ involvement. The latter may affect the lungs, nervous system, liver, kidneys, and digestive tract. Anomalies of the respiratory system are often identified as lymphocytic interstitial pneumonia. Facial nerve palsy, aseptic meningitis or polyneuropathy are among the more frequent neurological features. Hepatic lymphocytic infiltration, lymphocytic interstitial nephropathy and digestive tract lymphocytic infiltration account for more rarely noted complications. Sicca syndrome, organomegaly and/or organ dysfunction associated with polyclonal CD8⁺ T-cell organ-infiltration are greatly suggestive of DILS in people living with HIV. Labial salivary gland biopsy is therefore helpful when the focus score is equal or greater than 1 (or Chisholm Score ≥ 3). Primary Sjögren syndrome, chronic HCV or HTLV1 infection, graft versus host disease, IgG4-related disease, and immune reconstitution inflammatory syndrome are among the differential diagnoses that need to be considered. Treatment consists in highly active anti-retroviral therapy (HAART), which is usually effective in resolving clinical signs and symptoms. Steroids, however, may also be occasionally required when organ infiltration does not respond to HAART. This review should provide an insight into this rare entity complicating the course of HIV infection.

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REVIEWHuman Immunodeficiency Virus-Associated Peripheral Neuropathies

Section snippets

DISTAL SYMMETRICAL POLYNEUROPATHY

TOXIC NEUROPATHY FROM ANTIRETROVIRAL DRUGS

DIFFUSE INFILTRATIVE LYMPHOCYTOSIS SYNDROME

INFLAMMATORY DEMYELINATING POLYNEUROPATHIES

MONONEURITIS MULTIPLEX

PROGRESSIVE POLYRADICULOPATHY

PN ASSOCIATED WITH IMMUNE RECONSTITUTION

CONCLUSION

J Neurol Sci

Am J Med

J Infect

Immunobiology

J Infect

Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection

N Engl J Med

Neuropathy in HIV infection

Curr Opin Neurol

The neurology of HIV infection

J Neurol Neurosurg Psychiatry

Peripheral neuropathy associated with acquired immunodeficency syndrome: prevalence and clinical features from a population-based survey

Arch Neurol

Predominantly sensory neuropathy in AIDS: distal axonal degeneration and unmyelinated fiber loss [abstract]

Neurology

Incidence and prevalence of neurological disorders associated with HIV since the introduction of highly active antiretroviral therapy (HAART)

J Neurol Neurosurg Psychiatry

HIV-associated distal sensory polyneuropathy in the era of highly active antiretroviral therapy: the Manhattan HIV Brain Bank

Arch Neurol

Modification of the incidence of drug-associated symmetrical peripheral neuropathy by host and disease factors in the HIV outpatient study cohort

Clin Infect Dis

Predominantly sensory neuropathy in patients with AIDS and AIDS-related complex

Neurology

Peripheral neuropathy in the acquired immunodeficiency syndrome

Ann Neurol

Peripheral neuropathies associated with HIV infection

Isolation of HTLV-III from cerebrospinal fluid and neural tissues of patients with neurologic syndromes related to the acquired immunodeficiency syndrome

N Engl J Med

Role of HIV in the pathogenesis of distal symmetrical peripheral neuropathy

Acta Neuropathol (Berl)

Nucleoside analogue-associated peripheral neuropathy in human immunodeficency virus infection

J Acquir Immune Defic Syndr Hum Retrovirol

Mitochondrial toxicity of antiviral drugs

Nat Med

Neuropathy in diffuse infiltrative lymphocytosis syndrome: an HIV neuropathy, not a lymphoma

Neurology

Controlling neuropathic pain in HIV

Curr Infect Dis Rep

A placebo-controlled trial of gabapentin for painful HIV-associated sensory neuropathies

J Neurol

Lamotrigine for HIV-associated painful sensory neuropathies: a placebo-controlled trial

Neurology

A randomized controlled trial of 5% lidocaine gel for HIV-associated distal symmetric polyneuropathy

J Acquir Immune Defic Syndr

A phase II trial of nerve growth factor for sensory neuropathy associated with HIV infection [published correction appears in Neurology. 2000;55:162]

Neurology

Acupuncture and amitriptyline for pain due to HIV-related peripheral neuropathy: a randomized controlled trial

JAMA

Risk factors for dideoxynucleoside-induced toxic neuropathy in patients with the human immunodeficiency virus infection

J Acquir Immune Defic Syndr Hum Retrovirol

Peripheral neuropathy with nucleoside antiretrovirals: risk factors, incidence and management

Drug Saf

Protease inhibitors and risk of developing HIV-related sensory neuropathy

AIDS

HIV-associated neuromuscular weakness syndrome [published correction appears in AIDS. 2004;18:1751]

AIDS

The pathogenesis of diffuse infiltrative lymphocytosis syndrome: an AIDS-related peripheral neuropathy [editorial]

Neurology

Peripheral neuropathy in human immunodeficiency virus-infected patients with the diffuse infiltrative lymphocytosis syndrome

Ann Neurol

REVIEW
Human Immunodeficiency Virus-Associated Peripheral Neuropathies