We searched PubMed from 1986 to March 2005 for “HIV-associated dementia”, “vacuolar myelopathy” or “sensory neuropathies”.
ReviewNeurological complications of HIV infection
Section snippets
Biology of HIV infection
HIV-1 is a retrovirus that produces profound CD4 depletion, possibly through an initial massive depletion of gut-associated memory T cells, and then chronic immune activation, leading to fatigue of homoeostatic T-cell responses and progressive immunodeficiency. The CD4 receptor is the main target for HIV-1, however, specific chemokine receptors are important secondary cellular receptors.1, 2 Additionally, specific lectins on dendritic cells may stabilise HIV for presentation to susceptible
Neurological symptoms of HIV infection
HIV may affect the nervous system directly, producing distinct neurological syndromes, or indirectly, by causing immunodeficiency with a resultant susceptibility to opportunistic infections. Nervous system infection with HIV-1 can produce a range of clinical disorders, but only dementia, myelopathy, and sensory neuropathies will be discussed here. These debilitating disorders generally do not develop until advanced stages of HIV infection. Typically, other AIDS-defining illnesses or
Epidemiology
HIV-D, also called HIV encephalopathy and AIDS dementia complex, rarely develops before profound immunosuppression. The lifetime prevalence of HIV-D in a group of 5000 homosexual men in the USA was about 15%,12 but may be different in other populations. Risk factors include high HIV set point early in HIV infection, low CD4 counts,13 anaemia, low body-mass index, age (risk increases with increasing age), systemic symptoms,12 injection-drug use,14 and female sex.15 In cohort studies of patients
HIV-1-associated myelopathies
Vacuolar myelopathy (VM) is the myelopathy most commonly associated with HIV-1; it is a slowly progressive painless spastic paraparesis, with sensory ataxia and neurogenic bladder, characterised by prominent vacuolar changes in the ascending and descending tracts that particularly affect the thoracic spinal cord. VM is symptomatic in 5–10% of patients with AIDS, but has been identified pathologically in almost 50% of cases at autopsy.107 This myelopathy commonly parallels the development of
Sensory neuropathies associated with HIV
The peripheral nervous system may be involved in diverse ways. Several diagnoses, which might be immune-mediated, have been described, such as cranial neuropathies, polymyositis, motor-neuron disease, and inflammatory demyelinating polyneuropathies; these are discussed elsewhere.114, 115
Conclusion
AIDS has caused 20 million deaths, and it is estimated that almost 38 million people worldwide are infected with HIV. The range of neurological disorders associated with HIV AIDS continues to increase, and HIV-D and HIV-SN will increase in prevalence as use of HAART increases, survival lengthens, and there are more people living with HIV. Generic antiretrovirals in resource-limited countries commonly contain neurotoxic nucleoside analogues, such as d4T, and the lengthy exposure to these
Search strategy and selection criteria
References (161)
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Cell
(2000)- et al.
AIDS dementia complex in the Italian National AIDS Registry: temporal trends (1987–1993) and differential incidence according to mode of transmission of HIV-1 infection
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CCR2 polymorphisms affect neuropsychological impairment in HIV-1-infected adults
J Neuroimmunol
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J Neuroimmunol
(2004)- et al.
Human immunodeficiency virus-1 infection of the nervous system: an autopsy study of 268 adult, pediatric, and fetal brains
Hum Pathol
(1991) - et al.
Cellular localization of tumor necrosis factor mRNA in neurological tissue from HIV-infected patients by combined reverse transcriptase polymerase chain reaction in situ hybridization and immunohistochemistry
J Neuroimmunol
(1997) - et al.
Cytotoxicity by matrix metalloprotease-1 in organotypic spinal cord and dissociated neuronal cultures
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Neurobiological aspects of human immunodeficiency virus infection: neurotoxic mechanisms
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Transient exposure to HIV-1 Tat protein results in cytokine production in macrophages and astrocytes: a hit and run phenomenon
J Biol Chem
(1999) - et al.
Biological characterization of paired human immunodeficiency virus type 1 isolates from blood and cerebrospinal fluid
Virology
(1989)
CCR3 and CCR5 are co-receptors for HIV-1 infection of microglia
Nature
Chemokine receptors—gateways to inflammation and infection
Nat Med
Viral DNA and mRNA expression correlate with the stage of human immunodeficiency virus (HIV) type 1 infection in humans: evidence for viral replication in all stages of HIV disease
J Virol
Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection
Nature
Use of HIV viral load in clinical practice: back to the future
Ann Intern Med
Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy
Science
Targeting neurotherapeutic agents through the blood-brain barrier
Arch Neurol
Recovery of replication-competent HIV despite prolonged suppression of plasma viremia
Science
HIV infection and dementia
Science
A unifying hypothesis for the pathogenesis of HIV-associated dementia complex, vacuolar myelopathy, and sensory neuropathy
J AIDS
Dementia in AIDS patients: incidence and risk factors
Neurology
Plasma viral load and CD4 lympocytes predict HIV-associated dementia and sensory neuropathy
Neurology
Epidemiology of human immunodeficiency virus encephalopathy in the United States
Neurology
Evaluation of HIV RNA and markers of immune activation as predictors of HIV-associated dementia
Neurology
The impact of zidovudine on dementia-free survival in a population of HIV-positive men and women on antiretroviral therapy
Int J STD AIDS
Circulating proviral HIV DNA and HIV-associated dementia
AIDS
Dysregulation of sphingolipid and sterol metabolism by ApoE4 in HIV dementia
Neurology
HIV-infected subjects with the E4 allele for APOE have excess dementia and peripheral neuropathy
Nat Med
HIV-1 infection and AIDS dementia are influenced by a mutant MCP-1 allele linked to increased monocyte infiltration of tissues and MCP-1 levels
Proc Natl Acad Sci USA
Increased frequency of the tumor necrosis factor-alpha-308 A allele in adults with human immunodeficiency virus dementia
Ann Neurol
Human immunodeficiency virus (HIV) infection and the nervous system: report from the American Academy of Neurology AIDS Task Force
Neurology
The epidemiology of human immunodeficiency virus-associated neurological disease in the era of highly active antiretroviral therapy
J Neurovirol
Medication adherence among HIV+ adults: effects of cognitive dysfunction and regimen complexity
Neurology
Mortality risks in gay men with human immunodeficiency virus infection and cognitive impairment
Neurology
Psychomotor slowing in HIV infection: a predictor of dementia, AIDS, and death
J Neurovirol
Neurocognitive dysfunction predicts postmortem findings of HIV encephalitis
Neurology
Pediatric acquired immunodeficiency syndrome: neurologic syndromes
Am J Dis Child
Progressive encephalopathy in children with acquired immune deficiency syndrome
Ann Neurol
Elevated serum levels of tumor necrosis factor are associated with progressive encephalopathy in children with acquired immunodeficiency syndrome
Am J Dis Child
Low blood CD8+ T-lymphocytes and high circulating monocytes are predictors of HIV-1-associated progressive encephalopathy in children
Pediatrics
HIV-1 infection of subcortical astrocytes in the pediatric central nervous system
Neurology
A neuronal and neuroanatomical correlate of HIV-1 encephalopathy relative to HIV-1 encephalitis in HIV-1-infected children
J Neuropathol Exp Neurol
Assessing HIV-associated dementia: modified HIV dementia scale versus the Grooved Pegboard
AIDS Read
The HIV Dementia Scale: a rapid screening test
J AIDS
Evidence for a change in AIDS dementia complex in the era of highly active antiretroviral therapy and the possibility of new forms of AIDS dementia complex
AIDS
Changing patterns in the neuropathogenesis of HIV during the HAART era
Brain Pathol
Cerebral CD8+ lymphocytosis in HIV-1 infected patients with immune restoration induced by HAART
Acta Neuropathol (Berl)
Multifocal vacuolar leucoencephalopathy: a distinct HIV-associated lesion of the brain
Neuropathol Appl Neurobiol
Relationship between human immunodeficiency virus-associated dementia and viral load in cerebrospinal fluid and brain
Ann Neurol
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