neurologic complications of hiv infection. history in 1985 –virus isolated from csf, brain, spinal...
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Neurologic Complications of HIV Infection
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History• In 1985 –virus isolated from CSF, brain, spinal
cord, peripheral nerves of patients with AIDS. • virus, pleocytosis, and elevated
immunoglobulins in the CSF of 2/3 after seroconversion
• central nervous system was infected both early and asymptomatically
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General Mechanisms
– direct neurotoxicity due to the neurotrophic nature of the virus
– autoimmune disease due to immune dysregulation
– opportunistic infections– cerebrovascular complications, neoplasms, side
effects of retroviral therapy– malnutrition and vitamin deficiencies
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• HAART tx lead to almost 50% decrease in incidence of HIV dementia
• Infected macrophages carry HIV into the nervous system
• HIV-related neurologic disease becomes obvious after the development of AIDS (CD4 <200)
• 90% of infected individuals manifesting some form of neurologic involvement by the time of death
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Brain Primary HIV and autoimmune• HIV-associated dementia or encephalopathy (children)• Demyelinating syndromes• Parkinsonism and other movement disorders• Sleep disordersNeurologic opportunistic processes • Toxoplasmosis encephalitis, progressive multifocal
leukoencephalopathy• Cytomegalovirus and varicella zoster virus encephalitis• Fungal: aspergillus, mucormycosis, histoplasmosis• Bacterial: tuberculosis, syphilis• Neoplasm: primary central nervous system lymphomaMedications • Neuroleptic sensitivity
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Meninges
Primary HIV and autoimmune • Acute aseptic or chronic meningitisNeurologic opportunistic processes • Cryptococcal meningitis• Bacterial: tuberculosis, syphilis• Neoplasm: lymphomatous meningitis
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Spinal cord
Primary HIV and autoimmune • Vacuolar myelopathyNeurologic opportunistic processes • Herpesviruses: varicella zoster virus,
cytomegalovirus, Herpes simplex virus• Bacterial: syphilis, tuberculosis• Neoplasm: metastatic lymphoma
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Root and plexus
Neurologic opportunistic processes• Cytomegalovirus polyradiculitis, syphilis,
tuberculosis• Neoplasm: lymphomatous meningitis
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Nerve Primary HIV and autoimmune
• Distal symmetrical polyneuropathy• Diffuse infiltrative lymphomatosis syndrome• Acute and chronic inflammatory demyelinating polyneuropathies• Mononeuritis multiplex• Motor neuron diseaseNeurologic opportunistic processes • Cytomegalovirus mononeuritis multiplex• Varicella zoster virus (multidermatomal)Medications • Nucleosides: didanosine, zalcitabine, stavudine, Dapsone,
metronidazole, isoniazid, pyridoxine, vincristine
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Muscle
Primary HIV and autoimmune• Inflammatory myopathyNeurologic opportunistic processes • ToxoplasmosisMedications • Zidovudine, trimethoprim-sulfamethoxazole• Statins
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• New-onset neurologic complications often are superimposed on an ongoing process with a different etiology
• The first consideration must be the stage of systemic HIV infection, which influences both the risk of neurologic disease as well as possible etiologies
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• Risk depends CD4 count, past and current exposure to infectious agents, HAART agents, use of antibacterial prophylaxis
• CD4 count provides critical information to guide evaluation
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CD4 Cell Count: >500/mm3
Infectious complications• Acute retroviral syndrome Noninfectious complications• Acute inflammatory demyelinating
polyneuropathy • Mononeuritis multiplex• Aseptic meningitis• HIV-associated headache
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CD4 Cell Count: <200/mm3
Infectious complications• Cytomegalovirus encephalitis and polyradiculitis• Progressive multifocal• Leukoencephalopathy (PML)• Toxoplasmosis encephalitis• Cryptococcosis meningitisNoninfectious complications • HIV-associated dementia• HIV-associated polymyositis • Vacuolar myelopathy• Distal sensory polyneuropathy• Diffuse infiltrative lymphomatosis syndrome
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CD4 Cell Count: 200 to 500/mm3
Infectious complications• Herpes zoster (multidermatomal)• Tuberculous meningitis • NeurosyphilisNoninfectious complications• Mononeuritis multiplex• AZT-induced myopathy• HIV-associated headache• Motor neuron disease
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HIV Dementia• Prevalence of 5% to 20% among untreated
AIDS patients and an annual incidence of 7% per year
• Is an AIDS-defining illness • Subcortical dementia - clinical triad
progressive motor (tremor, gait instability, and loss of fine motor control), cognitive (mental slowing, forgetfulness, and impaired concentration) and behavioral (mania, apathy, emotional lability) abnormalities
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HIV Dementia• Must be discriminated from other causes of
cognitive impairment. • Must always consider opportunistic infections• Primary CNS lymphoma can also present in
later stages of AIDS • Multi-infarct or vascular dementia may be
considered in particular cases• Vasculitis secondary to infection or illicit drug
use may rarely be found.
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HIV Dementia
• Illicit drugs, alcohol, or prescription drugs may account for cognitive difficulties
• Depression should also be excluded/treated• Always r/o encephalopathy (delirium)• Causes of dementia in the general population
may need to be considered, which will likely become a larger issue as the HIV-infected population ages
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HIV Dementia• Cerebral and basal ganglia atrophy and diffuse
WM hyperintensities on T2• MRS - diminished NAA = neuronal injury• Neuropsych testing with HIV dementia scale• MRS identifies higher Cho/Cr in the basal ganglia,
with reduced NAA/Cr and higher MI/Cr in frontal white matter, confirming a subcortical predominance
• Continuous arterial spin labeled MRI shows decrease in both caudate blood flow and volume
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HIV Dementia• Leads to a significant increase in the overall
morbidity due to AIDS. • Increased number of hospitalizations, increased
duration of hospital stays, and decreased life expectancy as compared to patients with
• Average life span may be as low as 6 mo unless HAART is administered.
• With HAART impairment can be reversed to some extent and the likelihood of survival greatly improved
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HIV Dementia• CSF typically demonstrates a mild pleocytosis +/- protein elevation• HIV-1 antigen, intrathecal production of anti–HIV-1 antibodies,
presence of oligoclonal bands and presence of cytokines• CSF viral RNA levels correlate with severity of cognitive impairment • EEG - diffuse slowing of background rhythms but lacks specificity in
the diagnosis of HIV-associated dementia or minor cognitive and motor disorder.
• CSF interleukin-18 levels may be useful in the detection of HIV-positive patients with opportunistic infections, being elevated in this patient population but not elevated in HIV-positive or HIV-associated dementia patients.
• Serum interleukin-18 levels are elevated in HIV-positive or HIV-associated dementia patients but not in HIV patients with opportunistic infections or HIV-negative controls