Post on 14-Dec-2015
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Neurologic Complications of HIV Infection
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
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
• 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
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
Meninges
Primary HIV and autoimmune • Acute aseptic or chronic meningitisNeurologic opportunistic processes • Cryptococcal meningitis• Bacterial: tuberculosis, syphilis• Neoplasm: lymphomatous meningitis
Spinal cord
Primary HIV and autoimmune • Vacuolar myelopathyNeurologic opportunistic processes • Herpesviruses: varicella zoster virus,
cytomegalovirus, Herpes simplex virus• Bacterial: syphilis, tuberculosis• Neoplasm: metastatic lymphoma
Root and plexus
Neurologic opportunistic processes• Cytomegalovirus polyradiculitis, syphilis,
tuberculosis• Neoplasm: lymphomatous meningitis
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
Muscle
Primary HIV and autoimmune• Inflammatory myopathyNeurologic opportunistic processes • ToxoplasmosisMedications • Zidovudine, trimethoprim-sulfamethoxazole• Statins
• 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
• 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
CD4 Cell Count: >500/mm3
Infectious complications• Acute retroviral syndrome Noninfectious complications• Acute inflammatory demyelinating
polyneuropathy • Mononeuritis multiplex• Aseptic meningitis• HIV-associated headache
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
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
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
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.
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
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
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
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