1. Neurologic Complications of HIV Infection

2. 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

3. 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

4. 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

6. Brain Primary HIV and autoimmune
Primary HIV and autoimmune
• HIV-associated dementia or encephalopathy (children)
• Demyelinating syndromes
• Parkinsonism and other movement disorders
• Sleep disorders
Neurologic 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 lymphoma
Medications
 • Neuroleptic sensitivity

7. Meninges Primary HIV and autoimmune
 • Acute aseptic or chronic meningitis
Neurologic opportunistic processes 
• Cryptococcal meningitis
• Bacterial: tuberculosis, syphilis
• Neoplasm: lymphomatous meningitis

8. Spinal cord Primary HIV and autoimmune • Vacuolar myelopathy
Neurologic opportunistic processes
 • Herpesviruses: varicella zoster virus, cytomegalovirus, Herpes simplex virus
• Bacterial: syphilis, tuberculosis
• Neoplasm: metastatic lymphoma

9. Root and plexus Neurologic opportunistic processes
• Cytomegalovirus polyradiculitis, syphilis, tuberculosis
• Neoplasm: lymphomatous meningitis

10. Nerve  
Primary HIV and autoimmune • Distal symmetrical polyneuropathy • Diffuse infiltrative lymphomatosis syndrome • Acute and chronic inflammatory demyelinating polyneuropathies • Mononeuritis multiplex • Motor neuron disease Neurologic opportunistic processes • Cytomegalovirus mononeuritis multiplex • Varicella zoster virus (multidermatomal) Medications • Nucleosides: didanosine, zalcitabine, stavudine, Dapsone, metronidazole, isoniazid, pyridoxine, vincristine

11. Muscle Primary HIV and autoimmune • Inflammatory myopathy
Neurologic opportunistic processes
 • Toxoplasmosis
Medications
 • Zidovudine, trimethoprim-sulfamethoxazole
• Statins

12. 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

13. 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

14. CD4 Cell Count: >500/mm3 Infectious complications
• Acute retroviral syndrome
Noninfectious complications
• Acute inflammatory demyelinating polyneuropathy 
• Mononeuritis multiplex
• Aseptic meningitis
• HIV-associated headache

15. CD4 Cell Count: <200/mm3
Infectious complications • Cytomegalovirus encephalitis and polyradiculitis • Progressive multifocal • Leukoencephalopathy (PML) • Toxoplasmosis encephalitis • Cryptococcosis meningitis Noninfectious complications • HIV-associated dementia • HIV-associated polymyositis • Vacuolar myelopathy • Distal sensory polyneuropathy • Diffuse infiltrative lymphomatosis syndrome

16. CD4 Cell Count: 200 to 500/mm3 Infectious complications
• Herpes zoster (multidermatomal)
• Tuberculous meningitis
• Neurosyphilis
Noninfectious complications
• Mononeuritis multiplex
• AZT-induced myopathy
• HIV-associated headache
• Motor neuron disease

17. 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

18. 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.

19. 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

20. 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

21. 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

22. 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