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HIV INFECTION AND THE NERVOUS SYSTEM

HIV INFECTION AND THE NERVOUS SYSTEM. Carolyn Barley Britton, M.D. Associate Professor of Clinical Neurology Columbia University College of Physicians & Surgeons. HIV and the Nervous System. HIV enters the nervous system early, at the time of initial infection, and may

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HIV INFECTION AND THE NERVOUS SYSTEM

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  1. HIV INFECTION AND THE NERVOUS SYSTEM Carolyn Barley Britton, M.D. Associate Professor of Clinical Neurology Columbia University College of Physicians & Surgeons

  2. HIV and the Nervous System HIV enters the nervous system early, at the time of initial infection, and may immediately cause symptoms, or may cause symptoms any time during the person’s lifetime.

  3. HIV and the Nervous System • All levels of the neuraxis are potential sites of involvement: • Meninges • Brain • Spinal cord • Cranial and peripheral nerves • Autonomic nervous system • Muscle

  4. HIV and the Nervous System • Multiple areas of the nervous system may be involved simultaneously or sequentially. • Without anti-retroviral treatment, up to 80% of patients are symptomatic and for 30%, neurologic symptoms are the initial clinical problem. • Neurologic syndromes may be the sole clinical problem or cause of death.

  5. HIV and the Nervous SystemClinical Syndromes • BRAIN SYNDROMES • Meningitis • Dementia • Stroke • Seizures • Degenerative Disorders

  6. HIV and the Nervous SystemClinical Syndromes • SPINAL CORD SYNDROMES • Transverse myelitis • Progressive myelopathy

  7. HIV and the Nervous SystemClinical Syndromes • NERVE AND MUSCLE • Bell’s palsy • Hearing loss • Peripheral neuropathies • Autonomic neuropathy • Myopathy

  8. HIV and the Nervous System • The differential diagnosis of a neurologic syndrome is derived from consideration of: • History • Clinical findings or localization • HIV disease stage • Seroconversion • Early disease • Late disease

  9. HIV and the Nervous System • Causes or etiologic considerations for neurologic disorders include: • Primary or HIV-related: Acute or chronic • Secondary opportunistic infections or malignancy • Metabolic or nutritional derangements • Complications of medical therapy • Unrelated to HIV infection

  10. HIV and the Nervous System • Primary or HIV-Related Syndromes of Acute Infection • Meningitis or encephalitis • Seizures, generalized or focal • Transverse myelitis • Cranial or peripheral neuropathy ( Bell’s palsy or Guillain-Barre-type neuropathy ) • Polymyositis +/- myoglobinuria

  11. HIV and the Nervous System • Primary or HIV-related Syndromes of Chronic Infection: common disorders • Meningeal pleocytosis +/- symptoms • Dementia and / or psychiatric disturbances (AIDS dementia complex, ADC ) • Strokes • Seizures • Progressive myelopathy • Neuropathy or myopathy

  12. HIV and the Nervous System • Primary or HIV-related Neurologic Syndromes of Chronic Infection: Infrequent or rare • Cerebellar ataxia • Multisystem degeneration • Anterior horn cell disease

  13. HIV and the Nervous System • PRIMARY SYNDROMES: MENINGITIS • May occur in acute infection or seroconversion or in the chronic stage of HIV infection • Clinically indistinguishable from non-HIVcases • Symptoms include fever, malaise, stiff neck, and photophobia • HIV is the usual cause in early infection; opportunistic infection, malignancy in late infection.

  14. HIV and the Nervous System • PRIMARY SYNDROMES: MENINGITIS • Laboratory evaluation • CSF: lymphocytic pleocytosis; normal glucose and normal or slightly elevated protein • HIV serology: may be negative; repeat at 3 and 6 months • HIV antigen and viral determination positive • T cell studies: normal or borderline • EEG, CT or MRI of brain normal or non-diagnostic

  15. HIV and the Nervous System • PRIMARY SYNDROMES: MENINGITIS • Outcome: • Clinical course is self-limited, without sequelae • Cranial neuropathy, typically Bell’s palsy, may co-exist • After recovery, underlying HIV may be asymptomatic

  16. HIV and the Nervous System • PRIMARY SYNDROMES: BELL’S PALSY • May be uni- or bi-lateral • Syndrome of seroconversion or early infection • CSF may show lymphocytic pleocytosis • HIV Serology may be negative • Outcome is similar to non-HIV Bell’s palsy with recovery the rule.

  17. HIV and the Nervous System • PRIMARY SYNDROMES: ACUTE INFLAMMATORY DEMYELINATING POLYNEUROPATHY ( AIDP ) • Ascending limb weakness, sensory loss and areflexia • Differentiated from Guillain - Barre, non-HIV, by lymphocytic CSF pleocytosis • Recovery dependent on severity; may respond to plasmapharesis or intravenous immune globulin

  18. HIV and the Nervous System • PRIMARY SYNDROMES: TRANSVERSE MYELITIS • Limb weakness, sensory loss, bowel and bladder involvement below a sensory level, usually thoracic • CSF with lymphocytic pleocytosis • May respond to plasmapharesis, intravenous steroids or immune globulin with outcome dependent on severity of paresis.

  19. HIV and the Nervous System • PRIMARY SYNDROMES: POLYMYOSITIS • Muscle pain and proximal weakness • +/- myoglobinuria • Elevated creatine kinase • Myopathic changes on EMG • Self - limited or steroid - responsive; rare as seroconversion or early HIV syndrome

  20. HIV and the Nervous System • PRIMARY SYNDROMES OF CHRONIC INFECTION: HIV - ASSOCIATED DEMENTIA, Classification System • I. Severe manifestations • A. HIV-1-Associated Dementia Complex • B. HIV-1-Associated Myelopathy • II. Mild manifestations • HIV-1-Associated minor Cognitive/Motor Disorder

  21. HIV and the Nervous System • AIDS Dementia: Clinical features • Slowed processing and reaction times (subcortical features indicating white matter involvement) • Memory loss, subjective if early • Psychiatric symptoms such as anxiety, psychosis or mania • May co-exist with myelopathy or peripheral neuropathy

  22. HIV and the Nervous System • AIDS Dementia: Laboratory Findings • Risk increases with disease severity, i.e., more common in AIDS, CD4 < 200 • Cerebrospinal fluid: normal or non-specific pleocytosis , normal glucose and protein. CSF gamma-globulin often elevated • CT/MRI: cortical atrophy, ventricular dilatation, white matter rarefaction on CT, T2 signal hyperintensity on MRI

  23. HIV and the Nervous System • AIDS Dementia: Differential Diagnosis • Toxic/metabolic factors: medication; hypoxia, electrolyte disturbance, B-12 deficiency • Secondary opportunistic infection • Secondary malignancy • Unrelated to HIV

  24. HIV and the Nervous System • AIDS Dementia: Evaluation • Stage infection with CD4 and viral load • CBC, electrolyte and hepatic panel, serum RPR or FTA, B12 level, thyroid function studies, arterial blood gas where indicated • Lumbar puncture • Blood culture for MAI, CMV, fungus • MRI of brain +/- gadolinium

  25. HIV and the Nervous System • AIDS Dementia: Treatment • Highly active anti-retroviral treatment may have reduced incidence of dementia • Clinical trials ongoing to evaluate other potential therapies

  26. HIV and the Nervous System • PROGRESSIVE MYELOPATHY • Clinical: Progressive spastic leg weakness, impotence and sphincter involvement. Dementia or peripheral neuropathy may co-exist • Diagnosis: Based on exclusion of other causes. Evaluation includes MRI or myelography of spine, B12 level, lumbar puncture for RPR or VDRL and oligoclonal bands

  27. HIV and the Nervous System • PROGRESSIVE MYELOPATHY • Treatment: No known effective treatment. Anecdotal reports of response to anti-retrovirals, immune globulin or supplemental parenteral B12

  28. HIV and the Nervous System • MYOPATHY OF CHRONIC INFECTION • Clinical: progressive proximal limb weakness • Laboratory: elevated creatine kinase; myopathic features on EMG; +/- myoglobinuria • Diagnosis: muscle biopsy • Causes: Drug treatment (AZT); HIV; secondary infection • Treatment: discontinue AZT; steroids or plasmapharesis; treat infection

  29. HIV and the Nervous System • NEUROPATHIES OF CHRONIC HIV INFECTION • Distal symmetrical polyneuropathy • Inflammatory demyelinating polyneuropathy • Mononeuritis multiplex • Isolated mononeuropathy • Progressive polyradiculopathy • Autonomic neuropathy

  30. HIV and the Nervous System • DISTAL SYMMETRICAL POLYNEUROPATHY ( DSPN ) • Clinical: Painful paresthesias of feet and soles, shooting leg pains, numbness; weakness, subjective or mild • Stocking-glove sensory loss, decreased vibratory sense in ankles, normal position sense, absent or reduced ankle jerks

  31. HIV and the Nervous System • DISTAL SYMMETRICAL POLYNEUROPATHY (DSPN) • Most common neuropathy of HIV infection and may be disabling • Prevalence increases with disease stage, most prevalent in chronic HIV infection or advanced disease • Concurrent conditions may include myelopathy, dementia, constitutional symptoms and weight loss

  32. HIV and the Nervous System • DSPN: DIFFERENTIAL DIAGNOSIS • HIV- related • Drug or treatment related • Metabolic or Nutritional disorder • Secondary infection • Unrelated to HIV illness

  33. HIV and the Nervous System • DSPN: ETIOLOGY • Infectious: HIV, CMV, Hepatitis virus, MAI, other infections • Nutritional: B12 deficiency, Acetyl carnitine deficiency • Auto-immune: Anti-sulfatide, anti-Mag and other auto-antibodies • Neurotoxic drugs: Antiretrovirals, INH, chemotherapy, others

  34. HIV and the Nervous System • AUTONOMIC NEUROPATHY • Clinical : Orthostatic hypotension; impotence, diarrhea • Etiology: Presumed HIV-related sympathetic ganglioneuropathy • Important as potential cause of sudden cardiac arrest during procedures

  35. HIV and the Nervous System • PROGRESSIVE POLYRADICULOPATHY • Clinical: Progressive paraparesis, areflexia, urinary retention, ascending sensory loss • Etiology: Cytomegalovirus • Diagnosis: Polymorphonuclear pleocytosis may be present in cerebrospinal fluid; EMG/NCV, acute denervation; CSF PCR and positive blood cultures help in diagnosis.

  36. HIV and the Nervous System • NEUROPATHY IN HIV INFECTION: EVALUATION • Stage disease: CD4 count; viral load • Family History • Environmental or toxic exposure • Other: Tick bite or exposure risk; malnutrition and weight loss • Medication history

  37. HIV and the Nervous System • NEUROPATHY IN HIV INFECTION: EVALUATION • Serology: Cytomegalovirus (CMV), Lyme, Hepatitis, MAG, sulfatide, GM1 ganglioside • Cultures: Blood for CMV, MAI; rectal and throat swab for CMV • Other: B12, thyroid function, heavy metals

  38. HIV and the Nervous System • NEUROPATHY IN HIV INFECTION: EVALUATION • Cerebrospinal fluid: cell count; glucose; protein; VDRL; cultures for bacteria, fungus, viruses and acid fast bacilli (AFB, includes MAI); Lyme serology. Polymerase chain reaction (PCR) for CMV, Lyme or AFB as indicated. • Electromyography, nerve conduction; nerve biopsy in select cases

  39. HIV and the Nervous System • NEUROPATHY IN HIV INFECTION: TREATMENT • Immune therapy: useful for AIDP/CIDP and may control disabling pain of DSPN • Plasmapharesis • Immune globulin* • Steroids *preferred treatment

  40. HIV and the Nervous System • NEUROPATHY AND HIV INFECTION: TREATMENT • Pain treatment • Anticonvulsants: Carbamazepine, phenytoin, gabapentin, lamotrigine • Tricyclic antidepressants: amitriptyline, nortriptyline • Mexilitine • Opioids

  41. HIV and the Nervous System • NEUROPATHY IN HIV INFECTION: TREATMENT • Neuropathy due to secondary infection (CMV, MAI or Lyme) responds to specific anti-viral or antibiotic therapy • Failed therapies: Peptide T; nerve growth factor

  42. HIV and the Nervous System • SECONDARY NEUROLOGIC SYNDROMES IN CHRONIC HIV INFECTION: • Etiology: Opportunistic infection ( viral, fungal, bacterial or parasitic ) or malignancy • Prevalence has declined because of more potent anti-retroviral therapy and prophylaxis • Clinically important in medication naïve and treatment failures

  43. HIV and the Nervous System • MENINGITIS IN CHRONIC HIV INFECTION • Clinical: Fever, headache, nucchal rigidity, mental confusion; cranial neuropathy in chronic basilar meningitis such as cryptococcus or mycobacterial. Stroke syndromes or mass lesions may occur.

  44. HIV and the Nervous System • MENINGITIS IN CHRONIC HIV INFECTION • Etiology • Viral: CMV, HSV, VZV, EBV, Hepatitis • Fungal: Cryptococcus, Histoplasma, Coccidioides, Candida • Bacterial: Listeria, T. pallidum, pyogenic bacteria (Salmonella, S. aureus), atypical or conventional mycobacteria • Neoplasm: Lymphoma

  45. HIV and the Nervous System • MENINGITIS IN CHRONIC HIV INFECTION: EVALUATION • Stage HIV infection: CD 4 count; viral load • Blood culture: bacteria,including Listeria; atypical mycobacteria (MAI); fungus; viral. • Serology: RPR or FTA, CMV, Epstein Barr virus, hepatitis, Lyme, toxoplasmosis. Cryptococcal antigen in serum.

  46. HIV and the Nervous System • MENINGITIS IN CHRONIC HIV INFECTION: EVALUATION • Cerebrospinal fluid: Cell count; glucose; protein; VDRL; cultures for bacteria, AFB and MAI, fungus, virus; Lyme serology; cryptococcal antigen; PCR as indicated for AFB, Lyme, CMV, HSV. • PPD with controls

  47. HIV and the Nervous System • MENINGITIS: NEUROSYPHILIS • Clinical: Asymptomatic; headache; stroke • Laboratory: Positive serology in blood (RPR or FTA) and spinal fluid (VDRL). CSF otherwise normal or pleocytosis, elevated protein. • Caveat: In acute syphilis with HIV infection, seroconversion may be delayed, resulting in false negative syphilis serology

  48. HIV and the Nervous System • MENINGITIS: NEUROSYPHILIS • Treatment: Penicillin G 24 million units in divided dose per 24 hours X 24 hours. • Outcome: Response is similar to non-HIV infected. Follow serology after treatment, monthly for three months, then every three months for a year. If titer rises, repeat LP and re-treat for relapse.

  49. HIV and the Nervous System • MENINGITIS: CRYPTOCOCCAL • Clinical: Fever, headache, nucchal rigidity, cranial neuropathy • Laboratory: CSF lymphocytic pleocytosis, low glucose, elevated protein • Organism cultured from CSF +/- sputum, blood • Antigen detected in CSF and blood

  50. HIV and the Nervous System • MENINGITIS: CRYPTOCOCCAL • Treatment: Amphotericin B +/- flucytosine; fluconazole; itraconazole. • Outcome: Dependent on clinical severity pre-treatment. Coma associated with high mortality. Long-term suppression necessary after acute therapy.

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