Hiv Infection And The Nervous System

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Hiv Infection And The Nervous System

  1. 1. HIV INFECTION AND THE NERVOUS SYSTEM Carolyn Barley Britton, M.D. Associate Professor of Clinical Neurology Columbia University College of Physicians & Surgeons
  2. 2. HIV and the Nervous System <ul><li>HIV enters the nervous system early, at the </li></ul><ul><li>time of initial infection, and may </li></ul><ul><li>immediately cause symptoms, or may </li></ul><ul><li>cause symptoms any time during the </li></ul><ul><li>person’s lifetime. </li></ul>
  3. 3. HIV and the Nervous System <ul><li>All levels of the neuraxis are potential sites of involvement: </li></ul><ul><ul><ul><ul><ul><li>Meninges </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Brain </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Spinal cord </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Cranial and peripheral nerves </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Autonomic nervous system </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Muscle </li></ul></ul></ul></ul></ul>
  4. 4. HIV and the Nervous System <ul><li>Multiple areas of the nervous system may be involved simultaneously or sequentially. </li></ul><ul><li>Without anti-retroviral treatment, up to 80% of patients are symptomatic and for 30%, neurologic symptoms are the initial clinical problem. </li></ul><ul><li>Neurologic syndromes may be the sole clinical problem or cause of death. </li></ul>
  5. 5. HIV and the Nervous System Clinical Syndromes <ul><li>BRAIN SYNDROMES </li></ul><ul><ul><li>Meningitis </li></ul></ul><ul><ul><li>Dementia </li></ul></ul><ul><ul><li>Stroke </li></ul></ul><ul><ul><li>Seizures </li></ul></ul><ul><ul><li>Degenerative Disorders </li></ul></ul>
  6. 6. HIV and the Nervous System Clinical Syndromes <ul><li>SPINAL CORD SYNDROMES </li></ul><ul><ul><li>Transverse myelitis </li></ul></ul><ul><ul><li>Progressive myelopathy </li></ul></ul>
  7. 7. HIV and the Nervous System Clinical Syndromes <ul><li>NERVE AND MUSCLE </li></ul><ul><ul><li>Bell’s palsy </li></ul></ul><ul><ul><li>Hearing loss </li></ul></ul><ul><ul><li>Peripheral neuropathies </li></ul></ul><ul><ul><li>Autonomic neuropathy </li></ul></ul><ul><ul><li>Myopathy </li></ul></ul>
  8. 8. HIV and the Nervous System <ul><li>The differential diagnosis of a neurologic syndrome is derived from consideration of: </li></ul><ul><ul><li>History </li></ul></ul><ul><ul><li>Clinical findings or localization </li></ul></ul><ul><ul><li>HIV disease stage </li></ul></ul><ul><ul><ul><ul><li>Seroconversion </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Early disease </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Late disease </li></ul></ul></ul></ul>
  9. 9. HIV and the Nervous System <ul><li>Causes or etiologic considerations for neurologic disorders include: </li></ul><ul><ul><li>Primary or HIV-related: Acute or chronic </li></ul></ul><ul><ul><li>Secondary opportunistic infections or malignancy </li></ul></ul><ul><ul><li>Metabolic or nutritional derangements </li></ul></ul><ul><ul><li>Complications of medical therapy </li></ul></ul><ul><ul><li>Unrelated to HIV infection </li></ul></ul>
  10. 10. HIV and the Nervous System <ul><li>Primary or HIV-Related Syndromes of Acute Infection </li></ul><ul><ul><li>Meningitis or encephalitis </li></ul></ul><ul><ul><li>Seizures, generalized or focal </li></ul></ul><ul><ul><li>Transverse myelitis </li></ul></ul><ul><ul><li>Cranial or peripheral neuropathy ( Bell’s palsy or Guillain-Barre-type neuropathy ) </li></ul></ul><ul><ul><li>Polymyositis +/- myoglobinuria </li></ul></ul>
  11. 11. HIV and the Nervous System <ul><li>Primary or HIV-related Syndromes of Chronic Infection: common disorders </li></ul><ul><ul><li>Meningeal pleocytosis +/- symptoms </li></ul></ul><ul><ul><li>Dementia and / or psychiatric disturbances (AIDS dementia complex, ADC ) </li></ul></ul><ul><ul><li>Strokes </li></ul></ul><ul><ul><li>Seizures </li></ul></ul><ul><ul><li>Progressive myelopathy </li></ul></ul><ul><ul><li>Neuropathy or myopathy </li></ul></ul>
  12. 12. HIV and the Nervous System <ul><li>Primary or HIV-related Neurologic Syndromes of Chronic Infection: Infrequent or rare </li></ul><ul><ul><li>Cerebellar ataxia </li></ul></ul><ul><ul><li>Multisystem degeneration </li></ul></ul><ul><ul><li>Anterior horn cell disease </li></ul></ul>
  13. 13. HIV and the Nervous System <ul><li>PRIMARY SYNDROMES: MENINGITIS </li></ul><ul><ul><li>May occur in acute infection or seroconversion or in the chronic stage of HIV infection </li></ul></ul><ul><ul><li>Clinically indistinguishable from non-HIVcases </li></ul></ul><ul><ul><li>Symptoms include fever, malaise, stiff neck, and photophobia </li></ul></ul><ul><ul><li>HIV is the usual cause in early infection; opportunistic infection, malignancy in late infection. </li></ul></ul>
  14. 14. HIV and the Nervous System <ul><li>PRIMARY SYNDROMES: MENINGITIS </li></ul><ul><li>Laboratory evaluation </li></ul><ul><ul><ul><li>CSF: lymphocytic pleocytosis; normal glucose and normal or slightly elevated protein </li></ul></ul></ul><ul><ul><ul><li>HIV serology: may be negative; repeat at 3 and 6 months </li></ul></ul></ul><ul><ul><ul><li>HIV antigen and viral determination positive </li></ul></ul></ul><ul><ul><ul><li>T cell studies: normal or borderline </li></ul></ul></ul><ul><ul><ul><li>EEG, CT or MRI of brain normal or non-diagnostic </li></ul></ul></ul>
  15. 15. HIV and the Nervous System <ul><li>PRIMARY SYNDROMES: MENINGITIS </li></ul><ul><li>Outcome: </li></ul><ul><ul><ul><li>Clinical course is self-limited, without sequelae </li></ul></ul></ul><ul><ul><ul><li>Cranial neuropathy, typically Bell’s palsy, may co-exist </li></ul></ul></ul><ul><ul><ul><li>After recovery, underlying HIV may be asymptomatic </li></ul></ul></ul>
  16. 16. HIV and the Nervous System <ul><li>PRIMARY SYNDROMES: BELL’S PALSY </li></ul><ul><ul><li>May be uni- or bi-lateral </li></ul></ul><ul><ul><li>Syndrome of seroconversion or early infection </li></ul></ul><ul><ul><li>CSF may show lymphocytic pleocytosis </li></ul></ul><ul><ul><li>HIV Serology may be negative </li></ul></ul><ul><ul><li>Outcome is similar to non-HIV Bell’s palsy with recovery the rule. </li></ul></ul>
  17. 17. HIV and the Nervous System <ul><li>PRIMARY SYNDROMES: ACUTE INFLAMMATORY DEMYELINATING POLYNEUROPATHY ( AIDP ) </li></ul><ul><ul><li>Ascending limb weakness, sensory loss and areflexia </li></ul></ul><ul><ul><li>Differentiated from Guillain - Barre, non-HIV, by lymphocytic CSF pleocytosis </li></ul></ul><ul><ul><li>Recovery dependent on severity; may respond to plasmapharesis or intravenous immune globulin </li></ul></ul>
  18. 18. HIV and the Nervous System <ul><li>PRIMARY SYNDROMES: TRANSVERSE MYELITIS </li></ul><ul><ul><li>Limb weakness, sensory loss, bowel and bladder involvement below a sensory level, usually thoracic </li></ul></ul><ul><ul><li>CSF with lymphocytic pleocytosis </li></ul></ul><ul><ul><li>May respond to plasmapharesis, intravenous steroids or immune globulin with outcome dependent on severity of paresis. </li></ul></ul>
  19. 19. HIV and the Nervous System <ul><li>PRIMARY SYNDROMES: POLYMYOSITIS </li></ul><ul><ul><li>Muscle pain and proximal weakness </li></ul></ul><ul><ul><li>+/- myoglobinuria </li></ul></ul><ul><ul><li>Elevated creatine kinase </li></ul></ul><ul><ul><li>Myopathic changes on EMG </li></ul></ul><ul><ul><li>Self - limited or steroid - responsive; rare as seroconversion or early HIV syndrome </li></ul></ul>
  20. 20. HIV and the Nervous System <ul><li>PRIMARY SYNDROMES OF CHRONIC INFECTION: HIV - ASSOCIATED DEMENTIA, Classification System </li></ul><ul><li>I. Severe manifestations </li></ul><ul><ul><li>A. HIV-1-Associated Dementia Complex </li></ul></ul><ul><ul><li>B. HIV-1-Associated Myelopathy </li></ul></ul><ul><ul><li>II. Mild manifestations </li></ul></ul><ul><ul><li>HIV-1-Associated minor Cognitive/Motor Disorder </li></ul></ul>
  21. 21. HIV and the Nervous System <ul><li>AIDS Dementia: Clinical features </li></ul><ul><ul><li>Slowed processing and reaction times (subcortical features indicating white matter involvement) </li></ul></ul><ul><ul><li>Memory loss, subjective if early </li></ul></ul><ul><ul><li>Psychiatric symptoms such as anxiety, psychosis or mania </li></ul></ul><ul><ul><li>May co-exist with myelopathy or peripheral neuropathy </li></ul></ul>
  22. 22. HIV and the Nervous System <ul><li>AIDS Dementia: Laboratory Findings </li></ul><ul><ul><li>Risk increases with disease severity, i.e., more common in AIDS, CD4 < 200 </li></ul></ul><ul><ul><li>Cerebrospinal fluid: normal or non-specific pleocytosis , normal glucose and protein. CSF gamma-globulin often elevated </li></ul></ul><ul><ul><li>CT/MRI: cortical atrophy, ventricular dilatation, white matter rarefaction on CT, T2 signal hyperintensity on MRI </li></ul></ul>
  23. 23. HIV and the Nervous System <ul><li>AIDS Dementia: Differential Diagnosis </li></ul><ul><ul><li>Toxic/metabolic factors: medication; hypoxia, electrolyte disturbance, B-12 deficiency </li></ul></ul><ul><ul><li>Secondary opportunistic infection </li></ul></ul><ul><ul><li>Secondary malignancy </li></ul></ul><ul><ul><li>Unrelated to HIV </li></ul></ul>
  24. 24. HIV and the Nervous System <ul><li>AIDS Dementia: Evaluation </li></ul><ul><ul><li>Stage infection with CD4 and viral load </li></ul></ul><ul><ul><li>CBC, electrolyte and hepatic panel, serum RPR or FTA, B12 level, thyroid function studies, arterial blood gas where indicated </li></ul></ul><ul><ul><li>Lumbar puncture </li></ul></ul><ul><ul><li>Blood culture for MAI, CMV, fungus </li></ul></ul><ul><ul><li>MRI of brain +/- gadolinium </li></ul></ul>
  25. 25. HIV and the Nervous System <ul><li>AIDS Dementia: Treatment </li></ul><ul><ul><li>Highly active anti-retroviral treatment may have reduced incidence of dementia </li></ul></ul><ul><ul><li>Clinical trials ongoing to evaluate other potential therapies </li></ul></ul>
  26. 26. HIV and the Nervous System <ul><li>PROGRESSIVE MYELOPATHY </li></ul><ul><ul><li>Clinical: Progressive spastic leg weakness, impotence and sphincter involvement. Dementia or peripheral neuropathy may co-exist </li></ul></ul><ul><ul><li>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 </li></ul></ul>
  27. 27. HIV and the Nervous System <ul><li>PROGRESSIVE MYELOPATHY </li></ul><ul><ul><li>Treatment: No known effective treatment. Anecdotal reports of response to anti-retrovirals, immune globulin or supplemental parenteral B12 </li></ul></ul>
  28. 28. HIV and the Nervous System <ul><li>MYOPATHY OF CHRONIC INFECTION </li></ul><ul><ul><li>Clinical: progressive proximal limb weakness </li></ul></ul><ul><ul><li>Laboratory: elevated creatine kinase; myopathic features on EMG; +/- myoglobinuria </li></ul></ul><ul><ul><li>Diagnosis: muscle biopsy </li></ul></ul><ul><ul><li>Causes: Drug treatment (AZT); HIV; secondary infection </li></ul></ul><ul><ul><li>Treatment: discontinue AZT; steroids or plasmapharesis; treat infection </li></ul></ul>
  29. 29. HIV and the Nervous System <ul><li>NEUROPATHIES OF CHRONIC HIV INFECTION </li></ul><ul><ul><li>Distal symmetrical polyneuropathy </li></ul></ul><ul><ul><li>Inflammatory demyelinating polyneuropathy </li></ul></ul><ul><ul><li>Mononeuritis multiplex </li></ul></ul><ul><ul><li>Isolated mononeuropathy </li></ul></ul><ul><ul><li>Progressive polyradiculopathy </li></ul></ul><ul><ul><li>Autonomic neuropathy </li></ul></ul>
  30. 30. HIV and the Nervous System <ul><li>DISTAL SYMMETRICAL POLYNEUROPATHY ( DSPN ) </li></ul><ul><li>Clinical: Painful paresthesias of feet and soles, shooting leg pains, numbness; weakness, subjective or mild </li></ul><ul><li>Stocking-glove sensory loss, decreased vibratory sense in ankles, normal position sense, absent or reduced ankle jerks </li></ul>
  31. 31. HIV and the Nervous System <ul><li>DISTAL SYMMETRICAL POLYNEUROPATHY (DSPN) </li></ul><ul><ul><li>Most common neuropathy of HIV infection and may be disabling </li></ul></ul><ul><ul><li>Prevalence increases with disease stage, most prevalent in chronic HIV infection or advanced disease </li></ul></ul><ul><ul><li>Concurrent conditions may include myelopathy, dementia, constitutional symptoms and weight loss </li></ul></ul>
  32. 32. HIV and the Nervous System <ul><li>DSPN: DIFFERENTIAL DIAGNOSIS </li></ul><ul><ul><li>HIV- related </li></ul></ul><ul><ul><li>Drug or treatment related </li></ul></ul><ul><ul><li>Metabolic or Nutritional disorder </li></ul></ul><ul><ul><li>Secondary infection </li></ul></ul><ul><ul><li>Unrelated to HIV illness </li></ul></ul>
  33. 33. HIV and the Nervous System <ul><li>DSPN: ETIOLOGY </li></ul><ul><ul><li>Infectious: HIV, CMV, Hepatitis virus, MAI, other infections </li></ul></ul><ul><ul><li>Nutritional: B12 deficiency, Acetyl carnitine deficiency </li></ul></ul><ul><ul><li>Auto-immune: Anti-sulfatide, anti-Mag and other auto-antibodies </li></ul></ul><ul><ul><li>Neurotoxic drugs: Antiretrovirals, INH, chemotherapy, others </li></ul></ul>
  34. 34. HIV and the Nervous System <ul><li>AUTONOMIC NEUROPATHY </li></ul><ul><ul><li>Clinical : Orthostatic hypotension; impotence, diarrhea </li></ul></ul><ul><ul><li>Etiology: Presumed HIV-related sympathetic ganglioneuropathy </li></ul></ul><ul><ul><li>Important as potential cause of sudden cardiac arrest during procedures </li></ul></ul>
  35. 35. HIV and the Nervous System <ul><li>PROGRESSIVE POLYRADICULOPATHY </li></ul><ul><li>Clinical: Progressive paraparesis, areflexia, urinary retention, ascending sensory loss </li></ul><ul><li>Etiology: Cytomegalovirus </li></ul><ul><li>Diagnosis: Polymorphonuclear pleocytosis may be present in cerebrospinal fluid; EMG/NCV, acute denervation; CSF PCR and positive blood cultures help in diagnosis. </li></ul>
  36. 36. HIV and the Nervous System <ul><li>NEUROPATHY IN HIV INFECTION: EVALUATION </li></ul><ul><ul><li>Stage disease: CD4 count; viral load </li></ul></ul><ul><ul><li>Family History </li></ul></ul><ul><ul><li>Environmental or toxic exposure </li></ul></ul><ul><ul><li>Other: Tick bite or exposure risk; malnutrition and weight loss </li></ul></ul><ul><ul><li>Medication history </li></ul></ul>
  37. 37. HIV and the Nervous System <ul><li>NEUROPATHY IN HIV INFECTION: EVALUATION </li></ul><ul><ul><li>Serology: Cytomegalovirus (CMV), Lyme, Hepatitis, MAG, sulfatide, GM1 ganglioside </li></ul></ul><ul><ul><li>Cultures: Blood for CMV, MAI; rectal and throat swab for CMV </li></ul></ul><ul><ul><li>Other: B12, thyroid function, heavy metals </li></ul></ul>
  38. 38. HIV and the Nervous System <ul><li>NEUROPATHY IN HIV INFECTION: EVALUATION </li></ul><ul><ul><li>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. </li></ul></ul><ul><ul><li>Electromyography, nerve conduction; nerve biopsy in select cases </li></ul></ul>
  39. 39. HIV and the Nervous System <ul><li>NEUROPATHY IN HIV INFECTION: TREATMENT </li></ul><ul><ul><li>Immune therapy: useful for AIDP/CIDP and may control disabling pain of DSPN </li></ul></ul><ul><ul><ul><li>Plasmapharesis </li></ul></ul></ul><ul><ul><ul><li>Immune globulin* </li></ul></ul></ul><ul><ul><ul><li>Steroids </li></ul></ul></ul><ul><ul><ul><ul><ul><li>*preferred treatment </li></ul></ul></ul></ul></ul>
  40. 40. HIV and the Nervous System <ul><li>NEUROPATHY AND HIV INFECTION: TREATMENT </li></ul><ul><ul><li>Pain treatment </li></ul></ul><ul><ul><ul><li>Anticonvulsants: Carbamazepine, phenytoin, gabapentin, lamotrigine </li></ul></ul></ul><ul><ul><ul><li>Tricyclic antidepressants: amitriptyline, nortriptyline </li></ul></ul></ul><ul><ul><ul><li>Mexilitine </li></ul></ul></ul><ul><ul><ul><li>Opioids </li></ul></ul></ul>
  41. 41. HIV and the Nervous System <ul><li>NEUROPATHY IN HIV INFECTION: TREATMENT </li></ul><ul><ul><li>Neuropathy due to secondary infection (CMV, MAI or Lyme) responds to specific anti-viral or antibiotic therapy </li></ul></ul><ul><ul><li>Failed therapies: Peptide T; nerve growth factor </li></ul></ul>
  42. 42. HIV and the Nervous System <ul><li>SECONDARY NEUROLOGIC SYNDROMES IN CHRONIC HIV INFECTION: </li></ul><ul><ul><li>Etiology: Opportunistic infection ( viral, fungal, bacterial or parasitic ) or malignancy </li></ul></ul><ul><ul><li>Prevalence has declined because of more potent anti-retroviral therapy and prophylaxis </li></ul></ul><ul><ul><li>Clinically important in medication naïve and treatment failures </li></ul></ul>
  43. 43. HIV and the Nervous System <ul><li>MENINGITIS IN CHRONIC HIV INFECTION </li></ul><ul><li>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. </li></ul>
  44. 44. HIV and the Nervous System <ul><li>MENINGITIS IN CHRONIC HIV INFECTION </li></ul><ul><li>Etiology </li></ul><ul><ul><ul><li>Viral: CMV, HSV, VZV, EBV, Hepatitis </li></ul></ul></ul><ul><ul><ul><li>Fungal: Cryptococcus, Histoplasma, Coccidioides, Candida </li></ul></ul></ul><ul><ul><ul><li>Bacterial: Listeria, T. pallidum, pyogenic bacteria (Salmonella, S. aureus), atypical or conventional mycobacteria </li></ul></ul></ul><ul><ul><ul><li>Neoplasm: Lymphoma </li></ul></ul></ul>
  45. 45. HIV and the Nervous System <ul><li>MENINGITIS IN CHRONIC HIV INFECTION: EVALUATION </li></ul><ul><ul><li>Stage HIV infection: CD 4 count; viral load </li></ul></ul><ul><ul><li>Blood culture: bacteria,including Listeria; atypical mycobacteria (MAI); fungus; viral. </li></ul></ul><ul><ul><li>Serology: RPR or FTA, CMV, Epstein Barr virus, hepatitis, Lyme, toxoplasmosis. Cryptococcal antigen in serum. </li></ul></ul>
  46. 46. HIV and the Nervous System <ul><li>MENINGITIS IN CHRONIC HIV INFECTION: EVALUATION </li></ul><ul><ul><li>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. </li></ul></ul><ul><ul><li>PPD with controls </li></ul></ul>
  47. 47. HIV and the Nervous System <ul><li>MENINGITIS: NEUROSYPHILIS </li></ul><ul><ul><li>Clinical: Asymptomatic; headache; stroke </li></ul></ul><ul><ul><li>Laboratory: Positive serology in blood (RPR or FTA) and spinal fluid (VDRL). CSF otherwise normal or pleocytosis, elevated protein. </li></ul></ul><ul><ul><li>Caveat : In acute syphilis with HIV infection, seroconversion may be delayed, resulting in false negative syphilis serology </li></ul></ul>
  48. 48. HIV and the Nervous System <ul><li>MENINGITIS: NEUROSYPHILIS </li></ul><ul><ul><li>Treatment: Penicillin G 24 million units in divided dose per 24 hours X 24 hours. </li></ul></ul><ul><ul><li>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. </li></ul></ul>
  49. 49. HIV and the Nervous System <ul><li>MENINGITIS: CRYPTOCOCCAL </li></ul><ul><ul><li>Clinical: Fever, headache, nucchal rigidity, cranial neuropathy </li></ul></ul><ul><ul><li>Laboratory: CSF lymphocytic pleocytosis, low glucose, elevated protein </li></ul></ul><ul><ul><ul><li>Organism cultured from CSF +/- sputum, blood </li></ul></ul></ul><ul><ul><ul><li>Antigen detected in CSF and blood </li></ul></ul></ul>
  50. 50. HIV and the Nervous System <ul><li>MENINGITIS: CRYPTOCOCCAL </li></ul><ul><li>Treatment: Amphotericin B +/- flucytosine; fluconazole; itraconazole. </li></ul><ul><li>Outcome: Dependent on clinical severity pre-treatment. Coma associated with high mortality. Long-term suppression necessary after acute therapy. </li></ul>
  51. 51. HIV and the Nervous System <ul><li>MENINGITIS: TUBERCULOSIS </li></ul><ul><ul><li>Clinical: Fever, headache, nucchal rigidity, cranial neuropathy </li></ul></ul><ul><ul><li>Caveat: Meningitis due to atypical species more likely to present as non-focal confusional state or encephalopathy. Stroke or focal syndromes with conventional species may be due to vasculitis or mass lesion (tuberculoma) </li></ul></ul>
  52. 52. HIV and the Nervous System <ul><li>MENINGITIS: TUBERCULOSIS </li></ul><ul><ul><li>Laboratory: </li></ul></ul><ul><ul><ul><li>CSF - lymphocytic pleocytosis; low glucose; elevated protein. PCR may be useful. </li></ul></ul></ul><ul><ul><ul><li>MRI brain with gadolinium: meningeal enhancement especially basal; some cases, infarct or mass lesions (tuberculomas) </li></ul></ul></ul><ul><ul><ul><li>PPD may be negative if anergic; chest X-ray may be normal </li></ul></ul></ul><ul><ul><ul><li>Screen for extra-CNS TBC, e.g. bone, liver, lung </li></ul></ul></ul>
  53. 53. HIV and the Nervous System <ul><li>MENINGITIS: TUBERCULOSIS </li></ul><ul><ul><li>Treatment: Four drug regimen - Isoniazid, rifampin, ethambutol, pyrazinamide ( streptomycin, an alternate if necessary ) for 18 to 24 months, adjusted for culture results. </li></ul></ul><ul><ul><li>Corticosteroids increased intracranial pressure, incipient herniation. </li></ul></ul><ul><ul><li>Pyridoxine supplement to prevent INH neuropathy </li></ul></ul>
  54. 54. HIV and the Nervous System <ul><li>MENINGITIS: CYTOMEGALOVIRUS </li></ul><ul><ul><li>Clinical: subacute, progressive confusional state; meningeal symptoms or signs may be minimal or mild </li></ul></ul><ul><ul><li>Laboratory: CSF mixed pleocytosis without distinguishing features, normal glucose, normal or slightly elevated protein; PCR may help in diagnosis. Blood cultures usually positive. </li></ul></ul>
  55. 55. HIV and the Nervous System <ul><li>MENINGITIS: CYTOMEGALOVIRUS </li></ul><ul><ul><li>MRI of brain +/-gadolinium: meningeal enhancement; periventricular hyperintensities or enhancement. </li></ul></ul><ul><ul><li>Treatment: Ganciclovir; foscarnet; cidofovir. </li></ul></ul><ul><ul><li>Outcome: Treatment successful if diagnosis is timely. </li></ul></ul>
  56. 56. HIV and the Nervous System <ul><li>FOCAL SYNDROMES AND MASS LESIONS </li></ul><ul><ul><li>Viral: Herpes simplex; Varicella zoster; progressive multifocal leukoencephalopathy </li></ul></ul><ul><ul><li>Fungal: Abscess due to Cryptococcus, Candida, Zygomycetes, Histoplasma, Aspergillus </li></ul></ul>
  57. 57. HIV and the Nervous System <ul><li>FOCAL SYNDROMES AND MASS LESIONS </li></ul><ul><ul><li>Bacterial: Abscess due to pyogenic bacteria, mycobacteria (tuberculoma), Listeria, Nocardia </li></ul></ul><ul><ul><li>Parasitic: Trypanosoma cruzei; Taenia solium; toxoplasmosis </li></ul></ul><ul><ul><li>Neoplasm: Primary or metastatic lymphoma; glioma; metastatic Kaposi’s sarcoma </li></ul></ul>
  58. 58. HIV and the Nervous System <ul><ul><li>TOXOPLASMOSIS </li></ul></ul><ul><ul><ul><li>Clinical: Confusion, focal signs, seizures. Most common mass lesion. </li></ul></ul></ul><ul><ul><ul><li>Laboratory: Positive serum serology. CSF is non-diagnostic but PCR positive in up to 70%. </li></ul></ul></ul><ul><ul><ul><li>MRI brain +/- gadolinium: enhancing lesions with mass effect, typically involving deep structures. </li></ul></ul></ul>
  59. 59. HIV and the Nervous System <ul><li>TOXOPLASMOSIS </li></ul><ul><ul><li>Treatment: sulfadiazine/pyrimethamine; clindamycin/ azithromycin </li></ul></ul><ul><ul><li>Outcome: Usually excellent. Suppresive therapy indicated after acute treatment. </li></ul></ul>
  60. 60. HIV and the Nervous System <ul><li>PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY </li></ul><ul><ul><li>Clinical: Progressive focal signs; seizures rare </li></ul></ul><ul><ul><li>Laboratory: CSF is normal; PCR positive in 70% </li></ul></ul><ul><ul><li>MRI of brain +/- gadolinium: non-enhancing T2 signal lesion, hypodense on CT. </li></ul></ul>
  61. 61. HIV and the Nervous System <ul><li>PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY </li></ul><ul><ul><li>Treatment: Antiretroviral therapy sometimes effective in treatment naïve patients. Anecdotal reports of response to cytosine arabinoside, cidofovir and interferon alpha. </li></ul></ul><ul><ul><li>Outcome: Rare spontaneous stabilization; if no response to therapy, death in 3 to 6 months </li></ul></ul>
  62. 62. HIV and the Nervous System <ul><li>LYMPHOMA </li></ul><ul><ul><li>Cllinical: focal signs, seizures, cranial neuropathy or confusional state </li></ul></ul><ul><ul><li>Laboratory: CSF is usually non-diagnostic but may show tumor cells indicating seeding. </li></ul></ul><ul><ul><li>MRI of brain +/- gadolinium: single or multiple enhancing lesions that may have similar appearance to toxoplasmosis </li></ul></ul>
  63. 63. HIV and the Nervous System <ul><li>LYMPHOMA </li></ul><ul><ul><li>Diagnosis: Brain biopsy </li></ul></ul><ul><ul><li>Treatment: Whole brain radiotherapy; intrathecal chemotherapy for relapse </li></ul></ul><ul><ul><li>Outcome: Without treatment, 1 to 2 month survival. Improved response to treatment and more prolonged survival with highly active anti-retroviral therapy. </li></ul></ul>
  64. 64. HIV and the Nervous System <ul><li>BRAIN BIOPSY FOR CEREBRAL MASS: INDICATIONS </li></ul><ul><ul><li>Solitary lesions </li></ul></ul><ul><ul><li>Negative serum serology for toxoplasmosis </li></ul></ul><ul><ul><li>No clinical or radiographic response to one week of toxoplasmosis treatment </li></ul></ul><ul><ul><li>CSF PCR is helpful only when positive; negative result does not exclude a potential agent, except for Herpes simplex </li></ul></ul>
  65. 65. HIV and the Nervous System <ul><li>NUTRITIONAL DISORDERS AND COMPLICATIONS OF MEDICAL TREATMENT </li></ul><ul><ul><li>Nutritional: vitamin deficiency states - thiamine, folic acid, glutathione, B12 </li></ul></ul><ul><ul><li>Drug toxicity: myopathy due to AZT; neuropathy due to ddI, ddC and other anti-retrovirals, INH </li></ul></ul>

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