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Cns illnesses eng_d4-2

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  • 1. Disorders of the CNS
  • 2. The purpose of the session• The purpose of the session: to discuss common causes, diagnosis and differential diagnosis, treatment and prophylaxis of neurologic complications in patients with HIV/AIDS• Objectives: after completing this session, the participants will be able to: – Identify common causes of neurologic complications in patients with HIV/AIDS – Recognize common neurologic complications in patients with HIV/AIDS and provide a differential diagnosis – Provide prophylaxis and treatment of the most common neurologic complications in patients with HIV/AIDS
  • 3. CNS illnesses with HIV infection• Toxoplasmosis• HSV Encephalitis• Cytomegalovirus Encephalitis• Cryptococcal meningitis• Dementia• Primary CNS Lymphoma• Progressive Multifocal Leukoencephalopathy
  • 4. Toxoplasmosis • CAUSE: Latent T. gondii infection • In HIV-infected persons toxoplasmosis mainly appears as encephalitis or as disseminated disease • FREQUENCY: 30% of AIDS patients with latent T. gondii infection (positive serology) and no prophylaxisWHO HIV/AIDS Treatment and Care Protocols for countries of the Commonwealth of Independent States. March. 2004.
  • 5. PRESENTATION of TOXOPLASMOSIS• Toxoplasmosis may be suspected by the clinical findings: – altered mental status – fever – seizures – headaches – focal neurologic findings, including motor deficits, cranial nerve palsies, movement disorders, dysmetria, visual-field loss, and aphasia – over 80% have CD4 <100 cells/mm3WHO HIV/AIDS Treatment and Care Protocols for countries of the Commonwealth of Independent States. March. 2004.
  • 6. Toxoplasmosis diagnosis• CT or MRI scans: multiple ring enhancing lesions• IgG for toxoplasma may help in establishing the diagnosis in the absence of neuroimaging techinques (T. gondii serology is positive in >95%)• PCR for T. gondii in CSF is 50% sensitive and 96% to 100% specific.• Can be confirmed by histologic examination of tissue obtained by brain biopsy• Response to therapy is characteristically prompt and impressiveWHO HIV/AIDS Treatment and Care Protocols for countries of the Commonwealth of Independent States. March. 2004.
  • 7. Toxoplasmosis treatment Pyrimethamine 200mg Single PO Single dose THEN Pyrimethamine 25-50mg TID PO 6-8 weeks PLUS Folinic acid 15mg OD PO 6-8 weeks PLUS Sulphadiazine 1g Every 6 h PO 6-8 weeks• Instead of sulphadiazine in this regimen, the following may be used:- Clindamycin 600mg every 6 h IV/PO for 6 weeks then 300-450mg QID PO for life, OR- Azithromycin 1200mg OD PO for 6 weeks then 600mg OD PO for life, OR- Clarithromycin 1g BID PO for 6 weeks then 500mg BID PO for life, OR- Atovaquone 750mg QID PO for 6 weeks then 750mg BID PO for life WHO HIV/AIDS Treatment and Care Protocols for countries of the Commonwealth of Independent States. March. 2004.
  • 8. Herpes simplex virus • HSV may also cause meningoencephalitis and meningitis • HSV encephalitis leads to the development of multiple lesions in different parts of the brain and typical changes may be seen on CT scan studies of the brain • First line treatment: Aciclovir 10mg/kg every 8 hours IV 14-21 days OR • Second line treatment: Foscarnet (suspected resistance to aciclovir) 40 mg/kg every 8 to 12 h IV 14 dWHO HIV/AIDS Treatment and Care Protocols for countries of the Commonwealth of Independent States. March. 2004.
  • 9. Cytomegalovirus Encephalitis• CAUSE: CMV + CD4 count <50 cells/mm3• FREQUENCY: <0.5% of AIDS patients• PRESENTATION: Rapid progressive delirium, cranial nerve deficits, nystagmus, ataxia, headache with fever ± CMV retinitis• DIAGNOSIS: - MRI shows periventricular confluent lesions with enhancement - CMV PCR in CSF shows sensitivity of >80% and specificity of 90% - Cultures of CSF for CMV are usually negative• TREATMENT: Ganciclovir, foscarnet, or both IV John G. Bartlett. Medical management of HIV infection, 2003
  • 10. Cryptococcal meningitis • INCIDENCE: 8% to 10% • PRESENTATION: Fever, headache, alert (75%), less common are visual changes, stiff neck, cranial nerve deficits, seizures (10%); no focal neurologic deficits • CD4 count <100 cells/mm3 • CT, MRI: Usually normal • DIAGNOSIS: Culture positive (95-100%), Crypt Ag (>95% sensitive and specific) - Definitive diagnosis: CSF antigen and/or positive culture • TREATMENT: see handout D4-2WHO HIV/AIDS Treatment and Care Protocols for countries of the Commonwealth of Independent States. March. 2004. John G. Bartlett. Medical management of HIV infection, 2003
  • 11. Dementia• CAUSE: Chronic encephalitis with progressive or static encephalopathy due to CNS HIV infection with prominent immune activation• INCIDENCE: 7% after AIDS in pre-HAART era; 2% to 3% more recently. Prevalence is increasing with longer survival• PRESENTATION: - Early symptoms: Apathy, memory loss, cognitive slowing, depression, and withdrawal. Motor defects include gait instability and reduced hand coordination - Late stages: global loss of cognition, severe psychomotor retardation, and mutismJohn G. Bartlett. Medical management of HIV infection, 2003
  • 12. Dementia (continued)• PHYSICAL EXAMINASTIONS - in early stages: defective rapid eye movement, rapid limb movement, and generalized hyperreflexia - In late stages: tremor, clonus, and frontal release signs• DIAGNOSIS: History, physical examination, and screening with HIV Dementia Scale as noted above (see handout D4-2)• TREATMENT: HAART has reduced the frequency of dementia John G. Bartlett. Medical management of HIV infection, 2003
  • 13. Primary CNS Lymphoma• CAUSE: Virtually all are EBV-associated• FREQUENCY: 2% to 6% in pre-HAART era – 1000x higher than in the general population• PRESENTATION: Focal or non-focal signs• CD4 count is usually <50 cells/mm3• DIAGNOSIS: - MRI (single lesion or multiple lesions that are isodense or hypodense and usually homogeneous, but sometimes ring forms) - CSF EBV DNA is >94% specific and 80% sensitive - brain biopsy John G. Bartlett. Medical management of HIV infection, 2003
  • 14. Factors favoring CNS lymphoma• Typical neuro imaging results (above)• Negative T. gondii serology• Failure to respond to empiric treatment of toxoplasmosis within 1 to 2 weeks• Lack of fever• Thallium SPECT scan with early thallium uptake John G. Bartlett. Medical management of HIV infection, 2003
  • 15. Therapy of primary CNS Lymphoma - Standard: Radiation + corticosteroids - Chemotherapy: May be +Standard. Usually for patients with elevated CD4 counts. Preliminary results with methotrexate without radiation were promising• RESPONSE: Response rates to radiation treatment plus corticosteroids is 20% to 50%, but these results are temporaryJohn G. Bartlett. Medical management of HIV infection, 2003
  • 16. Progressive Multifocal Leukoencephalopathy• CAUSE: Activation of JC virus (which is ubiquitous) in patients who are immunodeficient• FREQUENCY: 1% to 2%• PRESENTATION: Cognitive impairment, visual field deficits, hemiparesis speech defects, incoordination with no fever.• CD4 count is usually 35-100 cells/mm3, but a subset of 7% to 25% have CD4 counts >200 cells/mm3 John G. Bartlett. Medical management of HIV infection, 2003
  • 17. Progressive Multifocal Leukoencephalopathy (continued)• DIAGNOSIS - MRI shows hypodense lesions of white matter without edema or enhancement - PCR for JCV in CSF with sensitivity of 80% and specificity of 95%• TREATMENT: None with established merit• PROGNOSIS: Median duration of survival is 1 to 6 monthsJohn G. Bartlett. Medical management of HIV infection, 2003

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