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Neurologic Diseases and HIV

Neurologic Diseases and HIV. HAIVN Harvard Medical School AIDS Initiative in Vietnam. Learning Objectives. By the end of this session, participants should be able to: Outline the 2 most common causes of headache and fever in PLHIV

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Neurologic Diseases and HIV

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  1. Neurologic Diseases and HIV HAIVN Harvard Medical School AIDS Initiative in Vietnam

  2. Learning Objectives By the end of this session, participants should be able to: • Outline the 2 most common causes of headache and fever in PLHIV • Describe how to diagnose, including potential differential diagnoses, a focal neurological deficit • Describe causes and treatment for peripheral neuropathy in PLHIV

  3. I. Headache

  4. Differential Diagnoses of Headache and Fever Meningitis: • Cryptococcal Meningitis • Tuberculosis Meningitis • Bacterial Meningitis • Strep pneumoniae, Neisseriameningitidis • Syphilitic Meningitis Other Infectious Causes: • Toxoplasma Encephalitis • Brain Abscess (Staph aureus especially with IDU) • Sinusitis (bacterial or viral) • Herpes Meningoencephalitis

  5. Cryptococcal Meningitis • Occurs in advanced AIDS: CD4<100 • Clinical manifestations: • Headache • Fever • Nuchal rigidity (only 25%) • Vomiting • Confusion • Blurred vision, photophobia Often associated with elevated intracranial pressure

  6. Cryptococcus Neoformans • Disseminated disease may occur • Fungal pneumonias • Skin lesions • 10-40% of patients with disseminated cryptococcal disease have no neurological symptoms

  7. Cryptococcus Meningitis: Diagnosis (1) Lumbar Puncture: • High CSF pressure • WBC often not elevated (usually < 50 cells/μl) • Glucose normal to low • Protein normal to high

  8. Cryptococcus Meningitis: Diagnosis (2) • Positive CSF India Ink in 75% • Cryptococcal Antigen (CRAG) • CSF > 90% positive • Serum > 99% positive

  9. Cryptococcus Meningitis:Management Vietnam MOH, HIV/AIDS Treatment Guidelines, 2009

  10. Cryptococcus Meningitis:Management of High Intracranial Pressure (1) • Normal pressure < 20 cm/H2O (200 mm/H2O) • Elevated pressure causes severe headache and results in increased mortality and morbidity • Visual loss as consequence of high pressure

  11. Cryptococcus Meningitis:Management of High Intracranial Pressure (2) • Daily lumbar punctures (LP) • Each time remove 15-20 CC CSF or until the patient’s headache improves • Mannitol and corticosteroids not effective for lowering pressure

  12. Tuberculosis Meningitis • Common in HIV, slow chronic onset is usual • Typical symptoms: fever, headache, confusion • May be focal signs or cranial nerve palsies due to space occupying lesions and/or cerebral mass effect • Often other features of TB • examine chest and lymph nodes • Main differential is cryptococcal meningitis

  13. TB Meningitis: Diagnosis CSF: • Pressure may be raised • Lymphocytosis or mixed cells in CSF • Typically: • Protein very high (2-6 g/dL) • Low glucose (<45 mg/dL) • AFB are difficult to find in CSF • Perform India Ink staining to help exclude or confirm cryptococcal meningitis • Look for TB elsewhere in body by CXR, sputum, and aspiration of lymph nodes where appropriate

  14. TB: National Treatment Protocol 9-12 month regimens recommended for TB meningitis

  15. TB Meningitis Treatment: Steroids • Concurrent steroid treatment reduces mortality by 31% • Doses: Thwaites, NEJM, 2004; CDC, MMWR 58:RR-4, 2009 • or...

  16. II. Focal Neurological Deficit

  17. Focal Neurologic Deficit Common causes in HIV: • Toxoplasma encephalitis • Tuberculoma • Progressive Multifocal Leukoencephalopathy (PML) • Primary CNS lymphoma • Abscess • Bacterial brain abscess in active IDUs • Cryptococcoma • Stroke

  18. Tuberculoma • Less common than meningitis, but should be considered in any patient with a history of TB • Lesions may present as single or multiple mass lesions • Look for TB elsewhere in body by CXR, sputum, etc

  19. Tuberculomas

  20. Cerebral Toxoplasmosis • Seen in patients with CD4<100 • Manifestations: • Focal neurological signs (unilateral paralysis) • Generalized neurological signs (confusion, epilepsy, coma, etc.) • Meningeal signs are rare

  21. Cerebral Toxoplasmosis – Diagnosis (1) • MRI of cerebral toxoplasmosis showing 2 ring enhancing lesions – “lighting up” with intravenous contrast

  22. Cerebral Toxoplasmosis – Diagnosis (2) • CT scan of brain done without intravenous contrast showing edema around multiple lesions

  23. Cerebral Toxoplasmosis: Treatment OR: + OR: +

  24. Progressive Multifocal Leukoencephalopathy (PML) (1) • Etiology: JC Virus (JCV) • Polyomavirus • Most adults colonized • Clinical: • Focal deficit • Gate disturbance, • Visual loss, sensory loss • Diagnosis: CT or MRI • Hypodense white-matter lesions • No mass effect, no contrast enhancement • CSF examination normal • Treatment: ARV

  25. Progressive Multifocal Leukoencephalopathy (PML) (2) • 27 year old male patient in HCMC with right arm weakness and dysarthria

  26. Bacterial Brain Abscess and Emboli • Etiology: • Endocarditis secondary to IDU • Staphylococcus aureusinfection • Clinical: • Signs of recent injecting • Embolic events: subungal hematoma, Osler’s nodes (palms and feet), hematuria • Diagnosis: • Cardiac ultrasound • Positive blood culture

  27. Primary Cerebral Lymphoma (1) Etiology • Associated with Epstein-Barr Virus (EBV) • CD4 < 100 cells/mm3 Clinical • Headache, usually no fever • Onset usually slower than toxoplasmosis

  28. Primary Cerebral Lymphoma (2) Diagnosis and Treatment: • Difficult to distinguish from toxoplasmosis on CT/MRI • Incurable • so rule out and try empiric treatment for treatable causes before making diagnosis • Treatment: radiation, chemotherapy • May show brief initial response to steroids • ARV may improve survival

  29. Diagnostic Approach to Focal CNS Deficit

  30. III. Peripheral Neuropathy

  31. Causes of Peripheral Neuropathy • Vitamin deficiency • B12 • Folate • Pyridoxine • Thiamine • Infectious Diseases • Syphilis • CMV • HIV • Metabolic Diseases • Diabetes • Drug induced • Alcohol • ARV: d4T, ddI • TB: INH

  32. Clinical Manifestations of Neuropathy • Usually starts distally (toes or finger tips) and progresses towards center • Numbness, burning, cold • Reduced sensation of: • Pain • Temperature • vibration • Reflexes reduced • Strength and joint position usually normal unless severe • With treatment can improve, but very slowly • Can be irreversible if not treated

  33. Peripheral Neuropathy: Prevention

  34. Peripheral Neuropathy: Treatment 1. Treat the Cause 2. Treat the pain

  35. Quick Quiz

  36. CSF Profile of HIV-related OIs Cryptococcal meningitis Veryhigh Slightly elevated or normal Slightly elevated or normal + India ink stain + TB meningitis High or normal Slightly elevated to very high Elevated (lymphocytes predominate) +/- - - +/- Toxoplasmal encephalitis Normal Normal or slightly elevated - - Normal

  37. Key Points • Fever and headache in PLHIV are indications for a lumbar puncture to evaluate for meningitis • The most common causes of focal neurologic deficits are Toxoplasma, TB, and CNS Lymphoma • Medications (d4T, INH) are common causes of peripheral neuropathy

  38. Thank you! Questions?

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