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Common neurological diseases in HIV-infected children

Common neurological diseases in HIV-infected children. HAIVN Harvard Medical School AIDS Initiatives in Vietnam. Learning objectives. At the end of this lecture, each trainee should be able to: List the 2 most common causes of headache and fever in HIV-infected children.

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Common neurological diseases in HIV-infected children

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  1. Common neurological diseases in HIV-infected children HAIVN Harvard Medical School AIDS Initiatives in Vietnam

  2. Learning objectives At the end of this lecture, each trainee should be able to: • List the 2 most common causes of headache and fever in HIV-infected children. • List 2 common causes of a patient with a focal neurological deficit and know what investigations to do to make the diagnosis. • List the causes for peripheral neuropathy in HIV-infected children

  3. Outline of lecture • Neurological manifestation in HIV-infected children • Focal neurological deficit • Peripheral neuropathy

  4. Neurological involvement in HIV-infected children • Incidence of CNS involvement in perinatally infected children 40-90% • Median onset at 19 month of age

  5. CNS manifestations • CNS of HIV-infected children can be affected by: • HIV itself, • other infections and • malignancies as a result of immunosuppression • Opportunistic infections less common in children (Cryptoccocus, bacterial meningitis) • Primary CNS lymphomas

  6. HIV encephalopathy • Primary HIV-1 infection of the CNS • Children with perinatal infection, clinical signs of neurological dysfunction appear as early as 2 months and as late as 5 years of age or older • Reported in 21% in HIV-infected children in Africa (no data in Asian population)

  7. HIV encephalopathy HIV should be considered in any child with progressive neurological deterioration who has not been previously tested for HIV or who might have it despite a previous negative test.

  8. HIV encephalopathy: diagnosis • Clinical diagnosis mostly, includes at least two of following for at least 2 months in the absence of a concurrent illnessother than HIV infection that could explain the findings

  9. HIV encephalopathy: diagnosis (2) • Developmental delay or loss of previously acquired milestones • In young children, may manifest as stagnation in development or loss of developmental milestones • In older children and adolescents, may develop HIV dementia indistinguishable from that described in adults

  10. Impaired brain growth or acquired microcephaly (head circumference measurements)

  11. Symmetrical motor deficits • > 2 of the following: -paresis -pathologic reflexes • Hyperreflexia • Clonus -ataxia -gait disturbance HIV encephalopathy rarely, if ever, exhibits focal neurologic signs.

  12. MRI or CT scan: diffuse brain atrophy Basal ganglia calcification 15%

  13. CSF findings • Usually normal • Or non-specific: • Mild pleocytosis • Elevated protein concentration. Rarely > 100mg/dl • CSF viral load: utility is limited because of a significant overlap in CSF viral load among children with and without encephalopathy

  14. HIV encephalopathy: management • Reduce the viral load: ARV • ARV may prevent, stabilize or reverse the HIV encephalopathy • Ensure adequate nutritional support • a poor nutrition will hamper a child’s development

  15. Infections of the Central Nervous System • The prevalence of CNS infections (HIV related and opportunistic) in HIV-infected children is not known • Much less frequent in children than in adults • The neurologic impairment most frequently observed in children is due to HIV infection of the CNS rather than to opportunistic infection or CNS tumors

  16. Etiologies • Mycobacterium tuberculosis • Cryptococcus neoformans • Herpes simplex virus • Herpes zoster virus • Cytomegalovirus • Toxoplasma gondii • JC virus • Syphilis (Treponema pallidum)

  17. Laboratory evaluation for children with Acute CNS manifestations • Blood: • Complete blood count (CBC) • Blood culture • Electrolytes • Toxoplasmosis serum antibody • Cryptococcal antigen and culture

  18. Lumbar puncture (unless contraindicated) • Opening pressure • Gram stain • Cell count • Protein • Glucose • Bacterial culture • Cryptococcal antigen and culture • PCR for EBV, CMV, VZV and HSV • Fungal and mycobacterial cultures • VDRL

  19. Cryptococcus neoformans • Meningitis in patients with advanced HIV disease and severely depressed CD4+ cells • Fever, headache, vomiting • Meningeal sign: present or absent • CSF findings: • High CSF pressure • Cells: normal or lymphocyte predominant • Protein: normal or slightly increased • Sugar: normal or slightly decreased • India Ink: positive • CSF cryptococcal antigen: positive • Serum cryptococcal antigen: positive

  20. Focal Neurologic Deficit • Tuberculosis • Toxoplasma encephalitis • Primary CNS lymphoma • Progressive Multifocal Leukoencephalopathy (PML) • Abscess • Stroke

  21. Tuberculosis in children • Children with TB almost always were infected by an adult in the daily environment • TB is the progression of primary infection rather than a reactivation disease (common in adults) • Identification and treatment of the source patient (family members, school, etc)

  22. Tuberculosis meningitis • Common in HIV, slow chronic onset is usual. • 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 Cryptococcus meningitis

  23. TB Meningitis: Diagnosis CSF: • Pressure may be raised • Lymphocytosis or mixed cells in the CSF. • Protein typically very high (2-6 g/dL) and low glucose (<45 mg/dL). • AFB are rarely found in CSF • PCR MTB with sensitivity about 56 % • Always request India Ink staining to help exclude or confirm Cryptococcus meningitis. Look for TB elsewhere in the body by CXR, sputum, gastric or lymph nodes aspiration where appropriate

  24. TB meningitis

  25. 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 the body by CXR, sputum, etc

  26. Tuberculoma

  27. Differential diagnosis

  28. Toxoplasmosis • Rare in young infants, may occur in HIV-infected adolescent • CNS infection < 1% • Toxoplasma encephalitis in HIV infected children: • In most cases occurred in-utero • More rarely, in older children: primary acquired toxoplasmosis • Occur in patients with advanced HIV disease and severely depressed CD4 +cell (<50 cells)

  29. Clinical manifestations Congenital toxoplasmosis: 70-90% asymptomatic at birth Late sequelae: retinitis, visual impairment, intellectual or neurological impairment New borns: Generalized disease: maculopapular rash, generalized lymph nodes, hepatosplenomegaly, anemia, thrombocytopenia, neutropenia CNS disease: hydrocephalus, intracerebral calcifications, microcephaly, chorioretinitis and seizures

  30. Toxoplasmosis acquired after birth: • Nonspecific: malaise, fever, sore throat, myalgia, cervical lymph nodes, rash and hepasplenomegaly. • CNS: neurological findings are more typical. Fever, headache, seizure, focal neurologic abnormalities, altered consciousness. • Isolated ocular toxoplasmosis is rare

  31. Diagnosis • Congenital toxoplasmosis: • IgM, IgA or IgE in neonatal serum within the first 6 months of life or • Persistence of IgG antibody at 12 months • DNA PCR (CSF)

  32. Diagnosis:CNS Toxoplasmosis • Location: basal ganglia, gray-white junction • Sites: usually multiple • Enhancement: prominent, usually ring lesions • Edema/mass effects: usually not a great as lymphoma • MRI is more sensitive

  33. CNS Toxoplasmosis • CSF: normal 20-30% • Protein 10 - 150 mg/dL • Wbc 0 - 40 (monos) • Toxoplasma antigen (ELISA) or PCR

  34. CT scan without contrast CT scan with contrast

  35. Lymphoma • Clinical manifestation: • Headache • Seizure • Mental status changes • Neurological imaging • Hyperdense or isodense mass with variable contrast enhancement or diffusely infiltrating contrast-enhancing mass

  36. Peripheral neuropathies and myopathies: rare • Peripheral neuropathy • Inflammatory demyelinating polyneuropathy • Medication e.g. ddC, ddI, d4T, INH • Myopathy eg. • HIV-associated polymyositis • ZDV-associated myopathy

  37. Conclusion • HIV-associated encephalopathy is commonly found in pediatric HIV. • Acute episodes of neurological abnormalities in HIV-infected children may occur in advanced disease especially in adolescents with severe immunodeficiency status.

  38. Thank youQuestions?

  39. Treatment of CNS Infections

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