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Monitoring brain function in adults with HIV: what can we learn for children?

Monitoring brain function in adults with HIV: what can we learn for children?. Alan Winston St. Mary’s Hospital, London 10 th October 2008. HIV enters CNS. Useless brain. Diseased brain. Healthy brain. Cerebral atrophy. HIV and CNS EuroSIDA. Ann Neurol 2004;55:320–328.

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Monitoring brain function in adults with HIV: what can we learn for children?

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  1. Monitoring brain function in adults with HIV: what can we learn for children? Alan Winston St. Mary’s Hospital, London 10th October 2008

  2. HIV enters CNS

  3. Useless brain

  4. Diseased brain Healthy brain Cerebral atrophy

  5. HIV and CNS EuroSIDA Ann Neurol 2004;55:320–328

  6. HIV dementia in HAART era Dore: AIDS, Volume 17(10).July 4, 2003.1539-1545

  7. HIV dementia in HAART era Dore: AIDS, Volume 17(10).July 4, 2003.1539-1545

  8. Monitoring brain function in HIV infection • Monitoring brain function 1. Definition impairment and neurocognitive testing in adults 2. Brain imaging in adults • What does this mean for children?

  9. Monitoring brain function in HIV infection • Monitoring brain function 1. Definition impairment and neurocognitive testing in adults 2. Brain imaging in adults • What does this mean for children?

  10. HIV associated dementia • Described 1986 • AIDS dementia complex • Associated low CD4 count other OI • Sub cortical dementia • involving the deep gray (ie, basal ganglia, thalamus)

  11. Risk factors HAD • Pre-HAART • CD4 count • Post HAART era • Nadir CD4 count • HCV • CSF parameters including HIV RNA • Plasma HIV RNA • Antiretroviral regimens • Co-morbidities

  12. HIV associated dementia (classification) Neurology 2007;69;1789-1799 • HAD • Marked interference with daily life • Symptomatic NCI • impairment >1 SD in 2 or more domains * • does interfere with daily life • Asymptomatic NCI • impairment >1 SD in 2 or more domains * • does not interfere with daily life * The neuropsychological assessment must survey at least the following abilities: verbal/language; attention/working memory; abstraction/executive; memory (learning; recall); speed of information processing; sensory-perceptual, motor skills

  13. Prevalence of HIV NCI % with disorder n=113 n=212 n=437 n=213 Antinori, A. et al. Neurology 2007;69:1789-1799

  14. Prevalence of HIV NCI % with disorder n=113 n=212 n=437 n=213 Antinori, A. et al. Neurology 2007;69:1789-1799

  15. Outcome neurocognitive impairment Tozzi V, et al.AIDS Res Hum Retroviruses. 2005 Aug;21(8):706-13

  16. Neurocognitive assessment

  17. In-house results Log10 msec * * * p=0.011 p=0.021 * Accuracy values assessed (arcsine transformation of the proportion of correct responses)

  18. Treatment outcomes HIV and HCV HIV Med. 2007 Nov;8(8):520-8

  19. Monitoring brain function in HIV infection • Monitoring brain function 1. Definition impairment and neurocognitive testing in adults 2.Brain imaging in adults • What does this mean for children?

  20. Diagnostic imaging

  21. Cerebral atrophy and non specific white matter changes • Child with cerebral atrophy Non specific white matter changes

  22. magnetic resonance spectroscopy • frontal white matter frontal grey matter right basal ganglia

  23. magnetic resonance spectroscopy

  24. Proton magnetic resonance spectroscopy • NAA (n-acetly-aspartate) • Neuronal marker • Cr (creatine) • Metabolism marker • Cho (choline) • Inflammatory marker • mI (myo-Inositols) • Inflammatory marker NAA Cr Cho mI 2 PPM volunteer

  25. Proton magnetic resonance spectroscopy NAA NAA mI Cr Cho mI 2 PPM 2 PPM volunteer HIV-1 subject naïve therapy

  26. MR Spectroscopy and ART

  27. MR Spectroscopy and ART Frontal White Matter NAA Total months exposure NRTIs Journal of NeuroVirology, 11: 356–364, 2005

  28. fMRI and BOLD

  29. fMRI and BOLD

  30. fMRI and BOLD

  31. fMRI and HIV J Neuroimmune Pharmacol. 2008 Jun;3(2):95-104

  32. Monitoring brain function in HIV infection • Monitoring brain function 1. Definition impairment and neurocognitive testing in adults 2. Brain imaging in adults • What does this mean for children?

  33. What does this mean for children? • In adults (neurodeveloped) • HIV infection affects a mature CNS • May improve with antiretroviral therapy • Effects between different therapies largely unknown • In children (neurodeveloping) • Effects HIV and antiretrovirals in utero • Effects of HIV on the developing CNS • Effects of antiretroviral therapy on developing brain • Effects of co-morbidities on neurodevelopment

  34. % 1 - 12 months 12 - 24 months 24 - 36 months Neurodevelopment after birth in children with HIV • CAT (Clinical Adaptive Test) and CLAMS (Clinical Linguistic and Auditory Milestone Scale) Braz J Infect Dis. 2006 Oct;10(5):322-6

  35. MRS in children with HIV NAA right frontal white matter NAA right frontal white matter Age at MRS investigation (years)

  36. Monitoring brain function in HIV infection • Brain disease exists in ART era • Different picture of disease in this era • Minimal knowledge on: • Long term effects of HIV on CNS • Antiretroviral agents on CNS • Monitoring brain function possible • Non-invasive • Non time consuming

  37. Diseased brain Healthy brain Cerebral atrophy

  38. Thank you • a.winston@imperial.ac.uk

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