OUP user menu

Cerebral malaria in children: using the retina to study the brain

(CC)
Ian J. C. MacCormick, Nicholas A. V. Beare, Terrie E. Taylor, Valentina Barrera, Valerie A. White, Paul Hiscott, Malcolm E. Molyneux, Baljean Dhillon, Simon P. Harding
DOI: http://dx.doi.org/10.1093/brain/awu001 2119-2142 First published online: 27 February 2014

Summary

Cerebral malaria is a dangerous complication of Plasmodium falciparum infection, which takes a devastating toll on children in sub-Saharan Africa. Although autopsy studies have improved understanding of cerebral malaria pathology in fatal cases, information about in vivo neurovascular pathogenesis is scarce because brain tissue is inaccessible in life. Surrogate markers may provide insight into pathogenesis and thereby facilitate clinical studies with the ultimate aim of improving the treatment and prognosis of cerebral malaria. The retina is an attractive source of potential surrogate markers for paediatric cerebral malaria because, in this condition, the retina seems to sustain microvascular damage similar to that of the brain. In paediatric cerebral malaria a combination of retinal signs correlates, in fatal cases, with the severity of brain pathology, and has diagnostic and prognostic significance. Unlike the brain, the retina is accessible to high-resolution, non-invasive imaging. We aimed to determine the extent to which paediatric malarial retinopathy reflects cerebrovascular damage by reviewing the literature to compare retinal and cerebral manifestations of retinopathy-positive paediatric cerebral malaria. We then compared retina and brain in terms of anatomical and physiological features that could help to account for similarities and differences in vascular pathology. These comparisons address the question of whether it is biologically plausible to draw conclusions about unseen cerebral vascular pathogenesis from the visible retinal vasculature in retinopathy-positive paediatric cerebral malaria. Our work addresses an important cause of death and neurodisability in sub-Saharan Africa. We critically appraise evidence for associations between retina and brain neurovasculature in health and disease, and in the process we develop new hypotheses about why these vascular beds are susceptible to sequestration of parasitized erythrocytes.

  • cerebral malaria
  • cerebral microvasculature
  • retinal microvasculature
  • haemorheology
  • surrogate marker
  • Abbreviation
    CI
    confidence interval
    CM
    cerebral malaria
    CMRgluc
    cerebral metabolic rate (glucose)
    CMRO2
    cerebral metabolic rate (oxygen)
    CNP
    capillary non-perfusion
    CRAE
    central retinal artery equivalent
    CRVE
    central retinal vein equivalent
    DD
    disc diameter
    FA
    fluorescein angiogram
    FAZ
    foveal avascular zone
    ICAM-1
    intercellular adhesion molecule 1
    LDR
    length to diameter ratio
    MRI
    magnetic resonance imaging
    OR
    odds ratio
    PfEMP-1
    Plasmodium falciparum erythrocyte membrane protein 1
    SD
    standard deviation
  • This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

    View Full Text