Brain MRI of Children with Retinopathy-Negative Cerebral Malaria

Douglas G. Postels International Neurologic and Psychiatric Epidemiology Program, Michigan State University, East Lansing, Michigan; Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, Michigan; Department of Neurology, University of Rochester, Rochester, New York; Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi; College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan; Department of Radiology, Queen Elizabeth Central Hospital, Blantyre, Malawi; Department of Anatomy, University of St. Andrews, St. Andrews, Scotland; Department of Imaging Sciences, University of Rochester, Rochester, New York

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Chenxi Li International Neurologic and Psychiatric Epidemiology Program, Michigan State University, East Lansing, Michigan; Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, Michigan; Department of Neurology, University of Rochester, Rochester, New York; Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi; College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan; Department of Radiology, Queen Elizabeth Central Hospital, Blantyre, Malawi; Department of Anatomy, University of St. Andrews, St. Andrews, Scotland; Department of Imaging Sciences, University of Rochester, Rochester, New York

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Gretchen L. Birbeck International Neurologic and Psychiatric Epidemiology Program, Michigan State University, East Lansing, Michigan; Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, Michigan; Department of Neurology, University of Rochester, Rochester, New York; Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi; College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan; Department of Radiology, Queen Elizabeth Central Hospital, Blantyre, Malawi; Department of Anatomy, University of St. Andrews, St. Andrews, Scotland; Department of Imaging Sciences, University of Rochester, Rochester, New York

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Terrie E. Taylor International Neurologic and Psychiatric Epidemiology Program, Michigan State University, East Lansing, Michigan; Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, Michigan; Department of Neurology, University of Rochester, Rochester, New York; Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi; College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan; Department of Radiology, Queen Elizabeth Central Hospital, Blantyre, Malawi; Department of Anatomy, University of St. Andrews, St. Andrews, Scotland; Department of Imaging Sciences, University of Rochester, Rochester, New York

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Karl B. Seydel International Neurologic and Psychiatric Epidemiology Program, Michigan State University, East Lansing, Michigan; Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, Michigan; Department of Neurology, University of Rochester, Rochester, New York; Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi; College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan; Department of Radiology, Queen Elizabeth Central Hospital, Blantyre, Malawi; Department of Anatomy, University of St. Andrews, St. Andrews, Scotland; Department of Imaging Sciences, University of Rochester, Rochester, New York

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Sam D. Kampondeni International Neurologic and Psychiatric Epidemiology Program, Michigan State University, East Lansing, Michigan; Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, Michigan; Department of Neurology, University of Rochester, Rochester, New York; Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi; College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan; Department of Radiology, Queen Elizabeth Central Hospital, Blantyre, Malawi; Department of Anatomy, University of St. Andrews, St. Andrews, Scotland; Department of Imaging Sciences, University of Rochester, Rochester, New York

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Simon J. Glover International Neurologic and Psychiatric Epidemiology Program, Michigan State University, East Lansing, Michigan; Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, Michigan; Department of Neurology, University of Rochester, Rochester, New York; Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi; College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan; Department of Radiology, Queen Elizabeth Central Hospital, Blantyre, Malawi; Department of Anatomy, University of St. Andrews, St. Andrews, Scotland; Department of Imaging Sciences, University of Rochester, Rochester, New York

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Michael J. Potchen International Neurologic and Psychiatric Epidemiology Program, Michigan State University, East Lansing, Michigan; Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, Michigan; Department of Neurology, University of Rochester, Rochester, New York; Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi; College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan; Department of Radiology, Queen Elizabeth Central Hospital, Blantyre, Malawi; Department of Anatomy, University of St. Andrews, St. Andrews, Scotland; Department of Imaging Sciences, University of Rochester, Rochester, New York

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DOI:
https://doi.org/10.4269/ajtmh.14-0216
Volume/Issue:
Volume 91: Issue 5
Page(s):
943–949
Restricted access
Get Permissions

Our goals were to understand the brain magnetic resonance imaging (MRI) findings in children with retinopathy-negative cerebral malaria (CM) and investigate whether any findings on acute MRI were associated with adverse outcomes. We performed MRI scans on children admitted to the hospital in Blantyre, Malawi with clinically defined CM. Two hundred and seventeen children were imaged during the study period; 44 patients were malarial retinopathy-negative; and 173 patients were retinopathy-positive. We compared MRI findings in children with retinopathy-negative and retinopathy-positive CM. In children who were retinopathy-negative, we identified MRI variables that were associated with death and adverse neurologic outcomes. On multivariate analysis, cortical diffusion weighted imaging (DWI) abnormality and increased brain volume were strongly associated with neurologic morbidity in survivors. Investigations to explore the underlying pathophysiologic processes responsible for these MRI changes are warranted.

Author Notes

* Address correspondence to Douglas G. Postels, International Neurologic and Psychiatric Epidemiology Program, Michigan State University, 909 Fee Road, 324 West Fee Hall, East Lansing, MI 48824. E-mail: douglas.postels@ht.msu.edu

Financial support: This study was supported by National Institutes of Health Grant 5R01AI034969.

Authors' addresses: Douglas G. Postels, International Neurologic and Psychiatric Epidemiology Program, Michigan State University, East Lansing, MI, E-mail: douglas.postels@ht.msu.edu. Chenxi Li, Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI, E-mail: cli@epi.msu.edu. Gretchen L. Birbeck, Department of Neurology, University of Rochester, Rochester, NY, E-mail: Gretchen_Birbeck@URMC.Rochester.edu. Terrie E. Taylor, Department of Osteopathic Medical Specialties, Michigan State University, East Lansing, MI, and Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi, E-mail: ttmalawi@msu.edu. Karl B. Seydel, Department of Osteopathic Medical Specialties, Michigan State University, East Lansing, MI, E-mail: seydel@msu.edu. Sam D. Kampondeni, Department of Radiology, University of Malawi College of Medicine, Blantyre, Malawi, E-mail: s.kampo154@gmail.com. Simon J. Glover, Anatomy Department, School of Medicine, University of St. Andrews, St. Andrews, Scotland, E-mail: simontheeyeman@hotmail.com. Michael J. Potchen, Department of Imaging Sciences, University of Rochester, Rochester, NY, E-mail: Michael_Potchen@URMC.Rochester.edu.

Copyright:
© The American Society of Tropical Medicine and Hygiene 2014
Received:
09 Apr 2014
|
Accepted:
25 Jul 2014
|
Published Online:
05 Nov 2014
Cover The American Journal of Tropical Medicine and Hygiene
The American Journal of Tropical Medicine and Hygiene
Print ISSN:
0002-9637
Online ISSN:
1476-1645
  • 1.

    World Health Organization, 2000. Severe falciparum malaria. World Health Organization, Communicable Diseases Cluster. Trans R Soc Trop Med Hyg 94 (Suppl 1): S1–S90.

    • Search Google Scholar
    • Export Citation
  • 2.

    World Health Organization, 2012. World Malaria Report. Geneva: World Health Organization.

  • 3.

    Taylor TE, Fu WJ, Carr RA, Whitten RO, Mueller JS, Fosiko NG, Lewallen S, Liomba NG, Molyneux ME, 2004. Differentiating the pathologies of cerebral malaria by postmortem parasite counts. Nat Med 10: 143–145.

    • Search Google Scholar
    • Export Citation
  • 4.

    Lewallen S, Taylor TE, Molyneux ME, Wills BA, Courtright P, 1993. Ocular fundus findings in Malawian children with cerebral malaria. Ophthalmology 100: 857–861.

    • Search Google Scholar
    • Export Citation
  • 5.

    Lewallen S, Wills BA, 1993. Retinal haemorrhage in children with malaria. Lancet 341: 442.

  • 6.

    Beare NA, Glover SJ, Molyneux M, 2009. Malarial retinopathy in cerebral malaria. Am J Trop Med Hyg 80: 171.

  • 7.

    Beare NA, Taylor TE, Harding SP, Lewallen S, Molyneux ME, 2006. Malarial retinopathy: a newly established diagnostic sign in severe malaria. Am J Trop Med Hyg 75: 790–797.

    • Search Google Scholar
    • Export Citation
  • 8.

    Lewallen S, Bronzan RN, Beare NA, Harding SP, Molyneux ME, Taylor TE, 2008. Using malarial retinopathy to improve the classification of children with cerebral malaria. Trans R Soc Trop Med Hyg 102: 1089–1094.

    • Search Google Scholar
    • Export Citation
  • 9.

    Postels DG, Birbeck GL, 2011. Children with retinopathy-negative cerebral malaria: a pathophysiological puzzle. Pediatr Infect Dis J 30: 953–956.

    • Search Google Scholar
    • Export Citation
  • 10.

    Birbeck GL, Beare N, Lewallen S, Glover SJ, Molyneux M, Kaplan P, Taylor TE, 2010. Identification of malaria retinopathy improves the specificity of the clinical diagnosis of cerebral malaria: findings from a prospective cohort study. Am J Trop Med Hyg 82: 231–234.

    • Search Google Scholar
    • Export Citation
  • 11.

    Potchen MJ, Kampondeni SD, Seydel KB, Birbeck GL, Hammond CA, Bradley WG, DeMarco JK, Glover SJ, Ugorji JO, Latourette M, Siebert J, Molyneux M, Taylor TE, 2012. Acute brain MRI findings in 120 Malawian children with cerebral malaria: new insights into an ancient disease. AJNR Am J Neuroradiol 33: 1740–1746.

    • Search Google Scholar
    • Export Citation
  • 12.

    Taylor TE, 2009. Caring for children with cerebral malaria: insights gleaned from 20 years on a research ward in Malawi. Trans R Soc Trop Med Hyg 103 (Suppl 1): S6–S10.

    • Search Google Scholar
    • Export Citation
  • 13.

    Potchen MJKS, Ibrahim K, Bonner J, Seydel KB, Taylor TE, Birbeck GL, 2013. NeuroInterp: a method for facilitating neuroimaging research on cerebral malaria. Neurology 81: 585–588.

    • Search Google Scholar
    • Export Citation
  • 14.

    Zou HHT, 2005. Regularization and variable selection via the Elastic Net. J R Stat Soc Ser A Stat Soc 67: 301–320.

  • 15.

    Firth D, 1993. Bias reduction of maximum likelihood estimates. Biometrika 80: 27–38.

  • 16.

    Birbeck GL, Molyneux ME, Kaplan PW, Seydel KB, Chimalizeni YF, Kawaza K, Taylor TE, 2010. Blantyre Malaria Project EpilepsyStudy (BMPES) of neurological outcomes in retinopathy positive paediatric cerebral malaria survivors: a prospective cohort study. Lancet Neurol 9: 1173–1181.

    • Search Google Scholar
    • Export Citation
  • 17.

    Gupta RK, Soni N, Kumar S, Khandelwal N, 2012. Imaging of central nervous system viral diseases. J Magn Reson Imaging 35: 477–491.

  • 18.

    Schubart CD, Mturi N, Beld MG, Wertheim PM, Newton CR, 2006. Role of viruses in Kenyan children presenting with acute encephalopathy in a malaria-endemic area. Am J Trop Med Hyg 75: 1148–1150.

    • Search Google Scholar
    • Export Citation
  • 19.

    Mallewa M, Vallely P, Faragher B, Banda D, Klapper P, Mukaka M, Khofi H, Pensulo P, Taylor T, Molyneux M, Solomon T, 2013. Viral CNS infections in children from a malaria-endemic area of Malawi: a prospective cohort study. Lancet Glob Health 1: e153–e160.

    • Search Google Scholar
    • Export Citation
  • 20.

    Sili U, Kaya A, Mert A, 2014. Herpes simplex virus encephalitis: clinical manifestations, diagnosis and outcome in 106 adult patients. J Clin Virol 60: 112–118.

    • Search Google Scholar
    • Export Citation
  • 21.

    Lee KY, Lee YJ, Kim TH, Cheon DS, Nam SO, 2014. Clinico-radiological spectrum in enterovirus 71 infection involving the central nervous system in children. J Clin Neurosci 21: 416–420.

    • Search Google Scholar
    • Export Citation
  • 22.

    Crawford JR, 2010. Advances in pediatric neurovirology. Curr Neurol Neurosci Rep 10: 147–154.

  • 23.

    Takanashi J, Barkovich AJ, Yamaguchi K, Kohno Y, 2004. Influenza-associated encephalitis/encephalopathy with a reversible lesion in the splenium of the corpus callosum: a case report and literature review. AJNR Am J Neuroradiol 25: 798–802.

    • Search Google Scholar
    • Export Citation
  • 24.

    Beattie GC, Glaser CA, Sheriff H, Messenger S, Preas CP, Shahkarami M, Venkatesan A, 2013. Encephalitis with thalamic and basal ganglia abnormalities: etiologies, neuroimaging, and potential role of respiratory viruses. Clin Infect Dis 56: 825–832.

    • Search Google Scholar
    • Export Citation
  • 25.

    Kobuchi N, Tsukahara H, Kawamura Y, Ishimori Y, Ohshima Y, Hiraoka M, Hiraizumi Y, Ueno M, Mavumi M, 2003. Reversible diffusion-weighted MR findings of Salmonella enteritidis-associated encephalopathy. Eur Neurol 49: 182–184.

    • Search Google Scholar
    • Export Citation
  • 26.

    Ogura H, Takaoka M, Kishi M, Kimoto M, Shimazu T, Yoshioka T, Sugimoto H, 1998. Reversible MR findings of hemolytic uremic syndrome with mild encephalopathy. AJNR Am J Neuroradiol 19: 1144–1145.

    • Search Google Scholar
    • Export Citation
  • 27.

    Lin YW, Yu CY, 2009. Reversible focal splenium lesion–MRS study of a different etiology. Acta Neurol Taiwan 18: 203–206.

  • 28.

    Postels DG, Taylor TE, Molyneux M, Mannor K, Kaplan PW, Seydel KB, Chimalizeni YF, Kawaza K, Birbeck GL, 2012. Neurologic outcomes in retinopathy-negative cerebral malaria survivors. Neurology 79: 1268–1272.

    • Search Google Scholar
    • Export Citation
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