1921
Volume 98, Issue 2
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract.

The hallmark of pediatric cerebral malaria (CM) is sequestration of parasitized red blood cells in the cerebral microvasculature. Malawi-based research using 0.35 Tesla (T) magnetic resonance imaging (MRI) established that severe brain swelling is associated with fatal CM, but swelling etiology remains unclear. Autopsy and clinical studies suggest several potential etiologies, but limitations of 0.35 T MRI precluded optimal investigations into swelling pathophysiology. A 1.5 T MRI in Zambia allowed for further investigations including susceptibility-weighted imaging (SWI). SWI is an ideal sequence for identifying regions of sequestration and microhemorrhages given the ferromagnetic properties of hemozoin and blood. Using 1.5 T MRI, Zambian children with retinopathy-confirmed CM underwent imaging with SWI, T2, T1 pre- and post-gadolinium, diffusion-weighted imaging (DWI) with apparent diffusion coefficients and T2/fluid attenuated inversion recovery sequences. Sixteen children including two with moderate/severe edema were imaged; all survived. Gadolinium extravasation was not seen. DWI abnormalities spared the gray matter suggesting vasogenic edema with viable tissue rather than cytotoxic edema. SWI findings consistent with microhemorrhages and parasite sequestration co-occurred in white matter regions where DWI changes consistent with vascular congestion were seen. Imaging findings consistent with posterior reversible encephalopathy syndrome were seen in children who subsequently had a rapid clinical recovery. High field MRI indicates that vascular congestion associated with parasite sequestration, local inflammation from microhemorrhages and autoregulatory dysfunction likely contribute to brain swelling in CM. No gross radiological blood brain barrier breakdown or focal cortical DWI abnormalities were evident in these children with nonfatal CM.

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References

  1. WHO, 2011. World Malaria Report. Geneva, Switzerland: World Health Organization.
  2. Dondorp AM, 2011. Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial. Lancet 376: 16471657. [Google Scholar]
  3. Molyneux ME, Taylor TE, Wirima JJ, Borgstein A, , 1989. Clinical features and prognostic indicators in paediatric cerebral malaria: a study of 131 comatose Malawian children. Q J Med 71: 441459. [Google Scholar]
  4. Potchen MJ, 2012. Acute brain MRI findings in 120 Malawian children with cerebral malaria: new insights into an ancient disease. AJNR Am J Neuroradiol 33: 17401746. [Google Scholar]
  5. Paul F, Roath S, Melville D, Warhurst DC, Osisanya JO, , 1981. Separation of malaria-infected erythrocytes from whole blood: use of a selective high-gradient magnetic separation technique. Lancet 2: 7071. [Google Scholar]
  6. Rasalkar DD, Paunipagar BK, Sanghvi D, Sonawane BD, Loniker P, , 2011. Magnetic resonance imaging in cerebral malaria: a report of four cases. Br J Radiol 84: 380385. [Google Scholar]
  7. Vyas S, Gupta V, Hondappanavar A, Sakhuja V, Bhardwaj N, Singh P, Khandelwal N, , 2012. Magnetic resonance imaging of cerebral malaria. J Emerg Med 42: e117e119. [Google Scholar]
  8. Maude RJ, 2014. Magnetic resonance imaging of the brain in adults with severe falciparum malaria. Malar J 13: 177. [Google Scholar]
  9. Seydel KB, 2015. Brain swelling and death in children with cerebral malaria. N Engl J Med 372: 11261137. [Google Scholar]
  10. Brown H, Rogerson S, Taylor T, Tembo M, Mwenechanya J, Molyneux M, Turner G, , 2001. Blood-brain barrier function in cerebral malaria in Malawian children. Am J Trop Med Hyg 64: 207213. [Google Scholar]
  11. Dorovini-Zis K, Schmidt K, Huynh H, Fu W, Whitten RO, Milner D, Kamiza S, Molyneux M, Taylor TE, , 2011. The neuropathology of fatal cerebral malaria in Malawian children. Am J Pathol 178: 21462158. [Google Scholar]
  12. Beare NA, Harding SP, Taylor TE, Lewallen S, Molyneux ME, , 2009. Perfusion abnormalities in children with cerebral malaria and malarial retinopathy. J Infect Dis 199: 263271. [Google Scholar]
  13. Ponsford MJ, Medana IM, Prapansilp P, Hien TT, Lee SJ, Dondorp AM, Esiri MM, Day NP, White NJ, Turner GD, , 2012. Sequestration and microvascular congestion are associated with coma in human cerebral malaria. J Infect Dis 205: 663671. [Google Scholar]
  14. Brodersen P, Paulson OB, Bolwig TG, Rogon ZE, Rafaelsen OJ, Lassen NA, , 1973. Cerebral hyperemia in electrically induced epileptic seizures. Arch Neurol 28: 334338. [Google Scholar]
  15. Prohovnik I, Pavlakis SG, Piomelli S, Bello J, Mohr JP, Hilal S, De Vivo DC, , 1989. Cerebral hyperemia, stroke, and transfusion in sickle cell disease. Neurology 39: 344348. [Google Scholar]
  16. Bartynski WS, , 2008. Posterior reversible encephalopathy syndrome, part 1: fundamental imaging and clinical features. AJNR Am J Neuroradiol 29: 10361042. [Google Scholar]
  17. Haacke EM, Xu Y, Cheng YC, Reichenbach JR, , 2004. Susceptibility weighted imaging (SWI). Magn Reson Med 52: 612618. [Google Scholar]
  18. Hackett S, Hamzah J, Davis TM, St Pierre TG, , 2009. Magnetic susceptibility of iron in malaria-infected red blood cells. Biochim Biophys Acta 1792: 9399. [Google Scholar]
  19. Bosemani T, Verschuuren SI, Poretti A, Huisman TA, , 2014. Pitfalls in susceptibility-weighted imaging of the pediatric brain. J Neuroimaging 24: 221225. [Google Scholar]
  20. 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: 790797. [Google Scholar]
  21. Molyneux ME, Taylor TE, Wirima JJ, Borgstein A, , 1989. Clinical features and prognostic indicators in paediatric cerebral malaria: a study of 131 comatose Malawian children. Q J Med 71: 441459. [Google Scholar]
  22. Siemens, 2010. MRI Protocols. Available at: http://www.healthcare.siemens.com/magnetic-resonance-imaging/magnetom-world/clinical-corner/protocols. Accessed March 22, 2017.
  23. Potchen MJ, Kampondeni SD, Ibrahim K, Bonner J, Seydel KB, Taylor TE, Birbeck GL, , 2013. NeuroInterp: a method for facilitating neuroimaging research on cerebral malaria. Neurology 81: 585588. [Google Scholar]
  24. Hall CE, Slayter HS, , 1959. The fibrinogen molecule: its size, shape, and mode of polymerization. J Biophys Biochem Cytol 5: 1116. [Google Scholar]
  25. Moustafa RR, Baron JC, , 2007. Clinical review: imaging in ischaemic stroke–implications for acute management. Crit Care 11: 227. [Google Scholar]
  26. Guimiot F, Garel C, Fallet-Bianco C, Menez F, Khung-Savatovsky S, Oury JF, Sebag G, Delezoide AL, , 2008. Contribution of diffusion-weighted imaging in the evaluation of diffuse white matter ischemic lesions in fetuses: correlations with fetopathologic findings. AJNR Am J Neuroradiol 29: 110115. [Google Scholar]
  27. Bartynski WS, , 2008. Posterior reversible encephalopathy syndrome, part 2: controversies surrounding pathophysiology of vasogenic edema. AJNR Am J Neuroradiol 29: 10431049. [Google Scholar]
  28. Haacke EM, Mittal S, Wu Z, Neelavalli J, Cheng YC, , 2009. Susceptibility-weighted imaging: technical aspects and clinical applications, part 1. AJNR Am J Neuroradiol 30: 1930. [Google Scholar]
  29. Kennan RP, Machado FS, Lee SC, Desruisseaux MS, Wittner M, Tsuji M, Tanowitz HB, , 2005. Reduced cerebral blood flow and N-acetyl aspartate in a murine model of cerebral malaria. Parasitol Res 96: 302307. [Google Scholar]
  30. Lacout A, Guidoux C, Carlier CY, , 2010. Posterior reversible encephalopathy syndrome in neuro-malaria. Indian J Radiol Imaging 20: 198201. [Google Scholar]
  31. Pharmaceuticals BH, 2009. MAGNEVIST® (brand of gadopentetate dimeglumine) Injection and Pharmacy Bulk Package. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/019596s043,021037s018lbl.pdf. Accessed December 20, 2017.
  32. Tofts PS, Kermode AG, , 1991. Measurement of the blood-brain barrier permeability and leakage space using dynamic MR imaging. 1. Fundamental concepts. Magn Reson Med 17: 357367. [Google Scholar]
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  • Received : 12 Apr 2017
  • Accepted : 14 Nov 2017

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