TY - JOUR
T1 - Brain Magnetic Resonance Imaging Reveals Different Courses of Disease in Pediatric and Adult Cerebral Malaria
AU - Sahu, Praveen K.
AU - Hoffmann, Angelika
AU - Majhi, Megharay
AU - Pattnaik, Rajyabardhan
AU - Patterson, Catriona
AU - Mahanta, Kishore C.
AU - Mohanty, Akshaya K.
AU - Mohanty, Rashmi R.
AU - Joshi, Sonia
AU - Mohanty, Anita
AU - Bage, Jabamani
AU - Maharana, Sameer
AU - Seitz, Angelika
AU - Bendszus, Martin
AU - Sullivan, Steven A.
AU - Turnbull, Ian W.
AU - Dondorp, Arjen M.
AU - Gupta, Himanshu
AU - Pirpamer, Lukas
AU - Mohanty, Sanjib
AU - Wassmer, Samuel C.
N1 - Publisher Copyright: © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.
PY - 2021/10/5
Y1 - 2021/10/5
N2 - BACKGROUND: Cerebral malaria is a common presentation of severe Plasmodium falciparum infection and remains an important cause of death in the tropics. Key aspects of its pathogenesis are still incompletely understood, but severe brain swelling identified by magnetic resonance imaging (MRI) was associated with a fatal outcome in African children. In contrast, neuroimaging investigations failed to identify cerebral features associated with fatality in Asian adults. METHODS: Quantitative MRI with brain volume assessment and apparent diffusion coefficient (ADC) histogram analyses were performed for the first time in 65 patients with cerebral malaria to compare disease signatures between children and adults from the same cohort, as well as between fatal and nonfatal cases. RESULTS: We found an age-dependent decrease in brain swelling during acute cerebral malaria, and brain volumes did not differ between fatal and nonfatal cases across both age groups. In nonfatal disease, reversible, hypoxia-induced cytotoxic edema occurred predominantly in the white matter in children, and in the basal ganglia in adults. In fatal cases, quantitative ADC histogram analyses also demonstrated different end-stage patterns between adults and children: Severe hypoxia, evidenced by global ADC decrease and elevated plasma levels of lipocalin-2 and microRNA-150, was associated with a fatal outcome in adults. In fatal pediatric disease, our results corroborate an increase in brain volume, leading to augmented cerebral pressure, brainstem herniation, and death. CONCLUSIONS: Our findings suggest distinct pathogenic patterns in pediatric and adult cerebral malaria with a stronger cytotoxic component in adults, supporting the development of age-specific adjunct therapies.
AB - BACKGROUND: Cerebral malaria is a common presentation of severe Plasmodium falciparum infection and remains an important cause of death in the tropics. Key aspects of its pathogenesis are still incompletely understood, but severe brain swelling identified by magnetic resonance imaging (MRI) was associated with a fatal outcome in African children. In contrast, neuroimaging investigations failed to identify cerebral features associated with fatality in Asian adults. METHODS: Quantitative MRI with brain volume assessment and apparent diffusion coefficient (ADC) histogram analyses were performed for the first time in 65 patients with cerebral malaria to compare disease signatures between children and adults from the same cohort, as well as between fatal and nonfatal cases. RESULTS: We found an age-dependent decrease in brain swelling during acute cerebral malaria, and brain volumes did not differ between fatal and nonfatal cases across both age groups. In nonfatal disease, reversible, hypoxia-induced cytotoxic edema occurred predominantly in the white matter in children, and in the basal ganglia in adults. In fatal cases, quantitative ADC histogram analyses also demonstrated different end-stage patterns between adults and children: Severe hypoxia, evidenced by global ADC decrease and elevated plasma levels of lipocalin-2 and microRNA-150, was associated with a fatal outcome in adults. In fatal pediatric disease, our results corroborate an increase in brain volume, leading to augmented cerebral pressure, brainstem herniation, and death. CONCLUSIONS: Our findings suggest distinct pathogenic patterns in pediatric and adult cerebral malaria with a stronger cytotoxic component in adults, supporting the development of age-specific adjunct therapies.
KW - Plasmodium falciparum
KW - apparent diffusion coefficient maps
KW - cerebral malaria
KW - hypoxia
KW - magnetic resonance imaging
UR - http://www.scopus.com/inward/record.url?scp=85118283369&partnerID=8YFLogxK
U2 - https://doi.org/10.1093/cid/ciaa1647
DO - https://doi.org/10.1093/cid/ciaa1647
M3 - Article
C2 - 33321516
SN - 1058-4838
VL - 73
SP - e2387-e2396
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 7
ER -