Brain Magnetic Resonance Imaging Reveals Different Courses of Disease in Pediatric and Adult Cerebral Malaria.
Publisher DOI
PubMed ID
33321516
Abstract
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.
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.
Date Issued
2021-10-05
Publication Type
Article
Subject(s)
Subjects
Plasmodium falciparum
apparent diffusion coefficient maps cerebral malaria hypoxia magnetic resonance imaging
apparent diffusion coefficient maps cerebral malaria hypoxia magnetic resonance imaging
Language(s)
en
Author(s)
Sahu, Praveen K | |
Majhi, Megharay | |
Pattnaik, Rajyabardhan | |
Patterson, Catriona | |
Mahanta, Kishore C | |
Mohanty, Akshaya K | |
Mohanty, Rashmi R | |
Joshi, Sonia | |
Mohanty, Anita | |
Bage, Jabamani | |
Maharana, Sameer | |
Seitz, Angelika | |
Bendszus, Martin | |
Sullivan, Steven A | |
Turnbull, Ian W | |
Dondorp, Arjen M | |
Gupta, Himanshu | |
Pirpamer, Lukas | |
Mohanty, Sanjib | |
Wassmer, Samuel C |
Additional Credits
Journal
Clinical infectious diseases
Publisher
Oxford University Press
ISSN
1537-6591
Access(Rights)
open.access