Brain Magnetic Resonance Imaging Reveals Different Courses of Disease in Pediatric and Adult Cerebral Malaria. (16th December 2020)

• Record Type: Journal Article
• Authors: Sahu, Praveen K; Hoffmann, Angelika; 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
• Is Part Of: Clinical infectious diseases. Volume 73:Number 7(2021)
• Page Start: e2387
• Page End: e2396
• Publication Date: 2020-12-16
• Subjects: cerebral malaria -- Plasmodium falciparum -- magnetic resonance imaging -- apparent diffusion coefficient maps -- hypoxia; Communicable diseases -- Periodicals; 616.905
• DOI: 10.1093/cid/ciaa1647
• Languages: English
• ISSNs: 1058-4838

Abstract

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. Abstract : Using quantitative magnetic resonance imaging analyses of brain volume and cerebral tissue water diffusion, we demonstrate that children and adults with cerebral malaria have a different disease evolution and show that pronounced, global brain hypoxia is associated with death in adults.