Magnetic Resonance Imaging of Cerebral Malaria Patients Reveals Distinct Pathogenetic Processes in Different Parts of the Brain

ABSTRACT The mechanisms underlying the rapidly reversible brain swelling described in patients with cerebral malaria (CM) are unknown. Using a 1.5-Tesla (T) magnetic resonance imaging (MRI) scanner, we undertook an observational study in Rourkela, India, of 11 Indian patients hospitalized with CM an...

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Autores principales:	Sanjib Mohanty, Laura A. Benjamin, Megharay Majhi, Premanand Panda, Sam Kampondeni, Praveen K. Sahu, Akshaya Mohanty, Kishore C. Mahanta, Rajyabardhan Pattnaik, Rashmi R. Mohanty, Sonia Joshi, Anita Mohanty, Ian W. Turnbull, Arjen M. Dondorp, Terrie E. Taylor, Samuel C. Wassmer
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	MRI PRES Plasmodium falciparum vasogenic edema cerebral malaria Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/758c90c49515420582454e8db74c34fb
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spelling	oai:doaj.org-article:758c90c49515420582454e8db74c34fb2021-11-15T15:21:45ZMagnetic Resonance Imaging of Cerebral Malaria Patients Reveals Distinct Pathogenetic Processes in Different Parts of the Brain10.1128/mSphere.00193-172379-5042https://doaj.org/article/758c90c49515420582454e8db74c34fb2017-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00193-17https://doaj.org/toc/2379-5042ABSTRACT The mechanisms underlying the rapidly reversible brain swelling described in patients with cerebral malaria (CM) are unknown. Using a 1.5-Tesla (T) magnetic resonance imaging (MRI) scanner, we undertook an observational study in Rourkela, India, of 11 Indian patients hospitalized with CM and increased brain volume. Among the 11 cases, there were 5 adults and 6 children. All patients had reduced consciousness and various degrees of cortical swelling at baseline. The latter was predominately posterior in distribution. The findings on diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps were consistent with vasogenic edema in all cases. Reversibility after 48 to 72 h was observed in >90% of cases. DWI/ADC mismatch suggested the additional presence of cytotoxic edema in the basal nuclei of 5 patients; all of these had perfusion parameters consistent with vascular engorgement and not with ischemic infarcts. Our results suggest that an impairment of the blood-brain barrier is responsible for the brain swelling in CM. In 5 cases, vasogenic edema occurred in conjunction with changes in the basal nuclei consistent with venous congestion, likely to be caused by the sequestration of Plasmodium falciparum-infected erythrocytes. While both mechanisms have been individually postulated to play an important role in the development of CM, this is the first demonstration of their concurrent involvement in different parts of the brain. The clinical and radiological characteristics observed in the majority of our patients are consistent with posterior reversible encephalopathy syndrome (PRES), and we show for the first time a high frequency of PRES in the context of CM. IMPORTANCE The pathophysiology and molecular mechanisms underlying cerebral malaria (CM) are still poorly understood. Recent neuroimaging studies demonstrated that brain swelling is a common feature in CM and a major contributor to death in pediatric patients. Consequently, determining the precise mechanisms responsible for this swelling could open new adjunct therapeutic avenues in CM patients. Using an MRI scanner with a higher resolution than the ones used in previous reports, we identified two distinct origins of brain swelling in both adult and pediatric patients from India, occurring in distinct parts of the brain. Our results support the hypothesis that both endothelial dysfunction and microvascular obstruction by Plasmodium falciparum-infected erythrocytes make independent contributions to the pathogenesis of CM, providing opportunities for novel therapeutic interventions.Sanjib MohantyLaura A. BenjaminMegharay MajhiPremanand PandaSam KampondeniPraveen K. SahuAkshaya MohantyKishore C. MahantaRajyabardhan PattnaikRashmi R. MohantySonia JoshiAnita MohantyIan W. TurnbullArjen M. DondorpTerrie E. TaylorSamuel C. WassmerAmerican Society for MicrobiologyarticleMRIPRESPlasmodium falciparumvasogenic edemacerebral malariaMicrobiologyQR1-502ENmSphere, Vol 2, Iss 3 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	MRI PRES Plasmodium falciparum vasogenic edema cerebral malaria Microbiology QR1-502
spellingShingle	MRI PRES Plasmodium falciparum vasogenic edema cerebral malaria Microbiology QR1-502 Sanjib Mohanty Laura A. Benjamin Megharay Majhi Premanand Panda Sam Kampondeni Praveen K. Sahu Akshaya Mohanty Kishore C. Mahanta Rajyabardhan Pattnaik Rashmi R. Mohanty Sonia Joshi Anita Mohanty Ian W. Turnbull Arjen M. Dondorp Terrie E. Taylor Samuel C. Wassmer Magnetic Resonance Imaging of Cerebral Malaria Patients Reveals Distinct Pathogenetic Processes in Different Parts of the Brain
description	ABSTRACT The mechanisms underlying the rapidly reversible brain swelling described in patients with cerebral malaria (CM) are unknown. Using a 1.5-Tesla (T) magnetic resonance imaging (MRI) scanner, we undertook an observational study in Rourkela, India, of 11 Indian patients hospitalized with CM and increased brain volume. Among the 11 cases, there were 5 adults and 6 children. All patients had reduced consciousness and various degrees of cortical swelling at baseline. The latter was predominately posterior in distribution. The findings on diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps were consistent with vasogenic edema in all cases. Reversibility after 48 to 72 h was observed in >90% of cases. DWI/ADC mismatch suggested the additional presence of cytotoxic edema in the basal nuclei of 5 patients; all of these had perfusion parameters consistent with vascular engorgement and not with ischemic infarcts. Our results suggest that an impairment of the blood-brain barrier is responsible for the brain swelling in CM. In 5 cases, vasogenic edema occurred in conjunction with changes in the basal nuclei consistent with venous congestion, likely to be caused by the sequestration of Plasmodium falciparum-infected erythrocytes. While both mechanisms have been individually postulated to play an important role in the development of CM, this is the first demonstration of their concurrent involvement in different parts of the brain. The clinical and radiological characteristics observed in the majority of our patients are consistent with posterior reversible encephalopathy syndrome (PRES), and we show for the first time a high frequency of PRES in the context of CM. IMPORTANCE The pathophysiology and molecular mechanisms underlying cerebral malaria (CM) are still poorly understood. Recent neuroimaging studies demonstrated that brain swelling is a common feature in CM and a major contributor to death in pediatric patients. Consequently, determining the precise mechanisms responsible for this swelling could open new adjunct therapeutic avenues in CM patients. Using an MRI scanner with a higher resolution than the ones used in previous reports, we identified two distinct origins of brain swelling in both adult and pediatric patients from India, occurring in distinct parts of the brain. Our results support the hypothesis that both endothelial dysfunction and microvascular obstruction by Plasmodium falciparum-infected erythrocytes make independent contributions to the pathogenesis of CM, providing opportunities for novel therapeutic interventions.
format	article
author	Sanjib Mohanty Laura A. Benjamin Megharay Majhi Premanand Panda Sam Kampondeni Praveen K. Sahu Akshaya Mohanty Kishore C. Mahanta Rajyabardhan Pattnaik Rashmi R. Mohanty Sonia Joshi Anita Mohanty Ian W. Turnbull Arjen M. Dondorp Terrie E. Taylor Samuel C. Wassmer
author_facet	Sanjib Mohanty Laura A. Benjamin Megharay Majhi Premanand Panda Sam Kampondeni Praveen K. Sahu Akshaya Mohanty Kishore C. Mahanta Rajyabardhan Pattnaik Rashmi R. Mohanty Sonia Joshi Anita Mohanty Ian W. Turnbull Arjen M. Dondorp Terrie E. Taylor Samuel C. Wassmer
author_sort	Sanjib Mohanty
title	Magnetic Resonance Imaging of Cerebral Malaria Patients Reveals Distinct Pathogenetic Processes in Different Parts of the Brain
title_short	Magnetic Resonance Imaging of Cerebral Malaria Patients Reveals Distinct Pathogenetic Processes in Different Parts of the Brain
title_full	Magnetic Resonance Imaging of Cerebral Malaria Patients Reveals Distinct Pathogenetic Processes in Different Parts of the Brain
title_fullStr	Magnetic Resonance Imaging of Cerebral Malaria Patients Reveals Distinct Pathogenetic Processes in Different Parts of the Brain
title_full_unstemmed	Magnetic Resonance Imaging of Cerebral Malaria Patients Reveals Distinct Pathogenetic Processes in Different Parts of the Brain
title_sort	magnetic resonance imaging of cerebral malaria patients reveals distinct pathogenetic processes in different parts of the brain
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/758c90c49515420582454e8db74c34fb
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Magnetic Resonance Imaging of Cerebral Malaria Patients Reveals Distinct Pathogenetic Processes in Different Parts of the Brain

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