Last Updated: 21/07/2023

Investigating the role of cerebral vasoconstriction in cerebral malaria

Objectives

The main objectives of this study are:

  1. to investigate the occurrence, frequency and amplitude of cerebral vasoconstriction in CM patients at IGH by combining for the first time serial vascular imaging including time-­of-­flight and phase-­contrast magnetic resonance angiography , as well as cerebral perfusion measurements and assessment of subtle blood-­brain barrier disruption; and
  2. evaluate the clinical relevance of known vasoconstrictors and endothelial permeability factors as biomarkers of this phenomenon by comparing imaging results with plasma levels of endothelin-­1 (ET-­1), angiopoietin-­1(Ang-­1), Ang-­2 and free heme in adults and pediatric CM patients at Ispat General Hospital (IGH).
Principal Investigators / Focal Persons

Samuel Wassmer

Rationale and Abstract

Plasmodium falciparum malaria is a major cause of mortality and morbidity in the developing world and cerebral malaria (CM), its most severe form, accounts for the majority of malaria-­associated deaths. The pathophysiology and the molecular mechanisms underlying this complex neurologic syndrome are still poorly understood, which has hindered the development of effective adjunct therapies. For this exploratory project, the researchers will leverage LSHTM International Center of Excellence for Malaria Research in India to expand the unique ongoing MRI investigations in both adults and pediatric CM patients admitted at Ispat General Hospital (IGH) in Rourkela, and apply advanced magnetic resonance imaging techniques in the first comprehensive vascular imaging analysis of its kind. Novel findings suggest that reversible cerebral vasoconstriction syndrome (RCVS) alone or in combination with posterior reversible encephalopathy syndrome (PRES) may play a role in the pathophysiology of CM. The primary outcome of this project will be a better understanding of the different pathogenetic processes involved in pediatric and adult CM, which will guide the development of new adjunct therapies.

Date

Feb 2019 — Jan 2021

Total Project Funding

$290,362

Project Site

India

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