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

What is it about?

Cerebral malaria is a severe complication of infection by the malaria parasite Plasmodium falciparum, and is fatal in ~20% of cases despite appropriate antimalarial treatment. The mechanisms leading to death in this neurologic syndrome have until recently been unclear, hindering the development of adjunct therapies. In 2015, a study using magnetic resonance imaging (MRI) in Malawi showed that severe brain swelling was associated with fatal cerebral malaria in children. However, the researchers were unable to identify the mechanisms responsible for this increase in volume due to the low MRI resolution. Here, we used high-field MRI techniques to investigate the origin of brain swelling in cerebral malaria patients, the first such approach. We studied both paediatric and adult patients at our clinical site in Rourkela, India, which has never been done before. Our findings show that brain swelling in both age groups is mainly due to a phenomenon called vasogenic oedema in posterior areas of the brain. This happens when the cerebral vasculature is injured and allows the passage of plasma fluid from the blood into the brain tissue, leading to an increase of volume locally. In half of the patients, signatures of vascular congestion were also seen in a different part of the brain, likely to be due to the accumulation of parasitised red blood cells.

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Why is it important?

Understanding the origin of brain swelling is crucial to design targeted treatments aimed at improving patient survival. Our results indicate that preventing breaches of the blood-brain barrier may reduce brain swelling in cerebral malaria, and thereby open the door to development of novel adjunctive therapies for this deadly complication.