Abstract
Understanding the mechanisms underlying the pathophysiology of cerebral malaria in patients with Plasmodium falciparum infection is necessary to implement new curative interventions. While autopsy-based studies shed some light on several pathological events that are believed to be crucial in the development of this neurologic syndrome, their investigative potential is limited and has not allowed the identification of causes of death in patients who succumb to it. This can only be achieved by comparing features between patients who die from cerebral malaria and those who survive. In this review, several alternative approaches recently developed to facilitate the comparison of specific parameters between fatal, non-fatal cerebral malaria and uncomplicated malaria patients are described, as well as their limitations. The emergence of neuroimaging as a revolutionary tool in identifying critical structural and functional modifications of the brain during cerebral malaria is discussed and highly promising areas of clinical research using magnetic resonance imaging are highlighted.
Highlights
An estimated 3.3 billion people were at risk of malaria in 2011, with populations living in sub-Saharan Africa representing approximately 80% of cases and 90% of malaria-related deaths [1]
A study performed in Malaŵi and restricted to retinopathy-positive cerebral malaria (CM) patients demonstrated that acute computed tomography (CT) scans reveal findings consistent with autopsy reports, and that the presence of diffuse brain swelling, whether it involves the brainstem or not, was associated with protracted coma and death [53]
It revealed that increased brain volume and swelling was common in patients with CM, but this difference was attributed to an increase of the volume of intracerebral blood caused by sequestration of infected erythrocytes (IE) rather than cerebral oedema [63]
Summary
An estimated 3.3 billion people were at risk of malaria in 2011, with populations living in sub-Saharan Africa representing approximately 80% of cases and 90% of malaria-related deaths [1]. A study performed in Malaŵi and restricted to retinopathy-positive CM patients demonstrated that acute CT scans reveal findings consistent with autopsy reports, and that the presence of diffuse brain swelling, whether it involves the brainstem or not, was associated with protracted coma and death [53]. The first MRI study of a large series of patients with malaria living in an endemic area was performed in Thailand in 1995 in adults using a 0.2 Tesla scanner It revealed that increased brain volume and swelling was common in patients with CM, but this difference was attributed to an increase of the volume of intracerebral blood caused by sequestration of IE rather than cerebral oedema [63]. All of these limiting factors need to be carefully considered for any prospective study of CM patients using MRI techniques
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