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Published on: January 2, 2013
Pathophysiology and neurologic sequelae of cerebral malaria
Nicoline Schiess1, Andres Villabona-Rueda2, Karissa E Cottier2,3
1Department of Neurology, Johns Hopkins School of Medicine, 600 N. Wolfe St., Meyer 6-113, Baltimore, MD, 21287, USA.
Abstract:
Cerebral malaria (CM), results from Plasmodium falciparum infection, and has a high mortality rate. CM survivors can retain life-long post CM sequelae, including seizures and neurocognitive deficits profoundly affecting their quality of life. As the Plasmodium parasite does not enter the brain, but resides inside erythrocytes and are confined to the lumen of the brain's vasculature, the neuropathogenesis leading to these neurologic sequelae is unclear and under-investigated. Interestingly, postmortem CM pathology differs in brain regions, such as the appearance of haemorragic punctae in white versus gray matter. Various host and parasite factors contribute to the risk of CM, including exposure at a young age, parasite- and host-related genetics, parasite sequestration and the extent of host inflammatory responses. Thus far, several proposed adjunctive treatments have not been successful in the treatment of CM but are highly needed. The region-specific CM neuro-pathogenesis leading to neurologic sequelae is intriguing, but not sufficiently addressed in research. More attention to this may lead to the development of effective adjunctive treatments to address CM neurologic sequelae.
Insights
Cerebral malaria (CM) causes severe neurological issues, even in survivors. Understanding the brain
Area of Science:
- Neurology
- Infectious Diseases
- Pathology
Background:
- Cerebral malaria (CM), a severe Plasmodium falciparum infection, has high mortality rates.
- Survivors often experience life-long neurological sequelae, including seizures and neurocognitive deficits.
- The exact neuropathogenesis of these sequelae remains unclear as the parasite does not invade brain tissue.
Purpose of the Study:
- To investigate the region-specific neuropathogenesis of cerebral malaria.
- To explore the underlying mechanisms leading to post-CM neurological deficits.
- To identify potential targets for adjunctive treatments for CM sequelae.
Main Methods:
- Analysis of postmortem CM pathology.
- Examination of regional differences in brain lesions (e.g., white vs. gray matter).
- Review of host and parasite factors influencing CM risk and severity.
Main Results:
- Postmortem CM pathology exhibits regional variations, notably hemorrhagic punctae in white matter compared to gray matter.
- Host and parasite factors, including genetics and inflammatory responses, influence CM risk.
- Current adjunctive treatments have shown limited success in managing CM.
Conclusions:
- Region-specific neuropathogenesis is a critical, under-investigated aspect of CM.
- Further research into these mechanisms may facilitate the development of effective adjunctive therapies.
- Addressing neurological sequelae requires a deeper understanding of CM's impact on the brain.
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