According to a study published in Clinical Infectious Diseases, pediatric and adult patients with cerebral malaria have distinct pathogenic patterns. Based on quantitative magnetic resonance imaging (MRI) of brains in 65 patients, investigators report that the data supports the development of age-specific adjunct therapies.

Investigators assessed brain volume and performed apparent diffusion coefficient (ADC) histogram analysis in this cohort to compare disease signatures between patients with fatal and nonfatal outcomes, as well as between adults and children.

Investigators did not find significant differences in brain volume between patients with fatal and nonfatal cerebral malaria, but they did observe an age-dependent decrease in brain swelling during acute cerebral malaria. Evidence for brain stem herniation was observed in a third pediatric patients who died, but it was not observed in 4 adults who died. Of those adults who died, 2 had evidence of moderate brain swelling and 2 had no swelling.

Among patients who survived cerebral malaria, a rapid decrease in brain volume at the follow-up MRI as compared with the scan at admission (P =.014) indicated reversible brain swelling is possible after treatment.


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A prominent finding in pediatric patients who survived was diffusion restriction in the deep and subcortical white matter. This was characterized by decreases in ADC, which suggest hypoxia-related cytotoxic edema. In adult patients who survived, however, ADC decreases in the basal ganglia were a prominent feature, indicating focal hypoxia-related cytotoxic edema in deep gray matter structures.

The pediatric patient who experienced brain stem herniation and died had significantly decreased ADCpeak values, suggesting severe cytotoxic brain swelling caused by brain stem herniation as an end stage of fatal pediatric cerebral malaria, said investigators.

The concentration of miRNA-150 upon admission discriminated between adults who died and those who survived but did not discriminate that way in pediatric patients. Concentrations of plasma lipocalin-2 were significantly higher in adults with cerebral malaria when compared with both uncomplicated malaria and pediatric cerebral malaria, and also discriminated between adult patients who survived and those who died. The elevated plasma levels of miRNA-150 and lipocalin-2 along with a global ADC decrease evidenced a different end-stage pattern in adults of severe hypoxia.

According to the investigators, these are the first results to indicate the potential to target these distinct disease courses by specific adjunctive therapy according to age group. In children, alleviating  brain swelling would be more relevant and might be achieved by reducing perivascular inflammation, said investigators. In adults, approaches such as using glutamate agonists, which could ameliorate cytotoxic edema, or other approaches that focus on improving neuroprotection and brain cell survival, may reduce mortality.

Reference

Sahu PK, Hoffmann A, Majhi M, et al. Brain magnetic resonance imaging reveals different courses of disease in pediatric and adult cerebral malaria. Clin Infect Dis. Published online December 16, 2020. doi:10.1093/cid/ciaa1647