Background: Dysphagia has been reported in up to 70% of patients with stroke, predisposing them to aspiration and pneumonia. Despite this, the mechanism for aspiration remains unclear. Aims: To determine the relationship between bolus flow and laryngeal closure during swallowing in patients with stroke and to examine the sensorimotor mechanisms leading to aspiration. Methods: Measures of swallowing and bolus flow were taken from digital videofluoroscopic images in 90 patients with stroke and 50 healthy adults, after repeated volitional swallows of controlled volumes of thin liquid. Aspiration was assessed using a validated Penetration-Aspiration Scale. Oral sensation was also measured by electrical stimulation at the faucial pillars. Results: After stroke, laryngeal ascent was delayed (mean (standard deviation (SD)) 0.31 (0.06) s, p,0.001), resulting in prolongation of pharyngeal transit time (1.17 (0.07) s, p,0.001) without a concomitant increase in laryngeal closure duration (0.84 (0.04) s, p = 0.9). The delay in laryngeal elevation correlated with both the severity of aspiration (r = 0.5, p,0.001) and oral sensation (r = 0.5, p,0.001). Conclusions: After stroke, duration of laryngeal delay and degree of sensory deficit are associated with the severity of aspiration. These findings indicate a role for sensorimotor interactions in control of swallowing and have implications for the assessment and management of dysphagia after stroke.

Deglutitive aspiration is common after stroke, affecting up to 50% of patients and predisposing them to pneumonia, yet it is virtually impossible to predict those patients at greatest risk. The aim of this study was to develop a robust predictive model for aspiration after stroke. Swallowing was assessed by digital videofluoroscopy (VF) in 90 patients following hemispheric stroke. Lesion characteristics were determined by computerized tomography (CT) brain scan using the Alberta Stroke Programme Early CT Score (ASPECTS). Aspiration severity was measured using a validated penetration-aspiration scale. The probability of aspiration was then determined from measures of swallowing pathophysiology and lesion location by discriminant analysis. Aspiration was observed in 47 (52%) patients, yet despite disrupted swallowing physiology, intrasubject aspiration scores were variable. The best discriminant model combined pharyngeal transit time, swallow response time, and laryngeal closure duration to predict 73.11% of those aspirating (sensitivity = 66.54, specificity = 80.22, p > 0.001). The addition of lesion location did not add anything further to the predictive model. We conclude that the pathophysiology of poststroke aspiration is multifactorial but in most cases can be predicted by three key swallowing measurements. These measurements, if translatable into clinical bedside evaluation, may assist with the development of novel measurement and intervention techniques to detect and treat poststroke aspiration.

The pathophysiology and molecular mechanisms underlying cerebral malaria (CM) are still poorly understood. Recent neuroimaging studies demonstrated that brain swelling is a common feature in CM and a major contributor to death in pediatric patients. Consequently, determining the precise mechanisms responsible for this swelling could open new adjunct therapeutic avenues in CM patients. Using an MRI scanner with a higher resolution than the ones used in previous reports, we identified two distinct origins of brain swelling in both adult and pediatric patients from India, occurring in distinct parts of the brain. Our results support the hypothesis that both endothelial dysfunction and microvascular obstruction by Plasmodium falciparum-infected erythrocytes make independent contributions to the pathogenesis of CM, providing opportunities for novel therapeutic interventions.

Background Cerebral malaria is a common presentation of severe Plasmodium falciparum infection and remains an important cause of death in the tropics. Key aspects of its pathogenesis are still incompletely understood, but severe brain swelling identified by magnetic resonance imaging (MRI) was associated with a fatal outcome in African children. In contrast, neuroimaging investigations failed to identify cerebral features associated with fatality in Asian adults. Methods Quantitative MRI with brain volume assessment and apparent diffusion coefficient (ADC) histogram analyses were performed for the first time in 65 patients with cerebral malaria to compare disease signatures between children and adults from the same cohort, as well as between fatal and nonfatal cases. Results We found an age-dependent decrease in brain swelling during acute cerebral malaria, and brain volumes did not differ between fatal and nonfatal cases across both age groups. In nonfatal disease, reversible, hypoxia-induced cytotoxic edema occurred predominantly in the white matter in children, and in the basal ganglia in adults. In fatal cases, quantitative ADC histogram analyses also demonstrated different end-stage patterns between adults and children: Severe hypoxia, evidenced by global ADC decrease and elevated plasma levels of lipocalin-2 and microRNA-150, was associated with a fatal outcome in adults. In fatal pediatric disease, our results corroborate an increase in brain volume, leading to augmented cerebral pressure, brainstem herniation, and death. Conclusions Our findings suggest distinct pathogenic patterns in pediatric and adult cerebral malaria with a stronger cytotoxic component in adults, supporting the development of age-specific adjunct therapies.