Brain Magnetic Resonance Imaging Reveals Different Courses of Disease in Pediatric and Adult Cerebral Malaria.

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.

An overview of the management of pseudoaneurysm of the maxillary artery: a report of a case following mandibular subcondylar osteotomy.

BACKGROUND: Aneurysms, pseudoaneurysms, and arteriovenous malformations of the maxillary artery are rare. This is why this case report and current opinions regarding therapy are presented. PATIENT: A 41 year old woman presented in 1991 with recurrent pain and swelling in the right infra-auricular region of 3 years duration which was unresponsive to antibiotics. She had undergone subcondylar osteotomies elsewhere 5 years previously. Imaging revealed a rounded radiolucency of the upper posterior border of the right mandibular ramus with calcification posterior to the radiolucency. The lesion was surgically treated by packing, diathermy and ligation of the external carotid artery and has now resolved completely. Methods for the management of pseudoaneurysms, arteriovenous fistulae and haemorrhage from the maxillary artery include angiography both for initial diagnosis of pseudoaneurysm, arteriovenous malformation and haemorrhage and, if suitable their treatment with endovascular occlusants. The advantages and drawbacks of surgery versus endarterial occlusion are rehearsed. CONCLUSION: Although endovascular intervention has become the first line approach, particulate embolization is more commonly used as a pre-operative technique. Lesions like one described here can of course be managed by surgery alone if sophistizated facilities and skill were not available.

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

The mechanisms underlying the rapidly reversible brain swelling described in patients with cerebral malaria (CM) are unknown. Using a 1.5-Tesla (T) magnetic resonance imaging (MRI) scanner, we undertook an observational study in Rourkela, India, of 11 Indian patients hospitalized with CM and increased brain volume. Among the 11 cases, there were 5 adults and 6 children. All patients had reduced consciousness and various degrees of cortical swelling at baseline. The latter was predominately posterior in distribution. The findings on diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps were consistent with vasogenic edema in all cases. Reversibility after 48 to 72 h was observed in >90% of cases. DWI/ADC mismatch suggested the additional presence of cytotoxic edema in the basal nuclei of 5 patients; all of these had perfusion parameters consistent with vascular engorgement and not with ischemic infarcts. Our results suggest that an impairment of the blood-brain barrier is responsible for the brain swelling in CM. In 5 cases, vasogenic edema occurred in conjunction with changes in the basal nuclei consistent with venous congestion, likely to be caused by the sequestration of Plasmodium falciparum-infected erythrocytes. While both mechanisms have been individually postulated to play an important role in the development of CM, this is the first demonstration of their concurrent involvement in different parts of the brain. The clinical and radiological characteristics observed in the majority of our patients are consistent with posterior reversible encephalopathy syndrome (PRES), and we show for the first time a high frequency of PRES in the context of CM. IMPORTANCE 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.

Reliability of a semi-automated technique of cerebral infarct volume measurement with CT.

BACKGROUND: A reliable method of infarct volume measurement is needed if infarct volume is to be used as an outcome measure in clinical stroke trials. We investigated the reproducibility of a semi-automated method of computed tomography (CT) infarct volume measurement amongst three stroke research fellows with no formal neuroradiology training and two consultant neuroradiologists. METHODS: CT brain scans for volumetric analysis were performed at 5 to 7 days in 34 patients with acute ischaemic stroke, of which 28 scans showed visible recent infarction. Five observers independently traced the infarct boundary on digitised images with a cursor. Volumetric analysis incorporated pixel thresholding with preset Hounsfield thresholds. One of the observers repeated the analyses on 21 of the scans in order to assess intraobserver variation. RESULTS: Median infarct volume was 35.7 cm3 (range 0.2-318 cm3). The closest limits of observed agreement (mean +/- 1.96 SD) between pairs of observers were between a research fellow and neuroradiologist (-29 to 21 cm3). The widest limits of agreement were between a different research fellow and the same neuroradiologist (-39.1 to 41.4 cm3). The limits of agreement between infarct volumes measured on two separate occasions by one of the research fellows were -7 to 8 cm3. CONCLUSIONS: Intraobserver reliability of CT infarct volume measurements performed by a stroke research fellow was superior to interobserver reliability between any pair of observers. The wide limits of agreement between different observers using manual tracing may not be acceptable in multicentre trials of acute ischaemic stroke treatment, but volume measurement by a single observer appears to be more reliable.