Alternative oblique head CT scanning technique reduces bone artifact and improves interpretability of brainstem anatomy

Brainstem pathology due to infections, infarcts and tumors are common in developing countries, but neuroimaging technology in these resource-poor settings is often limited to single slice, and occasionally spiral, CT. Unlike multislice CT and MRI, single slice and spiral CT are compromised by bone artifacts in the posterior fossa due to the dense petrous bones, often making imaging of the brainstem non-diagnostic. With appropriate head positioning, the petrous ridges can be avoided with 40° sagittal oblique scans parallel to either petrous ridge. We describe an alternative sagittal oblique scanning technique that significantly reduces brainstem CT artifacts thereby improving clarity of anatomy. With Institutional Ethical approval, 13 adult patients were enrolled (5 males; 39%). All patients had routine axial brain CT and sagittal oblique scans with no lesions found. Images were read by 2 readers who gave a score for amount of artefact and clarity of structures in the posterior fossa. The mean artifact score was higher for routine axial images compared to sagittal oblique (2.92 vs. 1.23; P<0.0001). The mean anatomical certainty scores for the brainstem were significantly better in the sagittal oblique views compared to routine axial (1.23 vs. 2.77; P<0.0001). No difference was found between the two techniques with respect to the fourth ventricle or the cerebellum (axial vs. sag oblique: 1.15 vs. 1.27; P=0.37). When using single slice CT, the sagittal oblique scanning technique is valuable in improving clarity of anatomy in the brainstem if axial images are non-diagnostic due to bone artifacts

Magnetic Resonance Imaging in Malawi: Contributions to Clinical Care, Medical Education and Biomedical Research

Advanced medical imaging technologies are generally unavailable in low income, tropical settings despite the reality that neurologic disorders are disproportionately common in such environments. Through a series of donations as well as extramural research funding support, an MRI facility opened in Blantyre, Malawi in July 2008. Resulting opportunities for studying common tropical disorders, such as malaria and schistosomiasis, in vivo are promising. The subsequent improvements in local patient care were expected and exceptional and include major revisions in basic care protocols that may eventually impact care protocols at facilities in the region that do not have recourse to MRI. In addition, advanced neuroimaging technology has energized the medical education system, possibly slowing the brain drain. Advanced technologies, though potentially associated with significant fiscal opportunity costs, may bring unexpected and extensive benefits to the healthcare and medical education systems involved

Magnetic resonance imaging during life: the key to unlock cerebral malaria pathogenesis?

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

Superficial Endobronchial Lung Cancer: Radiologic-Pathologic Correlation

Objective: To analyze the plain chest radiographic and CT findings of superficial endobronchial lung cancer and to correlate these with the findings of histopathology. Materials and Methods: This study involved 19 consecutive patients with pathologically proven lung cancer confined to the bronchial wall. Chest radiographs and CT scans were reviewed for the presence of parenchymal abnormalities, endobronchial nodules, bronchial obstruction, and bronchial wall thickening and stenosis. The CT and histopathologic findings were compared. Results: Sixteen of the 19 patients had abnormal chest radiographic findings, while in 15 (79%), CT revealed bronchial abnormalities: an endobronchial nodule in seven, bronchial obstruction in five, and bronchial wall thickening and stenosis in three. Histopathologically, the lesions appeared as endobronchial nodules in 11 patients, irregular thickening of the bronchial wall in six, elevated mucosa in one, and carcinoma in situ in one. Conclusion: CT helps detect superficial endobronchial lung cancer in 79 % of these patients, though there is some disagreement between the CT findings and the pathologic pattern of bronchial lesions. Although nonspecific, findings of bronchial obstruction or bronchial wall thickening and stenosis should not be overlooked, and if clinically necessary, bronchoscopy should be performed. Index terms: Lung, radiograph

How Does Blood-Retinal Barrier Breakdown Relate to Death and Disability in Pediatric Cerebral Malaria?

Background In cerebral malaria, the retina can be used to understand disease pathogenesis. The mechanisms linking sequestration, brain swelling and death remain poorly understood. We hypothesized that retinal vascular leakage would be associated with brain swelling. Methods We used retinal angiography to study blood-retinal barrier integrity. We analyzed retinal leakage, histopathology, brain MRI, and associations with death and neurological disability in prospective cohorts of Malawian children with cerebral malaria. Results Three types of retinal leakage were seen: Large focal leak (LFL), punctate leak (PL) and vessel leak. LFL and PL were associated with death (OR 13.20, 95%CI 5.21-33.78 and 8.58, 2.56-29.08 respectively), and brain swelling (p<0.05). Vessel leak and macular non-perfusion were associated with neurological disability (3.71, 1.26-11.02 and 9.06, 1.79-45.90). LFL was observed as an evolving retinal hemorrhage. A core of fibrinogen and monocytes was found in 39 (93%) white-centered hemorrhages. Conclusions Blood-retina barrier breakdown occurs in three patterns in cerebral malaria. Associations between LFL, brain swelling, and death suggest that the rapid accumulation of cerebral hemorrhages, with accompanying fluid egress, may cause fatal brain swelling. Vessel leak from barrier dysfunction, and non-perfusion were not associated with severe brain swelling, but with neurological deficits, suggesting hypoxic injury in survivors

Safety of lumbar puncture in comatose children with clinical features of cerebral malaria

Objective: We assessed the independent association of lumbar puncture (LP) and death in Malawian children admitted to the hospital with the clinical features of cerebral malaria (CM). Methods: This was a retrospective cohort study in Malawian children with clinical features of CM. Allocation to LP was nonrandom and was associated with severity of illness. Propensity score-based analyses were used to adjust for this bias and assess the independent association between LP and mortality. Results: Data were available for 1,075 children: 866 (80.6%) underwent LP and 209 (19.4%) did not. Unadjusted mortality rates were lower in children who underwent LP (15.3% vs 26.7% in the no-LP group) but differences in covariates between the 2 groups suggested bias in LP allocation. After propensity score matching, all covariates were balanced. Propensity score-based analyses showed no change in mortality rate associated with LP: by inverse probability weighting, the average risk reduction was 2.0% at 12 hours (95% confidence interval -1.5% to 5.5%, p = 0.27) and 1.7% during hospital admission (95% confidence interval -4.5% to 7.9%, p = 0.60). Undergoing LP did not change the risk of mortality in subanalyses of children with severe brain swelling on MRI or in those with papilledema. Conclusion: In comatose children with suspected CM who were clinically stable, we found no evidence that LP increases mortality, even in children with objective signs of raised intracranial pressur

Parasite histones are toxic to brain endothelium and link blood barrier breakdown and thrombosis in cerebral malaria

Microvascular thrombosis and blood–brain barrier (BBB) breakdown are key components of cerebral malaria (CM) pathogenesis in African children and are implicated in fatal brain swelling. How Plasmodium falciparum infection causes this endothelial disruption and why this occurs, particularly in the brain, is not fully understood. In this study, we have demonstrated that circulating extracellular histones, equally of host and parasite origin, are significantly elevated in CM patients. Higher histone levels are associated with brain swelling on magnetic resonance imaging. On postmortem brain sections of CM patients, we found that histones are colocalized with P falciparum–infected erythrocytes sequestered inside small blood vessels, suggesting that histones might be expelled locally during parasite schizont rupture. Histone staining on the luminal vascular surface colocalized with thrombosis and leakage, indicating a possible link between endothelial surface accumulation of histones and coagulation activation and BBB breakdown. Supporting this, patient sera or purified P falciparum histones caused disruption of barrier function and were toxic to cultured human brain endothelial cells, which were abrogated with antihistone antibody and nonanticoagulant heparin. Overall, our data support a role for histones of parasite and host origin in thrombosis, BBB breakdown, and brain swelling in CM, processes implicated in the causal pathway to death. Neutralizing histones with agents such as nonanticoagulant heparin warrant exploration to prevent brain swelling in the development or progression of CM and thereby to improve outcomes