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

The spectrum of heart disease in adults in Malawi: A review of the literature with reference to the importance of echocardiography as a diagnostic modality

No Abstrac

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

Stroke Outcomes in Malawi, a Country with High Prevalence of HIV: A Prospective Follow-Up Study

Peer reviewe

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

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

The Role of Human Immunodeficiency Virus-Associated Vasculopathy in the Etiology of Stroke

Background: Human immunodeficiency virus (HIV) infection is a recognized risk factor for stroke among young populations, but the exact mechanisms are poorly understood. We studied the clinical, radiologic, and histologic features of HIV-related ischemic stroke to gain insight into the disease mechanisms. Methods: We conducted a prospective, in-depth analysis of adult ischemic stroke patients presenting to Queen Elizabeth Central Hospital, Blantyre, Malawi, in 2011. Results: We recruited 64 HIV-infected and 107 HIV-uninfected patients. Those with HIV were significantly younger (P < .001) and less likely to have established vascular risk factors. Patients with HIV were more likely to have large artery disease (21% vs 10%; P < .001). The commonest etiology was HIV-associated vasculopathy (24 [38%]), followed by opportunistic infections (16 [25%]). Sixteen of 64 (25%) had a stroke soon after starting antiretroviral therapy (ART), suggesting an immune reconstitution-like syndrome. In this group, CD4+ T-lymphocyte count was low, despite a significantly lower HIV viral load in those recently started on treatment (P < .001). Conclusions: HIV-associated vasculopathy and opportunistic infections are common causes of HIV-related ischemic stroke. Furthermore, subtypes of HIV-associated vasculopathy may manifest as a result of an immune reconstitution-like syndrome after starting ART. A better understanding of this mechanism may point toward new treatments

Utilization of ultrasound in medical inpatients in Malawi.

BACKGROUND Ultrasound utilization studies in the developing world are important to support appropriate use. METHODS A prospective, cross-sectional study in the medical wards at Queen Elizabeth Central Hospital, Blantyre, Malawi, was performed which aimed to assess referrals, reports and usefulness of scans to develop local recommendations. The primary outcome of a 'useful scan' was based on scan results and utilization of the report. Indication, quality of requests and reports, and operator were documented. Recommendations for request and report writing were developed. RESULTS During 28 April-1 June 2011, 96 scans were analysed of which 66 (69%) were useful. Scans were not useful when the report was non-diagnostic, not documented or not acted upon. Seventy-eight scans (82%) were requested without prior laboratory investigations. A working diagnosis of a pericardial effusion was significantly associated with a useful scan (p = 0.01) as was a medical history of HIV (p ≤ 0.001). The quality of requests and reports in terms of clinical information was moderate or poor in 73% and 33% of cases respectively. Scans by clinicians were at greater odds (OR = 4.0, p = 0.01) of being useful compared with those by radiology technicians. CONCLUSION Despite the majority of ultrasound scans being useful, underutilization and non-useful scans were common, indicating the need to identify appropriate indications and develop relevant guidance and training