Douglas G. Postels

The Interaction of Malnutrition and Neurologic Disability in Africa

Malnutrition and neurodisability are both major public health problems in Africa. This review highlights key areas where they interact. This happens throughout life and starts with maternal malnutrition affecting fetal neurodevelopment with both immediate (eg, folate deficiency causing neural tube defects) and lifelong implications (eg, impaired cognitive function). Maternal malnutrition can also increase the risk of perinatal problems, including birth asphyxia, a major cause of neurologic damage and cerebral palsy. Macronutrient malnutrition can both cause and be caused by neurodisability. Mechanisms include decreased food intake, increased nutrient losses, and increased nutrient requirement. Specific micronutrient deficiencies can also lead to neurodisability, for example, blindness (vitamin A), intractable epilepsy (vitamin B6), and cognitive impairment (iodine and iron). Toxin ingestion (eg, from poorly processed cassava) can cause neurodisability including a peripheral polyneuropathy and a spastic paraparesis. We conclude that there is an urgent need for nutrition and disability programs to work more closely together.

Neurologic outcomes in retinopathy- negative cerebral malaria survivors

Objectives: Patients surviving retinopathy-positive cerebral malaria (CM) are at high risk for the development of epilepsy, developmental disabilities, and behavioral abnormalities. We aimed to establish whether retinopathy-negative CM is also a risk factor for these outcomes. Methods: Between 2005 and 2007, survivors of CM and concurrently hospitalized controls in Blantyre, Malawi, were followed to assess the development of neurologic abnormalities. At discharge and every 3 months thereafter, incident cases of epilepsy and developmental disabilities were ascertained using screening questionnaires and confirmatory neurologic examinations. Incident cases of epilepsy and developmental disabilities were compared in retinopathy-negative CM survivors to controls and retinopathy-positive CM survivors. Results: Thirty-five retinopathy-negative CM survivors were enrolled. Their neurologic outcomes were compared to 132 retinopathy-positive CM survivors and 272 controls. Compared to survivors of retinopathy-positive CM, children without malaria retinopathy have an equal odds of adverse neurologic outcome (odds ratio [OR] = 1.0, 95% confidence interval [CI] 0.4–2.2). Eleven of 35 survivors of retinopathy-negative CM had at least 1 adverse neurologic outcome compared to 2 of 272 controls (OR 61.9, 95% CI 13.0–295.5). In retinopathy-negative CM survivors, a Blantyre Coma Scale score ≤1 on admission was associated with an adverse outcome. Conclusions: Compared with controls, children surviving either retinopathy-negative or -positive CM are at similar high risk for adverse neurologic outcomes. Studies to evaluate preventive and therapeutic strategies in children with both retinopathy-negative and -positive CM are needed to improve mortality, morbidity, or both.

Assessment of Neurodisability and Malnutrition in Children in Africa

Neurodevelopmental delay, neurodisability, and malnutrition interact to contribute a significant burden of disease in global settings. Assessments which are well integrated with plans of management or advice are most likely to improve outcomes. Assessment tools used in clinical research and programming to evaluate outcomes include developmental and cognitive tools that vary in complexity, sensitivity, and validity as well as the target age of assessment. Few tools have been used to measure socioemotional outcomes and fewer to assess the disabled child with malnutrition. There is a paucity of tools used clinically which actually provide families and professionals with advice to improve outcomes. Brain imaging, electroencephalography, audiology, and visual assessment can also be used to assess the effect of malnutrition on brain structure and function. The interaction of neurodisability and malnutrition is powerful, and both need to be considered when assessing children. Without an integrated approach to assessment and management, we will not support children and families to reach their best potential outcomes.

Children with retinopathy-negative cerebral malaria: a pathophysiologic puzzle.

Background: Cerebral malaria, defined as otherwise unexplained coma in a patient with circulating parasitemia, is a common disease in the developing world. The clinical diagnosis lacks specificity and children with other underlying causes of coma might be misdiagnosed as having cerebral malaria. The presence of malarial retinopathy can be used to differentiate children whose comas are caused by Plasmodium falciparum and its attendant pathophysiologies from those with other reasons for their abnormal mental status. Children with cerebral malaria who lack malarial retinopathy have not previously been described. Methods: All patients admitted to Queen Elizabeth Central Hospital in Blantyre, Malawi, during a 12-month period with a clinical diagnosis of cerebral malaria were evaluated for the presence of malarial retinopathy. Thirty-two patients lacked retinopathy findings. Clinical, laboratory, and radiologic information data were collected. Results: Thirty-two cases of retinopathy-negative cerebral malaria are presented. Conclusions: Children with retinopathy-negative cerebral malaria share a common clinical phenotype with lower rates of mortality compared with those who have malarial retinopathy. There are at least 4 possible pathophysiologic explanations for this common condition.

Chapter 6 - Cerebral malaria

Malaria, the most significant parasitic disease of man, kills approximately one million people per year. Half of these deaths occur in those with cerebral malaria (CM). The World Health Organization (WHO) defines CM as an otherwise unexplained coma in a patient with malarial parasitemia. Worldwide, CM occurs primarily in African children and Asian adults, with the vast majority (greater than 90%) of cases occurring in children 5 years old or younger in sub-Saharan Africa. The pathophysiology of the disease is complex and involves infected erythrocyte sequestration, cerebral inflammation, and breakdown of the blood-brain barrier. A recently characterized malarial retinopathy is visual evidence of Plasmodium falciparums pathophysiological processes occurring in the affected patient. Treatment consists of supportive care and antimalarial administration. Thus far, adjuvant therapies have not been shown to improve mortality rates or neurological outcomes in children with CM. For those who survive CM, residual neurological abnormalities are common. Epilepsy, cognitive impairment, behavioral disorders, and gross neurological deficits which include motor, sensory, and language impairments are frequent sequelae. Primary prevention strategies, including bed nets, vaccine development, and chemoprophylaxis, are in varied states of development and implementation. Continuing efforts to find successful primary prevention options and strategies to decrease neurological sequelae are needed.

Prevalence of depression in Parkinson’s disease patients in Ethiopia

BackgroundParkinson’s disease (PD) is associated with cognitive and psychiatric disturbances including depression, anxiety, psychotic symptoms and sleep disturbances. These psychiatric manifestations have a negative impact on disease course and the medical management of PD patients. Major depression has a greater negative impact on patients’ quality of life than abnormal motor function, and is associated with faster cognitive decline and progression of motor deficits. Thus, the objective of this study was to determine the prevalence and pattern of depression in PD outpatients in Ethiopia. We determined the age range in which depression in PD patients is most common, the most common symptoms of depression, and the epidemiologic confounders associated with depression in PD patients.MethodsWe conducted a cross-sectional point prevalence study of all PD patients attending the follow-up clinics of the departments of neurology at Black Lion Teaching and Zewuditu Memorial Hospitals in Addis Ababa, Ethiopia, from May 2013 to August 2013. We collected information using a structured questionnaire which assessed demographic information, clinical history, and neurologic function.ResultOf the 101 patients surveyed, the prevalence of depression was 58/101(57.4%). Of these patients, 1 of 58(1.7%) was on antidepressant medications. These low proportions likely indicate a low index of suspicion and under treatment of depression in PD outpatients.ConclusionIn Ethiopian PD outpatients, depression is under recognized and undertreated. We recommend routine use of screening tools. In those who screen positive for depression, treatment is warranted. Further studies are needed to confirm these findings, and to increase our understanding of specific signs and symptoms of depression in the context of PD.

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 pressure.

Evidence from a natural experiment that malaria parasitemia is pathogenic in retinopathy-negative cerebral malaria

Cerebral malaria (CM) can be classified as retinopathy-positive or retinopathy-negative, based on the presence or absence of characteristic retinal features. While malaria parasites are considered central to the pathogenesis of retinopathy-positive CM, their contribution to retinopathy-negative CM is largely unknown. One theory is that malaria parasites are innocent bystanders in retinopathy-negative CM and the etiology of the coma is entirely non-malarial. Because hospitals in malaria-endemic areas often lack diagnostic facilities to identify non-malarial causes of coma, it has not been possible to evaluate the contribution of malaria infection to retinopathy-negative CM. To overcome this barrier, we studied a natural experiment involving genetically inherited traits, and find evidence that malaria parasitemia does contribute to the pathogenesis of retinopathy-negative CM. A lower bound for the fraction of retinopathy-negative CM that would be prevented if malaria parasitemia were to be eliminated is estimated to be 0.93 (95% confidence interval: 0.68, 1). DOI: http://dx.doi.org/10.7554/eLife.23699.001

Seasonal differences in retinopathy-negative versus retinopathy-positive cerebral malaria.

Children with traditionally defined cerebral malaria (CM) can be subcategorized by the presence or absence of malaria retinopathy. We retrospectively reviewed the seasonal pattern of retinopathy status in patients admitted with CM in Blantyre, Malawi from 1997 to 2010. The proportion of children with CM who were retinopathy-positive was significantly greater during the peak seasonal rains when the community incidence of uncomplicated malaria is higher. This finding supports the hypothesis that retinopathy-negative and retinopathy-positive CM categories have different underlying etiologies.

Brain MRI of Children with Retinopathy-Negative Cerebral Malaria

Our goals were to understand the brain magnetic resonance imaging (MRI) findings in children with retinopathy-negative cerebral malaria (CM) and investigate whether any findings on acute MRI were associated with adverse outcomes. We performed MRI scans on children admitted to the hospital in Blantyre, Malawi with clinically defined CM. Two hundred and seventeen children were imaged during the study period; 44 patients were malarial retinopathy-negative; and 173 patients were retinopathy-positive. We compared MRI findings in children with retinopathy-negative and retinopathy-positive CM. In children who were retinopathy-negative, we identified MRI variables that were associated with death and adverse neurologic outcomes. On multivariate analysis, cortical diffusion weighted imaging (DWI) abnormality and increased brain volume were strongly associated with neurologic morbidity in survivors. Investigations to explore the underlying pathophysiologic processes responsible for these MRI changes are warranted.