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Objective: To investigate the rate of transient thyroid deficiency and treatment compliance among cases with congenital hypothyroidism diagnosed and followed-up after age 3 years by newborn screening (NBS). Study design: Cases detected by Michigan NBS between October 1, 2003, and December 31, 2007, and followed-up after age 3 years were included. The χ2 and Fisher exact tests were used to test differences among followed and lost cases. Logistic regression models were used to investigate predictors of treatment cessation. Results: Roughly 45% of eligible cases were lost to follow-up, and disease state (transient or permanent congenital hypothyroidism) could not be determined for 12 cases (7.9%). Of the 72 followed cases, 34 (47%) were considered permanent congenital hypothyroidism based on thyroid imaging findings (n = 7) or an increase in medication dosage over time (n = 27). One-quarter of followed cases with congenital hypothyroidism were no longer being treated, and of these, just over 83% stopped treatment without medical supervision. Of 23 cases that underwent a medically supervised trial without thyroid hormone medication, treatment was reinstated in 20. Laboratory confirmation of euthyroidism was available for 6 of 18 cases clinically deemed transient. After adjustment, black race was the strongest predictor of treatment cessation (OR, 9.86; 95% CI, 1.82-53.31). Treatment cessation was also more common among low birth weight infants and those admitted to the neonatal intensive care unit at birth. Conclusion: We recommend that NBS programs include long-term follow-up through at least age 3 years to determine treatment compliance and disease permanence. Further research is needed to determine ideal follow-up program operations and reassessment methods for congenital hypothyroidism disease permanence. Guidelines that provide evidence-based reassessment methods would be beneficial for the healthcare providers of children with congenital hypothyroidism. [Copyright &y& Elsevier]

Summary: Background: Cerebral malaria, a disorder characterised by coma, parasitaemia, and no other evident cause of coma, is challenging to diagnose definitively in endemic regions that have high rates of asymptomatic parasitaemia and limited neurodiagnostic facilities. A recently described malaria retinopathy improves diagnostic specificity. We aimed to establish whether retinopathy-positive cerebral malaria is a risk factor for epilepsy or other neurodisabilities. Methods: Between 2005 and 2007, we did a prospective cohort study of survivors of cerebral malaria with malaria retinopathy in Blantyre, Malawi. Children with cerebral malaria were identified at the time of their index admission and age-matched to concurrently admitted children without coma or nervous system infection. Initially matching of cases to controls was 1:1 but, in 2006, enrolment criteria for cerebral malaria survivors were revised to limit inclusion to children with cerebral malaria and retinopathy on the basis of indirect ophthalmoscopic examination; matching was then changed to 1:2 and the revised inclusion criteria were applied retrospectively for children enrolled previously. Clinical assessments at discharge and standardised nurse-led follow-up every 3 months thereafter were done to identify children with new seizure disorders or other neurodisabilities. A Kaplan-Meier survival analysis was done for incident epilepsy. Findings: 132 children with retinopathy-positive cerebral malaria and 264 age-matched, non-comatose controls were followed up for a median of 495 days (IQR 195–819). 12 of 132 cerebral malaria survivors developed epilepsy versus none of 264 controls (odds ratio [OR] undefined; p<0·0001). 28 of 121 cerebral malaria survivors developed new neurodisabilities, characterised by gross motor, sensory, or language deficits, compared with two of 253 controls (OR 37·8, 95% CI 8·8–161·8; p<0·0001). The risk factors for epilepsy in children with cerebral malaria were a higher maximum temperature (39·4°C [SD 1·2] vs 38·5°C [1·1]; p=0·01) and acute seizures (11/12 vs 76/120; OR 6·37, 95% CI 1·02–141·2), and male sex was a risk factor for new neurodisabilities (20/28 vs 38/93; OR 3·62, 1·44–9·06). Interpretation: Almost a third of retinopathy-positive cerebral malaria survivors developed epilepsy or other neurobehavioural sequelae. Neuroprotective clinical trials aimed at managing hyperpyrexia and optimising seizure control are warranted. Funding: US National Institutes of Health and Wellcome Trust. [Copyright &y& Elsevier]

Abstract: Purpose: To describe brain CT findings in retinopathy-confirmed, paediatric cerebral malaria. Materials and methods: In this outcomes study of paediatric cerebral malaria, a subset of children with protracted coma during initial presentation was scanned acutely. Survivors experiencing adverse neurological outcomes also underwent a head CT. All children had ophthalmological examination to confirm the presence of the retinopathy specific for cerebral malaria. Independent interpretation of CT images was provided by two neuroradiologists. Results: Acute brain CT findings in three children included diffuse oedema with obstructive hydrocephalus (2), acute cerebral infarctions in multiple large vessel distributions with secondary oedema and herniation (1), and oedema of thalamic grey matter (1). One child who was reportedly normal prior to admission had parenchymal atrophy suggestive of pre-existing CNS injury. Among 56 survivors (9–84 months old), 15 had adverse neurologic outcomes—11/15 had a follow-up head CT, 3/15 died and 1/15 refused CT. Follow-up head CTs obtained 7–18 months after the acute infection revealed focal and multifocal lobar atrophy correlating to regions affected by focal seizures during the acute infection (5/11). Other findings were communicating hydrocephalus (2/11), vermian atrophy (1/11) and normal studies (3/11). Conclusions: The identification of pre-existing imaging abnormalities in acute cerebral malaria suggests that population-based studies are required to establish the rate and nature of incidental imaging abnormalities in Malawi. Children with focal seizures during acute cerebral malaria developed focal cortical atrophy in these regions at follow-up. Longitudinal studies are needed to further elucidate mechanisms of CNS injury and death in this common fatal disease. [Copyright &y& Elsevier]

Summary: Background: Among the 40 million people with epilepsy worldwide, 80% reside in low-income regions where human and technological resources for care are extremely limited. Qualitative and experiential reports indicate that people with epilepsy in Africa are also disadvantaged socially and economically, but few quantitative systematic data are available. We sought to assess the social and economic effect of living with epilepsy in sub-Saharan Africa. Methods: We did a cross-sectional study of people with epilepsy concurrently matched for age, sex, and site of care to individuals with a non-stigmatised chronic medical condition. Verbally administered questionnaires provided comparison data for demographic characteristics, education, employment status, housing and environment quality, food security, healthcare use, personal safety, and perceived stigma. Findings: People with epilepsy had higher mean perceived stigma scores (1·8 vs 0·4; p<0·0001), poorer employment status (p=0·0001), and less education (7·1 vs 9·4 years; p<0·0001) than did the comparison group. People with epilepsy also had less education than their nearest-age same sex sibling (7·1 vs 9·1 years; p<0·0001), whereas the comparison group did not (9·4 vs 9·6 years; p=0·42). Housing and environmental quality were poorer for people with epilepsy, who had little access to water, were unlikely to have electricity in their home (19%vs 51%; p<0·0001), and who had greater food insecurity than did the control group. During pregnancy, women with epilepsy were more likely to deliver at home rather than in a hospital or clinic (40%vs 15%; p=0·0007). Personal safety for people with epilepsy was also more problematic; rape rates were 20% among women with epilepsy vs 3% in the control group (p=0·004). Interpretation: People with epilepsy in Zambia have substantially poorer social and economic status than do their peers with non-stigmatised chronic medical conditions. Suboptimum housing quality differentially exposes these individuals to the risk of burns and drowning during a seizure. Vulnerability to physical violence is extreme, especially for women with epilepsy. [Copyright &y& Elsevier]

Those uninitiated to medicine in the tropics may consider neurology and neurologists superfluous in this environment. In actual fact, the high burden of neurologic disorders combined with a dearth of physician-level care providers brings such expertise into high demand. Clinical work in sub-Saharan Africa offers the neurologist an opportunity to care for a wide range of conditions, including disorders Westerners may only be familiar with via historical accounts. Physicians starved of academic exchange and paramedical-care providers who frequently function without physician-level support are equally enthusiastic for additional training in the diagnosis and treatment of the nervous system disorders which are encountered daily. [Copyright &y& Elsevier]

There are an estimated 1.5 million children living with human immunodeficiency virus (CLHIV), most residing in sub-Saharan Africa. A common hospital presentation of CLHIV is new-onset seizure, for which imaging is helpful but not routinely performed due to scarce resources. We present imaging findings and their association with clinical risk factors and outcomes in a cohort of Zambian CLHIV presenting with new-onset seizure. In this prospective cohort study, participants were recruited at the University Teaching Hospital in Lusaka, Zambia. Various clinical and demographic characteristics were obtained. Computed tomography (CT), magnetic resonance imaging (MRI), or both were obtained during admission or shortly after discharge. If both studies were available, MRI data was used. Two neuroradiologists interpreted images using REDCap-based NeuroInterp, a tool that quantifies brain imaging findings. Age-dependent neuropsychologic assessments were administered. Nineteen of 39 (49%) children had a brain MRI, 16 of 39 (41%) had CT, and four of 39 (10%) had both. Mean age was 6.8 years (S.D. = 4.8). Children with advanced HIV disease had higher odds of atrophy (odds ration [OR] 7.2, 95% confidence interval [CI] 1.1 to 48.3). Focal abnormalities were less likely in children receiving antiretroviral therapy (ART) (OR 0.22, 95% CI 0.05 to 1.0). Children with neurocognitive impairment were more likely to have atrophy (OR 8.4, 95% CI 1.3 to 55.4) and less likely to have focal abnormalities (OR 0.2, 95% CI 0.03 to 0.9). Focal brain abnormalities on MRI were less likely in CLHIV on ART. Brain atrophy was the most common imaging abnormality, which was linked to severe neurocognitive impairment. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Among the 50 million people with epilepsy (PWE) worldwide ∼15 to 60% likely also suffer from depression and/or anxiety and 80% reside in low-income regions where human and technological resources for care are extremely limited. Methods: In Zambia, we carried out a retrospective chart review of 200 randomly selected files of PWE using a structured abstraction form to systematically collect socio-demographic data and clinical details on the detection and treatment of depression and/or anxiety. Results: Only 2 PWE (1%) had depression diagnosed and none were given a diagnosis of an anxiety disorder. Complaints suggestive of underlying depressive and/or anxiety disorders were documented in 120 (60%), but no diagnoses were made and no referrals, investigations or treatment were offered. Conclusions: Further research is required to establish the prevalence of depression and anxiety among PWE in sub-Saharan Africa and efforts are needed to improve screening and treatment for common, treatable psychiatric comorbidities in PWE in resource limited settings. [Copyright &y& Elsevier]

Background: Cerebral malaria, a disorder characterised by coma, parasitaemia, and no other evident cause of coma, is challenging to diagnose definitively in endemic regions that have high rates of asymptomatic parasitaemia and limited neurodiagnostic facilities. A recently described malaria retinopathy improves diagnostic specificity. We aimed to establish whether retinopathy-positive cerebral malaria is a risk factor for epilepsy or other neurodisabilities.Methods: Between 2005 and 2007, we did a prospective cohort study of survivors of cerebral malaria with malaria retinopathy in Blantyre, Malawi. Children with cerebral malaria were identified at the time of their index admission and age-matched to concurrently admitted children without coma or nervous system infection. Initially matching of cases to controls was 1:1 but, in 2006, enrolment criteria for cerebral malaria survivors were revised to limit inclusion to children with cerebral malaria and retinopathy on the basis of indirect ophthalmoscopic examination; matching was then changed to 1:2 and the revised inclusion criteria were applied retrospectively for children enrolled previously. Clinical assessments at discharge and standardised nurse-led follow-up every 3 months thereafter were done to identify children with new seizure disorders or other neurodisabilities. A Kaplan-Meier survival analysis was done for incident epilepsy.Findings: 132 children with retinopathy-positive cerebral malaria and 264 age-matched, non-comatose controls were followed up for a median of 495 days (IQR 195-819). 12 of 132 cerebral malaria survivors developed epilepsy versus none of 264 controls (odds ratio [OR] undefined; p<0·0001). 28 of 121 cerebral malaria survivors developed new neurodisabilities, characterised by gross motor, sensory, or language deficits, compared with two of 253 controls (OR 37·8, 95% CI 8·8-161·8; p<0·0001). The risk factors for epilepsy in children with cerebral malaria were a higher maximum temperature (39·4°C [SD 1·2] vs 38·5°C [1·1]; p=0·01) and acute seizures (11/12 vs 76/120; OR 6·37, 95% CI 1·02-141·2), and male sex was a risk factor for new neurodisabilities (20/28 vs 38/93; OR 3·62, 1·44-9·06).Interpretation: Almost a third of retinopathy-positive cerebral malaria survivors developed epilepsy or other neurobehavioural sequelae. Neuroprotective clinical trials aimed at managing hyperpyrexia and optimising seizure control are warranted.Funding: US National Institutes of Health and Wellcome Trust. [ABSTRACT FROM AUTHOR]

Medical and rehabilitative advances increasingly transform management of rare genetic neuromuscular diseases (GNMDs) for children in the global north. Lack of information about GNMDs and related health care needs in sub-Saharan Africa threatens to widen pre-existing health disparities. This is a cross-sectional study of probands enrolling in a study of GNMDs at the University Teaching Hospital in Lusaka, Zambia, a member of the International Consortium for Genomic Medicine in Neuromuscular Disease. Probands/caregivers were interviewed about utilization of medical, rehabilitative, and other support services by a research assistant. A neuromuscular neurologist and/or physiotherapist examined each case and completed an independent questionnaire regarding health service utilization for each proband. Diagnoses were made on available clinical and electrophysiologic data. Molecular findings were unavailable at the time of this analysis. Among 50 probands, 52% were male with median age 12 (absolute range 2 months to 54 years). Motor neuron diseases (n = 16; 32%), muscle disorders (n = 20; 40%), and inherited polyneuropathies (n = 5; 10%) were most common. Six (15%) cases had insufficient clinical data to classify the GNMDs. Outside of primary care, patient/caregiver-reported access to recommended health services (n = 34; 69%) was challenging. Large disparities in current utilization of health care services versus clinician-recommended services are reported. Paradigms to improve access to diagnostics and therapeutic interventions are needed for GNMDs in Zambia. Multidisciplinary clinics may improve access and utilization of needed health services. Qualitative and other research focused on improving referrals, access, and quality of available health services are greatly needed. [ABSTRACT FROM AUTHOR]

Background: High rates of cerebrovascular disease (CVD) have previously been described in pediatric human immunodeficiency virus (HIV). However, little is known about pediatric CVD in the era of antiretroviral therapy or about the contribution of CVD to HIV-associated neurocognitive disorders.Methods: We completed a neuroimaging substudy of the HIV-Associated Neurocognitive Disorders in Zambia study, a prospective cohort study of neurocognitive complications of pediatric HIV. Brain magnetic resonance imaging (1.5 T) was acquired for 34 HIV+ children on antiretroviral therapy and 17 HIV-exposed uninfected children (aged eight to 17 years). Demographics, medical history, neurological examination, and neuropsychologic testing results were collected. Two neuroradiologists, unaware of HIV status and clinical course, read the scans.Results: CVD was identified in seven of 34 children with HIV (HIV+ CVD+) and no HIV-exposed uninfected children (21% vs 0%, P = 0.05). Three participants had white matter changes suggestive of small vessel disease, four had infarcts, and two had evidence of intracranial artery stenosis. Age of antiretroviral therapy initiation and exposure to protease inhibitors or efavirenz was not significantly different between children with and without CVD. HIV+ CVD+ children had significantly worse scores on a summary measure of cognition than the HIV+ CVD- group (NPZ8 score -0.57 vs 0.33, P = 0.04).Conclusions: This study demonstrates high rates of CVD in children with HIV despite antiretroviral therapy, and worse cognitive performance in children with CVD. Longitudinal studies are necessary to determine the mechanisms and incidence of new-onset CVD in children with HIV. [ABSTRACT FROM AUTHOR]

Background: Neurocysticercosis is the most common parasitic infection of the brain and a leading cause of epilepsy in resource-limited settings. Although neurocysticercosis and human immunodeficiency virus coinfections have commonly been reported, there are few data on how they interact. As part of an observational study of human immunodeficiency virus and cognition in Lusaka, Zambia, we identified a cluster of subjects with neurocysticercosis. We hypothesized that the neighborhood of residence may be an important factor driving clustering of neurocysticercosis and used a geographic information systems approach to investigate this association.Methods: A total of 34 subjects with human immunodeficiency virus and 13 subjects without human immunodeficiency virus (aged eight to 17 years) enrolled in the HIV-Associated Neurocognitive Disorders in Zambia study, had magnetic resonance imaging of the brain performed, and were evaluated for neurocysticercosis. Quantitative geographic information systems was utilized to investigate the relationship between neighborhood of residence, HIV, and neurocysticercosis.Results: Three of 34 subjects with human immunodeficiency virus (8.82%) and one of 13 controls were found to have neurocysticercosis. Geographic cluster analysis demonstrated that all subjects with neurocysticercosis were clustered in two adjacent neighborhoods (Chawama and Kanyama) with lower rates of piped water (Chawama: 22.8%, Kanyama: 26.7%) and flush toilets (Chawama: 14.0%, Kanyama: 14.0%) than the surrounding neighborhoods.Conclusion: We describe a cluster of patients with both neurocysticercosis and human immunodeficiency virus in Lusaka. Cases of neurocysticercosis clustered in neighborhoods with low rates of piped water and limited access to flush toilets. Geographic information systems may be a useful approach for studying the relationship between human immunodeficiency virus and neurocysticercosis. Larger studies are necessary to further investigate this association. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment is common in children and adolescents with human immunodeficiency virus (HIV). Brain magnetic resonance imaging (MRI) is a potentially useful tool to investigate the pathophysiology of HIV-associated cognitive impairment and may serve as a biomarker in future clinical trials. There are few published data on brain imaging in children with HIV in sub-Saharan Africa.Methods: Thirty-four perinatally infected subjects with HIV and age-matched HIV-exposed uninfected controls between the ages nine and 17 years were recruited from the Pediatric Center of Excellence in Lusaka, Zambia, as part of the HIV-associated Neurocognitive Disorders in Zambia study. Brain MRI sequences were acquired, and clinical and volumetric assessments were performed. Subjects underwent a comprehensive neuropsychologic battery, and cognitive impairment status was classified using a global deficit score approach. Regression models were used to evaluate relationships between MRI findings and cognitive function.Results: We identified cerebrovascular disease in seven of 34 subjects with HIV compared with zero of 17 controls (21% vs 0%, P = 0.04). We also identified decreased total brain volumes (1036 vs 1162 cm3, P = 0.03) and decreased cortical thickness in the right temporal lobes (3.12 vs 3.29 mm; P = 0.01) and right fusiform gyri (3.10 vs 3.25 mm; P = 0.02) of HIV-infected subjects with cognitive impairment.Conclusions: These findings support the hypothesis that brain volumes may be useful biomarkers for cognitive outcomes in children with HIV. Further studies are necessary to investigate mechanisms of cerebrovascular disease and volume loss in children with HIV. [ABSTRACT FROM AUTHOR]

Purpose To investigate the reliability of diffusion weighted image (DWI) measurements obtained on a 0.35 T MR scanner in Malawi for malaria research. Materials and methods The same healthy volunteers (n = 6) were scanned on a 0.35 T MR scanner in Malawi and a 3 T scanner in the US. Three subjects had two repeated DWI scans at 0.35 T. Due to scanner constraints, only three diffusion gradient directions for DWI on 0.35 T could be obtained. An apparent diffusion coefficient (ADC) map was reconstructed from the 0.35 T and the result was compared to standard DWI acquisition on the 3 T scanner. The mean ADC from 15 different regions and the voxel-wise coefficient of variation (CV) were calculated to investigate the intra-scanner and inter-scanner variability. Reproducibility was calculated using intra-class correlation coefficient (ICC). Results The 0.35 T intra-scanner ADC repeatability was high for all three subjects with repeated scans (ICC > 0.7). The intra-scanner correlation between repeated scans was also high (r > 0.67, p < 0.01). Comparing the ADC findings from the 0.35 T and 3 T MRs, the high inter-scanner correlation suggested that the 0.35 T ADC results were valid (ICC > 0.7, r > 0.5, p < 0.01). Voxel-wise CV revealed a few regions with larger variation (CV > 20%), which were primarily located in peripheral regions and the boundary of lateral ventricles, and likely due to partial volume effects in low field scans. Conclusion These findings support the validity of DWI obtained from low field MR scanners used in many low income countries. [ABSTRACT FROM AUTHOR]