Objective: We assessed the independent association of lumbar puncture (LP) and death in Malawian ... more 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 scorebased 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 21.5% to 5.5%, p 5 0.27) and 1.7% during hospital admission (95% confidence interval 24.5% to 7.9%, p 5 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. Neurology ® 2016;87:2355-2362 GLOSSARY CI 5 confidence interval; CM 5 cerebral malaria; ICP 5 intracranial pressure; LP 5 lumbar puncture. Cerebral malaria (CM)-defined as coma, Plasmodium falciparum parasitemia, and the exclusion of other causes of encephalopathy-is a leading cause of death in sub-Saharan Africa. 1,2 CNS coinfections are well recognized in these patients, 3 and can only be reliably excluded by lumbar puncture (LP). Despite its diagnostic utility, performing LPs in children with suspected CM is controversial because the disease may cause raised intracranial pressure (ICP). 2 Brain swelling has recently been shown to be an independent predictor of death in CM. 4 Some physicians are concerned that LP in the context of diffusely increased ICP may precipitate fatal herniation 2,5,6 ; others believe the procedure is safe in the absence of overt brain shift. 7,8 Executing a randomized clinical trial to determine if LP is associated with death in children with CM would be problematic. Instead, we carried out a retrospective analysis of children with
Background: Cerebral malaria (CM) is often fatal, and severe brain swelling is a predictor of CM-... more Background: Cerebral malaria (CM) is often fatal, and severe brain swelling is a predictor of CM-related mortality. CM is characterized by elevated circulating pro-inflammatory cytokines TNF and IFN-γ and anti-inflammatory cytokine IL-10, however whether cytokine levels correlate with brain swelling severity is unknown. This study therefore was conducted to investigate the relationship between cytokine levels and brain swelling severity in children presenting with CM. Methods: A total of 195 Malawian children presenting with CM were recruited and had the concentrations of plasma cytokines determined and compared to brain swelling severity, determined by MRI examination, and graded as severe, moderate, mild or none. Results: Levels of IL-1β, IL-6, IL-8 and IL-10 did not differ between CM patients with and without severe brain swelling. Compared to children without brain swelling, IL-12 levels were higher in children with severe swelling (p < 0.01, no swelling 1 pg/mL, IQR [1] vs. severe swelling 18.7 pg/mL, IQR [1-27]), whereas TNF concentrations were higher in children with moderate brain swelling compared to children with no swelling (p < 0.01, no swelling 3 pg/mL, IQR [1-20] vs. moderate swelling 24 pg/mL, IQR [8-58]. Multivariate analysis showed that no single cytokine independently predicted brain swelling. Conclusion: Severe brain swelling in paediatric CM was independent of tested blood pro-inflammatory and antiinflammatory cytokines which are markers of systemic inflammation.
Introduction Malaria is a major public health problem in terms of both morbidity and mortality. D... more Introduction Malaria is a major public health problem in terms of both morbidity and mortality. Due to severe health economic costs of malaria, there is a need for methods that will help to understand the geographical variation of the disease risk and its association with climate. This paper analyses the variation of hospital diagnosed malaria incidences in relation to Rainfall, Temperatures and Humidity that are measured at district level from 2002 to 2010 in Malawi. Methods Using district hospital and health facilities malaria case records and climatic factors, a non-parametric regression model based on generalized additive mixed models (GAMM) was developed. Modeling and inference is within full Bayesian framework through Markov Chain Monte Carlo (MCMC) simulation techniques. Results There is a decreasing trend of malaria incidences in the study period and an evidence of spatial variation in the risk of having malaria which is higher in Warm Wet Season (November to March) with RR ...
Advanced medical imaging technologies are generally unavailable in low income, tropical settings ... more 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.
Background: Cerebral malaria (CM) is often fatal, and severe brain swelling is a predictor of CM-... more Background: Cerebral malaria (CM) is often fatal, and severe brain swelling is a predictor of CM-related mortality. CM is characterized by elevated circulating pro-inflammatory cytokines TNF and IFN-γ and anti-inflammatory cytokine IL-10, however whether cytokine levels correlate with brain swelling severity is unknown. This study therefore was conducted to investigate the relationship between cytokine levels and brain swelling severity in children presenting with CM. Methods: A total of 195 Malawian children presenting with CM were recruited and had the concentrations of plasma cytokines determined and compared to brain swelling severity, determined by MRI examination, and graded as severe, moderate, mild or none. Results: Levels of IL-1β, IL-6, IL-8 and IL-10 did not differ between CM patients with and without severe brain swelling. Compared to children without brain swelling, IL-12 levels were higher in children with severe swelling (p < 0.01, no swelling 1 pg/mL, IQR [1] vs. severe swelling 18.7 pg/mL, IQR [1-27]), whereas TNF concentrations were higher in children with moderate brain swelling compared to children with no swelling (p < 0.01, no swelling 3 pg/mL, IQR [1-20] vs. moderate swelling 24 pg/mL, IQR [8-58]. Multivariate analysis showed that no single cytokine independently predicted brain swelling. Conclusion: Severe brain swelling in paediatric CM was independent of tested blood pro-inflammatory and antiinflammatory cytokines which are markers of systemic inflammation.
Background: Cerebral malaria (CM) is often fatal, and severe brain swelling is a predictor of CM-... more Background: Cerebral malaria (CM) is often fatal, and severe brain swelling is a predictor of CM-related mortality. CM is characterized by elevated circulating pro-inflammatory cytokines TNF and IFN-γ and anti-inflammatory cytokine IL-10, however whether cytokine levels correlate with brain swelling severity is unknown. This study therefore was conducted to investigate the relationship between cytokine levels and brain swelling severity in children presenting with CM. Methods: A total of 195 Malawian children presenting with CM were recruited and had the concentrations of plasma cytokines determined and compared to brain swelling severity, determined by MRI examination, and graded as severe, moderate, mild or none. Results: Levels of IL-1β, IL-6, IL-8 and IL-10 did not differ between CM patients with and without severe brain swelling. Compared to children without brain swelling, IL-12 levels were higher in children with severe swelling (p < 0.01, no swelling 1 pg/mL, IQR [1] vs. severe swelling 18.7 pg/mL, IQR [1-27]), whereas TNF concentrations were higher in children with moderate brain swelling compared to children with no swelling (p < 0.01, no swelling 3 pg/mL, IQR [1-20] vs. moderate swelling 24 pg/mL, IQR [8-58]. Multivariate analysis showed that no single cytokine independently predicted brain swelling. Conclusion: Severe brain swelling in paediatric CM was independent of tested blood pro-inflammatory and antiinflammatory cytokines which are markers of systemic inflammation.
Tropical medicine & international health : TM & IH, 2013
To collect normative MRI data for effective clinical and research applications. Such data may als... more To collect normative MRI data for effective clinical and research applications. Such data may also offer insights into common neurological insults. We identified a representative, community-based sample of children aged 9-14 years. Children were screened for neurodevelopmental problems. Demographic data, medical history and environmental exposures were ascertained. Eligible children underwent the Neurologic Examination for Subtle Signs (NESS) and a brain MRI. Descriptive findings and analyses to identify risk factors for MRI abnormalities are detailed. One hundred and two of 170 households screened had age-appropriate children. Two of 102 children had neurological problems - one each with cerebral palsy and epilepsy. Ninety-six of 100 eligible children were enrolled. Mean age was 11.9 years (SD 1.5), and 43 (45%) were boys. No acute MRI abnormalities were seen. NESS abnormalities were identified in 6 of 96 children (6%). Radiographic evidence of sinusitis in 29 children (30%) was th...
Recent improvements in MR gradient technology allow significant increases in diffusion weighting ... more Recent improvements in MR gradient technology allow significant increases in diffusion weighting without prohibitive signal-to-noise degradation. The purpose of our investigation was to establish normative references for the signal intensity characteristics and apparent diffusion coefficient values of the adult brain at high b values. Fifty adults underwent diffusion-weighted single-shot spin-echo echo-planar MR imaging. Isotropic diffusion-weighted images were obtained with b values of 0, 1,000, 2,000, 2,500, 3,000, and 3,500 s/mm2. Qualitative assessments were made in multiple regions of interest in gray and white matter. Three apparent diffusion coefficient maps were generated for each of six patients with a 2-point technique at a b value of 0 and at b values of 1,000, 2,000, and 3,000 s/mm2. Increasing b values result in a progressive decrease in the gray to white matter signal intensity ratio. Isointensity between gray and white matter results at b values between 1,000 and 2,00...
To use a standardized set of chest radiographs to quantify interobserver differences and to provi... more To use a standardized set of chest radiographs to quantify interobserver differences and to provide a basis for comparing the diagnostic performance of physicians. A standardized set of 60 chest radiographs was presented to 162 study participants. Each participant reviewed the radiographs and recorded his or her diagnostic impression by using a fixed five-point scale. These response data were used to generate receiver operating characteristic curves and to establish performance benchmarks. The variations in performance were tested for statistical significance. Significant interobserver variability was identified during these assessments. The composite group of board-certified radiologists demonstrated performance superior to that of the radiology residents and nonradiologist physicians. By using a receiver operating characteristic approach and a standardized set of chest radiographs, observer accuracy and variability are easily quantified. This approach provides a basis for comparin...
To describe acute EEG findings in HIV-infected adults with new-onset seizure, assess baseline cli... more To describe acute EEG findings in HIV-infected adults with new-onset seizure, assess baseline clinical characteristics associated with EEG abnormalities, and evaluate the relationship between EEG abnormalities and recurrent seizure. Eighty-one HIV-infected adults with new-onset seizure had EEG recordings during their index admission. Baseline characteristics assessed included HIV stage, seizure semiology, serum and CSF studies, neuroimaging, cognitive function based on the Zambian Mini-Mental State Examination and International HIV Dementia Scale, and psychiatric symptoms using the Shona Symptom Questionnaire. We evaluated the relationship between baseline characteristics and EEG abnormalities. Patients were followed for seizure recurrence, and the association between acute EEG abnormalities and seizure recurrence was assessed. Death was a secondary outcome. Fifty-five patients had abnormal EEGs (68%): 18 (22%) had interictal spikes (12) or a recorded seizure (6). Among baseline clinical characteristics, more advanced HIV disease (p = 0.039) and any imaging abnormality (p = 0.027) were associated with abnormal EEGs. Cortical (p = 0.008) and white matter (p = 0.004) abnormalities were associated with slow posterior dominant rhythm. Patients were followed for a median of 303 days (interquartile range 103-560). Twenty-four (30%) died and 23 (28%) had recurrent seizures. EEG abnormalities were not associated with recurrent seizure. There was a nonsignificant association between seizures recorded during EEG and death (67% vs 26%, p = 0.051). EEG abnormalities are common in this population, particularly in patients with imaging abnormalities and advanced HIV. Acute EEG abnormalities were not associated with recurrent seizure, but high mortality rates during follow-up limited this analysis.
American Journal of Tropical Medicine and Hygiene, 2014
Our goals were to understand the brain magnetic resonance imaging (MRI) findings in children with... more 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.
Magnetic resonance imaging using a 1.5 tesla magnet and a spin echo technique has revealed a rema... more Magnetic resonance imaging using a 1.5 tesla magnet and a spin echo technique has revealed a remarkably intense signal from abnormal tissue in the human paranasal sinuses. Inflammatory disease in the maxillary, sphenoid, ethmoid, and frontal sinuses has been detected and demonstrated with greater clarity than any other available technique. The pathophysiologic basis for the intense signal has not been defined. These observations do, however, provide an opportunity to discover, clarify, and study paranasal sinus disease. Acute upper respiratory disease, allergic episodes, and the effect of drug treatment based on the MR signal and pathology can now be investigated with this technique. In addition, this may form a basis for assessing the epidemiology of paranasal sinus pathology.
ABSTRACT Radiologic data are increasingly important in clinical care guidelines for neurologic di... more ABSTRACT Radiologic data are increasingly important in clinical care guidelines for neurologic disorders and in the conduct of clinical trials assessing novel therapies. The infrastructure and expertise for neuroradiologic evaluations remain scarce in resource-limited settings, but where available, MRI and CT capacity can offer new insights into common, globally devastating diseases. In vivo data for frequently fatal tropical conditions such as cerebral malaria have been largely limited to autopsy studies, which only provide information on nonsurvivors at a single point in time. New imaging facilities in sub-Saharan African offer opportunities for expanded research on tropical neurologic disorders.(1) However, data management challenges hamper the research utility of radiologic evaluations.
American Journal of Tropical Medicine and Hygiene, 2013
Abstract. A prospective cohort study of retinopathy-confirmed cerebral malaria (CM) survivors ide... more Abstract. A prospective cohort study of retinopathy-confirmed cerebral malaria (CM) survivors identified 42 of 132 with neurologic sequelae. The 38 survivors with sequelae who were alive when magnetic resonance imaging (MRI) technology became available underwent brain MRIs. Common MRI abnormalities included periventricular T2 signal changes (53%), atrophy (47%), subcortical T2 signal changes (18%), and focal cortical defects (16%). The χ(2) tests assessed the relationship between chronic MRI findings, acute clinical and demographic data, and outcomes. Children who were older at the time of CM infection (P = 0.01) and those with isolated behavioral problems (P = 0.02) were more likely to have a normal MRI. Acute focal seizures were associated with atrophy (P = 0.05). Acute papilledema was associated with subcortical T2 signal changes (P = 0.02). Peripheral retinal whitening (P = 0.007) and a higher admission white blood cell count (P = 0.02) were associated with periventricular T2 signal changes. Chronic MRI findings suggest seizures, increased intracranial pressure, and microvascular ischemia contribute to clinically relevant structural brain injury in CM.
Objective: We assessed the independent association of lumbar puncture (LP) and death in Malawian ... more 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 scorebased 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 21.5% to 5.5%, p 5 0.27) and 1.7% during hospital admission (95% confidence interval 24.5% to 7.9%, p 5 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. Neurology ® 2016;87:2355-2362 GLOSSARY CI 5 confidence interval; CM 5 cerebral malaria; ICP 5 intracranial pressure; LP 5 lumbar puncture. Cerebral malaria (CM)-defined as coma, Plasmodium falciparum parasitemia, and the exclusion of other causes of encephalopathy-is a leading cause of death in sub-Saharan Africa. 1,2 CNS coinfections are well recognized in these patients, 3 and can only be reliably excluded by lumbar puncture (LP). Despite its diagnostic utility, performing LPs in children with suspected CM is controversial because the disease may cause raised intracranial pressure (ICP). 2 Brain swelling has recently been shown to be an independent predictor of death in CM. 4 Some physicians are concerned that LP in the context of diffusely increased ICP may precipitate fatal herniation 2,5,6 ; others believe the procedure is safe in the absence of overt brain shift. 7,8 Executing a randomized clinical trial to determine if LP is associated with death in children with CM would be problematic. Instead, we carried out a retrospective analysis of children with
Background: Cerebral malaria (CM) is often fatal, and severe brain swelling is a predictor of CM-... more Background: Cerebral malaria (CM) is often fatal, and severe brain swelling is a predictor of CM-related mortality. CM is characterized by elevated circulating pro-inflammatory cytokines TNF and IFN-γ and anti-inflammatory cytokine IL-10, however whether cytokine levels correlate with brain swelling severity is unknown. This study therefore was conducted to investigate the relationship between cytokine levels and brain swelling severity in children presenting with CM. Methods: A total of 195 Malawian children presenting with CM were recruited and had the concentrations of plasma cytokines determined and compared to brain swelling severity, determined by MRI examination, and graded as severe, moderate, mild or none. Results: Levels of IL-1β, IL-6, IL-8 and IL-10 did not differ between CM patients with and without severe brain swelling. Compared to children without brain swelling, IL-12 levels were higher in children with severe swelling (p < 0.01, no swelling 1 pg/mL, IQR [1] vs. severe swelling 18.7 pg/mL, IQR [1-27]), whereas TNF concentrations were higher in children with moderate brain swelling compared to children with no swelling (p < 0.01, no swelling 3 pg/mL, IQR [1-20] vs. moderate swelling 24 pg/mL, IQR [8-58]. Multivariate analysis showed that no single cytokine independently predicted brain swelling. Conclusion: Severe brain swelling in paediatric CM was independent of tested blood pro-inflammatory and antiinflammatory cytokines which are markers of systemic inflammation.
Introduction Malaria is a major public health problem in terms of both morbidity and mortality. D... more Introduction Malaria is a major public health problem in terms of both morbidity and mortality. Due to severe health economic costs of malaria, there is a need for methods that will help to understand the geographical variation of the disease risk and its association with climate. This paper analyses the variation of hospital diagnosed malaria incidences in relation to Rainfall, Temperatures and Humidity that are measured at district level from 2002 to 2010 in Malawi. Methods Using district hospital and health facilities malaria case records and climatic factors, a non-parametric regression model based on generalized additive mixed models (GAMM) was developed. Modeling and inference is within full Bayesian framework through Markov Chain Monte Carlo (MCMC) simulation techniques. Results There is a decreasing trend of malaria incidences in the study period and an evidence of spatial variation in the risk of having malaria which is higher in Warm Wet Season (November to March) with RR ...
Advanced medical imaging technologies are generally unavailable in low income, tropical settings ... more 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.
Background: Cerebral malaria (CM) is often fatal, and severe brain swelling is a predictor of CM-... more Background: Cerebral malaria (CM) is often fatal, and severe brain swelling is a predictor of CM-related mortality. CM is characterized by elevated circulating pro-inflammatory cytokines TNF and IFN-γ and anti-inflammatory cytokine IL-10, however whether cytokine levels correlate with brain swelling severity is unknown. This study therefore was conducted to investigate the relationship between cytokine levels and brain swelling severity in children presenting with CM. Methods: A total of 195 Malawian children presenting with CM were recruited and had the concentrations of plasma cytokines determined and compared to brain swelling severity, determined by MRI examination, and graded as severe, moderate, mild or none. Results: Levels of IL-1β, IL-6, IL-8 and IL-10 did not differ between CM patients with and without severe brain swelling. Compared to children without brain swelling, IL-12 levels were higher in children with severe swelling (p < 0.01, no swelling 1 pg/mL, IQR [1] vs. severe swelling 18.7 pg/mL, IQR [1-27]), whereas TNF concentrations were higher in children with moderate brain swelling compared to children with no swelling (p < 0.01, no swelling 3 pg/mL, IQR [1-20] vs. moderate swelling 24 pg/mL, IQR [8-58]. Multivariate analysis showed that no single cytokine independently predicted brain swelling. Conclusion: Severe brain swelling in paediatric CM was independent of tested blood pro-inflammatory and antiinflammatory cytokines which are markers of systemic inflammation.
Background: Cerebral malaria (CM) is often fatal, and severe brain swelling is a predictor of CM-... more Background: Cerebral malaria (CM) is often fatal, and severe brain swelling is a predictor of CM-related mortality. CM is characterized by elevated circulating pro-inflammatory cytokines TNF and IFN-γ and anti-inflammatory cytokine IL-10, however whether cytokine levels correlate with brain swelling severity is unknown. This study therefore was conducted to investigate the relationship between cytokine levels and brain swelling severity in children presenting with CM. Methods: A total of 195 Malawian children presenting with CM were recruited and had the concentrations of plasma cytokines determined and compared to brain swelling severity, determined by MRI examination, and graded as severe, moderate, mild or none. Results: Levels of IL-1β, IL-6, IL-8 and IL-10 did not differ between CM patients with and without severe brain swelling. Compared to children without brain swelling, IL-12 levels were higher in children with severe swelling (p < 0.01, no swelling 1 pg/mL, IQR [1] vs. severe swelling 18.7 pg/mL, IQR [1-27]), whereas TNF concentrations were higher in children with moderate brain swelling compared to children with no swelling (p < 0.01, no swelling 3 pg/mL, IQR [1-20] vs. moderate swelling 24 pg/mL, IQR [8-58]. Multivariate analysis showed that no single cytokine independently predicted brain swelling. Conclusion: Severe brain swelling in paediatric CM was independent of tested blood pro-inflammatory and antiinflammatory cytokines which are markers of systemic inflammation.
Tropical medicine & international health : TM & IH, 2013
To collect normative MRI data for effective clinical and research applications. Such data may als... more To collect normative MRI data for effective clinical and research applications. Such data may also offer insights into common neurological insults. We identified a representative, community-based sample of children aged 9-14 years. Children were screened for neurodevelopmental problems. Demographic data, medical history and environmental exposures were ascertained. Eligible children underwent the Neurologic Examination for Subtle Signs (NESS) and a brain MRI. Descriptive findings and analyses to identify risk factors for MRI abnormalities are detailed. One hundred and two of 170 households screened had age-appropriate children. Two of 102 children had neurological problems - one each with cerebral palsy and epilepsy. Ninety-six of 100 eligible children were enrolled. Mean age was 11.9 years (SD 1.5), and 43 (45%) were boys. No acute MRI abnormalities were seen. NESS abnormalities were identified in 6 of 96 children (6%). Radiographic evidence of sinusitis in 29 children (30%) was th...
Recent improvements in MR gradient technology allow significant increases in diffusion weighting ... more Recent improvements in MR gradient technology allow significant increases in diffusion weighting without prohibitive signal-to-noise degradation. The purpose of our investigation was to establish normative references for the signal intensity characteristics and apparent diffusion coefficient values of the adult brain at high b values. Fifty adults underwent diffusion-weighted single-shot spin-echo echo-planar MR imaging. Isotropic diffusion-weighted images were obtained with b values of 0, 1,000, 2,000, 2,500, 3,000, and 3,500 s/mm2. Qualitative assessments were made in multiple regions of interest in gray and white matter. Three apparent diffusion coefficient maps were generated for each of six patients with a 2-point technique at a b value of 0 and at b values of 1,000, 2,000, and 3,000 s/mm2. Increasing b values result in a progressive decrease in the gray to white matter signal intensity ratio. Isointensity between gray and white matter results at b values between 1,000 and 2,00...
To use a standardized set of chest radiographs to quantify interobserver differences and to provi... more To use a standardized set of chest radiographs to quantify interobserver differences and to provide a basis for comparing the diagnostic performance of physicians. A standardized set of 60 chest radiographs was presented to 162 study participants. Each participant reviewed the radiographs and recorded his or her diagnostic impression by using a fixed five-point scale. These response data were used to generate receiver operating characteristic curves and to establish performance benchmarks. The variations in performance were tested for statistical significance. Significant interobserver variability was identified during these assessments. The composite group of board-certified radiologists demonstrated performance superior to that of the radiology residents and nonradiologist physicians. By using a receiver operating characteristic approach and a standardized set of chest radiographs, observer accuracy and variability are easily quantified. This approach provides a basis for comparin...
To describe acute EEG findings in HIV-infected adults with new-onset seizure, assess baseline cli... more To describe acute EEG findings in HIV-infected adults with new-onset seizure, assess baseline clinical characteristics associated with EEG abnormalities, and evaluate the relationship between EEG abnormalities and recurrent seizure. Eighty-one HIV-infected adults with new-onset seizure had EEG recordings during their index admission. Baseline characteristics assessed included HIV stage, seizure semiology, serum and CSF studies, neuroimaging, cognitive function based on the Zambian Mini-Mental State Examination and International HIV Dementia Scale, and psychiatric symptoms using the Shona Symptom Questionnaire. We evaluated the relationship between baseline characteristics and EEG abnormalities. Patients were followed for seizure recurrence, and the association between acute EEG abnormalities and seizure recurrence was assessed. Death was a secondary outcome. Fifty-five patients had abnormal EEGs (68%): 18 (22%) had interictal spikes (12) or a recorded seizure (6). Among baseline clinical characteristics, more advanced HIV disease (p = 0.039) and any imaging abnormality (p = 0.027) were associated with abnormal EEGs. Cortical (p = 0.008) and white matter (p = 0.004) abnormalities were associated with slow posterior dominant rhythm. Patients were followed for a median of 303 days (interquartile range 103-560). Twenty-four (30%) died and 23 (28%) had recurrent seizures. EEG abnormalities were not associated with recurrent seizure. There was a nonsignificant association between seizures recorded during EEG and death (67% vs 26%, p = 0.051). EEG abnormalities are common in this population, particularly in patients with imaging abnormalities and advanced HIV. Acute EEG abnormalities were not associated with recurrent seizure, but high mortality rates during follow-up limited this analysis.
American Journal of Tropical Medicine and Hygiene, 2014
Our goals were to understand the brain magnetic resonance imaging (MRI) findings in children with... more 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.
Magnetic resonance imaging using a 1.5 tesla magnet and a spin echo technique has revealed a rema... more Magnetic resonance imaging using a 1.5 tesla magnet and a spin echo technique has revealed a remarkably intense signal from abnormal tissue in the human paranasal sinuses. Inflammatory disease in the maxillary, sphenoid, ethmoid, and frontal sinuses has been detected and demonstrated with greater clarity than any other available technique. The pathophysiologic basis for the intense signal has not been defined. These observations do, however, provide an opportunity to discover, clarify, and study paranasal sinus disease. Acute upper respiratory disease, allergic episodes, and the effect of drug treatment based on the MR signal and pathology can now be investigated with this technique. In addition, this may form a basis for assessing the epidemiology of paranasal sinus pathology.
ABSTRACT Radiologic data are increasingly important in clinical care guidelines for neurologic di... more ABSTRACT Radiologic data are increasingly important in clinical care guidelines for neurologic disorders and in the conduct of clinical trials assessing novel therapies. The infrastructure and expertise for neuroradiologic evaluations remain scarce in resource-limited settings, but where available, MRI and CT capacity can offer new insights into common, globally devastating diseases. In vivo data for frequently fatal tropical conditions such as cerebral malaria have been largely limited to autopsy studies, which only provide information on nonsurvivors at a single point in time. New imaging facilities in sub-Saharan African offer opportunities for expanded research on tropical neurologic disorders.(1) However, data management challenges hamper the research utility of radiologic evaluations.
American Journal of Tropical Medicine and Hygiene, 2013
Abstract. A prospective cohort study of retinopathy-confirmed cerebral malaria (CM) survivors ide... more Abstract. A prospective cohort study of retinopathy-confirmed cerebral malaria (CM) survivors identified 42 of 132 with neurologic sequelae. The 38 survivors with sequelae who were alive when magnetic resonance imaging (MRI) technology became available underwent brain MRIs. Common MRI abnormalities included periventricular T2 signal changes (53%), atrophy (47%), subcortical T2 signal changes (18%), and focal cortical defects (16%). The χ(2) tests assessed the relationship between chronic MRI findings, acute clinical and demographic data, and outcomes. Children who were older at the time of CM infection (P = 0.01) and those with isolated behavioral problems (P = 0.02) were more likely to have a normal MRI. Acute focal seizures were associated with atrophy (P = 0.05). Acute papilledema was associated with subcortical T2 signal changes (P = 0.02). Peripheral retinal whitening (P = 0.007) and a higher admission white blood cell count (P = 0.02) were associated with periventricular T2 signal changes. Chronic MRI findings suggest seizures, increased intracranial pressure, and microvascular ischemia contribute to clinically relevant structural brain injury in CM.
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