Admission Clinical and EEG Features Associated With Mortality and Long-term Neurologic and Cognitive Outcomes in Pediatric Cerebral Malaria.

BACKGROUND AND OBJECTIVES: For children with cerebral malaria, mortality is high, and in survivors, long-term neurologic and cognitive dysfunctions are common. While specific clinical factors are associated with death or long-term neurocognitive morbidity in cerebral malaria, the association of EEG features with these outcomes, particularly neurocognitive outcomes, is less well characterized. METHODS: In this prospective cohort study of 149 children age 6 months to 12 years who survived cerebral malaria in Kampala, Uganda, we evaluated whether depth of coma, number of clinical seizures, or EEG features during hospitalization were associated with mortality during hospitalization, short-term and long-term neurologic deficits, or long-term cognitive outcomes (overall cognition, attention, memory) over the 2-year follow-up. RESULTS: Higher Blantyre or Glasgow Coma Scores (BCS and GCS, respectively), higher background voltage, and presence of normal reactivity on EEG were each associated with lower mortality. Among clinical and EEG features, the presence of >4 seizures on admission had the best combination of negative and positive predictive values for neurologic deficits in follow-up. In multivariable modeling of cognitive outcomes, the number of seizures and specific EEG features showed independent association with better outcomes. In children younger than 5 years throughout the study, seizure number and presence of vertex sharp waves were independently associated with better posthospitalization cognitive performance, faster dominant frequency with better attention, and higher average background voltage and faster dominant background frequency with better associative memory. In children younger than 5 years at CM episode but 5 years or older at cognitive testing, seizure number, background dominant frequency, and the presence of vertex sharp waves were each associated with changes in cognition, seizure number and variability with attention, and seizure number with working memory. DISCUSSION: In children with cerebral malaria, seizure number is strongly associated with the risk of long-term neurologic deficits, while seizure number and specific EEG features (average background voltage, dominant rhythm frequency, presence of vertex sharp waves, presence of variability) are independently associated with cognitive outcomes. Future studies should evaluate the predictive value of these findings.

Theta-Alpha Variability on Admission EEG Is Associated With Outcome in Pediatric Cerebral Malaria.

PURPOSE: Pediatric cerebral malaria has high rates of mortality and neurologic morbidity. Although several biomarkers, including EEG, are associated with survival or morbidity, many are resource intensive or require skilled interpretation for clinical use. Automation of quantitative interpretation of EEG may be preferable in resource-limited settings, where trained interpreters are rare. As currently used quantitative EEG factors do not adequately describe the spectrum of variability seen in studies from children with cerebral malaria, the authors developed and validated a new quantitative EEG variable, theta-alpha variability (TAV). METHODS: The authors developed TAV, a new quantitative variable, as a composite of multiple automated EEG outputs. EEG records from 194 children (6 months to 14 years old) with cerebral malaria were analyzed. Independent EEG interpreters performed standard quantitative and qualitative analyses, with the addition of the newly created variable. The associations of TAV with other quantitative EEG factors, a qualitative assessment of variability, and outcomes were assessed. RESULTS: Theta-alpha variability was not highly correlated with alpha, theta, or delta power and was not associated with qualitative measures of variability. Children whose EEGs had higher values of TAV had a lower risk of death (odds ratio = 0.934, 95% confidence interval = 0.902-0.966) or neurologic sequelae (odds ratio = 0.960, 95% confidence interval = 0.932-0.990) compared with those with lower values. Receiver operating characteristic analysis in predicting death at a TAV threshold of 0.244 yielded a sensitivity of 74% and specificity of 70% for an area under the receiver operating characteristic curve of 0.755. CONCLUSIONS: Theta-alpha variability is independently associated with outcome in pediatric cerebral malaria and can predict death with high sensitivity and specificity. Automated determination of this newly created EEG factor holds promise as a potential method to increase the clinical utility of EEG in resource-limited settings by allowing interventions to be targeted to those at higher risk of death or disability.

Using EEG in Resource-Limited Areas: Comparing Qualitative and Quantitative Interpretation Methods in Cerebral Malaria.

BACKGROUND: Our goal was to compare the strength of association and predictive ability of qualitative and quantitative electroencephalographic (EEG) factors with the outcomes of death and neurological disability in pediatric cerebral malaria (CM). METHODS: We enrolled children with a clinical diagnosis of CM admitted to Queen Elizabeth Central Hospital (Blantyre, Malawi) between 2012 and 2017. A routine-length EEG was performed within four hours of admission. EEG data were independently interpreted using qualitative and quantitative methods by trained pediatric neurophysiologists. EEG interpreters were unaware of patient discharge outcome. RESULTS: EEG tracings from 194 patients were reviewed. Multivariate modeling revealed several qualitative and quantitative EEG variables that were independently associated with outcomes. Quantitative methods modeled on mortality had better goodness of fit than qualitative ones. When modeled on neurological morbidity in survivors, goodness of fit was better for qualitative methods. When the probabilities of an adverse outcome were calculated using multivariate regression coefficients, only the model of quantitative EEG variables regressed on the neurological sequelae outcome showed clear separation between outcome groups. CONCLUSIONS: Multiple qualitative and quantitative EEG factors are associated with outcomes in pediatric CM. It may be possible to use quantitative EEG factors to create automated methods of study interpretation that have similar predictive abilities for outcomes as human-based interpreters, a rare resource in many malaria-endemic areas. Our results provide a proof-of-concept starting point for the development of quantitative EEG interpretation and prediction methodologies useful in resource-limited settings.

Determining Trendelenburg test validity and reliability using 3-dimensional motion analysis and muscle dynamometry.

BACKGROUND: The hip abductor muscle group stabilises the pelvis during gait to prevent excessive pelvic drop. Hip abductor weakness has been linked to musculoskeletal conditions such as chronic low-back pain. As such, it is important that practitioners can correctly diagnose hip abductor weakness in a clinical setting. Although the Trendelenburg test is commonly used by practitioners, the validity of this test to assess hip abductor weakness in the absence of musculoskeletal injury remains questionable. The aim of this study was to determine the validity of the Trendelenburg test, as observed by a practitioner, to assess frontal plane pelvic motion and hip abductor strength in a population without intra-articular hip disorders. METHODS: This study was performed between June 14th and October 16th 2019. Eighteen participants were recruited for this study. Peak normalised isometric and isokinetic hip abductor torque were measured bilaterally (n = 36) using the Biodex System 4 isokinetic dynamometer. Each participant performed the Trendelenburg test bilaterally (n = 36) while a graduate year chiropractic practitioner assessed for a "positive" or "negative" sign. The test was simultaneously recorded using Vicon 3-Dimensional motion capture to measure frontal plane pelvic motion and elevation. Correlation analyses were performed between the measures of peak hip abductor torque and pelvic motion to determine if any relationship existed. Agreement between the practitioner and 3-Dimensional analysis was calculated using the kappa (κ) statistic. RESULTS: Weak, non-significant correlations were found between hip abductor strength and pelvic motion before outlier removal. Significant (p < 0.05) yet weak correlations were found after outlier removal, except for isometric hip abductor strength. Weak agreement was found between the chiropractic practitioner and 3-Dimesnional analysis for the Trendelenburg test assessment (κ = 0.22-0.25). CONCLUSIONS: This study found no significant relationship between normalised peak isometric and isokinetic hip abductor torque and frontal plane pelvic motion during the Trendelenburg test in a healthy young adult population. There was also poor agreement between the practitioner and pelvic motion assessments. Caution should be used when using this test, in the absence of intra-articular hip pathology, to assesses hip abductor weakness. Before any definitive conclusion can be made, studies with a larger sample size should be performed.

Classification of activity engagement in individuals with severe physical disabilities using signals of the peripheral nervous system.

Communication barriers often result in exclusion of children and youth with disabilities from activities and social settings that are essential to their psychosocial development. In particular, difficulties in describing their experiences of activities and social settings hinder our understanding of the factors that promote inclusion and participation of this group of individuals. To address this specific communication challenge, we examined the feasibility of developing a language-free measure of experience in youth with severe physical disabilities. To do this, we used the activity of the peripheral nervous system to detect patterns of psychological arousal associated with activities requiring different patterns of cognitive/affective and interpersonal involvement (activity engagement). We demonstrated that these signals can differentiate among patterns of arousal associated with these activities with high accuracy (two levels: 81%, three levels: 74%). These results demonstrate the potential for development of a real-time, motor- and language-free measure for describing the experiences of children and youth with disabilities.

Unusual, strained heterocycles: 3-alkylidene-2-methyleneoxetanes from Morita-Baylis-Hillman-type adducts.

[reaction: see text] 3-Alkylidene-2-methyleneoxetanes have been prepared by treating alpha-alkylidene-beta-lactones, derived from Morita-Baylis-Hillman-type adducts, with dimethyltitanocene. Preliminary studies of the reactivity of these little known, strained heterocycles are also described.