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Background: Identification of convulsive epilepsy in sub-Saharan Africa relies on access to resources that are often unavailable. Infrastructure and resource requirements can further complicate case verification. Using machine-learning techniques, we have developed and tested a region-specific questionnaire panel and predictive model to identify people who have had a convulsive seizure. These findings have been implemented into a free app for health-care workers in Kenya, Uganda, Ghana, Tanzania, and South Africa.
Methods: In this retrospective case-control study, we used data from the Studies of the Epidemiology of Epilepsy in Demographic Sites in Kenya, Uganda, Ghana, Tanzania, and South Africa. We randomly split these individuals using a 7:3 ratio into a training dataset and a validation dataset. We used information gain and correlation-based feature selection to identify eight binary features to predict convulsive seizures. We then assessed several machine-learning algorithms to create a multivariate prediction model. We validated the best-performing model with the internal dataset and a prospectively collected external-validation dataset. We additionally evaluated a leave-one-site-out model (LOSO), in which the model was trained on data from all sites except one that, in turn, formed the validation dataset. We used these features to develop a questionnaire-based predictive panel that we implemented into a multilingual app (the Epilepsy Diagnostic Companion) for health-care workers in each geographical region.
Findings: We analysed epilepsy-specific data from 4097 people, of whom 1985 (48·5%) had convulsive epilepsy, and 2112 were controls. From 170 clinical variables, we initially identified 20 candidate predictor features. Eight features were removed, six because of negligible information gain and two following review by a panel of qualified neurologists. Correlation-based feature selection identified eight variables that demonstrated predictive value; all were associated with an increased risk of an epileptic convulsion except one. The logistic regression, support vector, and naive Bayes models performed similarly, outperforming the decision-tree model. We chose the logistic regression model for its interpretability and implementability. The area under the receiver operator curve (AUC) was 0·92 (95% CI 0·91-0·94, sensitivity 85·0%, specificity 93·7%) in the internal-validation dataset and 0·95 (0·92-0·98, sensitivity 97·5%, specificity 82·4%) in the external-validation dataset. Similar results were observed for the LOSO model (AUC 0·94, 0·93-0·96, sensitivity 88·2%, specificity 95·3%).
Interpretation: On the basis of these findings, we developed the Epilepsy Diagnostic Companion as a predictive model and app offering a validated culture-specific and region-specific solution to confirm the diagnosis of a convulsive epileptic seizure in people with suspected epilepsy. The questionnaire panel is simple and accessible for health-care workers without specialist knowledge to administer. This tool can be iteratively updated and could lead to earlier, more accurate diagnosis of seizures and improve care for people with epilepsy.
Funding: The Wellcome Trust, the UK National Institute of Health Research, and the Oxford NIHR Biomedical Research Centre.
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http://dx.doi.org/10.1016/S2589-7500(22)00255-2 | DOI Listing |
Br J Pharmacol
September 2025
Department of Physiology and Medical Physics, RCSI University of Medicine and Health Sciences, Dublin, Ireland.
Background And Purpose: Neuroinflammation is increasingly recognised to contribute to drug-resistant epilepsy. Activation of ATP-gated P2X7 receptors has emerged as an important upstream mechanism, and increased P2X7 receptor expression is present in the seizure focus in rodent models and patients. Pharmacological antagonists of P2X7 receptors attenuate seizures in rodents, but this has not been explored in human neural networks.
View Article and Find Full Text PDFBMJ Case Rep
September 2025
Gandhi Medical College and Hospital, Secunderabad, Telangana, India
Fahr's syndrome is a rare neurological condition marked by unusual calcifications in the basal ganglia and other brain regions, often resulting from metabolic disorders, such as hypoparathyroidism. Secondary hypoparathyroidism, a frequent complication of total thyroidectomy, can lead to Fahr's syndrome, manifesting as movement disorders, seizures, psychiatric symptoms and indications of calcium deficiency. This case report discusses a woman in her mid-30s who developed Fahr's syndrome due to secondary hypoparathyroidism after total thyroidectomy.
View Article and Find Full Text PDFNeurobiol Dis
September 2025
Department of Neuroscience, Developmental and Regenerative Biology, The University of Texas at San Antonio, San Antonio, TX, USA; Brain Health Consortium, The University of Texas at San Antonio, San Antonio, TX, USA. Electronic address:
Temporal lobe epilepsy is associated with aberrant neurogenesis and ectopic migration of adult-born granule cells (abGCs), yet the molecular mechanisms driving these changes remain poorly defined. Using a pilocarpine-induced mouse model of temporal lobe epilepsy and chemogenetic silencing of abGCs via Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), we previously demonstrated that abGC inhibition reduces both ectopic migration and seizure susceptibility. To identify underlying molecular regulators, we performed RNA sequencing of FACS-isolated abGCs and identified Rrm2 and Timp3 as top candidate genes modulated by seizure activity and neuronal silencing.
View Article and Find Full Text PDFNeurobiol Dis
September 2025
Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Major Neurological and Mental Disorders, Chongqing Key Laboratory of Neurology, Chongqing, China. Electronic address:
Ubiquilin 4 (UBQLN4) is an important molecule that regulates protein degradation through the ubiquitin-proteasome pathway. This study found that UBQLN4 expression is significantly reduced in a chronic epilepsy mouse model induced by kainic acid, primarily localized in neurons and widely distributed at excitatory post-synapses. Experiments involving adeno-associated virus-mediated overexpression or knockdown of UBQLN4 indicate that a reduction in UBQLN4 increases susceptibility to and severity of epilepsy, while its overexpression has a protective effect.
View Article and Find Full Text PDFNeurobiol Dis
September 2025
Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China. Electronic address:
The effect of recurrent seizures on the gradual deterioration of the white matter structural network and the potential molecular mechanisms that underlie the baseline and longitudinal changes in network topology in temporal lobe epilepsy (TLE) remain unclear. Therefore, we used diffusion tensor imaging (DTI) scans and neuropsychiatric assessments for 28 patients with unilateral TLE at baseline and follow-up, and for 28 healthy controls (HC). The topological properties of the structural network were calculated using graph theoretical analyses.
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