Background: Micronutrient levels play a critical role in epilepsy. This study investigates the impact of micronutrient levels on epilepsy via Mendelian randomization (MR).
Methods: A two-sample MR framework evaluated the genetic association between 15 serum micronutrients and epilepsy phenotypes. The analysis included calcium, iron, zinc, selenium, copper, magnesium, potassium, folate, vitamins B6, B12, C, D, E, retinol, and carotene against all epilepsy, generalized epilepsy, childhood absence epilepsy (CAE), juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy (JME), generalized tonic-clonic seizures alone and with spike-wave electroencephalography (GTCS), and various focal epilepsy phenotypes [with hippocampal sclerosis (HS), lesions other than HS, lesion-negative]. The random-effects inverse-variance weighted (IVW) model was the primary method used, supported by heterogeneity and pleiotropy assessments. Multivariable Mendelian randomization analyses (MVMR) were used to identify micronutrients that are significantly causally associated with different epilepsy subtypes and to confirm the most potential causal risk factors for these subtypes.
Results: Zinc conferred an increased risk of focal epilepsy with HS (OR = 1.01; = 0.045). Carotene was similarly linked to higher risks of lesion-negative cases (OR = 1.129; = 0.037). Conversely, vitamin B6 was associated with reduced risks of focal epilepsy with HS (OR = 0.949; = 0.020), and vitamin D was linked to decreased risks of both CAE (OR = 0.976, 95% CI: 0.959-0.993, = 0.006) and JAE (OR = 0.986, 95% CI: 0.973-0.999, = 0.032). These associations were robust, showing minimal heterogeneity and no evidence of pleiotropy across various sensitivity analyses. After adjustment using MVMR, significant causal relationships between vitamin D and both CAE and JAE remained. Furthermore, the causal relationship between zinc and vitamin B6 on focal epilepsy with HS became non-significant, while carotene shifted from a risk factor to a protective factor for focal epilepsy lesion-negative after adjusting for vitamin D.
Conclusion: MR estimates provide robust evidence for the causal effects of vitamin D on reducing the risk of CAE, and JAE, which might provide alternative treatment strategies.
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http://dx.doi.org/10.3389/fneur.2024.1419289 | DOI Listing |
Eur J Med Genet
December 2024
Rare Diseases and Medical Genetics Unit, Bambino Gesù Children's Hospital, IRCSS, Rome, Italy.
O'Donnell-Luria-Rodan (ODLURO) syndrome is an autosomal dominant neurodevelopmental disorder mainly characterized by global development delay/intellectual disability, white matter abnormalities, and behavioral manifestations. It is caused by pathogenic variants in the KMT2E gene. Here we report seven new patients with loss-of-function KMT2E variants, six harboring frameshift/nonsense changes, and one with a 7q22.
View Article and Find Full Text PDFEpilepsia
December 2024
Comprehensive Epilepsy Center, New York University Grossman School of Medicine, New York, New York, USA.
Objective: Randomized controlled trials (RCTs) are necessary to evaluate the efficacy of novel treatments for epilepsy. However, there have been concerning increases in the placebo responder rate over time. To understand these trends, we evaluated features associated with increased placebo responder rate.
View Article and Find Full Text PDFNeuroimage
December 2024
Lille University Hospital, Department of Clinical Neurophysiology, 59037 Lille, France; INSERM U1172, LilNCog - Lille Neuroscience & Cognition, 59000 Lille, France. Electronic address:
Background And Objectives: Focal epilepsies disrupt long-range networks with seizure recurrence driving both regional and global alterations in connectivity networks. While prior studies have focused on the interictal consequences, limited data exist on the direct aftermath of focal seizures. We hypothesize that mesial temporal lobe seizures lead to enduring cortical disorganization.
View Article and Find Full Text PDFCNS Neurosci Ther
December 2024
Department of Neurosurgery, SanBo Brain Hospital, Capital Medical University, Beijing, China.
Aims: Previous studies suggest potential associations between epilepsy, anti-epileptic drugs (AEDs), and levels of vitamin D and vitamin D-binding protein (VDBP). This study aims to investigate the causal relationships among these variables using Mendelian Randomization (MR) methods.
Methods: Using summary data from genome-wide association studies on serum 25-hydroxyvitamin D [25(OH)D] levels (N = 417,580), VDBP concentrations (N = 65,589), and various types of epilepsy (Ncases = 27,559), MR analyses were conducted to determine bidirectional causal relationships among these variables.
Eur Radiol
December 2024
Department of Neuroradiology, Medical Center-University of Freiburg, Freiburg, Germany.
Epilepsy, a neurological disorder characterised by recurrent seizures, poses significant challenges in diagnosis, treatment, and management. Understanding the underlying causes and identifying precise anatomical locations of epileptogenic foci are critical for effective management strategies, particularly in drug-resistant patients. Neuroimaging techniques, particularly magnetic resonance (MR), play a pivotal role in the evaluation of epilepsy patients, offering insights into structural abnormalities, epileptogenic lesions, and functional alterations within the brain.
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