New treatments for epilepsy

BACKGROUND: Cerebral palsy (CP) describes a group of disorders affecting movement, balance, and posture. Disturbances in motor functions constitute the main body of CP symptoms. These symptoms surface in early childhood and patients are affected for the rest of their lives. Currently, treatment involves various pharmacotherapies for different types of CP, including antiepileptics for epilepsy and Botox A for focal spasticity. However, none of these methods can provide full symptom relief...

INTRODUCTION: Epilepsies are a group of heterogeneous brain disorder, and antiseizure medications (ASMs) are the mainstay of treatment. Despite the availability of more than 30 drugs, at least one third of individuals with epilepsy are drug-resistant. This emphasizes the need for novel compounds that combine efficacy with improved tolerability. AREAS COVERED: A literature review on the pharmacology, efficacy, tolerability, and safety of azetukalner (XEN1101), a second-generation opener of neuronal potassium channels currently in Phase 3 development as ASM...

GPR37L1 is an orphan receptor that couples through heterotrimeric G proteins to regulate physiological functions. Since its role in humans is not fully defined, we used an unbiased computational approach to assess the clinical significance of rare GPR37L1 genetic variants found among 51,289 whole exome sequences from the DiscovEHR cohort. Briefly, rare GPR37L1 coding variants were binned according to predicted pathogenicity and analyzed by Sequence Kernel Association testing to reveal significant associations with disease diagnostic codes for epilepsy and migraine, among others...

Despite the significant advances in understanding the genetic architecture of epilepsy, many patients do not receive a molecular diagnosis after genomic testing. Re-analysing existing genomic data has emerged as a potent method to increase diagnostic yields-providing the benefits of genomic-enabled medicine to more individuals afflicted with a range of different conditions. The primary drivers for these new diagnoses are the discovery of novel gene-disease and variants-disease relationships; however, most decisions to trigger re-analysis are based on the passage of time rather than the accumulation of new knowledge...

BACKGROUND: This study aimed to evaluate the effects of a nurse-led cognitive behavioral intervention for parents of children with epilepsy (CWE). METHODS: The study recruited 238 CWE from the neurology ward of Xiangya Hospital from March 2019 to August 2022. According to the interventions after discharge, the children and their parents were randomly divided into 117 parent-child dyads in the intervention group and 121 parent-child dyads in the control group. The seizure severity and treatment compliance in CWE as well as the parents' psychological states and satisfaction with the care provided by nurses were compared before and after intervention...

BACKGROUND: Methylation analysis has become a powerful diagnostic tool in modern neurooncology. This technique is valuable to diagnose new brain tumor types. OBJECTIVE: To describe the MRI and histological pattern of neuroepithelial tumor with PLAGL1 gene fusion. MATERIAL AND METHODS: We present a 6-year-old patient with small right frontal intraaxial tumor causing drug resistant epilepsy. Despite indolent preoperative clinical course and MRI features suggesting glioneuronal tumor, histological evaluation revealed characteristics of high-grade glioma, ependymoma and neuroblastoma...

OBJECTIVES: Primidone is an anticonvulsive drug used in the treatment of epilepsy and essential tremor. It offers beneficial effects in controlling seizures, but its usage is also associated with possible side effects. To ensure optimal therapy, it is crucial to measure its concentration through accurate quantification methods. Therefore, our main goal was to develop and validate a new reference measurement procedure (RMP) for accurately measuring primidone levels in human serum and plasma...

Over the past few decades, many current uses for cannabinoids have been described, ranging from controlling epilepsy to neuropathic pain and anxiety treatment. Medicines containing cannabinoids have been approved by both the FDA and the EMA for the control of specific diseases for which there are few alternatives. However, the molecular-level mechanism of action of cannabinoids is still poorly understood. Recently, cannabinoids have been shown to interact with autotaxin (ATX), a secreted lysophospholipase D enzyme responsible for catalyzing lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA), a pleiotropic growth factor that interacts with LPA receptors...

This study investigates the dose-dependent EEG effects of Vagus Nerve Stimulation (VNS) in patients with drug-resistant epilepsy. This research examines how varying VNS intensities impacts EEG power spectrum and synchronization in a cohort of 28 patients. Patients were categorized into responders, partial-responders, and non-responders based on seizure frequency reduction. The methods involved EEG recordings at incremental VNS intensities, followed by spectral and synchronization analysis. The results reveal significant changes in EEG power, particularly in the delta and beta bands across different intensities...

Neuropathology-based studies in neurosurgically resected brain tissue obtained from carefully examined patients with focal epilepsies remain a treasure box for excellent insights into human neuroscience, including avenues to better understand the neurobiology of human brain organization and neuronal hyperexcitability at the cellular level including glio-neuronal interaction. It also allows to translate results from animal models in order to develop personalized treatment strategies in the near future. A nice example of this is the discovery of a new disease entity in 2017, termed mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy or MOGHE, in the frontal lobe of young children with intractable seizures...

Epilepsy remains a major health concern as anti-seizure medications frequently fail, and there is currently no treatment to stop or prevent epileptogenesis, the process underlying the onset and progression of epilepsy. The identification of the pathological processes underlying epileptogenesis is instrumental to the development of drugs that may prevent the generation of seizures or control pharmaco-resistant seizures, which affect about 30% of patients. mTOR signalling and neuroinflammation have been recognized as critical pathways that are activated in brain cells in epilepsy...

Darier disease (DD) is a rare monogenetic skin disorder with limited data on its potential association with neurological disorders. This study aimed to investigate the association between DD and neurological disorders, specifically Parkinson's disease, dementias, and epilepsy. Using Swedish national registers in a period spanning between 1977 and 2013, 935 individuals with DD were compared with up to 100 comparison individuals each, randomly selected from the general population based on birth year, sex, and county of residence at the time of the first diagnosis of DD...

The treatment of epilepsy has advanced over the past 30 years through the development of new antiseizure medications (ASMs). Unfortunately, not all of them have been approved yet in Brazil, and many are still underused. When comparing new ASMs to older ones, they are generally not more effective in treating epilepsy. However, they offer better tolerability, with fewer interactions and long-term side effects, especially for patients with comorbidities or those requiring polytherapy. Enzyme induction caused by older ASMs is associated with increased cholesterol levels, drug interactions with decreased effects of statins and other cardiovascular medications, anticoagulants, chemotherapy, immunosuppressors, anti-infective agents (including HIV treatment), antidepressants, and contraceptives...

BACKGROUND AND OBJECTIVES: The occurrence of seizures after aneurysmal subarachnoid hemorrhage (aSAH) is associated with a poorer functional and cognitive prognosis and less favorable quality of life. It would be of value to promptly identify patients at risk of epilepsy to optimize follow-up protocols and design preventive strategies. Our aim was to develop a predictive score to help stratify epilepsy risk in patients with aSAH. METHODS: This is a retrospective, longitudinal study of all adults with aSAH admitted to our center (2012-2021)...

There are no well-validated treatments for functional seizures. While specialist psychotherapy is usually recommended, the evidence for its benefit is qualified, and it can be difficult to obtain. Given the association between hyperventilation and functional seizures we explored an alternative modality, breathing control training, in a multi-site open label pilot trial. Participants with functional seizures over the age of 16 received an hour of breathing training from a respiratory physiotherapist, with a half-hour booster session a month later...

Lennox Gastaut Syndrome (LGS) is characterized by drug-resistant epilepsy that typically leads to decreased quality of life and deleterious neurodevelopmental comorbidities from medically refractory seizures. In recent years there has been a dramatic increase in the development and availability of novel treatment strategies for Lennox Gastaut Syndrome patient to improve seizure. Recent advances in neuromodulation and minimally invasive magnetic resonance guided laser interstitial thermal therapy (MRgLITT) have paved the way for new treatments strategies including deep brain stimulation (DBS), responsive neurostimulation (RNS), and MRgLITT corpus callosum ablation...

Racial disparities affect multiple dimensions of epilepsy care including epilepsy surgery. This study aims to further explore these disparities by determining the utilization of invasive neuromodulation devices according to race and ethnicity in a multicenter study of patients living with focal drug-resistant epilepsy (DRE). We performed a post hoc analysis of the Human Epilepsy Project 2 (HEP2) data. HEP2 is a prospective study of patients living with focal DRE involving 10 sites distributed across the United States...

Traumatic brain injuries are a large societal and individual burden. In the first year of life, the vast majority of these injuries are the result of inflicted abusive events by a trusted caregiver. Abusive head trauma (AHT) in infants, formerly known as shaken baby syndrome, is the leading cause of inflicted mortality and morbidity in this population. In this review we address clinical diagnosis, symptoms, prognosis, and neuropathology of AHT, emphasizing the burden of repetitive AHT. Next, we consider existing animal models of AHT, and evaluate key features of an ideal model, highlighting important developmental milestones in children most vulnerable to AHT...

Deep brain stimulation (DBS) is a viable treatment for a variety of neurological conditions, however, the mechanisms through which DBS modulates large-scale brain networks are unresolved. Clinical effects of DBS are observed over multiple timescales. In some conditions, such as Parkinson's disease and essential tremor, clinical improvement is observed within seconds. In many other conditions, such as epilepsy, central pain, dystonia, neuropsychiatric conditions or Tourette syndrome, the DBS related effects are believed to require neuroplasticity or reorganization and often take hours to months to observe...

Epilepsy is a chronic neurological disease characterized by a persistent susceptibility to seizures. Pharmaco-resistant epilepsies, impacting around 30 % of patients, highlight the urgent need for improved treatments. Neuroinflammation, prevalent in epileptogenic brain regions, is a key player in epilepsy, prompting the search for new mechanistic therapies. Hence, in this study, we explored the anti-inflammatory potential of pyrazole benzenesulfonamide derivative (T1) against pentylenetetrazole (PTZ) induced epilepsy-like conditions in in-vivo zebrafish model...