Ley Sander

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Verified

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• MD PhD FRCP FEAN
• Professor at University College London

BACKGROUND Acute symptomatic seizures (ASyS) increase the risk of epilepsy and mortality after a stroke. The impact of the timing and type of ASyS remains unclear. METHODS This multicenter cohort study included data from 9 centers between 2002 and 2018, with a final analysis in February 2024. The study included 4552 adults (2005 female; median age...

Objective We aimed to assess the prevalence, clinical characteristics, and risk factors for psychosis in a cohort of people with epilepsy in West China. Methods We used retrospective information from databases of three tertiary epilepsy centers, which included follow‐up records from 2006 onward. Those with complete baseline data and at least one f...

Objective Antiseizure medications (ASMs), which may influence cortical excitability, are the mainstay of epilepsy treatment. Transcranial magnetic stimulation (TMS) helps evaluate cortical excitability. We assessed changes in TMS responses using serial TMS measurements in people treated with an adjunctive noncompetitive AMPA‐receptor antagonist. M...

Despite the introduction of newer antiseizure medications (ASMs) with improved safety profiles over the past several years, rates of treatment‐related intolerable adverse events (AEs) for people with epilepsy have not changed substantially. Tolerability issues can potentially jeopardize optimal dosing and effectiveness, regimen adherence, and treat...

Background Mesial temporal lobe epilepsy (mTLE) is the most common form of focal epilepsy, often associated with hippocampal sclerosis. Increasing evidence suggests the pivotal role of neuroinflammation in mTLE onset and progression. Methods We used morphometric similarity network (MSN) analysis and the Allen Human Brain Atlas (AHBA) database to i...

Objectives Approximately 80% of people with epilepsy live in low- and middle-income countries (LMICs), where limited resources and stigma hinder accurate diagnosis and treatment. Clinical machine learning models have demonstrated substantial promise in supporting the diagnostic process in LMICs by aiding in preliminary screening and detection of po...

Objective Data on seizure and pregnancy outcomes in Asian women with epilepsy are limited. We used a Chinese pregnancy registry to assess the impact of seizures and antiseizure medications (ASMs) on pregnant women with epilepsy and their children. Methods This is an ongoing prospective multicenter study of pregnant women with epilepsy that has bee...

Background and objectives: People with epilepsy are at risk of cardiac arrhythmias. Whether this association results from epilepsy, antiseizure medications (ASMs) such as sodium channel blockers (NABs), or other factors has not been systematically assessed. The aims of this study were to quantify the odds of cardiac conduction delays (CCDs) on ele...

Introduction The prevalence of epilepsy in sub-Saharan Africa varies considerably, and the exact estimate for Ghana remains unclear, particularly in peri-urban areas where data are scarce. More community-based studies are required to understand better the actual burden of epilepsy in these areas and the difficulties in accessing healthcare. Object...

Objective Temporal lobe epilepsy with hippocampal sclerosis (HS) is a surgically remediable syndrome. We determined temporal trends in the prevalence of hippocampal sclerosis surgeries and related factors. Methods We analysed a prospective cohort of adults who underwent epilepsy surgery at the NHNN, London, between 1990 and 2019. HS group was comp...

Social determinants of health (SDHs) are significant and potentially modifiable drivers of neurologic diseases, including childhood epilepsy. Social determinants of health greatly influence the epidemiology, management, and outcomes associated with these conditions. Social determinants of health affect every aspect of a family’s journey with epilep...

Purpose Managing epilepsy may require using more than one anti-seizure medication (ASM). While combination therapy may help, risks, including psychiatric problems, are not fully explored in Africa. We examined the relationship between polytherapy and psychiatric comorbidities among attendees of an epilepsy community clinic. Methods We prospectivel...

Background: Acute symptomatic seizures (ASyS) increase the risk of epilepsy and mortality after a stroke. The impact of the timing and type of ASyS remains unclear. Methods: This multicenter cohort study included data from nine centers between 2002 and 2018, with final analysis in February 2024. The study included 4,552 adults (2,005 female; median...

A 29-year-old woman presented with a witnessed convulsion, with semiology consistent with a focal-to-bilateral tonic-clonic seizure. Routine EEG supported a syndromic diagnosis of idiopathic generalised epilepsy with photosensitivity. We discuss the clinical utility of seizure semiology, highlighting the caveat that over-reliance or sole reliance o...

The availability of quality and timely data for routine monitoring of mental, neurological and substance use (MNS) disorders is a challenge, particularly in Africa. We assessed the feasibility of using an open-source data science technology (R Shiny) to improve health data reporting in Nairobi City County, Kenya. Based on a previously used manual t...

Objectives Artificial intelligence (AI) is thought to improve lesion detection. However, a lack of knowledge about human performance prevents a comparative evaluation of AI and an accurate assessment of its impact on clinical decision-making. The objective of this work is to quantitatively evaluate the ability of humans to detect focal cortical dys...

Neurocysticercosis is one of the main risk factors of seizures and epilepsy in many regions of the world, which are Taenia solium-endemic but resource-constrained to control the parasite. The nosology of seizures and the classification of epilepsy in the context of neurocysticercosis are somewhat uncertain. Many seizures associated with the infecti...

People with epilepsy are at risk of premature death, of which sudden unexpected death in epilepsy (SUDEP), sudden cardiac death (SCD) and sudden arrhythmic death syndrome (SADS) are the primary, partly overlapping, clinical scenarios. We discuss the epidemiologies, risk factors and pathophysiological mechanisms for these sudden death events. We rev...

Epilepsy remains a significant public health concern in Tanzania, with affected individuals enduring stigma, whether through actions or perceptions. Myths, misunderstandings, and misconceptions about epilepsy have persisted due to a multitude of factors. Here, we assessed attitudes and perceptions toward epilepsy in Mahenge. A cross-sectional stud...

Introduction Epidemiological evidence suggests that Onchocerca volvulus is associated with epilepsy, although the exact pathophysiological mechanism is unknown. Mahenge is an endemic focus of onchocerciasis, with the longest-running ivermectin treatment intervention in Tanzania. We assessed the prevalence of onchocerciasis and epilepsy after 25 yea...

Objective To characterize the experience of people with epilepsy and aligned healthcare workers (HCWs) during the first 18 months of the COVID‐19 pandemic and compare experiences in high‐income countries (HICs) with non‐HICs. Methods Separate surveys for people with epilepsy and HCWs were distributed online in April 2020. Responses were collected...

Objective To assess whether arterial spin labeling perfusion images of healthy controls can enhance ictal single‐photon emission computed tomography analysis and whether the acquisition of the interictal image can be omitted. Methods We developed 2 pipelines: The first uses ictal and interictal images and compares these to single‐photon emission c...

Objective Using Optical coherence tomography (OCT), we evaluated the association between peripapillary retinal nerve fiber, macular thickness, macular ganglion cell‐inner plexiform layer, and drug resistance. Methods In this cross‐sectional study, we recruited people diagnosed with epilepsy and healthy controls. People with epilepsy were further s...

Progressive inflammation of one hemisphere characterises Rasmussen’s encephalitis (RE), but contralesional epileptiform activity has been repeatedly reported. We aimed to quantify contralesional epileptiform activity in RE and uncover its functional and structural underpinnings. We retrospectively ascertained people with RE treated between 2000 and...

Sudden unexpected death in epilepsy (SUDEP) is responsible for most epilepsy-related deaths. It is mainly related to unwitnessed nocturnal convulsions, either focal to bilateral or generalised tonic–clonic seizures (TCS). Targeted preventive strategies are currently lacking as underlying mechanisms are largely unknown. Antiseizure medications (ASMs...

In the last decades, epilepsy has shifted from being a condition defined purely by seizures to one also characterised by its comorbidities. This conceptualisation of epilepsy as an index disease to a set of comorbidities has been helpful but now faces challenges. Epilepsy is not always “the root of the problem”, nor is it inherently a homogeneous d...

Background: Premature mortality is a significant part of the epilepsy burden and may vary across populations, especially between high-income and lower- and middle-income countries. People with epilepsy in China are approximately a fifth of the global population with epilepsy. Previous studies were unlikely to represent the situation in China due t...

Objective This study was undertaken to develop a model and perform a preliminary internal validation study of the Scale for Objective Diagnostic Components of Paroxysmal Events (STAMP). Methods We developed STAMP, which builds on the International League Against Epilepsy task force scale for functional seizures with additional categories for epile...

Background WHO estimates that more than 50 million people worldwide have epilepsy and 80% of cases are in low-income and middle-income countries. Most studies in Africa have focused on active convulsive epilepsy in rural areas, but there are few data in urban settings. We aimed to estimate the prevalence and spatial distribution of all epilepsies i...

Introduction: The prevalence of epilepsy in sub-Saharan Africa varies considerably, and the exact estimate in Ghana is unknown, with few data available from peri-urban areas. More community-based studies are required to understand the tangible burden of epilepsy in these areas and the difficulties in healthcare access. Objective: To validate a hous...

Background In addition to other stroke-related deficits, the risk of seizures may impact driving ability after stroke. Methods We analysed data from a multicentre international cohort, including 4452 adults with acute ischaemic stroke and no prior seizures. We calculated the Chance of Occurrence of Seizure in the next Year (COSY) according to the...

Objective To assess asymptomatic rates and severity of SARS‐CoV‐2 infection in people with epilepsy and their healthcare workers in a long‐term care facility which had implemented weekly surveillance testing between April 2020 and June 2022. Methods Questionnaires focused on objective and subjective COVID‐19 symptoms for people with epilepsy resid...

Objectives Approximately 80% of people with epilepsy live in low- and middle-income countries (LMICs), where limited resources and stigma hinder accurate diagnosis and treatment. Clinical machine learning models have demonstrated substantial promise in supporting the diagnostic process in LMICs without relying on specialised or trained personnel. H...

Cognition and behaviour are thought to be underpinned by seven segregated brain networks, whose tasks range from the sensory role of the visual network to intrinsic mental processes such as consciousness carried out by the default-mode network. However, it is unclear whether functional integrity of these networks is retained when the brain is devoi...

Epilepsy is one of the most common neurologic conditions. Its clinical manifestations are not restricted to seizures but often include cognitive disturbances and psychiatric disorders. Prospective population-based studies have shown that people with epilepsy have an increased risk of developing mood disorders, and people with a primary mood disorde...

Objective To describe long-term seizure remission and relapse patterns, psychiatric comorbidity, and socioeconomic outcomes following frontal lobe epilepsy surgery. Methods We reviewed data on frontal lobe epilepsy procedures at the National Hospital for Neurology & Surgery, UK, between 1990 and 2020. This included the presurgical evaluation, oper...

Objective Focal epilepsy is common in low‐ and middle‐income countries. The frequency and nature of possible underlying structural brain abnormalities have, however, not been fully assessed. Methods We evaluated the possible structural causes of epilepsy in 331 people with epilepsy (240 from Kenya and 91 from South Africa) identified from communit...

Introduction and Aims Functional seizures (also known historically as hysterical, dissociative or psychogenic non-epileptic seizures) are seizures that look like epileptic seizures but are not associated with epileptogenic brain discharges. They are the most common form of functional neurological disorder and have been written about since Babylonia...

Background and purpose The aim was to investigate the neurological complications associated with coronavirus disease 19 (COVID‐19) during the 2022 Omicron wave. Methods and analysis The medical records of a cohort of people admitted to neurological wards of three participating tertiary centres in Sichuan from 12 December 2022 to 12 January 2023 we...

Artificial intelligence (AI)-based tools are widely employed, but their use for diagnosis and prognosis of neurological disorders is still evolving. Here we analyse a cross-sectional multicentre structural MRI dataset of 696 people with epilepsy and 118 control subjects. We use an innovative machine-learning algorithm, Subtype and Stage Inference,...

Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here we report a multi-ancestry genome-wide association study including 29,944 cases, stratified into three broad categories and seven subtypes of epilepsy, and 52,538 controls. We identify 26 genome-wide...

Objective Genes associated with Long QT syndromes (LQTS), such as KCNQ1, KCNH2, and SCN5A, are common causes of epilepsy. The Arg 744* variant of KCNH2 has been previously reported in people with epilepsy or LQTS, but none of these patients were reported to simultaneously suffer from epilepsy and LQTS. Herein, we report the case of a family with ep...

Importance: Acute symptomatic seizures occurring within 7 days after ischemic stroke may be associated with an increased mortality and risk of epilepsy. It is unknown whether the type of acute symptomatic seizure influences this risk. Objective: To compare mortality and risk of epilepsy following different types of acute symptomatic seizures. D...

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 p...

Transcranial magnetic stimulation (TMS) with electroencephalography (EEG), that is TMS-EEG, may assist in managing epilepsy. We systematically reviewed the quality of reporting and findings in TMS-EEG studies on people with epilepsy and healthy controls, and on healthy individuals taking anti-seizure medication. We searched the Cochrane Library, Em...

The World Health Assembly approved the Intersectoral Global Action Plan for epilepsy and neurological disorders. Member states, including those in Southeast Asia, must now prepare to achieve IGAP's strategic targets by embracing novel approaches and strengthening existing policies and practices. We propose and present evidence to support four such...

Objective This study was undertaken to estimate the cost‐effectiveness of add‐on cenobamate in the UK when used to treat drug‐resistant focal seizures in adults who are not adequately controlled with at least two prior antiseizure medications, including at least one used adjunctively. Methods We estimated the cost per quality‐adjusted life‐year (Q...

Migraine is associated with altered sensory processing, that may be evident as changes in cortical responsivity due to altered excitability, especially in migraine with aura. Cortical excitability can be directly assessed by combining transcranial magnetic stimulation with electroencephalography (TMS-EEG). We measured TMS evoked potential (TEP) amp...

Background: Epilepsy is clinically defined as two or more unprovoked epileptic seizures more than 24 hours apart. Given that, a diagnosis of epilepsy can be associated with significant morbidity and mortality, it is imperative that clinicians (and people with seizures and their relatives) have access to accurate and reliable prognostic estimates,...

Objective. Presurgical long‐term video‐EEG monitoring (LT‐VEEG) is an important part of the presurgical evaluation in patients with focal epilepsy. Multiple seizures need to be recorded, often in limited time and with the need to taper anti‐seizure medication (ASM). The aim of this study was to systematically study the yield – in terms of success –...

Perampanel, a noncompetitive antagonist of the postsynaptic a‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic (AMPA) receptor, is effective for controlling focal to bilateral tonic–clonic seizures but is also known to increase feelings of anger. Using statistical parametric mapping–derived measures of activation and task‐modulated functional connecti...

Objective This study was undertaken to characterize somatic symptoms and related disorders (SSD) in epilepsy. Methods Adults with epilepsy under active follow‐up at a tertiary epilepsy center were consecutively enrolled. The diagnosis of SSD was performed by an experienced psychologist based on the structured clinical interview for Statistical Man...

Objectives: As part of the COVID-19 and Epilepsy (COV-E) global study, we aimed to understand the impact of COVID-19 on the medical care and well-being of people with epilepsy (PWE) in the United States, based on their perspectives and those of their caregivers. Methods: Separate surveys designed for PWE and their caregivers were circulated from Ap...

More than half of adults with epilepsy undergoing resective epilepsy surgery achieve long-term seizure freedom and might consider withdrawing antiseizure medications (ASMs). We aimed to identify predictors of seizure recurrence after starting postoperative ASM withdrawal and develop and validate predictive models. We performed an international mult...

Artificial intelligence (AI)-based tools are widely employed, but their use for diagnosis and prognosis of neurological disorders is still evolving. We capitalise on a large-scale, cross-sectional structural MRI dataset of 814 people with epilepsy. We use a recently developed machine-learning algorithm, Subtype and Stage Inference (SuStaIn), to dev...

Psychiatric disorders are frequent among people with epilepsy but often under-recognized. The diagnosis and treatment of these disorders in low-and low-middle-income countries (LMICs) are challenging. Methods: This cross-sectional survey included people recruited during a community epilepsy screening program involving 59,509 individuals from poor c...

Background A third of people with juvenile myoclonic epilepsy (JME) are drug-resistant. Three-quarters have a seizure relapse when attempting to withdraw anti-seizure medication (ASM) after achieving seizure-freedom. It is currently impossible to predict who is likely to become drug-resistant and safely withdraw treatment. We aimed to identify pred...

Objective To ascertain whether home‐based care with community and primary healthcare workers' support improves adherence to antiseizure medications, seizure control, and quality of life over routine clinic‐based care in community samples of people with epilepsy in a resource‐poor country. Methods Participants included consenting individuals with a...

Introduction Brivaracetam (BRV) is licensed as an adjunctive treatment for focal epilepsy. We describe our clinical experience with BRV at a large UK tertiary center. Methods Adults initiated on BRV between July 2015 and July 2020 were followed up until they discontinued BRV or September 2021. Data on epilepsy syndrome, duration, seizure types, co...

Background Epilepsy is one of the most common neurological conditions worldwide. As a chronic condition, epilepsy imposes a significant burden on people with epilepsy and society. We aimed to assess the burden and unmet need of individuals with epilepsy and their caregivers, focusing on focal seizures, the main type of seizure in adults and childre...

Objective Resective surgery for selected individuals with frontal lobe epilepsy can be effective, although multimodal outcomes are less established than in temporal lobe epilepsy. We describe long-term seizure remission and relapse patterns, psychiatric comorbidity, and socioeconomic outcomes following frontal lobe epilepsy surgery. Methods We rev...

More than half of adults with epilepsy undergoing resective epilepsy surgery achieve long-term seizure freedom and might consider withdrawing antiseizure medications (ASMs). We aimed to identify predictors of seizure recurrence after starting postoperative ASM withdrawal and develop and validate predictive models. We performed an international mult...

Purpose Most people with epilepsy receive chronic, long-term treatment with ≥1 anti-seizure medication. Retention rates provide can act as a proxy measure for clinical efficacy/safety over time. We present long-term exposure and retention data from open-label extensions (OLEs) of 3 trials in adults with uncon- trolled focal onset seizures (FOS) rec...

Drug-resistant epilepsy is associated with poor health outcomes and increased economic burden. In the last three decades, various new antiseizure medications have been developed, but the proportion of people with drug-resistant epilepsy remains relatively unchanged. Developing strategies to address drug-resistant epilepsy is essential. Here, we def...

Objective Levetiracetam (LEV) is an effective antiseizure medicine, but 10%–20% of people treated with LEV report psychiatric side‐effects, and up to 1% may have psychotic episodes. Pharmacogenomic predictors of these adverse drug reactions (ADRs) have yet to be identified. We sought to determine the contribution of both common and rare genetic var...

Objective A recent FDA warning concerning an arrhythmogenic potential of lamotrigine created concern in the neurological community. This warning was based on in vitro studies, but no clinically relevant risk was considered. This rapid systematic review aims to elucidate the risk of lamotrigine on sudden death or electrocardiogram abnormalities. Me...

Objective To estimate the cost and time taken to evaluate adults with drug-resistant focal epilepsy for potentially curative surgery. Methods We reviewed data on 100 consecutive individuals at a tertiary referral center evaluated for epilepsy surgery in 2017. The time elapsed between referral and either surgery or a definitive decision not to prog...

Background: The burden of premature mortality associated with human cysticercosis is largely ignored mainly due to poor record-keeping in Taenia solium endemic regions. Objective: To document mortality and survival characteristics of an historical cohort with cysticercosis. Methods: The years of onset of symptoms and death untill 1957 were ext...

Background In epilepsy, cognitive difficulties are common, partly a consequence of anti-seizure medications (ASM), and cognitive side-effects are often considered to be more disabling than seizures and significantly affect quality of life. Functional MRI during verbal fluency tasks demonstrated impaired frontal activation patterns and failed defaul...

Introduction Earlier systematic reviews estimated the epilepsy treatment gap in low- and low-middle-income countries to be above 75%. Reduction in the gap since then due to healthcare improvements and socio-economic changes is plausible but unproven. Aim To review the epilepsy treatment gap evidence and determine if it has decreased over time. Me...

Diabetes mellitus may arise abruptly and decompensate suddenly, leading to a hyperglycaemic hyperosmolar state. Coma often ensues, although this usually reverses after the metabolic abnormalities have resolved. Acute symptomatic seizures can also occur in patients who are conscious, although these usually resolve after osmolarity and glycaemia have...

Better drugs are needed for common epilepsies. Drug repurposing offers the potential of significant savings in the time and cost of developing new treatments. In order to select the best candidate drug(s) to repurpose for a disease, it is desirable to predict the relative clinical efficacy that drugs will have against the disease. Common epilepsy c...