Martin J Brodie's research while affiliated with University of Glasgow and other places

Publications (465)

Article
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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...
Article
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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...
Article
Importance: Selection of antiseizure medications (ASMs) for epilepsy remains largely a trial-and-error approach. Under this approach, many patients have to endure sequential trials of ineffective treatments until the "right drugs" are prescribed. Objective: To develop and validate a deep learning model using readily available clinical informatio...
Article
Purpose The results of the double-blind (DB), placebo-controlled trial C017 demonstrated that ceno- bamate achieved highly significant rates of seizure freedom vs placebo in patients with uncontrolled FOS. Here we assess the long-term efficacy of cenobamate during the open-label extension (OLE) of the 017 study. Methods Subjects who completed the...
Article
Purpose Results from two double-blind, placebo-controlled studies demonstrated that adjunctive ceno- bamate significantly reduced the frequency of seizures vs placebo. Cenobamate 200mg/day achieved seizure freedom in 28.3% vs 8.8% placebo (P<0.0003; 013 study maintenance phase) and 21.1%, 11.2% for cenobamate 400mg/d and 200mg/d, respectively, vs 1...
Article
People with epilepsy (PWE) may die suddenly and unexpectedly and without a clear under-lying pathological etiology; this is called SUDEP (sudden unexpected death in epilepsy). The pooled estimated incidence rate for SUDEP is 23 times the incidence rate of sudden death in the general population with the same age. Empowering healthcare professionals,...
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The aim of this document is to provide evidence‐based recommendations for the medical treatment of depression in adults with epilepsy. The working group consisted of members of an ad hoc Task Force of the International League Against Epilepsy (ILAE) Commission on Psychiatry, ILAE Executive and the International Bureau for Epilepsy (IBE) representat...
Article
Currently no sensitive and specific biomarkers exist to predict drug‐resistant epilepsy. We determined whether blood levels of high‐mobility group box 1 (HMGB1), a mediator of neuroinflammation implicated in drug‐resistant epilepsies, identifies patients with drug‐resistant seizures. Patients with drug‐resistant epilepsy express significantly highe...
Article
People with epilepsy have variable and dynamic trajectories in response to antiseizure medications. Accurately modelling long-term treatment response will aid prognostication at the individual level and health resource planning at the societal level. Unfortunately, a robust model is lacking. We aimed to develop a Markov model to predict the probabi...
Article
The COVID-19 pandemic has had an unprecedented impact on people and healthcare services. The disruption to chronic illnesses, such as epilepsy, may relate to several factors ranging from direct infection to secondary effects from healthcare reorganization and social distancing measures. Objectives As part of the COVID-19 and Epilepsy (COV-E) global...
Article
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Objective To develop and validate a tool for individualised prediction of Sudden Unexpected Death in Epilepsy (SUDEP) risk, we re-analysed data from one cohort and three case-control studies undertaken 1980-2005. Methods We entered 1273 epilepsy cases (287 SUDEP, 986 controls) and 22 clinical predictor variables into a Bayesian logistic regression...
Article
Objective Brivaracetam (BRV), is licensed in Europe as adjunctive treatment, and in the United States of America as adjunctive and monotherapy for focal seizures with or without secondary generalization in adults, adolescents, and children ≥4 years. As BRV becomes available globally, this prospective audit was undertaken to gain an understanding of...
Article
The World Health Organization (WHO) has recognized epilepsy as a public health imperative due to its occurrence at all ages in all regions of the world, its high impact on disability‐adjusted life years and psychosocial aspects, and the accompanying stigma. The International League Against Epilepsy and the International Bureau for Epilepsy have est...
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OBJECTIVE: We assessed the efficacy, safety, and tolerability of cannabidivarin (CBDV) as add-on therapy in adults with inadequately controlled focal seizures. MATERIALS AND METHODS: One hundred and sixty-two participants (CBDV n=81; placebo n=81) were enrolled. After a 4-week baseline, participants titrated from 400 to 800 mg CBDV twice daily (b.i...
Article
The COVID-19 pandemic has caused global anguish unparalleled in recent times. As cases rise, increased pressure on health services, combined with severe disruption to people’s everyday lives, can adversely affect individuals living with chronic illnesses, including people with epilepsy. Stressors related to disruption to healthcare, finances, menta...
Preprint
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There is growing interest in machine learning based approaches to assist clinicians in treatment selection. In the treatment of epilepsy, a common neurological disorder that affects 70 million people worldwide, previous research has employed scoring methods generated from traditional machine learning methods based on pre-treatment patient character...
Article
Objectives To describe the clinical characteristics and evaluate the long‐term treatment outcomes in older people with newly diagnosed epilepsy over the past 30 years. Methods We included patients newly diagnosed with epilepsy and commenced on antiseizure medications (ASMs) at age 65 years or older between July 1982 and October 2012 at the Western...
Article
Access to quality healthcare remains a challenge that is complicated by mounting pressures to control costs, and now, as we witness, the unprecedented strain placed on our healthcare delivery systems due to the COVID-19 pandemic. Challenges in healthcare access have driven a need for innovative approaches ensuring connectivity to health providers....
Article
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Objectives To provide information on the impact of the COVID-19 pandemic on people with epilepsy and provide consensus recommendations on how to provide the best possible care for people with epilepsy while avoiding visits to urgent care facilities and hospitalizations during the Novel Coronavirus pandemic. Methods The authors developed consensus...
Article
Importance Tolerability is a key determinant of the effectiveness of epilepsy treatment. It is important to evaluate whether the overall tolerability has improved. Objective To identify factors associated with poor tolerability of antiseizure medications (ASMs) and examine temporal changes in tolerability. Design, Setting, and Participants This w...
Article
Since 1989, 18 second-generation antiseizure medications have reached the market, resulting in a greatly increased range of treatment options for patients and prescribers. 30 years have passed and now is the time for an appraisal of the effect of these medications on clinical outcomes. Every antiseizure medication needs to be assessed individually,...
Article
Purpose of review: Nearly two dozen antiseizure medications (ASMs) with different mechanisms of action have been introduced over the past three decades with the aim of providing better efficacy or safety profile than the previous drugs. Several new ASMs with improvement on a classic drug family or have novel mechanisms of action have been recently...
Article
Common genetic generalised epilepsy syndromes encountered by clinicians include childhood and juvenile absence epilepsies, juvenile myoclonic epilepsy and generalised tonic–clonic seizures on awakening. Treatment of these syndromes involves largely the use of broad-spectrum antiseizure drugs. Those effective for the generalised epilepsies include s...
Article
Understanding the natural history of and factors associated with pharmacoresistant epilepsy provides the foundation for formulating mechanistic hypotheses that can be evaluated to drive the development of novel treatments. This article reviews the modern definition of drug-resistant epilepsy, its prevalence and incidence, risk factors, hypothesized...
Article
Objective To evaluate the long‐term pharmacological outcomes in teenagers with different epilepsies. Method This study included teenagers aged 13‐19 years at treatment initiation who were newly treated with antiepileptic drugs (AEDs) at the epilepsy unit of the Western Infirmary in Glasgow, Scotland, between 1 September 1982 and 30 September 2012....
Article
Epilepsy is a common neurological condition in women worldwide. Hormonal changes occurring throughout a woman's life can influence and be influenced by seizure mechanisms and antiepileptic drugs, presenting unique management challenges. Effective contraception is particularly important for women with epilepsy of childbearing potential because of an...
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Objective To pool observational data on the routine use of perampanel to obtain information on real‐world outcomes and data in populations typically underrepresented in clinical trials. Methods Individual‐level data of people with epilepsy treated with perampanel at 45 European centers were merged into a single dataset. Prespecified outcomes were:...
Article
To assess the association, if any, between brivaracetam (BRV)-induced elevated carbamazepine-10,11-epoxide (CBZ-E) and toxicity and efficacy in patients with epilepsy. Data were pooled from three double-blind, placebo-controlled, Phase III studies of adjunctive BRV in adults with uncontrolled focal seizures (N01252/NCT00490035, N01253/NCT00464269,...
Article
Introduction Epilepsy is a common and often highly morbid disease, associated with a not insignificant mortality. Some aspects of epilepsy have been well studied, for example the genetic basis and phenomenology of certain epilepsy syndromes, while other aspects such as long-term outcomes in large cohorts of epilepsy patients are less well studied....
Article
The International League against Epilepsy (ILAE) published in the April 2017 edition of Epilepsia three companion articles on the classification of seizures and the epilepsies. These represent a long-awaited update on the original 1981 and 1989 publications and provide a modern descriptive template. The new classification presents three levels of t...
Article
Background: Evidence for the comparative teratogenic risk of antiepileptic drugs is insufficient, particularly in relation to the dosage used. Therefore, we aimed to compare the occurrence of major congenital malformations following prenatal exposure to the eight most commonly used antiepileptic drugs in monotherapy. Methods: We did a longitudin...
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Objective: To characterize, among European and Han Chinese populations, the genetic predictors of maculopapular exanthema (MPE), a cutaneous adverse drug reaction common to antiepileptic drugs. Methods: We conducted a case-control genome-wide association study of autosomal genotypes, including Class I and II human leukocyte antigen (HLA) alleles...
Article
Importance A study published in 2000 showed that more than one-third of adults with epilepsy have inadequate control of seizures with antiepileptic drugs (AEDs). This study evaluates overall treatment outcomes in light of the introduction of more than 1 dozen new AEDs in the past 2 decades. Objective To assess long-term treatment outcome in patien...
Article
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The most common forms of acquired epilepsies arise following acute brain insults such as traumatic brain injury, stroke, or central nervous system infections. Treatment is effective for only 60%-70% of patients and remains symptomatic despite decades of effort to develop epilepsy prevention therapies. Recent preclinical efforts are focused on likel...
Article
Over the past decade there has been an increasing interest in using cannabinoids to treat a range of epilepsy syndromes following reports of some remarkable responses in individual patients. The situation is complicated by the fact that these agents do not appear to work via their attachment to endogenous cannabinoid receptors. Their pharmacokineti...
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Brivaracetam (BRV), the n-propyl analogue of levetiracetam (LEV), is the latest antiepileptic drug (AED) to be licensed in Europe and the USA for the adjunctive treatment of focal-onset seizures with or without secondary generalization in patients aged 16 years or older. Like LEV, BRV binds to synaptic vesicle protein 2A (SV2A), but BRV has more se...
Article
Psychiatric comorbidities are common in people with epilepsy. A retrospective study of characteristics associated with withdrawal due to psychiatric side effects was undertaken in patients with treated epilepsy participating in prospective audits with new antiepileptic drugs (AEDs). A total of 1058 treated patients with uncontrolled seizures (942 f...
Article
Sodium channel blockers have been the mainstay of the pharmacological management of focal and generalised tonic-clonic seizures for more than 70 years. The focus of this paper will be on phenytoin, carbamazepine, lamotrigine, oxcarbazepine, rufinamide, lacosamide and eslicarbazepine acetate. All these antiepileptic drugs have similar efficacy and s...
Article
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Approximately 30% of epilepsy patients do not respond to antiepileptic drugs, representing an unmet medical need. There is evidence that neuroinflammation plays a pathogenic role in drug-resistant epilepsy. The high-mobility group box 1 (HMGB1)/TLR4 axis is a key initiator of neuroinflammation following epileptogenic injuries, and its activation co...
Article
This paper discusses the issues surrounding the tolerability and safety of the commonly used antiepileptic drugs (AEDs) in adolescents and adults. The content includes dose-related adverse effects, idiosyncratic reactions, behavioural and psychiatric comorbidities, chronic problems, enzyme induction and teratogenesis. Twenty-one AEDs are discussed...
Article
Objective: This Phase I, open-label, dose-escalation study investigated the effects of steady-state brivaracetam on the pharmacokinetics of carbamazepine in patients with epilepsy, with and without valproate co-administration. Valproate and brivaracetam inhibit epoxide hydrolase and increase carbamazepine epoxide levels. Methods: Adult patients...
Article
The outpatient services at the Epilepsy Unit in the Western Infirmary, Glasgow, Scotland was set up in September 1982. From the outset patient data were collected prospectively. A focused approach to patients with newly diagnosed epilepsy was developed and a series of 4 analyses have been undertaken over the intervening years, with results from the...
Article
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Introduction: This analysis was conducted to assess the tolerability, safety, and efficacy of brivaracetam (BRV) for adjunctive treatment of focal (partial-onset) seizures in patients aged ≥65 years. Methods: Safety/tolerability and efficacy data for patients aged ≥65 years were pooled from three randomized, double-blind, placebo-controlled, fix...
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More than 30 % of adults with epilepsy do not fully control on the currently available antiepileptic drugs (AEDs). For these and many other patients, combinations of agents, often possessing different mechanisms of actions, are employed with the aim of achieving seizure freedom or the best available prognosis in terms of reduced seizure numbers and...
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Antiepileptic drugs (AEDs) have many benefits but also many side effects, including aggression, agitation, and irritability, in some patients with epilepsy. This article offers a comprehensive summary of current understanding of aggressive behaviors in patients with epilepsy, including an evidence-based review of aggression during AED treatment. Ag...
Article
Juvenile myoclonic epilepsy (JME) is a common genetic epilepsy syndrome usually presenting in adolescence and characterized by myoclonic jerks, predominately in the arms, associated with tonic-clonic seizures and less often generalized absences. Although the evidence base for treating JME is weak, most experts regard sodium valproate as drug of fir...
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Objective: To compare patient characteristics and treatment patterns among clobazam (CLB) and clonazepam (CZP)-treated patients with epilepsy in a longitudinal primary care database. Methods: In this pharmacoepidemiological study, real-life usage data from the Clinical Practice Research Database (CPRD) were evaluated. The CPRD collects data from...
Article
Purpose: Perampanel (PER) was first licensed in the United Kingdom in 2012 for the adjunctive treatment of focal seizures with or without secondary generalization in adults and children over 12years of age. It has recently also been approved for use as add-on therapy for patients with primary generalized tonic-clonic seizures. This prospective aud...
Article
Purpose: Juvenile myoclonic epilepsy (JME) is one of the most frequently diagnosed of the idiopathic generalised epilepsy syndromes, but long term outcome data still remain sparse. Methods: A retrospective audit was undertaken in 186 patients (male: n=78; female: n=108) diagnosed with JME at the Epilepsy Unit at the Western Infirmary in Glasgow,...
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Perampanel is approved for adjunctive therapy of focal epilepsy with or without secondarily generalized seizures in patients aged >12 years. This narrative review uses real-world and clinical trial data to elucidate perampanel's role in the clinic. Audit data show good tolerability with perampanel and higher freedom-from-seizure rates in elderly vs...
Article
This article lays the background for, and discusses the practical issues surrounding, the adjunctive use of the last four antiepileptic drugs (AEDs) to be licensed for the treatment of pharmacoresistant focal seizures in the UK and elsewhere. More than 30 % of adolescent and adult patients will not be fully controlled on the currently available the...
Article
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Background: Dyspigmentation of the oral mucosa has a multitude of aetiological causes. Retigabine, a new antiepileptic drug, has the potential side effect of inducing a blue/purple pigmentation of the oral mucosa in addition to the skin, lips, nails and retina of the eyes. This article presents a unique case of dyspigmentation present in the oral...
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Aim: To further explore the impact of concomitant antiepileptic drugs (AEDs) on the efficacy and tolerability of adjunctive perampanel for focal epilepsy. Methods: Data were pooled from three phase III trials of adjunctive perampanel in patients (≥12 years of age) with refractory partial-onset seizures. Concomitant AEDs were categorized accordin...
Article
Purpose: In 2008, lacosamide (LCM) was licensed in Europe for the adjunctive treatment of focal-onset seizures. At that time a prospective audit was initiated at the Western Infirmary to assess outcomes with this antiepileptic drug (AED) in everyday clinical practice. Methods: A total of 160 patients (74 M; 86 F, aged 14-74 years [median 42 year...
Article
Integrated data from 3 double-blind, randomized, placebo-controlled trials were analyzed to evaluate the efficacy and tolerability of ezogabine (EZG; US adopted name)/retigabine (RTG; international non-proprietary name) when used in combination with ≥1 sodium channel blocking antiepileptic drug (AED), ≥1 non-sodium channel blocking AED, or ≥1 AED f...
Article
Despite the availability of a wide range of new antiepileptic drugs (AEDs), there is little evidence that their introduction has substantially altered outcomes. This paper reviews data from 5 consecutive prospective audits with new AEDs using similar methodology. Prospective audits with topiramate (TPM; n=135), levetiracetam (LEV; n=136), zonisamid...
Article
Retigabine (RTG; international nonproprietary name)/ezogabine (EZG; US adopted name) is an antiepileptic drug (AED) that prolongs neuronal voltage-gated potassium-channel KCNQ2-5 (Kv 7.2-7.5) opening. This double-blind study evaluated different RTG/EZG dose-titration rates. Patients (N=73) with partial-onset seizures receiving concomitant AEDs were...
Article
A proportion of patients with seemingly "uncontrolled" epilepsy could still control their epilepsy with further pharmacological manipulations. It is possible that their epilepsy might not be truly "drug-resistant". We audited the patients with "uncontrolled epilepsy" using the recent ILAE definition of drug-resistant epilepsy. Patients with newly d...
Article
There are now a handful of published meta-analyses surrounding the efficacy and tolerability of, particularly, the newer antiepileptic drugs (AEDs) as adjunctive treatment for patients with refractory focal (partial) seizures [1-4]. All have included numerous published studies with largely similar designs and have come to largely similar non-specif...
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This short article reviews 30 years of prospective observations on outcomes relevant to an expanding cohort of adolescent and adult patients with newly diagnosed epilepsy, who received their first antiepileptic drug (AED) and subsequent long-term follow-up at the Epilepsy Unit at the Western Infirmary in Glasgow, United Kingdom. Despite the fact th...
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Longitudinal studies of newly diagnosed epilepsy in children and adults have identified prognostic factors that allow early identification of patients whose seizures are likely to remain uncontrolled with antiepileptic medication. Results from outcome studies may be subject to bias, depending on the setting (community versus clinic), design (retros...
Article
Purpose: Autoantibodies to specific neurologic proteins are associated with subacute onset encephalopathies, which often present with seizures that are poorly controlled by conventional antiepileptic drugs (AEDs). Previous cross-sectional studies have found specific neurologic antibodies in a small proportion of people with established epilepsy, b...
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Much time, money and effort on behalf of patients, doctors, statisticians, pharmaceutical personnel and regulators are spent in planning and undertaking clinical trial programmes that result in antiepileptic drugs reaching the marketplace and thereafter becoming available for treating people with epilepsy in everyday clinical practice. Rather unusu...
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Zonisamide is a benzisoxazole derivative, chemically unrelated to other antiepileptic drugs, that appears to have multiple mechanisms of action, including inhibition of Na(+) channels and reduction of T-type Ca(2+) currents. It is currently licensed in Europe and the USA for adjunctive treatment of partial seizures in adults, and in Europe as monot...
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This article reviews the current position of phenobarbital using articles published since 2000 and speculates on its likely future contribution to epilepsy care. Over the last decade there have been no major double-blind randomized placebo-controlled or comparative trials with phenobarbital. Previous studies have suggested that phenobarbital is as...
Article
Purpose: The recent definition of drug-resistant epilepsy proposed by the International League Against Epilepsy (ILAE) stipulated failure of an adequate trial of two tolerated, appropriately chosen and used antiepileptic drug (AED) schedules to achieve seizure freedom. Doses failed were not specifically discussed. We explored the effect of the dos...
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Several commonly prescribed antiepileptic drugs (AEDs)-including phenobarbital, phenytoin, and carbamazepine-stimulate the synthesis of a broad range of monooxygenase and conjugating enzymes. These agents are well known to reduce the duration and action of many lipid- and non-lipid-soluble drugs, including anticoagulants, cytotoxics, analgesics, an...
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Recent evidence indicates that the licensing of a range of novel antiepileptic drugs during the last two decades has slightly improved the prognosis of adult epilepsy. However, drug resistance still remains a major challenge in epilepsy management, with approximately 30% of patients in whom seizure freedom cannot be achieved despite adequate drug t...
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Interim results of two open-label extension studies assessed ezogabine/retigabine safety and tolerability for partial-onset seizures. At data cutoff, 336 (60%) patients received ≥12 months' open-label ezogabine/retigabine. The most common TEAEs included dizziness (22%), somnolence (19%), headache (14%), and fatigue (10%). Change in seizure frequenc...
Article
Additional options are needed for monotherapy treatment of adults newly diagnosed with partial epilepsy. This trial compares the efficacy and tolerability of once-daily zonisamide with twice-daily controlled-release carbamazepine monotherapy for such patients. In this phase 3, randomised, double-blind, parallel-group, non-inferiority trial, adults...
Article
Unlike many other areas of therapeutics, specific regulatory trial programmes are required to be undertaken in newly diagnosed epilepsy to support the licensing of novel antiepileptic drugs for use in drug-naïve patients. To complicate matters further, American and European regulators have taken markedly different approaches to this issue, with the...
Article
To delineate the temporal patterns of outcome and to determine the probability of seizure freedom with successive antiepileptic drug regimens in newly diagnosed epilepsy. Patients in whom epilepsy was diagnosed and the first antiepileptic drug prescribed between July 1, 1982, and April 1, 2006, were followed up until March 31, 2008. Outcomes were c...