Background and Objectives A recent Food and Drug Administration warning concerning an arrhythmogenic potential of lamotrigine created concern in the neurologic community. This warning was based on... Show moreBackground and Objectives A recent Food and Drug Administration warning concerning an arrhythmogenic potential of lamotrigine created concern in the neurologic 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 ECG abnormalities. Methods We conducted a systematic search of Ovid Medline and Ovid Embase, including randomized controlled trials and observational studies and studies of people with or without epilepsy, with the outcome measures sudden unexpected death in epilepsy (SUDEP) or sudden cardiac death as well as the development or worsening of ECG abnormalities. We evaluated the sudden death definitions used in all included studies, as some could have used unclear or overlapping definitions. We used the American Academy of Neurology risk of bias tool to evaluate the class of evidence and the GRADE approach to evaluate our confidence in the evidence. Results We included 26 studies with 24,962 participants, of whom 2,326 used lamotrigine. Twelve studies showed no significant risk of SUDEP for lamotrigine users. One study reporting on sudden cardiac death and 3 studies with unclear sudden death definitions did not report an elevated risk of death in lamotrigine users compared to controls. In 10 studies reporting on ECG measures, there was no statistically significant increased risk among lamotrigine users except in 2 studies. These 2 studies reported either "slight increases" in PR interval or an increased PQ interval that the primary study authors believed to be related to structural cardiac differences rather than an effect of lamotrigine. One study was rated Class II; all others were Class III or IV. We had very low confidence in the evidence following the GRADE assessment. None of the studies examined the risk of lamotrigine in people with preexisting cardiac conditions. Discussion There is insufficient evidence to support or refute that lamotrigine is associated with sudden death or ECG changes in people with or without epilepsy as compared to antiseizure medication or placebo, due to the high risk of bias in most studies and low precision and inconsistency in the reported results. Show less
Introduction: The lack of reliable biomarkers constrain epilepsy management. We assessed the potential of repeated transcranial magnetic stimulation with electromyography (TMS-EMG) to track... Show moreIntroduction: The lack of reliable biomarkers constrain epilepsy management. We assessed the potential of repeated transcranial magnetic stimulation with electromyography (TMS-EMG) to track dynamical changes in cortical excitability on a within-subject basis. Methods: We recruited people with refractory focal epilepsy who underwent video-EEG monitoring and drug tapering as part of the presurgical evaluation. We performed daily TMS-EMG measurements with additional postictal assessments 1- 6 h following seizures to assess resting motor threshold (rMT), and motor evoked potentials (MEPs) with single- and paired-pulse protocols. Anti-seizure medication (ASM) regimens were recorded for the day before each measurement and expressed in proportion to the dosage before tapering. Additional measurements were performed in healthy controls to evaluate day-to-day rMT variability. Results: We performed 77 (58 baseline, 19 postictal) measurements in 16 people with focal epilepsy and 35 in seven healthy controls. Controls showed minimal day-to-day rMT variation. Withdrawal of ASMs was associated with a lower rMT without affecting MEPs of single- and paired-pulse TMS-EMG paradigms. Postictal measurements following focal to bilateral tonic- clonic seizures demonstrated unaltered rMT and increased short interval intracortical inhibition, while measurements following focal seizures with impaired awareness showed decreased rMT's and reduced short and long interval intracortical inhibition. Conclusion: Serial withinsubject rMT measurements yielded reproducible, stable results in healthy controls. ASM tapering and seizures had distinct effects on TMS-EMG excitability indices in people with epilepsy. Drug tapering decreased rMT, indicating increased overall corticospinal excitability, whereas seizures affected intracortical inhibition with contrasting effects between seizure types. Show less
Westrhenen, A. van; Wijnen, B.M.; Thijs, R.D. 2022
Objective: Previous studies identified essential user preferences for seizure detection devices (SDDs), without addressing their relative strength. We performed a discrete choice experiment (DCE)... Show moreObjective: Previous studies identified essential user preferences for seizure detection devices (SDDs), without addressing their relative strength. We performed a discrete choice experiment (DCE) to quantify attributes' strength, and to identify the determinants of user SDD preferences. Methods: We designed an online questionnaire targeting parents of children with epilepsy to define the optimal balance between SDD sensitivity and positive predictive value (PPV) while accounting for individual seizure frequency. We selected five DCE attributes from a recent study. Using a Bayesian design, we constructed 11 unique choice tasks and analyzed these using a mixed multinomial logit model. Results: One hundred parents responded to the online questionnaire link; 49 completed all tasks, whereas 28 completed the questions, but not the DCE. Most parents preferred a relatively high sensitivity (80%-90%) over a high PPV (>50%). The preferred sensitivity-to-PPV ratio correlated with seizure frequency (r = -.32), with a preference for relative high sensitivity and low PPV among those with relative low seizure frequency (p = .04). All DCE attributes significantly impacted parental choices. Parents expressed preferences for consulting a neurologist before device use, personally training the device's algorithm, interaction with their child via audio and video, alarms for all seizure types, and an interface detailing measurements during an alarm. Preferences varied between subgroups (learning disability or not, SDD experience, relative low vs. high seizure frequency based on the population median). Significance: Various attributes impact parental SDD preferences and may explain why preferences vary among users. Tailored approaches may help to meet the contrasting needs among SDD users. Show less
The pathophysiology of vasovagal syncope (VVS) is reviewed, focusing on hemodynamic aspects. Much more is known about orthostatic than about emotional VVS, probably because the former can be... Show moreThe pathophysiology of vasovagal syncope (VVS) is reviewed, focusing on hemodynamic aspects. Much more is known about orthostatic than about emotional VVS, probably because the former can be studied using a tilt table test (TTT). Recent advances made it possible to quantify the relative contributions of the three factors that control blood pressure: heart rate (HR), stroke volume (SV) and total peripheral resistance (TPR). Orthostatic VVS starts with venous pooling, reflected in a decrease of SV. This is followed by cardioinhibition (CI), which is a decrease of HR that accelerates the ongoing decrease of BP, making the start of CI a literal as well as fundamental turning point.The role of hormonal and other humoral factors, respiration and of psychological influences is reviewed in short, leading to the conclusion that a multidisciplinary approach to the study of the pathophysiology of VVS may yield new insights. Show less
Introduction: Caring for a child with epilepsy has a significant impact on parental quality of life. Seizure unpredictability and complications, including sudden unexpected death in epilepsy (SUDEP... Show moreIntroduction: Caring for a child with epilepsy has a significant impact on parental quality of life. Seizure unpredictability and complications, including sudden unexpected death in epilepsy (SUDEP), may cause high parental stress and increased anxiety. Nocturnal supervision with seizure detection devices may lower SUDEP risk and decrease parental burden of seizure monitoring, but little is known about their added value in family homes. Methods: We conducted semi-structured in-depth interviews with parents of children with refractory epilepsy participating in the PROMISE trial (NCT03909984) to explore the value of seizure detection in the daily care of their child. Children were aged 4-16 years, treated at a tertiary epilepsy center, had at least one nocturnal major motor seizure per week, and used a wearable seizure detection device (NightWatch) for two months at home. Data were analyzed using inductive thematic analysis. Results: Twenty three parents of nineteen children with refractory epilepsy were interviewed. All parents expressed their fear of missing a large seizure and the possible consequences of not intervening in time. Some parents felt the threat of child loss during every seizure, while others thought about it from time to time. The fear could fluctuate over time, mainly associated with fluctuations of seizure frequency. Most parents described how they developed a protective behavior, driven by this fear. The way parents handled the care of their child and experienced the burden of care influenced their perceptions on the added value of NightWatch. The experienced value of NightWatch depended on the amount of assurance it could offer to reduce their fear and the associated protective behavior as well as their resilience to handle the potential extra burden of care, due to false alarms or technical problems. Conclusion: Healthcare professionals and device companies should be aware of parental protective behavior and the high parental burden of care and develop tailored strategies to optimize seizure detection device care. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/). Show less
The close connection between epileptic networks and the autonomic nervous system is illustrated by a range of autonomic manifestations during a seizure. This article reviews the spectrum and... Show moreThe close connection between epileptic networks and the autonomic nervous system is illustrated by a range of autonomic manifestations during a seizure. This article reviews the spectrum and diagnostic value of these manifestations, focusing on presentations that could contribute to sudden unexpected death in epilepsy.Epileptic networks are intimately connected with the autonomic nervous system, as exemplified by a plethora of ictal (during a seizure) autonomic manifestations, including epigastric sensations, palpitations, goosebumps and syncope (fainting). Ictal autonomic changes might serve as diagnostic clues, provide targets for seizure detection and help us to understand the mechanisms that underlie sudden unexpected death in epilepsy (SUDEP). Autonomic alterations are generally more prominent in focal seizures originating from the temporal lobe, demonstrating the importance of limbic structures to the autonomic nervous system, and are particularly pronounced in focal-to-bilateral and generalized tonic-clonic seizures. The presence, type and severity of autonomic features are determined by the seizure onset zone, propagation pathways, lateralization and timing of the seizures, and the presence of interictal autonomic dysfunction. Evidence is mounting that not all autonomic manifestations are linked to SUDEP. In addition, experimental and clinical data emphasize the heterogeneity of SUDEP and its infrequent overlap with sudden cardiac death. Here, we review the spectrum and diagnostic value of the mostly benign and self-limiting autonomic manifestations of epilepsy. In particular, we focus on presentations that are likely to contribute to SUDEP and discuss how wearable devices might help to prevent SUDEP. Show less
Introduction In patients with ictal asystole (IA) both cardioinhibition and vasodepression may contribute to syncopal loss of consciousness. We investigated the temporal relationship between onset... Show moreIntroduction In patients with ictal asystole (IA) both cardioinhibition and vasodepression may contribute to syncopal loss of consciousness. We investigated the temporal relationship between onset of asystole and development of syncope in IA, to estimate the frequency with which pacemaker therapy, by preventing severe bradycardia, may diminish syncope risk. Methods In this retrospective cohort study, we searched video-EEG databases for individuals with focal seizures and IA (asystole >= 3 s preceded by heart rate deceleration) and assessed the durations of asystole and syncope and their temporal relationship. Syncope was evaluated using both video observations (loss of muscle tone) and EEG (generalized slowing/flattening). We assumed that asystole starting <= 3 s before syncope onset, or after syncope began, could not have been the dominant cause. Results We identified 38 seizures with IA from 29 individuals (17 males; median age: 41 years). Syncope occurred in 22/38 seizures with IA and was more frequent in those with longer IA duration (median duration: 20 [range: 5-32] vs. 5 [range: 3-9] s; p < .001) and those with the patient seated vs. supine (79% vs. 46%; p = .049). IA onset always preceded syncope. In 20/22 seizures (91%), IA preceded syncope by >3 s. Thus, in only two instances was vasodepression rather than cardioinhibition the dominant presumptive syncope triggering mechanism. Conclusions In IA, cardioinhibition played an important role in most seizure-induced syncopal events, thereby favoring the potential utility of pacemaker implantation in patients with difficult to suppress IA. Show less
Saal, D.P.; Thijs, R.D.; Bootsma, M.; Brignole, M.; Dijk, J.G. van 2021
Aims We describe five patients with syncope caused by a complete atrioventricular block (AVB) while they were bending forward, not rising after bending, and aim to describe the occurrence and the... Show moreAims We describe five patients with syncope caused by a complete atrioventricular block (AVB) while they were bending forward, not rising after bending, and aim to describe the occurrence and the association between bending forward and AVB.Methods and results In two patients, bending forward was the exclusive trigger for syncope, while in the remaining three, other postural changes (sitting down, standing up, and exertion) could also provoke syncope. Complete AVB as the cause of syncope was documented using ECG monitoring in two cases and an implantable loop recorder in the other three. Ectopic beats without preceding sinus slowing occurred before syncope in four cases. Two cases had a left bundle branch block. All patients responded favourably to cardiac pacing.Conclusion This is the first case series on complete AVB provoked by bending forward. Syncope during bending forward should suggest a search for an AVB. Arguments in favour of a vagal mechanism were syncope triggered by bending forward, and that other triggers could also evoke syncope. However, the absence of sinus slowing before syncope in some cases and the fact that bending forward did not seem to provoke reflex syncope without AVB, cast doubts on a reflex mechanism. There were also arguments favouring conduction disorder: i.e. ectopic beats before syncope and pre-existing conduction disturbances in two cases. The cases are reminiscent of paroxysmal AVB. Discrimination between paroxysmal AVB and vagal AVB is important because a pacemaker is warranted in arrhythmic complete AVB, while the benefit is limited or absent in reflex AVB. Show less
An expert committee was formed to reach consensus on the use of Tilt Table Testing (TTT) in the diagnosis of disorders that may cause transient loss of consciousness (TLOC) and to outline when... Show moreAn expert committee was formed to reach consensus on the use of Tilt Table Testing (TTT) in the diagnosis of disorders that may cause transient loss of consciousness (TLOC) and to outline when other provocative cardiovascular autonomic tests are needed. While TTT adds to history taking, it cannot be a substitute for it. An abnormal TTT result is most meaningful if the provoked event is recognised by patients or eyewitnesses as similar to spontaneous ones. The minimum requirements to perform TTT are a tilt table, a continuous beat-to-beat blood pressure monitor, at least one ECG lead, protocols for the indications stated below and trained staff. This basic equipment lends itself to perform (1) additional provocation tests, such as the active standing test carotid sinus massage and autonomic function tests; (2) additional measurements, such as video, EEG, transcranial Doppler, NIRS, end-tidal CO2 or neuro-endocrine tests; (3) tailor-made provocation procedures in those with a specific and consistent trigger of TLOC.TTT and other provocative cardiovascular autonomic tests are indicated if the initial evaluation does not yield a definite or highly likely diagnosis, but raises a suspicion of (1) reflex syncope, (2) the three forms of orthostatic hypotension (OH), i.e. initial, classic and delayed OH, as well as delayed orthostatic blood pressure recovery, (3) postural orthostatic tachycardia syndrome or (4) psychogenic pseudosyncope. A therapeutic indication for TTT is to teach patients with reflex syncope and OH to recognise hypotensive symptoms and to perform physical counter manoeuvres. Show less
Ghariq, M.; Kerkhof, F.I.; Reijntjes, R.H.; Thijs, R.D.; Dijk, J.G. van 2021
Objective To define and evaluate hemodynamic criteria to distinguish between classical orthostatic hypotension (cOH) and vasovagal syncope (VVS) in tilt table testing (TTT). Methods Inclusion... Show moreObjective To define and evaluate hemodynamic criteria to distinguish between classical orthostatic hypotension (cOH) and vasovagal syncope (VVS) in tilt table testing (TTT). Methods Inclusion criteria for VVS were a history of VVS and tilt-induced syncope defined as a blood pressure (BP) decrease and electroencephalographic changes during syncope with complaint recognition. Criteria for cOH were a history of cOH and a BP decrease meeting published criteria. Clinical diagnoses were established prior to TTT. We assessed (1) whether the decrease of systolic BP accelerated, "convex," or decelerated, "concave"; (2) the time from head-up tilt to when BP reached one-half its maximal decrease; (3) the difference between baseline heart rate (HR) and HR at BP nadir. We calculated the diagnostic yield of optimized thresholds of these features and their combinations. Results We included 82 VVS cases (40% men, median age 44 years) and 65 cOH cases (66% men, median age 70 years). BP decrease was concave in cOH in 79% and convex in VVS in 94% (p < 0.001). The time to reach half the BP decrease was shorter in cOH (median 34 sec, interquartile range (IQR) 19-98 sec) than in VVS (median 1571 sec, IQR 1381-1775 sec, p < 0.001). Mean HR increased by 11 +/- 11 bpm in cOH and decreased by 20 +/- 19 bpm in VVS (p < 0.001). When all three features pointed to VVS, sensitivity for VVS was 82% and specificity was 100%. When all three pointed to cOH, sensitivity for cOH was 71% and specificity was 100%. Interpretation These new hemodynamic criteria reliably differentiate cOH from VVS. Show less
Ghariq, M.; Bodegom-Vos, L. van; Brignole, M.; Peeters, S.Y.G.; Groot, B. de; Kaal, E.C.A.; ... ; SYNERGY Consortium 2021
Aims: Syncope care is often fragmented and inefficient. Structuring syncope care through implementation of guidelines and Syncope Units has been shown to improve diagnostic yield, reduce costs and... Show moreAims: Syncope care is often fragmented and inefficient. Structuring syncope care through implementation of guidelines and Syncope Units has been shown to improve diagnostic yield, reduce costs and improve quality of life. We implemented the European Society of Cardiology (ESC) 2018 syncope guidelines at the Emergency Departments (ED) and established Syncope Units in five Dutch hospitals. We evaluated the implementation process by identifying factors that hinder ('barriers') and facilitate ('facilitators') the implementation.Methods and results: We conducted, recorded and transcribed semi-structured interviews with 19 specialists and residents involved in syncope care from neurology, cardiology, internal medicine and emergency medicine. Two researchers independently classified the reported barriers and facilitators, according to the framework of qualitative research (Flottorp), which distinguished several separate fields ('levels'). Software package Atlas.ti was used for analysis.We identified 31 barriers and 22 facilitators. Most barriers occurred on the level of the individual health care professional (e.g. inexperienced residents having to work with the guideline at the ED) and the organizational context (e.g. specialists not relinquishing preceding procedures). Participants reported most facilitators at the level of innovation (e.g. structured work -flow at the ED). The multidisciplinary Syncope Unit was welcomed as useful solution to a perceived need in clinical practice.Conclusion: Implementing ESC syncope guidelines at the ED and establishing Syncope Units facilitated a structured multidisciplinary work-up for syncope patients. Most identified barriers related to the individual health care professional and the organizational context. Future implementation of the multidisciplinary guideline should be tailored to address these barriers.(c) 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/). Show less
Head-up tilt test (TT) has been used for >50 years to study heart rate/blood pressure adaptation to positional changes, to model responses to haemorrhage, to assess orthostatic hypotension, and... Show moreHead-up tilt test (TT) has been used for >50 years to study heart rate/blood pressure adaptation to positional changes, to model responses to haemorrhage, to assess orthostatic hypotension, and to evaluate haemodynamic and neuroendocrine responses in congestive heart failure, autonomic dysfunction, and hypertension. During these studies, some subjects experienced syncope due to vasovagal reflex. As a result, tilt testing was incorporated into clinical assessment of syncope when the origin was unknown. Subsequently, clinical experience supports the diagnostic value of TT. This is highlighted in evidence-based professional practice guidelines, which provide advice for TT methodology and interpretation, while concurrently identifying its limitations. Thus, TT remains a valuable clinical asset, one that has added importantly to the appreciation of pathophysiology of syncope/collapse and, thereby, has improved care of syncopal patients.[GRAPHICS]. Show less
Thijs, R.D.; Brignole, M.; Falup-Pecurariu, C.; Fanciulli, A.; Freeman, R.; Guaraldi, P.; ... ; Dijk, J.G. van 2021
An expert committee was formed to reach consensus on the use of tilt table testing (TTT) in the diagnosis of disorders that may cause transient loss of consciousness (TLOC) and to outline when... Show moreAn expert committee was formed to reach consensus on the use of tilt table testing (TTT) in the diagnosis of disorders that may cause transient loss of consciousness (TLOC) and to outline when other provocative cardiovascular autonomic tests are needed. While TTT adds to history taking, it cannot be a substitute for it. An abnormal TTT result is most meaningful if the provoked event is recognised by patients or eyewitnesses as similar to spontaneous events. The minimum requirements to perform TTT are a tilt table, a continuous beat-to-beat blood pressure monitor, at least one ECG lead, protocols for the indications stated below and trained staff. This basic equipment lends itself to the performance of (1) additional provocation tests, such as the active standing test, carotid sinus massage and autonomic function tests; (2) additional measurements, such as video, EEG, transcranial Doppler, NIRS, end-tidal CO2 or neuro-endocrine tests; and (3) tailor-made provocation procedures in those with a specific and consistent trigger of TLOC. TTT and other provocative cardiovascular autonomic tests are indicated if the initial evaluation does not yield a definite or highly likely diagnosis, but raises a suspicion of (1) reflex syncope, (2) the three forms of orthostatic hypotension (OH), i.e. initial, classic and delayed OH, as well as delayed orthostatic blood pressure recovery, (3) postural orthostatic tachycardia syndrome or (4) psychogenic pseudosyncope. A therapeutic indication for TTT is to teach patients with reflex syncope and OH to recognise hypotensive symptoms and to perform physical counter manoeuvres. Show less
Westrhenen, A. van; Souhoka, T.; Ballieux, M.E.; Thijs, R.D. 2021
Introduction: User preferences for seizure detection devices (SDDs) have been previously assessed using surveys and interviews, but these have not addressed the latent needs and wishes. Context... Show moreIntroduction: User preferences for seizure detection devices (SDDs) have been previously assessed using surveys and interviews, but these have not addressed the latent needs and wishes. Context mapping is an approach in which designers explore users' dreams and fears to anticipate potential future experiences and optimize the product design.Methods: A generative group session was held using the context mapping approach. Two types of nocturnal SDD users were included: three professional caregivers at a residential care facility and two informal caregivers of children with refractory epilepsy and learning disabilities. Participants were invited to share their personal SDD experiences and briefed to make their needs and wishes explicit. The audiotaped session was transcribed and analyzed together with the collected material using inductive content analysis. The qualitative data was classified by coding the content, grouping codes into categories and themes, and combining those into general statements (abstraction).Results: "Trust" emerged as the most important theme, entangling various emotional and practical factors that influence caregiver's trust in a device. Caregivers expressed several factors that could help to gain their trust in an SDD, including integration of different modalities, insight on all parameters overnight, personal adjustment of the algorithm, recommendation by a neurologist, and a set-up period. Needs regarding alerting seemed to differ between the two types of caregivers in our study: professional caregivers preferred to be alerted only for potentially dangerous seizures, whereas informal caregivers emphasized the urge to be alerted for every event, thus indicating the need for personal adjustment of SDD settings.Conclusion: In this explorative study, we identified several key elements for nocturnal SDD implementation including the importance of gaining trust and the possibility to adjust SDD settings for different types of caregivers. (C) 2020 The Author(s). Published by Elsevier Inc. Show less
Gagaouzova, B.S.; Datema, M.; Thijs, R.D.; Tannemaat, M.R.; Steenmeijer, S.R.; Notting, I.C.; Dijk, J.G. van 2021
Background: Pure autonomic failure (PAF) and multiple system atrophy (MSA) are rare disorders causing severe autonomic failure. Their initially similar clinical presentation may lead to years of... Show moreBackground: Pure autonomic failure (PAF) and multiple system atrophy (MSA) are rare disorders causing severe autonomic failure. Their initially similar clinical presentation may lead to years of diagnostic difficulties. Improving the differentiation would have an important impact on patients and families in view of better prediction of disease progression. Objective: To investigate whether several new non-invasive autonomic tests are beneficial in discriminating between PAF and MSA. Methods: Patients and controls underwent two tests examining the autonomic innervation of the skin (Sudoscan and water-induced skin wrinkling) and one test measuring retinal nerve fiber layer thickness in the eye. Results: The skin vasomotor tests yielded differences between the disease and control groups, but did not discriminate between PAF and MSA. No differences in retinal nerve fiber layer thickness were found between the groups. Conclusion: The tests applied in this study may help to confirm autonomic failure but did not support the differential diagnosis between PAF and MSA. Show less
Climate change is with us. As professionals who place value on evidence-based practice, climate change is something we cannot ignore. The current pandemic of the novel coronavirus, SARS-CoV-2, has... Show moreClimate change is with us. As professionals who place value on evidence-based practice, climate change is something we cannot ignore. The current pandemic of the novel coronavirus, SARS-CoV-2, has demonstrated how global crises can arise suddenly and have a significant impact on public health. Global warming, a chronic process punctuated by acute episodes of extreme weather events, is an insidious global health crisis needing at least as much attention. Many neurological diseases are complex chronic conditions influenced at many levels by changes in the environment. This review aimed to collate and evaluate reports from clinical and basic science about the relationship between climate change and epilepsy. The keywords climate change, seasonal variation, temperature, humidity, thermoregulation, biorhythm, gene, circadian rhythm, heat, and weather were used to search the published evidence. A number of climatic variables are associated with increased seizure frequency in people with epilepsy. Climate change-induced increase in seizure precipitants such as fevers, stress, and sleep deprivation (e.g. as a result of more frequent extreme weather events) or vector-borne infections may trigger or exacerbate seizures, lead to deterioration of seizure control, and affect neurological, cerebrovascular, or cardiovascular comorbidities and risk of sudden unexpected death in epilepsy. Risks are likely to be modified by many factors, ranging from individual genetic variation and temperature-dependent channel function, to housing quality and global supply chains. According to the results of the limited number of experimental studies with animal models of seizures or epilepsy, different seizure types appear to have distinct susceptibility to seasonal influences. Increased body temperature, whether in the context of fever or not, has a critical role in seizure threshold and seizure-related brain damage. Links between climate change and epilepsy are likely to be multifactorial, complex, and often indirect, which makes predictions difficult. We need more data on possible climate-driven altered risks for seizures, epilepsy, and epileptogenesis, to identify underlying mechanisms at systems, cellular, and molecular levels for better understanding of the impact of climate change on epilepsy. Further focussed data would help us to develop evidence for mitigation methods to do more to protect people with epilepsy from the effects of climate change. (C) 2021 Elsevier Inc. All rights reserved. Show less
