An integrated approach to neuroscience care: An innovative model to support the new integrated care system.

Integrated care systems join up health and care services, so that people have the support they need, in the right place, at the right time. The aims include improving outcomes in healthcare, tackling inequalities in access and enhancing productivity and value for money. This is needed for neuroscience care as the traditional delivery of neuroscience care is inefficient, outdated and expensive, and can involve complex referral pathways and long waiting times. In preparation for the formation of the integrated care system (ICS), a novel innovative collaboration across multiple NHS trusts developed across North Central London in 2021. We developed a model where neuroscience specialists engage in collaborative care with clinicians outside the specialist hospital setting. Pivotal to the pathway is a multidisciplinary meeting, and collaborative working enables joint clinical reviews, diagnostics and medication initiation. This innovative collaboration has already significantly improved access, addressed inequalities due to borough variation and enhanced the delivery and quality of neuroscience care in our ICS. It is a translatable model that can be adapted to suit other regions in the UK. It fulfils many of the objectives of the integrated care system and these benefits are seen without the need for significantly more resource.

Functional seizures and their mimics: a retrospective service review of cases from a tertiary video telemetry database.

Objective: Identify the proportion of patients referred with putative functional seizures (FS) that were subsequently re-diagnosed as epileptic seizures (ES), or an alternative diagnosis, following video telemetry EEG (VTEEG). In addition, describe the characteristics of those seizures. Methods: The VTEEG reports from patients admitted to the Chalfont Centre for Epilepsy between 2019 and 2022 were reviewed. Pre-VTEEG and post-VTEEG diagnoses were compared to identify whether a diagnostic revision was made from suspected FS to ES or another diagnosis. Diagnostic revision cases were then grouped into cohorts with associated features and reviewed to characterise and describe FS mimics. Results: 444 VTEEG reports where patients had habitual events were identified. 4.7% of patients were referred with FS and were subsequently diagnosed with ES or another diagnosis. In this group, several cohorts could be identified including frontal lobe epileptic seizures, ES with functional overlay, insular or temporal lobe epileptic seizures associated with autonomic or marked experiential peri-ictal symptoms, and individuals who had both ES and FS but whose ES were revealed on medication withdrawal. Conclusion: In patients referred to a tertiary epilepsy unit, a small minority of cases had seizures diagnosed as functional and reclassified as epileptic or an alternative diagnosis. It is clinically important to be aware of these FS mimics.

Interictal magnetoencephalography abnormalities to guide intracranial electrode implantation and predict surgical outcome.

Intracranial EEG is the gold standard technique for epileptogenic zone localization but requires a preconceived hypothesis of the location of the epileptogenic tissue. This placement is guided by qualitative interpretations of seizure semiology, MRI, EEG and other imaging modalities, such as magnetoencephalography. Quantitative abnormality mapping using magnetoencephalography has recently been shown to have potential clinical value. We hypothesized that if quantifiable magnetoencephalography abnormalities were sampled by intracranial EEG, then patients' post-resection seizure outcome may be better. Thirty-two individuals with refractory neocortical epilepsy underwent magnetoencephalography and subsequent intracranial EEG recordings as part of presurgical evaluation. Eyes-closed resting-state interictal magnetoencephalography band power abnormality maps were derived from 70 healthy controls as a normative baseline. Magnetoencephalography abnormality maps were compared to intracranial EEG electrode implantation, with the spatial overlap of intracranial EEG electrode placement and cerebral magnetoencephalography abnormalities recorded. Finally, we assessed if the implantation of electrodes in abnormal tissue and subsequent resection of the strongest abnormalities determined by magnetoencephalography and intracranial EEG corresponded to surgical success. We used the area under the receiver operating characteristic curve as a measure of effect size. Intracranial electrodes were implanted in brain tissue with the most abnormal magnetoencephalography findings-in individuals that were seizure-free postoperatively (T = 3.9, P = 0.001) but not in those who did not become seizure-free. The overlap between magnetoencephalography abnormalities and electrode placement distinguished surgical outcome groups moderately well (area under the receiver operating characteristic curve = 0.68). In isolation, the resection of the strongest abnormalities as defined by magnetoencephalography and intracranial EEG separated surgical outcome groups well, area under the receiver operating characteristic curve = 0.71 and area under the receiver operating characteristic curve = 0.74, respectively. A model incorporating all three features separated surgical outcome groups best (area under the receiver operating characteristic curve = 0.80). Intracranial EEG is a key tool to delineate the epileptogenic zone and help render individuals seizure-free postoperatively. We showed that data-driven abnormality maps derived from resting-state magnetoencephalography recordings demonstrate clinical value and may help guide electrode placement in individuals with neocortical epilepsy. Additionally, our predictive model of postoperative seizure freedom, which leverages both magnetoencephalography and intracranial EEG recordings, could aid patient counselling of expected outcome.

Identifying epileptogenic abnormalities through spatial clustering of MEG interictal band power.

Successful epilepsy surgery depends on localizing and resecting cerebral abnormalities and networks that generate seizures. Abnormalities, however, may be widely distributed across multiple discontiguous areas. We propose spatially constrained clusters as candidate areas for further investigation and potential resection. We quantified the spatial overlap between the abnormality cluster and subsequent resection, hypothesizing a greater overlap in seizure-free patients. Thirty-four individuals with refractory focal epilepsy underwent pre-surgical resting-state interictal magnetoencephalography (MEG) recording. Fourteen individuals were totally seizure-free (ILAE 1) after surgery and 20 continued to have some seizures post-operatively (ILAE 2+). Band power abnormality maps were derived using controls as a baseline. Patient abnormalities were spatially clustered using the k-means algorithm. The tissue within the cluster containing the most abnormal region was compared with the resection volume using the dice score. The proposed abnormality cluster overlapped with the resection in 71% of ILAE 1 patients. Conversely, an overlap only occurred in 15% of ILAE 2+ patients. This effect discriminated outcome groups well (AUC = 0.82). Our novel approach identifies clusters of spatially similar tissue with high abnormality. This is clinically valuable, providing (a) a data-driven framework to validate current hypotheses of the epileptogenic zone localization or (b) to guide further investigation.

Interictal MEG abnormalities to guide intracranial electrode implantation and predict surgical outcome.

Intracranial EEG (iEEG) is the gold standard technique for epileptogenic zone (EZ) localisation, but requires a preconceived hypothesis of the location of the epileptogenic tissue. This placement is guided by qualitative interpretations of seizure semiology, MRI, EEG and other imaging modalities, such as magnetoencephalography (MEG). Quantitative abnormality mapping using MEG has recently been shown to have potential clinical value. We hypothesised that if quantifiable MEG abnormalities were sampled by iEEG, then patients' post-resection seizure outcome may be better. Thirty-two individuals with refractory neocortical epilepsy underwent MEG and subsequent iEEG recordings as part of pre-surgical evaluation. Eyes-closed resting-state interictal MEG band power abnormality maps were derived from 70 healthy controls as a normative baseline. MEG abnormality maps were compared to iEEG electrode implantation, with the spatial overlap of iEEG electrode placement and cerebral MEG abnormalities recorded. Finally, we assessed if the implantation of electrodes in abnormal tissue, and subsequent resection of the strongest abnormalities determined by MEG and iEEG corresponded to surgical success. Intracranial electrodes were implanted in brain tissue with the most abnormal MEG findings - in individuals that were seizure-free post-operatively (T=3.9, p=0.003), but not in those who did not become seizure free. The overlap between MEG abnormalities and electrode placement distinguished surgical outcome groups moderately well (AUC=0.68). In isolation, the resection of the strongest abnormalities as defined by MEG and iEEG separated surgical outcome groups well, AUC=0.71, AUC=0.74 respectively. A model incorporating all three features separated surgical outcome groups best (AUC=0.80). Intracranial EEG is a key tool to delineate the EZ and help render individuals seizure-free post-operatively. We showed that data-driven abnormality maps derived from resting-state MEG recordings demonstrate clinical value and may help guide electrode placement in individuals with neocortical epilepsy. Additionally, our predictive model of post-operative seizure-freedom, which leverages both MEG and iEEG recordings, could aid patient counselling of expected outcome.

MEG abnormalities and mechanisms of surgical failure in neocortical epilepsy.

OBJECTIVE: Epilepsy surgery fails to achieve seizure freedom in 30%-40% of cases. It is not fully understood why some surgeries are unsuccessful. By comparing interictal magnetoencephalography (MEG) band power from patient data to normative maps, which describe healthy spatial and population variability, we identify patient-specific abnormalities relating to surgical failure. We propose three mechanisms contributing to poor surgical outcome: (1) not resecting the epileptogenic abnormalities (mislocalization), (2) failing to remove all epileptogenic abnormalities (partial resection), and (3) insufficiently impacting the overall cortical abnormality. Herein we develop markers of these mechanisms, validating them against patient outcomes. METHODS: Resting-state MEG recordings were acquired for 70 healthy controls and 32 patients with refractory neocortical epilepsy. Relative band-power spatial maps were computed using source-localized recordings. Patient and region-specific band-power abnormalities were estimated as the maximum absolute z-score across five frequency bands using healthy data as a baseline. Resected regions were identified using postoperative magnetic resonance imaging (MRI). We hypothesized that our mechanistically interpretable markers would discriminate patients with and without postoperative seizure freedom. RESULTS: Our markers discriminated surgical outcome groups (abnormalities not targeted: area under the curve [AUC] = 0.80, p = .003; partial resection of epileptogenic zone: AUC = 0.68, p = .053; and insufficient cortical abnormality impact: AUC = 0.64, p = .096). Furthermore, 95% of those patients who were not seizure-free had markers of surgical failure for at least one of the three proposed mechanisms. In contrast, of those patients without markers for any mechanism, 80% were ultimately seizure-free. SIGNIFICANCE: The mapping of abnormalities across the brain is important for a wide range of neurological conditions. Here we have demonstrated that interictal MEG band-power mapping has merit for the localization of pathology and improving our mechanistic understanding of epilepsy. Our markers for mechanisms of surgical failure could be used in the future to construct predictive models of surgical outcome, aiding clinical teams during patient pre-surgical evaluations.

Predictive models for starting antiseizure medication withdrawal following epilepsy surgery in adults.

More than half of adults with epilepsy undergoing resective epilepsy surgery achieve long-term seizure freedom and might consider withdrawing antiseizure medications. We aimed to identify predictors of seizure recurrence after starting postoperative antiseizure medication withdrawal and develop and validate predictive models. We performed an international multicentre observational cohort study in nine tertiary epilepsy referral centres. We included 850 adults who started antiseizure medication withdrawal following resective epilepsy surgery and were free of seizures other than focal non-motor aware seizures before starting antiseizure medication withdrawal. We developed a model predicting recurrent seizures, other than focal non-motor aware seizures, using Cox proportional hazards regression in a derivation cohort (n = 231). Independent predictors of seizure recurrence, other than focal non-motor aware seizures, following the start of antiseizure medication withdrawal were focal non-motor aware seizures after surgery and before withdrawal [adjusted hazard ratio (aHR) 5.5, 95% confidence interval (CI) 2.7-11.1], history of focal to bilateral tonic-clonic seizures before surgery (aHR 1.6, 95% CI 0.9-2.8), time from surgery to the start of antiseizure medication withdrawal (aHR 0.9, 95% CI 0.8-0.9) and number of antiseizure medications at time of surgery (aHR 1.2, 95% CI 0.9-1.6). Model discrimination showed a concordance statistic of 0.67 (95% CI 0.63-0.71) in the external validation cohorts (n = 500). A secondary model predicting recurrence of any seizures (including focal non-motor aware seizures) was developed and validated in a subgroup that did not have focal non-motor aware seizures before withdrawal (n = 639), showing a concordance statistic of 0.68 (95% CI 0.64-0.72). Calibration plots indicated high agreement of predicted and observed outcomes for both models. We show that simple algorithms, available as graphical nomograms and online tools (predictepilepsy.github.io), can provide probabilities of seizure outcomes after starting postoperative antiseizure medication withdrawal. These multicentre-validated models may assist clinicians when discussing antiseizure medication withdrawal after surgery with their patients.

Retention of brivaracetam in adults with drug-resistant epilepsy at a single tertiary care center.

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, concomitant and previous antiseizure medication (ASM) use, BRV dosing, efficacy, and side effects were recorded. Efficacy was categorized as temporary (minimum three months) or ongoing (at last follow-up) seizure freedom, ≥50% seizure reduction, or other benefits (e.g., no convulsions or daytime seizures). Brivaracetam retention was estimated using Kaplan-Meier survival analysis. RESULTS: Two-hundred people were treated with BRV, of whom 81% had focal epilepsy. The mean (interquartile range [IQR]) follow-up time was 707 (688) days, and the dose range was 50-600 mg daily. The mean (IQR) of the previous number of used ASMs was 6.9 (6.0), and concomitant use was 2.2 (1.0). One-hundred and eighty-eight people (94%) had previously discontinued levetiracetam (LEV), mainly due to side effects. 13/200 (6.5%) were seizure free for a minimum of six months during treatment, and 46/200 (23%) had a ≥50% reduction in seizure frequency for six months or more. Retention rates were 83% at six months, 71% at 12 months, and 57% at 36 months. Brivaracetam was mostly discontinued due to side effects (38/75, 51%) or lack of efficacy (28/75, 37%). Concomitant use of carbamazepine significantly increased the hazard ratio of discontinuing BRV due to side effects (p = 0.006). The most commonly reported side effects were low mood (20.5%), fatigue (18%) and aggressive behavior (8.5%). These side effects were less prevalent than when the same individuals took LEV (low mood, 59%; aggressive behavior, 43%). Intellectual disability was a risk factor for behavioral side effects (p = 0.004), and a pre-existing mood disorder significantly increased the likelihood of further episodes of low mood (p = 0.019). CONCLUSIONS: Brivaracetam was effective at a broad range of doses in managing drug-resistant epilepsy across various phenotypes, but less effective than LEV in those who switched due to poor tolerability on LEV. There were no new tolerability issues, but 77% of the individuals experiencing side effects on BRV also experienced similar side effects on LEV.

The use of simultaneous stereo-electroencephalography and magnetoencephalography in localizing the epileptogenic focus in refractory focal epilepsy.

Both magnetoencephalography and stereo-electroencephalography are used in presurgical epilepsy assessment, with contrasting advantages and limitations. It is not known whether simultaneous stereo-electroencephalography-magnetoencephalography recording confers an advantage over both individual modalities, in particular whether magnetoencephalography can provide spatial context to epileptiform activity seen on stereo-electroencephalography. Twenty-four adult and paediatric patients who underwent stereo-electroencephalography study for pre-surgical evaluation of drug-resistant focal epilepsy, were recorded using simultaneous stereo-electroencephalography-magnetoencephalography, of which 14 had abnormal interictal activity during recording. The 14 patients were divided into two groups; those with detected superficial (n = 7) and deep (n = 7) brain interictal activity. Interictal spikes were independently identified in stereo-electroencephalography and magnetoencephalography. Magnetoencephalography dipoles were derived using a distributed inverse method. There was no significant difference between stereo-electroencephalography and magnetoencephalography in detecting superficial spikes (P = 0.135) and stereo-electroencephalography was significantly better at detecting deep spikes (P = 0.002). Mean distance across patients between stereo-electroencephalography channel with highest average spike amplitude and magnetoencephalography dipole was 20.7 ± 4.4 mm. for superficial sources, and 17.8 ± 3.7 mm. for deep sources, even though for some of the latter (n = 4) no magnetoencephalography spikes were detected and magnetoencephalography dipole was fitted to a stereo-electroencephalography interictal activity triggered average. Removal of magnetoencephalography dipole was associated with 1 year seizure freedom in 6/7 patients with superficial source, and 5/6 patients with deep source. Although stereo-electroencephalography has greater sensitivity in identifying interictal activity from deeper sources, a magnetoencephalography source can be localized using stereo-electroencephalography information, thereby providing useful whole brain context to stereo-electroencephalography and potential role in epilepsy surgery planning.

An evaluation of the effectiveness of perampanel in people with epilepsy who have previously undergone resective surgery and/or implantation of a vagal nerve stimulator.

About 30% of people with epilepsy (PWE) are drug-resistant. Those with focal seizures may be suitable for epilepsy surgery. Those not amenable to resective surgery can be considered for vagus nerve stimulation (VNS). However, after operative procedures, around 50% of patients continue to experience seizures. A multi-center retrospective study assessing perampanel effectiveness and tolerability for PWE who have undergone surgical resection and/or VNS implantation was performed. The primary outcome was ≥50% reduction in seizure frequency while secondary outcomes included side effects (SEs), dose-related effectiveness, and toxicity. The median perampanel dose was 6 mg. Only one PWE became seizure free. A ≥50% decrease in seizure frequency was observed in 52.8% of the post-resection group and 16.9% of the VNS group (p < 0.001), while SEs were seen in 44.8% and 41.1%, respectively. Perampanel doses greater than 8 mg led to better response in both groups, especially in the post-VNS cohort. SEs were not dose-related and the safety profile was similar to previous observational studies. Perampanel can be beneficial in these two super-refractory epilepsy groups, particularly in PWE with seizures after surgical resection. Doses of more than 8 mg appear to be well tolerated and may be more effective than lower doses in PWE after surgical interventions.

Moyamoya and progressive myoclonic epilepsy secondary to CLN6 bi-allelic mutations - A previously unreported association.

The neuronal ceroid lipofuscinoses (NCL) are a collection of lysosomal storage diseases characterised by the accumulation of characteristic inclusions containing lipofuscin in various tissues of the body and are one of the causes of progressive myoclonic epilepsy. Mutations in at least thirteen genes have been identified as causes of NCL, which can present as infantile, late-infantile, juvenile or adult forms. CLN6 codes for an endoplasmic reticulum transmembrane protein of unknown function. Homozygous and compound heterozygous mutations of the gene are associated with both late-infantile (LINCL) and adult onset (ANCL) forms of NCL, including Kufs disease, comprising ANCL without associated visual loss. Moyamoya, a rare vasculopathy of the circle of Willis, has been reported in conjunction with a number of inflammatory and other diseases, as well as a handful of lysosomal storage diseases. To our knowledge, this is the first reported case of Moyamoya in the context of the neuronal ceroid lipofuscinoses or a CLN6-related disease.

Removal of Interictal MEG-Derived Network Hubs Is Associated With Postoperative Seizure Freedom.

Objective: To investigate whether MEG network connectivity was associated with epilepsy duration, to identify functional brain network hubs in patients with refractory focal epilepsy, and assess if their surgical removal was associated with post-operative seizure freedom. Methods: We studied 31 patients with drug refractory focal epilepsy who underwent resting state magnetoencephalography (MEG), and structural magnetic resonance imaging (MRI) as part of pre-surgical evaluation. Using the structural MRI, we generated 114 cortical regions of interest, performed surface reconstruction and MEG source localization. Representative source localized signals for each region were correlated with each other to generate a functional brain network. We repeated this procedure across three randomly chosen one-minute epochs. Network hubs were defined as those with the highest intra-hemispheric mean correlations. Post-operative MRI identified regions that were surgically removed. Results: Greater mean MEG network connectivity was associated with a longer duration of epilepsy. Patients who were seizure free after surgery had more hubs surgically removed than patients who were not seizure free (AUC = 0.76, p = 0.01) consistently across three randomly chosen time segments. Conclusion: Our results support a growing literature implicating network hub involvement in focal epilepsy, the removal of which by surgery is associated with greater chance of post-operative seizure freedom.

The role of devices in managing risk.

Over the last few years, there has been significant expansion of wearable technologies and devices into the health sector, including for conditions such as epilepsy. Although there is significant potential to benefit patients, there is a paucity of well-conducted scientific research in order to inform patients and healthcare providers of the most appropriate technology. In addition to either directly or indirectly identifying seizure activity, the ideal device should improve quality of life and reduce the risk of sudden unexpected death in epilepsy (SUDEP). Devices typically monitor a number of parameters including electroencephalographic (EEG), cardiac, and respiratory patterns and can detect movement, changes in skin conductance, and muscle activity. Multimodal devices are emerging with improved seizure detection rates and reduced false positive alarms. While convulsive seizures are reliably identified by most unimodal and multimodal devices, seizures associated with no, or minimal, movement are frequently undetected. The vast majority of current devices detect but do not actively intervene. At best, therefore, they indicate the presence of seizure activity in order to accurately ascertain true seizure frequency or facilitate intervention by others, which may, nevertheless, impact the rate of SUDEP. Future devices are likely to both detect and intervene within an autonomous closed-loop system tailored to the individual and by self-learning from the analysis of patient-specific parameters. The formulation of standards for regulatory bodies to validate seizure detection devices is also of paramount importance in order to confidently ascertain the performance of a device; and this will be facilitated by the creation of a large, open database containing multimodal annotated data in order to test device algorithms. This paper is for the Special Issue: Prevent 21: SUDEP Summit - Time to Listen.

Epilepsy surgery.

Epilepsy surgery offers the chance of seizure remission for the 30%-40% of patients with focal epilepsy whose seizures continue despite anti-epileptic medications. Epilepsy surgery encompasses curative resective procedures, palliative techniques such as corpus callosotomy and implantation of stimulation devices. Pre-surgical evaluation aims to identify the epileptogenic zone and to prevent post-operative neurological and cognitive deficits. This entails optimal imaging, prolonged video-electroencephalogram (EEG) recordings, and neuropsychological and psychiatric assessments; some patients may then require nuclear medicine imaging and intracranial EEG recording. The best outcomes are in those with an electro-clinically concordant structural lesion on MRI (60%-70% seizure freedom). Lower rates of seizure freedom are expected in people with extra-temporal lobe foci, focal-to-bilateral tonic-clonic seizures, normal structural imaging, psychiatric co-morbidity and learning disability. Nevertheless, surgery for epilepsy is under-used and should be considered for all patients with refractory focal epilepsy in whom two or three anti-epileptic medications have been ineffective.

Neuropsychological outcomes following traumatic brain injury.

This review examines the clinical and neuroradiological features of traumatic brain injury that are most frequently associated with persistent cognitive complaints. Neuropsychological outcomes do not depend solely on brain injury severity but result from a complex interplay between premorbid factors, the extent and nature of the underlying structural damage, the person's neuropsychological reserve and the impact of non-neurological factors in the recovery process. Brain injury severity is only one of these factors and has limited prognostic significance with respect to neuropsychological outcome. We examine the preinjury and postinjury factors that interact with the severity of a traumatic brain injury to shape outcome trajectories. We aim to provide a practical base on which to build discussions with the patient and their family about what to expect following injury and also to plan appropriate neurorehabilitation.

Diagnostic accuracy of interictal source imaging in presurgical epilepsy evaluation: A systematic review from the E-PILEPSY consortium.

OBJECTIVE: Interictal high resolution (HR-) electric source imaging (ESI) and magnetic source imaging (MSI) are non-invasive tools to aid epileptogenic zone localization in epilepsy surgery candidates. We carried out a systematic review on the diagnostic accuracy and quality of evidence of these modalities. METHODS: Embase, Pubmed and the Cochrane database were searched on 13 February 2017. Diagnostic accuracy studies taking post-surgical seizure outcome as reference standard were selected. Quality appraisal was based on the QUADAS-2 framework. RESULTS: Eleven studies were included: eight MSI (n = 267), three HR-ESI (n = 127) studies. None was free from bias. This mostly involved: selection of operated patients only, interference of source imaging with surgical decision, and exclusion of indeterminate results. Summary sensitivity and specificity estimates were 82% (95% CI: 75-88%) and 53% (95% CI: 37-68%) for overall source imaging, with no statistical difference between MSI and HR-ESI. Specificity is higher when partially concordant results were included as non-concordant (p < 0.05). Inclusion of indeterminate test results as non-concordant lowered sensitivity (p < 0.05). CONCLUSIONS: Source imaging has a relatively high sensitivity but low specificity for identification of the epileptogenic zone. SIGNIFICANCE: We need higher quality studies allowing unbiased test evaluation to determine the added value and diagnostic accuracy of source imaging in the presurgical workup of refractory focal epilepsy.

Bitemporal seizure spread and its effect on autonomic dysfunction.

OBJECTIVE: Autonomic dysregulation is a possible pathomechanism of sudden unexpected death in epilepsy (SUDEP). Cardiac arrhythmias and autonomic symptoms are most commonly associated with seizures arising from the temporal lobes. The aim of this study was to investigate whether simultaneous seizure activity in both temporal lobes affects the autonomic nervous system differently from seizure activity in one temporal lobe as assessed by heart rate variability (HRV). METHODS: Electrocardiography (ECG) and intracranial electroencephalography (iEEG) data from 13 patients with refractory temporal lobe epilepsy who had seizures that propagated electrically from one temporal lobe to the other during video-EEG-ECG monitoring were retrospectively reviewed. The time domain, frequency domain, and nonlinear parameters of HRV were evaluated by analyzing 4-minute-long ECG epochs, sampling from baseline, preictal and postictal periods as well as epochs constituting unitemporal and bitemporal ictal activity. RESULTS: Heart rate was significantly higher during bitemporal ictal activity compared with all other time points. The time domain and nonlinear parameters of HRV were significantly decreased during bitemporal activity compared with baseline, and multiple components of HRV (standard deviation of RR intervals (SDNN), coefficient of variation (CV), root mean square of successive differences (RMSSD), and standard deviation of short-term variability (SD1)) were significantly lower during bitemporal activity compared with unitemporal activity. Frequency domain analysis showed no significant differences. CONCLUSION: This study shows that bitemporal seizure activity significantly increases heart rate and decreases HRV, indicating increased autonomic imbalance with a shift towards sympathetic predominance, and this may increase the risk of SUDEP.