Interictal Discharges Research Articles

Striatum- and Cerebellum-Modulated Epileptic Networks Varying Across States with and without Interictal Epileptic Discharges.

Idiopathic generalized epilepsy (IGE) is characterized by cryptogenic etiology and the striatum and cerebellum are recognized as modulators of epileptic network. We collected simultaneous electroencephalogram and functional magnetic resonance imaging data from 145 patients with IGE, 34 of whom recorded interictal epileptic discharges (IEDs) during scanning. In states without IEDs, hierarchical connectivity was performed to search core cortical regions which might be potentially modulated by striatum and cerebellum. Node-node and edge-edge moderation models were constructed to depict direct and indirect moderation effects in states with and without IEDs. Patients showed increased hierarchical connectivity with sensorimotor cortices (SMC) and decreased connectivity with regions in the default mode network (DMN). In the state without IEDs, striatum, cerebellum, and thalamus were linked to weaken the interactions of regions in the salience network (SN) with DMN and SMC. In periods with IEDs, overall increased moderation effects on the interaction between regions in SN and DMN, and between regions in DMN and SMC were observed. The thalamus and striatum were implicated in weakening interactions between regions in SN and SMC. The striatum and cerebellum moderated the cortical interaction among DMN, SN, and SMC in alliance with the thalamus, contributing to the dysfunction in states with and without IEDs in IGE. The current work revealed state-specific modulation effects of striatum and cerebellum on thalamocortical circuits and uncovered the potential core cortical targets which might contribute to develop new clinical neuromodulation techniques.

Efficacy and cognitive impact of modified Atkins diet in adults with drug-resistant epilepsy

This study aims to explore the efficacy and cognitive impact of the modified Atkins diet (MAD) in adults with drug-resistant epilepsy, as well as to analyze changes in epileptiform activity during ketogenic diet (KD) intervention. We performed a prospective, open-label study with patients aged 16 – 60 years who met the International League Against Epilepsy (ILAE) criteria for drug-resistant epilepsy. Sixteen patients were enrolled in this study, and baseline clinical and electroencephalography (EEG) characteristics, along with neuropsychological tests, were collected before and after 3 months of KD. Patients were divided into responders (≥50% seizure reduction) and non-responders (<50% seizure reduction) according to the clinical efficacy of the KD. Results indicate that 37.5% of patients reported a ≥50% seizure reduction after 3 months. In terms of safety, 37.5% of patients reported adverse effects, including constipation, abdominal pain, and nausea. In addition, a statistically significant increase in the level of total cholesterol was observed (P = 0.037) after diet treatment. Regarding cognitive impact, there was a significant improvement in auditory verbal learning test (AVLT) instant recall scale scores (P = 0.017). In terms of EEG characteristics, MAD significantly reduces interictal epileptic discharge (IED) index in non-rapid eye movement 2 (NREM2) after 3 months. No clinical predictors or EEG characteristics of MAD efficacy were identified. In conclusion, MAD can be safely and effectively practiced by adults with drug-resistant epilepsy. KD treatment has a significant impact on AVLT instant recall and can reduce the IED index in NREM2.

Postoperative interictal epileptiform discharges predict seizure recurrence after antiepileptic drug withdrawal regardless of concordance with surgical site

ObjectiveThe study aimed to explore the association between the site of interictal epileptic discharges (IEDs) on postoperative electroencephalogram (EEG) and seizure recurrence after antiepileptic drug (AED) withdrawal. The study hypothesizes...

Subclinical epileptiform activity in the Alzheimer continuum: association with disease, cognition and detection method

BackgroundEpileptic seizures are an established comorbidity of Alzheimer’s disease (AD). Subclinical epileptiform activity (SEA) as detected by 24-h electroencephalography (EEG) or magneto-encephalography (MEG) has been reported in temporal regions of clinically diagnosed AD patients. Although epileptic activity in AD probably arises in the mesial temporal lobe, electrical activity within this region might not propagate to EEG scalp electrodes and could remain undetected by standard EEG. However, SEA might lead to faster cognitive decline in AD.Aims1. To estimate the prevalence of SEA and interictal epileptic discharges (IEDs) in a well-defined cohort of participants belonging to the AD continuum, including preclinical AD subjects, as compared with cognitively healthy controls.2. To evaluate whether long-term-EEG (LTM-EEG), high-density-EEG (hd-EEG) or MEG is superior to detect SEA in AD.3. To characterise AD patients with SEA based on clinical, neuropsychological and neuroimaging parameters.MethodsSubjects (n = 49) belonging to the AD continuum were diagnosed according to the 2011 NIA-AA research criteria, with a high likelihood of underlying AD pathophysiology. Healthy volunteers (n = 24) scored normal on neuropsychological testing and were amyloid negative. None of the participants experienced a seizure before. Subjects underwent LTM-EEG and/or 50-min MEG and/or 50-min hd-EEG to detect IEDs.ResultsWe found an increased prevalence of SEA in AD subjects (31%) as compared to controls (8%) (p = 0.041; Fisher’s exact test), with increasing prevalence over the disease course (50% in dementia, 27% in MCI and 25% in preclinical AD). Although MEG (25%) did not withhold a higher prevalence of SEA in AD as compared to LTM-EEG (19%) and hd-EEG (19%), MEG was significantly superior to detect spikes per 50 min (p = 0.002; Kruskall–Wallis test). AD patients with SEA scored worse on the RBANS visuospatial and attention subset (p = 0.009 and p = 0.05, respectively; Mann–Whitney U test) and had higher left frontal, (left) temporal and (left and right) entorhinal cortex volumes than those without.ConclusionWe confirmed that SEA is increased in the AD continuum as compared to controls, with increasing prevalence with AD disease stage. In AD patients, SEA is associated with more severe visuospatial and attention deficits and with increased left frontal, (left) temporal and entorhinal cortex volumes.Trial registrationClinicaltrials.gov, NCT04131491. 12/02/2020.

Consistency of electrical source imaging in presurgical evaluation of epilepsy across different vigilance states.

The use of electrical source imaging (ESI) in assessing the source of interictal epileptic discharges (IEDs) is gaining increasing popularity in presurgical work-up of patients with drug-resistant focal epilepsy. While vigilance affects the ability to locate IEDs and identify the epileptogenic zone, we know little about its impact on ESI. We studied overnight high-density electroencephalography recordings in focal drug-resistant epilepsy. IEDs were marked visually in each vigilance state, and examined in the sensor and source space. ESIs were calculated and compared between all vigilance states and the clinical ground truth. Two conditions were considered within each vigilance state, an unequalized and an equalized number of IEDs. The number, amplitude, and duration of IEDs were affected by the vigilance state, with N3 sleep presenting the highest number, amplitude, and duration for both conditions (P < 0.001), while signal-to-noise ratio only differed in the unequalized condition (P < 0.001). The vigilance state did not affect channel involvement (P > 0.05). ESI maps showed no differences in distance, quality, extent, or maxima distances compared to the clinical ground truth for both conditions (P > 0.05). Only when an absolute reference (wakefulness) was used, the channel involvement (P < 0.05) and ESI source extent (P < 0.01) were impacted during rapid-eye-movement (REM) sleep. Clustering of amplitude-sensitive and -insensitive ESI maps pointed to amplitude rather than the spatial profile as the driver (P < 0.05). IED ESI results are stable across vigilance states, including REM sleep, if controlled for amplitude and IED number. ESI is thus stable and invariant to the vigilance state.

Is there a rationale for treating interictal epileptic discharges in self-limiting epilepsy with centrotemporal spikes (SeLECTS)?

Is there a rationale for treating interictal epileptic discharges in self-limiting epilepsy with centrotemporal spikes (SeLECTS)?

Resting-state brain activity distinguishes patients with generalised epilepsy from others

PurposeEpilepsy is a prevalent neurological disorder characterised by repetitive seizures. It is categorised into three types: generalised epilepsy (GE), focal epilepsy (FE), and combined generalised and focal epilepsy. Correctly subtyping the epilepsy is important to select appropriate treatments. The types are mainly determined (i.e., diagnosed) by their semiologies supported by clinical examinations, such as electroencephalography and magnetoencephalography (MEG). Although these examinations are traditionally based on visual inspections of interictal epileptic discharges (IEDs), which are not always visible, alternative analyses have been anticipated. We examined if resting-state brain activities can distinguish patients with GE, which would help us to diagnose the type of epilepsy. MethodsThe 5 min resting-state brain activities acquired using MEG were obtained retrospectively from 15 patients with GE. The cortical source of the activities was estimated at each frequency band from delta to high-frequency oscillation (HFO). These estimated activities were compared with reference datasets from 133 healthy individuals and control data from 29 patients with FE. ResultsPatients with GE showed larger theta in the occipital, alpha in the left temporal, HFO in the rostral deep regions, and smaller HFO in the caudal ventral regions. Their area under the curves of the receiver operating characteristic curves was around 0.8–0.9. The distinctive pattern was not found for data from FE. ConclusionPatients with GE show distinctive resting-state brain activity, which could be a potential biomarker and used complementarily to classical analysis based on the visual inspection of IEDs.

Resting state connectivity biomarkers of seizure freedom after epilepsy surgery

Alterations in brain networks may cause the lowering of the seizure threshold and hypersynchronization that underlie the recurrence of unprovoked seizures in epilepsy. The aim of this work is to estimate functional network characteristics, which may help predicting outcome of epilepsy surgery.Twenty patients were studied (11 females, 9 males, mean age 33 years) with scalp-recorded HD-EEG in resting state (eyes closed, no interictal discharges) before intracranial evaluation, which allowed the precise determination of the epileptogenic zone. Dipole source time courses in the brain were estimated using Weighted Minimum Norm Estimate based on HD-EEG signals. Information inflow and outflow of atlas-based brain regions were computed using partial directed connectivity. A set of graph measures for pairwise connections in standard EEG frequency bands was calculated.After epilepsy surgery 10 patients were seizure-free (Engel 1a) and 10 patients continued suffering from seizures (Engel outcome worse than 1a). Inflow of the regions containing the epileptogenic zone in the beta and delta frequency bands was significantly lower in patients who achieved seizure-freedom after surgery, compared with patients who continued to have seizures (p = 0.012, and p = 0.026, respectively). Average path length in the beta frequency band was significantly higher in patients who achieved seizure freedom (p = 0.012). In the delta frequency band, local efficiency and clustering coefficient were significantly higher in patients who achieved seizure freedom (0.033, 0.046).In patients who achieved seizure freedom after surgery, the preoperative analysis of the epileptic network exhibited stronger separation of the region containing the seizure onset zone, with less inflow of information. In contrast, shorter paths within the epileptic network may facilitate hypersynchronous neuronal activity and thus the recurrence of seizures in non-seizure free patients. This study supports the hypothesis that epileptic network properties might help to define suitable candidates for epilepsy surgery.

EEG Source Imaging-Clinical Considerations for EEG Acquisition and Signal Processing for Improved Temporo-Spatial Resolution.

EEG source imaging (ESI) has gained traction in recent years as a useful clinical tool for the noninvasive surgical work-up of patients with drug-resistant focal epilepsy. Despite its proven benefits for the temporo-spatial modeling of spike and seizure sources, ESI remains widely underused in clinical practice. This partly relates to a lack of clarity around an optimal approach to the acquisition and processing of scalp EEG data for the purpose of ESI. Here, we describe some of the practical considerations for the clinical application of ESI. We focus on patient preparation, the impact of electrode number and distribution across the scalp, the benefit of averaging raw data for signal analysis, and the relevance of modeling different phases of the interictal discharge as it evolves from take-off to peak. We emphasize the importance of recording high signal-to-noise ratio data for reliable source analysis. We argue that the accuracy of modeling cortical sources can be improved using higher electrode counts that include an inferior temporal array, by averaging interictal waveforms rather than limiting ESI to single spike analysis, and by careful interrogation of earlier phase components of these waveforms. No amount of postacquisition signal processing or source modeling sophistication, however, can make up for suboptimally recorded scalp EEG data in a poorly prepared patient.

Epileptic brain network mechanisms and neuroimaging techniques for the brain network.

Epilepsy can be defined as a dysfunction of the brain network, and each type of epilepsy involves different brain-network changes that are implicated differently in the control and propagation of interictal or ictal discharges. Gaining more detailed information on brain network alterations can help us to further understand the mechanisms of epilepsy and pave the way for brain network-based precise therapeutic approaches in clinical practice. An increasing number of advanced neuroimaging techniques and electrophysiological techniques such as diffusion tensor imaging-based fiber tractography, diffusion kurtosis imaging-based fiber tractography, fiber ball imaging-based tractography, electroencephalography, functional magnetic resonance imaging, magnetoencephalography, positron emission tomography, molecular imaging, and functional ultrasound imaging have been extensively used to delineate epileptic networks. In this review, we summarize the relevant neuroimaging and neuroelectrophysiological techniques for assessing structural and functional brain networks in patients with epilepsy, and extensively analyze the imaging mechanisms, advantages, limitations, and clinical application ranges of each technique. A greater focus on emerging advanced technologies, new data analysis software, a combination of multiple techniques, and the construction of personalized virtual epilepsy models can provide a theoretical basis to better understand the brain network mechanisms of epilepsy and make surgical decisions.

Anti-seizure gene therapy for focal cortical dysplasia.

Focal cortical dysplasias are a common subtype of malformation of cortical development, which frequently presents with a spectrum of cognitive and behavioural abnormalities as well as pharmacoresistant epilepsy. Focal cortical dysplasia type II is typically caused by somatic mutations resulting in mammalian target of rapamycin (mTOR) hyperactivity, and is the commonest pathology found in children undergoing epilepsy surgery. However, surgical resection does not always result in seizure freedom, and is often precluded by proximity to eloquent brain regions. Gene therapy is a promising potential alternative treatment and may be appropriate in cases that represent an unacceptable surgical risk. Here, we evaluated a gene therapy based on overexpression of the Kv1.1 potassium channel in a mouse model of frontal lobe focal cortical dysplasia. An engineered potassium channel (EKC) transgene was placed under control of a human promoter that biases expression towards principal neurons (CAMK2A) and packaged in an adeno-associated viral vector (AAV9). We used an established focal cortical dysplasia model generated by in utero electroporation of frontal lobe neural progenitors with a constitutively active human Ras homolog enriched in brain (RHEB) plasmid, an activator of mTOR complex 1. We characterized the model by quantifying electrocorticographic and behavioural abnormalities, both in mice developing spontaneous generalized seizures and in mice only exhibiting interictal discharges. Injection of AAV9-CAMK2A-EKC in the dysplastic region resulted in a robust decrease (∼64%) in the frequency of seizures. Despite the robust anti-epileptic effect of the treatment, there was neither an improvement nor a worsening of performance in behavioural tests sensitive to frontal lobe function. AAV9-CAMK2A-EKC had no effect on interictal discharges or behaviour in mice without generalized seizures. AAV9-CAMK2A-EKC gene therapy is a promising therapy with translational potential to treat the epileptic phenotype of mTOR-related malformations of cortical development. Cognitive and behavioural co-morbidities may, however, resist an intervention aimed at reducing circuit excitability.

Maturation-dependent changes in cortical and thalamic activity during sleep slow waves: Insights from a combined EEG-fMRI study

IntroductionStudies using scalp EEG have shown that slow waves (0.5–4 Hz), the most prominent hallmark of NREM sleep, undergo relevant changes from childhood to adulthood, mirroring brain structural modifications and the acquisition of cognitive skills. Here we used simultaneous EEG-fMRI to investigate the cortical and subcortical correlates of slow waves in school-age children and determine their relative developmental changes. MethodsWe analyzed data from 14 school-age children with self-limited focal epilepsy of childhood who fell asleep during EEG-fMRI recordings. Brain regions associated with slow-wave occurrence were identified using a voxel-wise regression that also modelled interictal epileptic discharges and sleep spindles. At the group level, a mixed-effects linear model was used. The results were qualitatively compared with those obtained from 2 adolescents with epilepsy and 17 healthy adults. ResultsSlow waves were associated with hemodynamic-signal decreases in bilateral somatomotor areas. Such changes extended more posteriorly relative to those in adults. Moreover, the involvement of areas belonging to the default mode network changes as a function of age. No significant hemodynamic responses were observed in subcortical structures. However, we identified a significant correlation between age and thalamic hemodynamic changes. ConclusionsPresent findings indicate that the somatomotor cortex may have a key role in slow-wave expression throughout the lifespan. At the same time, they are consistent with a posterior-to-anterior shift in slow-wave distribution mirroring brain maturational changes. Finally, our results suggest that slow-wave changes may not reflect only neocortical modifications but also the maturation of subcortical structures, including the thalamus.

AsHC 360 Exposure Influence on Epileptiform Discharges in Hippocampus of Infantile Male Rats In Vitro

Arsenic-containing hydrocarbons (AsHCs) are typical arsenolipids found in various marine organisms. They can penetrate the blood–brain barrier, specifically affecting synaptic plasticity and the learning and memory ability of hippocampal neurons. Temporal lobe epilepsy often occurs in the hippocampus. Thus, the possible influence of AsHCs exposure to temporal lobe epilepsy garnered attention. The present study investigated the effects of epileptiform discharges (EDs) signals introduced by low-magnesium ACSF in the hippocampus of infantile male rats in vitro, using electrophysiological techniques with multi-electrode arrays under AsHC 360 exposure. In our study of the effects of AsHC 360 on EDs signals, we found that inter-ictal discharges (IIDs) were not significantly impacted. When AsHC 360 was removed, any minor effects observed were reversed. However, when we examined the impact of AsHC 360 on ictal discharges (IDs), distinct patterns emerged based on the concentration levels. For low-concentration groups (5, 20, 60 μg As L−1), both the frequency and duration effects on IDs returned to normal post-elimination of AsHC 360. However, this recovery was not evident for concentrations of 100 μg As L−1 or higher. IDs were only observed in EDs signals during exposures to AsHC 360 concentrations up to 60 μg As L−1. In these conditions, ID frequencies significantly enhanced with the increased of AsHC 360 concentration. At high concentrations of AsHC 360 (≥100 μg As L−1), the transition from IIDs or pre-ictal discharges (PIDs) to IDs was notably inhibited. Additional study on co-exposure of AsHC 360 (100 μg As L−1) and agonist (10 nM (S)-(-)-Bay-K-8644) indicated that the regulation of EDs signals under AsHC 360 exposure could be due to directly interference with the α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) expression which influences the binding of excitatory glutamate neurotransmitter to AMPAR. The results suggest that EDs activities in the hippocampus of infantile Sprague Dawley rats are concentration-dependent on AsHC 360 exposure. Thus, it provides a basis for the seafood intake with AsHCs for epileptic patients and those with potential seizures.

How the Spreading and Intensity of Interictal Epileptic Activity Are Associated with Visuo-Spatial Skills in Children with Self-Limited Focal Epilepsy with Centro-Temporal Spikes.

This paper investigates brain-behaviour associations between interictal epileptic discharges and cognitive performance in a population of children with self-limited focal epilepsy with centro-temporal spikes (SeLECTS). Sixteen patients with SeLECTS underwent an extensive neuropsychological assessment, including verbal short-term and episodic memory, non-verbal short-term memory, attentional abilities and executive function. Two quantitative EEG indices were analysed, i.e., the Spike Wave Index (SWI) and the Spike Wave Frequency (SWF), and one qualitative EEG index, i.e., the EEG score, was used to evaluate the spreading of focal SW to other parts of the brain. We investigated associations between EEG indices and neuropsychological performance with non-parametric Spearman correlation analyses, including correction for multiple comparisons. The results showed a significant negative correlation between (i) the awake EEG score and the Block Tapping Test, a visuo-spatial short-term memory task, and (ii) the sleep SWI and the Tower of London, a visuo-spatial planning task (pcorr < 0.05). These findings suggest that, in addition to the usual quantitative EEG indices, the EEG analysis should include the qualitative EEG score evaluating the spreading of focal SW to other parts of the brain and that neuropsychological assessment should include visuo-spatial skills.

Detection of Interictal epileptiform discharges with semi-supervised deep learning

Interictal discharges (IEDs) in EEG recordings are important signatures of epilepsy as their presence is strongly associated with an increased risk of seizures. IEDs are relatively short-duration events (typically 70–250 ms) that can be viewed as stochastic anomalies in such recordings. Currently, visual analysis of the EEG by clinical experts is the gold standard. This process, however, is time-consuming, error prone, and associated with a long learning period.Automatizing the detection of IEDs has the potential to significantly reduce review time, and may serve to complement the visual analysis. Supervised deep learning methods have shown potential for this purpose, but the scarceness of annotated data has limited their performance, which motivates to explore unsupervised and semi-supervised approaches, that do not require (extensive) expert annotations.We trained different unsupervised deep learning models, Autoencoders (AE) and Variational Autoencoders (VAE) for anomaly (IED) detection in these recordings. These models are dimensionality reduction based approaches, that can compress the data to lower dimensional representations, learning the notion of normality within data and reconstruct samples accordingly. Our data set comprised 203 clinical EEGs, 115 from patients with epilepsy, that contained IEDs, and 88 normal EEGs. Performance was assessed qualitatively through visual analysis of reconstructed samples and quantified as Area Under the Curve (AUC), sensitivity and specificity.The best performance was obtained using a semi-supervised approach, allowing the detection of IEDs with a sensitivity of 81.9% and specificity of 91.7%.Our work shows that unsupervised approaches and other approaches with limited supervision perform satisfactorily and have the potential to assist visual assessment of interictal discharges in epilepsy diagnostics.

Yield of non-invasive imaging in MRI-negative focal epilepsy.

The absence of MRI-lesion reduces considerably the probability of having an excellent outcome (International League Against Epilepsies [ILAE] class I-II) after epilepsy surgery. Surgical success in magnetic-resonance imaging (MRI)-negative cases relies therefore mainly on non-invasive techniques such as positron-emission tomography (PET), subtraction ictal/inter-ictal single-photon-emission-computed-tomography co-registered to MRI (SISCOM), electric source imaging (ESI) and morphometric MRI analysis (MAP). We were interested in identifying the optimal imaging technique or combination to achieve post-operative class I-II in patients with MRI-negative focal epilepsy. We identified 168 epileptic patients without MRI lesion. Thirty-three (19.6%) were diagnosed with unifocal epilepsy, underwent surgical resection and follow-up ⩾ 2 years. Sensitivity, specificity, predictive values, and diagnostic odds ratio (OR) were calculated for each technique individually and in combination (after co-registration). 23/33 (70%) were free of disabling seizures (75.0% with temporal and 61.5% extratemporal lobe epilepsy). None of the individual modalities presented an OR > 1.5, except ESI if only patients with interictal epileptiform discharges (IEDs) were considered (OR 3.2). On a dual combination, SISCOM with ESI presented the highest outcome (OR = 6). MAP contributed to detecting indistinguishable focal cortical dysplasia in particular in extratemporal epilepsies with a sensitivity of 75%. Concordance of PET, ESI on interictal epileptic discharges, and SISCOM was associated with the highest chance for post-operative seizure control (OR = 11). If MRI is negative, the chances to benefit from epilepsy surgery are almost as high as in lesional epilepsy, provided that multiple established non-invasive imaging tools are rigorously applied and co-registered together.

Abstract 105: Limb Shaking Transient Ischemic Attack: A Rare Presentation of Internal Carotid Artery Occlusion

Introduction Limb‐shaking transient ischemic attack (LS‐TIA) is a rare disorder characterized by brief, irregular, involuntary movements of the extremities with or without loss of consciousness. Associated paroxysmal hyperkinetic extremity movements often described by patients as “shaking,” “tremors,” or “twitching” are an uncommon and under‐reported presentation of cerebral hypoperfusion. Vascular etiology must remain on the differential as these transient but hemodynamically significant episodes are associated with severe carotid steno‐occlusive disease and carry an elevated risk for stroke. Methods The patient was evaluated in routine clinical practice. Results A man in his 50s with medical history of chronic right internal carotid artery (ICA) occlusion, coronary artery disease and tobacco use disorder presented with two months of intermittent, progressive worsening of left extremity tremors associated with ipsilateral weakness and mild confusion during the spells. These involuntary paroxysmal spells—precipitated by standing up, exertion and neck hyperextension—initially occurred 4 to 5 times per week in left upper extremity but progressed to 4 to 5 times per day with prolonged durations reaching 20 minutes and involving the left lower extremity. The initial event involved loss of consciousness, but no further syncopal episodes were noted. While ipsilateral hemiparesis and mild confusion occurred during the spells, spontaneous resolution and immediate return to baseline were reported afterward. On presentation, the National Institutes of Health Stroke Scale (NIHSS) was zero. Computed tomography (CT) head did not show acute intracranial process. CT angiography (CTA) re‐demonstrated right ICA occlusion at its origin. A load of Clopidogrel 300 mg and Aspirin 325 mg was administered. Orthostatic blood pressure measurements were normal. CT perfusion of brain demonstrated a perfusion decrease within the right frontoparietal lobes in the right middle cerebral artery (MCA) region. Routine EEG was performed, and it did not show interictal discharges. Brain MRI did not show acute infarcts. Catheter cerebral angiogram was then pursued, confirming right ICA occlusion at its origin and additionally showed mild atherosclerosis of the left ICA without flow‐limiting stenosis. After thorough evaluation, these events of unilateral extremity shaking and hemiparesis were deemed to be LS‐TIA. Neurosurgery was consulted and offered extracranial‐intracranial (EC‐IC)/ superficial temporal artery‐MCA bypass surgery. He was discharged in stable condition to continue DAPT and high‐dose statin while pending surgical intervention. Conclusion This case not only provides a descriptive narration of the presentation of LS‐TIA along with the steps in management undertaken but also encourages the consideration of vascular etiology as a potential cause for acute onset paroxysmal hyperkinetic movements. Early diagnosis and appropriate treatment are crucial to reduce burden of poor outcomes and prevention of stroke.

Interictal epileptiform discharges contribute to word-finding difficulty in epilepsy through multiple cognitive mechanisms.

Cognitive impairment often impacts quality of life in epilepsy even if seizures are controlled. Word-finding difficulty is particularly prevalent and often attributed to etiological (static, baseline) circuit alterations. We sought to determine whether interictal discharges convey significant superimposed contributions to word-finding difficulty in patients, and if so, through which cognitive mechanism(s). Twenty-three patients undergoing intracranial monitoring for drug-resistant epilepsy participated in multiple tasks involving word production (auditory naming, short-term verbal free recall, repetition) to probe word-finding difficulty across different cognitive domains. We compared behavioral performance between trials with versus without interictal discharges across six major brain areas and adjusted for intersubject differences using mixed-effects models. We also evaluated for subjective word-finding difficulties through retrospective chart review. Subjective word-finding difficulty was reported by the majority (79%) of studied patients preoperatively. During intracranial recordings, interictal epileptiform discharges (IEDs) in the medial temporal lobe were associated with long-term lexicosemantic memory impairments as indexed by auditory naming (p = .009), in addition to their established impact on short-term verbal memory as indexed by free recall (p = .004). Interictal discharges involving the lateral temporal cortex and lateral frontal cortex were associated with delayed reaction time in the auditory naming task (p = .016 and p = .018), as well as phonological working memory impairments as indexed by repetition reaction time (p = .002). Effects of IEDs across anatomical regions were strongly dependent on their precise timing within the task. IEDs appear to act through multiple cognitive mechanisms to form a convergent basis for the debilitating clinical word-finding difficulty reported by patients with epilepsy. This was particularly notable for medial temporal spikes, which are quite common in adult focal epilepsy. In parallel with the treatment of seizures, the modulation of interictal discharges through emerging pharmacological means and neurostimulation approaches may be an opportunity to help address devastating memory and language impairments in epilepsy.

Effects of inverse methods and spike phases on interictal high-density EEG source reconstruction

ObjectiveTo determine the effect of inverse methods and timepoints of interictal epileptic discharges (IEDs) used for high-density electric source imaging (hd-ESI) in pharmacoresistant focal epilepsies. MethodsWe retrospectively evaluated the hd-ESI and [18F]fluorodeoxyglucose positron emission tomography (18FDG-PET) of 21 operated patients with pharmacoresistant focal epilepsy (Engel I). Volumetric hd-ESI was performed with three different inverse methods such as the inverse solution linearly constrained minimum variance (LCMV, a beamformer method), standardized low resolution electromagnetic tomography (sLORETA) and weighted minimum-norm estimation (wMNE) and at different IED phases. Hd-ESI accuracy was determined by volumetric overlap and distance between hd-ESI source maximum, as well as 18FDG-PET hypometabolic region relative to the resection zone (RZ). ResultsIn our cohort, the shortest distances and greatest volumetric overlaps to the RZ were found in the half-rise and peak-phase for all inverse methods. The distance to the RZ was not different between the centroid of the clinical hypothesis-based cluster and the source maximum in peak-phase. However, the distance of the hypothesis-based cluster was significantly shorter compared to the cluster selected by the smallest p-value. ConclusionsHd-ESI provides the greatest accuracy in determining the RZ at the IED half-rise and peak-phase for all applied inverse methods, whereby sLORETA and LCMV were equally accurate. SignificanceOur results offer guidance in selecting inverse methods and IED phases for hd-ESI, compare the performance of hd-ESI and 18FDG-PET and encourage future studies in investigating the relationship between interictal ESI and 18FDG-PET hypometabolism.

Estimation of fMRI responses related to epileptic discharges using Bayesian hierarchical modeling.

Simultaneous electroencephalography-functional MRI (EEG-fMRI) is a unique and noninvasive method for epilepsy presurgical evaluation. When selecting voxels by null-hypothesis tests, the conventional analysis may overestimate fMRI response amplitudes related to interictal epileptic discharges (IEDs), especially when IEDs are rare. We aimed to estimate fMRI response amplitudes represented by blood oxygen level dependent (BOLD) percentage changes related to IEDs using a hierarchical model. It involves the local and distributed hemodynamic response homogeneity to regularize estimations. Bayesian inference was applied to fit the model. Eighty-two epilepsy patients who underwent EEG-fMRI and subsequent surgery were included in this study. A conventional voxel-wise general linear model was compared to the hierarchical model on estimated fMRI response amplitudes and on the concordance between the highest response cluster and the surgical cavity. The voxel-wise model overestimated fMRI responses compared to the hierarchical model, evidenced by a practically and statistically significant difference between the estimated BOLD percentage changes. Only the hierarchical model differentiated brief and long-lasting IEDs with significantly different BOLD percentage changes. Overall, the hierarchical model outperformed the voxel-wise model on presurgical evaluation, measured by higher prediction performance. When compared with a previous study, the hierarchical model showed higher performance metric values, but the same or lower sensitivity. Our results demonstrated the capability of the hierarchical model of providing more physiologically reasonable and more accurate estimations of fMRI response amplitudes induced by IEDs. To enhance the sensitivity of EEG-fMRI for presurgical evaluation, it may be necessary to incorporate more appropriate spatial priors and bespoke decision strategies.