Ictal Central Apnea Is Predictive of Mesial Temporal Seizure Onset: An Intracranial Investigation.

OBJECTIVE: Ictal central apnea (ICA) is a semiological sign of focal epilepsy, associated with temporal and frontal lobe seizures. In this study, using qualitative and quantitative approaches, we aimed to assess the localizational value of ICA. We also aimed to compare ICA clinical utility in relation to other seizure semiological features of focal epilepsy. METHODS: We analyzed seizures in patients with medically refractory focal epilepsy undergoing intracranial stereotactic electroencephalographic (SEEG) evaluations with simultaneous multimodal cardiorespiratory monitoring. A total of 179 seizures in 72 patients with reliable artifact-free respiratory signal were analyzed. RESULTS: ICA was seen in 55 of 179 (30.7%) seizures. Presence of ICA predicted a mesial temporal seizure onset compared to those without ICA (odds ratio = 3.8, 95% confidence interval = 1.3-11.6, p = 0.01). ICA specificity was 0.82. ICA onset was correlated with increased high-frequency broadband gamma (60-150Hz) activity in specific mesial or basal temporal regions, including amygdala, hippocampus, and fusiform and lingual gyri. Based on our results, ICA has an almost 4-fold greater association with mesial temporal seizure onset zones compared to those without ICA and is highly specific for mesial temporal seizure onset zones. As evidence of symptomatogenic areas, onset-synchronous increase in high gamma activity in mesial or basal temporal structures was seen in early onset ICA, likely representing anatomical substrates for ICA generation. INTERPRETATION: ICA recognition may help anatomoelectroclinical localization of clinical seizure onset to specific mesial and basal temporal brain regions, and the inclusion of these regions in SEEG evaluations may help accurately pinpoint seizure onset zones for resection. ANN NEUROL 2024;95:998-1008.

The value of additional electrodes when stereo-electroencephalography is inconclusive.

OBJECTIVE: Stereo-electroencephalography (SEEG) is the preferred method for intracranial localization of the seizure-onset zone (SOZ) in drug-resistant focal epilepsy. Occasionally SEEG evaluation fails to confirm the pre-implantation hypothesis. This leads to a decision tree regarding whether the addition of SEEG electrodes (two-step SEEG - 2sSEEG) or placement of subdural electrodes (SDEs) after SEEG (SEEG2SDE) would help. There is a dearth of literature encompassing this scenario, and here we aimed to characterize outcomes following unplanned two-step intracranial EEG (iEEG). METHODS: All 225 adult SEEG cases over 8 years at our institution were reviewed to extract patient data and outcomes following a two-step evaluation. Three raters independently quantified benefits of additional intracranial electrodes. The relationship between two-step iEEG benefit and clinical outcome was then analyzed. RESULTS: Fourteen patients underwent 2sSEEG and nine underwent SEEG2SDE. In the former cohort, the second SEEG procedure was performed for these reasons-precise localization of the SOZ (36%); defining margins of eloquent cortex (21%); and broadening coverage in the setting of non-localizable seizure onsets (43% of cases). Sixty-four percent of 2sSEEG cases were consistently deemed beneficial (Light's κ = 0.80). 2sSEEG performed for the first two indications was much more beneficial than when onsets were not localizable (100% vs 17%, p = .02). In the SEEG2SDE cohort, SDEs identified the SOZ and enabled delineation of margins relative to eloquent cortex in all cases. SIGNIFICANCE: The two-step iEEG is useful if the initial evaluation is broadly concordant with the original electroclinical hypothesis, where it can clarify onset zones or delineate safe surgical margins; however, it provides minimal benefit when the implantation hypothesis is erroneous, and we recommend that 2sSEEG not be generally utilized in such cases. SDE implantation after SEEG minimizes the need for SDEs and is helpful in delineating surgical boundaries relative to ictal-onset zones and eloquent cortex.

Reliable detection of generalized convulsive seizures using an off-the-shelf digital watch: A multisite phase 2 study.

OBJECTIVE: The aim of this study was to develop a machine learning algorithm using an off-the-shelf digital watch, the Samsung watch (SM-R800), and evaluate its effectiveness for the detection of generalized convulsive seizures (GCS) in persons with epilepsy. METHODS: This multisite epilepsy monitoring unit (EMU) phase 2 study included 36 adult patients. Each patient wore a Samsung watch that contained accelerometer, gyroscope, and photoplethysmographic sensors. Sixty-eight time and frequency domain features were extracted from the sensor data and were used to train a random forest algorithm. A testing framework was developed that would better reflect the EMU setting, consisting of (1) leave-one-patient-out cross-validation (LOPO CV) on GCS patients, (2) false alarm rate (FAR) testing on nonseizure patients, and (3) "fixed-and-frozen" prospective testing on a prospective patient cohort. Balanced accuracy, precision, sensitivity, and FAR were used to quantify the performance of the algorithm. Seizure onsets and offsets were determined by using video-electroencephalographic (EEG) monitoring. Feature importance was calculated as the mean decrease in Gini impurity during the LOPO CV testing. RESULTS: LOPO CV results showed balanced accuracy of .93 (95% confidence interval [CI] = .8-.98), precision of .68 (95% CI = .46-.85), sensitivity of .87 (95% CI = .62-.96), and FAR of .21/24 h (interquartile range [IQR] = 0-.90). Testing the algorithm on patients without seizure resulted in an FAR of .28/24 h (IQR = 0-.61). During the "fixed-and-frozen" prospective testing, two patients had three GCS, which were detected by the algorithm, while generating an FAR of .25/24 h (IQR = 0-.89). Feature importance showed that heart rate-based features outperformed accelerometer/gyroscope-based features. SIGNIFICANCE: Commercially available wearable digital watches that reliably detect GCS, with minimum false alarm rates, may overcome usage adoption and other limitations of custom-built devices. Contingent on the outcomes of a prospective phase 3 study, such devices have the potential to provide non-EEG-based seizure surveillance and forecasting in the clinical setting.

Stimulation-induced respiratory enhancement in corticothalamic regions.

OBJECTIVE: We aimed to identify corticothalamic areas and electrical stimulation paradigms that optimally enhance breathing. METHODS: Twenty-nine patients with medically intractable epilepsy were prospectively recruited in an epilepsy monitoring unit while undergoing stereoelectroencephalographic evaluation. Direct electrical stimulation in cortical and thalamic regions was carried out using low (<1 Hz) and high (≥10 Hz) frequencies, and low (<5 mA) and high (≥5 mA) current intensities, with pulse width of .1 ms. Electrocardiography, arterial oxygen saturation (SpO2 ), end-tidal carbon dioxide (ETCO2 ), oronasal airflow, and abdominal and thoracic plethysmography were monitored continuously during stimulations. Airflow signal was used to estimate breathing rate, tidal volume, and minute ventilation (MV) changes during stimulation, compared to baseline. RESULTS: Electrical stimulation increased MV in the amygdala, anterior cingulate, anterior insula, temporal pole, and thalamus, with an average increase in MV of 20.8% ± 28.9% (range = 0.2%-165.6%) in 19 patients. MV changes were associated with SpO2 and ETCO2 changes (p < .001). Effects on respiration were parameter and site dependent. Within amygdala, low-frequency stimulation of the medial region produced 78.49% greater MV change (p < .001) compared to high-frequency stimulation. Longer stimulation produced greater MV changes (an increase of 4.47% in MV for every additional 10 s, p = .04). SIGNIFICANCE: Stimulation of amygdala, anterior cingulate gyrus, anterior insula, temporal pole, and thalamus, using certain stimulation paradigms, enhances respiration. Among tested paradigms, low-frequency, low-intensity, long-duration stimulation of the medial amygdala is the most effective breathing enhancement stimulation strategy. Such approaches may pave the way for the future development of neuromodulatory techniques that aid rescue from seizure-related apnea, potentially as a targeted sudden unexpected death in epilepsy prevention method.

Forecasting seizure clusters from chronic ambulatory electrocorticography.

Seizure clusters are seizures that occur in rapid succession during periods of heightened seizure risk and are associated with substantial morbidity and sudden unexpected death in epilepsy. The objective of this feasibility study was to evaluate the performance of a novel seizure cluster forecasting algorithm. Chronic ambulatory electrocorticography recorded over an average of 38 months in 10 subjects with drug-resistant epilepsies was analyzed pseudoprospectively by dividing data into training (first 85%) and validation periods. For each subject, the probability of seizure clustering, derived from the Kolmogorov-Smirnov statistic using a novel algorithm, was forecasted in the validation period using individualized autoregressive models that were optimized from training data. The primary outcome of this study was the mean absolute scaled error (MASE) of 1-day horizon forecasts. From 10 subjects, 394 ± 142 (mean ± SD) electrocorticography-based seizure events were extracted for analysis, representing a span of 38 ± 27 months of recording. MASE across all subjects was .74 ± .09, .78 ± .09, and .83 ± .07 at .5-, 1-, and 2-day horizons. The feasibility study demonstrates that seizure clusters are quasiperiodic and can be forecasted to clinically meaningful horizons. Pending validation in larger cohorts, the forecasting approach described herein may herald chronotherapy during imminent heightened seizure vulnerability.

Limbic and paralimbic respiratory modulation: From inhibition to enhancement.

OBJECTIVE: Increased understanding of the role of cortical structures in respiratory control may help the understanding of seizure-induced respiratory dysfunction that leads to sudden unexpected death in epilepsy (SUDEP). The aim of this study was to characterize respiratory responses to electrical stimulation (ES), including inhibition and enhancement of respiration. METHODS: We prospectively recruited 19 consecutive patients with intractable epilepsy undergoing stereotactic electroencephalography (EEG) evaluation from June 2015 to June 2018. Inclusion criteria were patients ≥18 years in whom ES was indicated for clinical mapping of ictal onset or eloquent cortex as part of the presurgical evaluation. ES was carried out at 50 Hz, 0.2 msec, and 1-10 mA current intensity. Common brain regions sampled across all patients were amygdala (AMY), hippocampus (HG), anterior cingulate gyrus (CING), orbitofrontal cortex (OrbF), temporal neocortex (TNC), temporal pole (TP), and entorhinal cortex (ERC). Seven hundred fifty-five stimulations were conducted. Quantitative analysis of breathing signal, that is, changes in breathing rate (BR), depth (TV), and minute ventilation (MV), was carried out during ES using the BreathMetrics breathing waveform analysis toolbox. Electrocardiography, arterial oxygen saturation, end-tidal and transcutaneous carbon dioxide, nasal airflow, and abdominal and thoracic plethysmography were monitored continuously during stimulations. RESULTS: Electrical stimulation of TP and CING (at lower current strengths <3 mA) increased TV and MV. At >7-10 mA, CING decreased TV and MV. On the other hand, decreased TV and MV occurred with stimulation of mesial temporal structures such as AMY and HG. Breathing changes were dependent on stimulation intensity. Lateral temporal, entorhinal, and orbitofrontal cortices did not affect breathing either way. SIGNIFICANCE: These findings suggest that breathing responses other than apnea can be induced by ES. Identification of two regions-the temporal pole and anterior cingulate gyrus-for enhancement of breathing may be important in paving the way to future development of strategies for prevention of SUDEP.

Optimizing therapies for neurobehavioral comorbidities of epilepsy using chronic ambulatory electrocorticography.

There is an unmet need to improve therapy for neuropsychiatric comorbidities that are highly prevalent in persons with epilepsy (PWE). However, diagnosing and monitoring the neurobehavioral symptoms is challenging as their presentation can overlap with seizures. In this retrospective study, we report the advantage of chronic ambulatory electrocorticography (ECoG) from implanted Responsive Neurostimulator System (RNS®) in characterizing these psychosomatic paroxysms as a possible ictal, postictal, or interictal phenomenon and how the diagnosis guided the therapy choices. Five out of 21 patients with RNS had neuropsychiatric symptoms (panic attack, psychosis, conversion, and somatization disorders) that overlapped with their seizure semiology and were found to benefit from the use of RNS ECoG data by timely diagnosing and titrating targeted therapies. The cases illustrate the use of RNS ECoG data in diagnosing and improving the management of comorbidities in PWE. The ability to access RNS ECoG data and correlate it with patient symptoms is unique among available therapeutic options for PWE.

Robot-assisted stereoelectroencephalography exploration of the limbic thalamus in human focal epilepsy: implantation technique and complications in the first 24 patients.

OBJECTIVE: Despite numerous imaging studies highlighting the importance of the thalamus in a patient's surgical prognosis, human electrophysiological studies involving the limbic thalamic nuclei are limited. The objective of this study was to evaluate the safety and accuracy of robot-assisted stereotactic electrode placement in the limbic thalamic nuclei of patients with suspected temporal lobe epilepsy (TLE). METHODS: After providing informed consent, 24 adults with drug-resistant, suspected TLE undergoing evaluation with stereoelectroencephalography (SEEG) were enrolled in the prospective study. The trajectory of one electrode planned for clinical sampling of the operculoinsular cortex was modified to extend it to the thalamus, thereby preventing the need for additional electrode placement for research. The anterior nucleus of the thalamus (ANT) (n = 13) and the medial group of thalamic nuclei (MED) (n = 11), including the mediodorsal and centromedian nuclei, were targeted. The postimplantation CT scan was coregistered to the preoperative MR image, and Morel's thalamic atlas was used to confirm the accuracy of implantation. RESULTS: Ten (77%) of 13 patients in the ANT group and 10 (91%) of 11 patients in the MED group had electrodes accurately placed in the thalamic nuclei. None of the patients had a thalamic hemorrhage. However, trace asymptomatic hemorrhages at the cortical-level entry site were noted in 20.8% of patients, who did not require additional surgical intervention. SEEG data from all the patients were interpretable and analyzable. The trajectories for the ANT implant differed slightly from those of the MED group at the entry point-i.e., the precentral gyrus in the former and the postcentral gyrus in the latter. CONCLUSIONS: Using judiciously planned robot-assisted SEEG, the authors demonstrate the safety of electrophysiological sampling from various thalamic nuclei for research recordings, presenting a technique that avoids implanting additional depth electrodes or compromising clinical care. With these results, we propose that if patients are fully informed of the risks involved, there are potential benefits of gaining mechanistic insights to seizure genesis, which may help to develop neuromodulation therapies.

Dynamics of seizure-induced behavioral and autonomic arousal.

PURPOSE: Arousal is the most primitive, powerful instinct with survival benefit present in all vertebrates. Even though the arousal systems are classically viewed as "ascending" brainstem phenomena, there is a "descending" cortical feedback system that maintains consciousness. In this study, we provide electrophysiological confirmation that seizures localized to the anterior cingulum can behaviorally manifest as paroxysms of arousal from sleep. METHODS: Temporal dynamics of arousal induced by anterior cingulate seizures were analyzed by using multiple modalities including stereoelectroencephalography (phase lag index and phase amplitude coupling), lead-1 ECG (point-process heart rate variability analysis) and diffusion tractography (DTI). RESULTS: The ictal arousal was associated with an increase in synchronization in the alpha band and an increase in local theta or alpha-gamma phase-amplitude coupling. In comparison to seizures that lacked clinical manifestations, ictal arousal was associated with an increase in heart rate but not heart rate variability. Finally, DTI demonstrated degeneration in white fiber tracts passing between the anterior cingulum and anterior thalamus ipsilateral to the epileptogenic cortex. The patient underwent resection of the anterior cingulum, and histopathology confirmed focal cortical dysplasia type II. CONCLUSION: Anterior cingulate seizures inducing behavioral arousal have identifiable autonomic and EEG signatures.

Acute Increases in Protein O-GlcNAcylation Dampen Epileptiform Activity in Hippocampus.

O-GlcNAcylation is a ubiquitous and dynamic post-translational modification involving the O-linkage of ß-N-acetylglucosamine to serine/threonine residues of membrane, cytosolic, and nuclear proteins. This modification is similar to phosphorylation and regarded as a key regulator of cell survival and homeostasis. Previous studies have shown that phosphorylation of serine residues on synaptic proteins is a major regulator of synaptic strength and long-term plasticity, suggesting that O-GlcNAcylation of synaptic proteins is likely as important as phosphorylation; however, few studies have investigated its role in synaptic efficacy. We recently demonstrated that acutely increasing O-GlcNAcylation induces a novel form of LTD at CA3-CA1 synapses, O-GlcNAc LTD. Here, using hippocampal slices from young adult male rats and mice, we report that epileptiform activity at CA3-CA1 synapses, generated by GABAAR inhibition, is significantly attenuated when protein O-GlcNAcylation is pharmacologically increased. This dampening effect is lost in slices from GluA2 KO mice, indicating a requirement of GluA2-containing AMPARs, similar to expression of O-GlcNAc LTD. Furthermore, we find that increasing O-GlcNAcylation decreases spontaneous CA3 pyramidal cell activity under basal and hyperexcitable conditions. This dampening effect was also observed on cortical hyperexcitability during in vivo EEG recordings in awake mice where the effects of the proconvulsant pentylenetetrazole are attenuated by acutely increasing O-GlcNAcylation. Collectively, these data demonstrate that the post-translational modification, O-GlcNAcylation, is a novel mechanism by which neuronal and synaptic excitability can be regulated, and suggest the possibility that increasing O-GlcNAcylation could be a novel therapeutic target to treat seizure disorders and epilepsy.SIGNIFICANCE STATEMENT We recently reported that an acute pharmacological increase in protein O-GlcNAcylation induces a novel form of long-term synaptic depression at hippocampal CA3-CA1 synapses (O-GlcNAc LTD). This synaptic dampening effect on glutamatergic networks suggests that increasing O-GlcNAcylation will depress pathological hyperexcitability. Using in vitro and in vivo models of epileptiform activity, we show that acutely increasing O-GlcNAc levels can significantly attenuate ongoing epileptiform activity and prophylactically dampen subsequent seizure activity. Together, our findings support the conclusion that protein O-GlcNAcylation is a regulator of neuronal excitability, and it represents a promising target for further research on seizure disorder therapeutics.

Facial emotion processing in patients with seizure disorders.

Studies of emotion processing are needed to better understand the pathophysiology of psychogenic nonepileptic seizures (PNES). We examined the differences in facial emotion processing between 12 patients with PNES, 12 patients with temporal lobe epilepsy (TLE), and 24 matched healthy controls (HCs) using fMRI with emotional faces task (EFT) (happy/sad/fearful/neutral) and resting state connectivity. Compared with TLE, patients with PNES exhibited increased fMRI response to happy, neutral, and fearful faces in visual, temporal, and/or parietal regions and decreased fMRI response to sad faces in the putamen bilaterally. Regions showing significant differences between PNES and TLE were used as functional seed regions of interest (ROIs), in addition to amygdala structural seed ROIs for resting state functional connectivity analyses. Whole brain analyses showed that compared with TLE and HCs, patients with PNES exhibited increased functional connectivity of the functional seed ROIs to several brain regions, particularly to cerebellar, visual, motor, and frontotemporal regions. Connectograms showed increased functional connections between left parahippocampal gyrus/uncus ROIs and right temporal ROIs in PNES compared with both the TLE and HC groups. Resting state functional connectivity of the left and right amygdala to various brain regions including emotion regulation and motor control circuits was increased in PNES when compared with those with TLE. This study provides preliminary evidence that patients with PNES exhibit altered facial emotion processing compared with patients with TLE and HCs and increased amygdala functional connectivity compared with TLE. These findings identify potential key differences in facial emotion processing reflective of neurophysiologic markers of neural circuitry alterations that can be used to generate further hypotheses for developing studies that examine the contributions of emotion processing to the development and maintenance of PNES.

White Matter Abnormalities in Patients with Treatment-Resistant Genetic Generalized Epilepsies.

BACKGROUND Genetic generalized epilepsies (GGEs) are associated with microstructural brain abnormalities that can be evaluated with diffusion tensor imaging (DTI). Available studies on GGEs have conflicting results. Our primary goal was to compare the white matter structure in a cohort of patients with video/EEG-confirmed GGEs to healthy controls (HCs). Our secondary goal was to assess the potential effect of age at GGE onset on the white matter structure. MATERIAL AND METHODS A convenience sample of 23 patients with well-characterized treatment-resistant GGEs (13 female) was compared to 23 HCs. All participants received MRI at 3T. DTI indices, including fractional anisotropy (FA) and mean diffusivity (MD), were compared between groups using Tract-Based Spatial Statistics (TBSS). RESULTS After controlling for differences between groups, abnormalities in DTI parameters were observed in patients with GGEs, including decreases in functional anisotropy (FA) in the hemispheric (left>right) and brain stem white matter. The examination of the effect of age at GGE onset on the white matter integrity revealed a significant negative correlation in the left parietal white matter region FA (R=-0.504; p=0.017); similar trends were observed in the white matter underlying left motor cortex (R=-0.357; p=0.103) and left posterior limb of the internal capsule (R=-0.319; p=0.148). CONCLUSIONS Our study confirms the presence of widespread white matter abnormalities in patients with GGEs and provides evidence that the age at GGE onset may have an important effect on white matter integrity.

Personalities of patients with nonepileptic psychogenic status.

The purposes of this study were to determine whether personalities of patients with nonepileptic psychogenic status (NEPS) are different from those of patients with typical intermittent psychogenic nonepileptic seizures (iPNES) using the Personality Assessment Inventory (PAI) and to compare their PAI profiles with the population norms. We hypothesized that patients with NEPS have more psychopathology compared with patients with iPNES and that, as a group, patients with PNES (iPNES+NEPS) would have more psychopathology compared with healthy individuals. We first compared the PAI profiles of patients with iPNES and NEPS and then the profiles of patients with NEPS, iPNES, and PNES with population norms in order to assess which PAI specific scales differed between groups in order to better characterize the psychopathology of PNES. All patients admitted for diagnostic evaluation to the epilepsy monitoring unit (EMU) were prospectively approached for participation. All patient/family interviews were conducted by an epileptologist, and the diagnosis of iPNES or NEPS was confirmed in all cases through video/EEG and/or family interview. The population norms for PAI were obtained from the manual. Of the 224 approached patients, 130 completed the PAI, and included 43 iPNES and 11 with NEPS. There were no significant differences between the two groups in regard to demographic or PAI profiles. Comparison with population norms revealed the presence of abnormal personality profiles on all scales in patients with iPNES, NEPS, or PNES. We conclude that while the occurrence of NEPS is relatively common in patients with PNES, the demographic characteristics and personality profiles of patients with NEPS are not different from those of patients with iPNES. We also confirmed the presence of significant psychopathology in the group with PNES when compared with population norms.

Case report: Nocturnal low-frequency stimulation of the centromedian thalamic nucleus improves sleep quality and seizure control.

Sleep disturbances and drug-resistant seizures significantly impact people with idiopathic generalized epilepsy (IGE). Thalamic deep brain stimulation (DBS) offers potential treatment, but its effect on sleep and seizure control needs clarification. In this study, we combined wearable sleep monitoring with electroencephalogram (EEG) confirmation to investigate the impact of nocturnal centromedian nucleus (CM) DBS parameters in a patient with drug-resistant IGE. We found that high-frequency (125 Hz) CM stimulation during sleep severely disrupted sleep macro architecture and exacerbated seizures. Conversely, switching to low-frequency (10 Hz) stimulation enhanced both sleep quality and seizure control. This study underscores the critical need to personalize DBS settings, tailoring them to individual patients' sleep patterns to maximize therapeutic benefits. While larger-scale trials are needed, our findings pave the way for patient-centric approaches to thalamic neuromodulation, offering a transformative path to improve treatment outcomes and quality of life for those with refractory epilepsy.

Stereoelectroencephalography of the Deep Brain: Basal Ganglia and Thalami.

SUMMARY: Stereoelectroencephalography (SEEG) has emerged as a transformative tool in epilepsy surgery, shedding light on the complex network dynamics involved in focal epilepsy. This review explores the role of SEEG in elucidating the role of deep brain structures, namely the basal ganglia and thalamus, in epilepsy. SEEG advances understanding of their contribution to seizure generation, propagation, and control by permitting precise and minimally invasive sampling of these brain regions. The basal ganglia, comprising the subthalamic nucleus, globus pallidus, substantia nigra, and striatum, have gained recognition for their involvement in both focal and generalized epilepsy. Electrophysiological recordings reveal hyperexcitability and increased synchrony within these structures, reinforcing their role as critical nodes within the epileptic network. Furthermore, low-frequency and high-frequency stimulation of the basal ganglia have demonstrated potential in modulating epileptogenic networks. Concurrently, the thalamus, a key relay center, has garnered prominence in epilepsy research. Disrupted thalamocortical connectivity in focal epilepsy underscores its significance in seizure maintenance. The thalamic subnuclei, including the anterior nucleus, centromedian, and medial pulvinar, present promising neuromodulatory targets, suggesting pathways for personalized epilepsy therapies. The prospect of multithalamic SEEG and thalamic SEEG stimulation trials has the potential to revolutionize epilepsy management, offering tailored solutions for challenging cases. SEEG's ability to unveil the dynamics of deep brain structures in epilepsy promises enhanced and personalized epilepsy care in our new era of precision medicine. Until deep brain SEEG is accepted as a standard of care, a rigorous informed consent process remains paramount for patients for whom such an exploration is proposed.

Characteristics of falls in the epilepsy monitoring unit: a retrospective study.

Falls are an important adverse event in an epilepsy monitoring unit (EMU). We identified patterns of falls in an EMU and compared them with risk factors for inpatient falls. Twenty-six patients with 26 falls (2.3% of admissions) in the EMU were compared with 50 general neurology inpatients with 56 falls over a 4-year period. In the EMU, the majority (62%) of falls happened during the first 3 days of admission, mostly in the bathroom (74%), in patients with a normal mental status (77%). Most general inpatients fell after the third day (64%), inside their rooms (68%), and had an altered mental status before the fall (68%). All 26 EMU patients were identified as high risk at admission, in spite of which falls were not prevented. We outline these differences between EMU patients and general inpatients and highlight the practice gap in preventing falls in an EMU.

Pro-Ictal State in Human Temporal Lobe Epilepsy.

BACKGROUND: Studies of continuous electroencephalography (EEG) suggest that seizures in individuals with focal-onset epilepsies preferentially occur during periods of heightened risk, typified by pathologic brain activities, termed pro-ictal states; however, the presence of (pathologic) pro-ictal states among a plethora of otherwise physiologic (e.g., sleep­wake cycle) states has not been established. METHODS: We studied a prospective, consecutive series of 15 patients with temporal lobe epilepsy who underwent limbic thalamic recordings in addition to routine (cortical) intracranial EEG for seizure localization. For each participant, pro-ictal (45 minutes before seizure onset) and interictal (4 hours removed from all seizures) EEG segments were divided into 10-minute, nonoverlapping windows, which were randomly distributed into training and validation cohorts in a 1:1 ratio. A deep neural classifier was applied to distinguish pro-ictal from interictal brain activities in a patient-specific fashion. RESULTS: We analyzed 1800 patient-hours of continuous thalamocortical EEG. Distinct pro-ictal states were detected in each participant. The median area under the receiver-operating characteristic curve of the classifier was 0.92 (interquartile range, 0.90­0.96). Pro-ictal states were distinguished at least 45 minutes before seizure onset in 13 of 15 participants; in 2 of 15 participants, they were distinguished up to 35 minutes prior. CONCLUSIONS: On the basis of thalamocortical EEG, pro-ictal states ­ pathologic brain activities during periods of heightened seizure risk ­ could be identified in patients with temporal lobe epilepsy and were detected, in our small sample, more than one half hour before seizure onset.

Advancing the frontiers of thalamic neuromodulation: A review of emerging targets and paradigms.

The thalamus is a key structure that plays a crucial role in initiating and propagating seizures. Recent advancements in neuroimaging and neurophysiology have identified the thalamus as a promising target for neuromodulation in drug-resistant epilepsies. This review article presents the latest innovations in thalamic targets and neuromodulation paradigms being explored in pilot or pivotal clinical trials. Multifocal temporal plus or posterior quadrant epilepsies are evaluated with pulvinar thalamus neuromodulation, while centromedian thalamus is explored in generalized epilepsies and Lennox Gastaut syndrome. Multinodal thalamocortical neuromodulation with novel stimulation paradigms such as long bursting or low-frequency stimulation is being investigated to quench the epileptic network excitability. Beyond seizure control, thalamic neuromodulation to restore consciousness is being studied. This review highlights the promising potential of thalamic neuromodulation in epilepsy treatment, offering hope to patients who have not responded to conventional medical therapies. However, it also emphasizes the need for larger randomized controlled trials and personalized stimulation paradigms to improve patient outcomes further.

Safety and efficacy of bihemispheric sampling via transmidline stereoelectroencephalography.

OBJECTIVE: Stereoelectroencephalography (SEEG) is designed to target distributed cortical networks responsible for electroclinical seizure syndrome and to enable localization of the site of seizure onset in patients with intractable epilepsy. When the preimplantation hypothesis invokes the bilateral mesial frontal lobes, sampling of several deep-seated cortical sites in both hemispheres is required. In this study, the authors have demonstrated the feasibility of sampling bihemispheric areas with intentional implantation of an SEEG electrode crossing the midline (SECM) for sampling the cortex on both sides of the interhemispheric fissure. METHODS: An analysis of 231 consecutive SEEG procedures over 8 years was used to identify instances of bihemispheric sampling by using the transmidline SEEG technique. RESULTS: The authors identified 53 SEEG cases, with a total of 126 electrodes that crossed the interhemispheric fissure; all were in the frontal lobes. Eighty-three electrodes targeted the cingulate gyrus (18 rostral, 43 anterior, and 22 middle), 31 targeted the posterior orbitofrontal region, 8 sampled the medial prefrontal cortex, and 4 targeted nodular heterotopia around the frontal horns. The ictal onset zone was localized to the frontal lobe in 16 cases. SECM isolated interictal and ictal activity in the contralateral hemisphere in 6 cases and independent bihemispheric seizure activity in 2 cases. No hemorrhagic or infectious complications were noted in any of these cases. CONCLUSIONS: Based on this extensive experience of bihemispheric sampling, the authors concluded that this technique is safe and effective. In this series, SECM showed contralateral interictal and/or ictal epileptiform activity in 8 (15%) cases, and 9 (16%) cases (with unilateral implantation) had sufficient data to discard contralateral involvement, contributing to support of the epileptogenic network. SECM may reduce the number of electrodes used to sample bilateral mesial frontal or orbitofrontal cortices, and such an approach may lower the risk of hemorrhage and costs.

Pulvinar neuromodulation for seizure monitoring and network modulation in temporal plus epilepsy.

Deep brain stimulation (DBS) is a promising treatment for drug-refractory epilepsies (DRE) when targeting the anterior nuclei of thalamus (ANT). However, targeting other thalamic nuclei, such as the pulvinar, shows therapeutic promise. Our pioneering case study presents the application of ambulatory seizure monitoring using spectral fingerprinting (12.15-17.15 Hz) recorded through Medtronic Percept DBS implanted bilaterally in the medial pulvinar thalami. This technology offers unprecedented opportunities for real-time monitoring of seizure burden and thalamocortical network modulation for effective seizure reduction in patients with bilateral mesial temporal and temporal plus epilepsies that are not suitable for resection.