A retrospective, naturalistic study of deep brain stimulation and vagal nerve stimulation in young patients.

INTRODUCTION: Invasive neuromodulation interventions such as deep brain stimulation (DBS) and vagal nerve stimulation (VNS) are important treatments for movement disorders and epilepsy, but literature focused on young patients treated with DBS and VNS is limited. This retrospective study aimed to examine naturalistic outcomes of VNS and DBS treatment of epilepsy and dystonia in children, adolescents, and young adults. METHODS: We retrospectively assessed patient demographic and outcome data that were obtained from electronic health records. Two researchers used the Clinical Global Impression scale to retrospectively rate the severity of neurologic and psychiatric symptoms before and after patients underwent surgery to implant DBS electrodes or a VNS device. Descriptive and inferential statistics were used to examine clinical effects. RESULTS: Data from 73 patients were evaluated. Neurologic symptoms improved for patients treated with DBS and VNS (p < .001). Patients treated with DBS did not have a change in psychiatric symptoms, whereas psychiatric symptoms worsened for patients treated with VNS (p = .008). The frequency of postoperative complications did not differ between VNS and DBS groups. CONCLUSION: Young patients may have distinct vulnerabilities for increased psychiatric symptoms during treatment with invasive neuromodulation. Child and adolescent psychiatrists should consider a more proactive approach and greater engagement with DBS and VNS teams that treat younger patients.

Pediatric neuromodulation for drug-resistant epilepsy: Survey of current practices, techniques, and outcomes across US epilepsy centers.

Neuromodulation via Responsive Neurostimulation (RNS) or Deep Brain Stimulation (DBS) is an emerging treatment strategy for pediatric drug-resistant epilepsy (DRE). Knowledge gaps exist in patient selection, surgical technique, and perioperative care. Here, we use an expert survey to clarify practices. Thirty-two members of the Pediatric Epilepsy Research Consortium were surveyed using REDCap. Respondents were from 17 pediatric epilepsy centers (missing data in one): Four centers implant RNS only while 13 implant both RNS and DBS. Thirteen RNS programs commenced in or before 2020, and 10 of 12 DBS programs began thereafter. The busiest six centers implant 6-10 new RNS devices per year; all DBS programs implant <5 annually. The youngest RNS patient was 3 years old. Most centers (11/12) utilize MP2RAGE and/or FGATIR sequences for planning. Centromedian thalamic nuclei were the unanimous target for Lennox-Gastaut syndrome. Surgeon exposure to neuromodulation occurred mostly in clinical practice (14/17). Clinically significant hemorrhage (n = 2) or infection (n = 3) were rare. Meaningful seizure reduction (>50%) was reported by 81% (13/16) of centers. RNS and DBS are rapidly evolving treatment modalities for safe and effective treatment of pediatric DRE. There is increasing interest in multicenter collaboration to gain knowledge and facilitate dialogue. PLAIN LANGUAGE SUMMARY: We surveyed 32 pediatric epilepsy centers in USA to highlight current practices of intracranial neuromodulation. Of the 17 that replied, we found that most centers are implanting thalamic targets in pediatric drug-resistant epilepsy using the RNS device. DBS device is starting to be used in pediatric epilepsy, especially after 2020. Different strategies for target identification are enumerated. This study serves as a starting point for future collaborative research.

Vagus nerve stimulation and heart rate variability: A scoping review of a somatic oscillatory signal.

The goal of this review is to synthesize the literature on vagus nerve stimulator (VNS)-related changes in heart rate variability (HRV) in patients with drug-resistant epilepsy (DRE) and assess the role of these changes in seizure relief. A scoping literature review was performed with the following inclusion criteria: primary articles written in English, involved implantable VNS in humans, and had HRV as a primary outcome. Twenty-nine studies were retrieved, however with considerable heterogeneity in study methods. The overall depression in HRV seen in DRE patients compared to healthy controls persisted even after VNS implant, indicating that achieving "healthy" HRV is not necessary for VNS therapeutic success. Within DRE patients, changes in frequency domain parameters six months after VNS implant returned to baseline after a year. The mechanism of how VNS reduces seizure burden does not appear to be significantly related to alterations in baseline HRV. However, the subtlety of sympathetic/parasympathetic signaling likely requires a more structured approach to experimental and analytic techniques than currently found in the literature.

Predictors of therapeutic response following thalamic neuromodulation for drug-resistant pediatric epilepsy: A systematic review and individual patient data meta-analysis.

We sought to perform a systematic review and individual participant data meta-analysis to identify predictors of treatment response following thalamic neuromodulation in pediatric patients with medically refractory epilepsy. Electronic databases (MEDLINE, Ovid, Embase, and Cochrane) were searched, with no language or data restriction, to identify studies reporting seizure outcomes in pediatric populations following deep brain stimulation (DBS) or responsive neurostimulation (RNS) implantation in thalamic nuclei. Studies featuring individual participant data of patients with primary or secondary generalized drug-resistant epilepsy were included. Response to therapy was defined as >50% reduction in seizure frequency from baseline. Of 417 citations, 21 articles reporting on 88 participants were eligible. Mean age at implantation was 13.07 ± 3.49 years. Fifty (57%) patients underwent DBS, and 38 (43%) RNS. Sixty (68%) patients were implanted in centromedian nucleus and 23 (26%) in anterior thalamic nucleus, and five (6%) had both targets implanted. Seventy-four (84%) patients were implanted bilaterally. The median time to last follow-up was 12 months (interquartile range = 6.75-26.25). Sixty-nine percent of patients achieved response to treatment. Age, target, modality, and laterality had no significant association with response in univariate logistic regression. Until thalamic neuromodulation gains widespread approval for use in pediatric patients, data on efficacy will continue to be limited to small retrospective cohorts and case series. The inherent bias of these studies can be overcome by using individual participant data. Thalamic neuromodulation appears to be a safe and effective treatment for epilepsy. Larger, prolonged prospective, multicenter studies are warranted to further evaluate the efficacy of DBS over RNS in this patient population where resection for curative intent is not a safe option.

Vagus nerve stimulation in medically refractory epilepsy: Adverse effects and clinical correlates.

OBJECTIVES: To assess the frequency of adverse effects among pediatric and adult patients and the clinical variables associated with a higher probability of developing side effects. METHODS: This retrospective study enrolled pediatric and adult patients who underwent Vagus nerve stimulation (VNS) implantation at our institution and had documented follow-up during clinic visits for at least 6 months after implantation. Data collected included demographic information, epilepsy diagnosis, and device data. RESULTS: A total of 43 patients with drug-resistant epilepsy who received a VNS device at our institution were enrolled. The median follow-up period was 12 months. Fourteen patients (32.55%) reported no side effects from VNS therapy. Side effects ranged from mild to severe, with significant side effects observed in 8 patients. Data on therapy efficacy were collected, and 10 patients (23.26%) reported no change in seizure frequency following device implantation. CONCLUSION: This study demonstrates that VNS is an important adjunct treatment option for epilepsy patients. Dysphagia and dyspnea can be significant adverse effects leading to treatment discontinuation, aspiration pneumonia, intensive care unit (ICU) admission, and prolonged hospital stay. These effects are more frequent in patients with symptomatic generalized epilepsy, global developmental delay at baseline, previous ICU admissions, abnormal brain magnetic resonance imaging findings, and seizures with multiple semiologies.

Insights From Chronic ECoG by RNS.

SUMMARY: The NeuroPace responsive neurostimulation system (RNS) has revolutionized the care of patients suffering from focal epilepsy since its approval in 2014. One major advantage of this device is its innate ability to gather long-term electrocorticographic (ECoG) data that the device uses in its novel closed-loop treatment paradigm. Beyond the standard stimulation treatments, which have been demonstrated to be safe and well-tolerated, the data collected by the RNS provide valuable information, such as the long-term circadian and ultradian variations that affect seizure risk, obtained under naturalistic conditions. Additionally, these data inform future surgical procedures, supplementing clinically reported seizures by patients, assessing the response to newly added anti-seizure medications, helping to forecast the risk of future seizures, and understanding the mechanisms of certain long-term outcomes in patients with postsurgical epilepsy. By leveraging these data, the delivery of high-quality clinical care for patients with epilepsy can only be enhanced. Finally, these data open significant avenues of research, including machine learning and artificial intelligence algorithms, which may also translate to improved outcomes in patients who struggle with recurrent seizures.

Longitudinal EpiTrack assessment of executive functions following vagus nerve stimulation therapy in patients with drug-resistant epilepsy.

OBJECTIVE: To investigate executive functions and attention with repeated EpiTrack evaluations in a group of DR patients with drug-resistant epilepsy (DRE) receiving vagus nerve stimulation (VNS) during a follow-up duration of up to 5 years. METHODS: The study involved 33 patients with DRE who were assessed with EpiTrack as a part of the clinical VNS protocol. Evaluations were scheduled prior to VNS implantation and then at 6 months, 12 months, and yearly thereafter. However, the COVID-19 pandemic disrupted follow-up. Therefore, changes in EpiTrack total scores over time were analyzed using a linear mixed-effects (LMEs) model to compensate for the variation in follow-up duration when predicting EpiTrack total score changes over 5 years. RESULTS: The median follow-up time was 29 months. During each month, the EpiTrack total score was predicted to increase by 0.07 units (95% confidence interval [CI]: 0.01-0.12, P = 0.02), corresponding to a change from a baseline score of 27.3 (severe impairment) to a score of 28.9 (mild impairment) at 2 years and a score of 31.5 (almost normal) at 5 years. In the group of patients with psychiatric comorbidities, the EpiTrack total score increased by 0.14 units per month (P = 0.003), which was 3.5-fold higher than the increase of patients without psychiatric comorbidities. For the patients taking 1-2 antiseizure medications (ASMs), the EpiTrack total score increased by 0.11 units per month (P = 0.005), which was almost quadruple the rate of patients taking 3-4 ASMs. SIGNIFICANCE: Based on EpiTrack total scores, the LME model predicted a four-point improvement in executive functions among patients with DRE at 5 years after the initiation of VNS, representing a clinically meaningful change. DRE patients with comorbid depression seemed to experience the most cognitive benefits. In addition, better cognitive outcomes were achieved if the patient took less than three ASMs. PLAIN LANGUAGE SUMMARY: Executive functions and attention may improve during vagus nerve stimulation therapy in patients with drug-resistant epilepsy. Epilepsy patients who have depression or use fewer than three antiseizure medications are likely to benefit cognitively more from the treatment.

Identification of metabolic biomarkers of chronic vagus nerve stimulation (VNS) in subjects with drug-resistant epilepsy (DRE).

Neuromodulation by means of vagus nerve stimulation (VNS) therapy, reduces seizure frequency and improves quality of life in subjects with drug-resistant epilepsy (DRE), yet its molecular mechanism remains unclear. This study investigates the impact of chronic VNS on lipid bioactive metabolites and fatty acids (FA) in the plasma and red blood cells of seven subjects with DRE. By measuring expression levels of peroxisome proliferator-activated receptor α (PPARα) and sirtuin1 (SIRT1) genes-key regulators in energy and lipid metabolism-and lipid profiles before and after various stages of VNS, this study identifies potential mechanisms by which VNS may reduce seizure frequency. Blood samples collected before VNS device implantation, after acute VNS stimulus, and following gradual intensity increments up to therapeutic levels revealed that VNS increases SIRT1 and PPARα expression and erythrocyte concentrations of PPARα ligands. Additionally, we observe reduced de novo lipogenesis biomarkers in erythrocytes, indicating that VNS may influence systemic lipid and energy metabolism. Our findings suggest that VNS could enhance neuronal function by modulating energy metabolism, thus potentially reducing seizure frequency in subjects with DRE. Future research targeting SIRT1 and PPARα may provide innovative therapeutic strategies for managing DRE. Plain Language Summary: The exact mechanism of VNS is still unknown. This study investigated the effects of VNS Therapy on energetic metabolism, suggesting possible novel biomarkers for DRE subjects and neuromodulation therapies.

Responsive neurostimulation as a treatment for super-refractory focal status epilepticus: a systematic review and case series.

OBJECTIVE: Super-refractory status epilepticus (SRSE) has high rates of morbidity and mortality. Few published studies have investigated neurostimulation treatment options in the setting of SRSE. This systematic literature review and series of 10 cases investigated the safety and efficacy of implanting and activating the responsive neurostimulation (RNS) system acutely during SRSE and discusses the rationale for lead placement and selection of stimulation parameters. METHODS: Through a literature search (of databases and American Epilepsy Society abstracts that were last searched on March 1, 2023) and direct contact with the manufacturer of the RNS system, 10 total cases were identified that utilized RNS acutely during SE (9 SRSE cases and 1 case of refractory SE [RSE]). Nine centers obtained IRB approval for retrospective chart review and completed data collection forms. A tenth case had published data from a case report that were referenced in this study. Data from the collection forms and the published case report were compiled in Excel. RESULTS: All 10 cases presented with focal SE: 9 with SRSE and 1 with RSE. Etiology varied from known lesion (focal cortical dysplasia in 7 cases and recurrent meningioma in 1) to unknown (2 cases, with 1 presenting with new-onset refractory focal SE [NORSE]). Seven of 10 cases exited SRSE after RNS placement and activation, with a time frame ranging from 1 to 27 days. Two patients died of complications due to ongoing SRSE. Another patient's SE never resolved but was subclinical. One of 10 cases had a device-related significant adverse event (trace hemorrhage), which did not require intervention. There was 1 reported recurrence of SE after discharge among the cases in which SRSE resolved up to the defined endpoint. CONCLUSIONS: This case series offers preliminary evidence that RNS is a safe and potentially effective treatment option for SRSE in patients with 1-2 well-defined seizure-onset zone(s) who meet the eligibility criteria for RNS. The unique features of RNS offer multiple benefits in the SRSE setting, including real-time electrocorticography to supplement scalp EEG for monitoring SRSE progress and response to treatment, as well as numerous stimulation options. Further research is indicated to investigate the optimal stimulation settings in this unique clinical scenario.

[Evaluation of the relevance of the pharmaceutical educational interview on the knowledge and satisfaction of patients who received a vagus nerve neurostimulator implantation]. / Évaluation de la pertinence de l'entretien pharmaceutique éducatif sur les connaissances et la satisfaction de patients ayant bénéficié d'une implantation d'un neurostimulateur du nerf vague.

INTRODUCTION: Vagal neurostimulation (VNS) medical devices (MDs) are used to treat drug-resistant epilepsy. Using a magnet, the patient can activate on the stimulations in order to stop a seizure or interrupt the adverse effects (AEs) of the device. The objective is to evaluate the improvement of the patients' knowledge about the VNS following a pharmaceutical educational interview (PEI) as well as their satisfaction. MATERIALS AND METHODS: The pharmaceutical educational interview regarding drugs and DMs was performed by the clinical pharmacist at the patient's bed after VNS implantation. A questionnaire about VNS devices (operation, adverse effects, recommendations) and assessing knowledge was submitted to patients before and after the PEI. Satisfaction was assessed by the Likert scale. RESULTS: From March 2020 to August 2021, 18 implanted patients were included in the study. In 78% of cases (14/18), the total number of good responses after PEI increased. The mean good response was significantly increased from 16.11/25 (64%) before PEI to 22.33/25 (89%) after PEI (P-value<0.01). The maximum satisfaction score (4/4) was given in 71% of the items. DISCUSSION-CONCLUSION: The results support the relevance of PEI. Patients feel a need for information and consider the interview useful. An improvement in knowledge was observed, which allows us to hope for an optimization of the effectiveness of the device, in particular, a reduction in seizures and AE. This study shows the feasibility and the interest of the development of clinical pharmacy applied to medical devices in complementarity with the expertise on drugs.

Neurostimulation for childhood epilepsy.

The experience with neurostimulation for childhood epilepsy is far less extensive than for adults. Nevertheless, the implementation of these techniques could be of great value, especially considering the detrimental effects of ongoing seizures on the developing brain. In this review, we discuss the available evidence for neurostimulation for childhood epilepsy. Vagus nerve stimulation (VNS) is the most studied neurostimulation modality in children. Based on mostly retrospective, open-label studies, we can conclude that VNS has a similar safety and efficacy profile in children compared to adults. Although there is little available evidence for deep brain stimulation (DBS) and responsive neurostimulation (RNS) in children, both DBS and RNS show promise in reducing seizure frequency with few complications. The implementation of non-invasive techniques with a more appealing safety profile has gained interest. Small randomized control trials and open-label studies have investigated transcranial direct current simulation for childhood epilepsy, demonstrating promising but inconsistent findings.

Closed-loop stimulation in periods with less epileptiform activity drives improved epilepsy outcomes.

In patients with drug-resistant epilepsy, electrical stimulation of the brain in response to epileptiform activity can make seizures less frequent and debilitating. This therapy, known as closed-loop responsive neurostimulation (RNS), aims to directly halt seizure activity via targeted stimulation of a burgeoning seizure. Rather than immediately stopping seizures as they start, many RNS implants produce slower, long-lasting changes in brain dynamics that better predict clinical outcomes. Here we hypothesize that stimulation during brain states with less epileptiform activity drives long-term changes that restore healthy brain networks. To test this, we quantified stimulation episodes during low- and high-risk brain states-that is, stimulation during periods with a lower or higher risk of generating epileptiform activity-in a cohort of 40 patients treated with RNS. More frequent stimulation in tonic low-risk states and out of rhythmic high-risk states predicted seizure reduction. Additionally, stimulation events were more likely to be phase-locked to prolonged episodes of abnormal activity for intermediate and poor responders when compared to super-responders, consistent with the hypothesis that improved outcomes are driven by stimulation during low-risk states. These results support the hypothesis that stimulation during low-risk periods might underlie the mechanisms of RNS, suggesting a relationship between temporal patterns of neuromodulation and plasticity that facilitates long-term seizure reduction.

Multitarget deep brain stimulation for epilepsy.

OBJECTIVE: Deep brain stimulation (DBS) is a rapidly growing surgical option for patients with drug-resistant epilepsy who are not candidates for resective/ablative surgery. Recent randomized controlled trials have demonstrated efficacy of DBS of the anterior nucleus of the thalamus (ANT), particularly in frontal or temporal epilepsy, whereas DBS of the centromedian (CM) nucleus appears to be most suitable in well-defined generalized epilepsy syndromes. At the authors' institution, DBS candidates who did not fit the populations represented in these trials were managed with DBS of multiple distinct targets, which included ANT, CM, and less-studied nuclei-i.e., mediodorsal nucleus, pulvinar, and subthalamic nucleus. The goal of this study was to present the authors' experience with these types of cases, and to motivate future investigations that can determine the long-term efficacy of multitarget DBS. METHODS: This single-center retrospective study of adult patients with drug-resistant epilepsy who underwent multitarget DBS was performed to demonstrate the feasibility and safety of this approach, and to present seizure outcomes. Patients in this cohort had epilepsy with features that were difficult to treat with DBS of the ANT or CM nucleus alone, including multifocal/multilobar, diffuse-onset, and/or posterior-onset seizures; or both generalized and focal seizures. RESULTS: Eight patients underwent DBS of 2-3 distinct thalamic/subthalamic nuclei. DBS was performed with 2 electrodes in each hemisphere. All leads in each patient were implanted with either frontal or parietal trajectories. There were no surgical complications. Among those with > 6 months of follow-up (n = 5; range 7-21 months), all patients were responders in terms of overall seizure frequency and/or convulsive seizure frequency (i.e., ≥ 50% reduction). Two patients had adverse stimulation effects, which resolved with further programming. CONCLUSIONS: Multitarget DBS is a procedurally feasible and safe treatment strategy to maximize outcomes in patients with complex epilepsy. The authors highlight their approach to inform future studies that are sufficiently powered to assess its efficacy.

Cathodal HD-tDCS and attention: A study on patients with intractable left lateral frontal lobe epilepsy.

OBJECTIVE: Defects in the attentional network in patients with epilepsy are influenced by factors such as the location of epileptic foci. Examining the impact of cathodal high-definition transcranial direct current stimulation (HD-tDCS) on attention components could provide insights into potential attention-related side effects of tDCS. This study aimed to investigate the effect of cathodal HD-tDCS on interictal epileptiform discharges (IEDs), auditory/visual (A/V) attention components, and reaction time (RT) in patients with intractable focal left lateral frontal lobe epilepsy (LFLE). METHODS: To control for variations in individual epilepsy syndrome, 12 adult participants diagnosed with drug-resistant left LFLE with focal cortical IEDs on C3 underwent repeated measurements at pretest, posttest, and follow-up steps. 4 × 1 ring electrodes (cathode on C3 and four anodes on F3, P3, T3, and Cz) delivered 2 mA DC for 20 min per session for 10 consecutive days. The integrated visual and auditory continuous performance test (IVA+) assessed the A/V attention components and RT. One-way repeated-measure ANOVA was used. RESULTS: The findings suggest a significant effect in reducing IEDs. The IVA+ results showed a significant improvement in auditory divided attention and visual selective and focused attention (p < 0.05). In the follow-up, these changes demonstrated lasting efficacy. A/V speed scales increased (p < 0.05), showing a significant decrease in reaction time. CONCLUSIONS: Cathodal HD-tDCS significantly reduced IEDs and improved the components of auditory divided attention, visual focused attention, and visual selective attention, with a reduction in patient reaction time. A significant lasting, side-effect-free positive effect was observed for up to one month after the intervention.

Epilepsia y desigualdad: descripción demográfica y análisis de la dificultad para el acceso a recursos avanzados en una población de un área de salud pequeña / Epilepsy and inequality: demographic description and analysis of the difficulty in accessing advanced resources in a population in a small health area

Introducción: La epilepsia es una enfermedad neurológica muy frecuente que implica una elevada morbimortalidad. La epilepsia farmacorresistente (EFR) supone un desafío terapéutico superior, incluso para expertos en la materia. A pesar de ello, el acceso a recursos avanzados para este tipo de pacientes continúa siendo dificultoso y desigual. El objetivo de este estudio es analizar la desigualdad en una población perteneciente a un hospital de primer nivel. Pacientes y métodos Se llevó a cabo un estudio transversal observacional analítico con pacientes epilépticos que acuden a consultas de neurología del área IX del Servicio Murciano de Salud. Se describen variables demográficas, clínicas, terapéuticas, pronósticas y de equidad, y se analizan diferencias significativas entre distintos subgrupos. Resultados En el estudio se incluyó a 68 pacientes con una media de edad de 42,93 años. El tipo de epilepsia principal fue la focal (64,7%), y los fármacos más usados fueron el levetiracetam (33,8%), el ácido valproico (27,9%) y la lamotrigina (22,1%). La EFR se dio en 18 pacientes (el 26,5% del total) y sólo cuatro se encontraban en seguimiento activo en una unidad de epilepsia, lo que implica que el 71% no accedía a un recurso necesario (advanced therapeutic gap). Conclusiones Este estudio demuestra que la desigualdad en la epilepsia continúa siendo un problema, especialmente en ciertas áreas geográficas, con una falta de acceso a atención avanzada en pacientes que más lo necesitan. La solución puede conseguirse aumentando recursos humanos y materiales que mejoren la atención global del paciente, reforzando así tanto los hospitales de referencia como las unidades de epilepsia. (AU)

INTRODUCTION: Epilepsy is a very common neurological disease with high morbidity and mortality. Drug-resistant epilepsy (DRE) poses a major therapeutic challenge, even for experts in the field. Despite this, access to advanced resources for this type of patient remains difficult and unequal. The aim of this study is to analyse inequality in a population belonging to a first level hospital. PATIENTS AND METHODS An analytical observational cross-sectional study was conducted on epileptic patients attending neurology consultations in Area IX of the Murcian Health Service. Demographic, clinical, therapeutic, prognostic and equity variables are described, and significant differences between different subgroups are analysed. RESULTS The study included 68 patients with a mean age of 42.93 years. Focal epilepsy was the main type (64.7%), and the most commonly used drugs were levetiracetam (33.8%), valproic acid (27.9%) and lamotrigine (22.1%). DRE occurred in 18 patients (26.5% of the total) and only four were under active follow-up in an epilepsy unit, meaning that 71% did not have access to a necessary resource (advanced therapeutic gap). CONCLUSIONS This study demonstrates that epilepsy inequality continues to be a problem, especially in certain geographical areas, with a lack of access to advanced care for patients who need it most. The solution can be achieved by increasing human and material resources to improve overall patient care, thus strengthening both referral hospitals and epilepsy units. (AU)

The effects of Vagal Nerve Stimulation on time perception in epilepsy patients.

In this study, it was aimed to investigate the effects of switching off stimulation on time perception in patients with drug-resistant epilepsy who underwent Vagal Nerve Stimulation (VNS). In accordance with the literature, a cognitive battery of tests for motor timing and perceptual timing was utilized. Computerized time perception tests; Paced Motor Timing Test, Duration Discrimination Test, Temporal Reproduction Test, and Time Estimation Test were administered to the patients while VNS was on and off. A total of 14 patients who met the inclusion criteria of 23 VNS patients followed in the Epilepsy Outpatient Clinic were included in the study. In the Temporal Reproduction Test, for time durations of 1000 ms (ms), 2000 ms, 3000 ms, 4000 ms, and 5000 ms the comparison of reported time values between VNS on and VNS off yielded respective p values; p = 0.73, p = 0.03, p = 0.176, p = 0.418, p = 0,873. The reported time is thus significantly shorter only for 2000 ms when the VNS was on. Positive effect of VNS on attention, alertness and focusing are expected to cause acceleration of the internal clock resulting in perceiving time running slower than actual. In our study, it was concluded that the internal clock runs faster when the VNS is on, and time is perceived as running slower than it actually is. This result can also be accepted as an indirect indicator of increased attention in the period when VNS is on.

Entropy in scalp EEG can be used as a preimplantation marker for VNS efficacy.

Vagus nerve stimulation (VNS) is a therapeutic option in drug-resistant epilepsy. VNS leads to ≥ 50% seizure reduction in 50 to 60% of patients, termed "responders". The remaining 40 to 50% of patients, "non-responders", exhibit seizure reduction < 50%. Our work aims to differentiate between these two patient groups in preimplantation EEG analysis by employing several Entropy methods. We identified 59 drug-resistant epilepsy patients treated with VNS. We established their response to VNS in terms of responders and non-responders. A preimplantation EEG with eyes open/closed, photic stimulation, and hyperventilation was found for each patient. The EEG was segmented into eight time intervals within four standard frequency bands. In all, 32 EEG segments were obtained. Seven Entropy methods were calculated for all segments. Subsequently, VNS responders and non-responders were compared using individual Entropy methods. VNS responders and non-responders differed significantly in all Entropy methods except Approximate Entropy. Spectral Entropy revealed the highest number of EEG segments differentiating between responders and non-responders. The most useful frequency band distinguishing responders and non-responders was the alpha frequency, and the most helpful time interval was hyperventilation and rest 4 (the end of EEG recording).

Benefits of vagus nerve stimulation on psychomotor functions in patients with severe drug-resistant epilepsy.

PURPOSE: Patients with severe drug-resistant epilepsy (DRE) experience psychomotor disorders. Our study aimed to assess the psychomotor outcomes after vagus nerve stimulation (VNS) in this population. METHODS: We prospectively evaluated psychomotor function in 17 adult patients with severe DRE who were referred for VNS. Psychomotor functions were examined, in the preoperative period and at 18 months post-surgery, by a psychomotor therapist using a full set of the following specific tests: the Rey-Osterrieth complex figure (ROCF) test, the Zazzo's cancelation task (ZCT), the Piaget-Head test and the paired images test. RESULTS: At 18 months post-VNS surgery, the Piaget-head scores increased by 3 points (p = 0.008) compared to baseline. Performances were also improved for ROCF test both in copy (+2.4 points, p = 0.001) and recall (+2.0 points, p = 0.008) tasks and for the paired images test (accuracy index: +28.6 %, p = 0.03). Regarding the ZCT findings, the efficiency index increased in both single (+16 %, p = 0.005) and dual (+17.1 %, p < 0.001) tasks. QoL improved in 88.2 % of patients. CONCLUSIONS: Patients with severe DRE treated with VNS experienced improved performance in terms of global psychomotor functions. Perceptual organization, visuospatial memory, laterality awareness, sustained attention, concentration, visual scanning, and inhibition were significantly improved.

Stimulation of the pulvinar nucleus of the thalamus in epilepsy: A systematic review and individual patient data (IPD) analysis.

Emerging neuromodulatory treatments, such as deep brain stimulation (DBS) and responsive neurostimulation (RNS), have shown promise in reducing drug-resistant seizures. While centromedian thalamic nucleus and anterior thalamic nucleus stimulation have been effective in certain types of seizures, limited research has explored pulvinar nucleus stimulation for epilepsy. To address this gap, we conducted a systematic review and individual patient data analysis. Of 78 resultant articles, 5 studies with transient stimulation and chronic stimulation of the pulvinar nucleus were included. Of the 20 patients reviewed, 65% of patients had temporal lobe seizures, while 20% had temporooccipital/occipital lobe seizures. Transient stimulation studies via stereoelectroencephalography (SEEG) showed pulvinar evoked potential response rates of 80% in the mesial temporal region, 76% in the temporal neocortex, and 67% in the TP junction. Another study reported clinically less severe seizures in 62.5% of patients with pulvinar stimulation. In chronic stimulation studies, 80% of patients responded to RNS or DBS, and 2 of 4 patients experienced > 90% seizure reduction. The pulvinar nucleus of the thalamus emerges as a potential target for chronic stimulation in drug-resistant epilepsy. However, knowledge regarding pulvinar connectivity and chronic stimulation remains limited. Further research should investigate specific subregions of the pulvinar for epilepsy treatment. Understanding the role of pulvinar stimulation and its cortical connectivity will advance therapeutic interventions for epilepsy patients.

Patient family engagement and partnership: Pilot survey results in assessing behavior, communication, and quality of life in children with Lennox-Gastaut syndrome and other drug-resistant epilepsy.

OBJECTIVES: Lennox-Gastaut Syndrome (LGS) and other drug-resistant epilepsy (DRE) can impact behavior, communication, and quality of life (QoL). In collaboration with community engagement efforts with the Lennox-Gastaut Syndrome Foundation (LGSF), we aimed to gain an initial snapshot of patient and family perspectives and experiences with evaluation of behavior, communication, and QoL. METHODS: A cross-sectional survey was conducted to collect self-reported information from caregivers of children with LGS and other DRE regarding their perspectives and experiences with healthcare providers' evaluation of behavior, communication, and QoL. The survey tool was developed by the study investigators in partnership with the LGS Foundation and had diffused to caregivers online by epilepsy advocacy groups including the Pediatric Epilepsy Surgery Alliance (PESA). Responses were analyzed. Descriptive statistics were calculated. The survey asked for caregiver perspectives and assessed which instruments the caregivers had previously been given for measuring these domains. RESULTS: Responses from 245 caregivers were included, with 132 (54%) caregivers of an individual with LGS and 113 (46%) caregivers of an individual with non-LGS related DRE. Respondents reported that 66% of their loved ones had undergone epilepsy-related surgery. Over 90% agreed that measuring behavior, communication, and QoL was important, but fewer than half felt that their healthcare providers evaluated these domains well. LGS caregivers largely shared non-LGS caregivers' perspectives; however, they reported more frequently that communication was not evaluated enough. Barriers to measuring these domains included a lack of good surveys (developmentally appropriate and specific to the type of epilepsy) or not receiving any survey instruments for these domains during clinic appointments. Caregivers play a crucial role for individuals with DRE, and their input is essential in identifying challenges and needs. Caregivers believe that measuring behavior, communication, and quality of life is important, and most of them feel that their loved ones are not adequately evaluated during their healthcare encounters. There is a need for appropriately scaled survey instruments to measure areas of importance for patients and caregivers, as well as incorporation of these outcomes in the healthcare discussion.