Resistant Focal Epilepsy Research Articles

Neuropsychological characteristics of drug resistant epilepsy patients with and without comorbid functional seizures

IntroductionNeuropsychological testing is a mandatory component in the evaluation of drug resistant epilepsy. The results of testing may assist with both the localization of an epilepsy as well as assessment of surgical risk. Previous studies have demonstrated differences in the neuropsychological performance of patients with epilepsy and functional seizures. We hypothesized that comorbid functional seizures could potentially influence neuropsychological test performance. Therefore, we evaluated whether there is a difference in the neuropsychological test results between drug resistant epilepsy patients with and without comorbid functional seizures. MethodNeuropsychological test results were compared between 25 patients with drug resistant focal epilepsy and 25 patients that also had documented functional seizures. Univariate analyses and multiple logistic regression models were used to both assess performance differences between the groups and to assess whether test results could be used to accurately identify which patients had comorbid functional seizures. ResultsEpilepsy patients with comorbid functional seizures performed significantly worse on the FAS Verbal Fluency Test compared to ES patients (p = 0.047). Digit Span Backwards (p = 0.10), Digit Span Forwards (p = 0.14) and Working Memory Index (p = 0.10) tended to be lower in the epilepsy and functional seizures group but was not statistically significant. A multiple logistic regression model using the results of four neuropsychological tests was able to identify patients with comorbid functional seizures with 83.33% accuracy. ConclusionsThere are appeared to be some differences in the neuropsychological performance among drug resistant epilepsy patients based on whether they have comorbid functional seizures. These findings may have relevant implications for the interpretation of neuropsychological test results.

Effective connectivity relates seizure outcome to electrode placement in responsive neurostimulation.

Responsive neurostimulation is a closed-loop neuromodulation therapy for drug resistant focal epilepsy. Responsive neurostimulation electrodes are placed near ictal onset zones so as to enable detection of epileptiform activity and deliver electrical stimulation. There is no standard approach for determining the optimal placement of responsive neurostimulation electrodes. Clinicians make this determination based on presurgical tests, such as MRI, EEG, magnetoencephalography, ictal single-photon emission computed tomography and intracranial EEG. Currently functional connectivity measures are not being used in determining the placement of responsive neurostimulation electrodes. Cortico-cortical evoked potentials are a measure of effective functional connectivity. Cortico-cortical evoked potentials are generated by direct single-pulse electrical stimulation and can be used to investigate cortico-cortical connections in vivo. We hypothesized that the presence of high amplitude cortico-cortical evoked potentials, recorded during intracranial EEG monitoring, near the eventual responsive neurostimulation contact sites is predictive of better outcomes from its therapy. We retrospectively reviewed 12 patients in whom cortico-cortical evoked potentials were obtained during stereoelectroencephalography evaluation and subsequently underwent responsive neurostimulation therapy. We studied the relationship between cortico-cortical evoked potentials, the eventual responsive neurostimulation electrode locations and seizure reduction. Directional connectivity indicated by cortico-cortical evoked potentials can categorize stereoelectroencephalography electrodes as either receiver nodes/in-degree (an area of greater inward connectivity) or projection nodes/out-degree (greater outward connectivity). The follow-up period for seizure reduction ranged from 1.3-4.8 years (median 2.7) after responsive neurostimulation therapy started. Stereoelectroencephalography electrodes closest to the eventual responsive neurostimulation contact site tended to show larger in-degree cortico-cortical evoked potentials, especially for the early latency cortico-cortical evoked potentials period (10-60 ms period) in six out of 12 patients. Stereoelectroencephalography electrodes closest to the responsive neurostimulation contacts (≤5 mm) also had greater significant out-degree in the early cortico-cortical evoked potentials latency period than those further away (≥10 mm) (P < 0.05). Additionally, significant correlation was noted between in-degree cortico-cortical evoked potentials and greater seizure reduction with responsive neurostimulation therapy at its most effective period (P < 0.05). These findings suggest that functional connectivity determined by cortico-cortical evoked potentials may provide additional information that could help guide the optimal placement of responsive neurostimulation electrodes.

Clinical outcomes following responsive neurostimulation implantation: a single center experience.

Responsive neurostimulation (RNS) is an implantable device for persons with medically refractory focal-onset epilepsy. We report a single-center experience for RNS outcomes with special focus on stereoelectroencephalography (sEEG) for seizure onset localization. We performed retrospective review of patients with drug resistant focal epilepsy implanted with the RNS System for a minimum of six months between July 2014 and July 2019. Records were reviewed for demographic data, epilepsy duration, seizure frequency, number of prior antiepileptic drugs (AEDs), number of AEDs at RNS System implantation, prior epilepsy surgery or device use, previous seizure localization with sEEG, and RNS system information. Clinical response was defined as a 50% reduction in seizures. Differing response rates were calculated using Fisher Exact test. 30 patients met inclusion criteria. Seventeen (57%) underwent previous sEEG. Average clinical follow up was 3.0 years. Overall response rate was 70%. Median seizure reduction was 74.5%. Response rate was 82.3% for patients with sEEG compared to 53.8% without (p = 0.08); 37.5% for prior epilepsy surgery compared to 81.8% without (p = 0.02); 70% for mesial temporal onset; 50% for previous vagal nerve stimulator compared to 77.3% without (p = 0.13). Our response rates match or surpass outcome metrics of previous studies. Although limited by small study size, subpopulation analyses show positive response rates in patients with previous sEEG versus no sEEG and in temporal versus extratemporal pathology. Additional research is needed to evaluate efficacy of RNS in patients with previous epilepsy surgery, and utility of sEEG in this population.

Gabapentin monotherapy for epilepsy: A review.

Epilepsy is one of the most common chronic neurological disorders, affecting more than 50 million people globally. In this review we summarised the evidence from randomised controlled trials of gabapentin used as monotherapy for the treatment of focal epilepsy, both newly diagnosed and drug-resistant, with or without secondary generalisation. To assess the effects of gabapentin monotherapy for people with epileptic focal seizures with and without secondary generalisation. We searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid, 1946 to 24 February 2020) on 25 February 2020. CRS Web includes randomised or quasi-randomised controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, the Cochrane Central Register of Controlled Trials (CENTRA), and the specialised registers of Cochrane Review Groups including the Cochrane Epilepsy Group. We also searched several Russian databases, reference lists of relevant studies, ongoing trials registers, conference proceedings, and we contacted trial authors. We found five randomised controlled trials (3167 participants) comparing gabapentin to other antiepileptic drugs (AEDs) and differing doses of gabapentin as monotherapy for newly diagnosed focal epilepsy and drug- resistant focal epilepsy with or without secondary generalisation. Two review authors independently applied the inclusion criteria, assessed trial quality, risk of bias, and extracted data. We used the GRADE approach to assess the certainty of evidence and present seven patient-important outcomes in the "Summary of findings" tables. The quality of evidence was very low to moderate due to poor reporting quality, poor trial design, and other risks of bias, such as selective presentation of findings and potential heavy industry input. Better quality research may change our certainty in the effect estimates. None of the included trials reported on the number of people with 50% or greater reduction in seizures and time to withdrawal (retention time) in an extractable way. Gabapentin-treated participants were more likely to withdraw from treatment for any cause (285/539) than those treated with lamotrigine, oxcarbazepine, or topiramate pooled together (695/1317) (RR 1.13, 95% CI 1.02 to 1.25; 3 studies, 1856 participants; moderate-certainty evidence), but not carbamazepine. Fewer people treated with gabapentin withdrew from treatment owing to adverse events (190/525) than those treated with carbamazepine, oxcarbazepine, or topiramate (479/1238), (RR 0.79, 95% CI 0.69 to 0.91; 1763 participants, 3 studies; moderate-certainty evidence), but not lamotrigine.CONCLUSIONGabapentin as monotherapy probably controlled seizures no better and no worse than comparator AEDs (lamotrigine, carbamazepine, oxcarbazepine, and topiramate). Compared to carbamazepine, gabapentin was probably better in retaining people in studies and preventing withdrawals due to adverse events. The most common side effects associated with gabapentin were ataxia (poor co-ordination and unsteady gait), dizziness, fatigue, and drowsiness.

When in doubt, return to fundamentals (seizure semiology).

This case of drug resistant focal epilepsy highlights several invaluable teaching points. Hypotheses grounded in seizure semiology provide the best framework to ensure accurate interpretation of diagnostic testing. Without a hypothesis, information gathered from tests can be difficult to linearly piece together and can lead to poor patient outcomes. The case also provides a real-world conundrum of discordant test results that were ultimately rectified by re-visiting the initial hypothesis and cross-testing. Perinatal stroke continues to be a common etiology of drug resistant epilepsy. Patients can achieve seizure freedom and good quality of life with appropriate workup and in appropriate cases, surgery.

Safety profile of subdural and depth electrode implantations in invasive EEG exploration of drug-resistant focal epilepsy

PurposeTo analyze the safety profile of subdural and depth electrode implantation in a large monocentric cohort of patients of all ages undergoing intracranial EEG exploration because of drug resistant focal epilepsy diagnosed and implanted by a constant team of epileptologists and neurosurgeons. MethodsWe retrospectively analyzed data from 452 implantations in 420 patients undergoing invasive presurgical evaluation at the Freiburg Epilepsy Center from 1999 to 2019 (n = 160 subdural electrodes, n = 156 depth electrodes and n = 136 combination of both approaches). Complications were classified as hemorrhage with or without clinical manifestations, infection-associated and other complications. Furthermore, possible risk factors (age, duration of invasive monitoring, number of electrode contacts used) and changes in complication rates during the study period were analyzed. ResultsThe most frequent complications in both implantation groups were hemorrhages. Subdural electrode explorations caused significantly more symptomatic hemorrhages and required more operative interventions (SDE 9.9%, DE 0.3%, p < 0.05). Hemorrhage risk was higher for grids with 64 contacts than for smaller grids (p < 0.05). The infection rate was very low (0,2%). A transient neurological deficit occurred in 8.8% of all implantations and persisted for at least 3 months in 1.3%. Transient, but not persistent neurological deficits were more common in patients with implanted subdural electrodes than in the depth electrode group. ConclusionThe use of subdural electrodes was associated with a higher risk of hemorrhage and transient neurological symptoms. However persistent deficits were rare with either approach, demonstrating that intracranial investigations using either subdural electrodes or depth electrodes carry acceptable risks in patients with drug-resistant focal epilepsy.

Yield of Stereotactic Electroencephalography for evaluation of Drug Resistant Focal Epilepsy: Single-Center Experience. (P2-1.009)

<h3>Objective:</h3> This study aims to report our initial experience with the effectiveness, safety, and outcomes following the adoption of stereotactic electroencephalography (sEEG) technique for surgical evaluation of patients with drug-resistant focal epilepsy. <h3>Background:</h3> A growing number of North American epilepsy centers are looking to offer intracranial evaluation for epilepsy surgery. This invasive procedure can result in symptomatic and asymptomatic hemorrhage, neurologic deficits, electrode malfunction, and failure to complete investigation. <h3>Design/Methods:</h3> This was a retrospective, single-center, observational study which reviewed every patient undergoing Phase II monitoring at our center from 2019 to 2022. At our center, 21 patients underwent sEEG monitoring, and 225 sEEG electrodes were implanted. Variables collected included demographic data, Phase I data, type of coverage (unilateral vs. bilateral), length of in-hospital stay, rate of complications, and seizure-free outcome using the ENGEL surgical outcome scale. <h3>Results:</h3> Among the 21 patients who were implanted, 7 (33.3%) were completely asymptomatic following the procedure. The most common complication was a headache in 9 patients (42.8%), followed by asymptomatic hemorrhage in 3 patients (14.2%). Only one patient (4.76%) experienced symptomatic hemorrhage but required no surgical intervention. Other less common complications included vasogenic edema at the surgical site, perceived cognitive slowing, visual hallucinations, and dislodged electrodes requiring revision. One patient had a complete resolution of seizures following sEEG implantation. The average duration of hospitalization was eight days, with a trend towards more extended hospitalization in patients experiencing procedural complications. SEEG method confirmed the epileptogenic zone in 15 patients (68%). Of these, 11 patients (50%) underwent surgical resection or ablation, and four (18%) received neuromodulation. 72% (n=8/11) achieved seizure freedom (i.e., ENGEL-I outcome). <h3>Conclusions:</h3> New surgical epilepsy centers can safely adopt sEEG while anticipating a relatively low rate of debilitating complications from the procedure. The rate of complications documented in our cohort is comparable to other established surgical epilepsy programs. <b>Disclosure:</b> Dr. Luan has nothing to disclose. Dr. Singh has nothing to disclose.

Safe Use of Cenobamate in Super Refractory Status Epilepticus: A Case Series.

Cenobamate is an effective new adjunctive antiseizure medication (ASM) for treatment resistant focal epilepsy. It has broad spectrum anticonvulsant activity and may be a useful medication for super refractory status epilepticus (SRSE), but has not yet been studied in generalized seizures or an inpatient setting. Here we describe 2 SRSE cases where cenobamate was added safely to other treatments. It was uptitrated slowly to reduce the risk of hypersensitivity reactions which have been observed previously with rapid increasing dosages. Both patients achieved seizure control and liberation from intensive care. They have remained seizure free with continued treatment and have not experienced any side effects attributable to cenobamate. Cenobamate warrants further examination in patients with refractory status epilepticus.

Unmet needs and perspectives in management of drug resistant focal epilepsy: An Italian study

This study aimed to evaluate the consensus level between a representative group of Italian neurologists and people with Drug-Resistant Epilepsy (DRE) regarding a series of statements about different aspects involved in the management of epilepsy to identify the unmet needs of the People with Epilepsy (PwE) and the future perspectives for the management of this disease.This observational study was conducted using a classic Delphi technique. A 19-statement questionnaire was administered anonymously through an online platform to a panel of expert clinicians and a panel of PwE, analyzing three main topics of interest: drug resistance, access to care, and PwE’s experience.The consensus was achieved on 8 of the 19 statements administered to the panel of medical experts and on 4 of the 14 submitted to the panel of PwE, particularly on the definition of DRE and its consequences on treatment, Quality of Life (QoL), and autonomy of PwE. Most of the items, however, did not reach a consensus and highlighted the lack of a shared univocal view on some topics, such as accessibility to care throughout the country and the role of emerging tools such as telemedicine, narrative medicine, and digital devices. In many cases, the two panels expressed different views on the statements.The results outlined many fields of possible intervention, such as the need for educational initiatives targeted at physicians and PwE – for example, regarding telemedicine, digital devices, and narrative medicine – as well as the spread of better knowledge about epilepsy among the general population, in order to reduce epilepsy stigma. Institutions, moreover, could take a cue from this survey to develop facilities aimed at enhancing PwE’s autonomy and promoting more equal access to care throughout the country.

18F-FDG-PET hypometabolism as a predictor of favourable outcome in epilepsy surgery: protocol for a systematic review and meta-analysis

IntroductionA substantial proportion of patients who undergo surgery for drug resistant focal epilepsy do not become seizure free. While some factors, such as the detection of hippocampal sclerosis or a...

Spatiotemporal patterns of sleep spindle activity in human anterior thalamus and cortex

Sleep spindles (8 - 16 Hz) are transient electrophysiological events during non-rapid eye movement sleep. While sleep spindles are routinely observed in the cortex using scalp electroencephalography (EEG), recordings of their thalamic counterparts have not been widely studied in humans. Based on a few existing studies, it has been hypothesized that spindles occur as largely local phenomena. We investigated intra-thalamic and thalamocortical spindle co-occurrence, which may underlie thalamocortical communication. We obtained scalp EEG and thalamic recordings from 7 patients that received bilateral deep brain stimulation (DBS) electrodes to the anterior thalamus for the treatment of drug resistant focal epilepsy. Spindles were categorized into subtypes based on their main frequency (i.e., slow (10±2 Hz) or fast (14±2 Hz)) and their level of thalamic involvement (spanning one channel, or spreading uni- or bilaterally within the thalamus). For the first time, we contrasted observed spindle patterns with permuted data to estimate random spindle co-occurrence. We found that multichannel spindle patterns were systematically coordinated at the thalamic and thalamocortical level. Importantly, distinct topographical patterns of thalamocortical spindle overlap were associated with slow and fast subtypes of spindles. These observations provide further evidence for coordinated spindle activity in thalamocortical networks.

Brain network analysis of interictal epileptiform discharges from ECoG to identify epileptogenic zone in pediatric patients with epilepsy and focal cortical dysplasia type II: A retrospective study.

ObjectiveFor patients with drug–resistant focal epilepsy, intracranial monitoring remains the gold standard for surgical intervention. Focal cortical dysplasia (FCD) is the most common cause of pharmacoresistant focal epilepsy in pediatric patients who usually develop seizures in early childhood. Timely removal of the epileptogenic zone (EZ) is necessary to achieve lasting seizure freedom and favorable developmental and cognitive outcomes to improve the quality of life. We applied brain network analysis to investigate potential biomarkers for the diagnosis of EZ that will aid in the resection for pediatric focal epilepsy patients with FCD type II.MethodsTen pediatric patients with focal epilepsy diagnosed as FCD type II and that had a follow–up after resection surgery (Engel class I [n = 9] and Engel class II [n = 1]) were retrospectively included. Time–frequency analysis of phase transfer entropy, graph theory analysis, and power spectrum compensation were combined to calculate brain network parameters based on interictal epileptiform discharges from ECoG.ResultsClustering coefficient, local efficiency, node out–degree, and node out–strength with higher values are the most reliable biomarkers for the delineation of EZ, and the differences between EZ and margin zone (MZ), and EZ and normal zone (NZ) were significant (p < 0.05; Mann–Whitney U-test, two–tailed). In particular, the difference between MZ and NZ was significant for patients with frontal FCD (MZ > NZ; p < 0.05) but was not significant for patients with extra–frontal FCD.ConclusionsBrain network analysis, based on the combination of time–frequency analysis of phase transfer entropy, graph theory analysis, and power spectrum compensation, can aid in the diagnosis of EZ for pediatric focal epilepsy patients with FCD type II.

Stereoelectroencephalography in pre-surgical evaluation of patients with drug-resistant focal epilepsy

Background. Surgical treatment has shown its effectiveness for patients with drug-resistant focal epilepsy: resection or disconnection of the epileptogenic zone leads to relief from epileptic seizures. However, in some cases non-invasive examination may not be sufficient for localization of epileptogenic zone boundaries. Hence, such patients undergo invasive encephalography (EEG) to clarify zone location accounting for seizure development. Objective: to evaluate effectiveness of invasive stereo-EEG in the diagnostics of drug-resistant focal epilepsy. Material and methods. The data collected from 65 patients who underwent stereo-EEG during pre-surgical examination for pharmacoresistant focal epilepsy were retrospectively analyzed within the period of 2016–2019. According to the results of magnetic resonance imaging (MRI), 34 patients had MRI-negative forms of epilepsy, and 31 patients had MRI-positive forms with multiple structural changes in the brain or discrepancies between electro-clinical data and MRI findings. Results. Based on the information obtained by stereo-EEG, 49 patients (75.4%) underwent resection operations. In 16 (24.6%) cases surgical treatment was not carried out due to detected bilateral epileptogenic zone, the lack of convincing data on its location or detecting an epileptogenic zone in a functionally significant region. In 44 operated patients, the follow-up comprised more than 12 months; it was not possible to contact 5 patients. Engel outcomes: I class – 27 (61.3%) patients, II class – 7 (15.9%), III class – 4 (9.1%), IV class – 6 (13.6%). As a result of stereo-EEG, hemorrhagic complications developed in 2 (3.1%) patients: epidural hematoma in 1 case (1.5%), and intracerebral hematoma in 1 case (1.5%). No persistent neurological deficit was noted during continued monitoring. Conclusion. The method of stereo-EEG is effective for determining the epileptogenic zone boundaries in patients with drug- resistant focal epilepsy.

Relation of Brain Perfusion Patterns to Sudden Unexpected Death Risk Stratification: A Study in Drug Resistant Focal Epilepsy.

To explore the role of the interictal and ictal SPECT to identity functional neuroimaging biomarkers for SUDEP risk stratification in patients with drug-resistant focal epilepsy (DRFE). Twenty-nine interictal-ictal Single photon emission computed tomography (SPECT) scans were obtained from nine DRFE patients. A methodology for the relative quantification of cerebral blood flow of 74 cortical and sub-cortical structures was employed. The optimal number of clusters (K) was estimated using a modified v-fold cross-validation for the use of K means algorithm. The two regions of interest (ROIs) that represent the hypoperfused and hyperperfused areas were identified. To select the structures related to the SUDEP-7 inventory score, a data mining method that computes an automatic feature selection was used. During the interictal and ictal state, the hyperperfused ROIs in the largest part of patients were the bilateral rectus gyrus, putamen as well as globus pallidus ipsilateral to the seizure onset zone. The hypoperfused ROIs included the red nucleus, substantia nigra, medulla, and entorhinal area. The findings indicated that the nearly invariability in the perfusion pattern during the interictal to ictal transition observed in the ipsi-lateral putamen F = 12.60, p = 0.03, entorhinal area F = 25.80, p = 0.01, and temporal middle gyrus F = 12.60, p = 0.03 is a potential biomarker of SUDEP risk. The results presented in this paper allowed identifying hypo- and hyperperfused brain regions during the ictal and interictal state potentially related to SUDEP risk stratification.

816 Traveling Waves Reveal a Dynamic Source of Human Focal Seizures and Interictal Spikes

INTRODUCTION: Treatment of patients with drug resistant focal epilepsy relies upon accurate seizure localization. Ictal activity captured in intracranial EEG (iEEG) has traditionally been interpreted to suggest that the underlying cortex is actively seizing. On the other hand, an emerging hypothesis suggests that seizures may in fact emerge from focal regions, which emit discharges that travel over the surface of the cortex as traveling waves. METHODS: 20 patients underwent placement of subdural electrodes for invasive monitoring at the National Instutes of Health, underwent surgical resection for epilepsy, and had at least 1 year of follow-up. Outcomes were measured by the Engel scale. In these patients, we measured the time delay in discharge receipt at adjacent electrodes to compute the location of the seizure source. This algorithm, known as multilateration, has been used for signal source localization with sparsely-spaced sensors for over a century in geophysics, radar, and acoustics, but has not been used in epilepsy until the present. RESULTS: In patients with good outcome, but not in patients with poor outcome, the seizure source tends to localize to the resection territory. The source is a focal, dynamic entity that moves and evolves over the time course of a seizure. Our approach also successfully localizes interictal spikes. We find that interictal spikes emerge from multiple distinct foci in each patient. Seizures either arise from or travel to interictal spike generators. CONCLUSIONS: The seizure source appears to be more focal than has traditionally been conceptualized. This focal source may be localized by measuring the time difference of discharge receipt in intracranial electrodes. Algorithmic source localization, as performed here, may guide pre-surgical planning for drug-resistant epilepsy and may improve outcomes.

Resective, Ablative and Radiosurgical Interventions for Drug Resistant Mesial Temporal Lobe Epilepsy: A Systematic Review and Meta-Analysis of Outcomes

Objectives: One-third of individuals with focal epilepsy do not achieve seizure freedom despite best medical therapy. Mesial temporal lobe epilepsy (MTLE) is the most common form of drug resistant focal epilepsy. Surgery may lead to long-term seizure remission if the epileptogenic zone can be defined and safely removed or disconnected. We compare published outcomes following open surgical techniques, radiosurgery (SRS), laser interstitial thermal therapy (LITT) and radiofrequency ablation (RF-TC).Methods: PRISMA systematic review was performed through structured searches of PubMed, Embase and Cochrane databases. Inclusion criteria encompassed studies of MTLE reporting seizure-free outcomes in ≥10 patients with ≥12 months follow-up. Due to variability in open surgical approaches, only comparative studies were included to minimize the risk of bias. Random effects meta-analysis was performed to calculate effects sizes and a pooled estimate of the probability of seizure freedom per person-year. A mixed effects linear regression model was performed to compare effect sizes between interventions.Results: From 1,801 screened articles, 41 articles were included in the quantitative analysis. Open surgery included anterior temporal lobe resection as well as transcortical and trans-sylvian selective amygdalohippocampectomy. The pooled seizure-free rate per person-year was 0.72 (95% CI 0.66–0.79) with trans-sylvian selective amygdalohippocampectomy, 0.59 (95% CI 0.53–0.65) with LITT, 0.70 (95% CI 0.64–0.77) with anterior temporal lobe resection, 0.60 (95% CI 0.49–0.73) with transcortical selective amygdalohippocampectomy, 0.38 (95% CI 0.14–1.00) with RF-TC and 0.50 (95% CI 0.34–0.73) with SRS. Follow up duration and study sizes were limited with LITT and RF-TC. A mixed-effects linear regression model suggests significant differences between interventions, with LITT, ATLR and SAH demonstrating the largest effects estimates and RF-TC the lowest.Conclusions: Overall, novel “minimally invasive” approaches are still comparatively less efficacious than open surgery. LITT shows promising seizure effectiveness, however follow-up durations are shorter for minimally invasive approaches so the durability of the outcomes cannot yet be assessed. Secondary outcome measures such as Neurological complications, neuropsychological outcome and interventional morbidity are poorly reported but are important considerations when deciding on first-line treatments.

A.6 Vagus Nerve Stimulation in patients with therapy resistant generalized epilepsy

Background: For patients with generalized epilepsy who do not respond to anti-seizure medications, the therapeutic options are limited. Vagus nerve stimulation (VNS) is a treatment mainly approved for therapy resistant focal epilepsy. There is limited information on the use of VNS on generalized epilepsies, including Lennox Gastaut Syndrome(LGS) and genetic generalized epilepsy(GGE). Methods: We identified patients with a diagnosis of Lennox-Gastaut Syndrome or Genetic Generalized Epilepsy, who underwent VNS implantation, between1997 and July 2018. Results: A total of 46 patients were included in this study with a history of therapy resistant generalized epilepsy. The mean age at implantation was 24 years(IQR= 17.8-31 years) and 50%(n=23) were female. The most common etiologies were GGE in 37%(n=17) and LGS in 63%(n=29). Median follow-up since VNS implantation was 63 months(IQR:31-112.8months). 41.7%(n=12) of the LGS group became responders, and 64.7%(n=11) in the GGE group. The best response in seizure reduction was seen in generalized tonic-clonic seizures. There was a reduction of seizure-related hospital admissions from 89.7%(N=26) pre-implantation, to 41.4%(N=12) post-implantation (p&lt;0.0001). The frequency of side effects due to the stimulation was similar in both groups(62.1% in LGS and 61.1% in GGE). Conclusions: VNS is an effective treatment in patients with therapy resistant generalized epilepsy, especially GGE.

Clinico-radiological Profile in Children with Drug Resistant Focal Epilepsy

Abstract Objective To assess the clinical and neuroimaging findings of pediatric patients with drug-resistant focal epilepsy, comparing conventional MR technique to the "essential 6” protocol. Methods An observational study of 18 children with drug resistant focal seizures identified both clinically and/or by EEG findings. Available clinical data as well as EEG and MRI data in patients’ files at the pediatric neurology clinic at Ain Shams University was retrospectively evaluated and documented. All patients then underwent a new MRI study using a novel MR technique - the essential six sequence protocol to determine whether the latter technique was superior to standard at picking subtle anatomical abnormalities in children with drug resistant focal epilepsy. Results 18 children (10 males and 8 females) with a mean age of 8.49 ±3.20 years were enrolled. The mean age at onset of epilepsy was 3.24 ±2.79 years. 15 out of 18 patients (83%) had an abnormal EEG. The mean Chalfont Seizure Severity Scale Score was 63.71 ±34.35. There was no statistically significant difference in Chalfont seizure severity scores between patients with normal vs abnormal EEG, and with normal vs abnormal MRI. The novel MRI technique could pick on an abnormality in 12 out of the 18 cases (66%), which is six times more than what could be identified using the baseline/conventional MRI technique. Conclusions The essential 6 MRI protocol is superior to conventional MRI protocols at picking structural abnormalities in patients with drug resistant focal epilepsy.

Unilateral Blinking: Insights from Stereo-EEG and Tractography

To study the neuroanatomical correlate of involuntary unilateral blinking in humans, using the example of patients with focal epilepsy. Patients with drug resistant focal epilepsy undergoing presurgical evaluation with stereotactically implanted EEG-electrodes (sEEG) were recruited from the local epilepsy monitoring unit. Only patients showing ictal unilateral blinking or unilateral blinking elicited by direct electrical stimulation were included (n = 16). MRI and CT data were used for visualization of the electrode positions. In two patients, probabilistic tractography with seeding from the respective electrodes was additionally performed. Three main findings were made: (1) involuntary unilateral blinking was associated with activation of the anterior temporal region, (2) tractography showed widespread projections to the ipsilateral frontal, pericentral, occipital, limbic and cerebellar regions and (3) blinking was observed predominantly in female patients with temporal lobe epilepsies. Unilateral blinking was found to be associated with an ipsilateral activation of the anterior temporal region. We suggest that the identified network is not part of the primary blinking control but might have modulating influence on ipsilateral blinking by integrating contextual information.

Acute effects of spaced cathodal transcranial direct current stimulation in drug resistant focal epilepsies

ObjectiveTo evaluate the safety and temporal dynamic of the antiepileptic effect of spaced transcranial direct current stimulation (tDCS) in different focal epilepsies. MethodsCathodal tDCS with individual electrode placement was performed in 15 adults with drug resistant focal epilepsy. An amplitude of 2 mA was applied twice for 9 minutes, with an interstimulation interval of 20 minutes. Tolerability was assessed via the Comfort Rating Questionnaire and the frequency of interictal epileptiform discharges (IEDs) was sequentially compared between the 24 hours before and after tDCS. ResultsTDCS led to a significant reduction in the total number of IEDs/24 h by up to 68% (mean ± SD: −30.4 ± 21.1%, p = 0.001) as well as in seizure frequency (p = 0.041). The maximum IED reduction was observed between the 3rd and 21st hour after stimulation. Favorable clinical response was associated with structural etiology and clearly circumscribed epileptogenic foci but did not differ between frontal and temporal epilepsies. Overall, the tDCS treatment was well tolerated and did not lead to severe adverse events. ConclusionsThe spaced stimulation approach proved to be safe and well-tolerated in patients with drug-resistant unifocal epilepsies, leading to sustained IED and seizure frequency reduction. SignificanceSpaced tDCS induces mediate antiepileptic effects with promising therapeutic potential.