Resistant Epilepsy Research Articles

Glycemic biomarkers in children with drug-resistant epilepsy on various types of ketogenic diet therapies: A cross-sectional study.

This study was undertaken to determine the hemoglobin A1c (HbA1c) and modified glucose-ketone index (mGKI) in children on different types of ketogenic diet (KD) for treatment of drug-resistant epilepsy, with attempts to evaluate their relationships with components of diet regime and other biomarkers. We conducted a cross-sectional study in children with drug resistant epilepsy aged between 6months and 18years, who were on various types of KD therapies without any change in regime for at least 3months. Parental interview, review of medical records, and a single measurement for blood ketone, HbA1c, and plasma carnitine were performed. mGKI was the ratio of an average plasma glucose estimated from HbA1c to blood β-hydroxybutyrate level. Thirty-four patients were recruited with a median blood ketone of 2.90mmol·L-1 and median HbA1c of 4.55%. Those on classical KD (cKD) had higher blood ketone (p=.031) and lower HbA1c (p=.010) and mGKI (p=.021) than those receiving modified Atkins diet, although both shared similar percentages of calories from carbohydrate (p=.211). The cKD and medium-chain triglyceride (MCT) KD groups had similar HbA1c (p=.252) and mGKI (p=.510). Blood ketone (p=.045) and the percentage of calories from MCT (p=.037) were the two main independent variables, inversely correlating with HbA1c. Other than plasma acylcarnitine (p=.047), neither blood ketone (p=.188) nor HbA1c (p=.170) could predict seizure reduction reliably. Both plasma acylcarnitine ≥ 6μmol·L-1 (p=.013) and mGKI ≤ 2.2 (p=.013) were significantly associated with good seizure control. HbA1c could potentially be useful for monitoring KD adherence or, indirectly, systemic ketosis in nondiabetic children on KD for drug-resistant epilepsy. Plasma acylcarnitine and mGKI could be important biomarkers in the management of KD therapy.

Pilot study evaluating everolimus molecular mechanisms in tuberous sclerosis complex and focal cortical dysplasia.

Tuberous sclerosis complex (TSC) and some focal cortical dysplasias (FCDs) are associated with dysfunctional mTOR signaling, resulting in increased cell growth and ribosomal S6 protein phosphorylation (phospho-S6). mTOR inhibitors can reduce TSC tumor growth and seizure frequency, and preclinical FCD studies indicate seizure suppression. This pilot study evaluated safety of mTOR inhibitor everolimus in treatment resistant (failure of >2 anti-seizure medications) TSC and FCD patients undergoing surgical resection and to assess mTOR signaling and molecular pathways. We evaluated everolimus in 14 treatment resistant epilepsy patients undergoing surgical resection (4.5 mg/m2 daily for 7 days; n = 4 Active, mean age 18.3 years, range 4-26; n = 10, Control, mean age 13.1, range 3-45). Everolimus was well tolerated. Mean plasma everolimus in Active participants were in target range (12.4 ng/ml). Brain phospho-S6 was similar in Active and Control participants with a lower trend in Active participants, with Ser235/236 1.19-fold (p = 0.67) and Ser240/244 1.15-fold lower (p = 0.66). Histologically, Ser235/236 was 1.56-fold (p = 0.37) and Ser240/244 was 5.55-fold lower (p = 0.22). Brain proteomics identified 11 proteins at <15% false discovery rate associated with coagulation system (p = 1.45x10-9) and acute phase response (p = 1.23x10-6) activation. A weighted gene correlation network analysis (WGCNA) of brain proteomics and phospho-S6 identified 5 significant modules. Higher phospho-S6 correlated negatively with cellular respiration and synaptic transmission and positively with organophosphate metabolic process, nuclear mRNA catabolic process, and neuron ensheathment. Brain metabolomics identified 14 increased features in Active participants, including N-acetylaspartylglutamic acid. Plasma proteomics and cytokine analyses revealed no differences. Short-term everolimus before epilepsy surgery in TSC and FCD resulted in no adverse events and trending lower mTOR signaling (phospho-S6). Future studies should evaluate implications of our findings, including coagulation system activation and everolimus efficacy in FCD, in larger studies with long-term treatment to better understand molecular and clinical effects. ClinicalTrials.gov NCT02451696.

Discriminative neural pathways for perception-cognition activity of color and face in the human brain.

Human performance can be examined using a visual lens. The identification of psychophysical colors and emotional faces with perceptual visual pathways may remain invalid for simple detection tasks. In particular, how the visual dorsal and ventral processing streams handle discriminative visual perceptions and subsequent cognition activities are obscure. We explored these issues using stereoelectroencephalography recordings, which were obtained from patients with pharmacologically resistant epilepsy. Delayed match-to-sample paradigms were used for analyzing the processing of simple colors and complex emotional faces in the human brain. We showed that the angular-cuneus gyrus acts as a pioneer in discriminating the 2 features, and dorsal regions, including the middle frontal gyrus (MFG) and postcentral gyrus, as well as ventral regions, such as the middle temporal gyrus (MTG) and posterior superior temporal sulcus (pSTS), were involved in processing incongruent colors and faces. Critically, the beta and gamma band activities between the cuneus and MTG and between the cuneus and pSTS would tune a separate pathway of incongruency processing. In addition, posterior insular gyrus, fusiform, and MFG were found for attentional modulation of the 2 features via alpha band activities. These findings suggest the neural basis of the discriminative pathways of perception-cognition activities in the human brain.

Drug resistant epilepsy of the insular lobe: A review and update article.

Background: Epilepsy is a chronic disease that affects millions of people around the world generating great expenses and psychosocial problems burdening the public health in different ways. A considerable number of patients are refractory to the drug treatment requiring a more detailed and specialized investigation to establish the most appropriate therapeutic option. Insular epilepsy is a rare form of focal epilepsy commonly drug resistant and has much of its investigation and treatment involved with the surgical management at some point. The insula or the insular lobe is a portion of the cerebral cortex located in the depth of the lateral sulcus of the brain; its triangular in shape and connects with the other adjacent lobes. The insular lobe is a very interesting and complex portion of the brain related with different functions. Insula in Latin means Island and was initially described in the 18th century but its relation with epilepsy was first reported in the 1940–1950s. Insular lobe epilepsy is generally difficult to identify and confirm due to its depth and interconnections. Initial non-invasive studies generally demonstrate frustrating or incoherent information about the origin of the ictal event. Technological evolution made this pathology to be progressively better recognized and understood enabling professionals to perform the correct diagnosis and choose the ideal treatment for the affected population.Methods: A literature review was performed using MEDLINE/PubMed, Scopus, and Web of Science databases. The terms epilepsy/epileptic seizure of the insula and surgical treatment was used in various combinations. We included studies that were published in English, French, or Portuguese; performed in humans with insular epilepsy who underwent some surgical treatment (microsurgery, laser ablation, or radiofrequency thermocoagulation).Results: Initial search results in 1267 articles. After removing the duplicates 710 remaining articles were analyzed for titles and abstracts applying the inclusion and exclusion criteria. 70 studies met all inclusion criteria and were selected.Conclusion: At present, the main interests and efforts are in the attempt to achieve and standardize the adequate management of the patient with refractory epilepsy of the insular lobe and for that purpose several forms of investigation and treatment were developed. In this paper, we will discuss the characteristics and information regarding the pathology and gather data to identify and choose the best therapeutic option for each case.

Integrating Network Neuroscience Into Epilepsy Care: Progress, Barriers, and Next Steps.

Drug resistant epilepsy is a disorder involving widespread brain network alterations. Recently, many groups have reported neuroimaging and electrophysiology network analysis techniques to aid medical management, support presurgical planning, and understand postsurgical seizure persistence. While these approaches may supplement standard tests to improve care, they are not yet used clinically or influencing medical or surgical decisions. When will this change? Which approaches have shown the most promise? What are the barriers to translating them into clinical use? How do we facilitate this transition? In this review, we will discuss progress, barriers, and next steps regarding the integration of brain network analysis into the medical and presurgical pipeline.

Quality of Life of Parents of Children With Refractory Seizures Referred to a Hospital in Ahvaz, Iran

Background and Objectives Up to 25% of children with epilepsy experience resistance to treatment and recurrence of seizures and have low quality of life (QoL) in various dimensions. Limited evidence is available on the QoL of the parents of these patients in the south of Iran. Therefore, this study aims to evaluate the QoL of parents with children having refractory epilepsy in Ahvaz, Iran Subjects and Methods Using a sequential sampling method, 157 parents of 113 children with refractory epilepsy who referred to the neurology clinic of Golestan Hospital in Ahvaz city during 2009-2016 were selected to participate in the study. The 36-item short form health survey (SF-36) was used to assess the QoL of parents. The significance level of statistical tests was set at 0.05. Results The mean age of parents was 35.2±8.5 years and the mean age of children was 7.1±2.6 years. Of 157 parents, 98 (62.4%) were mothers and the rest were fathers. The children had seizures for 3.1±1.6 years. The mean score of SF-36 was 62.6±21.4. In all domains of the SF-36, mothers had significantly lower scores than fathers (P&lt;0.000). Conclusion The QoL of parents with children having resistant epilepsy, especially their mothers, in Ahvaz is lower compared to the general population of Iranian

Outside-in IL1b-HMGB1 signaling axis may drive astrocytic response in drug resistant epilepsies.

Abstract We recently reported normalization of CSF cytokine levels following successful treatment of drug-resistant epilepsy (DRE) with recombinant interleukin-1 receptor antagonist (rIL1RA). To further understand the mechanism of this therapeutic outcome, we interrogated the ability of serum and CSF factors that are elevated in drug resistant-seizure disorders to promote inflammatory responses in astrocytes and human brain microvessel endothelial cells (HBMVECs). We report that CCL2, TNFa, IL6, and CXCL8/1 were strongly induced in 1) astrocytes and HBMVECs stimulated with IL1β (blocked by rIL1RA) and 2) astrocytes but not HBMVECs in response to DRE patient serum but not control serum (partially blocked by rIL1RA). This suggested that other serum factors contribute to astrocyte activation in this DRE. HMGB1 and IL18 were also dysregulated in DRE patient serum; however, IL18 failed to stimulate cytokine secretion from astrocytes. In contrast, HMGB1 induced cytokine secretion from astrocytes, which was blocked by the TLR4 inhibitor TAK242. Remarkably, TAK242 also prevented cytokine production by astrocytes in response to serum from some patients with DRE. Finally, IL1β induced the polarized uptake and secretion of HMGB1 across transwell inserts harboring confluent monolayers of HBMVECs suggesting that IL1b signaling may cause endothelial cells to transport serum HMGB1 into the perivascular space—promoting TLR4-dependent cytokine release from astrocytes. This translation of an “outside” inflammatory signal into an “inside” inflammatory response may underlie seizure disorders that are resistant to anti-seizure drugs.

Virtual implantation using conventional scalp EEG delineates seizure onset and predicts surgical outcome in children with epilepsy

ObjectiveDelineation of the seizure onset zone (SOZ) is required in children with drug resistant epilepsy (DRE) undergoing neurosurgery. Intracranial EEG (icEEG) serves as gold standard but has limitations. Here, we examine the utility of virtual implantation with electrical source imaging (ESI) on ictal scalp EEG for mapping the SOZ and predict surgical outcome. MethodsWe retrospectively analyzed EEG data from 35 children with DRE who underwent surgery and dichotomized into seizure-free (SF) and non-seizure-free (NSF). We estimated virtual sensors (VSs) at brain locations that matched icEEG implantation and compared ictal patterns at VSs vs icEEG. We calculated the agreement between VSs SOZ and clinically defined SOZ and built receiver operating characteristic (ROC) curves to test whether it predicted outcome. ResultsTwenty-one patients were SF after surgery. Moderate agreement between virtual and icEEG patterns was observed (kappa = 0.45, p < 0.001). Virtual SOZ agreement with clinically defined SOZ was higher in SF vs NSF patients (66.6% vs 41.6%, p = 0.01). Anatomical concordance of virtual SOZ with clinically defined SOZ predicted outcome (AUC = 0.73; 95% CI: 0.57–0.89; sensitivity = 66.7%; specificity = 78.6%; accuracy = 71.4%). ConclusionsVirtual implantation on ictal scalp EEG can approximate the SOZ and predict outcome. SignificanceSOZ mapping with VSs may contribute to tailoring icEEG implantation and predict outcome.

Cyclooxygenase-2 Inhibition as an Add-On Strategy in Drug Resistant Epilepsy-A Canine Translational Study.

Drug-resistant epilepsy is a common complaint in dogs and affects up to 30% of dogs with idiopathic epilepsy. Experimental data suggest that targeting cyclooxygenase-2 (COX-2) mediated signaling might limit excessive excitability and prevent ictogenesis. Moreover, the role of COX-2 signaling in the seizure-associated induction of P-glycoprotein has been described. Thus, targeting this pathway may improve seizure control based on disease-modifying effects as well as enhancement of brain access and efficacy of the co-administered antiseizure medication. The present open-label non-controlled pilot study investigated the efficacy and tolerability of a COX-2 inhibitor (firocoxib) add-on therapy in a translational natural occurring chronic epilepsy animal model (client-owned dogs with phenobarbital-resistant idiopathic epilepsy). The study cohort was characterized by frequent tonic–clonic seizures and cluster seizures despite adequate phenobarbital treatment. Enrolled dogs (n = 17) received a firocoxib add-on therapy for 6 months. Tonic–clonic seizure and cluster seizure frequencies were analyzed at baseline (6 months) months during the study (6 months). The responders were defined by a substantial reduction of tonic–clonic seizure and cluster seizure frequency (≥50%). In total, eleven dogs completed the study and were considered for the statistical analysis. Two dogs (18%, 2/11) were classified as responders based on their change in seizure frequency. Interestingly, those two dogs had the highest baseline seizure frequency. The overall tolerability was good. However, given the low percentage of responders, the present data do not support an overall considerable efficacy of COX-2 inhibitor add-on therapy to overcome naturally occurring phenobarbital-resistant epilepsy in dogs. Further translational evaluation should only be considered in the canine patients with a very high baseline seizure density.

Surgical nuances in corpus callosotomy as a palliative epilepsy surgery.

Background: Corpus callosotomy is a well-established palliative procedure in selected patients with drug resistant epilepsy (DRE). It has a beneficial role in ameliorating generalized seizures mainly drop attacks. Here, we present some technical tips for performing callosotomy depending on the anatomical basis, to minimize craniotomy size and guard against inadvertently entering the lateral ventricles.Methods: This study was a retrospective review of patients who received corpus callosotomy at our institute as a palliative epilepsy surgery. We present our experience and surgical tips with the extraventricular technique of corpus callosotomy with comparison of surgery-related complications and operative time between extraventricular and conventional techniques in selected patients with DRE.Results: Our study included 34 patients. First group of patients included 14 patients who received conventional approach, while the extraventricular approach was done in 20 patients. Extraventricular approach showed significantly lower wound complications rate of 10% compared to 78% in intraventricular approach (P < 0.001). Mean operative time was significantly lower in extraventricular versus conventional technique with 52 min versus 94 min, respectively (P < 0.001). Planned extent of corpus callosotomy resection was achieved in all our patients using both approaches.Conclusion: The cleft of the septum pellucidum offers a natural pursuit to section corpus callosum strictly midline and completely extraventricular in well selected patients of DRE candidate for callosotomy. Performing corpus callosotomy in extraventricular approach provided better patients outcomes regarding surgery and wound-related complications when compared to conventional approach.

Impact of the COVID-19 Pandemic on Epilepsy Center Practice in the United States.

Background and ObjectivesPersons with epilepsy, especially those with drug resistant epilepsy (DRE), may benefit from inpatient services such as admission to the epilepsy monitoring unit (EMU) and epilepsy surgery. The COVID-19 pandemic caused reductions in these services within the US during 2020. This article highlights changes in resources, admissions, and procedures among epilepsy centers accredited by the National Association of Epilepsy Centers (NAEC).MethodsWe compared data reported in 2019, prior to the COVID-19 pandemic, and 2020 from all 260 level 3 and level 4 NAEC accredited epilepsy centers. Data were described using frequency for categorical variables and median for continuous variables and were analyzed by center level, center population category, and geographical location. Qualitative responses from center directors to questions regarding the impact from COVID-19 were summarized utilizing thematic analysis. Responses from the NAEC center annual reports as well as a supplemental COVID-19 survey were included.ResultsEMU admissions declined 23% (-21,515) in 2020, with largest median reductions in level 3 centers [-55 admissions (-44%)] and adult centers [-57 admissions (-39%)]. The drop in admissions was more substantial in the East North Central, East South Central, Mid Atlantic, and New England US Census divisions. Survey respondents attributed reduced admissions to re-assigning EMU beds, restrictions on elective admissions, reduced staffing, and patient reluctance for elective admission. Treatment surgeries declined by 371 cases (5.7%), with the largest reduction occurring in VNS implantations [-486 cases (-19%)] and temporal lobectomies [-227 cases (-16%)]. All other procedure volumes increased, including a 35% (54 cases) increase in corpus callosotomies.DiscussionIn the US, access to care for persons with epilepsy declined during the COVID-19 pandemic in 2020. Adult patients, those relying on level 3 centers for care, and many persons in the eastern half of the US were most affected.

Characterization of spontaneous seizures and EEG abnormalities in a mouse model of the human A350V IQSEC2 mutation and identification of a possible target for precision medicine based therapy

IQSEC2 is an X-linked gene localized to the post synaptic density encoding a GTP exchange factor that regulates NMDA mediated changes in synaptic function. Mutations in the IQSEC2 gene are associated with drug resistant epilepsy, intellectual disability and autism. Precision medicine based therapeutics to treat IQSEC2 associated epilepsy requires the development and characterization of mutation specific animal models. To date no EEG recordings have been presented for any mouse model of any IQSEC2 mutation showing seizures. In this study we characterize the seizures and EEG brain wave abnormalities present in mice with a A350V IQSEC2 missense mutation that is associated with drug resistant epilepsy in man. We show that seizures are associated with a greater than 40% mortality rate in male mice and occur exclusively from post-natal day 16–20. EEG recordings of mouse pups during this window demonstrate seizures and the presence of spikes with a marked increase in delta waves. EEG recordings in adult male mice have persistent excessive slow frequency activity and spikes, but seizures were not recorded. RNAseq analysis of the hippocampi of mice prior to the development of seizures demonstrated marked abnormalities in canonical pathways involved in synaptogenesis and dendritic maturation with the most prominently dysregulated gene being that for TRH suggesting a potential target for therapy given the previous demonstration of TRH to decrease seizures in several forms of drug resistant epilepsy.

Expert advice for prescribing cannabis medicines for patients with epilepsy-drawn from the Australian clinical experience.

There is international interest for consensus advice for prescribers working in the field of drug resistant epilepsy intending to trial potential therapies that are nonregistered or off‐label. Cannabinoids are one such therapy. In 2017, the New South Wales State Government (Australia) set up a cannabinoid prescribing guidance service for a wide variety of indications, based on known pharmacology together with the relevant new literature as it became available. Increasing interest in cannabis medicines use outside this State over the following 5 years together with a paucity of registration‐standard clinical trials, lack of information around dosing issues, drug interactions and biological plausibility meant there remained a large unmet need for such advice. To address the unmet need in epilepsy, and until medicines were registered or regulator quality data were available, it was agreed to bring together a working group comprising paediatric and adult epilepsy specialists, clinical pharmacists., clinical pharmacologists and cannabis researchers from across Australia to develop interim consensus advice for prescribers. Although interim, this consensus advice addresses much of the current practice gap by providing an informed overview of the different cannabis medicines currently available for use in the treatment of epilepsy in paediatric and adult settings, with information on dose, drug interactions, toxicity, type of seizure and frequency of symptom relief. As such it supplements the limited evidence currently available from clinical trials with experience from front‐line practice. It is expected that this consensus advice will be updated as new evidence emerges and will provide guidance for a subsequent Guideline.

Multimodal prognostic features of seizure freedom in epilepsy surgery

ObjectiveAccurate preoperative predictions of seizure freedom following surgery for focal drug resistant epilepsy remain elusive. Our objective was to systematically evaluate all meta-analyses of epilepsy surgery with seizure freedom as...

Effects of Stable Vagus Nerve Stimulation Efficacy on Autistic Behaviors in Ten Pediatric Patients With Drug Resistant Epilepsy: An Observational Study.

Vagus nerve stimulation (VNS) is a safe and effective therapy for pediatric patients with drug-resistant epilepsy (DRE). However, in children with DRE, the effects of VNS on autistic behaviors remain controversial. We retrospectively collected data from 10 children with DRE who underwent VNS implantation and regular parameter regulation in three pediatric epilepsy centers, and completed the behavioral assessments, including the autistic behavior checklist and the child behavior checklist, at follow-ups 1 (mean 2.16 years) and 2 (mean 2.98 years). The 10 children maintained stable seizure control between the two follow-ups. Their autistic behaviors, especially in language, social and self-help, were reduced at follow-up 2 compared to follow-up 1 (p = 0.01, p = 0.01, respectively). Moreover, these improvements were not associated with their seizure control, whether it was positive or negative. These results suggested that the VNS had a positive effect on autistic behaviors, which provided a preliminary clinical basis that VNS may benefit to younger children with DRE comorbidity autism spectrum disorder (ASD).

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.

333 First FDA Cleared Thin Film Electrode for Intracranial Recording and Monitoring of Brain Activity – Device Testing and Initial Clinical Use

INTRODUCTION: Subdural strip and grid (SDG) electrodes are routinely used for pre-surgical evaluation of patients with drug resistant epilepsy (DRE). Although these electrodes have been in the US market since their first FDA clearance in 1985, their fabrication, materials and properties have hardly changed. They are made of silicone, are thick (&gt;0.5 mm), manufactured by hand, and do not optimally conform to brain convolutions. Technological solutions that overcome these limitations are needed. METHODS: Thin film electrode (0.08 mm) arrays were manufactured from polyimide with platinum contacts (multiple configurations, 3 mm contact diameter, spaced 10 mm apart). Electrochemical and electrical testing include electrolyte interface impedance, cyclic voltammetry and other impedance and isolation tests, according to the International Electrotechnical Commission 60601 for proving device safety and performance. Biocompatibility was tested using standard methods according to International Organization for Standardization 10993. Post-market data were collected employing a user feedback questionnaire using a rating scale (1 to 5, with 5 being the highest). RESULTS: Thin film electrodes passed all electrochemical, electrical and biocompatibility testing required for FDA clearance (obtained Nov 2019). Electrodes (n = 19) were used in clinical practice between Nov 23, 2020 and May 3, 2021 in the epilepsy monitoring units and for intraoperative monitoring (IOM) for recording brain activity in (a) DRE patients undergoing evaluation for potential surgical resection, and (b) patients undergoing tumor resection. Users (neurosurgeons; n = 6) provided ratings between 4 and 5 regarding the properties (thickness, flexibility, weight), features (ease of placement, conformability to the brain areas) and performance (qualitative signal recording quality) of the electrodes during surgical implantation. CONCLUSION: This is the first thin film electrode technology FDA cleared for use in clinical practice. The properties of these thin, flexible polyimide electrode arrays may overcome many limitations of the existing technology. Initial clinical use indicated that the technology is feasible for surgical implantation with greater flexibility compared to silicone based cortical electrodes.

Brainstem Associated Somatosensory Evoked Potentials and Response to Vagus Nerve Stimulation: An Investigation of the Vagus Afferent Network.

Despite decades of clinical usage, selection of patients with drug resistant epilepsy who are most likely to benefit from vagus nerve stimulation (VNS) remains a challenge. The mechanism of action of VNS is dependent upon afferent brainstem circuitry, which comprises a critical component of the Vagus Afferent Network (VagAN). To evaluate the association between brainstem afferent circuitry and seizure response, we retrospectively collected intraoperative data from sub-cortical recordings of somatosensory evoked potentials (SSEP) in 7 children with focal drug resistant epilepsy who had failed epilepsy surgery and subsequently underwent VNS. Using multivariate linear regression, we demonstrate a robust negative association between SSEP amplitude (p < 0.01), and seizure reduction. There was no association between SSEP latency and seizure outcomes. Our findings provide novel insights into the mechanism of VNS and inform our understanding of the importance of brainstem afferent circuitry within the VagAN for seizure responsiveness following VNS.

The diagnosis to be kept in mind in resistant epilepsy; tuberous sclerosis

Drug-Resistant Epilepsy is the continuation of seizures despite administering two tolerable antiepileptic drugs at the appropriate dose and time, which are selected according to the type of seizure. Growth retardation, focal neurological findings, organic brain lesions, specific EEG disorders, and epilepsy in the family are risk factors for resistant epilepsy. Tuberous sclerosis is a multisystemic and autosomal dominant genetic disease with hamartomas in many organs such as the skin, central nervous system, kidney, and lungs. Brain hamartomas and other central nervous system lesions cause resistant epilepsy in tuberous sclerosis. In this article, we present a 16-year-old patient with tuberous sclerosis who was followed up with the diagnosis of resistant epilepsy, despite typical physical examination findings. This research emphasised that tuberous sclerosis should be kept in mind in the aetiology of resistant epilepsy and how important physical examination is.

Extraoperative electrical stimulation mapping in epilepsy presurgical evaluation: a proposal and review of the literature

BackgroundElectrical stimulation mapping (ESM) is an important tool for the localization of the seizure onset zone (SOZ) in patients with medically resistant epilepsy (MRE). ESM is the gold standard for the identification of eloquent cortex in epilepsy surgery candidates. However, there is no standard protocol outlining how to perform ESM, to obtain the most useful information possible. The objective of this study, after reviewing the literature concerning ESM, is to propose a unifying technique to validate reliable data across different centers. MethodsIn this manuscript we summarize this technique from its origin to present, and review protocols used in other centers. We also describe a protocol that has been used in our institution, which utilizes depth electrodes. ResultsThe most common type of ESM uses a “close-loop” system, bipolar and high frequency stimulation (50 Hz). We propose to use a pulse width of 300 µs, current spanning 1–6 mA in depth electrodes and 1–11 mA in subdural-grids. Stimulation time of 5 s maximum and at least 10 s break in between the stimulations. ConclusionsESM is a useful tool for understanding eloquent cortex as well as the epilepsy network, although there is no clear consensus regarding how it should be performed.