Resistant Epilepsy Research Articles

Deep anomaly detection of seizures with paired stereoelectroencephalography and video recordings

Real-time seizure detection is a resource intensive process as it requires continuous monitoring of patients on stereoelectroencephalography. This study improves real-time seizure detection in drug resistant epilepsy (DRE) patients by developing patient-specific deep learning models that utilize a novel self-supervised dynamic thresholding approach. Deep neural networks were constructed on over 2000 h of high-resolution, multichannel SEEG and video recordings from 14 DRE patients. Consensus labels from a panel of epileptologists were used to evaluate model efficacy. Self-supervised dynamic thresholding exhibited improvements in positive predictive value (PPV; difference: 39.0%; 95% CI 4.5–73.5%; Wilcoxon–Mann–Whitney test; N = 14; p = 0.03) with similar sensitivity (difference: 14.3%; 95% CI − 21.7 to 50.3%; Wilcoxon–Mann–Whitney test; N = 14; p = 0.42) compared to static thresholds. In some models, training on as little as 10 min of SEEG data yielded robust detection. Cross-testing experiments reduced PPV (difference: 56.5%; 95% CI 25.8–87.3%; Wilcoxon–Mann–Whitney test; N = 14; p = 0.002), while multimodal detection significantly improved sensitivity (difference: 25.0%; 95% CI 0.2–49.9%; Wilcoxon–Mann–Whitney test; N = 14; p < 0.05). Self-supervised dynamic thresholding improved the efficacy of real-time seizure predictions. Multimodal models demonstrated potential to improve detection. These findings are promising for future deployment in epilepsy monitoring units to enable real-time seizure detection without annotated data and only minimal training time in individual patients.

Psychotic symptoms in drug resistant epilepsy patients after cortical stimulation

PurposeThe use of invasive EEG (iEEG) recordings before epilepsy surgery has increased as more complex focal epilepsies are evaluated. Psychotic symptoms (PS) during iEEG have been scarcely reviewed. We aim to report our series of patients with psychotic symptoms (PS) brought about by cortical stimulation (CS) and to identify triggers. MethodsRetrospective cohort of patients who underwent iEEG and CS. We report patients who developed delusional thinking and/or disorganized behaviour within 24 h after CS. Exclusion criteria were primary psychiatric disorders or absence of CS. ResultsWe evaluated 32 (SEEG 23; subdural 9) patients with a median age of 38 years, 6 with PS. Patients underwent 2586 stimulations over 1130 contacts. Age at CS was significantly higher in patients with PS. Temporal lobe epilepsy was significantly more often documented in patients with PS (χ2: 3.94; p< 0.05). We found no correlation between stimulation of the limbic system and development of psychosis. Four (66.7 %) patients were stimulated in the non-dominant limbic system and developed psychosis compared to 7 (27 %) who did not [χ2: 3.41; p= 0.06].Epilepsy duration was significantly higher in PS patients (p=0.002). Patients with history of postictal psychosis were twice more likely to experience PS(p=0.04). ConclusionsPS may arise more frequently in patients with PIP history, older age and longer epilepsy duration. The neurobiology and physiology of psychosis, that may share common mechanisms with epilepsy, is yet to be identified but we hypothesize that it may be triggered by CS due to alteration of brain networks dynamics.

Behavior problems associated with brain heterotopia

IntroductionBrain heterotopia represent a group of rare malformations with a heterogeneous phenotype, ranging from asymptomatic to severe clinical picture (resistant epilepsy, severe developmental delay). The etiology is multifactorial, including both genetic and environmental factors.ObjectivesIn this paper we present our experience regarding behavior problems in patients with heterotopia.MethodsA cohort of 16 pediatric patients with brain heterotopia, six females and ten males, with age at last follow-up ranging from 2 months to 24 years were investigated by clinical examination, electroencephalographic studies, brain imaging, and genomic tests. Specific psychological tests and psychiatric evaluation were performed in all children for behavior problems assessment.ResultsSix individuals presented behavioral problems: autism (three patients) and hyperkinesia with attention deficit (three patients). All of them had intellectual disability or learning problems; five patients had epilepsy, with drug-resistant seizures in four cases. In two cases the behavioral problems occurred before the onset of epileptic seizures.ConclusionsBehavior problems are important features in patients with brain heterotopia, making the management of these patients more difficult, especially when they occur in association with drug-resistant epilepsy. Acknowledgements: This work was supported partially by grants of the Romanian National Authority for Scientific Research and Innovation CCCDI – UEFISCDI, Projects COFUND-ERANET E-RARE 3-HETER-OMICS-2 Number 87/2019 and 88/2019 within PNCDI III.DisclosureNo significant relationships.

Newer versus older antiseizure medications: further forward?

Since 1990, many new antiseizure medications have been launched. Many have been licensed on the basis of evidence from add-on therapy in resistant epilepsies; there have been few head-to-head comparative data in patients who are newly diagnosed. 1 Lattanzi S Zaccara G Giovannelli F et al. Antiepileptic monotherapy in newly diagnosed focal epilepsy. A network meta-analysis. Acta Neurol Scand. 2019; 139: 33-41 Crossref PubMed Scopus (46) Google Scholar Findings from Standard and New Antiepileptic Drugs (SANAD) I, the first SANAD trial, provided the first comprehensive data to address this question; lamotrigine was shown to be superior to carbamazepine, gabapentin, oxcarbazepine, and topiramate in time to treatment failure, 2 Marson AG Al-Kharusi AM Alwaidh M et al. The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial. Lancet. 2007; 369: 1000-1015 Summary Full Text Full Text PDF PubMed Scopus (677) Google Scholar and valproate was a clinically and cost-effective alternative to lamotrigine or topiramate. 3 Marson AG Al-Kharusi AM Alwaidh M et al. The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: an unblinded randomised controlled trial. Lancet. 2007; 369: 1016-1026 Summary Full Text Full Text PDF PubMed Scopus (645) Google Scholar However, since these trials were done, other medications have been licensed for use, and levetiracetam has been increasingly considered a safe alternative in the treatment of both focal and generalised epilepsies, despite few head-to-head comparative data, 4 Shih JJ Whitlock JB Chimato N Vargas E Karceski SC Frank RD Epilepsy treatment in adults and adolescents: expert opinion, 2016. Epilepsy Behav. 2017; 69: 186-222 Summary Full Text Full Text PDF PubMed Scopus (56) Google Scholar specifically with the increasing concern about the effect of valproate in pregnancy on the unborn child. The SANAD II study of the effectiveness and cost-effectiveness of levetiracetam, zonisamide, or lamotrigine for newly diagnosed focal epilepsy: an open-label, non-inferiority, multicentre, phase 4, randomised controlled trialThese findings do not support the use of levetiracetam or zonisamide as first-line treatments for patients with focal epilepsy. Lamotrigine should remain a first-line treatment for patients with focal epilepsy and should be the standard treatment in future trials. Full-Text PDF Open AccessThe SANAD II study of the effectiveness and cost-effectiveness of valproate versus levetiracetam for newly diagnosed generalised and unclassifiable epilepsy: an open-label, non-inferiority, multicentre, phase 4, randomised controlled trialCompared with valproate, levetiracetam was found to be neither clinically effective nor cost-effective. For girls and women of child-bearing potential, these results inform discussions about benefit and harm of avoiding valproate. Full-Text PDF Open Access

Cognitive impairments in patients with treatment resistant epilepsy: Complex rehabilitation in university clinic

IntroductionСognitive deficit significantly affects the quality of life of patients. Aims of research was detection of cognitive impairments of varying degrees in epilepsy, and as well as studying the results of complex treatment in conditions of University clinic, physical and psychological rehabilitation, cognitive training and VNS included.ObjectivesWe studied the features of clinical and psychopathological manifestations of cognitive impairments in patients suffering from epilepsy.MethodsThe study was attended by 100 patients (35 men and 65 women) who were inpatient care. The following psychodiagnostic techniques were used: the Toronto Cognitive Assessment TorCA, the test of 10 words of Luria, the MOCA test, the Münsterberg test, the quality of life scale, the Hamilton scale of depression and anxiety.ResultsMCI was observed in 88 % patients, dementia in 12 % (50 % - mild dementia, in 24 % - moderate dementia and in 16% - severe dementia). We used non-pharmacological rehabilitation methods for correction of cognitive impairment in epileptic patients with MCI and mild dementia during 3 mounth.. Improving of cognitive function was observed in 48 % patients, stable level of cognitive function - in 36 %, progressing of cognitive imparment - in 16 % patiens with epilepsy.ConclusionsThe results of the conducted research indicate the need for further study of the features of cognitive disorders in pharmacologically treatment resistant epilepsy and implementation of training aimed at improving cognitive function and preventing the progression of cognitive impairment in complex treatment of those patients.

Ketogenic diet for anxiety disorders: Dietary regimen for relapse prevention?

IntroductionAnxiety disorders are a mental disorder that is widespread all over the world and are associated with a high burden of the disease. While poor dietary habits are common in depression, they can lead to worsening of the illness or prolong the treatment, which also leads to a higher risk of developing chronic diseases.ObjectivesWith the array of the treatment modalities including monoaminergic antidepressants, benzodiazepines, psychotherapy, there is the unmet need for the effective treatment of anxiety disorders resulting in full remission and relapse prevention. Benzodiazepines can quickly resolve anxiety due to their positive allosteric GABA modulation mechanism of action. Although, they are not recommended for chronic use.Methods Ketogenic diet(KD) may be hypothesized as the promising strategy impacting treatment strategies, in particularly facilitating full remission, recovery and preventing relapses. In this popular high-fat diet, where daily calories intake is consists in at least 70% from fat, up to 25 % from protein and as little sugar as possible is mainly known for its helpful role in drug resistant epilepsy treatment, glucose levels balance or fast way for weight-loss.ResultsCould be effective in anxiety disorders treatment due to its possible role in GABA:glutamate balance change in favor of GABA levels, which may enhance the anxiolytic effect in sustaining remission and preventing relapse.ConclusionsKD in some anxiety disorders may provide a rewarding outcome, but more research is needed. The evidence mentioned in this paper should encourage psychiatrists to recommend KD as advice somewhere between psychotherapy, pharmacology or as an add-on to those two.

Surgical treatment of epilepsy at the Russian Children’s Clinical Hospital: substrates and imaging aspects

Introduction. MRI revealing the epileptogenic foci is the central part of the presurgical evaluation of children with focal-resistant epilepsy. Besides that, MRI seems to be a reliable instrument of treatment optimization and good prognosis. Aim. To identify epileptogenic lesions in children with resistant focal epilepsy by high resolution (HR) MRI and comparing obtained data with postsurgical morphology. Materials and methods. We assessed the results of neuroimaging, EEG, clinical neurological status, and postsurgical morphological data in 65 children with focal epilepsy who had undergone antiepileptic surgery in Russian State Children Hospital, neurosurgery department (Moscow, Russia) from 2016 to 2020. Results. The broad spectrum of epileptogenic lesions was revealed by HR MRI, including focal and diffuse cortical dysplasias (44.6%), cortical post hypoxic gliosis (27.7%), glial tumors (7.7%), Rasmussen encephalitis (10.8%), tuberous sclerosis, and Sturge-Weber syndrome (3%), small angiodysplasias (4.6%) and other. Focal cerebral dysplasia had an obvious superiority as the main etiological factor in focal epilepsy and was approved in 33.8% of all patients. In all cases, epilepsy is characterized by frequent and resistant seizures, inflicting motor arrest, and psycho-emotional deterioration. Conclusion. HR MRI and multidisciplinary investigation have to be unchangeable standards in the presurgical evaluation of children with focal epilepsy. This approach’s effectiveness has reassuring confirmation by high level (95.2%) of total coincidence MRI and morphological results.

One Month of Classic Therapeutic Ketogenic Diet Decreases Short Chain Fatty Acids Production in Epileptic Patients.

Ketogenic diet (KD), a high fat and very low carbohydrates diet, is used worldwide for the treatment of drug resistant epilepsy but, due to its composition, it might exert an impact on gut health. Even though data of KD effects on intestinal microbiota changes are recently emerging, its influence on the gut environment has been scarcely addressed so far. The aim of this study was to investigate whether 1 month of KD affects the gut environment in epileptic patients, by analyzing short chain fatty acids (SCFA) production and fecal water toxicity. A total of seven patients were enrolled. Stool samples were collected before (T0) and after 1 month of KD (4:1 ketogenic ratio) (T1). SCFA were determined by GC-FID and fecal water toxicity in Caco-2 cell culture by comet assay. Concentrations of SCFA significantly decreased after KD (p < 0.05): in particular, we found a 55% reduction of total SCFA level, a 64% reduction of acetate, 33% of propionate, and 20% of butyrate (p < 0.05). Cytotoxicity of fecal water extracted from stool samples was not significantly altered by diet, while genotoxicity was slightly decreased after KD (p < 0.05). Genotoxicity values were consistent with data previously obtained from a healthy Italian population. The present study suggests that 1 month of KD significantly reduce SCFA production. Since SCFA produced by gut microbiota exert many health promoting effects on either the gut environment or human metabolism, these results open a new branch of investigation into KD effects.

Presurgical accuracy of dipole clustering in MRI-negative pediatric patients with epilepsy: Validation against intracranial EEG and resection

ObjectiveTo assess the utility of interictal magnetic and electric source imaging (MSI and ESI) using dipole clustering in magnetic resonance imaging (MRI)-negative patients with drug resistant epilepsy (DRE). MethodsWe localized spikes in low-density (LD-EEG) and high-density (HD-EEG) electroencephalography as well as magnetoencephalography (MEG) recordings using dipoles from 11 pediatric patients. We computed each dipole’s level of clustering and used it to discriminate between clustered and scattered dipoles. For each dipole, we computed the distance from seizure onset zone (SOZ) and irritative zone (IZ) defined by intracranial EEG. Finally, we assessed whether dipoles proximity to resection was predictive of outcome. ResultsLD-EEG had lower clusterness compared to HD-EEG and MEG (p < 0.05). For all modalities, clustered dipoles showed higher proximity to SOZ and IZ than scattered (p < 0.001). Resection percentage was higher in optimal vs. suboptimal outcome patients (p < 0.001); their proximity to resection was correlated to outcome (p < 0.001). No difference in resection percentage was seen for scattered dipoles between groups. ConclusionMSI and ESI dipole clustering helps to localize the SOZ and IZ and facilitate the prognostic assessment of MRI-negative patients with DRE. SignificanceAssessing the MSI and ESI clustering allows recognizing epileptogenic areas whose removal is associated with optimal outcome.

Risk estimation of SUDEP during COVID-19 pandemic era in a tertiary referral center

ObjectiveNo data exist regarding the impact of the lockdown due to the COVID-19 pandemic on the risk factors of sudden unexpected death in epilepsy (SUDEP). This study aimed to stratify risk factors of SUDEP in relation to COVID-19 lockdown, among patients with epilepsy (PWE) in Cairo University epilepsy unit (CUEU). Therefore, we can detect risk factors and mitigate such factors in the second wave of the virus. Methodsan observational, cross-sectional study carried on 340 Egyptian patients with active epilepsy. Individual risk identification and stratification was done by using The SUDEP and seizure Safety Checklist, after which sharing risk knowledge to PWE and their caregivers was undertaken. ResultsThe mean age of patients was 29.72 ± 12.12. The median of the static factors was 4 (IQR 3–5) whereas, the median of the modifiable factors was 2 (IQR 1–3). Epilepsy emergencies (serial seizures or status epilepticus) were reported in 24.1 % of patients, for which non-compliance was the commonest cause, followed by deferral of epilepsy surgery for patients with drug resistant epilepsy (DRE). Stepwise logistic regression analysis showed that use of anxiolytic medications, non-compliance, keeping patients with DRE on dual anti-seizure medications (ASMs), or adding third medication increased the odds of increased seizure frequency by 2.7, 3.5, 16.6 and 6.1 times, respectively. ConclusionSome COVID-19 related issues had influenced the risk of seizure worsening including postponing epilepsy surgery for patients with DRE, non-compliance, and psychiatric comorbidities. Special attention should be paid to these issues to mitigate the risk of SUDEP.

White matter integrity after cannabidiol administration for treatment resistant epilepsy

ObjectiveThe effects of individual cannabinoids on white matter integrity are unclear. Human studies have shown white matter maturation alterations in regular recreational cannabis users with the magnitude of these effects dependent on the age of exposure. However, studies have yet to determine which phytocannabinoids are most responsible for these changes. In the current study, we analyzed the effects of pharmaceutical grade cannabidiol oral solution (CBD; Epidiolex® in the U.S.; Epidyolex® in the EU; 100 mg/mL oral solution) on white matter integrity using diffusion MRI in patients with treatment resistant epilepsy (TRE). Methods15 patients with TRE underwent 3 T diffusion MRI prior to receiving CBD and then again approximately 12 weeks later while on a stable dose of CBD for at least two weeks. DTI analyzes were conducted using DSI Studio and tract-based spatial statistics (TBSS). ResultsDTI analysis using DSI Studio showed significant increases in fractional anisotropy (FA) in the right medial lemniscus (p = 0.03), right superior cerebellar peduncle (p = 0.03) and the pontine crossing tract (p = 0.04); decreased mean diffusivity (MD) in the left uncinate fasciculus (p = 0.02) and the middle cerebellar peduncle (p = 0.04); decreased axial diffusivity (AD) in the left superior cerebellar peduncle (p = 0.05), right anterior limb of the internal capsule (p = 0.03), and right posterior limb of the internal capsule (p = 0.02); and decreased radial diffusivity (RD) in the middle cerebellar peduncle (p = 0.03) and left uncinate fasiculus (p = 0.01). The follow-up ANCOVA also yielded significant results when controlling for covariates of CBD dosage, age, sex, change in seizure frequency, and scanner type: FA increased in the pontine crossing tract (p = 0.03); RD decreased in the middle cerebellar peduncle (p = 0.04) and left uncinate fasciculus (p = 0.04). Subsequent TBSS analysis controlling for the same variables yielded no significant white matter differences between groups. ConclusionThese findings indicate relatively minor short-term effects of highly-purified plant-derived CBD on white matter structural integrity in patients with TRE.

Mood and quality of life in patients treated with brain-responsive neurostimulation: The value of earlier intervention

ObjectiveTo establish whether earlier treatment using direct brain-responsive neurostimulation for medically intractable focal-onset seizures is associated with better mood and Quality of Life (QoL) compared to later treatment intervention. MethodsData were retrospectively analyzed from prospective clinical trials of a direct brain-responsive neurostimulator (RNS® System) for treatment of adults with medically intractable focal-onset epilepsy. Participants completed the Quality of Life in Epilepsy Inventory (QOLIE-31) yearly through 9 years of follow-up and the Beck Depression Inventory-II (BDI-II) through 2 years of follow-up. Changes in each assessment after treatment with responsive neurostimulation were calculated for patients who began treatment within 10 years of seizure onset (early) and those who began treatment 20 years or more after seizure onset (late). ResultsThe median duration of epilepsy was 18.3 years at enrollment. At 9 years, both the early (N = 51) and late (N = 109) treatment groups experienced similar and significant reductions in the frequency of disabling seizures (73.4% and 77.8%, respectively). The early treatment patients had significant improvements in QoL and mood. However, the late treatment patients not only failed to show these improvements but also declined in the emotional QoL subscale. ConclusionsPatients treated with brain-responsive neurostimulation earlier in the course of their epilepsy show significant improvements in multiple domains of QoL and mood that are not observed in patients treated later in the course of their epilepsy despite similar efficacy in seizure reduction. Even with similar and substantial reductions in seizure frequency, the comorbidities of uncontrolled epilepsy may be less responsive to treatment when too many years have passed. The results of this study suggest that, as with resective and ablative surgery, treatment with brain-responsive neurostimulation should be delivered as early as possible in the course of medically resistant epilepsy to maximize the opportunity for improvements in mood and QoL.

Mesial Temporal Sclerosis as Late Consequence of Posterior Reversible Encephalopathy Syndrome in Pediatric Hemato-oncologic Patients.

Drug resistant epilepsy has rarely been reported following posterior reversible encephalopathy syndrome (PRES), with few cases of mesial temporal sclerosis (MTS). The aim of this study was to report clinical and neuroimaging features of MTS subsequent to PRES in hemato-oncologic/stem cell transplanted children. Among 70 children treated in 2 pediatric hemato-oncologic Italian centers between 1994 and 2018 and presenting an episode of PRES, we retrospectively identified and analyzed a subgroup of patients who developed epilepsy and MTS. Nine of 70 patients (12.8%) developed post-PRES persistent seizures with magnetic resonance imaging evidence of MTS. One patient died few months after MTS diagnosis, because of hematologic complications; the remaining 8 patients showed unprovoked seizures over time leading to the diagnosis of epilepsy, focal in all and drug resistant in 4. At PRES diagnosis, all patients with further evidence of epilepsy and MTS suffered of convulsive seizures, evolving into status epilepticus in 3. In 3 patients a borderline cognitive level or intellectual disability were diagnosed after the onset of epilepsy, and 2 had behavioral problems impacting their quality of life. MTS and long-term focal epilepsy, along with potential cognitive and behavioral disorders, are not uncommon in older pediatric patients following PRES.

Quality of life and its determinants in patients with drug resistant focal epilepsy

Objective: to determine the factors influencing quality of life (QoL) in patients with drug-resistant focal epilepsy (DRFE). Material and methods. 111 adult patients with DRFE were included in the study. Quality of life was measured using the Quality Of Life In Patients with Epilepsy – 31 questionnaire (QOLIE-31). The severity of the disease (frequency and subjective assessment of the severity of seizures), the effect of pharmacotherapy (drug load and composition of the treatment regimen), the social status of patients, comorbid conditions (anxiety and depressive disorders, pathological fatigue) were assessed. Results. In the studied sample, a pronounced decrease in QoL was shown, the median of the final QOLIE-31 score was 65.4 points (interquartile range 53.0–72.6 points). A statistically significant decrease in QoL was found in subgroups of patients with seizures during the previous three months; taking carbamazepine or benzobarbital; with anxiety and depressive disorders; with pathological fatigue; and in unemployed patients. A multiple linear regression model (R2=0.66) was developed, which included the following determinants: Fatigue Severity Scale, Liverpool Seizure Severity Scale, and the risk of depression according to the NDDI-E questionnaire. Conclusion. In patients with drug-resistant focal epilepsy, there is a pronounced decrease in the quality of life due to combination of factors associated with the characteristics of the disease, treatment, comorbidities, and social status. The key QoL determinants in patients with DRFE are pathological fatigue, anxiety and depression, and subjective severity of epileptic seizures; employment is a positive factor. The role of epileptic seizures frequency in QoL formation in these patients requires further research.

Pre-ictal heart rate variability alterations in focal onset seizures and response to vagus nerve stimulation

PurposeVagus nerve stimulation (VNS) is an effective and well-known treatment for drug resistant epilepsy (DRE) patients since 1997, yet prediction of treatment response before implantation is subject of ongoing research. Neuroimaging and neurophysiological studies investigating the vagal afferent network in resting state documented that differences in between epilepsy patients were related to treatment response. This study investigated whether an event-related parameter, pre-ictal heart rate variability (HRV) is associated with response to VNS therapy. MethodsDRE patients underwent video-electroencephalography (EEG) recording before VNS implantation. HRV parameters (time, non-linear and frequency domain) were assessed for every seizure during two 10 min timeframes: baseline (60 min before seizure onset) and pre-ictal (10 min before seizure onset). Pre-ictal HRV parameter alterations were correlated with VNS response after one year of VNS therapy and seizure characteristics (temporal/extratemporal, left/right or bilateral). Results104 seizures from 22 patients were evaluated. Eleven patients were VNS responders with a seizure frequency reduction of ≥ 50 % after one year of VNS. In VNS responders no changes in HRV parameters were found while in VNS non-responders the time domain and non-linear HRV variables decreased significantly (p = 0.024, p = 0.005, p = 0.005) during the pre-ictal time frame. 10/11 VNS non-responders had a seizure lateralization to the left compared to 4/11 VNS responders. ConclusionVNS non-responders were characterized by a significant decrease of pre-ictal HRV (time domain/non-linear variables) suggesting a sudden autonomic imbalance probably due to an impaired central autonomic function that makes it at the same time unlikely to respond to VNS.

Comparative contribution of magnetoencephalography (MEG) and single-photon emission computed tomography (SPECT) in pre-operative localization for epilepsy surgery: A prospective blinded study

PurposeThe aim of this study was to compare the diagnostic value and accuracy of ictal SPECT and inter-ictal magnetoencephalography (MEG) in localizing the site for surgery in persons with drug resistant epilepsy. MethodThis was a prospective observational study. Patients expected to undergo epilepsy surgery were enrolled consecutively and the localization results from different imaging modalities were discussed in an epilepsy surgery meet. Odds ratio of good outcome (Engel I) were calculated in patients who underwent surgery in concordance with MEG and SPECT findings. Post-surgical seizure freedom lasting at least 36 months or more was considered the gold standard for determining the diagnostic output of SPECT and MEG. ResultsMEG and SPECT were performed in 101 and 57 patients respectively. In 45 patients SPECT could not be done due to delay in injection or technical factors. The accuracy of MEG and SPECT in localizing the epileptogenic zone was found to be 74.26 % and 78.57 % respectively. The diagnostic odds ratio for Engel I surgical outcome was reported as 2.43 and 5.0 for MEG and SPECT respectively. The diagnostic odds ratio for MEG in whom SPECT was non-informative was found to be 6.57 [95 % CI 1.1, 39.24], although it was not significantly associated with good surgical outcome. MEG was useful in indicating sites for SEEG implantation. ConclusionSPECT was found to be non-informative for most patients, but reported better diagnostic output than MEG. MEG may be a useful alternative for patients in whom SPECT cannot be done or was non-localizing.

Tongue as a Wire? Glossokinetic Artifact and Insights From Intracranial EEG.

Glossokinetic artifact (GKA) is a well-known scalp EEG artifact characterized by deflections within the delta to low-theta frequency bands and dynamic polarity typically attributed to the direction of tongue movement. This study aims to investigate intracranial EEG correlations of scalp-GKA. If the tongue is a dipole, per the conventional view, then volume-conducted deflections are expected in the nearest frontal intracranial EEG contacts. Simultaneous scalp and intracranial EEG recordings were evaluated in five consecutive medically resistant epilepsy patients at Yale Epilepsy Center in 2017 and 2018, who had classic GKA deflections on scalp EEG. The EEG was sampled at 2,048 to 4,096 Hz and analyzed visually, using a reference placed in the diploic space or over the convexity, and confirmed quantitatively by a statistical framework. Ten GKA deflections were analyzed per case. The medians of age at the time of recording, contacts per case, and amplitude of scalp GKA deflections were 35 years (range: 20-41 years), 171 contacts (range: 165-241 contacts), and 56 μV (range: 51-72 μV), respectively. There were no slow discharges in the frontal intracranial EEG contacts synchronized with the scalp GKA, either in the delta (1-3 Hz) or in the sub-delta (0.1-1 Hz) bands. However, the expected physiologic attenuation of alpha and beta rhythms and the emergence of high-gamma activity were observed over the peri-Rolandic regions in the invasive recordings. The traditional view of the tongue as a dipole generator of scalp GKA is simplistic and does not account for the findings reported herein. The tongue most probably shunts other scalp and soft-tissue currents. Knowledge of tongue potentials is of interest in the education and the design of tongue-computer interfaces.

Clinical safety of intracranial EEG electrodes in MRI at 1.5 T and 3 T: a single-center experience and literature review.

Intracranial electroencephalography (EEG) can be a critical part of presurgical evaluation for drug resistant epilepsy. With the increasing use of intracranial EEG, the safety of these electrodes in the magnetic resonance imaging (MRI) environment remains a concern, particularly at higher field strengths. However, no studies have reported the MRI safety experience of intracranial electrodes at 3 T. We report an MRI safety review of patients with intracranial electrodes at 1.5 and 3 T. One hundred and sixty-five consecutive admissions for intracranial EEG monitoring were reviewed. A total of 184 MRI scans were performed on 135 patients over 140 admissions. These included 118 structural MRI studies at 1.5 T and 66 functional MRI studies at 3 T. The magnetic resonance (MR) protocols avoided the use of high specific energy absorption rate sequences that could result in electrode heating. The intracranial implantations included 114 depth, 15 subdural, and 11 combined subdural and depth electrodes. Medical records were reviewed for patient-reported complications and radiologic complications related to these studies. Pre-implantation, post-implantation, and post-explantation imaging studies were reviewed for potential complications. No adverse events or complications were seen during or after MRI scanning at 1.5 or 3 T apart from those attributed to electrode implantation. There was also no clinical or imaging evidence of worsening of pre-existing implantation-related complications after MR imaging. No clinical or radiographic complications are seen when performing MRI scans at 1.5 or 3 T on patients with implanted intracranial EEG electrodes while avoiding high specific energy absorption rate sequences.

Evaluation of serum ghrelin, nesfatin-1, irisin, and vasoactive intestinal peptide levels in temporal lobe epilepsy patients with and without drug resistance: a cross-sectional study.

Epilepsy is a common disorder that affects the nervous systems of 1% of worldwide population. In epilepsy, one-third of patients are unresponsive to current drug therapies and develop drug-resistant epilepsy. Alterations in ghrelin, nesfatin-1, and irisin levels with epilepsy were reported in previous studies. Vasoactive intestinal peptide is among the most common neuropeptides in the hippocampus, which is the focus of the seizures in temporal lobe epilepsy. However, there is also lack of evidence of whether these four neuropeptide levels are altered with drug resistant temporal lobe epilepsy or not. The aim herein was the evaluation of the serum levels of nesfatin-1, ghrelin, irisin, and Vasoactive intestinal peptide in drug-resistant temporal lobe epilepsy patients and temporal lobe epilepsy (TLE) without drug resistance, and to compare them to healthy controls. This cross-sectional study group included 58 temporal lobe epilepsy patients (24 with drug resistant temporal lobe epilepsy and 34 with temporal lobe epilepsy who were not drug-resistant) and 28 healthy subjects. Nesfatin-1, ghrelin, irisin, and Vasoactive intestinal peptide serum levels were determined using enzyme-linked immunosorbent assay. The serum ghrelin levels of patients with drug resistant temporal lobe epilepsy were seen to have significantly decreased when compared to those of the control group (p<0.05). Serum nesfatin-1, vasoactive intestinal peptide, and irisin levels were seen to have decreased in the drug resistant temporal lobe epilepsy group when compared to those of the control and temporal lobe epilepsy groups; however, the difference was non-significant (p>0.05). The results herein suggested that ghrelin might contribute to the pathophysiology of drug resistant temporal lobe epilepsy. However, further studies are needed to confirm this hypothesis.

Responsive Vagus Nerve Stimulation for Drug Resistant Epilepsy: A Review of New Features and Practical Guidance for Advanced Practice Providers.

Vagus nerve stimulation (VNS) is a safe and effective therapy that has been available for over 20 years for adults and children with drug resistant epilepsy (DRE). Since U.S. Food and Drug Administration approval in 1997, VNS has been implanted in over 100,000 patients including over 30,000 children as an adjunctive therapy in reducing the frequency of seizures in patients 4 years of age and older with focal seizures that are refractory to antiseizure medications. VNS Therapy® has evolved over time and currently offers closed-loop, responsive stimulation as well as advanced features that streamline dosing and patient management. Advanced Practice Providers (APPs) such as nurse practitioners, physician assistants and clinical nurse specialists are integral in a comprehensive healthcare team, and dedicated VNS clinics have formed at comprehensive epilepsy centers across the world that are often managed by APPs. This approach improves access, education, and continuity of care for those with VNS or those considering VNS. Here we provide a review for APPs on the VNS Therapy® system focused on new features, dosing, and troubleshooting strategies with the goal to provide guidance to those managing VNS patients.