Nonlesional Epilepsy Research Articles

MEG Node Degree Differences in Patients with Focal Epilepsy vs. Controls-Influence of Experimental Conditions.

Drug-resistant epilepsy can be most limiting for patients, and surgery represents a viable therapy option. With the growing research on the human connectome and the evidence of epilepsy being a network disorder, connectivity analysis may be able to contribute to our understanding of epilepsy and may be potentially developed into clinical applications. In this magnetoencephalographic study, we determined the whole-brain node degree of connectivity levels in patients and controls. Resting-state activity was measured at five frequency bands in 15 healthy controls and 15 patients with focal epilepsy of different etiologies. The whole-brain all-to-all imaginary part of coherence in source space was then calculated. Node degree was determined and parcellated and was used for further statistical evaluation. In comparison to controls, we found a significantly higher overall node degree in patients with lesional and non-lesional epilepsy. Furthermore, we examined the conditions of high/reduced vigilance and open/closed eyes in controls, to analyze whether patient node degree levels can be achieved. We evaluated intraclass-correlation statistics (ICC) to evaluate the reproducibility. Connectivity and specifically node degree analysis could present new tools for one of the most common neurological diseases, with potential applications in epilepsy diagnostics.

The role of stereo-electroencephalography to localize the epileptogenic zone in children with nonlesional brain magnetic resonance imaging

ObjectiveThis study aimed to assess the clinical outcome and outcome predictive factors in pediatric epilepsy patients evaluated with stereo-electroencephalography (SEEG). MethodsThirty-eight patients who underwent SEEG implantation at the Pediatric Epilepsy Center in New York Presbyterian Hospital between June 2014 and December 2019 were enrolled for retrospective chart review. Postoperative seizure outcomes were evaluated in patients with at least 12-months follow up. Meta-analysis was conducted via electronic literature search of data reported from 2000 to 2020 to evaluate significant surgical outcome predictors for SEEG evaluation in the pediatric population. ResultsIn the current case series of 25 postsurgical patients with long-term follow up, 16 patients (64.0%) were seizure free. An additional 7 patients (28.0%) showed significant seizure improvement and 2 patients (8.0%) showed no change in seizure activity. Patients with nonlesional magnetic resonance imaging (MRI) achieved seizure freedom in 50% (5/10) of cases. By comparison, 73% (11/15) of patients with lesional MRI achieved seizure freedom.Out of 12 studies, 158 pediatric patients were identified for inclusion in a meta-analysis of the effectiveness of SEEG. Seizure freedom was reported 54.4% (n = 86/158) of patients at last follow up. Among patients with nonlesional MRI, 45% (n = 24) achieved seizure freedom compared with patients with lesional MRI findings (61.2%, n:= 60) (p = 0.02). The risk for seizure recurrence was 2.15 times higher [95% confidence interval [CI] 1.06–4.37, p = 0.033] in patients diagnosed with nonlesional focal epilepsy compared to those with lesional epilepsy [ 1.49 (95% CI 1.06–2.114, p = 0.021]. ConclusionEvaluation by SEEG implantation in pediatric epilepsy is effective in localizing the epileptogenic zone with favorable outcome. Presence of a non-lesional brain MRI was associated with lower chances of seizure freedom. Further research is warranted to improve the efficacy of SEEG in localizing the epileptogenic zone in pediatric patients with non-lesional brain MRI.

Underutilization of advanced presurgical studies and high rates of vagus nerve stimulation for drug-resistant epilepsy: a single-center experience and recommendations.

Epilepsy surgery continues to be profoundly underutilized despite its safety and effectiveness. We sought to investigate factors that may contribute to this phenomenon, with a particular focus on the antecedent underutilization of appropriate preoperative studies. We reviewed patient data from a pediatric epilepsy clinic over an 18-month period. Patients with drug-resistant epilepsy (DRE) were categorized according to brain magnetic resonance imaging (MRI) findings (lesional, MRI-negative, or multifocal abnormalities) and type of epilepsy diagnosis based on semiology and electroencephalography (EEG) (focal or generalized). We then analyzed the rates of diagnostic test utilization, surgical referral, and subsequent epilepsy surgery as well as vagus nerve stimulation (VNS). Of the 249 patients with a diagnosis of epilepsy, 138 (55.4%) were found to have DRE. Excluding the 10 patients with DRE who did not undergo MRI, 76 patients (59.4%) were found to be MRI-negative (non-lesional epilepsy), 37 patients (28.9%) were found to have multifocal abnormalities, and 15 patients (11.7%) were found to have a single epileptogenic lesion on MRI (lesional epilepsy). Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) were each completed in nine patients (7.0%) and magnetoencephalography (MEG) in four patients (3.1%). Despite the low utilization rate of adjunctive studies, over half (56.3%) ultimately underwent VNS alone, and 8.6% ultimately underwent definitive intracranial resection or disconnection surgery. The underutilization of appropriate non-invasive, presurgical testing in patients with focal DRE may in part explain the continued underutilization of definitive, resective/disconnective surgery. For patients without access to a high-volume, multidisciplinary surgical epilepsy center, adjunctive presurgical studies [e.g., PET, SPECT, MEG, electrical source imaging (ESI), EEG-functional magnetic resonance imaging (fMRI)], even when available, are rarely ordered, and this may contribute to excessive rates of VNS in lieu of definitive intracranial surgery.

Inferior temporal electrodes in 24-h EEG

To improve the sensitivity of the EEG in the diagnosis and classification of seizures or epilepsy, long-term recording with inferior temporal electrodes are recommended. The spatial distribution of epileptiform discharges from 24‑h EEG with 25electrodes (10-20, extended by F9/F10, T9/T10, P9/P10) was retrospectively analyzed in 25cases. Maximum negativity was located below the 10-20 electrodes in 84%. Epileptiform discharges were more clearly detected on inferior temporal electrodes in 64%. In the intention-to-test population of 77patients the number needed to test with extra electrodes was estimated as5. Recording EEG with 25electrodes for 24 h improves the detection and localization of temporal epileptiform discharges also in geriatric patients with suspected nonlesional epilepsy.

Drug-resistant 'Non-Lesional' Visual Sensitive Epilepsies of Childhood - Electroclinical Phenotype-Genotype Associations.

Sporadic nonlesional intractable visual-sensitive epilepsies of childhood represent a challenging subset of epilepsies in terms of management and prognostication given a propensity to evolve as epileptic encephalopathy. To study the genetic heterogeneity of drug-resistant visual sensitive epilepsy of childhood. A retrospective chart review was conducted on patients in the pediatric age group between 2016 and 2018, with drug-resistant epilepsy (DRE) and video electro encephalography (VEEG) documented reflex photosensitivity, eye-condition sensitivity. Those patients who underwent genetic testing with targeted next-generation sequencing using an epilepsy gene panel were selected. During the study period, out of 96 patients who underwent genetic testing, 4 patients (4.17%) with sporadic DRE presented with clinical phenotypes ranging from myoclonic-atonic epilepsy, generalized epilepsy with eyelid myoclonia as well as febrile and unprovoked seizures, along with visual sensitivity. Video EEG documented abnormalities ranged from occipital, posterior-cortex and generalized discharges with "eyes-closed state" triggered, self-induced "smart-phone" triggered, photosensitive focal-onset and generalized myoclonic seizures. Accompanying developmental impairment was noted. These patients who were investigated with clinical exome sequencing were detected to have mutations in not only SCN1A genes (pathogenic exonic and intronic variants) but also CHD2 (pathogenic) and CACNA1H genes (a familial febrile-seizure susceptibility variant of unknown significance). The series highlights the complex genetics of drug-resistant visual-sensitive epilepsy of childhood. Such genotype-phenotype associations throw light on the role of ion-channel and non-ion channel genes on reflex epileptogenesis in this group of patients.

Seizure control does not predict hippocampal subfield volume change in children with focal drug-resistant epilepsy.

Background and purposeRecurrent seizures have been reported to induce neuronal loss in the hippocampus. It is unclear whether seizure control influences hippocampal volume. The aims of this study were to determine if there was a change in total or subfield hippocampal volume over time in children with focal drug-resistant epilepsy, and whether seizure control influenced total or subfield hippocampal volumes.MethodsUsing FreeSurfer’s automated segmentation of brain magnetic resonance imaging scans, we calculated the total and subfield (including CA1, CA3, CA4, subiculum, presubiculum, parasubiculum, molecular layer and dentate gyrus) hippocampal volumes of children with non-lesional focal epilepsy. Seizure frequency and hippocampal volumes were assessed at baseline and follow-up. Patients were classified into those who were seizure free or have improvement in seizures (group 1) and those with no improvement in seizures (group 2) at follow-up.ResultsThirty-seven patients were included, with mean age 10.31 ± 3.68 years at baseline. The interval between the two magnetic resonance imaging scans was 2.59 ± 1.25 years. There was no significant difference in the total and subfield hippocampal volumes for the whole cohort at follow-up compared to baseline (all P > 0.002). Seizure control of the two groups did not predict total or subfield hippocampal volume, after controlling for baseline volume, age, severity of seizure frequency at baseline and time interval between the magnetic resonance imaging scans (all P > 0.002).ConclusionWe have found that total and subfield hippocampal volumes did not change, and seizure control did not predict hippocampal volumes at follow-up in children with drug-resistant epilepsy.

Epilepsy in the mTORopathies: opportunities for precision medicine.

The mechanistic target of rapamycin signalling pathway serves as a ubiquitous regulator of cell metabolism, growth, proliferation and survival. The main cellular activity of the mechanistic target of rapamycin cascade funnels through mechanistic target of rapamycin complex 1, which is inhibited by rapamycin, a macrolide compound produced by the bacterium Streptomyces hygroscopicus. Pathogenic variants in genes encoding upstream regulators of mechanistic target of rapamycin complex 1 cause epilepsies and neurodevelopmental disorders. Tuberous sclerosis complex is a multisystem disorder caused by mutations in mechanistic target of rapamycin regulators TSC1 or TSC2, with prominent neurological manifestations including epilepsy, focal cortical dysplasia and neuropsychiatric disorders. Focal cortical dysplasia type II results from somatic brain mutations in mechanistic target of rapamycin pathway activators MTOR, AKT3, PIK3CA and RHEB and is a major cause of drug-resistant epilepsy. DEPDC5, NPRL2 and NPRL3 code for subunits of the GTPase-activating protein (GAP) activity towards Rags 1 complex (GATOR1), the principal amino acid-sensing regulator of mechanistic target of rapamycin complex 1. Germline pathogenic variants in GATOR1 genes cause non-lesional focal epilepsies and epilepsies associated with malformations of cortical development. Collectively, the mTORopathies are characterized by excessive mechanistic target of rapamycin pathway activation and drug-resistant epilepsy. In the first large-scale precision medicine trial in a genetically mediated epilepsy, everolimus (a synthetic analogue of rapamycin) was effective at reducing seizure frequency in people with tuberous sclerosis complex. Rapamycin reduced seizures in rodent models of DEPDC5-related epilepsy and focal cortical dysplasia type II. This review outlines a personalized medicine approach to the management of epilepsies in the mTORopathies. We advocate for early diagnostic sequencing of mechanistic target of rapamycin pathway genes in drug-resistant epilepsy, as identification of a pathogenic variant may point to an occult dysplasia in apparently non-lesional epilepsy or may uncover important prognostic information including, an increased risk of sudden unexpected death in epilepsy in the GATORopathies or favourable epilepsy surgery outcomes in focal cortical dysplasia type II due to somatic brain mutations. Lastly, we discuss the potential therapeutic application of mechanistic target of rapamycin inhibitors for drug-resistant seizures in GATOR1-related epilepsies and focal cortical dysplasia type II.

Intracranial EEG and laser interstitial thermal therapy in MRI-negative insular and/or cingulate epilepsy: case series.

The goal of this study was to assess the success rate and complications of stereo-electroencephalogra-phy (sEEG) and laser interstitial thermal therapy (LITT) in the treatment of nonlesional refractory epilepsy in cingulate and insular cortex. The authors retrospectively analyzed the treatment response in 9 successive patients who underwent insular or cingulate LITT for nonlesional refractory epilepsy at their center between 2011 and 2019. Localization of seizures was based on inpatient video-EEG monitoring, neuropsychological testing, 3-T MRI, PET scan, magnetoencephalography scan, and/or ictal SPECT scan. Eight patients underwent sEEG, and 1 patient had implantation of both sEEG electrodes and subdural grids for localization of epileptogenic zones. LITT was performed in 5 insular cases (4 left and 1 right) and 3 cingulate cases (all left-sided). One patient also underwent both insular and cingulate LITT on the left side. All of the patients who underwent insular LITT as well as 2 of the 3 who underwent cingulate LITT were right-hand dominant. The patient who underwent insular plus cingulate LITT was also right-hand dominant. Following LITT, 67% of the patients were seizure free (Engel class I) at follow-up (mean 1.35 years, range 0.6-2.8 years). All patients responded favorably to treatment (Engel class I-III). Two patients developed small intracranial hemorrhages during the sEEG implantation that did not require surgical management. One patient developed a large intracranial hemorrhage during an insular LITT procedure that did require surgical management. That patient experienced aphasia, incoordination, and hemiparesis, which resolved with inpatient rehabilitation. No permanent neurological deficits were noted in any of the patients at last follow-up. Neuropsychological status was stable in this cohort before and after LITT. sEEG can be safely used to localize seizures originating from insular and cingulate cortex. LITT can successfully treat seizures arising from these deep-seated structures. The insula and cingulum should be evaluated more frequently for seizure onset zones.

Adopting MR-guided stereotactic laser ablations for epileptic lesions: initial clinical experience and lessons learned.

MR-guided laser interstitial thermal therapy (MRgLITT) is a minimally invasive technique for ablating brain lesions under real-time MRI feedback and control of the ablation process. The Medtronic Visualase system was recently approved for use in Europe and Israel. We report our initial technical experience using the system in the first 16 cases in which the system was used to ablate focal epileptogenic lesions. We included all consecutive patients with intractable epilepsy who underwent MRgLITT procedures between 2018 and 2020. We reviewed medical charts and imaging studies of patients. Post-ablation MRIs were used to calculate ablation volumes. Seventeen MRgLITT procedures were performed in 16 patients. One cooling catheter/laser fiber assemblies were placed per patient. Indications for surgery were intractable epilepsy due to TLE (n = 7),suspected low-grade glioma (n = 4), radiological cortical dysplasia (n = 1), hypothalamic hamartoma (n = 1), and MR-negative foci (n = 3). Ablations were made using 30 to 70% of the maximal energy of the Visualase system. We used serial ablations as needed along the tract of the catheter by pulling back the optic fiber; the length of the lesion ranged between 7.4 and 38.1mm. Ablation volume ranged between 0.27 and 6.78 mm3. Immediate post-ablation MRI demonstrated good ablation of the epileptic lesion in 16/17 cases. In one case with mesial temporal sclerosis, no ablation was performed due to suboptimal position of the catheter. That patient was successfully reoperated at a later date. Mean follow-up was 14.9months (± 11.6months). Eleven patients had follow-up longer than 12months. Good seizure control (Engel I, A) was achieved in 7/11 patients (63%) and 1/11 (9%) had significant improvement in seizure frequency (Angle IIIa). Three patients (27%) did not experience improvement in their seizure frequency (Engel IV, B), and one of these patients died during the follow-up period from sudden unexpected death of epilepsy (SUDEP). No immediate or delayed neurological complications were documented in any of the cases during the follow-up period. MRgLITT is a promising technique and can be used safely as an alternative to open resection in both lesional and non-lesional intractable epilepsy cases. In our local series, the success rate of epilepsy surgery was comparable to recent publications.

Volumetric glutamate imaging (GluCEST) using 7T MRI can lateralize nonlesional temporal lobe epilepsy: A preliminary study.

IntroductionDrug‐resistant epilepsy patients show worse outcomes after resection when standard neuroimaging is nonlesional, which occurs in one‐third of patients. In prior work, we employed 2‐D glutamate imaging, Glutamate Chemical Exchange Saturation Transfer (GluCEST), to lateralize seizure onset in nonlesional temporal lobe epilepsy (TLE) based on increased ipsilateral GluCEST signal in the total hippocampus and hippocampal head. We present a significant advancement to single‐slice GluCEST imaging, allowing for three‐dimensional analysis of brain glutamate networks.MethodsThe study population consisted of four MRI‐negative, nonlesional TLE patients (two male, two female) with electrographically identified left temporal onset seizures. Imaging was conducted on a Siemens 7T MRI scanner using the CEST method for glutamate, while the advanced normalization tools (ANTs) pipeline and the Automated Segmentation of the Hippocampal Subfields (ASHS) method were employed for image analysis.ResultsVolumetric GluCEST imaging was validated in four nonlesional TLE patients showing increased glutamate lateralized to the hippocampus of seizure onset (p = .048, with a difference among ipsilateral to contralateral GluCEST signal percentage ranging from −0.05 to 1.37), as well as increased GluCEST signal in the ipsilateral subiculum (p = .034, with a difference among ipsilateral to contralateral GluCEST signal ranging from 0.13 to 1.57).ConclusionsThe ability of 3‐D, volumetric GluCEST to localize seizure onset down to the hippocampal subfield in nonlesional TLE is an improvement upon our previous 2‐D, single‐slice GluCEST method. Eventually, we hope to expand volumetric GluCEST to whole‐brain glutamate imaging, thus enabling noninvasive analysis of glutamate networks in epilepsy and potentially leading to improved clinical outcomes.

Perampanel treatment in highly drug-resistant epilepsies including nonsurgical candidates and failed surgery

ObjectiveTo evaluate the effectiveness and tolerability of perampanel (PER) treatment for patients with highly drug-resistant epilepsies (HDRE) including nonsurgical candidates and failed surgery in real-world setting. MethodsAll patients who were treated with PER during June 2015 to August 2019 were selected. Primary outcomes were percentage of seizure reduction, responder rate, and seizure freedom rate. Seizure frequency after taking PER at 3 and 12 months were compared with baseline seizure frequency within the same time period prior to starting PER. Secondary outcomes were retention rate, side effects, and predictors for a response to PER. Descriptive statistics and the Kernel regression model were employed. ResultsForty-one patients received PER treatment during the study period. Six patients who had no baseline seizure frequency recordings were excluded, for a total of 35 patients included for analysis. Mean age was 40.06 years (SD 12.34). All were highly resistant to several antiseizure drugs (ASDs) with a median number of previously failed ASDs of 8 items. Eleven, 16, 5, and 3 patients were lesional, nonlesional focal epilepsy, nonsurgical candidate, and failed surgery, respectively. At 3 months after PER treatment, the median percentage of seizure reduction was 20 % (-35.71, 100), the responder rate was 22.86 % (8/35), and the seizure freedom rate was 17.14% (6/35). At 12 months after PER treatment, the corresponding outcomes were 25% (-20.57, 91.60), 22.58% (7/31), and 9.68% (3/31), respectively. Retention rates at 3 and 12 months were 100% and 91.43% (32/35), respectively. Nineteen patients (54.29%) experienced side effects from PER. Side effects were somnolence (6/35), dizziness (3/35), irritability (2/35), and ataxia (2/35), and one each for weight loss, nausea, headache, insomnia, verbal aggressivity, and depression. Median duration for 2-mg dose increment was 2.2 months. ConclusionsIn real-world practice, slow-titration PER regimen is well-tolerable and shows benefit in helping control seizures in patients with very difficult-to-treat HDRE.

Magnetic source imaging in presurgical evaluation of paediatric focal drug-resistant epilepsy and its predictive value of surgical outcome in lesional cases: A single-centre experience from South India

ObjectiveThis study aims to evaluate the utility of magnetoencephalography in presurgical planning and in predicting post-surgical seizure outcome. MethodsThis study included a cohort of 231 children (1–18 years) with focal drug-resistant epilepsy who underwent MEG as a part of their presurgical workup. Characteristics of MEG observations were described in all children. The concordance and agreement of Magnetic Source Imaging (MSI) of interictal discharges (IED) was estimated with either of the 3 subgroups - MRI lesion; presumed epileptogenic zone (EZ); or resection cavity. In operated children group, MEG dipole characteristics between good and poor outcome groups were assessed. ResultsA total of 153 cases (66.2%) showed frequent IEDs (60 spikes/60 min). Of the 173 cases where MSI showed clusters (74.9%), 151 had lesions and 22 were non-lesional. amongst patients with lesional epilepsy and MEG clusters, class I concordance (MEG localization either completely included or overlapped at least 60% with the MRI lesion) was seen in 60.92% with a Cohen's kappa of 0.608. In non-lesional epilepsy, class I concordance of MEG with presumed EZ was found in (81.81%) with an agreement of 0.317. Fifty-three children underwent surgery of whom 39 (73.58%) showed a good outcome (Engel I). In operated children, concordance between MEG focus and resection cavity was observed in 23 (58.97%) with good outcome and in 12 (86.72%) with poor outcome with no significant difference (p>0.05). However, MEG cluster regular organization and clusterectomy are associated with good seizure outcome postoperatively (p< 0.05). Presence of scatters were associated with poor outcome (p<0.05) in children with focal cortical dysplasia. ConclusionsMEG provides useful information that can serve as a biomarker for prognosticating the surgical outcome in paediatric epilepsy. Cluster removal and regular cluster organization shows predictive power in post-surgical prognostication in children and the presence of scatters predicts poor outcome in children with focal cortical dysplasia.

Assessing the role of rare genetic variants in drug-resistant, non-lesional focal epilepsy.

ObjectiveResistance to antiseizure medications (ASMs) is one of the major concerns in the treatment of epilepsy. Despite the increasing number of ASMs available, the proportion of individuals with drug‐resistant epilepsy remains unchanged. In this study, we aimed to investigate the role of rare genetic variants in ASM resistance.MethodsWe performed exome sequencing of 1,128 individuals with non‐familial non‐acquired focal epilepsy (NAFE) (762 non‐responders, 366 responders) and were provided with 1,734 healthy controls. We undertook replication in a cohort of 350 individuals with NAFE (165 non‐responders, 185 responders). We performed gene‐based and gene‐set‐based kernel association tests to investigate potential enrichment of rare variants in relation to drug response status and to risk for NAFE.ResultsWe found no gene or gene set that reached genome‐wide significance. Yet, we identified several prospective candidate genes – among them DEPDC5, which showed a potential association with resistance to ASMs. We found some evidence for an enrichment of truncating variants in dominant familial NAFE genes in our cohort of non‐familial NAFE and in association with drug‐resistant NAFE.InterpretationOur study identifies potential candidate genes for ASM resistance. Our results corroborate the role of rare variants for non‐familial NAFE and imply their involvement in drug‐resistant epilepsy. Future large‐scale genetic research studies are needed to substantiate these findings.

Awake craniotomy for epilepsy surgery on eloquent speech areas: a single-centre experience.

In patients with intractable partial epilepsy who are eligible for epilepsy surgery, the best seizure control requires complete resection of the epileptogenic zone. When the epileptogenic zone is located very near to, or even with the eloquent cortex, this can be a challenge. In this study, we investigated the efficacy of awake craniotomy techniques to completely resect these epileptic zones while preserving the neural functions. We conducted a retrospective cohort study of 17 consecutive patients with intractable partial seizures of different aetiologies (non-lesional epilepsy [n=3], tuberous sclerosis [n=1], hypoxic ischaemic insult [n=1], dysembryoplastic neuroepithelial tumours [DNET] [n=2], focal cortical dysplasia type 2 [FCD] [n=4], and other malformations of cortical development [n=6]), located in eloquent language cortex (frontal [n=7], insular [n=5], and latero-temporal [n=5] regions). All patients were operated on between 2010 and 2019 for resective epilepsy surgery under awake conditions, with the aid of direct cortical stimulation. This report aimed to study the feasibility, efficacy and limitations of using the awake craniotomy technique for surgical resections of epileptogenic zones involving eloquent language cortex. Postoperative epilepsy control and neurological function were assessed and followed. The mean follow-up period was 5.7 years. In one patient, the surgery was aborted before resection. In the other patients, Engel Class I was achieved in seven patients (43.75%) and Engel Class II in four patients (25%), and worthwhile improvement (Engel Class I and II) was achieved in 11 patients (68.75%). Postoperative neurological deficits were encountered in four patients (23.5%). However, all these deficits were regressive and were absent at the last follow-up visit. Using the awake craniotomy technique, seizure freedom can be achieved in a high proportion of patients with epileptogenic zones located in language areas, who were previously considered only candidates for palliative measures.

Arterial Spin Labeling is a Useful MRI Method for Presurgical Evaluation in MRI-Negative Focal Epilepsy.

Arterial spin labeling (ASL) is an MRI technique measuring brain perfusion using magnetically labeled blood as a tracer. The clinical utility of ASL for presurgical evaluation in non-lesional epilepsy as compared with the quantitative analysis of interictal [18F] fluorodeoxyglucose PET (FDG-PET) was studied. In 10 patients (4 female; median age 29years) who underwent a complete presurgical evaluation followed by surgical resection, the presurgical FDG-PET and ASL scans were compared with the resection masks using asymmetry index (AI) maps. The positive predictive value (PPV) and sensitivity (SEN), were calculated from the number of voxels inside the mask (true positive), and outside the mask (false positive). The comparison of the PPVs showed better PPV in 6 patients using ASL and in 2 patients with PET. SEN was better in 4 patients using ASL and in 5 patients with PET. According to the Wilcoxon signed rank test for PPV (p = 0.74) and for SEN (p = 0.43), these methods have similar predictive power. ASL is a useful method for presurgical evaluation in non-lesional epilepsy. The main benefits of ASL over PET are that it avoids radiation exposure for patients, and it offers lower costs, higher availability, and better time efficiency.

Seizure outcome after epilepsy surgery for patients with normal MRI: A Single center experience

ObjectiveTo analyze the surgical outcome in non-lesional intractable focal epilepsies in our center and to find possible predictors for better outcome. MethodsThis is a retrospective study for 40 adult patients with intractable focal epilepsy following at KFSHRC-Riyadh, who underwent presurgical evaluation followed by resective surgery and continued follow up for a minimum of 2 years. The surgery outcome was evaluated based on the type of surgical procedure and histopathology results. ResultsOut of all 40 patients studied, seizure freedom was achieved in 19 (47.5 %) and 17 (42.5 %) patients at the first and second year respectively in all non-lesional cases. Seizure freedom in non-lesional temporal lobe surgery was achieved in 10 (45 %) of patients at 2 years, 5 (38 %) in non-lesional frontal lobe patients at 2 years and 8 (44 %), 7 (38 %) for all extratemporal at 1 and 2 years respectively. Good prognosis was seen in patients with localized positron emission tomography (PET), had no aura and had a clear ictal onset either on scalp electroencephalogram (EEG) or subdural invasive electroencephalogram. SignificanceThe best surgical outcome is achievable in patients with non-lesional focal epilepsy. This study highlights the prognostic value of the PET scan and ictal scalp/subdural invasive EEG.

Surgical treatment of nonlesional temporal lobe epilepsy

PurposeOne-third of the patients with drug-resistant temporal lobe epilepsy (TLE) have a normal MRI, but there are only a few studies regarding the surgical outcomes and the efficacy of anterior temporal lobectomy (ATL) in patients with nonlesional TLE. The objective of this study is to evaluate the surgical outcomes and efficacy of ATL in patients with nonlesional TLE. MethodsWe included 77 consecutive patients without MRI-identifiable lesions who had undergone surgical resection for drug-resistant TLE. We performed univariate and multivariate logistic regression analyses to identify the predictors of surgical outcomes, and the efficacy of ATL in patients with nonlesional TLE. ResultsMore than two-thirds of patients (51/76, 67.3 %) had achieved seizure freedom at the last follow-up. Presence of oroalimentary automatism, localized hypometabolism in FDG-PET, and concordant results in presurgical evaluations were associated with better surgical outcomes. Only 15 out of 77 patients (19.2 %) with nonlesional TLE were treated with ATL, and the surgically resected areas were located within the resection margin of ATL in one-third of the patients (26/77, 33.8 %). Patients with auras suggesting neocortical ictal onset and lateralizing semiological features had a higher chance that their potentially epileptogenic areas were located beyond or outside the resection margin of ATL. ConclusionOur study showed that the potentially epileptogenic areas were located beyond or outside the margin of the ATL in nearly two-thirds of the patients. Several clinical factors may be useful in predicting the location of an epileptogenic area, which can help optimize a surgical strategy in these patients.

Altered functional network connectivity and working memory dysfunction in adolescents with epilepsy.

Adolescents with epilepsy are at risk for deficits in working memory, which could lead to learning difficulties and poor academic outcomes. We used task-based functional magnetic resonance imaging (fMRI) to examine potential disruption in working memory function in adolescents with epilepsy as compared to healthy controls. We recruited 29 adolescents (13-17years) with non-lesional epilepsy and 20 healthy controls. All participants performed an N-back fMRI task and neuropsychological testing. A general linear model approach was used to create group activation maps of N-back fMRI for epilepsy and control groups and both groups combined (p < 0.05 corrected for multiple comparisons). Functionally defined regions of interest (ROIs) were identified based on clusters of combined group activation (z > 5). Subsets of these functional ROIs corresponding to cingulo-opercular and fronto-parietal networks were selected and differences in functional connectivity between the epilepsy and control groups were assessed. Adolescents with epilepsy had significantly poorer working memory scores compared to controls. For the N-back fMRI task, there were no significant differences in group activation. Functional connectivity was significantly reduced between the left frontal operculum and anterior cingulate gyrus (cingulo-opercular network) in adolescents with epilepsy compared to controls. This study demonstrates working memory deficits and an altered pattern of connectivity in brain networks supporting working memory in adolescents with epilepsy. Working memory performance was worse in adolescents with epilepsy; though scores were not directly correlated with reduced connectivity. These results suggest the neural substrates of working memory in adolescents with epilepsy may differ from those in typically-developing adolescents, and require further investigation to understand the reasons for poorer working memory performance.

Cognition in adult patients with newly diagnosed non-lesional temporal lobe epilepsy

ObjectiveTo evaluate whether cognitive performance is affected in newly diagnosed temporal lobe epilepsy (TLE) and to determine the most vulnerable cognitive domains. MethodsIn this baseline longitudinal study, differences in memory and non-memory cognitive functions were assessed using comprehensive neuropsychological test batteries in 21 adult patients with newly diagnosed non-lesional TLE and individually matched controls. In addition, the analyses included ratings of self-perceived emotional status. ResultsThe patients performed more poorly than the control group regarding delayed visual memory (p = 0.013) and executive function tasks related to switching (Trail Making Test and verbal fluency shifting; p = 0.025 and p = 0.03, respectively). We found no differences in verbal learning and memory, attention/working memory/processing speed, and other executive functions. SignificanceOur results show that patients with TLE often have specific cognitive deficits at time of diagnosis, even in the absence of structural brain abnormalities. This supports the hypothesis that memory dysfunction is linked to an underlying pathology rather than to the effect of recurrent seizures, long-term use of anti-seizure medication, or other epilepsy-related factors. As certain executive functions are affected at an early stage, the pathology may involve brain regions beyond the temporal lobe and may comprise larger brain networks. These results indicate the need for greater awareness of cognition at the time of diagnosis of TLE and before initiation of treatment, and integration of neuropsychological assessment into early routine clinical care.

Magnetic resonance imaging (MRI) volumetry in children with nonlesional epilepsy, does it help?

BackgroundEpilepsy is a chronic condition characterized by repeated spontaneous seizures. It affects up to 1% of the population worldwide. Children with magnetic resonance imaging (MRI) negative (or “nonlesional”) focal epilepsy constitute the most challenging pharmacoresistant group undergoing pre-neurosurgical evaluation. Volumetric magnetic resonance imaging (VMRI) is a non-invasive brain imaging technique done to measure the volume and structure of specific regions of the brain. It is useful for many things, but primarily for discovering atrophy (wasting away of body tissue) and measuring its progression. The aim of this study is to assess role of volumetric magnetic resonance imaging in evaluation of nonlesional childhood epilepsy in which no specific findings detected in conventional MRI.ResultsThere were 20 children with normal MRI brain volumetry (33.3%) and 40 children (66.6%) with abnormal MRI brain volumetry.Grey matter volume in the abnormal group was significantly higher (P value was 0.001*) than the normal group (mean ± S.D 934.04 ± 118.12 versus 788.57 ± 57.71 respectively). White matter volume in the abnormal group was significantly smaller (P value was < 0.0001*) than in the normal group (mean ± S.D 217.79 ± 65.22 versus 418.07 ± 103.76 respectively). Right hippocampus CA4-DG volume in the abnormal volume group was found to be significantly smaller (P value < 0.0001*) than that of the normal group volume (mean ± S.D 0.095 ± 0.04 versus 0.32 ± 0.36 respectively). Right hippocampus subiculum volume in the abnormal volume group were found to be significantly smaller (P value was < 0.0001*) than that of the normal group volume (mean ± S.D 0.42 ± 0.11 versus 0.84 ± 0.09 respectively). Thalamus volume in the abnormal group was significantly smaller (P value 0.048*) than in the normal group (mean ± S.D 10.235 ± 3.22 versus 11.82 ± 0.75 respectively). Right thalamus was significantly smaller (P value was 0.028*) than in the normal group (mean ± S.D 5.01 ± 1.62 versus 5.91 ± 0.39 respectively). The sensitivity of the right hippocampus subiculum volume and right hippocampus CA4-DG was 100%. The sensitivity of white matter volume and grey matter volume and thalamus was 85% and 75% and 55% respectively. The specificity of the right hippocampus subiculum volume and right hippocampus CA4-DG was 90% and 90% respectively. The specificity of the right hippocampus subiculum volume and right hippocampus CA4-DG and grey matter volume and white matter volume and total hippocampus and thalamus was 100%. The specificity of brain volume was 60%. The accuracy of the right hippocampus subiculum volume and right hippocampus CA4-DG was 100%. The specificity of white matter volume, grey matter volume, thalamus, total hippocampus, and brain volume was 97%, 87%, 65%, 61%, and 57% respectively.ConclusionVolumetric magnetic resonance imaging is a promising imaging technique that can provide assistance in evaluation of nonlesional pharmacoresistant childhood epilepsy.