Nonlesional Focal Epilepsy Research Articles

Relationship between plasma brain-derived neurotrophic factor levels and neurological disorders: An investigation using Mendelian randomisation

BackgroundAltered brain-derived neurotrophic factor (BDNF) concentrations have been detected in the central nervous system tissues and peripheral blood. These alterations are associated with a series of neurological disorders. ObjectiveTo investigate the potential causal relationships between genetically determined plasma BDNF levels and various neurological diseases using a two-sample Mendelian randomisation study. MethodsWe selected single nucleotide polymorphisms strongly related to plasma BDNF levels as instrumental variables. Within the Mendelian randomisation framework, we used summary-level statistics for exposure (plasma BDNF levels) and outcomes (neurological disorders). ResultsWe observed suggestive evidence of a relation between higher plasma BDNF levels and less risk of nontraumatic intracranial haemorrhage (nITH) (odds ratio [OR] = 0.861, 95 % confidence interval [CI]: 0.774–0.958, P = 0.006, PFDR = 0.078), epilepsy (OR = 0.927, 95 % CI: 0.880–0.976, P = 0.004, PFDR = 0.078), focal epilepsy (OR = 0.928, 95 % CI: 0.874–0.986, P = 0.016, PFDR = 0.139), and non-lesional focal epilepsy (OR = 0.981, 95 % CI: 0.964–0.999, P = 0.041, PFDR = 0.267). Combined with the UK Biobank dataset, the association of plasma BDNF levels with nITH remained significant (OR = 0.88, 95 % CI: 0.81–0.96, P < 0.01). The combined analysis of three consortium datasets demonstrated a considerable impact of plasma BDNF on epilepsy (OR = 0.94, 95 % CI: 0.90–0.98, P < 0.01) and a suggestive impact on focal epilepsy (OR = 0.94, 95 % CI: 0.89–0.99, P = 0.02). However, there was no apparent correlation between plasma BDNF levels and other neurological disorders or related subtypes. ConclusionsOur study supports a possible causal relationship between elevated plasma BDNF levels and a reduced risk of nITH, epilepsy, and focal epilepsy.

Familial occurrence of seizure disorders across MRI defined structural focal epilepsy etiology

BackgroundPrevious studies have established familial occurrence of epilepsy and seizure disorders and early age of epilepsy onset as predictors of genetic epilepsy, but have not evaluated the rate of their occurrence in patients with different epilepsy etiology. Our study determines the distribution of familial occurrence and age of epilepsy onset across structural focal epilepsy (FE) etiology in a large FE cohort. MethodsRecords of 1354 consecutive patients evaluated for epilepsy and seizure disorders in The Neurology Clinic, University Clinical Center of Serbia from 2008 to 2019 were screened for FE. Structural etiology, lobar diagnosis, familial occurrence, and age at epilepsy onset were determined. Patients with a. nonlesional focal epilepsy (NLFE), b. hippocampal sclerosis (HS) and c. congenital or perinatal etiology (CPE) were classified as NAFE, while patients with an identified acquired focal epilepsy (AFE) constituted the control group. ResultsWe identified 965 patients with FE, 329 (34.1 %) with NLFE, 213 (22.1 %) with HS, 174 (18.0 %) with CPE and 249 (25.8 %) with AFE. Familial occurrence was identified in 160 (16.6 %), 19.1 % of patients with NAFE and 9.2 % of AFE (p = 0.003). Patients with NAFE had a younger age of epilepsy onset (13 vs. 18 years, p < 0.001). The highest proportion of familial occurrence was found in patients with NLFE (23.7 %), while the youngest median age of epilepsy onset was identified in patients with HS (12 years) and CPE (11 years). ConclusionPatients with NAFE frequently have familial occurrence of epilepsy and have an earlier age of epilepsy onset than patients with AFE.

Somatic variants as a cause of drug-resistant epilepsy including mesial temporal lobe epilepsy with hippocampal sclerosis.

The contribution of somatic variants to epilepsy has recently been demonstrated, particularly in the etiology of malformations of cortical development. The aim of this study was to determine the diagnostic yield of somatic variants in genes that have been previously associated with a somatic or germline epilepsy model, ascertained from resected brain tissue from patients with multidrug-resistant focal epilepsy. Forty-two patients were recruited across three categories: (1) malformations of cortical development, (2) mesial temporal lobe epilepsy with hippocampal sclerosis, and (3) nonlesional focal epilepsy. Participants were subdivided based on histopathology of the resected brain. Paired blood- and brain-derived DNA samples were sequenced using high-coverage targeted next generation sequencing to high depth (585× and 1360×, respectively). Variants were identified using Genome Analysis ToolKit (GATK4) MuTect-2 and confirmed using high-coverage Amplicon-EZ sequencing. Sequence data on 41 patients passed quality control. Four somatic variants were validated following amplicon sequencing: within CBL, ALG13, MTOR, and FLNA. The diagnostic yield across 41 patients was 10%, 9% in mesial temporal lobe epilepsy with hippocampal sclerosis and 20% in malformations of cortical development. This study provides novel insights into the etiology of mesial temporal lobe epilepsy with hippocampal sclerosis, highlighting a potential pathogenic role of somatic variants in CBL and ALG13. We also report candidate diagnostic somatic variants in FLNA in focal cortical dysplasia, while providing further insight into the importance of MTOR and related genes in focal cortical dysplasia. This work demonstrates the potential molecular diagnostic value of variants in both germline and somatic epilepsy genes.

Clinical characteristics, course and prognosis of Multiple Sclerosis patients with epilepsy. A case control study: MS and epilepsy

Background and purposeAlthough more common than in the general population, seizures are an atypical manifestation of multiple sclerosis (MS) and their pathophysiology is not well understood. This study aims to examine the prevalence, clinical characteristics, brain imaging findings and course of epilepsy, presenting in patients with MS. MethodsObservational retrospective study of MS patients evaluated at a single MS reference center in Buenos Aires, Argentina, between 2011 and 2022, focusing on those who developed epilepsy (EMS). Clinical, demographic, and prognostic factors were evaluated and compared to a control group of non-epileptic MS patients (NEMS). To analyze specific epilepsy characteristics, a second control group of patients with non-lesional focal epilepsy (FNLE) was also included. ResultsTwenty-five patients (18 women), were diagnosed with epilepsy, corresponding to a prevalence of 1.95%. Comparison of brain imaging characteristics between EMS and NEMS patients showed brain atrophy (32% vs 6.1%, p<0.01), as well as cortical (26% vs 4%, p=0.03) and juxtacortical lesions (84% vs 55%, p=0.05), were more frequent in EMS patients. However, after multivariate analysis, cortical atrophy was the only variable linked to a significant increase in risk of epilepsy (OR 24, 95%CI=2.3-200, p<0.01). No significant differences in clinical characteristics, disease activity, disability levels, response to disease modified treatment (DMT) or lack of DMT efficacy were observed between MS patients with or without epilepsy. Most patients received anti-seizure medication (ASM), and seizure control was better in EMS than in FNLE patients (92% vs 58%, p=0.022) with no differences found in drug resistance. We did not find predictors of seizure recurrence in the population studied. ConclusionWe observed a lower prevalence of epilepsy in this group of MS patients, compared to other reported cohorts. Although epilepsy seems to have a benign course in MS patients, cortical atrophy appears to be an important contributor to the development of secondary epilepsy in MS patients. Further investigations will be necessary to identify risk factors or biomarkers predicting increased epilepsy risk in MS.

Breath-Hold-Triggered BOLD fMRI in Drug-Resistant Nonlesional Focal Epilepsy-APilot Study.

Individuals with drug-resistant epilepsy may benefit from epilepsy surgery. In nonlesional cases, where no epileptogenic lesion can be detected on structural magnetic resonance imaging, multimodal neuroimaging studies are required. Breath-hold-triggered BOLD fMRI (bh-fMRI) was developed to measure cerebrovascular reactivity in stroke or angiopathy and highlights regional network dysfunction by visualizing focal impaired flow increase after vasodilatory stimulus. This regional dysfunction may correlate with the epileptogenic zone. In this prospective single-center single-blind pilot study, we aimed to establish the feasibility and safety of bh-fMRI in individuals with drug-resistant non-lesional focal epilepsy undergoing presurgical evaluation. In this prospective study, 10consecutive individuals undergoing presurgical evaluation for drug-resistant focal epilepsy were recruited after case review at amultidisciplinary patient management conference. Electroclinical findings and results of other neuroimaging were used to establish the epileptogenic zone hypothesis. To calculate significant differences in cerebrovascular reactivity in comparison to the normal population, bh-fMRIs of 16healthy volunteers were analyzed. The relative flow change of each volume of interest (VOI) of the atlas was then calculated compared to the flow change of the whole brain resulting in an atlas of normal cerebral reactivity. Consequently, the mean flow change of every VOI of each patient was tested against the healthy volunteers group. Areas with significant impairment of cerebrovascular reactivity had decreased flow change and were compared to the epileptogenic zone localization hypothesis in asingle-blind design. Acquisition of bh-fMRI was feasible in 9/10cases, with one patient excluded due to noncompliance with breathing maneuvers. No adverse events were observed, and breath-hold for intermittent hypercapnia was well tolerated. On blinded review, we observed full or partial concordance of the local network dysfunction seen on bh-fMRI with the electroclinical hypothesis in 6/9cases, including cases with extratemporal lobe epilepsy and those with nonlocalizing 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). This represents the first report of bh-fMRI in individuals with epilepsy undergoing presurgical evaluation. We found bh-fMRI to be feasible and safe, with apromising agreement to electroclinical findings. Thus, bh-fMRI may represent apotential modality in the presurgical evaluation of epilepsy. Further studies are needed to establish clinical utility.

Parasomnia in children and adults as a differential diagnosis to non-lesional focal epilepsy—English version

Parasomnia in children and adults as a differential diagnosis to non-lesional focal epilepsy—English version

Real-world experience with cannabidiol as add-on treatment in drug-resistant epilepsy

PurposeTo evaluate the efficacy and safety of cannabidiol (CBD) for the treatment of epilepsy in a real-world setting. MethodsIn this retrospective observational study, we included PwE with epilepsy who received a prescription for CBD between 01.03.2019 and 30.11.2022 and had a follow-up period ≥ 3 months. Participants were evaluated at baseline and after 3, 6, and 12 months. "Responders" were defined as individuals experiencing a reduction in seizure frequency > 30% but < 80% compared to baseline, while "super responders" were those with a reduction ≥ 80%. Adverse events were recorded to assess safety. ResultsForty-two PwE were included (mean age 36.1 ± 10.9 years; 14 females). In 24 patients CBD was prescribed on-label (Lennox-Gastaut syndrome, n = 18; Dravet syndrome, n = 5; tuberous sclerosis, n = 1), while 18 patients were treated off-label (ring chromosome 20 syndrome, n = 1; ring chromosome 17 syndrome, n = 1; Lafora disease, n = 3; Unverricht-Lundborg disease, n = 1; polymicrogyria, n = 2; febrile infection-related epilepsy syndrome, n = 1; non-lesional focal epilepsy, n = 2; developmental and/or epileptic encephalopathy of unknown etiology n = 6). The mean number of concomitant antiseizure medications was 3.4 (≥2 for all patients). At 3 months, 10 subjects (23%) were “responders” and 12 (29%) were “super-responders”. Efficacy was sustained at 6 and 12 months of follow-up. Twenty-two patients (52.3%) developed AEs, with drowsiness (36.5%) and diarrhea (9.8%) being the most common. The retention rate was 85.7%, 78.6%, and 71.4% at 3, 6, and 12 months, respectively. ConclusionsIn this monocentric real-world study, CBD was a safe and effective therapeutic option for highly drug-resistant patients, leading to a dramatic reduction in seizure frequency in over one-fourth of them, including off-label indications.

SPECT and PET in nonlesional epilepsy

AbstractBackgroundPositron emission tomography (PET) and single-photon emission computed tomography (SPECT) are applied in epilepsy mostly during presurgical assessment. Nonlesional focal epilepsy is very challenging for presurgical evaluation in cases of refractory epilepsy.ObjectivesWe aimed to investigate the contribution of PET and SPECT to focus localization in nonlesional epilepsy.MethodsThe basic principles of SPECT and PET including different tracers were reviewed. The literature and the most recent publications are discussed in view of findings in nonlesional epilepsy.ResultsIctal SPECT shows a high sensitivity of over 80% for ictal onset zone in nonlesional epilepsy. Postprocessing with subtraction ictal SPECT co-registered with MRI (SISCOM) or statistical parametric mapping are the gold standard. Histopathological findings in nonlesional epilepsies with concordant ictal SPECT imaging show focal cortical dysplasia in up to 75% of cases. Ictal injection is unsuccessful in approximately 20% of cases and the procedure is very time consuming and labor intensive. Fluorodeoxyglucose (FDG)-PET in nonlesional epilepsy shows variable sensitivity of 46–76%. As with ictal SPECT, it benefits from postprocessing of co-registration with magnetic resonance imaging (MRI) or even statistical parametric mapping. Hybrid PET/magnetic resonance imaging (MRI) scanners provide additional benefits for identifying lesions. Other PET tracers (11C‑Flumazenil (FMZ), α-11C‑methyl-L-tryptophane (AMT)) are clinically applied in special cases only. Both procedures contribute complementary information in multimodal imaging diagnostics.ConclusionsIctal SPECT and PET are optional diagnostic tools for presurgical assessment in nonlesional epilepsies. They may reverse nonlesional to lesional epilepsy status and identify nonlesional epileptic foci with a fair chance of seizure freedom after epilepsy surgery.

Parasomnien bei Kindern und Erwachsenen als Differenzialdiagnose zu nichtläsionellen fokalen Epilepsien

ZusammenfassungAls Parasomnien werden auffällige Verhaltensweisen während des Schlafes definiert. Aufwachstörungen wie Pavor Nocturnus (Nachtschreck) und Schlafwandeln treten aus dem Non-Rapid-Eye-Movement(NREM)-Schlaf heraus auf und ereignen sich in der Regel während der 1. Nachthälfte. Albträume und Rapid-Eye-Movement(REM)-Schlafverhaltensstörungen werden vermehrt in der 2. Nachthälfte mit Zunahme des REM-Schlafes beobachtet. Alle Parasomnien müssen differenzialdiagnostisch von schlafgebundenen epileptischen Anfällen abgegrenzt werden. Der Goldstandard zur Differenzierung unklarer Fälle ist die Video-EEG-Dokumentation der nächtlichen Verhaltensstörungen.

Genetics of nonlesional focal epilepsy in adults and surgical implications

AbstractNonlesional focal epilepsies (nlFE) represent a heterogenous group of syndromes. They encompass self-limited focal epilepsies of childhood and youth, rare focal, familial epilepsies, epilepsies associated with brain somatic variants, and to a large extent nonfamilial epilepsies that have a complex genetic or unknown background. Genetic testing should be performed in cases of a family history suggestive of monogenic inheritance and in cases that show additional symptoms, such as intellectual impairment, autism, or dysmorphic features. Whole-exome or whole-genome sequencing is the method of choice. Growing evidence suggests including genetic testing also in the presurgical workup of individuals with drug-resistant epilepsy. While individuals that harbor variants in genes of the mammalian target of rapamycin (mTOR) pathway tend to achieve better seizure control following epilepsy surgery, the postsurgical outcome of genetic epilepsies associated with channel function or synaptic transmission appears to be poor. The aim of this article is to review the genetic background of focal epilepsies that occur or persist in adults, provide guidance for genetic testing, and discuss potential implications for presurgical evaluation.

Neurophysiological assessment of cortical activity in DEPDC5- and NPRL3-related epileptic mTORopathies

BackgroundMutations in the GATOR1 complex genes, DEPDC5 and NPRL3, play a major role in the development of lesional and non-lesional focal epilepsy through increased mTORC1 signalling. We aimed to assess the effects of mTORC1 hyperactivation on GABAergic inhibitory circuits, in 3 and 5 individuals carrying DEPDC5 and NPRL3 mutations respectively using a multimodal approach including transcranial magnetic stimulation (TMS), magnetic resonance spectroscopy (MRS), and electroencephalography (EEG).ResultsInhibitory functions probed by TMS and MRS showed no effect of mutations on cortical GABAergic receptor-mediated inhibition and GABA concentration, in both cortical and subcortical regions. However, stronger EEG theta oscillations and stronger and more synchronous gamma oscillations were observed in DEPDC5 and NPRL3 mutations carriers.ConclusionsThese results suggest that DEPDC5 and NPRL3-related epileptic mTORopathies may not directly modulate GABAergic functions but are nonetheless characterized by a stronger neural entrainment that may be reflective of a cortical hyperexcitability mediated by increased mTORC1 signaling.

Cognitive features of adult focal epilepsy with unknown etiology revealed by the trail making test

PurposeThe purpose of this study was to investigate whether the Trail Making Test (TMT) can clarify cognitive dysfunction in focal epilepsy with unknown etiology. MethodsTrail Making Test data were obtained from patients with focal epilepsy with no structural abnormalities on magnetic resonance imaging, history or coexistence of central nerve system diseases, intellectual disability, psychiatric disorders, or medications that might interfere with cognitive function. We performed multiple regression analyses with TMT scores as dependent variables and clinical features as independent variables. ResultsWe enrolled 125 patients in the study. The statistical analyses revealed that taking fewer antiseizure medications, having a longer duration of education, exhibiting left non-temporal epileptic discharge, and exhibiting right temporal epileptic discharge were associated with shorter time to complete the TMT-A and TMT-B. Older age at the time of last seizure was associated with longer time to complete the TMT-B. In addition, a longer active seizure period was associated with longer time to complete the TMT-A subtracted from time to complete the TMT-B. ConclusionsThis study indicated that the TMT can be used for assessing the cumulative effects of seizures and the effects of polypharmacy on cognitive function in patients with focal epilepsy. Furthermore, our results indicated that the visuospatial cognitive ability associated with the TMT may depend on the site of epileptic focus of non-lesional focal epilepsy.

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.

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.

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.

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.

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.

All that glitters: Contribution of stereo-EEG in patients with lesional epilepsy

ObjectiveTo determine the contribution of stereo-EEG for localization purpose in patients with a visible lesion on MRI. BackgroundIntracranial EEG is often used to localize the epileptogenic focus in patients with non-lesional focal epilepsy. Its role in cases where a lesion is visible on MRI can be even more complex and the relationship between the lesion and the seizure onset has rarely been addressed. MethodsAll consecutive patients between February 2013 and May 2018 who underwent stereo-EEG and had a lesion visible on MRI were included. We assessed the localization of the seizure onset and its relationship with the lesion. Clinical, radiological, and electrographic analyses were performed. ResultsStereo-EEG revealed a seizure onset with either partial or no overlap with the lesion seen on MRI in 42 (56 %) of the 75 lesions included. Mesial temporal sclerosis was the only lesion type associated with an exclusively lesional seizure onset (p = 0.003). ConclusionEpilepsy surgery in MRI-positive cases should rely not only the results of lesions seen on MRI, which might be potentially misleading; SEEG is a gold standard method in these cases to define resective borders.

Distinguishing type II focal cortical dysplasias from normal cortex: A novel normative modeling approach

ObjectiveFocal cortical dysplasias (FCDs) are a common cause of apparently non-lesional drug-resistant focal epilepsy. Visual detection of subtle FCDs on MRI is clinically important and often challenging. In this study, we implement a set of 3D local image filters adapted from computer vision applications to characterize the appearance of normal cortex surrounding the gray-white junction. We create a normative model to serve as the basis for a novel multivariate constrained outlier approach to automated FCD detection. MethodsStandardized MPRAGE, T2 and FLAIR MR images were obtained in 15 patients with radiologically or histologically diagnosed FCDs and 30 healthy volunteers. Multiscale 3D local image filters were computed for each MR contrast then sampled onto the gray-white junction surface. Using an iterative Gaussianization procedure, we created a normative model of cortical variability in healthy volunteers, allowing for identification of outlier regions and estimates of similarity in normal cortex and FCD lesions. We used a constrained outlier approach following local normalization to automatically detect FCD lesions based on projection onto the mean FCD feature vector. ResultsFCDs as well as some normal cortical regions such as primary sensorimotor and paralimbic regions appear as outliers. Regions such as the paralimbic regions and the anterior insula have similar features to FCDs. Our constrained outlier approach allows for automated FCD detection with 80% sensitivity and 70% specificity. SignificanceA normative model using multiscale local image filters can be used to describe the normal cortical variability. Although FCDs appear similar to some cortical regions such as the anterior insula and paralimbic cortices, they can be identified using a constrained outlier detection approach. Our method for detecting outliers and estimating similarity is generic and could be extended to identification of other types of lesions or atypical cortical areas.

Arterial spin-labelling and magnetic resonance spectroscopy as imaging biomarkers for detection of epileptogenic zone in non-lesional focal impaired awareness epilepsy

BackgroundThe proper identification of an epileptic focus is a pivotal diagnostic issue; particularly in non-lesional focal impaired awareness epilepsy (FIAE). Seizures are usually accompanied by alterations of regional cerebral blood flow (rCBF) and metabolism. Arterial spin labeling-MRI (ASL-MRI) and proton magnetic resonance spectroscopy (1H-MRS) are MRI techniques that can, non-invasively, define the regions of cerebral perfusion and metabolic changes, respectively. The aim of the current study was to recognize the epileptogenic zone in patients with non-lesional FIAE by evaluating the interictal changes in rCBF and cerebral metabolic alterations, using PASL-MRI and 1H-MRS.ResultsFor identification of the epileptogenic zone, increased ASLAI% assessed by PASL-MRI (at a cut-off value ≥ 5.96%) showed 95.78% accuracy, and increased %AF (at a cut-off value ≥ 9.98%) showed 98.14% accuracy, while decreased NAA/(Cho + Cr) ratio estimated by multi-voxels (MV) 1H-MRS (at a cut-off value ≥ 0.59) showed 97.74% accuracy. Moreover, the combined use of PASL-MRI and MV 1H-MRS yielded 100% sensitivity, 98.45% specificity and 98.86% accuracy.ConclusionThe combined use of PASL-MRI and MV 1H-MRS can be considered as in-vivo proficient bio-marker for proper identification of epileptogenic zone in patients with non-lesional FIAE.