Long-term seizure outcome after epilepsy surgery in patients with mild malformation of cortical development and focal cortical dysplasia.
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ABSTRACT:
SUBMITTER: Veersema TJ
PROVIDER: S-EPMC6398095 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:This study aims to explore the relationship between neuropathologic and the post-surgical prognosis of focal cortical dysplasia (FCD) typed-Ⅲ-related medically refractory epilepsy. A total of 266 patients with FCD typed-Ⅲ-related medically refractory epilepsy were retrospectively studied. Presurgical clinical data, type of surgery, and postsurgical seizure outcome were analyzed. The minimum post-surgical follow-up was 1 year. A total of 266 patients of FCD type Ⅲ were included in this study and the median follow-up time was 30 months (range, 12~48 months). Age at onset ranged from 1.0 years to 58.0 years, with a median age of 12.5 years. The number of patients under 12 years old was 133 (50%) in patients with FCD type Ⅲ. A history of febrile seizures was present in 42 (15.8%) cases. In the entire postoperative period, 179 (67.3%) patients were seizure-free. Factors with p < 0.15 in univariate analysis, such as age of onset of epilepsy (p = 0.145), duration of epilepsy (p = 0.004), febrile seizures (p = 0.150), being MRI-negative (p = 0.056), seizure type (p = 0.145) and incomplete resection, were included in multivariate analysis. Multivariate analyses revealed that MRI-negative findings of FCD (OR 0.34, 95% CI 0.45-0.81, p = 0.015) and incomplete resection (OR 0.12, 95% CI 0.05-0.29, p < 0.001) are independent predictors of unfavorable seizure outcomes. MRI-negative finding of FCD lesions and incomplete resection were the most important predictive factors for poor seizure outcome in patients with FCD type Ⅲ.
| S-EPMC8699898 | biostudies-literature
Project description:PurposeThe results of surgery in patients with mesial temporal lobe epilepsy (MTLE) associated with hippocampal sclerosis (HS) are favorable, with a success rate over 70% following resection. An association of HS with focal cortical dysplasia (FCD) in the temporal lobe is one of the potential causes for poor surgical outcome in MTLE. We aimed to analyzed seizure outcome in a population of MTLE patients and recognize the role of occult FCD in achieving postoperative seizure control.MethodsWe retrospectively analyzed postoperative outcomes for 82 consecutive adult patients with the syndrome of MTLE due to HS, who had no concomitant lesions within temporal lobe in MRI and who underwent surgical treatment in the years 2005-2016, and correlated factors associated with seizure relapse.ResultsAt the latest follow-up evaluation after surgery, 59 (72%) were free of disabling seizures (Engel Class I) and 48 (58,5%) had an Engel Class Ia. HS associated with FCD in neocortical structures were noted in 33 patients (40%). Analyzes have shown that dual pathology was the most significant negative predictive factor for Engel class I and Engel class Ia outcome.ConclusionsThe incidence of dual pathology in patients with temporal lobe epilepsy seems to be underestimated. An incomplete epileptogenic zone resection of occult focal temporal dysplasia within temporal lobe is supposed to be the most important negative prognostic factor for seizure freedom after epilepsy surgery in MTLE-HS patients. The study indicates the need to improve diagnostics for other temporal lobe pathologies, despite the typical clinical and radiological picture of MTLE-HS.
| S-EPMC8483375 | biostudies-literature
Project description:OBJECTIVE:To localize the seizure onset zone (SOZ) and irritative zone (IZ) using electric source imaging (ESI) on intracranial EEG (iEEG) and assess their clinical value in predicting epilepsy surgery outcome in children with focal cortical dysplasia (FCD). METHODS:We analyzed iEEG data from 25 children with FCD-associated medically refractory epilepsy (MRE) who underwent surgery. We performed ESI on ictal onset to localize SOZ (ESI-SOZ) and on interictal discharges to localize IZ (ESI-IZ). We tested whether resection of ESI-SOZ and ESI-IZ predicted good surgical outcome (Engel 1). We further compared the prediction performance of ESI-SOZ and ESI-IZ to those of SOZ and IZ defined using conventional methods, i.e. by identifying iEEG-contacts showing ictal onsets (conventional-SOZ) or being the most interictally active (conventional-IZ). RESULTS:The proximity of ESI-SOZ (p = 0.043, odds-ratio = 3.9) and ESI-IZ (p = 0.011, odds-ratio = 7.04) to resection has higher effect on patients' outcome than proximity of conventional-SOZ (p = 0.17, odds-ratio = 1.7) and conventional-IZ (p = 0.038, odds-ratio = 2.6). Resection of ESI-SOZ and ESI-IZ presented higher discriminative power in predicting outcome (68% and 60%) than conventional-SOZ and conventional-IZ (48% and 53%). CONCLUSIONS:Localizing SOZ and IZ via ESI on iEEG offers higher predictive value compared to conventional-iEEG interpretation. SIGNIFICANCE:iEEG-ESI may help surgical planning and facilitate prognostic assessment of children with FCD-associated MRE.
| S-EPMC7093832 | biostudies-literature
Project description:Focal cortical dysplasias are a common subtype of malformation of cortical development, which frequently presents with a spectrum of cognitive and behavioural abnormalities as well as pharmacoresistant epilepsy. Focal cortical dysplasia type II is typically caused by somatic mutations resulting in mammalian target of rapamycin (mTOR) hyperactivity, and is the commonest pathology found in children undergoing epilepsy surgery. However, surgical resection does not always result in seizure freedom, and is often precluded by proximity to eloquent brain regions. Gene therapy is a promising potential alternative treatment and may be appropriate in cases that represent an unacceptable surgical risk. Here, we evaluated a gene therapy based on overexpression of the Kv1.1 potassium channel in a mouse model of frontal lobe focal cortical dysplasia. An engineered potassium channel (EKC) transgene was placed under control of a human promoter that biases expression towards principal neurons (CAMK2A) and packaged in an adeno-associated viral vector (AAV9). We used an established focal cortical dysplasia model generated by in utero electroporation of frontal lobe neural progenitors with a constitutively active human Ras homolog enriched in brain (RHEB) plasmid, an activator of mTOR complex 1. We characterized the model by quantifying electrocorticographic and behavioural abnormalities, both in mice developing spontaneous generalized seizures and in mice only exhibiting interictal discharges. Injection of AAV9-CAMK2A-EKC in the dysplastic region resulted in a robust decrease (∼64%) in the frequency of seizures. Despite the robust anti-epileptic effect of the treatment, there was neither an improvement nor a worsening of performance in behavioural tests sensitive to frontal lobe function. AAV9-CAMK2A-EKC had no effect on interictal discharges or behaviour in mice without generalized seizures. AAV9-CAMK2A-EKC gene therapy is a promising therapy with translational potential to treat the epileptic phenotype of mTOR-related malformations of cortical development. Cognitive and behavioural co-morbidities may, however, resist an intervention aimed at reducing circuit excitability.
| S-EPMC10834237 | biostudies-literature
Project description:ObjectiveFocal cortical dysplasia (FCD) represents a heterogeneous group of disorders of the cortical formation and is one of the most common causes of epilepsy. Magnetic resonance imaging (MRI) is the modality of choice for detecting structural lesions, and the surgical prognosis in patients with MR lesions is favorable. However, the surgical prognosis of patients with MR-negative FCD is unknown. We aimed to evaluate the long-term surgical outcomes and prognostic factors in MR-negative FCD patients through comprehensive presurgical data.MethodsWe retrospectively reviewed data from 719 drug-resistant epilepsy patients who underwent resective surgery and selected cases in which surgical specimens were pathologically confirmed as FCD Type I or II. If the epileptogenic focus and surgical specimens were obtained from brain areas with a normal MRI appearance, they were classified as MR-negative FCD. Surgical outcomes were evaluated at 2 and 5 years, and clinical, neurophysiological, and neuroimaging data of MR-negative FCD were compared to those of MR-positive FCD.ResultsFinally, 47 MR-negative and 34 MR-positive FCD patients were enrolled in the study. The seizure-free rate after surgery (Engel classification I) at postoperative 2 year was 59.5% and 64.7% in the MR-negative and positive FCD groups, respectively (p = 0.81). This rate decreased to 57.5% and 44.4% in the MR-negative and positive FCD groups (p = 0.43) at postoperative 5 years. MR-negative FCD showed a higher proportion of FCD type I (87.2% vs. 50.0%, p = 0.001) than MR-positive FCD. Unilobar cerebral perfusion distribution (odds ratio, OR 5.41) and concordance of interictal epileptiform discharges (OR 5.10) were significantly associated with good surgical outcomes in MR-negative FCD.ConclusionIn this study, MR-negative and positive FCD patients had a comparable surgical prognosis, suggesting that comprehensive presurgical evaluations, including multimodal neuroimaging studies, are crucial for obtaining excellent surgical outcomes even in epilepsy patients with MR-negative FCD.
| S-EPMC8046256 | biostudies-literature
Project description:Background and purposeThis study investigated the seizure recurrence rate and potential predictors of seizure recurrence following antiepileptic drug (AED) withdrawal after resective epilepsy surgery in children with focal cortical dysplasia (FCD).MethodsWe retrospectively analyzed the records of 70 children and adolescents with FCD types I, II, and IIIa who underwent resective epilepsy surgery between 2004 and 2015 and were followed for at least 2 years after surgery.ResultsWe attempted AED withdrawal in 40 patients. The median time of starting the AED reduction was 10.8 months after surgery. Of these 40 patients, 14 patients (35%) experienced seizure recurrence during AED reduction or after AED withdrawal. Half of the 14 patients who experienced recurrence regained seizure freedom after AED reintroduction and optimization. Compared with their preoperative status, the AED dose or number was decreased in 57.1% of patients, and remained unchanged in 14.3% after surgery. A multivariate analysis found that incomplete resection (p=0.004) and epileptic discharges on the postoperative EEG (p=0.025) were important predictors of seizure recurrence after AED withdrawal. Over the mean follow-up duration of 4.5 years after surgery, 34 patients (48.6% of the entire cohort) were seizure-free with and without AEDs.ConclusionsChildren with incomplete resection and epileptic discharges on postoperative EEG are at a high risk of seizure recurrence after drug withdrawal. Complete resection of FCD may lead to a favorable surgical outcome and successful AED withdrawal after surgery.
| S-EPMC6325372 | biostudies-literature
Project description:ObjectiveThis study explored the association between long-term epilepsy surgery outcome and changes in depressive symptoms.MethodsAdults were enrolled between 1996 and 2001 in a multicenter prospective study to evaluate outcomes of resective epilepsy surgery. The extent of depressive symptoms and depression case status (none, mild, or moderate/severe) were assessed using the Beck Depression Inventory (BDI) preoperatively and 3, 12, 24, 48, and 60 months postoperatively. A mixed-model repeated-measures analysis was performed, adjusting for covariates of seizure location, gender, age, race, education, and seizure control.ResultsOf the total 373 subjects, 256 were evaluated at baseline and 5 years after surgery. At baseline, 164 (64.1%) were not depressed, 34 (13.3%) were mildly depressed, and 58 (22.7%) had moderate to severe depression. After 5 years, 198 (77.3%) were not depressed, 20 (7.8%) were mildly depressed, and 38 (14.8%) were moderately to severely depressed. Five years after surgery, the reduction in mean change from baseline in BDI score was greater in subjects with excellent seizure control than in the fair and poor seizure control groups (p = 0.0006 and p = 0.02 respectively). Those with good seizure control had a greater reduction in BDI score than the poor seizure control group (p = 0.02) and borderline significant reduction compared with the fair seizure control group (p = 0.055).ConclusionAlthough study participants had initial improvement in depressive symptoms, on average, after resective surgery, only patients with good or excellent seizure control had sustained long-term improvement in mood.
| S-EPMC3235357 | biostudies-literature
Project description:Since prediction of long-term seizure outcome using preoperative diagnostic modalities remains suboptimal in epilepsy surgery, we evaluated whether interictal spike frequency measures obtained from extraoperative subdural electrocorticography (ECoG) recording could predict long-term seizure outcome. This study included 61 young patients (age 0.4-23.0 years), who underwent extraoperative ECoG recording prior to cortical resection for alleviation of uncontrolled focal seizures. Patient age, frequency of preoperative seizures, neuroimaging findings, ictal and interictal ECoG measures were preoperatively obtained. The seizure outcome was prospectively measured [follow-up period: 2.5-6.4 years (mean 4.6 years)]. Univariate and multivariate logistic regression analyses determined how well preoperative demographic and diagnostic measures predicted long-term seizure outcome. Following the initial cortical resection, Engel Class I, II, III and IV outcomes were noted in 35, 6, 12 and 7 patients, respectively. One child died due to disseminated intravascular coagulation associated with pseudomonas sepsis 2 days after surgery. Univariate regression analyses revealed that incomplete removal of seizure onset zone, higher interictal spike-frequency in the preserved cortex and incomplete removal of cortical abnormalities on neuroimaging were associated with a greater risk of failing to obtain Class I outcome. Multivariate logistic regression analysis revealed that incomplete removal of seizure onset zone was the only independent predictor of failure to obtain Class I outcome. The goodness of regression model fit and the predictive ability of regression model were greatest in the full regression model incorporating both ictal and interictal measures [R(2) 0.44; Area under the receiver operating characteristic (ROC) curve: 0.81], slightly smaller in the reduced model incorporating ictal but not interictal measures (R(2) 0.40; Area under the ROC curve: 0.79) and slightly smaller again in the reduced model incorporating interictal but not ictal measures (R(2) 0.27; Area under the ROC curve: 0.77). Seizure onset zone and interictal spike frequency measures on subdural ECoG recording may both be useful in predicting the long-term seizure outcome of epilepsy surgery. Yet, the additive clinical impact of interictal spike frequency measures to predict long-term surgical outcome may be modest in the presence of ictal ECoG and neuroimaging data.
| S-EPMC2668945 | biostudies-literature
Project description:The aim of this study is to determine whether the use of 7 tesla (T) MRI in clinical practice leads to higher detection rates of focal cortical dysplasias in possible candidates for epilepsy surgery.In our center patients are referred for 7 T MRI if lesional focal epilepsy is suspected, but no abnormalities are detected at one or more previous, sufficient-quality lower-field MRI scans, acquired with a dedicated epilepsy protocol, or when concealed pathology is suspected in combination with MR-visible mesiotemporal sclerosis-dual pathology. We assessed 40 epilepsy patients who underwent 7 T MRI for presurgical evaluation and whose scans (both 7 T and lower field) were discussed during multidisciplinary epilepsy surgery meetings that included a dedicated epilepsy neuroradiologist. We compared the conclusions of the multidisciplinary visual assessments of 7 T and lower-field MRI scans.In our series of 40 patients, multidisciplinary evaluation of 7 T MRI identified additional lesions not seen on lower-field MRI in 9 patients (23%). These findings were guiding in surgical planning. So far, 6 patients underwent surgery, with histological confirmation of focal cortical dysplasia or mild malformation of cortical development.Seven T MRI improves detection of subtle focal cortical dysplasia and mild malformations of cortical development in patients with intractable epilepsy and may therefore contribute to identification of surgical candidates and complete resection of the epileptogenic lesion, and thus to postoperative seizure freedom.
| S-EPMC5719847 | biostudies-other
Project description:CpG methylation analysis of MeDIP DNA using Agilent Human DNA methylation Microarray slides (G4495A, AMADID 023795) Using methylated DNA immunoprecipitation microarray (MeDIP-chip) and Agilent Human DNA methylation Microarray slides (G4495A, AMADID 023795) we report genomic methylation signatures of tissues resected from Mesial temporal epilepsy (MTLE) and Focal cortical dysplasia (FCD) type II patients undergoing surgery. Control samples were obtained from the non-epileptic post mortem cases without any brain pathology
2018-03-10 | GSE96067 | GEO