Recently, a large number of surgical studies based on the objective evaluation of EOR have been published, suggesting that EOR has a significant effect not only on the rate of tumor progression and OS but also on the decrease Object. A growing number of published studies have recently demonstrated the role of resection in overall survival (OS) for patients with gliomas. In this retrospective study, the authors objectively investigated the role of the extent of resection (EOR) in OS in patients with low-grade gliomas (LGGs).Methods. Between 1998 and 2011, 190 patients underwent surgery for LGGs. All surgical procedures were conducted under corticosubcortical stimulation. The EOR was established by analyzing the pre-and postoperative volumes of the gliomas on T2-weighted MRI studies. The difference between the preoperative tumor volumes was also investigated by measuring the volumetric difference between the T2-and T1-weighted MRI images (DVT2T1) to evaluate how the diffusive tumor-growing pattern affected the EOR achieved.Results. The median preoperative tumor volume was 55 cm 3 , and in almost half of the patients the EOR was greater than 90%. In this study, patients with an EOR of 90% or greater had an estimated 5-year OS rate of 93%, those with EOR between 70% and 89% had a 5-year OS rate of 84%, and those with EOR less than 70% had a 5-year OS rate of 41% (p < 0.001). New postoperative deficits were noted in 43.7% of cases, while permanent deficits occurred in 3.16% of cases. There were 41 deaths (21.6%), and the median follow-up was 4.7 years.A further volumetric analysis was also conducted to compare 2 different intraoperative protocols (Series 1 [intraoperative electrical stimulation alone] vs Series 2 [intraoperative stimulation plus overlap of functional MRI/fiber tracking diffusion tensor imaging data on a neuronavigation system]). Patients in Series 1 had a median EOR of 77%, while those in Series 2 had a median EOR of 90% (p = 0.0001). Multivariate analysis showed that OS is influenced not only by EOR (p = 0.001) but also by age (p = 0.003), histological subtype (p = 0.005), and the DVT2T1 value (p < 0.0001). Progression-free survival is similarly influenced by histological subtype (fibrillary astrocytoma, p = 0.003), EOR (p < 0.0001), and DVT2T1 value (p < 0.0001), as is malignant progression-free survival (p = 0.003, p < 0.0001, and p < 0.0001, respectively). Finally, the study shows that the higher the DVT2T1 value, the less extensive the currently possible resection, highlighting an apparent correlation between the DVT2T1 value itself and EOR (p < 0.0001).Conclusions. The EOR and the DVT2T1 values are the strongest independent predictors in improving OS as well as in delaying tumor progression and malignant transformation. Furthermore, the DVT2T1 value may be useful as a predictive index for EOR. Finally, due to intraoperative corticosubcortical mapping and the overlap of functional data on the neuronavigation system, major resection is possible with an acceptable risk and a significant increase ...
With intraoperative cortico-subcortical mapping and neurophysiological monitoring, a major resection is possible with an acceptable risk and a significant result in the follow-up.
Object. Although a number of recent studies on the surgical treatment of insular low-grade glioma (LOG) have demonstrated that aggressive resection leads to increased overall patient survival and decreased malignant progression, less attention has been given to the results with respect to tumor-related epilepsy. The aim of this investigation was to evaluate the impact of volumetric, histological, and intraoperative neurophysiological factors on seizure outcome in patients with insular LGG. \ud Methods. The authors evaluated predictors of seizure outcome with special emphasis on both the extent of tumor resection (EOR) and the tumor's infiltrative pattern quantified by computing the difference between the preoperative T2- and Ti-weighted MR images (Delta VT2T1) in 52 patients with preoperative drug-resistant epilepsy. \ud Results. The 12-month postoperative seizure outcome (Engel class) was as follows: seizure free (Class I), 67.31%; rare seizures (Class II), 7.69%; meaningful seizure improvement (Class III), 15.38%; and no improvement or worsening (Class IV), 9.62%. Poor seizure control was more common in patients with a longer preoperative seizure history (p < 0.002) and higher frequency of seizures (p = 0.008). Better seizure control was achieved in cases with EOR >= 90% (p < 0.001) and Delta VT2T1 < 30 cm(3) (p < 0.001). In the final model, Delta VT2T1 proved to be the strongest independent predictor of seizure outcome in insular LGG patients (p < 0.0001). \ud Conclusions. No or little postoperative seizure improvement occurs mainly in cases with a prevalent infiltrative tumor growth pattern, expressed by high Delta VT2T1 values, which consequently reflects a smaller BOR
The importance of the extent of resection (EOR) has been widely demonstrated as the main predictor for survival, nevertheless its effect on tumor related epilepsy is less investigated. A total of 155 patients were enrolled after a first-line surgery for supratentorial Diffuse Low Grade Gliomas (DLGGs). Postoperative seizure outcome was analyzed stratifying the results by tumor volumetric data and molecular markers according to 2016 WHO classification. Receiver operating characteristic (ROC) curves were computed to asses EOR, residual tumor volume, and ∆T2T1 MRI index (expressing the tumor growing pattern) corresponding to optimal seizure outcome. A total of 70.97% of patients were seizure-free 18 months after surgery. Better seizure outcome was observed in IDH1/2 mutated and 1p/19q codeleted subgroup. At multivariate analysis, age (p = 0.014), EOR (p = 0.030), ∆T2T1 MRI index (p = 0.016) resulted as independent predictors of postoperative seizure control. Optimal parameters to improve postoperative seizure outcome were EOR ≥ 85%, ∆T2T1 MRI index ≤ 18 cm 3 , residual tumor volume ≤ 15 cm 3 . This study confirms the role of EOR and tumor growing pattern on postoperative seizure outcome independently from the molecular class. Higher ∆T2T1 MRI index, representing the infiltrative component of the tumor, is associated with worse seizure outcome and strengthens the evidence of common pathogenic mechanisms underlying tumor growth and postoperative seizure outcome.to manifest with focal and focal-to-bilateral tonic-clonic seizures, and more than 50% of cases show pharmaco-resistance, which contributes negatively on quality of life [3][4][5]. Recent studies have pointed out that epileptogenesis and tumor growth in DLGG may share common pathogenic mechanisms that can influence each other, thus representing two aspects of the same disease [6]. In this context, several genetic alterations have been identified as risk factors of glioma-related epilepsy. Mutations of the gene encoding the isocitrate-dehydrogenase1 (IDH1) and 2 (IDH2) can be found in about 70%-80% of DLGG [7]. These mutations have been associated with metabolic changes that are potentially epileptogenic, in accordance with the capability of IDH-mutated glioma cells to penetrate and surround the neurons in the gray matter [8,9].Seizure outcome represents an important challenge in the daily management of DLGG patients. In particular, decision-making still varies across surgical centers given the lack of well-established and universally recognized predictors of seizure outcomes.In the last decades, numerous studies, based on the objective evaluation of the extent of resection (EOR) has been published, demonstrating that an extensive surgery leads to increased overall patient survival and decreased malignant progression [10][11][12][13][14].Although EOR has also been shown to be one of the main strongest significant predictor markers for seizure outcome [7,[15][16][17][18], its predictive role has not been completely clarified in complex predictor models for epilep...
Background Clinical data regarding use of newer antiseizure medications (ASMs) in an older population are limited. In randomized-controlled, placebo-controlled trials, older patients are under-represented, and protocols deviate markedly from routine clinical practice, limiting the external validity of results. Studies performed in a naturalistic setting are a useful complement to characterize the drug profile. Perampanel is a third-generation ASM and the first and only non-competitive alfa-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor antagonist. Objective The aim of this study was to assess the effectiveness and tolerability of adjunctive perampanel over a 1-year period in a population of older patients with epilepsy treated in a real-world setting. Methods Older (≥ 65 years of age) patients prescribed add-on perampanel at 12 Italian epilepsy centers were retrospectively identified. Seizure occurrence, adverse events (AEs), and drug withdrawal were analyzed. Effectiveness outcomes included the rates of seizure response (≥ 50% reduction in baseline monthly seizure frequency), seizure freedom, and treatment discontinuation. Safety and tolerability outcomes were the rate of treatment discontinuation due to AEs and the incidence of AEs. Results A total of 92 patients with a median age of 69 (range 65-88) years were included. The median daily dose of perampanel at 12 months was 6 mg (interquartile range 4-6 mg). At 12 months, 53 (57.6%) patients were seizure responders, and 22 (23.9%) patients were seizure free. Twenty (21.7%) patients discontinued perampanel; the reasons for treatment withdrawal were insufficient efficacy (n = 6/20; 30.0%), AEs (n = 12/20; 60.0%), and a combination of both (n = 2/20; 10%). The most common AEs included irritability (8.7%), somnolence (4.3%), and dizziness/vertigo (4.3%). The rate of behavioral and psychiatric AEs was higher in patients with history of psychiatric comorbidities (p = 0.044). There were no differences in the occurrence of behavioral and psychiatric AEs according to the concomitant use of levetiracetam (p = 0.776) and history of cognitive decline (p = 0.332). Conclusions Adjunctive perampanel was associated with improvement in seizure control and good tolerability in a real-life setting and can represent a viable therapeutic option in older patients with epilepsy.
Summary Objective Although many studies have attempted to describe treatment outcomes in patients with drug‐resistant epilepsy, results are often limited by the adoption of nonhomogeneous criteria and different definitions of seizure freedom. We sought to evaluate treatment outcomes with a newly administered antiepileptic drug (AED) in a large population of adults with drug‐resistant focal epilepsy according to the International League Against Epilepsy (ILAE) outcome criteria. Methods This is a multicenter, observational, prospective study of 1053 patients with focal epilepsy diagnosed as drug‐resistant by the investigators. Patients were assessed at baseline and 6, 12, and 18 months, for up to a maximum of 34 months after introducing another AED into their treatment regimen. Drug resistance status and treatment outcomes were rated according to ILAE criteria by the investigators and by at least two independent members of an external expert panel (EP). Results A seizure‐free outcome after a newly administered AED according to ILAE criteria ranged from 11.8% after two failed drugs to 2.6% for more than six failures. Significantly fewer patients were rated by the EP as having a “treatment failure” as compared to the judgment of the investigator (46.7% vs 62.9%, P < 0.001), because many more patients were rated as “undetermined outcome” (45.6% vs 27.7%, P < 0.001); 19.3% of the recruited patients were not considered drug‐resistant by the EP. Significance This study validates the use of ILAE treatment outcome criteria in a real‐life setting, providing validated estimates of seizure freedom in patients with drug‐resistant focal epilepsy in relation to the number of previously failed AEDs. Fewer than one in 10 patients achieved seizure freedom on a newly introduced AED over the study period. Pseudo drug resistance could be identified in one of five cases.
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