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<jats:title>Abstract</jats:title><jats:p>We conducted a systematic review and meta‐analysis to evaluate postoperative seizure and memory outcomes of temporal lobe epilepsy with different hippocampal sclerosis (HS) subtypes classified by International League Against Epilepsy (ILAE) Consensus Guidelines in 2013. Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‐Analyses) and MOOSE (Meta‐Analysis of Observational Studies in Epidemiology) guidelines, we searched PubMed, Embase, Web of Science, and Cochrane Library from January 1, 2013 to August 6, 2023. Observational studies reporting seizure and memory outcomes among different HS subtypes were included. We used the Newcastle–Ottawa scale to assess the risk of bias and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to grade the quality of evidence. Seizure freedom and improved outcome (Engel 1 or ILAE class 1–2) ≥1 year after surgery were defined as the primary and secondary seizure outcome. A random‐effects meta‐analysis by DerSimonian and Laird method was performed to obtain pooled risk ratio (RRs) with 95% confidence interval (CIs). The memory impairment was narratively reviewed because of various evaluation tools. Fifteen cohort studies with 2485 patients were eligible for the meta‐analysis of seizure outcome. Six cohorts with detailed information on postoperative memory outcome were included. The pooled RRs of seizure freedom, with moderate to substantial heterogeneity, were .98 (95% CI = .84–1.15) between HS type 2 and type 1, 1.11 (95% CI = .82–1.52) between type 3 and type 1, and .80 (95% CI = .62–1.03) between the no‐HS and HS groups. No significant difference of improved outcome was found between different subtypes (<jats:italic>p</jats:italic> &gt; .05). The quality of evidence was deemed to be low to very low according to GRADE. The long‐term seizure outcome (≥5 years after surgery) and memory impairment remained controversial.</jats:p>

<jats:title>Abstract</jats:title><jats:p>Despite progress in the development of anti‐seizure medications (ASMs), one third of people with epilepsy have drug‐resistant epilepsy (DRE). The working definition of DRE, proposed by the International League Against Epilepsy (ILAE) in 2010, helped identify individuals who might benefit from presurgical evaluation early on. As the incidence of DRE remains high, the TASK1 workgroup on DRE of the ILAE/American Epilepsy Society (AES) Joint Translational Task Force discussed the heterogeneity and complexity of its presentation and mechanisms, the confounders in drawing mechanistic insights when testing treatment responses, and barriers in modeling DRE across the lifespan and translating across species. We propose that it is necessary to revisit the current definition of DRE, in order to transform the preclinical and clinical research of mechanisms and biomarkers, to identify novel, effective, precise, pharmacologic treatments, allowing for earlier recognition of drug resistance and individualized therapies.</jats:p>

<jats:title>Abstract</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>Predicting memory morbidity after temporal lobectomy in patients with temporal lobe epilepsy (TLE) relies on indices of preoperative temporal lobe structural and functional integrity. However, epilepsy is increasingly considered a network disorder, and memory a network phenomenon. We assessed the utility of functional network measures to predict postoperative memory changes.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Seventy‐two adults with TLE (37 left/35 right) underwent preoperative resting‐state functional magnetic resonance imaging and pre‐ and postoperative neuropsychological assessment. We compared functional connectivity throughout the memory network of each patient to a healthy control template (<jats:italic>n</jats:italic> = 19) to identify differences in global organization. A second metric indicated the degree of integration of the to‐be‐resected temporal lobe with the rest of the memory network. We included these measures in a linear regression model alongside standard clinical variables as predictors of memory change after surgery.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Left TLE patients with more atypical memory networks, and with greater functional integration of the to‐be‐resected region with the rest of the memory network preoperatively, experienced the greatest decline in verbal memory after surgery. Together, these two measures explained 44% of variance in verbal memory change, outperforming standard clinical and demographic variables. None of the variables examined was associated with visuospatial memory change in patients with right TLE.</jats:p></jats:sec><jats:sec><jats:title>Significance</jats:title><jats:p>Resting‐state connectivity provides valuable information concerning both the integrity of to‐be‐resected tissue and functional reserve across memory‐relevant regions outside of the to‐be‐resected tissue. Intrinsic functional connectivity has the potential to be useful for clinical decision‐making regarding memory outcomes in left TLE, and more work is needed to identify the factors responsible for differences seen in right TLE.</jats:p></jats:sec>

<jats:title>Abstract</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>To investigate changes in depressive and suicidality status and their relationship with seizure outcomes after the addition or substitution of another antiseizure medication (ASM) in adults with drug‐resistant focal epilepsy.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Seven hundred seventy consecutively enrolled patients were assessed and followed prospectively for seizure outcome and depressive status over a 6‐month period after starting treatment with a newly introduced ASM. The Neurological Disorders Depression Inventory for Epilepsy (NDDIE) was used to screen for depression and suicidality. Correlations of NDDIE results with clinical and treatment‐related variables were assessed by using a stepwise logistic regression model.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>At baseline, 50% of patients had a positive screening test result for depression and 13% had a positive screening test result for suicidal ideation. A psychiatric comorbidity at baseline was associated with a 2.3 times increased risk of an initially negative NDDIE screening result becoming positive at re‐assessment after 6 months. In addition, the number of ASMs taken at baseline correlated with an increased risk of a change in depression screening test results from negative to positive during follow‐up, whereas no association was identified with sociodemographic and epilepsy‐related variables, including seizure outcomes. Approximately 6% of patients who were initially negative at screening for suicidal ideation became positive at the 6‐month re‐assessment. The risk of switch from a negative to a positive screening test result for suicidal ideation was increased more than two‐fold in individuals who screened positive for depression at baseline, and was unrelated to the type of ASM introduced, sociodemographic variables, or seizure outcomes.</jats:p></jats:sec><jats:sec><jats:title>Significance</jats:title><jats:p>Almost 1 in 5 adults with drug‐resistant focal epilepsy who screen negative for depression become positive when re‐assessed 6 months after a treatment change. At re‐assessment 6 months later, 6.1% who screen initially negative for passive suicidal ideation become positive. These changes in screening status are independent of type of ASM introduced or seizure outcomes but correlate with psychiatric status at baseline.</jats:p></jats:sec>

<jats:title>Abstract</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>This study was undertaken to conduct external validation of previously published epilepsy surgery prediction tools using a large independent multicenter dataset and to assess whether these tools can stratify patients for being operated on and for becoming free of disabling seizures (International League Against Epilepsy stage 1 and 2).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We analyzed a dataset of 1562 patients, not used for tool development. We applied two scales: Epilepsy Surgery Grading Scale (ESGS) and Seizure Freedom Score (SFS); and two versions of Epilepsy Surgery Nomogram (ESN): the original version and the modified version, which included electroencephalographic data. For the ESNs, we used calibration curves and concordance indexes. We stratified the patients into three tiers for assessing the chances of attaining freedom from disabling seizures after surgery: high (ESGS = 1, SFS = 3–4, ESNs &gt; 70%), moderate (ESGS = 2, SFS = 2, ESNs = 40%–70%), and low (ESGS = 2, SFS = 0–1, ESNs &lt; 40%). We compared the three tiers as stratified by these tools, concerning the proportion of patients who were operated on, and for the proportion of patients who became free of disabling seizures.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The concordance indexes for the various versions of the nomograms were between .56 and .69. Both scales (ESGS, SFS) and nomograms accurately stratified the patients for becoming free of disabling seizures, with significant differences among the three tiers (<jats:italic>p</jats:italic> &lt; .05). In addition, ESGS and the modified ESN accurately stratified the patients for having been offered surgery, with significant difference among the three tiers (<jats:italic>p</jats:italic> &lt; .05).</jats:p></jats:sec><jats:sec><jats:title>Significance</jats:title><jats:p>ESGS and the modified ESN (at thresholds of 40% and 70%) stratify patients undergoing presurgical evaluation into three tiers, with high, moderate, and low chance for favorable outcome, with significant differences between the groups concerning having surgery and becoming free of disabling seizures. Stratifying patients for epilepsy surgery has the potential to help select the optimal candidates in underprivileged areas and better allocate resources in developed countries.</jats:p></jats:sec>

<jats:title>Abstract</jats:title><jats:p>Nodular heterotopia (NH)–related drug‐resistant epilepsy is challenging due to the deep location of the NH and the complexity of the underlying epileptogenic network. Using ictal stereo‐electroencephalography (SEEG) and functional connectivity (FC) analyses in 14 patients with NH‐related drug‐resistant epilepsy, we aimed to determine the leading structure during seizures. For this purpose, we compared node IN and OUT strength between bipolar channels inside the heterotopia and inside gray matter, at the group level and at the individual level. At seizure onset, the channels within NH belonging to the epileptogenic and/or propagation network showed higher node OUT‐strength than the channels within the gray matter (<jats:italic>p</jats:italic> = .03), with higher node OUT‐strength than node IN‐strength (<jats:italic>p</jats:italic> = .03). These results are in favor of a “leading” role of NH during seizure onset when involved in the epileptogenic‐ or propagation‐zone network (50% of patients). However, when looking at the individual level, no significant difference between NH and gray matter was found, except for one patient (in two of three seizures). This result confirms the heterogeneity and the complexity of the epileptogenic network organization in NH and the need for SEEG exploration to characterize more precisely patient‐specific epileptogenic network organization.</jats:p>