Defining benchmark outcomes for mesial temporal lobe epilepsy surgery: A global multicenter analysis of 1119 cases.

OBJECTIVE: Benchmarking has been proposed to reflect surgical quality and represents the highest standard reference values for desirable results. We sought to determine benchmark outcomes in patients after surgery for drug-resistant mesial temporal lobe epilepsy (MTLE). METHODS: This retrospective multicenter study included patients who underwent MTLE surgery at 19 expert centers on five continents. Benchmarks were defined for 15 endpoints covering surgery and epilepsy outcome at discharge, 1 year after surgery, and the last available follow-up. Patients were risk-stratified by applying outcome-relevant comorbidities, and benchmarks were calculated for low-risk ("benchmark") cases. Respective measures were derived from the median value at each center, and the 75th percentile was considered the benchmark cutoff. RESULTS: A total of 1119 patients with a mean age (range) of 36.7 (1-74) years and a male-to-female ratio of 1:1.1 were included. Most patients (59.2%) underwent anterior temporal lobe resection with amygdalohippocampectomy. The overall rate of complications or neurological deficits was 14.4%, with no in-hospital death. After risk stratification, 377 (33.7%) benchmark cases of 1119 patients were identified, representing 13.6%-72.9% of cases per center and leaving 742 patients in the high-risk cohort. Benchmark cutoffs for any complication, clinically apparent stroke, and reoperation rate at discharge were ≤24.6%, ≤.5%, and ≤3.9%, respectively. A favorable seizure outcome (defined as International League Against Epilepsy class I and II) was reached in 83.6% at 1 year and 79.0% at the last follow-up in benchmark cases, leading to benchmark cutoffs of ≥75.2% (1-year follow-up) and ≥69.5% (mean follow-up of 39.0 months). SIGNIFICANCE: This study presents internationally applicable benchmark outcomes for the efficacy and safety of MTLE surgery. It may allow for comparison between centers, patient registries, and novel surgical and interventional techniques.

Adjunctive brivaracetam and sustained seizure frequency reduction in very active focal epilepsy.

OBJECTIVE: This study aimed to explore the effectiveness of brivaracetam (BRV) according to baseline seizure frequency and past treatment history in subjects with focal epilepsy who were included in the Brivaracetam Add-On First Italian Network Study (BRIVAFIRST). METHODS: BRIVAFIRST was a 12-month retrospective, multicenter study including adults prescribed adjunctive BRV. Study outcomes included sustained seizure response (SSR), sustained seizure freedom (SSF), and the rates of treatment discontinuation and adverse events (AEs). Baseline seizure frequency was stratified as <5, 5-20, and >20 seizures per month, and the number of prior antiseizure medications (ASMs) as <5 and ≥6. RESULTS: A total of 994 participants were included. During the 1-year study period, SSR was reached by 45.8%, 39.3%, and 22.6% of subjects with a baseline frequency of <5, 5-20, and >20 seizures per month (p < .001); the corresponding figures for the SSF were 23.4%, 9.8%, and 2.8% (p < .001). SSR was reached by 51.2% and 26.5% participants with a history of 1-5 and ≥6 ASMs (p < .001); the corresponding rates of SSF were 24.7% and 4.5% (p < .001). Treatment discontinuation due to lack of efficacy was more common in participants with >20 seizures compared to those with <5 seizures per month (25.8% vs. 9.3%, p < .001), and in participants with history of ≥6 prior ASMs compared to those with history of 1-5 ASMs (19.6% vs. 12.2%, p = .002). There were no differences in the rates of BRV withdrawal due to AEs and the rates of AEs across the groups of participants defined according to the number of seizures at baseline and the number of prior ASMs. SIGNIFICANCE: The baseline seizure frequency and the number of previous ASMs were predictors of sustained seizure frequency reduction with adjunctive BRV in subjects with focal epilepsy.

Distinctive electro-clinical, neuroimaging and histopathological features of temporal encephaloceles associated to epilepsy.

OBJECTIVE: Encephaloceles (ENCs) may cause clinical complications, including drug-resistant epilepsy that can be cured with epilepsy surgery. METHODS: We describe clinical, diagnostic, and neuropathological findings of 12 patients with temporal ENC and epilepsy evaluated for surgery and compare them with a control group of 26 temporal lobe epilepsy (TLE) patients. RESULTS: Six patients had unilateral and 6 bilateral temporal ENCs. Compared to TLEs, ENCs showed i) later epilepsy onset, ii) higher prevalence of psychiatric comorbidities, iii) no history of febrile convulsions, and iv) ictal semiology differences. Seven patients had MRI signs of gliosis, and 9 of intracranial hypertension. Interictal EEG analysis in ENCs demonstrated significant differences with controls: prominent activity in the beta/gamma frequency bands in frontal regions, interictal short sequences of low-voltage fast activity, and less frequent and more localized interictal epileptiform discharges. Ictal EEG patterns analyzed in 9 ENCs showed delayed and slower contralateral spread compared to TLEs. All ENCs that underwent surgery (7 lobectomies and 1 lesionectomy) are in Engel class I. Neuropathological examination revealed 4 patterns: herniated brain fragments, focal layer I distortion, white matter septa extending into the cortex, and altered gyral profile. CONCLUSIONS AND SIGNIFICANCE: The described peculiarities might help clinicians to suspect the presence of largely underdiagnosed ENCs.

3D4K exoscope in epilepsy surgery: a seminal experience.

BACKGROUND AND OBJECTIVES: To report the progressive introduction of the exoscope (EX) from surface lesionectomy to antero-mesial temporal lobectomy (AMTL) in an epilepsy surgery practice. METHODS: We describe a population of ten consecutive patients undergoing EX surgery, with a minimum follow-up of 6 months, that was compared to a similar population of patients referred to operative microscopic surgery (OM). RESULTS: All surgeries were performed with the use of EX or OM alone. Transient neurological complications for surgery in eloquent regions were recorded in one patient for each population. Nine and seven patients undergoing, respectively, EX and OM surgery resulted in Engel class Ia (90% vs. 70%). The mean duration of EX and OM surgery resulted in 265.5 and 237.9 min, respectively, with a mean of 308.3 and 253.3 min for AMTL cases, respectively. CONCLUSIONS: This preliminary study revealed that ORBEYE EX can be safe and effective in different types of epilepsy surgeries. The transition from OM to EX is fast, even though it is slower for the more challenging mesial temporal structure removal. Ergonomic and operative team interaction is improved by the use of EX. Our data need to be confirmed by larger studies.

Sustained seizure freedom with adjunctive brivaracetam in patients with focal onset seizures.

The maintenance of seizure control over time is a clinical priority in patients with epilepsy. The aim of this study was to assess the sustained seizure frequency reduction with adjunctive brivaracetam (BRV) in real-world practice. Patients with focal epilepsy prescribed add-on BRV were identified. Study outcomes included sustained seizure freedom and sustained seizure response, defined as a 100% and a ≥50% reduction in baseline seizure frequency that continued without interruption and without BRV withdrawal through the 12-month follow-up. Nine hundred ninety-four patients with a median age of 45 (interquartile range = 32-56) years were included. During the 1-year study period, sustained seizure freedom was achieved by 142 (14.3%) patients, of whom 72 (50.7%) were seizure-free from Day 1 of BRV treatment. Sustained seizure freedom was maintained for ≥6, ≥9, and 12 months by 14.3%, 11.9%, and 7.2% of patients from the study cohort. Sustained seizure response was reached by 383 (38.5%) patients; 236 of 383 (61.6%) achieved sustained ≥50% reduction in seizure frequency by Day 1, 94 of 383 (24.5%) by Month 4, and 53 of 383 (13.8%) by Month 7 up to Month 12. Adjunctive BRV was associated with sustained seizure frequency reduction from the first day of treatment in a subset of patients with uncontrolled focal epilepsy.

Sleep disorders and mental health in hospital workers during the COVID-19 pandemic: a cross-sectional multicenter study in Northern Italy.

INTRODUCTION: From the beginning of the COVID-19 pandemic, healthcare workers had to face unprecedented emergency needs associated with an extraordinary amount of psychological distress. In this cross-sectional multicenter study, we investigated sleep disturbances, and the level of anxiety and depression among the healthcare and non-healthcare staff of three hospitals in Milan (Italy) during the COVID-19 outbreak. Moreover, we explored potential predisposing factors for affective symptoms and poor sleep. METHODS: Between June and July 2020, we administered an online questionnaire to evaluate the presence of sleep disorders (Pittsburgh Sleep Quality Index), insomnia (Sleep Condition Indicator), anxiety (State Trait Anxiety Inventory), and depression (Beck Depression Inventory-II). We used univariate and multivariate analysis to evaluate the association between the personal conditions and sleep and affective disorders. RESULTS: The 964 participants reported high rates of sleep disorders (80.3%)-mainly insomnia (30.5%)-anxiety (69.7%), and depression (32.8%). The multivariate analysis showed a strong association of sleep disorders, especially insomnia, with female gender (p = 0.004), divorced marital status (p = 0.015), self-isolation (p = 0.037), and chronic diseases (p = 0.003). Anxiety was significantly associated with teleworking (p = 0.001), while depressive symptoms were associated with self-isolation (p = 0.028), modified work schedules (p = 0.03), and chronic diseases (p = 0.027). CONCLUSION: In hospital workers, the high prevalence of sleep and psychiatric symptoms during the COVID-19 outbreak appears to be determined mainly by modifications of personal or work habits. Teleworking was associated with increased anxiety. An accurate planning of hospital activities and a psychological support are needed to prevent and manage sleep and mental disorders.

Brivaracetam as add-on treatment in focal epilepsy: A real-world time-based analysis.

The study assessed the clinical response to add-on brivaracetam (BRV) in real-world practice by means of time-to-baseline seizure count methodology. Patients with focal epilepsy who were prescribed add-on BRV were identified. Primary endpoint was the time-to-baseline seizure count defined as the number of days until each patient experienced the number of focal seizures that occurred in the 90 days before BRV initiation. Subgroup analysis was performed according to levetiracetam (LEV) status (naive vs prior use). Three-hundred eighty-seven patients were included. The overall median time-to-baseline seizure count was 150 (95% confidence interval [CI] = 130-175) days. The median time-to-baseline seizure count was 198 (lower limit of 95% CI = 168) days for LEV-naive patients, 126 (95% CI = 105-150) days for patients with prior LEV use and withdrawal due to insufficient efficacy, and 170 (95% CI = 128-291) days for patients who discontinued LEV due to adverse events (P = .002). The number of prior antiseizure medications (adjusted hazard ratio [adj HR] = 1.07, 95% CI = 1.02-1.13, P = .009) and baseline monthly seizure frequency (adj HR = 1.004, 95% CI = 1.001-1.008, P = .028) were independently associated with the primary endpoint. Add-on BRV improved seizure control in LEV-naive and LEV-prior patients. The time-to-baseline seizure count represents an informative endpoint alongside traditional study outcomes and designs.

Temporal lobe epilepsy surgery in children and adults: A multicenter study.

OBJECTIVE: To assess seizure and cognitive outcomes and their predictors in children (<16 years at surgery) and adults undergoing temporal lobe epilepsy (TLE) surgery in eight Italian centers. METHODS: This is a retrospective multicenter study. We performed a descriptive analysis and subsequently carried out multivariable mixed-effect models corrected for multiple comparisons. RESULTS: We analyzed data from 511 patients (114 children) and observed significant differences in several clinical features between adults and children. The possibility of achieving Engel class IA outcome and discontinuing antiepileptic drugs (AEDs) at last follow-up (FU) was significantly higher in children (P = .006 and < .0001). However, percentages of children and adults in Engel class I at last FU (mean ± SD, 45.9 ± 17 months in children; 45.9 ± 20.6 months in adults) did not differ significantly. We identified different predictors of seizure outcome in children vs adults and at short- vs long-term FU. The only variables consistently associated with class I outcome over time were postoperative electroencephalography (EEG) in adults (abnormal, improved,odds ratio [OR] = 0.414, P = .023, Q = 0.046 vs normal, at 2-year FU and abnormal, improved, OR = 0.301, P = .001, Q = 0.002 vs normal, at last FU) and the completeness of resection of temporal magnetic resonance (MR) abnormalities other than hippocampal sclerosis in children (OR = 7.93, P = .001, Q = 0.003, at 2-year FU and OR = 45.03, P < .0001, Q < 0.0001, at last FU). Cognitive outcome was best predicted by preoperative performances in either age group. SIGNIFICANCE: Clinical differences between adult and pediatric patients undergoing TLE surgery are reflected in differences in long-term outcomes and predictors of failures. Children are more likely to achieve sustained seizure freedom and withdraw AEDs after TLE surgery. Earlier referral should be encouraged as it can improve surgical outcome.

Neuro-telehealth for fragile patients in a tertiary referral neurological institute during the COVID-19 pandemic in Milan, Lombardy.

BACKGROUND: Lombardy was severely hit by the COVID-19 pandemic since February 2020 and the Health System underwent rapid reorganization. Outpatient clinics were stopped for non-urgent patients: it became a priority to manage hundreds of fragile neurological patients who suddenly had less reference points. In Italy, before the pandemic, Televisits were neither recognized nor priced. METHODS: At the Fondazione IRCCS Istituto Neurologico C. Besta, we reorganized outpatient clinics to deliver Neuro-telemedicine services, including Televisits and Teleneurorehabilitation, since March 2020. A dedicated Working Group prepared the procedure, tested the system, and designed satisfaction questionnaires for adults and children. RESULTS: After a pilot phase, we prepared a procedure for Telemedicine outpatient clinics which was approved by hospital directions. It included prescription, booking, consenting, privacy and data protection, secure connection with patients (Teams Microsoft 365), electronic report preparation and delivery, reporting, and accountability of the services. During the March-September 2020 period, we delivered 3167 Telemedicine services, including 1618 Televisits, to 1694 patients (972 adults, 722 children) with a wide range of chronic neurological disorders. We successfully administered different clinical assessment and scales. Satisfaction among patients and caregivers was very high. CONCLUSIONS: During the dramatic emergency, we were able to take care of more than 1600 patients by organizing Neuro-telehealth in a few weeks, lessening the impact of the pandemic on fragile patients with chronic neurological disorders; this strategy is now stably embedded in our care pathways. In Italy, Telehealth is at present recognized and priced and is becoming a stable pillar of the health system.

pCREB expression in human tissues from epilepsy surgery.

OBJECTIVE: Activity-dependent changes have been reported in animal models and in human epileptic specimens and could potentially be used as tissue biomarkers to evaluate the propensity of a tissue to generate seizure activity. In this context, cAMP-response element binding protein (CREB) activation was specifically reported in human epileptic foci and related mainly to interictal spike activity. To get further insights into CREB activation in human epilepsy, we analyzed pCREB expression on brain tissue samples from patients who underwent surgery for drug-resistant focal epilepsy, correlating this expression with intracranial stereo-electroencephalography (SEEG) recording in a subgroup. METHODS: Neocortical specimens from patients with neuropathological diagnosis of no lesion (cryptogenic), malformations of cortical development,mainly type II focal cortical dysplasia (FCD), and hippocampi with and without hippocampal sclerosis have been analyzed by immunohistochemistry. Peritumoral cortex from non-epileptic patients and autoptic samples were used as controls, whereas rat brains were used to test possible loss of pCREB antigenicity due to fixation procedures and postmortem delay. RESULTS: pCREB was consistently expressed in layer II neuronal nuclei in regions with normal cortical lamination both in epileptic and non-epileptic surgical tissues. In patients with SEEG recordings, this anatomical pattern was unrelated to the presence of interictal spike activity. Conversely, in the core of type II FCD, as well as in other developmental malformations, pCREB was scattered without any laminar specificity. Furthermore, quantitative data did not reveal significant differences between epileptic and non-epileptic tissues, except for an increased immunoreactivity in the core of type IIB FCD lesion related mainly to reactive glial and balloon cells. SIGNIFICANCE: The present data argue against the reliability of pCREB immunohistochemistry as a marker of epileptic focus but underscores its layer-related expression, suggesting a potential application in the study of malformations of cortical development, a wide range of diseases arising from perturbations of normal brain development.

Quality of life, psychiatric symptoms, and stigma perception in three groups of persons with epilepsy.

OBJECTIVE: The current study aimed to describe quality of life (QoL) levels, psychiatric symptoms prevalence, and perceived stigma levels in persons with either drug-resistant epilepsy (DRE) or drug-sensitive epilepsy (DSE) and in persons with epilepsy (PwE) with DRE that underwent epilepsy surgery (DREES). METHODS: Persons with epilepsy diagnosed as having DRE according to International League Against Epilepsy (ILAE) criteria, DSE, and DREES were enrolled at the Epilepsy Unit of the Neurological Institute Carlo Besta of Milan. Sociodemographic and clinical data, Quality of Life in Epilepsy Inventory (QOLIE-31), Symptom Checklist-90 (SCL-90), and the Epilepsy Stigma Scale (ESS) were collected based on self-reported information and on medical records. RESULTS: Sociodemographic, medical, and psychological data were obtained from 181 PwE: 80 with DRE, 31 with DSE, and 70 with DREES. We found that QoL is higher and psychiatric symptoms are lower in persons with DSE compared with DRE and that patients with DREES, who were drug-resistant before surgery, are in between DSE and DRE for both measures. Perceived stigma level is different in DSE and in DRE, that report the highest levels of stigma, and is between the other two groups in DREES. SIGNIFICANCE: This study suggests that low QoL levels and high psychiatric symptoms prevalence in drug-resistant PwE may be significantly improved after epilepsy surgery and suggests the importance of a biopsychosocial approach when planning therapeutic intervention.

Epilepsy course during COVID-19 pandemic in three Italian epilepsy centers.

During epidemic outbreaks, epilepsy course can be modified by different physical and psychological stressors and, most importantly, by irregular therapy intake. The effect of COVID-19 and quarantine isolation on the course of epilepsy and on incidence of new-onset seizures is still unclear. With the aim of managing epilepsy in quarantined patients, three Italian Epilepsy Centers set up telephone consultations using a semistructured interview, allowing a prospective collection of data on seizure course and other seizure-related problems during pandemic. The collected data on seizure course were compared with the analogous period of 2019. The level of patients' concern relating to the COVID-19 pandemic was also assessed using a numeric rating scale. To address the effect of COVID-19 pandemic on seizure incidence, data collection included the number of consultations for first seizures, relapse seizures, and status epilepticus (SE) in the emergency department of one of the participating centers. Clinical telephone interviews suggest the absence of quarantine effect on epilepsy course in our cohort. No differences in incidence of emergency consultations for seizures over a two-month period were also observed compared with a control period. As demonstrated in other infective outbreaks, good antiepileptic drug (AED) supplying, precise information, and reassurance are the most important factors in chronic conditions to minimize psychological and physical stress, and to avoid unplanned treatment interruptions.

Sporadic Fatal Insomnia in Europe: Phenotypic Features and Diagnostic Challenges.

OBJECTIVE: Comprehensively describe the phenotypic spectrum of sporadic fatal insomnia (sFI) to facilitate diagnosis and management of this rare and peculiar prion disorder. METHODS: A survey among major prion disease reference centers in Europe identified 13 patients diagnosed with sFI in the past 20 years. We undertook a detailed analysis of clinical and histopathological features and the results of diagnostic investigations. RESULTS: Mean age at onset was 43 years, and mean disease duration 30 months. Early clinical findings included psychiatric, sleep, and oculomotor disturbances, followed by cognitive decline and postural instability. In all tested patients, video-polysomnography demonstrated a severe reduction of total sleep time and/or a disorganized sleep. Cerebrospinal fluid (CSF) levels of proteins 14-3-3 and t-tau were unrevealing, the concentration of neurofilament light protein (NfL) was more consistently increased, and the real-time quaking-induced conversion assay (RT-QuIC) revealed a positive prion seeding activity in 60% of cases. Electroencephalography and magnetic resonance imaging showed nonspecific findings, whereas fluorodeoxyglucose positron emission tomography (FDG-PET) demonstrated a profound bilateral thalamic hypometabolism in 71% of cases. Molecular analyses revealed PrPSc type 2 and methionine homozygosity at PRNP codon 129 in all cases. INTERPRETATION: sFI is a disease of young or middle-aged adults, which is difficult to reconcile with the hypothesis of a spontaneous etiology related to stochastic, age-related PrP misfolding. The combination of psychiatric and/or sleep-related symptoms with oculomotor abnormalities represents an early peculiar clinical feature of sFI to be valued in the differential diagnosis. Video-polysomnography, FDG-PET, and especially CSF prion RT-QuIC and NfL constitute the most promising supportive diagnostic tests in vivo. Ann Neurol 2018;84:347-360.

The impact of perampanel treatment on quality of life and psychiatric symptoms in patients with drug-resistant focal epilepsy: An observational study in Italy.

An observational, prospective study has been conducted to evaluate the effects of adjunctive treatment with perampanel (PER) on psychological functioning and quality of life (QoL) in patients with drug-resistant focal epilepsy. Fifty-six adult patients treated with PER in addition to antiepileptic drugs (AEDs) were recruited in 2 Italian Epilepsy Centers. Irritability in Adult Patients with Epilepsy (I-EPI), Quality of Life in Epilepsy (QOLIE-31), Beck Depression Inventory II (BDI-II), and State-Trait Anxiety Inventory Y-1 and Y-2 (STAI) questionnaires were administered at baseline and 3 and 6 months after the treatment onset. Adverse events (AEs) were collected during the observational 6 months period. Retention rate of treatment with PER was 82.1% at 3 months and 64.3% at 6 months. Thirteen patients reported a significant seizure frequency reduction, and one seizure freedom case was observed after 4 months of PER treatment. Perampanel was stopped because of inefficacy or paradoxical effects in 28.6% of cases and because of AEs in 7.1%. The peak dose was not associated with discontinuation probability. Irritability, QoL, depression, trait, and state anxiety did not change significantly during the PER therapy. A tendency of association between higher level of irritability at baseline and PER discontinuation was found. The results of this observational study have shown that the addition of PER to AEDs may improve seizure control, does not increase levels of irritability, depression, and anxiety, and does not reduce patients' QoL. This study also confirms the importance of a comprehensive clinical assessment, including psychiatric symptoms evaluation before offering a new treatment, to improve therapy compliance.

Seizure activity per se does not induce tissue damage markers in human neocortical focal epilepsy.

OBJECTIVE: The contribution of recurring seizures to the progression of epileptogenesis is debated. Seizure-induced brain damage is not conclusively demonstrated either in humans or in animal models of epilepsy. We evaluated the expression of brain injury biomarkers on postsurgical brain tissue obtained from 20 patients with frequent seizures and a long history of drug-resistant focal epilepsy. METHODS: The expression patterns of specific glial, neuronal, and inflammatory molecules were evaluated by immunohistochemistry in the core of type II focal cortical dysplasias (FCD-II), at the FCD boundary (perilesion), and in the adjacent normal-appearing area included in the epileptogenic region. We also analyzed surgical specimens from cryptogenic patients not presenting structural alterations at imaging. RESULTS: Astroglial and microglial activation, reduced neuronal density, perivascular CD3-positive T-lymphocyte clustering, and fibrinogen extravasation were demonstrated in the core of FCD-II lesions. No pathological immunoreactivity was observed outside the FCD-II or in cryptogenetic specimens, where the occurrence of interictal and ictal epileptiform activity was confirmed by either stereo-electroencephalography or intraoperative electrocorticography. INTERPRETATION: Recurrent seizures do not induce the expression of brain damage markers in nonlesional epileptogenic cortex studied in postsurgical tissue from cryptogenic and FCD patients. This evidence argues against the hypothesis that epileptiform activity per se contributes to focal brain injury, at least in the neocortical epilepsies considered here. Ann Neurol 2017;82:331-341.

Type II focal cortical dysplasia: Ex vivo 7T magnetic resonance imaging abnormalities and histopathological comparisons.

OBJECTIVE: In the present report, the correlations between ex vivo high-resolution imaging and specific histological and ultrastructural patterns in type II focal cortical dysplasia (FCD) have been studied to explain the differences in the magnetic resonance imaging (MRI) detection of dysplasia and to contribute to the presurgical imaging evaluation of this pathology. METHODS: Surgical specimens from 13 patients with FCD IIa/b were submitted to 7T MRI scanning, and then analyzed histologically and ultrastructurally to compare the results with the MRI findings. Region of interest (ROI)-based measures on T2-weighted images (T2wi) were quantitatively evaluated in the lesion and in adjacent perilesional gray and white matter. RESULTS: Matched histological sections and 7T T2wi showed that the core of the lesion was characterized by patchy aggregates of abnormal cells and fiber disorganization related to inhomogeneity of intracortical signal intensity. The quantitative approach on T2wi can help to distinguish the lesions and perilesional areas even in a clinical MRI-negative case. The ultrastructural study showed that the strong signal hyperintensity in the white matter of FCD IIb was related to a dysmyelination process associated with severe fiber loss and abnormal cells. Less severe histopathological features were found in FCD IIa, thus reflecting their less evident MRI alterations. INTERPRETATION: We suggest that white matter abnormalities in type IIb FCD are due to defects of the myelination processes and maturation, impaired by the presence of balloon cells. To reveal the presence and the border of type II cortical dysplasia on MRI, a quantitative ROI-based analysis (coefficient of variation) is also proposed.

Epilepsy surgery of "low grade epilepsy associated neuroepithelial tumors": A retrospective nationwide Italian study.

OBJECTIVE: To analyze the attitude and results of Italian epilepsy surgery centers in the surgical management of "low grade epilepsy associated neuroepithelial tumors" (LEATs). METHODS: We conducted a retrospective study enrolling 339 consecutive patients with LEATs who underwent surgery between January 2009 and June 2015 at eight Italian epilepsy surgery centers. We compared demographic, clinical, pathologic, and surgical features of patients with favorable (Engel class I) and unfavorable (Engel class II, III, and IV) seizure outcome. In addition, we compared patients with tumor-associated focal cortical dysplasia (FCD) and patients with solitary tumors to identify factors correlated with FCD diagnosis. RESULTS: Fifty-five (98.2%) of 56 patients with medically controlled epilepsy were seizure-free after surgery, compared to 249 (88.0%) of 283 patients with refractory epilepsy. At multivariate analysis, three variables independently predict unfavorable seizure outcome in the drug-resistant group. Age at surgery is largely the most significant (p = 0.001), with an odds ratio (OR) of 1.04. This means that the probability of seizure recurrence grows by 4% for every waited year. The resection site is also significant (p = 0.039), with a relative risk (RR) of 1.99 for extratemporal tumors. Finally, the completeness of tumor resection has a trend toward significance (p = 0.092), with an RR of 1.82 for incomplete resection. Among pediatric patients, a longer duration of epilepsy was significantly associated with preoperative neuropsychological deficits (p < 0.001). A statistically significant association was observed between FCD diagnosis and the following variables: tailored surgery (p < 0.001), temporal resection (p = 0.001), and surgical center (p = 0.012). SIGNIFICANCE: Our nationwide LEATs study gives important insights on factors predicting seizure outcome in refractory epilepsy and determining variability in FCD detection. Timely surgery, regardless of pharmacoresistance and oriented to optimize epileptologic, neuropsychological, and oncologic outcomes should be warranted.

Increasing volume and complexity of pediatric epilepsy surgery with stable seizure outcome between 2008 and 2014: A nationwide multicenter study.

OBJECTIVE: The objective of the study was to assess common practice in pediatric epilepsy surgery in Italy between 2008 and 2014. METHODS: A survey was conducted among nine Italian epilepsy surgery centers to collect information on presurgical and postsurgical evaluation protocols, volumes and types of surgical interventions, and etiologies and seizure outcomes in pediatric epilepsy surgery between 2008 and 2014. RESULTS: Retrospective data on 527 surgical procedures were collected. The most frequent surgical approaches were temporal lobe resections and disconnections (133, 25.2%) and extratemporal lesionectomies (128, 24.3%); the most frequent etiologies were FCD II (107, 20.3%) and glioneuronal tumors (105, 19.9%). Volumes of surgeries increased over time independently from the age at surgery and the epilepsy surgery center. Engel class I was achieved in 73.6% of patients (range: 54.8 to 91.7%), with no significant changes between 2008 and 2014. Univariate analyses showed a decrease in the proportion of temporal resections and tumors and an increase in the proportion of FCDII, while multivariate analyses revealed an increase in the proportion of extratemporal surgeries over time. A higher proportion of temporal surgeries and tumors and a lower proportion of extratemporal and multilobar surgeries and of FCD were observed in low (<50surgeries/year) versus high-volume centers. There was a high variability across centers concerning pre- and postsurgical evaluation protocols, depending on local expertise and facilities. SIGNIFICANCE: This survey reveals an increase in volume and complexity of pediatric epilepsy surgery in Italy between 2008 and 2014, associated with a stable seizure outcome.

Expanding the spectrum of cognitive outcomes after temporal lobe epilepsy surgery: A prospective study of theory of mind.

OBJECTIVE: Because temporal lobe epilepsy (TLE) can impair theory of mind (ToM), we examined the effects of anterior temporal lobectomy (ATL) by comparing the preoperative to postoperative ToM course with that of other cognitive functions characteristically impaired in TLE. METHODS: Eighty-five patients with left (n = 39) or right (n = 46) drug-resistant TLE and an age at epilepsy onset of >12 (n = 54) or ≤12 years (n = 31) were evaluated before and 1 year after surgery; 40 healthy controls were assessed at baseline. The participants' recognition and comprehension of faux pas (FPs) or correct rejection of nonexistent FPs was assessed using the Faux Pas task; and their language, memory, and planning were, respectively, assessed using the Boston Naming, Short Story, and Tower of London tests. RESULTS: Baseline ToM was impaired in the patients with left or right TLE in comparison with the controls, and significantly influenced by education and age at seizure onset, with more severe deficits being observed in those with less education and an age at onset of ≤12 years. After ATL, their recognition and comprehension of FPs was unchanged, whereas the rejection of nonexistent FPs improved in the patients with early seizure onset. Education, preoperative ToM, postoperative executive function, and fluid intelligence and the number of antiepileptic drugs predicted postoperative ToM. Postoperative naming and episodic memory were associated with ATL laterality and education, and planning was associated with age at seizure onset and chronological age. SIGNIFICANCE: After ATL, the components of ToM may be unchanged or slightly improved depending on cognitive reserve and age at seizure onset, thus suggesting that ATL does not further aggravate the deficits caused by TLE. Moreover, the course of ToM is distinct from that of other cognitive functions. These findings expand the spectrum of the cognitive phenotypes associated with TLE and ATL, and offer potential elements for individual prognoses.

PARADISE 24 instrument: An observational study on psychosocial difficulties, quality of life, and disability levels in patients with epilepsy.

AIM: The aim of this observational study was to test the effectiveness of the PARADISE 24 instrument in describing the psychosocial difficulties (PSDs) reported by people with epilepsy, their relation with disability, and quality-of-life (QoL) levels and, overall, to explore a horizontal epidemiology methodology applied to a sample of patients with epilepsy. METHODS: A convenience sample of 80 adult patients with epilepsy was included in this cross-sectional study. Patients were interviewed using a structured protocol composed of demographic, clinical, and patient-reported outcome measures to collect PSDs associated with epilepsy. RESULTS: There were 80 patients, 40 females; mean age was 41.2years; mean disease duration was 18.7years; and mean number of AED was 2.09. Moderate severity rating according to clinicians' rating scale, low impact of comorbidities (mean: 2.36, SD: 2.97), high levels of QoL (mean: 30.00, SD: 4.4), medium levels of resilience (mean: 13.56, SD: 2.66), high levels of perceived empathy (mean: 15.05, SD: 4.74), poor or moderate perceived social support, and low levels of disability (mean: 10.85, SD: 10.05) were observed. The most frequently reported PSDs were related to tiredness (80%), emotional problems (73.75%), anxiety (68.75%), depressive mood (66.25%), and driving problems (61.25%). The EUROHIS-QOL (p=.003) had a negative significant relationship with PARADISE 24 while WHODAS-12 (p=.000) and CRS (p=.027) had a positive significant relationship with PARADISE 24. CONCLUSIONS: The PARADISE 24 permits data comparison and the creation of a complete description of a person's functioning and of all of his/her PSDs and allows better and more tailored interventions.