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Cenobamate is a new antiseizure medication (ASM) recently introduced in the USA for the treatment of adults with focal-onset seizures. In March 2021, the European Commission authorized its use for the adjunctive treatment of focal-onset seizures with or without secondary generalization (focal seizures with or without progression to bilateral tonic-clonic seizures, according to current ILAE terminology) in adults with epilepsy not adequately controlled despite the treatment with at least two ASMs. This review summarizes the mechanism of action, efficacy, and safety of Cenobamate. The authors provide their expert opinions on the use of this drug. The aim of this paper is to report on the Italian preliminary experience with the use of cenobamate, focusing on treatment goals, optimal dosing and titration schedules, strategies to minimize adverse effects, and identification of suitable candidates for treatment. There was agreement that slow titration may improve tolerability, and that clinically significant benefit can be achieved in many patients at relatively low doses. A favorable response to relatively low doses of cenobamate could be an early predictor of ultimate responsiveness. Overall, cenobamate is a welcome new treatment for adults with focal seizures resistant to conventional ASMs.

Abstract Introduction During the COVID-19 pandemic, electroencephalography (EEG) proved to be a useful tool to demonstrate brain involvement. Many studies reported non-reactive generalized slowing as the most frequent pattern and epileptiform activity in a minority of patients. Objective To investigate the prevalence of diffuse unreactive background attenuation or suppression and its correlation with outcome in a cohort of COVID-19 patients. Methods The EEGs recorded during the first year of the COVID-19 pandemic were retrospectively evaluated to identify the main pattern and focus on the occurrence of a low-voltage background, either attenuated (10–20 μV) or suppressed ( Results Among 98 EEG performed in 50 consecutive patients, diffuse unreactive slowing was the most prevalent pattern (54%), followed by unreactive attenuation or suppression pattern (26%), being the latter significantly correlated with an unfavourable outcome (p = 0.0004). Survivors showed significantly lower interleukine-6 values compared to non-survivors. Patients with attenuated EEG and non-survivors also showed lower PaO2/FiO2 values. Neuroradiological findings were very heterogeneous with a prevalence of lesions suggestive of a microangiopathic substrate. Conclusions EEG attenuation or suppression may be more frequent than previously reported and significantly associated with a poor outcome. SARS-CoV-2 infection may result in encephalopathy and reduced EEG voltage through mechanisms that are still unknown but deserve attention given its negative impact on prognosis.

OBJECTIVE Lateral periinsular hemispherotomy (LPH) and vertical parasagittal hemispherotomy (VPH) are the most popular disconnective techniques for intractable epilepsies associated with unilateral hemispheric pathologies. The authors aimed to investigate possible differences in seizure outcome and complication rates between patients who underwent LPH and VPH. METHODS A comprehensive literature search of PubMed and Embase identified English-language articles published from database inception to December 2019 that reported series (minimum 12 patients with follow-up ≥ 12 months) on either LPH or VPH. Pooled rates of seizure freedom and complications (with a particular focus on hydrocephalus) were analyzed using meta-analysis to calculate both fixed and random effects. Heterogeneity (Cochran’s Q test) and inconsistency (fraction of Q due to actual heterogeneity) were also calculated. RESULTS Twenty-five studies were included. Data from 825 patients were available for seizure outcome analysis (583 underwent LPH and 242 underwent VPH), and data from 692 patients were available for complication analysis (453 underwent LPH and 239 underwent VPH). No differences were found in the pooled rates of Engel class I seizure outcome between patients who underwent LPH (80.02% and 79.44% with fixed and random effects, respectively) and VPH (79.89% and 80.69% with fixed and random effects, respectively) (p = 0.953). No differences were observed in the pooled rates of shunted hydrocephalus between patients who underwent LPH (11.34% and 10.63% with fixed and random effects, respectively) and VPH (11.07% and 9.98% with fixed and random effects, respectively) (p = 0.898). Significant heterogeneity and moderate inconsistency were determined for hydrocephalus occurrence in patients who underwent both LPH and VPH. CONCLUSIONS LPH and VPH techniques present similar excellent seizure outcomes, with comparable and acceptable safety profiles.

Objective: This study was undertaken to elicit patients' preferences for attributes characterizing antiseizure medication (ASM) monotherapy options before treatment consultation, and to explore the trade‐offs patients consider between treatment efficacy and risks of side effects. Further objectives were to explore how treatment consultation may affect patient preferences, to elicit physicians' preferences in selecting treatment, and to compare patient and physician preferences for treatment. Methods: This prospective, observational study (EP0076; VOTE) included adults with focal seizures requiring a change in their ASM monotherapy. Patients completed a discrete choice experiment (DCE) survey before and after treatment consultation. Physicians completed a similar survey after the consultation. The DCE comprised 12 choices between two hypothetical treatments defined by seven attributes. The conditional relative importance of each attribute was calculated. Results: Three hundred ten patients (mean [SD] age = 46.8 [18.3] years, 52.3% female) were enrolled from eight European countries, of whom 305 completed the survey before consultation and 273 completed the survey before and after consultation. Overall, this preference study in patients who intended to receive a new ASM monotherapy suggests that patient preferences were ordered as expected, with better outcomes being preferred to worse outcomes; patients preferred a higher chance of seizure freedom, lower risk of developing clinical depression, and fewer severe adverse events; avoiding moderate‐to‐severe “trouble thinking clearly” was more important than avoiding any other side effect. There were qualitative differences in what patients and physicians considered to be the most important aspects of treatment for patients; compared with patients, physicians had a qualitatively stronger preference for greater chance of seizure freedom and avoiding personality changes. Patients' preference weights were qualitatively similar before and after treatment consultation. Significance: For patients, seizure freedom and avoiding trouble thinking clearly were the most important treatment attributes. Physicians and patients may differ in the emphasis they place on specific attributes.

The study of dementia and epilepsy may provide particular insight into behavioural alterations. We describe a rare case of ictal aggressive behaviour in a patient with focal epilepsy associated with a non-dominant dorso-lateral prefrontal lesion. During focal seizures, our patient showed intense agitation and anger, for a long time misinterpreted as psychogenic attacks, which disappeared after epilepsy surgery. The defined anatomical origin of such ictal emotional behaviour is not fully understood, however, the dorso-lateral prefrontal area appears to correlate less frequently with aggressiveness compared to the antero-mesial area. We describe the electroclinical data of our patient and provide a brief review of the mechanisms underlying aggressive conduct in epilepsy and dementia. An understanding of this mechanism could help to clarify the neural basis and treatment of violence associated with these and other neurological disorders. [Published with video sequence].

Hybrid operating room represents nowadays an important tool in the management of a constantly increasing number of complex surgical procedures which necessitate appropriate settings in order to be performed safely. We herein present the peculiarities and applications of such a versatile operating environment which is capable of guaranteeing the best performances in terms of equipment and imaging tools respecting the standards of asepsis that a simple angiographic room could not offer. In particular, we focus on its relevance in the field of complex vascular pathology, and on the importance of setting an appropriate management process in order to make the most of its potentialities without sacrificing the not negligible costs connected to it.

Background: Hippocampal sclerosis (HS) may be associated with focal cortical dysplasia IIIa (FCD IIIa) in patients undergoing surgery for temporal lobe epilepsy (TLE). Objective: To investigate whether the anatomo-electro-clinical profile and surgical outcome in patients with HS-related TLE are affected by coexisting FCD IIIa. Methods: A total of 220 patients, operated in 5 centers, with at least 24 mo follow-up (FU), were retrospectively studied. Preliminary univariate and subsequent multivariate analyses were performed to investigate possible associations between several potential presurgical, surgical, and postsurgical predictors and different variables (Engel's class I and Engel's class Ia, co-occurrence of FCD IIIa). Results: At last available postoperative control (FU: range 24-95 mo, median 47 mo), 182 (82.7%) patients were classified as Engel's class I and 142 (64.5%) as Engel's class Ia. At multivariate analysis, extension of neocortical resection and postoperative electroencephalogram were significantly associated with Engel's class I, whereas length of FU had a significant impact on class Ia in the whole cohort and in isolated HS (iHS) patients, but not in the FCD IIIa group. No differences emerged in the anatomo-electro-clinical profile and surgical results between patients with FCD IIIa and with iHS. Conclusion: Coexistence of FCD IIIa did not confer a distinct anatomo-electro-clinical profile to patients with HS-related epilepsy. Postoperative seizure outcome was similar in FCD IIIa and iHS cases. These findings indicate limited clinical relevance of FCD IIIa in HS-related epilepsy and might be useful for refining future FCD classifications. Further studies are needed to clarify the correlation of class Ia outcome with the duration of FU.

BACKGROUND: The management of epilepsy in older adults has become part of daily practice because of an aging population. Older patients with epilepsy represent a distinct and more vulnerable clinical group as compared with younger patients, and they are generally under-represented in randomized placebo-controlled trials. Real-world studies can therefore be a useful complement to characterize the drug's profile. Brivaracetam is a rationally developed compound characterized by high-affinity binding to synaptic vesicle protein 2A and approved as adjunctive therapy for focal seizures in adults with epilepsy. OBJECTIVE: The aim of this study was to assess the 12-month effectiveness and tolerability of adjunctive brivaracetam in older patients (≥65 years of age) with epilepsy treated in a real-world setting. METHODS: The BRIVAFIRST (BRIVAracetam add-on First Italian netwoRk STudy) was a 12-month retrospective multicenter study including adult patients prescribed adjunctive brivaracetam. Effectiveness outcomes included the rates of seizure response (≥50% reduction in baseline seizure frequency), seizure freedom, and treatment discontinuation. Safety and tolerability outcomes included the rate of treatment discontinuation due to adverse events and the incidence of adverse events. Data were compared for patients aged ≥65 years of age ('older') vs those aged

Objective: Post-stroke epilepsy (PSE) is one of the most common causes of acquired epilepsy and accounts for about 10-15% of all newly diagnosed epilepsy cases. However, evidence about the clinical profile of antiseizure medications in the PSE setting is currently limited. Brivaracetam (BRV) is a rationally developed compound characterized by high-affinity binding to synaptic vesicle protein 2A. The aim of this study was to assess the 12-month effectiveness and tolerability of adjunctive BRV in patients with PSE treated in a real-world setting. Methods: This was a subgroup analysis of patients with PSE included in the BRIVAracetam add-on First Italian netwoRk Study (BRIVAFIRST). The BRIVAFIRST was a 12-month retrospective, multicentre study including adult patients prescribed adjunctive BRV. Effectiveness outcomes included the rates of seizure response (≥50% reduction in baseline seizure frequency), seizure‐freedom, and treatment discontinuation. Safety and tolerability outcomes included the rate of treatment discontinuation due to adverse events (AEs) and the incidence of AEs. Results: Patients with PSE included in the BRIVAFIRST were 75 and had a median age of 57 (interquartile range, 42-66) years. The median daily doses of BRV at 3, 6, and 12 months from starting treatment were 100 (100-150) mg, 125 (100-200) mg and 100 (100-200) mg, respectively. At 12 months, 32 (42.7%) patients had a reduction in their baseline seizure frequency by at least 50%, and the seizure freedom rates was 26/75 (34.7%). During the 1-year study period, 10 (13.3%) patients discontinued BRV. The reasons of treatment withdrawal were insufficient efficacy in 6 (8.0%) patients and poor tolerability in 4 (5.3%) patients. Adverse events were reported by 13 (20.3%) patients and were rated as mild in 84.6% and moderate in 15.4% of cases. Significance: Adjunctive BRV was efficacious and generally well-tolerated when used in patients with PSE in clinical practice. Adjunctive BRV can be a suitable therapeutic option for patients with PSE.

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 12months 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.

The current study, conceived with the contribution of the Commission for Epilepsy Surgery of the Italian League Against Epilepsy (LICE) and the Epilepsy Study Group of the Italian Neurological Society (SIN), aimed to assess potential physician-related barriers to refer subjects for epilepsy surgery. All the members of SIN and LICE were invited by email to complete a 28-item online questionnaire. The survey items included: (1) individual and medical practice characteristics, (2) knowledge of current indications to select candidates for epilepsy surgery, (3) factors potentially affecting the attitude toward epilepsy surgery. Overall, 210 physicians completed the survey. More than half (63.3%) of the participants showed proper knowledge of the ILAE drug-resistance. Definition and almost two-thirds of them (71.9%) considered themselves adequately informed about indications, risks, and benefits of epilepsy surgery. Surgery was regarded as a valid option to be used as early as possible by 84.8% of the interviewees, and 71% of them estimated its complication rate to be low. However, more than half (63%) of the respondents reportedly referred patients for surgery only after the failure of 3-5 antiseizure medications. Overestimation of risks/complications of surgery and inadequate healthcare resources were identified as the main factor contrasting the patient referral for surgery by 43% and 40.5% of the participants, respectively. In conclusion, this survey confirms the existence of knowledge gap within both physicians and the healthcare system, as well as an educational need regarding epilepsy surgery. Further researches are warranted to define learning outcomes and optimize educational tools.

BACKGROUND Evaluation of the impact of aneurysm sac behavior in terms of either stability or shrinkage after endovascular aneurysm repair (EVAR) on long-term clinical outcomes. METHODS A retrospective study was conducted on 1483 consecutive patients who underwent EVAR from 1999 to 2021 at our institution. 1037 patients met inclusion criteria (1037/1483, 69.9%): abdominal aortic or aorto-iliac aneurysm, elective surgery, follow-up (FU) ≥ 12 months. Patients who had sac stability (330/1037, 31.8%) and patients who demonstrated sac shrinkage (542/1037, 52.2%) at FU were compared; patients who presented sac increase at FU were excluded (165/1037, 16%). Primary endpoints: rupture rates, need for surgical conversion, and long-term aneurysm-related mortality. Secondary endpoints: all type endoleak rates and long-term reintervention rates. RESULTS Mean FU was 61.2 months (IQ 26-85.7 months). In terms of comorbidities, the group of patients with stable sac showed greater association with polidistrectual atherosclerotic manifestations. Estimated 12-year survival was 42.9% in the stable sac group and 65% in the shrinked group (p

Purpose: To report a rare case of giant aortic coarctation (CoA)-related descending thoracic aneurysmal degeneration, complicated by an acute aortic dissection. Case Report: A 57-year-old man referred with acute chest pain to the emergency department. A computed tomography angiography (CTA) revealed a CoA with a giant post-stenotic descending thoracic aneurysm (14 cm) and a concomitant left subclavian artery (LSA) aneurysm, complicated by an acute type B aortic dissection. A single-stage hybrid procedure was planned in an urgent setting. Initially, a left common carotid-to-left subclavian artery (LCCA-LSA) bypass was performed to gain a suitable proximal landing zone, the procedure was then completed with 3 thoracic endografts and 1 aortic dissection stent through a percutaneous femoral approach. The patient was discharged in postoperative day 8th without complications; the CTA performed at 1 month demonstrated patency of supra-aortic and visceral vessels, dilation of CoA site and exclusion of the false lumen. Conclusions: CoA is a congenital malformation rarely found in adults that may represent a challenge for the surgeon, especially when combined with a complication like an acute aortic dissection. This case shows that a hybrid approach is a safe and feasible treatment option even in such complex anatomies.

Background: Epilepsy and hypertension are common chronic conditions, both showing high prevalence in older age groups. This review outlines current experimental and clinical evidence on both direct and indirect role of hypertension in epileptogenesis and discusses the principles of drug treatment in patients with hypertension and epilepsy. Methods: We selected English-written articles on epilepsy, hypertension, stroke, and cerebrovascular disease until December, 2018. Results: Renin-angiotensin system might play a central role in the direct interaction between hypertension and epilepsy, but other mechanisms may be contemplated. Large-artery stroke, small vessel disease and posterior reversible leukoencephalopathy syndrome are hypertension-related brain lesions able to determine epilepsy by indirect mechanisms. The role of hypertension as an independent risk factor for post-stroke epilepsy has not been demonstrated. The role of hypertension-related small vessel disease in adult-onset epilepsy has been demonstrated. Posterior reversible encephalopathy syndrome is an acute condition, often caused by a hypertensive crisis, associated with the occurrence of acute symptomatic seizures. Chronic antiepileptic treatment should consider the risk of drug-drug interactions with antihypertensives. Conclusions: Current evidence from preclinical and clinical studies supports the vision that hypertension may be a cause of seizures and epilepsy through direct or indirect mechanisms. In both post-stroke epilepsy and small vessel disease-associated epilepsy, chronic antiepileptic treatment is recommended. In posterior reversible encephalopathy syndrome blood pressure must be rapidly lowered and prompt antiepileptic treatment should be initiated.

To analyze relationships between CD34 expression and several demographic, clinical, and pathologic features in patients with histopathologic evidence of low-grade epilepsy-associated tumors who underwent epilepsy surgery.A retrospective study enrolling 187 patients with low-grade epilepsy-associated tumors who underwent surgery between January 2009 and June 2015 at 8 Italian epilepsy surgery centers was conducted. All cases were histologically diagnosed according to the World Health Organization classification of central nervous system tumors. Univariate and multivariate analyses were performed to identify variables associated with CD34 expression.Of 187 patients, 95 (50.8%) were CD34 positive. Tumor type and duration of epilepsy were independently associated with CD34 expression on multivariate analysis. Ganglioglioma and pleomorphic xanthoastrocytoma were the histologic types with the strongest association with CD34 positivity with an odds ratio of 9.2 and 10.4, respectively, compared with dysembryoplastic neuroepithelial tumors. Patients with a duration of epilepsy10 years had a significantly greater likelihood to show CD34 expression, with an odds ratio of 2.8 compared with patients with a duration of epilepsy2 years. On univariate analysis, CD34 expression appeared to be significantly related to older age at surgery, higher antiepileptic drug intake, and female sex.CD34 expression holds promise as a useful biomolecular marker for patients with low-grade epilepsy-associated tumors with evidence of a link with clinicopathologic features. This study confirmed the association between CD34 expression and tumor type and demonstrated a significantly higher probability of CD34 expression in patients with longer duration of epilepsy, independent of histology.

People with epilepsy often suffer psychiatric symptoms or exhibit maladaptive personality characteristics which can impact them more than seizures. This case illustrates a selective association of a Theory of Mind dysfunction, including an impaired comparison of reality and others' behavior, with an obsessive-compulsive personality disorder in a patient with left temporal lobe epilepsy and crossed cognitive functions. The patient revealed visual memory deficits and impaired interpretation of other people's behavior, mental rigidity, and a tendency to formulate inflexible judgements. Moreover, she shows impairment in understanding and sharing the emotional states of others in reference to herself (Empathic Quotient); her social relations are limited to her parents. Patients with right temporal lobe epilepsy frequently report persistent and rigid actions and thoughts, and this can have substantial psychological and social consequences for everyday life. We suggest that this could be a case of crossed cognitive functions, in particular ToM, and crossed psychobehavioral functions linked to right-hemisphere damage.

Introduction Factors influencing self-perceived health status over Corona Virus Disease 2019 (COVID-19) emergency in vulnerable populations, such as patients with chronic neurological diseases, are still unknown. In this work, we aimed at testing whether clinical care changes imposed by the quarantine, together with certain demographic and disease-specific features, might have determined a self-perceived worsening of health status in patients with amyotrophic lateral sclerosis (ALS). Methods A brief web-based questionnaire investigating self-perceived anxiety, depression, and motor worsening, as well as clinical care changes over COVID-19 emergency, was administered to ALS patients currently followed at San Martino Hospital. Ordinal and logistic regression analyses were applied to identify significant predictors of health status. Results Fifty-seven ALS patients completed the questionnaire. A total of 35.08% of cases reported anxiety symptoms, 36.84% depressive symptoms, and 35.08% reported worsening of motor symptoms. Significant predictors of anxiety symptoms severity included female gender, greater motor impairment, more aggressive disease course, and rehabilitation therapy suspension. The only significant predictor of depressive symptoms severity was a more aggressive disease course. Significant predictors of motor worsening were shorter disease duration and exams/visits cancelation. Discussion COVID-19 emergency and its management exerted a significant impact on self-perceived health status in patients with ALS, particularly in those cases in the earliest disease phases and with a more aggressive disease course. These findings have potential to improve personalized medicine strategies in the next phase.

In 2009, the Commission for Epilepsy Surgery of the Italian League Against Epilepsy (LICE) conducted an overview about the techniques used for the pre-surgical evaluation and the surgical treatment of epilepsies. The recognition that, in selected cases, surgery can be considered the first-line approach, suggested that the experience gained by the main Italian referral centers should be pooled in order to provide a handy source of reference. In light of the progress made over these past years, some parts of that first report have accordingly been updated. The present revision aims to harmonize the general principles regulating the patient selection and the pre-surgical work-up, as well as to expand the use of epilepsy surgery, that still represents an underutilized resource, regrettably. The objective of this contribution is drawing up a methodological framework within which to integrate the experiences of each group in this complex and dynamic sector of the neurosciences.

Background: In cases undergoing epilepsy surgery, postoperative psychogenic nonepileptic seizures (PNES) may be underdiagnosed complicating the assessment of postsurgical seizures outcome and the clinical management. We conducted a survey to investigate the current practices in the European epilepsy monitoring units (EMUs) and the data that EMUs could provide to retrospectively detect cases with postoperative PNES and to assess the feasibility of a subsequent postoperative PNES research project for cases with postoperative PNES. Methods: We developed and distributed a questionnaire survey to 57 EMUs. Questions addressed the number of patients undergoing epilepsy surgery, the performance of systematic preoperative and postoperative psychiatric evaluation, the recording of sexual or other abuse, the follow-up period of patients undergoing epilepsy surgery, the performance of video-electroencephalogram (EEG) and postoperative psychiatric assessment in suspected postoperative cases with PNES, the existence of electronic databases to allow extraction of cases with postoperative PNES, the data that these bases could provide, and EMUs' interest to participate in a retrospective postoperative PNES project. Results: Twenty EMUs completed the questionnaire sheet. The number of patients operated every year/per center is 26.7 (+/- 19.1), and systematic preoperative and postoperative psychiatric evaluation is performed in 75% and 50% of the EMUs accordingly. Sexual or other abuse is systematically recorded in one-third of the centers, and the mean follow-up period after epilepsy surgery is 10.5 +/- 7.5 years. In suspected postoperative PNES, video-EEG is performed in 85% and psychiatric assessment in 95% of the centers. An electronic database to allow extraction of patients with PNES after epilepsy surgery is used in 75% of the EMUs, and all EMUs that sent the sheet completed expressed their interest to participate in a retrospective postoperative PNES project. Conclusion: Postoperative PNES is an underestimated and not well-studied entity. This is a European survey to assess the type of data that the EMUs surgical cohorts could provide to retrospectively detect postoperative PNES. In cases with suspected PNES, most EMUs perform video-EEG and psychiatric assessment, and most EMUs use an electronic database to allow extraction of patients developing PNES. (C) 2020 Elsevier Inc. All rights reserved.

Background: The etiology of delayed-onset spinal cord injury (SCI) following endovascular repair of thoraco-abdominal aortic aneurysms (TAAA) is still unclear and may be related to multiple factors. Extravascular factors, such as lumbar spinal stenosis (LSS), may play a significant role in the selection of patient at risk of SCI. In this report we describe a case of paraplegia following thoracic endovascular aortic repair (TEVAR) in a patient suffering from severe and symptomatic LSS and undergoing staged endovascular repair of a TAAA.Case presentation: A 70-year-old man was admitted to our department with an asymptomatic type III TAAA in previous open repair for abdominal aortic aneurysm. The patient complained of buttock and thigh claudication in the absence of defects in the pelvic perfusion; a spinal magnetic resonance angiography (MRA) showed a severe narrowing of the lumbar canal. The first-step procedure was estimated at intermediate risk of SCI and considering a recent cardiac procedure requiring double antiplatelet therapy, in agreement with anesthesiologists, a preoperative cerebrospinal fluid (CSF) drainage was not performed during the first-step. After 24 hours from TEVAR paraplegia was detected. The drainage was then placed with incomplete recovery. The second stage was performed in urgency three weeks after, without complications and changes in neurological status.Conclusions: Stenotic damage to the spinal cord is thought to be the result of direct compression of the neural elements and ischemic disruption of arterial and venous structures surrounding the spinal cord. This comorbidity may constitute an additional anatomic risk factor in those patients currently recognized as prognostically associated to the development of SCI.

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., Highlights • The effect of COVID-19 and quarantine isolation on the course of epilepsy is still unclear. • Epilepsy course during COVID-19 pandemic was assessed through telephone consultations. • COVID-19 pandemic did not change seizure incidence and prevalence in our patient cohort. • In pandemic situations, telemedicine can be a useful tool for epilepsy care.

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.

Background Seizures are common in patients with dementia but precise epidemiologic data of epilepsy in neurodegenerative dementia is lacking. Objective The first aim of the study was to investigate prevalence and clinical characteristics of epilepsy in a large cohort of patients with neurodegenerative dementias. Subsequently, we explored clinical, neuropsychological, and quantitative electroencephalogram (qEEG) data of Alzheimer's disease (AD) patients with epilepsy (AD-EPI) as compared to AD patients without epilepsy (AD-CTR). Methods We retrospectively evaluated consecutive patients with a diagnosis of a neurodegenerative dementia and a clinically diagnosed epilepsy that required antiepileptic drugs (AED). All patients underwent baseline comprehensive neuropsychological assessment. A follow-up of at least one year was requested to confirm the dementia diagnosis. In AD patients, qEEG power band analysis was performed. AD-CTR and AD-EPI patients were matched for age, Mini-Mental State Examination score, and gender. Results Thirty-eight out of 2,054 neurodegenerative dementia patients had epilepsy requiring AED. The prevalence of epilepsy was 1.82% for AD, 1.28% for the behavioral variant of frontotemporal dementia (bvFTD), 2.47% for dementia with Lewy bodies (DLB), and 12% for primary progressive aphasia. Epilepsy were more drug-responsive in AD than in non-AD dementias. Finally, no significant differences were found in neuropsychological and qEEG data between AD-EPI and AD-CTR patients. Conclusion In our cohort, AD, FTD, and DLB dementias have similar prevalence of epilepsy, even if AD patients were more responsive to AED. Moreover, AD-EPI patients did not have significant clinical, neuropsychological qEEG differences compared with AD-CTR patients.

Background Surgery is a widely accepted treatment option for drug-resistant focal epilepsy. A detailed analysis of longitudinal postoperative seizure outcomes and use of antiepileptic drugs for different brain lesions causing epilepsy is not available. We aimed to analyse the association between histopathology and seizure outcome and drug freedom up to 5 years after epilepsy surgery, to improve presurgical decision making and counselling.Methods In this retrospective, multicentre, longitudinal, cohort study, patients who had epilepsy surgery between Jan 1, 2000, and Dec 31, 2012, at 37 collaborating tertiary referral centres across 18 European countries of the European Epilepsy Brain Bank consortium were assessed. We included patients of all ages with histopathology available after epilepsy surgery. Histopathological diagnoses and a minimal dataset of clinical variables were collected from existing local databases and patient records. The primary outcomes were freedom from disabling seizures (Engel class 1) and drug freedom at 1, 2, and 5 years after surgery. Proportions of individuals who were Engel class 1 and drug-free were reported for the 11 main categories of histopathological diagnosis. We analysed the association between histopathology, duration of epilepsy, and age at surgery, and the primary outcomes using random effects multivariable logistic regression to control for confounding.Findings 9147 patients were included, of whom seizure outcomes were available for 8191 (89.5%) participants at 2 years, and for 5577 (61.0%) at 5 years. The diagnoses of low-grade epilepsy associated neuroepithelial tumour (LEAT), vascular malformation, and hippocampal sclerosis had the best seizure outcome at 2 years after surgery, with 77.5% (1027 of 1325) of patients free from disabling seizures for LEAT, 74.0% (328 of 443) for vascular malformation, and 71.5% (2108 of 2948) for hippocampal sderosis. The worst seizure outcomes at 2 years were seen for patients with focal cortical dysplasia type I or mild malformation of cortical development (50.0%, 213 of 426 free from disabling seizures), those with malformation of cortical development-other (52.3%, 212 of 405 free from disabling seizures), and for those with no histopathological lesion (53.5%, 396 of 740 free from disabling seizures). The proportion of patients being both Engel class 1 and drug-free was 0-14% at 1 year and increased to 14-51% at 5 years. Children were more often drug-free; temporal lobe surgeries had the best seizure outcomes; and a longer duration of epilepsy was associated with reduced chance of favourable seizure outcomes and drug freedom. This effect of duration was evident for all lesions, except for hippocampal sclerosis.Interpretation Histopathological diagnosis, age at surgery, and duration of epilepsy are important prognostic factors for outcomes of epilepsy surgery. In every patient with refractory focal epilepsy presumed to be lesional, evaluation for surgery should be considered. Copyright (C) 2020 Elsevier Ltd. All rights reserved.

Background: Vagus nerve stimulation (VNS) is a palliative treatment for medical intractable epileptic syndromes not eligible for resective surgery. Health technology assessment (HTA) represents a modern approach to the analysis of technologies used for healthcare. The purpose of this study is to assess the clinical, organizational, financial, and economic impact of VNS therapy in drug-resistant epilepsies and to establish the congruity between costs incurred and health service reimbursement. Methods: The present study used an HTA approach. It is based on an extensive detailed bibliographic search on databases (Medline, Pubmed, Embase and Cochrane, sites of scientific societies and institutional sites). The HTA study includes the following issues: (a) social impact and costs of the disease; (b) VNS eligibility and clinical results; (c) quality of life (QoL) after VNS therapy; (d) economic impact and productivity regained after VNS; and (e) costs of VNS. Results: Literature data indicate VNS as an effective treatment with a potential positive impact on social aspects and on quality of life. The diagnosis-related group (DRG) financing, both on national and regional levels, does not cover the cost of the medical device. There was an evident insufficient coverage of the DRG compared to the full cost of implanting the device. Conclusions: VNS is a palliative treatment for reducing seizure frequency and intensity. Despite its economic cost, VNS should improve patients’ quality of life and reduce care needs.

We describe the case of a COVID-19 patient with severely impaired consciousness after sedation hold, showing magnetic resonance imaging (MRI) findings of (i) acute bilateral supratentorial ischemic lesions involving the fronto-parietal white matter and the corpus callosum and (ii) multiple diffuse susceptibility weighted imaging (SWI) hypointense foci, infra and supratentorial, predominantly bithalamic, suggestive of microhemorrhage or alternatively microthrombi. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RNA was detected in the cerebrospinal fluid. Our findings suggest the occurrence of vascular damage, predominantly involving microvessels. The underlying mechanisms, which include direct and indirect penetration of the virus to the central nervous system and systemic cardiorespiratory complications, are yet to be elucidated, and a direct correlation with SARS-CoV-2 infection remains uncertain.

Background: Vagal nerve stimulation (VNS) is an effective palliative therapy in drug-resistant epileptic patients and is also approved as a therapy for treatment-resistant depression. Depression is a frequent comorbidity in epilepsy and it affects the quality of life of patients more than the seizure frequency itself. The aim of this systematic review is to analyze the available literature about the VNS effect on depressive symptoms in epileptic patients. Material and methods: A comprehensive search of PubMed, Medline, Scopus, and Google Scholar was performed, and results were included up to January 2020. All studies concerning depressive symptom assessment in epileptic patients treated with VNS were included. Results: Nine studies were included because they fulfilled inclusion criteria. Six out of nine papers reported a positive effect of VNS on depressive symptoms. Eight out of nine studies did not find any correlation between seizure reduction and depressive symptom amelioration, as induced by VNS. Clinical scales for depression, drug regimens, and age of patients were broadly different among the examined studies. Conclusions: Reviewed studies strongly suggest that VNS ameliorates depressive symptoms in drug-resistant epileptic patients and that the VNS effect on depression is uncorrelated to seizure response. However, more rigorous studies addressing this issue are encouraged.

Summary Objective The contribute of recurring seizures to the progression of epileptogenesis is debated. Seizure-induced brain damage is not conclusively demonstrated both in humans and in animal models of epilepsy. We evaluated the expression of brain injury biomarkers on post-surgical 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 was 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 analysed surgical specimens from cryptogenic patients not presenting structural alterations at imaging. Results Astroglial and microglial activation, reduced neuronal density, peri-vascular CD3-positive T lymphocytes clustering and fibrinogen extravasation were demonstrated in the core of FCD-II lesions. No pathological immunoreactivity was observed outside the FCD-II and in cryptogenetic specimens, where the occurrence of interictal and ictal epileptiform activity was confirmed by either stereo-EEG or intraoperative electrocorticography. Interpretation Recurrent seizures do not induce the expression of brain damage markers in non-lesional epileptogenic cortex studied on post-surgical 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 here considered. This article is protected by copyright. All rights reserved.

We report the case of a 42-year-old woman who presented with vertigo and migraine and rapidly developed cognitive decline and seizures. Both serum and cerebro-spinal fluid samples showed high titer of anti-glutamic acid decarboxylase (anti-GAD65) antibodies (998,881 IU/ml and 54,687 IU/ml respectively). Limbic encephalitis was diagnosed and high dose steroids treatment started. During one-year follow-up, without further immunomodulatory therapy, the patient became seizure free, and cognitive functions returned to normal. Serum anti-GAD65 antibodies titer decreased significantly but remained elevated (192,680 IU/ml). We discuss the prognostic and pathogenic value of high titer anti-GAD65 antibodies and its variations in a case of autoimmune limbic encephalitis.

Epilepsy in brain tumors (BTE) may require medical attention for a variety of unique concerns: epileptic seizures, possible serious adverse effects of antineoplastic and antiepileptic drugs (AEDs), physical disability, and/or neurocognitive disturbances correlated to tumor site. Guidelines for the management of tumor-related epilepsies are lacking. Treatment is not standardized, and overall management might differ according to different specialists. The aim of this document was to provide directives on the procedures to be adopted for a correct diagnostic-therapeutic path of the patient with BTE, evaluating indications, risks, and benefits. A board comprising neurologists, epileptologists, neurophysiologists, neuroradiologists, neurosurgeons, neuro-oncologists, neuropsychologists, and patients' representatives was formed. The board converted diagnostic and therapeutic problems into seventeen questions. A literature search was performed in September-October 2017, and a total of 7827 unique records were retrieved, of which 148 constituted the core literature. There is no evidence that histological type or localization of the brain tumor affects the response to an AED. The board recommended to avoid enzyme-inducing antiepileptic drugs because of their interference with antitumoral drugs and consider as first-choice newer generation drugs (among them, levetiracetam, lamotrigine, and topiramate). Valproic acid should also be considered. Both short-term and long-term prophylaxes are not recommended in primary and metastatic brain tumors. Management of seizures in patients with BTE should be multidisciplinary. The panel evidenced conflicting or lacking data regarding the role of EEG, the choice of therapeutic strategy, and timing to withdraw AEDs and recommended high-quality long-term studies to standardize BTE care.

Autoimmune encephalitides and inflammatory encephalopathies are frequently characterized by seizures refractory to antiepileptic drugs associated with neurological, cognitive, and behavioral manifestations suggestive of a multifocal or diffuse cortical-subcortical dysfunction. Despite the increasing number of autoantibodies directed against neuronal antigens identified in recent years, conventional neurological evaluation, cerebrospinal fluid analysis, electroencephalography, and magnetic resonance imaging are still essential means to entertain a correct diagnosis. Indeed, electroencephalographic features, such as extreme delta brush, as well as electro-clinical phenomena, such as faciobrachial dystonic seizures and epilepsia partialis continua, have been recognized to be associated with specific forms of non-infective immune-mediated encephalitis. A prompt diagnosis of these neurological disorders, facilitated by a knowledgeable use of electroencephalography, is highly desirable in order to begin an early appropriate treatment and achieve a better outcome.

Glucose transporter type 1 deficiency syndrome (Glut1 DS) is a rare neurological disorder caused by impaired glucose delivery to the brain. The clinical spectrum of Glut1 DS mainly includes epilepsy, paroxysmal dyskinesia (PD), developmental delay and microcephaly. Glut1 DS diagnosis is based on the identification of hypoglycorrhachia and pathogenic mutations of the SLC2A1 gene. Here, we report the molecular screening of SLC2A1 in 354 patients clinically suspected for Glut1 DS. From this cohort, we selected 245 patients for whom comprehensive clinical and laboratory data were available. Among them, we identified 19 patients carrying nucleotide variants of pathological significance, 5 of which were novel. The symptoms of onset, which varied from neonatal to adult age, included epilepsy, PD or non-epileptic paroxysmal manifestations. The comparison of the clinical features between the 19 SLC2A1 mutated and the 226 non-mutated patients revealed that the onset of epilepsy within the first year of life (when associated with developmental delay or other neurological manifestations), the association of epilepsy with PD and acquired microcephaly are more common in mutated subjects. Taken together, these data confirm the variability of expression of the phenotypes associated with mutation of SLC2A1 and provide useful clinical tools for the early identification of subjects highly suspected for the disease.

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

Summary 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.

Summary Objective Hippocampal sclerosis (HS) is the most frequent neuropathologic finding in patients undergoing surgery for intractable temporal lobe epilepsy (TLE). The International League Against Epilepsy (ILAE) has recently proposed a new classification of HS based on specific patterns of cell loss. The aim of this study was to investigate the relationships between HS types, their etiologic factors, and the short- and long-term postsurgical outcomes of patients undergoing surgery because of drug-resistant TLE with HS. Methods Two hundred thirteen patients with a neuropathologic diagnosis of HS and a minimum follow-up of 2 years were divided on the basis of their ILAE HS type and further classified into: (1) isolated HS, (2) HS associated with focal cortical dysplasia (FCD IIIa), or (3) HS associated with other lesions. Their clinical and neuropathologic data were correlated with their Engel class postsurgical outcomes. Results The main findings were the following: (1) HS type 1 was associated with a longer duration of epilepsy; (2) >80% of the patients had an Engel class I short- and long-term outcomes, regardless of HS type and associated pathology; (3) short- and long-term postsurgical outcomes were less satisfactory in the patients who were completely seizure-free (Engel class Ia), and patients with HS type 2 had better long-term seizure outcomes than those with type 1; (4) the concomitant presence of FCD contributed to a worse outcome, regardless of HS type; and (5) a shorter duration of epilepsy significantly correlated with an Engel class Ia outcome. Significance These data suggest that HS type and associated pathologies may predict the risk of recurrence, but other variables such as the duration of epilepsy need to be considered. A common neuropathologic classification system may help to identify preoperative predictive factors and improve the selection of patients who may benefit from epilepsy surgery.