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Background: Cortico-cortical evoked potentials (CCEPs) recorded by stereo-electroencephalography (SEEG) are a valuable tool to investigate brain reactivity and effective connectivity. However, invasive recordings are spatially sparse since they depend on clinical needs. This sparsity hampers systematic comparisons across-subjects, the detection of the whole-brain effects of intracortical stimulation, as well as their relationships to the EEG responses evoked by non-invasive stimuli. Objective: To demonstrate that CCEPs recorded by high-density electroencephalography (hd-EEG) provide additional information with respect SEEG alone and to provide an open, curated dataset to allow for further exploration of their potential. Methods: The dataset encompasses SEEG and hd-EEG recordings simultaneously acquired during Single Pulse Electrical Stimulation (SPES) in drug-resistant epileptic patients (N = 36) in whom stimulations were delivered with different physical, geometrical, and topological parameters. Differences in CCEPs were assessed by amplitude, latency, and spectral measures. Results: While invasively and non-invasively recorded CCEPs were generally correlated, differences in pulse duration, angle and stimulated cortical area were better captured by hd-EEG. Further, intracranial stimulation evoked site-specific hd-EEG responses that reproduced the spectral features of EEG responses to transcranial magnetic stimulation (TMS). Notably, SPES, albeit unperceived by subjects, elicited scalp responses that were up to one order of magnitude larger than the responses typically evoked by sensory stimulation in awake humans. Conclusions: CCEPs can be simultaneously recorded with SEEG and hd-EEG and the latter provides a reliable descriptor of the effects of SPES as well as a common reference to compare the whole-brain effects of intracortical stimulation to those of non-invasive transcranial or sensory stimulations in humans.

Wind turbines occur on every continent of the world. Although, many species of wildlife have been negatively affected by the construction of wind turbines, risk of negative effects on wildlife is not equal among wind facilities or among individual wind turbines. Because wildlife and industry select resources to maximize either biological fitness or economic return, we can estimate risk by overlaying models of resource selection for both.

Background: Carbamazepine (CBZ) is a first-choice anti-seizure medication (ASM) whose efficacy is often invalidated by adverse effects (AEs). Eslicarbazepine (ESL) is a structural derivative of CBZ with better pharmacokinetic/tolerability profiles. We describe our experience of the overnight CBZ to ESL switch in people with epilepsy (PwE) to improve seizure control, AEs, and ASMs adherence., Methods: We retrospectively included 19 PwE (12 females, 53 ± 21 years old) who underwent CBZ to ESL overnight switch due to single/multiple issues: poor efficacy (pEff, N = 8, 42%), tolerability (pToll, N = 11, 58%), adherence (pAdh, N = 2, 10%). 9/19 (47%) had psychiatric comorbidities. Clinical variables, seizure frequency, and AEs were recorded at switch time (T0) after 3.5 ± 3 (T1) and 6.5 ± 1.5 months (T2)., Results: At T1, in pEff group, 1/8 (13%) was seizure free, 2/8 (25%) were responders (> 50% seizure reduction), 2/8 (25%) had no seizure changes, 3/8 (37%) had seizure worsening; the latter were those with the most severe epilepsy and encephalopathy. In pToll group, all PwE experienced AEs disappearance/amelioration. In pAdh group, all PwE reported adherence amelioration. Four dropouts. At T2, no changes were recorded within groups, while in the whole sample, 6/15 (40%) were responders, and 4/15 (27%) were seizure-free. No one complained of Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation psychiatric worsening, while 6/19 (32%) experienced mood/behavior benefits., Conclusions: CBZ to ESL overnight switch offers an opportunity to improve efficacy, tolerability, adherence, and psychiatric symptoms., (© 2024. Fondazione Società Italiana di Neurologia.)

Purpose: Resilience is conceptually characterized as a dynamic process encompassing positive adaptation in the context of significant adversity. Our goal was to assess the resilience in people with epilepsy (PWE) and how it impacts longitudinally on psychosocial factors, with a particular focus on the manifestation of stigmatization-related feelings., Methods: We consecutively enrolled 78 adults PWE (42.5 ± 16.2 years old); among them 36 (46.1 %) were seizure-free. All subjects completed at baseline (T0) the Resilience Scale (RS-14) and questionnaires for the assessment of depressive symptoms, anxiety and quality of life: respectively, Beck Depression Inventory-II (BD-II), Generalized Anxiety Disorder-7 (GAD-7) and QOLIE-31 (Q31). All patients were followed up prospectively and re-evaluated after 6-22 months (T1; mean: 14 ± 8 months; median 14 months); at follow up they also completed the Stigma Scale of Epilepsy (SSE) for the assessment of the stigma associated with epilepsy. We correlated resilience values with all psychosocial scores at T0 and T1. Factors associated with resilient and vulnerable outcomes were identified. Finally, a multiple stepwise regression analysis was applied to identify predictors for resilience and stigma perception., Results: The results showed for the RS-14 score a significant direct correlation with the Q31 (p < 0.001) and an inverse correlation with the depressive and anxiety symptoms at both times (T0 and T1), as evaluated with BDI-II (p < 0.001) and GAD-7 (p < 0.001). Finally, we found a significant inverse correlation between RS-14 at T0 and the levels of stigmatization assessed with SSE at T1 (p =.015). Using a multiple stepwise regression analysis separately for resilience and stigma perception, depressive symptoms turned out as the best predictors for both variables. Finally, considering longitudinal evaluation we did not observe significant changes in depressive and anxious symptoms, despite a significant reduction in the total number of seizures at follow up., Conclusions: Our study showed that depressive symptoms, anxiety and quality of life were significantly associated with resilience in PwE. Finally, as a novel finding resilience was proved to affect the perception of stigma related to epilepsy more than seizures., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

In the last two decades, the scientific literature on so-called body representations has been increasing, and the notion of body awareness (BA) is particularly interesting for neurorehabilitation. In this article, we present results derived from recent studies on this representation, considering the different definitions and explicative models proposed as well as the empirical settings used to test it, providing an extensive overview of these issues. This article discusses the challenge of understanding how we integrate the sensory experiences of proprioception (knowing where our body is in space) and interoception (sensing internal bodily sensations, like hunger of thirst) with our perception of self. This is a difficult problem to analyze because our awareness of our body is inherently linked to our perspective, since the body is the means through which we interact with the world. Presenting the different viewpoints offered by recent theories on this concern, we highlighted that the neurorehabilitation and psychiatric settings offer two important fields useful for the study of BA because in them it is possible to analyze bodily representations by inducing/observing a controlled discrepancy between dysfunctional content and sensory inputs.

Objective: The Education and Career Task Force of the Young Epilepsy Section-Italy focuses on educational and career development needs of young Italian epileptologists. Two surveys were developed (pre- and post COVID-19 pandemic) in order to identify the needs of members of the Lega Italiana Contro l'Epilessia under 40 years of age., Methods: The first was distributed during the 42nd National Congress (Rome, June 5-7, 2019); the second during the 45th National Congress (Padova, June 8-10, 2022) and subsequently by e-mail until July 9, 2022. Data from the 2019 survey were analyzed descriptively. Data from the 2022 survey were further analyzed with Pearson's chi-square test to establish if gender, field of clinical practice, and professional role were associated with different needs., Results: Sixty surveys were completed in 2019 and 69 in 2022. Attendance to courses and congresses as the preferred way to keep medical knowledge updated reduced between 2019 and 2022. The reason was different between trainees (mostly elevated costs) and early-career consultants (mostly organizational issues) (p = 0.005). The main needs for improvement also diverged: trainees indicated differential diagnosis and diagnostic approach to the first seizure while consultants indicated diagnostic approach to genetic epilepsies (p = 0.004); in the genetic field, priority needs were selection of genetic investigations for trainees versus genotype-phenotype correlations for consultants (p = 0.022). The field of practice (pediatric vs. adult) also impacted on the main needs for improvement that is, acquisition of expertise in neuroradiology and drug therapy for pediatric versus genetics for adult neurology trainees or consultants (p = 0.018); in the clinical area, differential diagnosis and approach to the first seizure versus status epilepticus (p = 0.027); in the genetic field, precision medicine versus genotype-phenotype correlations (p = 0.034). No differences were found based on gender., Significance: The surveys identified different needs based on professional role and discipline., Plain Language Summary: The Education and Career Task Force of the Young Epilepsy Section-Italy (YES-I) launched two surveys among young Italian epileptologists. Our research shows that the educational and professional needs of young Italian epileptologists vary based on their job role and field of practice, but not on gender. Their preference for on-site congresses and courses reduced after the pandemic, and the main reason is linked to financial constraints for trainees and to organizational issues for consultants. The main expectation toward YES-I is to receive support for education and career development. Thus, we collected useful suggestions on how to organize our future YES-I activities., (© 2024 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Introduction: Understanding the residual recovery potential in stroke patients is crucial for tailoring effective neurorehabilitation program s. We propose using EEG and plasmatic Neurofilament light chain (NfL) levels as a model to depict longitudinal patterns of stroke recovery., Methods: We enrolled 13 patients (4 female, mean age 74.7 ± 8.8) who underwent stroke in the previous month and were hospitalized for 2-months rehabilitation. Patients underwent blood withdrawal, clinical evaluation and high-definition EEG at T1 (first week of rehabilitation) and at T2 (53 ± 10 days after). We assessed the levels of NfL and we analyzed the EEG signal extracting Spectral Exponent (SE) values. We compared our variables between the two timepoint and between cortical and non-cortical strokes., Results: We found a significant difference in the symmetry of SE values between cortical and non-cortical stroke at both T1 ( p  = 0.005) and T2 ( p  = 0.01). SE in the affected hemisphere showed significantly steeper values at T1 when compared with T2 ( p  = 0.001). EEG measures were consistently related to clinical scores, while NfL at T1 was related to the volume of ischemic lesions ( r  = 0.75; p  = 0.003). Additionally, the combined use of NfL and SE indicated varying trends in longitudinal clinical recovery., Conclusion: We present proof of concept of a promising approach for the characterization of different recovery patterns in stroke patients., Competing Interests: SS is an advisor of Intrinsic Powers Inc., a spin-off of the University of Milan. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lanzone, Zulueta, Boscarino, Gallotta, Argentieri, Viganò, Sarasso, Colombo, D’Ambrosio, Lunetta and Parati.)

Background: Transcutaneous vagus nerve stimulation (VNS) showed early evidence of efficacy for the gait treatment of Parkinson's disease (PD)., Objectives: Providing data on neurophysiological and clinical effects of transauricular VNS (taVNS)., Methods: Ten patients with recording deep brain stimulation (DBS) have been enrolled in a within participant design pilot study, double-blind crossover sham-controlled trial of taVNS. Subthalamic local field potentials (β band power), Unified Parkinson's Disease Rating Scales (UPDRS), and a digital timed-up-and-go test (TUG) were measured and compared with real versus sham taVNS during medication-off/DBS-OFF condition., Results: The left taVNS induced a reduction of the total β power in the contralateral (ie, right) subthalamic nucleus and an improvement of TUG time, speed, and variability. The taVNS-induced β reduction correlated with the improvement of gait speed. No major clinical changes were observed at UPDRS., Conclusions: taVNS is a promising strategy for the management of PD gait, deserving prospective trials of chronic neuromodulation. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Object: Quantitative electroencephalography (qEEG) has shown promising results as a predictor of clinical impairment in stroke. We systematically reviewed published papers that focus on qEEG metrics in the resting EEG of patients with mono-hemispheric stroke, to summarize current knowledge and pave the way for future research., Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically searched the literature for papers that fitted our inclusion criteria. Rayyan QCRR was used to allow deduplication and collaborative blinded paper review. Due to multiple outcomes and non-homogeneous literature, a scoping review approach was used to address the topic., Results: Or initial search (PubMed, Embase, Google scholar) yielded 3200 papers. After proper screening, we selected 71 papers that fitted our inclusion criteria and we developed a scoping review thar describes the current state of the art of qEEG in stroke. Notably, among selected papers 53 (74.3%) focused on spectral power; 11 (15.7%) focused on symmetry indexes, 17 (24.3%) on connectivity metrics, while 5 (7.1%) were about other metrics (e.g. detrended fluctuation analysis). Moreover, 42 (58.6%) studies were performed with standard 19 electrodes EEG caps and only a minority used high-definition EEG., Conclusions: We systematically assessed major findings on qEEG and stroke, evidencing strengths and potential pitfalls of this promising branch of research., (© 2023. Fondazione Società Italiana di Neurologia.)

Several reports have described the autoimmune encephalitis' (AE) possible onset during pregnancy. In this systematic review, we summarize the available data on the diagnostic and therapeutic approach to AE during pregnancy, highlighting the associated maternal and fetal clinical outcomes. A systematic search of the literature was performed. The following databases were used: PubMed, Google Scholar, EMBASE, and CrossRef. The revision was registered on the PROSPERO platform (CRD42022336357). Forty-nine patients were included. AE onset was mainly observed during the first and the second trimester of pregnancy with psychiatric manifestations and seizures as main onset symptoms. CSF analysis showed AE-specific autoantibody positivity in 33 patients (anti-NMDA receptor as the most frequent). EEG generally showed normal findings. MRI revealed pathological findings in less than half of patients. Tumor screening was positive in 14 cases. First-line immunotherapy (single or combined) was generally employed while second line was administered in a minority of patients. Levetiracetam was the most used antiseizure medication. Cesarean section was performed in 18 women. Most of the women had an excellent early outcome after delivery but 22 showed persistent neurological deficits in long-term follow-up. Fetal outcome was positive in 33 cases, whereas 12 cases of fetal death were reported. A logistic regression showed that no variable significantly influenced the odds of good/bad maternal and fetal clinical outcome. Diagnosis and treatment of AE during pregnancy is challenging. The rate of miscarriage in women with AE seems to be higher than the general population. In addition, mothers may show long-term neurological deficits., (© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Given the widespread debate on the definition of the terms "Body Schema" and "Body Image", this article presents a broad overview of the studies that have investigated the nature of these types of body representations, especially focusing on the innovative information about these two representations that could be useful for the rehabilitation of patients with different neurological disorders with motor deficits (especially those affecting the upper limbs). In particular, we analyzed (i) the different definitions and explicative models proposed, (ii) the empirical settings used to test them and (iii) the clinical and rehabilitative implications derived from the application of interventions on specific case reports. The growing number of neurological diseases with motor impairment in the general population has required the development of new rehabilitation techniques and a new phenomenological paradigm placing body schema as fundamental and intrinsic parts for action in space. In this narrative review, the focus was placed on evidence from the application of innovative rehabilitation techniques and case reports involving the upper limbs, as body parts particularly involved in finalistic voluntary actions in everyday life, discussing body representations and their functional role.

Background: Anxiety is one of the most relevant psychiatric comorbidities in people with epilepsy (PwE). The role of resilience (RES) in the development of anxiety is not well understood. We purposed to better characterize RES impact on anxiety severity in PwE., Materials and Methods: One hundred and seventy-six PwE underwent online surveys including a collection of socio-demographic, seizure-related, and psychological variables. PwE were grouped according to the data collected; anxiety levels were compared through non-parametric statistics. Hierarchical regression analysis (HRA) and logistic regression were performed to characterize RES contribute in predicting the presence and the severity of anxiety. Mediation/moderation analysis was performed to evaluate causal effects among RES, depression, and anxiety., Results: Anxiety did not differ according to socio-demographic and seizure-related variables, exemption for the presence of drug-related adverse effects. Depression, RES, and sleep quality provided the major contribute on anxiety variance. The addiction of RES level in HRA and logistic regression provided a significant increase of R-squared value (p-value = 0.02) and of area under the curve (p-value = 0.03), respectively. RES modulated depression/anxiety relationship (p-value < 0.001), whereas depression did not mediate RES/anxiety correlation (p-value = 0.68)., Conclusions: We demonstrated that RES is a significant independent predictor of anxiety in PwE and is able to modulate depression impact on anxiety. Moreover, we confirmed the relevance of depression and sleep quality on anxiety severity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Multiple Sclerosis (MS) is a chronic disease with a high prevalence of neuropsychiatric symptoms. Mindfulness is a practice that encourages individuals to cultivate a present-focused, acceptance-based approach for managing psychological distress. Its positive effect on MS has been demonstrated, but learning such technique is expensive and time-consuming. In this study, we investigated the feasibility and efficacy of an 8-week, at-home, smart-device aided mindfulness program in a cohort of MS patients. Specifically, we explored the role of a brain-sensing headband providing real-time auditory feedback as supportive tool for meditation exercises., Methods: The study included two visits, one at baseline and another after the mindfulness program. We measured adherence to the proposed mindfulness treatment and its effect on questionnaires investigating different psychological domains, cognition, fatigue, quality of life and quantitative EEG parameters. All participants received a smart biofeedback device to be used during the therapeutic program consisting of daily meditative exercises., Results: Twenty-nine patients were recruited for the present study. Among them, 27 (93%) completed the entire program and 17 (63%) completed more than 80% of the scheduled sessions. We observed a statistically significant reduction of the Ruminative Response Scale score and a significant increase of the Digit Span Backward. Regarding neurophysiological data, we found a significant reduction of the whole-scalp beta and parieto-occipital theta power post intervention., Conclusion: Our results show that an at-home, smart-device aided mindfulness program is feasible for people with MS. The efficacy in terms of reappraisals of stress, cognitive and emotional coping responses is also supported by our neurophysiological data. Further studies are warranted to better explore the role of such approaches in managing the psychological impact of MS diagnosis., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: FC has received travel grants and/or speaking honoraria from Biogen, Merck, Sanofi-Genzyme, and Roche and research grants from Merck. The other authors have no conflicting interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Sudden unexpected death in epilepsy (SUDEP) is a sudden, unexpected death in people with epilepsy, with or without evidence of an epileptic seizure. The pathophysiological mechanism underlying SUDEP appears to be partly associated with an autonomic nervous system (ANS) dysfunction. Heart rate variability (HRV) analysis is a reliable, non-invasive method for detecting fluctuations in the ANS. In this systematic review we analyzed the data available in the literature on changes in HRV parameters in patients with SUDEP., Methods: We carried out a systematic search of the literature to identify the quantitative variations of HRV in epileptic patients with SUDEP. The following databases were used: Pubmed, Google Scholar, EMBASE, and CrossRef. A pooled analysis was carried out, and the results obtained were compared using mean difference (MD). The review was registered on the PROSPERO platform (CRD42021291586)., Results: Seven articles were included, with a total of 72 SUDEP cases associated with altered HRV parameters. Generally, a reduction of SDNN (standard deviation of the RR intervals) and RMSSD (root mean square differences of successive RR intervals) was reported in most SUDEP patients. According to MD, the SUDEP patients showed no differences in time and frequency domain parameters compared to controls. However, a trend toward increased low frequency and high frequency ratio (LF/HF) was observed in the SUDEP patients., Conclusions: HRV analysis is a valuable method for assessing cardiovascular risk and cardioautonomic impairment. Although a possible association between HRV variation and SUDEP has been reported, further studies are needed to assess the potential role of HRV modifications as a SUDEP biomarker., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Objective: Catamenial epilepsy (CE) is defined as an increase in seizure frequency during specific phases of the menstrual cycle in women with epilepsy. The treatment usually includes a combination of non-hormonal and hormonal therapies. This systematic review summarizes the available data on the efficacy of progesterone and its derivates to treat CE., Methods: We performed a systematic search of the literature to identify studies reporting data on the use of progesterone and its derivatives (any type and dose) for the treatment of CE. The main outcome included the efficacy of progesterone and its derivatives on seizure frequency., Results: Nineteen articles (457 patients) were included; four were randomized controlled trials (two comparing progesterone vs placebo and two comparing norethisterone vs placebo). Progesterone was generally administered during the luteal phase (from day 15 to 25) or during perimenstrual exacerbations (from day 23 to 25), with an average dose of 10-30 mg/day to a maximum of 300 mg/day. The therapy, usually well tolerated, was ineffective in the randomized controlled trials; conversely, it was associated with an overall reduction in seizure frequency in case reports and uncontrolled studies., Conclusions: Although data from uncontrolled studies suggest that hormone therapy with progesterone may be useful in the treatment of CE, its efficacy has not been demonstrated in controlled trials. The possible antiseizure effect of progesterone could be mediated by its active metabolite allopregnanolone, making the plasmatic measurement of these hormones mandatory to evaluate efficacy. Further randomized controlled trials should investigate the efficacy of progesterone and its derivatives, addressing these pharmacological issues., Competing Interests: Declaration of Competing Interest This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. All the authors declare no conflict of interest., (Copyright © 2023 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Ischemic stroke is characterized by a complex cascade of events starting from vessel occlusion. The term "penumbra" denotes the area of severely hypo-perfused brain tissue surrounding the ischemic core that can be potentially recovered if blood flow is reestablished. From the neurophysiological perspective, there are local alterations-reflecting the loss of function of the core and the penumbra-and widespread changes in neural networks functioning, since structural and functional connectivity is disrupted. These dynamic changes are closely related to blood flow in the affected area. However, the pathological process of stroke does not end after the acute phase, but it determines a long-term cascade of events, including changes of cortical excitability, that are quite precocious and might precede clinical evolution. Neurophysiological tools-such as Transcranial Magnetic Stimulation (TMS) or Electroencephalography (EEG)-have enough time resolution to efficiently reflect the pathological changes occurring after stroke. Even if they do not have a role in acute stroke management, EEG and TMS might be helpful for monitoring ischemia evolution-also in the sub-acute and chronic stages. The present review aims to describe the changes occurring in the infarcted area after stroke from the neurophysiological perspective, starting from the acute to the chronic phase., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer AM declared a past co-authorship with the author FP to the handling editor., (Copyright © 2023 Motolese, Lanzone, Todisco, Rossi, Santoro, Cruciani, Capone, Di Lazzaro and Pilato.)

Although widely studied, the association between migraines (M) and breast cancer (BC) risk remains evasive. In this prospective single-center study, 440 early or locally advanced BC patients were enrolled at IRCCS Humanitas Research Hospital. Clinical and demographical data were collected. Those who suffered from headaches were evaluated with the International Classification of Headache Disorders. M was found to be significantly more prevalent in BC patients: 56.1% versus an expected prevalence of 17% in the global population. M patients showed a higher risk of having stage II or III BC than stage I, which was more frequently found in the non-headache population. Interestingly, the frequency of headache attacks was positively correlated with estrogen ( r = 0.11, p = 0.05) and progesterone ( r = 0.15, p = 0.007) expression, especially in patients with migraine without aura. The higher the expression of hormone receptors in BC, the higher the headache frequency. Moreover, patients suffering from headaches showed an overall earlier onset of BC. Our findings challenge the idea of a net preventive role of M on BC, suggesting a rather complex interaction in which M mostly influences some BC subtypes and vice versa. Further multi-center studies with extended follow-up are needed.

Objectives: Poor medication adherence in people with epilepsy (PwE) increases mortality, hospitalization, and poor quality of life, representing a critical challenge for clinicians. Several demographic, clinical, and neuropsychological factors were singularly found associated with medication adherence in several studies, but the literature lacks a comprehensive study simultaneously assessing all these variables., Methods: We performed a multicenter and cross-sectional study using online questionnaires with the following clinical scales: Morisky Medication Adherence Scale (MMAS-8), Quality of Life in Epilepsy Inventory 31 (QoLIE-31), Beck Depression Inventory-II (BDI-II), Generalized Anxiety Disorder-7 (GAD-7) and 14-item Resilience scale (RES14) in a population of 200 PwE. We used the ANOVA test and Spearman's correlation to evaluate the relationship between medication adherence and demographic, clinical (seizure frequency, number of anti-seizure medications), and neuropsychological characteristics. We trained separate machine learning models (logistic regression, random forest, support vector machine) to classify patients with medium-high adherence (MMAS-8 ≥ 6) and poor adherence (MMAS-8 < 6) and to identify the main features that influence adherence., Results: Women were more adherent to medication (p-value = 0.035). Morisky Medication Adherence Scale -8 showed a direct correlation with RES14 (p-value = 0.001) and age (p-value = 0.001), while was inversely correlated with BDI-II (p-value = 0.001) and GAD-7 (p-value = 0.001). In our model, the variables mostly predicting treatment adherence were QoLIE-31 subitems, followed by age, resilience, anxiety, years of school, and disease duration., Conclusion: Our study confirms that gender, age, and neuropsychological traits are relevant factors in predicting medication adherence to PwE. Furthermore, our data provided the first evidence that machine learning on multidimensional self-report questionnaires could help to develop a decisional support system in outpatient epilepsy clinics., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Equistasi ® is a vibrotactile device composed of nanotechnology fibers that converts temperature change into mechanical energy by self-producing a focal vibration. It is used in non-pharmacological rehabilitation in patients with movement disorders and multiple sclerosis sequelae. Nonetheless, the mechanism underlying such an improvement in motor functions is still poorly understood., Objectives: We designed a small uncontrolled pilot trial to explore the effect of Equistasi ® on the somatosensory pathway through the analysis of high-frequency oscillations (HFOs)., Methods: For all the included subjects, we recorded somatosensory-evoked potentials (SEPs) at the baseline (T0) and at 60 min after the application of Equistasi ® (T1) on the seventh cervical vertebra level and at the forearm over each flexor carpi radialis, bilaterally. Then, we extracted the HFOs from the N20 signal and compared the HFO duration and area under the curve pre- and post-Equistasi ® application., Results: In a head-to-head comparison of T0 to T1 data, there was a statistically significant reduction in the total HFO area ( p < 0.01), which was prominent for the late component ( p = 0.025). No statistical differences have been found between T0 and T1 HFO duration ( p > 0.05). We further evaluated the N20 amplitude from the onset to the N20 peak to avoid possible interpretational bias. No statistical differences have been found between T0 and T1 ( p = 0.437)., Conclusion: Our clinical hypothesis, supported by preliminary data, is that vibrotactile afference delivered by the device could work by interfering with the somatosensory processing, rather than by peripheral effects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cruciani, Lanzone, Musumeci, Di Lazzaro and Marano.)

To determine the effects of Levetiracetam (LEV) therapy using EEG microstates analysis in a population of newly diagnosed Temporal Lobe Epilepsy (TLE) patients. We hypothesized that the impact of LEV therapy on the electrical activity of the brain can be globally explored using EEG microstates. Twenty-seven patients with TLE were examined. We performed resting-state microstate EEG analysis and compared microstate metrics between the EEG performed at baseline (EEG pre ) and after 3 months of LEV therapy (EEG post ). The microstates A, B, C and D emerged as the most stable. LEV induced a reduction of microstate B and D mean duration and occurrence per second (p < 0.01). Additionally, LEV treatment increased the directional predominance of microstate A to C and microstate B to D (p = 0.01). LEV treatment induces a modulation of resting-state EEG microstates in newly diagnosed TLE patients. Microstates analysis has the potential to identify a neurophysiological indicator of LEV therapeutic activity. This study of EEG microstates in people with epilepsy opens an interesting path to identify potential LEV activity biomarkers that may involve increased neuronal inhibition of the epileptic network., (© 2022. The Author(s).)

Objective: Vagal Nerve Stimulation (VNS) is an effective treatment for Drug-Resistant (DR) epilepsy. Albeit the corroborated effectiveness of VNS, little is known about how VNS works. We aim to leverage quantitative Electroencephalography (qEEG) to study how the brain responds to VNS cycles., Methods: Eighteen subjects with DR epilepsy were enrolled in our study. 64-channel EEG was recorded during VNS stimulation. Periods of stimulation (VNS), preceding (preVNS) and following stimulation (postVNS) were identified via an electrode placed on the stimulator. We used qEEG analysis to assess changes in spectral and network activity that characterize these conditions. Graph theory metrics were used to calculate differences in network connectivity., Results: No differences were found in spectral activity between preVNS, VNS, and postVNS. Graph theory showed consistent changes in network organization expressed by Small World Index (SWI), Betweenness Centrality (BtwC), and Global Efficiency (gE). These changes were most significant in the slow EEG bands., Conclusions: In DR epilepsy, VNS has a significant effect on brain network activity, as assessed by EEG connectivity, acting on widespread network distribution rather than band-power., Significance: Our findings support the hypothesis that VNS acts on epilepsy by influencing diffuse network connectivity in the brain., (Copyright © 2022 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: Cortico-cortical evoked potentials (CCEPs) recorded by stereo-electroencephalography (SEEG) are a valuable tool to investigate brain reactivity and effective connectivity. However, invasive recordings are spatially sparse since they depend on clinical needs. This sparsity hampers systematic comparisons across-subjects, the detection of the whole-brain effects of intracortical stimulation, as well as their relationships to the EEG responses evoked by non-invasive stimuli., Objective: To demonstrate that CCEPs recorded by high-density electroencephalography (hd-EEG) provide additional information with respect SEEG alone and to provide an open, curated dataset to allow for further exploration of their potential., Methods: The dataset encompasses SEEG and hd-EEG recordings simultaneously acquired during Single Pulse Electrical Stimulation (SPES) in drug-resistant epileptic patients (N = 36) in whom stimulations were delivered with different physical, geometrical, and topological parameters. Differences in CCEPs were assessed by amplitude, latency, and spectral measures., Results: While invasively and non-invasively recorded CCEPs were generally correlated, differences in pulse duration, angle and stimulated cortical area were better captured by hd-EEG. Further, intracranial stimulation evoked site-specific hd-EEG responses that reproduced the spectral features of EEG responses to transcranial magnetic stimulation (TMS). Notably, SPES, albeit unperceived by subjects, elicited scalp responses that were up to one order of magnitude larger than the responses typically evoked by sensory stimulation in awake humans., Conclusions: CCEPs can be simultaneously recorded with SEEG and hd-EEG and the latter provides a reliable descriptor of the effects of SPES as well as a common reference to compare the whole-brain effects of intracortical stimulation to those of non-invasive transcranial or sensory stimulations in humans., Competing Interests: Declarations of competing interest None of the authors have conflicts of interest to disclose in relationship with the current work., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Quantitative Electroencephalography (qEEG) can capture changes in brain activity following stroke. qEEG metrics traditionally focus on oscillatory activity, however recent findings highlight the importance of aperiodic (power-law) structure in characterizing pathological brain states. We assessed neurophysiological alterations and recovery after mono-hemispheric stroke by means of the Spectral Exponent (SE), a metric that reflects EEG slowing and quantifies the power-law decay of the EEG Power Spectral Density (PSD)., Methods: Eighteen patients (n = 18) with mild to moderate mono-hemispheric Middle Cerebral Artery (MCA) ischaemic stroke were retrospectively enrolled for this study. Patients underwent EEG recording in the sub-acute phase (T0) and after 2 months of physical rehabilitation (T1). Sixteen healthy controls (HC; n = 16) matched by age and sex were enrolled as a normative group. SE values and narrow-band PSD were estimated for each recording. We compared SE and band-power between patients and HC, and between the affected (AH) and unaffected hemisphere (UH) at T0 and T1 in patients., Results: At T0, stroke patients showed significantly more negative SE values than HC (p = 0.003), reflecting broad-band EEG slowing. Most important, in patients SE over the AH was consistently more negative compared to the UH and showed a renormalization at T1. This SE renormalization significantly correlated with National Institute of Health Stroke Scale (NIHSS) improvement (R = 0.63, p = 0.005)., Conclusions: SE is a reliable readout of the neurophysiological and clinical alterations occurring after an ischaemic cortical lesion., Significance: SE promise to be a robust method to monitor and predict patients' functional outcome., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Introduction: The coronavirus disease 2019 (COVID-19) pandemic represented a relevant issue for people with epilepsy (PwE). Medical care and social restrictions exposed PwE to a high risk of seizure worsening. Medical institutions answered to the pandemic assuring only emergency care and implementing a remote assistance that highlighted the technological obsolescence of the medical care paradigms for PwE., Area Covered: We reviewed the literature on the COVID-19-related factors influencing the epilepsy course, from the evidence of seizure risk in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infected PwE to anti-Sars-Cov-2 drugs interactions with antiseizure medications and the perceived changes of seizures in PwE., Expert Opinion: COVID-19 pandemic was a problematic experience for PwE. We must make treasure of the lessons learned during this period of social restrictions and employ the recent technological advances to improve PwE assistance, in particular telemedicine and electronic media for patients' education.

Objective: To determine the predictive power for seizure-freedom of 19-channels EEG, measured both before and after three months the initiation of the use of Levetiracetam (LEV), in a cohort of people after a new diagnosis of temporal-lobe epilepsy (TLE) using a machine-learning approach., Methods: Twenty-three individuals with TLE were examined. We dichotomized clinical outcome into seizure-free (SF) and non-seizure-free (NSF) after two years of LEV. EEG effective power in different frequency bands was compared using baseline EEG (T0) and the EEG after three months of LEV therapy (T1) between SF and NSF patients. Partial Least Square (PLS) analysis was used to test and validate the prediction of the model for clinical outcome., Results: A total of 152 features were extracted from the EEG recordings. When considering only the features calculated at T1, a predictive power for seizure-freedom (AUC = 0.750) was obtained. When employing both T0 and T1 features, an AUC = 0.800 was obtained., Conclusions: This study provides a proof-of-concept pipeline for predicting the clinical response to anti-seizure medications in people with epilepsy., Significance: Future studies may benefit from the pipeline proposed in this study in order to develop a model that can match each patient to the most effective anti-seizure medication., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Purpose: To assess quality of life (QoL) in adult people with epilepsy (PWE) and identify the main factors affecting it., Methods: We enrolled consecutively 122 PWE. They were interviewed for a careful collection of demographic and clinical data. Patients completed dedicated questionnaires for the assessment of the quality of life (Quality of Life in Epilepsy Scale-31) (Q31) as well as psychosocial features: depressive symptoms (DS) (Beck Depression Inventory-II/BDI-II), difficulties of emotion regulation (Difficulties of Emotion Regulation Scale/DERS), and stigma related to epilepsy (Stigma Scale of Epilepsy/SSE and Jacoby's Stigma Scale/JSS). The results of Q31 and their subscales were correlated with clinical details of PWE, as well as the other scores. A stepwise multiple regression analysis was applied to identify the main factors affecting QoL., Results: Quality of life is inversely correlated mostly with psychosocial features, as DS, emotion dysregulation, and stigma perception, as well as with epilepsy-related factors, as the seizure frequency and number of antiseizure medications (ASMs). The combination of DS, perceived stigma, and number of ASMs best explained the QoL. Worse features of QoL were detected in females and in patients with age of epilepsy onset in adulthood., Conclusion: Quality of life in adult PWE is predominantly affected by psychosocial factors more than epilepsy-related ones. These findings suggest that effective epilepsy management requires more than seizure control, and early detection of psychological dysfunction and tailored interventions to improve the QoL should be considered., (© 2021. Fondazione Società Italiana di Neurologia.)

Objective: Quantitative Encephalography (qEEG) depicts synthetically the features of EEG signal and represents a promising tool in the assessment of neurophysiological changes brought about by Anti-Seizure Medications (ASMs). In this study we characterized qEEG alterations related to add-on therapy with Perampanel (PER). PER is the only ASM presenting a direct glutamatergic antagonism, hence the characterization of PER induced EEG changes could help to better understand its large spectrum of efficacy., Methods: We analysed standard-19 channel-EEG from 25 People with Epilepsy (PwE) both before (T0) and after (T1) the introduction of PER as add-on treatment. Normal values were obtained in 30 healthy controls (HC) matched for sex and age. EEGs were analysed using Matlab™ and the EEGlab and Brainstorm toolkits. We extracted spectral power and connectivity (Phase locking Value) of EEG signal and then compared these features between T0 and T1 and across groups (PwE, HC), we also evaluated the correlations with clinical features., Results: PwE showed increased theta power (p = 0.036) after the introduction of PER but no significant change of EEG connectivity. We also found that PwE have reduced beta power (p = 0.012) and increased connectivity in delta (p = 0.013) and theta (p = 0.007) range as compared to HC, but no significant change was observed between T0 and T1 in PwE. Finally, we found that PwE classified as drug responders to PER have greater alpha power both at T0 and at T1 (p = 0.024) suggesting that this parameter may predict response to treatment., Conclusions: PER causes slight increase of theta activity and does not alter connectivity as assessed by standard EEG. Moreover, greater alpha power could be a good marker of response to PER therapy, and potentially ASM therapy in general., Significance: Our results corroborate the hypothesis that pharmaco-EEG is a viable tool to study neurophysiological changes induced by ASM. Additionally, our work highlights the role of alpha power as a marker of ASM therapeutic response., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: The goal of this study is to understand how very elderly patients (VEP) after ischemic stroke are currently treated in a Stroke Unit (SU) Hub in Italy. We designed a retrospective monocentric study on patients admitted in the SU of "AO San Camillo Forlanini" over an 8-year period., Material and Methods: Data were collected among patients with acute ischemic stroke admitted to SU between January 2012 and December 2019. Patients were divided into three sub-groups: Adults (18-65 years); Elderly (66-85 years); and VEP (>85 years). Vascular risk factors and clinical variables as predictors of short-term clinical outcome were compared among age groups., Results: A total of 1979 patients were enrolled, 254 were VEP (12.8%). The proportion of VEP showed no significant modifications during the 8-year period (11.9% in 2012-2015 and 13.7% in 2016-2019; p=0.93). The proportion of women, hypertension and atrial fibrillation was significantly higher in VEP compared to other age groups (p<0.001). The rate of VEP being treated with rt-PA increased from 2012-2015 to 2016-2019 (from 12.8% to 25.5%, p<0.001). Endovascular thrombectomy was rarely performed in VEP (1.5% of VEP). Rt-PA treatment was associated with favorable outcome for all three age groups (p<0.05)., Conclusions: We showed that VEP present different vascular risk factor profiles, clinical features, and prognostic elements for short-term stroke outcome. Future studies will reveal whether we will observe an increasing trend in the use of rt-PA and endovascular thrombectomy and whether it will result in improved functional outcome for VEP., Competing Interests: Declaration of Competing Interest Authors have no conflicts of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Wedesignedalongitudinalcohortstudyon People with Epilepsy (PwE) with the aimofassessingthe effect of Perampanel (PER) oncortico-subcortical networks, as measured by high-frequency oscillations of somatosensory evoked potentials (SEP-HFOs). SEP-HFOs measure the excitability of both thalamo-corticalprojections(early HFOs) and intracortical GABAergic synapses (late HFOs), thus they could be used to study the anti-glutamatergic action of PER, a selective antagonist of the AMPA receptor., Methods: 15 PwE eligible for PER add-on therapy, were enrolled prospectively. Subjects underwent SEPs recording from the dominant hand at two times: PwE T0 (baseline, before PER titration) and PwE T1 (therapeutic dose of 4 mg). HFOs were obtained by filtering N20 scalp response in the 400-800 Hz range. Patients were compared with a normative population of 15 healthy controls (HC) matched for age and sex., Results: We found a significant reduction ofTotal HFOs and mostly early HFOs area between PwE T0 and PwE T1 (p = 0.05 and p = 0.045 respectively) and between HC and PwE T1 (p = 0.01). Furthermore, we found a significant reduction of P24/N24 Amplitude between PwE T0 and HC and between PwE T0 and PwE T1 (p = 0.006 and p = 0.032, respectively)., Conclusions: Introduction of PER as add-on therapy reduced the area of total HFOs, acting mainly on the early burst, related to thalamo-cortical pathways. Furthermore P24/N24 amplitude, which seems to reflect a form of cortico-subcortical integration, resulted increased in PwE at T0 and normalized at T1., Significance: Our findings suggest that PER acts on cortico-subcortical excitability. This could explain the broad spectrum of PER and its success in forms of epilepsy characterized by thalamo-cortical hyperexcitability., Competing Interests: Declaration of Competing Interest The authors declared that there is no conflict of interest., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Purpose: In March 2020, the World Health Organization declared the SARS-CoV-2 infection-related coronavirus Disease (COVID-19) a pandemic. During the first and second waves of the pandemic spread, there have been several reports of COVID-19-associated neurological manifestations, including acute seizures and status epilepticus (SE). In this systematic review, we summarized the available data on clinical features, diagnosis, and therapy of COVID-19-related SE., Methods: We performed a systematic search of the literature to identify data on demographics, clinical, neurophysiological, and neuroradiological data of patients with COVID-19-related SE. We used regression models (linear or logistic) with a stepwise forward method to identify features associated with mortality or severity of SE., Results: Thirty-nine articles were included with a total of 47 cases of SE associated with COVID-19. Age, time between the acute respiratory phase of SARS-CoV-2 infection and SE onset, and hospitalization correlated with a higher SE severity as assessed by quantitative validated scales., Conclusions: SE can be a neurological manifestation of SARS-CoV-2 infection. Although a possible association between SE and COVID-19 has been reported, the exact mechanisms are still not fully understood. Systemic inflammatory syndrome due to cytokine release could play a role in COVID-19-related SE., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Increasing evidence coming from both experimental and humans' studies strongly suggest the existence of a link between epilepsy, in particular temporal lobe epilepsy (TLE), and Alzheimer's disease (AD). Patients with mild cognitive impairment and AD are more prone to have seizures, and seizures seem to facilitate amyloid-β and tau deposits, thus promoting neurodegenerative processes. Consistent with this view, long-lasting drug-resistant TLE and AD have been shown to share several pathological and neuroimaging features. Even if studies addressing prevalence of interictal and subclinical epileptiform activity in these patients are not yet conclusive, their findings raise the possibility that epileptiform activity might negatively impact memory and hasten cognitive decline, either directly or by association with unrecognized silent seizures. In addition, data about detrimental effect of network hyperexcitability in temporal regions in the premorbid and early stages ofADopen up newtherapeutic opportunities for antiseizure medications and/or antiepileptic strategies that might complement or enhance existing therapies, and potentially modify disease progression. Here we provide a review of evidence linking epileptiform activity, network hyperexcitability, and AD, and their role promoting and accelerating neurodegenerative process. Finally, the effects of antiseizure medications on cognition and their optimal administration in patients with AD are summarized., Competing Interests: The authors have no conflict of interest to report., (© 2021 – The authors. Published by IOS Press.)

Background: The aim of the present systematic revision is to analyze existing published reports about the use of home-videos recordings (HVRs) to support physicians in the differential diagnosis of paroxysmal seizure-like episodes (PSLE). We also developed practical recommendations in order to ensure adequate quality standards and safety advice for HVRs., Material and Methods: A comprehensive search of PubMed, Medline, Scopus, and Google Scholar was performed, and results were included up to July 2020. All studies concerning the use of HVRs as a diagnostic tool for patients presenting PSLE were included., Results: Seventeen studies satisfied all inclusion and exclusion criteria and were considered for the review. A consistent boost in diagnostic and clinical decision-making was reported across all studies in the literature. One study found that HVRs decreased the stress level in many families and improved their quality of life. Training in performing good-quality videos is necessary and increases the diagnostic value of HVRs., Conclusions: HVRs can be of diagnostic value in epilepsy diagnosis and management. HVRs are low cost, widespread, and may provide great support for neurologists. It is important to train patients and caregivers in performing good quality videos to optimize this useful tool and to guarantee safety standards during the recording.

Objectives: Restrictive measures adopted during the COVID-19 pandemic, in order to limit contagion, have had a severe impact on mental health. The burden of lockdown has been particularly heavy on patients with chronic neurologic diseases such as People with Epilepsy (PwE). Our survey aims to describe the struggles and needs of Drug-Resistant (DR) PwE with implanted Vagal Nerve Stimulator (VNS) during the first wave of the COVID-19 lockdown in order to find strategies that help patients cope with present or future periods of restriction. Methods: We collected answers from 30 respondents who underwent an online survey including socio-demographic and clinical information and COVID-19-related information. Depression, anxiety symptoms, and sleep quality were investigated in patients through BDI II, GAD-7, and the PSQI scale. Results: In all, 46% of our sample reported an increase in the number of seizures; the entire sample complained of epilepsy-related issues (medication availability, VSN adjustments, anxiety, sleep disturbance); one out of three participants reported major epilepsy issues felt urgent; 30% had to postpone scheduled examination. Significantly higher scores for depression and anxiety scales were found in patients who perceived seizure frequency worsening and reported major epilepsy-related issues. Conclusion: Preliminary findings showed that the first lockdown influenced the clinical and psychological status of PwE and was related to seizures worsening. The lack of medical assistance and control on VNS therapy left patients to cope with the situation without a chance to contact a specialist. We discuss how a wider implementation of telemedicine programs could facilitate remote assistance of PwE with a VNS implant., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Grande, Tufo, Ciavarro, Di Muccio, Fuggetta, Silvestri, Bevacqua, Lanzone and Assenza.)

Objective: To determine the quantitative EEG responses in a population of drug-naïve patients with Temporal Lobe Epilepsy (TLE) after Levetiracetam (LEV) initiation as first antiepileptic drug (AED). We hypothesized that the outcome of AED treatment can be predicted from EEG data in patients with TLE., Methods: Twenty-three patients with TLE and twenty-five healthy controls were examined. Clinical outcome was dichotomized into seizure-free (SF) and non-seizure-free (NSF) after two years of LEV. EEG parameters were compared between healthy controls and patients with TLE at baseline (EEG pre ) and after three months of AED therapy (EEG pre-post ) and between SF and NSF patients. Receiver Operating Characteristic curves models were built to test whether EEG parameters predicted outcome., Results: AED therapy induces an increase in EEG power for Alpha (p = 0.06) and a decrease in Theta (p < 0.05). Connectivity values were lower in SF compared to NSF patients (p < 0.001). Quantitative EEG predicted outcome after LEV treatment with an estimated accuracy varying from 65.2% to 91.3% (area under the curve [AUC] = 0.56-0.93) for EEG pre and from 69.9% to 86.9% (AUC = 0.69-0.94) for EEG pre-post ., Conclusions: AED therapy induces EEG modifications in TLE patients, and such modifications are predictive of clinical outcome., Significance: Quantitative EEG may help understanding the effect of AEDs in the central nervous system and offer new prognostic biomarkers for patients with epilepsy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

This study identified a genotype of respiratory syncytial virus (RSV) associated with increased acute respiratory disease severity in a cohort of previously healthy term infants. The genotype (2stop+A4G) consists of two components. The A4G component is a prevalent point mutation in the 4th position of the gene end transcription termination signal of the G gene of currently circulating RSV strains. The 2stop component is two tandem stop codons at the G gene terminus, preceding the gene end transcription termination signal. To investigate the biological role of these RSV G gene mutations, recombinant RSV strains harboring either a wild-type A2 strain G gene (one stop codon preceding a wild-type gene end signal), an A4G gene end signal preceded by one stop codon, or the 2stop+A4G virulence-associated combination were generated and characterized. Infection with the recombinant A4G (rA4G) RSV mutant resulted in transcriptional readthrough and lower G and fusion (F) protein levels than for the wild type. Addition of a second stop codon preceding the A4G point mutation (2stop+A4G) restored G protein expression but retained lower F protein levels. These data suggest that RSV G and F glycoprotein expression is regulated by transcriptional and translational readthrough. Notably, while rA4G and r2stop+A4G RSV were attenuated in cells and in naive BALB/c mice compared to that for wild-type RSV, the r2stop+A4G RSV was better able to infect BALB/c mice in the presence of preexisting immunity than rA4G RSV. Together, these factors may contribute to the maintenance and virulence of the 2stop+A4G genotype in currently circulating RSV-A strains. IMPORTANCE Strain-specific differences in respiratory syncytial virus (RSV) isolates are associated with differential pathogenesis in mice. However, the role of RSV genotypes in human infection is incompletely understood. This work demonstrates that one such genotype, 2stop+A4G, present in the RSV attachment (G) gene terminus is associated with greater infant disease severity. The genotype consists of two tandem stop codons preceding an A-to-G point mutation in the 4th position of the G gene end transcription termination signal. Virologically, the 2stop+A4G RSV genotype results in reduced levels of the RSV fusion (F) glycoprotein. A recombinant 2stop+A4G RSV was better able to establish infection in the presence of existing RSV immunity than a virus harboring the common A4G mutation. These data suggest that regulation of G and F expression has implications for virulence and, potentially, immune evasion., (Copyright © 2020 American Society for Microbiology.)

Objective: The concept of alexithymia refers to difficulty perceiving, identifying, and describing emotions. We aimed at evaluating the prevalence of alexithymia in a sample of adult people with epilepsy (PWE) with and without psychogenic nonepileptic seizures (PNES) and healthy control subjects (HC) and identifying major factors able to affect it., Materials and Methods: We enrolled consecutively 91 PWE (12 of which with PNES in addition to seizures) and 146 HC age- and gender-matched. Both groups' subjects completed the following questionnaires: TAS-20, Beck Depression Inventory-II (BDI-II), Difficulties in Emotion Regulation Scale (DERS) and the Italian translation of Stigma Scale of Epilepsy (SSE), able to evaluate stigma related to epilepsy both in epileptic and nonepileptic subjects. Moreover, PWE completed the well-known Jacoby's Stigma Scale (JSS), dedicated to the evaluation of stigma only by patients with epilepsy and QOLIE-31 (Q31) for evaluating the quality of life. We analyzed correlations between alexithymia and several epilepsy-related (seizure frequency, antiseizure medications-ASMs) and psychosocial factors. Finally, a stepwise multiple regression analysis was performed to identify major factor affecting alexithymia in both groups., Results: Alexithymia was prevalent in PWE compared to controls (17.6% of alexithymic subjects in PWE vs 11% in HC), without discriminating epileptic subjects with and without PNES. This predominance disappeared when depressive symptoms (DS) were controlled for. The difficulties of identifying feelings and emotions resulted to be clearly higher in PWE, even when DS are controlled for, and significantly correlated with stigma perception. Alexithymia in PWE was also strongly associated with lower quality of life and education and greater number of ASMs and difficulties in emotion regulation (ER), that turned out to be the main factor affecting alexithymia in both groups (PWE and HC)., Conclusions: Alexithymia is prevalent in PWE, mostly influenced by DS and significantly associated with worse quality of life and higher emotion dysregulation and stigma perception. The latter finding could be explained by difficulty identifying emotions (DIE) that selectively characterizes PWE., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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.

Transcutaneous vagus nerve stimulation (tVNS) is an alternative non-invasive method for the electrical stimulation of the vagus nerve with the goal of treating several neuropsychiatric disorders. The objective of this study is to assess the effects of tVNS on cerebral cortex activity in healthy volunteers using resting-state microstates and power spectrum electroencephalography (EEG) analysis. Eight male subjects aged 25-45 years were recruited in this randomized sham-controlled double-blind study with cross-over design. Real tVNS was administered at the left external acoustic meatus, while sham stimulation was performed at the left ear lobe, both of them for 60 min. The EEG recording lasted 5 min and was performed before and 60 min following the tVNS experimental session. We observed that real tVNS induced an increase in the metrics of microstate A mean duration ( p = 0.039) and an increase in EEG power spectrum activity in the delta frequency band ( p < 0.01). This study confirms that tVNS is an effective way to stimulate the vagus nerve, and the mechanisms of action of this activation can be successfully studied using scalp EEG quantitative metrics. Future studies are warranted to explore the clinical implications of these findings and to focus the research of the prognostic biomarkers of tVNS therapy for neuropsychiatric diseases.

Transient epileptic amnesia (TEA) is a rare epileptic condition, often confused with transient global amnesia (TGA). In a real-life scenario, differential diagnosis between these two conditions can be hard. In this study we use power spectral analysis empowered by exact Low Resolution Brain Electromagnetic Tomography (eLORETA) to evidence the differences between TEA and TGA. Fifteen patients affected by TEA (64.2 ± 5.2 y.o.; 11 female/4 male; 10 left and 5 right temporal epileptic focus) and 15 patients affected by TGA (65.8 ± 7.2 y.o.; 11 females/4 males) were retrospectively identified in our clinical records. All patients recorded EEGs after symptoms offset. EEGs were analyzed with eLORETA to evidence power spectral contrast between the two conditions. We used an inverse problem solution to localize the source of spectral differences. We found a significant increase in beta band power over the affected hemisphere of TEA patients. Significant results corresponded to the uncus and para-hippocampal gyrus, respectively Brodmann's Areas: 36, 35, 28, 34. We present original evidence of an increase in beta power in the affected hemisphere (AH) of TEA as compared to TGA. These differences involve key areas of the memory network located in the mesial temporal lobe. Spectral asymmetries could be used in the future to recognize cases of amnesia with a high risk of epilepsy.

Objectives: To describe how the recent lock-down, related to SARS-COV-II outbreak in Italy, affected People With Epilepsy (PwE), we designed a survey focused on subjective reactions. Using Natural Language Processing (NLP), we analyzed words PwE and People without Epilepsy (PwoE) chose to express their reactions. Methods: As a subset of a larger survey, we collected from both PwE (427) and PwoE (452) single words (one per subject) associated to the period of lock down. The survey was spread thanks to the efforts of Italian league against epilepsy Foundation during the days of maximum raise of the pandemic. Data were analyzed via bag of word and sentiment analysis techniques in R. Results: PwoE and PwE showed significantly different distribution in word choice (X 2 , p = 4.904e-13). A subset of subject used positive words to describe this period, subjects with positive feelings about the lock down were more represented in the PwE group (X 2 , p = 0.045). Conclusion: PwoE developed reactive stress response to the restrictions enacted during lock-down. PwE, instead, chose words expressing sadness and concern with their disease. PwE appear to internalize more the trauma of lock down. Interestingly PwE also expressed positive feelings about this period of isolation more frequently than PwoE. Our study gives interesting insights on how People with Epilepsy react to traumatic events, using methods that evidence features that do not emerge with psychometric scales., (Copyright © 2020 Lanzone, Cenci, Tombini, Ricci, Tufo, Piccioli, Marrelli, Mecarelli and Assenza.)