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Unmet needs and perspectives in management of drug resistant focal epilepsy: An Italian study

Open AccessPublished:November 05, 2022DOI:https://doi.org/10.1016/j.yebeh.2022.108950

      Highlights

      • The responses of epileptologists and People with Epilepsy (PwE) in this Delphi survey revealed the lack of a shared univocal view on several aspects of epilepsy management.
      • Consensus was reached on the definition of drug-resistant epilepsy and its consequences on treatment, quality of life, and autonomy of PwE.
      • No consensus was reached regarding the uniformity of accessibility to anti-seizure drugs and innovative/new drugs across the country and the role of emerging tools such as telemedicine, digital devices, and narrative medicine.
      • The results outlined many fields of possible intervention, such as the need for educational initiatives targeted at physicians and PwE and for facilities aimed at enhancing PwE’s autonomy and promoting equal access to care throughout the country.
      • This survey represents a preliminary study to better understand drug-resistant focal epilepsy reality and how to improve epilepsy management and PwE’s quality of life.

      Abstract

      This study aimed to evaluate the consensus level between a representative group of Italian neurologists and people with Drug-Resistant Epilepsy (DRE) regarding a series of statements about different aspects involved in the management of epilepsy to identify the unmet needs of the People with Epilepsy (PwE) and the future perspectives for the management of this disease.
      This observational study was conducted using a classic Delphi technique. A 19-statement questionnaire was administered anonymously through an online platform to a panel of expert clinicians and a panel of PwE, analyzing three main topics of interest: drug resistance, access to care, and PwE’s experience.
      The consensus was achieved on 8 of the 19 statements administered to the panel of medical experts and on 4 of the 14 submitted to the panel of PwE, particularly on the definition of DRE and its consequences on treatment, Quality of Life (QoL), and autonomy of PwE. Most of the items, however, did not reach a consensus and highlighted the lack of a shared univocal view on some topics, such as accessibility to care throughout the country and the role of emerging tools such as telemedicine, narrative medicine, and digital devices. In many cases, the two panels expressed different views on the statements.
      The results outlined many fields of possible intervention, such as the need for educational initiatives targeted at physicians and PwE – for example, regarding telemedicine, digital devices, and narrative medicine – as well as the spread of better knowledge about epilepsy among the general population, in order to reduce epilepsy stigma. Institutions, moreover, could take a cue from this survey to develop facilities aimed at enhancing PwE’s autonomy and promoting more equal access to care throughout the country.

      Keywords

      1. Introduction

      Epilepsy is a complex pathological condition frequently resulting from multiple risk factors and a complex genetic predisposition, often associated with neurobiological, cognitive, psychological, and social consequences [
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      ]. Its incidence ranges between 40 and 60 per 100,000 inhabitants per year in high-income countries and above 80 and 100 per 100,000 people per year in low-income countries, while prevalence of active epilepsy is considered to be between 4 and 12 per 1000 [
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      Prevalence and incidence of epilepsy: a systematic review and meta-analysis of international studies.
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      ,
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      ]. Epilepsy is, therefore, one of the most common neurological diseases.
      Epilepsy’s panorama is very complex, and managing this condition involves facing several specific and difficult challenges. One of these is represented by drug resistance: despite the increasing number of anti-seizure medications (ASMs) available, pharmacological treatment – which constitutes the main therapeutic option for most people with epilepsy, especially in wealthy countries – shows efficacy in determining long-term remission in only two-thirds of cases [
      • Thijs R.D.
      • Surges R.
      • O’Brien T.J.
      • Sander J.W.
      Epilepsy in adults.
      ,
      • Bell G.S.
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      • Novy J.
      • Peacock J.L.
      • et al.
      Outcome of seizures in the general population after 25 years: a prospective follow-up, observational cohort study.
      ]. Up to one-third of people with epilepsy, instead, do not achieve seizure control, presenting Drug-Resistant Epilepsy (DRE) [
      • Kalilani L.
      • Sun X.
      • Pelgrims B.
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      • Villanueva V.
      The epidemiology of drug-resistant epilepsy: a systematic review and meta-analysis.
      ,
      • Chen Z.
      • Brodie M.J.
      • Liew D.
      • Kwan P.
      treatment outcomes in patients with newly diagnosed epilepsy treated with established and new antiepileptic drugs: a 30-year longitudinal cohort study.
      ]. Most of them are people with focal epilepsy [
      • Picot M.C.
      • Baldy-Moulinier M.
      • Daurès J.P.
      • Dujols P.
      • Crespel A.
      The prevalence of epilepsy and pharmacoresistant epilepsy in adults: a population-based study in a Western European country.
      ]. The mechanisms underlying drug resistance are not fully understood. Different hypotheses were formulated regarding disease-related mechanisms, drug-related phenomena, and genetic variants. However, DRE is likely to be a variable and multifactorial condition [
      • Regesta G.
      • Tanganelli P.
      Clinical aspects and biological bases of drug-resistant epilepsies.
      ,
      • Berg A.T.
      Understanding the delay before epilepsy surgery: who develops intractable focal epilepsy and when?.
      ,
      • Luciano A.L.
      • Shorvon S.D.
      Results of treatment changes in patients with apparently drug-resistant chronic epilepsy.
      ,
      • Schiller Y.
      • Najjar Y.
      Quantifying the response to antiepileptic drugs: effect of past treatment history.
      ,
      • Brodie M.J.
      • Barry S.J.E.
      • Bamagous G.A.
      • Norrie J.D.
      • Kwan P.
      Patterns of treatment response in newly diagnosed epilepsy.
      ]. Anyway, DRE has important consequences on mortality, morbidity, and QoL of patients and their caregivers due to the increased mortality, cognitive deficits, emotional distress, stigmatization, dependence on caregivers, reduced educational and occupational opportunities, and social isolation which may derive from this condition [
      • Silva B.
      • Canas-Simião H.
      • Cordeiro S.
      • Velosa A.
      • Oliveira-Maia A.J.
      • Barahona-Corrêa J.B.
      Determinants of quality of life in patients with drug-resistant focal epilepsy.
      ,
      • Taylor R.S.
      • Sander J.W.
      • Taylor R.J.
      • Baker G.A.
      Predictors of health-related quality of life and costs in adults with epilepsy: a systematic review.
      ,
      • Laxer K.D.
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      • Hirsch L.J.
      • Cendes F.
      • Langfitt J.
      • Delanty N.
      • et al.
      The consequences of refractory epilepsy and its treatment.
      ].
      The complexity of epilepsy’s panorama is also increased by the fact that people with epilepsy are often affected by numerous comorbidities, both psychiatric and somatic, so some Authors have proposed to consider epilepsy as the sum of seizures and comorbidities caused by a systemic dysfunction [
      • Keezer M.R.
      • Sisodiya S.M.
      • Sander J.W.
      Comorbidities of epilepsy: current concepts and future perspectives.
      ,
      • Yuen A.W.C.
      • Keezer M.R.
      • Sander J.W.
      Epilepsy is a neurological and a systemic disorder.
      ].
      Epilepsy is also characterized by important social implications: a recent systematic review by an International League Against Epilepsy (ILAE) task force, for example, evidenced that a significant stigma – both perceived and enacted - exists regarding people with epilepsy, with an important impact on employment, education, social inclusion and overall QoL [
      • Kwon C.S.
      • Jacoby A.
      • Ali A.
      • Austin J.
      • Birbeck G.L.
      • Braga P.
      • et al.
      Systematic review of frequency of felt and enacted stigma in epilepsy and determining factors and attitudes toward persons living with epilepsy- Report from the International League Against Epilepsy Task Force on Stigma in Epilepsy.
      ]. The use itself of the term “epileptic” was found to promote the production of stigma [
      • Kwon C.S.
      • Jacoby A.
      • Ali A.
      • Austin J.
      • Birbeck G.L.
      • Braga P.
      • et al.
      Systematic review of frequency of felt and enacted stigma in epilepsy and determining factors and attitudes toward persons living with epilepsy- Report from the International League Against Epilepsy Task Force on Stigma in Epilepsy.
      ,
      • Fernandes P.T.
      • Noronha A.L.A.
      • Sander J.W.
      • Li L.M.
      Stigma scale of epilepsy: the perception of epilepsy stigma in different cities in Brazil.
      ,
      • Fernandes P.T.
      • de Barros N.F.
      • Li L.M.
      Stop saying epileptic.
      ,
      • Bishop M.
      • Stenhoff D.M.
      • Bradley K.D.
      • Allen C.A.
      The differential effect of epilepsy labels on employer perceptions: report of a pilot study.
      ]. The ILAE task force recently published also a systematic review summarizing the instruments developed to measure stigma and the possible interventions to reduce it [
      • Austin J.K.
      • Birbeck G.
      • Parko K.
      • Kwon C.S.
      • Fernandes P.T.
      • Braga P.
      • et al.
      Epilepsy-related stigma and attitudes: Systematic review of screening instruments and interventions – Report by the International League Against Epilepsy Task Force on Stigma in Epilepsy.
      ]. Even when adequately treated, therefore, people with epilepsy present specific needs both socially, environmentally, and culturally speaking.
      Nowadays, new emerging tools that could help tackle some of the needs of people with epilepsy. New possibilities are provided, for example, by telemedicine, which started to be implemented during the COVID-19 crisis in managing several chronic conditions, and by developing different devices for seizure detection, which could improve patients’ management [
      • Bloem B.R.
      • Dorsey E.R.
      • Okun M.S.
      The Coronavirus Disease 2019 crisis as catalyst for telemedicine for chronic neurological disorders.
      ]. Moreover, new scenarios are opened by spreading new approaches, such as narrative medicine, aimed at a more comprehensive consideration of the patient.
      All the above factors contribute to delineating a very complex and rapidly evolving scenario. This study aimed to evaluate the consensus level between a representative group of Italian neurologists and People with Epilepsy (PwE) on a series of statements about different aspects involved in the management of this condition, focusing specifically on drug-resistant focal epilepsy, in order to identify the unmet needs of PwE and the future perspectives for the management of this disease.

      2. Methods

      2.1 Study design and the Delphi technique

      This observational study was conducted using a classic Delphi technique, which allows to develop of consensual guidance or to explore the consensus level about a matter through the administration of a standardized questionnaire, consisting of a series of statements, to a panel of experts who have to express – anonymously - agreement or disagreement according to a scale. The results are expressed as percentages of respondents expressing agreement, disagreement, or uncertainty. The process can be performed in a single round or multistage iteration in which controlled feedback and research materials are given to participants between rounds [
      • Walker A.
      • Selfe J.
      The Delphi method: a useful tool for the allied health researcher.
      ,
      • McPherson S.
      • Reese C.
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      Methodology update: Delphi studies.
      ,
      • De Meyer D.
      • Kottner J.
      • Beele H.
      • Schmitt J.
      • Lange T.
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      • et al.
      Delphi procedure in core outcome set development: rating scale and consensus criteria determined outcome selection.
      ,
      • Varndell W.
      • Fry M.
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      • Elliott D.
      Use of the Delphi method to generate guidance in emergency nursing practice: a systematic review.
      ].
      Since this study aimed to explore the level of agreement on the statements and not to build a consensus, it was conducted in a single round. The level of agreement was expressed using a classic 5-point Likert scale (in which 1 = strongly disagree; 2 = disagree; 3 = neither agree nor disagree; 4 = agree; 5 = strongly agree). The Likert scale was used as it allowed for more variation in the answers than a classic yes/no questionnaire. The percentage of consensus threshold was 66%: an agreement was reached when the sum of items 4 and 5 was >66%; disagreement was reached when the sum of items 1 and 2 was >66%; no consensus was reached when the sum of the responses for disagreement (1 and 2) or agreement (4 and 5) was <66%.
      The problem area was identified by an Italian Steering Committee following an in-depth discussion and literature review and based on needs analysis by Italian experts in this field. Three epileptologists were identified for this committee, experts in the field of diagnosis and treatment of epilepsy. They identified the main topics of interest: drug resistance, access to care, and PwE’s experience. Nineteen statements were then developed: 6 were related to drug resistance, 7 to care access, and 6 were about the patient’s experience. The Delphi questionnaire was formulated in Italian.
      The statements were then submitted to a validation process by 4 external validators – 3 clinicians and 1 expert patient –in order to evaluate the comprehensibility of each statement. The final questionnaire was then approved.

      2.2 Respondents characteristics

      The questionnaire was administered through an online platform to two different panels. According to the Delphi technique, participants expressed their opinion anonymously.
      The first expert panel was composed of epileptologists with solid clinical experience. All were associated with the Italian League Against Epilepsy (LICE) and had leading roles in epilepsy referral centers. Panel size was determined based on the regional distribution of epilepsy referral centers in Italy, involving experts from all over the country. Fifty-four panelists from 18 Italian regions out of the selected 63 completed the Delphi questionnaire (response rate 86%). Twenty-three of them (42,5%) worked in northern Italy, 17 (31,5%) in central Italy, and 14 (26%) in southern Italy. Regarding the experts’ years of experience, more than two-thirds of the experts (68,5%) had 20 or more years of experience in the field of epilepsy, 25,9% had worked between 11 and 20 years in this sector, while 5,6% had between 5 and 10-years long experiences.
      The second panel consisted of a group of PwE with a diagnosis of DRE. To proceed with the recruitment, a preliminary online mapping of all patients’ associations in Italy was performed, and nineteen patient advocacy groups were found. The associations involved were representative of territoriality, gender homogeneity, and experience and were well distributed throughout the country, but only a few considered participating. Thirty-seven panelists out of the 40 involved completed the Delphi questionnaire (response rate 93%), unevenly distributed in 8 Italian regions. Twenty-three (62%) of them lived in southern Italy, 10 (27%) were in central Italy, and only 4 of them (11%) were from northern Italy. Regarding disease history, 54,1% of the involved PwE presented a history of disease more than 20 years long, 27% had an 11–20-year long history of illness, 13,5% had been affected between 1 and 10 years, and 5,4% for less than 1 year (Fig. 1).
      Figure thumbnail gr1
      Fig. 1History of disease of PwE respondents.

      2.3 Questionnaire

      The questionnaire consisted of 19 statements. The panel of experts received the full questionnaire, whereas the PwE panel only received 14 questions from this questionnaire. In the questionnaire, the statements were presented in random order and not divided by topic. The first 4 statements were administered only to the panel of clinicians and were related to the definition of drug resistance, its stability over time, the implications of surgical treatment, and further changes in therapy. Statements 1.5 and 1.6 were submitted to both panels, and concerned the tolerability of treatment and the influence of seizures on QoL. Six statements regarding access to care were administered to both panels and one statement was administered only to the expert panel of clinicians. The topic “PwE’s experience” was explored through 6 statements administered to both panels regarding different aspects of the PwE’s life.

      2.4 Survey procedures

      An invitation letter was sent to all selected panelists to participate in the Delphi survey. The letter explained the objectives of the project and the Delphi technique with the methods used to evaluate the results (1–2 disagreement, 3 uncertainty, 4–5 agreement). The questionnaire was administered via the web through a dedicated platform using a link and credentials to access it. The questionnaire required approximately 15 minutes to be completed and was available online from February 22, 2022, to March 6, 2022. The responses were analyzed anonymously.
      The collected data were then discussed at different times by a commission consisting of three clinicians and three representatives of two patients’ associations.

      3. Results

      The consensus was achieved on 8 of the 19 statements administered to the panel of medical experts (statements 1.1, 1.4, 1.5, 1.6, 2.3, 2.7, 3.2, 3.5) and 4 of the 14 submitted to the panel of PwE (statements 1.6, 2.4, 3.5, 3.6). In many cases, the two panels expressed different views on the statements. Most items did not reach a consensus and highlighted the lack of a shared univocal view on some topics.
      During the debate of the survey results, the PwE’s representatives referred to some difficulties among PwE in comprehending statements and answering the questions due to the use of complex language and lack of comprehension by the PwE of the meaning of some terms.

      3.1 Drug resistance

      The first topic analyzed was drug resistance. The results and response rates for each statement related to this first topic for the epileptologists panel and the PwE group are shown in Fig. 2 and Fig. 3, respectively. A consensus was reached on the shareability of the definition of drug resistance as the failure of at least two drugs used and appropriately chosen (statement 1.1), with 74% of the participants agreeing. Six percent of participants disagreed with this definition, and 20% expressed neither agreement nor disagreement. Moreover, 63% of participants agreed that drug resistance is not a stable condition over time (Statement 1.2), although the threshold for a consensus was not reached.
      Figure thumbnail gr2
      Fig. 2Response rate (%) by Likert scale score of the panel of Epileptologists (n = 54) on each statement of the Delphi questionnaire for Topic # 1: “Drug Resistance”. Statements that have reached a consensus (in agreement or in disagreement) are indicated by a star.
      Figure thumbnail gr3
      Fig. 3Response rate (%) by Likert scale score of the panel of PwE (n = 37) on each statement of the Delphi questionnaire for Topic # 1: “Drug Resistance”. Statements that have reached a consensus (in agreement or in disagreement) are indicated by a star.
      Statement 1.3 defined drug resistance as a necessary condition for receiving surgical treatment and saw different responses, with an imbalance towards the intermediate grades of the scale (2 and 4). Conversely, the benefit of further changes in therapy in drug-resistant subjects (statement 1.4) was supported by a large consensus among physicians (85%).
      Statement 1.5 (Tolerability of drug therapy matters less than seizure control) showed 83% of clinicians disagreeing, while in the PwE panel, only 62% disagreed, with 14% expressing uncertainty and 24% manifesting agreement. On the other hand, 92% of PwE and 70% of clinicians agreed with statement 1.6, which considered complete seizure control essential for a good QoL.

      3.2 Access to care

      The second topic investigated was access to care. The results and response rates for each statement related to this second topic for the epileptologists panel and the PwE group are shown in Fig. 4 and Fig. 5, respectively. No consensus was reached regarding these statements in either panel, with a high percentage of uncertainty (grade 3) between clinicians’ answers. The answers from the PwE group could be conditioned by their unbalanced distribution all over the country.
      Figure thumbnail gr4
      Fig. 4Response rate (%) by Likert scale score of the panel of Epileptologists (n = 54) on each statement of the Delphi questionnaire for Topic # 2: “Access to care”. Statements that have reached a consensus (in agreement or in disagreement) are indicated by a star.
      Figure thumbnail gr5
      Fig. 5Response rate (%) by Likert scale score of the panel of PwE (n = 37) on each statement of the Delphi questionnaire for Topic # 2: “Access to care”. Statements that have reached a consensus (in agreement or in disagreement) are indicated by a star.
      Regarding 2nd and 3rd level center distribution, those centers with more advanced care being available according to the LICE criteria (https://www.lice.it/pdf/Norme_Riconoscimeno_Centri_LICE_251021.pdf) throughout the country (statement 2.1), 57% of the clinicians agreed that it is uneven, while an unexpected 33% of medical specialists and 43% of PwE expressed neither agreement nor disagreement (grade 3).
      No consensus was reached also regarding the uniformity of accessibility to ASMs across the country (statement 2.2): 30% of clinicians agreed with this statement, 28% expressed uncertainty, and 43% expressed disagreement, while 49% of PwE expressed agreement with this statement, and 30% of them expressed uncertainty.
      With regards to innovative drugs availability all over the national territory (statement 2.5), a consensus for disagreement was nearly reached by the clinicians, pointing out disparities between regions, even if a high percentage of panelists (22% and 41% of clinicians and PwE, respectively) expressed uncertainty.
      A large consensus (76 and 78% of agreement, respectively) was reached among clinicians on the importance of a network of different levels of centers working together (statement 2.3) and on the negative influence of healthcare system regionalization on equal access to care (statement 2.7). People with Epilepsy expressed varying opinions, partially headed in the same direction as clinician’s answers, but without reaching a consensus and with a high percentage of uncertainty.
      A consensus was nearly reached, instead, about statement 2.6 (Admission appropriateness criteria affect timing and quality of the diagnosis), which was administered only to the clinicians’ panel.
      Statement 2.4 dealt with the perception of the role of telemedicine in replacing face-to-face follow-up visits. People with Epilepsy manifested a sharp disagreement (76%), while clinicians manifested a high level of uncertainty (39%) and disagreement (43%).

      3.3 PwE’s experience

      The third topic explored was PwE’s experience. The results and response rates for each statement related to this third topic for the epileptologists panel and the PwE group are shown in Fig. 6 and Fig. 7, respectively. There was almost a consensus among clinicians (63%) on using Narrative Medicine as a tool to improve communication between PwE and physicians (statement 3.1). Almost half of PwE (46%), though, expressed neither agreement nor disagreement, probably because of a lack of knowledge about this topic.
      Figure thumbnail gr6
      Fig. 6Response rate (%) by Likert scale score of the panel of Epileptologists (n = 54) on each statement of the Delphi questionnaire for Topic # 3: “PwE’s experience”. Statements that have reached a consensus (in agreement or in disagreement) are indicated by a star.
      Figure thumbnail gr7
      Fig. 7Response rate (%) by Likert scale score of the panel of PwE (n = 37) on each statement of the Delphi questionnaire for Topic # 3: “PwE’s experience”. Statements that have reached a consensus (in agreement or in disagreement) are indicated by a star.
      Fifty-six percent of clinicians and 59% of PwE agreed that the support of digital technologies for active or passive self-monitoring improves the self-management of the PwE (statement 3.3), while a high percentage of clinicians (41%) expressed uncertainty.
      A large consensus (83%) was reached among clinicians on the importance of multidisciplinary management of people affected by epilepsy (statement 3.2). On the other hand, 24% of PwE considered multidisciplinary management unnecessary, while another 24% expressed uncertainty. Both PwE (70%) and clinicians (93%), moreover, significantly agreed that the transition from childhood to adulthood does require dedicated structures and skills (statement 3.5).
      Regarding the role of patients’ associations, 44% of clinicians and 24% of PwE disagreed with statement 3.4 (I believe that PwE’s associations are adequately represented in decision-making processes (protocols, guidelines, organization, etc.)), while 41% and 46% of them, respectively, expressed uncertainty. Among clinicians, only 15% agreed.
      PwE significantly agreed (93%) that drug resistance is incompatible with an autonomous and independent life (statement 3.6), outlining the effect of uncontrolled seizures on QoL perception. However, clinicians showed different opinions, with 33% disagreeing with this incompatibility.

      4. Discussion

      As expected, a very complex scenario emerges from this survey’s results: most of the items, which analyzed very different aspects of epilepsy management, showed uncertainty or did not reach a consensus, highlighting the lack of a shared univocal opinion; moreover, in many cases, expert clinicians and PwE expressed different views on the topic investigated.
      Interesting results emerged regarding the definition of DRE. Statement 1.1 referred to the definition given by ILAE, which - having been drug resistance defined over time according to different definitions, focusing on different criteria [
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      ,

      Arzimanoglou A, Ryvlin P. Towards a clinically meaningful definition of drug-resistance. In: Drug Resistant Epilepsy. Progress in Epileptic Disorders. John Libbey EUROTEXT; 2008:1-6.

      ], and given the major implications that such a diagnosis has on patient care and clinical research - in 2010 formulated a consensus definition of DRE [
      • Kwan P.
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      ], defining it as the failure of adequate trials of two tolerated, appropriately chosen and used antiepileptic drug schedules (as monotherapy or as a combination of drugs) to achieve sustained seizure freedom. According to this definition, for the proper evaluation of outcomes, the intervention must be appropriated (literature providing a high level of evidence) and adequately applied (i.e., with the correct dosage for a sufficient period of time, which usually depends on the frequency of pre-intervention seizure). Seizure freedom was defined as the absence of seizures of any type for a period of time longer than 12 months or a minimum of three times the longest pre-intervention interval between seizures occurring in the previous year [
      • Kwan P.
      • Arzimanoglou A.
      • Berg A.T.
      • Brodie M.J.
      • Hauser W.A.
      • Mathern G.
      • et al.
      Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies: definition of drug resistant epilepsy.
      ].
      In our survey, only 74% of clinicians agreed with the ILAE definition of DRE, with 6% of participants disagreeing and 20% expressing neither agreement nor disagreement. Since this definition was formulated in 2010 [
      • Kwan P.
      • Arzimanoglou A.
      • Berg A.T.
      • Brodie M.J.
      • Hauser W.A.
      • Mathern G.
      • et al.
      Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies: definition of drug resistant epilepsy.
      ], these data could be interpreted as the expression of an evolution of the concept and would indicate the need for an update. Not reaching a consensus on the stability of DRE over time could reflect a misinterpretation of the statement or a lack of knowledge about the patterns of drug resistance [
      • Schmidt D.
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      ] among clinicians who are not specialized in the treatment of drug-resistant epilepsy, being the epilepsy centers increasingly hyperspecialized.
      More than half of the participants did not agree with drug resistance being a necessary condition to receive surgical treatment. Some clinicians may have answered thinking about treatment on an etiopathological basis; moreover, these data could reflect the complexity of real-life factors conditioning treatment. Many studies highlighted the existence of an important knowledge gap regarding epilepsy surgery and the need for educational interventions [
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      ], as also evidenced by a recent Italian survey on the attitudes of neurologists toward this treatment [
      • Casciato S.
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      ]. Despite being an evidence-based therapeutic option [
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      • Wiebe S.
      • Langfitt J.T.
      • Stern J.M.
      • Dewar S.
      • et al.
      Early surgical therapy for drug-resistant temporal lobe epilepsy: a randomized trial.
      ,
      • Dwivedi R.
      • Ramanujam B.
      • Chandra P.S.
      • Sapra S.
      • Gulati S.
      • Kalaivani M.
      • et al.
      Surgery for drug-resistant epilepsy in children.
      ,
      • Téllez-Zenteno J.F.
      • Dhar R.
      • Wiebe S.
      Long-term seizure outcomes following epilepsy surgery: a systematic review and meta-analysis.
      ,
      • Consales A.
      • Casciato S.
      • Asioli S.
      • Barba C.
      • Caulo M.
      • Colicchio G.
      • et al.
      The surgical treatment of epilepsy.
      ], especially for Temporal Lobe Epilepsy (TLE), epilepsy surgery is an underutilized treatment [
      • Roberts J.I.
      • Hrazdil C.
      • Wiebe S.
      • Sauro K.
      • Vautour M.
      • Wiebe N.
      • et al.
      Neurologists’ knowledge of and attitudes toward epilepsy surgery.
      ,
      • de Flon P.
      • Kumlien E.
      • Reuterwall C.
      • Mattsson P.
      Empirical evidence of underutilization of referrals for epilepsy surgery evaluation.
      ,
      • Samanta D.
      • Ostendorf A.P.
      • Willis E.
      • Singh R.
      • Gedela S.
      • Arya R.
      • et al.
      Underutilization of epilepsy surgery: Part I: A scoping review of barriers.
      ,
      • Samanta D.
      • Singh R.
      • Gedela S.
      • Scott Perry M.
      • Arya R.
      Underutilization of epilepsy surgery: Part II: Strategies to overcome barriers.
      ]; major causes of this phenomenon include an overestimation of risks and complications and the availability of few specialized centers and, overall, inadequate knowledge among neurologists. Our results are coherent with the literature, highlighting the need for educational activities on epilepsy surgery and to spread awareness about this therapeutic option [
      • Casciato S.
      • Morano A.
      • Ricci L.
      • Asioli S.
      • Barba C.
      • Caulo M.
      • et al.
      Knowledge and attitudes of neurologists toward epilepsy surgery: an Italian survey.
      ].
      Conversely, the use of further changes in therapy in drug-resistant subjects (statement 1.4) was supported by a large consensus among physicians (85%). This result is consistent with the literature showing that DRE should not be considered synonymous with intractability, although the probability of a treatment failure with a newly introduced AED increases at the increase of the number of previously pharmacological trials tested [
      • Mula M.
      • Zaccara G.
      • Galimberti C.A.
      • Ferrò B.
      • Canevini M.P.
      • Mascia A.
      • et al.
      Validated outcome of treatment changes according to International League Against Epilepsy criteria in adults with drug-resistant focal epilepsy.
      ].
      Important results emerge regarding statements 1.5, 1.6, and 3.6, related to the consequence of drug side effects and uncontrolled seizures on QoL and people’s autonomy perception. Statement 1.5 (Tolerability of drug therapy matters less than seizure control) reached a large consensus for disagreement among clinicians (83%) but, unexpectedly, not among PwE (62%), who also expressed uncertainty (14%) and agreement (24%). This result is coherent with the outcomes of different studies, which show a larger variety of opinions among PwE when it comes to topics related to QoL. People with Epilepsy’s perception of the treatments’ impact on QoL is becoming increasingly important in the scientific literature, as demonstrated by the development of different tools to evaluate perceptions among patients regarding treatments, healthcare, and their impact on QoL. For example, the Patient Reported Outcomes (PROs) – introduced by FDA in 2009 - are a multidimensional tool aimed at analyzing different aspects of patient’s life and represent outcome measures used by pharmaceutical companies in the report of new drugs [
      • U.S. Department of Health and Human Services FDA Center for Drug Evaluation and Research
      • U.S. Department of Health and Human Services FDA Center for Biologics Evaluation and Research
      • U.S. Department of Health and Human Services FDA Center for Devices and Radiological Health
      Guidance for industry: patient-reported outcome measures: use in medical product development to support labeling claims: draft guidance.
      ,

      Higgins JPH, Green SG. Cochrane Handbook for Systematic Reviews of Interventions. Published online 2008:674.

      ,
      • Patrick D.L.
      • Burke L.B.
      • Powers J.H.
      • Scott J.A.
      • Rock E.P.
      • Dawisha S.
      • et al.
      Patient-reported outcomes to support medical product labeling claims: FDA perspective.
      ,
      • Leidy N.K.
      • Vernon M.
      Perspectives on patient-reported outcomes : content validity and qualitative research in a changing clinical trial environment.
      ].
      Ninety-two percent of PwE and 70% of clinicians agreed to consider complete seizure control essential for a good QoL. Similarly, 93% of PwE agreed that drug resistance is incompatible with an autonomous and independent life; only 38,9% of clinicians agreed, while 61.1% expressed uncertainty or disagreement. These answers are consistent with the responses to statement 1.5: clinicians could have taken more into account the importance of further factors affecting QoL, such as treatment tolerability, while PwE tended once more to emphasize the need for complete seizure control, even if it is well-known that ASMs could be an important source of disease burden, especially in people with DRE [
      • Beghi E.
      Addressing the burden of epilepsy: many unmet needs.
      ,
      • Canevini M.P.
      • De Sarro G.
      • Galimberti C.A.
      • Gatti G.
      • Licchetta L.
      • Malerba A.
      • et al.
      Relationship between adverse effects of antiepileptic drugs, number of coprescribed drugs, and drug load in a large cohort of consecutive patients with drug-refractory epilepsy.
      ]. Clinicians may also have expressed the opinion that a meaningful life is possible even with drug resistance and that there are chances to compensate for limitations derived from this condition. However, discrepancies between PwE’s and clinicians’ answers, highlight differences in the perception of everyday-life limitations, asking physicians to be more sensitive to patients’ perspectives, and are coherent with numerous studies showing that physicians and patients’ priorities are different. An Italian national survey including 21 epilepsy centers and 787 PwE, for example, showed that clinicians tended to be more concerned with diagnosis and treatment of epilepsy, while PwE’s priorities also involved the impact of seizure on daily living activities and the overall QoL and the need to understand the causes of their seizures [
      • Giussani G.
      • Enia G.
      • Bianchi E.
      • Mecarelli O.
      • Beghi E.
      • EPINEEDS Study Group
      The management of epilepsy in clinical practice: Do the needs manifested by the patients correspond to the priorities of the caring physicians? Findings from the EPINEEDS Study.
      ,
      • Enia G.
      • Giussani G.
      • Bianchi E.
      • Mecarelli O.
      • Beghi E.
      • EPINEEDS Study Group
      The management of epilepsy in clinical practice: Do the timing and severity of the disease influence the priorities of patients and the caring physicians? Data from the EPINEEDS study.
      ]. Several factors seem to remarkably influence PwE’s perception of lack of autonomy, first of all, the inability to drive and the existence of activity restrictions imposed by external or internal barriers caused by fear of injury and stigma [
      • Kerr C.
      • Nixon A.
      • Angalakuditi M.
      The impact of epilepsy on children and adult patients’ lives: development of a conceptual model from qualitative literature.
      ,
      • Mcewan M.J.
      • Espie C.A.
      • Metcalfe J.
      • Brodie M.J.
      • Wilson M.T.
      Quality of life and psychosocial development in adolescents with epilepsy: a qualitative investigation using focus group methods.
      ,
      • Wilde M.
      • Haslam C.
      Living with epilepsy: a qualitative study investigating the experiences of young people attending outpatients clinics in Leicester.
      ,
      • Bishop M.
      • Allen C.A.
      The impact of epilepsy on quality of life: a qualitative analysis.
      ]. Moreover, for most PwE, epilepsy impacts emotions, education, job success, development of social and romantic relationships and can result in lower self-esteem [
      • Kerr C.
      • Nixon A.
      • Angalakuditi M.
      The impact of epilepsy on children and adult patients’ lives: development of a conceptual model from qualitative literature.
      ]. There is an important need for actions aimed at limiting the negative impact of epilepsy on PwE’s lives: some studies evidenced that some moderators of epilepsy impact exist, such as the quality of medical support, the support from close friends and family and the dissemination of increased knowledge of epilepsy [
      • Kerr C.
      • Nixon A.
      • Angalakuditi M.
      The impact of epilepsy on children and adult patients’ lives: development of a conceptual model from qualitative literature.
      ,
      • Wilde M.
      • Haslam C.
      Living with epilepsy: a qualitative study investigating the experiences of young people attending outpatients clinics in Leicester.
      ,
      • Sample P.L.
      • Ferguson P.L.
      • Wagner J.L.
      • Elisabeth Pickelsimer E.
      • Selassie A.W.
      Experiences of persons with epilepsy and their families as they look for medical and community care: A focus group study from South Carolina.
      ]. It is important to find ways to enhance PwE’s independence, and Institutions could take a cue from these results to develop facilities for them: the strong limitations derived from the impossibility of driving, for example, could be relieved by the implementation of public transportation benefits that, in most regions, are not currently present.
      The second topic investigated by the survey was access to care. Regarding clinicians’ answers, two interesting elements emerge. On the one hand, most of them shared the opinion that the distribution of high-expertise epilepsy centers and the accessibility to drugs and innovative drugs is uneven throughout Italy. Actually, an important criticism in the management of epilepsy in Italy is the geographic dislocation of centers of excellence, which are located mainly in the North of the country [

      Fondazione Epilessia LICE. Il Libro Bianco dell’Epilessia in Italia. Published 2019. [Accessed 5 May 2022]. Available from: https://fondazionelice.it/il-libro-bianco-dellepilessia-in-italia.

      ]. Among the 62 centers approved by LICE, 30 are in the North, 19 in central Italy, and 13 in the South; moreover, no centers in Basilicata and Valle d’Aosta asked for accreditation to LICE [

      LICE. Centri riconosciuti. [Accessed 5 May 2022]. Available from: http://www.lice.it/LICE_ita/centri/centri.php?id=16.

      ]. Another important criticism is the lack of epilepsy-specific diagnostic-therapeutic pathways in most regions, these being present only in Lombardia [

      Regione Lombardia. DELIBERAZIONE N° XI / 3677 Seduta del 13/10/2020 - ULTERIORI DETERMINAZIONI IN MERITO ALLA RETE REGIONALE DELLE NEUROSCIENZE - Allegato 2) Percorsi diagnostico-terapeutici ed assistenziali dell’epilessia in Lombardia. Published 2020. [Accessed 28 April 2022]. Available from: https://www.regione.lombardia.it/wps/portal/istituzionale/HP/istituzione/Giunta/sedute-delibere-giunta-regionale/DettaglioDelibere/delibera-3677-legislatura-11.

      ], Emilia Romagna [

      Regione Emilia Romagna. Documento di indirizzo per l’organizzazione dell’assistenza integrata alla persona con epilessia. Published 2010. [Accessed 5 May 2022]. Available from: http://bur.regione.emilia-romagna.it/bur/area-bollettini/febbraio-periodico-parte-seconda-1a-quindicina-2/percorso-epilessia-approvazione-linee-guida-per-le-aziende-sanitarie-della-regione-emilia-romagna-per-lorganizzazione-dellassistenza-integrata-alla-persona-con-epilessia/gpg20102344_allegato.pdf.

      ,

      Regione Emilia Romagna. Being published. [Accessed 20 April 2022]. Available from: https://salute.regione.emilia-romagna.it/epilessia.

      ], Toscana [

      Organismo Toscano per il Governo Clinico. PERCORSO ASSISTENZIALE PER LA PRESA IN CARICO DELLE PERSONE CON EPILESSIA. Published 2019. [Accessed 5 May 2022]. Available from:https://www.regione.toscana.it/documents/10180/23792978/allegatoa+decisione+12_2019+-+PDTA_Epilessie.pdf/8f8b4462-23d4-abbe-b12a-b69d6a539780?t=1578657587030.

      ], and Veneto [

      Regione del Veneto, giunta regionale. Decreto n 11 del 26 aprile 2021 - Approvazione del Percorso Diagnostico Terapeutico Assistenziale (PDTA) delle persone affette da epilessia. Published 2021. [Accessed 3 May 2022]. Available from: https://www.lice.it/pdf/2021.04.26_Decreto_11_Approvazione_PDTA_Epilessia.pdf.

      ,

      Regione Veneto. Bur n. 71S del 28/05/2021 DECRETO DEL DIRETTORE DELLA DIREZIONE PROGRAMMAZIONE SANITARIA - LEA n. 11 del 26 aprile 2021 Approvazione del Percorso Diagnostico Terapeutico Assistenziale (PDTA) delle persone affette da epilessia. Published 2021. [Accessed 3 May 2022]. Available from: https://bur.regione.veneto.it/BurvServices/Pubblica/DettaglioDecreto.aspx?id=446879.

      ]. On the other hand, an important percentage of medical specialists expressed neither agreement nor disagreement. This could state a remarkable lack of knowledge about the centers’ distribution outside their local area. Regarding the accessibility to anti-seizure drugs, clinicians expressed various opinions: these answers could also be influenced by the presence of many differences between regions in drug’s access control systems, being these necessarily computerized in some regions and controlled by a higher level of bureaucracy. A large consensus (78%) was reached, instead, regarding the negative influence of healthcare system regionalization on equal access to care.
      Regarding PwE, most of them expressed uncertainty about these statements. This could be due to a lack of knowledge about the concept of 2nd and 3rd level expertise or, more likely, the structure of centers’ territorial network and distribution. The 49% of PwE agreeing with uniform accessibility to drugs was quite unexpected and could be because most of them were taken in charge by a 2nd or 3rd-level center.
      These data underline the need for more widespread and uniform dissemination of centers and distribution of drugs and innovative drugs, a more efficient epilepsy network, and the demand for educational initiatives targeted at clinicians and patients.
      Accordingly to international guidelines [

      NICE. National Institute for Health and Care Excellence. Epilepsies in children, young people and adults. Published 2022. [Accessed 15 April 2022]. Available from: https://www.nice.org.uk/guidance/ng217/resources/epilepsies-in-children-young-people-and-adults-pdf-66143780239813.

      ,

      NICE. National Institute for Health and Care Excellence. Transition from children’s to adults’ services for young people using health or social care services. Published 2016. [Accessed 15 April 2022]. Available from: https://www.nice.org.uk/guidance/ng43.

      ,
      • Labiner D.M.
      • Bagic A.I.
      • Herman S.T.
      • Fountain N.B.
      • Walczak T.S.
      • Gumnit R.J.
      • et al.
      Essential services, personnel, and facilities in specialized epilepsy centers-Revised 2010 guidelines: Guidelines for Specialized Epilepsy Centers.
      ], most clinicians agreed about the importance of multidisciplinarity as a network of different levels of centers working together and about the need for dedicated structures and skills to transition from childhood to adulthood. People with Epilepsy’s opinions were similar regarding childhood-adulthood transition, while a large uncertainty was expressed about the need for multidisciplinary management and a network of centers working together. These data could have been influenced by the current state of implementation of multidisciplinarity, which is often not carried out most efficiently, and by patients’ skepticism towards a network, maybe because they fear that it would lead to a fragmentation of care and it would require traveling to different structures to access the services. These data highlight the need for educational initiatives to raise awareness about the benefits of a well-organized widespread network centered on taking charge of PwE.
      The high percentage of uncertainty between clinicians about the involvement of PwE’s associations in decisional processes could reflect that not all of them are involved in decision-making processes. Similarly, the same result among PwE could be explained by the fact that most participants did not join associations. Debating the results with patients’ representatives, they outlined that many PwE do not join any association because they fear exposing themselves and being stigmatized. This stresses the importance of educational and social intervention to reduce the stigmatization of this condition.
      Our survey also analyzed the attitude of participants toward some new emerging elements in the epilepsy scenario.
      An important skepticism towards the role of telemedicine in replacing face-to-face follow-up visits emerges from the answers. Telemedicine, which spread diffusely during the COVID-19 crisis in the management of chronic conditions [
      • Bloem B.R.
      • Dorsey E.R.
      • Okun M.S.
      The Coronavirus Disease 2019 crisis as catalyst for telemedicine for chronic neurological disorders.
      ,
      • Assenza G.
      • Lanzone J.
      • Brigo F.
      • Coppola A.
      • Di Gennaro G.
      • Di Lazzaro V.
      • et al.
      Epilepsy Care in the Time of COVID-19 Pandemic in Italy: Risk Factors for Seizure Worsening.
      ], is the use of telecommunications technologies to provide medical information and services [
      • Perednia D.A.
      • Allen A.
      Telemedicine technology and clinical applications.
      ], and its appropriate use was recommended by WHO in the Health-for-all strategy for global health development in 21st Century [

      WHO Executive Board 101st session. Health-for-All Policy for the 21st Century.; 1998. [Accessed 15 April 2022]. Available from: https://apps.who.int/iris/handle/10665/79425.

      ]. Numerous studies explored the possibilities of telemedicine in the management of epilepsy, often showing promising results [
      • Datta P.
      • Barrett W.
      • Bentzinger M.
      • Jasinski T.
      • Jayagopal L.A.
      • Mahoney A.
      • et al.
      Ambulatory care for epilepsy via telemedicine during the COVID-19 pandemic.
      ,
      • Kuroda N.
      Decision making on telemedicine for patients with epilepsy during the Coronavirus Disease 2019 (COVID-19) crisis.
      ,
      • Kissani N.
      • Lengané Y.T.M.
      • Patterson V.
      • Mesraoua B.
      • Dawn E.
      • Ozkara C.
      • et al.
      Telemedicine in epilepsy: how can we improve care, teaching, and awareness?.
      ,
      • Fesler J.R.
      • Stanton S.
      • Merner K.
      • Ross L.
      • McGinley M.P.
      • Bena J.
      • et al.
      Bridging the gap in epilepsy care: a single-center experience of 3700 outpatient tele-epilepsy visits.
      ,
      • Patterson V.
      Managing epilepsy by telemedicine in resource-poor settings.
      ,
      • Trivisano M.
      • Specchio N.
      • Pietrafusa N.
      • Calabrese C.
      • Ferretti A.
      • Ricci R.
      • et al.
      Impact of COVID-19 pandemic on pediatric patients with epilepsy – the caregiver perspective.
      ]. A large single-center retrospective study on a 3700 televisits experience, for example, showed that for most PwE, it was a positive experience and that tele-epilepsy is sustainable and scalable [
      • Fesler J.R.
      • Stanton S.
      • Merner K.
      • Ross L.
      • McGinley M.P.
      • Bena J.
      • et al.
      Bridging the gap in epilepsy care: a single-center experience of 3700 outpatient tele-epilepsy visits.
      ]. Telemedicine has many advantages, such as saving time and money on travel, the possibility of having follow-up visits in a more familiar environment - promoting a less stigmatized concept of the disease - and the accessibility to follow-up visits for people who live far away from their reference center. Moreover, telemedicine, through teleconsultations, offers the possibility of sharing data – such as laboratory, genetics, neurophysiological and neuroimaging data – among different experts, with important advantages in terms of saving time and better implementation of multidisciplinarity in the approach of every PwE’s case. Even neurophysiology can take advantage of telemedicine by developing teleneurophysiology [
      • Brunnhuber F.
      • Slater J.
      • Goyal S.
      • Amin D.
      • Thorvardsson G.
      • Freestone D.R.
      • et al.
      Past, Present and Future of Home video-electroencephalographic telemetry: a review of the development of in-home video-electroencephalographic recordings.
      ,
      • Stipa G.
      • Gabbrielli F.
      • Rabbito C.
      • Di Lazzaro V.
      • Amantini A.
      • Grippo A.
      • et al.
      The Italian technical/administrative recommendations for telemedicine in clinical neurophysiology.
      ,
      • Biondi A.
      • Laiou P.
      • Bruno E.
      • Viana P.F.
      • Schreuder M.
      • Hart W.
      • et al.
      Remote and long-term self-monitoring of electroencephalographic and noninvasive measurable variables at home in patients with epilepsy ([email protected]): protocol for an observational study.
      ]. It is becoming increasingly important, then, to properly implement telemedicine, elaborating adequate criteria to address patients to televisits or physical visits based on their condition [
      • Kuroda N.
      Decision making on telemedicine for patients with epilepsy during the Coronavirus Disease 2019 (COVID-19) crisis.
      ], integrating these two options in a correct way and making telemedicine an integrative and complementary tool to improve PwE management, particularly in follow up visits, and not an absolute replacement for physical visits.
      The distrust that emerged from our survey could be affected by different factors, such as PwE’s age, availability of electronic devices and Internet connection, as well as telemedicine implementation methods used by the referral centers and distance from the referral center. Moreover, it is important to note the use of the word “replaces” instead of “can replace” in statement 2.4: this could have been interpreted as considering the current state of things and not the future telemedicine potentials and could have influenced the strong disagreement with the statement. These data could reflect the problems in implementing telemedicine in Italy and highlight the need for a collective cultural revolution involving both patients and physicians, and the importance of developing further concrete strategies to improve telemedicine implementation. In the debate on the survey’s results with the patients’ representatives, it emerged that PwE are concerned that telemedicine could have a negative impact on care quality and fear losing their relationship with their physicians. Therefore, it is important to reassure PwE about how telemedicine could improve the quality of care.
      A more open-minded opinion was expressed, instead, about the utility of digital technologies to improve the self-management of PwE, with 56% of clinicians and 59% of PwE expressing a positive view. Nowadays, the development of different devices for seizure detection – using different modalities, such as EEG, video, accelerometry, electromyography, electrocardiography, photoplethysmography, electrodermal activity, and a combination of them [
      • Bruno E.
      • Viana P.F.
      • Sperling M.R.
      • Richardson M.P.
      Seizure detection at home: Do devices on the market match the needs of people living with epilepsy and their caregivers?.
      ,
      • Hubbard I.
      • Beniczky S.
      • Ryvlin P.
      The challenging path to developing a mobile health device for epilepsy: the current landscape and where we go from here.
      ] – is providing promising perspectives. Different studies showed how these devices could improve PwE’s management by increasing PwE’s safety and preventing Sudden Unexpected Death in Epilepsy (SUDEP) [
      • Hubbard I.
      • Beniczky S.
      • Ryvlin P.
      The challenging path to developing a mobile health device for epilepsy: the current landscape and where we go from here.
      ] and by enabling better seizure detection, which is a very important element in limiting seizures underdiagnosis or overdiagnosis since numerous studies suggest that PwE’s history is often reliable only in part [
      • Bruno E.
      • Viana P.F.
      • Sperling M.R.
      • Richardson M.P.
      Seizure detection at home: Do devices on the market match the needs of people living with epilepsy and their caregivers?.
      ,
      • Hubbard I.
      • Beniczky S.
      • Ryvlin P.
      The challenging path to developing a mobile health device for epilepsy: the current landscape and where we go from here.
      ,
      • Hoppe C.
      • Poepel A.
      • Elger C.E.
      Epilepsy: accuracy of patient seizure counts.
      ,
      • Elger C.E.
      • Hoppe C.
      Diagnostic challenges in epilepsy: seizure under-reporting and seizure detection.
      ,
      • Blachut B.
      • Hoppe C.
      • Surges R.
      • Stahl J.
      • Elger C.E.
      • Helmstaedter C.
      Counting seizures: the primary outcome measure in epileptology from the patients’ perspective.
      ,
      • Tatum W.O.
      • Winters L.
      • Gieron M.
      • Passaro E.A.
      • Benbadis S.
      • Ferreira J.
      • et al.
      Outpatient seizure identification: results of 502 patients using computer-assisted ambulatory EEG.
      ,
      • Cook M.J.
      • O’Brien T.J.
      • Berkovic S.F.
      • Murphy M.
      • Morokoff A.
      • Fabinyi G.
      • et al.
      Prediction of seizure likelihood with a long-term, implanted seizure advisory system in patients with drug-resistant epilepsy: a first-in-man study.
      ]. International League Against Epilepsy and the International Federation of Clinical Neurophysiology have recently published a guideline based on a systematic review of the published literature, in which they recommend the use of wearable devices for selected patients with generalized tonic-clonic seizures (GCTS) and focal-to-bilateral tonic-clonic seizures (FBTCS), because of the high level of evidence of the accuracy of these devices in detecting these types of seizures. To date, the use for other seizure types shows only a moderate level of evidence, but further research and development are recommended since most of the results are very promising [
      • Beniczky S.
      • Wiebe S.
      • Jeppesen J.
      • Tatum W.O.
      • Brazdil M.
      • Wang Y.
      • et al.
      Automated seizure detection using wearable devices: a clinical practice guideline of the International League Against Epilepsy and the International Federation of Clinical Neurophysiology.
      ], and studies involving PwE and caregivers showed that most of them had a high level of satisfaction with their experience with wearable devices [
      • Hadady L.
      • Klivényi P.
      • Fabó D.
      • Beniczky S.
      Real-world user experience with seizure detection wearable devices in the home environment.
      ]. Yet, these are innovative tools - currently under development and maybe still not diffusely spread among patients - and represent something new in the professional environment into which until now clinicians have grown. The high percentage of uncertainty between clinicians (41%) in our survey could result from this and the fact that digital technologies would probably result in an increased workload. It could be interesting to evaluate the agreement to this statement in a few years’ time.
      Another important topic analyzed in our survey was Narrative Medicine or medicine practiced with narrative competencies [
      • Charon R.
      Narrative medicine: a model for empathy, reflection, profession, and trust.
      ,
      • Charon R.
      Narrative medicine: form, function, and ethics.
      ], aimed at setting a relationship between the physician and the patient-focused not only on clinical and biological issues but also on the psychological, social, and ontological consequences of illness on the patient. Narrative medicine proved to enhance clinical expertise in different therapeutic fields - as outlined by the WHO recommends the use of narrative research in improving healthcare policies [

      Cultural contexts of health: the use of narrative research in the health sector (2016). [Accessed 2 May 2022]. Available from: https://www.euro.who.int/en/publications/abstracts/cultural-contexts-of-health-the-use-of-narrative-research-in-the-health-sector-2016.

      ] and by the guidelines published by the Italian Institute of Health (ISS) [

      Istituto Superiore di Sanità, Centro Nazionale Malattie Rare. Consensus Conference – Linee di indirizzo per l’utilizzo della medicina narrativa in ambito clinico-assistenziale, per le malattie rare e cronico-degenerative. Published December 11, 2013. [Accessed 20 April 2022]. Available from: https://www.medicinanarrativa.network/wp-content/uploads/2021/03/Quaderno_n._7_02_CONSENSUS-CONF-FINALE_compressed.pdf.

      ] – even more when dealing with a complex condition such as epilepsy [
      • Vaccarella M.
      Narrative epileptology.
      ,
      • Gilliam F.
      • Penovich P.E.
      • Eagan C.A.
      • Stern J.M.
      • Labiner D.M.
      • Onofrey M.
      • et al.
      Conversations between community-based neurologists and patients with epilepsy: results of an observational linguistic study.
      ], enabling a more personalized and all-round approach to PwE. Nowadays, moreover, Narrative Medicine is offered new instruments by the digital revolution, which provides new spaces – the digital ones - where the narrative setting can take place. Studies on Narrative Medicine provided promising results: some Italian studies, for example, showed how its application resulted in a greater quality in clinical practice. Most of the PwE involved in a project on digital Narrative Medicine declared a positive experience and thought it should be implemented in routine clinical practice [
      • Cenci C.
      • Mecarelli O.
      Digital narrative medicine for the personalization of epilepsy care pathways.
      ], while positive evaluations were also expressed by physicians, among which Narrative Medicine demonstrated a role in decreasing the level of stress and preventing burnouts [
      • Chesi P.
      • Marini M.G.
      • Scarlata P.
      • Mecarelli O.
      ERE study project group. Epileptologists telling their experiences caring for patients with epilepsy.
      ]. In our survey, a consensus was nearly reached among clinicians regarding the use of Narrative Medicine as a tool to improve communication between PwE and physicians, while almost half of the PwE (46%) expressed neither agreement nor disagreement, probably because of a lack of knowledge about this topic. These data outline the need for improvement and support of such a tool, especially with educational interventions on PwE.

      5. Conclusions

      This survey represents a preliminary study to better understand the drug-resistant focal epilepsy reality and how to improve epilepsy management and PwE’s quality of life.
      This study has some strengths, such as the great number of specialists involved and the variety of topics investigated.
      This study also has several limitations, such as the imbalance in the distribution of PwE involved in the Delphi process (most of them living in southern Italy) and the use of technical vocabulary, which – according to PwE’s representatives involved in the results’ debate – may have had an impact on PwE’s comprehension of the statements and, therefore, on their answers.
      The results outlined many fields of possible intervention, such as the need for educational initiatives targeted at physicians and PwE – for example, regarding tools like telemedicine, digital devices, and narrative medicine – as well as the spread of better knowledge about epilepsy among the general population, in order to reduce epilepsy stigma. Moreover, institutions could take a cue from this survey to develop facilities aimed at enhancing PwE’s autonomy and promoting equal access to care throughout the country. In addition, discrepancies between PwE’s and clinicians’ answers highlight differences in the perception of everyday-life limitations, asking physicians to be more sensitive to PwE’s points of view.

      6. Ethics approval and consent to participate

      This Delphi study was aimed at the collection of panelists’ opinions, therefore, did not involve the sharing of sensitive data. Consequently, this study did not require ethical approval. All experts involved in the Delphi process were informed of the study's objectives and the possibility of publishing the results in a peer-reviewed article. Participation was voluntary by invitation, and participants did not receive any compensation or benefits for participating in the survey. Participants, by accessing the secure online survey platform using their credentials, gave their consent to participate in the survey by clicking on the appropriate button to submit the completed questionnaire. All survey results are anonymous and presented in aggregate form.

      Author contributions

      All Authors conceived the project, discussed the results, and contributed to the final manuscript.

      Declaration of Competing Interest

      OM has participated in advisory boards and pharmaceutical industry-sponsored symposia for Angelini, Arvelle, Bial, Eisai, Lusofarmaco, Gw, UCB Pharma.
      GDG has participated in advisory boards and pharmaceutical industry-sponsored symposia for Eisai, UCB Pharma, Bial, Lusofarmaco, Livanova, Arvelle, Angelini.
      FV has participated in advisory boards and pharmaceutical industry-sponsored symposia for Zogenix, Neuraxpharm, Angelini, Eisai.

      Acknowledgements

      The authors thank the participants who participated in the Delphi consensus. The study group includes experienced epileptologists according to the recommended Delphi procedures. The contributors to the Delphi questionnaire validation are listed below: Ms. Simona Borroni (EUPATI Patient Expert), Dr. Alessandra Morano (Rome), Dr. Barbara Mostacci (Bologna), Dr. Nicola Specchio (Rome). List of the Panel of Experts of the Delphi Survey: Umberto Aguglia (Reggio Calabria); Francesca Anzellotti (Chieti); Giovanni Assenza (Roma); Daniela Audenino (Genova); Domenica Immacolata Battaglia (Roma); Vincenzo Belcastro (Lodi); Leonilda Bilo (Napoli); Francesca Bisulli (Bologna); Giovanni Boero (Taranto); Paolo Bonanni (Conegliano, TV); Francesco Brigo (Merano); Maria Paola Canevini (Milano); Roberto Cantello (Novara); Teresa Anna Cantisani (Perugia); Vittoria Cianci (Reggio Calabria); Antonietta Coppola (Napoli); Cinzia Costa (Perugia); Filippo Dainese (Venezia); Alfredo D’Aniello (Pozzilli, IS); Carlo Di Bonaventura (Roma); Giuseppe Didato (Milano); Giuseppe D'Orsi (Foggia); Maurizio Elia (Troina, EN); Carlo Andrea Galimberti (Pavia); Rosita Galli (Arezzo); Antonio Gambardella (Catanzaro); Loretta Giuliano (Catania); Renzo Guerrini (Firenze); Francesca Izzi (Roma); Edoardo Ferlazzo (Catanzaro); Nicoletta Foschi (Ancona); Angela La Neve (Bari); Simona Lattanzi (Ancona); Monica Lodi (Milano); Alfonso Marrelli (L’Aquila); Roberto Michelucci (Bologna); Elisa Montalenti (Torino); Francesca Operto (Salerno); Giada Pauletto (Udine); Piero Pignatta (Torino); Monica Maria Francesca Puligheddu (Cagliari); Patrizia Pulitano (Roma); Federica Ranzato (Vicenza); Romana Rizzi (Reggio Emilia); Eleonora Rosati (Firenze); Rosario Rossi (Nuoro); Pasquale Striano (Genova); Laura Tassi (Milano); Paolo Tinuper (Bologna); Giampaolo Vatti (Siena); Anna Elisabetta Vaudano (Modena); Aglaia Vignoli (Milano); Flavio Villani (Genova); Gaetano Zaccara (Firenze). In addition, the authors express their sincere thanks to all PwE that took part in this survey. The research, relationship, and contact with patients’ associations on the national territory was provided by Fondazione The Bridge. Medical writing assistance were provided by Dr. Veronica Bettoni. Editorial assistance for the organization and technical support during the manuscript finalization and submission process was provided by Ethos s.r.l.

      Financial support

      This publication was supported by an unrestricted grant from Angelini Pharma.

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