Barriers to epilepsy surgery in pediatric patients: A scoping review
儿童患者癫痫手术的障碍：一项范围审查

A scoping review is conducted to characterize the landscape of research activity on a topic, summarize and disseminate research findings, identify research gaps in the existing literature, or determine the value of undertaking a full systematic review [28]. In contrast to systematic reviews meta-analyses, scoping reviews do not address quality appraisal and the relative weight of evidence [28]. We chose to utilize a scoping review given our goals were to characterize the landscape of research activity and summarize research findings. A systematic review or meta-analysis would not have been appropriate given the likely heterogeneity in the existing literature.

This scoping review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension - Scoping Reviews (PRISMA-ScR) and Arksey and O'Malley methodological approach [28,29]. After establishing a straightforward research question, we identified and selected relevant studies.

What difficulties do parents face when contemplating ES for their children?

We collaboratively developed a comprehensive research strategy including the following key terms: “pediatric”, “epilepsy”, “surgery”, “parents” and “decision-making”. We searched the PubMed MEDLINE (National Library of Medicine), Embase (Elsevier), and Scopus (Elsevier) databases. The search strategies are outlined in Appendix 1. No restrictions were applied on language, date, or study design. No protocol was registered. No funding was received.

Following the primary search, duplicates were eliminated. All remaining articles were screened by title and abstract to identify relevant studies for further screening via full-text review. Subsequently, articles included in the full-text review were assessed for eligibility according to the following inclusion criteria: full-text availability, providing quantitative or qualitative primary data, population of pediatric patients with epilepsy or their caregivers, and describing barriers pertaining to pediatric ES. Abstracts, all types of literature reviews, non-human studies, studies not focused on epilepsy, studies focused exclusively on adult patients with epilepsy, and studies solely focusing on clinical or technical factors impeding pediatric ES were excluded. Study selection was conducted independently by two reviewers (N.N-K. and R.H.) with a high level of inter-observer agreement (Cohen's kappa k = 0.93). Any disagreement was reconciled by a discussion with a predetermined third author (N.A.S.).

We collected study characteristics, including study design, country of origin, income classification of country of origin according to the World Bank [30], reporting source, and barriers to ES. The authors discussed the choice of the analytical approach a priori. We agreed on a flexible thematic analysis to identify themes in the included articles. We adopted an inductive approach, where data coding and themes selection were determined by the content of data rather than preexisting concepts or ideas, allowing us to capture the relevant literature. Classifying barriers into different semantic themes followed a reflexive and iterative process [31].

First, two authors (R.H., N.N-K.) independently reviewed full texts for familiarity with content. Then, the two raters independently thoroughly re-reviewed the articles, highlighting all potentially interesting features relevant to our research question. This phase involved manual color-coding of all datasets to identify potential patterns. Subsequently, codes and collated data were independently examined to identify broader patterns consisting of candidate themes. The authors then discussed and refined candidate themes. Disagreements were solved by consulting with a third predetermined member (N.A.S.). Next, this initial thematic framework was deliberated with the remainder of the authors to ensure clearly defined, mutually exclusive barriers. Barriers to pediatric ES were extracted, analyzed, and classified into four primary categories, namely parent-based, patient-based, physician-based, and healthcare system-based barriers. Each primary category was stratified into subcategories, ensuring a rigorous analytical overview of the barriers to ES.
首先，两位作者（R.H., N.N-K.）独立审查了全文，以熟悉内容。然后，两位评审者独立地彻底重新审查了文章，突出所有与我们的研究问题相关的潜在有趣特征。此阶段涉及手动对所有数据集进行颜色编码，以识别潜在模式。随后，代码和整理的数据被独立检查，以识别由候选主题组成的更广泛模式。作者随后讨论并完善候选主题。分歧通过咨询第三位预定成员（N.A.S.）来解决。接下来，这一初步主题框架与其余作者进行了讨论，以确保明确界定、相互排斥的障碍。儿童 ES 的障碍被提取、分析并分类为四个主要类别，即基于父母的、基于患者的、基于医生的和基于医疗系统的障碍。每个主要类别被细分为子类别，以确保对 ES 障碍的严格分析概述。

As reported by 11 included studies (65%), parents’ misperceptions concerning ES represented the most common perceived barrier to treatment. ES was often perceived by parents as a treatment of last resort and described as “unpredictable”, “horrific”, and “barbaric” [[36], [37], [38], [39],41,42,75]. Overestimation of the risks of surgery was a source of fear for parents as it guided their negative, apprehensive attitude towards ES. Some parents expressed specific worries regarding potential postoperative outcomes and complications, such as loss of function, change in personality, and lack of seizure improvement. Others exhibited more general apprehensions [33,35,40,72,74,77].

Gaining knowledge on the treatment of intractable epilepsy was described as an “arduous” and “mentally-draining” process for parents, analogous to learning a new language of medically complex terms [34,41]. Parents unfamiliar with epilepsy felt overwhelmed by the “avalanche of information” conveyed by physicians, favoring a state of inertia and indecision when considering ES [41]. A low level of knowledge regarding epilepsy represented an obstacle in the decision-making process in 33% of studies [32,34,36,41]. Conversely, parents who were adequately informed about epilepsy and the risks and benefits of ES were more inclined to be receptive to surgical treatment for their children. Similarly, parental level of education correlated with their attitudes towards ES, as parents with a higher level of education favored ES more [34,38,77].

The parental caregiving role was associated with high levels of stress, as demonstrated in 47% of studies. While attempting to navigate through gathered information on DRE and its management, parents also needed to process the emotional impact of this life-changing diagnosis and its prognosis. Consequently, the decision to proceed with ES carried an immense load of responsibility and pressure, compounded by the uncertainty and fear associated with ES [35,37,41,42,72,75,76]. Many parents required several years to assimilate this emotional charge and deal with factual risks and benefits before ultimately deciding to pursue surgery [38]. Studies also noted that family conflicts may arise when discussing ES, further complicating the decision [35,37].

Parents perceived the pre-referral period as a particularly arduous and emotionally burdensome journey marked by frustration in dealing with multiple medications and consultations and the constant stress of caring for their child, often with limited or no support [38,41,72,75,76]. The emotional burden of the journey to ES from the pre-referral period to the decision-making process represented a significant barrier [35,37,38,41,72,75,76].

Low socioeconomic or insurance statuses significantly altered the timeliness and receipt of ES, as parents might be less inclined to pursue surgery due to associated expenses. Lack of appropriate health insurance was associated with longer intervals from seizure onset to referral and surgery, as shown by 18% of studies [32,36,71].

The patient's age influenced parental attitude towards ES in 18% of included articles [[32], [33], [34],42]. Erba et al. reported that parents of children with epilepsy below 13 years old were significantly more receptive to ES than parents of children above 13 years old, suggesting that parental attitudes changed when children reach puberty [34]. Conversely, Baca et al. showed that older age was associated with shorter intervals to surgery; however, this association was blurred after excluding children older than 10 years [32]. Other factors obstructing pursuit of ES included the low intelligence level of children and their resistance against surgery [33,74].

The clinical severity of epilepsy was perceived as a very important factor affecting caregivers’ decision to undergo surgery [73] and was associated with a shorter time to ES [32]. Children with active and successfully treated infantile spasms and daily or more seizure frequency were more likely to receive surgery in a timely manner [32]. An MRI before referral was associated with the briefer time interval from epilepsy onset to surgery, regardless of the radiological findings [32].

As reported by 65% of articles, physician-based factors were among the most prevalent barriers to ES. All but one of these articles reported that a significant barrier to pediatric ES was the lack of trust and poor communication with physicians. Some studies reported that parents received vague and inadequate information regarding the risks and benefits of ES [33,34,[37], [38], [39],72,75,76]. Some parents felt “dismissed” and “disbelieved” by their physicians, which led them to navigate the healthcare system in the hope of finding a “gracious” and “approachable” physician. This process was time-consuming and increased parental stress while prolonging the time to surgical referral. As asserted by several articles, parental favorable attitudes towards ES were associated with the high level of trust in their physician. The physician's opinion greatly influenced the decision to pursue ES [33,34]. This indicates that the immense trust that parents had in physicians was crucial for an effective shared decision-making process [33,37,73]. Conversely, lack of trust diminished parental involvement in the decision-making process and added to their negative experiences with medical consultations [38].

In addition to poor communication and lack of trust in the physician, some parents perceived their physicians to lack clinical expertise regarding ES, which deterred them from accepting ES as a viable treatment [33,41]. Parental perceptions of poor physician expertise stemmed from inconsistent recommendations and lack of familiarity with epilepsy on the part of physicians during medical consultations [38]. In some studies, this perceived lack of expertise no longer acted as a barrier when parents were directed towards a team of specialists [75,76]. The lack of physician competence and sensitivity regarding pediatric ES represented a major obstacle to receiving ES, as demonstrated by 47% of studies. Erba et al. showed that 60% of surveyed pediatric neurologists failed to meet the published guideline standards of practice regarding ES referral [34]. Moreover, Samanta et al. reported that a lack of sufficient clinical expertise exists as a barrier in the shared decision-making process, as reported by neurologists themselves [77]. The failure of physicians to meet the expectations of parents often led parents to navigate arduously through the healthcare system to find a physician that matched their needs [33,34,38,41,42].

On the healthcare system-based level, a well-defined barrier to ES was the complexity of health insurance policies. Two studies (12%) found that parents encountered numerous obstacles navigating through complex insurance policies. Parents mentioned that insurance providers could be challenging to contact, were often non-collaborative, and sometimes provided ambiguous information. Parents felt helpless when interfacing with insurance companies. The process was time-consuming and emotionally exhausting, delaying the time to referral for presurgical evaluation and subsequent ES [38,41].

Severe childhood epilepsy is associated with deleterious effects on the developing brain, and the chronic use of AED may contribute to irreversible cognitive adverse effects [43]. Evidence of the benefits of ES on postoperative outcomes is consistent throughout the literature. Randomized controlled trials have highlighted the advantages of early surgical treatment over the long-term use of AEDs, recognizing that longer interval to ES is associated with lower cognitive outcomes [26,27,43,44]. Among these, only one randomized clinical trial examined postoperative seizure-freedom in children, reporting significant seizure improvement at 12 months in the surgically-treated group (77%) compared to the medical treatment group (7%) [27]. Achieving early seizure freedom may optimize the neurodevelopmental potential of afflicted children, contributing to a better quality of life, cognitive development, and social inclusion [12]. Hence ES should not be delayed, nor considered a last resort in children with medically intractable epilepsy. Despite the accumulating clinical evidence indicating better seizure-freedom, developmental outcomes, and quality of life following resective surgery, as well as evidence of its long-term cost effectiveness [45,70], ES remains underutilized. Although there are established referral guidelines for ES, there is a major deficit in their implementation in the clinical practice [7,34,46,47]. Limited physician knowledge on the management of DRE might lead to a higher referral threshold, hindering the receipt of ES [34,42]. Moreover, parents who received inconsistent recommendations were more likely to oppose ES [33]. A web-based intervention is under development to help evaluate ES candidacy. This type of intervention may mitigate the lack of appropriate hands-on training and consolidate referral guidelines in clinical practice [48]. Furthermore, the average time to surgery in the last two decades has remained stagnant at 5.3 years. The longest and most challenging aspect seems to be the presurgical evaluation window [38].

Developing countries account for 80% of the epilepsy-afflicted population. Socioeconomic limitations limit ES due to the lack of expertise, technology, and medical infrastructure [49], [50], [51]. In contrast, ES is readily available in high-income countries [18,21]. However, its accessibility may be obstructed by deeply rooted socioeconomic inequities. In the United States, public programs have restrictive coverage, and employers are encouraged but not obliged to provide private insurance. Low-income children are likely to be uninsured or have public insurance, decreasing access to specialists and high-quality epilepsy management [32,52,53]. Low-income children who rely on public insurance are 55% less likely to be referred to a specialist and undergo surgery than privately insured children [52]. Navigating insurance is complex and time-consuming for families [38]. Although the expansion of Medicare and implementation of state-sponsored health insurance like the State Children's Health Insurance Program has likely increased access to healthcare for vulnerable children, the effects of these actions on ES utilization are unknown [54,55]. In contrast, in a publicly-funded healthcare system with universal coverage, like in Canada, the receipt of ES is independent of marginalization index [24]. Still, Canadian patients with lower socioeconomic status have a longer time to surgery that can be explained by other socioeconomic factors such as transportation and an inability to take time off work. Additionally, the rural-urban divide is important to consider. Proximity to surgical centers, most of which are in cities, was positively associated with parental acceptance of ES [34]. Conversely, a Canadian study showed no association between rural/urban residence and access to neurosurgical treatment [56,57], and a systematic review assessing barriers to providing ES to children in the United States identified two studies that reported a longer delay in receiving ES for patients travelling shorter distance to the referral center [70]. This counterintuitive finding may result from the lower socioeconomic status of families living closer to epilepsy centres, mostly found in urban areas. Future studies should examine this factor in greater detail in children with epilepsy.

Another source of disparities is race/ethnicity. In North America, Hispanic and Black individuals are less likely to undergo ES than their White counterparts [53,58,59,70]. However, very few studies have investigated the effect of racial disparities on the receipt of ES in children. A study based on Kids’ Inpatient Database demonstrated that racial minorities were underrepresented in ES, even after adjusting for socioeconomic factors [59]. In Canada, aboriginals were less likely to visit an epilepsy specialist than to non-aboriginals [60]. However, other studies have found no or inverse associations between race and use of ES or time to ES [32,52]. Importantly, race exert its influence on ES as proxy for socioeconomic status or beliefs rather than directly. For example, African Americans tended to express more fear regarding ES, distrust in healthcare providers, and lack of social support [39,61]. Racial disparities in decision-making also originate from systemic racial discrimination by healthcare providers and institutions, leading to different referral patterns among different racial groups. Notwithstanding the evidence of reducing racial disparities after enrollment State Children's Health Insurance Program, the impact of governmental programs must be further evaluated in the context of ES [54,62].

Parental attitudes towards ES are based on social and environmental factors, such as community beliefs, culture, and educational background, and are further influenced by the use of external resources and information provided by physicians [36]. Fear and misperception were the main barriers in the decision-making process, mainly arising from lack of knowledge or misunderstanding of ES. Some parents overestimate the risk of the surgery and underestimate the consequences of lifelong epilepsy, while parents of cognitively impaired children were less hopeful about positive surgery outcomes, decreasing the favorability of brain surgery at baseline. Inadequate health literacy is a well-known risk factor for poor health. Moreover, some studies suggested that limited English language proficiency in English-predominant contexts may decrease the utilization of ES, presumably due to associated communication barriers during the surgical informed consenting process and cultural beliefs [63]. A positive attitude towards ES is associated with high parental educational attainment and knowledge of ES. Understanding ES is crucial for informed decision-making. Parents receiving factual information on the procedure were more likely to feel empowered to participate in the decision to pursue ES and were more receptive to ES [34,37,38]. Thus, establishing patient education interventions could serve as a promising strategy to increase the knowledge base of patients and caregivers on epilepsy in children and its treatment options, thereby increasing the likelihood of eligible candidates receiving ES. This recommendation is consistent with those of epilepsy care providers in Samanta et al.’s study, who proposed multimodal patient-facing educational interventions, such as written handouts in combination with digital apps, as tools to improve collaborative decision-making [77]. Interventions targeted to increase parent education regarding pediatric ES have proven to be effective according to the literature: in Erba et al.’s study of 138 parents of children with epilepsy, the completion of an informative questionnaire led parents of all survey groups, including those opposed to ES a priori, to adopt a more favorable attitude towards ES [34].

Lack of trust in the patient-physician relationship is associated with increased parental resistance towards ES [33,34,42]. Hence, establishing a patient-physician relationship based on trust is crucial to accepting ES. Healthcare providers must be cognizant of parents' emotional vulnerability during the decision-making process [38,42]. The findings of this study suggest that initial discussions regarding ES are often unexpected, shocking and anxiogenic. The physician must therefore introduce the topic of ES delicately yet directly, adapting the conversation to the emotional state of the parent. In line with the recommendations of multiple included studies, physicians should notify parents in advance about addressing ES at an upcoming meeting, yet they should initiate discussions on ES early on in the treatment plan so as to manage parents’ expectations and perspectives of surgery, to increase awareness, trust and transparency in the relationship, and to empower them in the shared decision-making process [72], [73], [74], [75].

In order to relieve the emotional burden experienced throughout the pre-surgical journey, families should benefit from psychosocial support interventions within and outside of the clinical setting. One of the primary causes of anxiety and frustration among caregivers was the lack of direction experienced during the long pre-referral period. To mitigate this source of distress, parents in Nelson et al.’s study recommended the creation of a step-by-step guide on the process to follow in the decision-making of ES with timelines and information on each required assessment or investigation [72]. Physicians and healthcare professionals themselves must provide enough time to validate and address parental concerns. The multidisciplinary care team is an integral component of patient-physician interactions given its ability to relieve parental distress, increase trust in providers, and increase attitudes in favor of ES when necessary [37,38,64]. Undoubtedly, the burden on families persists outside of the clinical encounter. A navigator – often a specialized nurse – may further assist in addressing parental emotional and logistical needs outside of the clinical encounter and promote continuity of care. Furthermore, it is important to emphasize that patient support groups, such as epilepsy foundations, and online may provide a valuable source of additional information and social support for pediatric patients with epilepsy and their caregivers [37,38]. Online forums and social media platforms may allow caregivers to engage virtually with families living similar challenges, thereby breaking isolation and offering peer-to-peer support [72,[74], [75], [76]]. Interestingly however, one study found that patients who decided on ES used fewer external resources than does who declined it [33]. Parents who received sufficient information in a clear manner from the physician may not have felt the need to look for information elsewhere.

Parents who decide to pursue ES tend to have a productive medical consultation, a clear overview of the risks and benefits of surgical treatment, and comprehensive answers to their questions [33,38]. This suggests the pivotal role of physicians in providing adequate education for parents [34,42]. In order to effectively convey factual information, physicians must understand baseline parental health literacy, understanding, expectations, perspectives [64], [65], [66], [67], [68]. During the educational process, physicians must calibrate the way they provide information with these parental factors, avoid jargon, and utilize multimodal interactive educational modalities to ensure maximal understanding [64], [65], [66], [67], [68]. Receiving digestible information was shown to be very helpful in engaging parents in a shared decision making-process, as it can help them to establish realistic expectations regarding outcomes and complications of ES [38].

Involving caregivers and their families in every step of the treatment plan according to the shared decision-making approach is fundamental in the shared decision-making approach. Although pediatric patients cannot generally provide consent and some children may have intellectual impairment, physicians should incorporate children given that the opinions of children may influence the perspectives of their patients [38]. Parents of postpubescent children might be prone to conservative approaches, acknowledging the ability of their post-pubertal children to express their preferences [34,42]. Additionally, addressing the psychosocial needs, such as stigma, of the children is an essential part of holistic epilepsy care and benefits from the multidisciplinary care team. This also affects ES utilization: adolescents who discuss these fears with their physicians are more likely to accept surgical treatment [39].

We acknowledge the limitations of this study. First, only published articles with full-text manuscripts were included, perhaps predisposing our study to publication bias. Second, all included studies arose from high-income countries, perhaps underemphasizing the role of health systems factors in underutilization of epilepsy surgery worldwide. Low- and middle-income countries are likely to lack access to neurosurgery. Rural communities were similarly not examined. Third, included studies were limited by retrospective nature and study design. Fourth, parents and patients were investigated at different time points in epilepsy diagnosis or treatment throughout the studies. Some studies reported parental opinions retrospectively after surgery, and one study placed parents in a hypothetical situation of their infants needing ES [34,40]. This heterogeneity rendered comparisons challenging. Included studies that evaluated barriers to ES post-hoc or in a hypothetical context are subject to hindsight bias. Families that are not confronted with an actual decision might tend to resist ES with certainty compared to parents who face an actual decision. Lastly, no meta-analysis was performed given the heterogeneity of study methodologies, populations, and outcomes, preventing us from drawing statistically significant conclusions from our results. However, we present a reproducible study that provides insight into barriers for ES.