Challenging behavior in children and adolescents with Dravet syndrome: Exploring the lived experiences of parents

Background: Dravet syndrome (DS) is a monogenic syndrome associated with SCN1A mutations in the majority of patients and characterized by devastating epilepsy, that may be life-threatening. Aside from refractory seizures, core symptoms of DS include behavioral difﬁculties, developmental delay, cognitive impairment, and motor dysfunction. Previous DS research has mainly focused on epileptic seizures and pharmacological management and less on behavioral difﬁculties. This study aims to explore the lived experience of parents supporting a child with DS, with a focus on behavioral aspects. Methods: We performed a qualitative study using focus groups and following the consolidated criteria for reporting qualitative research (COREQ) guidelines. We organized three focus groups with parents of children and adults with DS and used a pre-deﬁned topic list of open questions, similar for each focus group to ensure comparability. The focus groups were video recorded, transcribed, and anonymized. Data were analyzed using an iterative coding process where codes were sorted into themes. Differences in coding among the researchers were discussed until a consensus was reached. Results: In total, twenty parents (mothers only) participated in the study. The age of children with DS ranged between 3 to 22 years with a mean age of 11.8 years. A range of behavioral difﬁculties emerged from the thematic analysis. Overall, the most commonly mentioned behavioral difﬁculties were aggres- sion, dangerous behavior, impulsivity, hyperactivity, routinized and compulsive habits. Our results showed different behavior per age group, with more externalizing behaviors such as aggression and impulsivity in children aged 3–13 years; and more internalizing behavior such as routinized and compulsive habits in adolescents and young adults (14–22 years). This results in a different kind of support these families need and should be acknowledged when in consult with a healthcare professional. Parents reported that challenging behavior was a source of stress and impacted negatively on their family’s qual- ity of life. Parents reported feeling alone in their search for solutions, and many explored options outside the traditional medical context. Conclusion: Our results suggest that the challenging behavior associated with DS leads to a huge burden of care. Healthcare professionals working with DS patients may need to develop shared decision-making strategies that take into account challenging behavior.


Introduction
Dravet syndrome (DS) is a devastating epilepsy syndrome, that may be life-threatening, that was first described in 1978 [1,2].
Dravet syndrome consists of a wide phenotypic spectrum of seizures (e.g., febrile seizures, absences, status epilepticus) and is characterized as developmental and epileptic encephalopathy. The estimated incidence of DS caused by an SCN1A mutation is 1 in 20,900 births [3]. It is estimated that 10-20% of patients with DS die before 10 years of age most commonly due to sudden unexpected death in epilepsy (SUDEP) [4,5]. Many patients with DS experience major seizures weekly and minor seizures daily [6].
The refractoriness of these seizures typically requires medication and other sorts of therapies [7].
Aside from refractory seizures, the core symptoms of DS include behavioral difficulties, developmental delay, cognitive impairment, and motor dysfunction [4,8]. The prevalence of behavioral difficulties in DS ranges between 37% and 100% [6,[8][9][10]. These behavioral difficulties may comprise hyperactivity, attention deficit, limited concentration, mood instability, short temper, oppositional behavior, perseveration, impulsive actions, and autistic-like features [8][9][10]. A recent systematic review describes an age-specific evolvement of seizure-related manifestations and non-seizure-related manifestations such as attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) [11]. Previous studies reported behavioral difficulties to be the strongest predictor for health-related quality of life (HRQoL) in patients with DS [8][9][10]. In spite of the high prevalence, relatively little is known about how behavior develops from early childhood to adulthood. Families caring for a child with DS experience a considerable impact on their physical health, mental health, social functioning, and financial resources [12,13]. In one study the negative impact on sleep and enduring fatigue are reported as the most critical for parents [13]. Existing literature on DS mainly focuses on the impact of refractory seizures on the caregiver's life and not the impact of other comorbidities in DS [12,13]. The additional impact of challenging behavior on patients with DS and their families has not been described before.
In addition, little is known about parents' strategies for caring for a child with DS. A study by Nolan et al. described a few practical tips and practical coping mechanisms mentioned by parents, like conducting 'personal research' about DS. This study did not address coping with behavioral problems [14]. Actual literature on how parents experience behavioral difficulties of their child with DS does not exist [8][9][10]. A better understanding of these coping mechanisms regarding behavioral difficulties will give more insight into the impact of behavioral difficulties and the need for treatment or guidance. Due to the age-specific manifestations of DS, both the behavioral difficulties and the experiences of parents are likely to evolve over time [11].
In addition, parents may experience difficulties in healthcare provision due to the rarity of DS [15][16][17]. Dravet syndrome is a complex syndrome with many different manifestations. As a result, there may be a lack of expertise among healthcare professionals concerning manifestations like behavioral problems. This may hamper the search for the right care [15]. Therefore, more knowledge about the challenges that parents meet is much needed in order to manage the care of patients with DS [18].
In this qualitative study, we explored the 'lived experiences' of parents caring for a child with DS with respect to their child's behavior. The primary aims of this study were [1] to explore behavioral aspects of DS as experienced by parents caring for a child with DS and [2] potential differences in behavioral aspects between young children versus adolescents and young adults. Secondary aims were: (i) to explore the impact of DS and behavioral difficulties in DS on patients and their parents; (ii) to gain insight into the coping strategies of parents caring for a child with DS; and (iii) to explore whether parents feel able to address behavioral difficulties with healthcare professionals.

Study design overview
We conducted a qualitative study using focus groups, following the consolidated criteria for reporting qualitative research (COREQ) guidelines [19]. We were interested in the perspective of parents and asked parents caring for a child, adolescent or young adult about their experiences during focus groups. This approach was chosen to establish a collective perception of parents on behavioral difficulties and life impact as well as the personal opinions and experiences of these parents.

Ethical considerations
The study was approved by the Medical Research Ethical Committee Utrecht (METC 21-530). The coordinating researcher (AP) was responsible for explaining the research project to potential participants. All participants gave written informed consent and agreed with the video recording of the focus group.

Participants
Parents (biological or other) of children, adolescents, or young adults with DS were invited to participate. Potential participants were recruited through social media and the newsletter of the parent/patient organization 'Dravet syndrome Foundation Netherlands/Flanders' (Stichting Dravetsyndroom Nederland/ Vlaanderen) [20]. Potential participants expressed interest by contacting the researchers themselves by e-mail. Inclusion criteria were: having a child with SCN1A-related DS and speaking Dutch. Parents of patients with DS of all ages were included. Three focus groups were formed based on the age of the child with DS, of which the first focus group [1] primarily included parents of younger children (aged from 4 to 10 years and one was 18 years); the second focus group [2] primarily consisted of parents of older children (aged from 15 to 22 years); the third focus group [3] included a mixed group of parents (children aged from 3 to 16 years). The aim of this approach was to establish groups in which participants could relate to each other as well as groups in which participants could learn from each other. All focus groups met online through Microsoft Teams. Each participant engaged in an online test meeting to resolve any malfunctioning prior to the focus group. The online format further allowed for safe and easy participation during the COVID-19 pandemic without traveling. Afterwards, the participant provided additional background information about the family composition and characteristics of their child with DS.

Data collection
Each focus group session was facilitated by a moderator (AP) familiar with the subject of the study and with the participants. The moderator (AP) is a psychiatrist in training. Other observing researchers were a psychiatrist (JZ), and an expert on qualitative research (MM). The focus groups were semi-structured in nature, with a pre-defined topic list of open-ended questions, similar for each focus group to ensure comparability. Beforehand, the participants received a document with information on the topics of the focus groups and the first three questions. The first focus group was held on 29 June 2021, the second on 15 July 2021 and the third on 25 November 2021. The focus groups were video recorded after verbal consent was obtained at the onset of the focus group. The recordings were then transcribed and anonymized, with the inclusion of non-linguistic observations (e.g., facial expressions, laughing, sighs, and gestures).

Data analysis
We used inductive thematic analysis to analyze the data according to Braun & Clarke [21] because it allows for providing a ''thick description" of the dataset, which fits with our research objective of exploring 'lived experience'. Data were analyzed using an iterative coding process where codes were sorted into themes. The primary researcher (AP) read the transcripts and generated codes. The code structure was discussed among the research team. All members (AP, JZ, MM) coded parts of the transcript. Differences in coding among the researchers were discussed until a consensus was reached.

Results
The characteristics of the parents and their children are displayed in Table 1. In total, twenty parents participated in the study (mothers only). The age of their children with DS ranged from 3 to 22 years with a mean age of 11.8 years (±6.6). In the following sections, we will present [1] types of behavior described by parents; [2] changes in behavior with increasing age, as observed by parents; [3] the impact of challenging behavior on parents; [4] management strategies employed by parents; and [5] the place of behavioral problems in the medical management of DS. Each subsection includes a table with representative quotes from parents.

Type of behavior
The various categories of reported behavior per age group can be found in Table 2. Fig. 1 illustrates the difference in behaviors between the two age groups (the group younger than 14 years, and the group of 14 years and older). The results display a pattern where in the case of younger children (aged 3-13 years), parents more often mentioned externalizing behavior, such as dangerous behavior, impulsivity, aggression, and hyperactivity. Children with eating difficulties were reported to have many behavioral problems around mealtimes. Parents of older children (aged 14-22 years) more often mentioned internalizing behavior like routinized habits, compulsive and repetitive habits, and the behavior is challenging compared to peers.

The impact of challenging behavior on parents
As mentioned before, DS is a severe and complex syndrome. This may not only affect the patients themselves but also their families. Table 3 includes illustrative quotes about the impact of caring for a child with DS on families. Many parents reported feeling exhausted and admitted they needed help, as can be seen in quote 2A. Parents also discussed the ways in which parenting a child with DS influenced their own mental health (2A, 2B, 2C). In particular, they reported that refractory epilepsy and lifethreatening situations were very stressful. Moreover, they reported feeling like they must be alert constantly because 'anything can happen'. This was caused by the constant risk of seizures but also because of dangerous and disruptive behavior (2D, 2E).
The focus group data suggest that the impact of DS on patients and their families changes through the years. Parents mentioned that in the children's younger years, the primary energy and time-consuming element of DS were trying to 'survive' the epileptic seizures (2A, 2F). As the children aged, parents reported a shift in attention (2G) to other challenges like behavioral difficulties, walking issues, and the child's relationship with other family members. Parents reported concerns about the well-being of other children in the family. They reported that siblings of patients with DS also suffer because of the challenging behavior and were often on the receiving end of aggressive outbursts of the child with DS (2I). Parents felt powerless to prevent the DS child's outbursts, which increases the emotional burden of this behavior. Parents also worried about how the constant focus on their child with DS would affect their other children (2H). Finally, parents also discussed feelings of guilt for not paying enough attention to their other children.
Eating problems constituted another prominent stressor for parents (2J, 2K). Parents describe eating disturbances including poor appetite, decreased tolerance for food variety, prolonged mealtimes, and picky eating. Mealtimes were described as extremely stressful and frustrating for both the child with DS and their families. In some cases, mealtime stress became so acute that the child with DS refused food entirely and had to be fed with a feeding tube instead.

Parents' coping strategies for behavioral challenges
Parents reported trying multiple strategies to improve challenging behavior, with varied success. These included, among others, building routine and structure into the daily rhythm, distracting the child to prevent tantrums, parenting courses, seeing a child and youth psychiatrist, deep pressure stimulation, using essential oils, cannabidiol (CBD) oil, vitamins, and supplements. In each of the focus group sessions, parents discussed the fact that distracting their child was the most effective intervention for challenging behavior (see Table 4) (3A, 3B). Parents also reported having to consistently regulate the emotions and behavior of their child. Due to intellectual disabilities, children with DS are often incapable of learning these skills themselves (3C,3D). Consequently, they rely on parents to regulate their thoughts and feelings, which is a very difficult task. When parents noticed that their child was getting angry, overwhelmed, or exhibiting repetitive behavior, they actively intervened to prevent an escalation.
Besides the search for solutions to improve behavioral difficulties, parents were also searching for explanations and patterns in their children's behavior. For example, parents found associations between behavioral difficulties and anti-seizure medication, tonic-clonic seizures, over-stimulation, and emotional situations (3E, 3F). Among the 42 comments made on causality were 21 comments about the perceived effects of anti-seizure medication on behavior. Moreover, 14 of the 20 focus group participants actively supported this association. Parents reported that they had many unanswered questions on the causality of problem behavior and a need for answers (3G).
Despite the serious nature of the focus groups and the emphasis on 'difficult behavior' in the discussions, there were also jokes and laughter among the participants. Many mothers used humor as a way of coping with difficult situations and with uncertainty. In addition, they were all very keen to share the positive qualities of their children (3H).

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Self-harming behavior 'Her behavior changes when a seizure is coming. We observe a kind of increase of tension, also at night. She is restless, has difficulties sleeping, screams a lot, bangs her head. When the seizure has passed it is just like the tension has gone and then she is sweet again and we can interact with her.' 'Unfortunately, he started to self-harm. Whenever he had this tiny scab or wound, he would scratch and scratch and scratch, he just would not stop, untill it would bleed. And then he panicked: he wouldn't tolerate a band-aid or anything, and this tiny thing would be a huge thing for all of us for weeks.'

Challenging behavior as part of treatment and management plans
DS is a complex syndrome with different kinds of seizurerelated and non-seizure-related manifestations. Parents reported that they feel that the focus in current care seems to be primarily on seizure control. Several parents mentioned that they consider behavioral difficulties and eating problems to be just as significant as seizures. Parents reported that they struggle with how (4A,4B) and where (4C) to ask for help with the challenging behavior (see Table 5). As a result, their search for solutions was often unfocused and multidirectional, and sometimes outside the realm of the traditional medical context. Parents in the focus groups reported feeling lost and alone in this search and often felt misunderstood by healthcare professionals (4D, 4E). Parents expressed the need to have a say in the decisions made regarding the treatment of their child (4F). In addition, parents reported that they experience difficulties discussing priorities in the treatment of DS with healthcare professionals (4D, 4E, 4G). Although they mentioned that behavior is not usually a treatment focus in DS (4D), parents also reported that awareness of behavioral difficulties in DS is growing. In their opinion, this is driven by efforts of schools  'He's been going to school again for about a half year, and we feel like a normal family again and not just like we're surviving.' 2G 'The focus was the medical issues, and all other difficulties were secondary concerns. And currently the medical issues are under control. Although, Dravet is never really under control but maybe a little. And currently the behavior is the main concern.' 2H 'All the attention tends to go to her, but we try to control this. When there's something wrong with our other child, we catch ourselves thinking 'Oh no, not you as well'.' 2I 'When my daughter was less than a year old, her brother pulled out her hair on a regular basis. That was awful to see as a mother, but I just couldn't prevent it.' 2J 'Yes, eating problems. These problems have had the biggest impact on us. Our daughter has a feeding tube for almost a year now also because she completely stopped eating and drinking and she kept that up for a very long time.' 2K 'In regard to eating, we have that under control at the moment because she gets her nutrition through a feeding tube.
[. . .] The mealtimes used to be so stressful and frustrating for her. The plates literally flew through the room.' and/or daycare facilities where the staff is very willing to help with managing challenging behavior (4H).

Discussion
This qualitative study provides an overview of the lived experiences of parents caring for a child, adolescent, or young adult with DS, with a specific focus on behavioral aspects of DS. The most commonly mentioned behavioral difficulties by parents are aggression, dangerous behavior, impulsivity, hyperactivity, routinized and compulsive habits. Our results show different behaviors per age group with parents reporting externalizing behaviors such as aggression and impulsivity in young children with DS, and internalizing behaviors such as routinized and compulsive habits in adolescents and young adults with DS. Parents of a younger child with DS may face different challenges than those parenting an adolescent or young adult. Whereas a parent of a younger child may have concerns about dangerous behavior, hyperactivity, and aggression, a parent of an adolescent or young adult may experience frustration with the compulsive and routinized habits. These results suggest that challenging behavior associated with DS changes with age. Accordingly, the support needs of parents may also change with age. Currently, parents must interpret the thoughts and emotions of their child via behavior alone. It is challenging to interpret the meaning of unpredictable and changing behavior and impossible to verify if the interpretation is correct. This results for parents in a continuous search for new solutions and clarifications. The support needs of parents may be best addressed by a tailored and age-specific assessment of needs by healthcare professionals that is repeated every so many years throughout the development of the child with DS. To the best of our knowledge, this is the first qualitative study investigating the behavioral aspects of DS.
Previous quantitative studies investigating behavior in DS reported symptoms of hyperactivity and inattention [9,10,[22][23][24], with hyperactivity being the most characteristic behavioral aspect of DS [10,[22][23][24]. In addition, previous quantitative studies reported poor danger awareness, aggressive behavior, opposing and provocative behavior, autistic features, and self-harming behaviors [9,11,[22][23][24][25][26]. Consistent with these previous findings, dangerous behavior and impulsivity were among the most frequently mentioned behaviors by parents of patients with DS in our study. In addition, our results suggest that routinized and compulsive habits are recognizable symptoms in children and adolescents with DS. This is consistent with a body of literature reporting autistic features in DS [22,23,25,26]. Sullivan et al. described a prevalence of autism spectrum disorder (ASD) of 40% in children and 62% in adults with DS [11]. Likewise, in our study routinized and compulsive habits both were more common with increasing age. In addition, behavioral difficulties combined with eating problems were stressed repeatedly, which has not often been reported before [27].
From our data, it was clear that caring for a child with DS is often quite stressful and has an enormous impact on the patient and their families. The burden of care and associated stress may result in mental health issues in parents caring for a child with DS. Several studies identified that illness in a child affects the social functioning, physical and mental health, and professional life of the parents [12,13]. These data suggest that in the care management of a child with DS, the child's health is important but also the mental health of the primary caregivers. In addition, our results also shed further light on existing studies about the impact of having a sibling with DS [12][13][14]. Many parents reported feelings of guilt towards siblings of a child with DS because they spent so much time caring for and managing the child with DS that they felt almost neglectful of their other children. It is noted that we did not include siblings in our study, therefore we do not know the actual impact on siblings of a child with DS. Dravet syndrome affects not only the child but the whole family and this may warrant attention from healthcare professionals.
From the parents' experiences, it was clear that they apply a wide range of management strategies for their child, varying with age. The variety of solutions parents reported reflects their persistent desire and efforts to improve the situation and have some form of control.
Parents reported feeling alone in their search for how to best manage their child's behavior. Their experience was that healthcare appointments were often centered around seizure management with little space for other concerns (e.g., behavior). The way that the current healthcare for children with DS in the Netherlands is organized may not meet all the needs of these parents. This may explain our finding that many parents reported seeking out remedies outside the mainstream healthcare system. DS has many different manifestations, each with its own severity and impact, which may vary over time and between patients. Indeed, our results suggest that challenging behavior associated with DS changes with age. Accordingly, the support needs of parents may also change over time. This may be best addressed by a tailored and age-specific assessment of needs that is repeated every so many years throughout the development of the child with DS, carried out by a multidisciplinary expert team. In addition, parents expressed that they would like to play an active role in shaping their child's medical management, e.g., in decisions about seizure medication that may also impact behavior. This may be best addressed by incorporating a shared decision-making process, during which healthcare professionals actively engage parents in weighing up various treatment options. Shared decision-making is best viewed as a collaboration in all aspects of clinical care, with clinicians needing to fully engage with the patient's experience of illness and participation in treatment [28]. In the context of rare diseases associated with intellectual disability, such as DS, the shared-decision making process may involve the caregivers instead of patients. Shared-decision making in the context of rare diseases has gained recent attention [15,17] and may lead parents to feel more empowered.

Strengths and limitations
As far as the strengths of our study are a concern, organizing the focus groups online increased feasibility and made it possible for busy and burdened parents to participate. In advance, we were concerned that an online focus group would not allow for lively discussions. However, we found that participants felt free to speak up, and the 'hand raising' option in the online video conferencing app we used was helpful in this respect. The participants responded to the questions of the moderator but also commented on each other and asked each other questions. No malfunctioning of the video conferencing app occurred during the focus group meetings. A further strength of our study is the focus on parental experiences of behavioral aspects of DS. To our knowledge, this is the first comprehensive exploration of behavioral difficulties in DS from a parental perspective.
This study has, nonetheless, several limitations. First, although some fathers initially expressed interest, the participants were all mothers. Therefore, this study cannot compare similarities and differences in experiences and coping strategies or life impact based on gender. In addition, Nabbout et al. indeed described a perceived higher impact on mothers than on fathers [12]. A second limitation is potential recruitment bias. All participants contacted the research team after reading an email or advertisement via social media. It is likely that parents who experience difficulties with their child's behavior were more likely to participate in the study. Therefore, our results might reflect the severe end of the behavioral DS phenotype rather than the whole spectrum. A third limitation is that the topic of the focus group was 'behavioral difficulties', i.e., the presence of aberrant behavior. Therefore, examples of 'normal behavior' and behavior perceived as positive may have been mentioned less by parents. It is noted that the behavior described in this study is based on the observations and interpretations of parents. Finally, the results suggest that challenging behavior associated with DS changes with age. However, we cannot rule out the possibility that other factors contribute to this pattern. The older age group had been diagnosed at an older age, probably because the diagnostic process has improved over the last years [2]. An earlier study showed that older patients were more likely to have been diagnosed at a later age and to have used medication that is contraindicated in Dravet syndrome for a longer period of time, which is associated with a worse cognitive outcome. This may have influenced the pattern of behavioral problems [29]. Unfortunately, data on epilepsy, treatment, and other comorbidities were not available in the current study, therefore we were unable to take these factors into account.

Conclusion
Our results display an overview of behavioral aspects observed among patients with DS and their subsequent impact on patients and families. Although seizure management remains crucial, our results suggest that challenging behaviors associated with DS lead to a huge burden of care in the home environment. Healthcare professionals working with DS patients may need to develop shared decision strategies that consider both seizure management and challenging behavior. We would advise that parents actively discuss challenging behavior with healthcare professionals and express the impact of such behavior on the quality of life of the child and the families. In case of challenging behavior, healthcare professionals with expertise in this area should be part of the multidisciplinary treatment team, in order to provide proper care for these behavioral difficulties. We would recommend that healthcare professionals also consider the mental health of the caregivers of the child they are treating. In cases where the burden becomes too high, we would suggest that caregivers search for help in their social network, in the healthcare system, or with peers who might experience the same difficulties. Regarding future studies, we would recommend that these investigate the behavioral phenotype of DS in detail in a broad spectrum of DS patients of various ages. This will provide insight into the behavioral and psychiatric phenotype and will guide treatment and management strategies.

Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.