Integrating Palliative Care in Life-Limiting Pediatric Neuromuscular Conditions: The Case of SMA-Type 1 and Duchene Muscular Dystrophy

1School of Nursing, Johns Hopkins University, Baltimore, MD, USA 2Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA 3Berman Institute of Bioethics, Johns Hopkins University, Baltimore, MD, USA 4Department of Health, Behavior & Society, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA 5Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA 6McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA 7Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA


Introduction
Spinal Muscular Atrophy Type I (SMA-1) and Duchenne Muscular Dystrophy (DMD) are the two most common inherited pediatric lifethreatening neuromuscular disorders (NMDs) worldwide [1,2]. Both are fatal, but each is unique. Children with SMA-1 develop symptoms shortly a er birth and usually die by age 2 [3], while boys with DMD manifest symptoms in pre-and early school years. Advances in respiratory and cardiac management [4,5] allow DMD patients to live into their 20's, but their burden of disease is high, commensurate with the amount of weakness, and they o en undergo major operations or require extended hospitalizations for routine childhood illnesses [6].
In both SMA-1 and DMD, the ability of children to comprehend their illness depends on their stage of development and their parents' con dence in addressing their needs. Clinicians nd it di cult to predict when a ected children will die. ese uncertainties and the availability of technologies to extend the lifespan of patients with NMDs [6][7][8][9][10] necessitate frequent clinical management decisions as the disease progresses. Treatment decisions are complicated by the fragmented, highly specialized nature of the care these young patients receive [11,12]. Specialists may be unaccustomed to coordinating their e orts and have divergent approaches to clinical management. Recommendations for interventions, such as mechanical ventilation for children with SMA-1, vary widely; as a result [13], families working with several specialists may receive con icting information.
ese realities have fueled interest in applying the principles of palliative care, broadly understood, in the context of pediatric NMDs [11,12,[14][15][16]. A holistic interdisciplinary model of care, palliative care integrates emotional, spiritual, developmental, and physical dimensions into the care of individuals living with life-limiting diseases [17][18][19][20]. Emerging from the hospice movement, palliative care rst focused on end-of-life care, primarily in adult oncology and critical care settings. Now considered a model to relieve su ering and improve quality of life, as shown in (Figure 1), palliative care has expanded to include comprehensive care from the time of diagnosis of a variety of incurable, progressive diseases that may be life-limiting [21], including chronic pediatric diseases [22] such as HIV, cancer [23][24][25][26], and sickle cell disease [27][28]. e Association of Children's Palliative Care has identi ed four categories of patients with life-limiting conditions who may bene t from palliative care [29]. ese are re ected in (Table 1). Pediatric patients with conditions such as those with SMA-1 and DMD fall into the category of patients where premature death is inevitable. Although the timing of death varies by disease, their treatment is likely punctuated by periods of intensive life-prolonging treatment and full or partial resumption of prior activities and functional status. (Group 2). Arguably, these children could also be included in the group of children (Group 3) with progressive conditions without curative options where the focus is on the palliation, rather than cure, for their life span. e next horizon in palliative care is to integrate it more completely in honor of Mattie J.T.
Stepanek [36]. Held in Leeds, England, from April 16-19, 2008, the summit included "ambassadorial teams" of neuromuscular specialists, palliative care clinicians, and other health professionals (physical and occupational therapists, social workers, etc.), together with parents of a ected children and representatives of muscular dystrophy associations from seven countries. Selection criteria for team members included leadership experience, commitment to improving care for children with NMDs, and willingness to explore palliative care integration and new models of engagement (Table 2).
To foster dialogue, the summit rst divided participants into two groups, one for SMA-1, one for DMD. Drawing on the concept of disease trajectories in genetic conditions [30][31], each group described the typical trajectory for their respective condition, identi ed transition points, and created a visual representation of the trajectory. e rest of the summit involved group discussions led by interdisciplinary professionals who were experienced facilitators. Based on their experience and expertise, participants were assigned to six groups, three focused on SMA-1, three on DMD. All six groups addressed elements of palliative care, with one group from each disease focused on (1) communication and decision making, (2) ethical and cultural challenges, and (3) pain/su ering and spiritual care.

Results
A total of 53 interdisciplinary professionals and families, including the project team, attended the summit. As shown in (Table 2), 40% of the participants were clinicians with expertise in pediatric NMDs, 35% were specialists in PPC, and 25% were patients and family members or their advocates. Among the parents were those who had lost a child and those whose children were still living.
Participants identi ed four phases, predictable in sequence but variable in duration and velocity, in the life trajectories for children and families a ected by SMA-1 and DMD, as depicted in (Figure 2). e peri-diagnostic phase encompasses a long process that may begin prenatally, at birth, or during childhood. ere may be suspicions that the fetus is abnormal before birth, if parents already have an a ected child or non-speci c ndings such as ultrasound abnormalities are detected. Families characterize this process as an "odyssey" marked by uncertainty, anxiety, grief, and loss. e treatment decision-making phase focuses on managing Group 1 "Curative treatment is feasible but can fail"

Group 2 "Premature death is inevitable"
Group 3 "Progressive conditions without curative treatment options" Group 4 "Irreversible but non-progressive conditions causing severe disability, leading to susceptibility to health complications and likelihood of premature death." into managing other progressive, life-limiting conditions of childhood such as NMDs [30][31]. Because it is di cult to predict the rate and severity of disease progression in SMA-1 and DMD, the challenge is to o er guidance for living with these disorders. Pediatric palliative care (PPC) complements care with curative intent and o ers support for the child and family as the disease progresses [20]. With no cures for DMD and SMA-1 currently available, the focus of care is necessarily palliation. Some specialists are integrating palliative care into the care of children with advanced forms/ manifestations of NMDs [4,5,32,33]. However, many are not for several reasons: the broader notion of palliative care is not included in their education and training; formal collaboration with palliative care specialists has been inadequate to date; and systems of care reinforce hierarchical rather than relational models of interaction-a key feature of palliative care.
Reaching this new horizon requires better understanding of the progression and critical decision points of NMDs, and training for clinicians to raise their awareness and create new knowledge and skills they can apply to the integration of PPC practices [34][35].

Methods
To advance palliative care integration, we formed an international consortium of patients and families a ected by NMDs and an interdisciplinary group of clinicians who care for these families. We had three goals: identify transitions in disease progression; explore the challenges facing patients, families, and clinicians during these transitions; and identify opportunities for integrating PPC into the care of children a ected by these conditions. e clinical focus of the consortium was on SMA-1 and DMD, both life-limiting NMDs punctuated by life-threatening events but signi cantly di erent in onset and duration.
One of the consortium's activities was a summit, called "Heartsongs" symptoms, optimizing function, enhancing quality of life, and monitoring developmental progress. It involves initiating treatments (possibly enrollment in a clinical trial) to slow the disease progression and anticipating life-threatening events that will require decision making. ese decisions present a range of ethical considerations, such as whether to undergo genetic testing or involve their children in decision making. e third phase involves life-threatening events such as respiratory failure, sepsis, and pneumonia. Life-sustaining therapies including mechanical ventilation, medications, or other invasive technologies are initiated; periodic discussions regarding their continuation follow. Each event creates uncertainty: can the child's functional status be restored or does the latest crisis represent irreversible disease progression? Families characterize this phase as a "roller coaster ride", accompanied by a resurgence of grief and loss. Eventually, life-sustaining therapies lose their e cacy, and dying seems inevitable. e terminal phase involves a relatively predictable trajectory, although the length of the dying process is variable, especially for children with DMD who may live into their 20s, creating uncertainty as to when death will occur. is phase also includes the actual death and the bereavement process, times when families perceive the risk of abandonment to be high. e four phases are marked by changes in functional status. Progressive muscle weakness results in impaired mobility, breathing, and activities of daily living. Complications and the need for interventions increase. e disease progression a ects the developmental maturation that all children experience; children with DMD may develop learning disabilities or behavioral problems. Patients and families respond to declines in functional status with feelings of fear, anger, grief, loss, and spiritual distress.

Opportunities for Integration of Palliative Care
As shown in (Table 3), participants identi ed opportunities for integrating palliative care in each phase, while noting several distinctions due to di erences between SMA-1 and DMD.
First, the timeframes vary due to di erences in life expectancy. As we had anticipated, participants were receptive to early discussions about end-of-life care for families of patients with SMA-1, but not for families with DMD. When death is not imminent but expected at some unspeci ed time in the future, participants perceived the focus on the end of life as signifying the abandonment of curative e orts. When palliative care was reframed to encompass activities, such as "meaningmaking", that reinforce living life in the moment, participants embraced opportunities for early integration of palliative care, even for families with DMD.
Second, a distinction arises from the modes of inheritance. An X-linked disorder, DMD is transmitted by the mother alone; SMA-1 is an autosomal recessive condition shared between parents. Both diagnoses carry reproductive risks for family members, but the nature and impact of those risks vary. In the case of DMD, the family may struggle with feelings of guilt and blame. In the case of SMA-1, parents adjusting to life with a new baby are confronted with decisions about diagnostic and genetic testing, treatment, and end-of-life care. ese di erences in genetics impact communication and decision making in the early stages of diagnosis and treatment.
A third distinction, unique to families with DMD, is how and when to involve children and adolescents in decisions about treatment, endof-life care, and quality of life issues related to developmental concerns such as dating, sexuality, reproductive issues, college, career choices, and independent living.
Five themes emerged spanning all phases of the trajectories and both diagnoses, regarding the relevance of palliative care principles and practices to members of the healthcare team. Focused primarily on communication and relationships, these themes highlighted the importance of the following:

Peri-Diagnostic Phase
Communicating a new vision of hope and a commitment to companioning families throughout the process X X Establishing realistic timelines and expectations for the diagnostic process X X Considering all options, including hospice, when planning for the delivery of infants who are diagnosed prenatally with SMA-1 X Eliciting parental preferences for communication, decision-making and continuity of care X X Framing the diagnosis as living with the disease rather than focusing on dying X X Anticipating and acknowledging parental grief X X

Treatment Decision-Making
Offering the range of morally permissible options including hospice and end-of-life care X Disclosing the limits of clinicians' willingness to implement certain treatment options (including enrollment in clinical trial) X X Acknowledging the uncertainty in velocity of progression and severity throughout the disease process X X  Assessing family needs and preferences for bereavement services X X Making referrals for spiritual, emotional and psychological support for the entire family X X lingering questions, revisit genetic testing recommendations X X Offering involvement of health care team members in remembrance and memorial services X X Providing bereavement support for 1-2 years after the child's death X X *Different for DMD since mode of transmission is maternal vs. shared between parents, and more family members may be at higher risk 5. Formalized strategies to support clinicians who care for these children and families in their own self-care, coping, grief, bereavement, and moral distress.
e participants acknowledged that the uncertainties that arise in caring for children with life-threatening NMDs, coupled with the increasing availability of therapies and technologies, create complex ethical quandaries for families and clinicians [16]. Such quandaries are exacerbated by the certain knowledge, from an early age, that these diseases are fatal. Some of the ethical challenges include questions about the desirability and e ectiveness of life sustaining therapies-both proven and experimental, advance care planning including involving minors in decision-making, and the moral implications of inherited disease including the bene ts and risks of genetic testing and screening. Embedded in these issues are questions involving informed consent and end-of life care. e ethical permissibility of the various potential clinical paths is a source of concern and confusion for clinicians and parents.
Participants identi ed barriers to palliative care integration. Attitudinal barriers included, rst, concern that adopting a palliative care framework could be interpreted as losing hope and abandoning curative e orts and, second, resistance to communicating with families and clinicians about values and preferences for life-sustaining therapies, palliation, and end-of-life care. Structural barriers included a lack of infrastructure within communities and health systems to support the integration of palliative care, and lack of sustainable funding and models for collaboration, decision making, and communication across disciplines and care settings.
Clinicians acknowledged that the more medically oriented aspects of palliative care focused on functional status, mobility, and symptom management are currently part of clinical practice but not viewed as "palliative care" per se. With few exceptions, the components of palliative care focused on psychosocial and spiritual issues have yet to be integrated. Moreover, countries vary signi cantly on how to integrate end-of-life and neuromuscular care.

Discussion
e summit validated the relevance of palliative care principles in cases of SMA-1 and DMD, and articulated a framework to guide clinicians, families, and patients as they navigate the disease progression, regardless of timing or duration. e framework includes advance care planning, concurrent provision of disease-focused care and palliation, enhanced communication and decision making, attention to ethical issues, team functioning and support, and improved quality of life by reducing pain and su ering. ese are complementary to recent guidelines for the care of patients with Duchenne Musclar Dystrophy [4,5] which call for greater attention to wholistic, patient/family centered, coordinated care. e summit a rmed that restoring health means more than curing an illness or eradicating a disease. It enables children and their families to respond to health, illness, disability, and death in their own unique ways, while clinicians apply their knowledge and skills to achieve shared goals. A palliative care framework focused on goals and outcomes creates a shared process and language for communication and decision making [37], aspects o en lacking in neuromuscular care. e integration of PPC with curative interventions empowers healthcare professionals, patients, and families to simultaneously seek cures and pursue the day-to-day goal of optimizing life.
Participants, particularly clinicians, worried how acknowledging death as a predictable outcome of the disease would a ect children and their families. Several strategies may help resolve between this tension between "hoping for the best" while "planning for the worst" [38]: (1) Lessen resistance to end-of-life discussions by creating more opportunities early on for clinicians, children, and families to explore issues and engage in shared decision making; (2) Foster collaboration by addressing the perception of some clinicians that shared decision making requires them to relinquish control over decisions; and (3) Facilitate communication by reframing palliative care as a new vision of hope [39-43] focused on living rather than dying, and (4) developing systems to address the ethical issues that arise in the care of these patients [16].
Removing the barriers to PPC will require education about the intersection of palliative care and neuromuscular disease care. Implementing system-wide changes will be in uenced by broader healthcare system constraints that are unique to each country.
Barriers to integration vary between countries. For example, the United Kingdom has been a global leader in o ering comprehensive care through regional hospice programs [29]. Although we did not conduct a systematic comparison of participating countries, evidence suggests a number of cultural di erences [44][45]: willingness to talk about death and dying or to involve children in decision making; paternalistic vs. autonomous decision making; and di erences in integration of people with disabilities into their communities. Longitudinal studies exploring the disease trajectories and their impact on patients, families, and care provision are needed [46]. e generalizability of our ndings is limited by two aspects of study design. Selection criteria required a muscular dystrophy association as well as palliative care and neuromuscular disease teams, keeping the number of participating countries small. Interdisciplinary representation varied among teams; frequently clinician leaders did not identify nurses as key team members, perhaps re ecting countrywide di erences in the status of various disciplines.
Despite these limitations, our ndings support the early integration of palliative care for children with NMDs. Although perhaps more immediately relevant in cases of SMA-1[33], a palliative care framework can facilitate goals for DMD, including pain and symptom relief, enhanced quality of life, creation of meaningful experiences with family and friends, and spiritual well-being. Advance care planning [47] is especially important in cases of DMD, given the increasing life expectancy and periods of stability and crisis [48] that characterize its trajectory.
Integration of palliative care can help clinicians balance professional and ethical obligations. Clinician integrity is threatened by myriad factors: the competing interests of patients, families, and other team members; the organization where they practice; even their own behaviors and feelings. Pediatric professionals need support systems [49], and the palliative care framework provides clinicians with the knowledge and skills the care of children with NMDs demands. e summit underscored two conclusions. First, clinicians can discuss di cult issues with NMD patients and their families, explore challenges, and create a shared vision of care. Second, there are opportunities to integrate PPC at each point of transition in the progression of NMDs. ese ndings provide the foundation for a global dialogue about cultural di erences and spiritual aspects of palliative care [50] and experiences in integrating palliative principles into care for children with NMDs. In addition, these ndings o er a foundation for integrating palliative principles in the care of children with life-limiting conditions such as cystic brosis and sickle cell disease, and strengthen the recently released Practice Guidelines for Quality Palliative Care, developed as a blueprint for such care [22].