What Matters Most: A Perspective From Adult Spinal Muscular Atrophy Patients

Abstract

There are multiple symptoms that affect adults with spinal muscular atrophy (SMA). The extent of these symptoms and their impact on individuals’ lives is not fully known. We interviewed 15 adults with genetically confirmed SMA. Participants were asked to identify issues that have significant impact on their lives. Interviews were recorded, transcribed, coded, and analyzed. Participants provided 1045 direct quotes. 177 potential symptoms of importance were identified. Symptoms were grouped by like topics into fourteen symptomatic themes. The symptoms and issues identified by SMA patients alter their physical, mental, and social health and may be amendable to therapeutic intervention.

INTRODUCTION

Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by proximal muscle weakness, hypotonia, and areflexia due to alpha motor neuron losses at the anterior horn of the spinal cord and brain stem nuclei [1]. SMA is the second most common autosomal recessive genetic disorder after cystic fibrosis and the most common genetic cause of death in infants [2]. It affects 1 in 6,000–10,000 live births and is caused by mutations or deletions involving the survival of motor neuron (SMN) protein at the 5q13 chromosome region [3–6].

SMA has classically been divided into three types based on the onset and severity of symptoms [7]. Type I SMA, representing approximately 45% of cases, has a symptomatic onset between birth and 6 months of age and is marked by severe respiratory failure within the first two years of life. Type II SMA, representing approximately 20% of cases, has a symptomatic onset between 6–18 months of age and is marked by individuals able to sit but unable to ever independently stand or walk. Type III SMA, representing approximately 30% of cases, has a symptomatic onset after 18 months of age. Individuals with Type III SMA typically achieve the ability to stand or walk but may later lose these abilities as their disease progresses [8].

While previous studies have examined quality of life (QOL) in individuals with SMA, it is unknown which symptoms and issues have the greatest impact on adult SMA patients’ lives [9–11]. This study uses a comprehensive qualitative interview method to broadly identify all symptoms and health themes associated with SMA-related QOL.

MATERIALS AND METHODS

Individuals 18 years of age or older with genetically confirmed SMA Type 2 or SMA Type 3 were selected to participate in this study. A purposive sampling strategy was used to identify subjects with a broad range of ages and disability. Participants were enrolled in a subsequent manner to ensure a comprehensive representation of symptoms among individuals with varying disease severity. This study was performed with institutional review board approval in accord with the Helsinki Declaration of 1975.

An investigator trained in qualitative techniques conducted patient interviews. Interviews were completed by telephone. The investigator used a semi-structured approach to investigate which symptoms of SMA have the greatest disease-burden. Interviews were initiated with open-ended questions and subjects were permitted to expand on topics they felt had a significant effect on their lives. Interviews were recorded and transcribed for analysis.

A framework technique was used to qualitatively analyze the interviews [12, 13]. Quotes from interviews were coded to identify symptoms important to the study population. Similar quotes were matched to determine symptom frequency. Like symptoms were categorized into common themes and subsequently organized into physical, mental, social, or disease-specific domains. Interviews were continued until consecutive interviews suggested data saturation defined as failure to yield meaningful new symptoms. Investigators developed a model and frequency table to emphasize the most critical areas of patient-identified SMA health.

RESULTS

Fifteen adults participated in this study with 9 being male and 6 female. Ages ranged from 18 to 59 with a mean age of 33. 10 participants had SMA Type III and 5 individuals had SMA Type II. Of the fifteen participates, 9 were employed, 4 were full-time students, and 2 were unemployed at the time of interview. Only 1 participant was living independent of family and/or nursing care (Table 1).

A total of 1045 direct quotes were coded identifying 177 symptoms of importance. The most frequently mentioned symptoms included difficulty with personal hygiene (43), difficulty dressing (32), impaired walking (23), decreased independence (23), and decreased ability carrying a heavy load with arms (20). To illustrate the symptoms of personal hygiene one participant shared, “It would be nice to be able to, you know, do even the smallest task by myself. Whether that’s brushing my own teeth or using the restroom by myself or you know, just getting ready in general, feeding myself, something like that.” Concerning the symptom of impaired walking, one participant relates, “I was a very good athlete. Sport is what I loved the most. I was both able to achieve a lot physically, but by the time I was 11, I started to notice that I would stumble a little bit or not run as fast or that I fell down and I was... I just thought I was kind of clumsy almost even though I was so coordinated in other ways.”

Social performance and emotional issues were frequently mentioned. One patient illustrated these issues well by saying, “Early on, my biggest thing was self confidence. That was the biggest problem. Not blending well with the crowd and my biggest fear was ‘getting found out.’ You know, I was always so afraid of falling down, you know, and people finding out. Transitioning to the wheel chair was kind of a tough time in my life and I kind of got in a low spot as far as depression.”

Quotes represented 14 symptomatic themes and 4 major domains. The most commonly mentioned themes included an inability to do activities, limitations with mobility and walking, social role limitations, emotional distress, followed by lower extremity weakness (Fig. 1, 2).

DISCUSSION

Here we used patient-centered, qualitative interviews to determine symptoms and themes affecting QOL among adults with SMA. This study extends prior work in SMA, as it incorporates the patient’s point of view characterizing the physical, psychological, and social aspects of disease burden. This study emphasizes symptoms that are both important to individuals with SMA and potentially amendable to therapeutic intervention. Participants in our study highlighted the impact of activity limitation and mobility impairment in their lives. While genetic treatments are being developed, it is important to recognize that advances in mobility devices, physical therapy, and occupational therapy have the potential to ameliorate some of these important limitations.

Other issues related to social performance and emotional issues were also important to SMA-related QOL. The psychological and social stressors of SMA should not be ignored. Previous work has identified a relationship between psychological distress and the perception of disease severity [14–16]. An interdisciplinary approach including psychotherapy, pharmaceuticals, social work, and support groups should be used to treat these symptoms.

This study complements prior work that evaluated symptoms affecting QOL among different neuromuscular disease populations [17–19]. Interestingly, when comparing fascioscapulohumeral muscular dystrophy and Charcot-Marie-Tooth disease type 1A patients, our adult SMA population focused more on symptoms related to personal hygiene and getting dressed and less on difficulties walking and lower extremity weakness. While the reason for this is unclear, this can be explained by the distribution of weakness compared to these other neuromuscular diseases, or perhaps related to the ability of individuals with SMA to overcome transportation issues utilizing assistant devices such as motorized wheelchairs. An alternative hypothesis is that weakness in SMA is typically longstanding and thus it is possible that patients over time develop a partial acceptance of this issue while continuing to negate the significant challenges of maintaining their primary activities of daily living.

Prior work that investigated QOL among individuals with SMA primarily focused on the pediatric population [20–23]. This study provides the additional perspective of patients with a prolonged history of disease burden. Additional research to analyze QOL among the SMA pediatric population may provide additional symptoms and themes that were not captured in this study.

This qualitative study was limited by its sample size. Even though these participants were selected using a purposive sampling strategy, there is still potential for sampling error. Future corroboration with a more diverse and larger patient sample may be useful to confirm our results. All interviews were completed over the telephone and formal strength and functional testing was not included in the patient evaluation. The items identified are uniquely the participants’ stated demographics and our utilized interview techniques. Future research should be considered to determine the associations between a patient’s perception of their disease burden and objective measures of functional status. Such a study would provide additional insight into the stratification of symptomatology based on disease severity and would build upon the data collected through our patient interviews.

There are many symptoms and issues that affect the lives of adults with SMA. These symptoms alter the physical, mental, and social health of patients and may potentially be amenable to therapeutic intervention.

CONFLICT OF INTEREST

Dr. Johnson serves as an Associate Editor for Neurology: Genetics. He is funded by the NIH, grant #1K23NS091511-01. He has received research support from the Muscular Dystrophy Association, Valerion Therapeutics, Ionis Pharmaceuticals, and Biogen Idec.

Dr. Chad Heatwole receives grant funding from the NIH, FDA, and Cure SMA foundation and has previously received research support through New York State and the MDA. He is the founder and CEO of the Neuromuscular Quality of Life Institute. He provides consultation to Biogen, aTyr, and Acceleron Pharma.