Title: A Multidimensional Profile of Dysphagia in Myotonic Dystrophy Type 1 (DM1)
Funder: Health Education England

Abstract: Background Myotonic Dystrophy Type 1 (DM1) is the most prevalent neuromuscular condition presenting in adulthood. Dysphagia is the primary cause of acute respiratory failure and pneumonia in people living with DM1, accounting for >40% of deaths (Mathieu et al., 1999). Other consequences include malnutrition, dehydration, and sudden death from choking. There are no evidence-based tools to support the assessment and treatment of dysphagia in DM1. This raises concern about delays in diagnosis, inadequacies of treatment programmes and variably in care provision which inflict significant cost to the individual and healthcare system. The unique and complex profile of DM1 necessitates careful consideration before tools validated in other populations are integrated into clinical practice under a 'one size fits all' approach. This research will acquire new data about the profile of dysphagia in DM1 to inform novel recommendations for assessment and treatment. Aim To define the profile of dysphagia in DM1 across the domains of structure, function, patient experience and wellbeing. Methods A multi-phase cross-sectional cohort study of patients living with DM1 will be conducted to address the aims of this research: Phase 1 will investigate the size and structure of muscles involved in swallowing both in those with DM1 (n=84) and age and gender-matched controls (n=21). An ultrasound imaging protocol will be used to measure muscle size (indicative of atrophy) and echogenicity (indicative of fat infiltration) of pre-determined muscle groups. Linear regression will be used to compare measurements between patients and controls. Phase 2 will explore how muscle size and structure are associated with swallowing biomechanics (function) and symptoms (experience). Patients with DM1 (n=90) will undergo a battery of swallowing assessments, including videofluoroscopy (VFSS), assessments of muscle strength and speed, plus a symptom questionnaire. Logistic regression will be used to investigate the relationship between swallowing muscles size and structure and swallowing biomechanics, using VFSS as the reference standard. Descriptive analysis will be used to investigate the relationship with swallowing speed, strength and symptoms. Phase 3 will explore how swallowing biomechanics are associated with symptoms, patient and caregiver wellbeing, and motor and respiratory function. Patients with DM1 (n=90) will undergo additional assessments of their physical and respiratory function, plus wellbeing questionnaires. Primary caregivers (n=45) will also complete wellbeing questionnaires. Logistic regression will be used to investigate the relationship between swallowing biomechanics and patient and caregiver psychosocial wellbeing. Descriptive analyses will be used to investigate the relationship of swallowing biomechanics to motor and respiratory function, and symptoms to patient well-being. Impact The key deliverable from this research will be a set of recommendations for the assessment and treatment of dysphagia in DM1 which are ready to implement into clinical practice. These recommendations will improve the health, social, and quality of life dysphagia outcomes for patients with DM1 by providing a knowledge base for targeted assessment and treatment. The anticipated timeframe for implementation of these recommendations within tertiary centres is within 5 years. It will enable targeted treatment-focused research to commence, with potential for clinical impact within 10 years.

Lay abstract: Introduction This research explores swallowing difficulties caused by Myotonic Dystrophy Type 1 (DM1). DM1 is a rare and complex neuromuscular condition affecting the muscles and the brain. It is thought to affect 1 in 8,000 people across the world, though new research suggests it may affect 1 in 2,100 people. Swallowing difficulties (dysphagia) are common in DM1. Dysphagia causes food, drink and saliva to travel onto the lungs (aspiration) and can lead to pneumonia. Aspiration pneumonia is frequent and accounts for over 40% of deaths in this condition. Dysphagia also causes coughing and choking, eliciting fear and anxiety in patients and caregivers. This can lead to permanent lifestyle changes. Why is this research important? A patient and caregiver advisory panel developed a nationwide dysphagia survey for all people living with neuromuscular conditions. 37% of the survey responses were from people with DM1 or their caregivers. This highlights the motivation of this group to improve their lives. The survey found dysphagia to be the most common problem affecting people living with DM1. The biggest priority for this group was specialist assessment and treatment for dysphagia. A better understanding of dysphagia will improve assessment and treatment, and help to reduce its life-changing consequences. This research will: Investigate the size and structure of muscles involved in swallowing in patients with and without DM1. Explore how muscle size and structure are associated with: Swallowing function Symptoms Explore how swallowing function is associated with: Symptoms Patient and caregiver wellbeing Other aspects of DM1 e.g., walking and breathing. What does the research involve? The research aims will be addressed via three work packages: Investigating swallowing muscle size and structureThis will assess the swallowing muscles of patients with DM1 compared with a group of people of the same age and gender without DM1 or dysphagia. Muscles will be assessed with ultrasound, using an existing protocol and analysis technique. The differences between the two groups will be statistically analysed. Exploring swallowing muscle size and structure compared with function and symptomsThis will include a larger group of patients with DM1, including those who took part in work package 1. In addition to muscle ultrasound, patients will undergo assessments such as an x-ray swallowing study (videofluoroscopy) and swallowing questionnaires. These assessments will occur within 24 hours of one another. Exploring swallowing function compared with experience, wellbeing, mobility and respiratory functionThis will include the same patients who participated in work package 2. Data collection will take place in the same 24-hour period, with planned breaks. Patients will complete walking and breathing assessments, and a wellbeing questionnaire. Primary caregivers will be invited to complete a wellbeing questionnaire. Data from these studies will be analysed using statistical methods that have been designed to address the research aims. Findings will be used to develop clinical practice recommendations for the assessment and treatment of dysphagia in DM1. Who has designed this research? This research project has been developed with a neuromuscular patient and caregiver advisory panel. The aim of the research is designed to meet the needs of patients and caregivers identified by the nationwide survey. Members of the advisory panel have undergone the assessments proposed in this project. They will remain central to the project and advise on aspects including research recruitment and procedures. The panel will discuss the research findings and co-develop recommendations for clinicians, patients and caregivers. How will findings be shared? Findings will be shared via journal publications and conference presentations. They will also be shared by social media and neuromuscular charities, including information events and newsletters. The advisory panel will play a key role in sharing findings.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: NEUROLOGICAL;CONGENITAL DISORDERS