Jochem Helleman

Motor neuron disease (MND) is a rapidly progressive neurodegenerative disease that leads to loss of motor neurons and eventually leads to paralysis of most voluntary muscles. The initial symptoms of MND may occur in the arms or legs, known as a spinal onset, or show in difficulties with speech and swallowing, known as a bulbar onset. The average disease duration is 2 to 4 years, and the main cause of death in patients with MND is respiratory failure, due to severe respiratory muscle weakness. Patients with respiratory muscle weakness, can develop hypoventilation, which leads to shortness of breath, fatigue and sleepiness during the day, and restless sleep during the night.

Patients with MND require multidisciplinary care, which is aimed at optimizing participation and quality of life and includes 3 to 4 monthly visits to a multidisciplinary clinic. Besides improving quality of life, multidisciplinary MND care has shown to also prolong survival, compared to non-specialized care. One of the most effective treatments for improving survival in patients with MND is non-invasive ventilation (NIV), as it provides ventilatory support when patients are respiratory insufficient. A drawback of multidisciplinary MND care, is that accessing and receiving care at a multidisciplinary clinic can be time-consuming and physically challenging for patients with MND, due to their physical disability. This results in considerable burden of care, and may hinder the continuity of care, which can increase distress and negatively affect patients’ psychological well-being.

Telehealth, which is the remote provision of care, holds the potential to improve accessibility and personalization, and reduce burden of multidisciplinary MND care, by enabling frequent monitoring of patients from home. Despite these promising benefits of telehealth and the wide availability of digital technologies, the use of telehealth in care for patients with MND is limited. For these reasons it would be of great benefit to know what factors determine the success of the implementation of telehealth in MND care, and what methods can best be used for remote monitoring of patients with MND. In particular, the remote monitoring of respiratory function is important, as it can help healthcare professionals to detect respiratory decline earlier and optimize the timing of NIV. In order to determine which respiratory measures are appropriate for remote monitoring in a home setting, their validity and feasibility should be investigated.

This thesis aims to expand the knowledge on the use and implementation of telehealth in multidisciplinary MND care, and identify adequate methods for the remote monitoring of patients with MND.

Chapter 1 provides a general introduction on MND and multidisciplinary care. Furthermore, we introduce telehealth and remote monitoring as a way to improve multidisciplinary in MND care and highlight areas that require further investigation.

Part 1 Telehealth and digital technology
Chapter 2 describes a systematic review on the use of telehealth in the care for patients with ALS, and the barriers to and facilitators of telehealth implementation. We identified three types of telehealth: videoconferencing, home-based self-monitoring and remote NIV monitoring. Telehealth was mainly used by patients with respiratory impairment and focused on monitoring respiratory function. Facilitators for telehealth implementation were a positive attitude of patients and caregivers toward telehealth and the provision of training and ongoing support. Healthcare professionals were more likely to have a negative attitude toward telehealth, due to the lack of personal evaluation/contact and technical issues. Other important barriers to telehealth were lack of reimbursement and cost-effectiveness analyses. Based on these finding future endeavors should focus on improving the attitude of healthcare professionals towards telehealth, and investigate the cost-effectiveness of telehealth.

In Chapter 3 we evaluated the use of telehealth as part of specialized care for patients with ALS and the user experiences of patients and healthcare professionals. In total 50 patients with ALS used a telehealth service, which consisted of an ALS-app for self-monitoring and messaging, alerts for symptom-worsening, and regular nurse practitioner follow-up with personalized feedback and information. Patients self-monitored their well-being, body weight and functional status on average for 11 months. The adoption rate was high (80%), dropout rate was low (4%) and patients showed good adherence to home-monitoring protocol. Patients continued to use telehealth until shortly before death. Most patients experienced using telehealth as easy, helpful, not burdensome, and reported satisfaction with flexible clinic visits and the continuity of care. Healthcare professionals reported that telehealth was of added value in ALS care. From these findings we concluded that ALS care supplemented by home-monitoring and nurse practitioner follow-up was suitable and widely accepted by patients and healthcare professionals in our ALS clinic. Success factors were low self-monitoring burden, a user-friendly platform and the provision of personalized feedback.

Chapter 4 aimed to capture the opinion of patients with MND about remote monitoring in care and clinical trials, and their concerns and preferences regarding the use of digital technology. A multi-centre survey study was conducted in three MND clinics in The Netherlands, the United Kingdom (UK) and Australia. The survey was co-developed by investigators from participating clinics and eight patients with MND. The main topics included: patients’ attitude towards receiving remote care, monitoring frequency and devices, participating in decentralized clinical trials, and their preferences for and concerns with digital technology. Patients were invited either by e-mail or mail to participate in this study. In total, 332 patients with MND participated, of which most would like to self-monitor their health from home (70%), be remotely monitored by a multidisciplinary care team (75%), and would be more willing to participate in clinical trials from home (65%). Patients considered respiratory function and muscle strength to be most valuable for home-monitoring, and considered 3-4 measurements at a weekly frequency as acceptable for home-monitoring. Of all patients, 15% would not like to perform home-measurements; this subgroup was more concerned about the burden, distress due to self-monitoring of disease progression, privacy and data security. Our findings show that the majority of patients with MND holds a positive attitude towards the use of digital technology in both care and clinical trial settings. However, a subgroup of patients described a number of concerns that unless addressed risk being barriers to universal adoption. Addressing these barriers early in the design and implementation of remote digital technology with a user centred design approach will reduce the risk of technology exclusion.

Part 2 Remote monitoring and management of respiratory function
In Chapter 5 we determined which patient-reported hypoventilation symptoms are best for screening reduced respiratory function in patients with MND, and compared them to the respiratory domain of the amyotrophic lateral sclerosis functional rating scale (ALSFRS-R). We developed a 14-item hypoventilation symptom questionnaire (HYSQ) based on guidelines, expert opinion and think-aloud interviews with patients. Symptoms of the HYSQ were related to dyspnea, sleep quality, sleepiness/fatigue and pneumonia. A total of 100 patients with MND were included from 6 medical centers, who performed a supine vital capacity test and filled-out the HYSQ and ALSFRS-R. A supine vital capacity <80% of what is predicted was considered reduced respiratory function. Dyspnea-related symptoms were combined into the MND Dyspnea Scale (MND-DS), which showed better diagnostic performance than the sleep-quality symptoms, sleepiness/fatigue-related symptoms, and the respiratory domain of the ALSFRS-R. For this reason, we recommended the MND-DS for remotely monitoring respiratory function. In Chapter 6 we evaluated the validity and feasibility of home-monitoring vital capacity in patients with MND. We included 33 patients with MND who completed a 12-week home monitoring protocol, consisting of 4-weekly unsupervised home assessments of vital capacity and a functional rating scale. Patients and caregivers were trained in performing a vital capacity test during a home visit, and the investigator performed a supervised vital capacity test, which was repeated at final follow-up during a second home visit. In 88% of patients the difference between supervised and unsupervised vital capacity was less than 10%. Home-monitoring of vital capacity was generally experienced as easy and not burdensome, however, some patients were insecure about their vital capacity test performance without supervision. The majority of patients would like home-monitoring of vital capacity in MND care. In conclusion, unsupervised vital capacity testing at home, with prior face-to-face training, is a valid and time-efficient method for the remote monitoring of respiratory function, and well-accepted by patients with MND and their caregivers. In Chapter 7 we discuss the main findings of this thesis, which include the current use and (perceived) benefits of telehealth in MND healthcare, determinants of the implementation of telehealth in MND healthcare, and how to optimize remote monitoring of patients with MND. Furthermore we provide clinical implications for designing and developing the optimal telehealth platform, and how telehealth can best be implemented in MND healthcare. Lastly, we provide recommendations for future research.