Remote Assessment of Myotonic Dystrophy Type 1: A Feasibility Study

Abstract

Introduction/Aims:

Remote study visits (RSVs) are emerging as important tools for clinical research. We tested the feasibility of using RSVs to evaluate patients with myotonic dystrophy type 1 (DM1), including remote quantitative assessment of muscle function, and we assessed correlations of remote assessments with patient-reported function.

Methods:

23 subjects with DM1 were consented remotely. Toolkits containing a tablet computer, grip dynamometer, and spirometer were shipped to participants. The tablets were loaded with software for video-conferencing and questionnaires about functional impairment, patient experience with technology, and willingness to participate in future remote studies. Grip strength, forced vital capacity, peak cough flow, timed-up-and-go (TUG), and grip myotonia (hand opening time) were determined during RSVs. We assessed correlations of remote assessments with patient-reported outcomes of muscle function and with CTG repeat size.

Results:

All 23 subjects completed RSVs. 95% of participants were able to complete all components of the remote study. All toolkit components were returned upon completion. Grip strength and TUG demonstrated moderate to strong correlations with self-reported inventories of upper and lower extremity impairment, respectively (ρ=0.7 and ρ=−0.52). 91% of subjects expressed interest in participating in future RSVs.

Discussion:

Results of this study support the feasibility of using portable devices and video-conferencing for remote collection of patient-reported outcomes and quantitative assessment of muscle function in DM1.

Introduction

Myotonic dystrophy type 1 (DM1) is an autosomal dominant disease caused by CTG trinucleotide expansion in the DMPK gene.¹ Common features include muscle weakness, myotonia, heart block, daytime sleepiness, impaired cognition, cataracts, and gastrointestinal (GI) dysmotility.² The age of onset (AOO) and severity are variable between patients, which is partly explained by differences in length of the expanded CTG repeat.^3,4

Engagement of patient communities is an essential step in studying and developing treatments for neurological disorders, especially for rare diseases. Studies of rare diseases are limited by structural and socioeconomic barriers to research participation. For DM1, these barriers often include reduced mobility, caregiver responsibilities, employment commitments, travel limitations, and elevated risk during pandemics.⁵ Remote study visits (RSVs) have been proposed as one strategy to overcome barriers to research participation.^6,7 There is uncertainty, however, about whether and how this modality can best incorporate quantitative assessment of neuromuscular function. The primary goal of our study was to assess the feasibility of remote study visits in DM1, including the use of portable devices under video supervision to assess muscle function. A secondary goal was to evaluate associations of remote assessments with patient-reported outcomes.

Methods

The study was approved by the University of Rochester Research Subjects Review Board. All participants provided informed consent. Participants were recruited from the National Registry of Myotonic Dystrophy and previous research studies. Eligible subjects were ≥ 18 years old, able to provide informed consent, carried a clinical diagnosis of DM1, and had wireless internet access. A toolkit was sent to participants containing an iPad 7 tablet (Apple, Cupertino, CA) and stand (Manfrotto, Ramsey, NJ), spirometer (NuvoAir, Stockholm, Sweden), grip dynamometer (Jamar Plus Digital, JLW Instruments, Chicago, IL), and 3-meter tape measure. The tablets were digitally locked to prevent data carryover and non-study internet connections. Participants used tablets and REDCap⁸ to complete functional inventories including upper extremity function index (UEFI),⁹ lower extremity function index (LEFI),¹⁰ and questionnaires to assess familiarity and comfort with digital technology. UEFI and LEFI each consist of 20 items assessing functional problems. Total scores range from 0 to 80 and higher scores represent higher level of functioning. Next, a single investigator (JH) conducted a RSV using video-conferencing software (Zoom, San Jose, CA). RSVs included an interview to determine age of onset (AOO) of muscle (limb weakness or myotonia) or any symptoms of DM1 as an overall indicator of disease severity.^11,12 Subjects were asked to identify their three most bothersome symptoms. Then, muscle function was assessed under video supervision. Maximal isometric grip strength was determined for each hand using the dynamometer with the subject seated, and the elbow flexed to 90°. The best of three trials was selected for analysis. Results were also expressed as a percentage of the strength that would be predicted for a healthy person of the same age, sex and height.¹³ The grip dynamometer is digital, and the result from each successive trial was displayed to the investigator. Grip myotonia was assessed by recording video hand opening time (VHOT).¹⁴ Mobility was assessed using the timed up and go (TUG).¹⁵ Forced vital capacity (FVC) and peak cough flow (PCF) were determined in a seated position. The spirometry results were visible to the investigator in real-time via a cloud database. Participants completed a questionnaire on whether they had problems with technology and willingness to participate in future remote studies.

Statistical analysis

Data analysis was performed using SAS 9.4 (SAS Institute, Inc., Cary, North Carolina). Descriptive statistics were used to report demographic characteristics and symptom frequency. Correlation analysis was performed using Spearman correlation coefficient. Strong or very strong correlations were defined as those with coefficients of 0.70–1.00, moderate correlations as 0.40–0.69, and weak as 0.10–0.39.¹⁶

Results

Twenty-three individuals with DM1 aged 18–78 years (mean age 44) enrolled in the study. Participants’ demographics, genetic characteristics, and self-reported familiarity with computer technology are shown in Table 1. For 19 subjects, information about CTG expansion length was available from previous commercial testing or participation in research studies. Three participants had never participated in research activities prior to the RSV. Patient symptoms and AOO encompassed a wide spectrum (supplemental Figure A, Table 2). Most participants (70%) reported hand or oromandibular myotonia as their first symptom. Hypersomnolence was reported as the most bothersome non-motor symptom (supplemental Figure B).^17,18

Table 1.

Demographics, Genetic Characteristics, PC experience and comfort level with RSV

n		23
Age (years), mean (std)		44 (16)
Women, n (%)		15 (65)
CTG repeats, mean (std)		419 (270)
Education, n (%)	High school	6 (26)
	Technical school or college	11 (48)
	Graduate school	6 (26)
Employed, n (%)		11 (48)
PC skills, n	“Great, I have experience and can figure out most problems”	5
	“Ok, I know how to use a few programs, but need help at times”	13
	“Not so good, I struggle with it”	4
Technical difficulties with study, n	none	11
	Some, but able to manage	9
	Yes, I needed help	2*

RSV = Remote Study Visit, std = standard deviation,

^*one individual with high and one with moderate PC skills.

Table 2.

Remote Muscle Function Assessments

		n	median	Q1, Q3
Handgrip L (kg)		23	15.5	8.4, 21.0
Handgrip Left PP (%)		23	42.9	29.6, 53.6
Handgrip R (kg)		23	14.2	10.0, 21.2
Handgrip Right PP (%)		23	38.8	27.4, 70.9
FVC (liter)		23	3.3	2.6, 4.1
FVC PP (%)		23	83.6	68.6, 96.4
PCF (liter/min)		22	399.9	282.0, 464.4
PCF PP (%)		22	90.8	72.9, 100.3
TUG (sec)		23	6.8	5.5, 8.5
VHOT (sec)	middle finger	23	3.0	1.5, 7
	thumb	23	4.0	1.9, 6.8

Handgrip L= Handgrip Left; Handgrip R= Handgrip Right; FVC= Forced Vital Capacity; PP= percent predicted, based on age, sex and height; PCF= peak cough flow; TUG= Timed Up and Go; VHOT= video hand opening time.

Only five (22%) of our subjects self-identified as regular independent computer users (Table 1). Some participants required assistance from others to set up equipment due to hand weakness (n = 6) or to overcome difficulties operating the tablet (n=2). Nevertheless, all subjects completed RSVs and digital questionnaires. All participants completed all components of the remote assessments except one who elected not to perform the PCF (Table 2). No falls or injuries occurred during RSVs. Spirometry was readily completed by RSV, and ten subjects had FVCs and PCFs below 80% predicted. Handgrip strength showed a strong positive correlation with the upper extremity function index (ρ=0.70, p=<0.001) and a moderate negative correlation with CTG repeat size (ρ=−0.51, p=0.03). TUG showed a moderate negative correlation with the lower extremity function index (ρ=−0.52, p=0.01) and moderate positive correlation with CTG repeat size (TUG ρ=0.62, p=<0.01) (Table 3). Video quality was sufficient to monitor muscle function testing and assess VHOT in all cases. The average duration of RSVs was one hour (range 45–75 minutes). All participants returned toolkits promptly, and 91% indicated willingness and interest to take part in future remote studies. Two patients recommended an additional call from study staff to help with logging into the video conferencing software, and one participant recommended a video demonstrating the equipment set up.

Table 3.

Associations of patient-reported function and remote assessments

	LEFI (n=23)	UEFI (n=23)	CTG Repeats (n=19)
Handgrip, ρ, (p value)	0.60 (<0.01)	0.70 (<0.001)	−0.51 (0.03)
TUG, ρ, (p value)	−0.52 (0.01)	−0.41 (0.05)	0.62 (<0.01)
FVC PP (%), ρ, (p value)	0.24 (0.27)	0.33 (0.12)	−0.32 (0.18)

LEFI= Lower extremity function index, UEFI= upper extremity function index, FVC= Forced Vital Capacity; PP= percent predicted, based on age, sex and height; TUG= Timed Up and Go, ρ = Spearman correlation coefficient, p= p value.

Discussion

Our study indicates that RSVs including collection of quantitative data is feasible and safe in patients with DM1. The results of remote muscle function testing correlated moderately to strongly with the extent of functional impairment, as perceived by patients, and length of expanded CTG repeats in peripheral blood. These findings suggest that quantitative data collected by remote assessment may reflect symptoms that patients experience and underlying genetic determinants of disease severity. Our initial experience suggests that assistance by others may be necessary in a subset of participants, mainly to help with study set up due to hand weakness. Most of our subjects indicated they would be willing to participate in other RSVs in the future.

Our study has several limitations. First, while we demonstrated the feasibility of RSVs in DM1, further studies are needed to determine whether data collected in RSVs are comparable to on-site testing. Second, 20 of our participants had some previous experience with study visits. Thus, while we did not encounter any substantial limitation of RSVs for data collection, further studies in the research-naïve population are needed. Third, we relied on previous genetic analyses for CTG repeat length, which is known to vary between different laboratories.¹⁹ Fourth, our remote evaluation was far from comprehensive, and many aspects of the complex DM1 phenotype were not evaluated. While we foresee the likelihood that other devices may be added to toolkits, and that other kinds of assessments may be performed, we do not expect that RSVs can replace on-site visits if the study context requires comprehensive evaluation.

Abbreviations

AOO

Age of onset

DM1

Myotonic dystrophy type 1

FVC

Forced vital capacity

GI

Gastrointestinal

PCF

Peak cough flow

RSV

Remote study visits

TUG

Timed-up-and-go

VHOT

Video hand opening time