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Clinical recommendations to guide physical therapy practice for Huntington disease

Objective In the past decade, an increasing number of studies have examined the efficacy of physical therapy interventions in people with Huntington disease (HD). Methods We performed a mixed-methods systematic review using Joanna Briggs Institute (JBI) methodology and included experimental and observational study designs. The search resulted in 23 quantitative studies and 3 qualitative studies from which we extracted data using JBI standardized extraction tools. Results of this review suggested that physical therapy interventions may improve motor impairments and activity limitations in people with HD. Here, we expand on the review findings to provide specific recommendations to guide clinical practice. Results We recommend the following specific physical therapy interventions for people with HD: aerobic exercise (grade A evidence), alone or in combination with resistance training to improve fitness and motor function, and supervised gait training (grade A evidence) to improve spatiotemporal features of gait. In addition, there is weak (grade B) evidence that exercise training improves balance but does not show a reduction in the frequency of falls; inspiratory and expiratory training improves breathing function and capacity; and training of transfers, getting up from the floor, and providing strategies to caregivers for involvement in physical activity in the midstages of HD may improve performance. There is expert consensus for the use of positioning devices, seating adaptations, and caregiver training in late stages of HD. Conclusions There is strong evidence to support physical therapy interventions to improve fitness, motor function, and gait in persons with HD.


Introduction
In 2009, the Physiotherapy Working Group of the European Huntington Disease Network (EHDN) developed an evidencebased Clinical Guidance Document to inform optimal physical therapy management of people with HD and facilitate uniformity of care internationally. 3 Given the limited evidence at the time, this document was largely based on expert opinion. Seven treatment-based classifications were developed to facilitate translation of guidelines into clinical practice. These classifications provided a framework for management of the range of impairments and activity limitations across the disease stages. Since 2012, an increasing number of studies have examined the feasibility and efficacy of physical therapy interventions to improve physical function, mobility, cognition, mood, and quality of life in individuals with HD. In 2017, the Guidance Document was revised to incorporate the new literature within a concise, user-friendly Clinical Practice Guideline. Individuals with HD develop physical, cognitive, and psychological impairments that negatively affect their mobility and participation in life activities and that ultimately reduce quality of life. 4 Cognitive and psychological impairments manifest early in the disease. Mobility is negatively affected by key impairments of chorea, dystonia, and bradykinesia somewhat later. 3,4 Physical therapy encompasses a multitude of interventions ranging from exercise and physical activity promotion for people to gait and balance training and ultimately respiratory and palliative care as the disease progresses. A treatment-based classification, which is organized around impairments and activity limitations across disease stages, provides a framework for the current guidelines. As such, these guidelines encompass a range of physical therapy outcomes (gait, balance, and quality of life) and a range of physical therapy interventions (exercise, physical activity, balance and task-specific training, and respiratory training). Given the paucity of evidence available for any specific physical therapy intervention on any specific outcome, we believe that this approach is most pragmatic and will yield optimal benefit of providing guidelines to support evidence-based physical therapy intervention in people with HD.
A systematic review of the literature to determine that evidence exists to support exercise and physical therapy as a means to address impairments and activity limitations present in HD informed these guidelines. 5 Of 20 articles that met the inclusion criteria, the evidence provided preliminary support for physical therapy interventions for improving motor function, gait speed, balance, and a range of physical and social patient-reported outcomes. The authors discussed the results in terms of application to 7 treatment-based classifications to assist physical therapy treatment planning in HD. 6,7 The guideline is designed to answer the following PICO question: for individuals with HD (all stages) across practice settings, what is the effect of physical therapy interventions (e.g., exercise, physical activity interventions, task-specific training, gait and balance training, and respiratory training) on outcomes of mobility, balance, physical fitness, physical activity, respiratory function, and patient-reported outcomes compared with no intervention, wait list control, or social contact control?

Statement of intent
The target users of this guideline are physical therapists and physical therapist assistants. Other rehabilitation and referring physicians may also use these guidelines to support their practice or referral to physical therapy. It is not intended to serve as a legal standard of care. This guideline is a summary of practice recommendations supported by the current published literature reviewed by expert clinicians and stakeholders. Thus, the recommendations set forth herein should be considered guidelines only, not required directives. Adherence to these recommendations will not ensure a successful outcome in every patient. Clinical judgment on the part of the rehabilitation professional is critical for determining the treatment plan for the individual patient, accounting for clinical data collected from the patient, patient preferences and values, and clinician expertise and scope of practice.

Methods
In 2016, members of the Guideline Development Group were tasked by the Huntington Study Group (HSG) and the EHDN with the development of a clinical guideline for physical therapy in HD. Funding for this work was received from the Griffin Foundation, HSG, and EHDN. The workgroup solicited members to form a multidisciplinary (neurology, physical therapy, and occupational therapy) advisory board of people actively involved in management of persons with HD. The advisory board was involved with the development of the content and scope of the guideline.

External review process by stakeholders
External stakeholders were consulted throughout the process of guideline development so that views and preferences could be incorporated into the results and discussion sections. Relevant stakeholders included persons with HD and their families, physical therapists, speech therapists, neurologists, psychologists, nurses, and HD researchers.
The stakeholders reviewed the draft of the guideline that was released for public comment. Ninety-five percent (22/23) of patient and family stakeholders felt that the guideline was definitely informative, and 100% felt that the guideline would "definitely" or "probably" be a useful resource to a physical therapist or other health care professional. In addition, 100%

Literature search
The protocol for the systematic review has been published 8 and was developed using the guidelines set forth by the JBI. 9 JBI tools are widely used, with more than 70 collaborating entities across 34 countries. 10  The PICO question was framed as, "Are physical therapy interventions (i.e., exercise, physical activity interventions, and task-specific training) recommended for individuals with HD to improve mobility, balance, physical activity and patient-related outcomes across disease stages and practice settings?" The primary keywords used in the searches were: huntington* disease, physical therap*, physical activit*, exercise, and physiotherapy*. Additional text words included the specific forms of exercise and mobility intervention (see published systematic review 5 ).
Included articles were those in adults with HD across stages and care settings that evaluated physical therapy interventions such as aerobic exercise, strengthening exercise, walking training, balance training, task-specific training, seating and positioning, postural alignment or respiratory interventions, and included outcomes measuring physical or cognitive function. For qualitative studies, those that examined perceptions of physical therapy for the patient, family, or caregiver using qualitative methods were included. Additional details on inclusion and exclusion criteria may be found in our published systematic review. 5 Critical appraisal process Data were extracted from the studies using the standardized JBI data extraction tools. 9,37 Next, 2 authors within the guideline development group, who had been trained to use the JBI tools, independently assessed the methodologic validity before inclusion in the study, followed by verbal discussion in a group setting to resolve disagreements.
For areas where there was limited or no evidence from the literature available to guide treatment, we solicited expert opinion. A custom survey was developed to determine current treatment practices around the world for seating, secondary postural changes, and late-stage care. Respondents were asked to provide a description of specific interventions used with individuals with HD for each of these categories. The survey was distributed to members of the HSG, HD Centers of Excellence, Degenerative Disease Special Interest Group of the Academy of Neurologic Physical Therapy of the American Physical Therapy Association, and the Physiotherapy Working Group of the EHDN. The responses were pooled to determine consensus expert opinions for areas with limited evidence. Finally, the results were summarized in narrative format.
One hundred two individual respondents completed the survey. Of those, 74% were physical therapists, and 61% had treated individuals with HD for more than 5 years. Sixty-six percent of the respondents were from the United States, 21% from Europe, representing 10 countries, and the remainder from Canada, Australia, Israel, and New Zealand. Forty-four percent endorsed working with individuals with HD in the late stage of the disease; respondents endorsed the following strategies with individuals with HD with end-stage disease: positioning, range of motion exercises, active movement, respiratory exercises, and education (figure 1). These recommendations are summarized as level 5B evidence in table 3.

Data availability
All data are published within this article and associated tables, figures, and supplemental data.

Action statements
Action statements are listed first with the grade of the recommendation followed by the recommendation. A standardized profile of information for each action statement is available at aan.com/guidelines. A summary of the action statements, grades of recommendation, and research recommendations is found in table 4. These 2019 guidelines are based on the literature published between January 2003 and August 2018. These guidelines will be considered for review in 2024 or sooner if new evidence becomes available. Any updates to the guideline in the interim period will be noted on the American Academy of Neurology web site: aan.com/guidelines.
Action statement 1: Effectiveness of aerobic exercise paired with strengthening exercises in persons with HD Physical therapists should prescribe aerobic exercise (moderate intensity, 55%-90% heart rate maximum) paired with upper and lower body strengthening 3 times per week for a minimum of 12 weeks to improve fitness and to stabilize or improve motor function (evidence quality: 1-3; recommendation strength: strong).

Supporting evidence and clinical interpretation
Eight publications 12,15,16,19,27,29,31,32 evaluated the impact of exercise (aerobic, strengthening, and general conditioning) and/or physical activity interventions to address a range of outcomes from 6 separate studies. Two pairs of publications 12,15,16,29 included data from the same data set but evaluated different outcomes. Intervention durations were 8 weeks, 19 12 weeks, 12,16,27 14 weeks, 32 26 weeks, 31 and 9 months. 15,29 Frequency of exercise ranged from 3 to 4 times per week, which included center-based and home-based exercises.
Four of the 6 studies included aerobic exercise as a component of the intervention. 12,15,16,27,29,31 Exercise intensity varied from 55% to 90% VO 2 max (based on actual VO 2 max or age-predicted values), and duration ranged from 10 to 30 minutes (median duration = 25 minutes). Four studies incorporated strengthening and general conditioning exercises, involving core, upper body, and lower body musculature. 12,15,16,19,27,29 Four studies 12,16,19,32 used a progressive home walking program (average once per week). Two studies 20,32 incorporated use of an exercise DVD specific to persons with HD that included balance and circuit training, strengthening, flexibility, and relaxation exercises.

Action statement 2: Effectiveness of gait training in persons with HD
Physical therapists should prescribe one-on-one supervised gait training to improve spatiotemporal measures of gait (e.g., walking speed and step length) (evidence quality: 1-4; recommendation strength: strong).

Supporting evidence and clinical interpretation
Fourteen studies examined the effects of exercise programs on clinical and mobility measures. Six randomized controlled trials (level 1C) examined the use of exercise in outpatient, home, and gym settings to improve mobility. All studies provided individual supervision, and transportation was provided for the one gym-based study. Interventions to improve mobility included gait and transfer training, 26 stationary cycling with a home walking program and resistance exercise, 12 use of a dance-based video game, 21 home exercise with a DVD and a walking program, 19 a gymbased exercise program including aerobic and resistance  exercise, 27 and an outpatient-based multidisciplinary intervention of supervised aerobic and resistance training. 35 Gait speed (measured with the 10-meter walk test [10MWT]) improved after use of a DVD for home exercise and a walking program delivered 3 times a week over 8 weeks 19 and following 36 weeks of gait and resistance training. 35 Gait speed did not improve in the home-based, task-specific exercise program, but all participant-directed gait-related goals were met. 26 The gym-based aerobic and resistance training program, a feasibility study, and dance-based video game play, which did not incorporate walking training, did not improve gait speed. 21,27 The gym-based therapy was completed by 82% of participants, but only 7 of the clients achieved the expected 150 minutes of moderate exercise per week. 27 The dance-based video game led to a decrease in double support percent of gait cycle during forward and backward walking. 21 Mobility measures that did not demonstrate significant improvement in any study were the 30-second chair stand test, 12 step time, and step time coefficient of variation. 19,21  There were 6 pre/post-test control group studies addressing mobility and functional activities (level 2D). Four of these studies provided the intervention as part of an inpatient multidisciplinary program. 13,24,25,30 Clients were admitted for 3 weeks (intervention administered for 8 hours per day, 7 days a week) either once or 3 times per year. Studies that asked clients to return 3 times per year had higher dropout rates, with 60%-83% completing the intervention over 1-2 years. 24,25,30 Mobility improved as measured by gait speed, Timed Up and Go (TUG) test, 24,25 Tinetti performance oriented mobility assessment, 13,30 and the physical performance test 13 when assessed over a 1-year period. When the intervention was extended over 2 years, mobility (i.e., gait speed and TUG performance) did not decline. 25 All studies administered multidisciplinary intervention; given the design and quality of the studies, it is difficult to conclude that physical therapy or any specific physical therapy intervention led to the improvements in mobility.
Two studies (level 2D) examined the impact of outpatient physical therapy on gait. 11, 23 Mirek et al. 23 provided a proprioceptive neuromuscular facilitation-based intervention focused on gait and balance 3 times a week, 90 minutes per session. After 3 weeks, there was significant improvement in gait speed (measured by 10MWT) and mobility (measured by TUG and Tinetti Mobility Test). Bohlen et al. 11 reported significant changes in spatiotemporal parameters of gait, gait speed, and TUG time following one-on-one physical therapy focused on gait and transfer training performed 2 times a week, 60 minutes a session for 6 weeks, as well as excellent adherence with overall attendance of 90% for physical therapy sessions. These studies support the effectiveness of one-on-one physical A Researchers should conduct larger-scale clinical trials to determine the efficacy of aerobic and strengthening intervention on motor function and disease progression. In addition, studies should address optimal frequency, intensity, and timing of interventions.
Effectiveness of gait training in persons with Huntington disease: physical therapists should prescribe one-on-one supervised gait training to improve spatiotemporal measures of gait.
A Researchers should conduct larger-scale clinical trials to determine the efficacy of different gait training interventions (overground, treadmill, and other) on gait kinematics and kinetics across stages of the disease. In addition, studies should address optimal frequency, intensity, and timing of interventions.

Effectiveness of balance exercises in persons with
Huntington disease: physical therapists may prescribe individualized exercises, including balance exercises, delivered at a moderate frequency and intensity to improve balance and balance confidence.

B
Researchers should conduct larger-scale clinical trials that use interventions specifically focused on balance to confirm the benefits of balance training in persons with HD. Ideally, these studies should include persons with HD at all stages of the disease and be of sufficient duration to determine whether balance interventions will delay onset or decrease numbers of falls.

Effectiveness of breathing exercises in persons with
Huntington disease: physical therapists may provide regular breathing exercises, including inspiratory and expiratory training, to improve respiratory muscle strength and cough effectiveness.

B
Researchers should conduct larger-scale clinical trials to confirm the benefits of respiratory training in persons with HD. Inclusion of functional testing to determine benefits on functional performance and/or participation would be useful.

Effectiveness of postural control training in persons with
Huntington disease: physical therapists may prescribe an individually tailored program to improve postural control and may use positioning devices to optimize posture.

No Recommendation
Researchers should conduct larger-scale clinical trials to examine the effectiveness of postural control exercises in prevention of secondary postural changes. In addition, studies are needed to examine the effectiveness of positioning devices in improving posture, activities of daily living, and reducing caregiver burden in the advance stage of HD.
Role of physical therapy on ADL's, seating and positioning in end-stage care of persons with Huntington disease: physical therapists should ensure that care plans for individuals with HD with end-stage disease include appropriate positioning and seating, active movement, position, respiratory exercise, and education. Family and caregiver training to provide strategies for maintaining appropriate ongoing activity and participation for as long as possible is an important focus for the physical therapy team as part of end-stage care.

No recommendation
Researchers should conduct longitudinal evaluations of endstage care in HD. Qualitative and mixed-methods approaches may be useful, given that there is a consensus-based best practice standard. Evaluations of end-stage outcome may also be informed by long-term cohort studies in which the impact of lifestyle choices (such as participation in regular physical activity) is assessed.
To determine the level of evidence and the grade of recommendation of included studies, we used the JBI Levels of Evidence 1 and JBI Grades of Recommendation. 2 therapy focused on gait training to improve mobility. However, the findings are interpreted with caution, as both studies lacked adequate control groups.
The use of a rollator walker to improve gait parameters is supported by one single-session observational study without a control group (level 3E). 22 Three weeks of gait training and seated exercises resulted in improvements in gait speed in a hospital-based study with no control group (level 3E). 34 Finally, there is 1 case series (level 4C), examining the use of an outpatient group program to improve mobility. 14 Three individuals (2 manifest and 1 premanifest) participated once a week in a 60-minute group program. A circuit training design was used with each exercise individualized to the client's skill level. All 3 individuals improved gait speed on the 10 MWT and TUG. These 2 studies provide insight into the potential benefits of individualized circuit training and support the need for future research in these areas.

Action statement 3: Effectiveness of balance exercises in persons with HD
Physical therapists may prescribe individualized exercises, including balance exercises, delivered at a moderate frequency and intensity to improve balance and balance confidence (evidence quality: 1, 2, and 4; recommendation strength: weak).
Six of the 8 studies 11,14,[23][24][25]33 included balance-related interventions such as mobility and skills training (i.e., sit-to-stand transfers, walking over soft surfaces, reaching, stair-climbing, and turning), progressive static and dynamic standing balance exercises (that is, narrowed and altered base of support, forward and side lunges, standing with eyes open and closed, standing without arm support, and balance reaction training. Four studies used aerobic and/or strengthening exercises. 12,24,25,29 One study used task-specific training focused on walking, sit-tostand transfers, and standing. 26 One study 21 used supervised playing of the video game Dance Dance Revolution. Action statement 4: Effectiveness of breathing exercises in persons with HD Physical therapists may provide breathing exercises, including inspiratory and expiratory training, to improve respiratory muscle strength and cough effectiveness (evidence quality: 1C-D; 5B; recommendation strength: weak).

Supporting evidence and clinical interpretation
There is grade B evidence to support the use of respiratory training to improve respiratory function in persons with HD. In a randomized controlled trial, Reyes et al. 28 demonstrated that 4 months of progressive resistive inspiratory and expiratory training resulted in improved maximal inspiratory and expiratory pressures, as well as forced vital capacity and peak expiratory flow when compared with the control group, who completed fixed-resistance training.
In a pseudo-randomized controlled trial, Jones et al. 18 produced similar findings, showing that 6 weeks of resisted inspiratory exercise resulted in improved sniff nasal inspiratory pressure and peak cough flow. The control group, who performed breathing exercises without resistance, also demonstrated improvements, suggesting that regular breathing exercises could improve pulmonary function in persons with HD.

Supporting evidence and clinical interpretation
There are 2 pretest-posttest (level 2D) studies, 11,13 neither of which had a control group, to support physical therapy for secondary musculoskeletal and postural changes in people with HD.
Training of postural control and stability over 12 sessions in an outpatient setting did not result in improvement in length and speed of center of mass projection, as measured by a force plate. 11 In contrast, intensive inpatient multidisciplinary intervention (4 hours per day for 6 days a week), including exercises for postural alignment and stability, improved scores on the Tinetti Mobility Test. 13 However, improvement in Tinetti scores could have been due to the cumulative effects of the multifactorial nature of the intervention, rather than the specific effect of postural alignment and stability training. Future work needs to examine the specific effect of postural training.
The consensus among experts was that intervention for secondary musculoskeletal and postural changes should be tailored to the stage of the disease. For instance, early in the disease focus can be on active exercises to improve core stability, muscle strengthening, fall prevention, functional exercises such as sit to stand, getting up from the floor, and posture correction. In the later stages of the disease, the focus of intervention shifts to practice of bed mobility, transfer training, and getting in and out of bed. A second major theme among experts was the use of positioning devices and supports to promote better posture and prevent secondary musculoskeletal changes. Examples of supports include wedge cushions, bolsters, pillows and bed railings for positioning in bed, and cushions or pillows for positioning in a wheelchair and the use of safety belt to prevent sliding. In the later stages of the disease, experts recommended use of specialized wheelchairs such as the Broda chair (Broda Seating, Chesterfield, MO) for optimal positioning (including flexible seat-back angle, supported footrest, pelvic belt, and antitipping devices for safety). Consensus also included educating caregivers on the use and operation of positioning devices and wheelchairs, as well as proper body mechanics for safe transfer of patients. Additional interventions that are used frequently but have not been formally investigated include stretching for contracture management and prevention, range of motion exercise, and specific positioning to encourage feeding and swallowing. In terms of nursing and rehabilitation care, 39 tailored exercise programs and ongoing active engagement in goal-directed and social activities are critical to promote mood, motor function, and quality of life for as long as possible. Supporting evidence for these recommendations is summarized in Moskowitz and Rao, 39 but is limited to 1 randomized trial of multisensory stimulation in late-stage HD, 40 2 single-case studies 41,42 on the role of hydrotherapy for advanced HD and a 14-week video-based exercise program, and 2 articles detailing social and gardening activities in inpatient settings.
Recommendations for late-stage care in HD focus on supporting activities of daily living, optimizing attention, posture, positioning, and seating, particularly during meal and postmeal times. In addition, there is focus on prevention of falls, analysis of previous falls, and development of midfall strategies to minimize injury risk. Experts specifically mentioned environmental modifications and seating adaptations to maximize posture and positioning. Additional treatments that are used frequently but have not been formally investigated include prevention of decubiti and airway clearance.
The expert opinion survey confirmed that identified in the review and expert commentary. Therapists reported that their focus was on facilitation of ongoing participation in activities that were achievable for the person with HD. An important element was family and caregiver training to maintain ongoing activity for as long as possible. Postural adaptations, positioning range of motion activities, and seating advice were regular recommendations. The importance of providing caregivers with strategies to encourage activity was highlighted. Last, the risk benefit balance of falls vs inactivity was pointed out by several experts.

Limitations of recommendations
There are several limitations to this guideline. The recommendations provided in this guideline are based on a small number of available studies, some of which lack control groups or use multidisciplinary interventions that limit our ability to interpret intervention effects. The studies have been graded by their level of evidence (table 3) to highlight these limitations. The heterogeneity of disease levels and stages across studies affects our ability to determine outcomes across disease stages. Finally, studies in languages other than English were not captured in our previously published review 5 or this guideline; this could introduce language bias with respect to our results. To address this issue, we have gathered feedback from a wide range of professionals to provide a globally relevant guideline.

Guideline implementation recommendations
Many studies included in this review considered patient experiences, yielding important insights into how physical therapy interventions should be implemented in persons with HD. Qualitative analyses suggest that individuals with HD, their caregivers, and therapists perceive exercise as beneficial. The perceived benefits included physical benefits, such as improved gait and balance, 17 social benefits, such as improved self-confidence, socialization, and a sense of community, 17,36 and mental benefits, such as improved mindfulness and communication. 36 The evidence suggested that shared goal setting should be considered and that the influence of the caregiver should be a key factor to be explored during the initiation and implementation of exercise interventions. 20 These recommendations build on previous work 43 to develop a practice pathway for HD that can inform clinical assessment and intervention planning that is in line with the Guide to Physical Therapist's Patient/ Client Management Model ( figure 2).
There may be a benefit for people with HD to receive targeted exercise interventions multiple times over a year or longer, rather than relatively short interventions (often 6-8 weeks) that are abruptly discontinued with minimal follow-up. A clinical trial is currently underway evaluating this model of care in individuals with early-mid stage HD. 44 There is increasing recognition across neurologic diseases about the importance of strategies to maintain physical activity through the life course of the disease 32,45-48 Indeed, research across neurologic conditions provides evidence that secondary prevention strategies are crucial to maintaining function and warding off impairments that are secondary to mobility restrictions. 45 Although implementation of inpatient multidisciplinary programs, which require extended stays in hospital or rehabilitation centers, is currently not feasible in many countries, there is supporting evidence to suggest that such a model should be considered. Importantly, future work must include economic evaluation and the potential for such programs to maintain high quality years of living with the disease.
Overall, exercise can be tailored to enable participation by individuals with HD and to address HD-specific impairments.
The facilitators for exercise participation identified by patients and caregivers included individualized training plans and schedules, group therapy, cues to improve adherence, and involvement of a committed caregiver or contact person. 17,20 Barriers to exercise participation included cognitive impairments, poor balance, and lack of motivation. 17,20 Such barriers may affect success with rehabilitation; thus, it is important to maximize facilitators to exercise to ensure success and adherence.