Physical Therapy Evaluation and Management in Neuromuscular Diseases

Neuromuscular disorders (NMDs) are a group of myopathic or neuropathic diseases that directly or indirectly affect the functioning of muscle. Physical therapists (PTs) have extensive specialized training in musculoskeletal evaluation and assessment that gives them the tools to meet the significant needs of this population. This article reviews the role of PTs in treating the NMD population with a discussion of available evaluation techniques and interventions and with an effort to differentiate between treatments known to apply to this population and conventional practice of PTs. The status of currently available outcome measures used for research and their applicability to clinics are presented.

•

Physical therapists (PTs) have extensive specialized training in musculoskeletal evaluation and assessment, which enables them to provide skilled interventions and prophylactic care maximizing function in neuromuscular disorders (NMDs).
•

PTs must use their clinical judgment to differentiate between musculoskeletal symptoms that respond to conventional therapy interventions and those symptoms related to NMDs that do not.
•

Evidence for the effectiveness of physical therapy treatments in the NMD population is lacking and future research into the efficacy and benefits of PT treatment interventions in NMDs is recommended.
•

The development of reliable and valid outcome measures that are responsive to changes in the disease course and treatment interventions is needed to improve the evaluation and management of NMDs.

Key Points

NMDs are a group of myopathic or neuropathic diseases that directly or indirectly affect the functioning of muscle. Myopathic diseases primarily result in muscular degeneration rather than affecting the nerves themselves. Neuropathic diseases include motor neuron diseases that involve motor neurons in the brain, spinal cord, and periphery, leading to impaired muscle function. Many mechanisms account for the pathology in NMDs, including hereditable genetic deficits (eg, dystrophinopathies, metabolic myopathies, and spinal muscular atrophies), environmental-genome interactions (eg, acute idiopathic demyelinating polyradiculoneuropathy), and environmental causes (eg, tick paralysis and polio). The primary symptoms associated with most neuromuscular diseases include muscular weakness and fatigue but may also include rigidity, loss of muscular control, spasms, and muscle-associated pain. The disability associated with NMDs depends on the specific disease, its pathogenesis, the extent of clinical involvement, and the rate of progression.

PTs have extensive specialized training in musculoskeletal evaluation and assessment, giving them the tools to address and treat the significant needs of this population. Their knowledge of the pathophysiology and progression of disabling symptoms enables them to provide skilled hands-on interventions and prophylactic care. They provide services for NMD patients in a multitude of settings and across all ages. PTs are participating at the forefront of NMD research, developing outcome measures, assessing treatment interventions, and documenting the natural history progression of NMDs. Many of the standard practices of PTs, however, are only validated within a healthy population. This article reviews the role of PTs in assessing and treating patients with NMDs and discusses the available evaluation techniques and interventions with an effort to differentiate between treatments specific to this population and the more conventional practice of PTs. The status of current outcome measures available in research and their applicability to the clinic are also presented. Discussion regarding exercise and pain management related to NMDs is not addressed but can be found in the articles Abresch et al and Carter et al elsewhere in this issue.

The role of the physical therapist in neuromuscular diseases

In the NMD Clinic

In the clinic, a seasoned NMD PT has the expertise to perform many roles, from evaluator to educator and from equipment specialist to patient/family advocate. These services can provide crucial timely intervention and improve patient flow in an NMD clinic: addressing immediate concerns, facilitating communication between a patient’s community therapist or durable medical equipment (DME) provider and clinic staff, and providing specialized advice to direct outpatient services to maximize the therapy benefit for the client. Clinic therapists should be able to rapidly assess disease-specific symptoms or complaints and determine if immediate intervention will improve the issue. Their assessments should be focused, enabling them to determine the stage and rate of disease progression and to anticipate the development of future disease-related disability and initiate preventative or palliative measures. Clinic therapists then have a primary responsibility to communicate patient status changes to PTs who are responsible for patients in alternate settings.

Recognizing that each clinic functions differently, having varied resources, the services a clinic PT provides ultimately depends on the needs of the multidisciplinary team, who define the clinic roles according to staffing and expertise. Regional differences in delivery of care exist and reimbursement may drive the availability of a clinic therapist. Therapy reimbursement is typically based on productivity and billable time. The multidisciplinary clinic often does not have a mechanism for billing for services in this manner and then PT services may only be available if time is contracted to a clinic. Although insurance requirements, Medicare, and the increasing need for preauthorization may hinder staffing clinics with a therapist, standard of care recommends the participation of a PT in an NMD clinic. When a clinic therapist is not available or if the symptoms require ongoing intervention, a referral to outpatient therapy should be generated.

A clinic PT may use a multitude of assessments to document improvement or decline. When pharmaceutical intervention is initiated and ongoing for disease management, quantitative measures can be especially informative to a physician and provide evidence of treatment efficacy. Timed motor performance measures can be used to document objective functional changes in a patient’s mobility and may help a clinician identify rates of disease progression. Functional measures that document levels of functional mobility are helpful in making exercise or equipment recommendations. Outcome measures are discussed later.

The clinic is an excellent place to begin patient education regarding disease management. Designing a good home exercise program, to begin early after diagnosis, benefits patients and may encourage better long-term compliance. The structure of a clinic provides the opportunity to introduce only a few exercises and avoid overwhelming patients. Instruction in range-of-motion (ROM) exercises is important before the onset of joint contracture and follow-up at each subsequent visit can be used to correct techniques and add additional stretches as the disease progresses. In conjunction with stretching, patients may need education in proper positioning. Habitual poor postures, such as sacral sitting, thoracic flexion, leaning on a single wheelchair arm rest, sitting with unsupported feet, and prolonged immobilization, increase the risk of joint contractures in patients with NMD. Assessment of a patient’s wheelchair and other mobility assistive devices provides the opportunity to identify a poorly fitting wheelchair and quickly rectify the problem. When a patient complains of weakness and fatigue that interfere with activities of daily living, energy conservation techniques should be discussed. In addition, education regarding pulmonary hygiene with instruction in breathing exercises, airway clearance, and assisted cough techniques is easily done in clinic.

Therapists should assess functional mobility and recommend appropriate home equipment. A detailed history of the home environment, including existing DME and architectural details as well as the ability of the caregiver to provide transfer support, must be documented. With the progressive nature of many NMDs, equipment recommendations must be based on both present and future needs of a patient. A tub transfer bench may work now but if transfers will no longer be functional within the year, investing in a full bath transfer system is a better long-term solution. Power mobility recommendations must be made with a 5-year functional outcome in mind because reimbursement for power equipment is usually limited to 1 device every 5 years. Sometimes, a home health referral to evaluate a home for equipment and safety is appropriate.

In the Outpatient Clinic

Outpatient therapists traditionally treat symptoms, such as weakness, pain, or impaired mobility, related to a primary NMD. A referral for outpatient therapy should reference the specific symptom or disability requiring treatment intervention in addition to the NMD diagnosis. The therapist performs a thorough evaluation using strength testing, mobility assessment, musculoskeletal function, and alignment to confirm the diagnosis and determine a course of treatment. Finding and referring to a PT with experience in NMD is key to establishing appropriate goals and treatment plans. In this population, shoulder pain may not simply be due to the more common diagnosis of rotator cuff impingement but may involve the inability to stabilize proximal joints and/or prolonged muscle and nerve stretch due to weakened proximal muscles combined with limb dependence as well as overuse syndrome. Familiarity with NMD known patterns of weakness and gait deviations assists with treatment planning. A clinic NMD therapist should be available to consult with the treating therapist to ensure safe and effective treatment.

PTs establish a specific problem list with a corresponding treatment plan and set objective goals to be met within a specified time frame. Modalities are selected for their effectiveness on specific pathology, such as pain or muscle spasms. Exercise prescription, including body posture, stabilization, exercise repetitions, and duration, are established. Close monitoring for response to exercise, including levels of fatigue, changes in weakness, and reporting of pain, is necessary. Movement analysis of gait and transfers is followed with training in gait strategies and energy-efficient techniques. Trial with various ambulatory or transfer assistive devices is used to maximize mobility.

A unique but important role is performed by outpatient pediatric PTs. These therapists have expertise in normal and abnormal developmental movement patterns. Experienced therapists are able to recognize early signs and symptoms suggestive of an NMD, such as lack of developmental progression despite intervention in a floppy infant, and initiate referral to an NMD specialist for early diagnostic work-up and intervention. A pediatric therapist also provides developmental therapy to a young NMD infant or child, maximizing function and assisting progression through developmental stages.

In the Home

Home-based PT is reserved for homebound patients who cannot access a therapy facility for medical reasons. The home setting is unique in that the therapist may address a patient’s mobility limitations in the daily living space and recommend changes to the environment for optimal safety and mobility. Assessments may be performed to determine the most appropriate DME for a patient’s home. Problem solving and improvising with available home items is possible and can be valuable for easing the challenges of care giving. Providing treatment in the home affords greater privacy and, for the very ill, maximizes the energy available for treatment. Many home therapists, however, have little experience with NMD clients and may need to consult with a clinic NMD therapist.

Home therapists perform evaluation and assessment of a patient’s condition and set a treatment plan and goals that can be achieved in the home. Therapeutic exercises may be restricted due to limited availability of equipment but can include ROM exercises, resistance or isometric exercises, dynamic stabilization, gait training, or transfer training. Portable modalities may be available but are usually limited in scope. Home is a good place for caregiver training with focus on positioning and transfers. Educating caregivers in proper body mechanics and safety as well as community resources is invaluable. Once patients may safely leave the home to access outpatient therapy services, care should be transferred to an outside provider if they have continued functional therapy goals. In the United States, insurance companies do not usually cover physical therapy for maintenance or prophylactic services, so therapy must be discontinued when a patient does not have further functional goals.

In the School

The pediatric population spends a significant amount of time in the school environment. School-based therapy is often available and focuses primarily on educational goals, which are reflected in the treatment plan. Mobility, positioning, and staff training are frequent interventions to ensure accessibility and adaptability for pediatric NMD patients. Good communication between the NMD clinic therapist and the school therapist is important for implementing changes in DME or reporting changes in functional status that may have an impact on a patient’s performance in school.

Mobility is assessed as it relates to the classroom or school facility. Gait devices must be determined appropriate and safe for the classroom. Standers or gait trainers may be appropriate and allow a nonambulatory child to be upright for classroom activities or enable independent mobility for a marginally ambulatory child. Some children may be able to safely ambulate in the classroom but not beyond due to uneven terrain or risk of falls in a crowded hallway. A wheelchair may need to be provided before the complete loss of ambulation so a child can traverse the campus or participate in field trips. Power wheelchairs with recline, tilt, or standing functions must be accommodated into the classroom for nonambulatory children.

The most important role of the school therapist is to ensure that a child is able to participate in all educational tasks. Successful ergonomics in the classroom include a student’s posture and positioning at the desk, upper extremity support and position when writing, and type of writing utensils and/or communication device. The therapist may provide additional trunk support, modify seating, try alternate positioners, modify writing utensils, or apply wrist splints to decrease pain. For the more involved child with spinal muscular atrophy (SMA) or congenital muscular dystrophy, extensive adaptations may be necessary and involve the full educational team. PTs participate in developing an individual education plan for each child that guarantees students receive everything necessary to accommodate their disability in the classroom.

Finally, the school PT instructs the school staff in the safest methods to assist a child who has transfer needs for toileting and recommends appropriate transfer and or toileting equipment. Thorough training of the school staff in transfers ensures the safety for both child and staff caregiver.

In the Workplace

The Americans with Disability Act requires that employees with qualifying disabilities be reasonably accommodated in the workplace. An NMD clinic therapist may help determine when an adult needs special accommodation in a place of employment. These recommendations may include modification of the workstation, mobility device specific for the occupation, and bathroom equipment and workplace accessibility.

In Research

PTs have played a role in clinical research for NMD since the mid-1970s, participating in the design, standardization, implementation, and documentation of reliability of clinical outcome measures and assessments. They have and continue to serve as clinical evaluators for therapeutic trials, performing the physical and functional assessments that serve as outcome measures and endpoints. PTs also have the opportunity to be clinical evaluators in natural history studies, helping to document the phenotype in several genotype/phenotype studies in NMD.

Outcome measures in neuromuscular diseases

Although promising and novel therapeutic agents have recently emerged for muscular dystrophies and other neuromuscular diseases, significant barriers to the development of adequate clinical trials in these diseases remain. Crucial deficiencies include lack of a detailed understanding of the characteristics and natural history of specific neuromuscular diseases, lack of objective clinical outcome measures that are sufficiently sensitive to changes in disease course, and lack of data that directly link changes in clinical outcome measures to patient-perceived well-being.

To understand whether a specific therapeutic intervention is effective in NMDs requires explicit identification of the context of the population being studied (diagnosis, demographics, and so forth), assessing the health status before an intervention is performed with an appropriate clinical endpoint, delivering the prescribed intervention, and measuring health status after the prescribed intervention has been delivered. All 3 dimensions (context, intervention, and outcome measures) must be addressed. Until recently, the diagnosis, pathophysiology, and genetics of many of the NMDs were not understood. For example, in many studies, the dystrophinopathies were aggregated together based on similar progressive muscle wasting, without understanding the different pathophysiologies of the individual diseases. The intervention, whether a pharmaceutical treatment, exercise regimen, social support, or other intervention, needs to be clearly defined and documented with regard to dose, frequency, and timing. Studies need to be performed to show that the outcome measure chosen for a clinical trial is reliable, valid, and responsive to change with the number of subjects chosen for the trial and the length of the trial.

For trials in NMDs, which are rare diseases, the burden of determining a reliable and responsive outcome measure is much greater than in cancer and cardiovascular disease, where a much larger number of patients can be used to power the study. Because most NMDs are rare diseases, the outcome measures need to demonstrate that a therapeutic intervention will make a clinical meaningful difference over the short time period (6–12 months) typically assessed in a clinical trial with limited numbers of subjects. The correct choice of outcome measures in clinical trials is critical to generate meaningful data that enable a therapy to move toward regulatory approval.

The 6-minute walk test (6MWT) has been chosen as the primary clinical endpoint for several recent clinical trials of ambulant subjects with Duchenne muscular dystrophy (DMD), Becker muscular dystrophy, SMA, Pompe disease, mucopolysaccharidosis, facioscapulohumeral muscular dystrophy (FSHD), fibromyalgia, glycogen storage disease, and polio. The 6MWT has been shown valid, reliable, and responsive to change in several different disease populations and has already received regulatory approval by the US Food and Drug Administration and the European Medicines Agency. Some of the advantages of the 6MWT are that it is easy to understand, easy to perform, valid, reliable, and responsive to change. The 6MWT uses an interval scale (distance) that permits the use of parametric statistical analysis (use of mean, SD, correlation, regression, and analysis of variance). A change of approximately 30 meters in the 6-minute walk distance (6MWD) has been accepted as a clinically meaningful difference.

Although the 6MWT has received regulatory approval, it is not the ideal outcome measurement for all clinical trials in NMDs. The 6MWT is only applicable in ambulant subjects, which limits its usefulness in a wide range of potential studies, and it does not necessarily change linearly with disease progression. In a PTC Therapeutics trial of Ataluren for boys with DMD, the subject population was limited to boys greater than 4 years of age who could ambulate at least 75 meters. Even with this limitation, the 6MWT outcome measure was not ideal for this 12-month trial of 174 subjects. Several boys lost their ability to ambulate during the trial and the change in 6MWD was not linear. Because loss of muscle function in DMD occurs against the background of normal childhood growth and development, younger children with DMD can show an increase in distance walked during 6MWT over 1 year despite progressive muscular impairment. The analysis of the percent-predicted 6MWD data (using an age and height–based equation fitted to normative data), however, may reduce the variability of the 6MWD and account for normal growth and development. Henricson and colleagues have shown that increases in 6MWD are proportional to normal growth up to approximately age 7 in boys with DMD, which is consistent with the commonly held concept of the honeymoon period in DMD during which functional gains, that result from growth and development, outpace disease progression such that percent-predicted 6MWD is stable at approximately 80% of healthy controls. Past age 7, boys with DMD experience substantial declines in percent-predicted 6MWD.

Because NMDs are diverse and have a large range of symptoms, choosing an optimal outcome measure for clinical trials has been challenging. It is now recognized that it is unlikely that one outcome measure can be used for all studies of NMDs. Instead, the outcome measure should be selected according to the population included in the trial, functional status of the patients at recruitment, duration of the study, and possible effect of the treatment. In some diseases, such as spinal muscular atrophy (SMA) or myotonic dystrophy, patients may be relatively stable over time, whereas other NMDs are relentlessly progressive (amyotrophic lateral sclerosis [ALS] and DMD). Therefore, the outcome measures used to assess changes in a patient with SMA are significantly different from those used in a patient with ALS.

Outcome measures that have been used to assess interventions in NMDs have (1) assessed functional capacity using timed function test or quantitative measures of strength with interval or ratio outcome measures, (2) assessed function or activity using ordinal scales that are typically evaluated by PTs, (3) assessed cognitive and psychological function using ordinal neuropsychological scales, and (4) assessed health status by measuring health status with person-reported quality-of -life scales.

Outcome measures that have been used to assess functional capacity using timed motor performance tests in individuals with NMDs include the measures listed in Table 1 . The advantages of these outcome measures are that they are interval and ratio scales and are able to be analyzed using parametric statistics. The difficulties in using these measures are that, in themselves, they provide little information regarding clinical meaningfulness. It is not inherently known what a 5-second difference in time to run or walk 10 meters means to a patient. If these data are combined with natural history data in DMD, as done by McDonald and colleagues, the data can be used to predict the likelihood that a boy with DMD would lose his ability to ambulate 1 year later. The timed motor performance and strength data can also be correlated with personal reported outcomes of health status of individuals to determine the clinical meaningfulness of changes of these outcomes. Another way to better understand the meaning of these outcomes is to develop a percent-predicted value similar to the Centers for Disease Control and Prevention growth charts or spirometry values for pulmonary function.

Table 1

Commonly used functional capacity measures

Timed Motor Performance Measures	Ordinal Measures of Function
Time to stand from floor	Medical Research Council manual muscle test
Time to stand from chair	ALS Functional Rating Scale
10-Meter walk time test	Barthel index
Time to climb 4 stairs	Brooke upper limb scale
Time to descend 4 stairs	Vignos lower limb scale
Timed up and go	Gross motor function measure
Timed get up and go	Egen Klassifikation scale
9-Hole peg test	Motor function measure
2-Minute walk test	Hammersmith functional motor scale
6-Minute walk test	Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders

Functions of NMD subjects have typically been evaluated by trained PTs using ordinal scales of measurement (see Table 1 ; Table 2 ). Although these scales have been validated, they are ordinal scales that require the use of nonparametric statistics (medians, modes, and percentiles) for analyses. These items are based on classical test theory that recruits items arbitrarily, without weighting. These scales describe the order, but not the relative size or degree of difference, between the items measured. Therefore, summing these scores can lead to misinterpretation of the data. No information is provided regarding the minimally clinical important difference for these measures.

Table 2

Cognitive function, neuropsychological, and quality-of-life measures

Cognitive and Neuropsychological Measures	Quality-of-Life Measures
California Verbal Learning Test	Individualized Neuromuscular Quality of Life
Category fluency test and color word test	PedsQL
Delis-Kaplan executive function system	NIH Neuro-Qol
Design fluency test	Euroqol (EQ-5D)
Five-factor inventory	Perceived Quality of Life Scale
Hooper visual organization test	Quality of Well-Being Scale
Letter and category fluency test	SF-36v2 Health Survey
Proverb test	Schedule for the Evaluation of Individual Quality of Life
Raven standard progressive matrices	Schedule for the Evaluation of Individual Quality of Life
Rey-Osterrieth complex figure test	Questionnaire for Adults Health-Related Quality of Life
Rosenberg self-esteem scale 20	Questionnaire for Adults Health-Related Quality of Life
Self-efficacy scale, sorting test
Stroop color and word test
Trail making test
Twenty questions test
Wechsler Adult Intelligence Scale–revised
Word context test

Research has shown that a combination of outcomes measures may better document motor function than a single measure. In addition to measures of physical function, PTs have used a host of scales to assess the cognitive function, neuropsychological function, and health-related quality of life of individuals with NMDs (see Table 2 ). Although most of these measures use ordinal scales, most have been related to normal control values and provide clinical significance.

To overcome some of the limitations of ordinal scales, new techniques using Rasch model and item response theory have been used to transform ordinal scores, which are scale dependent and of limited accuracy, into linearly weighted interval measures that are scale independent. This methodology has already been applied to the ACTIVLIM, the National Institutes of Health (NIH) Neuro-QOL quality-of-life scale, and the North Star Ambulatory Assessment of DMD. These activities significantly improve the usefulness of these outcome measures, allow the examination of confounding factors, improve the sensitivity of these scales, test for unidimensionality, and potentially permit the development of a scale that can reliably and responsively assess results from individuals who experience a much broader range of impairments. The responsiveness of these scales over time needs to be examined as personal reported outcomes of health status are collected to determine the clinically meaningful important differences.

The lack of validated outcome measures has been identified as a major barrier that has held back therapeutic development in NMDs and limited the translation of promising research results into clinical trials and treatments. Therefore, the development of specific and sensitive tools for assessing the effects of treatments in patients with NMDs is starting to receive a significant amount of attention. The TREAT-NMD Neuromuscular Network is working to harmonize the use of the most appropriate outcome measures for different diseases at different stages of their progression and is collating information about existing outcome measures into a single and freely available online resource. As outcome measures gain clinical significance, PTs will start using them in clinics to document response to therapeutic interventions and disease progression.