Adult Spinal Muscular Atrophy: Introduction

About Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) is a group of genetically inherited neuromuscular disorders that cause serious muscle weakness, muscle degeneration, and atrophy. Globally, SMA prevalence is estimated to be around 1 to 2 individuals in 100,000, with an incidence rate of about 1 in 10,000 live births.¹ It is the most common genetic cause of spinal motor neuron disorder.

There are five types of SMA (see below) caused by a mutation or deficit of a specific gene known as survival motor neuron 1 (SMN-1) on chromosome 5q.¹ In healthy people, the SMN-1 gene produces survival motor neuron protein which is responsible for the proper functioning of neurons that control motor function.

People with SMA have inadequate levels of SMN protein which causes deterioration of anterior horn cell alpha motor neurons in the spinal cord and brain stem. This gap leads to progressive dysfunction and atrophy of skeletal muscles and, in severe cases, may even cause paralysis.

SMA is also considered to be an autosomal recessive disorder, which means both parents pass on the gene mutation for a child to develop the condition.

In less than 5% of cases, SMA is caused by mutations of other genes.¹ Two types of SMA caused by non-SMN gene mutations include distal SMA and spinobulbar muscular atrophy (also known as Kennedy’s disease). Kennedy’s disease is the most common type of adult-onset SMA. It is caused by a recessive X chromosome linked disorder that only affects men.² Distal SMA can be passed on from one parent and affects the muscles farthest away from the core causing weakness in the hands and feet.

There are five types of SMA categorized by the age of onset and clinical severity of compromised motor function.³ See Table I.

This primer focuses on adult SMA caused by an SMN-1 mutation.

SMA Type 4 primarily affects adults and is the least common type of SMA. There is limited data available regarding the prevalence and incidence rates of Type 4 due to delayed diagnosis stemming from similarities with other adult onset lower motor neuron disorders.² For SMA-4, differential diagnosis to rule out other causes of motor neuron disorders such as amyotrophic lateral sclerosis (ALS) are an important part of the diagnostic process. Delayed diagnosis can lead to increased loss of muscle strength, endurance, and functional abilities.

According to the National Institute of Health (NIH) Genetic and Rare Diseases Information Center, the prevalence of SMA-4 is around 1 in 300,000.⁴ SMA-4 is the mildest type of SMA disorder, representing less than 1% of overall SMA cases.

Adult SMA collectively encompasses both SMA-4 adult onset and those who develop SMA symptoms in childhood and survive beyond 18 years of age. However, adult-onset SMA-4 has unique implications for diagnosis, disease burden, quality of life, and treatment. Symptoms and disease progression associated with adult-onset SMA can significantly disrupt activities of daily living, work, and impact independence since it develops later in life. There are distinct areas of muscle weakness affecting the quadriceps, deltoid, and triceps in early stages of the disease.

Symptoms of SMA can depend on age of onset, type, and severity of the condition. The most common symptoms include poor or weak muscle tone and weakness in proximal limbs and the truncal area. Studies have shown individuals who have greater copies of the related SMN-2 gene (which also produces smaller amounts of SMN protein), have less severe disease.⁵

• muscle weakness

• decreased or absent deep tendon reflexes

• nutritional deficits

• loss of muscle tone

• involuntary tongue movements

• hand tremors

• scoliosis

• respiratory complications, infections

• tight joints

• serious functional limitations

SMA-4 symptoms specifically may also include gradual decline in gait, muscle degeneration, and function. Therefore, people with adult-onset SMA may also experience:⁶

• leg weakness

• waddling gait

• limb-girdle muscle weakness (hip and shoulder area)

• fasciculations

• lack of tendon reflexes

• muscle atrophy of extremities

• muscle discomfort

• fatigue

• tremors

• respiratory complications

A majority of SMA cases are caused by mutation or deletion of SMN-1 gene, therefore, definitive diagnosis includes genetic testing for the presence or absence of SMN-1. In addition, determining the number of copies of SMN-2 genes helps to predict SMA type and detect disease severity. Early diagnosis for SMA-4 is important in reducing disease progression and muscle atrophy.

Diagnosis may be based on:

• genetic testing for SMN-1 gene (mutation or missing), copies of SMN-2

• assessment of muscle weakness, respiratory, gastrointestinal, and associated factors

• electromyography (EMG) to measure electrical activity within nerves

Other functional assessments may include:

• Hammersmith Functional Motor Scale ‐ Expanded (HFMSE) to assess motor function⁷

• Spinal Muscular Atrophy Functional Rating Scale (SMAFRS)

• 6 Minute Walk Test (6MWT) to test endurance and exercise capacity⁸

While there is no cure for SMA, there are a range of available treatments to help manage the disease, which are tailored to type and disease severity. A multidisciplinary approach that combines medications with therapeutic programs including respiratory, nutritional, physical, and occupational therapy are core strategies across SMA types. Physical therapy is a mainstay of adult SMA management.

There are distinguishing physical therapy treatment components for adult SMA dependent on individual patient factors, such as muscle degeneration at the time of assessment. Physical therapists with Neurologic Clinical Specialist (NCS) certification work with patients to maintain muscle mass and prevent declines in strength, range of motion and quality of life.

Treatment objectives for adult onset SMA-4 are distinct in several ways. According to Alison Lichy, PT, PhD, DPT, NCS, and Elssa Federovich, PT, NCS with Neurological Physical Therapy PLLC & Evolution Pilates, evaluation is an important component of physical therapy programs to set baseline muscle tone, flexibility and to assess disease progression for adult-onset SMA-4.

Drs. Lichy and Federovich pointed out that people with SMA-4 tend to have impairments in postural control, muscle wasting, and spasticity. On the other hand, adults with SMA-3, for example, may have higher levels of dysfunction including a baseline lower bone density.

Therapists should be aware SMA-3 patients have less muscle mass, may not be weight-bearing, have other muscle related complications such as scoliosis, respiratory issues, and contractures as distinguishing features for PT management compared to SMA-4 patients.

Physical Therapy Strategies for SMA-3 and SMA-4

Dr. Lichy recommends the following:

• Focus on individualized treatment for the patient’s specific needs and adapt therapy based on patient impairments and responses to treatment.

• Early detection and treatment of muscle degeneration based on disease progression rather than muscle misuse are important in preventing further decline in range of motion, strength, and alignment.

• Establish whether the patient is compensating due to disuse or due to disease progression, especially due to an increased sedentary lifestyle during the ongoing COVID-19 pandemic; atrophy or too much tone may need bracing or an assistive device to control balance so the patient can stand and walk (distinct from tightening from disuse)

In addition, Dr. Lichy and Dr. Federoich suggest that physical therapy for adults with SMA-4 focus on:

• postural training (seating, positioning)

• chest mobility with breathing exercises to prevent pneumonia

• contracture prevention range of motion for efficiency of movement

• good biomechanics

• maintaining muscle mass

• progressive resistance training focused exercise

• orthotist resources (assistance with bracing, wheelchair specialists)

• support from other disciplines (eg, speech therapist, respiratory therapist)

Additional types of physical therapy for SMA management, depending on the case, may include:

• strength training, weight bearing exercises for adults with Type 4

• therapeutic exercise

• balance training

• aquatic therapy to improve balance, endurance, and strength

• adaptive sports to increase endurance

• range of motion, stretching to reduce contractures and improve flexibility

• breathing

The main goals of physical therapy for SMA-4 are to preserve flexibility, maintain optimal postural alignment, functional strength and muscle mass while also delaying declines in range of motion and strength. In addition, management of contractures (joint tightness) helps slow functional decline.¹²

Emerging Spinal Muscular Atrophy Treatments

In addition to physical therapy for SMA, new gene replacement therapy and disease-modifying drugs are improving outcomes and slowing progression of muscle degeneration.

These include:

• nusinersen – FDA approved in 2016, indicated for the treatment of SMA in both pediatric and adult patients⁹

• risdiplam – FDA approved in 2021, indicated for the treatment of SMA in patients 2 months of age and older ¹⁰

• onasemnogene abeparvovec – FDA approved in 2019, indicated for use in treating SMA type 1¹¹

Other treatments that may be used for SMA include:

• breathing support

• surgery to address scoliosis

• preventive medications related to lung infection, mucus

• nutritional support

• assistive medical devices (eg, walkers, canes, braces, wheelchair)

Early detection, particularly for adult-onset SMA-4, is crucial to slow muscle deterioration and loss of functional capacity.

Overall, physical therapists play a key role working with interdisciplinary teams (clinicians, respiratory, occupational and speech therapists) to improve daily function, endurance, and independence for those with adult onset SMA-4 who typically have mild disease and live a normal lifespan.

• SMA Standards of Care

• SMA Foundation

• Academy of Neurologic Physical Therapy

• CureSMA SMArt Moves

• SMA Diagnostic Toolkit

Additional Resources in our Spinal Muscular Atrophy Clinical Primer

• How to Introduce Physical Therapy to Patients: A Scripted Dialogue

• Part II: Best Practices in SMA Bedside Manner

• Part III: Physical Therapy Techniques and Strategies for Managing SMA in Adults

• Part IV: SMA Comorbidity Management