Muscular Dystrophy and SMA

NEUROMUSCULAR DISEASES: MUSCULAR DYSTROPHIES & SPINAL MUSCLE ATROPHY

Objectives

• Define Terms:

  • Muscular Dystrophy: A group of genetic disorders characterized by progressive weakness and degeneration of the skeletal muscles.

  • Myopathy: A disorder of the muscular system that leads to muscle weakness or dysfunction.

  • Neuromuscular Disease: A category of disorders that affect the motor unit including the anterior horn cell, peripheral nerve, muscle, or neuromuscular junction.

• Duchenne Muscular Dystrophy (DMD):

  • Epidemiology: Discuss the incidence and modes of inheritance.

  • Protein: Name the protein lacking in DMD.

  • Signs and Symptoms: Describe the physical examination findings categorized under three main groups.

  • Pseudohypertrophy: Identify which muscles are commonly affected.

  • Gait Deviations: Describe deviations in gait including toe walking and compensatory posture adjustments.

  • Muscle Weakness Progression: Note which muscle groups are affected first.

  • Gower’s Sign: Define and describe this important clinical sign.

  • Strengthening & Fatigue Impacts: Recognize how these factors influence DMD management.

  • Scoliosis Impact: Discuss the implications of scoliosis in DMD patients.

  • PT Evaluation & Treatment Focus: Discuss what physical therapy evaluates and targets in DMD.

  • Mortality Causes in DMD: Identify the primary causes of mortality associated with DMD.

Terminology

• Neuromuscular Disease Definition:

  • A disorder whose primary pathology affects any part of the motor unit from the anterior horn cell to the muscle itself (Tecklin).

  • Can be hereditary or acquired.

  • Classifications: Myopathy or dystrophy and neuropathy.

Muscular Dystrophy

• Characteristics:

  • Genetically determined conditions that follow a steady, progressive course.

  • Histopathologically, degenerative features are observed on microscopic examination.

  • See Table 12.1 in your text for detailed muscle disease characteristics.

Dystrophin-Glycoprotein Complex

• Location and Role:

  • Present in muscle cell membranes of skeletal muscles, heart, and smooth muscle.

  • Functions include stabilizing and protecting muscle fibers and transmitting force from the sarcomere to the extracellular matrix.

  • Deficiency leads to structural abnormalities and impairs the repair of normal muscle damage.

Muscular Dystrophy Protein Deficiencies

• Major Types & Their Proteins:

  • Dystrophin:

  • Associated with Duchenne Muscular Dystrophy (DMD) and Becker Muscular Dystrophy (BMD).

  • Sarcoglycan:

  • Related to Limb-girdle Muscular Dystrophy.

  • Merosin:

  • Found in Congenital Muscular Dystrophy.

Spinal Muscle Atrophy

• Nature of Disorder:

  • A neurogenic disorder characterized by anterior horn cell atrophy, affecting both sensory neurons and spinal interneurons (Tecklin).

Duchenne Muscular Dystrophy (DMD)

• Overview:

  • The most common X-linked disorder, affecting approximately 1 in 3500 live male births.

  • Also known as Pseudohypertrophic MD, caused by a defect mutation at the Xp21 gene, which codes for dystrophin.

Pathophysiology of DMD

• Mechanism:

  • Absence of dystrophin causes disruption of linkage between the sub-sarcolemmal cytoskeleton and the extracellular matrix, leading to sarcolemmal instability and resulting in micro-tears in the muscle membrane.

  • Increased intracellular calcium levels lead to muscle cell necrosis.

Early Symptoms of DMD

• Common early signs include:

  • Reluctance to walk or run.

  • Increased incidence of falls.

  • Difficulty with transitioning from ground to standing (notable Gower’s sign).

  • Toe walking and general clumsiness.

  • Pseudohypertrophy of the gastrocnemius, presenting as increased size.

  • Difficulty in ascending stairs and potential speech delays.

Medical Diagnosis of DMD

• Diagnostic Tools and Indicators:

  • Elevated serum creatine kinase (CK) levels.

  • Electromyography (EMG) shows non-specific myopathic features.

  • Muscle biopsy reveals degeneration and regeneration of fibers, along with inflammatory infiltrates and increased connective tissue and adipose cells.

  • Immunohistochemical staining demonstrates the absence of dystrophin in muscle cell membranes.

  • Genetic testing confirms diagnosis.

Clinical Presentation of DMD

• Age of Onset:

  • Symptoms often present between 1 to 5 years of age and can be misdiagnosed as developmental delays.

  • Confirmatory campaigns advocate checking CK when developmental delays are suspected.

  • Generally diagnosed around the age of 5 years, sometimes earlier.

  • Proximal muscle weakness is typically observed before distal weakness, leading to contractures in ankle plantar flexors and invertors, as well as hip and knee flexors.

  • Loss of unassisted ambulation occurs around age 9 to 10, with loss of capacity after age 13 raising questions about Becker Muscular Dystrophy versus other forms.

Gower’s Sign

• An observable sign where a child has difficulty rising from the floor and uses their hands to climb up their legs, indicative of proximal weakness.

DMD: Clinical Manifestation

• Notable physical features in DMD include:

  • Shoulders and arms held back while walking.

  • Posterior pelvic tilt and lordosis due to weak hip extensors.

  • Weak thighs, especially anterior segments leading to imbalance and frequent falls.

  • Bulging abdomen due to weakness in abdominal muscles.

  • Pseudohypertrophy of calf muscles, often mistaken for strength.

  • Spinal deformities and potential cardiopulmonary involvement noted.

Clinical Presentation of DMD - Continued

• Complications:

  • Cardiac issues such as dilated cardiomyopathy and arrhythmias contributive to congestive heart failure (CHF).

  • Respiratory muscle atrophy leading to reduced forced vital capacity, averaging a decline of 5% per year, though delayed with corticosteroid treatment.

  • Scoliosis tends to manifest once the individual is wheelchair-dependent; steroid use can lead to increased risk of scoliosis.

  • Orthoses have limited effectiveness in preventing curvature.

  • Gastrointestinal issues, including constipation, and the risk of acute gastric dilation or intestinal pseudo-obstruction.

  • Cognitive effects such as slightly decreased IQ and emotional disturbances are noted as well.

Steroid Use in DMD

• Role of Steroids:

  • Currently, the only pharmacological agent modifying the progression of DMD.

  • Prednisone and Deflazacort are commonly utilized.

  • Steroids can prolong ambulation by approximately 3 years while enhancing isometric muscle strength.

  • However, they may induce osteoporosis and necessitate careful stretching and fall risk education for patients.

PT Examination of DMD

• Purpose:

  • Evaluate patient's alignment and muscle strengthening.

  • Utilization of Manual Muscle Testing (MMT), dynamometry, and quantitative muscle testing (QMT).

  • Northstar Ambulatory Assessment provides insights into functional capacity.

PT Intervention of DMD

• **Goals:

  • Prevent deformity and prolong functional capacity.

  • Improve pulmonary function and facilitate appropriate family support.

  • Pain control is also prioritized.

  • Various intervention formats include Home Exercise Programs (HEP), outpatient physical therapy, and aquatic therapy, especially post-fracture.

Contracture Management

• Approach:

  • Implement daily stretching practices with a minimum hold time of 30 seconds, targeting hip & knee flexors, iliotibial band, and ankle musculature.

  • Night splinting and serial casting may be used, balancing the need for sarcomere length preservation.

Strengthening Practices

• Recommendations:

  • Careful monitoring of patients during strength training, avoiding eccentric loading.

  • Implement sub-maximal endurance programs, focusing on key muscle groups such as abdominals and lower extremities.

  • Engage in low-resistance activities such as cycling and swimming to promote strength without excessive strain.

Ambulation Challenges

• Impact of Weakness on Gait:

  • Weakness leads to decreased stride length, increased base of support, and lateral trunk sway commonly seen as Trendelenburg gait.

  • Toe walking can arise due to muscle compensation or heel cord tightness, while lordosis and reduced arm swing are also typical.

  • KAFOs (Knee-Ankle-Foot Orthoses) are generally not favored for functional ambulation but can assist in exercise.

Wheelchair Use

• Recommendations for Wheelchair Dependence:

  • Power wheelchairs or scooters are preferred over manually propelled ones to facilitate better mobility.

  • Initial setups should include simple controls like a joystick and supportive cushions for pressure relief.

  • Support and stabilization should be modified based on deteriorating voluntary muscle movement and postural asymmetries as the condition progresses.

Other Considerations with DMD

• Complications and Management:

  • Address medication side effects such as weight gain, growth suppression, cataract formation, and osteoporosis.

  • Prioritize pressure relief during sleep and facilitate activities of daily living (ADLs) through occupational therapy consultation.

  • Respiratory care may include inspiratory and expiratory aids, along with teaching effective coughing techniques and considering non-invasive ventilation options if necessary.

DMD - Think, Pair Share Exercise

• Situation A:

  • As a school PT, assessing a kindergarten child exhibiting Gower’s sign and a waddling gait, consider initiating an evaluation or referral.

• Situation B:

  • Evaluate the capacity of an 8-year-old child with DMD who can ambulate short distances for participating in a planned trip, providing guidance on pacing and activity allowances.

Other Types of Muscular Dystrophy

• Subtypes Reviewed:

  • Becker Muscular Dystrophy (BMD)

  • Congenital Muscular Dystrophy

  • Myotonic Dystrophy

  • For additional information, refer to the course text.

Becker Muscular Dystrophy (BMD)

• Overview:

  • A variant of DMD with a slower disease progression and a prevalence of 1 in 20,000 births.

  • Dystrophin is present but in reduced quantities, with symptoms manifesting in late childhood or early adolescence, typically by age 11.

  • Individuals experience loss of ambulation often by age 27, though steroid use can prolong functionality and strength; cardiac issues are also more common.

Congenital Muscular Dystrophy

• Characteristics:

  • Several types exist; some involve CNS complications.

  • Merosin deficiency is the most common subtype, leading to significant weakness and contractures evident at birth, often requiring ventilator support.

  • Intellectual disabilities are prevalent, impacting mobility choices.

Myotonic Dystrophy

• Characteristics:

  • Defined by myotonia, a delay in muscle relaxation.

  • Type I (DM1) presents mostly in adolescents with symptoms of muscle weakness (distal to proximal) and myotonia.

  • Congenital DM1 can lead to severe outcomes, including intellectual disabilities and diaphragm paralysis at birth.

Spinal Muscle Atrophy (SMA)

• Overview:

  • The second most common group of fatal recessive diseases after cystic fibrosis (CF).

  • An autosomal recessive disorder associated with a genetic defect on chromosome 5q13 resulting in decreased survival motor neuron (SMN) levels, leading to motor neuron loss.

  • Types are based on functional abilities, from Type I (no sitting or walking) to Type IV (adult onset).

SMA Type I

• Clinical Features:

  • Muscle fasciculations, particularly in the tongue, and paradoxical breathing necessitating respiratory care.

  • Limited anti-gravity movements, potentially requiring positioning aids.

  • Contracture management and feeding support through occupational therapy or speech-language therapy; often necessitating feeding tubes.

  • Risks leading to death typically stem from pneumonia or respiratory complications, with Spinraza emerging as a treatment option.

SMA Type II

• Clinical Features:

  • Symptoms onset occurs within the first year, with 90% able to sit independently by 12 months.

  • Contractures frequently develop, and tongue fasciculations occur in 50% of cases.

  • Trunk support may be necessary via TLSO, with standing programs initiated early, and power wheelchairs preferred for increased support.

  • Exercise and endurance programs must be monitored for fatigue.

SMA Type III

• Clinical Features:

  • Symptoms typically emerge once walking begins.

  • Individuals can be categorized by the age of onset of weakness; tongue fasciculations are commonly observed in about 50% of patients.

  • Minimyoclonus and fatigue are prevalent among this group.

  • Proximal weakness leads to increased lordosis and compensatory Trendelenburg gait.

  • Scoliosis often develops in late teens or early twenties.