Muscular Dystrophy and Related Disorders 2024 PDF

Muscular Dystrophy and Related Disorders Neuromuscular Diseases Neuromuscular diseases include: Disorders of the motor nerve (anterior horn cell and peripheral nerve) Polio, CMT (Charcot-Marie Tooth), ALS (Amyotrophic Lateral Sclerosis) Disorders at the neuromuscular junction...

Muscular Dystrophy and Related Disorders Neuromuscular Diseases Neuromuscular diseases include: Disorders of the motor nerve (anterior horn cell and peripheral nerve) Polio, CMT (Charcot-Marie Tooth), ALS (Amyotrophic Lateral Sclerosis) Disorders at the neuromuscular junction Myesthenia Gravis Disorders of the muscle Muscular Dystrophy and Spinal Muscular Atrophy Muscular Dystrophy & Spinal Muscular Atrophy MD, and SMA are characterized by: Progressive Weakness Muscle Atrophy Contracture Formation Progressive Disability At times shortened lifespan Usually have a genetic origin Not curable but TREATABLE Muscular Dystrophies Duschenne: Onset 1-4 years, x-linked, rapid progression Becker: Onset 5-10 years, x-linked, slower progression Congenital: Onset Birth, recessive, slow progression, shortened life-span Congenital Myotonic: Onset Birth, slow progression with significant intellectual impairment Facioscapulohumeral: Onset in 1st decade, slow progression, late loss of ambulation, variable life expectancy Duchenne Muscular Dystrophy 1 in 3,600-6000 live male births Dystrophinopathy mutation in the gene coding for the protein dystrophin Child becomes progressively weaker Morbidity related to respiratory insufficiency and/or heart failure X-linked inheritance pattern Male offspring inherit the disease from their asymptomatic  mdausa.org http://www.nytimes.com/2013/09/24/health/ gene-therapy-with-a-difference.html?_r=0# Duchenne Muscular Dystrophy New mutation (spontaneous occurrence without family history of DMD) rate of approx. 1 in 10,000. Thus 1/3 of cases are new mutations. Genetic marker: abnormal gene on the x chromosome at band Xp21.2 which encodes for dystrophin Pathophysiology Absence of dystrophin leads to a reduction in all of the dystrophin-associated proteins in the muscle cell membrane Causes a disruption in the linkage between the subsarcolemmal cytoskeleton and the extracellular matrix DMD - Pathogenesis Lack or absence of dystrophin Destabilizes the membrane Allows calcium influx Activation of a calcium-activated proteinase Destruction of the cell Muscle cells are replaced by fatty & connective tissue Diagnosis of DMD Blood Work: Creatine Kinase (CK) levels in the blood are significantly elevated, 100x in the early stages of the disease and are elevated even at birth. Genetic Testing: by blood work $$$$ Muscle Biopsy: specimens show degeneration and loss of fibers, increased fat and connective tissue EMG: Electromyography shows low amplitude, short duration polyphasic motor unit action potentials DMD – Clinical Picture Muscle weakness Becomes apparent at ages 3 to 5 (demonstrated on MMT) Symmetrical Proximal > distal Lower extremities and torso more affected than upper extremities Shoulder girdle weakness Excessive scapular winging Difficulty in performing overhead activities Inability to use assistive devices for ambulation Steady decline in strength from 6 to 11 years old DMD – Clinical Picture Calf hypertrophy Present at age 5 to 6 years Pseudohypertrophy Muscle tissue replaced by fat and fibrous tissue Other muscles may look enlarged Gluteus Vastus lateralis deltoid Clinical Presentation Possible delayed onset of motor milestones, especially late walking Tripping, falling, poor ability to run or resistance to running, inability to keep up with peers Toe Walking, Pseudohypertrophy of the calves Progressive weakness, lordosis, waddling gait Gower’s Sign JAMAnetwork.com Medical Management Pre-Natal Care: Genetic Counseling for families with history, possible in utero testing Early Diagnosis: CK levels, genetic testing, biopsy Nutritional Management: Obesity is a significant problem, bone health issues Orthopedic Management: Lengthening of contractures, Spinal stabilization for scoliosis Cardiopulmonary Management: Including pulmonary function testing Clinical Progression Weakness is steadily progressive Proximal muscles tend to be weaker earlier in the course of the illness and progress faster Lumbar lordosis Wide base of support with gait Contracture development Slow functional activities Progression Birth to 2 years: late acquisition of milestones, especially walking 3-5 years: toe walking,clumsiness, pseudohypertrophy of calves, Gower’s Sign 6-8 years: toe walking, lordosis, inability to climb stairs without assistance, wide based waddling gait, can not rise from floor without help. 9-11 years: walks with braces, scoliosis,may have orthopedic surgery, beginning respiratory insufficiency Progression 12-14 years: Loss of ambulation, increased respiratory difficulties, obesity, contractures, progression of scoliosis, dependant for transfers, needs assist with ADL’s 15-17 years: Dependant in most ADL’s, may need assisted ventilation 18+ years: Totally dependant, assisted ventilation, death comes after a period of declining respiratory function Scoliosis Scoliosis develops as the age of the child with DMD increases Significant curves are generally not noticed until after the age of 11 years Progress as the back muscles become weaker and as the child spends less time standing and more time sitting Over time, becomes fixed Respiratory Respiratory musculature atrophies Coughing becomes ineffective Pulmonary infections become more frequent The major cause of respiratory complications in DMD is the progressive weakness of the muscles of respiration Cardiac Deficiency of dystrophin resulting in cardiomyopathy, arrhythmias, and congestive heart failure The posterobasal portion of the left ventricle is affected more than other parts of the heart Heart muscle involvement generally occurs later than skeletal muscle involvement Cognitive A high rate of intellectual impairment and emotional disturbance This deficit is not progressive and is not related to the severity of disease IQ scores fall approximately 1 SD below the mean Verbal scores affected more than performance scores Importance of Treatment Proper treatment can prolong quality of life Parental counseling in an attempt to reduce the guilt, hostility, fear, depression, hopelessness, and numerous other emotions commonly experienced by the parents An active PT program may prolong ambulation and more closely approximate the normal independence of later childhood If a specific treatment ever becomes available, those in optimal physical condition are most apt to benefit Medical Treatment Corticosteroids (prednisone, and deflazacort) have been shown to increase strength and improve function for 6 months to 2 years Creatine monohydrate (natural body- building substance) Increase in levels of creatine in muscles, and improvements in maximal exercise performance and recovery from exercise in healthy subjects Investigation of myoblast transplant with the aim of replacing the missing protein dystrophin Experimental Treatment Cell Therapy Gene Therapy Mutation specific medication Other Drug Therapies: Utrophin/Myostatin Orthopedic Treatment Indications Spinal fixation recommended when scoliosis begins to progress rapidly, and spinal curve exceeds 30° Pelvic obliquity, skin breakdown, discomfort and decreased tolerance to sitting, and difficulty using upper extremities secondary to lack of trunk stability requiring propping on arms Achilles tendon lengthening, fasciotomies, tibialis posterior transpositions, and percutaneous tenotomies in an attempt to increase joint range of motion for prolonging ambulation Orthopedic Management – Muscle Lengthening Surgical Intervention: no solid consensus, must be planned on a highly individualized basis Tendo-Achilles lengthening, Hamstring lengthening, lengthening of TFL sometimes advocated in younger children 4-7 years, but much less than years ago Some suggest that in Middle ambulatory phase tendon lengthening may prolong ambulation for 1-3 years but again no consensus In non-ambulatory phase, tendon Achilles lengthening, posterior tibialis transfer or lengthening procedures to relive contractures to foster foot placement and LE alignment in the W/C and allow shoe ware Orthopedic Treatment: Scoliosis Monitoring for scoliosis should begin early Begin radiographs when ambulatory if scoliosis suspected clinically Radiographic Baseline needed when wheelchair dependency begins Annually for curves 15-20 Every 6 months for curves > 20 TLSO’s are not indicated in this population Spinal fixation recommended when scoliosis begins to progress rapidly and spinal curve exceeds 30 degrees. Pulmonary Treatment Nasal positive pressure ventilation at night to assist breathing and to provide a rest for overworked respiratory muscles An adjustment period is often necessary, but after a period the patient often derives the benefits of improved sleep and increased energy and alertness in the daytime Ventilatory assistance might be required both day and night for children with advanced respiratory Cardiac Treatment Regular cardiac echocardiogram (ECHO) and electrocardiogram (ECG or EKG) monitoring Cardiac medications for arrhythmias may be necessary Physical Therapy Examination 3 phases of presentation Early or ambulatory stage Transitional phase during loss of ambulation Later stage when the child or young adult uses a wheelchair for mobility and is dependent for most functional activities History Family, birth, and developmental history Review of systems Including cardiac, pulmonary, gastrointestinal, and musculoskeletal systems, functional mobility, social history, and current durable medical equipment The primary concerns of the child and family should also be understood prior to examining the child Developmental history Review of Systems Pulmonary, cardiac, GI, integumentary, and musculoskeletal systems Referral to specialist if necessary  Tests and Measures Functional abilities Stable performance or declining performance Assessing strength, pulmonary function, and functional tasks in combination PEDI 6-minute walk test Brooks grades for UE – Vignos for LE Energy Expenditure Index Tests and Measures (cont’d) Muscle strength MMT must be a routine part of the physical therapy evaluation of the child with myopathy No correlation between rate of decline and use of wheelchair Hand-held myometers and various fixed tensiometer systems have been used in attempts to better quantify muscle strength in boys with DMD Tests and Measures (cont’d) ROM Loss of full ankle dorsiflexion, knee extension, and hip extension, with resultant contractures Measurement of these are the most important aspects of goniometric testing Primary Physical Therapy Problems Weakness Decreased active and passive ROM Loss of ambulation Decreased functional ability Decreased pulmonary function Emotional trauma—individual and family Progressive scoliosis Pain Goals for Physical Therapy Prevent deformity Splinting and positioning Improve pulmonary function Respiratory aids Goals for Physical Therapy (cont’d) Prolong functional capacity Normal age-appropriate activity Avoid maximal resistive strength training and Avoid eccentric exercise – Lack of dystrophin increases susceptibility to muscle cell damage* Submaximal, endurance training such as swimming or cycling Orthopedic surgery for ambulation Standard or power wheelchair use Goals for Physical Therapy (cont’d) Facilitate the development and assistance of family support and support of others Control pain Management of pain should be addressed through education, positioning, proper lifting techniques, medical treatment with creatine. Pain may occur at the limits of ROM in all joints due to contractures, muscle pain due to overuse, impingement syndrome from lifting, or prolonged wheelchair positioning. Therapeutic Interventions Prevention of Contractures Exercise to maintain maximal function Prevention of Obesity Maintenance of Ambulation Respiratory Care Adaptive Equipment and Bracing Transition to Wheelchair Address Psychosocial issues Physical Therapy Intervention Home program is essential Stretching, stretching, stretching Weight control Weight Control improves mobility and self- esteem Better to prevent excessive weight gain in the young, ambulatory child than to initiate severe dietary restriction in an obese, seated adolescent Exercise and Neuromuscular Disease All Patients should be advised not to exercise to the point of exhaustion due to the risk of muscle damage Patients in exercise programs should be aware of the signs of overwork weakness Feeling weaker rather than stronger 30 minutes after exercise Excessive DOMS 24-48 hours after exercise Severe muscle cramping Heaviness in the extremities Prolonged shortness of breath Exercise and Neuromuscular Disease Strength Training can be prescribed but use caution and a common-sense approach In slow progressing NMD a 12- week moderate strengthening program have been found to increase strength without harmful effects (high resistance strengthening program does not offer better gains) Kilmer DD, McCrory MA, Wright NC, Aitkens SG, Bernauer EM. The effect of a high resistance exercise program in slowly progressive neuromuscular disease. Archives of Physical Medicine and Rehabilitation. 1994 May;75(5):560-563. PMID: 8185450. REMEMBER: Dystrophin deficient muscle is very susceptible to exercise induced muscle injury SO BE CAUTIOUS Exercise and Neuromuscular Disease Aerobic exercise can help improve cardiovascular performance and increase muscle efficiency thus help fight fatigue Gentle low impact exercise, walking, swimming, stationary bike, UBE Improves physical function as well as may help in fighting depression, maintaining body weight and improving pain tolerance Additional Muscular Dystrophies Duchenne: Onset 1-4 years, x-linked, rapid progression Becker: Onset 5-10 years, x-linked, slower progression Congenital: Onset Birth, recessive, slow progression, shortened life-span Congenital Myotonic: Onset Birth, slow progression with significant intellectual impairment Facioscapulohumeral: Onset in 1st decade, slow progression, late loss of ambulation, variable life expectancy Myotonic Dystrophy (MTD) Autosomal dominant disorder whose location is on chromosome 19 Symptoms are first noticed during adolescence and are characterized by myotonia, a delay in muscle relaxation time, and muscle weakness As the weakness progresses, the myotonia decreases Presentation to the clinic with complaints of weakness and stiffness Many patients also have cognitive impairment, cataracts, diabetes, cardiac arrhythmias  Limb Girdle Muscular Dystrophy A group of progressive muscular dystrophies that affect the proximal musculature The initial presentation can be quite variable extending from early childhood into adulthood The underlying pathology of LGMD is quite heterogeneous Gower to get up from chair, waddling gait Congenital Myopathy A group of diseases including nemaline myopathy, central core myopathy, and centronuclear (myotubular) myopathy Results from abnormalities of the sarcomeric proteins Characterized by weakness and muscle atrophy that typically presents at birth Congenital Muscular Dystrophy Incidence and Etiology 4.65 in 100,000 In Italian population Group of inherited disorders Autosomal recessive Onset At birth or shortly after Congenital Muscular Dystrophy Those with central nervous system involvement and those without central nervous system involvement Fukuyama congenital muscular dystrophy, Walker-Warburg syndrome, and muscle-eye- brain disease all demonstrate muscle, brain, and eye abnormalities Spinal Muscular Atrophy Spinal muscular atrophy is a disorder that is manifested by a loss of anterior horn cells Results in a phenotypic spectrum of disease states that have been divided into three types of SMA based on a functional classification system Spinal Muscular Atrophy SMA type 1: also known as Werdnig- Hoffman Acute. Onset at 0-3 months, Recessive, Severe hypotonia, death within 1st year SMA type 2: AKA Werdniq-Hoffman Chronic, Onset 3mo-4years, Recessive, Rapid progression, then stabilizes, moderate to severe hypotonia, shortened lifespan SMA type 3: AKA Juvenile onset, 5-10 years, Recessive, Slow progression, milder impairments  SMA type I Imagine you've been diagnosed with an incurable genetic disease and you are told you will not only lose your ability to walk and move your arms, but you will die between now and the next 18 months. What would you do? My name is Avery Lynn Canahuati, I'm almost 5 months old, and this has become my reality. But before I die, there's a few things I'd like to accomplish... this is my bucket list and my story. SHARE IT & HELP ME TELL THE WORLD ABOUT SMA!  SMA type II SMA type III Spinal Muscular Atrophy Type I (Werdnig-Hoffman Disease) Noted within the first 3 months of life Mother complains of decreased fetal movement during her pregnancy At birth, the affected child is hypotonic and may have difficulty feeding Muscle wasting is often severe, and spontaneous movements are infrequent and of small amplitude Presents with a head lag on pull to sit and will drape over the examiner’s hand when a Landau is performed Spinal Muscular Atrophy Type II Affects infants but is more benign than SMA type I Presentation is later in the first year of life when the child is not pulling to stand Characterized by weakness and wasting of the extremities and trunk musculature Fasciculations are common on examination of the tong in these patients Fine tremor when the child attempts to use the limbs Mini-polymyoclonus May learn to walk with bracing Spinal Muscular Atrophy Type III (Kugelberg-Welander Disease) Symptoms of progressive weakness, wasting, and fasciculations Age of presentation can vary from the toddler years into adulthood, the latter of which some would classify as type IV Proximal muscles are usually involved first, and because of the age of presentation, this disease may be confused with the muscular dystrophies Spinal Muscular Atrophy Type III (Kugelberg-Welander Disease) (cont’d) Deep tendon reflexes are decreased, but contractures are unusual, and progressive spinal deformities are uncommon as long as the child remains ambulatory Diagnosis is established on the basis of the clinical picture and the results of diagnostic laboratory studies, including an electromyogram and muscle biopsy, which show denervation as in the other forms of SMA Genetic testing will show a deletion of the SMN gene on the fifth chromosome Prognosis Can be aided by a good developmental history Symptoms that begin prior to 2 years of age have a relatively poorer prognosis If symptoms begin after 2 years of age, on average patients continue to ambulate until 44 years of age If symptoms begin prior to 2 years of age, ambulation is maintained until an average of 12 years of age  A device that assists with coughing can help clear respiratory secretions. Photo courtesy of Respironics This girl with type 2 SMA used a back brace as a toddler. At 9, she underwent surgery to correct a spinal curvature, Adults with SMA are often able to drive with and wore a temporary brace while specialized hand controls. recovering from surgery. https://www.mda.org/disease/spinal-muscular- https://www.mda.org/disease/spinal- atrophy/medical-management muscular-atrophy/medical-management Treatment Treatment focuses on the maintenance of function and flexibility Patients need to be braced appropriately while they are still ambulating and for standing after they stop ambulating Standers can be helpful to maintain flexibility and bone stock through a standing program Charcot Marie Tooth Disease Charcot-Marie-Tooth disease (CMT) is one of the most common inherited neurological disorders, affecting approximately 1 in 2,500 people in the United States. CMT, also known as hereditary motor and sensory neuropathy (HMSN) or peroneal muscular atrophy, comprises a group of disorders that affect peripheral nerves Charcot Marie Tooth Disease There are many forms of CMT disease, including CMT1, CMT2, CMT3, CMT4, and CMTX. CMT1, caused by abnormalities in the myelin sheath. CMT1A is an autosomal dominant disease that results from a duplication of the gene on chromosome 17 that carries the instructions for producing the peripheral myelin protein-22 (PMP-22). The PMP-22 protein is a critical component of the myelin sheath. Overexpression of this gene causes the structure and function of the myelin sheath to be abnormal. Patients experience weakness and atrophy of the muscles of the lower legs beginning in adolescence; later they experience hand weakness and sensory loss. Charcot Marie Tooth Disease A typical feature includes weakness of the foot and lower leg muscles, which may result in foot drop and a high-stepped gait with frequent tripping or falls. Foot deformities, such as cavus or cavo-varus and hammertoes are characteristic due to weakness of the small muscles in the feet. The lower legs may take on an "inverted champagne bottle" appearance due to the loss of muscle bulk. Later in the disease, weakness and muscle atrophy may occur in the hands, resulting in difficulty with carrying out fine motor skills Charcot Marie Tooth Disease Diagnosis of CMT begins with a standard medical history, family history, and neurological examination. During the neurological examination look for evidence of muscle weakness in the individual's arms, legs, hands, and feet, decreased muscle bulk, reduced tendon reflexes, and sensory loss. (touch, position sense, vibration) Nerve conduction studies and electromyography (EMG) Charcot Marie Tooth Disease PT & OT for CMT, involves muscle strength training, muscle and ligament stretching, and moderate aerobic exercise. It is suggested entering a treatment program early; muscle strengthening may delay or reduce muscle atrophy, so strength training is most useful if it begins before nerve degeneration and muscle weakness progress to the point of disability. Recommend low-impact or no-impact exercises, such as biking or swimming, rather than activities such as walking or jogging, which may put stress on fragile muscles and joints. Charcot Marie Tooth Disease Patients with CMT must be careful about caring for their feet and toes, often a podiatrist may be involved to keep toes and toenails in good condition and work with callous formation Common areas for increased pressure and callous formation is on the lateral border of the foot and heel, the head and base of the 5th metatarsal Shoe wear must be carefully chosen with a high toe box to accommodate the hammer/claw toes At times orthotics are worn in the shoes to accommodate the pes cavus and equally distribute pressure on the foot. Charcot Marie Tooth Disease Many CMT patients require AFO’s other orthopedic devices to maintain everyday mobility and prevent injury. Thumb splints can help with hand weakness and loss of fine motor skills. Assistive devices should be used before disability sets in because the devices may prevent muscle strain and reduce muscle weakening. Some individuals with CMT may decide to have orthopedic surgery to reverse foot and joint deformities. Tendon transfers and lengthening The Lancet Neurology, Volume 9, Issue 1, Pages 77 - 93, January 2010 Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management Original Text Katharine Bushby MD a , Richard Finkel MD b, David J Birnkrant MD d, Laura E Case DPT e, Paula R Clemens MD f, Linda Cripe MD g, Ajay Kaul MD h, Kathi Kinnett MSN g, Craig McDonald MD i, Shree Pandya PT j, James Poysky PhD k, Frederic Shapiro MD l, Jean Tomezsko PhD c, Carolyn Constantin PhD m, for the DMD Care Considerations Working Group ‡ The Lancet Neurology, Volume 9, Issue 2, Pages 177 - 189, February 2010 Diagnosis and management of Duchenne muscular dystrophy, part 2: implementation of multidisciplinary care Original Text Katharine Bushby MD a , Richard Finkel MD b, David J Birnkrant MD d, Laura E Case DPT e, Paula R Clemens MD f, Linda Cripe MD g, Ajay Kaul MD h, Kathi Kinnett MSN g, Craig McDonald MD i, Shree Pandya PT j, James Poysky PhD k, Frederic Shapiro MD l, Jean Tomezsko PhD c, Carolyn Constantin PhD m, for the DMD Care Considerations Working Group‡