Muscular Dystrophy

1. MuscularDystrophy Amjad Moiffak Moreden, M.D. Department of Orthopaedic Surgery The General Assembly of Damascus Hospital Ministry of Health Damascus, Syria Jun. 26, 2007

2. Introduction • Muscular dystrophy (MD) is a group of rare inherited muscle diseases in which muscle fibers are unusually susceptible to damage. Muscles, primarily voluntary muscles, become progressively weaker. In the late stages of muscular dystrophy, fat and connective tissue often replace muscle fibers. In some types of muscular dystrophy, heart muscles, other involuntary muscles and other organs are affected. • The most common types of muscular dystrophy appear to be due to a genetic deficiency of the muscle protein dystrophin. • There's no cure for muscular dystrophy, but medications and therapy can slow the course of the disease.

3. Definition “muscular dystrophy” (MD) describes a group of primary genetic disorders of muscle that often have a distinctive and recognizable clinical phenotype, accompanied by characteristic, but frequently not pathognemonic, pathological features.

4. Muscular Dystrophy Types and Genes • Duchenne MD DMD Dystrophinopathy Xp21 • Becker MD BMD Dystrophinopathy Xp21 • Emery-Dreifuss MD EDMD Xq28 • Dominant Emery-Dreifuss MD AD-EDMD 1q11 • Limb-girdle MD type 1A LGMD1A 5q • Limb-girdle MD type 1B LGMD1B 1q11 • Limb-girdle MD type 1C LGMD1C p25 • Limb-hirdle MD type 1D LGMD1D 6q22 • Limb-girdle MD type 1E LGMD1E 7q • Limb-girdle MD type 2A LGMD2A Calpainopathy 15q15 • Limb-girdle MD type 2B LGMD2B Dysferlinopathy 2p13 • Miyoshi myopathy MM Dysferlinopathy 2p13 • Miyoshi-type MD MMD 10 • α-Sarcoglycanopathy SGCA LGMD2D, SCARMD2 17q21 • β-Sarcoglycanopathy SGCB LGMD2E 4q12 • γ-Sarcoglycanopathy SGCC LGMD2C, SCARMD1 13q12 • δ-Sarcoglycanopathy SGCD LGMD2F 5q33 • Limb-girdle MD type 2G LGMD2G 17q11 • Limb-girdle MD type 2H LGMD2H 9q31 • Limb-girdle MD type 2I LGMD2I 19q13-3 • Merosin-negative congenital MD 6q22 • Congenital MD with rigid spine 1p35 • Fukuyama congenital MD FCMD 9q31 • Congenital Myopathy (or ?MD) 12q13 • Facioscapulohumeral MD FSHD 4q35 • Myotonic dystrophy DM 19q13 • Myotonic dystrophy type 2 DM2 3q • Oculopharyngeal MD OPMD 14q11 • Epidermolysis bullosa simplex MD-EBS 8q24

5. M.D. Types There are nine major types of MD affecting people of all ages, from infancy to middle age or later. The two most common types of MD affect children: • Duchenne muscular dystrophy (DMD) • Becker muscular dystrophy (BMD)

6. Signs and symptoms They vary according to the type of muscular dystrophy. In general, they may include: • Muscle weakness • Apparent lack of coordination • Progressive crippling, resulting in contractures of the muscles around your joints and loss of mobility • Many specific signs and symptoms vary from among the different forms of MD. Each type is different in the age of onset, what parts of the body the symptoms primarily affect and how rapidly the disease progresses.

7. Signs and symptomsCont.. • DystrophinopathiesThese types of muscular dystrophies are due to a genetic deficiency of the protein dystrophin.

9. Signs and symptomsCont.. Duchenne muscular dystrophy is the most severe form of dystrophinopathy. It occurs mostly in young boys and is the most common form of MD that affects children. Signs and symptoms of Duchenne MD may include: • Frequent falls • Large calf muscles • Difficulty getting up from a lying or sitting position • Weakness in lower leg muscles, resulting in difficulty running and jumping • Waddling gait • Mild mental retardation, in some cases

11. Gower's maneuver

12. Signs and symptomsCont.. • Duchenne usually appear between the ages of 2 and 5. It first affects the muscles of the pelvis, upper arms and upper legs. By late childhood, most children with this form of muscular dystrophy are unable to walk. Most die by their late teens or early 20s, often from pneumonia, respiratory muscle weakness or cardiac complications. Some people with Duchenne MD may exhibit curvature of their spine (scoliosis). • Becker's muscular dystrophy is a milder form of dystrophinopathy. It generally affects older boys and young men, and progresses more slowly, usually over several decades. Signs and symptoms of Becker's MD are similar to those of Duchenne. The onset of the signs and symptoms is generally later, and those affected by Becker's MD usually are able to walk until at least age 15, and often well into adulthood.

13. Signs and symptomsCont.. Myotonic dystrophy Also known as Steinert's disease, this form of muscular dystrophy produces stiffness of muscles and an inability to relax muscles at will (myotonia), as well as the muscle weakness of the other forms of muscular dystrophy. Although this form of MD can affect children, it often doesn't affect people until adulthood. It can vary greatly in its severity. Muscles may feel stiff after using them. Progression of this form of MD is slow.

14. Signs and symptomsCont.. Besides myotonia, signs and symptoms of adult-onset myotonic dystrophy may include: • Weakening of voluntary muscles that control your arms and legs, usually beginning with the limb muscles farthest from the torso — the muscles of the feet, hands, lower legs and forearms. • Weakening of head, neck and face muscles, which may result in the face having a hollow, drooped appearance. • Weakening of muscles involved in breathing and swallowing. Weaker breathing muscles may result in less oxygen intake and fatigue. Weaker swallowing muscles increase the risk of choking. • Fainting or dizziness, which may indicate that the disease is interfering with the conduction of electrical signals that keep the heart rate normal. • Weakening of muscles of hollow internal organs such as those in the digestive tract and the uterus. Depending on which part of the digestive tract is affected, you may experience problems with swallowing as well as constipation and diarrhea. Weakness of the uterine walls may cause problems during childbirth. • Difficulty sleeping well at night and daytime sleepiness, and inability to concentrate because of the effect of the disease on the brain. • Frontal balding in men. • Clouding of the lenses of the eyes (cataracts). • Mild diabetes.

15. Signs and symptomsCont.. Rarely, infants have this form of muscular dystrophy, in which case it's called congenital myotonic dystrophy. The infant form is more severe, although infants with myotonic dystrophy don't experience myotonia. Signs in infants may include: • Severe muscle weakness • Difficulty sucking and swallowing • Difficulty breathing • Cognitive impairment

16. Signs and symptomsCont.. Facioscapulohumeral DystrophyAlso known as Landouzy-Dejerine disease, this form involves progressive muscle weakness, usually in this order: • Face • Shoulders • Abdomen • Feet • Upper arms • Pelvic area • Lower arms When someone with facioscapulohumeral MD raises his or her arms, the shoulder blades may stick out like wings. Progression of this form is slow, with some spurts of rapidly increasing weakness. Onset usually occurs during the teen to early adult years.

17. Signs and symptomsCont.. The other major types of muscular dystrophy are rare. They include: • Limb-girdle muscular dystrophy • Congenital muscular dystrophy • Oculopharyngeal muscular dystrophy • Distal muscular dystrophy • Emery-Dreifuss muscular dystrophy

18. Causes

19. X-linked recessive inheritance pattern with carrier mother • Duchenne and Becker's muscular dystrophies are passed from mother to son through one of the mother's genes in a pattern called X-linked recessive inheritance. Boys inherit an X chromosome from their mothers and a Y chromosome from their fathers. The X-Y combination makes them male. Girls inherit two X chromosomes, one from their mothers and one from their fathers. The X-X combination determines that they are female.

21. Autosomal dominant inheritance pattern • Patterns differ for other types of MDMyotonic dystrophy is passed along in a pattern called autosomal dominant inheritance. If either parent carries the defective gene for myotonic dystrophy, there's a 50 percent chance the disorder will be passed along to a child. • Some of the less common types of muscular dystrophy are passed along in the same inheritance pattern that marks Duchenne and Becker's muscular dystrophies. Other types of muscular dystrophy can be passed on from generation to generation and affect males and females equally. Still others require a defective gene from both parents.

23. Screening and diagnosis • Blood tests. Damaged muscles release enzymes such as creatine kinase (CK) into the blood. High blood levels of CK suggest a muscle disease such as muscular dystrophy. • Electromyography. A thin-needle electrode is inserted through your skin into the muscle to be tested. Electrical activity is measured as you relax and as you gently tighten the muscle. Changes in the pattern of electrical activity can confirm a muscle disease. The distribution of the disease can be determined by testing different muscles. • Ultrasonography. High-frequency sound waves are used to produce precise images of tissues and structures within your body. An ultrasound is a noninvasive way of detecting certain muscle abnormalities, even in the early stages of the disease. • Muscle biopsy. A small piece of muscle is taken for laboratory analysis. The analysis distinguishes muscular dystrophies from other muscle diseases. Special tests can identify dystrophin and other markers associated with specific forms of muscular dystrophy. • Genetic testing. Blood samples are examined for mutations in the gene that produces dystrophin. Standard tests examine just the portions of the dystrophin gene responsible for most cases of Duchenne and Becker's muscular dystrophies. These tests identify deletions or duplications on the dystrophin gene in about two-thirds of people with Duchenne and Becker's MDs. The genetic defects responsible for Duchenne and Becker's muscular dystrophies are harder to identify in other cases of those affected, but new tests that examine the entire dystrophin gene are making it possible to pinpoint tiny, less common mutations.

25. Treatment There's currently no cure for any form of muscular dystrophy. Research into gene therapy may eventually provide treatment to stop the progression of some types of muscular dystrophy. Current treatment is designed to help prevent or reduce deformities in the joints and the spine and to allow people with MD to remain mobile as long as possible. Treatments may include various types of physical therapy, medications, assistive devices and surgery.

26. Treatment Cont.. Physical therapy:As muscular dystrophy progresses and muscles weaken, fixations (contractures) can develop in joints. Tendons can shorten, restricting the flexibility and mobility of joints. Contractures are uncomfortable and may affect the joints of your hands, feet, elbows, knees and hips. One goal of physical therapy is to provide regular range-of-motion exercises to keep your joints as flexible as possible, delaying the progression of contractures, and reducing or delaying curvature of your spine. Using hot baths (hydrotherapy) also can help maintain range of motion in joints.

27. Treatment Cont.. Medications: • For myotonic dystrophy. The medications mexiletine (Mexitil), phenytoin (Dilantin, Phenytek), carbamazepine (Tegretol, Carbatrol), quinine and procainamide (Procanbid, Pronestyl) may be used to treat the delayed muscle relaxation that occurs in myotonic dystrophy. • For Duchenne muscular dystrophy. The anti-inflammatory corticosteroid medication prednisone may help improve muscle strength and delay the progression of Duchenne MD.

28. Treatment Cont.. Assistive devices:Braces can both provide support for weakened muscles of your hands and lower legs and help keep muscles and tendons stretched and flexible, slowing the progression of contractures. Other devices such as canes, walkers and wheelchairs can help maintain mobility and independence. If respiratory muscles become weakened, using a ventilator may become necessary.

29. Treatment Cont.. Surgery: ( three approaches: ambulatory, rehabilitative, palliative ) • Surgical release of contractures: Cut through tendons to relieve contractures (tendon release surgery). • Spinal fusion for scoliosis: Scoliosis in a wheelchair-dependent child with MD can become so severe it causes breathing problems and pneumonia. Having spine surgery before this happens can preserve breathing function, lessen back pain and improve sitting balance. All these factors improve the child's quality of life. The surgery is recommended when the spinal curve reaches a certain size (i.e., more than 20 degrees).

30. Surgical Treatment • Percutaneous Release of Hip Flexion and Abduction Contractures and Tendo Calcaneus Contracture. • Open procedure technique

31. TECHNIQUE: • With the child supine on the operating table, prepare and drape both lower extremities from the iliac crests to the toes. First flex and then extend the hip to be released, holding the hip in adduction to place tension on the muscles to be released; keep the opposite hip in maximal flexion to flatten the lumbar spine. Insert a no. 15 knife blade percutaneously just medial and just distal to the anterosuperior iliac spine. Release the sartorius muscle first, then the tensor fasciae femoris muscle. Push the knife laterally and subcutaneously—without cutting the skin—to release the tensor fasciae latae completely. Bring the knife to the original insertion point and push it deeper to release the rectus femoris completely. Take care to avoid the neurovascular structures of the anterior thigh. Next, approximately 3 to 4 cm proximal to the upper pole of the patella, percutaneously release the fascia lata laterally through a stab wound in its midportion. Push the knife almost to the femur to release the lateral intermuscular septum completely. Now perform a percutaneous release of the tendo calcaneus. Apply long leg casts with the feet in neutral position and with the heels well padded to prevent pressure ulcers.

32. Surgical Treatment Cont.. • Transfer of Posterior Tibialis Tendon to Dorsum of Foot (posterior tibialis muscle overpull)

33. TECHNIQUE: • make a 3-cm incision starting medially at the neck of the talus and extending to the navicular. Open the sheath of the posterior tibial tendon from the distal extent of the flexor retinaculum to the navicular. Release the tendon from its bony insertions, preserving as much length as possible. Make a second incision 6 to 8 cm long vertically between the tendo calcaneus and the medial distal tibia. The tendo calcaneus can be lengthened through the same incision if necessary. Incise the posterior tibial tendon sheath and pull the distal portion of the tendon through the second operative wound. Make a third incision 6 cm long lateral to the anterior crest of the tibia and extend it to the superior extensor retinaculum. Incise the anterior compartment fascia and retract the tibialis anterior tendon laterally. Carefully incise the interosseous membrane on the lateral aspect of the tibia adjacent to its tibial insertion for a distance of 3 cm. Enlarge the opening by proximal and distal horizontal cuts, extending halfway across the interosseous membrane. Pass a curved clamp close to the tibia from the anterior compartment proximally into the second incision. Keep the curved clamp on the tibia to prevent injury to the peroneal vessels. After grasping the posterior tibialis tendon and pulling it into the third incision, inspect the tendon through the second incision to make sure that it has neither twisted on itself nor ensnared the flexor digitorum longus tendon. Make a fourth incision 3 cm long on the dorsum of the foot in the region of the middle cuneiform. Incise the periosteum of the middle cuneiform and expose the central portion of the bone. Drill a hole 5 to 8 mm to insert the tendon through the middle of the cuneiform. Pass a Kelly clamp subcutaneously from the third incision to the fourth incision distally to create a subcutaneous tract for the posterior tibialis tendon. Pull the tendon through the subcutaneous tract with a tendon passer. Holding on to the sutures tied to the end of the posterior tibialis tendon, pass the tendon into the hole in the middle cuneiform and pass the sutures through the dorsum of the foot with the aid of straight needles. Release the tourniquet. Inspect, irrigate, and close the wounds. After the wounds have been closed tie the suture over a felt pad and button on the plantar aspect on the foot with the foot in a neutral position. Apply a long leg cast with the knee extended and the ankle in neutral position.

34. Surgical Treatment Cont.. • Transfer of Posterior Tibialis Tendon to Dorsum of Base of Second Metatarsal (posterior tibialis muscle overpull)

35. TECHNIQUE: • With the patient supine and a tourniquet in place, make a 3-cm incision over the insertion of the posterior tibialis tendon on the navicular. Open the sheath of the posterior tibialis tendon from the anterior aspect of the medial malleolus to the navicular. Release the tendon from the bony insertions, preserving as much length as possible. Make a second incision in the posteromedial calf in the region of the myotendinous junction of the posterior tibialis tendon. A gastrocnemius recession can be performed through this incision if necessary, but excessive lengthening of the triceps surae complex should be avoided to prevent the development of a crouched gait postoperatively. Open the posterior tibial tendon sheath and pull the tendon through the sheath into the calf wound. At the myotendinous junction of the tibialis posterior, incise the tendon transversely halfway through its width. Extend this incision distally to within 0.5 cm of the cut insertion of the tibialis tendon. Secure the distal aspect of the tendon with a single suture to prevent the longitudinal cut from extending out to the end of the tendon. This procedure effectively doubles the length of the posterior tibialis tendon. Make a third incision, 6 cm long lateral to the anterior crest of the tibia, extending it to the superior extensor retinaculum. Perform an anterior compartment fasciotomy and retract the tibialis anterior tendon laterally. Incise the interosseous membrane of the lateral aspect of the tibia for a distance of 3 cm. Take a Kelly clamp and place it through the anterior compartment wound across the interosseous membrane and into the deep posterior compartment. Grasp the end of the lengthened posterior tibialis tendon and bring it through the interosseous membrane into the anterior compartment of the calf . Make another incision, 2 to 3 cm long, over the base of the second metatarsal. Dissect down to the base of the second metatarsal and subperiosteally dissect around the base of the second metatarsal circumferentially. Take the elongated tibialis posterior tendon and tunnel it subcutaneously into the incision over the dorsum of the second metatarsal. Loop the tendon around the base of the second metatarsal as a sling and tie it to itself with the appropriate tension on the ankle to hold it into a neutral plantar flexion and dorsiflexion. Release the tourniquet and inspect the tibial vessels to make sure that they are not being kinked by the transferred tendon. Irrigate the wounds and close them in a standard fashion.

36. Surgical Treatment Cont.. Lengthening of Tendo Calcaneus(Equinus deformity)

37. Surgical Treatment Cont.. Scapulothoracic Fusion (inability to functionally flex and abduct the shoulder )

38. TECHNIQUE: • Place the patient prone and manually position the scapula at 15 to 20 degrees of external rotation. Make an oblique 12-inch incision over the medial border of the scapula and transect the trapezius muscle. Release the rhomboids and levator scapula from their scapular insertions and elevate the supraspinatus, infraspinatus, and subscapularis muscles subperiosteally for 2 cm from the medial border of the scapula. Excise a 2-cm strip of subscapularis muscles to allow approximation of the scapula to the thoracic wall. Usually ribs 3 through 7 are exposed subperiosteally for 2 cm. Pass double 16-gauge Luque wires subperiosteally under each rib. Use a sharp towel clip to make holes 1 cm from the medial ledge of the scapular points corresponding from the wired ribs. Use a burr to decorticate the posterior surface of the exposed rib margins in the corresponding points along the anterior surface of the scapula. Place strips of cancellous allograft taken from the posterior iliac crest between the denuded ribs and scapula. Tighten the wires sequentially

39. Treatment Cont.. Other treatmentsBecause respiratory infections may become a problem in later stages of muscular dystrophy, it's important to be vaccinated for pneumonia and to keep up-to-date with influenza shots.

41. THE END

42. MoKazem.com • هذه المحاضرة هي من سلسلة محاضرات تم إعدادها و تقديمها من قبل الأطباء المقيمين في شعبة الجراحة العظمية في مشفى دمشق, تحت إشراف د. بشار ميرعلي. • الموقع غير مسؤول عن الأخطاء الواردة في هذه المحاضرة. • This lecture is one of a series of lectures were prepared and presented by residents in the department of orthopedics in Damascus hospital, under the supervision of Dr. Bashar Mirali. • This site is not responsible of any mistake may exist in this lecture. Dr. Muayad Kadhim د. مؤيد كاظم