You are in: eMedicine Specialties > Orthopedic Surgery > PEDIATRICS Muscular DystrophyArticle Last Updated: Mar 30, 2007AUTHOR AND EDITOR INFORMATIONSection 1 of 11
  Author: Twee Do, MD, Assistant Professor, Department of Pediatric Orthopedic Surgery, University of Cincinnati College of Medicine; Director, Neuromuscular Orthopedic Services, Cincinnati Children's Hospital Medical Center Twee Do is a member of the following medical societies: American Academy of Orthopaedic Surgeons and American Academy of Pediatrics Editors: Charles T Mehlman, DO, MPH, Director, Musculoskeletal Outcomes Research, Associate Professor, Division of Pediatric Orthopaedic Surgery, Cincinnati Children's Hospital Medical Center; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; George H Thompson, MD, Professor of Orthopedic Surgery and Pediatrics, Department of Pediatric Orthopedic Surgery, Case Western Reserve University; Director, Rainbow Babies and Children's Hospital; Dinesh Patel, MD, FACS, Associate Clinical Professor of Orthopedic Surgery, Harvard Medical School; Chief of Arthroscopic Surgery, Department of Orthopedic Surgery, Massachusetts General Hospital; Dennis P Grogan, MD, Clinical Professor, Department of Orthopedic Surgery, University of South Florida College of Medicine; Chief of Staff, Department of Orthopedic Surgery, Shriners Hospital for Children of Tampa Author and Editor Disclosure Synonyms and related keywords: MD, dystrophinopathies, Duchenne muscular dystrophy, Duchenne MD, Becker muscular dystrophy, Becker MD, dystrophin defects, Gower sign, Gower's sign, progressive muscle weakness, proximal muscle weakness, PTC124, PTC-124 INTRODUCTIONSection 2 of 11
  History of the ProcedureMuscular dystrophy (MD) is a collective group of inherited noninflammatory but progressive muscle disorders without a central or peripheral nerve abnormality. The disease affects the muscles with definite fiber degeneration but without evidence of morphologic aberrations. The first historical account of MD was reported by Conte and Gioja in 1836. They described 2 brothers with progressive weakness starting at age 10 years. These boys later developed generalized weakness and hypertrophy of multiple muscle groups, which are now known to be characteristic of the milder Becker MD. At the time, however, many thought that Conte and Gioia described tuberculosis; thus, they did not achieve recognition for their discovery. In 1852, Meryon reported in vivid details a family with 4 boys, all of whom were affected by significant muscle changes but had no central nervous system abnormality when examined at necropsy. Meryon subsequently wrote a comprehensive monograph on MD and even went on to suggest a sarcolemmal defect to be at the root of the disorder. He further suspected that the disorder is genetically transmitted through females and affects only males. Guillaume Duchenne was a French neurologist who was already famous for his application of faradism (the use of electric currents to stimulate muscles and nerves) in the treatment of neurologic disorders when he wrote about his first case of MD. In 1868, he gave a comprehensive account of 13 patients with the disease, which he called "paralysie musculaire pseudo-hypertrophique." Because Duchenne was already held in high esteem for his work in faradism and for his contributions to the understanding of muscle diseases, one of the most severe and classic forms of MD, Duchenne MD, now bears his name. The advancement of molecular biology techniques illuminates the genetic basis underlying all MD: defects in the genetic code for dystrophin, a 427-kd skeletal muscle protein (Dp427). These defects result in the various manifestations commonly associated with MD, such as weakness and pseudohypertrophy. Dystrophin can also be found in cardiac smooth muscles and in the brain (accounting for the slight mental retardation associated with this disease). ProblemDespite minor variations, all types of MD have in common progressive muscle weakness that tends to occur in a proximal-to-distal direction, although there are some rare distal myopathies that cause predominantly distal weakness. The decreasing muscle strength in those who are affected may compromise the patient's ambulation potential and, eventually, cardiopulmonary function. In addition, structural soft-tissue contractures and spinal deformities may develop from poor posturing caused by the progressive muscle weakness and imbalance, all of which can further compromise function and longevity. Equinovarus contractures start as flexible dynamic deformities and advance to rigid contractures. This altered anatomy prevents normal ambulation, proper shoe wear, and transfers (how patients can be picked up to transfer out of their chair). Once wheelchair bound, patients with MDs tend to develop worsening contractures and rapidly progressive scoliosis. On average, for each 10° of thoracic scoliosis curvature, the forced vital capacity (FVC) decreases by 4% (Hoffman et al, 1987). In a patient with an already-weakened cardiopulmonary system, this decrease in FVC could rapidly become fatal. The goal of orthopedic management is, therefore, to preserve or prolong patients' ambulatory status for as long as possible. This goal can be achieved with soft-tissue releases for contractures and early stabilization of the spine. FrequencyUnited States The incidence rates of MDs vary depending on the specific type. Duchenne MD is the most common MD and is sex-linked, with an inheritance pattern of 1 case per 3500 live male births (Dubowitz, 1995; Emery, 1993). One third of cases occurs as a result of spontaneous new mutations (Emery, 1991). Becker MD is the second most common form, with an incidence of 1 case per 30,000 live male births (Shapiro and Specht, 1993). Other types of MD are rare. For example, limb-girdle dystrophy occurs in only 1.3% of patients with MDs. International The incidence internationally is similar to that of the US for most of the dystrophies, except for the oculopharyngeal type, which is more common in French Canadians than in other groups (Pratt and Meyers, 1986). Distal MD tends to occur in Sweden. EtiologyClassification of types of MD The etiology of MD is an abnormality in the genetic code for specific muscle proteins. They all are classified according to the clinical phenotype, the pathology, and the mode of inheritance. The inheritance pattern includes the sex-linked, autosomal recessive, and autosomal dominant MDs. Within each group of heritable MDs (see below), several disorders exist. These are characterized by the clinical presentation and pathology. Heritable MDs include the following:
Genetic defects and dystrophin In the X-linked forms of MD, such as the Duchenne and Becker dystrophies, the defect is located on the short arm of the X chromosome. Hoffman and coworkers identified the locus of the defect in the Xp21 region, which includes approximately 2 million base pairs. The gene codes for Dp427, which is a component of the cytoskeleton of the cell membrane. Dystrophin is distributed not only in skeletal muscle but also in smooth and cardiac muscles and in the brain. The large size of the dystrophin gene explains the ease at which spontaneous new mutations can occur, as in Duchenne MD. The large size also allows mistakes in protein synthesis to occur at multiple sites. Defects that interfere with the translation reading frame or with the promoter sequence that initiates synthesis of dystrophin lead to an unstable, ineffective protein, as in Duchenne MD. Disruption of the translation process further down the sequence leads to production of proteins of lower molecular weight that, although present, are less active and result in the milder variety of Becker MD. As with Duchenne MD, Emery-Dreifuss MD is a sex-linked recessive disorder, but its defect is localized to the long arm of the X chromosome at the q28 locus. Some authors, however, have cited case reports of similar findings in Emery-Dreifuss that were transmitted in an autosomal dominant pattern (Miller et al, 1985). However, this finding is more of an aberration than a normal observation in Emery-Dreifuss MD. In autosomal recessive conditions such as limb-girdle MD, the genetic defect is localized to the 13q12 locus. In the autosomal dominant facioscapulohumeral MD, the defect is at the 4q35 locus. In distal MD, it is at the 2q12-14 loci. PathophysiologyMultiple proteins are involved in the complex interactions of the muscle membrane and extracellular environment. For sarcolemmal stability, dystrophin and the dystrophin-associated glycoproteins (DAGs) are important elements. The dystrophin gene is located on the short arm of chromosome X near the p21 locus and codes for the large protein Dp427, which contains 3685 amino acids. Dystrophin accounts for only approximately 0.002% of the proteins in striated muscle, but it has obvious importance in the maintenance of the muscle's membrane integrity (Hoffman et al). Dystrophin aggregates as a homotetramer at the costomeres in skeletal muscles, as well as associates with actin at its N-terminus and the DAG complex at the C-terminus, forming a stable complex that interacts with laminin in the extracellular matrix. Lack of dystrophin leads to cellular instability at these links, with progressive leakage of intracellular components; this results in the high levels of creatine phosphokinase (CPK) noted on routine blood workup of patients with Duchenne MD. Less-active forms of dystrophin may still function as a sarcolemmal anchor, but they may not be as effective a gateway regulator because they allow some leakage of intracellular substance. This is the classic Becker dystrophy. In both Duchenne and Becker MD, the muscle-cell unit gradually dies, and macrophages invade. Although the damage in MD is not reported to be immunologically mediated, class I human leukocyte antigens (HLAs) are found on the membrane of dystrophic muscles; this feature makes these muscles more susceptible to T-cell mediated attacks. Selective monoclonal antibody hybridization was used to identify cytotoxic T cells as the invading macrophages; complement-activated membrane attack complexes have been identified in dystrophic muscles as well. Over time, the dead muscle shell is replaced by a fibrofatty infiltrate, which clinically appears as pseudohypertrophy of the muscle. The lack of functioning muscle units causes weakness and, eventually, contractures. Other types of MDs are caused by alterations in the coding of one of the DAG complex proteins. The gene loci coding for each of the DAG complex proteins is located outside the X chromosomes. Gene defects in these protein products also lead to alterations in cellular permeability; however, because of the slightly different mechanism of action and because of the locations of these gene products within the body, there are other associated effects, such as those in ocular and limb-girdle type dystrophies. ClinicalIn Duchenne MD, unless a sibling has been previously affected to warrant a high index of suspicion, no abnormality is noted in the patient at birth, and manifestations of the muscle weakness do not begin until the child begins to walk. Three major time points for patients with Duchenne MD are when they begin to walk, when they lose their ability to ambulate, and when they die. The child's motor milestones may be at the upper limits of normal, or they may be slightly delayed. Some of the delays may be caused by inherent muscle weakness, but a component may stem from brain involvement. Although the association of intellectual impairment in MD has long been recognized, it was initially thought to be a result of limited educational opportunities (Prosser et al, 1969). Psychometric studies have since revealed a definitively lower intelligence quotient (IQ) in patients with Duchenne MD despite equalization of educational opportunities (Leibowitz and Dubowitz, 1981). The average IQ in patients with Duchenne MD is 85 points, compared with 105 points in healthy populations, as determined by using the Wechsler Adult Intelligence Scale (WAIS) (Dubowitz, 1995; Prosser et al; Leibowitz and Dubowitz). In addition to mental deficits, another milestone delay is the patient's age at ambulation. Children with Duchenne MD usually do not begin to walk until about age 18 months or later. In the Dubowitz study (1995), 74% of children with Duchenne MD manifested the disease by age 4 years. By age 5 years, awareness increases as the disease is manifested in all affected children when they experience difficulty with school-related activities (eg, getting to the bus, climbing stairs, reciprocal motions during activities). Other early features include a gait abnormality, which classically is a waddling, wide-based gait with hyperlordosis of the lumbar spine and toe walking. The waddle is due to weakness in the gluteus maximus and gluteus medius muscles and the patient's inability to support a single-leg stance. The child leans the body toward the other side to balance his or her center of gravity, and the motion is repeated with each step. Hip extensor weakness also results in a forward tilt of the pelvis, which translates to a hyperlordosis of the spine to maintain posture. The child then walks on his or her tiptoes because it is easier to stay vertical with an equinus foot position than on a flat foot, although no real tendo Achillis contracture exists at this early point. Gradually, noticeable difficulty with step taking by the child is observed. Frequent falls without tripping or stumbling often occur and are described as the feet being swept away from under the child. The child then begins having problems getting up from the sitting or supine position, and he or she can rise to an upright stance only by manifesting the Gower sign (see below). The Gower sign is a classic physical examination finding in MD and results from weakness in the child's proximal hip muscles. To get up from a sitting or supine position, the child must first become prone on the elbows and knees. Next, the knees and elbows are extended to raise the body. Then, the hands and feet are gradually brought together to move the body's center of gravity over the legs. At this point, the child may release one hand at a time and support it on the knee as he or she crawls up their legs to achieve an upright position. Although the Gower sign is a classic physical examination finding in Duchenne MD, it is by no means pathognomonic; other types of MD and disorders with proximal weakness may also cause this sign. While still ambulatory, the child may have minimal deformities, including iliopsoas or tendo Achillis tightness. Mild scoliosis may be present if the child has an asymmetrical stance. Upper-extremity involvement rarely occurs in the beginning, although proximal arm muscle weakness may be evident on manual strength testing. When upper-extremity involvement manifests in later stages of Duchenne MD, it is symmetrical and, along with distal weakness, usually follows a rapid worsening of the child's condition toward being wheelchair bound. The second important phase in Duchenne MD is the loss of ambulation. This usually occurs between the ages of 7 and 13 years, with some patients becoming wheelchair bound by age 6 years. If children with MD are still ambulating after age 13 years, the diagnosis of Duchenne MD should be questioned, because these patients usually have Becker MD, the milder form of MD. In Emery's work (1993), the 50th percentile for loss of ambulation in patients with Duchenne MD was age 8.5 years, with the 95th percentile at 11.9 years and the 99th percentile at 13.2 years. With the child's loss of ambulation, there is usually a rapidly progressive course of muscle or tendon contractures and scoliosis. Most authors recommend posterior spinal fusion at 20° when the vital capacity is at its best (Thompson and Berenson, 2000; Dubowitz, 1995; Shapiro and Specht; Sussman 1984; Weimann et al, 1983). However, recent and other reports showed that respiratory function after spinal fusion did not significantly differ (Almenrader and Patel, 2006; Kinali et al, 2006; Birnkrant, 2006; Miller et al, 1991; Miller et al, 1988). The investigators concluded that respiratory failure resulted from muscle weakness and not the mechanical bellows of the chest cage, as was previously assumed. Duchenne MD is a terminal disease in which death usually occurs by the third decade of life (mostly from cardiopulmonary compromise) (Dubowitz, 1995). The most common inciting event is a respiratory infection that progresses extremely rapidly despite its initial benign course. The resultant respiratory failure can easily occur from the underlying progressive nocturnal hypoventilation and hypoxia or from an acute cardiac insufficiency. Other clinical findings in Duchenne MD include absent deep tendon reflexes in the upper extremities and patella (though the tendo Achillis reflex remains intact even in the later stages of this disease), pain in the calves with activity ( <30% of patients), pseudohypertrophy of the calf (60%), and macroglossia (30%). Cardiopulmonary involvement is present from the beginning of the disease stages, but the findings are not so clinically obvious. Electrocardiogram (ECG) tracings show right ventricular strain, tall R waves, deep Q waves, and inverted T waves. Becker MD is similar to Duchenne MD, but because patients have some measure of functioning dystrophin, the manifestations of Becker MD occur later and are more mild. Patients tend to live past the fourth or fifth decades. Emery-Dreifuss MD is an uncommon sex-linked dystrophy that presents with early contractures and cardiomyopathy in affected patients; the typical presentation involves tendo Achillis contractures, elbow flexion contractures, neck extension contractures, tightness of the lumbar paravertebral muscles, and cardiac abnormalities. Death may occur in the fourth or fifth decade as a result of first-degree atrioventricular (AV) block, a condition that is usually not present at the initial presentation of this disease. Autosomal dominant distal MD is a rare form of MD and tends to become apparent in those aged 30 to 40 years; it is more commonly found in Sweden than in any other country and can cause a mild weakness that affects the arms before the legs. Autosomal dominant facioscapulohumeral dystrophy causes facial and upper extremity weakness, and scapulothoracic motion is decreased, with winging of the scapula. This type of dystrophy can occur in both sexes and appear at any age, although it is more common in late adolescence. Autosomal dominant oculopharyngeal dystrophy appears in those aged 20 to 30 years. The pharyngeal muscle involvement leads to dysarthria and dysphagia, which may necessitate palliative cricopharyngeal myotomy. The ocular component comprises ptosis, which may not become obvious until the patient's mid life. None of the autosomal dominant conditions significantly affects longevity. INDICATIONSSection 3 of 11
The indications for any operative intervention in patients with MD include making a diagnosis by means of muscle biopsy or prolonging the patient's function and/or ability to ambulate by specific procedures. Until the advent of molecular biology techniques, muscle biopsy was the definitive test for diagnosing and confirming MDs. The histologic changes found in MDs depend on the stage of the disease and the muscle selected, of which the optimal site is the vastus lateralis, wherein a small lateral thigh incision is made. Other indicated procedures include tendo Achillis and iliopsoas tenotomies for ease of fit into braces, tibialis posterior tendon transfers or tenotomies for more rigid equinovarus deformities of the foot, and segmental spinal stabilization for rapidly developing scoliosis (see Treatment, Surgical therapy). RELEVANT ANATOMYSection 4 of 11
The overall status of any patient must be considered before operative intervention is undertaken, and it becomes especially important in patients with muscle weakness, as in MD. For example, posterior spinal fusion to the pelvis straightens the scoliosis and allows better upright sitting balance. However, in patients with low vital capacity ( <30%), the risks of pulmonary complications are much higher, and these risks may tip the scale in favor of not operating on the scoliosis. Other examples include equinus contractures in patients who are very weak; tendon lengthening itself is necessarily a weakening procedure on the involved muscle. If the patient has to maintain a rigid equinus foot position for stability of gait and the tendon is lengthened by surgery, the patient will not be able to ambulate. After scoliosis surgery, patients may need additional pulmonary support and an extended stay in the intensive care unit (ICU). Preoperative tracheostomy is usually not any more effective in early mobilization of dystrophic patients; if necessary, this procedure is performed only after the patient's condition has been stabilized and after a mold has been obtained for a hard brace with chest and abdominal cutouts. CONTRAINDICATIONSSection 5 of 11
In patients with MD, some relative contraindications to surgery include obesity, rapidly progressive muscle weakness, poor cardiopulmonary status, and a patient's lack of motivation for participating in postoperative rehabilitation programs. WORKUPSection 6 of 11
Lab Studies
Imaging Studies
Other Tests
Diagnostic Procedures
Histologic FindingsHistologic specimens from muscle biopsy samples obtained early in the MD disease show only variations in muscle fiber sizes with focal areas of degenerating or regenerating fibers. In later stages of MD, the changes are more obvious, with marked variations in muscle fiber sizes, degeneration, and regeneration. Rounded opaque fibers, internal nuclei, splitting of fibers, and a proliferation of connective and adipose tissues are also present. As the disease progresses, fewer and fewer regenerative fibers are seen. In the end phase, the muscle is mostly replaced by adipose tissue, with residual islets of muscle fibers in a sea of fat. Histochemical staining with the standard adenosine triphosphatase (ATPase) reaction shows a predominance of type I muscle fibers, with loss of clear-cut distinction into the various fiber types. Electron microscopy demonstrates nonspecific degeneration of the fibers, and immunocytochemical techniques show a persistence of fetal and slow myosin in many of these fibers. TREATMENTSection 7 of 11
Medical therapySince Duchenne's time, multiple drug regimens have been tried in treatment of the muscle weakness. Of all the drugs that have come and gone, the only one with some proven benefit is prednisone. The beneficial effects were initially thought to be mediated through the suppression of cytotoxic T-cell expression from the necrotic muscles. In the early 1970s, Drachman et al (1974) treated 14 boys who had Duchenne MD with steroids and noted some benefits; however, because this was an uncontrolled study, the steroid therapeutic approach did not become a widely accepted treatment protocol. In 1989, Mendell and colleagues performed a randomized, double-blind, multicenter study of 103 male patients with Duchenne MD who ranged from age 5 to 15 years. Over a period of 6 months, the patients were given prednisone at a dose of 1.5 mg/kg/d, prednisone at a dose of 0.75 mg/kg/d, or placebo. The researchers, who followed the expected course outlined by natural history, noted definite improvement in muscle strength in the steroid-treated boys at 1, 2, and 3 months compared with the control subjects receiving placebo. The benefit of the dose-dependent steroid in Mendell et al's study, however, was short-lived. The children's gained strength leveled off after the third month, and then they again began to lose strength. In addition, the adverse effects of the higher-dose steroids, such as rapid weight gain, myopathy, osteoporosis, and growth retardation, offset the beneficial effects of temporary minimal increases in strength. As a result, deflazacort, an oxazoline derivative of prednisolone, has been the new therapeutic drug of choice. Deflazacort reportedly has more bone-sparing and carbohydrate-sparing properties with less weight-gain effects and improves strength and function. Due to the limited side effects and the beneficial properties of muscle sparing and delayed scoliosis progression, deflazacort is being used despite patients' permanent wheelchair status. Clinical investigations are exploring the possibility of limited courses of steroid bursts (which have shown lasting benefits <18 months) and other immunosuppressive drugs, such as azathioprine and cyclosporine. Although the glucocorticoid drugs delay the cytotoxic damage of MD to the necrosing muscle cells, these drugs cannot and do not make, or stimulate the synthesis of, the dystrophin and DAG proteins that are deficient, which is the root cause of the disease. PTC124 (PTC Therapeutics, Inc, South Plainfield, NJ) is an oxadiazole compound that, when taken orally, can override nonsense stop translation signals induced by the dystrophin gene mutation; the protein produced is thus the full-length protein (Hamed, 2006; PTC Therapeutics, Inc.). PTC124 is currently in phase II clinical trials for patients with Duchenne MD and cystic fibrosis. Another novel method of treatment under intense investigation is somatic gene therapy, wherein healthy immature myoblasts are introduced into the diseased muscles, which then fuse and stimulate production of enough dystrophin to reverse the degeneration that occurs in the affected muscles (Ragot et al, 1993). However, although somatic gene therapy has been achieved successfully in the X-linked muscular dystrophic mouse (murine MDX) model with the fusion of the donor and host muscle cells, which expressed some dystrophin, the benefit may not translate into human males (Ragot et al). The mice cannot demonstrate muscle strength, and the laboratory-raised mice were not able to mount a rejection response that may occur in humans. Other investigations have been conducted on the canine MDX model, which more closely approximates the human condition (Wang et al, 2007; Howell et al, 1998). Human trials of gene therapy began in 1990. The first was an uncontrolled trial of 8 patients who were injected with myoblasts from family donors (Griggs and Karparti, 1990). Strength testing and staining for dystrophin was performed after several months. Early results demonstrated no improvement in patients' muscle strength or dystrophin staining. Later studies showed an increase in the expression of dystrophin proteins. However, the clinical results remain unchanged. These preliminary results, although disappointing, do not dampen the promise of gene therapy. Most supporters believe that these failures were merely the result of a lack of expertise, as with once-novel techniques such as organ transplantation. Other molecular approaches to therapy include recombinant versions of the dystrophin gene using viral or nonviral vectors and antisense oligonucleotides (Rando, 2007; Wells, 2006). In the viral vector therapeutic approach, adenosine-associated virus leads the way. In nonviral gene therapy, plasmid-mediated gene delivery, antisense-mediated exon skipping, and oligonucleotide-mediated gene editing has moved from successful trials in the lab to the clinic. In approximately 10-20% of the preclinical cases (Wells), it is possible to chemically persuade the translational machinery to read through a premature stop codon, as noted with the dystrophin mutation, and lead to production of a more functional full-length protein. In spinal muscular atrophy (SMA), the molecular genetic basis is the loss of function of the survival motor neuron gene SMN1. The SMN2 gene, a near identical copy, has been detected as a possible target for therapy. Drugs such as valproic acid, phenylbutyrate, sodium butyrate, M344 (a benzamide and histone deacetylase [HDAC] inhibitor), and suberoylanilide hydroxamic acid (SAHA) can stimulate SMN2 and elevate levels of the protein. In phase II clinical trials and individual experimental curative approaches, patients show promising results. Phase III control drug trials are pending. Surgical therapyThe orthopedic problems in children with MD are progressive weakness with loss of ambulatory status, soft-tissue contractures, and spinal deformities. The role of the orthopedic surgeon is to correct the deformities and to help maintain the dystrophic child's ambulatory status for as long as possible, usually 1 to 3.5 years (Brooke et al, 1989; Heckmatt et al, 1985). The modalities available to obtain these goals have been well outlined by Drennan (1990); they include functional testing; physical therapy; use of orthoses; fracture management; soft-tissue, bone, and spinal surgeries; use of a wheelchair when indicated; and genetic and/or psychological testing. Functional testing, as its name implies, refers to frequent evaluation of the involved muscle's range of motion and strength. This modality provides therapists with goals for patients' individualized therapy programs. Regular therapy sessions are necessary because the therapist also works with patients for gait training and transfer techniques. The use of all adaptive equipment is considered necessary by the orthopedist to maintain the patient's ambulatory status. Drennan also recommends that a home program be taught to dystrophic patients, with stretching exercises for the lower extremities performed twice a day on a firm surface to mimimize contractures. Occasionally, serial casting may be necessary to manage significant flexion contractures at the knee or equinus contracture at the ankle. The goal for patients with MD is continued mobility despite the use of a cast to prevent rapid loss of strength and bone mineral density. Even with initial loss of muscle strength for weight bearing, flexible soft-tissue and rigid ankle–foot orthosis (AFO) or ischial supportive knee–ankle–foot orthosis (KAFO) can help the patient maintain standing balance for additional months to years. Significant upper-extremity contractures rarely occur in patients with MD. Occasionally, tightness of the long flexors may become problematic with hand function in operating an automatic wheelchair, but historically this has been treated with a nighttime orthosis. In patients with MD, lower-extremity contractures start with equinus deformities. Initially, the contractures are supple and can occur in children as young as 6 years. Patients may be treated with various types of procedures to lengthen the tendo Achillis, including Vulpius tendon lengthening (which avoids overlengthening the already weakened muscle), percutaneous Hoke-Miller triple cut (which limits the incision and, thus, the postoperative immobilization), Warren-White lengthening, or standard z-lengthening. Occasionally, when an associated varus deformity is present as a result of overpull of the unaffected tibialis posterior muscle, a posterior tibial tendon transfer through the interosseous membrane or a split-posterior tibial tendon transfer may also be indicated. In cases of severe contractures at the foot and ankle, posterior tibial lengthening or tenotomy may be necessary to achieve a plantigrade position. Hip and knee contractures develop later in MD. Once patients become wheelchair bound, hip and knee flexion contractures are more rapidly progressive. The abduction contracture was initially thought to be useful in obtaining stability with a wider base gait, but it also makes it difficult for patients to fit in standard wheelchairs or to be comfortable in bed. Various tenotomies are available, including the Yount (resection of the iliotibial band [ITB] distally at the knee), modified Souter-Strathclyde (resection of the ITB proximally), and complete resection of the ITB from the hip to the knee. Transfer of the iliopsoas has also been tried with limited success; this is no longer a procedure of choice in patients with MDs. Posterior capsulotomy of the knee can allow for maintenance of flexible extremities for bracing, although this is not routinely performed. KAFOs with locked knees may extend the ambulatory status of weakened patients by 1 to 3 years (Heckmatt et al; Shapiro and Specht). The locked knees, however, are not well tolerated, as they cause children to feel as if they are going to fall. This is a worse condition than buckling because of weakness at the quadriceps. Postoperatively, all patients are given some type of orthosis. The surgical approaches to contractures in dystrophic patients, especially those with Duchenne MD, can be summarized into ambulatory, rehabilitative, and palliative approaches. Within the ambulatory group, the approach can be aggressive, such that all contractures are addressed at the start, before patients lose ambulatory status or within the first month of their losing ambulatory status. The rehabilitative approach indicates that surgery is used only to correct deformities that may limit physical therapy and orthosis wear. The palliative approach, as its name implies, is used to treat only problems of immediate concern for the patient's comfort, such as difficulty with shoe wearing, ulcerations, and problematic positioning in wheelchairs. Early aggressive surgical releases can prolong the patient's ambulatory status as long as 3.5 years (Brooke et al, Heckmatt et al). Scoliosis is another common problem in patients with MD. It is more common in Duchenne MD than in other forms, with an incidence of 75-90% (Brooke et al, Heckmatt et al, Thompson and Berenson). The scoliosis develops early and tends to be rapidly progressive, especially when patients become nonambulatory. The curve is usually thoracolumbar or lumbar with associated pelvic obliquity, thoracic kyphosis, and lumbar hyperlordosis. The abnormal sagittal alignment may cause problems with seating systems, even modified systems, and the rapid progression of the scoliosis requires frequent wheelchair adjustments. Braces are not effective in progressive paralytic or neuromuscular curves, and surgery is often indicated. Advancement in pulmonary care and cardiac drugs may now negate the absolute need for scoliosis surgery in Duchenne MD, allowing patients to live into adulthood. A recent 10-year retrospective study showed that 44 of 123 nonambulatory patients aged 17 or older were managed satisfactorily without surgery (Kinali et al, 2006). Although this is only 1 recent report, it gives much hope for many dystrophic patients with scoliosis. The technique of choice for scoliosis when the curve measures 20° or more in patients who are nonambulatory is a posterior spinal fusion from T2 to the sacrum. The indication for earlier operative stabilization of the spine in these patients is due to the rapidly deteriorating cardiopulmonary function (Miller et al, 1988). The FVC is at its maximum in children younger than 10 years. After this point, the FVC rapidly declines, and anesthetic complications rise dramatically in those patients with an FVC less than 30%. Spinal fusion is extended to the pelvis, with complete obliteration of the facet joints to ensure arthrodesis. Often, the instrumentation used is a Luque rod with segmental sublaminar wires to the L5 level, with bone arthrodesis extending into the sacrum. Occasionally, instrumentation and fusion are extended only to L5 because of the diffuse osteopenia in the sacrum, early surgery and low magnitude curves, or because of the possible complications of instrument failure. The literature has cited a high incidence of failure and revision with fusion short of the sacrum; therefore, spinal fusions in patients with MD are extended to the pelvis, especially if done after the curve magnitude is over 30 degrees (Gaine et al, 2004; Sengupta et al, 2002; Mubarak et al, 1993). Preoperative detailsPreoperatively, patients should undergo a detailed cardiac assessment, a pulmonary evaluation with PFTs (including arterial blood gas analysis), and a hematologic workup. Because of potential cardiomyopathy, intraoperative monitoring is an essential component of administering anesthetics. Intraoperative blood loss is usually substantial in patients with MD due to muscle dysfunction, which causes ineffective vessel constriction. Another potential complication of anesthesia is malignant hyperthermia, which is more common in patients with muscle diseases than in patients with other disease entities; this risk is diminished with the use of nitrous oxide, intravenous narcotics, sedatives, and nondepolarizing muscle relaxants. COMPLICATIONSSection 8 of 11
Complications of MD usually include early wheelchair dependence in patients who develop minor musculoskeletal injuries (eg, ankle sprain) and those who are immobilized. Prolonged immobilization worsens the clinical weakness caused by MD and ultimately results in the patient's nonambulatory status. OUTCOME AND PROGNOSISSection 9 of 11
Despite modern advances in gene therapy and molecular biology, MD remains incurable. With proper care and attention, patients have a better quality of life than they would otherwise, but most still die by the time they are age 30 years, usually as a result of cardiopulmonary failure. FUTURE AND CONTROVERSIESSection 10 of 11
The ability of advancing technology and molecular biology with fetal blood detection of affected fetuses as early as the first trimester opens the door to many ethical issues. One such issue is whether pregnancy termination should be available as an option when a muscle disease is detected that may be fatal in the third decade of life. REFERENCESSection 11 of 11
Article Last Updated: Mar 30, 2007 |
