INTRODUCTION — The muscular dystrophies are an inherited group of progressive myopathic disorders resulting from defects in a number of genes required for normal muscle function [1]. The Duchenne and Becker muscular dystrophies are caused by mutations of the dystrophin gene and are therefore named dystrophinopathies. Weakness is the principal symptom as muscle fiber degeneration is the primary pathologic process.
The dystrophinopathies are inherited as X-linked recessive traits and have varying clinical characteristics. Duchenne muscular dystrophy (DMD) is associated with the most severe clinical symptoms. Becker muscular dystrophy (BMD) has a similar presentation to DMD but a relatively milder clinical course.
The management and prognosis of Duchenne and Becker muscular dystrophy will be discussed in this review. Other aspects of DMD and BMD are reviewed separately. (See "Duchenne and Becker muscular dystrophy: Genetics and pathogenesis" and "Duchenne and Becker muscular dystrophy: Clinical features and diagnosis" and "Duchenne and Becker muscular dystrophy: Glucocorticoid and disease-modifying treatment".)
GLUCOCORTICOID AND DISEASE-MODIFYING TREATMENT — Glucocorticoids are the mainstay of pharmacologic treatment for DMD because of their beneficial effects for improving motor function and pulmonary function, reducing the risk of scoliosis, delaying the loss of ambulation, and possibly for delaying progression of cardiomyopathy and improving survival. The use of glucocorticoids is discussed in detail separately. (See "Duchenne and Becker muscular dystrophy: Glucocorticoid and disease-modifying treatment", section on 'Glucocorticoid treatment'.)
Novel disease-modifying therapies offer the potential to ameliorate the genetic basis of these disorders by increasing the production of functional dystrophin. (See "Duchenne and Becker muscular dystrophy: Glucocorticoid and disease-modifying treatment", section on 'Genetic therapies'.)
REHABILITATION — Rehabilitation for DMD requires multidisciplinary care to coordinate the multiple specialized assessments and interventions needed to maximize function and quality of life for affected individuals.
Multidisciplinary care — In addition to muscle weakness, common problems associated with DMD and BMD include cardiac, pulmonary, orthopedic, nutritional, growth, and weight abnormalities. Pain is also a frequent symptom [2,3]. Intellectual, behavioral, and neuropsychiatric problems may impair development, learning, and socialization. The anticipation and early detection of these problems is important for optimal therapy, and a multidisciplinary care plan is essential to ensure access to appropriate specialists (table 1) [4,5].
Patients with DMD and BMD should have physical therapy, occupational therapy, and speech and language therapy according to their individual needs and stage of disease [4].
Orthopedic interventions — Patients should receive physical therapy to encourage mobility and to prevent or reduce the risk of contractures. The mainstays of physical therapy are passive stretching exercises at the ankles, knees and hips, four to six times a week, to prevent contractures of the Achilles tendons, iliotibial bands, and flexors of the hip [4]. In later stages of disease, stretching may be needed at the wrist, hands, and neck.
Multiple additional interventions and/or modalities may be used based upon the patient's requirements and severity of disease [4]:
●Lightweight plastic ankle-foot orthoses should be applied if the foot remains in plantar flexion during sleep.
●Standing and/or walking may be maintained by using long-leg braces.
●Surgery may be performed to release contractures of the hip flexors, iliotibial bands, and Achilles tendons.
●Standing and ambulation may prevent scoliosis.
●Power stand-up motorized wheelchairs are an option to provide standing mobility.
●Wrist or hand splints for stretching of wrist and long finger flexors and extensors may be helpful in nonambulatory phases.
Orthopedic evaluations should monitor for scoliosis and other complications and surgical interventions should be utilized as needed. Visual inspection of the spine to assess for scoliosis should be done every year in the ambulatory stage and every six months once patients become nonambulatory [6]. Spine radiography should be obtained if visual inspection reveals a curve or if visual inspection is problematic. In the nonambulatory stage, spine radiography should be performed every six months to one year if a curve is present, depending upon skeletal maturity. Patients with a curve >20 should be referred to an orthopedic surgeon. Spine surgery to stabilize or correct scoliosis may improve motor function, patient comfort, sitting balance and tolerance, quality of life, and possibly respiratory function [6]. However, potential outcomes of scoliosis surgery in DMD have not been evaluated in randomized controlled trials [7,8].
Exercise — Boys with DMD who are ambulatory or in the early non-ambulatory stage should participate in regular submaximum (ie, gentle), aerobic exercise to avoid disuse muscle atrophy, immobility, excessive weight gain, and social isolation [4]. Suggested exercises include swimming and cycling, continued in the nonambulatory phase if medically safe. Assisted cycling and robotic-assisted movement are also options in the nonambulatory stage. Low-resistance strength training and optimization of upper body function may provide additional benefits. However, activity should be reduced if patients develop significant muscle pain or myoglobinuria within the 24-hour period after a specific activity, as these may indicate overexertion and contraction-induced muscle injury. Overexertion, eccentric muscle exercises, and high-resistance strength training or activities should be avoided because of the possible adverse effects on fragile muscles in dystrophinopathy. A study of 20 ambulatory boys with DMD showed that a 10-minute standardized calf massage was safe and associated with increased muscle length and decreased stiffness; gait function remained stable [9].
HEALTH MAINTENANCE — Attention to nutrition, bone health, fracture and fall prevention, growth and endocrine management, and routine immunizations is important for optimizing the health and quality of life for patients with DMD.
Nutrition — Depending upon circumstances and treatment (eg, glucocorticoids), patients with DMD can be at risk of malnutrition and/or underweight or overweight for age. Consensus guidelines recommend evaluation with a dietician/nutritionist at every clinic visit, beginning at baseline [4]. The goals of nutritional care are to prevent overweight/obesity, underweight/malnutrition, and promote a healthy diet with optimum intake of calories, protein, fluid, and micronutrients, particularly Vitamin D and calcium. Height and weight should be routinely monitored. (See 'Endocrine management' below.)
We suggest dietary calcium and vitamin D intake in the form of dairy products, other foods rich in calcium and vitamin D, and sunshine exposure. Calcium supplementation (500 to 1000 mg/day) is suggested for children with diminished intake of calcium-containing foods (eg, for children who do not like milk and dairy products) or whose calcium intake is less than the recommended dietary allowance [4]. Vitamin D supplementation is indicated if the serum concentration of vitamin D is <30 ng/mL. Dosing for vitamin D deficiency is discussed separately. (See "Vitamin D insufficiency and deficiency in children and adolescents", section on 'Treatment' and "Vitamin D deficiency in adults: Definition, clinical manifestations, and treatment", section on 'Vitamin D replacement'.)
Patients with suspected dysphagia should be referred to a speech and language therapist for swallowing assessment [4]. Problems with constipation, gastroesophageal reflux, or gastrointestinal motility should prompt referral to a gastroenterologist. Indications for possible gastrostomy tube placement include weight loss, dehydration, malnutrition, aspiration, and moderate or severe dysphagia.
Endocrine management — Endocrine problems related to DMD and glucocorticoid treatment include decreased linear growth, delayed puberty, and adrenal insufficiency. Therefore, standing height and a nonstanding growth measure (eg, arm span, ulnar length, tibia length, knee height) should be measured every six months, beginning in the ambulatory phase; nonstanding measures allow growth assessment once ambulation is lost [4]. A decrease in growth trajectory (ie, downward crossing of a height percentile), an annual height velocity of <4 cm year, or height less than the third percentile should prompt referral to an endocrinologist. However, there are few data to support the use of recombinant human growth hormone for boys with DMD [4,10].
Pubertal development should be assessed every six months starting at age nine years [4]. Lack of pubertal development by age 14 years for boys should trigger referral to an endocrinologist. In such cases, testosterone replacement therapy is indicated. (See "Approach to the patient with delayed puberty", section on 'Testosterone therapy'.)
Adrenal insufficiency — Administration of exogenous glucocorticoids can suppress the hypothalamic-pituitary-adrenal axis (HPA). Abrupt cessation, or too rapid withdrawal, of glucocorticoids in patients on chronic glucocorticoid therapy may cause symptoms of acute adrenal insufficiency, which can be life-threatening. (See "Causes of central adrenal insufficiency in children", section on 'Chronic high-dose glucocorticoid therapy'.)
Therefore, patients, families, and caregivers should be taught the symptoms and signs of adrenal crisis [4], which include weakness, fatigue, myalgia, arthralgia, and hypoglycemia. They should also receive prescriptions for the emergency use of intramuscular hydrocortisone at home; appropriate doses are hydrocortisone 50 mg for children less than two years of age and 100 mg for children two or more years of age and adults.
Patients on chronic glucocorticoid therapy may require additional doses when subjected to physiologic stress (eg, surgery, major trauma, or severe disease) [4]. This is discussed separately. (See "Duchenne and Becker muscular dystrophy: Glucocorticoid and disease-modifying treatment", section on 'Stress-dose glucocorticoids'.)
Patients with a suppressed HPA axis should avoid abrupt stopping or rapid tapering of glucocorticoids. (See "Duchenne and Becker muscular dystrophy: Glucocorticoid and disease-modifying treatment", section on 'Glucocorticoid tapering'.)
Bone health — The approach to monitoring and diagnosis of bone health focuses on identifying the earliest signs of bone fragility, primarily low-trauma fractures of long bones or vertebra [6]. Some individuals with vertebral fractures are asymptomatic, and even mild vertebral fractures are recognized as a predictor of future fractures. Therefore, it is appropriate to monitor patients on glucocorticoid therapy with periodic spine imaging.
●Baseline blood tests (follow up as appropriate):
•Calcium
•Phosphate
•Magnesium
•Alkaline phosphatase
•Parathyroid hormone
●At baseline and annually:
•Calcium and vitamin D intake
•Spine dual energy x-ray absorptiometry (DXA) scanning to measure bone mineral density
•25-hydroxyvitamin D level
●At baseline and follow-up: Lateral thoracolumbar spine radiography every one to two years for patients on glucocorticoids and every two to three years for patients not on glucocorticoids to assess for low-trauma vertebral compression fractures
●Back pain or ≥0.5 standard deviation decline in spine bone mineral density Z score: Lateral thoracolumbar spine radiography
We refer children who develop vertebral or long bone fractures to a pediatric endocrinologist or bone specialist. Such fractures are indications for treatment with intravenous bisphosphonate, which is considered first-line therapy [6]. Prior to starting intravenous bisphosphonate therapy, calcium and vitamin D deficiency should be corrected, and normal renal function should be confirmed.
We refer patients to a dietitian/nutritionist for weight control and discussion of calcium and vitamin D intake. We also refer patients to a pediatric endocrinologist or bone specialist if the vitamin D level is <30 ng/mL (others use 20 ng/mL as the limit) or if DXA scan shows marked deviation from age-normal or baseline values.
Fracture and fall prevention — Proactive guidance and home environment assessment and modification may reduce the risk of vertebral and long bone fractures (table 2) [6]. Assessment and education should be directed by physical or occupational therapists. Important steps include consideration of walking surfaces, terrain, and obstacles. Patients, families, and caregivers should be trained in wheelchair safety and safe lifting when transferring patients (eg, from bed to chair). Interventions include removal of obstacles in the home, safety measures for uneven or slippery surfaces (eg, nonslip treads on ankle-foot orthoses and bare-wood steps), adaptive equipment and patient lift systems to minimize risk of falls or injury, and possible home modifications (eg, handrails on both sides of stairways, grab bars for showers).
Patients, families, and caregivers should be made aware of the fat embolism syndrome that can result from acute fracture or trauma [6]. Presenting signs typically occur 24 to 72 hours after the injury and may include altered mental status, respiratory distress, tachycardia, and a petechial rash. Immediate medical evaluation is indicated. (See "Fat embolism syndrome".)
Immunizations — Children with DMD and BMD should receive all vaccinations recommended by the US Centers for Disease Control and Prevention (see "Standard immunizations for children and adolescents: Overview"). Live virus vaccines should be given before the start of glucocorticoid treatment, as live-virus vaccines are contraindicated in patients with DMD receiving high-dose daily glucocorticoids, defined as >20 mg daily or >2 mg/kg per day of prednisone or equivalent [11].
Consensus guidelines recommend universal immunization of infants and children with pneumococcal vaccine, integrating pneumococcal conjugate vaccine (either 13-valent pneumococcal conjugate vaccine or 15-valent pneumococcal conjugate vaccine) with pneumococcal polysaccharide vaccine [11]. Pneumococcal vaccination for healthy and high-risk children and adults is reviewed in detail elsewhere. (See "Pneumococcal vaccination in adults" and "Pneumococcal vaccination in children", section on 'Immunization of high-risk children and adolescents' and "Pneumococcal vaccination in children".)
Consensus guidelines also recommend annual vaccination with an inactivated influenza vaccine for all individuals with DMD six months of age and older, and all close contacts [11]. Detailed recommendations for influenza vaccination in children and adults are discussed separately. (See "Seasonal influenza vaccination in adults" and "Seasonal influenza in children: Prevention with vaccines", section on 'Target groups'.)
CARDIAC MANAGEMENT — Early diagnosis and treatment of cardiomyopathy in patients with DMD and BMD is important for improving quality of life and maximizing survival [6,12].
Surveillance for boys — Consensus guidelines recommend a baseline assessment of cardiac function at the time of diagnosis of DMD, including electrocardiogram, noninvasive imaging with echocardiography or cardiac magnetic resonance imaging (MRI), and consultation with a cardiologist [6].
The cardiac evaluation, including electrocardiogram and noninvasive imaging, should be repeated at least annually for asymptomatic individuals [6]. The frequency of monitoring should be increased, as directed by the cardiologist, with the onset of heart failure symptoms or the appearance of abnormalities on cardiac imaging, such as myocardial fibrosis, left ventricular enlargement, or left ventricular dysfunction. The risk of cardiac arrhythmia is increased with disease progression, and surveillance in late nonambulatory stage should include periodic 24-hour Holter monitoring as directed by the cardiologist.
The choice of noninvasive imaging modality is usually made by the cardiologist following the patient. Echocardiography is often preferred for noninvasive imaging up until approximately the age of 15 years, when the degree of scoliosis may limit acoustic windows. Echocardiography is sufficiently informative for measuring the left ventricular ejection fraction, does not require sedation, and costs far less than cardiac MRI. The consensus guidelines consider cardiac MRI as the noninvasive imaging method of choice, but acknowledge that the need for sedation may limit its utility for younger children. The guidelines recommend echocardiography up until the age of six to seven years and cardiac MRI for older children, who are less likely to need sedation.
Surveillance for female carriers — For optimal cardiac care of females with a heterozygous DMD pathogenic variant, we recommend evaluation, including a cardiac MRI, by a cardiac specialist with experience in the treatment patients with neuromuscular disorders, in agreement with consensus guidelines [6,13,14]. The initial evaluation should take place in late adolescence or early adulthood (or earlier at the appearance of cardiac signs and symptoms). For female carriers who remain asymptomatic, the evaluation and cardiac MRI should be repeated every three to five years. Patients should also receive education about the risk of developing cardiomyopathy and about the signs and symptoms of heart failure.
Female carriers who develop symptoms or cardiac imaging abnormalities should have an increased frequency of cardiac assessment, as guided by a cardiologist, and treatment of cardiac disease similar to that for boys with dystrophinopathy [13].
Treatment — We agree with consensus guidelines, which recommend initiation of an angiotensin converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) for boys with DMD, beginning by age 10 years [6,12]. Overt heart failure is treated with other therapies such as diuretics and digoxin, as managed by the cardiologist. Cardiac transplantation is an option in patients with BMD who have severe dilated cardiomyopathy and limited or no clinical evidence of skeletal muscle disease. (See "Heart failure in children: Management".)
The possible preventive efficacy of ACE inhibitors was evaluated in a randomized trial of 57 children with DMD (mean age 10.7 years) who had a mean left ventricular ejection fraction (LVEF) of 65 percent [15]. The children were randomly assigned to perindopril (2 to 4 mg/day) or placebo. There was no difference in LVEF at three years. All of the children were then treated with open-label perindopril for up to 10 years. Although the mean LVEF was still not different (58.6 versus 56.0 percent with placebo), an LVEF less than 45 percent was noted in only one of the 27 patients originally treated with perindopril compared with 8 of the 29 treated with placebo. After an additional year, there were three deaths in the placebo group, all among the eight patients with an LVEF <45 percent. After 10 years of follow-up, survival status was available for all patients, and survival for the original perindopril and placebo groups was 93 and 66 percent, respectively [16]. However, more data are needed to prove that ACE inhibitors slow progression of heart disease in children with DMD who have a normal LVEF.
In a small randomized controlled trial of boys with DMD and early cardiomyopathy, the mineralocorticoid receptor antagonist eplerenone was effective for attenuating the decline in left ventricular systolic function [17], and this benefit was sustained in an open-label extension phase [18]. Further study is needed to confirm these findings [6].
Results from a retrospective observational study suggest that early diagnosis and treatment of dilated cardiomyopathy in patients with DMD and BMD may lead to ventricular remodeling [19]. Among 69 affected boys, an ACE inhibitor was started in 27 with DMD and four with BMD after the first abnormal echocardiogram indicative of dilated cardiomyopathy (eg, LVEF <55 percent or left ventricular dilation); the mean age was 15 years. A beta blocker (carvedilol or metoprolol) was added after three months if echocardiography showed no improvement. At a mean follow-up of 3.3 years among 29 of the 31 patients who had repeat echocardiography, left ventricular size and function showed normalization, improvement, or stabilization in 19, 8, and 2 patients, respectively (66, 26, and 8 percent). In addition, the mean LVEF increased from 36 to 53 percent and there was evidence of improved ventricular geometry as measured by reduced sphericity.
RESPIRATORY MANAGEMENT — Respiratory management is a critical component of DMD care. Respiratory complications include respiratory muscle fatigue, atelectasis, mucous plugging, pneumonia, and respiratory failure [6].
Surveillance — Serial monitoring of vital capacity should begin when the individual is five to six years of age and followed yearly during the ambulatory stage [6]. When patients become nonambulatory, monitoring should occur at least every six months and include the following parameters [6]:
●Seated vital capacity
●Maximum inspiratory pressure
●Maximum expiratory pressure
●Peak cough flow
●Blood oxygen saturation by pulse oximetry (SpO2)
●End-tidal or transcutaneous partial pressure of carbon dioxide in the blood (pCO2)
A sleep study with capnography should be obtained at any stage for patients with excessive weight gain, to exclude sleep apnea, or for those with symptoms of sleep-disordered breathing; these include fatigue, dyspnea, morning or continuous headaches, frequent nocturnal awakenings or difficult arousal, hypersomnolence, difficulty concentrating, awakenings with dyspnea and tachycardia, or frequent nightmares [6].
Core interventions — All patients should receive yearly immunizations with inactivated influenza vaccine and pneumococcal vaccines [6]. (See 'Immunizations' above.)
The core respiratory therapies for DMD are lung volume recruitment, assisted coughing, nocturnally assisted ventilation, and subsequent daytime ventilation [6]. These therapies are associated with prolonged survival [20-23]. Consensus guidelines recommend the following indications [6]:
●Lung volume recruitment, using a self-inflating manual ventilation bag or mechanical insufflation-exsufflation to achieve deep lung inflation once or twice daily, when vital capacity is <60 percent of predicted.
●Manual and mechanically assisted cough techniques when vital capacity is <50 of predicted, peak cough flow is <270 L/min, or maximum expiratory pressure is <60 cm water.
●Nocturnal ventilation with back-up rate of breathing (noninvasive preferred) when vital capacity is <50 of predicted, maximum inspiratory pressure is <60 cm H2O, or awake baseline SpO2 is <95 percent or pCO2 is >45 mmHg.
●Nocturnal ventilation is also indicated when there are symptoms or signs of sleep hypoventilation or other sleep-disordered breathing, regardless of the level of pulmonary function, or an abnormal sleep study characterized by a pCO2 of >50 mmHg for ≥2 percent of sleep time, a sleep-related increase in pCO2 of 10 mmHg above the awake baseline for ≥2 percent of sleep time, an SpO2 of ≤88 percent for ≥2 percent of sleep time or for at least five minutes continuously, or an apnea-hypopnea index of ≥5 events per hour.
●Assisted daytime ventilation is added when, despite nocturnal ventilation, daytime SpO2 is <95 percent, pCO2 is >45 mmHg, or symptoms of awake dyspnea are present.
In most cases, the need for these interventions arises after loss of ambulation [6].
Tracheostomy — The decision to consider tracheostomy is mainly dependent upon individual preference and clinical course. Our approach is to counsel patients, families, and caregivers together with the pulmonary and palliative care teams and support whatever decision they make. We emphasize that the decision regarding tracheostomy is best made early while the patient is stable on noninvasive ventilation and not during an emergency or medical crisis. Most patients do not choose tracheostomy. Consensus guidelines endorse the use of noninvasive ventilation, and note that clinical experience supports noninvasive assisted ventilation for up to 24 hours a day [6]. Observational evidence suggests that continuous noninvasive assisted ventilation can obviate the need for tracheostomy [21,24,25]. (See "Continuous noninvasive ventilatory support for patients with respiratory muscle dysfunction".)
Indications for tracheostomy include patient preference, inability to use noninvasive ventilation successfully, three failed extubation attempts during a critical illness despite optimum use of noninvasive ventilation and mechanically assisted coughing, or failure of noninvasive methods of cough assistance to prevent aspiration of secretions into the lungs due to bulbar muscle weakness [6].
Respiratory infection — Antibiotic therapy may be used during the late nonambulatory stage in the setting of acute respiratory illness, as determined by the pulmonologist or primary physician caring for the patient. Although arbitrary, consensus guidelines recommend antibiotics when there are three or more of the following signs of pneumonia [6]:
●Fever
●Elevated white blood cell count or C-reactive protein
●Sputum production
●Pulmonary infiltrate on chest radiography
●Hypoxemia or respiratory distress
During respiratory infections, use of a home pulse oximeter can guide the frequency of assisted coughing, which should be increased when SpO2 is <95 percent [6].
Noninvasive ventilation may be useful after procedures involving anesthesia or sedation, and may also be used together with assisted coughing to aid in extubating patients who are mechanically ventilated due to respiratory infections [26].
PSYCHOSOCIAL CARE — Promotion of age-appropriate independence and social development is a major goal for individuals with DMD [11].
Mental health — Psychosocial care for DMD and BMD includes routine assessment of the mental health of the patient and family at every clinic visit, with ongoing support and referrals to a psychiatrist or psychologist if needed (table 3) [11]. Patients with DMD appear to have increased rates of intellectual disability, learning disorders, autism spectrum disorder, and attention deficit hyperactivity disorder. In addition, patients and their family members have an increased risk of anxiety and depression. Patients should have neuropsychologic evaluations and interventions when developmental, emotional, or behavioral problems arise. Standard cognitive-behavioral and pharmacologic treatments should be used as appropriate.
Consensus guidelines recommend the pharmacologic interventions for the following indications [11]:
●Selective serotonin reuptake inhibitors for depression, anxiety, and obsessive-compulsive disorder
●Alpha-adrenergic agonists (first-line) or second-generation antipsychotics (second-line) for aggression and anger or emotional dysregulation
●Stimulants or alpha-adrenergic agonists for attention deficit hyperactivity disorder
Note that the presence of cardiac disease in DMD can increase the risk of adverse effects with medications such as stimulants, antipsychotic agents, and certain antidepressants.
Educational and vocational support — Educational support, accommodations, and special services should be incorporated into a formal educational plan, updated annually, according to individual needs [11]. Planning for vocational training and adult roles should begin early (figure 1), as part of education planning, and account for individual circumstances such as intellectual disability, physical challenges, and availability of social, community, and government resources.
Advanced planning and palliative care — Patients with muscular dystrophy should be informed of their long-term prognosis, though this may not be appropriate for those with early or mild disease, particularly in childhood [5]. When circumstances allow, clinicians should sensitively engage patients, families, and caregivers in discussions about treatment options, advanced care planning, advanced directives, palliative care, and other end-of-life issues, as guided by patient values and preferences.
Palliative care can help patients, families, and caregivers at various points in the course of disease, including diagnosis, major treatment decisions, decline in health status, life-threatening events, and end-of-life care [11]. In the nonambulatory phase, caregivers and families should be assisted with arranging respite care and home health care services as needed. Hospice care should be offered for patients at the end of life. Patients with DMD should be encouraged to express how they prefer to be treated and supported when unable to speak for themselves; even minors may be able to participate in formulating advanced care directives. Individuals with DMD should designate a health care power of attorney by age 18 years. (See "Pediatric palliative care" and "Communication of prognosis in palliative care" and "Advance care planning and advance directives".)
Support groups — Support and advocacy groups are invaluable for providing helpful information to individuals, caregivers, and families affected by DMD and BMD. In the United States, national organizations include the Muscular Dystrophy Association (MDA) and Parent Project Muscular Dystrophy (PPMD). The TREAT-NMD network based in Europe provides an online searchable list of worldwide DMD patient organizations.
SURGERY AND ANESTHESIA — Patients with DMD have a high risk of complications when they undergo surgery or procedures requiring anesthesia or sedation [6,27]. These potentially life-threatening risks include the following:
●Reactions (eg, rhabdomyolysis and hyperkalemia) to succinylcholine and certain inhaled anesthetics
●Upper airway obstruction
●Hypoventilation
●Atelectasis
●Respiratory failure
●Difficulty weaning from mechanical ventilation
●Cardiac arrhythmias and sudden cardiac arrest
●Heart failure
Patients with DMD or BMD should have preoperative evaluations by pulmonary, anesthesia, and cardiac specialists prior to any surgery [6,27].
●Cardiac care – Patients should be assessed with electrocardiography and noninvasive cardiac imaging before major surgery [6]. Patients with normal cardiac function having minor surgery should have a cardiac evaluation if more than one year has elapsed since the last cardiac assessment.
●Respiratory care – Assisted coughing techniques and noninvasive ventilation may be useful after procedures involving anesthesia or sedation to aid in extubating patients who are mechanically ventilated [11,26]. Preoperative training in the use of these interventions is advised. Manual and mechanically assisted cough techniques should be used for older teens and adults when peak cough flow is <270 L/min or maximum expiratory pressure is <60 cm water. Noninvasive ventilation is recommended when vital capacity is <50 of predicted, and particularly when vital capacity is <30 percent of predicted.
After extubation, supplemental oxygen should be used only with concomitant use of noninvasive ventilation [6]. Given the presence of neuromuscular respiratory muscle weakness, incentive spirometry is not indicated for patients with DMD.
●Anesthesia – Total intravenous anesthesia is indicated for patients with DMD [28]. Succinylcholine (a depolarizing neuromuscular blocking agent) is absolutely contraindicated because it carries an unacceptable risk of life-threatening hyperkalemia and rhabdomyolysis [6,29]. Hyperkalemia and rhabdomyolysis have also occurred in patients with DMD who were exposed to one of the potent inhaled halogenated anesthetics (ie, sevoflurane, desflurane, enflurane, isoflurane, and halothane). In this setting, rhabdomyolysis complications may be confused with malignant hyperthermia. (See "Susceptibility to malignant hyperthermia: Evaluation and management", section on 'Dystrophinopathies'.)
The American College of Chest Physicians (ACCP) published a consensus statement in 2007 regarding the management of patients with DMD undergoing anesthesia or sedation [27]. Key points of the ACCP recommendations regarding suggested management before (table 4), during (table 5), and after (table 6) anesthesia or sedation are shown in the tables.
●Hematologic issues – Options for managing intraoperative blood loss include cell-saver technology, and use of aminocaproic acid or tranexamic acid [6]. Compression stockings or pneumatic compression devices should be used for prevention of deep venous thrombosis and venous thromboembolism; postoperative antithrombotic treatment with heparin or aspirin is considered inappropriate for patients with DMD.
EMERGENCY CARE — Recognition of the key issues that affect the health of patients with DMD is important when they need emergency care [11]. These include advance directives, baseline health status, evaluation of respiratory, cardiac, endocrine, and orthopedic problems, the high likelihood they will need hospital admission, and disposition after discharge from emergency care (table 7).
PROGNOSIS — Patients with DMD may experience some improvement between three and six years of age. However, this is followed by gradual but relentless deterioration. Most patients lose ambulation before the age of 12 years and require noninvasive ventilation (NIV) by late teenage years. In our clinical experience, most patients initially use NIV during nighttime sleep, followed by NIV during daytime and nighttime sleep, and later by NIV throughout the day and night, a progression that generally occurs over 5 to 10 years.
Life expectancy is shortened with DMD, but survival into adulthood is now common [30,31]. In the earlier literature, most patients with DMD died in their late teens or early twenties from respiratory insufficiency (most commonly) or arrhythmia secondary to cardiomyopathy [1]. Survival, neuromuscular function, and quality of life in DMD are improving due to longer-term treatment with glucocorticoids, advances in cardiac and respiratory care, and increased utilization of assisted NIV [20,31-38]. However, despite these advances, survival beyond the fourth decade is uncommon. In one meta-analysis, patients with DMD born after 1990 had a median life expectancy of approximately 28 years [30]. Another meta-analysis found that patients who received ventilatory support (introduced in most settings in the 1990s) had a median life expectancy of approximately 30 years [31].
Patients with BMD typically have a milder clinical course than those with DMD, and remain ambulatory beyond the age of 16 years and into adult life; they usually survive beyond the age of 30 years and have a mean age of death in the mid-40s [1,39,40]. The most common cause of death with BMD is heart failure from dilated cardiomyopathy, which also causes considerable morbidity in these patients despite their milder skeletal muscle involvement [41]. (See "Duchenne and Becker muscular dystrophy: Clinical features and diagnosis", section on 'Becker muscular dystrophy'.)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Muscular dystrophy".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Muscular dystrophy (The Basics)")
●Beyond the Basics topics (see "Patient education: Overview of muscular dystrophies (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Disease-modifying therapy – Glucocorticoids are the mainstay of pharmacologic treatment for Duchenne muscular dystrophy (DMD) (figure 2). Genetic therapies (eteplirsen, golodirsen, viltolarsen, and ataluren) are available in some countries; these therapies increase dystrophin expression, but clinical benefit has not been established. (See "Duchenne and Becker muscular dystrophy: Glucocorticoid and disease-modifying treatment".)
●Rehabilitation – Patients with DMD requires multidisciplinary care to coordinate the multiple specialized assessments and interventions needed to maximize function and quality of life for affected individuals (table 1). Orthopedic interventions are specifically aimed at maintaining function and preventing contractures. For boys with DMD who are ambulatory or in the early nonambulatory stage of the disorder, we suggest regular submaximum (ie, gentle) exercise to avoid disuse muscle atrophy and other complications of inactivity. (See 'Rehabilitation' above.)
●Health maintenance – Attention to nutrition, bone health, fracture and fall prevention, growth and endocrine management, and routine immunizations is important for optimizing function and quality of life for patients with DMD. (See 'Health maintenance' above.)
•Nutrition – Weight and growth should be monitored, and evaluation by a dietician/nutritionist is indicated at diagnosis and at every clinic visit. For all patients with DMD, we suggest dietary calcium and vitamin D supplementation in the form of dairy products, other foods rich in calcium and vitamin D, and sunshine exposure (Grade 2C). For children with diminished intake of calcium-containing foods, we suggest calcium supplementation (500 to 1000 mg/day). Children with a serum concentration of vitamin D <30 ng/mL should receive vitamin D supplementation. (See 'Nutrition' above.)
•Endocrine management – A decrease in growth trajectory, an annual height velocity of <4 cm year, or height less than the third percentile should prompt referral to an endocrinologist. Lack of pubertal development by age 14 years for boys should also trigger referral to an endocrinologist. (See 'Endocrine management' above.)
•Bone health – Patients with DMD often have risk factors for poor bone health that may include decreased mobility, muscle weakness, and side effects of glucocorticoid therapy. The approach to monitoring bone health focuses on identifying the earliest signs of bone fragility with periodic spine imaging and measurement of bone mineral density. Proactive guidance and home environment assessment and modification may reduce the risk of vertebral and long bone fractures (table 2). (See 'Bone health' above and 'Fracture and fall prevention' above.)
●Cardiac management – For patients with DMD, a baseline assessment of cardiac function, including electrocardiogram and noninvasive cardiac imaging, is recommended at the time of diagnosis and at least annually thereafter. Female DMD carriers should have a baseline cardiac assessment in early adulthood. For boys with DMD, we recommend initiation of an angiotensin converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) beginning by age 10 years (Grade 1B). (See 'Cardiac management' above.)
●Respiratory management – This is a critical component of DMD care. Serial monitoring of vital capacity should begin when the individual is five to six years of age and followed yearly during the ambulatory stage. When patients become nonambulatory, more extensive monitoring should occur at least every six months. The core respiratory therapies for DMD are lung volume recruitment, assisted coughing, nocturnally assisted ventilation, and subsequent daytime ventilation. In most cases, the need for these interventions arises after loss of ambulation. Detailed indications are listed above. (See 'Respiratory management' above.)
●Psychosocial care – For DMD and Becker muscular dystrophy (BMD), psychosocial care includes routine assessment of the mental health of the patient and family at every clinic visit, with ongoing support and referrals to a psychiatrist or psychologist if needed (table 3). Multidisciplinary care should include educational support, vocational training, and planning for adult roles (figure 1). Clinicians should sensitively engage patients, families, and caregivers in discussions about treatment options, advanced care planning, advanced directives, palliative care, and other end-of-life issues, as guided by patient values and preferences. (See 'Psychosocial care' above.)
●Surgery and anesthesia – Patients with DMD have a high risk of complications when they undergo surgery or procedures requiring anesthesia or sedation, and should have preoperative evaluations by pulmonary, anesthesia, and cardiac specialists prior to any surgery. Total intravenous anesthesia is indicated for patients with DMD. Succinylcholine (a depolarizing neuromuscular blocking agent) and certain inhalational anesthetics are absolutely contraindicated because they carry an unacceptable risk of life-threatening hyperkalemia and rhabdomyolysis. (See 'Surgery and anesthesia' above.)
