Cardiology > Myopathies 

Background

Myopathies are a heterogeneous group of disorders characterized by primary dysfunction of skeletal muscle fibers, leading to weakness, fatigue, and sometimes muscle pain or atrophy. Unlike neurogenic conditions, myopathies originate within the muscle itself and are not caused by nerve damage. Depending on the cause, they may be inherited (e.g., muscular dystrophies, congenital myopathies) or acquired (e.g., inflammatory, metabolic, toxic, or endocrine-related). 

II) Classification or Types 

By Etiology: 

• • Inherited Myopathies: 

• • • Muscular Dystrophies: Duchenne, Becker, limb-girdle, facioscapulohumeral, Emery-Dreifuss 

• • • Congenital Myopathies: Central core disease, nemaline myopathy 

• • • Metabolic Myopathies: Pompe, McArdle, CPT-II deficiency 

• • • Mitochondrial Myopathies: MELAS, MERRF 

• • • Channelopathies: Hypokalemic periodic paralysis, myotonia congenita 

• • Acquired Myopathies: 

• • • Inflammatory: Polymyositis, dermatomyositis, inclusion body myositis 

• • • Toxic: Statins, alcohol, steroids, colchicine 

• • • Endocrine: Hypothyroidism, hyperthyroidism, Cushing’s disease 

• • • Critical illness myopathy 

By Clinical Course: 

• • Acute: Toxic, inflammatory 

• • Chronic: Muscular dystrophies, endocrine 

• • Episodic: Channelopathies, metabolic myopathies 

III) Pathophysiology 

The pathophysiology of myopathies varies depending on the underlying etiology—genetic, inflammatory, metabolic, toxic, or endocrine—but ultimately converges on impaired muscle fiber function or integrity leading to weakness, fatigue, and degeneration. 

In inherited myopathies (e.g., muscular dystrophies), mutations in structural proteins such as dystrophin, sarcoglycan, or lamin disrupt the stability of the muscle cell membrane (sarcolemma) during contraction. This mechanical fragility leads to repeated cycles of muscle fiber damage, inflammation, and necrosis, followed by ineffective regeneration and replacement by fat and connective tissue (fibrosis), contributing to progressive muscle weakness. 

In inflammatory myopathies (e.g., polymyositis, dermatomyositis), immune-mediated muscle injury is driven by cytotoxic T cells (CD8⁺) infiltrating and attacking myofibers in polymyositis, or complement-mediated vascular injury targeting perifascicular regions in dermatomyositis. Chronic inflammation leads to fiber atrophy, fibrosis, and loss of contractile strength. 

In metabolic myopathies, defects in enzymes involved in glycogenolysis (e.g., McArdle disease) or oxidative phosphorylation (e.g., mitochondrial disorders) impair ATP production. This energy deficit causes exercise-induced muscle fatigue, cramps, or rhabdomyolysis, especially under increased metabolic demand. 

Toxic myopathies, such as those induced by statins or alcohol, involve mitochondrial dysfunction, impaired protein synthesis, or direct myofibrillar injury, leading to myocyte necrosis or apoptosis. 

Endocrine-related myopathies result from hormonal imbalances affecting protein turnover, mitochondrial activity, and muscle metabolism. For instance, hypothyroidism reduces mitochondrial oxidative capacity, while hypercortisolism leads to protein catabolism and muscle atrophy, especially of proximal muscles. 

IV) Epidemiology 

• • Age: Varies widely; Duchenne manifests in early childhood, while polymyositis typically appears in middle age 

• • Sex: Some forms (e.g., Duchenne, Becker) are X-linked and thus more common in males 

• • Prevalence: Rare overall but significant in neuromuscular clinics 

• • Geography: Some types are more prevalent in specific ethnic groups due to founder mutations or consanguinity 

Etiology

I) What Causes It 

• • Genetic mutations in structural muscle proteins (e.g., dystrophin, sarcoglycan, myosin) 

• • Autoimmune-mediated muscle inflammation 

• • Metabolic enzyme deficiencies affecting energy production 

• • Mitochondrial DNA mutations 

• • Endocrine dysfunction (e.g., thyroid disorders) 

• • Drug or toxin exposure (e.g., statins, corticosteroids) 

• • Systemic illnesses (e.g., lupus, sarcoidosis) 

II) Risk Factors 

• • Family history of neuromuscular disease 

• • Autoimmune diseases (e.g., SLE, RA) 

• • Use of myotoxic drugs (e.g., statins, colchicine) 

• • Viral infections (e.g., HIV, HTLV-1) 

• • Endocrinopathies 

• • Advanced age (inclusion body myositis) 

Clinical Presentation

I) History (Symptoms) 

• • Symmetric proximal muscle weakness (e.g., difficulty climbing stairs, rising from chair) 

• • Fatigue with exertion 

• • Myalgias or muscle cramps (especially in metabolic/toxic types) 

• • Muscle atrophy in chronic stages 

• • Drooping eyelids (ptosis) and double vision (in ocular myopathies) 

• • Dysphagia or dysarthria in some advanced myopathies 

• • Respiratory symptoms (e.g., dyspnea, hypoventilation) in severe or late-stage disease 

• • Cardiac symptoms in dystrophinopathies, myotonic dystrophy 

II) Physical Exam (Signs) 

Vital Signs: 

• • May be normal; tachypnea in respiratory involvement 

Neurologic Exam: 

• • Symmetric weakness, often proximal > distal 

• • Normal sensation and reflexes (unless late-stage) 

• • Muscle atrophy or pseudohypertrophy 

• • Gower’s sign in Duchenne 

• • Facial and neck weakness in some congenital and mitochondrial forms 

Cardiac and Respiratory: 

• • Signs of cardiomyopathy (e.g., displaced PMI, S3) 

• • Decreased breath sounds or use of accessory muscles 

Differential Diagnosis (DDx)

• • Motor neuron disease (e.g., ALS) 

• • Myasthenia gravis 

• • Peripheral neuropathy 

• • Multiple sclerosis 

• • Guillain-Barré syndrome 

• • Polymyalgia rheumatica 

• • Drug-induced weakness (e.g., corticosteroids, colchicine) 

• • Musculoskeletal causes (e.g., fibromyalgia) 

Diagnostic Tests

Initial Tests: 

Creatine Kinase (CK): 

• • Elevated in most myopathies, especially dystrophinopathies and inflammatory types 

Electromyography (EMG): 

• • Myopathic pattern: small-amplitude, short-duration motor unit potentials 

Muscle Biopsy: 

• • Gold standard in many cases 

• • Shows inflammation, necrosis, dystrophic changes, or specific inclusions 

Genetic Testing: 

• • Essential for inherited myopathies 

• • Panels or whole-exome sequencing 

Autoimmune Panel: 

• • ANA, anti-Jo-1, anti-Mi-2 for inflammatory myopathies 

Thyroid Panel: 

• • TSH, free T4 to assess endocrine causes 

MRI of Muscle: 

• • Can show areas of inflammation, edema, or fatty replacement 

• • Guides biopsy location 

Pulmonary Function Tests: 

• • Especially in suspected respiratory muscle involvement 

Cardiac Workup: 

• • ECG, echocardiography, and cardiac MRI for cardiomyopathy screening 

• • Holter monitor if arrhythmias suspected 

Treatment

I) Medical Management: 

Inflammatory Myopathies: 

• • High-dose corticosteroids (initial treatment) 

• • Immunosuppressants (e.g., azathioprine, methotrexate) 

• • IVIG or rituximab in refractory cases 

Genetic Myopathies: 

• • No cure; focus on symptom management 

• • Corticosteroids in Duchenne can slow progression 

• • Eteplirsen for exon-skipping in select DMD mutations 

• • Enzyme replacement (e.g., alglucosidase alfa in Pompe) 

Toxic/Endocrine: 

• • Stop offending drug 

• • Correct hormonal imbalance 

Supportive Care: 

• • Physical and occupational therapy 

• • Respiratory support: Non-invasive ventilation or cough assist 

• • Nutritional optimization 

• • Speech therapy for dysphagia 

II) Interventional/Surgical: 

• • Pacemaker/ICD: For conduction defects or cardiomyopathy 

• • Spinal stabilization: In severe scoliosis affecting respiration 

• • Feeding tube (PEG): For severe dysphagia 

Patient Education, Screening, Vaccines

• • Emphasize medication and therapy adherence 

• • Avoid strenuous activity in metabolic myopathies 

• • Educate on signs of respiratory decompensation 

• • Genetic counseling for family planning 

• • Early recognition of cardiac symptoms 

• • Vaccines: Annual influenza, pneumococcal, COVID-19; crucial in those with respiratory involvement 

Consults/Referrals

• • Neurology: Primary diagnosis and management 

• • Cardiology: For cardiomyopathy, arrhythmias 

• • Pulmonology: For respiratory assessment and support 

• • Physical medicine and rehabilitation (PM&R): For mobility and ADLs 

• • Genetics: Counseling and testing 

• • Nutrition/Speech Therapy: For dysphagia, malnutrition 

• • Palliative care: In progressive or advanced disease 

Follow-Up

• • CK and inflammatory markers for monitoring disease activity 

• • Pulmonary function tests annually or more often if declining 

• • Echocardiogram and ECG annually in those at risk 

• • Therapy reassessments every 3–6 months 

• • • Monitor for treatment side effects (e.g., steroid-induced diabetes or osteoporosis) 

• • • Adjust care plan based on disease progression and patient goals