What are the management approaches for different muscle pathologies?

Management of Different Muscle Pathologies

Management of muscle pathologies requires a disease-specific approach centered on glucocorticoid therapy for inflammatory conditions and muscular dystrophies, multidisciplinary care coordination with cardiac and respiratory monitoring, and targeted interventions based on the underlying pathology. 1

Muscular Dystrophies

Duchenne Muscular Dystrophy (DMD)

Glucocorticoids are the only medications that slow decline in muscle strength and function in DMD. 1

• Initiate prednisone/prednisolone at 0.75 mg/kg daily or deflazacort at 0.9 mg/kg daily immediately upon diagnosis 1, 2
• Delaying glucocorticoid therapy accelerates disease progression and worsens functional outcomes 3
• Assess function, strength, and range of motion every 6 months using standardized timed function tests and motor function scales 1, 2
• Implement early gentle exercise and activity programs to maintain function 1

Cardiac monitoring is mandatory: 1

• Perform echocardiogram at diagnosis or by age 6 years, with follow-up at least every 24 months 1
• Obtain ECG, echocardiogram, and Holter monitoring regularly 1
• Start ACE inhibitors and beta-blockers early for cardiac dysfunction 1, 2
• Failure to address cardiac complications early significantly increases mortality 3

Essential care coordination: 1

• Designate a care coordinator as the primary point of contact for families 1
• Screen regularly for depression, anxiety, and cognitive issues 1
• Develop individualized education plans for children 1

Myotonic Dystrophy

Cardiac manifestations occur in approximately 80% of DM1 patients and are major causes of mortality. 4, 2

• DM1 requires aggressive cardiac monitoring due to progressive conduction defects and tachyarrhythmias (ventricular and supraventricular) 2, 4
• DM2 has less frequent (10-20%) and typically less severe cardiac problems, usually limited to first-degree atrioventricular and bundle-branch block 2, 4
• Neurologists must collaborate with cardiologists or electrophysiologists for all myotonic dystrophy patients 4, 2
• Perform cardiac screening before any anesthesia or sedation due to high risk of cardiac complications 4

Inflammatory Myopathies

Immune-Related Myositis (from checkpoint inhibitors)

For Grade 1 (mild pain/weakness): 2

• Continue checkpoint inhibitor therapy 2
• Check creatine kinase, inflammatory markers (ESR, CRP), ANA, RF, anti-CCP 2
• Initiate acetaminophen and/or NSAIDs if no contraindications 2

For Grade 2 (moderate symptoms limiting instrumental activities): 2

• Hold checkpoint inhibitor until symptoms improve to Grade 1 or less 2
• Initiate prednisone or equivalent at 0.5-1 mg/kg 2
• May require permanent discontinuation if objective findings present (elevated enzymes, abnormal EMG, abnormal muscle MRI or biopsy) 2
• Refer to rheumatologist or neurologist 2

For Grade 3-4 (severe weakness limiting self-care): 2

• Hold checkpoint inhibitor and permanently discontinue if any myocardial involvement 2
• Hospitalize for severe weakness 2
• Initiate prednisone 1 mg/kg or methylprednisolone IV 1-2 mg/kg (higher-dose bolus if severe compromise with respiratory, cardiac, or dysphagia involvement) 2
• Consider plasmapheresis and IVIG therapy 2
• Add methotrexate, azathioprine, or mycophenolate mofetil if symptoms do not improve after 4-6 weeks 2

Idiopathic Inflammatory Myopathies

Anti-SRP antibody-positive patients show the most severe muscle involvement: 5

• Lowest muscle strength scores and highest creatine kinase levels 5
• Most severe necrosis and regeneration on biopsy 5
• Require aggressive immunosuppression 6

Anti-MDA5 antibody-positive patients demonstrate the mildest pathological changes: 5

• Fewest necrotic and regenerated muscle fibers 5
• Least inflammatory cell infiltration 5
• May require less aggressive therapy 5

Anti-NXP2 and anti-TIF1γ antibody-positive patients: 5

• Show typical dermatomyositis pathology with perifascicular atrophy 5
• Anti-NXP2 has most frequent inflammatory infiltrates, especially CD4+ T cells 5
• Require screening for malignancy, particularly in dermatomyositis 7

Congenital Myopathies

Cardiac involvement is rare but can be life-threatening when present. 2

• Monitor for hypertrophic, dilated, and left ventricular non-compaction cardiomyopathy phenotypes 2
• Recessive mutations in TTN and MYH7 genes are associated with early dilated cardiomyopathy, ventricular arrhythmias, and sudden cardiac death 2
• Refer to pediatric heart failure specialist when diagnosed in childhood 2

Metabolic and Endocrine Myopathies

Initial evaluation must identify reversible causes: 6

• Check creatine kinase, thyroid function, and 25(OH) vitamin D levels 6
• Remove offending agents (drugs, alcohol, toxins) 6
• Correct endocrine abnormalities (thyroid disease, osteomalacia) 6
• Most metabolic myopathies carry good prognosis when underlying cause is treated 7

Functional Neurological Disorder with Motor Symptoms

For functional tremor: 2

• Teach distraction techniques and entrainment to a new rhythm (tapping, opening/closing hand) 2
• Assist with muscle relaxation to prevent cocontraction 2
• Use gross rather than fine movements (large lettering on whiteboard versus normal handwriting) 2
• Discourage cocontraction or tensing as suppression method 2

For functional dystonia: 2

• Encourage optimal postural alignment with even weight distribution in sitting, transfers, standing, and walking 2
• Grade activity to increase affected limb use with normal movement techniques 2
• Avoid prolonged end-range joint positioning 2
• Avoid serial casting as it has been associated with worsening symptoms and complex regional pain syndrome 2

For functional limb weakness: 2

• Engage in tasks promoting normal movement, good alignment, and even weight-bearing 2
• Use bilateral tasks with upper limbs while standing in a standing frame for lower limb weakness 2

Universal Lifestyle Modifications

All patients with muscle pathologies benefit from: 2, 3

• Supervised, gentle exercise programs to maintain function and reduce pain 3
• Physical activity to maintain physical fitness 2
• Maintaining ideal weight with balanced diet meeting calcium and vitamin D requirements 2, 3
• Smoking cessation as tobacco worsens disease outcomes 2, 3
• Balanced alcohol use and avoidance of misuse 2
• Accident prevention programs to avoid musculoskeletal injuries 2

Critical Pitfalls to Avoid

• Never delay glucocorticoid therapy in muscular dystrophy or inflammatory myopathy as this leads to accelerated disease progression 3, 1
• Never overlook cardiac and respiratory complications as these significantly impact mortality 3, 1
• Never use serial casting for functional dystonia due to risk of worsening symptoms and complex regional pain syndrome 2
• Never fail to screen for malignancy in dermatomyositis as incidence is specifically increased in this condition 7
• Never rechallenge with checkpoint inhibitors if myocardial involvement occurred 2