What are the causes of muscle spasms in a patient with potential underlying medical conditions such as multiple sclerosis or peripheral artery disease?

Causes of Muscle Spasms

Neurological and Neuromuscular Causes

Muscle spasms in patients with multiple sclerosis result from spasticity affecting flexor muscles, causing painful involuntary contractions, clonus, and muscular rigidity that are specifically treatable with baclofen. 1

Multiple Sclerosis-Related Spasticity

• Spasticity in MS produces reversible flexor spasms with concomitant pain and muscular rigidity, representing altered neuromuscular control from central nervous system demyelination 1
• These spasms originate from peripheral nerve dysfunction and represent true cramps characterized by sudden, painful, involuntary muscle contractions 2

Exercise-Associated Muscle Cramps

• The primary mechanism involves neuromuscular fatigue creating an imbalance between excitatory drive from muscle spindles and inhibitory drive from Golgi tendon organs to alpha motor neurons 3, 4
• Muscle overload and fatigue affect this balance, resulting in localized muscle cramps in working muscle groups 3
• Dehydration and electrolyte depletion theories are less supported because these systemic abnormalities cannot explain why cramping occurs only in specific working muscle groups 3

Vascular and Ischemic Causes

Peripheral Arterial Disease

• PAD causes exertional muscle symptoms described as fatigue, aching, numbness, or pain in the buttock, thigh, calf, or foot, with discomfort related to exertion and relieved by rest 5
• Vasospastic diseases cause pathological vasoconstriction affecting any muscular vessel, including Raynaud's phenomenon and other vasospastic syndromes 5
• Small-vessel disease associated with rheumatoid arthritis, systemic lupus erythematosus, and other connective tissue diseases can produce muscle symptoms 5

Coronary Vasospasm

• Prinzmetal's angina demonstrates how vasospasm can cause muscle-related symptoms through dysfunctional endothelium exposing smooth muscle to vasoconstrictors (catecholamines, thromboxane A2, serotonin, histamine, endothelin) 5
• Autonomic nervous system involvement with reduced parasympathetic tone and enhanced alpha-adrenergic receptor reactivity contributes to spasm 5

Inflammatory and Autoimmune Myopathies

Idiopathic Inflammatory Myopathies

• Dermatomyositis and polymyositis cause proximal muscle weakness with cricopharyngeal weakness or spasm producing dysphagia evident on videofluoroscopy 5
• Immune-mediated necrotizing myopathy presents with acute or subacute proximal muscle weakness, sometimes triggered by statins, viruses, or malignancy 5
• Checkpoint inhibitor-induced myositis carries 20% mortality risk when concurrent myocarditis develops, requiring immediate withdrawal of immunotherapy and high-dose glucocorticoids 6

Drug-Induced Causes

Statin-Associated Myopathy

• Statins are the most common drug cause of muscle spasms, producing either statin-associated myopathy or immune-mediated necrotizing myopathy requiring aggressive immunosuppression 5, 6
• Statin-induced necrotizing myopathy associates with antibodies against HMGCR protein upregulated in regenerating muscle 5
• When mild to moderate muscle symptoms develop, discontinue the statin and evaluate for hypothyroidism, reduced renal or hepatic function, rheumatologic disorders (polymyalgia rheumatica), steroid myopathy, vitamin D deficiency, or primary muscle diseases 5

Other Medications

• Corticosteroids cause steroid myopathy through protein degradation via the FOXO3 pathway and intramuscular fat accumulation 5, 6
• SGLT2 inhibitors and alcohol can produce proximal myopathy with muscle spasms 6

Metabolic and Nutritional Causes

Endocrine Disorders

• Cushing's disease-related myopathy involves multifactorial protein degradation and intramuscular fat accumulation requiring definitive treatment of hypercortisolism 6
• Hypothyroidism increases risk for muscle symptoms and should be evaluated when spasms develop 5

Vitamin Deficiencies

• Isolated pyridoxine (vitamin B6) deficiency presents as painful muscle spasms in extremities, even without other B vitamin deficiencies, particularly in type 2 diabetes patients 7
• Vitamin D deficiency increases risk for muscle symptoms and should be assessed 5

Critical Diagnostic Pitfalls

• Do not assume all muscle spasms in MS patients are from spasticity—evaluate for concurrent metabolic, drug-induced, or inflammatory causes 5, 6, 1
• In PAD patients, distinguish true claudication (exertional, relieved by rest) from neurogenic causes or inflammatory myopathy 5
• When evaluating statin users, recognize that immune-mediated necrotizing myopathy may persist or worsen after statin discontinuation, requiring immunosuppression rather than simple drug withdrawal 5, 6
• Assess for life-threatening causes first: checkpoint inhibitor myositis with myocarditis, severe inflammatory myopathy with bulbar or respiratory involvement 6