What causes soleus muscle atrophy?

Causes of Soleus Muscle Atrophy

Soleus muscle atrophy results primarily from disuse/immobilization, denervation, peripheral neuropathy (including vitamin B6 deficiency), peripheral artery disease with ischemia-reperfusion injury, and systemic conditions like sarcopenia, neuromuscular blockade, and inflammatory myopathies.

Primary Mechanisms of Soleus Atrophy

Disuse and Immobilization

• Mechanical unloading is the most common cause of soleus atrophy, occurring with bed rest, immobilization, hindlimb suspension, or reduced weight-bearing activity 1, 2.
• The soleus, being a predominantly slow-twitch postural muscle, is particularly vulnerable to disuse compared to fast-twitch muscles 1.
• Disuse triggers decreased protein synthesis and increased protein degradation through activation of ubiquitin ligases (MuRF1 and MAFbx), leading to reduced muscle fiber cross-sectional area without fiber loss 2, 3.
• Muscle length during immobilization influences atrophy severity—shortened positions accelerate soleus atrophy more than stretched positions 1.
• The IGF-1/PI3K/Akt pathway inhibition and NF-kappaB activation are key intracellular signals driving disuse atrophy 3.

Denervation and Peripheral Neuropathy

• Motor neuron denervation, particularly affecting distal muscles like the soleus, causes progressive muscle fiber atrophy 4.
• Vitamin B6 deficiency induces peripheral neuropathy with axonal degeneration resembling Wallerian degeneration, preferentially affecting motor neurons feeding distal muscles 4.
• This leads to denervation of muscle fibers with ultrastructural changes including mitochondrial swelling, disruption of axoplasmic ground substance, and myelin disruption 4.
• Widespread muscle atrophy can occur within 3 days of nerve damage, with fragmentation of intramuscular nerve fibers by day 10 4.
• Vitamin B6 deficiency also directly reduces skeletal muscle protein synthesis independent of neuropathy 4.

Peripheral Artery Disease (PAD)

• Arterial insufficiency causes soleus atrophy through ischemia-reperfusion cycles during exercise and rest 4.
• PAD patients demonstrate reduced calf muscle area and increased muscle fat content inversely related to the degree of ischemia 4.
• Ischemia-reperfusion generates reactive oxygen species causing oxidative stress, mitochondrial dysfunction, muscle fiber type switching, apoptosis activation, and myofiber degeneration 4.
• Arterial insufficiency may be associated with distal motor neuropathy, which independently contributes to muscle atrophy 4.

Neuromuscular Blockade

• Prolonged continuous infusion of neuromuscular blocking agents (NMBAs) causes disuse atrophy even after recovery of neuromuscular transmission 4.
• Patients with train-of-four ratio recovery to 0.9 still demonstrate decreased strength attributed to disuse atrophy from immobility during NMBA administration 4.
• Immobility coupled with NMBAs leads to impaired neuromuscular transmission manifested by muscle weakness 4.

Tethered Cord Syndrome

• Progressive denervation from spinal cord tethering causes muscle atrophy, particularly in distal leg muscles including the soleus 4.
• Muscle atrophy may present as thinning of calf muscles or "saber shins" that can be misdiagnosed as Charcot-Marie-Tooth syndrome 4.
• Long-standing tethering results in progressive musculoskeletal deformities with autonomic changes causing thin, shiny, hairless skin over atrophied muscles 4.

Inflammatory Myopathies

• Dermatomyositis and juvenile dermatomyositis cause perifascicular atrophy from complement-mediated vasculopathy and tissue hypoperfusion 4.
• The small-vessel vasculopathy leads to ischemic microangiopathy in later stages, causing myofibril atrophy particularly in perifascicular areas 4.

Sarcopenia and Aging

• Age-related sarcopenia involves multiple mechanisms including reduced physical activity, vitamin B6 deficiency, and hormonal changes 4.
• Low vitamin B6 intake is associated with 10-18% reduction in sarcopenic individuals compared to controls 4.

Clinical Pitfalls and Caveats

• The soleus responds differently to atrophy stimuli than fast-twitch muscles—it shows greater susceptibility to disuse but may be partially protected by joint immobilization in certain positions 1.
• Muscle atrophy from vitamin B6 deficiency can occur with morphological nerve changes present before clinical neuromuscular dysfunction appears 4.
• Disuse atrophy is multi-dimensional, involving myonuclear changes, satellite cell responses, and multiple signaling pathways that interact rather than function in isolation 2, 3.
• Atrophy involves both decreased protein synthesis and increased degradation, with the balance determining the rate of muscle loss 2, 3, 5.

Prevention Strategies

• Resistance exercise 2-3 sessions per week on nonconsecutive days is essential to prevent disuse atrophy 6.
• Submaximal and aerobic exercise should be emphasized while avoiding excessive resistive exercise in conditions with muscle deterioration 4.
• Adequate protein intake supports muscle protein synthesis during periods of risk for atrophy 6.
• Early physiotherapy and structured regimens of passive range-of-motion or active exercise prevent complications of immobility 4.