Sensory Axonopathy in Mild to Moderate Peripheral Arterial Disease

Abstract

The effect of mild to moderate arterial occlusive disease on peripheral nervous system conduction was prospectively investigated in 18 subjects and 18 control subjects, aged 40 to 85 years. Experimental and control subjects underwent a thorough history and physical followed by vascular and electrophysiologic studies. The primary outcome measure was the sensory nerve action potential. Although 33% of the subjects with peripheral arterial disease had experienced paresthesias, the clinical evaluation of sensation was relatively unaffected. Sensory conduction studies revealed 30% absent sural responses and 56% absent superficial peroneal nerve responses in subjects with peripheral arterial disease compared with 3 and 14% absent responses in control subjects, respectively (P = 0.044; 0.025). There were no differences in distal latency or sensory amplitude, although the superficial peroneal amplitude did approach significance (P = 0.06). No significant differences were found in motor distal latency, amplitude, or conduction velocity. Age, leg length, temperature, disease severity, presence of paresthesias, cholesterol levels, and past alcohol or tobacco ingestion did not account for the difference in sensory responses. These results support the presence of a mild sensory axonopathy in subjects with peripheral arterial disease. Electromyographers should be cognizant of absent distal responses from peripheral arterial disease so as not to ascribe the findings to an alternative pathology and should not attribute abnormal motor conduction results to the presence of this degree of peripheral arterial disease.

Muscle strength and control characteristics are altered by peripheral artery disease

“…These deficits appear related to the neuropathy and myopathy previously described by our group 2–4,11,27–28 and others. 5–6,31–33 Our work demonstrates that there are functional tests, including the maximal isometric plantar flexion test we are describing in this paper, that can measure and stratify the degree of impairment in the legs of patients with PAD. Such measurements can be used both as diagnostic tools to assess the severity of PAD in each individual patient but also to potentially predict and guide therapy depending on the patient’s presentation.…”

“…Myopathic fiber type shifting from Type II to I 2,9 and the neuropathy in PAD muscle that has been shown to decrease conduction velocities and amplitude corroborate this trend. 31–33 …”

“…2,4–5 The effects of neuropathy in patients with PAD have been found to include decreased nerve conduction velocities, decreased amplitude of and increased duration of motor unit action potential. 31–33 The myopathy in patients with PAD involves defective mitochondrial bioenergetics, oxidative damage, myofiber degeneration and fibrosis of the affected skeletal muscles. 2–6,11,27–28,34–35 Increased oxidative damage in PAD muscle is associated with deterioration of the size and shape of myofibers in the gastrocnemius with preference for Type II myofibers while Type I fibers persist and are less damaged.…”

Management of pain in outpatients with critical limb ischemia

“…It has been reported that the nature of pain changes with the progress of limb ischemia, from nociceptive in character during the phase of intermittent claudication to neuropathic in character during CLI [13,14,15,16]. It is indicated that we are dealing here with sensory neuropathy [17,18]. Pain in CLI patients meets the criteria for chronic neuropathic pain [9].…”

Skeletal Muscle Mitochondrial Dysfunction and Oxidative Stress in Peripheral Arterial Disease: A Unifying Mechanism and Therapeutic Target

“…The underlying mechanisms that explain these changes are complex and still require further examination, but a number of studies in human and animal studies suggest that impaired proteostasis (i.e., altered signaling pathways that regulate protein synthesis and degradation) plays a central role in muscle atrophy [60,61]. A dysfunctional peripheral nervous system, such as identified demyelination or focal denervation on the neuromuscular junction, will also likely stimulate the process of muscle atrophy and contribute to the weakness and functional impairment [62,63]. Skeletal muscle abnormalities also include capillary rarefaction and impaired microcirculation in PAD patients with IC and these findings are more obvious in people suffering from CLTI [59,64,65].…”