Foot Small Muscle Atrophy Is Present Before the Detection of Clinical Neuropathy

Abstract

OBJECTIVE -To characterize structural changes and the metabolic profile of foot muscles and correlate them with diabetic neuropathy measurements using phosphorus-31 ( 31 P) rapid acquisition with relaxation enhancement (RARE) magnetic resonance imaging (MRI).RESEARCH DESIGN AND METHODS -We studied 12 control subjects, 9 nonneuropathic diabetic patients, and 12 neuropathic diabetic patients using 31 P RARE and proton ( 1 H) MRI at 3 Tesla. The ratio of the total cross-sectional area of the foot to that of the muscle tissue was calculated from transaxial 1 H and 31 P images. The average 31 P concentration across the metatarsal head region was measured from the 31 P images.RESULTS -The muscle areaϪtoϪtotal area ratio differed among all three groups (means Ϯ SD): 0.55 Ϯ 0.04 vs. 0.44 Ϯ 0.05 vs. 0.06 Ϯ 0.06 for control, nonneuropathic, and neuropathic subjects, respectively (P Ͻ 0.0001). The average 31 P concentration also differed among all groups: 27.7 Ϯ 3.8 vs. 21.7 Ϯ 4.8 vs. 7.9 Ϯ 8.8 mmol/l for control, nonneuropathic, and neuropathic subjects (P Ͻ 0.0001). The muscle areaϪtoϪtotal area ratio strongly correlated with clinical measurements: Neuropathy Disability Score, r ϭ Ϫ0.83, P Ͻ 0.0001; vibration perception threshold, r ϭ Ϫ0.79, P Ͻ 0.0001; and Semmes-Weinstein monofilaments, r ϭ Ϫ0.87, P Ͻ 0.0001.CONCLUSIONS -Small muscle atrophy is present in diabetes before clinical peripheral neuropathy can be detected using standard clinical techniques. The 31 P RARE MRI method evaluates the severity of muscle atrophy, even in the early stages when neuropathy is absent. This technique may prove to be a useful diagnostic tool in identifying early-stage diabetic foot problems. Diabetes Care 28:1425-1430, 2005A trophy of the small muscles of the foot is common in diabetes and is related to peripheral motor neuropathy (1). The atrophy is believed to be the main factor responsible for the development of an imbalance between the flexor and extensor muscles, which results in clawing of the toes, prominent metatarsal heads, and the development of high foot pressures that play a direct role in the development of foot ulceration (2). Currently, there are no established methods to evaluate and follow the progress of small muscle atrophy in diabetic patients. As a result, little information is available regarding the onset of muscle changes and the natural history of their progression in diabetes.Concentrations of phosphorus-31 ( 31 P) cellular metabolites in skeletal muscle change immediately with the onset of ischemia and return quickly to normal levels in viable muscle tissue after reperfusion (3,4). Thus a method that accurately quantifies 31 P metabolite concentrations in foot muscles in vivo and spatially maps the resulting values to an anatomic, radiological image of the foot would be a sensitive, direct indicator of the health of muscle tissue in the diabetic foot. Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) provide data for the noninvasive assessment of deep-lying soft tissue anatomy (5-7). R...

Accelerated atrophy of lower leg and foot muscles—a follow-up study of long-term diabetic polyneuropathy using magnetic resonance imaging (MRI)

“…Combining magnetic resonance imaging (MRI) with stereological principles for volume analysis, we have demonstrated atrophy of distal muscles of the leg and the foot in diabetic patients with polyneuropathy [8,9]. These findings have been confirmed by other study groups in MRI studies evaluating diabetic feet [10,11].…”

“…As suggested by Greenman et al [11], a difference in foot size might introduce bias. Thus if the diabetic patients have smaller feet, this will result in smaller muscle volume.…”

“…Reduced size of foot muscles using MRI has been reported by Greenman et al [11] and Bus et al [10], who calculated the ratio of muscle/total foot from one crosssectional image. Their results are in accordance with the lower muscle volumes observed in patients with and without neuropathy in this study.…”

Diabetic foot ulceration and amputation

“…The prominent metatarsal heads are now exposed to abnormally high plantar pressures during walking as plantar tissue thickness has been shown to be related to peak plantar pressures (Abouaesha et al, 2001). Findings of two recent studies have raised questions about the causal relationship between muscle atrophy and deformity noting that intrinsic muscle atrophy was present before clinical peripheral neuropathy could be detected and finding no significant difference in degree of intrinsic foot muscle atrophy between matched subjects with and without claw toe deformity (Greenman et al, 2005;Bus et al, 2009).…”

Biomechanical characteristics of peripheral diabetic neuropathy: A systematic review and meta-analysis of findings from the gait cycle, muscle activity and dynamic barefoot plantar pressure

“…1997). In addition, small foot muscle atrophy resulting from the effects of hyperglycaemia and small 510 nerve damage have also been confirmed in diabetes patients utilising MRI, before DPN becomes 511 clinically detectable (Greenman et al, 2005). Therefore, these factors may also influence gait findings 512 in DMC groups when compared to DPN patients.…”