Although amputation rates due to diabetes have decreased, a large number of amputations are still performed annually3. Toe deformity has been shown to have a prevalence of over 85% in patients with a history of ulcers and amputation6. Previous studies have shown that multiple factors have been associated with claw toe deformity, but the relationships between each of these factors remain unclear. In this study, explored the association between claw toes, peripheral neuropathy, intrinsic muscle volume, and PA thickness.
CT scans have sufficient resolution to distinguish bone and muscle21 and have been used in earlier studies to estimate muscle size22, 23. Robertson et al.23 performed CT scans to assess soft tissue density under the metatarsal shaft, as a proxy measure of intrinsic muscle size in a patient with diabetic neuropathy. However, they reported difficulty defining the borders of the individual intrinsic muscles, which may be related to the insufficient contrast resolution of CT scans. In our study, we reduced noise and enhanced the contrast of the plantar tissues relative to the surrounding regions. While systematic errors in the soft tissue appearance on the CT images may occur, we have no reason to believe the biases are correlated with the subject conditions of neuropathy or claw toe presence. All measurement errors in the study are assumed to be random and equally-distributed between subject groups.
This study quantified intrinsic muscle volume and PA thickness on the same cohort of patients. Our findings indicate that neuropathic feet have less intrinsic muscle volume than non-neuropathic feet. Reduction of intrinsic muscle volume in the diabetic neuropathic foot has been demonstrated previously8, 9. Our results also revealed that diabetic feet with claw toes have less intrinsic muscle volume than diabetic feet without claw toes. Cheuy et al.10 and Robertson et al.23 also found a relationship between intrinsic muscle volume and forefoot deformity. They reported that reduced lean muscle volume or muscle density was associated with increased hyperextension at the MTPJ in diabetic patients with neuropathy. However, conflicting results regarding the relationship between intrinsic muscle volume reduction and claw toes have been shown in other literature. Andersen et al.8 and Bus et al.9, 11 reported no relationship between muscle volume and MTPJ deformity. Bus et al. found a 73% decrease in intrinsic muscle cross sectional area between patients with diabetic neuropathy and non-neuropathic controls, but only two of eight patients with neuropathy had toe deformities9. Anderson et al. found that patients with diabetic neuropathy had an intrinsic muscle volume just over half that of either controls or patients with no diabetic neuropathy, but none of the diabetic patients with neuropathy had toe deformities8. The reasons for these differences are likely due to variations in experimental design or technique. For example, Andersen et al. was studying diabetic neuropathic feet and retrospectively considered the presence of claw toes8. Further, Bus et al. used a single CT slice to estimate intrinsic muscle volume9, 11. In contrast, Cheuy et al. reported that less forefoot lean muscle tissue was associated with greater MTPJ deformity10. This group, whose results agree with the current study, truly measured the 3D intrinsic muscle volume as we did. Even though image segmentation and 3D analysis of the muscle volume is time-consuming, thus far this methodology is showing relationships not elucidated by the two-dimensional methods.
Several studies have reported thicker PA in diabetic feet than in control feet 14, 15, 16, 18. Duffin et al. concluded that the pathogenesis of PA thickening may have been caused by non-enzymatic glycation and mechanical loading15. Our results indicated that diabetic neuropathic feet with claw toes had thicker PA than other groups, but we are unaware of a similar study comparing PA thickness between feet with or without claw toe deformity and with or without neuropathy. In our study, the mean PA thickness without claw toes and neuropathy was 3.68 ± 1.34 mm, which is similar to the average value 4.2 ± 0.9 mm reported by the measurements of Boulton et al. using CT images14 as we did. However, using ultrasound Duffin et al., Giacomozzi et al. and D’Ambrogi et al. measured diabetic PA thickness that was less than our results: 1.6 ± 1.8 mm, interquartile range, 2.9 ± 1.2 mm, and 2.9 ± 1.2 mm, respectively15, 16, 18. This difference is likely due to differences in imaging modality, i.e., CT vs. ultrasound.
There were several limitations to this study. First, the duration of neuropathy and claw toes was not determined. Second, we did not account for the possibility that the deformity might have been caused by ill-fitting footwear and congenital anomalies, especially for patients with claw toes without neuropathy. Third, we did not consider or quantify variation in patient daily activity levels (e.g., step counts), which may be related to a variety of health factors. Fourth, the threshold for diagnosing neuropathy is controversial. Wang et al. concluded in a meta-analysis review that monofilament tests have limited sensitivity for screening diabetic peripheral neuropathy24. Feng et al. suggests testing at three sites including the plantar aspects of the great toe, the third metatarsal, and the fifth metatarsal, to maximize the diagnostic value of Semmes Weinstein monofilament examination25. In our current study, we performed monofilament testing at eight plantar locations, including the three recommended sites by Feng et al. As such, we are confident in our classifications of neuropathic patients, despite the limitations of monofilament assessment described by Wang. Lastly, the CT scanning and image analysis presented multiple challenges. We had seven subjects in which there was incomplete contact between the heel and the foot plate on CT images (i.e., the subjects were not weight-bearing on their heels). We defined the profile line for measuring PA thickness as the “vertical” in the image coordinate system (see Fig. 1E). This was considered a potential source of bias in measurements of PA thickness because some of the subjects’ feet were tilted with respect to this vertical axis. The maximum angle error was approximately 10 degrees. However, even in the worst-case scenario of no heel contact, our values were within two percent of the “true PA thickness”. This equates to about 0.07 mm of error for the average 3.68 mm-thick PA tissue. Additionally, we did not quantify the function and strength of the intrinsic muscles and PA. Muscle volume and PA thickness do not necessarily reflect these factors. A final limitation of using CT to assess intrinsic muscle size is that CT is generally not the modality of choice for these kinds of soft tissue measurements. However, this paper is a secondary analysis of an osseous foot structure study and the CT scans were never intended to image the soft tissue of the foot.