The feasibility of using high frequency ultrasound to assess nerve ending neuropathy in patients with diabetic foot
Introduction
Diabetic foot ulcers affect 5–15% of the patients with diabetes [1] and cause the patients enormous physical, emotional, and financial burdens. Reports showed that almost 80% of amputations in patients with diabetes were preceded by foot ulcers [2]. Simple tests such as monofilament, tuning fork, vibration perception threshold determination, ankle reflexes, and pinprick sensation alone or in combination have been studied and shown useful for identification of patients at risk [3]. The diagnostic principle of conventional method for detecting diabetic neuropathy is based primarily on characteristic symptoms and is confirmed with nerve conduction studies (NCS), which are time-consuming, relatively invasive. Particularly, repeated evaluations, in these cases, have been correlated to poor patient tolerance. When it comes to the nerve conduction studies, albeit well standardized, they are large limited to the evaluation of the largest nerve fibers and cause too much discomforts to patients that, sometimes, they dissuade patients from serial evaluations.
Other than the before mentioned diagnostic techniques, the state-of-the-art imaging modalities were also been explored in the diagnosis of diabetic neuropathy. It has been shown that under magnetic resonance imaging (MRI), an elevated intraneural T2-weighted signal of the median nerve (MN) [4], possibly related to intranervous edema, was found in symptomatic patients. In recent years, US were also investigated to study several disorders, including carpal tunnel syndrome, of the peripheral nerves and has been shown to reduce the discomforts in patients.
Many of the available literatures focuses on the median nerve neuropathy at the carpal tunnel level [5] or the tibial nerve neuropathy at the tarsal tunnel level [6], and the median nerve (MN) and the tibial nerve (TN) are relatively bigger among the peripheral nerves. Inevitably, most of the non-invasive imaging studies of peripheral nervous systems has been biased focusing on the MN [7] or the TN [8] of the diabetic patients. Recent evidences have shown that the enlargement of MN [7] or TN [8] found in diabetic patients was related to the progress of diabetes; and the nerve ending [9] and microcirculation [10] problems were thought to be the causes for diabetic feet. However, to the best of our knowledge, no attention has been given in the literature to the non-invasive imaging evaluation of the nerve ending damages of the diabetic feet patients.
With the rapid development of high frequency ultrasound, the very small nerves close to the nerve endings, such as digital nerve [11] and palmar cutaneous nerve [12], could be clearly observed by high-resolution ultrasound.
The goals of this study were to (1) explore the potential value of high-resolution ultrasound for evaluation of the medial branch of deep peroneal nerve (mbDPN) of diabetic feet patients, and (2) determine whether the abnormalities of the nerve branch close to the nerve ending can serve as the diagnostic signatures for nerve ending problems in patients with diabetic foot. Our deep interest in imaging the mbDPN was prompted by two rationales. First, it is the simple anatomy of mbDPN, which is relatively straight, and allows the easy tracking by US. This rationale is supported by our preliminary results (Fig. 1). Second, in one study involving 169 patients with diabetes, common peroneal motor nerve conduction velocity was found to be the best and the only independent predictor for new foot ulceration within a period of 6 years compared with monofilament testing, vibration perception threshold (VPT) measurement, and temperature perception threshold measurement [13].
Section snippets
Patients
One experienced sonographer (Dr. Ping Zhang) examined a cohort of 19 clinically diagnosed diabetic feet patients [12 females and 7 males; age range, 56–79 years; height, 150–170 cm; disease duration range, 18–35 years] and a control group of healthy volunteers matched for sex, age and height [12 females and 7 males; age range, 56–83 years; height, 155–175 cm]. There were not any diabetes history or other clinically diagnosed nerve problems among these healthy volunteers. There were no significant
US studies
For the control group, US was able to depict the mbDPN in both the transverse (Fig. 2) and longitudinal planes (Fig. 3) with such ease that the dividing points at where the nerves divides into two digital nerves were clearly identifiable (Fig. 2). The sonographic appearances of these normal mbDPNs are characterized by several longitudinal hypoechoic bands which are separated by discontinuous bands of increased echogenicity (Fig. 3). Conversely, in the transverse plane, the mbDPN in patients
Discussion
At the early stage of diabetic feet, patients usually complain about sensory disturbances in their hands and feet, including tingling, numbness, dysaesthesia, and burning pain. In our study, 18/19 (95%) diabetic feet patients with feet ulcers reported these sensory disturbances. From the pathophysiological point of view, the literature consensus is strong explaining the involvement of nerves in diabetic patients, including histopathological changes [17], intraneural edema [18], and among others.
Limitations
This pilot study is not without limitations. First, the feasibility of using US for nerve ending evaluation did not explore other nerves other than the mbDPNs which is easier to image rendered by its straighter anatomy relative to other type of digital nerves. With experiences gained from currents studies on digital nerve imaging with US, we are in the process of designing future experiments in the aim to image those nerves with less straight anatomic structure. Secondly, the diameter, instead
Conflict of interest
We have no conflicts to disclose.
Acknowledgments
We thank Dr. Tianyi Ma Krupka from Standford University in the United States to help us with our written English and manuscript structure. This research is partially supported by the National Key Program (No. 81130025, 2011CB707900, 2011CB707700), National Natural Science Foundation of China (No. 30900371, 81270021, 30900370), Scientific Research Foundation for Returned Scholars (No. 2010609) and Foundation of Chongqing (2010AB50952).
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2015, IRBMCitation Excerpt :The reported prevalence of foot ulcers for a variety of population ranges from 2% up to 10% [1,2]. Simple tests such as monofilament, tuning fork, ankle reflexes, determination of a vibration perception threshold, and pinprick sensation alone or in combination have been studied and have shown to be useful tools for identification of patients at risk of diabetes foot disease [3,4]. Most of the available literature is focused on the median nerve neuropathy at the carpal tunnel level [5] or the tibia nerve neuropathy at the tarsal tunnel level [6], being the median and tibia nerves the relatively longest ones of all peripheral nerves.
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