Diffusion Tensor Imaging of the Sciatic Nerve as a Surrogate Marker for Nerve Functionality of the Upper and Lower Limb in Patients With Diabetes and Prediabetes

Abstract

Background: Nerve damage in diabetic neuropathy (DN) is assumed to begin in the distal legs with a subsequent progression to hands and arms at later stages. In contrast, recent studies have found that lower limb nerve lesions in DN predominate at the proximal sciatic nerve and that, in the upper limb, nerve functions can be impaired at early stages of DN.

Materials and methods: In this prospective, single-center cross-sectional study, participants underwent diffusion-weighted 3 Tesla magnetic resonance neurography in order to calculate the sciatic nerve's fractional anisotropy (FA), a surrogate parameter for structural nerve integrity. Results were correlated with clinical and electrophysiological assessments of the lower limb and an examination of hand function derived from the Purdue Pegboard Test.

Results: Overall, 71 patients with diabetes, 11 patients with prediabetes and 25 age-matched control subjects took part in this study. In patients with diabetes, the sciatic nerve's FA showed positive correlations with tibial and peroneal nerve conduction velocities (r = 0.62; p < 0.001 and r = 0.56; p < 0.001, respectively), and tibial and peroneal nerve compound motor action potentials (r = 0.62; p < 0.001 and r = 0.63; p < 0.001, respectively). Moreover, the sciatic nerve's FA was correlated with the Pegboard Test results in patients with diabetes (r = 0.52; p < 0.001), prediabetes (r = 0.76; p < 0.001) and in controls (r = 0.79; p = 0.007).

Conclusion: This study is the first to show that the sciatic nerve's FA is a surrogate marker for functional and electrophysiological parameters of both upper and lower limbs in patients with diabetes and prediabetes, suggesting that nerve damage in these patients is not restricted to the level of the symptomatic limbs but rather affects the entire peripheral nervous system.

Keywords: diabetes; diabetic polyneuropathy; diffusion tensor imaging; fractional anisotropy; magnetic resonance imaging; magnetic resonance neurography; prediabetes.

FIGURE 1

Process of patient recruitment.

FIGURE 2

Fiber tracking of the sciatic nerve. (a) T2-weighted, fat suppressed image of the right thigh, depicting the sciatic nerve (red circle). (b) Colored map of fractional anisotropy (sciatic nerve encirceled in red). (c) Reconstructed, 3-dimensional fiber track of the right sciatic nerve with color encoding according to the DTI eigenvector color map where voxel color reflects the direction of the diffusion tensor in that voxel. Color intensity is scaled with the FA.

FIGURE 3

Sciatic nerve fiber tracts with magnified views. (a) Female control, 67 years, neuropathy disability score (NDS) = 0. (b) Female prediabetes patient, 57 years, NDS = 3. (c) Male type 2 diabetes patient, 58 years, NDS = 7.

FIGURE 4

Correlative statistics of Purdue Pegboard Test scores and sciatic nerve fractional anisotropy. (A) Correlation of the sciatic nerve’s fractional anisotropy (FA) in patients with diabetes with the total Purdue Pegboard Test score (r = 0.52; p < 0.001; 95% confidence interval (CI) = 0.31 to 0.67). (B) Correlation of the sciatic nerve’s FA in patients with prediabetes with the total Purdue Pegboard Test score (r = 0.79; p = 0.007; 95% CI = 0.31 to 0.95). (C) Correlation of the sciatic nerve’s FA in controls with the total Purdue Pegboard Test score (r = 0.76; p < 0.001; 95%CI = 0.52 to 0.89). (D) Correlation of the sciatic nerve’s FA in patients with diabetes with the Purdue Pegboard Test score of the dominant hand (r = 0.61; p < 0.001; 95%CI = 0.43 to 0.74). (E) Correlation of the sciatic nerve’s FA in patients with prediabetes with the Purdue Pegboard Test score of the dominant hand (r = 0.65; p = 0.044; 95%CI = 0.52 to 0.90). (F) Correlation of the sciatic nerve’s FA in controls with the Purdue Pegboard Test score of the dominant hand (r = 0.64; p = 0.001; 95%CI = 0.22 to 0.77). (G) Correlation of the sciatic nerve’s FA in patients with diabetes with the Purdue Pegboard Test score of the non-dominant hand (r = 0.43; p = 0.0002; 95%CI = 0.22 to 0.60). (H) Correlation of the sciatic nerve’s FA in patients with prediabetes with the Purdue Pegboard Test score of the non-dominant hand (r = 0.71; p = 0.022; 95%CI = 0.21 to 0.92). (I) Correlation of the sciatic nerve’s FA in controls with the Purdue Pegboard Test score of the non-dominant hand (r = 0.55; p = 0.005; 95%CI = 0.19 to 0.76). (J) Correlation of the sciatic nerve’s FA in patients with diabetes with the Purdue Pegboard Test score of both hands (r = 0.38; p = 0.002; C95%CI = 0.14 to 0.54). (K) Correlation of the sciatic nerve’s FA in patients with prediabetes with the Purdue Pegboard Test score of both hands (r = 0.70; p = 0.024; 95%CI = 0.16 to 0.91). (L) Correlation of the sciatic nerve’s FA in controls with the Purdue Pegboard Test score of both hands (r = 0.59; p = 0.002; 95%CI = 0.37 to 0.84). (M) Correlation of the sciatic nerve’s FA in patients with diabetes with the Purdue Pegboard Test assembly score (r = 0.46; p < 0.001; 95%CI = 0.26 to 0.63). (N) Correlation of the sciatic nerve’s FA in patients with prediabetes with the Purdue Pegboard Test assembly score (r = 0.71; p = 0.022; 95%CI = 0.20 to 0.92). (O) Correlation of the sciatic nerve’s FA in controls with the Purdue Pegboard Test assembly score (r = 0.61; p = 0.001; 95%CI = 0.26 to 0.79).