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

BackgroundNerve 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 MethodsIn 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.ResultsOverall, 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).ConclusionThis 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.

MRI DTI and PDFF as Biomarkers for Lower Motor Neuron Degeneration in ALS

“…The assessment of multiple nerves, as mentioned above, especially motor nerves (e.g., femoral nerve) could provide even more specific results. The healthy controls tended to be of slightly younger age compared to the patients without revealing significant relevance; however, this needs to be considered as some studies showed that FA of the sciatic nerve is negatively associated with age in both healthy controls and patients with neuropathies (Kronlage et al, 2018;Jende et al, 2021). Of note, there was no significant correlation between age and FA values in our study cohort.…”

“…Our main findings are that ALS patients' sciatic nerves demonstrate significantly lower FA values than healthy controls, and the thigh muscles in ALS patients accumulate more fat than thigh muscles from healthy controls. Although DTI derived FA in rodent (Takagi et al, 2009;Lehmann et al, 2010;Morisaki et al, 2011) and human peripheral nerves is considered a valid measure for axonal integrity and can be used to monitor axonal loss and regeneration as well as for demyelinating conditions (Sheikh, 2010;Kakuda et al, 2011;Mathys et al, 2013;Jende et al, 2020Jende et al, , 2021, data about FA values in peripheral nerves of ALS patients are sparse. In line with our findings, Simon and colleagues reported 8-10% lower FA values in the tibial and peroneal nerves in ALS patients than controls.…”

“…Numerous studies using diffusion tensor imaging (DTI) demonstrated degeneration of the corticospinal tract and motor-associated brain regions. Most studies demonstrated a decrease of DTI-based fractional anisotropy (FA), a marker for axonal degeneration and demyelinating conditions (Jende et al, 2020(Jende et al, , 2021, which indicates an involvement of the UMN (Ellis et al, 1999;Toosy et al, 2003;Iwata et al, 2008;Blain et al, 2009;Metwalli et al, 2010;Cirillo et al, 2012;Bede et al, 2015).…”

Magnetic Resonance Imaging as a Biomarker in Diabetic and HIV-Associated Peripheral Neuropathy: A Systematic Review-Based Narrative

“…Similar blood-flow measures are unlikely to be of value in nerve imaging. That is not, however, to say that measures will not be able to be developed which probe the ability of nerves to function, and we refer readers to the paper in this edition by Jende et al ( 2021 ), exploring DTI as a surrogate measure of nerve function.…”

Peripheral and Autonomic Neuropathy Status of Young Patients With Type 1 Diabetes Mellitus at the Time of Transition From Pediatric Care to Adult-Oriented Diabetes Care

“…The majority of studies on diabetes consider peripheral sensorimotor neuropathy of the lower extremities, and only a few, mostly sensory and motor nerve conduction velocity studies have examined sensory function in the hands (57)(58)(59)(60)(61).…”