Longitudinal analysis of structural and functional changes in peripheral circuits determining the clinical symptoms of painful diabetic neuropathy

 

Diabetic polyneuropathy comprises a wide spectrum of painful, but also non-painful symptoms related to structural and functional changes of neural circuits within the peripheral and central neuronal system. Therefore a combined human-mouse approach will be used to describe and understand subtypes of diabetic neuropathy, with the long term goal to pave the way for specific novel therapies.

MRI neurography at 3T is performed to visualize structural changes of peripheral nerves in patients with diabetic neuropathy (DN) using anatomical sequences, diffusion-weighed sequences and sequences for quantification of proton-density (expl. see image 1). 

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Image1: visualization of proton-density (left)
and anatomic imaging oft he right isciadic nerve (right)
in a patient with painful diabetic neuropathy.

One objective is to identify morphological differences in nerves of patients affected by DN compared to an age-matched control group without diabetes or any symptoms of neuropathy. MRI perfusion is employed in order to determine whether a lack of perfusion and / or pathologic changes of the blood-nerve barrier occur in patients with DN and whether there is a difference in patients suffering from painful diabetic neuropathy (PDN) compared to those who suffer from non-painful diabetic neuropathy (NPDN). By visualizing neuropathic changes in vivo another goal is to determine whether neuropathic changes spread from distal nerve fibres to proximal axons in sense of a „dying back“ neuropathy, or, as suggested by recent studies (Pham et al., 2011, 2015), occur at the proximal level of the nerve first.

 

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Additionally to MRI sampling, quantitative sensory testing is used to clinically characterize peripheral neuropathy. This is a precise method to objectively detect impairment of different neuronal functions, such as pain perception by applying pressure as well as using sharp tools, sensation and pain thresholds for cold and warm temperatures by using a thermode (a device capable of heating and cooling the skin), vibration sensation thresholds using tuning forks, pain perception using pin pricks, and sensitivity threshold by using von Frey hairs. Moreover, advanced glycation endproduct and dicarbonyl measurements are performed in both peripheral blood, and skin biopsies. To further characterize the patients clinically, ultrasounds of carotid arteries and kidneys including perfusion, lung function testing, bioimpedance measurement, cardiac autonomous neuropathy testing as well as routine blood testing are performed.

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