Detection and monitoring of diabetic polyneuropathy with specialised markers of small and large nerve fibres

Abstract

Routine nerve conduction studies (NCS) are the current standard test for the evaluation of suspected peripheral neuropathy, but are often normal in patients with diabetic polyneuropathy (DPN). This is because: i. NCS are unable to detect dysfunction of small fibres, which may be affected earlier and are the cause of painful neuropathic symptoms; and ii. Significant large fibre axonal loss +/- demyelination may need to occur before NCS detect this is an abnormality.

This research project critically evaluates various newer/novel methods to detect and potentially monitor diabetic neuropathy, and to provide a feasible way that this can be routinely assessed in the neurophysiology laboratory. I chose to specifically analyse the diabetic population as this is by far the most common cause of peripheral neuropathy in the global community, causing significant burden of disease.

The various known novel techniques to assess and monitor DPN are evaluated, firstly through that which is available in current literature. These are compared in terms of diagnostic accuracy, as well as availability and cost-effectiveness. Based on the findings from this literature review, various prospective clinical studies are developed to further evaluate the more promising techniques identified. A focus was made towards techniques that can be performed in the neurophysiology laboratory, as routine NCS have, and will remain likely to have a significant role in the assessment of diabetes-related neuropathy. Thus, this clinical visit provides an opportune time to perform these additional tests as a way of providing supplementary information on patient’s peripheral nerve status.

Small and large nerve fibres are both affected by diabetes. However, these fibres display very different physiological properties, not just in terms of structure and function, but they are also evaluated by completely different techniques. Small fibres can then be further subdivided into different populations of thinly myelinated A-delta fibres and unmyelinated C-fibres, which again have very different properties and assessment modalities. This thesis is divided into two main sections with research focussed on providing more accurate measurement of the various small fibre populations in the first section, and then improving large fibre testing beyond that of routine NCS in the second section.