Carpal tunnel syndrome (CTS) is the most common peripheral nerve disorder. Despite its frequency, the exact pathophysiology remains elusive. It is, however, commonly accepted that CTS affects the large nerve fibres, induces non-inflammatory changes and is driven by mechanisms that remain localised to the lesion site. Clinical diagnosis therefore largely relies on local tests for the large fibre domain such as standard electrodiagnostics, vibrometry or von Frey hair testing within the median nerve territory.
In this review, the current beliefs and resulting clinical guidelines are challenged by summarising novel evidence which suggests the presence of hitherto unrecognised pathophysiological mechanisms. A focus is thereby placed on the contribution of small fibre degeneration, the presence of intraneural inflammation and remote mechanisms to the pathophysiology of CTS.?Since these mechanisms seem to be pertinent to CTS, potential approaches to integrate them in the diagnostic work-up of patients with suspected CTS are suggested.
Future work is, however, required to establish their diagnostic validity as well as impact on management and prognosis of patients with CTS.