One of the earliest theories of causation for CTS was the idea that inflammation of the tendons which pass through the carpal tunnel, or more accurately of their synovial sheaths, perhaps as a result of overuse, might result in swelling of the tenosynovium and thus raise the carpal tunnel pressure. Various groups have therefore examined tissue samples from operated carpal tunnel patients looking for microscopic evidence of such inflammation. They have almost universally failed to find evidence of an inflammatory cell infiltrate except in patients with disorders such as rheumatoid arthritis or with localised infections within the carpal tunnel. In most studies the tendons themselves appear essentially normal but there is an increase in fibrous connective tissue and proliferation of small blood vessels. A more detailed exploration of this literature follows for those who are interested but the casual reader may wish to skip to biochemistry.
Detailed histological studies of CTS
The section of the median nerve in and around the carpal tunnel is recognisably different in some way to the median nerve in the forearm on high resolution ultrasound, even in apparently normal, asymptomatic individuals. It generally appears more hypo-echoic (darker) with less visible internal structure. What this difference in appearance corresponds to in microscopic terms remains somehwat uncertain but as early as 1980 the same observation was made histologically in a study of cadaver arms (Castelli 1980). The nerve at the wrist was found to contain more intraneural connective tissue and its arterioles and venules had thicker walls than were seen in a section of the median nerve in the forearm. It was suggested that these features might be evidence that this section of nerve was specially adapted to withstand a higher pressure environment and greater mechanical stresses than the forearm section but it is of course impossible to determine whether these changes represented a 'designed in' preventive adaptation, or simply a response to a lifetime of mechanical stress.
In the synovial sheaths of the tendons the most consistent finding in one early study (24/29 cases) was simply oedema (an increased water content of the tissue) (Faithfull 1986), confirmed in a subsequent study which also described a variety of other changes, widely differing in different patients and including collagen proliferation, fibrosis, amyloid deposition (which is often seen in renal patients with CTS), thickening of vessel walls and thrombosis (Neal 1987). The latter authors commented on a "striking absence of inflammation" and suggested that pressure in the carpal tunnel and ischaemia are important factors in a majority of patients with spontaneous carpal tunnel syndrome. Yet another study made a special effort to look for evidence of synovial inflammation yet found it in only 10% of 177 wrists (Fuchs 1991). Once again the main findings were oedema and vascular sclerosis. The largest study available looked at 625 cases of idiopathic CTS and found evidence of chronic inflammation in only 23(4%) and acute inflammatory change in only 1 case (Kerr 1992)
An electron microscopic study of samples of the transverse carpal ligament (Stransky 1989) showed that the CTS patients had some collagen fibres of much larger diameter than normal controls. Similar changes have been found in the synovium (Ettema 2004). Cultured fibroblasts from the flexor retinaculum of patients behaved differently from those from normal controls (Allampallam 1996). There is thus evidence suggesting that there is some subtle structural difference in the transverse carpal ligament as well as in the nerve and synovium. It seems entirely possible that the same factors, genetic, mechanical and biochemical, are influencing all of these tissues in the area of the carpal tunnel.
Revision date - 4th March 2012