Fibrotic process in idiopathic carpal tunnel syndrome and myofibroblast presence

Carpal tunnel syndrome (CTS) is the most common compression neuropathy and accounts for approximately 90% of all entrapment neuropathies. It is caused by entrapment of median nerve in the carpal tunnel at the wrist. Carpal tunnel syndrome is mainly classified into two groups with respect to its etiology as idiopathic or seconder and idiopathic CTS is the most frequently seen type amongst all. No exact criterias have been defined up to date, so diagnosis is based upon a combination of symptoms and NCSs (nerve conduction study) .No matter how frequently seen, well defined and well studied CTS is, etiology of idiopathic carpal tunnel syndrome which accounts for approximately 50% of all cases still remains unclear. Some authors have speculated that the process begins on the bases of some sort of chronic, on going compression (eg. lumbrical muscle hyperthrophy, small wrist dimension) and complemented with ischemia-reperfusion episodes due to repetetif, compulsory movements of hand and wrist. As a second opinion, some authors think that subsynovial connective tissue which is unique for the wrist is exposed continously to shearing stresses thus responds as a wound healing reaction and gradually increasing fibrosis.In this study, our aim was to find the evidence of this prementioned fibrotic process, to discover the miyofibroblast cell existence and to correlate symptom severity also symptom duration with pathological changes. We hypothosize that, as a result of subsynovial connective tissue?s exposure to shearing forces, a wound healing or increased fibroblastic activity takes place in this tissue and with the addition of miyofibroblastic population the process leads to an abnormal increment of tissue volume thus compression within the tunnel. To make our results more realistic and less speculative we preferred to chose our control group from living individuals instead of cadavers in contrast to the most of the previous studies.This study was approved by Dokuz Eylul University ethical committee. Study group consisted of 25 specimens harvested from people undergoing surgery for idiopathic carpal tunnel syndrome, control group consisted of 15 specimens harvested from people undergoing surgery for distal radius fracture (12) and flexor tendon injury (3) as well. All patients were informed before participation and all of them filled informed constent form for the use of their tissue in the study. All 40 subjects met the inclusion criterias we have defined initially. Both group?s mean age was 50.85±11.25 (30-71). The patient?s age ranged from 40 to 71 (54.88±9.37), control group?s age ranged from 30 to 60 (44.13±11.16). All the individuals were given and completed BCTQ (Boston Carpal Tunnel Questionnaire) and VAS (visual analogue scale) for the assesment of symptom severity, symptom duration, functional status and correlation of these with the pathological changes of the tissue.In order to realise our results, we have excised subsynovial connective tissue and transvers carpal ligament specimens from a standart localization; middle finger FDS tendon?s palmar and ulnar side and transverse carpal ligament above. Also the approximate volume was taken to consideration to catch up the standartization (20-50 mm³). This tendon area was also used priorly by the other researchers as it is not encumbered by any lumbrical muscle attachment or a common muscle belly with other tendons. All specimens were studied histochemically (H&E) and both immunohistochemically ( CD3 ,CD20, ?-SMA and collagen type IV).Motor deficiency and thenar atrophy was the issues of late-phase patients (>12 month). Thenar atrophy seemed correlated with symptom severity and thus the severity of the illness and BCTQ points were significantly lower in mid-phase patiens (7-12 months) in accordance with the other phases (4-6 months, >12 months)There were no significant histopathological alterations in transvers carpal tunnel tissues in both groups. This finding verifies us that, as anticipated transvers carpal ligament seemed to have no part in this particular process. Whereas in subsynovialconnective tissue , fibrosis and vasculer wall thickness were significantly at higher levels in the patient group whilst edema was a common finding in both groups and vasculer proliferation and inflamation had no difference between either groups. Miyofibroblast existence in subsynovial connective tissue was found to be significantly higher in consideration of symptom duration.As a result; our findings suggest that there is evidence of fibrosis and increased vasculer wall thickness in this unique; subsynovial connective tissue. When we take the symptom and functional scores into account; we saw that the natural on going of the pathology seemed to be more symptomatic at early phases and functional loss became more obvious due to the structural changes in the median nerve at late phases. Miyofibroblast existence at early phase seemed supportive to our hypothesis and was as anticipated also. Since fibroblast-miyofibroblast differentiation is a dynamic process at all, what we did was taking a ?snapshot? of this whole big phase, it was reasonable for us to wait not to be able to expose miyofibroblasts in all the specimens. However if bigger sample size and individuals at the early phase of the illness can be included in future studies, to our opinion it can be possible to increase the numerical values and increase the reliability of statics thus the relevance between miyofibroblast existence and this pathology. By exploring and defining the whole fibrosis or increased fibroblastic action phase present in this pathology we can broaden our therapautic perspectives. Hence, further studies are needed in the future.