Splinting and nerve and tendon gliding exercises are commonly used to treat carpal tunnel syndrome (CTS). It has been postulated that both modalities reduce intraneural edema. To test this hypothesis, 20 patients with mild to moderate CTS were randomly allocated to either night splinting or a home program of nerve and tendon gliding exercises. Magnetic resonance images of the wrist were taken at baseline, immediately after 10 min of splinting or exercise, and following 1 week of intervention. Primary outcome measures were signal intensity of the median nerve at the wrist as a measure of intraneural edema and palmar bowing of the carpal ligament. Secondary outcome measures were changes in symptom severity and function. Following 1 week of intervention, but not immediately after 10 min, signal intensity of the median nerve was reduced by $11% at the radioulnar level for both interventions (p ¼ 0.03). This was accompanied by a mild improvement in symptoms and function (p < 0.004). A similar reduction in signal intensity is not observed in patients who only receive advice to remain active. No changes in signal intensity were identified further distally (p > 0.28). Ligament bowing remained unchanged (p > 0.08). Intraneural edema reduction is a likely therapeutic mechanism of splinting and exercise. Keywords: MRI; nerve and tendon gliding exercises; splinting; carpal tunnel syndrome; neurodynamics Carpal tunnel syndrome (CTS) is a peripheral neuropathy at the level of the wrist. Despite considerable efforts, the pathophysiology of CTS is not yet fully understood. 1 There is however a well-established link between an elevated pressure in the carpal tunnel and the development of CTS. 2,3 When the pressure on a peripheral nerve is experimentally increased, a reduction of intraneural microcirculation occurs with subsequent breakdown of the blood nerve barrier and the formation of intraneural and extraneural edema. 4 In CTS, swelling of the median nerve has been identified intra-operatively, 5,6 with ultrasound imaging 7 and with conventional magnetic resonance imaging (MRI). 8,9 If present for prolonged periods, intraneural edema may lead to potentially irreversible fibrotic changes. 4 These fibrotic changes are present in patients with severe CTS. 9 Edema reduction to prevent progression to a fibrotic stage is therefore a plausible target in the management of patients with mild to moderate CTS.Besides advice, splinting and nerve and tendon gliding exercises are the most frequently performed noninvasive treatment modalities for CTS. 10 The beneficial effect of night splinting in a neutral wrist position is commonly attributed to the avoidance of end-range positions associated with high carpal tunnel pressures. 11,12 Maintenance of a neutral wrist position is believed to promote adequate blood circulation with a subsequent reduction of edema. 13 Although further research is required, recent systematic reviews indicate that conservative management with nerve and tendon gliding exercises may be beneficial for patie...