Background:Carpal tunnel syndrome (CTS) is one of the most common focal entrapment neuropathies. Although the exact etiology remains unclear, high-pressure-related intracarpal tunnel compression of the median nerve (MN), progressing ischemia, and mechanical strangulation are common mechanisms. The therapeutic managements for CTS depend on the disease severity, varying from a conservative treatment to surgical interventions. Conservative treatment is helpful for most of the patients with mild-to-moderate CTS. Hydrodissection is a minimally invasive procedure of injecting solutions into some anatomical spaces to facilitate dissection and adhesiolysis. Steroids as an anti-inflammatory drugs are used to treat chronic pain conditions. Hyaluronidase as an adhesolysis agent can also be used for epidural injections with local anesthetics (LAs) and steroids for control of chronic back pain.Aim of the Study:This study was carried out to compare the efficacy of hyaluronidase versus dexamethasone as adjuvants to the mixture of LAs in ultrasound (US)-guided hydrodissection of the median nerve in mild to moderate cases of carpal tunnel syndrome.Settings and Design:This study was a prospective randomized controlled double-blinded clinical study.Methods:40 patients aged from 20 to 60 years old with clinical, electrophysiologic, and ultrasonographic evidence of mild to moderate CTS were included in this study. Each patient was assessed at the baseline (prior to injection) and at 1 week, 1 month, 3 months, and 6 months intervals after injection: (1) The Boston Carpal Tunnel Syndrome Questionnaire (BCTQ) which is a frequently used patient-based questionnaire for measurement of CTS. primary outcome. (2) Median motor and sensory nerve conduction studies (NCS) secondary outcome. (3) Median nerve ultrasonography. The ultrasound examination included measurement of the median nerve cross-sectional area (CSA) at the distal wrist crease (DWC). Also, the median nerve echogenicity, mobility, and vascularity at the DWC were assessed by US. Secondary outcome. All outcome assessments were assessed by single investigator who was blinded to the study details. All patients received US guided hydrodissection of the median nerve at the distal wrist crease. The selected patients were randomly allocated into 2 groups containing 20 patients each according to the study drugs; Group (D) received 5 mL (3 mL plain bupivacaine 0.5% and 2 mL (8 mg) dexamethasone), and Group (H) received 5 mL (3 mL plain bupivacaine 0.5% and 2 mL normal saline containing 300 international units (IU) hyaluronidase. Ultrasound-guided intracarpal injection using ultrasonography (Sono Scape A5; Shinzhen, China) with a 10-18-MHZ linear array transducer was performed by the same physician who was not aware of study groups, the MN was observed at the inlet of the carpal tunnel, 3 ml of solution was injected via the in-plane ulnar approach, to detach the MN from the transverse carpal ligament and an additional 2 ml was injected to separate the MN from underlying flexor tendons. All pa...