{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T17:09:30Z","timestamp":1778605770541,"version":"3.51.4"},"reference-count":25,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Introduction: Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy of the upper extremity and results from compression of the median nerve within the fibro-osseous carpal tunnel. Anatomical variants such as a bifid median nerve (BMN) and a persistent median artery (PMA) may increase tunnel occupancy and complicate both diagnosis and treatment. High-resolution musculoskeletal ultrasound enables detailed evaluation of these anatomical variations and facilitates image-guided interventions. Ultrasound-guided hydrodissection has emerged as a minimally invasive technique capable of mechanically releasing perineural adhesions and restoring nerve mobility. Alpha-2 macroglobulin (A2M), an autologous plasma protease inhibitor with anti-inflammatory and cytokine-binding properties, has recently been explored as a biologic adjunct in musculoskeletal conditions. Case Presentation: We report the case of a 60-year-old right-handed woman who presented with a one-year history of numbness, paresthesia, and pain within the median nerve distribution of her dominant hand. Ultrasound examination demonstrated a bifid median nerve accompanied by a persistent median artery and perineural edema within the proximal carpal tunnel. The patient underwent three weekly sessions of ultrasound-guided hydrodissection using autologous A2M prepared through the APEX filtration system. The patient reported progressive clinical improvement following treatment. Grip strength increased from 12 kg at baseline to 22 kg at week twelve. Follow-up ultrasound performed ten months after treatment showed restoration of median nerve fascicular architecture and normalization of nerve morphology, findings consistent with interval structural improvement. Discussion: This case highlights the role of ultrasound in the integrated evaluation and management of CTS with anatomical variants, including diagnosis, procedural guidance, and longitudinal assessment. Conclusions: Ultrasound-guided hydrodissection with A2M may represent a feasible minimally invasive approach in selected patients; however, further prospective studies are required to determine its safety and therapeutic efficacy.<\/jats:p>","DOI":"10.3390\/diagnostics16091362","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T14:35:53Z","timestamp":1777559753000},"page":"1362","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ultrasound-Guided Hydrodissection for Carpal Tunnel Syndrome with Bifid Median Nerve and Persistent Median Artery: An Imaging-Based Case Report with Alpha-2 Macroglobulin"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0148-1614","authenticated-orcid":false,"given":"Jeimylo C.","family":"de Castro","sequence":"first","affiliation":[{"name":"SMARTMD Clinic for Non-Surgical Interventions Pain Center, Centuria Medical Makati, Makati 1205, Philippines"},{"name":"Elohim Research Center, Adventist University of the Philippines, Silang, Cavite 4118, Philippines"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3488-7052","authenticated-orcid":false,"given":"Daniel","family":"Wang","sequence":"additional","affiliation":[{"name":"Miller School of Medicine, University of Miami, Miami, FL 33136, USA"},{"name":"University of Miami Health System, Miami, FL 33136, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey","family":"Strakowski","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine & Rehabilitation, The Ohio State University, Columbus, OH 43214, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8746-3718","authenticated-orcid":false,"given":"Yonghyun","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Gangnam Sacred Heart Hospital, College of Medicine, Hallym University, 1 Singil-ro, Yeongdeungpo-gu, Seoul 07441, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1002\/jor.25348","article-title":"A2M inhibits inflammatory mediators of chondrocytes by blocking IL-1\u03b2\/NF-\u03baB pathway","volume":"41","author":"Sun","year":"2023","journal-title":"J. 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