{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T20:50:50Z","timestamp":1771966250652,"version":"3.50.1"},"reference-count":32,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T00:00:00Z","timestamp":1702857600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Tomography"],"abstract":"<jats:p>Hereditary sensory and autonomic neuropathy type 4 (HSAN4), also known as congenital insensitivity to pain with anhidrosis (CIPA), is a rare genetic disorder caused by NTRK1 gene mutations, affecting nerve growth factor signaling. This study investigates the central nervous system\u2019s (CNS) involvement and its relation to pain insensitivity in HSAN4. We present a 15-year-old girl with HSAN4, displaying clinical signs suggestive of CNS impact, including spasticity and a positive Babinski\u2019s sign. Using Technetium-99m ethyl cysteinate dimer single-photon emission computed tomography (Tc\u221299m ECD SPECT) imaging, we discovered perfusion deficits in key brain regions, notably the cerebellum, thalamus, and postcentral gyrus. These regions process pain signals, providing insights into HSAN4\u2019s pain insensitivity. This study represents the first visualization of CNS perfusion abnormality in an HSAN4 patient. It highlights the intricate relationship between the peripheral and central nervous systems in HSAN4. The complexity of HSAN4 diagnosis, involving potential unidentified genes, underscores the need for continued research to refine diagnostic approaches and develop comprehensive treatments.<\/jats:p>","DOI":"10.3390\/tomography9060175","type":"journal-article","created":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T12:57:56Z","timestamp":1702904276000},"page":"2261-2269","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Exploring CNS Involvement in Pain Insensitivity in Hereditary Sensory and Autonomic Neuropathy Type 4: Insights from Tc\u221299m ECD SPECT Imaging"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8423-0767","authenticated-orcid":false,"given":"Cheng-Chun","family":"Chiang","sequence":"first","affiliation":[{"name":"Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan"},{"name":"School of Medicine, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Che","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiao-Hsin","family":"Lan","sequence":"additional","affiliation":[{"name":"School of Medicine, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kuan-Chieh","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Medicine, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsuan-Ching","family":"Tang","sequence":"additional","affiliation":[{"name":"School of Medicine, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4005-2094","authenticated-orcid":false,"given":"Shin-Tsu","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan"},{"name":"Department of Physical Medicine and Rehabilitation, Taichung Veterans General Hospital, Taichung 407, Taiwan"},{"name":"Department of Physical Medicine and Rehabilitation, Tri-Service General Hospital, Taipei 114, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1001\/archneur.1963.00460030083008","article-title":"Congenital insensitivity to pain with anhydrosis. 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