{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T19:50:53Z","timestamp":1788378653064,"version":"build-2803163510"},"reference-count":38,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurology International"],"abstract":"<jats:p>Transthyretin amyloidosis (ATTR) is a progressive multisystem disorder characterized by extracellular deposition of misfolded transthyretin fibrils, leading to neurological, cardiac, gastrointestinal, urogenital, sexual, and ophthalmological involvement. While disease-modifying therapies have significantly improved survival and slowed disease progression, a substantial proportion of patients continue to experience a high symptomatic burden that markedly impairs quality of life. Symptomatic manifestations often occur early, may precede the diagnosis, and frequently persist despite etiological treatment. This review provides a comprehensive overview of the symptomatic management of ATTR, with particular emphasis on autonomic dysfunction and its systemic consequences. We discuss current therapeutic strategies for orthostatic hypotension, gastrointestinal dysmotility, nutritional impairment, sexual dysfunction, lower urinary tract dysfunction, and ophthalmological involvement, highlighting both pharmacological and non-pharmacological approaches. Special attention is given to treatment limitations related to cardiac involvement, autonomic failure, and drug tolerability. Despite the clinical relevance of symptom control in ATTR, evidence-based recommendations remain scarce, and no dedicated guidelines currently exist. Most therapeutic approaches are derived from observational studies, expert opinion, and clinical experience. Improved awareness of symptomatic manifestations, early intervention, and a multidisciplinary, individualized approach are essential to optimize patient outcomes. Future research should focus on prospective studies and the development of structured symptomatic treatment algorithms to complement disease-modifying therapies and enhance patient-centered care in ATTR.<\/jats:p>","DOI":"10.3390\/neurolint18030053","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T15:06:22Z","timestamp":1773414382000},"page":"53","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Treating the Patient, Not Only the Amyloid: Symptomatic Management in Transthyretin Amyloidosis"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3027-7863","authenticated-orcid":false,"given":"Christian","family":"Messina","sequence":"first","affiliation":[{"name":"Azienda Sanitaria Provinciale Catania, Via Santa Maria La Grande, 95100 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1002\/mus.28026","article-title":"Diagnosis and treatment of hereditary transthyretin amyloidosis with polyneuropathy in the United States: Recommendations from a panel of experts","volume":"69","author":"Karam","year":"2024","journal-title":"Muscle Nerve"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s13023-025-03547-0","article-title":"Epidemiology of transthyretin (ATTR) amyloidosis: A systematic literature review","volume":"20","author":"Delgado","year":"2025","journal-title":"Orphanet J. 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