1688f56cb918f812b13eeb9c6d1c8f57 ijms-26-06220.pdf 894892aeca230cdabac5e78c1b8289f0309346f2 ijms-26-06220.pdf 10cbefa05a8ab04df13d87aef0d4465e0f2e602e0998aa88a6eec01f6e46d074 ijms-26-06220.pdf Title: Update on the Symptomatic Treatment of Huntington’s Disease: From Pathophysiology to Clinical Practice Subject: Huntington’s disease (HD) is the most common autosomal dominant neurodegenerative disorder, characterized by a triad of motor dysfunction, cognitive decline, and psychiatric disturbances. While recent efforts have focused on developing disease-modifying therapies, no treatment has yet demonstrated clinical efficacy. As a result, symptomatic treatment remains the cornerstone of care. However, high-quality evidence from large randomized trials is limited, and therapeutic decisions must rely on clinical expertise and extrapolation from other neurological or psychiatric conditions. This narrative review provides a comprehensive and practical overview of symptomatic treatment strategies for HD with emphasis on the pathophysiological underpinnings of each symptom and the molecular mechanisms of available and emerging therapies, aiming to support rational, individualized management. Finally, we highlight the critical role of non-pharmacological interventions and the need for multidisciplinary approaches to optimize patient outcomes and quality of life. Keywords: Huntington disease; chorea; movement disorders; cognitive dysfunction; psychiatric symptoms; pathophysiology Author: Gonzalo Olmedo-Saura, Eugenio Bernardi, Lidia Bojtos, Saül Martínez-Horta, Javier Pagonabarraga, Jaime Kulisevsky and Jesús Pérez-Pérez Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Fri Jun 27 17:12:55 2025 CEST ModDate: Fri Jun 27 17:28:18 2025 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 32 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 667437 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- QBLPJB+VnURWPalladioL Type 1 Custom yes yes yes 10 0 DENUWR+URWPalladioL-Roma Type 1 Custom yes yes yes 16 0 IQFBJD+URWPalladioL-Bold Type 1 Custom yes yes yes 22 0 HTXRKV+URWPalladioL-Ital Type 1 Custom yes yes yes 27 0 PXTEMV+CMSY10 Type 1 Builtin yes yes yes 32 0 OBCJHG+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 67 0 OBCJJG+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 73 0 OBCJKH+PalatinoLinotype-Italic CID TrueType Identity-H yes yes yes 79 0 OBCNGG+ArialMT TrueType WinAnsi yes yes no 85 0 QDCWHF+EURM10 Type 1 Builtin yes yes yes 107 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-09-17 03:09:40 CEST RepresentationInformation: ijms-26-06220.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2025-09-16 15:11:34 CEST Size: 667437 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 861 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Search Strategy Destination: section.2 Item: Title: Symptomatic Treatment of Huntington’s Disease Destination: section.3 Children: Item: Title: Motor Symptoms Destination: subsection.3.1 Children: Item: Title: Chorea Destination: subsubsection.3.1.1 Item: Title: Motor Impersistence Destination: subsubsection.3.1.2 Item: Title: Dystonia Destination: subsubsection.3.1.3 Item: Title: Parkinsonism Destination: subsubsection.3.1.4 Item: Title: Gait and Balance Disorders Destination: subsubsection.3.1.5 Item: Title: Other Motor Manifestations Destination: subsubsection.3.1.6 Item: Title: Cognitive Symptoms Destination: subsection.3.2 Children: Item: Title: Clinical Management Destination: subsubsection.3.2.1 Item: Title: Ongoing Research Destination: subsubsection.3.2.2 Item: Title: Author’s Recommendations Destination: subsubsection.3.2.3 Item: Title: Behavioral and Neuropsychiatric Symptoms (NPS) Destination: subsection.3.3 Children: Item: Title: Depression Destination: subsubsection.3.3.1 Item: Title: Anxiety Destination: subsubsection.3.3.2 Item: Title: Apathy Destination: subsubsection.3.3.3 Item: Title: Irritability and Aggressiveness Destination: subsubsection.3.3.4 Item: Title: Perseverative Ideation and Obsessive Compulsive Disorder (OCD) Destination: subsubsection.3.3.5 Item: Title: Psychosis Destination: subsubsection.3.3.6 Item: Title: Suicidal Ideation Destination: subsubsection.3.3.7 Item: Title: Impulsivity Destination: subsubsection.3.3.8 Item: Title: Other NPSs Destination: subsubsection.3.3.9 Item: Title: Conclusions Destination: section.4 Item: Title: References Destination: section.5 Info: Title: Update on the Symptomatic Treatment of Huntington’s Disease: From Pathophysiology to Clinical Practice Author: Gonzalo Olmedo-Saura, Eugenio Bernardi, Lidia Bojtos, Saül Martínez-Horta, Javier Pagonabarraga, Jaime Kulisevsky and Jesús Pérez-Pérez Subject: Huntington’s disease (HD) is the most common autosomal dominant neurodegenerative disorder, characterized by a triad of motor dysfunction, cognitive decline, and psychiatric disturbances. While recent efforts have focused on developing disease-modifying therapies, no treatment has yet demonstrated clinical efficacy. As a result, symptomatic treatment remains the cornerstone of care. However, high-quality evidence from large randomized trials is limited, and therapeutic decisions must rely on clinical expertise and extrapolation from other neurological or psychiatric conditions. This narrative review provides a comprehensive and practical overview of symptomatic treatment strategies for HD with emphasis on the pathophysiological underpinnings of each symptom and the molecular mechanisms of available and emerging therapies, aiming to support rational, individualized management. Finally, we highlight the critical role of non-pharmacological interventions and the need for multidisciplinary approaches to optimize patient outcomes and quality of life. 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