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Chang W, Ganz T, Kang S, Hu K, Mark C, Frank A, Lee B, Lee D, Coley RB, Ceasar RC, Mason X. Disparities in the Clinical Provision of Deep Brain Stimulation: A Systematic Scoping Review and Grounded-Theory Qualitative Analysis. Mov Disord Clin Pract 2025. [PMID: 40410926 DOI: 10.1002/mdc3.70132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2025] [Revised: 03/31/2025] [Accepted: 04/12/2025] [Indexed: 05/25/2025] Open
Abstract
BACKGROUND Deep Brain Stimulation (DBS) has been an established treatment for movement disorders since its FDA approval in 1996. However, disparities in DBS care, particularly concerning race, gender, socioeconomic status, and geography, remain a significant concern globally. OBJECTIVES This systematic scoping review and grounded theory qualitative analysis aimed to synthesize existing research on worldwide disparities in DBS provision and to develop theoretical solutions to enhance equity and improve the quality of research in DBS disparities. METHODS A systematic search identified 46 studies, which were critically appraised for quality and analyzed using grounded theory methods to extract core conceptual categories. RESULTS We characterized three principles of DBS disparities: intersectionality, reciprocal interactivity and influence of patients and providers, and the interposition of simultaneous barriers; together these highlight the role of individual, systemic, and structural factors in generating DBS disparities. Racial minorities, women, socioeconomically disadvantaged individuals, and patients in certain geographic regions were consistently found to have reduced access to DBS. Gaps in the research include a calcified research infrastructure, insufficient attention to cultural and societal contexts, and reliance on conjecture without empirical support. CONCLUSIONS We propose a multi-level approach to address DBS disparities, including reciprocal education between patients and clinicians, enhanced screening and referral networks, and policy reforms at institutional and governmental levels. These findings will facilitate further hypothesis-driven research and foster more equitable access to DBS globally.
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Affiliation(s)
- Wellington Chang
- Keck School of Medicine of the University of Southern California, Los Angeles, California, USA
| | - Talia Ganz
- York University, Toronto, Ontario, Canada
| | - Sara Kang
- Keck School of Medicine of the University of Southern California, Los Angeles, California, USA
| | - Kacey Hu
- Department of Neurology, Keck School of Medicine, Los Angeles, California, USA
| | - Catherine Mark
- Department of Neurological Surgery, Keck School of Medicine, Los Angeles, California, USA
| | - Adam Frank
- Department of Psychiatry, Keck School of Medicine, Los Angeles, California, USA
| | - Brian Lee
- Department of Neurological Surgery, Keck School of Medicine, Los Angeles, California, USA
| | - Darrin Lee
- Department of Neurological Surgery, Keck School of Medicine, Los Angeles, California, USA
| | | | - Rachel Carmen Ceasar
- Department of Population and Public Health Sciences, Keck School of Medicine, Los Angeles, California, USA
| | - Xenos Mason
- Department of Neurology, Keck School of Medicine, Los Angeles, California, USA
- Department of Neurological Surgery, Keck School of Medicine, Los Angeles, California, USA
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Cavaleri J, Stefanescu K, Lee D, Mason X. Deep brain stimulation access in 2025: geographic, gender, racial, and socioeconomic disparities re-examined. Curr Opin Neurol 2025:00019052-990000000-00245. [PMID: 40377666 DOI: 10.1097/wco.0000000000001377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/18/2025]
Abstract
PURPOSE OF REVIEW This review highlights recent studies examining disparities in access to deep brain stimulation (DBS), an effective but resource-intensive therapy for neurological and neuropsychiatric disorders. As DBS indications expand, understanding barriers to equitable provision is increasingly urgent to ensure that all eligible patients can benefit. RECENT FINDINGS Emerging literature confirms persistent disparities in DBS utilization based on geography, gender, race, and socioeconomic status. Geographic disparities reflect regional differences in healthcare infrastructure, with limited access in both rural areas of high-income countries and throughout low-income and middle-income nations. Women remain less likely than men to receive DBS for movement disorders, influenced by referral patterns, social support, and patient preference. Racial and ethnic minority patients - particularly Black and Hispanic individuals - consistently receive DBS at lower rates, in part due to reduced referrals. Socioeconomic factors, including insurance status and household income, strongly predict DBS access, favoring privately insured and wealthier patients. SUMMARY These findings underscore the need for systemic changes in referral practices, institutional policies, and healthcare funding to reduce structural barriers to DBS. Future research should focus on intersectional factors driving disparities and evaluate targeted interventions to promote equitable access.
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Affiliation(s)
- Jonathon Cavaleri
- Department of Neurological Surgery, Keck School of Medicine of the University of Southern California
- Department of Neurological Surgery, Los Angeles General Medical Center
| | - Kristen Stefanescu
- Department of Neurological Surgery, Keck School of Medicine of the University of Southern California
- Department of Neurological Surgery, Los Angeles General Medical Center
- Department of Neurology, Keck School of Medicine of the University of Southern California
| | - Darrin Lee
- Department of Neurological Surgery, Keck School of Medicine of the University of Southern California
- Department of Neurological Surgery, Los Angeles General Medical Center
- Neurorestoration Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Xenos Mason
- Department of Neurological Surgery, Keck School of Medicine of the University of Southern California
- Department of Neurology, Keck School of Medicine of the University of Southern California
- Neurorestoration Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
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Mercante A, Nardocci N, Fernández-Alvarez E, Lumsden DE, Hauer J, Bernadá M, Drake R, Kreicbergs U, Palomo-Carrión R, Gemma M, Coubes P, Fasano A, Lin JP, Benini F, Pediatric Dystonia and Palliative Care Group and the European Paediatric Neurology Society (EPNS). Towards new perspectives: International consensus guidance on dystonia in pediatric palliative care. Eur J Paediatr Neurol 2025; 56:24-37. [PMID: 40267817 DOI: 10.1016/j.ejpn.2025.04.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2024] [Revised: 03/23/2025] [Accepted: 04/03/2025] [Indexed: 04/25/2025]
Abstract
BACKGROUND Pediatric dystonias are associated with a broad spectrum of etiologies, resulting in a heterogeneous patient population in whom clinical presentation, evolution, and therapeutic needs may differ. These neurological symptoms are particularly common in children and adolescents with life-limiting and life-threatening conditions requiring pediatric palliative care (PPC). The impact on the child's quality of life is significant, as is distress for caregivers. Addressing and alleviating dystonia is key to providing good palliative care; however, there is limited evidence. A greater recognition and management of dystonia in this setting is urgently needed to provide appropriate interventions and care. OBJECTIVES To develop a standardized approach to dystonia in PPC. MATERIALS AND METHODS A two-round Delphi process explored the views of experts on the definition, assessment, monitoring, and treatment of dystonia in PPC. Professionals from different backgrounds and disciplines were invited worldwide. The final panel comprised 71 participants who completed a multi-statement online questionnaire. RESULTS Fifty-three items were endorsed, providing expert, consensus-based recommendations. CONCLUSIONS The limited clinical knowledge of childhood dystonia represents a challenge, especially in children with palliative care needs. This study is a first international consensus on dystonia in PPC and offers novel approaches to improving the dystonia-related burden and advancing clinical practice in this vulnerable population.
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Affiliation(s)
- Anna Mercante
- Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy.
| | - Nardo Nardocci
- Dipartimento di Neuroscienze Pediatriche Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milano, Italy
| | | | - Daniel E Lumsden
- Complex Motor Disorder Service, Evelina London Children's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK; Research Department of Early Life Imaging, School of Biomedical Engineering and Imaging Sciences, King's College London, London, UK
| | - Julie Hauer
- Division of General Pediatrics, Boston Children's Hospital, Boston, MA, USA
| | - Mercedes Bernadá
- Pereira Rossell Hospital Center and Asociación Española Pediatric Palliative Care Units, Montevideo, Uruguay
| | - Ross Drake
- Queensland Paediatric Palliative Care Service and Queensland Interdisciplinary Paediatric Persistent Pain Service, Queensland Children's Hospital, South Brisbane, Australia
| | - Ulrika Kreicbergs
- The Department of Women's and Children's Health, Paediatric Oncology and Haematology, Karolinska Institutet, Karolinska University Hospital, Astrid Lindgren Children's Hospital, Childhood Cancer Research Unit, Stockholm, Sweden; Department of Population, Policy and Practice, Great Ormond Street Institute of Child Health, University College London, London, UK
| | - Rocío Palomo-Carrión
- Nursing, Physiotherapy and Occupational Therapy Department. Faculty of Physiotherapy and Nursing, University of Castilla-La Mancha, Toledo, Spain
| | - Marco Gemma
- Neuroanesthesia and Intensive Care Unit Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy
| | - Philippe Coubes
- Unité Pathologies Cérébrales Résistantes et Unité de Recherche sur ses Comportements et Mouvements Anormaux (URCMA), Département de Neurochirurgie, CHU Montpellier, France
| | - Alfonso Fasano
- Edmond J. Safra Program in Parkinson's Disease, Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, UHN. Division of Neurology, University of Toronto, Toronto, Ontario, Canada; Krembil Brain Institute, Toronto, Ontario, Canada
| | - Jean-Pierre Lin
- Complex Motor Disorder Service, Evelina London Children's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK; Children's Neurosciences, Department of Women and Children, Faculty of Life Sciences and Medicine, King's College London, London, UK
| | - Franca Benini
- Pediatric Palliative Care, Pain Service, Department of Women's and Children's Health, University Hospital of Padua, Padua, Italy
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Carmona-Hidalgo B, Quintero J, Rodríguez-López R, Blasco-Amaro JA, Boesch S, Reinhard C. Efficacy of deep brain stimulation in treating monogenic dystonia symptoms: protocol for a systematic review. BMJ Open 2025; 15:e083127. [PMID: 40204321 PMCID: PMC11987142 DOI: 10.1136/bmjopen-2023-083127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Accepted: 03/28/2025] [Indexed: 04/11/2025] Open
Abstract
INTRODUCTION Complexity leads to some dystonias being considered as rare diseases with scarce synthesised evidence. Despite the deficit of scientific evidence, deep brain stimulation (DBS) is currently an effective treatment for dystonias using different brain targets, providing significant improvement of dystonic symptoms regardless of their cause. However, there is considerable variability and non-response rate due to factors such as classification, semiology, duration, aetiology and genetic cause of the disease. This protocol presents the methodology of a planned systematic review to assess the efficacy of DBS as a treatment for monogenic dystonia symptoms, a broad spectrum of pathogenic dystonias due to variants in single genes not yet explored. METHODS AND ANALYSIS This protocol follows the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols guidelines. With the aim to test the efficacy of DBS in monogenic dystonias, the research question in population, intervention, comparator and outcomes format will cover patients with monogenic dystonia treated with DBS with a minimum of 3 months' follow-up after surgery. The outcomes will be assessed using generic and specific scales to measure the efficacy and safety of the intervention. The search will be performed in generic and specific databases and bibliographic resources from 2000. We will include systematic reviews, randomised controlled trials and primary studies in English. In this protocol, the initial search strategy in MEDLINE is presented. Additionally, the protocol provides a description of the prospective assessment of the risk of bias in the selected studies. If studies appear homogeneous and the sample of patients is sufficiently large, a meta-analysis and a subgroup analysis are planned. ETHICS AND DISSEMINATION Ethics committee approval is not required. The results of the review will be published through an open access journal. PROSPERO REGISTRATION NUMBER CRD42023448145.
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Affiliation(s)
- Beatriz Carmona-Hidalgo
- Health Technology Assessment Area (AETSA), Andalusian Public Foundation Progress and Health (FPS), Seville, Spain
| | - Javier Quintero
- Health Technology Assessment Area (AETSA), Andalusian Public Foundation Progress and Health (FPS), Seville, Spain
| | - Rocío Rodríguez-López
- Health Technology Assessment Area (AETSA), Andalusian Public Foundation Progress and Health (FPS), Seville, Spain
| | - Juan Antonio Blasco-Amaro
- Health Technology Assessment Area (AETSA), Andalusian Public Foundation Progress and Health (FPS), Seville, Spain
| | - Sylvia Boesch
- Center for Rare Movement Disorders, Department of Neurology and Neurosurgery, Medical University Innsbruck, Innsbruck, Austria
| | - Carola Reinhard
- Institute for Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany
- Centre for Rare Diseases, University Hospital Tübingen, Tübingen, Germany
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Zetterberg L, Niemi Andersson E, Åsenlöf P, Nyholm D, de Roos P, Bring A. "I'm still the person I am. Not the body it has become." An active but challenging life with cervical dystonia. Physiother Theory Pract 2025; 41:763-771. [PMID: 38814175 DOI: 10.1080/09593985.2024.2359495] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2023] [Revised: 04/13/2024] [Accepted: 05/20/2024] [Indexed: 05/31/2024]
Abstract
BACKGROUND Improvement of activity and participation for the disabled and chronically ill is an important aim of rehabilitation. Cervical dystonia is a neurological movement disorder characterized by involuntary contractions of the neck muscles. Until now, research has identified factors contributing to disability rather than factors which may make it easier to be active and participate in the community. OBJECTIVE Explore and describe perceived experiences of activity and participation in daily life as experienced by persons with cervical dystonia. METHODS Sixteen informants participated in this semi-structured interview study. Inductive qualitative content analysis was performed to understand and interpret experiences shared by the informants. RESULTS Results from the analysis generated two themes "An active life" and "A challenging life" and six sub-themes: Using helpful coping strategies, Accepting a new life situation, Adhering to BT treatment, Facing the negative impact of stress, Experiencing a negative self-image and Suffering from pain and fatigue. CONCLUSIONS Our results support the importance of actions using a rehabilitation approach that consider both motor and non-motor symptoms. Future studies should compare the effects of physiotherapy taking into account wishes and challenges in patients' everyday life versus traditional physiotherapy addressing mostly the motor disorder.
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Affiliation(s)
- Lena Zetterberg
- Department of Women's and Children's Health, Physiotherapy, Uppsala University, Uppsala, Sweden
| | | | - Pernilla Åsenlöf
- Department of Women's and Children's Health, Physiotherapy, Uppsala University, Uppsala, Sweden
| | - Dag Nyholm
- Department of Medical Sciences, Neurology, Uppsala University, Uppsala, Sweden
| | - Paul de Roos
- Department of Medical Sciences, Neurology, Uppsala University, Uppsala, Sweden
| | - Annika Bring
- Department of Women's and Children's Health, Physiotherapy, Uppsala University, Uppsala, Sweden
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Hamami F, Prasuhn J, Well LCV, Lohmann K, Klein C, Brüggemann N, Bäumer T, Münchau A, Weissbach A. Functional movement disorders in dopa-responsive dystonia. Parkinsonism Relat Disord 2025; 132:107292. [PMID: 39848138 DOI: 10.1016/j.parkreldis.2025.107292] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 12/20/2024] [Accepted: 01/15/2025] [Indexed: 01/25/2025]
Abstract
BACKGROUND Functional neurological movement disorders are common and disabling. Little is known about their coexistence with other non-functional movement disorders and their impact on the general disease burden. OBJECTIVES Investigating frequency and characteristics of functional movement disorders in GCH1-positive dopa-responsive dystonia patients. METHODS Twenty-one patients underwent a detailed clinical motor examination and completed self-questionnaires evaluating non-motor characteristics. RESULTS Seven patients (33 %) had comorbid functional movement symptoms, including functional gait disorders (n = 7), balance disturbances (n = 7), and weakness (n = 5), dominating the clinical phenotype and resulting in disability with immobilization. None of them was previously diagnosed with or treated for the functional symptoms. Functional movement symptoms appeared suddenly (on average 18 years after the first dopa-responsive dystonia symptoms) and were unresponsive to L-Dopa. These patients showed significantly higher disability and received unnecessary treatments. CONCLUSION Functional neurological movement disorders are common in patients with dopa-responsive dystonia and impact the clinical picture and the degree of disability. Diagnosing both disorders in an individual patient has substantial therapeutical implications because increases in L-Dopa dosages to treat functional symptoms should be avoided, and physiotherapy should relocate attention away from the affected body region so that movements in the affected body part can be executed without external control to facilitates automatic movements. Physiotherapy should be complemented by psychoeducation and psychotherapeutic approaches.
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Affiliation(s)
- Feline Hamami
- Institute of Systems Motor Science, University Medical Center Schleswig-Holstein, University of Lübeck, Lübeck, Germany; Center for Brain, Behavior, and Metabolism, University of Lübeck, Lübeck, Germany
| | - Jannik Prasuhn
- Center for Brain, Behavior, and Metabolism, University of Lübeck, Lübeck, Germany; Department of Neurology, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany; Institute of Neurogenetics, University of Lübeck, Lübeck, Germany; F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States
| | - Leon-Claas van Well
- Center for Brain, Behavior, and Metabolism, University of Lübeck, Lübeck, Germany; Department of Neurology, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - Katja Lohmann
- Institute of Neurogenetics, University of Lübeck, Lübeck, Germany
| | - Christine Klein
- Institute of Neurogenetics, University of Lübeck, Lübeck, Germany
| | - Norbert Brüggemann
- Center for Brain, Behavior, and Metabolism, University of Lübeck, Lübeck, Germany; Department of Neurology, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany; Institute of Neurogenetics, University of Lübeck, Lübeck, Germany
| | - Tobias Bäumer
- Institute of Systems Motor Science, University Medical Center Schleswig-Holstein, University of Lübeck, Lübeck, Germany; Center for Brain, Behavior, and Metabolism, University of Lübeck, Lübeck, Germany; Center of Rare Diseases, University Medical Center Schleswig-Holstein, Lübeck, Germany
| | - Alexander Münchau
- Institute of Systems Motor Science, University Medical Center Schleswig-Holstein, University of Lübeck, Lübeck, Germany; Center for Brain, Behavior, and Metabolism, University of Lübeck, Lübeck, Germany; Center of Rare Diseases, University Medical Center Schleswig-Holstein, Lübeck, Germany
| | - Anne Weissbach
- Institute of Systems Motor Science, University Medical Center Schleswig-Holstein, University of Lübeck, Lübeck, Germany; Center for Brain, Behavior, and Metabolism, University of Lübeck, Lübeck, Germany; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Center of Rare Diseases, University Medical Center Schleswig-Holstein, Lübeck, Germany.
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Krause P, Mahlknecht P, Skogseid IM, Steigerwald F, Deuschl G, Erasmi R, Schnitzler A, Warnecke T, Müller J, Poewe W, Schneider GH, Vesper J, Warneke N, Eisner W, Prokop T, Müller JU, Volkmann J, Kühn AA. Long-Term Outcomes on Pallidal Neurostimulation for Dystonia: A Controlled, Prospective 10-Year Follow-Up. Mov Disord 2025. [PMID: 39907392 DOI: 10.1002/mds.30130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Revised: 12/13/2024] [Accepted: 01/13/2025] [Indexed: 02/06/2025] Open
Abstract
BACKGROUND Pallidal neurostimulation is an effective treatment for severe isolated dystonia, but long-term data from clinical trials are lacking. OBJECTIVES To evaluate long-term efficacy and safety of pallidal neurostimulation in patients with isolated generalized or segmental dystonia. METHODS Extension study of the prospective multicenter trial (n = 40; July 2002 to May 2004), all patients received effective stimulation and underwent regular follow-up. The 10-year follow-up (n = 31) included Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) motor and disability score, Beck Depression Inventory, Beck Anxiety Inventory, and Mattis Dementia Rating Scale. Primary and secondary endpoints compared motor symptoms, disability scores, mood, and cognition changes. RESULTS Thirty-one patients (12 female), aged 23-72 years, completed the 10-year study extension. Per protocol analysis showed sustained significant improvement in BFMDRS motor scores at 10 years compared with baseline, without significant change from the 6-month or 5-year follow-up. On average, motor scores decreased by 25.3 ± 5.2 points at 10 years (P < 0.0001; 56% improvement). Individual outcomes varied, with 27 responders (≥25% improvement; mean improvement 65.2 ± 21.4%) and 13 non-responders compared with baseline. Sustained improvements were seen in disability, mood, and anxiety scores. Cognition remained stable. CONCLUSIONS This study presents the longest prospective, multicenter follow-up of pallidal neurostimulation in generalized and segmental dystonia. Two-thirds of patients showed strong and stable long-term improvements of dystonia, confirming sustained efficacy and safety over 10 years in treatment-refractory dystonic patients. However, one-third experienced primary (3/40) or secondary (10/40) treatment failure. Diagnostic advances, including genetic testing, and technological progress in pallidal neurostimulation may help to reduce the non-responder rates in the future. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Affiliation(s)
- Patricia Krause
- Movement Disorder and Neuromodulation Unit, Charité, University Medicine Berlin, Berlin, Germany
| | - Philipp Mahlknecht
- Department of Neurology, Medical University Innsbruck, Innsbruck, Austria
| | | | | | - Günther Deuschl
- Department of Neurology, Christian-Albrechts-University, Kiel, Germany
| | - Richard Erasmi
- Department of Neurology, Christian-Albrechts-University, Kiel, Germany
| | - Alfons Schnitzler
- Institute of Clinical Neuroscience and Medical Psychology, and Department of Neurology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany
| | - Tobias Warnecke
- Department of Neurology, University of Münster, Münster, Germany
- Department of Neurology and Rehabilitation, Klinikum Osnabrück, Academic Teaching Hospital of the University of Münster, Osnabrück, Germany
| | - Jörg Müller
- Department of Neurology, Vivantes Klinikum Spandau, Berlin, Germany
| | - Werner Poewe
- Department of Neurology, Medical University Innsbruck, Innsbruck, Austria
| | - Gerd-Helge Schneider
- Department of Neurosurgery, Charité, University Medicine Berlin, Berlin, Germany
| | - Jan Vesper
- Department of Stereotactic and Functional Neurosurgery, University of Düsseldorf, Düsseldorf, Germany
| | - Nils Warneke
- Department of Neurosurgery, University of Münster, Münster, Germany
| | - Wilhelm Eisner
- Department of Neurosurgery, Medical University Innsbruck, Innsbruck, Austria
| | - Thomas Prokop
- Division of Stereotactic and Functional Neurosurgery, University of Freiburg, Freiburg, Germany
| | - Jan-Uwe Müller
- Department of Neurology, Universitätsmedizin Greifswald, Greifswald, Germany
| | - Jens Volkmann
- Department of Neurology, University of Würzburg, Würzburg, Germany
| | - Andrea A Kühn
- Movement Disorder and Neuromodulation Unit, Charité, University Medicine Berlin, Berlin, Germany
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Hu J, Mu Q, Ma F, Wang H, Chi L, Shi M. Combination of Pretarsal and Preseptal Botulinum Toxin Injections in the Treatment of Blepharospasm: A Prospective Nonrandomized Clinical Trial. Am J Ophthalmol 2025; 270:19-24. [PMID: 39424025 DOI: 10.1016/j.ajo.2024.10.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Revised: 10/02/2024] [Accepted: 10/10/2024] [Indexed: 10/21/2024]
Abstract
PURPOSE To compare the efficacy of two botulinum toxin (BoNT) injection methods, pretarsal (PT) combined with preseptal (PS) injection (PT-PS) and conventional PT injection, in the treatment of benign essential blepharospasm (BEB). DESIGN Prospective nonrandomized clinical trial. METHODS From January 2023 to April 2024, 95 BoNT injections into orbicularis oculi were performed in 45 BEB patients, including 52 PT-PS injections s and 43 PT injections. Jankovic Rating Scale (JRS) and Blepharospasm Disability Index (BSDI) were used to assess motor symptoms. The efficacy of two injection methods for BEB was compared in terms of latency to response (LTR), latency to the peak response (LPR), duration of peak response (DPR), duration of response (DOR), satisfaction degree, and possible complications. RESULTS Both injection methods significantly improved JRS and BSDI scores in patients with BEB. However, PT-PS injections showed a shorter LTR ([4.00 (3.00, 6.00] vs 5.00 [4.00, 7.00] days, P = .024) and LPR (23.50 [16.00, 26.00] vs 26.00 [20.00, 30.00] days, P = .040), a longer DPR (88.00 [80.50, 104.75] vs 75.00 [65.00, 92.00] days, P = .003) and DOR (135.00 [118.50, 153.75] vs 121.00 [107.00, 135.00] days, P = .003) than PT injections. Patients with PT-PS injections were more satisfied than those with PT injections (9.50 [8.50, 10.00] vs 8.00 [7.50, 9.00], P < .001), and around 2/3 of patients were more willing to receive the combined injection method later. Among patients receiving PT-PS injections, only one case experienced ptosis, and there were no significant differences in other complications such as lacrimation, dry eyes, and blurred vision between the two injection methods. CONCLUSIONS PT-PS injections of BoNT showed more advantages in the treatment of BEB than PT injections in terms of both their efficacy and patients' satisfactions.
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Affiliation(s)
- Junhao Hu
- From the Department of Neurology, Xijing Hospital, Air Force Medical University (J.H., Q.M., F.M., H.W., M.S.), Xi'an, Shaanxi Province, China; Department of Neurology, 987th Hospital of PLA Joint Service Support Force (J.H., F.M.), Baoji, Shaanxi Province, China
| | - Qinying Mu
- From the Department of Neurology, Xijing Hospital, Air Force Medical University (J.H., Q.M., F.M., H.W., M.S.), Xi'an, Shaanxi Province, China
| | - Fuhao Ma
- From the Department of Neurology, Xijing Hospital, Air Force Medical University (J.H., Q.M., F.M., H.W., M.S.), Xi'an, Shaanxi Province, China; Department of Neurology, 987th Hospital of PLA Joint Service Support Force (J.H., F.M.), Baoji, Shaanxi Province, China
| | - Hao Wang
- From the Department of Neurology, Xijing Hospital, Air Force Medical University (J.H., Q.M., F.M., H.W., M.S.), Xi'an, Shaanxi Province, China
| | - Liyi Chi
- Department of Neurology, 986th Hospital of PLA Air Force (L.C.), Xian, Shaanxi Province, China
| | - Ming Shi
- From the Department of Neurology, Xijing Hospital, Air Force Medical University (J.H., Q.M., F.M., H.W., M.S.), Xi'an, Shaanxi Province, China.
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Khasanova DR, Korenko AN, Pokhabov DB, Baikova AN, Grigoryan AA, Maisonobe P, Karpova MI. [Impact of botulinum therapy on long-term control of cervical dystonia symptoms and patient satisfaction with treatment: results of the international prospective observational study INTEREST IN CD2 in Russian subgroup of patients]. Zh Nevrol Psikhiatr Im S S Korsakova 2025; 125:74-82. [PMID: 40350732 DOI: 10.17116/jnevro202512504174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/14/2025]
Abstract
OBJECTIVE To evaluate effect of long-term BTA treatment on cervical dystonia (CD) symptoms control and patient satisfaction with botulinum therapy in real life setting. MATERIAL AND METHODS A total of 1050 patients took part in the international observational study INTEREST IN CD2, the analysis included data from 995 patients (overall population), of which 56 patients were enrolled In Russia. CD clinical assessment was performed at baseline and on the days of BTA injections using the TWSTRS scale and tremor component of the Tsui scale. Patient satisfaction with CD symptoms control was evaluated using 5-point Likert scale on the day of the visit (today satisfaction) and the highest level of satisfaction at any time since the last BTA injection (highest satisfaction). This article presents the results of the analysis of the Russian subgroup of patients in comparison with the overall study population. RESULTS In 5 Russian investigational sites, 44 (78.6%) women and 12 (21.4%) men were enrolled in the study; the patients' mean age was 51.1±9.6 years, the mean duration of the disease was 7.3±5.6 years. The baseline characteristics of the Russian patients were comparable to the overall population, but severity of CD symptoms was numerically higher in the Russian subgroup: the mean TWSTRS severity scores were 17.4±5.0 and 15.9±5.7, respectively; segmental dystonia was observed more frequently (14.3% and 7.4% of patients), as well as shoulder elevation (73.2% and 50.5%) and jerk (21.4% and 9.6%). The vast majority of Russian patients (82.1%) received treatment with abobotulinumtoxin (Dysport). In the Russian subgroup, higher doses of Dysport (median doses 800.0 U and 500.0 U), larger number of targeted muscles (4.3±1.5 and 3.5±1.5) and injection points (11.7±5.5 and 8.1±5.0) were used compared to the overall population. In the Russian subgroup, the mean TWSTRS total score (assessed at the end of each injection cycle) decreased from 32.3±11.2 to 25.2±15.7 over the 3 years follow-up; there was also decrease in severity score from 17.4±5.0 to 12.6±7.5 and disability score from 9.8±4.0 to 7.4±4.8, comparable to the overall population. Patients' satisfaction with CD symptoms control at peak of the BTA injection effect increased from 92.5% to 98.1% and was higher than in the overall population. At the end of the treatment cycle, patients' satisfaction was consistently lower than at peak effect. CONCLUSION The results of the Russian subgroup analysis showed a high level of long-term effectiveness of botulinum therapy in controlling CD symptoms and patients' satisfaction with treatment in real clinical practice. Dysport is the most frequently used BTA preparation In Russia, the optimal level of effectiveness with repeated injections of Dysport remains stable and is maintained within the framework of real-life practice, which supports the clinical guidelines recommendations of its use as the drug of choice in the treatment of patients with CD.
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Affiliation(s)
| | - A N Korenko
- Academian I.P. Pavlov First Saint Petersburg State Medical University, St. Petersburg, Russia
| | - D B Pokhabov
- Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, Krasnoyarsk, Russia
- Federal Siberian Research Clinical Center under Federal Medical-Biological Agency, Krasnoyarsk, Russia
| | | | | | | | - M I Karpova
- South Ural State Medical University, Chelyabinsk, Russia
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10
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Kokkonen A, Corp DT, Aaltonen J, Hirvonen J, Kirjavainen AK, Rajander J, Joutsa J. Brain metabolic response to repetitive transcranial magnetic stimulation to lesion network in cervical dystonia. Brain Stimul 2024; 17:1171-1177. [PMID: 39396800 DOI: 10.1016/j.brs.2024.10.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 07/21/2024] [Accepted: 10/10/2024] [Indexed: 10/15/2024] Open
Abstract
BACKGROUND A previous study identified a brain network underlying cervical dystonia (CD) based on causal brain lesions. This network was shown to be abnormal in idiopathic CD and aligned with connections mediating treatment response to deep brain stimulation, suggesting generalizability across etiologies and relevance for treatment. The main nodes of this network were located in the deep cerebellar structures and somatosensory cortex (S1), the latter of which can be easily reached via non-invasive brain stimulation. To date, there are no studies testing brain stimulation to networks identified using lesion network mapping. OBJECTIVES To assess target engagement by stimulating the S1 and testing the brain's acute metabolic response to repetitive transcranial magnetic stimulation in CD patients and healthy controls. METHODS Thirteen CD patients and 14 controls received a single session of continuous theta burst (cTBS) and sham to the right S1. Changes in regional brain glucose metabolism were measured using [18F]FDG-PET. RESULTS cTBS increased metabolism at the stimulation site in CD (P = 0.03) but not in controls (P = 0.15; group difference P = 0.01). In subcortical regions, cTBS increased metabolism in the brainstem in CD only (PFDR = 0.04). The remote activation was positively associated with dystonia severity and efficacy of sensory trick phenomenon in CD patients. CONCLUSIONS Our results provide further evidence of abnormal sensory system function in CD and show that a single session of S1 cTBS is sufficient to induce measurable changes in brain glucose metabolism. These findings support target engagement, motivating therapeutic trials of cTBS to the S1 in CD.
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Affiliation(s)
- Aleksi Kokkonen
- Turku Brain and Mind Center, Clinical Neurosciences, University of Turku, Turku, Finland; Neurocenter, Turku University Hospital, Turku, Finland; Turku PET Centre, Turku University Hospital, Turku, Finland.
| | - Daniel T Corp
- Turku Brain and Mind Center, Clinical Neurosciences, University of Turku, Turku, Finland; Cognitive Neuroscience Unit, School of Psychology, Deakin University, Geelong, Australia
| | - Juho Aaltonen
- Turku Brain and Mind Center, Clinical Neurosciences, University of Turku, Turku, Finland; Neurocenter, Turku University Hospital, Turku, Finland
| | - Jussi Hirvonen
- Department of Radiology, University of Turku and Turku University Hospital, Turku, Finland; Medical Imaging Center, Department of Radiology, Tampere University and Tampere University Hospital, Tampere, Finland
| | - Anna K Kirjavainen
- Radiopharmaceutical Chemistry Laboratory, Turku PET Centre, University of Turku, Finland
| | - Johan Rajander
- Turku PET Centre, Accelerator Laboratory, Åbo Akademi University, Turku, Finland
| | - Juho Joutsa
- Turku Brain and Mind Center, Clinical Neurosciences, University of Turku, Turku, Finland; Neurocenter, Turku University Hospital, Turku, Finland; Turku PET Centre, Turku University Hospital, Turku, Finland; Department of Clinical Neurophysiology, University of Turku, Finland
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11
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Dashtipour K, Sadeghi M, Charles D, Mehta S, Fernandez HH, Schwartz M, Jankovic J. Treatment response to onabotulinumtoxinA in cervical dystonia patients with anterocollis and retrocollis. Toxicon 2024; 248:108035. [PMID: 39059560 DOI: 10.1016/j.toxicon.2024.108035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Revised: 07/01/2024] [Accepted: 07/17/2024] [Indexed: 07/28/2024]
Abstract
Anterocollis (AC) and retrocollis (RC) are less common cervical dystonia (CD) subtypes that are often under-represented in CD clinical trials. Herein we describe real-world demographics, disease characteristics, and treatment response to onabotulinumtoxinA (onabotA) in AC or RC patients from an observational, multicenter, prospective registry, CD PROBE. After three onabotA treatments, outcomes (CDIP-58, PGIC, CGIC, CD severity, TWSTRS) in patients with predominant AC or RC were compared to torticollis (TC) and all CD subtypes combined. The mean dosages at each treatment ranged from 153.5 to 195.4 U (AC) to 184.0-213.4 U (RC). After treatment, AC and RC patients reported improvements in the CDIP-58. "Much" or "very much improved" on PGIC and CGIC was reported by AC patients (n = 11/23, 48%) and clinicians (n = 14/23, 61%); and by RC patients (n = 14/24, 58%) and clinicians (n = 19/24, 83%). The mean total TWSTRS decreased from 45.7 (n = 59) to 36.1 (n = 23, 21.0% improvement) for AC patients and from 40.1 (n = 55) to 31.6 (n = 23, 21.2% improvement) for RC patients; the proportion of AC and RC patients with severe CD decreased. Outcomes for AC and RC were generally consistent with those for TC and all subtypes combined. Dysphagia was reported in 4/59 (6.8%) of AC patients (one serious), 7/55 (12.7%) of RC patients (none serious), 29/494 (5.9%) of TC patients (none serious), and 64/1012 (6.3%) of all CD patients (two serious). No new safety signals were identified. In conclusion, treatment with onabotA may relieve CD symptoms in some patients with AC and RC, consistent with results for other CD subtypes and the known safety profile of onabotA for the treatment of CD.
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Affiliation(s)
- Khashayar Dashtipour
- Division of Movement Disorders, Department of Neurology/Movement Disorders, Loma Linda University School of Medicine, Faculty Medical Offices, 11370 Anderson, Suite B-100, Loma Linda, CA, 92354, USA.
| | - Marjan Sadeghi
- Allergan, an AbbVie Company, 2525 Dupont Drive, Irvine, CA, 92612, USA.
| | - David Charles
- Vanderbilt University Medical Center, 1161 21st Ave S, Suite A-1106 MCN, Nashville, TN, 37232-2551, USA.
| | - Shyamal Mehta
- Mayo Clinic College of Medicine, Mayo Clinic Arizona, 13400 E. Shea Boulevard, Scottsdale, AZ, 85259, USA.
| | - Hubert H Fernandez
- Cleveland Clinic Lerner College of Medicine of CWRU, Center for Neurological Restoration, Neurological Institute, Cleveland Clinic, 9500 Euclid Avenue, T-2, Cleveland, OH, 44195, USA.
| | - Marc Schwartz
- MS Biostatistics, LLC, 1045 Sadie Ridge Rd., Clermont, FL, 34715, USA.
| | - Joseph Jankovic
- Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Baylor St. Luke's Medical Center at the McNair Campus, 7200 Cambridge, 9th Floor, Suite 9A, Houston, TX, 77030-4202, USA.
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12
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Soares MC, Parmera JB, Bezerra MER, Cury RG. Dopa-responsive dystonia and paroxysmal dystonic attacks associated with ATP1A3 gene variant. Pract Neurol 2024; 24:326-328. [PMID: 38453474 DOI: 10.1136/pn-2023-004045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/18/2024] [Indexed: 03/09/2024]
Abstract
An 18-year-old man had episodes of severe generalised dystonia, from aged 7 months and becoming progressively more frequent. He also had gradually developed interictal limb dystonia. He was initially diagnosed with paroxysmal kinesigenic dyskinesia but he did not improve with several medications. A levodopa trial led to levodopa-induced dyskinetic movements. However, a lower titration of 25 mg of levodopa two times per day substantially improved his motor features and quality of life. Laboratory investigations and MR scans of the brain were unremarkable. Whole-exome sequencing identified a pathogenic variant in the ATP1A3 gene. The ATP1A3-spectrum disorders include non-classical phenotypes such as paroxysmal dystonic attacks. A response to dopamine response is unusual in these disorders. This case highlights the importance of levodopa trials in early-onset dystonia cases.
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Affiliation(s)
- Míriam Carvalho Soares
- Department of Neurology, Hospital das Clínicas, Federal University of Pernambuco, Recife, Brazil
- Department of Neurology, Hospital das Clínicas, University of São Paulo Medical School, São Paulo, Brazil
| | - Jacy Bezerra Parmera
- Department of Neurology, Hospital das Clínicas, University of São Paulo Medical School, São Paulo, Brazil
| | | | - Rubens Gisbert Cury
- Department of Neurology, Hospital das Clínicas, University of São Paulo Medical School, São Paulo, Brazil
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Onan D, Farham F, Martelletti P. Clinical Conditions Targeted by OnabotulinumtoxinA in Different Ways in Medicine. Toxins (Basel) 2024; 16:309. [PMID: 39057949 PMCID: PMC11280961 DOI: 10.3390/toxins16070309] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Revised: 07/01/2024] [Accepted: 07/04/2024] [Indexed: 07/28/2024] Open
Abstract
OnabotulinumtoxinA (BT-A) is used in different medical fields for its beneficial effects. BT-A, a toxin originally produced by the bacterium Clostridium botulinum, is widely known for its ability to temporarily paralyze muscles by blocking the release of acetylcholine, a neurotransmitter involved in muscle contraction. The literature continually reports new hypotheses regarding potential applications that do not consider blockade of acetylcholine release at the neuromuscular junction as a common pathway. In this opinion article, it is our aim to investigate the different pathway targets of BT-A in different medical applications. First of all, the acetylcholine effect of BT-A is used to reduce wrinkles for cosmetic purposes, in the treatment of urological problems, excessive sweating, temporomandibular joint disorders, obesity, migraine, spasticity in neurological diseases, and in various cases of muscle overactivity such as cervical dystonia, blepharospasm, and essential head tremor. In another potential pathway, glutamate A, CGRP, and substance P are targeted for pain inhibition with BT-A application in conditions such as migraine, trigeminal neuralgia, neuropathic pain, and myofascial pain syndrome. On the other hand, as a mechanism different from acetylcholine and pain mediators, BT-A is used in the treatment of hair loss by increasing oxygenation and targeting transforming growth factor-beta 1 cells. In addition, the effect of BT-A on the apoptosis of cancer cells is also known and is being developed. The benefits of BT-A applied in different doses to different regions for different medical purposes are shown in literature studies, and it is also emphasized in those studies that repeating the applications increases the benefits in the long term. The use of BT-A continues to expand as researchers discover new potential therapeutic uses for this versatile toxin.
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Affiliation(s)
- Dilara Onan
- Department of Physiotherapy and Rehabilitation, Faculty of Heath Sciences, Yozgat Bozok University, Yozgat 66000, Turkey
| | - Fatemeh Farham
- Department of Headache, Iranian Centre of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran 1417653761, Iran;
| | - Paolo Martelletti
- School of Health, Unitelma Sapienza University of Rome, 00161 Rome, Italy;
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14
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Duga V, Giossi R, Romito LM, Stanziano M, Levi V, Panteghini C, Zorzi G, Nardocci N. Long-Term Globus Pallidus Internus Deep Brain Stimulation in Pediatric Non-Degenerative Dystonia: A Cohort Study and a Meta-Analysis. Mov Disord 2024; 39:1131-1144. [PMID: 38646731 DOI: 10.1002/mds.29815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2023] [Revised: 03/24/2024] [Accepted: 03/27/2024] [Indexed: 04/23/2024] Open
Abstract
BACKGROUND The evidence in the effectiveness of deep brain stimulation in children with medication-refractory non-degenerative monogenic dystonia is heterogeneous and long-term results are sparse. OBJECTIVES The objective is to describe long-term outcomes in a single-center cohort and compare our results with a meta-analysis cohort form literature. METHODS We performed a retrospective single-center cohort study including consecutive pediatric patients with non-degenerative genetic or idiopathic dystonia treated with globus pallidus internus deep brain stimulation at our center and a systematic review and individual-patient data meta-analysis with the same inclusion criteria. The primary outcome was the change from baseline in the Burke-Fahn-Marsden Dystonia Rating Scale-movement (BFMDRS-M) score. RESULTS The clinical cohort included 25 patients with a mean study follow-up of 11.4 years. The meta-analysis cohort included 224 patients with a mean follow-up of 3 years. Overall, the BFMDRS-M mean improvements at 1 year and at last follow-up were 41% and 33% in the clinical cohort and 58.9% and 57.2% in the meta-analysis cohort, respectively. TOR1A-dystonia showed the greatest and most stable BFMDRS-M improvement in both cohorts at 1 year and at last follow-up (76.3% and 74.3% in the clinical cohort; 69.6% and 67.3% in the meta-analysis cohort), followed by SGCE-dystonia (63% and 63.9% in the meta-analysis cohort). THAP1-dystonia (70.1% and 29.8% in the clinical cohort; 52.3% and 42.0% in the meta-analysis cohort) and KMT2B-dystonia (33.3% and 41.3% in the clinical cohort; 38.0% and 26.7% in the meta-analysis cohort) showed a less pronounced or sustained response. CONCLUSION Globus pallidus deep brain stimulation long-term treatment seems effective with a possible gene-specific differential effect. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Affiliation(s)
- Valentina Duga
- Child Neuropsychiatry Unit, Department of Pediatric Neuroscience, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy
- Child and Adolescent Neuropsychiatric Unit, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
| | - Riccardo Giossi
- Poison Control Center and Clinical Pharmacology Unit, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy
- Department of Research and Clinical Development, Scientific Directorate, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy
| | - Luigi Michele Romito
- Movement Disorders Unit, Neurology Department, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy
| | - Mario Stanziano
- Neuroradiology Unit, Department of Technology and Diagnosis, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy
| | - Vincenzo Levi
- Functional Neurosurgery Unit, Neurosurgery Department, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy
| | - Celeste Panteghini
- Molecular Neurogenetics Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy
| | - Giovanna Zorzi
- Child Neuropsychiatry Unit, Department of Pediatric Neuroscience, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy
| | - Nardo Nardocci
- Child Neuropsychiatry Unit, Department of Pediatric Neuroscience, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy
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15
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de Souza JCC, Falcone ACM, Barbosa RMG, Soares MC, Munhoz R, Farah M, Capato T, Casagrande SCB, Cordellini MF, de Castro Micheli G, Limongi JCP, Barbosa ER, Listik C, Cury RG. Botulinum Toxin and Deep Brain Stimulation in Dystonia. Toxins (Basel) 2024; 16:282. [PMID: 38922176 PMCID: PMC11209614 DOI: 10.3390/toxins16060282] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Revised: 05/08/2024] [Accepted: 05/10/2024] [Indexed: 06/27/2024] Open
Abstract
Deep Brain Stimulation (DBS) is a recognized treatment for different dystonia subtypes and has been approved by the Food and Drug Administration (FDA) since 2003. The European Federation of Neurological Societies (EFNS) and the International Parkinson and Movement Disorders Society (MDS) recommend DBS for dystonia after failure of botulinum toxin (BoNT) and other oral medications for dystonia treatment. In addition, several long-term studies have demonstrated the continuous efficacy of DBS on motor and quality of life (QoL) scores. However, there are only a few reports comparing the overall impact of surgical treatment in BoNT protocols (e.g., dosage and number of selected muscles before and after surgery). This retrospective multicenter chart-review study analyzed botulinum toxin total dosage and dosage per muscle in 23 dystonic patients before and after DBS surgery. The study's primary outcome was to analyze whether there was a reduction in BoNT dosage after DBS surgery. The mean BoNT dosages difference between baseline and post-surgery was 293.4 units for 6 months, 292.6 units for 12 months, and 295.2 units at the last visit. The median total dose of BoNT in the preoperative period was 800 units (N = 23). At the last visit, the median was 700 units (p = 0.05). This represents a 12.5% reduction in BoNT median dosage. In conclusion, despite the limitations of this retrospective study, there was a significant reduction in BoNT doses after DBS surgery in patients with generalized dystonia.
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Affiliation(s)
- Julia Carvalhinho Carlos de Souza
- Movement Disorders Center, Department of Neurology, School of Medicine, University of São Paulo, São Paulo 05403-000, Brazil; (A.C.M.F.); (R.M.G.B.); (M.C.S.); (T.C.); (S.C.B.C.); (J.C.P.L.); (E.R.B.); (C.L.); (R.G.C.)
| | - Ananda Carolina Moraes Falcone
- Movement Disorders Center, Department of Neurology, School of Medicine, University of São Paulo, São Paulo 05403-000, Brazil; (A.C.M.F.); (R.M.G.B.); (M.C.S.); (T.C.); (S.C.B.C.); (J.C.P.L.); (E.R.B.); (C.L.); (R.G.C.)
| | - Renata Montes Garcia Barbosa
- Movement Disorders Center, Department of Neurology, School of Medicine, University of São Paulo, São Paulo 05403-000, Brazil; (A.C.M.F.); (R.M.G.B.); (M.C.S.); (T.C.); (S.C.B.C.); (J.C.P.L.); (E.R.B.); (C.L.); (R.G.C.)
| | - Miriam Carvalho Soares
- Movement Disorders Center, Department of Neurology, School of Medicine, University of São Paulo, São Paulo 05403-000, Brazil; (A.C.M.F.); (R.M.G.B.); (M.C.S.); (T.C.); (S.C.B.C.); (J.C.P.L.); (E.R.B.); (C.L.); (R.G.C.)
| | - Renato Munhoz
- Morton and Gloria Shulman Movement Disorders Centre and the Edmond J. Safra Program in Parkinson’s Disease, Toronto Western Hospital, University Health Network, Toronto, ON M5T 2S8, Canada;
| | - Marina Farah
- Cajuru University Hospital, Pontíficia Universidade Católica do Paraná, Curitiba 80050-350, Brazil;
| | - Tamine Capato
- Movement Disorders Center, Department of Neurology, School of Medicine, University of São Paulo, São Paulo 05403-000, Brazil; (A.C.M.F.); (R.M.G.B.); (M.C.S.); (T.C.); (S.C.B.C.); (J.C.P.L.); (E.R.B.); (C.L.); (R.G.C.)
- Department of Neurology, Radboud University Medical Center, 6525 Nijmegen, The Netherlands
| | - Sara Carvalho Barbosa Casagrande
- Movement Disorders Center, Department of Neurology, School of Medicine, University of São Paulo, São Paulo 05403-000, Brazil; (A.C.M.F.); (R.M.G.B.); (M.C.S.); (T.C.); (S.C.B.C.); (J.C.P.L.); (E.R.B.); (C.L.); (R.G.C.)
| | | | - Gabriel de Castro Micheli
- Department of Neurology, University Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro 21941-617, Brazil;
| | - João Carlos Papaterra Limongi
- Movement Disorders Center, Department of Neurology, School of Medicine, University of São Paulo, São Paulo 05403-000, Brazil; (A.C.M.F.); (R.M.G.B.); (M.C.S.); (T.C.); (S.C.B.C.); (J.C.P.L.); (E.R.B.); (C.L.); (R.G.C.)
| | - Egberto Reis Barbosa
- Movement Disorders Center, Department of Neurology, School of Medicine, University of São Paulo, São Paulo 05403-000, Brazil; (A.C.M.F.); (R.M.G.B.); (M.C.S.); (T.C.); (S.C.B.C.); (J.C.P.L.); (E.R.B.); (C.L.); (R.G.C.)
| | - Clarice Listik
- Movement Disorders Center, Department of Neurology, School of Medicine, University of São Paulo, São Paulo 05403-000, Brazil; (A.C.M.F.); (R.M.G.B.); (M.C.S.); (T.C.); (S.C.B.C.); (J.C.P.L.); (E.R.B.); (C.L.); (R.G.C.)
| | - Rubens Gisbert Cury
- Movement Disorders Center, Department of Neurology, School of Medicine, University of São Paulo, São Paulo 05403-000, Brazil; (A.C.M.F.); (R.M.G.B.); (M.C.S.); (T.C.); (S.C.B.C.); (J.C.P.L.); (E.R.B.); (C.L.); (R.G.C.)
- Hospital Israelita Albert Einstein, São Paulo 05652-900, Brazil
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Mohamed AA, Faragalla S, Khan A, Flynn G, Rainone G, Johansen PM, Lucke-Wold B. Neurosurgical and pharmacological management of dystonia. World J Psychiatry 2024; 14:624-634. [PMID: 38808085 PMCID: PMC11129150 DOI: 10.5498/wjp.v14.i5.624] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Revised: 04/20/2024] [Accepted: 04/26/2024] [Indexed: 05/16/2024] Open
Abstract
Dystonia characterizes a group of neurological movement disorders characterized by abnormal muscle movements, often with repetitive or sustained contraction resulting in abnormal posturing. Different types of dystonia present based on the affected body regions and play a prominent role in determining the potential efficacy of a given intervention. For most patients afflicted with these disorders, an exact cause is rarely identified, so treatment mainly focuses on symptomatic alleviation. Pharmacological agents, such as oral anticholinergic administration and botulinum toxin injection, play a major role in the initial treatment of patients. In more severe and/or refractory cases, focal areas for neurosurgical intervention are identified and targeted to improve quality of life. Deep brain stimulation (DBS) targets these anatomical locations to minimize dystonia symptoms. Surgical ablation procedures and peripheral denervation surgeries also offer potential treatment to patients who do not respond to DBS. These management options grant providers and patients the ability to weigh the benefits and risks for each individual patient profile. This review article explores these pharmacological and neurosurgical management modalities for dystonia, providing a comprehensive assessment of each of their benefits and shortcomings.
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Affiliation(s)
- Ali Ahmed Mohamed
- Charles E Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL 33431, United States
| | - Steven Faragalla
- Charles E Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL 33431, United States
| | - Asad Khan
- Charles E Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL 33431, United States
| | - Garrett Flynn
- Charles E Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL 33431, United States
| | - Gersham Rainone
- Department of Neurosurgery and Brain Repair, University of South Florida, Tampa, FL 33606, United States
| | - Phillip Mitchell Johansen
- Department of Neurosurgery and Brain Repair, University of South Florida, Tampa, FL 33606, United States
| | - Brandon Lucke-Wold
- Department of Neurosurgery, University of Florida, Gainesville, FL 32611, United States
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Koptielow J, Szyłak E, Szewczyk-Roszczenko O, Roszczenko P, Kochanowicz J, Kułakowska A, Chorąży M. Genetic Update and Treatment for Dystonia. Int J Mol Sci 2024; 25:3571. [PMID: 38612382 PMCID: PMC11011602 DOI: 10.3390/ijms25073571] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Revised: 03/17/2024] [Accepted: 03/21/2024] [Indexed: 04/14/2024] Open
Abstract
A neurological condition called dystonia results in abnormal, uncontrollable postures or movements because of sporadic or continuous muscular spasms. Several varieties of dystonia can impact people of all ages, leading to severe impairment and a decreased standard of living. The discovery of genes causing variations of single or mixed dystonia has improved our understanding of the disease's etiology. Genetic dystonias are linked to several genes, including pathogenic variations of VPS16, TOR1A, THAP1, GNAL, and ANO3. Diagnosis of dystonia is primarily based on clinical symptoms, which can be challenging due to overlapping symptoms with other neurological conditions, such as Parkinson's disease. This review aims to summarize recent advances in the genetic origins and management of focal dystonia.
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Affiliation(s)
- Jan Koptielow
- Department of Neurology, Medical University of Bialystok, 15-276 Bialystok, Poland; (E.S.); (J.K.); (A.K.); (M.C.)
| | - Emilia Szyłak
- Department of Neurology, Medical University of Bialystok, 15-276 Bialystok, Poland; (E.S.); (J.K.); (A.K.); (M.C.)
| | - Olga Szewczyk-Roszczenko
- Department of Synthesis and Technology of Drugs, Medical University of Bialystok, Kilinskiego 1, 15-089 Bialystok, Poland; (O.S.-R.); (P.R.)
| | - Piotr Roszczenko
- Department of Synthesis and Technology of Drugs, Medical University of Bialystok, Kilinskiego 1, 15-089 Bialystok, Poland; (O.S.-R.); (P.R.)
| | - Jan Kochanowicz
- Department of Neurology, Medical University of Bialystok, 15-276 Bialystok, Poland; (E.S.); (J.K.); (A.K.); (M.C.)
| | - Alina Kułakowska
- Department of Neurology, Medical University of Bialystok, 15-276 Bialystok, Poland; (E.S.); (J.K.); (A.K.); (M.C.)
| | - Monika Chorąży
- Department of Neurology, Medical University of Bialystok, 15-276 Bialystok, Poland; (E.S.); (J.K.); (A.K.); (M.C.)
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Sarasso E, Emedoli D, Gardoni A, Zenere L, Canu E, Basaia S, Doretti A, Ticozzi N, Iannaccone S, Amadio S, Del Carro U, Filippi M, Agosta F. Cervical motion alterations and brain functional connectivity in cervical dystonia. Parkinsonism Relat Disord 2024; 120:106015. [PMID: 38325256 DOI: 10.1016/j.parkreldis.2024.106015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Revised: 01/10/2024] [Accepted: 01/26/2024] [Indexed: 02/09/2024]
Abstract
INTRODUCTION Evaluating the neural correlates of sensorimotor control deficits in cervical dystonia (CD) is fundamental to plan the best treatment. This study aims to assess kinematic and resting-state functional connectivity (RS-FC) characteristics in CD patients relative to healthy controls. METHODS Seventeen CD patients and 14 age-/sex-matched healthy controls were recruited. Electromagnetic sensors were used to evaluate dystonic pattern, mean/maximal cervical movement amplitude and joint position error with eyes open and closed, and movement quality during target reaching with the head. RS-fMRI was acquired to compare the FC of brain sensorimotor regions between patients and controls. In patients, correlations between motion analysis and FC data were assessed. RESULTS CD patients relative to controls showed reduced mean and maximal cervical range of motion (RoM) in rotation both towards and against dystonia pattern and reduced total RoM in rotation both with eyes open and closed. They had less severe dystonia pattern with eyes open vs eyes closed. CD patients showed an altered movement quality and sensorimotor control during target reaching and a higher joint position error. Compared to controls, CD patients showed reduced FC between supplementary motor area (SMA), occipital and cerebellar areas, which correlated with lower cervical RoM in rotation both with eyes open and closed and with worse movement quality during target reaching. CONCLUSIONS FC alterations between SMA and occipital and cerebellar areas may represent the neural basis of cervical sensorimotor control deficits in CD patients. Electromagnetic sensors and RS-fMRI might be promising tools to monitor CD and assess the efficacy of rehabilitative interventions.
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Affiliation(s)
- Elisabetta Sarasso
- Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy; Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal Child Health, University of Genoa, Genoa, Italy
| | - Daniele Emedoli
- Department of Rehabilitation and Functional Recovery, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Andrea Gardoni
- Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Lucia Zenere
- Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Elisa Canu
- Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Silvia Basaia
- Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Alberto Doretti
- Department of Neurology, IRCCS Istituto Auxologico Italiano, Milan, Italy
| | - Nicola Ticozzi
- Department of Neurology, IRCCS Istituto Auxologico Italiano, Milan, Italy; Department of Pathophysiology and Transplantation, "Dino Ferrari" Center, Università degli Studi di Milano, Milan, Italy
| | - Sandro Iannaccone
- Department of Rehabilitation and Functional Recovery, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Stefano Amadio
- Neurophysiology Service, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Ubaldo Del Carro
- Neurophysiology Service, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Massimo Filippi
- Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy; Neurophysiology Service, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurorehabilitation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Federica Agosta
- Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy; Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
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19
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Hamami F, Bäumer T. [Pain and cervical dystonia]. Schmerz 2024; 38:41-47. [PMID: 38265520 DOI: 10.1007/s00482-024-00790-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/04/2024] [Indexed: 01/25/2024]
Abstract
BACKGROUND Dystonia is a hyperkinetic movement disorder that results in twisting, cramps and tremors due to sustained or intermittent muscle contractions. Cervical dystonia is the most common form of dystonia, in which the head, neck and/or shoulder areas are affected. In addition to these motor symptoms, pain and psychiatric symptoms are frequent in (cervical) dystonia. OBJECTIVE Description of the incidence and evaluation of pain in cervical dystonia, summary and discussion of treatment options and effects. MATERIAL AND METHODS In this review article the results in the scientific literature on pain in dystonia are summarized and discussed. RESULTS Compared to other forms of dystonia, pain occurs most frequently in patients with cervical dystonia. A large proportion of patients with cervical dystonia suffer from pain, which contributes most to impairment of the patient. The motor symptoms of dystonia are usually treated with botulinum toxin injections. These have a muscle relaxing effect and also relieve pain. The study situation on the occurrence and treatment of pain in other forms of dystonia is so far very limited. Pain can dominate the clinical picture in patients with cervical dystonia. Evaluation of pain in cervical dystonia can be performed using standardized questionnaires. CONCLUSION It is important to ask patients with cervical dystonia about pain and to consider it in treatment planning and evaluation. Vice versa, if pain is present the possibility of a causative dystonia should also be considered. For pain assessment there are some newly developed questionnaires to assess pain in a standardized way in patients with dystonia. Further research is needed to better understand the pathomechanisms of pain in dystonia.
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Affiliation(s)
- Feline Hamami
- Institut für Systemische Motorikforschung, Center of Brain, Behavior and Metabolism (CBBM), Universität zu Lübeck, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Deutschland
| | - Tobias Bäumer
- Institut für Systemische Motorikforschung, Center of Brain, Behavior and Metabolism (CBBM), Universität zu Lübeck, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Deutschland.
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20
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Kassaye SG, De Hertogh W, Crosiers D, Gudina EK, De Pauw J. The effectiveness of physiotherapy for patients with isolated cervical dystonia: an updated systematic review and meta-analysis. BMC Neurol 2024; 24:53. [PMID: 38302911 PMCID: PMC10832109 DOI: 10.1186/s12883-023-03473-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Accepted: 11/20/2023] [Indexed: 02/03/2024] Open
Abstract
BACKGROUND Cervical dystonia is a movement disorder typically characterized by a patterned and twisting movement of sustained or intermittent muscle contractions. Recently, new clinical trials are emerging, highlighting the potential benefit of physiotherapy (PT) on disease outcomes. Thus, the objective of this review is to update the effectiveness of PT on cervical dystonia disease outcomes and subsequently perform a meta-analysis. METHODS Interventional studies published in English with adult patients with isolated cervical dystonia following a physiotherapy program were included. Relevant articles were searched in PubMed (MEDLINE), Web of Science, and Scopus. Cochrane and Joanna Briggs Institute risk of bias checklists were used for quality reporting. Meta-analysis was done using Review Manager 5.3 statistical software and a pooled mean difference for pain was presented. RESULTS Fourteen articles were included in the review and two articles were included in the meta-analysis. The meta-analysis revealed that PT intervention had a significant effect on pain reduction scale (-5.00, 95% CI -6.26, -3.74) when used as an additional therapy with botulinum toxin (BoNT) injection. Additionally, findings indicate a possible positive effect of PT disease severity, disability, and quality of life. CONCLUSIONS Physiotherapy in addition to BoNT is recommended to decrease pain. The findings suggest a reduction of disease severity, disability, and improvement in quality of life. The variety in the type and duration of PT interventions did not allow a clear recommendation of a specific type of PT.
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Affiliation(s)
- Shimelis Girma Kassaye
- Institute of Health, Jimma University, Jimma, Ethiopia
- Department of Rehabilitation Sciences and Physiotherapy/Movant, Faculty of Medicine and Health Science, University of Antwerp, Antwerp, Belgium
| | - Willem De Hertogh
- Department of Rehabilitation Sciences and Physiotherapy/Movant, Faculty of Medicine and Health Science, University of Antwerp, Antwerp, Belgium
| | - David Crosiers
- Department of Neurology, Antwerp University Hospital, Antwerp, Belgium
- Translational Neurosciences, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
| | | | - Joke De Pauw
- Department of Rehabilitation Sciences and Physiotherapy/Movant, Faculty of Medicine and Health Science, University of Antwerp, Antwerp, Belgium.
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21
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Odorfer TM, Volkmann J. Deep Brain Stimulation for Focal or Segmental Craniocervical Dystonia in Patients Who Have Failed Botulinum Neurotoxin Therapy-A Narrative Review of the Literature. Toxins (Basel) 2023; 15:606. [PMID: 37888637 PMCID: PMC10611146 DOI: 10.3390/toxins15100606] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Revised: 10/07/2023] [Accepted: 10/08/2023] [Indexed: 10/28/2023] Open
Abstract
(1) Background: The first-line treatment for patients with focal or segmental dystonia with a craniocervical distribution is still the intramuscular injection of botulinum neurotoxin (BoNT). However, some patients experience primary or secondary treatment failure from this potential immunogenic therapy. Deep brain stimulation (DBS) may then be used as a backup strategy in this situation. (2) Methods: Here, we reviewed the current study literature to answer a specific question regarding the efficacy and safety of the use of DBS, particularly for cervical dystonia (CD) and Meige syndrome (MS) in patients with documented treatment failure under BoNT. (3) Results: There are only two studies with the highest level of evidence in this area. Despite this clear limitation, in the context of the narrowly defined research question of this paper, it is possible to report 161 patients with CD or MS who were included in studies that were able to show a statistically significant reduction in dystonic symptoms using DBS. Safety and tolerability data appeared adequate. However, much of the information is based on retrospective observations. (4) Conclusions: The evidence base in this area is in need of further scientific investigation. Most importantly, more randomized, controlled and double-blind trials are needed, possibly including a head-to-head comparison of DBS and BoNT.
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Affiliation(s)
- Thorsten M. Odorfer
- Department of Neurology, University Hospital Würzburg, Josef-Schneider-Str. 11, 97080 Würzburg, Germany
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Fan Y, Si Z, Wang L, Zhang L. DYT- TOR1A dystonia: an update on pathogenesis and treatment. Front Neurosci 2023; 17:1216929. [PMID: 37638318 PMCID: PMC10448058 DOI: 10.3389/fnins.2023.1216929] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Accepted: 07/24/2023] [Indexed: 08/29/2023] Open
Abstract
DYT-TOR1A dystonia is a neurological disorder characterized by involuntary muscle contractions and abnormal movements. It is a severe genetic form of dystonia caused by mutations in the TOR1A gene. TorsinA is a member of the AAA + family of adenosine triphosphatases (ATPases) involved in a variety of cellular functions, including protein folding, lipid metabolism, cytoskeletal organization, and nucleocytoskeletal coupling. Almost all patients with TOR1A-related dystonia harbor the same mutation, an in-frame GAG deletion (ΔGAG) in the last of its 5 exons. This recurrent variant results in the deletion of one of two tandem glutamic acid residues (i.e., E302/303) in a protein named torsinA [torsinA(△E)]. Although the mutation is hereditary, not all carriers will develop DYT-TOR1A dystonia, indicating the involvement of other factors in the disease process. The current understanding of the pathophysiology of DYT-TOR1A dystonia involves multiple factors, including abnormal protein folding, signaling between neurons and glial cells, and dysfunction of the protein quality control system. As there are currently no curative treatments for DYT-TOR1A dystonia, progress in research provides insight into its pathogenesis, leading to potential therapeutic and preventative strategies. This review summarizes the latest research advances in the pathogenesis, diagnosis, and treatment of DYT-TOR1A dystonia.
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Affiliation(s)
- Yuhang Fan
- Department of Neurology, the Second Hospital of Jilin University, Changchun, China
| | - Zhibo Si
- Department of Ophthalmology, the Second Hospital of Jilin University, Changchun, China
| | - Linlin Wang
- Department of Ultrasound, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Lei Zhang
- Department of Neurology, the Second Hospital of Jilin University, Changchun, China
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Albanese A, Bhatia KP, Cardoso F, Comella C, Defazio G, Fung VS, Hallett M, Jankovic J, Jinnah HA, Kaji R, Krauss JK, Lang A, Tan EK, Tijssen MA, Vidailhet M. Isolated Cervical Dystonia: Diagnosis and Classification. Mov Disord 2023; 38:1367-1378. [PMID: 36989390 PMCID: PMC10528915 DOI: 10.1002/mds.29387] [Citation(s) in RCA: 34] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Revised: 02/25/2023] [Accepted: 03/07/2023] [Indexed: 03/31/2023] Open
Abstract
This document presents a consensus on the diagnosis and classification of isolated cervical dystonia (iCD) with a review of proposed terminology. The International Parkinson and Movement Disorder Society Dystonia Study Group convened a panel of experts to review the main clinical and diagnostic issues related to iCD and to arrive at a consensus on diagnostic criteria and classification. These criteria are intended for use in clinical research, but also may be used to guide clinical practice. The benchmark is expert clinical observation and evaluation. The criteria aim to systematize the use of terminology as well as the diagnostic process, to make it reproducible across centers and applicable by expert and non-expert clinicians. Although motor abnormalities remain central, increasing recognition has been given to nonmotor manifestations, which are incorporated into the current criteria. Three iCD presentations are described in some detail: idiopathic (focal or segmental) iCD, genetic iCD, and acquired iCD. The relationship between iCD and isolated head tremor is also reviewed. Recognition of idiopathic iCD has two levels of certainty, definite or probable, supported by specific diagnostic criteria. Although a probable diagnosis is appropriate for clinical practice, a higher diagnostic level may be required for specific research studies. The consensus retains elements proven valuable in previous criteria and omits aspects that are no longer justified, thereby encapsulating diagnosis according to current knowledge. As understanding of iCD expands, these criteria will need continuous revision to accommodate new advances. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Affiliation(s)
- Alberto Albanese
- Department of Neurology, IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Kailash P. Bhatia
- Department of Clinical and Movement Neurosciences, UCL, Queen Square, Institute of Neurology, University College London, London, UK
| | - Francisco Cardoso
- Movement Disorders Unit Hospital das Clínicas, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | - Cynthia Comella
- Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA
| | - Giovanni Defazio
- Department of Translational Biomedicine and Neuroscience, University of Bari, Bari, Italy
| | - Victor S.C. Fung
- Sydney Medical School, Faculty of Medicine and Health, University of Sydney, Sydney, Australia
- Movement Disorders Unit, Neurology Department, Westmead Hospital, Westmead, Australia
| | - Mark Hallett
- National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
| | - Joseph Jankovic
- Parkinson’s Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, Texas, USA
| | - Hyder A. Jinnah
- Departments of Neurology, Human Genetics, and Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Ryuji Kaji
- Department of Neurology, National Hospital Organization Utano National Hospital, Kyoto, Japan
| | - Joachim K. Krauss
- Department of Neurosurgery, Medical School Hannover, Hannover, Germany
| | - Anthony Lang
- Edmond J. Safra Program in Parkinson’s Disease, Toronto Western Hospital, University of Toronto, Toronto, Canada
| | - Eng King Tan
- Department of Neurology, National Neuroscience Institute, Singapore General Hospital, Singapore, Singapore
| | - Marina A.J. Tijssen
- Expertise Center Movement Disorders Groningen, Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Marie Vidailhet
- Department of Neurology, Sorbonne Université, Paris, France
- Institut du Cerveau et de la Moelle épinière-Inserm U1127, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
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Bleton JP, Portero R, Zuber K, Sangla S, Brandel JP, Vidailhet M, Mesure S, Williams M, Savatovsky J. Assessment of axial rotation movement in cervical dystonia using cone-beam computed tomography. Clin Biomech (Bristol, Avon) 2023; 107:106037. [PMID: 37429102 DOI: 10.1016/j.clinbiomech.2023.106037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Revised: 06/28/2023] [Accepted: 06/30/2023] [Indexed: 07/12/2023]
Abstract
BACKGROUND Cervical dystonia is a neurological disorder characterized by involuntary muscle contractions and abnormal postures of the head and neck. Botulinum neurotoxin injection is the first-line treatment. Imaging determination of the cervical segments involved (lower or upper according to the torticollis-torticaput [COL-CAP] Classification) is an aid in determining the muscles to be injected. We aimed to clarify the impact of dystonia on posture and rotational movement of cervical vertebrae in the transverse plane. METHODS A comparative study was conducted in a movement disorders department. Ten people with cervical dystonia and 10 matched healthy subjects (without cervical dystonia) were recruited. 3-D images of posture and cervical range of motion in axial rotation in the sitting position were recorded by using a cone-beam CT scanner. Range of rotational motion of the upper cervical spine from the occipital bone to fourth cervical vertebra was measured and compared between the two groups. FINDINGS The head posture analysis showed that the total cervical spine position was more significantly distant from the neutral position for people with dystonia than healthy subjects (p = 0.007). The rotational range of motion of the cervical spine was significantly lower in cervical dystonia participants than in healthy subjects for the total (p = 0.026) and for upper cervical spine (p = 0.004). INTERPRETATION We demonstrated, by means of cone-beam CT, that the disorganization of movements due to cervical dystonia affected the upper cervical spine and mostly the atlantoaxial joint. The involvement of rotator muscles at this cervical level should be considered more in treatments.
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Affiliation(s)
- Jean-Pierre Bleton
- Neurology Department, Hôpital Fondation Adolphe de Rothschild, Paris, France; Clinical Research Department, Hôpital Fondation Adolphe de Rothschild, Paris, France.
| | - Raphaël Portero
- Clinical Research Department, Hôpital Fondation Adolphe de Rothschild, Paris, France
| | - Kévin Zuber
- Clinical Research Department, Hôpital Fondation Adolphe de Rothschild, Paris, France
| | - Sophie Sangla
- Neurology Department, Hôpital Fondation Adolphe de Rothschild, Paris, France
| | | | - Marie Vidailhet
- Sorbonne Université, F-75005 Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Paris, France, Department of Neurology, Groupe Hospitalier Pitié-Salpêtrière, 47 boulevard de l'Hôpital, F-75013 Paris, France; Inserm U1127, CNRS UMR 7225, UM 75, ICM, F-75013 Paris, France
| | - Serge Mesure
- Aix-Marseille University, CNRS, ISM UMR 7287, F-13288 Marseille, France
| | - Marc Williams
- Department of Radiology, Hôpital Fondation Adolphe de Rothschild, Paris, France
| | - Julien Savatovsky
- Department of Radiology, Hôpital Fondation Adolphe de Rothschild, Paris, France
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Vo A, Nguyen N, Fujita K, Schindlbeck KA, Rommal A, Bressman SB, Niethammer M, Eidelberg D. Disordered network structure and function in dystonia: pathological connectivity vs. adaptive responses. Cereb Cortex 2023; 33:6943-6958. [PMID: 36749014 PMCID: PMC10233302 DOI: 10.1093/cercor/bhad012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Revised: 12/21/2022] [Accepted: 01/10/2023] [Indexed: 02/08/2023] Open
Abstract
Primary dystonia is thought to emerge through abnormal functional relationships between basal ganglia and cerebellar motor circuits. These interactions may differ across disease subtypes and provide a novel biomarker for diagnosis and treatment. Using a network mapping algorithm based on resting-state functional MRI (rs-fMRI), a method that is readily implemented on conventional MRI scanners, we identified similar disease topographies in hereditary dystonia associated with the DYT1 or DYT6 mutations and in sporadic patients lacking these mutations. Both networks were characterized by contributions from the basal ganglia, cerebellum, thalamus, sensorimotor areas, as well as cortical association regions. Expression levels for the two networks were elevated in hereditary and sporadic dystonia, and in non-manifesting carriers of dystonia mutations. Nonetheless, the distribution of abnormal functional connections differed across groups, as did metrics of network organization and efficiency in key modules. Despite these differences, network expression correlated with dystonia motor ratings, significantly improving the accuracy of predictions based on thalamocortical tract integrity obtained with diffusion tensor MRI (DTI). Thus, in addition to providing unique information regarding the anatomy of abnormal brain circuits, rs-fMRI functional networks may provide a widely accessible method to help in the objective evaluation of new treatments for this disorder.
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Affiliation(s)
- An Vo
- Center for Neurosciences, The Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA
| | - Nha Nguyen
- Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA
| | - Koji Fujita
- Center for Neurosciences, The Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA
| | - Katharina A Schindlbeck
- Center for Neurosciences, The Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA
- Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany
| | - Andrea Rommal
- Center for Neurosciences, The Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA
| | - Susan B Bressman
- Department of Neurology, Mount Sinai Beth Israel, New York, NY 10003, USA
| | - Martin Niethammer
- Center for Neurosciences, The Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA
| | - David Eidelberg
- Center for Neurosciences, The Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA
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Albanese A, Wissel J, Jost WH, Castagna A, Althaus M, Comes G, Scheschonka A, Vacchelli M, Jinnah HA. Pain Reduction in Cervical Dystonia Following Treatment with IncobotulinumtoxinA: A Pooled Analysis. Toxins (Basel) 2023; 15:333. [PMID: 37235367 PMCID: PMC10224129 DOI: 10.3390/toxins15050333] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 05/04/2023] [Accepted: 05/06/2023] [Indexed: 05/28/2023] Open
Abstract
This analysis pooled pain severity data from four phase 3 and 4 studies of incobotulinumtoxinA (incoBoNT-A) for the treatment of cervical dystonia (CD) in adults. CD-related pain severity was assessed at baseline, each injection visit, and 4 weeks after each injection of incoBoNT-A using the Toronto Western Spasmodic Torticollis Rating Scale pain severity subscale or a pain visual analog scale. Both were analyzed using a score range of 0-10 and pain was categorized as mild, moderate, or severe. Data for 678 patients with pain at baseline were assessed and sensitivity analyses evaluated pain responses in the subgroup not taking concomitant pain medication (n = 384 at baseline). At Week 4 after the first injection, there was a mean change of -1.25 (standard deviation 2.04) points from baseline pain severity (p < 0.0001), with 48.1% showing ≥ 30% pain reduction from baseline, 34.4% showing ≥50% pain reduction from baseline, and 10.3% becoming pain free. Pain responses were sustained over five injection cycles with a trend to incremental improvements with each successive cycle. Pain responses in the subgroup not taking concomitant pain medication demonstrated the lack of confounding effects of pain medications. These results confirmed the pain relief benefits of long-term treatment with incoBoNT-A.
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Affiliation(s)
- Alberto Albanese
- Department of Neurology, IRCCS Humanitas Research Hospital, 20089 Rozzano, MI, Italy
| | - Jörg Wissel
- Department of Neurorehabilitation and Physical Therapy, Vivantes Hospital Spandau, 13585 Berlin, Germany;
| | | | - Anna Castagna
- IRCCS Fondazione Don Carlo Gnocchi, 20148 Milano, MI, Italy;
| | - Michael Althaus
- Merz Therapeutics GmbH, 60318 Frankfurt am Main, Germany; (M.A.); (G.C.); (A.S.); (M.V.)
| | - Georg Comes
- Merz Therapeutics GmbH, 60318 Frankfurt am Main, Germany; (M.A.); (G.C.); (A.S.); (M.V.)
| | - Astrid Scheschonka
- Merz Therapeutics GmbH, 60318 Frankfurt am Main, Germany; (M.A.); (G.C.); (A.S.); (M.V.)
| | - Matteo Vacchelli
- Merz Therapeutics GmbH, 60318 Frankfurt am Main, Germany; (M.A.); (G.C.); (A.S.); (M.V.)
| | - Hyder A. Jinnah
- Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA;
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Loens S, Hamami F, Lohmann K, Odorfer T, Ip CW, Zittel S, Zeuner KE, Everding J, Becktepe J, Marth K, Borngräber F, Kollewe K, Kamm C, Kühn AA, Gelderblom M, Volkmann J, Klein C, Bäumer T. Tremor is associated with familial clustering of dystonia. Parkinsonism Relat Disord 2023; 110:105400. [PMID: 37086575 DOI: 10.1016/j.parkreldis.2023.105400] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Revised: 03/17/2023] [Accepted: 04/11/2023] [Indexed: 04/24/2023]
Abstract
INTRODUCTION Dystonia is a movement disorder of variable etiology and clinical presentation and is accompanied by tremor in about 50% of cases. Monogenic causes in dystonia are rare, but also in the group of non-monogenic dystonias 10-30% of patients report a family history of dystonia. This points to a number of patients currently classified as idiopathic that have at least in part an underlying genetic contribution. The present study aims to identify clinical and demographic features associated with heritability of yet idiopathic dystonia. METHODS Seven hundred thirty-three datasets were obtained from the DysTract dystonia registry, patients with acquired dystonia or monogenic causes were excluded. Affected individuals were assigned to a familial and sporadic group, and clinical features were compared across these groups. Additionally, the history of movement disorders was also counted in family members. RESULTS 18.2% of patients reported a family history of dystonia. Groups differed in age at onset, disease duration and presence of tremor on a descriptive level. Logistic regression analysis revealed that tremor was the only predictor for a positive family history of dystonia (OR 2.49, CI = 1.54-4.11, p < 0.001). Tremor turned out to be the most common movement disorder in available relatives of patients, and presence of tremor in relatives was associated with tremor in index patients (X2(1) = 16.2, p < 0.001). CONCLUSIONS Tremor is associated with an increased risk of familial clustering of dystonia and with a family history of tremor itself. This indicates a hereditable dystonia-tremor syndrome with a clinical spectrum ranging from tremor-predominant diseases to dystonia.
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Affiliation(s)
- Sebastian Loens
- Institute of Systems Motor Science, University of Lübeck, Lübeck, Germany; Department of Rare Diseases, University Hospital Schleswig Holstein, Lübeck, Germany.
| | - Feline Hamami
- Institute of Systems Motor Science, University of Lübeck, Lübeck, Germany
| | - Katja Lohmann
- Institute of Neurogenetics, University of Lübeck, Lübeck, Germany
| | - Thorsten Odorfer
- Department of Neurology, University Hospital Würzburg, Würzburg, Germany
| | - Chi Wang Ip
- Department of Neurology, University Hospital Würzburg, Würzburg, Germany
| | - Simone Zittel
- Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Kirsten E Zeuner
- Department of Neurology, University Hospital Kiel, Kiel, Germany
| | - Judith Everding
- Department of Neurology, University Hospital Kiel, Kiel, Germany
| | - Jos Becktepe
- Department of Neurology, University Hospital Kiel, Kiel, Germany
| | - Katrin Marth
- Department of Neurology, University Hospital Rostock, Rostock, Germany
| | | | - Katja Kollewe
- Department of Neurology, Hannover Medical School, Hannover, Germany
| | - Christoph Kamm
- Department of Neurology, University Hospital Rostock, Rostock, Germany
| | - Andrea A Kühn
- Department of Neurology, Charité-Universitätsmedizin Berlin, Germany
| | - Mathias Gelderblom
- Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Jens Volkmann
- Department of Neurology, University Hospital Würzburg, Würzburg, Germany
| | - Christine Klein
- Institute of Neurogenetics, University of Lübeck, Lübeck, Germany
| | - Tobias Bäumer
- Institute of Systems Motor Science, University of Lübeck, Lübeck, Germany; Department of Rare Diseases, University Hospital Schleswig Holstein, Lübeck, Germany
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Söke F, Ataoğlu NEE, Öztekin MF, Koçer B, Karakoç S, Gülşen Ç, Çomoğlu SS, Bora HA. Impaired trunk control and its relationship with balance, functional mobility, and disease severity in patients with cervical dystonia. Turk J Med Sci 2023; 53:405-412. [PMID: 36945943 PMCID: PMC10388090 DOI: 10.55730/1300-0144.5597] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Accepted: 11/30/2022] [Indexed: 02/26/2023] Open
Abstract
BACKGROUND Impaired trunk control is common in neurological disorders; however, trunk control has not been examined in patients with cervical dystonia (CD). Therefore, the primary aim was to compare trunk control between patients with CD and healthy people. The secondary aim was to investigate the relationship between trunk control and balance, functional mobility, and disease severity in patients with CD. METHODS ]This cross-sectional study included 32 patients with CD and 32 healthy people. Trunk control was compared using the trunk impairment scale (TIS) that consists of three subscales: static sitting balance, dynamic sitting balance, and trunk coordination between two groups. Balance was assessed using Berg Balance Scale, four square step test, and one-leg stance test. The Timed Up and Go Test was measured to determine functional mobility. Toronto Western Spasmodic Torticollis Rating Scale was used to evaluate disease severity.]></AbstractText> <AbstractText Label="RESULTS"><![CDATA[ Patients with CD demonstrated worse performance on the TIS-total with TIS-dynamic sitting subscale and TIS-trunk coordination subscale (p < 0.001, p < 0.001, and p < 0.001), except for TIS-static sitting subscale (p = 0.078) compared to healthy people. TIS-total scores had moderate to strong correlations with balance, functional mobility, and disease severity (range r between 0.786 and 0.536, p < 0.05 for all). There was no correlation between TIS-total scores and disease severity (p = 0.102). DISCUSSION Patients with CD had impaired trunk control, especially in dynamic sitting balance and trunk coordination. Impaired trunk control was also associated with balance and functional mobility but not disease severity. These findings suggest that trunk control deficits should receive attention in the assessment and treatment of patients with CD.
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Affiliation(s)
- Fatih Söke
- Department of Physiotherapy and Rehabilitation, Gülhane Faculty of Physiotherapy and Rehabilitation, University of Health Sciences, Ankara, Turkey
| | | | - Mehmet Fevzi Öztekin
- Department of Neurology, Dışkapı Yıldırım Beyazıt Teaching and Research Hospital, University of Health Sciences, Ankara, Turkey
| | - Bilge Koçer
- Department of Neurology, Dışkapı Yıldırım Beyazıt Teaching and Research Hospital, University of Health Sciences, Ankara, Turkey
| | - Selda Karakoç
- Department of Physiotherapy and Rehabilitation, Gülhane Institute of Health Science, University of Health Sciences, Ankara, Turkey
| | - Çağrı Gülşen
- Department of Physiotherapy and Rehabilitation, Faculty of Health Sciences, Gazi University, Ankara, Turkey
| | - Selim Selçuk Çomoğlu
- Department of Neurology, Dışkapı Yıldırım Beyazıt Teaching and Research Hospital, University of Health Sciences, Ankara, Turkey
| | - Hatice Ayşe Bora
- Department of Neurology, Faculty of Medicine, Gazi University, Ankara, Turkey
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Nagel JM, Ghika J, Runge J, Wolf ME, Krauss JK. Case report: Pallidal deep brain stimulation for treatment of tardive dystonia/dyskinesia secondary to chronic metoclopramide medication. Front Neurol 2023; 13:1076713. [PMID: 36712453 PMCID: PMC9877408 DOI: 10.3389/fneur.2022.1076713] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Accepted: 12/19/2022] [Indexed: 01/13/2023] Open
Abstract
Objectives Tardive dystonia/dyskinesia (TDD) occurs as a side effect of anti-dopaminergic drugs, including metoclopramide, and is often refractory to medication. While pallidal deep brain stimulation (DBS) has become an accepted treatment for TDD secondary to neuroleptic medication, there is much less knowledge about its effects on metoclopramide-induced TDD. Methods We present the case of a woman with metoclopramide-induced TDD, whose symptoms were initially misjudged as "functional." After 8 years of ineffective medical treatments, she received bilateral implantation of quadripolar electrodes into the posteroventral lateral globus pallidus internus (GPi). Results GPi DBS led to significant symptom reduction [Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) motor score 24/44 at admission and 7/44 at discharge]. Chronic stimulation led to full recovery from TDD symptoms 9 years after surgery. The BFMDRS motor score decreased to 0.5 (98% improvement). Discussion Pallidal DBS may result in sustained improvement of TDD secondary to chronic metoclopramide intake in the long term.
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Affiliation(s)
- Johanna M. Nagel
- Department of Neurosurgery, Hannover Medical School, Hannover, Germany,*Correspondence: Johanna M. Nagel ✉
| | - Joseph Ghika
- Service de Neurologie, Hôpital du Valais, Sion, Switzerland
| | - Joachim Runge
- Department of Neurosurgery, Hannover Medical School, Hannover, Germany
| | - Marc E. Wolf
- Department of Neurology, Neurozentrum, Klinikum Stuttgart, Stuttgart, Germany,Department of Neurology, Universitätsmedizin Mannheim, University of Heidelberg, Mannheim, Germany
| | - Joachim K. Krauss
- Department of Neurosurgery, Hannover Medical School, Hannover, Germany
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30
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Safarpour D, Jabbari B. Botulinum toxin for motor disorders. HANDBOOK OF CLINICAL NEUROLOGY 2023; 196:539-555. [PMID: 37620089 DOI: 10.1016/b978-0-323-98817-9.00003-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/26/2023]
Abstract
Botulinum neurotoxins are a group of biological toxins produced by the gram-negative bacteria Clostridium botulinum. After intramuscular injection, they produce dose-related muscle relaxation, which has proven useful in the treatment of a large number of motor and movement disorders. In this chapter, we discuss the utility of botulinum toxin treatment in three major and common medical conditions related to the dysfunction of the motor system, namely dystonia, tremor, and spasticity. A summary of the existing literature is provided along with different techniques of injection including those recommended by the authors.
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Affiliation(s)
- Delaram Safarpour
- Department of Neurology, Oregon Health & Science University, Portland, OR, United States
| | - Bahman Jabbari
- Department of Neurology, Yale University School of Medicine, New Haven, CT, United States.
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31
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Morrison-Ham J, Clark GM, Ellis EG, Cerins A, Joutsa J, Enticott PG, Corp DT. Effects of non-invasive brain stimulation in dystonia: a systematic review and meta-analysis. Ther Adv Neurol Disord 2022; 15:17562864221138144. [PMID: 36583118 PMCID: PMC9793065 DOI: 10.1177/17562864221138144] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Accepted: 10/21/2022] [Indexed: 12/24/2022] Open
Abstract
Background Deep brain stimulation is a highly effective treatment of dystonia but is invasive and associated with risks, such as intraoperative bleeding and infections. Previous research has used non-invasive brain stimulation (NIBS) in an attempt to alleviate symptoms of dystonia. The results of these studies, however, have been variable, leaving efficacy unclear. Objectives This study aimed to evaluate the effects of NIBS on symptoms of dystonia and determine whether methodological characteristics are associated with variability in effect size. Methods Web of Science, Embase, and MEDLINE Complete databases were searched for articles using any type of NIBS as an intervention in dystonia patients, with changes in dystonia symptoms the primary outcome of interest. Results Meta-analysis of 27 studies demonstrated a small effect size for NIBS in reducing symptoms of dystonia (random-effects Hedges' g = 0.21, p = .002). Differences in the type of NIBS, type of dystonia, and brain region stimulated had a significant effect on dystonia symptoms. Meta-regression revealed that 10 sessions of active stimulation and the application of concurrent motor training programs resulted in significantly larger mean effect sizes. Conclusion NIBS has yielded small improvements to dystonic symptoms, but effect sizes depended on methodological characteristics, with more sessions of stimulation producing a larger response. Future research should further investigate the application of NIBS parallel to motor training, in addition to providing a greater quantity of sessions, to help define optimal parameters for NIBS protocols in dystonia. Registration PROSPERO 2020, CRD42020175944.
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Affiliation(s)
- Jordan Morrison-Ham
- Cognitive Neuroscience Unit, School of
Psychology, Deakin University, 221 Burwood Highway, Burwood, VIC 3125,
Australia
| | - Gillian M. Clark
- Cognitive Neuroscience Unit, School of
Psychology, Deakin University, Geelong, VIC, Australia
| | - Elizabeth G. Ellis
- Cognitive Neuroscience Unit, School of
Psychology, Deakin University, Geelong, VIC, Australia
| | - Andris Cerins
- Cognitive Neuroscience Unit, School of
Psychology, Deakin University, Geelong, VIC, Australia
| | - Juho Joutsa
- Turku Brain and Mind Center, Clinical
Neurosciences, University of Turku, Turku, Finland
- Turku PET Centre, Neurocenter, Turku University
Hospital, Turku, Finland
| | - Peter G. Enticott
- Cognitive Neuroscience Unit, School of
Psychology, Deakin University, Geelong, VIC, Australia
| | - Daniel T. Corp
- Cognitive Neuroscience Unit, School of
Psychology, Deakin University, 221 Burwood Highway, Burwood, VIC 3125,
Australia
- Center for Brain Circuit Therapeutics, Brigham
and Women’s Hospital, Boston, MA, USA
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32
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Neurophysiological Basis of Deep Brain Stimulation and Botulinum Neurotoxin Injection for Treating Oromandibular Dystonia. Toxins (Basel) 2022; 14:toxins14110751. [PMID: 36356002 PMCID: PMC9694803 DOI: 10.3390/toxins14110751] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 10/29/2022] [Accepted: 11/01/2022] [Indexed: 11/06/2022] Open
Abstract
Oromandibular dystonia (OMD) induces severe motor impairments, such as masticatory disturbances, dysphagia, and dysarthria, resulting in a serious decline in quality of life. Non-invasive brain-imaging techniques such as electroencephalography (EEG) and magnetoencephalography (MEG) are powerful approaches that can elucidate human cortical activity with high temporal resolution. Previous studies with EEG and MEG have revealed that movements in the stomatognathic system are regulated by the bilateral central cortex. Recently, in addition to the standard therapy of botulinum neurotoxin (BoNT) injection into the affected muscles, bilateral deep brain stimulation (DBS) has been applied for the treatment of OMD. However, some patients' OMD symptoms do not improve sufficiently after DBS, and they require additional BoNT therapy. In this review, we provide an overview of the unique central spatiotemporal processing mechanisms in these regions in the bilateral cortex using EEG and MEG, as they relate to the sensorimotor functions of the stomatognathic system. Increased knowledge regarding the neurophysiological underpinnings of the stomatognathic system will improve our understanding of OMD and other movement disorders, as well as aid the development of potential novel approaches such as combination treatment with BoNT injection and DBS or non-invasive cortical current stimulation therapies.
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Romano M, Bagnato S, Altavista MC, Avanzino L, Belvisi D, Bologna M, Bono F, Carecchio M, Castagna A, Ceravolo R, Conte A, Cosentino G, Eleopra R, Ercoli T, Esposito M, Fabbrini G, Ferrazzano G, Lalli S, Mascia MM, Osio M, Pellicciari R, Petrucci S, Valente EM, Valentino F, Zappia M, Zibetti M, Girlanda P, Tinazzi M, Defazio G, Berardelli A. Diagnostic and therapeutic recommendations in adult dystonia: a joint document by the Italian Society of Neurology, the Italian Academy for the Study of Parkinson’s Disease and Movement Disorders, and the Italian Network on Botulinum Toxin. Neurol Sci 2022; 43:6929-6945. [DOI: 10.1007/s10072-022-06424-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2022] [Accepted: 09/21/2022] [Indexed: 11/07/2022]
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di Biase L, Di Santo A, Caminiti ML, Pecoraro PM, Carbone SP, Di Lazzaro V. Dystonia Diagnosis: Clinical Neurophysiology and Genetics. J Clin Med 2022; 11:jcm11144184. [PMID: 35887948 PMCID: PMC9320296 DOI: 10.3390/jcm11144184] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Accepted: 07/16/2022] [Indexed: 12/12/2022] Open
Abstract
Dystonia diagnosis is based on clinical examination performed by a neurologist with expertise in movement disorders. Clues that indicate the diagnosis of a movement disorder such as dystonia are dystonic movements, dystonic postures, and three additional physical signs (mirror dystonia, overflow dystonia, and geste antagonists/sensory tricks). Despite advances in research, there is no diagnostic test with a high level of accuracy for the dystonia diagnosis. Clinical neurophysiology and genetics might support the clinician in the diagnostic process. Neurophysiology played a role in untangling dystonia pathophysiology, demonstrating characteristic reduction in inhibition of central motor circuits and alterations in the somatosensory system. The neurophysiologic measure with the greatest evidence in identifying patients affected by dystonia is the somatosensory temporal discrimination threshold (STDT). Other parameters need further confirmations and more solid evidence to be considered as support for the dystonia diagnosis. Genetic testing should be guided by characteristics such as age at onset, body distribution, associated features, and coexistence of other movement disorders (parkinsonism, myoclonus, and other hyperkinesia). The aim of the present review is to summarize the state of the art regarding dystonia diagnosis focusing on the role of neurophysiology and genetic testing.
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Affiliation(s)
- Lazzaro di Biase
- Neurology Unit, Campus Bio-Medico University Hospital Foundation, Via Álvaro del Portillo 200, 00128 Rome, Italy; (A.D.S.); (M.L.C.); (P.M.P.); (S.P.C.); (V.D.L.)
- Unit of Neurology, Neurophysiology, Neurobiology, Department of Medicine, Campus Bio-Medico University of Rome, Via Álvaro del Portillo 21, 00128 Rome, Italy
- Brain Innovations Lab., Campus Bio-Medico University of Rome, Via Álvaro del Portillo 21, 00128 Rome, Italy
- Correspondence: or ; Tel.: +39-062-2541-1220
| | - Alessandro Di Santo
- Neurology Unit, Campus Bio-Medico University Hospital Foundation, Via Álvaro del Portillo 200, 00128 Rome, Italy; (A.D.S.); (M.L.C.); (P.M.P.); (S.P.C.); (V.D.L.)
- Unit of Neurology, Neurophysiology, Neurobiology, Department of Medicine, Campus Bio-Medico University of Rome, Via Álvaro del Portillo 21, 00128 Rome, Italy
| | - Maria Letizia Caminiti
- Neurology Unit, Campus Bio-Medico University Hospital Foundation, Via Álvaro del Portillo 200, 00128 Rome, Italy; (A.D.S.); (M.L.C.); (P.M.P.); (S.P.C.); (V.D.L.)
- Unit of Neurology, Neurophysiology, Neurobiology, Department of Medicine, Campus Bio-Medico University of Rome, Via Álvaro del Portillo 21, 00128 Rome, Italy
| | - Pasquale Maria Pecoraro
- Neurology Unit, Campus Bio-Medico University Hospital Foundation, Via Álvaro del Portillo 200, 00128 Rome, Italy; (A.D.S.); (M.L.C.); (P.M.P.); (S.P.C.); (V.D.L.)
- Unit of Neurology, Neurophysiology, Neurobiology, Department of Medicine, Campus Bio-Medico University of Rome, Via Álvaro del Portillo 21, 00128 Rome, Italy
| | - Simona Paola Carbone
- Neurology Unit, Campus Bio-Medico University Hospital Foundation, Via Álvaro del Portillo 200, 00128 Rome, Italy; (A.D.S.); (M.L.C.); (P.M.P.); (S.P.C.); (V.D.L.)
- Unit of Neurology, Neurophysiology, Neurobiology, Department of Medicine, Campus Bio-Medico University of Rome, Via Álvaro del Portillo 21, 00128 Rome, Italy
| | - Vincenzo Di Lazzaro
- Neurology Unit, Campus Bio-Medico University Hospital Foundation, Via Álvaro del Portillo 200, 00128 Rome, Italy; (A.D.S.); (M.L.C.); (P.M.P.); (S.P.C.); (V.D.L.)
- Unit of Neurology, Neurophysiology, Neurobiology, Department of Medicine, Campus Bio-Medico University of Rome, Via Álvaro del Portillo 21, 00128 Rome, Italy
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Dystonia: Still a Mysterious Syndrome. LIFE (BASEL, SWITZERLAND) 2022; 12:life12070989. [PMID: 35888079 PMCID: PMC9321350 DOI: 10.3390/life12070989] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Accepted: 06/29/2022] [Indexed: 12/02/2022]
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Pilot Feasibility Study of a Multi-View Vision Based Scoring Method for Cervical Dystonia. SENSORS 2022; 22:s22124642. [PMID: 35746424 PMCID: PMC9230118 DOI: 10.3390/s22124642] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Revised: 06/09/2022] [Accepted: 06/17/2022] [Indexed: 11/19/2022]
Abstract
Abnormal movement of the head and neck is a typical symptom of Cervical Dystonia (CD). Accurate scoring on the severity scale is of great significance for treatment planning. The traditional scoring method is to use a protractor or contact sensors to calculate the angle of the movement, but this method is time-consuming, and it will interfere with the movement of the patient. In the recent outbreak of the coronavirus disease, the need for remote diagnosis and treatment of CD has become extremely urgent for clinical practice. To solve these problems, we propose a multi-view vision based CD severity scale scoring method, which detects the keypoint positions of the patient from the frontal and lateral images, and finally scores the severity scale by calculating head and neck motion angles. We compared the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) subscale scores calculated by our vision based method with the scores calculated by a neurologist trained in dyskinesia. An analysis of the correlation coefficient was then conducted. Intra-class correlation (ICC)(3,1) was used to measure absolute accuracy. Our multi-view vision based CD severity scale scoring method demonstrated sufficient validity and reliability. This low-cost and contactless method provides a new potential tool for remote diagnosis and treatment of CD.
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Yoshida K. Botulinum Toxin Therapy for Oromandibular Dystonia and Other Movement Disorders in the Stomatognathic System. Toxins (Basel) 2022; 14:282. [PMID: 35448891 PMCID: PMC9026473 DOI: 10.3390/toxins14040282] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Revised: 04/01/2022] [Accepted: 04/11/2022] [Indexed: 01/02/2023] Open
Abstract
Various movement disorders, such as oromandibular dystonia, oral dyskinesia, bruxism, functional (psychogenic) movement disorder, and tremors, exist in the stomatognathic system. Most patients experiencing involuntary movements due to these disorders visit dentists or oral surgeons, who may be the first healthcare providers. However, differential diagnoses require neurological and dental knowledge. This study aimed to review scientific advances in botulinum toxin therapy for these conditions. The results indicated that botulinum toxin injection is effective and safe, with few side effects in most cases when properly administered by an experienced clinician. The diagnosis and treatment of movement disorders in the stomatognathic system require both neurological and dental or oral surgical knowledge and skills, and well-designed multicenter trials with a multidisciplinary team approach must be necessary to ensure accurate diagnosis and proper treatment.
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Affiliation(s)
- Kazuya Yoshida
- Department of Oral and Maxillofacial Surgery, National Hospital Organization, Kyoto Medical Center, 1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto 612-8555, Japan
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38
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Dec-Ćwiek M, Porębska K, Sawczyńska K, Kubala M, Witkowska M, Zmijewska K, Antczak J, Pera J. KinesioTaping after botulinum toxin type A for cervical dystonia in adult patients. Brain Behav 2022; 12:e2541. [PMID: 35238494 PMCID: PMC9014990 DOI: 10.1002/brb3.2541] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2021] [Revised: 01/08/2022] [Accepted: 02/13/2022] [Indexed: 11/30/2022] Open
Abstract
INTRODUCTION Studies explored physiotherapeutic approaches in cervical dystonia (CD) patients with or without botulinum toxin (BoNT) injections, however the results are varying. There are no clinical trials investigating the effects of kinesiology taping in CD patients. The objective of this study is to investigate the efficacy of kinesiology taping as an adjunct to the BoNT injections in patients with CD. METHODS Twenty-five patients were enrolled to the study. Patients were randomly assigned to the experimental 1 (BoNT + KinesioTaping), experimental 2 (BoNT + ShamTaping) or control (BoNT) treatment. After 12 weeks they were moved to the next experimental group and finally every patient received all 3 proposed treatment options. The severity of CD was quantified with the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) including Torticollis severity, Disability, and Pain scales. Quality of life was evaluated using Craniocervical dystonia questionnaire (CDQ4). RESULTS In all treatment groups, there was a significant improvement in dystonia symptoms measured with TWSTRS (total score) after BoNT injection regardless of the allocation to the experimental treatment (p < .05). ANOVA analysis revealed no differences in any of the TWSTRS variables after the intervention. Quality of life was significantly improved after application of taping (p < .05, p = .03). CONCLUSIONS Application of KinesioTaping after BoNT injection provided no additional effect on the severity of dystonia, although the quality of life was improved in patients with CD. Further research investigating the effect of KinesioTaping prior to BoNT injection is required.
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Affiliation(s)
- Małgorzata Dec-Ćwiek
- Department of Neurology, Medical College, Jagiellonian University, Krakow, Poland
| | - Karolina Porębska
- Department of Neurology, Medical College, Jagiellonian University, Krakow, Poland
| | - Katarzyna Sawczyńska
- Department of Neurology, Medical College, Jagiellonian University, Krakow, Poland
| | - Marcin Kubala
- Faculty of Medicine and Health Sciences, Andrzej Frycz Modrzewski Krakow University, Krakow, Poland
| | - Magdalena Witkowska
- Department of Neurology, Medical College, Jagiellonian University, Krakow, Poland
| | - Kinga Zmijewska
- Faculty of Medicine and Health Sciences, Andrzej Frycz Modrzewski Krakow University, Krakow, Poland.,Department of Orthopedics and Physiotherapy, Medical College, Jagiellonian University, Krakow, Poland
| | - Jakub Antczak
- Department of Neurology, Medical College, Jagiellonian University, Krakow, Poland
| | - Joanna Pera
- Department of Neurology, Medical College, Jagiellonian University, Krakow, Poland
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Abstract
Smoothness (i.e. non-intermittency) of movement is a clinically important property of the voluntary movement with accuracy and proper speed. Resting head position and head voluntary movements are impaired in cervical dystonia. The current work aims to evaluate if the smoothness of voluntary head rotations is reduced in this disease. Twenty-six cervical dystonia patients and 26 controls completed rightward and leftward head rotations. Patients’ movements were differentiated into “towards-dystonia” (rotation accentuated the torticollis) and “away-dystonia”. Smoothness was quantified by the angular jerk and arc length of the spectrum of angular speed (i.e. SPARC, arbitrary units). Movement amplitude (mean, 95% CI) on the horizontal plane was larger in controls (63.8°, 58.3°–69.2°) than patients when moving towards-dystonia (52.8°, 46.3°–59.4°; P = 0.006). Controls’ movements (49.4°/s, 41.9–56.9°/s) were faster than movements towards-dystonia (31.6°/s, 25.2–37.9°/s; P < 0.001) and away-dystonia (29.2°/s, 22.9–35.5°/s; P < 0.001). After taking into account the different amplitude and speed, SPARC-derived (but not jerk-derived) indices showed reduced smoothness in patients rotating away-dystonia (1.48, 1.35–1.61) compared to controls (1.88, 1.72–2.03; P < 0.001). Poor smoothness is a motor disturbance independent of movement amplitude and speed in cervical dystonia. Therefore, it should be assessed when evaluating this disease, its progression, and treatments.
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Benson M, Albanese A, Bhatia KP, Cavillon P, Cuffe L, König K, Reinhard C, Graessner H. Development of a patient journey map for people living with cervical dystonia. Orphanet J Rare Dis 2022; 17:130. [PMID: 35313909 PMCID: PMC8935780 DOI: 10.1186/s13023-022-02270-4] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Accepted: 02/20/2022] [Indexed: 01/18/2023] Open
Abstract
Background Patient journey maps are increasingly used as a tool that enables healthcare providers to refine their service provision to best meet patient needs. We developed a cervical dystonia patient journey map (CDPJM) that describes the holistic patient experience from pre-diagnosis through to long-term treatment. Methods The CDPJM was developed in 2 stages; a patient survey (open questions and multichoice) of 15 patients with CD was conducted to inform the design of the CDPJM, which was then refined and validated by an expert-patient focus group. Results Qualitative analysis of the patient survey supported five key stages of the patient journey: symptom onset, diagnosis and therapeutic relationship with healthcare professionals, initiation of care for CD, start of CD treatment, and living with treated CD. Following symptom onset, survey respondents described having multiple visits to their family doctor who prescribed strong pain killers and muscle relaxants and referred their patient to up to 10 different specialists for diagnosis. Over half (53.3%) of respondents had received ≥ 1 misdiagnosis. Respondents reported relief at having a diagnosis but a lack of understanding of the prognosis and treatment options; 46.7% said their neurologist did not spend enough time addressing their concerns. Survey respondents reported using a variety of alternative sources of information, including the internet (86.7%), self-help groups (66.7%) and information leaflets provided by health care professionals (60.0%). While botulinum toxin (BoNT) was consistently discussed as the main treatment option, some neurologists also mentioned physiotherapy, counselling, and other complementary approaches. However, patients were often left to seek complementary services themselves. Patients reported a ‘rollercoaster’ of relief with BoNT treatment with symptoms (and subsequent impact on daily life) returning towards the end of an injection cycle. “When BoNT works well I can return to an almost normal life … when the injections stop working so well, I have to rest more and avoid going to work and experience life restrictions.” Conclusions We present the first patient journey map for CD that can be used to guide local service mapping and to compare current provision with what patients say they want and need. Supplementary Information The online version contains supplementary material available at 10.1186/s13023-022-02270-4.
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Wang C, Zhu X, Xia L, Xie P, Tian X, Shang J, Han Q. Botulinum toxin A improves psychological distress in patients with hemifacial spasm. Acta Neurol Belg 2022; 122:43-49. [PMID: 33515182 DOI: 10.1007/s13760-021-01601-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Accepted: 01/12/2021] [Indexed: 11/28/2022]
Abstract
OBJECTIVE This study aimed at assessing mental health in patients with hemifacial spasm (HFS) and determined the effect of botulinum toxin type A (BTX-A) on psychological distress in patients with HFS. METHODS Ninety-five HFS patients and 95 age- and sex-matched healthy controls were enrolled. Symptom checklist-90 (SCL-90) scores were used to measure psychological distress in HFS patients and healthy controls. The mental health status of HFS patients was also evaluated by SCL-90, before and after the injection of BTX-A. Moreover, for those patients with abnormal mental health, efficacy outcomes after treatment with BTX-A were compared with a propensity score-matched historical cohort without BTX-A treatment. RESULTS The mean scores for interpersonal sensitivity, phobia, anxiety, depression, and somatization were significantly higher among HFS patients than healthy people (P < 0.05). There was no significant difference between female patients and male patients in HFS group (P > 0.05). There were significant improvements in somatization, interpersonal sensitivity, depression, anxiety, and phobia scores before and after treatment (P < 0.05). At 2 months, more patients experienced an improvement in psychological distress in the BTX-A group (61.29% versus 38.71%; P = 0.03). CONCLUSION Patients with HFS are often accompanied by somatization, interpersonal sensitivity, depression, anxiety, and phobia. Our findings suggest that BTX-A can improve these symptoms. However, further well-designed prospective studies are warranted to validate our findings.
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Affiliation(s)
- Chengyun Wang
- Department of Neurology, Huai'an First People's Hospital, The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, No. 1 Huanghe West Road, Huai'an, 223000, Jiangsu, China
| | - Xiangyu Zhu
- ICU, The Second People's Hospital of Huai'an, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, 223000, Jiangsu, China
| | - Lei Xia
- Department of Neurology, Huai'an First People's Hospital, The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, No. 1 Huanghe West Road, Huai'an, 223000, Jiangsu, China
| | - Peng Xie
- Department of Neurosurgery, The Second People's Hospital of Huai'an, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, 223000, Jiangsu, China
| | - Xiangyang Tian
- Department of Neurology, Huai'an First People's Hospital, The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, No. 1 Huanghe West Road, Huai'an, 223000, Jiangsu, China
| | - Jin Shang
- Department of Neurology, Huai'an First People's Hospital, The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, No. 1 Huanghe West Road, Huai'an, 223000, Jiangsu, China.
| | - Qiu Han
- Department of Neurology, Huai'an First People's Hospital, The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, No. 1 Huanghe West Road, Huai'an, 223000, Jiangsu, China.
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Classification of Dystonia. Life (Basel) 2022; 12:life12020206. [PMID: 35207493 PMCID: PMC8875209 DOI: 10.3390/life12020206] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Revised: 01/15/2022] [Accepted: 01/24/2022] [Indexed: 12/23/2022] Open
Abstract
Dystonia is a hyperkinetic movement disorder characterized by abnormal movement or posture caused by excessive muscle contraction. Because of its wide clinical spectrum, dystonia is often underdiagnosed or misdiagnosed. In clinical practice, dystonia could often present in association with other movement disorders. An accurate physical examination is essential to describe the correct phenomenology. To help clinicians reaching the proper diagnosis, several classifications of dystonia have been proposed. The current classification consists of axis I, clinical characteristics, and axis II, etiology. Through the application of this classification system, movement disorder specialists could attempt to correctly characterize dystonia and guide patients to the most effective treatment. The aim of this article is to describe the phenomenological spectrum of dystonia, the last approved dystonia classification, and new emerging knowledge.
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Chueluecha C, Moore AP. LIVECHART
Patient‐Reported Outcome Tool for Botulinum Toxin Treatment in Cervical Dystonia. Mov Disord Clin Pract 2022; 9:198-205. [PMID: 35141354 PMCID: PMC8810418 DOI: 10.1002/mdc3.13401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Revised: 11/29/2021] [Accepted: 12/13/2021] [Indexed: 11/07/2022] Open
Affiliation(s)
- Chuenchom Chueluecha
- Department of Rehabilitation Medicine, Faculty of Medicine Thammasat University Bangkok Thailand
| | - Austen Peter Moore
- Department of Neurology The Walton Centre NHS Foundation Trust Liverpool United Kingdom
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Khatkova S, Orlova O, Pokhabov D, Diagileva V, Novikov S, Pogoreltseva O, Shevchenko V, Nikolaev E. Safety and efficacy of the Relatox in the treatment of patients with cervical dystonia (results of a multicenter simple blind comparative randomized study). Zh Nevrol Psikhiatr Im S S Korsakova 2022; 122:80-85. [DOI: 10.17116/jnevro202212211180] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Weissbach A, Pauly MG, Herzog R, Hahn L, Halmans S, Hamami F, Bolte C, Camargos S, Jeon B, Kurian MA, Opladen T, Brüggemann N, Huppertz HJ, König IR, Klein C, Lohmann K. Relationship of Genotype, Phenotype, and Treatment in Dopa-Responsive Dystonia: MDSGene Review. Mov Disord 2021; 37:237-252. [PMID: 34908184 DOI: 10.1002/mds.28874] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 10/26/2021] [Accepted: 11/08/2021] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Pathogenic variants in 5 genes (GCH1, TH, PTS, SPR, and QDPR), involved in dopamine/tetrahydrobiopterin biosynthesis or recycling, have been linked to Dopa-responsive dystonia (DRD). Diagnosis and treatment are often delayed due to high between- and within-group variability. OBJECTIVES Comprehensively analyzed individual genotype, phenotype, treatment response, and biochemistry information. METHODS 734 DRD patients and 151 asymptomatic GCH1 mutation carriers were included using an MDSGene systematic literature review and an automated classification approach to distinguish between different forms of monogenic DRDs. RESULTS Whereas dystonia, L-Dopa responsiveness, early age at onset, and diurnal fluctuations were identified as red flags, parkinsonism without dystonia was rarely reported (11%) and combined with dystonia in only 18% of patients. While sex was equally distributed in autosomal recessive DRD, there was female predominance in autosomal dominant DYT/PARK-GCH1 patients accompanied by a lower median age at onset and more dystonia in females compared to males. Accordingly, the majority of asymptomatic heterozygous GCH1 mutation carriers (>8 years of age) were males. Multiple other subgroup-specific characteristics were identified, showing high accuracy in the automated classification approach: Seizures and microcephaly were mostly seen in DYT/PARK-PTS, autonomic symptoms appeared commonly in DYT/PARK-TH and DYT/PARK-PTS, and sleep disorders and oculogyric crises in DYT/PARK-SPR. Biochemically, homovanillic acid and 5-hydroxyindoleacetic acid in CSF were reduced in most DRDs, but neopterin and biopterin were increased only in DYT/PARK-PTS and DYT/PARK-SPR. Hyperphenylalaninemia was seen in DYT/PARK-PTS, DYT/PARK-QDPR, and rarely reported in autosomal recessive DYT/PARK-GCH1. CONCLUSIONS Our indicators will help to specify diagnosis and accelerate start of treatment. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Affiliation(s)
- Anne Weissbach
- Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.,Institute of Systems Motor Science, University of Lübeck, Lübeck, Germany
| | - Martje G Pauly
- Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.,Institute of Systems Motor Science, University of Lübeck, Lübeck, Germany.,Department of Neurology, University Hospital Schleswig Holstein, Lübeck, Germany
| | - Rebecca Herzog
- Institute of Systems Motor Science, University of Lübeck, Lübeck, Germany.,Department of Neurology, University Hospital Schleswig Holstein, Lübeck, Germany
| | - Lisa Hahn
- Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.,Institute of Systems Motor Science, University of Lübeck, Lübeck, Germany
| | - Sara Halmans
- Institute of Systems Motor Science, University of Lübeck, Lübeck, Germany
| | - Feline Hamami
- Institute of Systems Motor Science, University of Lübeck, Lübeck, Germany
| | - Christina Bolte
- Institute of Systems Motor Science, University of Lübeck, Lübeck, Germany
| | - Sarah Camargos
- Department of Internal Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Beomseok Jeon
- Department of Neurology, Seoul National University College of Medicine, Seoul, South Korea
| | - Manju A Kurian
- Developmental Neurosciences, UCL Great Ormond Street Institute of Child Health, London, United Kingdom
| | - Thomas Opladen
- Division of Child Neurology and Metabolic Disorders, University Children's Hospital, Heidelberg, Germany
| | - Norbert Brüggemann
- Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.,Department of Neurology, University Hospital Schleswig Holstein, Lübeck, Germany
| | | | - Inke R König
- Institute of Medical Biometry and Statistics, University of Lübeck, Lübeck, Germany
| | - Christine Klein
- Institute of Neurogenetics, University of Lübeck, Lübeck, Germany
| | - Katja Lohmann
- Institute of Neurogenetics, University of Lübeck, Lübeck, Germany
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Kaji R, Endo A, Sugawara M, Ishii M. Efficacy of botulinum toxin type B (rimabotulinumtoxinB) in patients with cervical dystonia previously treated with botulinum toxin type A: A post-marketing observational study in Japan. eNeurologicalSci 2021; 25:100374. [PMID: 34877415 PMCID: PMC8627969 DOI: 10.1016/j.ensci.2021.100374] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Revised: 09/26/2021] [Accepted: 10/24/2021] [Indexed: 11/17/2022] Open
Abstract
To date, efficacy data on botulinum toxin type B (rimabotulinumtoxinB) in patients with cervical dystonia (CD) previously treated with botulinum toxin type A in a large population are lacking; thus, we aimed to evaluate type B efficacy in this patient population. In a post-marketing observational cohort study, 150 patients previously treated with botulinum toxin type A were enrolled, of whom 138 were followed up for 1 year after the initial type B injection. Final observation data were available for 122 patients. Efficacy was evaluated using the Toronto Western Spasmodic Torticollis Rating Scale. Total score improved from 39.9 at baseline to 34.3 at 4 weeks after the first injection, and pain score improved from 8.9 to 7.9. Improvements were maintained through six further injections in two subpopulations: patients who showed resistance to botulinum toxin type A and patients who were not type A resistant but switched to type B. For a number of patients, even low doses (<5000 units) of botulinum toxin type B demonstrated efficacy. These findings support the efficacy of botulinum toxin type B in clinical settings for the management of CD symptoms, including pain, even at low doses, regardless of the patient's botulinum toxin type A resistance status.
Botulinum toxin type B improved cervical dystonia symptoms and pain after 4 weeks. Botulinum toxin type B was effective even at low doses (<5000 units). The efficacy of toxin type B is not affected by toxin type A resistance status.
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Affiliation(s)
- Ryuji Kaji
- National Hospital Organization Utano National Hospital, 8 Narutaki Ondoyama-cho, Ukyo-ku, Kyoto, Japan.,Institute of Health Biosciences, Tokushima University Graduate School, 3-18-15 Kuramotocho, Tokushima, Japan
| | - Akira Endo
- Clinical Planning and Development, Medical HQs, Eisai Co., Ltd., 4-6-10 Koishikawa, Bunkyo-ku, Tokyo, Japan
| | - Michiko Sugawara
- Scientific Intelligence Group, Medical HQs, Eisai Co., Ltd., 4-6-10 Koishikawa, Bunkyo-ku, Tokyo, Japan
| | - Mika Ishii
- Clinical Planning and Development, Medical HQs, Eisai Co., Ltd., 4-6-10 Koishikawa, Bunkyo-ku, Tokyo, Japan
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Werner C, Loudovici-Krug D, Derlien S, Rakers F, Smolenski UC, Lehmann T, Best N, Günther A. Study protocol: multimodal physiotherapy as an add-on treatment to botulinum neurotoxin type A therapy for patients with cervical dystonia: DysPT-multi-a prospective, multicentre, single-blind, randomized, controlled study. Trials 2021; 22:740. [PMID: 34696821 PMCID: PMC8547107 DOI: 10.1186/s13063-021-05705-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Accepted: 10/08/2021] [Indexed: 11/14/2022] Open
Abstract
Background Botulinum neurotoxin (BoNT) is currently the best therapeutic option in the treatment for cervical dystonia (CD). Additional treatments like physiotherapy (PT) may even improve the results of the BoNT injection with type A (BoNT-A), but there are no definite recommendations. In the last few years, some studies showed tendencies for PT as an adjuvant therapy to benefit. However, high-quality studies are required. Methods This study is a multicentre, randomized, single-blind, controlled trial to demonstrate the effectiveness of a multimodal PT program compared to a nonspecific cupping therapy, additionally to the BoNT-A therapy. Two hundred participants will be assigned into the multimodal PT plus BoNT intervention arm or the BoNT plus cupping arm using randomization. Primary endpoint is the total Score of Toronto Western Spasmodic Rating Scale (TWSTRS). Secondary endpoints are the mobility of the cervical spine (range of motion, ROM), the TWSTRS subscales, and the quality of life (measured by questionnaires: CDQ-24 and SF-36). Patients will be single-blind assessed every 3 months according to their BoNT injection treatment over a period of 9 months. Discussion The study aims to determine the effectiveness and therefore potential benefit of an additional multimodal physiotherapy for standardized treatment with BoNT-A in patients with CD, towards the BoNT-therapy alone. This largest randomized controlled trial in this field to date is intended to generate missing evidence for therapy guidelines. Trial registration The study was registered in the German Clinical Study Register before the start of the patient recruitment (DRKS00020411; date: 21.01.2020).
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Affiliation(s)
- Christian Werner
- Department of Neurology, St. Georg Klinikum Eisenach, Eisenach, Germany
| | | | - Steffen Derlien
- Institute for Physiotherapy, Jena University Hospital, Jena, Germany
| | - Florian Rakers
- Hans-Berger-Department of Neurology, Jena University Hospital, Jena, Germany
| | | | - Thomas Lehmann
- Institute of Medical Statistics, Jena University Hospital, Jena, Germany
| | - Norman Best
- Institute for Physiotherapy, Jena University Hospital, Jena, Germany
| | - Albrecht Günther
- Hans-Berger-Department of Neurology, Jena University Hospital, Jena, Germany
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Rosales RL, Cuffe L, Regnault B, Trosch RM. Pain in cervical dystonia: mechanisms, assessment and treatment. Expert Rev Neurother 2021; 21:1125-1134. [PMID: 34569398 DOI: 10.1080/14737175.2021.1984230] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
INTRODUCTION In patients with cervical dystonia (CD), pain is a major contributor to disability and social isolation and is often the main reason patients seek treatment. Surveys evaluating patient perceptions of their CD symptoms consistently highlight pain as a troublesome and disabling feature of their condition with significant impact on daily life and work. AREAS COVERED In this article, the authors review the epidemiology, assessment, possible mechanisms and treatment of pain in CD, including a meta-analysis of randomized controlled trial data with abobotulinumtoxinA. EXPERT OPINION Mechanisms of pain in CD may be muscle-based and non-muscle based. Accumulating evidence suggests that non-muscle-based mechanisms (such as abnormal transmission and processing of nociceptive stimuli, dysfunction of descending pain inhibitory pathways as well as structural and network changes in the basal ganglia, cortex and other areas) may also contribute to pain in CD alongside prolonged muscle contraction. Chemodenervation with botulinum toxin is considered the first-line treatment for CD. Treatment with botulinum toxin is usually effective, but optimization of the injection parameters should include consideration of pain as a core symptom in addition to the motor problems.
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Affiliation(s)
- Raymond L Rosales
- Dept. of Neurology and Psychiatry, the Neuroscience Institute, University of Santo Tomas Hospital, Manila, Philippines.,The Institute for Neurosciences, St. Luke's Medical Center, Quezon City, Philippines
| | | | | | - Richard M Trosch
- The Parkinson's and Movement Disorders Center, Farmington Hills, MI, USA
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Gupta N, Pandey S. Treatment of focal hand dystonia: current status. Neurol Sci 2021; 42:3561-3584. [PMID: 34213695 DOI: 10.1007/s10072-021-05432-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Accepted: 06/23/2021] [Indexed: 10/21/2022]
Abstract
BACKGROUND Focal hand dystonia (FHD) is usually adult-onset focal dystonia that can be associated with marked occupational and functional disability leading to reduced quality of life. METHODS Relevant studies on treatment options for FHD, their limitations, and current recommendations were reviewed using the PubMed search until March 31, 2021. Besides, the reference lists of the retrieved publications were manually searched to explore other relevant studies. RESULTS and conclusion Currently, botulinum toxin has the best evidence for treatment of FHD, and 20-90% of patients experience symptomatic improvement. However, its benefit is often limited by the reduction of muscle tonus acting on the muscle spindle. Different surgical modalities that have been used to treat focal hand dystonia include lesional surgery, deep brain stimulation, and magnetic resonance-guided focused ultrasound thalamotomy. Recent studies exploring the role of behavioral techniques, sensorimotor training, and neuromodulation for the treatment of focal hand dystonia have reported good outcomes, but larger studies are required before implementing these interventions in practice.
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Affiliation(s)
- Navnika Gupta
- University of Nebraska Medical Center, Omaha, NE, USA
| | - Sanjay Pandey
- Department of Neurology, Govind Ballabh Pant Postgraduate Institute of Medical Education and Research, New Delhi, 110002, India.
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Kamel WA, Majumdar P, Matis G, Fenoy AJ, Balakrishnan S, Zirh AT, Cevik A, Tomar AK, Ouerchefani N. Surgical Management for Dystonia: Efficacy of Deep Brain Stimulation in the Long Term. Neurol Int 2021; 13:371-386. [PMID: 34449699 PMCID: PMC8395937 DOI: 10.3390/neurolint13030037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Revised: 07/22/2021] [Accepted: 07/25/2021] [Indexed: 11/16/2022] Open
Abstract
Introduction: Dystonia is a movement disorder substantially affecting the quality of life. Botulinum Neurotoxin (BoNT) is used intramuscularly as a treatment for dystonia; however, not all dystonia patients respond to this treatment. Deep brain stimulation (DBS) is an established treatment for Parkinson’s disease (PD) and essential tremor, but it can help in dystonia as well. Objectives: We studied a total of 67 dystonia patients who were treated with DBS over a period of 7 years to find out the long-term efficacy of DBS in those patients. First, we calculated patient improvement in post-surgery follow-up programs using the Global Dystonia Severity scale (GDS) and Burke–Fahn–Marsden dystonia rating scale (BFMDRS). Secondly, we analyzed the scales scores to see if there was any statistical significance. Methods: In our study we analyzed patients with ages from 38 to 78 years with dystonia who underwent DBS surgery between January 2014 and December 2020 in four different centers (India, Kuwait, Egypt, and Turkey). The motor response to DBS surgery was retrospectively measured for each patient during every follow-up visit using the GDS and the BFMDRS scales. Results: Five to 7 years post-DBS, the mean reduction in the GDS score was 30 ± 1.0 and for the BFMDRS score 26 ± 1.0. The longitudinal change in scores at 12 and 24 months post-op was also significant with mean reductions in GDS and BFMDRS scores of 68 ± 1.0 and 56 ± 1.0, respectively. The p-values were <0.05 for our post-DBS dystonia patients. Conclusions: This study illustrates DBS is an established, effective treatment option for patients with different dystonias, such as generalized, cervical, and various brain pathology-induced dystonias. Although symptoms are not completely eliminated, continuous improvements are noticed throughout the post-stimulation time frame.
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Affiliation(s)
- Walaa A. Kamel
- Neurology Department, Faculty of Medicine, Beni-Suef University, Beni-Suef 62511, Egypt;
- Neurology Department, Ibn-Sina Hospital, Kuwait City 25427, Kuwait
| | - Pritam Majumdar
- Department of Stereotactic and Functional Neurosurgery, University Cologne Hospital, 50931 Cologne, Germany;
- Correspondence:
| | - Georgios Matis
- Department of Stereotactic and Functional Neurosurgery, University Cologne Hospital, 50931 Cologne, Germany;
| | - Albert J. Fenoy
- Department of Neurosurgery, McGovern Medical School, The University of Texas at Houston, UTHealth Neurosciences, Houston, TX 77030, USA;
| | - Shankar Balakrishnan
- Department of Neurology and Neuromodulation, MIOT International Hospital, Hennai 600089, India;
| | - Ali T. Zirh
- Department of Neurosurgery, Istanbul Medipol University, Istanbul 34810, Turkey;
| | - Aslihan Cevik
- Department of Neurosurgery, Istanbul Aydin University, Istanbul Medical Park Florya, Istanbul 34295, Turkey;
| | - Amit Kumar Tomar
- Department of Anesthesia and Neurosurgery, Indo-Gulf Hospital, Noida 201301, India;
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