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Eapen BC, Tran J, Ballard-Hernandez J, Buelt A, Hoppes CW, Matthews C, Pundik S, Reston J, Tchopev Z, Wayman LM, Koehn T. Stroke Rehabilitation: Synopsis of the 2024 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guidelines. Ann Intern Med 2025; 178:249-268. [PMID: 39832369 DOI: 10.7326/annals-24-02205] [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] [Indexed: 01/22/2025] Open
Abstract
DESCRIPTION In July 2024, the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DOD) released a joint update of their 2019 clinical practice guideline (CPG) for the management of stroke rehabilitation. This synopsis is a condensed version of the 2024 CPG, highlighting the key aspects of the guideline development process and describing the major recommendations. METHODS The VA/DOD Evidence-Based Practice Work Group convened a joint VA/DOD guideline development work group (WG) that included clinical stakeholders and conformed to the Institute of Medicine's tenets for trustworthy CPGs. The guideline WG conducted a patient focus group, developed key questions, and systematically searched and evaluated the literature (English-language publications from 1 July 2018 to 2 May 2023). The GRADE (Grading of Recommendations Assessment, Development and Evaluation) system was used to evaluate the evidence. The WG developed 47 recommendations along with algorithms for stroke rehabilitation in the inpatient and outpatient settings. Stakeholders outside the WG reviewed the CPG before approval by the VA/DOD Evidence-Based Practice Work Group. RECOMMENDATIONS This synopsis summarizes where evidence is strongest to support guidelines in crucial areas relevant to primary care physicians: transition to community (case management, psychosocial or behavioral interventions); motor therapy (task-specific practice, mirror therapy, rhythmic auditory stimulation, electrical stimulation, botulinum toxin for spasticity); dysphagia, aphasia, and cognition (chin tuck against resistance, respiratory muscle strength training); and mental health (selective serotonin reuptake inhibitor use, psychotherapy, mindfulness-based therapies for treatment but not prevention of depression).
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Affiliation(s)
- Blessen C Eapen
- Physical Medicine and Rehabilitation Services, Veterans Affairs Greater Los Angeles Health Care, and Division of Physical Medicine and Rehabilitation, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California (B.C.E.)
| | - Johanna Tran
- Comprehensive Integrated Inpatient Rehabilitation Program, James A. Haley Veterans' Hospital, Tampa, Florida (J.T.)
| | - Jennifer Ballard-Hernandez
- Evidence-Based Practice, Office of Quality and Patient Safety, Veterans Affairs Central Office, Washington, DC (J.B.-H., L.M.W.)
| | - Andrew Buelt
- Bay Pines Veterans Affairs Healthcare System, Bay Pines, Florida (A.B.)
| | - Carrie W Hoppes
- Army-Baylor University Doctoral Program in Physical Therapy, San Antonio, Texas (C.W.H.)
| | - Christine Matthews
- Audiology and Speech Pathology, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania (C.M.)
| | - Svetlana Pundik
- Case Western Reserve University School of Medicine and Veterans Affairs Northeast Ohio Healthcare System, Cleveland, Ohio (S.P.)
| | | | - Zahari Tchopev
- 59th Medical Wing, U.S. Air Force, Wilford Hall Ambulatory Surgical Center, San Antonio, Texas (Z.T.)
| | - Lisa M Wayman
- Evidence-Based Practice, Office of Quality and Patient Safety, Veterans Affairs Central Office, Washington, DC (J.B.-H., L.M.W.)
| | - Tyler Koehn
- 959 Medical Operations Squadron, U.S. Air Force, Department of Neurology, Brooke Army Medical Center, San Antonio, Texas (T.K.)
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Yi KH, Hu H, Hwang SO, Ahn H, Lee JH, Lee HJ. Intramuscular neural distribution of the vastus medialis for botulinum neurotoxin injection: application to spasticity. Surg Radiol Anat 2024; 46:2067-2073. [PMID: 39400571 DOI: 10.1007/s00276-024-03482-y] [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: 04/20/2024] [Accepted: 09/06/2024] [Indexed: 10/15/2024]
Abstract
PURPOSE A comprehensive understanding of neural distribution within the vastus medialis is crucial for the effective administration of botulinum neurotoxin injections to manage spasticity. The aim of this study was to develop an anatomically informed approach to guide the administration of botulinum neurotoxin injections into the vastus medialis muscle. METHODS Using a modified Sihler's method, we examined the vastus medialis muscles (20 specimens) to delineate the distribution of nerves relative to a transverse line extending from the anterior superior iliac spine to the base of patella. The vastus medialis muscle was divided into 10 areas from top to bottom. Then, using two fresh cadavers, ultrasonography-guided injections were performed based on the distribution of nerves within the vastus medialis. Each specimen was subsequently dissected to verify if the dye was accurately directed to the most densely innervated regions of the vastus medialis and to assess the precision of the injections. RESULTS The intramuscular nerve distribution within the vastus medialis muscle showed distinct patterns, particularly in areas between 6 and 9. Four injections were successfully administered on each side, targeting the regions between 6 and 9 of the vastus medialis. Upon dissection of the cadavers, the dye was found to be distributed along the muscle fiber. CONCLUSION We recommend targeting botulinum neurotoxin injections toward regions displaying a prominent nerve distribution, specifically focusing on areas between 6 and 9. By adhering to these guidelines, clinicians can minimize doses and mitigate potential adverse effects, such as gait disturbances, antibody development, and bruising, resulting from multiple injections. Furthermore, these findings can be incorporated into electromyography practices.
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Affiliation(s)
- Kyu-Ho Yi
- Division in Anatomy and Developmental Biology, Department of Oral Biology, BK21 PLUS Project, Human Identification Research Institute, Yonsei University College of Dentistry, 50-1 Yonsei-ro, Seoul, 03722, Republic of Korea
- Maylin Clinic (Apgujeong), Seoul, Republic of Korea
| | - Hyewon Hu
- Division in Anatomy and Developmental Biology, Department of Oral Biology, BK21 PLUS Project, Human Identification Research Institute, Yonsei University College of Dentistry, 50-1 Yonsei-ro, Seoul, 03722, Republic of Korea
| | - Sung-Oh Hwang
- Thank You Plastic Surgery Clinic, Seoul, Republic of Korea
| | - Haeryun Ahn
- Division in Anatomy and Developmental Biology, Department of Oral Biology, BK21 PLUS Project, Human Identification Research Institute, Yonsei University College of Dentistry, 50-1 Yonsei-ro, Seoul, 03722, Republic of Korea
| | - Ji-Hyun Lee
- Department of Anatomy and Acupoint, College of Korean Medicine, Gachon University, Seongnam, 13120, Korea.
| | - Hyung-Jin Lee
- Department of Anatomy, School of Medicine, CHA University, 120, Haeryong-ro, Pocheon-si, Gyeonggi-do, 11160, Republic of Korea.
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Bavikatte G, Francisco GE, Jost WH, Baricich A, Duarte E, Tang SFT, Schwartz M, Nelson M, Musacchio T, Esquenazi A. Pain, disability, and quality of life in participants after concurrent onabotulinumtoxinA treatment of upper and lower limb spasticity: Observational results from the ASPIRE study. PM R 2024; 16:1175-1189. [PMID: 38813838 DOI: 10.1002/pmrj.13195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Revised: 02/23/2024] [Accepted: 03/25/2024] [Indexed: 05/31/2024]
Abstract
INTRODUCTION Upper and lower limb spasticity is commonly associated with central nervous system disorders including stroke, traumatic brain injury, multiple sclerosis, cerebral palsy, and spinal cord injury, but little is known about the concurrent treatment of upper and lower limb spasticity with botulinum toxins. OBJECTIVE To evaluate onabotulinumtoxinA (onabotA) utilization and to determine if concurrent onabotA treatment of the upper and lower limbs has supported improvements in participants with spasticity. DESIGN Sub-analysis of a 2-year, international, prospective, observational registry (ASPIRE, NCT01930786). SETTING International clinic sites (54). PARTICIPANTS Adult spasticity participants across etiologies, who received ≥1 concurrent onabotA treatment of the upper and lower limbs during the study. INTERVENTION Participants were treated with onabotA at the clinician's discretion. OUTCOMES Baseline characteristics and outcomes of disability (Disability Assessment Scale [DAS]), pain (Numeric Pain Rating Scale [NPRS]), participant satisfaction, physician satisfaction, and quality of life (QoL; Spasticity Impact Assessment [SIA]) were evaluated. Adverse events were monitored throughout the study. RESULTS Of 744 participants enrolled, 730 received ≥1 dose of onabotA; 275 participants received treatment with onabotA in both upper and lower limbs during ≥1 session; 39.3% of participants were naïve to onabotA for spasticity. The mean (SD) total dose per treatment session ranged from 421.2 (195.3) to 499.6 (188.6) U. The most common baseline upper limb presentation was clenched fist (n = 194, 70.5%); lower limb was equinovarus foot (n = 219, 66.9%). High physician and participant satisfaction and improvements in pain, disability and QoL were reported after most treatments. Nine participants (3.3%) reported nine treatment-related adverse events; two participants (0.7%) reported three serious treatment-related severe adverse events. No new safety signals were identified. CONCLUSION More than a third of enrolled participants received at least one concurrent onabotA treatment of the upper and lower limbs, with reduced pain, disability, and improved QoL after treatment, consistent with the established safety profile of onabotA for the treatment of spasticity.
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Affiliation(s)
| | - Gerard E Francisco
- UT Health Science Center McGovern Medical School and TIRR Memorial Hermann, Houston, Texas, USA
| | - Wolfgang H Jost
- Department of Neurology, University of Freiburg, Freiburg im Breisgau, Germany
| | | | | | - Simon F T Tang
- Chang Gung Memorial Hospital, Taoyuan City, Taiwan
- Lotung Poh Ai Hospital, Luodong, Taiwan
| | | | | | | | - Alberto Esquenazi
- Moss Rehab Gait and Motion Analysis Laboratory, Elkins Park, Pennsylvania, USA
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Tobinick E, Ucci D, Bermudo K, Asseraf S. Perispinal etanercept stroke trial design: PESTO and beyond. Expert Opin Biol Ther 2024; 24:1095-1108. [PMID: 39177653 DOI: 10.1080/14712598.2024.2390636] [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: 07/23/2024] [Accepted: 08/06/2024] [Indexed: 08/24/2024]
Abstract
INTRODUCTION Perispinal etanercept (PSE) is an innovative treatment designed to improve stroke recovery by addressing chronic post-stroke neuroinflammation. Basic science evidence, randomized clinical trial (RCT) evidence and 14 years of favorable clinical experience support the use of PSE to treat chronic stroke. This article provides guidance for the design of future PSE RCTs in accordance with current FDA recommendations. AREAS COVERED Scientific background and essential elements of PSE RCT design. EXPERT OPINION Intimate familiarity with PSE, its novel method of drug delivery, and the characteristics of ideal enriched study populations are necessary for those designing future PSE stroke trials. The design elements needed to enable a PSE RCT to generate valid results include a suitable research question; a homogeneous study population selected using a prospective enrichment strategy; a primary outcome measure responsive to the neurological improvements that result from PSE; trialists with expertise in perispinal delivery; optimal etanercept dosing; and steps taken to minimize the number of placebo responders. RCTs failing to incorporate these elements, such as the PESTO trial, are incapable of reaching reliable conclusions regarding PSE efficacy. SF-36 has not been validated in PSE trials and is unsuitable for use as a primary outcome measure in PSE RCTs.
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Affiliation(s)
| | - Danielle Ucci
- Institute of Neurological Recovery, Boca Raton, FL, USA
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Bavikatte G, Esquenazi A, Dimyan MA, Dashtipour K, Feng W, Mayadev A, Fanning K, Musacchio T, Zuzek A, Francisco GE. Safety and Real-World Dosing of OnabotulinumtoxinA for the Treatment of Adult Spasticity: Post Hoc Analysis of the Adult Spasticity International Registry Study. Am J Phys Med Rehabil 2024; 103:580-587. [PMID: 38206635 DOI: 10.1097/phm.0000000000002410] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2024]
Abstract
OBJECTIVE The aim of the study is to evaluate the safety of onabotulinumtoxinA treatment for spasticity across dose ranges in real-world practice. DESIGN Adult Spasticity International Registry was a multicenter, prospective, observational study (NCT01930786) of onabotulinumtoxinA treatment for adult spasticity over 2 yrs. Adverse events, serious adverse events, treatment-related adverse events, and serious treatment-related adverse events were sorted into five categories (≤200, 201-400, 401-600, 601-800, ≥801 U) based on cumulative dose per session. RESULTS In 3103 treatment sessions ( T ), 730 patients received ≥1 dose of onabotulinumtoxinA. Dose categories included the following: ≤200 U ( n = 312, T = 811), 201-400 U ( n = 446, T = 1366), 401-600 U ( n = 244, T = 716), 601-800 U ( n = 69, T = 149), and ≥801 U ( n = 29, T = 61). Of these patients, 261 reported 827 adverse events, 94 reported 195 serious adverse events, 20 reported 23 treatment-related adverse events, and 2 patients treated with 201-400 U onabotulinumtoxinA reported 3 serious treatment-related adverse events. Treatment-related adverse events reported included ≤200 U (8/811, 0.9%), 201-400 U (7/1366, 0.5%), 401-600 U (6/716, 0.8%), 601-800 U (1/149, 0.7%), and ≥801 U (1/61, 1.6%). CONCLUSIONS In this post hoc analysis, most treatment sessions were performed with 201-400 U onabotulinumtoxinA. Patients treated with 201-400 U onabotulinumtoxinA had an adverse event profile consistent with onabotulinumtoxinA package inserts globally (e.g., United States, European Union, United Kingdom, Canada). No new safety signals were identified.
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Affiliation(s)
- Ganesh Bavikatte
- From the Walton Centre, Liverpool, United Kingdom (GB); MossRehab Gait and Motion Analysis Laboratory, Elkins Park, Pennsylvania (AE); University of Maryland School of Medicine, Baltimore, Maryland (MAD); Loma Linda University School of Medicine, Loma Linda, California (KD); Duke University School of Medicine, Durham, North Carolina (WF); Swedish Neuroscience Institute, Seattle, Washington (AM); MIST Research and Statistical Consulting, Wilmington, North Carolina (KF); Allergan, an AbbVie Company, Rome, Italy (TM); Allergan, an AbbVie Company, Irvine, California (AZ); University of Texas McGovern Medical School and TIRR Memorial Hermann, Houston, Texas (GEF)
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Facciorusso S, Spina S, Picelli A, Baricich A, Francisco GE, Molteni F, Wissel J, Santamato A. The Role of Botulinum Toxin Type-A in Spasticity: Research Trends from a Bibliometric Analysis. Toxins (Basel) 2024; 16:184. [PMID: 38668609 PMCID: PMC11053519 DOI: 10.3390/toxins16040184] [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: 02/27/2024] [Revised: 04/01/2024] [Accepted: 04/08/2024] [Indexed: 04/29/2024] Open
Abstract
Botulinum toxin type-A (BoNT-A) has emerged as a key therapeutic agent for the management of spasticity. This paper presents a comprehensive bibliometric and visual analysis of research concerning BoNT-A treatment of spasticity to elucidate current trends and future directions in this research area. A search was conducted in the Web of Science database for articles focused on the use of BoNT-A in spasticity published between 2000 and 2022. We extracted various metrics, including counts of publications and contributions from different countries, institutions, authors, and journals. Analytical methods in CiteSpace were employed for the examination of co-citations, collaborations, and the co-occurrence of keywords. Our search yielded 1489 publications. Analysis revealed a consistent annual increase in research output. The United States, United Kingdom, and Italy were the leading contributors. The top institution in this research was Assistance Publique Hopitaux, Paris. The journal containing the highest number of relevant publications was Toxins. Key frequently occurring keywords were 'stroke', 'cerebral palsy', 'adult spasticity', and 'upper extremity'. This study identified 12 clusters of keywords and 15 clusters of co-cited references, indicating the main focus areas and emerging themes in this field. This study comprehensively analyzed and summarized trends in BoNT-A research in the field of spasticity over the past 22 years.
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Affiliation(s)
- Salvatore Facciorusso
- Spasticity and Movement Disorders “ReSTaRt”, Unit Physical Medicine and Rehabilitation Section, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy; (S.F.); (A.S.)
- Department of Medical and Surgical Specialties and Dentistry, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Stefania Spina
- Spasticity and Movement Disorders “ReSTaRt”, Unit Physical Medicine and Rehabilitation Section, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy; (S.F.); (A.S.)
| | - Alessandro Picelli
- Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37100 Verona, Italy;
| | - Alessio Baricich
- Physical Medicine and Rehabilitation, Department of Health Sciences, Università del Piemonte Orientale, 28100 Novara, Italy;
| | - Gerard E. Francisco
- Department of Physical Medicine & Rehabilitation, University of Texas Health McGovern Medical School, Houston, TX 77030, USA;
| | - Franco Molteni
- Villa Beretta Rehabilitation Center, Valduce Hospital Como, 23845 Costa Masnaga, Italy;
| | - Jörg Wissel
- Department of Neurorehabilitation and Physical Therapy, Vivantes Hospital Spandau, 13585 Berlin, Germany;
| | - Andrea Santamato
- Spasticity and Movement Disorders “ReSTaRt”, Unit Physical Medicine and Rehabilitation Section, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy; (S.F.); (A.S.)
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Yi KH, Choi YJ, Lee JH, Hu H, Gil YC, Hu KS, Kim HJ. Anatomical Considerations for the Injection of Botulinum Neurotoxin in Shoulder and Arm Contouring. Aesthet Surg J 2024; 44:319-326. [PMID: 37548270 DOI: 10.1093/asj/sjad250] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 07/24/2023] [Accepted: 08/04/2023] [Indexed: 08/08/2023] Open
Abstract
The utilization of botulinum neurotoxin in the field of body contouring is on the rise. Body contouring procedures typically focus on specific muscle groups such as the superior trapezius, deltoid, and lateral head of the triceps brachii. The authors propose identifying optimal injection sites for botulinum neurotoxin to achieve desired aesthetic contouring of the shoulders and arms. The authors conducted a modified Sihler's staining method on specimens of the superior trapezius, deltoid, and lateral head of the triceps brachii muscles, totaling 16, 14, and 16 specimens, respectively. The neural distribution exhibited the most extensive branching patterns within the horizontal section (between 1/5 and 2/5) and the vertical section (between 2/4 and 4/4) of the superior trapezius muscle. In the deltoid muscle, the areas between the anterior and posterior deltoid bellies, specifically within the range of the horizontal 1/3 to 2/3 lines, showed significant intramuscular arborization. Furthermore, the middle deltoid muscle displayed arborization patterns between 2/3 and the axillary line. Regarding the triceps brachii muscle, the lateral heads demonstrated arborization between 4/10 and 7/10. The authors recommend targeting these regions, where maximum arborization occurs, as the optimal and safest points for injecting botulinum toxin.
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Ye DH, Chun MH, Park YG, Paik NJ, Lee SU, Yoo SD, Kim DY. A Randomized, Double-Blind, Active Control, Multicenter, Phase 3 Study to Evaluate the Efficacy and Safety of Liztox ® versus Botox ® in Post-Stroke Upper Limb Spasticity. Toxins (Basel) 2023; 15:697. [PMID: 38133201 PMCID: PMC10748261 DOI: 10.3390/toxins15120697] [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: 11/07/2023] [Revised: 12/04/2023] [Accepted: 12/11/2023] [Indexed: 12/23/2023] Open
Abstract
Botulinum toxin type A (BTX-A) injection is a commonly used therapeutic intervention for upper limb spasticity in stroke patients. This study was designed as a randomized, active-drug-controlled, double-blind, multicenter, phase 3 clinical trial to evaluate the safety and efficacy of Liztox® in comparison to onabotulinum toxin A (Botox®) for individuals with post-stroke upper limb spasticity. The primary outcome was the alteration in wrist flexor muscle tone from the initial assessment to the fourth week, evaluated using the modified Ashworth scale (MAS). Secondary outcomes included MAS score changes for the wrist at weeks 8 and 12 from baseline; MAS score changes for finger and elbow flexors; and changes in the Disability Assessment Scale (DAS), Subject's Global Assessment (SGA), the Investigator's Global Assessment (IGA), and Caregiver Burden Scale (CBS) at weeks 4, 8, and 12 from baseline. The MAS score for wrist flexor spasticity decreased by -1.14 ± 0.59 in the Liztox® group and -1.22 ± 0.59 in the Botox® group from baseline to week 4. The difference [97.5% confidence interval (CI)] between the test and control groups was 0.08 [-∞, 0.26], confirming the non-inferiority of the test group compared to the control group. Furthermore, there were consistent improvements in the IGA, SGA, and CBS scores across all assessment intervals, with no statistically significant variances detected between the two groups. No safety-related concerns were reported during the study. In conclusion, Liztox® injection proved to be a secure and efficacious intervention for managing upper extremity spasticity in post-stroke patients.
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Affiliation(s)
- Dong Hyun Ye
- Department of Rehabilitation Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea;
| | - Min Ho Chun
- Department of Rehabilitation Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea;
| | - Yoon Ghil Park
- Department of Rehabilitation Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Republic of Korea;
| | - Nam-Jong Paik
- Department of Rehabilitation Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea;
| | - Shi-Uk Lee
- Department of Rehabilitation Medicine, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, Seoul 07061, Republic of Korea;
| | - Seung Don Yoo
- Department of Rehabilitation Medicine, Kyung Hee University Hospital at Gangdong, Kyung Hee University College of Medicine, Seoul 05278, Republic of Korea;
- Department of Medicine (AgeTech-Service Convergence Major), Kyung Hee University, Seoul 05278, Republic of Korea
| | - Deog Young Kim
- Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea;
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Yi KH, Lee KW, Hwang Y, An MH, Ahn HS, Hu H, Lee JH, Lee HJ. Intramuscular Neural Distribution of Adductor Pollicis Muscle Spasticity in Cadaver Model Regarding Botulinum Neurotoxin Treatment. Yonsei Med J 2023; 64:581-585. [PMID: 37634635 PMCID: PMC10462812 DOI: 10.3349/ymj.2023.0111] [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: 04/26/2023] [Revised: 06/01/2023] [Accepted: 06/19/2023] [Indexed: 08/29/2023] Open
Abstract
PURPOSE The adductor pollicis muscle is frequently targeted for botulinum neurotoxin injective treatment for spasticity. However, there are no injective guidelines for delivering injection to the muscle. MATERIALS AND METHODS A method known as the modified Sihler's method was used to stain the adductor pollicis muscle in 16 specimens to reveal intramuscular neural distribution of the muscle. RESULTS The most intramuscular neural distribution was located on 1/5 to 3/5 of the muscle regarding midline of 3rd metacarpal bone (0) to the base of the 1st proximal phalanx (5/5). The nerve entry point was mostly located on 0 to 1/5 of the muscle. CONCLUSION The result suggests that botulinum neurotoxin should be delivered at the middle of second metacarpal bone via deep injection.
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Affiliation(s)
- Kyu-Ho Yi
- Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, BK21 FOUR Project, Yonsei University College of Dentistry, Seoul, Korea
- Maylin Clinic (Apgujeong), Seoul, Korea
| | - Kang-Woo Lee
- Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, BK21 FOUR Project, Yonsei University College of Dentistry, Seoul, Korea
| | | | - Min Ho An
- Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Korea
| | - Hyo-Sang Ahn
- Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, BK21 FOUR Project, Yonsei University College of Dentistry, Seoul, Korea
| | - Hyewon Hu
- Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, BK21 FOUR Project, Yonsei University College of Dentistry, Seoul, Korea
| | - Ji-Hyun Lee
- Department of Anatomy and Acupoint, College of Korean Medicine, Gachon University, Seongnam, Korea.
| | - Hyung-Jin Lee
- Department of Anatomy, Catholic Institute for Applied Anatomy, College of Medicine, The Catholic University of Korea, Seoul, Korea.
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Yi KH, Park HJ, Kim JH, Kim SO, Cheon GW, An MH, Lee HJ, Lee JH. Intramuscular Neural Distribution of the Gastrocnemius for Botulinum Neurotoxin Injection: Application to Cosmetic Calf Shaping. Yonsei Med J 2023; 64:511-517. [PMID: 37488703 PMCID: PMC10375242 DOI: 10.3349/ymj.2023.0124] [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: 04/28/2023] [Revised: 06/01/2023] [Accepted: 06/09/2023] [Indexed: 07/26/2023] Open
Abstract
PURPOSE Anatomical landmarks can provide vital information on the distribution of nerves in the gastrocnemius muscle. We aimed to provide an anatomical perspective on appropriate locations for botulinum neurotoxin (BoNT) injections in the medial and lateral parts of the gastrocnemius for calf shaping. MATERIALS AND METHODS A modified Sihler's method was applied to both the medial and lateral parts of the gastrocnemius muscles (16 specimens). Intramuscular neural distributions were revealed by dissecting along a transverse line crossing the fibular head and superior margin of the calcaneal tuberosity. RESULTS The intramuscular neural distribution for the medial and lateral parts of the gastrocnemius had the greatest arborized patterns in the 7/10-8/10 section of the medial head and 7.5/10-8.5/10 section of the lateral part of the gastrocnemius. CONCLUSION We propose that BoNT injections should be directed to the 7/10-8/10 section of the medial head and the 7.5/10-8.5/10 section of the lateral part of the gastrocnemius. Following our guidelines, clinicians can ensure satisfactory results with the use of minimal doses to limit adverse effects, such as gait disturbance, antibody production, and bruising, due to multiple injections. The results can also be altered and applied to electromyography.
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Affiliation(s)
- Kyu-Ho Yi
- Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, BK21 FOUR Project, Yonsei University College of Dentistry, Seoul, Korea
| | - Hyun Jin Park
- Department of Anatomy, Daegu Catholic University School of Medicine, Daegu, Korea
| | | | | | | | - Min Ho An
- Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Korea
| | - Hyung-Jin Lee
- Department of Anatomy, Catholic Institute for Applied Anatomy, College of Medicine, The Catholic University of Korea, Seoul, Korea.
| | - Ji-Hyun Lee
- Department of Anatomy and Acupoint, College of Korean Medicine, Gachon University, Seongnam, Korea.
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Riganello F, Tonin P, Soddu A. I Feel! Therefore, I Am from Pain to Consciousness in DOC Patients. Int J Mol Sci 2023; 24:11825. [PMID: 37511583 PMCID: PMC10380260 DOI: 10.3390/ijms241411825] [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: 06/21/2023] [Revised: 07/13/2023] [Accepted: 07/20/2023] [Indexed: 07/30/2023] Open
Abstract
Pain assessment and management in patients with disorders of consciousness (DOC) is a challenging and important aspect of care, with implications for detecting consciousness and promoting recovery. This narrative review explores the role of pain in consciousness, the challenges of pain assessment, pharmacological treatment in DOC, and the implications of pain assessment when detecting changes in consciousness. The review discusses the Nociception Coma Scale and its revised version, which are behavioral scales used to assess pain in DOC patients, and the challenges and controversies surrounding the appropriate pharmacological treatment of pain in these patients. Moreover, we highlight recent evidence suggesting that an accurate pain assessment may predict changes in the level of consciousness in unresponsive wakefulness syndrome/vegetative state patients, underscoring the importance of ongoing pain management in these patients.
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Affiliation(s)
- Francesco Riganello
- Research in Advanced Neurorehabilitation, S. Anna Institute, 88900 Crotone, Italy
| | - Paolo Tonin
- Research in Advanced Neurorehabilitation, S. Anna Institute, 88900 Crotone, Italy
| | - Andrea Soddu
- Physics, and Astronomy Department, Western Institute for Neuroscience, University of Western Ontario, London, ON N6A 3K7, Canada
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Esquenazi A, Jost WH, Turkel CC, Wein T, Dimitrova R. Treatment of adult spasticity with Botox (onabotulinumtoxinA): Development, insights, and impact. Medicine (Baltimore) 2023; 102:e32376. [PMID: 37499086 PMCID: PMC10374184 DOI: 10.1097/md.0000000000032376] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/29/2023] Open
Abstract
Upper and lower limb spasticity (ULS, LLS) often occur following a stroke or in patients with other neurological disorders, leading to difficulties in mobility and daily living and decreased quality of life. Prior to the use of onabotulinumtoxinA, antispastic medications had limited efficacy and often caused sedation. Phenol injections were difficult for physicians to perform, painful, and led to tissue destruction. The success of onabotulinumtoxinA in treating cervical dystonia led to its use in spasticity. However, many challenges characterized the development of onabotulinumtoxinA for adult spasticity. The wide variability in the presentation of spasticity among patients rendered it difficult to determine which muscles to inject and how to measure improvement. Another challenge was the initial refusal of the Food and Drug Administration to accept the Ashworth Scale as a primary endpoint. Additional scales were designed to incorporate a goal-oriented, patient-centered approach that also accounted for the variability of spasticity presentations. Several randomized, double-blind, placebo-controlled trials of post-stroke spasticity of the elbow, wrist, and/or fingers showed significantly greater improvements in the modified Ashworth Scale and patient treatment goals and led to the approval of onabotulinumtoxinA for the treatment of ULS in adult patients. Lessons learned from the successful ULS trials were applied to design an LLS trial that led to approval for the latter indication. Additional observational trials mimicking real-world treatment have shown continued effectiveness and patient satisfaction. The use of onabotulinumtoxinA for spasticity has ushered in a more patient-centered treatment approach that has vastly improved patients' quality of life.
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Affiliation(s)
| | - Wolfgang H Jost
- Department of Neurology, University of Freiburg, Freiburg, Germany, and Parkinson-Hospital Ortenau, Wolfach, Germany
| | | | - Theodore Wein
- Department of Neurology, McGill University, Montreal, QC, Canada
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Yi KH, Lee JH, Hu H, Park HJ, Lee HJ, Choi YJ, Kim HJ. Botulinum neurotoxin injection in the deltoid muscle: application to cosmetic shoulder contouring. Surg Radiol Anat 2023:10.1007/s00276-023-03163-2. [PMID: 37178218 DOI: 10.1007/s00276-023-03163-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Accepted: 05/03/2023] [Indexed: 05/15/2023]
Abstract
BACKGROUND AND OBJECTIVES This study describes the intramuscular nerve branching of the deltoid muscle in relation to shoulder surface anatomy, with the aim of providing essential information regarding the most appropriate sites for botulinum neurotoxin injection during shoulder line contouring. METHODS The modified Sihler's method was used to stain the deltoid muscles (16 specimens). The intramuscular arborization areas of the specimens were demarcated using the marginal line of the muscle origin and the line connecting the anterior and posterior upper edges of the axillary region. RESULTS The intramuscular neural distribution of the deltoid muscle had the greatest arborization patterns in the area between the horizontal 1/3 and 2/3 lines of the anterior and posterior deltoid bellies, and 2/3 to axillary line in middle deltoid bellies. The greatest part of the posterior circumflex artery and axillary nerve ran below the areas with the highest aborizations. CONCLUSION We propose that botulinum neurotoxin injections should be administered in the area between the 1/3 and 2/3 lines of the anterior and posterior deltoid bellies, and 2/3 to axillary line on middle deltoid bellies. Accordingly, clinicians will ensure minimal dose injections and fewer adverse effects of the botulinum neurotoxin injection. Deltoid intramuscular injections, such as vaccines and trigger point injections, should ideally be adapted according to our results.
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Affiliation(s)
- Kyu-Ho Yi
- Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, BK21 PLUS Project, Yonsei University College of Dentistry, 50-1 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, Republic of Korea
- Maylin Clinic (Apgujeong), Seoul, 06005, Korea
- Department of Anatomy, College of Medicine, Konkuk University, Chungju, 27376, Republic of Korea
| | - Ji-Hyun Lee
- Department of Anatomy and Acupoint, College of Korean Medicine, Gachon University, Seongnam, 13120, Korea
- Department of Anatomy, College of Medicine, Konkuk University, Chungju, 27376, Republic of Korea
| | - Hyewon Hu
- Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, BK21 PLUS Project, Yonsei University College of Dentistry, 50-1 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, Republic of Korea
- Department of Anatomy, College of Medicine, Konkuk University, Chungju, 27376, Republic of Korea
| | - Hyun-Jun Park
- Department of Anatomy and Acupoint, College of Korean Medicine, Gachon University, Seongnam, 13120, Korea
- Department of Anatomy, College of Medicine, Konkuk University, Chungju, 27376, Republic of Korea
| | - Hyung-Jin Lee
- Department of Anatomy, Catholic Institute for Applied Anatomy, College of Medicine, The Catholic University of Korea, Seoul, 06591, Korea
- Department of Anatomy, College of Medicine, Konkuk University, Chungju, 27376, Republic of Korea
| | - You-Jin Choi
- Maylin Clinic (Apgujeong), Seoul, 06005, Korea
- Department of Anatomy, College of Medicine, Konkuk University, Chungju, 27376, Republic of Korea
| | - Hee-Jin Kim
- Maylin Clinic (Apgujeong), Seoul, 06005, Korea.
- Department of Anatomy, College of Medicine, Konkuk University, Chungju, 27376, Republic of Korea.
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14
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Takekawa T, Hara T, Yamada N, Sato T, Hasegawa Y, Takagi S, Kobayashi K, Kitajima T, Abo M. Treatment outcome of local injection of botulinum toxin for claw toe: Differences between cerebral hemorrhage and infarction. Clin Neurol Neurosurg 2023; 226:107620. [PMID: 36805253 DOI: 10.1016/j.clineuro.2023.107620] [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: 11/14/2022] [Revised: 01/20/2023] [Accepted: 02/06/2023] [Indexed: 02/11/2023]
Abstract
BACKGROUND Some patients with post-stroke claw toe respond well to botulinum toxin (BoNT) treatment while others do not. This study was designed to assess the impact of stroke type (cerebral hemorrhage and cerebral infarction) on the outcome of BoNT treatment for claw toe. METHODS We retrospectively examined the medical records of patients who received local BoNT (onabotulinumtoxin A) injections into the flexor hallucis longus (FHL) and flexor digitorum longus (FDL) muscles. All patients suffered stroke-related leg paralysis and spasticity. RESULTS The study participants were 58 patients (mean age, 61.4 ± 10.3 years, ± SD) with time since stroke of 6.7 ± 4.4 years. The stroke type was cerebral hemorrhage (n = 38) and cerebral infarction (n = 20). After a total of 124 BoNT administrations with medical records entries on the subjective symptoms, the odds for symptomatic improvement was approximately 5.8 times higher in patients of the infarction group compared with the hemorrhage group (OR = 5.787, 95% CI = 2.369-14.134, p = 0. 000). Fifty-one patients (32 with cerebral hemorrhage, 19 with cerebral infarction) received the first local BoNT injection and had available medical records, analysis of which showed a significantly higher rate of symptomatic improvement in patients of the infarction group than those of the hemorrhage group (p = 0.006). After adjustment by factors known to influence treatment outcome (degree of spasticity and paralysis, BoNT dosage, and extent of FDL muscle control of toe movements), the treatment effect was predominantly higher in patients with cerebral infarction. CONCLUSION The BoNT treatment response was better for claw toes in cerebral infarction patients than in hemorrhage patients, possibly suggesting that claw toe is associated with more severe spasticity in this group of patients.
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Affiliation(s)
- Toru Takekawa
- Department of Rehabilitation Medicine, The Jikei University School of Medicine, Tokyo 105-8461, Japan.
| | - Takatoshi Hara
- Department of Rehabilitation Medicine, The Jikei University School of Medicine, Tokyo 105-8461, Japan; Department of Rehabilitation Medicine, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8551, Japan.
| | - Naoki Yamada
- Department of Rehabilitation Medicine, The Jikei University School of Medicine, Tokyo 105-8461, Japan.
| | - Tomoharu Sato
- Motoyama Rehabilitation Hospital, Kobe, Hyogo 658-0015, Japan.
| | - Yuki Hasegawa
- Department of Rehabilitation Medicine, The Jikei University School of Medicine, Tokyo 105-8461, Japan; Department of Rehabilitation Medicine, Tokyo General Hospital, Tokyo 165-0022, Japan.
| | - Satoshi Takagi
- Department of Rehabilitation Medicine, The Jikei University School of Medicine, Tokyo 105-8461, Japan; Shinagawa Rehabilitation Hospital, Tokyo 141-0001, Japan.
| | - Kazushige Kobayashi
- Department of Rehabilitation Medicine, The Jikei University School of Medicine, Tokyo 105-8461, Japan.
| | - Tomohide Kitajima
- Department of Cerebrospinal Surgery, Narita Hospital, Narita, Chiba 286-0845, Japan.
| | - Masahiro Abo
- Department of Rehabilitation Medicine, The Jikei University School of Medicine, Tokyo 105-8461, Japan.
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Cox K, Ghebrehiwet M, Kee M, Rucker B, Flores H, Ottwell R, Vassar M. Assessing the Reporting of Harms in Systematic Reviews Focused on the Therapeutic and Cosmetic Uses of Botulinum Toxin. Clin Drug Investig 2023; 43:85-95. [PMID: 36626045 DOI: 10.1007/s40261-022-01235-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/24/2022] [Indexed: 01/11/2023]
Abstract
BACKGROUND AND OBJECTIVE The expanding use of botulinum toxin (BoNT) in medical practice demonstrates the need to highlight whether there is adequate information regarding its safety profile. The aim of our study was to identify completeness of harms reporting for BoNT treatment within systematic reviews (SRs), assess quality of SRs using the AMSTAR-2 tool, and determine the degree of overlap among primary studies within each SR. METHODS On May 31, 2022, we searched Embase, Epistemonikos, MEDLINE, and the Cochrane Database of Systematic Reviews for SRs on BoNT therapy. Screening and data extraction were performed in a masked, duplicate fashion. AMSTAR-2 was used to evaluate the methodological quality of included SRs. Corrected covered area (CCA) was calculated for SR dyads. RESULTS Of the 90 included SRs, we found that 70 completed less than 50% of harms items. The most reported items were BoNT as a favorable intervention (73/90, 81.1%) and harms as a primary outcome (72/90, 80.0%). The least reported items were grades and severity scales used to classify harms (8/90, 8.9%) and number of treatment discontinuations in each arm (10/90, 11.1%). Eighty-three SRs were rated "critically low" (83/90, 92.2%), while 5 SRs were rated "high" (5/90, 5.6%) via AMSTAR-2 tool. Significant associations were found between completion of harms reporting and: (1) a "critically low" appraisal on AMSTAR-2 tool (p = 0.0060) and (2) whether harms was reported as a primary outcome (p = 0.0001). The total CCA overlap was determined to be 0.8%. CONCLUSION Our results demonstrate that harms are underreported within BoNT SRs. Because healthcare professionals often refer to SRs to guide clinical decision making, it is important to continue to explore shortcomings among BoNT literature in future studies.
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Affiliation(s)
- Katherine Cox
- Office of Medical Student Research, Oklahoma State University Center for Health Sciences, 1111 W 17th St., Tulsa, OK, 74107, USA.
| | - Merhawit Ghebrehiwet
- Office of Medical Student Research, Oklahoma State University Center for Health Sciences, 1111 W 17th St., Tulsa, OK, 74107, USA
| | - Micah Kee
- Office of Medical Student Research, Oklahoma State University Center for Health Sciences, 1111 W 17th St., Tulsa, OK, 74107, USA
| | - Brayden Rucker
- Office of Medical Student Research, Oklahoma State University Center for Health Sciences, 1111 W 17th St., Tulsa, OK, 74107, USA
| | - Holly Flores
- Office of Medical Student Research, Oklahoma State University Center for Health Sciences, 1111 W 17th St., Tulsa, OK, 74107, USA
| | - Ryan Ottwell
- Department of Dermatology, St. Joseph Mercy Hospital, Ann Arbor, MI, USA
| | - Matt Vassar
- Office of Medical Student Research, Oklahoma State University Center for Health Sciences, 1111 W 17th St., Tulsa, OK, 74107, USA.,Department of Psychiatry and Behavioral Sciences, Oklahoma State University Center for Health Sciences, Tulsa, OK, USA
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16
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Lee J, Chun MH, Ko YJ, Lee SU, Kim DY, Paik NJ. Safety and efficacy of MT10107 in post-stroke upper limb spasticity treatment: A phase I randomized controlled trial. Medicine (Baltimore) 2022; 101:e31367. [PMID: 36343044 PMCID: PMC9646656 DOI: 10.1097/md.0000000000031367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND Botulinum toxin type A injection is widely used treatment option for the treatment of upper limb spasticity in stroke patients. The purpose of this study was to explore the safety and efficacy of MT10107, a new botulinum toxin type A, in patients with post-stroke upper limb spasticity. METHODS A prospective, randomized, double-blind, active drug-controlled, multi-center, phase I clinical trial. Thirty patients with post-stroke upper limb spasticity were received either MT10107 or onabotulinumtoxinA. Primary endpoint was change of modified Ashworth scale (MAS) score for wrist flexor from baseline to week 4. The secondary endpoints were changes of MAS scores for elbow and finger flexors, response rate, Disability Assessment Scale (DAS), and global assessment of treatment. The safety endpoints such as adverse events, vital signs, physical examination, and laboratory test were evaluated. The outcome measures were evaluated from baseline to week 4. RESULTS The primary endpoints were -1.07 ± 0.70 and -1.23 ± 0.56 for the MT10107 and onabotulinumtoxinA groups, respectively. The intergroup difference of change between the 2 groups was 0.17 (95% confidence interval -0.31 to 0.64, P = .5769). In secondary endpoints, both groups showed a significant improvement in both MAS and DAS. There was no significant between-group difference in all secondary endpoints and safety measures. CONCLUSION The safety and efficacy of MT10107 showed no significant difference compared to onabotulinumtoxinA in post-stroke upper limb spasticity treatment.
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Affiliation(s)
- Junekyung Lee
- Department of Rehabilitation Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Republic of Korea
| | - Min Ho Chun
- Department of Rehabilitation Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Young Jin Ko
- Department of Rehabilitation Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Shi-Uk Lee
- Department of Rehabilitation Medicine, Seoul National University College of Medicine, Seoul National University Boramae Medical Center, Seoul, Republic of Korea
| | - Deog Young Kim
- Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Nam-Jong Paik
- Department of Rehabilitation Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
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Lee J, Chun MH. Safety and Efficacy of HU-014 in the Treatment of Post-Stroke Upper Limb Spasticity: A Phase I Pilot Study. Toxins (Basel) 2022; 14:toxins14110730. [PMID: 36355980 PMCID: PMC9693132 DOI: 10.3390/toxins14110730] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Revised: 10/19/2022] [Accepted: 10/22/2022] [Indexed: 01/26/2023] Open
Abstract
Botulinum toxin type A (BTX-A) is widely used for treating post-stroke upper limb spasticity. We evaluated the safety and efficacy of HU-014 in treating post-stroke upper limb spasticity. Thirteen patients were administered with HU-014. The primary outcome was safety, including adverse events, vital signs, physical examination, laboratory tests, and antibody formation test. The secondary outcomes were changes in the Modified Ashworth Scale (MAS) score for wrist, elbow, and finger flexor; Disability Assessment Scale (DAS); Investigator's Global Assessment (IGA) and Subject's Global Assessment (SGA); Caregiver Burden Scale (CBS); and Columbia Suicide Severity Rating Scale (C-SSRS) at weeks 4, 8, and 12 from baseline. No notable safety-related issues were reported. MAS and DAS scores were significantly decreased from those at baseline at 4, 8, and 12 weeks (p < 0.05). At weeks 4, 8, and 12, the IGA and SGA scores were 5.85 ± 0.55, 5.69 ± 0.48, and 5.62 ± 0.65 and 5.46 ± 1.20, 5.85 ± 0.38, and 5.77 ± 0.73, respectively. CBS scores decreased at all timepoints and those for cutting fingernails significantly decreased at 8 and 12 weeks compared with baseline (p < 0.05). C-SSRS scores showed that suicidal ideation in all patients was "low" at all timepoints. HU-014 is a safe treatment that can improve post-stroke upper limb spasticity.
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Abstract
SUMMARY The hypertrophied temporalis and masseter muscles give a muscular shaped and bulky contour to the face. Botulinum neurotoxin injection methods are commonly used for facial contouring; however, adverse effects have been reported owing to a lack of delicate anatomical information. The anatomical considerations when injecting botulinum neurotoxin into the temporalis and masseter muscles have been reviewed in the present study. Current knowledge on the localization of the botulinum neurotoxin injection point with more recent anatomical dissection and modified Sihler's staining procedures was assessed. We found that for the muscles, the injection point can be more precisely demarcated. Optimal injection sites are presented for the temporalis and masseter muscles, and the injection technique has been suggested. We propose the optimal injection sites in relation to external anatomical landmarks for the frequently injected muscles of the face to facilitate the efficiency of botulinum neurotoxin injections. In addition, these guidelines would aid in more precise practice without the adverse effects of botulinum neurotoxin.
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Yi KH, Lee KL, Lee JH, Hu HW, Kim HJ. Guidance to trigger point injection for treating myofascial pain syndrome: Intramuscular neural distribution of the quadratus lumborum. Clin Anat 2022; 35:1100-1106. [PMID: 35655442 DOI: 10.1002/ca.23918] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Revised: 05/31/2022] [Accepted: 05/31/2022] [Indexed: 11/07/2022]
Abstract
Postural habits and repetitive motion contribute toward the progress of myofascial pain by affecting overload on specific muscles, the quadratus lumborum (QL) muscle being the most frequently involved. The therapy of myofascial pain syndrome includes the release of myofascial pain syndrome using injective agents such as botulinum neurotoxin, lidocaine, steroids, and normal saline. However, an optimal injection point has not been established for the QL muscle. This study aimed to propose an optimal injection point for this muscle by studying its intramuscular neural distribution using the whole mount staining method. A modified Sihler's procedure was completed on 15 QL muscles to visualize the intramuscular arborization areas in terms of the inferior border of the 12th rib, the transverse processes of L1-L4, and the iliac crest. The intramuscular neural distribution of the QL had the densely arborized areas in the three lateral portions of L3-L4 and L4-L5 and the medial portion between L4 and L5.
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Affiliation(s)
- Kyu-Ho Yi
- Wonju Public Health Center, COVID-19 Division, Wonju-si, South Korea
- Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, BK21 FOUR Project, Yonsei University College of Dentistry, Seoul, South Korea
| | - Kyu-Lim Lee
- Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, BK21 FOUR Project, Yonsei University College of Dentistry, Seoul, South Korea
| | - Ji-Hyun Lee
- Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, BK21 FOUR Project, Yonsei University College of Dentistry, Seoul, South Korea
| | - Hye-Won Hu
- Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, BK21 FOUR Project, Yonsei University College of Dentistry, Seoul, South Korea
| | - Hee-Jin Kim
- Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, BK21 FOUR Project, Yonsei University College of Dentistry, Seoul, South Korea
- Department of Materials Science & Engineering, College of Engineering, Yonsei University, Seoul, South Korea
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Lee HJ, Lee JH, Yi KH, Kim HJ. Intramuscular Innervation of the Supraspinatus Muscle Assessed Using Sihler’s Staining: Potential Application in Myofascial Pain Syndrome. Toxins (Basel) 2022; 14:toxins14050310. [PMID: 35622557 PMCID: PMC9143847 DOI: 10.3390/toxins14050310] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Revised: 04/25/2022] [Accepted: 04/26/2022] [Indexed: 11/30/2022] Open
Abstract
Despite the positive effects of botulinum neurotoxin (BoNT) injection into the neural arborized area, there is no anatomical evidence in the literature regarding the neural arborization of the supraspinatus muscle. The present study aimed to define the intramuscular neural arborized pattern of the supraspinatus muscle using the modified Sihler’s staining method to facilitate the establishment of safe and effective injection sites in patients with myofascial pain in the supraspinatus muscle. Seventeen supraspinatus muscles from 15 embalmed cadavers were dissected. Precise suprascapular nerve entry locations were also observed. Intramuscular neural arborization was visualized by Sihler’s staining. The supraspinatus muscle was divided into four portions named A, B, C, and D. The nerve entry points were observed in 88.2% (15 of 17 cases) of section B and 76.5% (13 of 17 cases) of section C of the supraspinatus muscle, respectively. The concentration of intramuscular neural arborization was highest in section B of the supraspinatus muscle, which was the center of the supraspinatus muscle. When the clinician performs a trigger point and a BoNT injection into the supraspinatus muscle, injection within the medial 25–75% of the supraspinatus muscle will lead to optimal results when using small amounts of BoNT and prevent undesirable paralysis.
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Affiliation(s)
- Hyung-Jin Lee
- Department of Anatomy, Catholic Institute for Applied Anatomy, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea;
| | - Ji-Hyun Lee
- BK21 FOUR Project, Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, Yonsei University College of Dentistry, Seoul 03722, Korea; (J.-H.L.); (K.-H.Y.)
| | - Kyu-Ho Yi
- BK21 FOUR Project, Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, Yonsei University College of Dentistry, Seoul 03722, Korea; (J.-H.L.); (K.-H.Y.)
- COVID-19 Division, Wonju City Public Health Center, Wonju-Si 26417, Korea
| | - Hee-Jin Kim
- BK21 FOUR Project, Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, Yonsei University College of Dentistry, Seoul 03722, Korea; (J.-H.L.); (K.-H.Y.)
- Department of Materials Science & Engineering, College of Engineering, Yonsei University, Seoul 03722, Korea
- Correspondence:
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The Effects of the Biceps Brachii and Brachioradialis on Elbow Flexor Muscle Strength and Spasticity in Stroke Patients. Neural Plast 2022; 2022:1295908. [PMID: 35283993 PMCID: PMC8906960 DOI: 10.1155/2022/1295908] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Revised: 12/27/2021] [Accepted: 01/11/2022] [Indexed: 12/02/2022] Open
Abstract
Objective Muscle weakness and spasticity are common consequences of stroke, leading to a decrease in physical activity. The effective implementation of precision rehabilitation requires detailed rehabilitation evaluation. We aimed to analyze the surface electromyography (sEMG) signal features of elbow flexor muscle (biceps brachii and brachioradialis) spasticity in maximum voluntary isometric contraction (MVIC) and fast passive extension (FPE) in stroke patients and to explore the main muscle groups that affect the active movement and spasticity of the elbow flexor muscles to provide an objective reference for optimizing stroke rehabilitation. Methods Fifteen patients with elbow flexor spasticity after stroke were enrolled in this study. sEMG signals of the paretic and nonparetic elbow flexor muscles (biceps and brachioradialis) were detected during MVIC and FPE, and root mean square (RMS) values were calculated. The RMS values (mean and peak) of the biceps and brachioradialis were compared between the paretic and nonparetic sides. Additionally, the correlation between the manual muscle test (MMT) score and the RMS values (mean and peak) of the paretic elbow flexors during MVIC was analyzed, and the correlation between the modified Ashworth scale (MAS) score and the RMS values (mean and peak) of the paretic elbow flexors during FPE was analyzed. Results During MVIC exercise, the RMS values (mean and peak) of the biceps and brachioradialis on the paretic side were significantly lower than those on the nonparetic side (p < 0.01), and the RMS values (mean and peak) of the bilateral biceps were significantly higher than those of the brachioradialis (p < 0.01). The MMT score was positively correlated with the mean and peak RMS values of the paretic biceps and brachioradialis (r = 0.89, r = 0.91, r = 0.82, r = 0.85; p < 0.001). During FPE exercise, the RMS values (mean and peak) of the biceps and brachioradialis on the paretic side were significantly higher than those on the nonparetic side (p < 0.01), and the RMS values (mean and peak) of the brachioradialis on the paretic side were significantly higher than those of the biceps (p < 0.01). TheMAS score was positively correlated with the mean RMS of the paretic biceps and brachioradialis (r = 0.62, p = 0.021; r = 0.74, p = 0.004), and the MAS score was positively correlated with the peak RMS of the paretic brachioradialis (r = 0.59, p = 0.029) but had no significant correlation with the peak RMS of the paretic biceps (r = 0.49, p > 0.05). Conclusions The results confirm that the biceps is a vital muscle in active elbow flexion and that the brachioradialis plays an important role in elbow flexor spasticity, suggesting that the biceps should be the focus of muscle strength training of the elbow flexors and that the role of the brachioradialis should not be ignored in the treatment of elbow flexor spasticity. This study also confirmed the application value of sEMG in the objective assessment of individual muscle strength and spasticity in stroke patients.
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Yi KH, Lee HJ, Seo KK, Kim HJ. Intramuscular Neural Arborization of the Latissimus Dorsi Muscle: Application of Botulinum Neurotoxin Injection in Flap Reconstruction. Toxins (Basel) 2022; 14:toxins14020107. [PMID: 35202134 PMCID: PMC8878018 DOI: 10.3390/toxins14020107] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Accepted: 01/27/2022] [Indexed: 01/27/2023] Open
Abstract
Postoperative pain after breast reconstruction surgery with the latissimus dorsi flap is a common occurrence. Botulinum neurotoxin (BoNT) injection during surgery is effective in reducing postoperative pain. This study aimed to determine the most appropriate locations for BoNT injection. A modified Sihler’s method was performed on the latissimus dorsi muscles in 16 specimens. Intramuscular nerve arborization was noted under the landmark of the medial side surgical neck of the humerus to the line crossing the spinous process of T5 and the middle of the iliac crest. The latissimus dorsi muscles were divided into medial, middle, and lateral segments with 10 transverse divisions to give 10 sections (each 10%). Intramuscular nerve arborization of the latissimus dorsi muscle was the largest from the medial and lateral part of the muscle ranging from 40 to 60%, middle part from 30 to 60% and medial, middle and lateral part from 70 to 90%. The nerve entry points were at the medial and lateral part with 20–40% regarding the medial side of surgical neck of the humerus to the line crossing spinous process of T5 to the middle of iliac crest. These outcomes propose that an injection of BoNT into the latissimus dorsi muscles should be administered into specific zones.
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Affiliation(s)
- Kyu-Ho Yi
- COVID-19 Division, Wonju Public Health Center, Wonju 26417, Korea;
- Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, BK21 PLUS Project, Yonsei University College of Dentistry, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea;
| | - Hyung-Jin Lee
- Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, BK21 PLUS Project, Yonsei University College of Dentistry, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea;
| | | | - Hee-Jin Kim
- Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, BK21 PLUS Project, Yonsei University College of Dentistry, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea;
- Department of Materials Science & Engineering, College of Engineering, Yonsei University, Seoul 03722, Korea
- Correspondence:
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Yi KH, Lee JH, Kim HM, Kim HJ. The botulinum neurotoxin for pain control after breast reconstruction: neural distribution of the pectoralis major muscle. Reg Anesth Pain Med 2022; 47:322-326. [PMID: 35039438 DOI: 10.1136/rapm-2021-102653] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Accepted: 01/02/2022] [Indexed: 12/24/2022]
Abstract
INTRODUCTION The use of the botulinum neurotoxin injection is a growing area of research and clinical activity, with a focus on its role in facilitating postoperative pain management after reconstructive breast surgery. The study aimed to find out the standard injection points for botulinum neurotoxin injection by revealing the intramuscular nerve arborization of the pectoralis major. METHODS Sihler's technique was conducted on the pectoralis major muscles (16 cadaveric specimens). The intramuscular nerve arborization was documented relative to the inferior border of the clavicle bone and lateral border of the sternum. RESULTS After the staining, the pectoralis major was divided into fifths transversely from the inferior border of the clavicle and vertically into fifths from the lateral border of the sternum. Intramuscular nerve arborization of the pectoralis major muscle was the largest in the middle sections of the muscle belly. DISCUSSION The results indicate that botulinum neurotoxin should be applied to the pectoralis major in certain regions. The regions of major arborization are optimal as the most effective and most reliable points for injecting botulinum neurotoxin.
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Affiliation(s)
- Kyu-Ho Yi
- Division of COVID-19, Wonju Public Health Center, Wonju, Korea
| | - Ji-Hyun Lee
- Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, BK21 FOUR Project, Yonsei University College of Dentistry, Seoul, Korea
| | | | - Hee-Jin Kim
- Yonsei University Medical Center, Seodaemun-gu, Korea
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Hsu PC, Chang KV, Chiu YH, Wu WT, Özçakar L. Comparative Effectiveness of Botulinum Toxin Injections and Extracorporeal Shockwave Therapy for Post-Stroke Spasticity: A Systematic Review and Network Meta-Analysis. EClinicalMedicine 2022; 43:101222. [PMID: 34927035 PMCID: PMC8649216 DOI: 10.1016/j.eclinm.2021.101222] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Revised: 10/29/2021] [Accepted: 11/17/2021] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND The anti-spasticity efficacy of botulinum toxin (BoNT) injection has been well established for patients with chronic stroke; however, extracorporeal shock wave therapy (ESWT), i.e. focused shockwave (FSW) and radial shockwave (RSW), has recently been applied. We aimed to investigate the comparative effectiveness of BoNT vs. ESWT in the reduction of spasticity among stroke survivors. METHODS PubMed, EMBASE, MEDLINE and Cochrane CENTRAL were searched from the earliest record to September 2021 for randomized controlled trials. Weighted mean differences (WMDs) on the reduction of the Modified Ashworth Scale before or at the 6th post-treatment week (short-term) and between the 7th and 12th weeks (mid-term) after the intervention were calculated. Ranking probabilities of the WMD were simulated to determine which treatment had the potential to possess the best effectiveness. inplasy.com registration: INPLASY202170018. FINDINGS A total of 33 studies comprising 1,930 patients were enrolled. The network meta-analysis revealed that BoNT injections, FSW and RSW were better in spasticity reduction than the control treatment(s) at the short term, with WMDs of -0.69 (95% CI, -0.87 to -0.50), -0.36 (95% CI, -0.69 to -0.03) and -0.62 (95% CI, -0.84 to -0.40), respectively. Likewise, mid-term effects of BoNT injections, FSW and RSW also revealed superiority, with WMDs of -0.44 (95% CI, -0.62 to -0.26), -0.74 (95% CI, -1.26 to -0.23) and -0.79 (95% CI, -1.07 to -0.51), respectively. Ranking probability analysis revealed that RSW had the highest probability of being the best treatment for spasticity reduction at the short-term (62.2%) and mid-term (72.3%) periods during the follow up. INTERPRETATION BoNT injections and ESWT are effective in alleviating post-stroke spasticity at the mid-term. The effectiveness of ESWT was comparable to BoNT injections, and RSW had the potential to be the best treatment for spasticity reduction among the three treatment options. More prospective trials incorporating head-to-head comparisons of BoNT injections vs. ESWT are needed to validate the role of ESWT in reducing post-stroke spasticity. FUNDING The current research project was supported by (1) National Taiwan University Hospital, Bei-Hu Branch; (2) Ministry of Science and Technology (MOST 106-2314-B-002-180-MY3 and 109-2314-B-002-114-MY3); 3) Taiwan Society of Ultrasound in Medicine.
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Affiliation(s)
- Po-Cheng Hsu
- Department of Physical Medicine and Rehabilitation, Taipei Veterans General Hospital, Taipei, Taiwan
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Ke-Vin Chang
- Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Bei-Hu Branch, Taipei, Taiwan
- Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- Center for Regional Anesthesia and Pain Medicine, Wang-Fang Hospital, Taipei Medical University, Taipei, Taiwan
- Corresponding author. Ke-Vin Chang, MD, PhD, Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Bei-Hu Branch and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yi-Hsiang Chiu
- Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Wei-Ting Wu
- Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital, Bei-Hu Branch, Taipei, Taiwan
- Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Levent Özçakar
- Department of Physical and Rehabilitation Medicine, Hacettepe University Medical School, Ankara, Turkey
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Vinehout K, Tynes K, Sotelo MR, Hyngstrom AS, McGuire JR, Schmit BD. Changes in Cortical Activity in Stroke Survivors Undergoing Botulinum Neurotoxin Therapy for Treatment of Focal Spasticity. FRONTIERS IN REHABILITATION SCIENCES 2021; 2:735819. [PMID: 36188774 PMCID: PMC9397708 DOI: 10.3389/fresc.2021.735819] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/03/2021] [Accepted: 11/25/2021] [Indexed: 11/24/2022]
Abstract
Background: Botulinum NeuroToxin-A (BoNT-A) relieves muscle spasticity and increases range of motion necessary for stroke rehabilitation. Determining the effects of BoNT-A therapy on brain neuroplasticity could help physicians customize its use and predict its outcome. Objective: The purpose of this study was to investigate the effects of Botulinum Toxin-A therapy for treatment of focal spasticity on brain activation and functional connectivity. Design: We used functional Magnetic Resonance Imaging (fMRI) to track changes in blood oxygen-level dependent (BOLD) activation and functional connectivity associated with BoNT-A therapy in nine chronic stroke participants, and eight age-matched controls. Scans were acquired before BoNT-A injections (W0) and 6 weeks after the injections (W6). The task fMRI scan consisted of a block design of alternating mass finger flexion and extension. The voxel-level changes in BOLD activation, and pairwise changes in functional connectivity were analyzed for BoNT-A treatment (stroke W0 vs. W6). Results: BoNT-A injection therapy resulted in significant increases in brain activation in the contralesional premotor cortex, cingulate gyrus, thalamus, superior cerebellum, and in the ipsilesional sensory integration area. Lastly, cerebellar connectivity correlated with the Fugl-Meyer assessment of motor impairment before injection, while premotor connectivity correlated with the Fugl-Meyer score after injection. Conclusion: BoNT-A therapy for treatment of focal spasticity resulted in increased brain activation in areas associated with motor control, and cerebellar connectivity correlated with motor impairment before injection. These results suggest that neuroplastic effects might take place in response to improvements in focal spasticity.
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Affiliation(s)
- Kaleb Vinehout
- Department of Biomedical Engineering, Marquette University and the Medical College of Wisconsin, Milwaukee, WI, United States
| | - Kelsey Tynes
- Department of Biomedical Engineering, Marquette University and the Medical College of Wisconsin, Milwaukee, WI, United States
| | - Miguel R. Sotelo
- Department of Biomedical Engineering, Marquette University and the Medical College of Wisconsin, Milwaukee, WI, United States
| | - Allison S. Hyngstrom
- Department of Physical Therapy, Marquette University, Milwaukee, WI, United States
| | - John R. McGuire
- Department of Physical Medicine and Rehabilitation, Medical College of Wisconsin, Milwaukee, WI, United States
| | - Brian D. Schmit
- Department of Biomedical Engineering, Marquette University and the Medical College of Wisconsin, Milwaukee, WI, United States
- Department of Physical Medicine and Rehabilitation, Medical College of Wisconsin, Milwaukee, WI, United States
- *Correspondence: Brian D. Schmit
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Sakamoto D, Hamaguchi T, Nakayama Y, Hada T, Abo M. Changes in motor paralysis involving upper extremities of outpatient chronic stroke patients from temporary rehabilitation interruption due to spread of COVID-19 infection: An observational study on pre- and post-survey data without a control group. PLoS One 2021; 16:e0260743. [PMID: 34882736 PMCID: PMC8659304 DOI: 10.1371/journal.pone.0260743] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 11/17/2021] [Indexed: 11/18/2022] Open
Abstract
Background Outpatient rehabilitation was temporarily suspended because of coronavirus disease (COVID-19), and there was a risk that patients’ activities of daily living (ADLs) would decrease and physical functions unmaintained. Therefore, we investigated the ADLs and motor functions of chronic stroke patients whose outpatient rehabilitation was temporarily interrupted. Methods In this observational study, the Fugl-Meyer Assessment of the Upper Extremity (FMA-UE), Action Research Arm Test (ARAT), and Barthel Index (BI) scores of 49 stroke hemiplegic patients at 6 and 3 months before rehabilitation interruptions were retrospectively determined and were prospectively investigated on resumption of outpatient rehabilitation. Presence or absence of symptoms and difficulties caused by the interruption period (IP) was investigated using a binomial method. Deltas were analyzed using a generalized linear model (GLM) according to the survey period. Age, sex, severity of FMA-UE immediately post-resumption and post-onset period were used as covariates. For survey items showing significant model fit, the 95% confidence interval of minimum detectable change (MDC95) was calculated, and the amount of change was compared. Questionnaire responses were tested via proportion ratio. Statistical significance was set at 5%. Results The FMA-UE part A and total scores were significantly model fit depending on periods. The estimated FMA-UE total score decreased by 1.64 (z = −2.38, p = 0.02) during the 3-month IP. No fits were observed by GLM in other parts of the FMA-UE, ARAT, or BI. The calculated MDC95 was 3.58 for FMA-UE part A and 4.50 for FMA-UE overall. Answers to questions regarding sleep disturbance and physical pain were significantly biased toward “no” in the psychosomatic function items (p<0.05). There was no bias in the distribution of answers to questions regarding joint stiffness, muscle weakness, muscle stiffness, and difficulty in moving arms and hands. All 16 questions regarding activities and participation items were significantly biased toward answers “no” (p<0.05). Conclusions The FMA-UE part A and total scores were affected. Patients complained of subjective symptoms related to upper limb paralysis after the IP. Since ADLs of patients were maintained, the therapist can recommend that patients not receiving outpatient treatments be evaluated in relation to the shoulder, elbow, and forearm and instructed on self-training to maintain motor function.
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Affiliation(s)
- Daigo Sakamoto
- Department of Rehabilitation Medicine, The Jikei University School of Medicine Hospital, Tokyo, Japan
- Department of Rehabilitation, Graduate School of Health Science, Saitama Prefectural University, Saitama, Japan
| | - Toyohiro Hamaguchi
- Department of Rehabilitation, Graduate School of Health Science, Saitama Prefectural University, Saitama, Japan
- * E-mail: (TH); (MA)
| | - Yasuhide Nakayama
- Department of Rehabilitation Medicine, The Jikei University School of Medicine Hospital, Tokyo, Japan
- Department of Rehabilitation Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Takuya Hada
- Department of Rehabilitation Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Masahiro Abo
- Department of Rehabilitation Medicine, The Jikei University School of Medicine, Tokyo, Japan
- * E-mail: (TH); (MA)
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27
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Şengül İ, Aşkın A, Tosun A. Effect of muscle selection for botulinum neurotoxin treatment on spasticity in patients with post-stroke elbow flexor muscle over-activity: an observational prospective study. Somatosens Mot Res 2021; 39:10-17. [PMID: 34632927 DOI: 10.1080/08990220.2021.1986383] [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: 10/20/2022]
Abstract
PURPOSE/AIM To investigate the effect of muscle selection for botulinum neurotoxin A (BoNT-A) treatment on spasticity in patients with post-stroke elbow flexor muscle over-activity. MATERIALS AND METHODS Chronic stroke patients with a deforming spastic paresis in the upper limb (elbow flexion with forearm pronation) who were injected BoNT-A into at least one of elbow flexor muscles (brachialis, brachioradialis, and biceps brachii) were included in this prospective observational study. The main outcome measure was spasticity angle by Tardieu Scale recorded at pre-treatment and week 4 after treatment. RESULTS Three muscle selection groups with sufficient sample size for statistical analysis were able to be created; brachialis (n = 14), biceps brachii (n = 21), and brachialis plus brachioradialis (n = 11). Although there was a significant improvement in spasticity angle within all groups over time (p < 0.05), the change in spasticity angle was not different between the groups (p > 0.05 for each pairwise comparison). However, the magnitude of the change in spasticity angle was larger in the groups in which brachialis was preferred. CONCLUSIONS In stroke patients with a spontaneous spastic posture of elbow flexion and forearm pronation, targeting brachialis for BoNT-A injection seems more effective in reducing the severity of spasticity. CLINICAL TRIAL REGISTRATION NO NCT04036981.
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Affiliation(s)
- İlker Şengül
- Department of Physical Medicine and Rehabilitation, School of Medicine, İzmir Kâtip Çelebi University, İzmir, Turkey
| | - Ayhan Aşkın
- Department of Physical Medicine and Rehabilitation, School of Medicine, İzmir Kâtip Çelebi University, İzmir, Turkey
| | - Aliye Tosun
- Department of Physical Medicine and Rehabilitation, School of Medicine, İzmir Kâtip Çelebi University, İzmir, Turkey
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28
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Dimitrova R, McCusker E, Gormley M, Fehlings D, Alter KE, Greaves S, Liu C, Brin MF. Efficacy and safety of onabotulinumtoxinA with standardized occupational therapy for treatment of pediatric upper limb spasticity: Phase III placebo-controlled randomized trial. NeuroRehabilitation 2021; 49:469-479. [PMID: 34334431 PMCID: PMC8673521 DOI: 10.3233/nre-210071] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
BACKGROUND: This is the first large study of onabotulinumtoxinA as treatment for pediatric upper limb spasticity. OBJECTIVE: Evaluate efficacy and safety of a single treatment with onabotulinumtoxinA plus occupational therapy (OT). METHODS: In this registrational phase III, multinational study (NCT01603602), participants were randomized 1:1:1 to onabotulinumtoxinA 3 U/kg/OT, 6 U/kg/OT, or placebo/OT. Primary endpoint was average change from baseline at weeks 4 and 6 in Modified Ashworth Scale-Bohannon (MAS) score. Secondary endpoints included Modified Tardieu Scale (MTS), Clinical Global Impression of Change (CGI) and functional Goal Attainment Scale (GAS). RESULTS: 235 participants were randomized. At weeks 4 and 6, onabotulinumtoxinA groups had greater mean reductions in MAS (both –1.9; p < 0.001) versus placebo (–1.2). OnabotulinumtoxinA doses improved dynamic tone per MTS. Mean CGI at weeks 4 and 6 was unchanged in the overall population, but improved in a post hoc analysis of patients with a single affected upper limb (UL) muscle group (elbow or wrist). GAS score for passive goals was significantly higher for 6 U/kg versus placebo at week 12. Most AEs were mild/moderate in severity; overall incidence was similar between groups. CONCLUSIONS: OnabotulinumtoxinA (3 and 6 U/kg) was safe and effective in reducing upper limb spasticity in pediatric participants.
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Affiliation(s)
| | | | - Mark Gormley
- Gillette Children's Specialty Healthcare, St Paul, MN, USA
| | - Darcy Fehlings
- Holland Bloorview Kids Rehab Hospital, Department of Paediatrics, Toronto, ON, Canada
| | | | - Susan Greaves
- The Royal Children's Hospital, Melbourne, Victoria, Australia
| | | | - Mitchell F Brin
- Allergan, an AbbVie company, Irvine, CA, USA.,University of California, Irvine, CA, USA
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29
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Yi KH, Lee HJ, Lee JH, Seo KK, Kim HJ. Application of Botulinum Neurotoxin Injections in TRAM Flap for Breast Reconstruction: Intramuscular Neural Arborization of the Rectus Abdominis Muscle. Toxins (Basel) 2021; 13:269. [PMID: 33918558 PMCID: PMC8070362 DOI: 10.3390/toxins13040269] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 04/06/2021] [Accepted: 04/07/2021] [Indexed: 02/06/2023] Open
Abstract
Breast reconstruction after mastectomy is commonly performed using transverse rectus abdominis myocutaneous (TRAM) flap. Previous studies have demonstrated that botulinum neurotoxin injections in TRAM flap surgeries lower the risk of necrosis and allow further expansion of arterial cross-sectional diameters. The study was designed to determine the ideal injection points for botulinum neurotoxin injection by exploring the arborization patterns of the intramuscular nerves of the rectus abdominis muscle. A modified Sihler's method was performed on 16 rectus abdominis muscle specimens. Arborization of the intramuscular nerves was determined based on the most prominent point of the xyphoid process to the pubic crest. All 16 rectus abdominis muscle specimens were divided into four muscle bellies by the tendinous portion. The arborized portions of the muscles were located on the 5-15%, 25-35%, 45-55%, and 70-80% sections of the 1st, 2nd, 3rd, and 4th muscle bellies, respectively. The tendinous portion was located at the 15-20%, 35-40%, 55-60%, and 90-100% sections. These results suggest that botulinum neurotoxin injections into the rectus abdominis muscles should be performed in specific sections.
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Affiliation(s)
- Kyu-Ho Yi
- Wonju City Public Health Center, Wonju-Si, Kangwondo 26417, Korea;
- Department of Oral Biology, Division in Anatomy and Developmental Biology, Human Identification Research Institute, BK 21 FOUR Project, Yonsei University College of Dentistry, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea; (H.-J.L.); (J.-H.L.)
| | - Hyung-Jin Lee
- Department of Oral Biology, Division in Anatomy and Developmental Biology, Human Identification Research Institute, BK 21 FOUR Project, Yonsei University College of Dentistry, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea; (H.-J.L.); (J.-H.L.)
| | - Ji-Hyun Lee
- Department of Oral Biology, Division in Anatomy and Developmental Biology, Human Identification Research Institute, BK 21 FOUR Project, Yonsei University College of Dentistry, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea; (H.-J.L.); (J.-H.L.)
| | | | - Hee-Jin Kim
- Department of Oral Biology, Division in Anatomy and Developmental Biology, Human Identification Research Institute, BK 21 FOUR Project, Yonsei University College of Dentistry, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea; (H.-J.L.); (J.-H.L.)
- Department of Materials Science & Engineering, College of Engineering, Yonsei University, Seoul 03722, Korea
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30
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Riganello F, Soddu A, Tonin P. Addressing Pain for a Proper Rehabilitation Process in Patients With Severe Disorders of Consciousness. Front Pharmacol 2021; 12:628980. [PMID: 33679413 PMCID: PMC7926206 DOI: 10.3389/fphar.2021.628980] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Accepted: 01/08/2021] [Indexed: 01/18/2023] Open
Abstract
Consciousness constitutes a fundamental prerequisite in the individual appraisal and experience of pain. In the same way, a person needs to be able to report on pain perception. Patients who suffered a severe brain injury with disorders of consciousness (DOC) represent a spectrum of pathologies affecting patients' capacity to interact with the external world. In these patients, the most relevant aspects in response to pain are physiologic and behavioral. The treatments and management of pain are challenging issues in these patients, arising serious ethical concerns and bringing emotional load among medical staff, caregivers, and relatives. In this review, we report the importance of having a correct pain management in DOC patients, to individuate the best pharmacological treatment that can make the difference in detecting a behavioral response, indicative of a change in the level of consciousness, and in planning a more effective rehabilitative approach.
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Affiliation(s)
- F. Riganello
- Research in Advanced NeuroRehabilitation, Istituto Sant’Anna, Crotone, Italy
| | - A. Soddu
- Department of Physics and Astronomy, Brain and Mind Institute, Western University, London, ON, Canada
| | - P. Tonin
- Research in Advanced NeuroRehabilitation, Istituto Sant’Anna, Crotone, Italy
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Abstract
Spasticity is one component of the upper motor neuron (UMN) syndrome resulting from a multitude of neurologic conditions, such as stroke, brain injury, spinal cord injury, multiple sclerosis, and cerebral palsy. It is clinically recognized as a phenomenon of velocity-dependent increase in resistance, i.e., hypertonia. Recent advances in the pathophysiology of spasticity improve our understanding of mechanisms underlying this complex phenomenon and its relations to other components of UMN syndrome (weakness and disordered motor control), as well as the resultant clinical problems. This theoretical framework provides a foundation to set up treatment goals and to guide goal-oriented clinical assessment and treatment. Among a spectrum of treatment options, botulinum toxin (BoNT) therapy is the preferred treatment for focal spasticity. The evidence is very robust that BoNT therapy effectively reduces spasticity; however, it does not improve voluntary movement. In this chapter, we highlight a few issues on how to achieve the best clinical outcomes of BoNT therapy, such as dosing, dilution, guidance techniques, adjunctive therapies, early treatment, repeated injections, and central effects, as well as the ways to improve motor function in selected subgroups of patients with spasticity. We also discuss the reasons of poor responses to BoNT therapy and when not to use BoNT therapy.
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Affiliation(s)
- Sheng Li
- Department of Physical Medicine and Rehabilitation, McGovern Medical School, University of Texas Health Science Center Houston (UTHealth), Houston, TX, USA.
- TIRR Memorial Hermann Hospital, Houston, TX, USA.
| | - Gerard E Francisco
- Department of Physical Medicine and Rehabilitation, McGovern Medical School, University of Texas Health Science Center Houston (UTHealth), Houston, TX, USA
- TIRR Memorial Hermann Hospital, Houston, TX, USA
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32
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Yi KH, Lee KL, Lee JH, Hu HW, Lee K, Seo KK, Kim HJ. Guidelines for botulinum neurotoxin injections in piriformis syndrome. Clin Anat 2020; 34:1028-1034. [PMID: 33347678 DOI: 10.1002/ca.23711] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Revised: 11/25/2020] [Accepted: 12/15/2020] [Indexed: 11/06/2022]
Abstract
BACKGROUND The piriformis muscle is normally involved in piriformis syndrome and can be treated with botulinum neurotoxin using several different injection methods. However, definitive injection guidelines for the muscle have not been reported previously. AIMS This study aimed to determine the ideal area for injections based on the intramuscular nerve distribution as obtained using a modified Sihler's staining technique. MATERIALS AND METHODS A modified Sihler's method was applied to the piriformis muscle in 15 specimens. The intramuscular arborization areas were identified based on two anatomical landmarks: (a) the lateral border of the sacrum bone and (b) the greater trochanter. RESULTS The nerve entry point for both piriformis muscles was found in the area between the lateral border of the sacrum and one-fifth of the distance toward the greater trochanter. The intramuscular nerve distribution for the piriformis muscle had the largest arborization patterns between one-fifth and two-fifths of the distance from the sacrum to the greater trochanter. The piriformis muscle was tendinous from two-fifths of the distance to the greater trochanter. DISCUSSION This study has yielded suggested optimal injection locations for the piriformis muscle relative to external anatomical landmarks. CONCLUSION Clinicians can use these guidelines to ensure the effectiveness of not only botulinum neurotoxin injections but also other agents such as steroids, anesthetics, and normal saline. These guidelines will also help to avoid adverse outcomes of injection treatments.
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Affiliation(s)
- Kyu-Ho Yi
- Inje County Public Health Center, Inje-gun, South Korea.,Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, BK21 PLUS Project, Yonsei University College of Dentistry, Seoul, South Korea
| | - Kyu-Lim Lee
- Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, BK21 PLUS Project, Yonsei University College of Dentistry, Seoul, South Korea
| | - Ji-Hyun Lee
- Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, BK21 PLUS Project, Yonsei University College of Dentistry, Seoul, South Korea
| | - Hye-Won Hu
- Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, BK21 PLUS Project, Yonsei University College of Dentistry, Seoul, South Korea
| | - Kangwoo Lee
- Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, BK21 PLUS Project, Yonsei University College of Dentistry, Seoul, South Korea
| | | | - Hee-Jin Kim
- Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, BK21 PLUS Project, Yonsei University College of Dentistry, Seoul, South Korea.,Department of Materials Science & Engineering, College of Engineering, Yonsei University, Seoul, South Korea
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Ayyoub Z, Brashear A, Banach M, Schoene R, Stringer W, Boodhoo T, Yushmanova I, Dimitrova R, Brin MF. Safety and Stability of Pulmonary Function in Patients with Decreased Respiratory Function Treated for Spasticity with OnabotulinumtoxinA. Toxins (Basel) 2020; 12:toxins12100661. [PMID: 33086749 PMCID: PMC7589715 DOI: 10.3390/toxins12100661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Revised: 09/25/2020] [Accepted: 10/07/2020] [Indexed: 11/27/2022] Open
Abstract
Two randomized, placebo-controlled studies evaluated the pulmonary function safety of onabotulinumtoxinA (onabotA) for treatment of upper and/or lower limb spasticity. Patients with stable baseline respiratory status received one or two treatments with placebo, 240 U, or 360 U of onabotA. Pulmonary function tests, adverse events, and efficacy were measured at least every 6 weeks for 18 weeks (Study 1) or 30 weeks (Study 2). Study 1 enrolled 109 patients (n = 36–37/group) and Study 2 enrolled 155 patients (n = 48–54/group). Mean baseline forced vital capacity (FVC) was 76–78% of predicted per group in Study 1 and 71% of predicted per group in Study 2. In Study 1, change from baseline FVC values were significantly (p < 0.05) decreased vs. placebo at weeks 3 (240 U −57 mL vs. placebo +110 mL) and 12 (360 U −6 mL vs. +167 mL placebo). In Study 2, change from baseline FVC values were significantly decreased in the 360 U group vs. placebo at weeks 6 (−78 mL vs. +49 mL placebo), 13 (−60 mL vs. +119 mL placebo), 18 (−128 mL vs. +80 mL placebo), and 24 (−82 mL vs. +149 mL placebo). Individual pulmonary function-related adverse events were not correlated with PFT decreases. The most frequent pulmonary-related adverse events were nasopharyngitis (Study 1) and upper respiratory tract infection (Study 2). Ashworth scores were significantly improved at multiple time points in both studies. Injection of onabotA for spasticity in patients with decreased pulmonary function, at single and repeated doses of up to 360 U, was associated with small but statistically significant decreases in FVC or forced expiratory volume 1 s (FEV1) (>12% and 200 mL) that were subclinical and not correlated with any adverse clinical pulmonary events.
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Affiliation(s)
- Ziyad Ayyoub
- Rancho Los Amigos National Rehabilitation Center, Downey, CA 90242, USA;
- Clinical Professor of Medicine, David Geffen School of Medicine at University of California, Los Angeles, CA 90095, USA
- Department of Physical Medicine and Rehabilitation, Western University of Health Sciences, Pomona, CA 91766, USA
| | - Allison Brashear
- Department of Neurology, University of California, Sacramento, CA 95817, USA;
| | - Marta Banach
- Department of Neurology, Jagiellonian University, 31-007 Krakow, Poland;
| | | | - William Stringer
- Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA 90502, USA;
| | - Terry Boodhoo
- Allergan plc, an AbbVie Company, Irvine, CA 92612, USA; (T.B.); (I.Y.); (R.D.)
| | - Irina Yushmanova
- Allergan plc, an AbbVie Company, Irvine, CA 92612, USA; (T.B.); (I.Y.); (R.D.)
| | - Rozalina Dimitrova
- Allergan plc, an AbbVie Company, Irvine, CA 92612, USA; (T.B.); (I.Y.); (R.D.)
| | - Mitchell F. Brin
- Allergan plc, an AbbVie Company, Irvine, CA 92612, USA; (T.B.); (I.Y.); (R.D.)
- Department of Neurology, University of California, Irvine, CA 92697, USA
- Correspondence: ; Tel.: +1-714-246-4429
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Yi KH, Lee HJ, Choi YJ, Lee K, Lee JH, Kim HJ. Anatomical guide for botulinum neurotoxin injection: Application to cosmetic shoulder contouring, pain syndromes, and cervical dystonia. Clin Anat 2020; 34:822-828. [PMID: 32996645 DOI: 10.1002/ca.23690] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2020] [Revised: 09/27/2020] [Accepted: 09/27/2020] [Indexed: 11/10/2022]
Abstract
INTRODUCTION This study proposes an ideal botulinum toxin injection point of the trapezius muscle for shoulder line contouring, pain management, and functional impairment. This study describes the intramuscular nerve branching in the trapezius muscle, providing essential information for botulinum neurotoxin injection. METHOD A modified Sihler's method was performed on the trapezius muscles (16 specimens). The intramuscular arborization areas were elucidated regarding the external occipital protuberance superiorly, spinous process of the 12th thoracic vertebra inferiorly and acromion of the scapula. RESULT The intramuscular neural distribution for the superior, middle, and inferior regions of the trapezius muscle had the greatest arborized patterns in the horizontal 1/5-2/5 and vertical 2/10-4/10 sections, the horizontal 1/5-3/5 and vertical 4/10-5/10 sections, and the horizontal 1/5-2/5 and vertical 5/10-7/10 sections, respectively. DISCUSSION We propose that BoNT treatments should be directed to the horizontal 1/5-2/5 and vertical 2/10-4/10 sections of the superior trapezius, the horizontal 1/5-3/5 and vertical 4/10-5/10 sections of the middle trapezius and the horizontal 1/5-2/5 and vertical 5/10-7/10 sections of the inferior trapezius. Additionally, injective treatment at the horizontal 2/5-3/5 and vertical 2/10-4/10 nerve entry points should be avoided to prevent nerve trunk damage causing paralysis. According to our guidelines, clinicians can ensure minimal dose injections and fewer adverse effects in botulinum neurotoxin injective treatment.
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Affiliation(s)
- Kyu-Ho Yi
- Inje County Public Health Center, Inje, Republic of Korea.,Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, BK21 PLUS Project, Yonsei University College of Dentistry, Seoul, Republic of Korea
| | - Hyung-Jin Lee
- Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, BK21 PLUS Project, Yonsei University College of Dentistry, Seoul, Republic of Korea
| | - You-Jin Choi
- Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, BK21 PLUS Project, Yonsei University College of Dentistry, Seoul, Republic of Korea
| | - Kangwoo Lee
- Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, BK21 PLUS Project, Yonsei University College of Dentistry, Seoul, Republic of Korea
| | - Ji-Hyun Lee
- Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, BK21 PLUS Project, Yonsei University College of Dentistry, Seoul, Republic of Korea
| | - Hee-Jin Kim
- Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, BK21 PLUS Project, Yonsei University College of Dentistry, Seoul, Republic of Korea.,Department of Materials Science & Engineering, College of Engineering, Yonsei University, Seoul, Republic of Korea
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Yi KH, Lee HJ, Lee JH, Lee KL, Kim HJ. Effective botulinum neurotoxin injection in treating iliopsoas spasticity. Clin Anat 2020; 34:431-436. [PMID: 32805076 DOI: 10.1002/ca.23670] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Revised: 07/25/2020] [Accepted: 08/10/2020] [Indexed: 01/07/2023]
Abstract
INTRODUCTION To detect ideal locations for botulinum toxin (BoNT) injection by exploring the intramuscular nerve arborization of the psoas major and iliacus muscles. METHOD A modified Sihler's method was performed on the psoas major and iliacus muscles (16 specimens each). Intramuscular nerve arborization was recorded according to the most prominent point of the anterior superior iliac spine (ASIS), the posterior superior iliac spine (PSIS), the lesser trochanter (LT), and the transverse process of the 12th thoracic vertebra. RESULTS Intramuscular nerve arborization of the psoas major muscle was the largest from 1/5 to 3/5 the distance from the transverse process of the 12th thoracic vertebra to the PSIS, and the tendinous portion of the muscle occupied from 3/5 to 5/5 this distance. In terms of the plane of the ASIS, the PSIS, and the LT, the arborization of the iliacus muscle was the largest from 1/5 to 3/5 the horizontal distance and 0 to 1/3, the distance longitudinally, and from 1/5 to 2/5, the horizontal distance and 1/3 to 2/3, the longitudinal distance. DISCUSSION These results suggest that an injection of BoNT to the psoas major and iliacus muscle should be applied in specific areas. Additionally, the posterior approach is an ideal method for targeting only the psoas major because the injection point is above the PSIS. However, when treating both the psoas major and iliacus muscles, the proximal anterior approach is an ideal method according to the arborization patterns.
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Affiliation(s)
- Kyu-Ho Yi
- Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, BK21 PLUS Project, Yonsei University College of Dentistry, Seoul, Republic of Korea
| | - Hyung-Jin Lee
- Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, BK21 PLUS Project, Yonsei University College of Dentistry, Seoul, Republic of Korea
| | - Ji-Hyun Lee
- Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, BK21 PLUS Project, Yonsei University College of Dentistry, Seoul, Republic of Korea
| | - Kyu-Lim Lee
- Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, BK21 PLUS Project, Yonsei University College of Dentistry, Seoul, Republic of Korea
| | - Hee-Jin Kim
- Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, BK21 PLUS Project, Yonsei University College of Dentistry, Seoul, Republic of Korea.,Department of Materials Science and Engineering, College of Engineering, Yonsei University, Seoul, Republic of Korea
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Francisco GE, Bandari DS, Bavikatte G, Jost WH, McCusker E, Largent J, Zuzek A, Esquenazi A. High clinician- and patient-reported satisfaction with individualized onabotulinumtoxinA treatment for spasticity across several etiologies from the ASPIRE study. Toxicon X 2020; 7:100040. [PMID: 32875289 PMCID: PMC7452133 DOI: 10.1016/j.toxcx.2020.100040] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2019] [Revised: 04/23/2020] [Accepted: 05/14/2020] [Indexed: 11/30/2022] Open
Abstract
Etiology-specific onabotulinumtoxinA utilization to manage spasticity is largely unknown. In this 1-year interim analysis, we evaluated real-world onabotulinumtoxinA utilization and effectiveness across several etiologies from the Adult Spasticity International Registry (ASPIRE) study. ASPIRE is a multicenter, prospective, observational registry (NCT01930786) examining stroke, multiple sclerosis [MS], cerebral palsy [CP], traumatic brain injury [TBI], and spinal cord injury [SCI] patients with spasticity treated with onabotulinumtoxinA at the clinician's discretion. Assessments included onabotulinumtoxinA utilization (each session), clinician (subsequent session)/patient (5±1 weeks post-treatment) satisfaction, and the Disability Assessment Scale (DAS; subsequent session). 730 patients received ≥1 onabotulinumtoxinA treatment, with 37% naïve to botulinum toxin(s) for spasticity. The most common etiology was stroke (n=411, 56%), followed by MS (N=119, 16%), CP (N=77, 11%), TBI (N=45, 6%), and SCI (N=42, 6%). The total body mean cumulative dose (±SD) of onabotulinumtoxinA per session ranged from 296 U (±145) in CP to 406 U (±152) in TBI. The most commonly treated upper limb presentations were clenched fist (stroke, MS, and SCI), flexed wrist (CP), and flexed elbow (TBI). Equinovarus foot was the most commonly treated lower limb presentation in all etiologies. Stroke patients showed improved DAS scores for nearly all subscales in both limbs, indicative of improved global function. All etiologies showed improved lower limb mobility DAS scores. Across all sessions, clinicians (range: 87.4% [SCI]-94.2% [CP]) and patients (range: 67.6% [TBI]-89.7% [SCI]) reported extreme satisfaction/satisfaction that onabotulinumtoxinA helped manage spasticity, and clinicians (range: 94.6% [TBI]-98.8% [CP]) and patients (range: 88.4% [stroke]-91.2% [TBI]) would definitely/probably continue treatment. Treatment-related adverse events (TRAEs) and treatment-related serious adverse events (TRSAEs) were reported as follows: stroke: 10 TRAEs (2.2% patients), 3 TRSAEs (0.5%); MS: 5 TRAEs (4.2%), 0 TRSAEs; CP: 0 TRAEs, 0 TRSAEs; TBI: 1 TRAEs (2.2%), 0 TRSAEs; SCI: 0 TRAEs, 0 TRSAEs. No new safety signals were identified. High clinician- and patient-reported satisfaction were observed following individualized onabotulinumtoxinA treatment, as well as improved global function. Interim results from ASPIRE demonstrate etiology-specific similarities and differences in clinical approaches to manage spasticity.
ASPIRE found etiology-specific similarities and differences in real-world onabotulinumtoxinA utilization for spasticity. Across all etiologies, there was high clinician- and patient-reported satisfaction with onabotulinumtoxinA treatment. In DAS, all etiologies showed improved global function in lower limb mobility following onabotulinumtoxinA treatment. Adverse event data varied by etiology of spasticity; however, no new safety signals were identified. ASPIRE data may guide clinical strategies and educational programs to improve onabotulinumtoxinA spasticity management.
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Affiliation(s)
- Gerard E Francisco
- The University of Texas Health Science Center McGovern Medical School and TIRR Memorial Hermann, Houston, TX, USA
| | - Daniel S Bandari
- Multiple Sclerosis Center of California & Research Group, Newport Beach, CA, USA
| | | | - Wolfgang H Jost
- University of Freiburg, Department of Neurology, Freiburg im Breisgau, Germany.,Parkinson-Klinik Ortenau, Wolfach, Germany
| | | | - Joan Largent
- IQVIA Real-World Evidence Solutions, Cambridge, MA, USA
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Singh R, Clarke A. Real-life outcomes in spasticity management: features affecting goal achievement. BMJ Neurol Open 2020; 2:e000015. [PMID: 33681772 PMCID: PMC7903178 DOI: 10.1136/bmjno-2019-000015] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2019] [Revised: 03/27/2020] [Accepted: 05/14/2020] [Indexed: 11/05/2022] Open
Abstract
BACKGROUND/OBJECTIVE Spasticity is a complex and common condition but there is a lack of 'real-world' data on goal setting and spasticity treatment, as well as identifying those features that might be associated with goal achievement. Our aim was to provide such data. METHODS Prospective attenders at a multi-disciplinary spasticity clinic over 2 years followed for consecutive appointments. Patient demographics and doses of botulinum toxin injected were documented. Main outcome was achievement of a primary goal but secondary goals were also recorded. Independent variables were examined for association to the outcome. RESULTS A total of 606 goals were set in 224 patients. The majority (75.2%) were achieved with similar levels across active (72.5%), passive (75.7%) and pain (78.6%) goals. However, in terms of the primary goal, active primary goals were achieved less frequently (59.7%) than non-active primary goal (74.2%). A logistic regression confirmed that this was the only independent variable associated with primary goal achievement. The majority of patients (61.6%) required changes to their treatment between appointments, irrespective of time since diagnosis, age or aetiology. CONCLUSIONS Most goals set in spasticity clinic can be achieved irrespective of type of goal. However, active goals may be harder to accomplish when they are set as a primary goal. This may reflect the desire of individuals to prioritise a desirable goal rather than one that is achievable. While goal setting is important in the management of spasticity patients, very few patient or treatment factors are associated with outcome prediction. Further work needs to identify features that may predict successful outcome.
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Affiliation(s)
- Rajiv Singh
- Department of Rehabilitation Medicine, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
- School of Health and Related Research, The University of Sheffield, Sheffield, UK
| | - Alison Clarke
- Mobility and Specialised Rehabilitation Centre, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
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Kinoshita S, Ikeda K, Yasuno S, Takahashi S, Yamada N, Okuyama Y, Sasaki N, Hada T, Kuriyama C, Suzuki S, Hama M, Ozaki N, Watanabe S, Abo M. Dose-response of rPMS for upper Limb hemiparesis after stroke. Medicine (Baltimore) 2020; 99:e20752. [PMID: 32541528 PMCID: PMC7302622 DOI: 10.1097/md.0000000000020752] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Accepted: 05/19/2020] [Indexed: 11/25/2022] Open
Abstract
INTRODUCTION Repetitive peripheral magnetic stimulation (rPMS) therapy is an innovative and minimally invasive neurorehabilitative technique and has been shown to facilitate neural plasticity. However, there is at present no research that clarifies the dose-response of rPMS therapy on the recovery of upper limb hemiparesis after stroke. This trial aims to clarify the dose-response of rPMS therapy combined with intensive occupational therapy (OT) for chronic stroke patients with moderate to severe upper limb hemiparesis. METHODS AND ANALYSIS This multicenter, prospective, assessor-blinded, randomized controlled study with 3 parallel groups will be conducted from January 20, 2020 to September 30, 2022. Fifty patients will be randomly assigned in a ratio of 1:2:2 to the control group, the group receiving daily 2400 pulses of rPMS, or the group receiving daily 4800 pulses of rPMS, respectively. From the day after admission (Day 1), rPMS therapy and intensive OT will be initiated. The primary outcome is the change in the motor function of the affected upper extremity (Fugl-Meyer Assessment) between the time of admission (Day 0) and the day after 2 weeks of treatment (Day 14). Secondary outcomes will include the changes in spasticity, active range of motion, motor evoked potential, and activity of daily living. ETHICS AND DISSEMINATION The study was approved by the Jikei University Certified Review Board for all institutions (reference number: JKI19-020). Results of the primary and secondary outcomes will be published in a peer-reviewed journal and presented at international congresses. The results will also be disseminated to patients. TRIAL REGISTRATION NUMBER jRCTs032190191.
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Affiliation(s)
| | | | - Shinji Yasuno
- Clinical Research Support Center, The Jikei University School of Medicine, Minato-Ku, Tokyo, Japan
| | - Sho Takahashi
- Clinical Research Support Center, The Jikei University School of Medicine, Minato-Ku, Tokyo, Japan
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Lee J, Chun MH, Ko YJ, Lee SU, Kim DY, Paik NJ, Kwon BS, Park YG. Efficacy and Safety of MT10107 (Coretox) in Poststroke Upper Limb Spasticity Treatment: A Randomized, Double-Blind, Active Drug-Controlled, Multicenter, Phase III Clinical Trial. Arch Phys Med Rehabil 2020; 101:1485-1496. [PMID: 32497599 DOI: 10.1016/j.apmr.2020.03.025] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Revised: 03/29/2020] [Accepted: 03/31/2020] [Indexed: 11/28/2022]
Abstract
OBJECTIVE To compare the efficacy and safety of MT10107 (Coretox) with those of onabotulinum toxin A (Botox) in patients with poststroke upper limb spasticity DESIGN: Prospective, randomized, double-blind, active drug-controlled, multicenter, phase III clinical trial. SETTING Seven university hospitals in the Republic of Korea. PARTICIPANTS Patients (N=220) with poststroke upper limb spasticity. INTERVENTIONS All participants received a single injection of either MT10107 (Coretox group) or onabotulinum toxin A (Botox group). MAIN OUTCOME MEASURES The primary outcome was change in wrist flexor spasticity from baseline to week 4, which was assessed using the modified Ashworth scale (MAS). The secondary outcomes were MAS scores for wrist, elbow, and finger flexors; percentage of treatment responders (response rate); Disability Assessment Scale (DAS) score, and global assessment of treatment. Safety was evaluated based on adverse events, vital signs, physical examination findings, and laboratory test results. The efficacy and safety were evaluated at 4, 8, and 12 weeks postintervention. RESULTS The primary outcome was found to be -1.32±0.69 and -1.40±0.69 for the Coretox and Botox groups, respectively. MT10107 showed a non-inferior efficacy compared with onabotulinum toxin A, as the 95% confidence interval for between-group differences was -0.10 to 0.27 and the upper limit was less than the non-inferiority margin of 0.45. Regarding the secondary outcomes, MAS scores for all muscles and DAS scores showed a significant improvement at all time points in both groups, with no significant between-group difference. No significant between-group differences were observed regarding response rate, global assessment of treatment, and safety measures. CONCLUSIONS MT10107 showed no significant difference in efficacy and safety compared with onabotulinum toxin A in poststroke upper limb spasticity treatment.
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Affiliation(s)
- Junekyung Lee
- Department of Rehabilitation Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul
| | - Min Ho Chun
- Department of Rehabilitation Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul.
| | - Young Jin Ko
- Department of Rehabilitation Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul
| | - Shi-Uk Lee
- Department of Rehabilitation Medicine, Seoul National University College of Medicine, Seoul National University Boramae Medical Center, Seoul
| | - Deog Young Kim
- Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul
| | - Nam-Jong Paik
- Department of Rehabilitation Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam
| | - Bum Sun Kwon
- Department of Rehabilitation Medicine, Dongguk University Ilsan Hospital, Goyang
| | - Yoon Ghil Park
- Department of Rehabilitation Medicine, Gangnam Severance Hospital Yonsei University College of Medicine, Seoul, Republic of Korea
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Yi KH, Lee HJ, Choi YJ, Lee JH, Hu KS, Kim HJ. Intramuscular Neural Distribution of Rhomboid Muscles: Evaluation for Botulinum Toxin Injection Using Modified Sihler's Method. Toxins (Basel) 2020; 12:toxins12050289. [PMID: 32375284 PMCID: PMC7291336 DOI: 10.3390/toxins12050289] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Revised: 04/23/2020] [Accepted: 04/30/2020] [Indexed: 11/16/2022] Open
Abstract
This study describes the nerve entry point and intramuscular nerve branching of the rhomboid major and minor, providing essential information for improved performance of botulinum toxin injections and electromyography. A modified Sihler method was performed on the rhomboid major and minor muscles (10 specimens each). The nerve entry point and intramuscular arborization areas were identified in terms of the spinous processes and medial and lateral angles of the scapula. The nerve entry point for both the rhomboid major and minor was found in the middle muscular area between levels C7 and T1. The intramuscular neural distribution for the rhomboid minor had the largest arborization patterns in the medial and lateral sections between levels C7 and T1. The rhomboid major muscle had the largest arborization area in the middle section between levels T1 and T5. In conclusion, botulinum neurotoxin injection and electromyography should be administered in the medial and lateral sections of C7-T1 for the rhomboid minor and the middle section of T1-T7 for the rhomboid major. Injections in the middle section of C7-T1 should also be avoided to prevent mechanical injury to the nerve trunk. Clinicians can administer safe and effective treatments with botulinum toxin injections and other types of injections by following the methods in our study.
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Affiliation(s)
- Kyu-Ho Yi
- Inje County Public Health Center, Inje 24633, Korea;
| | - Hyung-Jin Lee
- Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, BK21 PLUS Project, Yonsei University College of Dentistry, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea; (H.-J.L.); (Y.-J.C.); (J.-H.L.); (K.-S.H.)
| | - You-Jin Choi
- Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, BK21 PLUS Project, Yonsei University College of Dentistry, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea; (H.-J.L.); (Y.-J.C.); (J.-H.L.); (K.-S.H.)
| | - Ji-Hyun Lee
- Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, BK21 PLUS Project, Yonsei University College of Dentistry, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea; (H.-J.L.); (Y.-J.C.); (J.-H.L.); (K.-S.H.)
| | - Kyung-Seok Hu
- Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, BK21 PLUS Project, Yonsei University College of Dentistry, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea; (H.-J.L.); (Y.-J.C.); (J.-H.L.); (K.-S.H.)
| | - Hee-Jin Kim
- Division in Anatomy and Developmental Biology, Department of Oral Biology, Human Identification Research Institute, BK21 PLUS Project, Yonsei University College of Dentistry, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea; (H.-J.L.); (Y.-J.C.); (J.-H.L.); (K.-S.H.)
- Department of Materials Science & Engineering, College of Engineering, Yonsei University, Seoul 03722, Korea
- Correspondence:
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Jia S, Liu Y, Shen L, Liang X, Xu X, Wei Y. Botulinum Toxin Type A for Upper Limb Spasticity in Poststroke Patients: A Meta-analysis of Randomized Controlled Trials. J Stroke Cerebrovasc Dis 2020; 29:104682. [PMID: 32305277 DOI: 10.1016/j.jstrokecerebrovasdis.2020.104682] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2019] [Revised: 12/21/2019] [Accepted: 01/16/2020] [Indexed: 10/24/2022] Open
Abstract
BACKGROUND AND AIM Botulinum toxin type A is considered to be an effective antispasmodic in recent years. We assess the effectiveness of botulinum toxin type A for the treatment of poststroke spasticity in the upper extremity using a meta-analysis. METHODS We searched several databases including PubMed, Web of Science, Embase, and Cochrane database for relevant studies, up until October 2017. All randomized controlled trials of botulinum toxin type A treat poststroke upper limb spasticity published were included. The primary outcome measure was modified ashworth score at the elbow, finger and wrist, pain score, and barthel index. RESULTS Ten randomized controlled trials were identified and reported sufficient data for inclusion in the pooled analysis (n = 950). The results of modified ashworth score at different joints, pain score, barthel index showed no difference was found in the effectiveness of botulinum toxin type A compared with placebo in the treatment of the upper limb spasticity after stroke. But modified ashworth score at the elbow was improver in Dysport subgroups (standardized mean difference [SMD] = -.39, 95%CI = -.67 to -.10, P = .008) compared with Botox subgroups (SMD = .08, 95%CI = -.68 to .83, P = .84). CONCLUSIONS The meta-analysis of these studies showed that the overall effectiveness of botulinum toxin type A does not seem to differ from placebo for poststroke Patients. But the meta-analysis yielded a favorable effect of Dysport compared with placebo based on 4 trials.
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Affiliation(s)
- Shiyu Jia
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yang Liu
- Department of Electromyography, Xiangtan Central Hospital, Xiangtan, China
| | - Liuyan Shen
- Department of Neurology, Luzhou People's Hospital, Luzhou, Sichuan, China
| | - Xue Liang
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xiaomin Xu
- Department of Neurology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
| | - Youdong Wei
- Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
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Chiu SY, Patel B, Burns MR, Legacy J, Wagle Shukla A, Ramirez-Zamora A, Deeb W, Malaty IA. High-dose Botulinum Toxin Therapy: Safety, Benefit, and Endurance of Efficacy. Tremor Other Hyperkinet Mov (N Y) 2020; 10:tre-10-749. [PMID: 32149014 PMCID: PMC7052428 DOI: 10.7916/tohm.v0.749] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2019] [Accepted: 01/15/2020] [Indexed: 06/10/2023] Open
Abstract
BACKGROUND Botulinum neurotoxin therapy (BoNT) is a powerful tool for treating many neurologic disorders. The U.S. Food and Drug Administration (FDA)-approved maximum onabotulinum toxin A (OnaA) dose is 400 units (U) per visit, but higher doses are commonly necessary, particularly when treating multiple body regions. METHODS We collected demographics, OnaA dose, body regions injected and indications, patient-reported efficacy via 7-point Clinical Global Impression Scale (CGIS), and duration of benefit. RESULTS Sixty-eight patients were identified receiving OnaA >400 U/session. Dystonia (n = 44) and spasticity (n = 24) were the most common indications for high-dose OnaA. Mean duration of benefit was 9 weeks (standard deviation [SD] 3). More than 70% of patients self-reported "very much improved" or "much improved" at 6 month, 1 year, and last visit. No serious adverse effects were reported. DISCUSSION The majority of patients tolerated >400 U OnaA with continued benefit. OnaA doses >400 U may be safe and effective in appropriate patients.
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Francisco GE, Jost WH, Bavikatte G, Bandari DS, Tang SFT, Munin MC, Largent J, Adams AM, Zuzek A, Esquenazi A. Individualized OnabotulinumtoxinA Treatment for Upper Limb Spasticity Resulted in High Clinician- and Patient-Reported Satisfaction: Long-Term Observational Results from the ASPIRE Study. PM R 2020; 12:1120-1133. [PMID: 31953896 PMCID: PMC7687094 DOI: 10.1002/pmrj.12328] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Accepted: 11/23/2019] [Indexed: 11/17/2022]
Abstract
Introduction OnabotulinumtoxinA treatment for spasticity is dependent on numerous factors and varies according to selected treatment goals. Objective To examine real‐world onabotulinumtoxinA treatment utilization and effectiveness in patients with upper limb spasticity over 2 years from the Adult Spasticity International Registry (ASPIRE) study. Design Multicenter, prospective, observational registry (NCT01930786). Setting Fifty‐four international clinical sites in North America, Europe, and Asia. Patients Adults (naïve or non‐naïve to botulinum toxins for spasticity) with upper limb focal spasticity related to upper motor neuron syndrome across multiple etiologies. Interventions OnabotulinumtoxinA administered at clinician's discretion. Main Outcome Measures OnabotulinumtoxinA utilization, clinician and patient satisfaction. Results Four hundred eighty‐four patients received ≥1 treatment of onabotulinumtoxinA for upper limb spasticity. Patients were on average 55.1 years old, 50.8% male, predominantly Caucasian (72.3%), and 38.6% were naïve to botulinum toxins. Stroke was the most frequently reported underlying etiology (74.0%). Most patients (81.2%) had moderate to severe spasticity at baseline. The most commonly treated upper limb clinical presentation was clenched fist (79.1% of patients). Across all presentations, onabotulinumtoxinA doses ranged between 5‐600U. Electromyography (EMG) was most often utilized to localize muscles (≥57.0% of treatment sessions). Clinicians (92.9% of treatment sessions) and patients (85.7%) reported being extremely satisfied/satisfied that treatment helped manage spasticity, and clinicians (98.6%) and patients (92.2%) would definitely/probably continue onabotulinumtoxinA treatment. One hundred seventy‐nine patients (37.0%) reported 563 adverse events (AEs); 15 AEs in 14 patients (2.9%) were considered treatment related. Sixty‐nine patients (14.3%) reported 137 serious AEs; 3 serious AEs in 2 patients (0.4%) were considered treatment related. No new safety signals were identified. Conclusions ASPIRE captured the real‐world individualized nature of onabotulinumtoxinA utilization for upper limb spasticity over 2 years, with consistently high clinician‐ and patient‐reported satisfaction. Data in this primary analysis will guide clinical use of onabotulinumtoxinA, as well as provide insights to improve educational programs on spasticity management.
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Affiliation(s)
- Gerard E Francisco
- The University of Texas Health Science Center McGovern Medical School and TIRR Memorial Hermann, Houston, TX
| | - Wolfgang H Jost
- Department of Neurology, University of Freiburg, Freiburg im Breisgau, Germany
| | | | - Daniel S Bandari
- Multiple Sclerosis Center of California & Research Group, Newport Beach, CA
| | - Simon F T Tang
- Department of Physical Medicine and Rehabilitation, Lotung Poh-Ai Hospital, Yilan, Taiwan
| | - Michael C Munin
- Department of Physical Medicine and Rehabilitation, University of Pittsburgh School of Medicine, Pittsburgh, PA
| | - Joan Largent
- IQVIA Real-World Evidence Solutions, Cambridge, MA
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Dimitrova R, James L, Liu C, Orejudos A, Yushmanova I, Brin MF. Safety of OnabotulinumtoxinA with Concomitant Antithrombotic Therapy in Patients with Muscle Spasticity: A Retrospective Pooled Analysis of Randomized Double-Blind Studies. CNS Drugs 2020; 34:433-445. [PMID: 32170665 PMCID: PMC7125063 DOI: 10.1007/s40263-020-00709-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
BACKGROUND OnabotulinumtoxinA is approved as a treatment across multiple indications. For the treatment of spasticity, onabotulinumtoxinA is injected directly into affected muscles. Intramuscular injections may result in local bleeding and related complications, especially in patients receiving anticoagulant therapy. Despite anticoagulants being commonly used, there is limited information in the medical literature regarding the safety of intramuscular medications in patients receiving oral anticoagulants. This retrospective analysis included pooled safety data from Allergan-sponsored studies evaluating onabotulinumtoxinA for the treatment of patients with muscle spasticity. OBJECTIVE The objective of this study was to determine the risk of bleeding complications in patients with post-stroke spasticity receiving antithrombotic therapy and intramuscular onabotulinumtoxinA. METHODS We conducted a retrospective analysis of pooled safety data from 16 randomized, double-blind, placebo-controlled Allergan-sponsored studies of onabotulinumtoxinA for the treatment of post-stroke upper or lower limb muscle spasticity, including adult patients with at least moderate upper or lower limb spasticity and receiving at least one dose of the study drug. Bleeding-related adverse events starting within 4 weeks of study treatment were assessed. The incidence rates of bleeding complications were compared for patients receiving classes of antithrombotic therapy vs those not receiving antithrombotic therapy and for those receiving onabotulinumtoxinA vs placebo (with or without antithrombotic therapy). RESULTS Of 1877 patients, 1182 received antithrombotic therapy. The overall incidence of bleeding complications was < 2%. In those receiving any antithrombotic therapy, the incidence of bleeding was 1.0% vs 1.4% (no antithrombotic therapy); after onabotulinumtoxinA, it was 0.9% for those receiving antithrombotic therapy vs 1.4% (no antithrombotic therapy), and for placebo 1.2% vs 1.4%, respectively. Subgroup results were similar. CONCLUSIONS No apparent increased risk of bleeding complications was observed following administration of onabotulinumtoxinA to patients receiving antithrombotic therapy. Nonetheless, patient education and careful observation of the injection site in patients receiving antithrombotic therapy remains warranted.
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Affiliation(s)
| | - Lynn James
- Allergan plc, 2525 Dupont Drive; T1-1B, Irvine, CA 92623-9534 USA
| | | | | | - Irina Yushmanova
- Allergan plc, 2525 Dupont Drive; T1-1B, Irvine, CA 92623-9534 USA
| | - Mitchell F. Brin
- Allergan plc, 2525 Dupont Drive; T1-1B, Irvine, CA 92623-9534 USA ,grid.266093.80000 0001 0668 7243University of California, Irvine, CA USA
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Arai S, Fukase Y, Okii A, Suzukamo Y, Suga T. Selection process for botulinum toxin injections in patients with chronic-stage hemiplegic stroke: a qualitative study. BMC Med Inform Decis Mak 2019; 19:280. [PMID: 31856809 PMCID: PMC6923967 DOI: 10.1186/s12911-019-1003-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2018] [Accepted: 12/11/2019] [Indexed: 11/10/2022] Open
Abstract
Background Botulinum toxin (BT) injection is a new treatment for spasticity with hemiplegia after stroke. How a patient decides to receive BT injections after becoming aware of the treatment remains unclear. In this exploratory qualitative study, we aimed to investigate patients’ decision-making about treatment strategies in collaboration with family and health professionals and to identify conflicts in patients’ feelings about BT treatment. Methods The study included six patients with stroke sequelae. Data were collected using comprehensive interviews and were analyzed using the grounded theory approach and trajectory equifinality modeling. Results After patients learned about BT treatment, they clearly exhibited the following two concurrent perceptions: “the restriction of one’s life due to disabilities” and “the ability to do certain things despite one’s disabilities.” Some patients reported a “fear of not being able to maintain the status quo owing to the side effects of BT.” To alleviate this fear, timely support from family members was offered, and patients overcame anxiety through creative thinking. However, there were also expressions that revealed patients’ difficulties dealing with negative events. These factors influenced the patients’ development of “expectations of BT” or “hesitations about BT.” Conclusions To establish treatment strategies in collaboration with patients, healthcare professionals should show supportive attitudes and have discussions with patients and their family members to help patients resolve their conflicts and should establish treatment strategies that maintain the positive aspects of patients’ lives.
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Affiliation(s)
- Sawako Arai
- Department of Clinical Psychology, Kawasaki University of Medical Welfare, 288, Matsushima, Kurashiki, Okayama, Japan.
| | - Yuko Fukase
- Department of Health Science, School of Allied Health Sciences, Kitasato University, Sagamihara, Kanagawa, Japan
| | - Akira Okii
- Physical Medicine and Rehabilitation Okii Clinic, Iwakuni, Yamaguchi, Japan
| | - Yoshimi Suzukamo
- Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Toshimitsu Suga
- Kansai Medical University Medical Center, Moriguchi, Osaka, Japan
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Effectiveness of Botulinum Toxin Treatment for Upper Limb Spasticity Poststroke Over Different ICF Domains: A Systematic Review and Meta-Analysis. Arch Phys Med Rehabil 2019; 100:1703-1725. [DOI: 10.1016/j.apmr.2019.01.016] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2018] [Revised: 12/17/2018] [Accepted: 01/21/2019] [Indexed: 11/20/2022]
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Marque P, Denis A, Gasq D, Chaleat-Valayer E, Yelnik A, Colin C, Pérennou D. Botuloscope: 1-year follow-up of upper limb post-stroke spasticity treated with botulinum toxin. Ann Phys Rehabil Med 2019; 62:207-213. [DOI: 10.1016/j.rehab.2019.06.003] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2019] [Revised: 05/31/2019] [Accepted: 06/13/2019] [Indexed: 11/16/2022]
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Camargo CHF, Teive HAG. Use of botulinum toxin for movement disorders. Drugs Context 2019; 8:212586. [PMID: 31258617 PMCID: PMC6586173 DOI: 10.7573/dic.212586] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Revised: 05/23/2019] [Accepted: 05/23/2019] [Indexed: 01/04/2023] Open
Abstract
The term movement disorders encompasses all disorders hypokinetic and hyperkinetic, which were previously known as extrapyramidal syndromes. With the definition of movement disorders and their diagnostic criteria and classifications, new studies for therapeutics could be performed. New drugs were launched, functional neurosurgery was developed, and the introduction of botulinum toxin (BoNT) for hyperkinesias was introduced. BoNT is an important therapy for dystonia, tics, myoclonus, and tremors. The aim of this review is to present the new and well-established uses of BoNT for movement disorders.
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Affiliation(s)
- Carlos Henrique Ferreira Camargo
- Neurological Diseases Group, Graduate Program of Internal Medicine, Internal Medicine Department, Hospital de Clínicas, Federal University of Paraná, Curitiba, PR, Brazil
| | - Hélio Afonso Ghizoni Teive
- Neurological Diseases Group, Graduate Program of Internal Medicine, Internal Medicine Department, Hospital de Clínicas, Federal University of Paraná, Curitiba, PR, Brazil.,Movement Disorders Unit, Neurology Service, Internal Medicine Department, Hospital de Clínicas, Federal University of Paraná, Curitiba, PR, Brazil
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Efficacy and Safety of Botulinum Toxin Type A for Limb Spasticity after Stroke: A Meta-Analysis of Randomized Controlled Trials. BIOMED RESEARCH INTERNATIONAL 2019; 2019:8329306. [PMID: 31080830 PMCID: PMC6475544 DOI: 10.1155/2019/8329306] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/19/2018] [Revised: 01/22/2019] [Accepted: 03/13/2019] [Indexed: 01/10/2023]
Abstract
Background Inconsistent data have been reported for the effectiveness of intramuscular botulinum toxin type A (BTXA) in patients with limb spasticity after stroke. This meta-analysis of available randomized controlled trials (RCTs) aimed to determine the efficacy and safety of BTXA in adult patients with upper and lower limb spasticity after stroke. Methods An electronic search was performed to select eligible RCTs in PubMed, Embase, and the Cochrane library through December 2018. Summary standard mean differences (SMDs) and relative risk (RR) values with corresponding 95% confidence intervals (CIs) were employed to assess effectiveness and safety outcomes, respectively. Results Twenty-seven RCTs involving a total of 2,793 patients met the inclusion criteria, including 16 and 9 trials assessing upper and lower limb spasticity cases, respectively. For upper limb spasticity, BTXA therapy significantly improved the levels of muscle tone (SMD=-0.76; 95% CI -0.97 to -0.55; P<0.001), physician global assessment (SMD=0.51; 95% CI 0.35-0.67; P<0.001), and disability assessment scale (SMD=-0.30; 95% CI -0.40 to -0.20; P<0.001), with no significant effects on active upper limb function (SMD=0.49; 95% CI -0.08 to 1.07; P=0.093) and adverse events (RR=1.18; 95% CI 0.72-1.93; P=0.509). For lower limb spasticity, BTXA therapy was associated with higher Fugl-Meyer score (SMD=5.09; 95%CI 2.16-8.01; P=0.001), but had no significant effects on muscle tone (SMD=-0.12; 95% CI -0.83 to 0.59; P=0.736), gait speed (SMD=0.06; 95% CI -0.02 to 0.15; P=0.116), and adverse events (RR=1.01; 95% CI 0.71-1.45; P=0.949). Conclusions BTXA improves muscle tone, physician global assessment, and disability assessment scale in upper limb spasticity and increases the Fugl-Meyer score in lower limb spasticity.
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Joussain C, Le Coz O, Pichugin A, Marconi P, Lim F, Sicurella M, Salonia A, Montorsi F, Wandosell F, Foster K, Giuliano F, Epstein AL, Aranda Muñoz A. Botulinum Neurotoxin Light Chains Expressed by Defective Herpes Simplex Virus Type-1 Vectors Cleave SNARE Proteins and Inhibit CGRP Release in Rat Sensory Neurons. Toxins (Basel) 2019; 11:toxins11020123. [PMID: 30791373 PMCID: PMC6409900 DOI: 10.3390/toxins11020123] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2019] [Revised: 02/07/2019] [Accepted: 02/15/2019] [Indexed: 02/06/2023] Open
Abstract
A set of herpes simplex virus type 1 (HSV-1) amplicon vectors expressing the light chains (LC) of botulinum neurotoxins (BoNT) A, B, C, D, E and F was constructed. Their properties have been assessed in primary cultures of rat embryonic dorsal root ganglia (DRG) neurons, and in organotypic cultures of explanted DRG from adult rats. Following infection of primary cultures of rat embryonic DRG neurons, the different BoNT LC induced efficient cleavage of their corresponding target Soluble N-ethylmaleimide-sensitive-factor Attachment protein Receptor (SNARE) protein (VAMP, SNAP25, syntaxin). A similar effect was observed following infection by BoNT-A LC of organotypic cultures of adult rat DRG. To quantify and compare the functional activities of the different BoNT LC, the inhibition of calcitonin gene-related protein (CGRP) secretion was assessed in DRG neurons following infection by the different vectors. All BoNT-LC were able to inhibit CGRP secretion although to different levels. Vectors expressing BoNT-F LC displayed the highest inhibitory activity, while those expressing BoNT-D and -E LC induced a significantly lower CGRP release inhibition. Cleavage of SNARE proteins and inhibition of CGRP release could be detected in neuron cultures infected at less than one transducing unit (TU) per neuron, showing the extreme efficacy of these vectors. To our knowledge this is the first study investigating the impact of vector-expressed transgenic BoNT LC in sensory neurons.
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Affiliation(s)
- Charles Joussain
- UMR U1179 INSERM/Université de Versailles Saint Quentin en Yvelines (UVSQ)-Paris Saclay, 78180 Montigny-le-Bretonneux, France.
- Neuro-Urology R. Poincaré Hospital AP-HP, 92380 Garches, France.
- Ipsen Innovation SAS, 91940 Les Ulis, France.
| | - Olivier Le Coz
- UMR U1179 INSERM/Université de Versailles Saint Quentin en Yvelines (UVSQ)-Paris Saclay, 78180 Montigny-le-Bretonneux, France.
| | - Andrey Pichugin
- UMR U1179 INSERM/Université de Versailles Saint Quentin en Yvelines (UVSQ)-Paris Saclay, 78180 Montigny-le-Bretonneux, France.
| | - Peggy Marconi
- Department of Chemical and Pharmaceutical Sciences (DipSCF), University of Ferrara, 44121 Ferrara, Italy.
| | - Filip Lim
- Centro de Biologia Molecular Severo Ochoa, CSIC-UAM, Universidad Autonoma de Madrid (UAM), 28049 Cantoblanco, Madrid, Spain.
| | - Mariaconcetta Sicurella
- Department of Chemical and Pharmaceutical Sciences (DipSCF), University of Ferrara, 44121 Ferrara, Italy.
- Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, 20129 Milan, Italy.
| | - Andrea Salonia
- Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, 20129 Milan, Italy.
- University Vita-Salute San Raffaele, 20129 Milan, Italy.
| | - Francesco Montorsi
- Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, 20129 Milan, Italy.
- University Vita-Salute San Raffaele, 20129 Milan, Italy.
| | - Francisco Wandosell
- Centro de Biologia Molecular Severo Ochoa, CSIC-UAM, Universidad Autonoma de Madrid (UAM), 28049 Cantoblanco, Madrid, Spain.
| | - Keith Foster
- Ipsen Bioinnovation Ltd., Abingdon, Oxon OX14 4RY, UK.
| | - François Giuliano
- UMR U1179 INSERM/Université de Versailles Saint Quentin en Yvelines (UVSQ)-Paris Saclay, 78180 Montigny-le-Bretonneux, France.
- Neuro-Urology R. Poincaré Hospital AP-HP, 92380 Garches, France.
| | - Alberto L Epstein
- UMR U1179 INSERM/Université de Versailles Saint Quentin en Yvelines (UVSQ)-Paris Saclay, 78180 Montigny-le-Bretonneux, France.
| | - Alejandro Aranda Muñoz
- UMR U1179 INSERM/Université de Versailles Saint Quentin en Yvelines (UVSQ)-Paris Saclay, 78180 Montigny-le-Bretonneux, France.
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