Winfred Mugge PhD, Liset E.M. Elstgeest PhD, Milan van Ginkel MSc, Lucas Pol BSc, IJsbrand de Lange MSc, Nicola Pambakian MSc, Alvaro Assis de Souza MSc, Rick C. Helmich MD, PhD, Daan J. Kamphuis MD
Background
Essential tremor (ET) is characterized by action tremor of the arms, which can interfere substantially with daily activities. Pharmacotherapy may be ineffective or associated with side effects, and stereotactic surgery is invasive. Hence, new accessible treatment options are urgently needed. An easy-to-use and lightweight orthotic device that exerts joint damping may provide an alternative solution for reducing tremor in daily activities.
Objective
Our goal was to assess the efficacy of a novel anti-tremor orthosis (STIL) in reducing clinical and accelerometry measures of distal arm tremor in ET.
Methods
In a randomized crossover single-blinded trial in 24 ET patients in a hospital setting, we compared three conditions: no orthosis (baseline), a sham device, and the anti-tremor orthosis (order randomized). The orthosis, but not the sham device, passively damped joints in the forearm. Participants performed seven tasks from the Tremor Research Group Essential Tremor Rating Scale (TETRAS). The two co-primary outcome measures were: clinical tremor severity (video-scored TETRAS) and tremor power (accelerometry). Patient satisfaction was self-assessed using the Dutch Quebec User Evaluation of Satisfaction with assistive Technology. Conditions were compared using Wilcoxon signed-rank tests.
Results
The anti-tremor orthosis significantly reduced TETRAS scores compared to sham and baseline (baseline: 19.0 ± 3.2, sham: 13.7 ± 3.9, orthosis: 9.9 ± 3.6; mean ± standard deviation). Similar effects were observed for tremor power, which was reduced by 87.4% (orthosis vs. baseline) and 59.5% (orthosis vs. sham) across all tasks. A total of 71% of participants were (very) satisfied and 12.5% reported minor adverse events (discomfort/redness of skin).
Martin Paucar, Tianyi Li, Åsa Bergendal, Irina Savitcheva, Kaveh Pourhamidi, José M. Laffita‐Mesa, Ann Nordgren, Martin Engvall, Per Uhlén, Kristina Lagerstedt‐Robinson, Per Svenningsson
{"title":"It Takes Guts: A Novel Model for Gut-to-Brain Propagation of Alpha-Synuclein and Tau","authors":"Kasandra Scholz BS, Talene A. Yacoubian MD, PhD","doi":"10.1002/mds.30124","DOIUrl":"10.1002/mds.30124","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"40 2","pages":"241-242"},"PeriodicalIF":7.4,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142988846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Paula Trujillo, Kaitlyn R. O'Rourke, Olivia C. Roman, Alexander K. Song, Kilian Hett, Amy Cooper, Bonnie K. Black, Manus J. Donahue, Cyndya A. Shibao, Italo Biaggioni, Daniel O. Claassen
Arianna Braccia MD, Nico Golfrè Andreasi MD, Francesco Ghielmetti MSc, Domenico Aquino MSc, Anna Paola Savoldi MD, Roberto Cilia MD, Roberta Telese MD, Fabiana Colucci MD, Gianfranco Gaudiano MD, Luigi Michele Romito PhD, Antonio Emanuele Elia PhD, Valentina Leta PhD, Vincenzo Levi MD, Nicolò Castelli MD, Grazia Devigili PhD, Sara Rinaldo MSc, Mario Stanziano MD, Valentina Caldiera MD, Marina Grisoli MD, Elisa Francesca Maria Ciceri MD, Roberto Eleopra MD
Background
Magnetic resonance–guided focused ultrasound (MRgFUS) thalamotomy of ventral intermediate (Vim) nucleus is useful to treat drug-resistant tremor-dominant Parkinson's disease (TdPD), but tremor relapse may occur. Predictors of relapse have been poorly investigated so far.
Objective
The aim of this study is to evaluate the role of clinico-demographic, procedural, and neuroradiological variables in determining clinical response, relapse, and adverse events (AEs) in TdPD after MRgFUS Vim-thalamotomy.
Methods
Fifty-two TdPD patients who consecutively underwent unilateral MRgFUS Vim-thalamotomy were prospectively evaluated at baseline and after 24 hours, 1 month, 6 months, and 12 months using MDS-UPDRS-III in off and on medication conditions. AEs were collected at each evaluation. Lesion volume was calculated at 24-hour magnetic resonance imaging (MRI). Patients with tremor improvement <30% in off medication were considered nonresponders (when detected after 24 hours) or relapsers (if detected from 1-month visit onward).
Results
All patients showed tremor improvement >30% at 24 hours. Tremor relapse occurred in 12 patients (23%), exclusively during the first month after thalamotomy. Relapse was associated with younger age (P = 0.030) and smaller lesion volume (P = 0.030). At 1 month, 22 patients (42%) had AEs; at 6 and 12 months, AEs persisted in 19% and 6% of cases. AEs at 6 months were associated with larger lesions (P = 0.018). All AEs were mild.
Hong Wang, Zakir Ullah, Eran Gazit, Marina Brozgol, Jeffrey M Hausdorff, Peter B Shull, Penina Ponger
Background: Wider step width and lower step-to-step variability are linked to improved gait stability and reduced fall risk. It is unclear if patients with spinocerebellar ataxia (SCA) can learn to adjust these aspects of gait to reduce fall risk.
Objectives: The aims were to examine the possibility of using wearable step width haptic biofeedback to enhance gait stability and reduce fall risk in individuals with SCA.
Methods: Thirteen people with SCA type 3 performed step width training (single session) using real-time feedback.
Results: Step width increased post-training (19.3 cm, interquartile range [IQR] 16.3-20.2 cm) and at retention (16.6 cm, IQR 16.2-21.1 cm), compared to baseline (11.0 cm, IQR 5.2-15.2 cm; P < 0.001). Step width variability decreased during post-training (19.7%, IQR 17.4%-26.2%) and at retention (22.3%, IQR 18.6%-30.2%), compared to baseline (44.5%, IQR 28.5%-71.2%; P < 0.001). Crossover steps, another mark of instability, decreased after training (P < 0.031).
<p>We extend our gratitude to Dr. Weise and colleagues for their insightful comments regarding our manuscript published in <i>Movement Disorders</i>. We greatly appreciate their consideration of additional adverse skin reactions caused by foslevodopa-foscarbidopa (LDP/CDP). In response, we would like to clarify the following points.</p><p>The case reported by Dr. Weise (similar to the case we reported in our study) involved a clinical finding of a dome-shaped nodule accompanied by tenderness, and pathological findings revealed inflammation observed from the deep dermis to the subcutaneous panniculitis. The difference between our cases is that the inflammatory cell infiltration observed in Dr. Weise's case mainly involved neutrophils and that observed in our case mainly involved lymphocytes. This difference is thought to be due to the differences in findings depending on the stage of panniculitis. In erythema nodosum and erythema induratum of Bazin, which are representative conditions of panniculitis, infiltrative inflammatory cells include lymphocytes, histiocytes, and neutrophils; in particular, in early lesions, the infiltration of inflammatory cells, which are mainly composed of neutrophils, is observed.<span><sup>1</sup></span> According to a review of factitial panniculitis, which is a subcutaneous tissue injury caused by various injections, neutrophilic panniculitis is observed in the acute phase. Lymphocytic infiltration is observed in the later phase.<span><sup>2</sup></span> Because the cause of skin disorders induced by LDP/CDP is unknown, this difference in inflammatory cell infiltration is fascinating, and we would like to reexamine the pathological findings in more cases to understand the pathology of this disorder.</p><p>Based on the results of clinical trials of LDP/CDP, the most frequent adverse events on the skin have been reported to be “injection site erythema,” “injection site pain,” and “cellulitis.”<span><sup>3</sup></span> In our experience with actual cases, skin disorders can be generally divided into three manifestations: injection site erythema, injection site nodules, and injection site cellulitis. Injection site erythema is a skin reaction that occurs when LDP/CDP cannot be injected perpendicular to the skin surface, and we hypothesize that this skin reaction can be avoided by providing injection instructions. Additionally, injection site nodules are thought to be manifestations of panniculitis caused by irritation from the drug. Injection site cellulitis is associated with secondary infection due to the injection procedure, and the clinical findings are similar to those of the aforementioned findings of panniculitis; therefore, evaluating the presence or absence of the inflammatory findings in blood tests is necessary. However, we believe this outcome can be avoided by performing clean procedures. We believe that the accumulation and examination of cases are necessary to develop treatment strategies based to a greate
{"title":"Reply to: “Neutrophil-Rich Infusion Site Reactions after Continuous Subcutaneous Application of Foslevodopa/Foscarbidopa”","authors":"Nagisa Yoshihara MD, PhD, Rei Watanabe MD, PhD, Noriko Nishikawa MD, PhD, Nobutaka Hattori MD, PhD","doi":"10.1002/mds.30120","DOIUrl":"10.1002/mds.30120","url":null,"abstract":"<p>We extend our gratitude to Dr. Weise and colleagues for their insightful comments regarding our manuscript published in <i>Movement Disorders</i>. We greatly appreciate their consideration of additional adverse skin reactions caused by foslevodopa-foscarbidopa (LDP/CDP). In response, we would like to clarify the following points.</p><p>The case reported by Dr. Weise (similar to the case we reported in our study) involved a clinical finding of a dome-shaped nodule accompanied by tenderness, and pathological findings revealed inflammation observed from the deep dermis to the subcutaneous panniculitis. The difference between our cases is that the inflammatory cell infiltration observed in Dr. Weise's case mainly involved neutrophils and that observed in our case mainly involved lymphocytes. This difference is thought to be due to the differences in findings depending on the stage of panniculitis. In erythema nodosum and erythema induratum of Bazin, which are representative conditions of panniculitis, infiltrative inflammatory cells include lymphocytes, histiocytes, and neutrophils; in particular, in early lesions, the infiltration of inflammatory cells, which are mainly composed of neutrophils, is observed.<span><sup>1</sup></span> According to a review of factitial panniculitis, which is a subcutaneous tissue injury caused by various injections, neutrophilic panniculitis is observed in the acute phase. Lymphocytic infiltration is observed in the later phase.<span><sup>2</sup></span> Because the cause of skin disorders induced by LDP/CDP is unknown, this difference in inflammatory cell infiltration is fascinating, and we would like to reexamine the pathological findings in more cases to understand the pathology of this disorder.</p><p>Based on the results of clinical trials of LDP/CDP, the most frequent adverse events on the skin have been reported to be “injection site erythema,” “injection site pain,” and “cellulitis.”<span><sup>3</sup></span> In our experience with actual cases, skin disorders can be generally divided into three manifestations: injection site erythema, injection site nodules, and injection site cellulitis. Injection site erythema is a skin reaction that occurs when LDP/CDP cannot be injected perpendicular to the skin surface, and we hypothesize that this skin reaction can be avoided by providing injection instructions. Additionally, injection site nodules are thought to be manifestations of panniculitis caused by irritation from the drug. Injection site cellulitis is associated with secondary infection due to the injection procedure, and the clinical findings are similar to those of the aforementioned findings of panniculitis; therefore, evaluating the presence or absence of the inflammatory findings in blood tests is necessary. However, we believe this outcome can be avoided by performing clean procedures. We believe that the accumulation and examination of cases are necessary to develop treatment strategies based to a greate","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"40 2","pages":"391-392"},"PeriodicalIF":7.4,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mds.30120","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p>We read with great interest the article by Yoshihara et al.,<span><sup>1</sup></span> which provides insight into histopathologic features of cutaneous side effects caused by continuous subcutaneous injection of foslevodopa/foscarbidopa. Using a similar approach, we analyzed skin biopsies from two female patients with Parkinson's disease (PD) who developed an inflammatory injection site reaction 11 and 13 weeks, respectively, after initiating subcutaneous treatment with foslevodopa/foscarbidopa. Notably, our histopathologic findings differ from those reported by Yoshihara et al., revealing a neutrophil-rich inflammatory infiltrate.</p><p>Akinetic-rigid type, disease duration 24 years, Hoen and Yahr scale (H&Y) 4 ON, 5 OFF with severe motor fluctuations and dyskinesia, optic hallucinations and PD dementia, previously treated with continuous subcutaneous apomorphine for 3 years, immediate change to foslevodopa/foscarbidopa due to not well-controlled motor fluctuations and increasing optic hallucinations and delusion. Good improvement of motor fluctuations and dyskinesia. After 13 weeks of treatment (foslevodopa total dose 2592 mg, day rate 0.50 mL/hr, night rate 0.35 mL/hr, cannula change frequency [initially] 3 days) an oval, tender, poorly demarked, dome-shaped, erythematous swelling was noted around the infusion site (Fig. 1A,B). Patient denied itching or pain.</p><p>Akinetic-rigid type, disease duration 15 years, H&Y 3 ON, 5 OFF with severe motor fluctuations and severe dyskinesia, previously treated with continuous subcutaneous apomorphine for 6 months (cessation due to insufficient improvement of fluctuations and persistent nausea), start of foslevodopa/foscarbidopa 8 months later with very good improvement of motor fluctuations and dyskinesia. She developed a painless, oval, poorly demarked, erythematous plaque measuring 5 cm in diameter after 11 weeks of treatment (foslevodopa total dose 2861 mg, day rate 0.52 mL/hr, night rate 0.45 mL/hr, cannula change frequency 2 days, relevant concomitant medication with opicapone 50 mg 1×/day).</p><p>Histopathologic examination of both cases revealed a patchy inflammatory infiltrate in the deep dermis extending into the subcutaneous tissue, composed primarily of neutrophils mixed with lymphocytes and a few eosinophils (Fig. 1C,D). In contrast to our findings, Yoshihara et al. described the adverse skin reactions as lymphocyte-dominant inflammatory infiltrates in the adipose tissue. Interestingly, an eosinophil-rich panniculitis has been observed in response to subcutaneously administered apomorphine,<span><sup>2</sup></span> suggesting that the cellular components of immune responses to subcutaneous drug application may vary significantly. This notion is supported by the fact that a broad clinical spectrum of cutaneous side effects, including erythema, edema, cellulitis, panniculitis, subcutaneous nodule formation, and abscess formation, has been reported for both subcutaneous treatment regi
{"title":"Neutrophil-Rich Infusion Site Reactions After Continuous Subcutaneous Application of Foslevodopa/Foscarbidopa","authors":"David Weise MD, Sebastian Haferkamp MD, PhD","doi":"10.1002/mds.30121","DOIUrl":"10.1002/mds.30121","url":null,"abstract":"<p>We read with great interest the article by Yoshihara et al.,<span><sup>1</sup></span> which provides insight into histopathologic features of cutaneous side effects caused by continuous subcutaneous injection of foslevodopa/foscarbidopa. Using a similar approach, we analyzed skin biopsies from two female patients with Parkinson's disease (PD) who developed an inflammatory injection site reaction 11 and 13 weeks, respectively, after initiating subcutaneous treatment with foslevodopa/foscarbidopa. Notably, our histopathologic findings differ from those reported by Yoshihara et al., revealing a neutrophil-rich inflammatory infiltrate.</p><p>Akinetic-rigid type, disease duration 24 years, Hoen and Yahr scale (H&Y) 4 ON, 5 OFF with severe motor fluctuations and dyskinesia, optic hallucinations and PD dementia, previously treated with continuous subcutaneous apomorphine for 3 years, immediate change to foslevodopa/foscarbidopa due to not well-controlled motor fluctuations and increasing optic hallucinations and delusion. Good improvement of motor fluctuations and dyskinesia. After 13 weeks of treatment (foslevodopa total dose 2592 mg, day rate 0.50 mL/hr, night rate 0.35 mL/hr, cannula change frequency [initially] 3 days) an oval, tender, poorly demarked, dome-shaped, erythematous swelling was noted around the infusion site (Fig. 1A,B). Patient denied itching or pain.</p><p>Akinetic-rigid type, disease duration 15 years, H&Y 3 ON, 5 OFF with severe motor fluctuations and severe dyskinesia, previously treated with continuous subcutaneous apomorphine for 6 months (cessation due to insufficient improvement of fluctuations and persistent nausea), start of foslevodopa/foscarbidopa 8 months later with very good improvement of motor fluctuations and dyskinesia. She developed a painless, oval, poorly demarked, erythematous plaque measuring 5 cm in diameter after 11 weeks of treatment (foslevodopa total dose 2861 mg, day rate 0.52 mL/hr, night rate 0.45 mL/hr, cannula change frequency 2 days, relevant concomitant medication with opicapone 50 mg 1×/day).</p><p>Histopathologic examination of both cases revealed a patchy inflammatory infiltrate in the deep dermis extending into the subcutaneous tissue, composed primarily of neutrophils mixed with lymphocytes and a few eosinophils (Fig. 1C,D). In contrast to our findings, Yoshihara et al. described the adverse skin reactions as lymphocyte-dominant inflammatory infiltrates in the adipose tissue. Interestingly, an eosinophil-rich panniculitis has been observed in response to subcutaneously administered apomorphine,<span><sup>2</sup></span> suggesting that the cellular components of immune responses to subcutaneous drug application may vary significantly. This notion is supported by the fact that a broad clinical spectrum of cutaneous side effects, including erythema, edema, cellulitis, panniculitis, subcutaneous nodule formation, and abscess formation, has been reported for both subcutaneous treatment regi","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"40 2","pages":"389-390"},"PeriodicalIF":7.4,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mds.30121","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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