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}
Sarah R. Pickles, Jesus Gonzalez Bejarano, Anand Narayan, Lillian Daughrity, Candela Maroto Cidfuentes, Madison M. Reeves, Mei Yue, Paula Castellanos Otero, Virginia Estades Ayuso, Judy Dunmore, Yuping Song, Jimei Tong, Michael DeTure, Bailey Rawlinson, Monica Castanedes‐Casey, Jaroslaw Dulski, Catalina Cerquera‐Cleves, Yongjie Zhang, Keith A. Josephs, Dennis W. Dickson, Leonard Petrucelli, Zbigniew K. Wszolek, Mercedes Prudencio
Andrea Quattrone, Nicolai Franzmeier, Johannes Levin, Gabor C Petzold, Annika Spottke, Frederic Brosseron, Björn Falkenburger, Johannes Prudlo, Thomas Gasser, Günter U Höglinger
Background: The recent Movement Disorders Society (MDS)-progressive supranuclear palsy (PSP) diagnostic criteria conceptualized three clinical diagnostic certainty levels: "suggestive of PSP" for sensitive early diagnosis based on subtle clinical signs, "possible PSP" balancing sensitivity and specificity, and "probable PSP" highly specific for PSP pathology.
Objective: The aim of this study was to prospectively validate the criteria against long-term clinical follow-up and characterize the diagnostic certainty increase over time.
Methods: Patients with "possible PSP" or "suggestive of PSP" diagnosis and clinical follow-up were recruited in two German multicenter longitudinal observational studies (ProPSP and DescribePSP). The cumulative percentage of patients longitudinally increasing diagnostic certainty was assessed over up to 2.5 years of follow-up. The sample size per arm required to detect 30% attenuated rate in diagnostic certainty increase in trials was estimated over multiple time intervals.
Results: Of 254 patients with available longitudinal data, 61 patients had low diagnostic certainty at baseline (48 suggestive of PSP, 13 possible PSP) and multiple clinical visits (median: 3, range: 2-4). The cumulative percentage of patients increasing diagnostic certainty progressed with follow-up duration (30.4% at 6 months, 51.7% at 1 year, 80.4% at 2.5 years). The sample size required to detect 30% reduction in diagnostic certainty increase rate within 1 year was 163, slightly smaller than that required using the PSP rating scale.
Background: Essential tremor (ET) is a common type of tremor. Previous research has shown that wearable orthoses and biomechanical loading methods can suppress tremors.
Objective: This study aims to investigate the effect of a harmonic liquid dampener on upper extremity ET.
Methods: The study involved 9 women and 5 men from a neurology outpatient clinic. A 285-g liquid-based harmonic dampening wristband was used. Tremors were recorded from the wrist along the x-y-z axes using a vibrometer, and the Bain-Findley Rating Scale (BFRS) was employed for assessment.
Results: BFRS scores significantly improved after the wristband was used (mean difference 35.64, P = 0.001, Cohen's d effect size =2.979). The tremor amplitude decreased significantly along the x-axis (Cohen's d: 1.35, P = 0.001), y-axis (Cohen's d: 3.232, P = 0.001), and z-axis (Cohen's d: 3.321, P = 0.001).
Marco Falletti, Francesco Asci, Alessandro Zampogna, Martina Patera, Giulia Pinola, Diego Centonze, Mark Hallett, John Rothwell, Antonio Suppa
Background: Quantitative evidence of levodopa-induced beneficial effects on parkinsonian rigidity in Parkinson's disease (PD) is lacking. Recent research has demonstrated the velocity-dependent nature of objective rigidity in PD and revealed its neural underpinning.
Objective: The present study aimed to examine the effect of levodopa on objective rigidity in PD.
Methods: Eighteen patients with PD underwent clinical and instrumental evaluations of muscle tone in the OFF and ON states. The clinical assessments focused on rigidity in the most affected upper limb. The biomechanical components of objective rigidity were assessed using robot-assisted wrist extensions at seven angular velocities (5-280°/s). Surface electromyography of the flexor carpi radialis muscle enabled the concurrent evaluation of short- and long-latency stretch reflexes (SLR and LLR).
Results: Levodopa improved the clinical scores of rigidity. Biomechanical measurements showed that levodopa reduced the total and neural components of force but had no effect on viscoelastic components. Levodopa reduced the velocity dependence of the LLRs but did not affect the SLRs. Finally, we found significant clinical-instrumental correlations between levodopa-induced changes and biomechanical and neurophysiological measures of objective rigidity in PD.
Anna Sadnicka MBChB, PhD, Mark J. Edwards MBBS, PhD
{"title":"The Lows of High Reward: Choking Under Pressure","authors":"Anna Sadnicka MBChB, PhD, Mark J. Edwards MBBS, PhD","doi":"10.1002/mds.30092","DOIUrl":"10.1002/mds.30092","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"40 2","pages":"243-244"},"PeriodicalIF":7.4,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941892","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}
Andona Milovanović MD, Ana Westenberger PhD, Nataša Dragašević-Mišković MD
{"title":"Reply to: “Two Families with ANO10-Related Spinocerebellar Ataxia with Novel Exon Deletions: A First Report from India”","authors":"Andona Milovanović MD, Ana Westenberger PhD, Nataša Dragašević-Mišković MD","doi":"10.1002/mds.30108","DOIUrl":"10.1002/mds.30108","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"40 2","pages":"387-388"},"PeriodicalIF":7.4,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941886","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号