Pub Date : 2024-10-22DOI: 10.1007/s12311-024-01748-0
Paulo Figueroa-Taiba, Joel Álvarez-Ruf, Paulette Ulloa, Trinidad Bruna-Melo, Liam Espinoza-Maraboli, Pablo Ignacio Burgos, Juan J Mariman
Motor adaptation is critical to update motor tasks in new or modified environmental conditions. While the cerebellum supports error-based adaptations, its neural implementation is partially known. By controlling the frequency of cerebellar transcranial alternating current stimulation (c-tACS), we can test the influence of neural oscillation from the cerebellum for motor adaptation. Two independent experiments were conducted. In Experiment 1, 16 participants received four c-tACS protocols (45 Hz, 50 Hz, 55 Hz, and sham) on four different days while they practiced a visuomotor adaptation task (30 degrees CCW) with variable intensity (within-subject design). In Experiment 2, 45 participants separated into three groups received the effect of 45 Hz, 55 Hz c-tACS, and sham, respectively (between-subject design), performing the same visuomotor task with a fixed intensity (0.9 mA). In Experiment 1, 45 Hz and 50 Hz of c-tACS accelerated motor adaptation when participants performed the task only for the first time, independent of the time interval between sessions or the stimulation intensity. The effect of active c-tACS was ratified in Experiment 2, where 45 Hz c-tACS benefits motor adaptation during the complete practice period. Reaction time, velocity, or duration of reaching are not affected by c-tACS. Cerebellar alternating current stimulation is an effective strategy to potentiate visuomotor adaptations. Frequency-dependent effects on the gamma band, especially for 45 Hz c-tACS, ratify the oscillatory profile of cerebellar processes behind the motor adaptation. This can be exploited in future interventions to enhance motor learning.
{"title":"Potentiation of Motor Adaptation Via Cerebellar tACS: Characterization of the Stimulation Frequency.","authors":"Paulo Figueroa-Taiba, Joel Álvarez-Ruf, Paulette Ulloa, Trinidad Bruna-Melo, Liam Espinoza-Maraboli, Pablo Ignacio Burgos, Juan J Mariman","doi":"10.1007/s12311-024-01748-0","DOIUrl":"https://doi.org/10.1007/s12311-024-01748-0","url":null,"abstract":"<p><p>Motor adaptation is critical to update motor tasks in new or modified environmental conditions. While the cerebellum supports error-based adaptations, its neural implementation is partially known. By controlling the frequency of cerebellar transcranial alternating current stimulation (c-tACS), we can test the influence of neural oscillation from the cerebellum for motor adaptation. Two independent experiments were conducted. In Experiment 1, 16 participants received four c-tACS protocols (45 Hz, 50 Hz, 55 Hz, and sham) on four different days while they practiced a visuomotor adaptation task (30 degrees CCW) with variable intensity (within-subject design). In Experiment 2, 45 participants separated into three groups received the effect of 45 Hz, 55 Hz c-tACS, and sham, respectively (between-subject design), performing the same visuomotor task with a fixed intensity (0.9 mA). In Experiment 1, 45 Hz and 50 Hz of c-tACS accelerated motor adaptation when participants performed the task only for the first time, independent of the time interval between sessions or the stimulation intensity. The effect of active c-tACS was ratified in Experiment 2, where 45 Hz c-tACS benefits motor adaptation during the complete practice period. Reaction time, velocity, or duration of reaching are not affected by c-tACS. Cerebellar alternating current stimulation is an effective strategy to potentiate visuomotor adaptations. Frequency-dependent effects on the gamma band, especially for 45 Hz c-tACS, ratify the oscillatory profile of cerebellar processes behind the motor adaptation. This can be exploited in future interventions to enhance motor learning.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-18DOI: 10.1007/s12311-024-01752-4
Chidinma P Anyachor, Chinna N Orish, Anthonet N Ezejiofor, Ana Cirovic, Aleksandar Cirovic, Baridoo Donatus Dooka, Kenneth M Ezealisiji, Xavier Siwe Noundou, Orish E Orisakwe
{"title":"Correction: Silica Nanoparticles from Melon Seed Husk Abrogated Binary Metal(loid) Mediated Cerebellar Dysfunction by Attenuation of Oxido-inflammatory Response and Upregulation of Neurotrophic Factors in Male Albino Rats.","authors":"Chidinma P Anyachor, Chinna N Orish, Anthonet N Ezejiofor, Ana Cirovic, Aleksandar Cirovic, Baridoo Donatus Dooka, Kenneth M Ezealisiji, Xavier Siwe Noundou, Orish E Orisakwe","doi":"10.1007/s12311-024-01752-4","DOIUrl":"https://doi.org/10.1007/s12311-024-01752-4","url":null,"abstract":"","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-09DOI: 10.1007/s12311-024-01751-5
Davide Costa, Sofia Grandolfo, Daniele Birreci, Luca Angelini, Massimiliano Passaretti, Antonio Cannavacciuolo, Adriana Martini, Martina De Riggi, Giulia Paparella, Alfonso Fasano, Matteo Bologna
In the past few years, SARS-CoV-2 infection has substantially impacted public health. Alongside respiratory symptoms, some individuals have reported new neurological manifestations or a worsening of pre-existing neurological conditions. We previously documented two cases of essential tremor (ET) who experienced a deterioration in tremor following SARS-CoV-2 infection. However, the effects of SARS-CoV-2 on ET remain largely unexplored. This study aims to evaluate the impact of SARS-CoV-2 infection on a relatively broad sample of ET patients by retrospectively comparing their clinical and kinematic data collected before and after the exposure to SARS-CoV-2. We surveyed to evaluate the impact of SARS-CoV-2 infection on tremor features in ET. Subsequently, we retrospectively analysed clinical and kinematic data, including accelerometric recordings of postural and kinetic tremor. We included 36 ET patients (14 females with a mean age of 71.1 ± 10.6 years). Among the 25 patients who reported SARS-CoV-2 infection, 11 (44%) noted a subjective worsening of tremor. All patients reporting subjective tremor worsening also exhibited symptoms of long COVID, whereas the prevalence of these symptoms was lower (50%) in those without subjective exacerbation. The retrospective analysis of clinical data revealed a tremor deterioration in infected patients, which was not observed in non-infected patients. Finally, kinematic analysis revealed substantial stability of tremor features in both groups. The study highlighted a potential correlation between the SARS-CoV-2 infection and clinical worsening of ET. Long COVID contributes to a greater impact of tremor on the daily life of ET patients.
在过去几年中,SARS-CoV-2 感染对公众健康产生了重大影响。除呼吸系统症状外,一些人还报告了新的神经系统表现或原有神经系统疾病的恶化。我们曾记录了两例感染 SARS-CoV-2 后震颤恶化的本质性震颤 (ET) 患者。然而,SARS-CoV-2 对 ET 的影响在很大程度上仍未得到探讨。本研究旨在通过回顾性比较 ET 患者在感染 SARS-CoV-2 前后的临床和运动学数据,评估 SARS-CoV-2 感染对相对广泛的 ET 患者样本的影响。我们调查评估了 SARS-CoV-2 感染对 ET 震颤特征的影响。随后,我们回顾性地分析了临床和运动学数据,包括姿势震颤和运动震颤的加速度记录。我们共纳入了 36 名 ET 患者(14 名女性,平均年龄为 71.1 ± 10.6 岁)。在报告感染 SARS-CoV-2 的 25 名患者中,有 11 人(44%)主观感觉震颤加重。所有报告主观震颤加重的患者都表现出长COVID症状,而在没有主观震颤加重的患者中,这些症状的发生率较低(50%)。对临床数据的回顾性分析表明,感染患者的震颤会恶化,而非感染患者则不会出现这种情况。最后,运动学分析显示,两组患者的震颤特征都非常稳定。该研究强调了 SARS-CoV-2 感染与 ET 临床恶化之间的潜在相关性。长COVID会导致震颤对ET患者的日常生活产生更大的影响。
{"title":"Impact of SARS-CoV-2 Infection on Essential Tremor: A Retrospective Clinical and Kinematic Analysis.","authors":"Davide Costa, Sofia Grandolfo, Daniele Birreci, Luca Angelini, Massimiliano Passaretti, Antonio Cannavacciuolo, Adriana Martini, Martina De Riggi, Giulia Paparella, Alfonso Fasano, Matteo Bologna","doi":"10.1007/s12311-024-01751-5","DOIUrl":"https://doi.org/10.1007/s12311-024-01751-5","url":null,"abstract":"<p><p>In the past few years, SARS-CoV-2 infection has substantially impacted public health. Alongside respiratory symptoms, some individuals have reported new neurological manifestations or a worsening of pre-existing neurological conditions. We previously documented two cases of essential tremor (ET) who experienced a deterioration in tremor following SARS-CoV-2 infection. However, the effects of SARS-CoV-2 on ET remain largely unexplored. This study aims to evaluate the impact of SARS-CoV-2 infection on a relatively broad sample of ET patients by retrospectively comparing their clinical and kinematic data collected before and after the exposure to SARS-CoV-2. We surveyed to evaluate the impact of SARS-CoV-2 infection on tremor features in ET. Subsequently, we retrospectively analysed clinical and kinematic data, including accelerometric recordings of postural and kinetic tremor. We included 36 ET patients (14 females with a mean age of 71.1 ± 10.6 years). Among the 25 patients who reported SARS-CoV-2 infection, 11 (44%) noted a subjective worsening of tremor. All patients reporting subjective tremor worsening also exhibited symptoms of long COVID, whereas the prevalence of these symptoms was lower (50%) in those without subjective exacerbation. The retrospective analysis of clinical data revealed a tremor deterioration in infected patients, which was not observed in non-infected patients. Finally, kinematic analysis revealed substantial stability of tremor features in both groups. The study highlighted a potential correlation between the SARS-CoV-2 infection and clinical worsening of ET. Long COVID contributes to a greater impact of tremor on the daily life of ET patients.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-09DOI: 10.1007/s12311-024-01749-z
Xin Huang, Zhiqin Xu, Lingxiang Zhou, Ke Dong, Qingqing Liu, Jiating Li, Di Lei, Hanjun Liu, Xi Chen
Cerebellar transcranial direct current stimulation (tDCS) has been shown to influence movement functions, but little is known about the specific effects of stimulation polarity on balance control. This study investigated the impact of bilateral cerebellar tDCS on balance functions as a function of stimulation polarity. In this randomized, controlled trial, thirty-nine healthy young adults were assigned to one of three groups: right anodal/left cathodal cerebellar stimulation (AC group), right cathodal/left anodal cerebellar stimulation (CA group), and a control sham group. Each participant underwent a daily 30-minute session of tDCS at 2 mA for one week. Balance function was assessed pre- and post-intervention and the data were analyzed using generalized estimating equations. The CA group exhibited a significant reduction in sway area when standing on the left leg and on both stable and unstable surfaces with eyes open, compared to both the AC and sham groups. However, there were no significant differences among the groups in terms of sway length, anteroposterior velocity, or mediolateral velocity. Our results indicate the polarity-dependent effects of bilateral cerebellar tDCS on balance functions, with enhanced stability observed only following cathodal tDCS over the right cerebellum paired with anodal tDCS over the left cerebellum. This polarity-specific modulation may have implications for developing cerebellar neuromodulation interventions for movement disorders.
{"title":"The Impact of Bilateral Cerebellar Transcranial Direct Current Stimulation on Balance Control in Healthy Young Adults.","authors":"Xin Huang, Zhiqin Xu, Lingxiang Zhou, Ke Dong, Qingqing Liu, Jiating Li, Di Lei, Hanjun Liu, Xi Chen","doi":"10.1007/s12311-024-01749-z","DOIUrl":"https://doi.org/10.1007/s12311-024-01749-z","url":null,"abstract":"<p><p>Cerebellar transcranial direct current stimulation (tDCS) has been shown to influence movement functions, but little is known about the specific effects of stimulation polarity on balance control. This study investigated the impact of bilateral cerebellar tDCS on balance functions as a function of stimulation polarity. In this randomized, controlled trial, thirty-nine healthy young adults were assigned to one of three groups: right anodal/left cathodal cerebellar stimulation (AC group), right cathodal/left anodal cerebellar stimulation (CA group), and a control sham group. Each participant underwent a daily 30-minute session of tDCS at 2 mA for one week. Balance function was assessed pre- and post-intervention and the data were analyzed using generalized estimating equations. The CA group exhibited a significant reduction in sway area when standing on the left leg and on both stable and unstable surfaces with eyes open, compared to both the AC and sham groups. However, there were no significant differences among the groups in terms of sway length, anteroposterior velocity, or mediolateral velocity. Our results indicate the polarity-dependent effects of bilateral cerebellar tDCS on balance functions, with enhanced stability observed only following cathodal tDCS over the right cerebellum paired with anodal tDCS over the left cerebellum. This polarity-specific modulation may have implications for developing cerebellar neuromodulation interventions for movement disorders.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-05DOI: 10.1007/s12311-024-01750-6
Rodrigo Brito, João Victor Fabrício, Aurine Araujo, Mariana Sacchi, Adriana Baltar, Fernanda Albuquerque Lima, Ana Cecília Ribeiro, Bárbara Sousa, Camilla Santos, Clarice Tanaka, Kátia Monte-Silva
Cerebellar transcranial direct current stimulation (ctDCS) has emerged as a promising, non-invasive, and safe neuromodulatory intervention capable of reducing ataxia symptoms and restoring cerebellum-motor connectivity. However, previous studies have only applied ctDCS in isolation, without association with specific training. This study aimed to assess the effect of ctDCS combined with gait training on functional mobility, balance, and symptoms and severity of ataxia. A randomized, triple-blind, sham-controlled, bi-center clinical trial was conducted with forty-four adults with cerebellar ataxia. Volunteers were randomized to receive five daily sessions of either real ctDCS (n = 11; 2 mA for 25 min) or sham ctDCS (n = 11) during gait training. Functional mobility, balance, and symptoms and severity of ataxia were assessed using the Time Up and Go test, the MiniBESTest, and the Scale for the Assessment and Rating of Ataxia (SARA), respectively, before and after the interventions. Both groups showed improvement in functional mobility, but there was no significant difference between the ctDCS and sham groups. However, the ctDCS group demonstrated significant improvements in cerebellar ataxia severity as reflected by SARA scores, particularly in tests of stance, sitting, speech disturbance, nose-finger test, and heel-shin slide test. Notably, no improvements were observed in balance. This study indicates that while ctDCS combined with gait training may improve specific symptoms of cerebellar ataxia, it does not significantly enhance overall functional mobility compared to sham treatment.
小脑经颅直流电刺激(ctDCS)是一种很有前途的非侵入性安全神经调节干预方法,能够减轻共济失调症状并恢复小脑与运动的连接。然而,以往的研究只是孤立地应用ctDCS,而没有将其与特定的训练结合起来。本研究旨在评估ctDCS与步态训练相结合对共济失调的功能活动度、平衡、症状和严重程度的影响。研究人员对 44 名患有小脑共济失调的成人进行了随机、三盲、假对照、双中心临床试验。志愿者被随机安排在步态训练期间每天接受五次真实 ctDCS(n = 11;2 mA,25 分钟)或假 ctDCS(n = 11)治疗。在干预前后,分别使用 "向上走时间测试"(Time Up and Go test)、"MiniBESTest "和 "共济失调评估和评级量表"(Scale for the Assessment and Rating of Ataxia,SARA)对共济失调的功能活动度、平衡能力、症状和严重程度进行评估。两组患者的功能活动能力均有所改善,但ctDCS组和假组间无显著差异。不过,ctDCS组的小脑共济失调严重程度有了明显改善,这体现在SARA评分上,尤其是在站立、坐姿、言语障碍、鼻指测试和跟胫滑动测试方面。值得注意的是,平衡能力没有得到改善。这项研究表明,虽然ctDCS结合步态训练可以改善小脑共济失调的特定症状,但与假治疗相比,它并不能显著提高整体功能活动能力。
{"title":"Differential Effects of Cerebellar Transcranial Direct Current Stimulation with Gait Training on Functional Mobility, Balance, and Ataxia Symptoms.","authors":"Rodrigo Brito, João Victor Fabrício, Aurine Araujo, Mariana Sacchi, Adriana Baltar, Fernanda Albuquerque Lima, Ana Cecília Ribeiro, Bárbara Sousa, Camilla Santos, Clarice Tanaka, Kátia Monte-Silva","doi":"10.1007/s12311-024-01750-6","DOIUrl":"https://doi.org/10.1007/s12311-024-01750-6","url":null,"abstract":"<p><p>Cerebellar transcranial direct current stimulation (ctDCS) has emerged as a promising, non-invasive, and safe neuromodulatory intervention capable of reducing ataxia symptoms and restoring cerebellum-motor connectivity. However, previous studies have only applied ctDCS in isolation, without association with specific training. This study aimed to assess the effect of ctDCS combined with gait training on functional mobility, balance, and symptoms and severity of ataxia. A randomized, triple-blind, sham-controlled, bi-center clinical trial was conducted with forty-four adults with cerebellar ataxia. Volunteers were randomized to receive five daily sessions of either real ctDCS (n = 11; 2 mA for 25 min) or sham ctDCS (n = 11) during gait training. Functional mobility, balance, and symptoms and severity of ataxia were assessed using the Time Up and Go test, the MiniBESTest, and the Scale for the Assessment and Rating of Ataxia (SARA), respectively, before and after the interventions. Both groups showed improvement in functional mobility, but there was no significant difference between the ctDCS and sham groups. However, the ctDCS group demonstrated significant improvements in cerebellar ataxia severity as reflected by SARA scores, particularly in tests of stance, sitting, speech disturbance, nose-finger test, and heel-shin slide test. Notably, no improvements were observed in balance. This study indicates that while ctDCS combined with gait training may improve specific symptoms of cerebellar ataxia, it does not significantly enhance overall functional mobility compared to sham treatment.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-04DOI: 10.1007/s12311-024-01744-4
Kyota Bando, Yuki Kondo, Yuta Miyazaki, Takatoshi Hara, Yuji Takahashi
Multiple system atrophy-cerebellar type (MSA-C) exhibits faster disease progression than does hereditary spinocerebellar degeneration (hSCD). In this study, we aimed to investigate the differences in the treatment effects and sustainability of intensive rehabilitation between patients with hSCD and those with MSA-C. Forty-nine patients (hSCD = 30, MSA-C = 19) underwent a 2- or 4-week intensive rehabilitation program. Balance function was evaluated using the scale for the assessment and rating of ataxia (SARA) and the balance evaluation systems test (BESTest) at pre-intervention, post-intervention, and 6-month follow-up. Notably, both groups demonstrated beneficial effects from the rehabilitation intervention. However, differences were observed in the magnitude and duration of these effects. In the hSCD group, the SARA scores at follow-up remained similar to those at baseline, indicating sustained benefits. However, the MSA-C group showed some deterioration in SARA scores compared with baseline scores but maintained improvements on the BESTest, demonstrating partial sustainability. Differences, mainly in sustainability, were observed between the hSCD and MSA-C groups. This may be due to varying rates of symptom progression. The findings of this study are significant when considering the frequency of follow-ups based on disease type.
与遗传性脊髓小脑变性(hSCD)相比,多系统萎缩-小脑型(MSA-C)的疾病进展更快。在这项研究中,我们旨在研究hSCD患者和MSA-C患者在强化康复治疗效果和可持续性方面的差异。49名患者(hSCD=30人,MSA-C=19人)接受了为期2周或4周的强化康复训练。在干预前、干预后和 6 个月的随访中,使用共济失调评估和评级量表(SARA)和平衡评估系统测试(BESTest)对患者的平衡功能进行了评估。值得注意的是,两组患者都从康复干预中获益。然而,在这些效果的程度和持续时间上却出现了差异。在 hSCD 组中,随访时的 SARA 分数与基线时的分数相似,这表明疗效具有持续性。然而,与基线分数相比,MSA-C 组的 SARA 分数有所下降,但 BESTest 分数仍有改善,这表明了部分持续性。在 hSCD 组和 MSA-C 组之间观察到了差异,主要是持续性方面的差异。这可能是由于症状进展的速度不同造成的。考虑到根据疾病类型进行随访的频率,本研究的结果具有重要意义。
{"title":"Differences in the Impact of Intensive Rehabilitation on Hereditary Ataxias and the Cerebellar Subtype of Multiple System Atrophy.","authors":"Kyota Bando, Yuki Kondo, Yuta Miyazaki, Takatoshi Hara, Yuji Takahashi","doi":"10.1007/s12311-024-01744-4","DOIUrl":"https://doi.org/10.1007/s12311-024-01744-4","url":null,"abstract":"<p><p>Multiple system atrophy-cerebellar type (MSA-C) exhibits faster disease progression than does hereditary spinocerebellar degeneration (hSCD). In this study, we aimed to investigate the differences in the treatment effects and sustainability of intensive rehabilitation between patients with hSCD and those with MSA-C. Forty-nine patients (hSCD = 30, MSA-C = 19) underwent a 2- or 4-week intensive rehabilitation program. Balance function was evaluated using the scale for the assessment and rating of ataxia (SARA) and the balance evaluation systems test (BESTest) at pre-intervention, post-intervention, and 6-month follow-up. Notably, both groups demonstrated beneficial effects from the rehabilitation intervention. However, differences were observed in the magnitude and duration of these effects. In the hSCD group, the SARA scores at follow-up remained similar to those at baseline, indicating sustained benefits. However, the MSA-C group showed some deterioration in SARA scores compared with baseline scores but maintained improvements on the BESTest, demonstrating partial sustainability. Differences, mainly in sustainability, were observed between the hSCD and MSA-C groups. This may be due to varying rates of symptom progression. The findings of this study are significant when considering the frequency of follow-ups based on disease type.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This study aimed to generate evidence to support psychometric validity of the modified functional Scale for the Assessment and Rating of Ataxia (f-SARA) among patients with spinocerebellar ataxia (SCA). Psychometric measurement properties and minimal change thresholds of the f-SARA were evaluated using data from a cohort of SCA subjects (recruited at Massachusetts General Hospital [MGH]; n = 33) and data from a phase 3 trial of troriluzole in adults with SCA (NCT03701399 [Study 206]; n = 217), including a subset of patients with the SCA3 genotype (n = 89). f-SARA item ceiling effects were absent within the MGH cohort, while floor effects were present. Excellent internal consistency reliability was demonstrated (αtotal = 0.90; αitems-removed = 0.86-0.90), and item-to-total correlations were strong (r = 0.82-0.91, per item). High test-retest reliability was demonstrated with intraclass correlation coefficients of 0.91 (total) and 0.73-0.92 (items). Convergent and divergent validity was supported, with strong correlations observed between the f-SARA and similarly constructed scales (FARS-FUNC, BARS, PROM-ADL, and FARS-ADL; all p < 0.001) and weaker correlations observed among measures of differing constructs. Mean item and total scores increased with disease severity (by FARS-FUNC quartile; p < 0.001). A 1-point threshold for meaningful changes was supported as 0.5 × SD = 0.89, SEM = 1.12, and mean changes from baseline for patients classified as "improved," "no change," or "deteriorated" were -0.68, 0.02, and 0.58, respectively. Similar trends were observed in Study 206 all-SCA and SCA3 cohorts. The measurement properties of the f-SARA provide evidence of its psychometric validity, responsiveness, and suitability as a clinical outcome measure in patients with SCA, including those with SCA3.
{"title":"Psychometric Validation of the Modified Functional Scale for the Assessment and Rating of Ataxia (f-SARA) in Patients With Spinocerebellar Ataxia.","authors":"Michele Potashman, Evan Popoff, Lauren Powell, Ainsley Mackenzie, Melissa Wolfe Beiner, Vlad Coric, Jeremy Schmahmann, Gilbert L'Italien","doi":"10.1007/s12311-024-01707-9","DOIUrl":"10.1007/s12311-024-01707-9","url":null,"abstract":"<p><p>This study aimed to generate evidence to support psychometric validity of the modified functional Scale for the Assessment and Rating of Ataxia (f-SARA) among patients with spinocerebellar ataxia (SCA). Psychometric measurement properties and minimal change thresholds of the f-SARA were evaluated using data from a cohort of SCA subjects (recruited at Massachusetts General Hospital [MGH]; n = 33) and data from a phase 3 trial of troriluzole in adults with SCA (NCT03701399 [Study 206]; n = 217), including a subset of patients with the SCA3 genotype (n = 89). f-SARA item ceiling effects were absent within the MGH cohort, while floor effects were present. Excellent internal consistency reliability was demonstrated (α<sub>total</sub> = 0.90; α<sub>items-removed</sub> = 0.86-0.90), and item-to-total correlations were strong (r = 0.82-0.91, per item). High test-retest reliability was demonstrated with intraclass correlation coefficients of 0.91 (total) and 0.73-0.92 (items). Convergent and divergent validity was supported, with strong correlations observed between the f-SARA and similarly constructed scales (FARS-FUNC, BARS, PROM-ADL, and FARS-ADL; all p < 0.001) and weaker correlations observed among measures of differing constructs. Mean item and total scores increased with disease severity (by FARS-FUNC quartile; p < 0.001). A 1-point threshold for meaningful changes was supported as 0.5 × SD = 0.89, SEM = 1.12, and mean changes from baseline for patients classified as \"improved,\" \"no change,\" or \"deteriorated\" were -0.68, 0.02, and 0.58, respectively. Similar trends were observed in Study 206 all-SCA and SCA3 cohorts. The measurement properties of the f-SARA provide evidence of its psychometric validity, responsiveness, and suitability as a clinical outcome measure in patients with SCA, including those with SCA3.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11489232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141307263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01Epub Date: 2024-05-07DOI: 10.1007/s12311-024-01697-8
Gilbert L'Italien, Evan Popoff, Basia Rogula, Lauren Powell, Michele Potashman, Sam Dickson, Patrick O'Keefe, Melissa Beiner, Vlad Coric, Susan Perlman, Jeremy D Schmahmann, Suzanne Hendrix
Spinocerebellar ataxias (SCA) are rare inherited neurodegenerative disorders characterized by a progressive impairment of gait, balance, limb coordination, and speech. There is currently no composite scale that includes multiple aspects of the SCA experience to assess disease progression and treatment effects. Applying the method of partial least squares (PLS) regression, we developed the Spinocerebellar Ataxia Composite Scale (SCACOMS) from two SCA natural history datasets (NCT01060371, NCT02440763). PLS regression selected items based on their ability to detect clinical decline, with optimized weights based on the item's degree of progression. Following model validation, SCACOMS was leveraged to examine disease progression and treatment effects in a 48-week SCA clinical trial cohort (NCT03701399). Items from the Clinical Global Impression-Global Improvement Scale (CGI-I), the Friedreich Ataxia Rating Scale (FARS) - functional stage, and the Modified Functional Scale for the Assessment and Rating of Ataxia (f-SARA) were objectively selected with weightings based on their sensitivity to clinical decline. The resulting SCACOMS exhibited improved sensitivity to disease progression and greater treatment effects (compared to the original scales from which they were derived) in a 48-week clinical trial of a novel therapeutic agent. The trial analyses also provided a SCACOMS-derived estimate of the temporal delay in SCA disease progression. SCACOMS is a useful composite measure, effectively capturing disease progression and highlighting treatment effects in patients with SCA. SCACOMS will be a powerful tool in future studies given its sensitivity to clinical decline and ability to detect a meaningful clinical impact of disease-modifying treatments.
{"title":"Development and Validation of SCACOMS, a Composite Scale for Assessing Disease Progression and Treatment Effects in Spinocerebellar Ataxia.","authors":"Gilbert L'Italien, Evan Popoff, Basia Rogula, Lauren Powell, Michele Potashman, Sam Dickson, Patrick O'Keefe, Melissa Beiner, Vlad Coric, Susan Perlman, Jeremy D Schmahmann, Suzanne Hendrix","doi":"10.1007/s12311-024-01697-8","DOIUrl":"10.1007/s12311-024-01697-8","url":null,"abstract":"<p><p>Spinocerebellar ataxias (SCA) are rare inherited neurodegenerative disorders characterized by a progressive impairment of gait, balance, limb coordination, and speech. There is currently no composite scale that includes multiple aspects of the SCA experience to assess disease progression and treatment effects. Applying the method of partial least squares (PLS) regression, we developed the Spinocerebellar Ataxia Composite Scale (SCACOMS) from two SCA natural history datasets (NCT01060371, NCT02440763). PLS regression selected items based on their ability to detect clinical decline, with optimized weights based on the item's degree of progression. Following model validation, SCACOMS was leveraged to examine disease progression and treatment effects in a 48-week SCA clinical trial cohort (NCT03701399). Items from the Clinical Global Impression-Global Improvement Scale (CGI-I), the Friedreich Ataxia Rating Scale (FARS) - functional stage, and the Modified Functional Scale for the Assessment and Rating of Ataxia (f-SARA) were objectively selected with weightings based on their sensitivity to clinical decline. The resulting SCACOMS exhibited improved sensitivity to disease progression and greater treatment effects (compared to the original scales from which they were derived) in a 48-week clinical trial of a novel therapeutic agent. The trial analyses also provided a SCACOMS-derived estimate of the temporal delay in SCA disease progression. SCACOMS is a useful composite measure, effectively capturing disease progression and highlighting treatment effects in patients with SCA. SCACOMS will be a powerful tool in future studies given its sensitivity to clinical decline and ability to detect a meaningful clinical impact of disease-modifying treatments.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11489241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140861127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01Epub Date: 2024-03-16DOI: 10.1007/s12311-024-01679-w
Anna Sobanska, Leszek Czerwosz, Anna Sulek, Rafal Rola, Iwona Stepniak, Maria Rakowicz
The aim of this study was to determine the time between the first detection of postural control impairments and the evident manifestation of ataxia in preclinical SCA1 individuals. Twenty five preclinical SCA1 mutation carriers: 13 with estimated disease onset ≤ 6 years (SCA1 +) aged 27.8 ± 8.1 years; 12 with expected disease onset > 6 years (SCA1-) aged 26.6 ± 3.1 years and 26 age and sex matched healthy controls (HCs) underwent static posturography during 5 years of observation. The movements of the centre of feet pressure (COP) during quiet standing with eyes open (EO) and closed (EC) were quantified by calculating the mean radius (R), developed surface area (A) and mean COP movement velocity (V). Ataxia was evaluated by use of the Scale for Assessment and Rating of Ataxia (SARA).SCA1 + exhibited significantly worse quality of stance with EC vs. SCA1- (p < 0.05 for V) and HCs (p < 0.001) even 5 to 6 years before estimated disease onset. There were no statistically significant differences between SCA1- and HCs. A slow increase in Cohen's d effect size was observed for VEO up to the clinical manifestation of ataxia. VEO and AEC recorded in preclinical SCA1 individuals correlated slightly but statistically significantly with SARA (r = 0.47).The study confirms that static posturography detects COP sway changes in SCA1 preclinical gene carriers even 5 to 6 years before estimated disease onset. The quantitative evaluation of stance in preclinical SCA is a sensitive biomarker for the monitoring of the disease progression and may be useful in clinical trials.
{"title":"Quantitative Evaluation of Stance as a Sensitive Biomarker of Postural Ataxia Development in Preclinical SCA1 Mutation Carriers.","authors":"Anna Sobanska, Leszek Czerwosz, Anna Sulek, Rafal Rola, Iwona Stepniak, Maria Rakowicz","doi":"10.1007/s12311-024-01679-w","DOIUrl":"10.1007/s12311-024-01679-w","url":null,"abstract":"<p><p>The aim of this study was to determine the time between the first detection of postural control impairments and the evident manifestation of ataxia in preclinical SCA1 individuals. Twenty five preclinical SCA1 mutation carriers: 13 with estimated disease onset ≤ 6 years (SCA1 +) aged 27.8 ± 8.1 years; 12 with expected disease onset > 6 years (SCA1-) aged 26.6 ± 3.1 years and 26 age and sex matched healthy controls (HCs) underwent static posturography during 5 years of observation. The movements of the centre of feet pressure (COP) during quiet standing with eyes open (EO) and closed (EC) were quantified by calculating the mean radius (R), developed surface area (A) and mean COP movement velocity (V). Ataxia was evaluated by use of the Scale for Assessment and Rating of Ataxia (SARA).SCA1 + exhibited significantly worse quality of stance with EC vs. SCA1- (p < 0.05 for V) and HCs (p < 0.001) even 5 to 6 years before estimated disease onset. There were no statistically significant differences between SCA1- and HCs. A slow increase in Cohen's d effect size was observed for V<sub>EO</sub> up to the clinical manifestation of ataxia. V<sub>EO</sub> and A<sub>EC</sub> recorded in preclinical SCA1 individuals correlated slightly but statistically significantly with SARA (r = 0.47).The study confirms that static posturography detects COP sway changes in SCA1 preclinical gene carriers even 5 to 6 years before estimated disease onset. The quantitative evaluation of stance in preclinical SCA is a sensitive biomarker for the monitoring of the disease progression and may be useful in clinical trials.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140141062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01Epub Date: 2024-03-18DOI: 10.1007/s12311-024-01680-3
Mike Gilbert, Anders Rasmussen
In the cerebellum, granule cells make parallel fibre contact on (and excite) Golgi cells and Golgi cells inhibit granule cells, forming an open feedback loop. Parallel fibres excite Golgi cells synaptically, each making a single contact. Golgi cells inhibit granule cells in a structure called a glomerulus almost exclusively by GABA spillover acting through extrasynaptic GABAA receptors. Golgi cells are connected dendritically by gap junctions. It has long been suspected that feedback contributes to homeostatic regulation of parallel fibre signals activity, causing the fraction of the population that are active to be maintained at a low level. We present a detailed neurophysiological and computationally-rendered model of functionally grouped Golgi cells which can infer the density of parallel fibre signals activity and convert it into proportional modulation of inhibition of granule cells. The conversion is unlearned and not actively computed; rather, output is simply the computational effect of cell morphology and network architecture. Unexpectedly, the conversion becomes more precise at low density, suggesting that self-regulation is attracted to sparse code, because it is stable. A computational function of gap junctions may not be confined to the cerebellum.
{"title":"Gap Junctions May Have A Computational Function In The Cerebellum: A Hypothesis.","authors":"Mike Gilbert, Anders Rasmussen","doi":"10.1007/s12311-024-01680-3","DOIUrl":"10.1007/s12311-024-01680-3","url":null,"abstract":"<p><p>In the cerebellum, granule cells make parallel fibre contact on (and excite) Golgi cells and Golgi cells inhibit granule cells, forming an open feedback loop. Parallel fibres excite Golgi cells synaptically, each making a single contact. Golgi cells inhibit granule cells in a structure called a glomerulus almost exclusively by GABA spillover acting through extrasynaptic GABA<sub>A</sub> receptors. Golgi cells are connected dendritically by gap junctions. It has long been suspected that feedback contributes to homeostatic regulation of parallel fibre signals activity, causing the fraction of the population that are active to be maintained at a low level. We present a detailed neurophysiological and computationally-rendered model of functionally grouped Golgi cells which can infer the density of parallel fibre signals activity and convert it into proportional modulation of inhibition of granule cells. The conversion is unlearned and not actively computed; rather, output is simply the computational effect of cell morphology and network architecture. Unexpectedly, the conversion becomes more precise at low density, suggesting that self-regulation is attracted to sparse code, because it is stable. A computational function of gap junctions may not be confined to the cerebellum.</p>","PeriodicalId":50706,"journal":{"name":"Cerebellum","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11489243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140159466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}