Pub Date : 2024-05-01Epub Date: 2023-11-28DOI: 10.1080/21678421.2023.2288110
Andrew Brown, Carmel Armon, Paul Barkhaus, Morgan Beauchamp, Tulio Bertorini, Mark Bromberg, Javier Mascias Cadavid, Gregory T Carter, Jesse Crayle, Eva L Feldman, Terry Heiman-Patterson, Sartaj Jhooty, Alexandra Linares, Xiaoyan Li, Elise Mallon, Christopher Mcdermott, Tasnim Mushannen, George Nathaniel, Gary Pattee, Kaitlyn Pierce, Dylan Ratner, Lenka Slactova, Paul Wicks, Richard Bedlack
ALSUntangled reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). Here we review insulin, which has at least one plausible mechanism for slowing ALS progression. However, pre-clinical studies are limited and there have been no trials in PALS yet. Insulin use in patients without a metabolic need may cause very serious and potentially lethal side effects. While further studies to evaluate potential benefits may be warranted, at this time we cannot endorse insulin treatment to slow ALS progression.
{"title":"ALSUntangled #72: Insulin.","authors":"Andrew Brown, Carmel Armon, Paul Barkhaus, Morgan Beauchamp, Tulio Bertorini, Mark Bromberg, Javier Mascias Cadavid, Gregory T Carter, Jesse Crayle, Eva L Feldman, Terry Heiman-Patterson, Sartaj Jhooty, Alexandra Linares, Xiaoyan Li, Elise Mallon, Christopher Mcdermott, Tasnim Mushannen, George Nathaniel, Gary Pattee, Kaitlyn Pierce, Dylan Ratner, Lenka Slactova, Paul Wicks, Richard Bedlack","doi":"10.1080/21678421.2023.2288110","DOIUrl":"10.1080/21678421.2023.2288110","url":null,"abstract":"<p><p>ALSUntangled reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). Here we review insulin, which has at least one plausible mechanism for slowing ALS progression. However, pre-clinical studies are limited and there have been no trials in PALS yet. Insulin use in patients without a metabolic need may cause very serious and potentially lethal side effects. While further studies to evaluate potential benefits may be warranted, at this time we cannot endorse insulin treatment to slow ALS progression.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138453254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-01Epub Date: 2023-12-05DOI: 10.1080/21678421.2023.2288106
Sanjana Shellikeri, Sunghye Cho, Sharon Ash, Carmen Gonzalez-Recober, Corey T Mcmillan, Lauren Elman, Colin Quinn, Defne A Amado, Michael Baer, David J Irwin, Lauren Massimo, Christopher A Olm, Mark Y Liberman, Murray Grossman, Naomi Nevler
Objective: To evaluate automated digital speech measures, derived from spontaneous speech (picture descriptions), in assessing bulbar motor impairments in patients with ALS-FTD spectrum disorders (ALS-FTSD).
Methods: Automated vowel algorithms were employed to extract two vowel acoustic measures: vowel space area (VSA), and mean second formant slope (F2 slope). Vowel measures were compared between ALS with and without clinical bulbar symptoms (ALS + bulbar (n = 49, ALSFRS-r bulbar subscore: x¯ = 9.8 (SD = 1.7)) vs. ALS-nonbulbar (n = 23), behavioral variant frontotemporal dementia (bvFTD, n = 25) without a motor syndrome, and healthy controls (HC, n = 32). Correlations with bulbar motor clinical scales, perceived listener effort, and MRI cortical thickness of the orobuccal primary motor cortex (oral PMC) were examined. We compared vowel measures to speaking rate, a conventional metric for assessing bulbar dysfunction.
Results: ALS + bulbar had significantly reduced VSA and F2 slope than ALS-nonbulbar (|d|=0.94 and |d|=1.04, respectively), bvFTD (|d|=0.89 and |d|=1.47), and HC (|d|=0.73 and |d|=0.99). These reductions correlated with worse bulbar clinical scores (VSA: R = 0.33, p = 0.043; F2 slope: R = 0.38, p = 0.011), greater listener effort (VSA: R=-0.43, p = 0.041; F2 slope: p > 0.05), and cortical thinning in oral PMC (F2 slope: β = 0.0026, p = 0.017). Vowel measures demonstrated greater sensitivity and specificity for bulbar impairment than speaking rate, while showing independence from cognitive and respiratory impairments.
Conclusion: Automatic vowel measures are easily derived from a brief spontaneous speech sample, are sensitive to mild-moderate stage of bulbar disease in ALS-FTSD, and may present better sensitivity to bulbar impairment compared to traditional assessments such as speaking rate.
{"title":"Digital markers of motor speech impairments in spontaneous speech of patients with ALS-FTD spectrum disorders.","authors":"Sanjana Shellikeri, Sunghye Cho, Sharon Ash, Carmen Gonzalez-Recober, Corey T Mcmillan, Lauren Elman, Colin Quinn, Defne A Amado, Michael Baer, David J Irwin, Lauren Massimo, Christopher A Olm, Mark Y Liberman, Murray Grossman, Naomi Nevler","doi":"10.1080/21678421.2023.2288106","DOIUrl":"10.1080/21678421.2023.2288106","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate automated digital speech measures, derived from spontaneous speech (picture descriptions), in assessing bulbar motor impairments in patients with ALS-FTD spectrum disorders (ALS-FTSD).</p><p><strong>Methods: </strong>Automated vowel algorithms were employed to extract two vowel acoustic measures: vowel space area (VSA), and mean second formant slope (F2 slope). Vowel measures were compared between ALS with and without clinical bulbar symptoms (ALS + bulbar (n = 49, ALSFRS-r bulbar subscore: x¯ = 9.8 (SD = 1.7)) vs. ALS-nonbulbar (n = 23), behavioral variant frontotemporal dementia (bvFTD, n = 25) without a motor syndrome, and healthy controls (HC, n = 32). Correlations with bulbar motor clinical scales, perceived listener effort, and MRI cortical thickness of the orobuccal primary motor cortex (oral PMC) were examined. We compared vowel measures to speaking rate, a conventional metric for assessing bulbar dysfunction.</p><p><strong>Results: </strong>ALS + bulbar had significantly reduced VSA and F2 slope than ALS-nonbulbar (|d|=0.94 and |d|=1.04, respectively), bvFTD (|d|=0.89 and |d|=1.47), and HC (|d|=0.73 and |d|=0.99). These reductions correlated with worse bulbar clinical scores (VSA: R = 0.33, <i>p</i> = 0.043; F2 slope: R = 0.38, <i>p</i> = 0.011), greater listener effort (VSA: R=-0.43, <i>p</i> = 0.041; F2 slope: <i>p</i> > 0.05), and cortical thinning in oral PMC (F2 slope: β = 0.0026, <i>p</i> = 0.017). Vowel measures demonstrated greater sensitivity and specificity for bulbar impairment than speaking rate, while showing independence from cognitive and respiratory impairments.</p><p><strong>Conclusion: </strong>Automatic vowel measures are easily derived from a brief spontaneous speech sample, are sensitive to mild-moderate stage of bulbar disease in ALS-FTSD, and may present better sensitivity to bulbar impairment compared to traditional assessments such as speaking rate.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11023759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138489250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-01Epub Date: 2024-01-24DOI: 10.1080/21678421.2023.2300963
Mark R Janse van Mantgem, Maaike L Soors D'Ancona, Myrte Meyjes, Leonard H Van Den Berg, Elles Steenhagen, Annemieke Kok, Ruben P A Van Eijk
Aim: To determine the validity of bioelectrical impedance analysis (BIA) in quantifying fat-free mass (FFM) compared to air-displacement plethysmography (ADP) in patients with a motor neurone disease (MND).
Methods: FFM of 140 patients diagnosed with MND was determined by ADP using the BodPod (i.e. the gold standard), and by BIA using the whole-body Bodystat. FFM values were translated to predicted resting energy expenditure (REE); the actual REE was measured using indirect calorimetry, resulting in a metabolic index. Validity of the BIA compared to the ADP was assessed using Bland-Altman analysis and Pearson's r. To assess the clinical relevance of differences, we evaluated changes in metabolic index and in individualized protein demand.
Results: Despite the high correlation between ADP and BIA (r = 0.93), averaged across patients, the assessed mean fat-free mass was 51.7 kg (± 0.9) using ADP and 54.2 kg (± 1.0) using BIA. Hence, BIA overestimated fat-free mass by 2.5 kg (95% CI 1.8-3.2, p < 0.001). Clinically, an increased metabolic index would be more often underdiagnosed in patients with MND using BIA (31.4% according to BIA versus 44.2% according to ADP, p = 0.048). A clinically relevant overestimation of ≥ 15 g in protein demand was observed for 4 (2.9%) patients using BIA.
Conclusions: BIA systematically overestimates FFM in patients with MND. Although the differences are limited with ADP, underscoring the utility of BIA for research, overestimation of fat-free mass may have consequences for clinical decision-making, especially when interest lies in determining the metabolic index.
{"title":"A comparison between bioelectrical impedance analysis and air-displacement plethysmography in assessing fat-free mass in patients with motor neurone diseases: a cross-sectional study.","authors":"Mark R Janse van Mantgem, Maaike L Soors D'Ancona, Myrte Meyjes, Leonard H Van Den Berg, Elles Steenhagen, Annemieke Kok, Ruben P A Van Eijk","doi":"10.1080/21678421.2023.2300963","DOIUrl":"10.1080/21678421.2023.2300963","url":null,"abstract":"<p><strong>Aim: </strong>To determine the validity of bioelectrical impedance analysis (BIA) in quantifying fat-free mass (FFM) compared to air-displacement plethysmography (ADP) in patients with a motor neurone disease (MND).</p><p><strong>Methods: </strong>FFM of 140 patients diagnosed with MND was determined by ADP using the BodPod (i.e. the gold standard), and by BIA using the whole-body Bodystat. FFM values were translated to predicted resting energy expenditure (REE); the actual REE was measured using indirect calorimetry, resulting in a metabolic index. Validity of the BIA compared to the ADP was assessed using Bland-Altman analysis and Pearson's <i>r</i>. To assess the clinical relevance of differences, we evaluated changes in metabolic index and in individualized protein demand.</p><p><strong>Results: </strong>Despite the high correlation between ADP and BIA (<i>r =</i> 0.93), averaged across patients, the assessed mean fat-free mass was 51.7 kg (± 0.9) using ADP and 54.2 kg (± 1.0) using BIA. Hence, BIA overestimated fat-free mass by 2.5 kg (95% CI 1.8-3.2, <i>p</i> < 0.001). Clinically, an increased metabolic index would be more often underdiagnosed in patients with MND using BIA (31.4% according to BIA versus 44.2% according to ADP, <i>p</i> = 0.048). A clinically relevant overestimation of ≥ 15 g in protein demand was observed for 4 (2.9%) patients using BIA.</p><p><strong>Conclusions: </strong>BIA systematically overestimates FFM in patients with MND. Although the differences are limited with ADP, underscoring the utility of BIA for research, overestimation of fat-free mass may have consequences for clinical decision-making, especially when interest lies in determining the metabolic index.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139543681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-01Epub Date: 2024-03-01DOI: 10.1080/21678421.2024.2322539
Carolyn A Young, Amina Chaouch, Christopher J Mcdermott, Ammar Al-Chalabi, Suresh K Chhetri, Kevin Talbot, Andrea Malaspina, Roger Mills, Alan Tennant
Background: The Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) total score is a widely used measure of functional status in Amyotrophic Lateral Sclerosis/Motor Neuron Disease (ALS), but recent evidence has raised doubts about its validity. The objective was to examine the measurement properties of the ALSFRS-R, aiming to produce valid measurement from all 12 scale items.
Method: Longitudinal ALSFRS-R data were collected between 2013-2020 from 1120 people with ALS recruited from 35 centers, together with other scales in the Trajectories of Outcomes in Neurological Conditions-ALS (TONiC-ALS) study. The ALSFRS-R was analyzed by confirmatory factor analysis (CFA), Rasch Analysis (RA) and Mokken scaling.
Results: No definite factor structure of the ALSFRS-R was confirmed by CFA. RA revealed the raw score total to be invalid even at the ordinal level because of multidimensionality; valid interval level subscale measures could be found for the Bulbar, Fine-Motor and Gross-Motor domains but the Respiratory domain was only valid at an ordinal level. All four domains resolved into a single valid, interval level measure by using a bifactor RA. The smallest detectable difference was 10.4% of the range of the interval scale.
Conclusion: A total ALSFRS-R ordinal raw score can lead to inferential bias in clinical trial results due to its non-linear nature. On the interval level transformation, more than 5 points difference is required before a statistically significant detectable difference can be observed. Transformation to interval level data should be mandatory in clinical trials.
{"title":"Improving the measurement properties of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R): deriving a valid measurement total for the calculation of change.","authors":"Carolyn A Young, Amina Chaouch, Christopher J Mcdermott, Ammar Al-Chalabi, Suresh K Chhetri, Kevin Talbot, Andrea Malaspina, Roger Mills, Alan Tennant","doi":"10.1080/21678421.2024.2322539","DOIUrl":"10.1080/21678421.2024.2322539","url":null,"abstract":"<p><strong>Background: </strong>The Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) total score is a widely used measure of functional status in Amyotrophic Lateral Sclerosis/Motor Neuron Disease (ALS), but recent evidence has raised doubts about its validity. The objective was to examine the measurement properties of the ALSFRS-R, aiming to produce valid measurement from all 12 scale items.</p><p><strong>Method: </strong>Longitudinal ALSFRS-R data were collected between 2013-2020 from 1120 people with ALS recruited from 35 centers, together with other scales in the Trajectories of Outcomes in Neurological Conditions-ALS (TONiC-ALS) study. The ALSFRS-R was analyzed by confirmatory factor analysis (CFA), Rasch Analysis (RA) and Mokken scaling.</p><p><strong>Results: </strong>No definite factor structure of the ALSFRS-R was confirmed by CFA. RA revealed the raw score total to be invalid even at the ordinal level because of multidimensionality; valid interval level subscale measures could be found for the Bulbar, Fine-Motor and Gross-Motor domains but the Respiratory domain was only valid at an ordinal level. All four domains resolved into a single valid, interval level measure by using a bifactor RA. The smallest detectable difference was 10.4% of the range of the interval scale.</p><p><strong>Conclusion: </strong>A total ALSFRS-R ordinal raw score can lead to inferential bias in clinical trial results due to its non-linear nature. On the interval level transformation, more than 5 points difference is required before a statistically significant detectable difference can be observed. Transformation to interval level data should be mandatory in clinical trials.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11262430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139998386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-01Epub Date: 2024-02-10DOI: 10.1080/21678421.2024.2314064
Jong-Su Kim, Minae Park, Sojeong Park, Juhee Chae, Yoon-Ho Hong, Kyung Seok Park, Jung-Joon Sung, Seok-Jin Choi
Background: Tracheostomy invasive ventilation (TIV) is applied to a subset of amyotrophic lateral sclerosis (ALS) patients; however, its frequency and impact on prognosis vary across countries. Methods: We conducted a nationwide retrospective cohort study using Korean National Health Insurance claims data. All patients diagnosed with sporadic ALS from 2012 to 2017 were included, with the observation period until 2020. The survival time between the TIV and non-TIV groups was compared using propensity score matching analysis, and prognostic factors were assessed within the TIV group. Results: This study included 3484 ALS patients (mean [standard deviation] age, 62.4 [11.9] years, 60.4% male), among whom 1230 (35.3%) underwent TIV. After 1:1 propensity score matching, the survival duration between the two groups was not significantly different (28 vs. 25 months, p = 0.057). Cox regression indicated that older age (hazard ratios [HRs] for each decade compared to <40 years: 3.89, 3.83, 5.30, 6.78, and 8.40 [80 years]; p < 0.005 for all) and lower income (HR, 1.28; 95% confidence interval [CI], 1.09-1.52; p = 0.003) negatively impacted survival, while gastrostomy (HR, 0.57; 95% CI, 0.50-0.66; p < 0.001) and supportive care services (HR, 0.43; 95% CI, 0.32-0.59; p < 0.001) were associated with prolonged survival. Conclusions: TIV was administered to more than one-third of Korean ALS patients without significant survival prolongation. Older age, lower income, lack of gastrostomy, and insufficient supportive care were independent poor prognostic factors for survival, underscoring the importance of comprehensive management for ALS patients.
背景:气管插管有创通气(TIV)适用于一部分肌萎缩侧索硬化症(ALS)患者;然而,其使用频率和对预后的影响因国家而异。方法:我们利用韩国国民健康保险理赔数据开展了一项全国性回顾性队列研究。研究纳入了 2012 年至 2017 年确诊的所有散发性 ALS 患者,观察期至 2020 年。使用倾向得分匹配分析比较了TIV组和非TIV组的生存时间,并评估了TIV组的预后因素。研究结果该研究共纳入 3484 例 ALS 患者(平均 [标准差] 年龄为 62.4 [11.9] 岁,60.4% 为男性),其中 1230 例(35.3%)接受了 TIV 治疗。经过 1:1 倾向评分匹配后,两组患者的存活时间无明显差异(28 个月 vs. 25 个月,p = 0.057)。Cox回归表明,年龄越大(与≥80岁相比,每十年的危险比[HRs]; p p = 0.003)对存活率有负面影响,而胃造口术(HR,0.57; 95% CI,0.50-0.66; p p结论:超过三分之一的韩国 ALS 患者接受了 TIV 治疗,但存活时间并未明显延长。年龄较大、收入较低、缺乏胃造瘘术和支持性护理不足是影响存活率的独立不良预后因素,这凸显了对 ALS 患者进行综合管理的重要性。
{"title":"Prognosis of amyotrophic lateral sclerosis patients after tracheostomy invasive ventilation in Korea.","authors":"Jong-Su Kim, Minae Park, Sojeong Park, Juhee Chae, Yoon-Ho Hong, Kyung Seok Park, Jung-Joon Sung, Seok-Jin Choi","doi":"10.1080/21678421.2024.2314064","DOIUrl":"10.1080/21678421.2024.2314064","url":null,"abstract":"<p><p><i>Background</i>: Tracheostomy invasive ventilation (TIV) is applied to a subset of amyotrophic lateral sclerosis (ALS) patients; however, its frequency and impact on prognosis vary across countries. <i>Methods</i>: We conducted a nationwide retrospective cohort study using Korean National Health Insurance claims data. All patients diagnosed with sporadic ALS from 2012 to 2017 were included, with the observation period until 2020. The survival time between the TIV and non-TIV groups was compared using propensity score matching analysis, and prognostic factors were assessed within the TIV group. <i>Results</i>: This study included 3484 ALS patients (mean [standard deviation] age, 62.4 [11.9] years, 60.4% male), among whom 1230 (35.3%) underwent TIV. After 1:1 propensity score matching, the survival duration between the two groups was not significantly different (28 vs. 25 months, <i>p</i> = 0.057). Cox regression indicated that older age (hazard ratios [HRs] for each decade compared to <40 years: 3.89, 3.83, 5.30, 6.78, and 8.40 [<math><mrow><mo>≥</mo></mrow></math>80 years]; <i>p</i> < 0.005 for all) and lower income (HR, 1.28; 95% confidence interval [CI], 1.09-1.52; <i>p</i> = 0.003) negatively impacted survival, while gastrostomy (HR, 0.57; 95% CI, 0.50-0.66; <i>p</i> < 0.001) and supportive care services (HR, 0.43; 95% CI, 0.32-0.59; <i>p</i> < 0.001) were associated with prolonged survival. <i>Conclusions</i>: TIV was administered to more than one-third of Korean ALS patients without significant survival prolongation. Older age, lower income, lack of gastrostomy, and insufficient supportive care were independent poor prognostic factors for survival, underscoring the importance of comprehensive management for ALS patients.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139716729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-01Epub Date: 2024-02-23DOI: 10.1080/21678421.2024.2320880
Angela Genge, Jesse M Cedarbaum, Jeremy Shefner, Adriano Chio, Ammar Al-Chalabi, Philip Van Damme, Chris McDermott, Jonathan Glass, James Berry, Ruben P A van Eijk, Christina Fournier, Julian Grosskreutz, Jinsy Andrews, Vanessa Bertone, Tommy M Bunte, Mathias Couillard, Cathy Cummings, Gale Kittle, John Polzer, Kristiana Salmon, Corey Straub, Leonard H van den Berg
The Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) was developed more than 25 years ago as an instrument to monitor functional change over time in patients with ALS. It has since been revised and extended to meet the needs of high data quality in ALS trials (ALSFRS-R), however a full re-validation of the scale was not completed. Despite this, the scale has remained a primary outcome measure in clinical trials. We convened a group of clinical trialists to discuss and explore opportunities to improve the scale and propose alternative measures. In this meeting report, we present a call to action on the use of the ALSFRS-Revised scale in clinical trials, focusing on the need for (1) harmonization of the ALSFRS-R administration globally, (2) alignment on a set of recommendations for clinical trial design and statistical analysis plans (SAPs), and (3) use of additional outcome measures.
{"title":"The ALSFRS-R Summit: a global call to action on the use of the ALSFRS-R in ALS clinical trials.","authors":"Angela Genge, Jesse M Cedarbaum, Jeremy Shefner, Adriano Chio, Ammar Al-Chalabi, Philip Van Damme, Chris McDermott, Jonathan Glass, James Berry, Ruben P A van Eijk, Christina Fournier, Julian Grosskreutz, Jinsy Andrews, Vanessa Bertone, Tommy M Bunte, Mathias Couillard, Cathy Cummings, Gale Kittle, John Polzer, Kristiana Salmon, Corey Straub, Leonard H van den Berg","doi":"10.1080/21678421.2024.2320880","DOIUrl":"10.1080/21678421.2024.2320880","url":null,"abstract":"<p><p>The Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) was developed more than 25 years ago as an instrument to monitor functional change over time in patients with ALS. It has since been revised and extended to meet the needs of high data quality in ALS trials (ALSFRS-R), however a full re-validation of the scale was not completed. Despite this, the scale has remained a primary outcome measure in clinical trials. We convened a group of clinical trialists to discuss and explore opportunities to improve the scale and propose alternative measures. In this meeting report, we present a call to action on the use of the ALSFRS-Revised scale in clinical trials, focusing on the need for (1) harmonization of the ALSFRS-R administration globally, (2) alignment on a set of recommendations for clinical trial design and statistical analysis plans (SAPs), and (3) use of additional outcome measures.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139941351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-01Epub Date: 2024-01-02DOI: 10.1080/21678421.2023.2299204
Jade Howard, Hilary L Bekker, Christopher J Mcdermott, Alisdair Mcneill
Genetic testing is a key decision-making point for people with motor neuron disease (MND); to establish eligibility for clinical trials, better understand the cause of their condition, and confirm the potential risk to relatives, who may be able to access predictive testing. Given the wide-reaching implications of MND genetic and predictive testing, it is essential that families are given adequate information, and that staff are provided with appropriate training. In this report we overview the information resources available to people with MND and family members around genetic testing, and the educational and training resources available to staff, based on information obtained through a freedom of information request to UK-based NHS Trusts. MND Association resources were most commonly used in information sharing, though we highlight distinctions between neurology and genetics centers. No respondents identified comprehensive training around MND genetic testing. We conclude with practice implications and priorities for the development of resources and training.
{"title":"A report of resources used by clinicians in the UK to support motor neuron disease genomic testing.","authors":"Jade Howard, Hilary L Bekker, Christopher J Mcdermott, Alisdair Mcneill","doi":"10.1080/21678421.2023.2299204","DOIUrl":"10.1080/21678421.2023.2299204","url":null,"abstract":"<p><p>Genetic testing is a key decision-making point for people with motor neuron disease (MND); to establish eligibility for clinical trials, better understand the cause of their condition, and confirm the potential risk to relatives, who may be able to access predictive testing. Given the wide-reaching implications of MND genetic and predictive testing, it is essential that families are given adequate information, and that staff are provided with appropriate training. In this report we overview the information resources available to people with MND and family members around genetic testing, and the educational and training resources available to staff, based on information obtained through a freedom of information request to UK-based NHS Trusts. MND Association resources were most commonly used in information sharing, though we highlight distinctions between neurology and genetics centers. No respondents identified comprehensive training around MND genetic testing. We conclude with practice implications and priorities for the development of resources and training.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11262425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139075998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-01Epub Date: 2024-02-09DOI: 10.1080/21678421.2024.2314061
Sean White, Alicia O'Cathain, Vanessa Halliday, Michael Bradburn, Christopher J McDermott
Objective: Understand the practice and beliefs of healthcare professionals (HCPs) supporting the decision-making of people with MND (pwMND) about gastrostomy placement, including identifying differences between professions.
Methods: An online cross-sectional survey disseminated to HCPs who support the decision-making of pwMND about gastrostomy placement.
Results: A total of 139 participants completed the survey including representation from a range of healthcare professions. A third (36/101, 36%) initiated discussions about gastrostomy later in practice than they believed was ideal. In relation to the outcome of declining compared to accepting gastrostomy, participants were more likely to discuss aspiration (80% vs. 68%), choking (76% vs. 58%) and prognosis (36% vs. 22%). Participants believed gastrostomies should be placed after a mean 8.1% weight loss since symptom-onset. More participants favored gastrostomy placement before pwMND presented with respiratory symptoms (45%) compared to onset of dysphagia (11%). Half believed pwMND placed gastrostomies too late. Participants were more likely to 'often'/'always' recommend pwMND to have a gastrostomy (23%) than continue without (7%) or decline (4%) gastrostomy, when believing these were the best option for pwMND. Nurses and dietitians discussed the broadest range of information, while doctors were more likely to discuss mortality risk and prognosis.
Conclusion: There is variation in HCPs practice and beliefs about initiating discussions, the sharing of information and recommendations, and timing, about gastrostomy placement. The information shared varies by profession and there is evidence of sub-optimal communication between HCPs. Further research is required to understand how these findings may impact on the decision-making of pwMND about gastrostomy.
{"title":"Supporting people with Motor Neuron Disease (MND) to make decisions about gastrostomy feeding tube placement: a survey of UK healthcare professionals' practice and beliefs.","authors":"Sean White, Alicia O'Cathain, Vanessa Halliday, Michael Bradburn, Christopher J McDermott","doi":"10.1080/21678421.2024.2314061","DOIUrl":"10.1080/21678421.2024.2314061","url":null,"abstract":"<p><strong>Objective: </strong>Understand the practice and beliefs of healthcare professionals (HCPs) supporting the decision-making of people with MND (pwMND) about gastrostomy placement, including identifying differences between professions.</p><p><strong>Methods: </strong>An online cross-sectional survey disseminated to HCPs who support the decision-making of pwMND about gastrostomy placement.</p><p><strong>Results: </strong>A total of 139 participants completed the survey including representation from a range of healthcare professions. A third (36/101, 36%) initiated discussions about gastrostomy later in practice than they believed was ideal. In relation to the outcome of declining compared to accepting gastrostomy, participants were more likely to discuss aspiration (80% vs. 68%), choking (76% vs. 58%) and prognosis (36% vs. 22%). Participants believed gastrostomies should be placed after a mean 8.1% weight loss since symptom-onset. More participants favored gastrostomy placement before pwMND presented with respiratory symptoms (45%) compared to onset of dysphagia (11%). Half believed pwMND placed gastrostomies too late. Participants were more likely to 'often'/'always' recommend pwMND to have a gastrostomy (23%) than continue without (7%) or decline (4%) gastrostomy, when believing these were the best option for pwMND. Nurses and dietitians discussed the broadest range of information, while doctors were more likely to discuss mortality risk and prognosis.</p><p><strong>Conclusion: </strong>There is variation in HCPs practice and beliefs about initiating discussions, the sharing of information and recommendations, and timing, about gastrostomy placement. The information shared varies by profession and there is evidence of sub-optimal communication between HCPs. Further research is required to understand how these findings may impact on the decision-making of pwMND about gastrostomy.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11262427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139713478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-26DOI: 10.1080/21678421.2024.2346825
Laurel Officer, Carmel Armon, Paul Barkhaus, Morgan Beauchamp, Michael Benatar, Tulio E. Bertorini, Robert Bowser, Mark B. Bromberg, Andrew Brown, O. Carbunar, Gregory T. Carter, J. Crayle, Keelie Denson, Eva Feldman, Timothy R Fullam, Terry Heiman-Patterson, Carlayne Jackson, Sartaj Jhooty, Danelle Levinson, Xiaoyan Li, Alexandra Linares, Elise Mallon, Javier Mascías Cadavid, C. Mcdermott, Tasnim Mushannen, L. Ostrow, Ronak Patel, Gary L. Pattee, Dylan Ratner, Yuyao Sun, J. Sladky, Paul Wicks, Richard Bedlack
Spurred by patient interest, ALSUntangled herein examines the potential of the Portable Neuromodulation Stimulator (PoNS™) in treating amyotrophic lateral sclerosis (ALS). The PoNS™ device, FDA-approved for the treatment of gait deficits in adult patients with multiple sclerosis, utilizes translingual neurostimulation to stimulate trigeminal and facial nerves via the tongue, aiming to induce neuroplastic changes. While there are early, promising data for PoNS treatment to improve gait and balance in multiple sclerosis, stroke, and traumatic brain injury, no pre-clinical or clinical studies have been performed in ALS. Although reasonably safe, high costs and prescription requirements will limit PoNS accessibility. At this time, due to the lack of ALS-relevant data, we cannot endorse the use of PoNS as an ALS treatment.
在患者兴趣的推动下,ALSUntangled 在此研究了便携式神经调控刺激器 (PoNS™) 在治疗肌萎缩侧索硬化症 (ALS) 方面的潜力。PoNS™ 设备经 FDA 批准用于治疗成年多发性硬化症患者的步态障碍,它利用跨语言神经刺激,通过舌头刺激三叉神经和面部神经,旨在诱导神经可塑性变化。虽然 PoNS 治疗改善多发性硬化症、中风和脑外伤患者的步态和平衡的早期数据很有希望,但尚未对 ALS 进行临床前或临床研究。尽管 PoNS 相当安全,但高昂的费用和处方要求将限制 PoNS 的使用。目前,由于缺乏与 ALS 相关的数据,我们无法认可将 PoNS 用作 ALS 的治疗方法。
{"title":"ALSUntangled #75: Portable neuromodulation stimulator therapy.","authors":"Laurel Officer, Carmel Armon, Paul Barkhaus, Morgan Beauchamp, Michael Benatar, Tulio E. Bertorini, Robert Bowser, Mark B. Bromberg, Andrew Brown, O. Carbunar, Gregory T. Carter, J. Crayle, Keelie Denson, Eva Feldman, Timothy R Fullam, Terry Heiman-Patterson, Carlayne Jackson, Sartaj Jhooty, Danelle Levinson, Xiaoyan Li, Alexandra Linares, Elise Mallon, Javier Mascías Cadavid, C. Mcdermott, Tasnim Mushannen, L. Ostrow, Ronak Patel, Gary L. Pattee, Dylan Ratner, Yuyao Sun, J. Sladky, Paul Wicks, Richard Bedlack","doi":"10.1080/21678421.2024.2346825","DOIUrl":"https://doi.org/10.1080/21678421.2024.2346825","url":null,"abstract":"Spurred by patient interest, ALSUntangled herein examines the potential of the Portable Neuromodulation Stimulator (PoNS™) in treating amyotrophic lateral sclerosis (ALS). The PoNS™ device, FDA-approved for the treatment of gait deficits in adult patients with multiple sclerosis, utilizes translingual neurostimulation to stimulate trigeminal and facial nerves via the tongue, aiming to induce neuroplastic changes. While there are early, promising data for PoNS treatment to improve gait and balance in multiple sclerosis, stroke, and traumatic brain injury, no pre-clinical or clinical studies have been performed in ALS. Although reasonably safe, high costs and prescription requirements will limit PoNS accessibility. At this time, due to the lack of ALS-relevant data, we cannot endorse the use of PoNS as an ALS treatment.","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140652007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}