Xiaoyan Li, Paul Wicks, Andrew Brown, Akhil Shivaprasad, Maxwell Greene, Jesse Crayle, Benjamin Barnes, Sartaj Jhooty, Dylan Ratner, Natasha Olby, Jonathan D Glass, Carlayne Jackson, Nicholas Cole, Carmel Armon, Javier Mascias Cadavid, Gary Pattee, Christopher J Mcdermott, Vincent Chang, Nicholas Maragakis, Tulio Bertorini, Robert Bowser, Richard Bedlack
{"title":"ALSUntangled #76: Wahls protocol.","authors":"Xiaoyan Li, Paul Wicks, Andrew Brown, Akhil Shivaprasad, Maxwell Greene, Jesse Crayle, Benjamin Barnes, Sartaj Jhooty, Dylan Ratner, Natasha Olby, Jonathan D Glass, Carlayne Jackson, Nicholas Cole, Carmel Armon, Javier Mascias Cadavid, Gary Pattee, Christopher J Mcdermott, Vincent Chang, Nicholas Maragakis, Tulio Bertorini, Robert Bowser, Richard Bedlack","doi":"10.1080/21678421.2024.2407407","DOIUrl":"https://doi.org/10.1080/21678421.2024.2407407","url":null,"abstract":"<p><p>The Wahls diet is a modified Paleolithic diet that emphasizes dark green leafy vegetables, colorful fruits, high-quality animal proteins, and omega-3 polyunsaturated fatty acids, while limiting grains, legumes, dairy products, sugar, and processed foods containing proinflammatory omega-6 fatty acids. The Wahls diet may reduce inflammation, oxidative stress, and mitochondrial dysfunction and has plausible mechanisms for slowing amyotrophic lateral sclerosis (ALS) progression. However, research on its dietary components in the ALS animal models has yielded conflicting results. Though multiple cohort studies suggest high carotenoids, omega-3 fatty acids and fruit intake are associated with reduced ALS risks, neither the diet nor its components has been demonstrated to slow down ALS progression in case studies or clinical trials. On the contrary, the Wahls diet, a restrictive, low-carbohydrate and low glycemic index diet, caused an average weight loss of 7.2% BMI in multiple sclerosis clinical trials, which is a significant concern for people living with amyotrophic lateral sclerosis (PALS) as weight loss is associated with faster ALS progression and shorter survival. Considering the above, we cannot endorse the Wahls diet for slowing ALS progression.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395665","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}
{"title":"Graph theory network analysis reveals widespread white matter damage in brains of patients with classic ALS.","authors":"Venkateswaran Rajagopalan, Erik P Pioro","doi":"10.1080/21678421.2024.2410281","DOIUrl":"https://doi.org/10.1080/21678421.2024.2410281","url":null,"abstract":"<p><p><i>Objective</i>: Amyotrophic lateral sclerosis (ALS) exhibits several different presentations and clinical phenotypes. Of these, classic ALS (ALS-Cl), which is the most common phenotype, presents with relatively equal amounts of upper motor neuron and lower motor neuron signs. Magnetic resonance imaging (MRI) provides a noninvasive way to assess central nervous system damage in these patients. To our knowledge no study is available where exploratory whole brain grey matter (GM) and white matter (WM) network analysis is performed considering only the ALS-Cl subgroup of ALS patients. <i>Methods</i>: GM voxel-based morphometry analysis and WM network analysis using graph theory was performed in the MRI dataset of 14 neurologic controls and 25 ALS-Cl patients<b>.</b> <i>Results and Conclusions:</i> No significant GM differences were observed between ALS-Cl and neurologic controls. WM network revealed significant (<i>p</i> < 0.05) reduction and increase in degree measure in several extramotor brain regions of ALS-Cl patients. Both global and local graph metrics revealed significant abnormal values in ALS-Cl patients when compared to neurologic controls. Significant WM changes in ALS-Cl patients with no significant GM changes suggest that neurodegeneration may onset as an \"axonopathy\" in this ALS subtype.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382587","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}
David Paul Capelle, Wafa Sabirin, Nurul Angelyn Zulhairy-Liong, Suzanna Edgar, Khean-Jin Goh, Azlina Ahmad-Annuar, Nortina Shahrizaila
{"title":"Multistep modeling applied to a Malaysian ALS registry.","authors":"David Paul Capelle, Wafa Sabirin, Nurul Angelyn Zulhairy-Liong, Suzanna Edgar, Khean-Jin Goh, Azlina Ahmad-Annuar, Nortina Shahrizaila","doi":"10.1080/21678421.2024.2410280","DOIUrl":"https://doi.org/10.1080/21678421.2024.2410280","url":null,"abstract":"<p><strong>Objective: </strong>To apply the multistep model of pathogenesis in amyotrophic lateral sclerosis (ALS) to data from a multiethnic Malaysian registry.</p><p><strong>Methods: </strong>Clinical data, including age at symptom onset, was collected from 289 patients who presented to our multidisciplinary clinic from 2016 until 2024. A least squares linear regression model was constructed from the logarithm of approximated incidence and the logarithm of age. Population incidence was approximated by adjusting the absolute numbers of patients in 5 year groups by the size of the general population in the respective age group.</p><p><strong>Results: </strong>A linear relationship between log of incidence versus log of age was observed, with a slope of 4.57 (95% CI, 3.3-5.8) and an <i>r<sup>2</sup></i> value of 0.93, suggesting a 6-step process.</p><p><strong>Conclusion: </strong>Progression toward symptom onset in Malaysian ALS patients appears consistent with a multistep model of disease as observed in other cohorts.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373658","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}
{"title":"Alteration in ornithine metabolism due to mutation in <i>ALDH18A1</i> masquerading as ALS in pregnancy.","authors":"Suzanne Quigley, Brian McNamara, Simon Cronin","doi":"10.1080/21678421.2024.2410982","DOIUrl":"https://doi.org/10.1080/21678421.2024.2410982","url":null,"abstract":"<p><p>Clinical onset and exacerbation of autosomal dominant SPG9A hereditary spastic paraplegia, including reversible wasting, has been described during pregnancy. SPG9A is due to <i>ALDH18A1</i> mutations resulting in proline and ornithine deficiency. We present the case of a 29 year old primagravida at 32 weeks who presented with six months of upper limb amyotrophic wasting on a background unrecognized progressive spasticity due to SPG9A. The wasting reversed significantly following delivery. Our report highlights the unusual clinical features including cataract and joint laxity which may suggest SPG9A, echoes the existing descriptions of pregnancy-related provocation of amyotrophy in this condition and documents the outcome of two subsequent pregnancies following dietary intervention.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367731","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}
Inês Alves, Marta Gromicho, Miguel Oliveira Santos, Susana Pinto, Mamede de Carvalho
{"title":"Assessing disease progression in ALS: prognostic subgroups and outliers.","authors":"Inês Alves, Marta Gromicho, Miguel Oliveira Santos, Susana Pinto, Mamede de Carvalho","doi":"10.1080/21678421.2024.2407412","DOIUrl":"https://doi.org/10.1080/21678421.2024.2407412","url":null,"abstract":"<p><p><i>Background</i>: The rate of disease progression, measured by the decline of ALS Functional Rating Scale-Revised (ALSFRS-R) from symptom onset to diagnosis (ΔFS) is a well-established prognostic biomarker for predicting survival. <i>Objectives</i>: This study aims to categorize a large patient cohort based on the initial ΔFS and subsequently investigate survival deviations from the expected prognosis defined by ΔFS. <i>Methods</i>: 1056 ALS patients were stratified into three progression categories based on their ΔFS: slow progressors (below 25th percentile), intermediate progressors (between 25th and 75th percentiles), and fast progressors (above 75th percentile). Survival outcomes were classified as short survivors (<2 years), average survivors (2-5 years), and long survivors (>5 years). Clinical and demographic characteristics within each subgroup were then analyzed. <i>Results</i>: ΔFS stratification yielded cutoff values of <0.29, 0.29-1.03, and >1.03 points/month. Long survivors comprised 26% and 21% were short survivors. Six percent of the fast progressors had a life expectancy of more than 5 years, and none of the clinical and demographic characteristics analyzed could fully explain this discrepancy. Conversely, 13% of intermediate progressors lived less than 2 years, according to a short-diagnostic delay in these patients. <i>Discussion</i>: Our study reaffirms ΔFS as a prognostic biomarker for ALS. We disclosed outliers defying anticipated patterns. The observed shift in progression categories underscores the non-linear nature of disease progression. Genetic and unknown biological reasons may explain these deviations. Further research is needed to fully understand modulation of ALS survival.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333580","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}
Ikjae Lee, Matteo Vestrucci, Seonjoo Lee, Michael Rosenbaum, Hiroshi Mitsumoto
{"title":"Blood glycated hemoglobin level is not associated with disease progression in amyotrophic lateral sclerosis.","authors":"Ikjae Lee, Matteo Vestrucci, Seonjoo Lee, Michael Rosenbaum, Hiroshi Mitsumoto","doi":"10.1080/21678421.2024.2407409","DOIUrl":"https://doi.org/10.1080/21678421.2024.2407409","url":null,"abstract":"<p><p><i>Objective:</i> A high glycemic index and high glycemic load diet has been associated with slower progression of amyotrophic lateral sclerosis (ALS), suggesting a benefit from high blood glucose levels. We examined the association between average blood glucose level and ALS progression in two independent cohorts. <i>Methods:</i> Sporadic ALS patients enrolled in the ALS Multicenter Cohort Study of Oxidative Stress (ALS COSMOS) who completed a 3-month follow-up visit and had available blood samples were included. Hemoglobin A1c (HbA1c) was measured from whole blood collected at the 3-month follow-up. From the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database, we included ALS patients with one or more HbA1c measurements at enrollment and available death information. Associations between HbA1c with revised ALS functional rating scale (ALSFRS-R)/ALSFRS total score change, and tracheostomy-free survival/survival were examined in these cohorts using linear regression, linear mixed-effects models, and Cox proportional hazard models, adjusted for covariates. <i>Results:</i> In the ALS COSMOS cohort (<i>n</i> = 193), HbA1c level was not significantly associated with the change in the ALSFRS-R total score from baseline to the 3-month follow-up (<i>p</i> = 0.8) nor baseline to the 6-month follow-up (<i>p</i> = 0.4). No significant association was found between HbA1c level and tracheostomy-free survival (<i>p</i> = 0.8). In the PRO-ACT cohort (<i>n</i> = 928), no significant association was found between HbA1c level and the rate of ALSFRS decline in the first 200 days (<i>p</i> = 0.81 for interaction) nor between HbA1c level and survival (<i>p</i> = 0.45). <i>Interpretation:</i> We did not find convincing evidence that mean blood glucose level is associated with disease progression among ALS patients.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333581","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}
Cathrine Goberg Olsen, Vetle Nilsen Malmberg, Maria Fahlström, Karl Bjørnar Alstadhaug, Ingrid Kristine Bjørnå, Geir Julius Braathen, Geir Bråthen, Natasha Demic, Erika Hallerstig, Ineke Hogenesch, Morten Andreas Horn, Margitta T Kampman, Grethe Kleveland, Unn Ljøstad, Angelina Maniaol, Åse Hagen Morsund, Ola Nakken, Katrin Schlüter, Stephan Schuler, Elin Seim, Heidi Øyen Flemmen, Ole-Bjørn Tysnes, Trygve Holmøy, Helle Høyer
{"title":"Amyotrophic lateral sclerosis caused by the <i>C9orf72</i> expansion in Norway - prevalence, ancestry, clinical characteristics and sociodemographic status.","authors":"Cathrine Goberg Olsen, Vetle Nilsen Malmberg, Maria Fahlström, Karl Bjørnar Alstadhaug, Ingrid Kristine Bjørnå, Geir Julius Braathen, Geir Bråthen, Natasha Demic, Erika Hallerstig, Ineke Hogenesch, Morten Andreas Horn, Margitta T Kampman, Grethe Kleveland, Unn Ljøstad, Angelina Maniaol, Åse Hagen Morsund, Ola Nakken, Katrin Schlüter, Stephan Schuler, Elin Seim, Heidi Øyen Flemmen, Ole-Bjørn Tysnes, Trygve Holmøy, Helle Høyer","doi":"10.1080/21678421.2024.2405118","DOIUrl":"10.1080/21678421.2024.2405118","url":null,"abstract":"<p><strong>Objective: </strong>The most common genetic cause of amyotrophic lateral sclerosis (ALS) is the <i>C9orf72</i> expansion. A high incidence of this expansion has been detected in Sweden and Finland. This Norwegian population-based study aimed to identify the prevalence, geographic distribution, ancestry, and relatedness of ALS patients with a <i>C9orf72</i> expansion (C9<sub>pos</sub>). Further, we compared C9<sub>pos</sub> and C9<sub>neg</sub> patients' clinical presentation, family history of ALS and other neurodegenerative disorders, and sociodemographic status.</p><p><strong>Methods: </strong>We recruited ALS patients from all 17 Departments of neurology in Norway. Blood samples and questionnaires regarding clinical characteristics, sociodemographic status and family history of ALS, and other neurodegenerative disorders were collected. The <i>C9orf72</i> expansion was examined for all patients.</p><p><strong>Results: </strong>The study enrolled 500 ALS patients, 8.8% of whom were C9<sub>pos</sub>, with half being sporadic ALS cases. The proportion of C9<sub>pos</sub> cases differed between regions, ranging from 17.9% in the Northern region to 1.9% in the Western region. The majority of C9<sub>pos</sub> patients had non-Finnish European descent and were not closely related. C9<sub>pos</sub> patients exhibited a significantly shorter mean survival time, had a higher frequency of relatives with ALS or dementia, and were more often unmarried/single and childless than C9<sub>neg</sub> patients.</p><p><strong>Conclusion: </strong>C9<sub>pos</sub> patients constitute a large portion of the Norwegian ALS population. Ancestry and relatedness do not adequately explain regional differences. Relying on clinical information to identify C9<sub>pos</sub> patients has proven to be challenging. Half of C9<sub>pos</sub> patients were reported as having sporadic ALS, underlining the importance of carefully assessing family history and the need for genetic testing.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142309219","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}
Jana Kleinerova, Angela Garcia-Gallardo, Asya Tacheva, Peter Bede
{"title":"Subcortical grey matter involvement in ALS and PLS - vulnerable hubs of cortico-cortical and cortico-basal circuits: extrapyramidal, cognitive, bulbar and respiratory correlates.","authors":"Jana Kleinerova, Angela Garcia-Gallardo, Asya Tacheva, Peter Bede","doi":"10.1080/21678421.2024.2405130","DOIUrl":"https://doi.org/10.1080/21678421.2024.2405130","url":null,"abstract":"<p><p>Evidence from neuroimaging studies suggests that the cardinal clinical manifestations of ALS stem from the dysfunction of specific neural networks. The majority of cortico-cortical and cortico-basal networks are physiologically relayed by deep cerebral and cerebellar grey matter nuclei which have been increasingly implicated in the pathophysiology of ALS. A series of recent human imaging papers revealed volume reductions, shape deformations, metabolic alterations and more recently, susceptibility changes in hippocampal subfields, thalamic, striatal, amygdalar and cerebellar nuclei. Thalamic changes have been identified in presymptomatic mutation carriers long before symptom onset and longitudinal studies have consistently confirmed progressive subcortical degeneration during the symptomatic phase of the disease. The dysfunction of circuits relayed by specific subcortical nuclei has been associated with apathy, amnestic deficits, limbic symptoms, extrapyramidal manifestations, sensory disturbances, pseudobulbar affect and cerebellar deficits. In light of emerging imaging data, the clinical heterogeneity of ALS is probably best approached from a network integrity perspective. Accordingly, the comprehensive assessment of subcortical grey matter nuclei seems imperative to untangle complex clinical phenomena in ALS.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333582","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}
{"title":"Low CD3 level is a risk factor for amyotrophic lateral sclerosis: a Mendelian randomization study.","authors":"Wenzhi Yang, Xiangyi Liu, Dongsheng Fan","doi":"10.1080/21678421.2024.2407408","DOIUrl":"https://doi.org/10.1080/21678421.2024.2407408","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a progressive and fatal disease characterized by neuronal degeneration of the spinal cord and brain and believed to be related to the immune system. In this study, our aim is to use Mendelian randomization (MR) to search for immune markers related to ALS. A total of 731 immune cell traits were included in this study. MR analysis was used to identify the causality between 731 immune cell traits (with 3,757 Europeans) and ALS (with 138,086 Europeans). Colocalization analysis was used to verify the found causality, protein-protein interaction prediction was used to look for the interacting proteins that are known to be involved in ALS. We found low expression levels of CD3 on central memory CD8+ T cell is risk factor for ALS (OR = 0.90, 95% CI: 0.86-0.95, <i>P</i> = 0.0000303). CD3 can interact with three ALS-related proteins: VCP, HLA-DRA and HLA-DRB5, which are associated with adaptive immune response. Our study reported for the first time that low-level CD3 is a risk factor for ALS and the possible mechanism, which could provide a potential strategy for ALS diagnosis and therapy.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142309229","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}
Frank Baas, Anneke van der Kooi, Jan Stam, Marianne de Visser
{"title":"Jean Marie Baptiste Vianney de Jong (1937-2024).","authors":"Frank Baas, Anneke van der Kooi, Jan Stam, Marianne de Visser","doi":"10.1080/21678421.2024.2405125","DOIUrl":"https://doi.org/10.1080/21678421.2024.2405125","url":null,"abstract":"","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302257","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}