Survival in patients with spinocerebellar ataxia types 1, 2, 3, and 6 (EUROSCA): a longitudinal cohort study

Diallo, Alhassane; Jacobi, Heike; Cook, Arron; Labrum, Robyn; Dürr, Alexandra; Brice, Alexis; Charles, Perrine; Marelli, Cécilia; Mariotti, Caterina; Nanetti, Lorenzo; Panzeri, Marta; Rakowicz, Maria; Sobańska, Anna; Sulek, Anna; Schmitz‐Hübsch, Tanja; Schöls, Lüdger; Hengel, Holger; Melegh, Béla; Filla, Alessandro; Antenora, Antonella; Infante, Jon; Berciano, José; Warrenburg, Bart P. van de; Timmann, Dagmar; Boesch, Sylvia; Pandolfo, Massimo; Schulz, Jörg B.; Bauer, Péter; Giunti, Paola; Kang, Jun Suk; Klockgether, Thomas; Montcel, Sophie Tezenas du

doi:10.1016/s1474-4422(18)30042-5

Cited by 83 publications

(71 citation statements)

References 25 publications

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“…Survival was more highly influenced by severity of ataxia at a given time point t (current value) than by rate of disease progression for all genotypes. The strongest contributing risk factors of death from the joint model were similar to those previously identified by Cox models, except for SCA3 patients . We failed to replicate the significant negative interaction between age at baseline and number of CAG repeats, probably attributable to the lack of power following restriction of the analysis to patients who had at least two visits, which decreased the number of events from 34 to 26.…”

Section: Discussionmentioning

confidence: 56%

“…Given the average follow‐up of patients of 20 years after ataxia onset, this 10‐year observation period might seem short, especially in light of an estimated survival of patients with SCA of 20 to 30 years after onset . Information about vital status was incomplete, as in our previous survival analysis . We updated the vital status by the records from the civil registry offices and interviews with family members to reduce the bias attributed to censorship, allowing us to recover 31% (32 of 102) of the deaths.…”

Section: Discussionmentioning

confidence: 99%

“…We randomly selected a new patient, not included in building the model, to illustrate how joint modeling can be used in practice to perform individual dynamic predictions. Subsequent analyses were performed separately for each genotype, given that survival and disease progression differed between genotypes . All data analyses were performed using the “ JM ” and “ lcmm ” R packages (R Foundation for Statistical Computing, Vienna, Austria).…”

Section: Methodsmentioning

confidence: 99%

“…The European prospective cohort study (EUROSCA) of patients with SCA1, SCA2, SCA3, and SCA6 was initiated in 2005 to study the natural history of ataxia. Longitudinal clinical and survival data from EUROSCA allowed us to establish genotype‐specific progression and survival rates and identify factors that influence disease course and survival. These analyses identified SCA1 as the genotype with the fastest disease progression and shortest survival among these SCAs .…”

mentioning

confidence: 99%

“…Longitudinal clinical and survival data from EUROSCA allowed us to establish genotype‐specific progression and survival rates and identify factors that influence disease course and survival. These analyses identified SCA1 as the genotype with the fastest disease progression and shortest survival among these SCAs . Nevertheless, type I autosomal‐dominant cerebellar ataxias are often complex in terms of clinical manifestations, meaning that it is not self‐evident that severity of ataxia per se is the best predictor of survival.…”

mentioning

confidence: 99%

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Prediction of Survival With Long‐Term Disease Progression in Most Common Spinocerebellar Ataxia

Diallo

Jacobi

Cook³

et al. 2019

Movement Disorders

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Background Spinocerebellar ataxias are rare dominantly inherited neurodegenerative diseases that lead to severe disability and premature death. Objective To quantify the impact of disease progression measured by the Scale for the Assessment and Rating of Ataxia on survival, and to identify different profiles of disease progression and survival. Methods Four hundred sixty‐two spinocerebellar ataxia patients from the EUROSCA prospective cohort study, suffering from spinocerebellar ataxia type 1, spinocerebellar ataxia type 2, spinocerebellar ataxia type 3, and spinocerebellar ataxia type 6, and who had at least two measurements of Scale for the Assessment and Rating of Ataxia score, were analyzed. Outcomes were change over time in Scale for the Assessment and Rating of Ataxia score and time to death. Joint model was used to analyze disease progression and survival. Results Disease progression was the strongest predictor for death in all genotypes: An increase of 1 standard deviation in total Scale for the Assessment and Rating of Ataxia score increased the risk of death by 1.28 times (95% confidence interval: 1.18–1.38) for patients with spinocerebellar ataxia type 1; 1.19 times (1.12–1.26) for spinocerebellar ataxia type 2; 1.30 times (1.19–1.42) for spinocerebellar ataxia type 3; and 1.26 times (1.11–1.43) for spinocerebellar ataxia type 6. Three subgroups of disease progression and survival were identified for patients with spinocerebellar ataxia type 1: “severe” (n = 13; 12%), “intermediate” (n = 31; 29%), and “moderate” (n = 62; 58%). Patients in the severe group were more severely affected at baseline with higher Scale for the Assessment and Rating of Ataxia scores and frequency of nonataxia signs compared to those in the other groups. Conclusion Rapid ataxia progression is associated with poor survival of the most common spinocerebellar ataxia. Theses current results have implications for the design of future interventional studies of spinocerebellar ataxia. © 2019 International Parkinson and Movement Disorder Society

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Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Prediction of Survival With Long‐Term Disease Progression in Most Common Spinocerebellar Ataxia

Diallo

Jacobi

Cook³

et al. 2019

Movement Disorders

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Safety and Efficacy of Acetyl-DL-Leucine in Certain Types of Cerebellar Ataxia

et al. 2021

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Key Points Question Is the modified amino acid acetyl-DL-leucine effective and safe in patients with cerebellar ataxia of different etiologies? Findings In this randomized clinical crossover trial including 108 patients with cerebellar ataxia, a 6-week treatment with acetyl-DL-leucine was not effective. Adverse events were mild. Meaning This study’s findings suggest that further symptom-oriented trials evaluating the long-term effects of acetyl-DL-leucine for well-defined subgroups of cerebellar ataxia are needed.

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Spinocerebellar ataxia clinical trials: opportunities and challenges

Brooker

Edamakanti

Akasha

et al. 2021

Ann Clin Transl Neurol

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The spinocerebellar ataxias (SCAs) are a group of dominantly inherited diseases that share the defining feature of progressive cerebellar ataxia. The disease process, however, is not confined to the cerebellum; other areas of the brain, in particular, the brainstem, are also affected, resulting in a high burden of morbidity and mortality. Currently, there are no disease-modifying treatments for the SCAs, but preclinical research has led to the development of therapeutic agents ripe for testing in patients. Unfortunately, due to the rarity of these diseases and their slow and variable progression, there are substantial hurdles to overcome in conducting clinical trials. While the epidemiological features of the SCAs are immutable, the feasibility of conducting clinical trials is being addressed through a combination of strategies. These include improvements in clinical outcome measures, the identification of imaging and fluid biomarkers, and innovations in clinical trial design. In this review, we highlight current challenges in initiating clinical trials for the SCAs and also discuss pathways for researchers and clinicians to mitigate these challenges and harness opportunities for clinical trial development.

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Survival in patients with spinocerebellar ataxia types 1, 2, 3, and 6 (EUROSCA): a longitudinal cohort study

Abstract: European Union 6th Framework programme, German Ministry of Education and Research, Polish Ministry of Scientific Research and Information Technology, European Union 7th Framework programme, and Fondation pour la Recherche Médicale.

Cited by 83 publications

References 25 publications

Prediction of Survival With Long‐Term Disease Progression in Most Common Spinocerebellar Ataxia

Prediction of Survival With Long‐Term Disease Progression in Most Common Spinocerebellar Ataxia

Safety and Efficacy of Acetyl-DL-Leucine in Certain Types of Cerebellar Ataxia

Spinocerebellar ataxia clinical trials: opportunities and challenges

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