Survival and severity in dominant cerebellar ataxias

Monin, Marie‐Lorraine; Montcel, Sophie Tezenas du; Marelli, Cécilia; Cazeneuve, Cécile; Charles, Perrine; Tallaksen, Chantal; Forlani, Sylvie; Stevanin, Giovanni; Brice, Alexis; Dürr, Alexandra

doi:10.1002/acn3.156

Cited by 37 publications

(33 citation statements)

References 17 publications

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“…Strengths of our report include the large number of patients and the long‐term observational period (up to 10 years). 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 .…”

Section: Discussionmentioning

confidence: 88%

“…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. 21,22 Information about vital status was incomplete, as in our previous survival analysis. 3 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%

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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: 88%

Section: Discussionmentioning

confidence: 99%

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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“…A decline in cognitive function and episodes of psychosis have also been reported [ 101 ]. The mean age of onset is about 32 years (range of 1–72 years) [ 102 ]. Clinical features differ between patients with an adult onset and patients with an onset in infancy or early childhood with the disease starting in childhood showing a more rapid and aggressive progression within a few years.…”

Section: Sca7mentioning

confidence: 99%

“…Furthermore, SCA17 patients are known to suffer from psychiatric symptoms, as well as dementia [ 108 , 109 ]. The mean age of onset is 35 years with a broad range of 3 to 75 years, and the mean disease duration of about 20 years [ 102 , 110 ].…”

Section: Sca17mentioning

confidence: 99%

Genetics, Mechanisms, and Therapeutic Progress in Polyglutamine Spinocerebellar Ataxias

Buijsen¹,

Toonen²,

et al. 2019

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Autosomal dominant cerebellar ataxias (ADCAs) are a group of neurodegenerative disorders characterized by degeneration of the cerebellum and its connections. All ADCAs have progressive ataxia as their main clinical feature, frequently accompanied by dysarthria and oculomotor deficits. The most common spinocerebellar ataxias (SCAs) are 6 polyglutamine (polyQ) SCAs. These diseases are all caused by a CAG repeat expansion in the coding region of a gene. Currently, no curative treatment is available for any of the polyQ SCAs, but increasing knowledge on the genetics and the pathological mechanisms of these polyQ SCAs has provided promising therapeutic targets to potentially slow disease progression. Potential treatments can be divided into pharmacological and gene therapies that target the toxic downstream effects, gene therapies that target the polyQ SCA genes, and stem cell replacement therapies. Here, we will provide a review on the genetics, mechanisms, and therapeutic progress in polyglutamine spinocerebellar ataxias.

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“…1 Affected persons progressively lose motor control, leading to death within 10 to 20 years. 2 The progressive changes in SCA3 reflect widespread degenerative and neuropathological changes, including neuronal loss and gliosis in the deep cerebellar nuclei (DCN), pons, vestibular nuclei and other brainstem nuclei, spinocerebellar tracts, substantia nigra, thalamus, and globus pallidus. 3,4 SCA3 is 1 of 9 neurodegenerative diseases caused by an expanded, polyglutamine-coding repeat in the disease gene.…”

mentioning

confidence: 99%