Long-term evolution of patient-reported outcome measures in spinocerebellar ataxias

Jacobi, Heike; Montcel, Sophie Tezenas du; Bauer, Peter; Giunti, Paola; Cook, Arron; Labrum, Robyn; Parkinson, Michael M.H.; Dürr, Alexandra; Brice, Alexis; Charles, Perrine; Marelli, Cecila; Mariotti, Caterina; Nanetti, Lorenzo; Sarro, Lidia; Rakowicz, Maria; Sulek, Anna; Sobańska, Anna; Schmitz‐Hübsch, Tanja; Schöls, Lüdger; Hengel, Holger; Balikó, László; Melegh, Béla; Filla, Alessandro; Antenora, Antonella; Infante, Jon; Berciano, José; Warrenburg, B.P.C. van de; Timmann, Dagmar; Szymanski, Sandra; Boesch, Sylvia; Nachbauer, Wolfgang; Kang, Jun Suk; Pandolfo, Massimo; Schulz, Jörg B.; Melac, Audrey Tanguy; Diallo, Alhassane; Klockgether, Thomas

doi:10.1007/s00415-018-8954-0

Cited by 38 publications

(33 citation statements)

References 29 publications

(33 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…29 The slow evolution is also reflected by the fact that SPG7 patients were still able to walk with a cane after 20 years of the disease, which is, for example, not the case for SCA1 patients. 30 Obviously, SARA does not quantify spasticity and the lack of the Spastic Paraplegia Rating Scale (SPRS) scores 31 Intriguingly, this was uncoupled form optic atrophy, which appeared to be present from disease onset, without decreased visual acuity for most patients. 6 The presence of cerebellar atrophy by MRI was consistently associated with SPG7 but its degree did not correlate with severity of cerebellar signs (Figure 3).…”

Section: Discussionmentioning

confidence: 99%

Loss of paraplegin drives spasticity rather than ataxia in a cohort of 241 patients with SPG7

Coarelli

Schüle

Warrenburg³

et al. 2019

Neurology

Self Cite

View full text Add to dashboard Cite

word count: 239 Character count for the title: 88 Number of references: 32 Number of tables: 3 Number of figures: 4 Search terms: cerebellar ataxia, hereditary spastic paraplegia, SPG7, paraplegin, Ala510Val variant Study fundingThe study received funding from the "Agence Nationale de la Recherche" (SPATAX-QUEST, to GS), the "Connaitre les Syndromes Cérébelleux" association (to GS), Verum foundation (to AD and GS), and SPATAX Hospital Abstract Objective: We took advantage of a large multinational recruitment to delineate genotypephenotype correlations in a large, trans-European multicenter cohort of SPG7 patients. Methods:We analyzed clinical and genetic data from 241 SPG7 patients, integrating neurological follow-up data. One case was examined neuropathologically.Results: SPG7 patients had a mean age of 35.5±14.3 years (n=233) at onset and presented with either spasticity (n=89), ataxia (n=74), or both (n=45). At the first visit, patients with a longer disease duration (>20 years, n=62) showed more cerebellar dysarthria (p<0.05), deep sensory loss (p<0.01), muscle wasting (p<0.01), ophthalmoplegia (p<0.05), sphincter dysfunction (p<0.05) than those with a shorter duration (<10 years, n=93). Progression, measured by SARA evaluations, showed a mean annual increase of 1.0±1.4 points in a subgroup of 30 patients. Patients homozygous for loss of function (LOF) variants (n=65) presented significantly more often with pyramidal signs (p<0.05), diminished visual acuity due to optic atrophy (p<0.0001), and deep sensory loss (p<0.0001) than those with at least one missense variant (n=176). Patients with at least one Ala510Val variant (58%) were older (37.6±13.7 vs 32.8±14.6, p<0.05) and showed ataxia at onset (p<0.05). Neuropathological examination revealed reduction of the pyramidal tract in the medulla oblongata and moderate loss of Purkinje cells and substantia nigra neurons.Conclusions: This is the largest SPG7 cohort study to date, and shows a spasticitypredominant phenotype of LOF variants and more frequent cerebellar ataxia and later onset in patients carrying at least one Ala510Val variant. Word 239/250 6 Abbreviations AD: autosomal dominant AR: autosomal recessive LOF: loss of function MBP-SF: myelin basic protein serum factor MLPA: multiplex ligation-dependent probe amplification PolyQ: polyglutamine SARA: Scale for the Assessment and Rating of AtaxiaSCA: spinocerebellar ataxia SPRS: Spastic Paraplegia Rating Scale XL: X-linked Cerebellar ataxia, % (n) 66% (87/132) 58% (56/97) 0.2 Cerebellar dysarthria, % (n) 36% (51/131) 36% (35/93) 0.7 Brisk reflexes, % (n) 76% (96/126) 92% (80/87) 0.003 Babinski sign, % (n) 71% (89/125) 77% (66/86) 0.4 Pyramidal syndrome, % (n) 86% (116/134) 97% (93/96) 0.01 Pes cavus, % (n) 17% (22/129) 30% (28/92) 0.02 Parkinsonism, % (n) 4% (5/131) 5% (5/94) 0.74

show abstract

Section: Discussionmentioning

confidence: 99%

Loss of paraplegin drives spasticity rather than ataxia in a cohort of 241 patients with SPG7

Coarelli

Schüle

Warrenburg³

et al. 2019

Neurology

Self Cite

View full text Add to dashboard Cite

show abstract

“…It involves mostly the executive functions and verbal memory, as shown in one of the first cognitive studies to compare the profiles of SCA1, 2, and 3 patients 59 . Cognitive decline was more prominent and rapid in SCA1 than in the other genotypes 59 – 61 and was associated with an increase in the incidence of depression 61 . In another study, SCA2 patients were found to have more visuospatial and visuoperceptive deficits than SCA1 patients 62 .…”

Section: Biological Biomarkersmentioning

confidence: 92%

Recent advances in understanding dominant spinocerebellar ataxias from clinical and genetic points of view

2018

Self Cite

View full text Add to dashboard Cite

Spinocerebellar ataxias (SCAs) are rare types of cerebellar ataxia with a dominant mode of inheritance. To date, 47 SCA subtypes have been identified, and the number of genes implicated in SCAs is continually increasing. Polyglutamine (polyQ) expansion diseases ( ATXN1/SCA1, ATXN2/SCA2, ATXN3/SCA3, CACNA1A/SCA6, ATXN7/SCA7, TBP/SCA17, and ATN1/DRPLA) are the most common group of SCAs. No preventive or curative treatments are currently available, but various therapeutic approaches, including RNA-targeting treatments, such as antisense oligonucleotides (ASOs), are being developed. Clinical trials of ASOs in SCA patients are already planned. There is, therefore, a need to identify valid outcome measures for such studies. In this review, we describe recent advances towards identifying appropriate biomarkers, which are essential for monitoring disease progression and treatment efficacy. Neuroimaging biomarkers are the most powerful markers identified to date, making it possible to reduce sample sizes for clinical trials. Changes on brain MRI are already evident at the premanifest stage in SCA1 and SCA2 carriers and are correlated with CAG repeat size. Other potential biomarkers have also been developed, based on neurological examination, oculomotor study, cognitive assessment, and blood and cerebrospinal fluid analysis. Longitudinal studies based on multimodal approaches are required to establish the relationships between parameters and to validate the biomarkers identified.

show abstract

“…The studies on the severity of ataxia via the SARA scale in SCA patients have shown that the natural progression of SCA2, as well as SCA3 and SCA6, seems to be similar between the Chinese and Caucasians [31]. The analysis of the long-term evolution of the patient-reported outcome measures in SCA patients revealed that functional capacity, health-related quality of life, and mood deteriorated over the 8-year observation period in SCA2 [32].…”

Section: Epidemiologymentioning

confidence: 99%

Molecular Mechanisms and Therapeutics for Spinocerebellar Ataxia Type 2

Egorova

Bezprozvanny

2019

Neurotherapeutics

View full text Add to dashboard Cite

The effective therapeutic treatment and the disease-modifying therapy for spinocerebellar ataxia type 2 (SCA2) (a progressive hereditary disease caused by an expansion of polyglutamine in the ataxin-2 protein) is not available yet. At present, only symptomatic treatment and methods of palliative care are prescribed to the patients. Many attempts were made to study the physiological, molecular, and biochemical changes in SCA2 patients and in a variety of the model systems to find new therapeutic targets for SCA2 treatment. A better understanding of the uncovered molecular mechanisms of the disease allowed the scientific community to develop strategies of potential therapy and helped to create some promising therapeutic approaches for SCA2 treatment. Recent progress in this field will be discussed in this review article.

show abstract

Long-term evolution of patient-reported outcome measures in spinocerebellar ataxias

Abstract: In the common SCAs, PROMs give complementary information to the information provided by neurological scales. This underlines the importance of PROMs as additional outcome measures in future interventional trials.

Cited by 38 publications

References 29 publications

Loss of paraplegin drives spasticity rather than ataxia in a cohort of 241 patients with SPG7

Loss of paraplegin drives spasticity rather than ataxia in a cohort of 241 patients with SPG7

Recent advances in understanding dominant spinocerebellar ataxias from clinical and genetic points of view

Molecular Mechanisms and Therapeutics for Spinocerebellar Ataxia Type 2

Contact Info

Product

Resources

About