Prospective study of individuals at risk for spinocerebellar ataxia type 1, type 2, type 3 and type 6 (SCA1, SCA2, SCA3, SCA6)
The spinocerebellar ataxias (SCAs) are a clinically and genetically heterogeneous group of autosomal dominantly inherited progressive ataxia disorders. It is estimated that there are 30,000 individuals in the European Community that directly descend from individuals affected by a SCA disorder and thus carry a 50% risk of having inherited an SCA mutation. These at risk individuals provide a unique research opportunity to prospectively study the presymptomatic phase of SCA disorders and to identify the earliest and most sensitive clinical signs and biological markers that herald the onset of the illness. This information is of critical importance for the development of future therapeutic interventions aimed at postponing the clinical onset of ataxia.
We therefore perform a prospective observational study of individuals at risk for the most common SCA disorders, SCA1, SCA2, SCA3 and SCA6 (RISCA). It is our aim to answer the following questions:
- What is the incidence of disease manifestation in mutation carriers?
- Which clinical signs precede the onset of manifest ataxia in SCA1, SCA2, SCA3 and SCA6?
- What are the prevalence and incidence of preceding signs?
- Are the prevalence and incidence of preceding signs affected by genotype, gender, age, estimated time until disease manifestation and repeat length?
- Does the presence of certain preceding signs predict the manifestation of ataxia?
- Are there MRI alterations that precede the onset of ataxia?
Study participants are followed at regular intervals over six years. At each visit, study participants are asked in a structured interview for a number of predefined clinical signs that potentially precede the onset of ataxia. In addition, the following self-assessment scales are applied: Pittsburgh Sleep Quality Index (PSQI), Diagnostic Criteria for Restless Legs Syndrome, Patient´s Health Questionnaire (PHQ-9). All study participants undergo a physical examination including the Scale for the Assessment and Rating of Ataxia (SARA). Study participants further perform the SCA Functional Composite (SCA-FC) and the Composite Cerebellar Functional Severity Score (CCFS). In a subset of study participants, we record eye movements and obtain volumetric MRIs. The study is also be used to collect and store blood and urine samples for proteomic and gene expression studies as well as for genetic modifier analysis.
RISCA is funded by the E-Rare program (www.e-rare.eu).
Principal investigator: Thomas Klockgether, MD
Contact person: Heike Jacobi, MD
Dept. of Neurology
University Hospital Bonn
D-53105 Bonn, Germany
Jacobi H, Reetz K, du Montcel ST, Bauer P, Mariotti C, Nanetti L, Rakowicz M, Sulek A, Durr A, Charles P, Filla A, Antenora A, Schöls L, Schicks J, Infante J, Kang JS, Timmann D, Fabio RD, Masciullo M, Baliko L, Bela M, Boesch S, Bürk K, Peltz A, Schulz JB, Dufaure-Garé I, Klockgether T. Biological and clinical characteristics of individuals at risk for spinocerebellar ataxia types 1, 2, 3, and 6 in the longitudinal RISCA study: analysis of baseline data.Lancet Neurol. 2013 May 21. doi:pii: S1474-4422(13)70104-2. 10.1016/S1474-4422(13)70104-2. [Epub ahead of print]