Research Project

Looking beyond the central nervous system in SCA3: nerve and muscle ultrasound as potential imaging markers to quantify and monitor peripheral nervous system degeneration

Principal researchers: Roderick Maas, Bart van de Warrenburg, and Nens van Alfen, Department of Neurology, Radboud University Medical Center, Nijmegen (The Netherlands) 

Lay Summary  

As well as difficulties with co-ordination and balance, people with spinocerebellar ataxia type 3 (SCA3) might experience other symptoms such as muscle cramps, pain, tingling, numbness, and loss of muscle mass. This is due to the common involvement of the peripheral nervous system, which are the nerves that branch out from the spinal cord to the limbs. So far very few studies have looked at how these symptoms change over time and whether they are associated with visible changes in the nerves and muscles.  

In this project, the researchers plan to use ultrasound to measure nerve sizes, muscle volumes, and muscle structures in the arms and legs of people with SCA3. The study will include 30 people with SCA3, 10 people who have the SCA3 mutation but have not yet developed ataxia symptoms, and 20 people without ataxia. After their initial measurements, participants will be followed up after 1 year to see if any differences detected by ultrasound progress over time, and whether these changes are related to the severity of symptoms.  

This work is important as it will increase our understanding of these other, often-overlooked symptoms of SCA3, as well as aiming to provide a sensitive measurement of SCA3 symptoms which could be used to test whether a treatment is working in future clinical trials. It also sets up a framework for carrying out this type of study in other types of SCA in the future. 

Scientific Summary  

The widespread degeneration of the peripheral nervous system (PNS) in spinocerebellar ataxia type 3 (SCA3) not only causes complaints that impair the quality of life of those with this condition, but also contributes to the severity of sensory ataxia, clinically leading to an acceleration of ataxia progression. These researchers aim to investigate whether nerve and muscle ultrasound can yield reliable biomarkers of PNS involvement in SCA3.  

30 people with SCA3, 10 preclinical SCA3 mutation carriers, and 20 healthy controls will undergo a detailed PNS examination at baseline and 1-year follow-up. The researchers will investigate whether nerve and muscle ultrasound can adequately distinguish people with SCA3 and preclinical mutation carriers from healthy controls, and evaluate associations between imaging abnormalities and various clinician-reported and patient-reported outcomes and serum neurofilament light chain concentrations. They will also examine whether these imaging techniques detect changes at 1-year follow-up.  

The results of this study will contribute to a better understanding of common yet frequently overlooked symptoms in SCA3, hopefully yield markers of PNS degeneration that can be applied in future therapeutic trials, and may prelude similar studies in other types of SCA. 

For more support or information please contact:  
Ataxia UK, 12 Broadbent Close, London, N6 5JW 
Website: www.ataxia.org.uk.   
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