Spinocerebellar ataxia type-3 (SCA3) is one of the most common types of SCA worldwide, and is characterised by progressive decline in daily function and quality of life. Whilst cerebellar ataxia is the main feature of the condition, there are many non-motor and non-cerebellar features that contribute to the disease burden. These include symptoms relating to the peripheral nervous system (outside of the brain and spinal cord) and the autonomic nervous system, which typically receive less attention than central nervous system features.
Dr Roderick Maas and Prof Bart van de Warrenburg and their team at Radboud University Medical Center in the Netherlands studied 40 adults carrying the SCA3 mutation, including 30 ataxic and 10 pre-ataxic individuals (not yet showing ataxia symptoms), and compared them with 16 healthy controls to explore peripheral and autonomic nervous system symptoms in SCA3. This project follows on from the ongoing work of the Ataxia UK-funded 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’, which you can read about here.
The researchers asked participants to complete questionnaires about a number of symptoms including muscle cramps, neuropathic pain, activities of daily living and quality of life. Participants also underwent a clinical examination of their ataxia and neuropathy severity.
The researchers found a very high prevalence of muscle cramps in SCA3, with 97% of the ataxic and 60% of the pre-ataxic participants experiencing these at least weekly. The most common sites of muscle cramps across ataxic and pre-ataxic groups are shown in the figure below.
25% of participants with the SCA3 mutation reported moderate to severe impairments in daily activities due to the muscle cramps, such as disruptions to work and sleep.
Neuropathic pain was commonly reported by both pre-ataxic participants (20%) and ataxic participants (16.7%).
The most reported symptoms suggesting autonomic nervous system involvement in the ataxic and pre-ataxic groups are shown in the figure below.
Higher scores on the Total Neuropathy Score clinical scale (indicating greater
levels of neuropathy) were linked to longer disease duration, more severe ataxia, and greater impact on daily function, as shown by higher SARA, FARS-ADL and PROM ataxia scores. Of note, neuropathy severity scores were already significantly higher in pre-ataxic participants than in healthy controls, which indicates that peripheral nervous system involvement is a very early disease feature in SCA3.
This research highlights that symptoms relating to peripheral and autonomic nervous system are very common in SCA3, significantly contribute to overall disease burden, and can be seen already in pre-ataxic individuals. As SCA3 is a multisystem disorder, disease monitoring and future therapeutic developments should cover the broad range of its impacts.
In addition to these subjective, patient-reported outcomes, the researchers are currently analysing data to more objectively quantify peripheral nervous system degeneration in SCA3. Read the paper here.
