Abnormal corticospinal tract function and motor cortex excitability in non-ataxic SCA2 mutation carriers: A TMS study

Area of Science:

• Neuroscience
• Genetics
• Neurology

Background:

• Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disorder.
• Prodromal stage of SCA2 is characterized by subclinical changes.
• Corticospinal tract (CST) integrity in prodromal SCA2 is not well understood.

Purpose of the Study:

• To investigate CST involvement in non-ataxic SCA2 mutation carriers.
• To assess electrophysiological markers of CST dysfunction prior to cerebellar syndrome onset.

Main Methods:

• Cross-sectional study of 37 SCA2 mutation carriers and healthy controls.
• Clinical assessment and transcranial magnetic stimulation (TMS).
• Evaluation of motor thresholds, cortical silent periods, and central motor conduction times (CMCT).

Main Results:

• SCA2 carriers exhibited elevated motor thresholds and prolonged cortical silent periods and CMCT.
• CMCT to tibialis anterior correlated with CAG repeat size and predicted time to ataxia onset.
• Electrophysiological abnormalities suggest CST and motor cortex affection.

Conclusions:

• Prodromal SCA2 affects the corticospinal tract and motor cortex.
• Slowed CST conduction reflects polyglutamine neurotoxicity and predicts ataxia onset.
• Early identification of CST damage enables disease monitoring for future neuroprotective therapies.