Luis Velázquez-Pérez1, Roberto Rodríguez-Labrada2, Reidenis Torres-Vega2, Jacqueline Medrano Montero2, Yaimeé Vázquez-Mojena3, Georg Auburger4, Ulf Ziemann5. 1. Dept. Clinical Neurophysiology, Centre for the Research and Rehabilitation of Hereditary Ataxias, Libertad Street 26, Holguin 80100, Cuba. Electronic address: luis.velazquez@infomed.sld.cu. 2. Dept. Clinical Neurophysiology, Centre for the Research and Rehabilitation of Hereditary Ataxias, Libertad Street 26, Holguin 80100, Cuba. 3. Dept. Molecular Neurobiology, Centre for the Research and Rehabilitation of Hereditary Ataxias, Libertad Street 26, Holguin 80100, Cuba. 4. Exp. Neurology, Building 89, Goethe University Medical School, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany. 5. Dept. Neurology & Stroke, and Hertie Institute for Clinical Brain Research, University Tübingen, Hoppe-Seyler-Straße 3, 72076 Tübingen, Germany.
Abstract
OBJECTIVE: To evaluate if the corticospinal tract is affected in the prodromal stage of spinocerebellar ataxia type 2 (SCA2), prior to development of the cerebellar syndrome. METHODS: A cross-sectional study was conducted in 37 non-ataxic SCA2 mutation carriers and in age- and sex-matched healthy controls. All subjects underwent clinical assessment and transcranial magnetic stimulation to determine corticospinal tract integrity to the right abductor pollicis brevis and tibialis anterior muscles. RESULTS: Non-ataxic SCA2 mutation carriers showed significantly higher resting and active motor thresholds for both muscles, and prolonged cortical silent periods and central motor conduction times (CMCT), compared to controls. CMCT to the tibialis anterior correlated directly with CAG repeat size, and inversely with predicted time to ataxia onset. CONCLUSION: Findings provide novel electrophysiological evidence for affection of the corticospinal tract and motor cortex in prodromal SCA2. Slowed conduction in the corticospinal tract to the lower limbs reflects polyglutamine neurotoxicity, and predicts time to ataxia onset. SIGNIFICANCE: Identification of corticospinal tract damage and decreases motor cortical excitability in the prodromal stage of SCA2 allows early disease monitoring. This will become important as soon as effective neuroprotective treatment will be available.
OBJECTIVE: To evaluate if the corticospinal tract is affected in the prodromal stage of spinocerebellar ataxia type 2 (SCA2), prior to development of the cerebellar syndrome. METHODS: A cross-sectional study was conducted in 37 non-ataxicSCA2 mutation carriers and in age- and sex-matched healthy controls. All subjects underwent clinical assessment and transcranial magnetic stimulation to determine corticospinal tract integrity to the right abductor pollicis brevis and tibialis anterior muscles. RESULTS:Non-ataxicSCA2 mutation carriers showed significantly higher resting and active motor thresholds for both muscles, and prolonged cortical silent periods and central motor conduction times (CMCT), compared to controls. CMCT to the tibialis anterior correlated directly with CAG repeat size, and inversely with predicted time to ataxia onset. CONCLUSION: Findings provide novel electrophysiological evidence for affection of the corticospinal tract and motor cortex in prodromal SCA2. Slowed conduction in the corticospinal tract to the lower limbs reflects polyglutamine neurotoxicity, and predicts time to ataxia onset. SIGNIFICANCE: Identification of corticospinal tract damage and decreases motor cortical excitability in the prodromal stage of SCA2 allows early disease monitoring. This will become important as soon as effective neuroprotective treatment will be available.
Keywords:
Corticospinal tract; Motor cortex; Motor evoked potentials; Prodromal disease stage; Spinocerebellar ataxia type 2; Transcranial magnetic stimulation
Authors: W Ilg; M Branscheidt; A Butala; P Celnik; L de Paola; F B Horak; L Schöls; H A G Teive; A P Vogel; D S Zee; D Timmann Journal: Cerebellum Date: 2018-10 Impact factor: 3.847