Anne Weissbach1,2, Elisa Werner1, Julien F Bally3, Sinem Tunc1,2, Sebastian Löns1, Dagmar Timmann4, Kirsten E Zeuner5, Vera Tadic1,2, Norbert Brüggemann1,2, Anthony Lang3, Christine Klein1, Alexander Münchau1, Tobias Bäumer1. 1. Institute of Neurogenetics, University of Lübeck, Lübeck, Germany. 2. Department of Neurology, University of Lübeck, Lübeck, Germany. 3. Morton and Gloria Shulman Movement Disorder Clinic and Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada. 4. Department of Neurology, University of Duisburg-Essen, Duisburg and Essen, Germany. 5. Department of Neurology, University of Kiel, Kiel, Germany.
Abstract
OBJECTIVE: To characterize neurophysiological subcortical abnormalities in myoclonus-dystonia and their modulation by alcohol administration. METHODS: Cerebellar associative learning and basal ganglia-brainstem interaction were investigated in 17 myoclonus-dystonia patients with epsilon-sarcoglycan (SGCE) gene mutation and 21 age- and sex-matched healthy controls by means of classical eyeblink conditioning and blink reflex recovery cycle before and after alcohol intake resulting in a breath alcohol concentration of 0.08% (0.8g/l). The alcohol responsiveness of clinical symptoms was evaluated by 3 blinded raters with a standardized video protocol and clinical rating scales including the Unified Myoclonus Rating Scale and the Burke-Fahn-Marsden Dystonia Rating Scale. RESULTS: Patients showed a significantly reduced number of conditioned eyeblink responses before alcohol administration compared to controls. Whereas the conditioning response rate decreased under alcohol intake in controls, it increased in patients (analysis of variance: alcohol state × group, p = 0.004). Blink reflex recovery cycle before and after alcohol intake did not differ between groups. Myoclonus improved significantly after alcohol intake (p = 0.016). The severity of action myoclonus at baseline correlated negatively with the conditioning response in classical eyeblink conditioning in patients. INTERPRETATION: The combination of findings of reduced baseline acquisition of conditioned eyeblink responses and normal blink reflex recovery cycle in patients who improved significantly with alcohol intake suggests a crucial role of cerebellar networks in the generation of symptoms in these patients. Ann Neurol 2017;82:543-553.
OBJECTIVE: To characterize neurophysiological subcortical abnormalities in myoclonus-dystonia and their modulation by alcohol administration. METHODS: Cerebellar associative learning and basal ganglia-brainstem interaction were investigated in 17 myoclonus-dystoniapatients with epsilon-sarcoglycan (SGCE) gene mutation and 21 age- and sex-matched healthy controls by means of classical eyeblink conditioning and blink reflex recovery cycle before and after alcohol intake resulting in a breath alcohol concentration of 0.08% (0.8g/l). The alcohol responsiveness of clinical symptoms was evaluated by 3 blinded raters with a standardized video protocol and clinical rating scales including the Unified Myoclonus Rating Scale and the Burke-Fahn-Marsden Dystonia Rating Scale. RESULTS:Patients showed a significantly reduced number of conditioned eyeblink responses before alcohol administration compared to controls. Whereas the conditioning response rate decreased under alcohol intake in controls, it increased in patients (analysis of variance: alcohol state × group, p = 0.004). Blink reflex recovery cycle before and after alcohol intake did not differ between groups. Myoclonus improved significantly after alcohol intake (p = 0.016). The severity of action myoclonus at baseline correlated negatively with the conditioning response in classical eyeblink conditioning in patients. INTERPRETATION: The combination of findings of reduced baseline acquisition of conditioned eyeblink responses and normal blink reflex recovery cycle in patients who improved significantly with alcohol intake suggests a crucial role of cerebellar networks in the generation of symptoms in these patients. Ann Neurol 2017;82:543-553.
Authors: Johanna Junker; Valerie Brandt; Brian D Berman; Marie Vidailhet; Emmanuel Roze; Anne Weissbach; Cynthia Comella; Irene A Malaty; Joseph Jankovic; Mark S LeDoux; Alfredo Berardelli; Richard Barbano; Stephen G Reich; Joel S Perlmutter; H A Jinnah; Norbert Brüggemann Journal: Neurology Date: 2018-10-19 Impact factor: 9.910