TY - JOUR
T1 - Abnormal motor cortical adaptation to external stimulus in unverricht-lundborg disease (Progressive myoclonus type 1, EPM1)
AU - Julkunen, Petro
AU - Löfberg, Olli
AU - Kallioniemi, Elisa
AU - Hyppönen, Jelena
AU - Kälviäinen, Reetta
AU - Mervaala, Esa
N1 - Publisher Copyright:
© 2018 American Physiological Society.
PY - 2018/8
Y1 - 2018/8
N2 - Unverricht-Lundborg disease (EPM1) is associated with progressive functional and anatomic changes in the thalamus and motor cortex. The neurophysiological mechanisms behind the impaired thalamocortical system were studied through short-term adaptation of the motor cortex to transcranial magnetic stimulation (TMS) via repetition suppression (RS) phenomenon. RS is considered to be related to neural processing of external stimuli. We hypothesized that this neural processing is progressively impaired in EPM1 from adolescence to adulthood. Eight adult patients with EPM1 (age: 40 ± 13 yr), six adolescent patients with EPM1 (age: 16 ± 1 yr), and ten adult controls (age: 35 ± 12 yr) were studied using navigated TMS and RS study protocol including trains of four repeated stimuli with intertrain interval of 20 s and interstimulus interval of 1 s. Changes in RS were investigated from adolescence to adulthood in EPM1 by comparing with adult controls. In controls, the RS was seen as 50–55% reduction in motor response amplitudes to TMS after the first stimulus. RS was mild or missing in EPM1. RS from first to second stimulus within the stimulus trains was significantly stronger in adolescent patients than in adult patients (P = 0.046). Abnormal RS correlated with the myoclonus severity of the patients. In agreement with our hypothesis, neural processing of external stimuli is progressively impaired in EPM1 possibly due to anatomically impaired thalamocortical system or inhibitory tonus preventing sufficient adaptive reactiveness to stimuli. Our results suggest that RS abnormality might be used as a biomarker in the therapeutic trials for myoclonus. NEW & NOTEWORTHY Unverricht-Lundborg disease (EPM1) is associated with impaired thalamocortical function, which we studied in 8 adult and 6 adolescent patients and in 10 adult controls through repetition suppression (RS) of the motor cortex. We hypothesized that neural processing is progressively impaired in EPM1 from adolescence to adulthood. RS was normal in controls, whereas it was mild or missing in EPM1. Stronger RS was seen in adolescent patients than in adult patients correlating with the myoclonus severity.
AB - Unverricht-Lundborg disease (EPM1) is associated with progressive functional and anatomic changes in the thalamus and motor cortex. The neurophysiological mechanisms behind the impaired thalamocortical system were studied through short-term adaptation of the motor cortex to transcranial magnetic stimulation (TMS) via repetition suppression (RS) phenomenon. RS is considered to be related to neural processing of external stimuli. We hypothesized that this neural processing is progressively impaired in EPM1 from adolescence to adulthood. Eight adult patients with EPM1 (age: 40 ± 13 yr), six adolescent patients with EPM1 (age: 16 ± 1 yr), and ten adult controls (age: 35 ± 12 yr) were studied using navigated TMS and RS study protocol including trains of four repeated stimuli with intertrain interval of 20 s and interstimulus interval of 1 s. Changes in RS were investigated from adolescence to adulthood in EPM1 by comparing with adult controls. In controls, the RS was seen as 50–55% reduction in motor response amplitudes to TMS after the first stimulus. RS was mild or missing in EPM1. RS from first to second stimulus within the stimulus trains was significantly stronger in adolescent patients than in adult patients (P = 0.046). Abnormal RS correlated with the myoclonus severity of the patients. In agreement with our hypothesis, neural processing of external stimuli is progressively impaired in EPM1 possibly due to anatomically impaired thalamocortical system or inhibitory tonus preventing sufficient adaptive reactiveness to stimuli. Our results suggest that RS abnormality might be used as a biomarker in the therapeutic trials for myoclonus. NEW & NOTEWORTHY Unverricht-Lundborg disease (EPM1) is associated with impaired thalamocortical function, which we studied in 8 adult and 6 adolescent patients and in 10 adult controls through repetition suppression (RS) of the motor cortex. We hypothesized that neural processing is progressively impaired in EPM1 from adolescence to adulthood. RS was normal in controls, whereas it was mild or missing in EPM1. Stronger RS was seen in adolescent patients than in adult patients correlating with the myoclonus severity.
KW - Motor evoked potential
KW - Progressive myoclonus epilepsy
KW - Repetition suppression
KW - Transcranial magnetic stimulation
KW - Unverricht-Lundborg disease
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U2 - 10.1152/jn.00063.2018
DO - 10.1152/jn.00063.2018
M3 - Article
C2 - 29742025
AN - SCOPUS:85051296433
SN - 0022-3077
VL - 120
SP - 617
EP - 623
JO - Journal of neurophysiology
JF - Journal of neurophysiology
IS - 2
ER -