Alterations of motor cortical excitability and anatomy in Unverricht-Lundborg disease.
Unverricht-Lundborg disease is the most common form of progressive myoclonus epilepsies. In addition to generalized seizures, it is characterized by myoclonus, which usually is the most disabling feature of the disease. Classically, the myoclonus has been attributed to increased excitability of the primary motor cortex. However, inhibitory cortical phenomena have also been described along with anatomical alterations. We aimed to characterize the relationship between the excitability and anatomy of the motor cortex and their association with the severity of the clinical symptoms. Seventy genetically verified patients were compared with forty healthy controls. The symptoms were evaluated with the Unified Myoclonus Rating Scale. Navigated transcranial magnetic stimulation was applied to characterize the excitability of the primary motor cortex by determining the motor thresholds and cortical silent periods. In addition, the induced cortical electric fields were estimated using individual scalp-to-cortex distances measured from MRIs. A cortical thickness analysis was performed to elucidate possible disease-related anatomical alterations. The motor thresholds, cortical electric fields, and silent periods were significantly increased in the patients (P < 0.01). The silent periods correlated with the myoclonus scores (r = 0.48 to r = 0.49, P < 0.001). The scalp-to-cortex distance increased significantly with disease duration (r = 0.56, P < 0.001) and correlated inversely with cortical thickness. The results may reflect the refractory nature of the myoclonus and indicate a possible reactive cortical inhibitory mechanism to the underlying disease process. This is the largest clinical series on Unverricht-Lundborg disease and the first study describing parallel pathophysiological and structural alterations associated with the severity of the symptoms.
Institute of Clinical Medicine, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland; Department of Clinical Neurophysiology, Kuopio University Hospital, Kuopio, Finland.
Nils
N
Danner
Petro
P
Julkunen
Jelena
J
Hyppönen
Eini
E
Niskanen
Laura
L
Säisänen
Mervi
M
Könönen
Päivi
P
Koskenkorva
Ritva
R
Vanninen
Reetta
R
Kälviäinen
Esa
E
Mervaala
D000328:Adult; D055313:Cystatin B / Q000235:genetics; D004576:Electromyography; D019054:Evoked Potentials, Motor / Q000235:genetics / Q000502:physiology*; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000503:physiopathology*; D009154:Mutation / Q000235:genetics; D012720:Severity of Illness Index; D050781:Transcranial Magnetic Stimulation; D020194:Unverricht-Lundborg Syndrome / Q000235:genetics / Q000473:pathology*; D055815:Young Adult
C524994:CSTB protein, human; D055313:Cystatin B
EPM1; Unverricht-Lundborg disease; progressive myoclonus epilepsy; transcranial magnetic stimulation motor cortex