Abstracts

Rationale: Typical symptoms of Unverricht-Lundborg disease (EPM1) are involuntary action-activated myoclonic jerks (Lehesjoki & Kälviäinen, Gene Reviews, 2007;Feb 12). Antiepileptic drugs (AEDs) in EPM1 are targeted to suppress the myoclonus by inhibitory mechanisms. With MRI-navigated brain stimulation (NBS) the inhibitory mechanisms of cortical motoneurons can be studied on the primary motor cortex (J Physiol, 1996;15:519-28). Cortical silent period (SP) is the refractory time during which voluntary muscle contraction cannot be induced after being interrupted with transcranial magnetic stimulation. We studied changes in the NBS-induced SP as well as the sensitivity of motor cortex in EPM1.Methods: Twelve genetically verified EPM1-patients (4 male, 8 female, age: 28±9 years) were studied and compared with healthy, age- and sex-matched subjects (4 male, 8 female, age: 29±8 years) (OHBM 2007;abstract 213). Nine of the EPM1-patients were homozygous for the dodecamer repeat expansion mutation and three were compound heterozygous for the dodecamer repeat expansion mutation and for the c.202C>T mutation. T1-weighted MR-images were used together with NBS to study the changes in SP and motor thresholds (MTs). The exact representation area of the thenar muscle on the primary motor cortex was located by using NBS. MTs for the subjects were determined from that precise location as a percentage of the maximum stimulator output which gave 5 motor responses out of 10 stimuli. Maximum voluntary muscle contraction (MVC) for each subject was determined by using force sensors. 40% of the MVC was used for SP measurements. SPs were determined by averaging 5 consecutive trials, induced with 1.2×MT-intensity. Using the navigation software at MT-intensity, maximum electric field (mEF) at the stimulation location was determined (Hum Brain Mapp, 2005;26:100-9).Results: The SPs were significantly (p<0.05) prolonged for EPM1-patients (95±23ms) when compared to the healthy subjects (76±29ms). The MTs and mEFs were significantly (p<0.001) higher for EPM1 (74±13% and 94±25V/m, respectively) than for healthy subjects (42±7% and 65±9V/m, respectively). In 3 EPM1-patients, the maximum MVC could not be determined due to myoclonus disabling muscle contraction control. One EPM1-patient exhibited no response at all to the NBS with maximal stimulation intensity. Four EPM1-patients showed myoclonus during the stimulation session.Conclusions: Significantly reduced excitation of primary motor cortex to NBS was seen in EPM1. This could be partly explained by AEDs, increasing cortical inhibitory tonus (increasing MT, prolonging SP). However, in spite of increased MT, patients preserve normal motor strength, as well as still exhibit clinical myoclonus. NBS provides non-invasive direct measures of cortical excitability, and it may be a very important tool when studying effect of new AEDs to patients with clinically increased motor excitability (i.e., cortical myoclonus). (The study was funded by the Academy of Finland/the NEURO Research Programme, Vaajasalo Foundation and UCB Pharma.)