Abstracts

Rationale: The majority of idiopathic generalised epilepsies (IGE) have a complex genetic inheritance, (Trends Neurosci 2006; 29(7): 391-397). Although the exact mechanisms underlying the pathogenesis of epilepsy are unknown, it is thought to result from an imbalance from excitatory and inhibitory pathways. Transcranial magnetic stimulation (TMS) allows investigation of both excitatory and inhibitory functions of central motor pathways in vivo providing non -invasive clinical measurements of neuronal excitability (Clin Neurophys 2003; 114 (5): 777-798). Previous studies using TMS measures have shown altered excitability in patients with IGE including prolonged cortical silent period (CSP). (Neurology 2001; 57(4): 706-8, Seizure 2004; 13(7):481-485). CSP is thought to be mediated by intracortical inhibitory mechanisms involving GABA in the primary motor cortex (J Physiol 1999; 517(2): 591-7). Endophenotypes are heritable traits with a simpler genetic basis than the full disorder and may be present in family members who do not have the disease (Am J Psych 2003; 160(4): 636-45). Endophenotypes can help increase our understanding of the pathophysiology of complex genetic diseases. TMS parameters have been shown to be heritable (J Neurosci 2009; 28(6): 464-73). In this study we used TMS to investigate cortical silent period as a potential endophenotype for idiopathic generalised epilepsy by testing whether CSP is prolonged in a group of patients with IGE and their first degree relatives. Methods: We studied thirty-two patients with IGE (7 JME, 4 JAE, 4 CAE, 11 with GTCS only, 1 with absences with eyelid myoclonia), 35 of their first-degree relatives and 37 age and sex-matched healthy controls. Magnetic stimulation was performed using two Magstim 200 stimulators connected via a MagStim BiStim Unit (Magstim, Dyfed, UK) with EMG activity measured from first dorsal interossei muscle bilaterally. Single pulse TMS was used to measure resting and active motor threshold (R/AMT) and CSP. To reduce observer bias, CSP duration was analysed using an automated method cumulative sum (Cusum) technique (J NeuroSci Meth 2006; 150(1): 96-104. Group differences were investigated using Kruskal-Wallis test. Results: Patients with IGE showed significantly higher motor thresholds (dominant RMT p=0.006, non-dominant RMT p=0.005, dominant AMT p=0.008, non-dominant AMT p=0.001) compared with controls). There were no significant differences in motor thresholds between relatives and controls. First-degree relatives had significantly prolonged cortical silent periods compared with controls in both hemispheres (dominant p=0.020, non-dominant p=0.005). Patients also exhibited longer CSP than control subjects in the dominant hemisphere (p=0.006). See Figure 1. Conclusions: Higher motor threshold in patients may be related to medication effects. However, the presence of prolonged cortical silent period in IGE patients and their first-degree relatives may reflect an inherited alteration in cortical excitability ie. an endophenotype in epilepsy.