Neuropediatrics 2012; 43 - FV12_02
DOI: 10.1055/s-0032-1307056

Characterization of endophenotypes in juvenile idiopathic generalized epilepsies by transcranial magnetic stimulation

C Ebbersmeyer 1, A Genthner 1, S Welcker 1, A Kropp 1, B Neubauer 1, A Hahn 1
  • 1Zentrum für Kinder- und Jugendmedizin, Gießen, Germany

Aims: Juvenile idiopathic generalized epilepsies (IGE) show overlapping clinical and encephalographic features. The genetic basis of these disorders remains poorly understood due their polygenic inheritance pattern. The aim of this study was to investigate whether transcranial magnetic stimulation (TMS) allows the characterization of specific endophenotypes, thereby facilitating the identification of individual susceptibility genes.

Methods: We examined 18 healthy controls, 10 subjects with juvenile myoclonic epilepsy (JME), 11 with epilepsy with grand mal on awakening (EGMA), and 10 with juvenile absence epilepsy (JAE), ranging in age from 10 and 19 years by means of TMS. 24 out of 31 patients were treated with antiepileptic drugs. We measured resting motor threshold (RMT), active motor threshold (AMT), cortical stimulation-induced silent period (CSP), intracortical inhibition (ICF) at an interstimulus interval (ISI) of 2ms, and intracortical facilitation at an ISI of 15ms. All TMS-parameters were compared between the groups by means of the ANOVA on ranks. In case a significant difference was detected, the Wilcoxon rank sum test was used for further pairwise comparisons between the single groups.

Results: Only ICI differed significantly between all groups (p=.009). The post-hoc-analysis revealed that this was due to significant differences between patients with JME and healthy controls (median: 87 [69;123]% vs. 37 [26;74]%, p=0.001), and between patients with JME and JAE (87 [69;123]% vs. 41 [31;68]%, p=0.005). Patients with EGMA also showed higher ICI values (52 [19;88]%) than normal controls and patients with JAE, but these differences did not reach significance (p>0.05).

Conclusion: TMS revealed an impaired cortical inhibition in a substantial amount of patients with juvenile IGE. This specific neurophysiologic deficit appears to contribute predominantly to the phenotype of JME, while is seems not to play a role in the pathogenesis of JAE. The endophenotype of a decreased cortical inhibition can add as a TMS-marker to the elucidation of the genetic basis of IGE.

endophenotypes - juvenile idiopathic generalized epilepsie - transcranial magnetic stimulation