Abstracts

Rationale: VNS is a palliative treatment in pharmacoresistent epilepsy with largely unknown mecanism of action. We tested by the means of TMS the evolution of cortical exitabiliy after 1 and 2 years of VNS.Methods: The ethics committee CCPPRB of Cochin medical school, Paris, approved the protocol without direct benefit. Three sessions of TMS, testing motor threshold (MT), intracortical inhibition (ICI), intracortical facilitation (ICF) and cortical silence (CS) were performed before (T0), after one (T1) and after two years (T2) of VNS with a minimum intensity of 1 mA. Antiepileptic drugs have been maintained unchanged in most cases, the dosage could slightly vary Study population: 35 consecutive patients selected for implantation of a VNS device at our epilepsy center between November 2005 and October 2009. Inclusion criteria: aged over 18, pharmacoresistant epilepsy, not amendable to resective epilepsy surgery. Exclusion criteria: cortex unexcitable, VNS-device not implanted or stopped after informed consent, refusal to sign the informed consent. - 21 subjects were analyzed, 12 males (57.1%). Mean age at VNS implantation was 38years (SD: 9) Patients having under VNS a seizure reduction of ≥ 50% were considered responders. Statistical Analysis: Patients' characteristics are presented using median and interquartile range (IQR25-75), or mean and standard deviation (SD. Student or Wilcoxon Mann Withney test for continuous variables and Chi-square or Fisher test for categorical ones, mixed model regressions, a log transformation and Tukey’s adjustment to control the type 1 error in multiple comparisons with p-values adjusted (pTUKEY) were performed when appropriate. Statistical bilateral significance threshold was set at 5%Results: 13 patients (61.9%). were non-responders Significant changes after 2 years of VNS: Motor threshold: the MT increases significantly with time; a minor increase is observed after one year of VNS (difference of LS-means for T1 – T0 = 0.029 (SE=0.016), p=0.077, pUKEY=0.178), which becomes significant one year later (difference of LS-means for T2 – T0 = 0.044 (SE=0.016), p=0.007, PTUKEY=0.019) ICI with an interstimulus interval (ISI) of 2 msec: After 2 years of VNS the amplitude of the motor evoked potential (MEP) is significantly higher among responders (LS-means for log (MEP2MS) = 5.42 µV (SE=0.126)) than among non-responders (LS-means for log(MEP2MS) = 4.69 µV (SE=0.120) (p = 0.0007). ICI with ISI of 4 msec: The MEP increases in responders (p=0.004) after one year (T0-T1: p=0.006, pTUKEY=0.067) and becomes very significant after two years of VNS (T0-T2 : p=0.002 and pTUKEY=0.024)Conclusions: The progressive and after 2 years of chronic VNS significant increase of the MT is a major result of our prospective study, which is the first long term follow-up study of this kind. VNS may decrease cortical excitability with time. The decrease of cortical inhibition in responders is unexpected, raises new questions and needs confirmation.