EPV 7. PAS-induced plasticity relates to symptom severity and benefit from deep brain stimulation in cervical dystonia

Abstract

Deep brain stimulation (DBS) of the globus pallidus internus (GPi-DBS) is an established treatment for patients with medication-refractory cervical dystonia ( Volkmann et al., 2014 ), but individual response to DBS is highly variable and predictive factors for the clinical outcome have not been identified yet. Cortical plasticity induced by paired associative stimulation is modulated by DBS in patients with generalized dystonia and has been related to the stability of the DBS effect after switching off stimulation ( Ruge et al., 2011 ). Here, we investigated DBS-induced changes in cortical plasticity over time in patients with cervical dystonia and explored whether differences in response to DBS might be explained by individual variability of neurophysiological markers of plasticity. Methods PAS25 was applied using transcranial magnetic stimulation (TMS) to investigate cortical plasticity in 9 patients with cervical dystonia preoperatively and 3 months after activation of pallidal DBS. PAS response was calculated as mean MEP response at timepoints 0, 15 and 30 min after PAS and expressed as percentage of pre-PAS MEP. Clinical changes were assessed using the TWSTRS severity subscore. Spearman’s correlation coefficient was calculated to evaluate the relationship between neurophysiological measures and clinical scores. Three out of 9 patients were lost to neurophysiological follow up due to intra- and postoperative complications or incompatibility of the neurostimulator for TMS. Results Mean TWSTRS pre OP (17.4 ± 2.1) was reduced with pallidal DBS by 49.5% (post OP TWSTRS: 8.8 ± 2.8; Wilcoxon signed rank test: p = 0.0078; n = 9). Mean PAS response post OP (125.0% ±24.7; n = 6) was smaller compared to pre OP (165.1 ± 26.3) but did not reach significance. Individual courses of both clinical and neurophysiological changes were highly variable across subjects. Preoperative TWSTRS correlated significantly with pre-operative PAS-response ( n = 9; R = 0.78; p = 0.018). In the 6 patients that could be followed up by TMS, the decrease in PAS-response correlated with the decrease in TWSTRS score absolute values at timepoint 6 months after DBS ( n = 6; p = 0.028; R = 0.89). Conclusions Maladaptive plasticity has been discussed to play a major role in the pathophysiology of dystonia ( Quartarone et al., 2003 ). On the other hand, increased cortical plasticity might also imply a greater capability for neuromodulation ( Ruge et al., 2011 ). We found a significant correlation between symptom severity and PAS-induced cortical plasticity as well as a relation of both clinical benefit and neurophysiological change during DBS in patients with cervical dystonia. The individual susceptibility for plastic changes may partially explain the broad range of clinical benefit from DBS in dystonia. Furthermore, the correlation of plasticity with clinical benefit might indicate PAS-induced plasticity as a potential predictive factor for DBS outcome that should be explored in larger studies.