Amelioration of Parkinsonian tremor evoked by DBS: which role play cerebello-(sub)thalamic fiber tracts?

BACKGROUND: Current pathophysiological models of Parkinson's disease (PD) assume a malfunctioning network being adjusted by the DBS signal. As various authors showed a main involvement of the cerebellum within this network, cerebello-cerebral fiber tracts are gaining special interest regarding the mediation of DBS effects. OBJECTIVES: The crossing and non-decussating fibers of the dentato-rubro-thalamic tract (c-DRTT/nd-DRTT) and the subthalamo-ponto-cerebellar tract (SPCT) are thought to build up an integrated network enabling a bidimensional communication between the cerebellum and the basal ganglia. The aim of this study was to investigate the influence of these tracts on clinical control of Parkinsonian tremor evoked by DBS. METHODS: We analyzed 120 electrode contacts from a cohort of 14 patients with tremor-dominant or equivalence-type PD having received bilateral STN-DBS. Probabilistic tractography was performed to depict the c-DRTT, nd-DRTT, and SPCT. Distance maps were calculated for the tracts and correlated to clinical tremor control for each electrode pole. RESULTS: A significant difference between "effective" and "less-effective" contacts was only found for the c-DRTT (p = 0.039), but not for the SPCT, nor the nd-DRTT. In logistic and linear regressions, significant results were also found for the c-DRTT only (pmodel logistic = 0.035, ptract logistic = 0,044; plinear = 0.027). CONCLUSIONS: We found a significant correlation between the distance of the DBS electrode pole to the c-DRTT and the clinical efficacy regarding tremor reduction. The c-DRTT might therefore play a major role in the mechanisms of alleviation of Parkinsonian tremor and could eventually serve as a possible DBS target for tremor-dominant PD in future.

Validation of diffusion tensor imaging tractography to visualize the dentatorubrothalamic tract for surgical planning.

OBJECTIVE The dentatorubrothalamic tract (DRTT) has been suggested as the anatomical substrate for deep brain stimulation (DBS)-induced tremor alleviation. So far, little is known about how accurately and reliably tracking results correspond to the anatomical DRTT. The objective of this study was to systematically investigate and validate the results of different tractography approaches for surgical planning. METHODS The authors retrospectively analyzed 4 methodological approaches for diffusion tensor imaging (DTI)-based fiber tracking using different regions of interest in 6 patients with essential tremor. Tracking results were analyzed and validated with reference to MRI-based anatomical landmarks, were projected onto the stereotactic atlas of Morel at 3 predetermined levels (vertical levels -3.6, -1.8, and 0 mm below the anterior commissure-posterior commissure line), and were correlated to clinical outcome. RESULTS The 4 different methodologies for tracking the DRTT led to divergent results with respect to the MRI-based anatomical landmarks and when projected onto the stereotactic atlas of Morel. There was a statistically significant difference in the lateral and anteroposterior coordinates at the 3 vertical levels (p < 0.001, 2-way ANOVA). Different fractional anisotropy values ranging from 0.1 to 0.46 were required for anatomically plausible tracking results and led to varying degrees of success. Tracking results were not correlated to postoperative tremor reduction. CONCLUSIONS Different tracking methods can yield results with good anatomical approximation. The authors recommend using 3 regions of interest including the dentate nucleus of the cerebellum, the posterior subthalamic area, and the precentral gyrus to visualize the DRTT. Tracking results must be cautiously evaluated for anatomical plausibility and accuracy in each patient.

Effects of spinal cord stimulation on cortical excitability in patients with chronic neuropathic pain: a pilot study.

BACKGROUND: Despite a broad clinical use, the mechanism of action of SCS is poorly understood. Current information suggests that the effects of SCS are mediated by a complex set of interactions at several levels of the nervous system including spinal and supraspinal mechanisms. AIMS: The study was undertaken to investigate the influence of SCS on distinct parameters of cortical excitability using single- and paired-pulse transcranial magnetic stimulation (TMS). METHODS: Five patients with chronic neuropathic pain were examined with the SCS stimulator on and off by means of TMS. Pain was assessed using a visual-analogue scale. Electrophysiological and pain parameters of patients during this procedure were compared by means of a linear mixed effect model. RESULTS: SCS induced a significant modulation of cortical excitability, especially by influencing the parameter "intracortical facilitation" (t=-2.657; df=8; p=0.029). A significant relationship between this parameter and "perceived pain" could be obtained (t=-4.798; df=8; p=0.002). CONCLUSIONS: These results suggest that SCS is able to influence neurobiological processes at the supraspinal level and that clinical effects of SCS may be at least in part of cortical origin.