Cerebello-Motor Paired Associative Stimulation and Motor Recovery in Stroke: a Randomized, Sham-Controlled, Double-Blind Pilot Trial.

Cerebellum is a key structure for functional motor recovery after stroke. Enhancing the cerebello-motor pathway by paired associative stimulation (PAS) might improve upper limb function. Here, we conducted a randomized, double-blind, sham-controlled pilot trial investigating the efficacy of a 5-day treatment of cerebello-motor PAS coupled with physiotherapy for promoting upper limb motor function compared to sham stimulation. The secondary objectives were to determine in the active treated group (i) whether improvement of upper limb motor function was associated with changes in corticospinal excitability or changes in functional activity in the primary motor cortex and (ii) whether improvements were correlated to the structural integrity of the input and output pathways. To that purpose, hand dexterity and maximal grip strength were assessed along with TMS recordings and multimodal magnetic resonance imaging, before the first treatment, immediately after the last one and a month later. Twenty-seven patients were analyzed. Cerebello-motor PAS was effective compared to sham in improving hand dexterity (p: 0.04) but not grip strength. This improvement was associated with increased activation in the ipsilesional primary motor cortex (p: 0.04). Moreover, the inter-individual variability in clinical improvement was partly explained by the structural integrity of the afferent (p: 0.06) and efferent pathways (p: 0.02) engaged in this paired associative stimulation (i.e., cortico-spinal and dentato-thalamo-cortical tracts). In conclusion, cerebello-motor-paired associative stimulation combined with physiotherapy might be a promising approach to enhance upper limb motor function after stroke.Clinical Trial Registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT02284087.

The silver effect of admission glucose level on excellent outcome in thrombolysed stroke patients.

Higher admission glucose levels (AGL) are associated with less favorable outcome in thrombolysis. But, could AGL's impact on outcome vary by onset-to-treatment (OTT) time? Is hyperglycemia associated with a shorter therapeutic time window for excellent outcome for thrombolysed stroke patients? We assessed predictive values of AGL, baseline NIHSS, age, and OTT time quartiles on excellent outcome (3-month modified Rankin score of 0-1) in 773 patients treated by rt-Pa. We added the AGL × OTT time quartile interaction in the model and separately analyzed the predictive values of AGL, age, and NIHSS for each OTT time quartile if the interaction was significant. AGL, baseline NIHSS, age, and OTT time quartiles were significant predictors. When added in the model, the AGL × OTT interaction was significant (OR: 0.96, 95% CI: 0.94-0.99, p: 0.0009). AGL was predictive only during the third OTT time quartile (181-224 min). During this period, the predicted rate of excellent outcome was 16% for AGL = 6.5 mmol/L and 8% for AGL = 8 mmol/L. The rate of excellent outcome was not decreased in hyperglycemic patients for OTT time ≤ 180 min (20 vs. 24.5% p: 0.37), but was decreased for OTT time > 180 min (9.6 vs. 26.7% p: 0.00001). Similar results were found in patients with MCA recanalization, but not in patients without recanalization. The therapeutic time window for excellent outcome is shortened in hyperglycemic patients. This would support the design of "freezing penumbra" randomized trials based on ultra-early AGL control.