Acute Attenuation of Motor Impairments With a Noradrenergic Pharmacological Agent in Chronic Hemiparetic Stroke

Research Objectives: To investigate the dependence of stroke-induced loss of independent joint control and spinal motoneuron excitability on noradrenergic drive. Chronic stroke-induced limitations in upper extremity motor function commonly manifest as a loss of independent joint control and augmented spinal motoneuron excitability, with accumulating evidence attributing these findings to increased monoaminergic (norepinephrine) drive and greater reliance on contralesional corticoreticulospinal tracts.

Design: A single-blind and single-dose pharmacological case study, quantifying spinal motoneuron discharge profiles and independent joint control in chronic hemiparetic stroke with a novel robotic device before and 1.5 hr. after oral administration of 4 mg tizanidine.

Setting: Academic research laboratory.

Participants: A 69-year-old male with a focal pontine stroke (>2 yrs).

Interventions: The participant was seated with their forearm rigidly fixed to a six degree-of-freedom load cell and coupled to a robotic device capable of generating three-dimensional haptic environments. We then asked the participant to generate various isometric elbow flexion and shoulder abduction (SABD) torque profiles, designed to investigate spinal motoneuron excitability. For elbow flexion tasks, an additional dynamic condition was conducted with a downward SABD load and free-floating z-axis. For all trials, we estimated motor unit (MU) spike times via convolutive blind source separation of high-density surface electromyograms of the biceps brachii and anterior/intermediate deltoid muscles.

Main Outcome Measures: Primary outcome metrics include measures of spinal motoneuron excitability (paired MU analysis (ΔF), proportion of MUs exhibiting sustained discharge), and loss of independent joint control (involuntary SABD-induced elbow flexion).

Results: Across all trials, we decomposed 359 biceps MUs and observed a decrease in MU excitability, with a 1.29 pps decrease in ΔF (95% CI: [0.8, 2.5]) and a decreased proportion of MUs exhibiting sustained discharge (63.2% - 47.5%). Similarly, we observed the proportion of involuntary elbow flexion generated during sub-maximal SABD to decrease by an average of 10.5% post tizanidine.

Conclusions: The results presented indicate that tizanidine decreases motoneuron excitability and facilitates upper extremity independent joint control in chronic hemiparetic stroke. This highlights the noradrenergic effects on motor impairments in this population.

Author(s) Disclosures: None