Botulinum Toxin Dilution and Endplate Targeting in Spasticity: A Double-Blind Controlled Study

Abstract

Gracies J-M, Lugassy M, Weisz DJ, Vecchio M, Flanagan S, Simpson DM. Botulinum toxin dilution and endplate targeting in spasticity: a double-blind controlled study. Objective To determine the effects of botulinum neurotoxin type A (BTX-A) dilution and endplate-targeting in spastic elbow flexors. Design Double blind randomized controlled trial; 4-month follow-up after a 160-unit injection of BTX-A into spastic biceps brachii (4 sites). Randomization into: group 1: 100 mouse units (MU)/mL dilution, 0.4cc/site, 4-quadrant injection; group 2: 100MU/mL dilution, 0.4cc/site, 4 sites along endplate band; group 3: 20MU/mL dilution, 2cc/site, 4-quadrant injection (n=7 per group). Setting Institutional tertiary care ambulatory clinic. Participants Referred sample of 21 adults with spastic hemiparesis. No participant withdrew due to adverse effects. Intervention A 160-unit injection of BTX-A of different dilutions and locations into biceps brachii. Main Outcome Measures Primary: agonist and antagonist (cocontraction) mean rectified voltage (MRV) of elbow flexors/extensors during maximal isometric flexion/extension; secondary: maximal voluntary power of elbow flexion/extension; spasticity angle and grade in elbow flexors/extensors (Tardieu Scale); active range of elbow extension/flexion. Results BTX-A injection overall reduced agonist flexor MRV (–47.5%, P<0.0001), antagonist flexor MRV (–12%, P=.037), antagonist extensor MRV (–19%, P<.01), flexion maximal voluntary power (–33%, P<.001), elbow flexor spasticity angle (–30%, P<.001) and grade (–17%, P=.03), and increased extension maximal voluntary power (24%, P=.037) and active range of elbow extension (5.5%, 8°, P=.002). Agonist and antagonist flexor MRV reductions in group 3 (–81% and –31%) were greater than in groups 1 and 2, whereas increase in active range of elbow extension was greater in group 2 (10%) than in groups 1 and 3 ( P<.05, analysis of covariance [ANCOVA]). Elbow flexor spasticity was significantly reduced in groups 2 and 3 only ( P<.05, ANCOVA). Conclusions In spastic biceps, high-volume or endplate-targeted BTX-A injections achieve greater neuromuscular blockade, cocontraction and spasticity reduction, and active range of elbow extension improvement, than low volume, nontargeted injections.