Botulinum Toxin Dilution and Endplate Targeting in Spasticity: A Double-Blind Controlled Study  Jean-Michel Gracies, MD, Mara Lugassy, MD, Donald J. Weisz, PhD, Michele Vecchio, MD, Steve Flanagan, MD, David M. Simpson, MD  Archives of Physical Medicine and Rehabilitation  Volume 90, Issue 1, Pages 9-16.e2 (January 2009) DOI: 10.1016/j.apmr.2008.04.030 Copyright © 2009 American Congress of Rehabilitation Medicine Terms and Conditions

Fig 1 Flow diagram from screening to study completion. Of the 21 patients screened, 21 were randomized into the trial and all were treated and followed up until study completion. Archives of Physical Medicine and Rehabilitation 2009 90, 9-16.e2DOI: (10.1016/j.apmr.2008.04.030) Copyright © 2009 American Congress of Rehabilitation Medicine Terms and Conditions

Fig 2 Schematic diagram from a previous human cadaver study showing the inverted V-shaped area dense in endplates at the junction between the lower third and the upper two thirds of the biceps. Archives of Physical Medicine and Rehabilitation 2009 90, 9-16.e2DOI: (10.1016/j.apmr.2008.04.030) Copyright © 2009 American Congress of Rehabilitation Medicine Terms and Conditions

Fig 3 Overall effects of the injection of 160U of BTX-A into biceps brachii on isometric efforts: Open columns, preinjection; hatched columns, 1 month postinjection. (A) Flexion, (B) extension. The 4 columns on the left of each graph represent the changes in MRV of the agonist and antagonist muscle group for each isometric effort. The last 2 columns on the right represent the corresponding changes in MVP (kg). Error bars, standard error of the mean. Abbreviations: MRV, mean rectified voltage (in volts in the figure); MVP, maximal voluntary power (in kg in the figure). Y-axis is scaled for both V and kg. *P<.05; **P<.01. Archives of Physical Medicine and Rehabilitation 2009 90, 9-16.e2DOI: (10.1016/j.apmr.2008.04.030) Copyright © 2009 American Congress of Rehabilitation Medicine Terms and Conditions

Fig 4 Overall effects of the injection of 160U of BTX-A into biceps brachii on spasticity and active range of elbow extension. (A) Spasticity grade, (B) spasticity angle, (C) active range of motion. Open columns, preinjection; hatched columns, 1 month postinjection. Note the reduction in flexor spasticity angle and the increase in active range of elbow extension. Error bars, standard error of the mean. *P<.05; **P<.01. Archives of Physical Medicine and Rehabilitation 2009 90, 9-16.e2DOI: (10.1016/j.apmr.2008.04.030) Copyright © 2009 American Congress of Rehabilitation Medicine Terms and Conditions

Fig 5 Effects of dilution and endplate targeting on isometric efforts. (A) Flexor agonist MRV, (B) flexor antagonist MRV, (C) extensor agonist MRV, (D) extensor antagonist MRV. Open columns, preinjection; hatched columns, 1 month postinjection. Error bars, standard error of the mean. MRV (in volts). *P<.05. Non-targ, nontargeted 4-quadrants injection technique. The elbow flexors are significantly more blocked in the highly diluted group (ANCOVA), including when recruited as cocontracting antagonist, while there is no difference between groups in the effects on the noninjected extensors. Archives of Physical Medicine and Rehabilitation 2009 90, 9-16.e2DOI: (10.1016/j.apmr.2008.04.030) Copyright © 2009 American Congress of Rehabilitation Medicine Terms and Conditions

Fig 6 Effects of dilution and endplate targeting on the changes in spasticity and active range of elbow extension. (A) Flexor spasticity grade, (B) flexor spasticity angle, (C) active range of extension. Post 1-2, mean of the values at 1 month and 2 months postinjection; Post 3-4, mean of the values 3 and 4 months postinjection; Open circles, non-diluted nontargeted group; filled squares, endplate-targeted group; filled triangles, diluted nontargeted group. Error bars, standard error of the mean. *P<.05. Overall ANCOVA was significant only for range of motion (P=.045). Pairwise comparisons Post 1-2 versus baseline were significant only in the targeted and diluted groups for spasticity angle and in the targeted group for AROM. Archives of Physical Medicine and Rehabilitation 2009 90, 9-16.e2DOI: (10.1016/j.apmr.2008.04.030) Copyright © 2009 American Congress of Rehabilitation Medicine Terms and Conditions

Supplemental Fig 1 Isometric set up. An angular strain gauge measures the flexor and extensor force exerted around the elbow during isometric efforts, while 2 pairs of surface electrodes monitor the activity of the flexors and extensors of the elbow. EMG, electromyography. Archives of Physical Medicine and Rehabilitation 2009 90, 9-16.e2DOI: (10.1016/j.apmr.2008.04.030) Copyright © 2009 American Congress of Rehabilitation Medicine Terms and Conditions

Supplemental Fig 2 Methodology of measuring mean rectified voltage. Bottom trace, force transducer signal in volts during a maximal isometric effort of elbow flexion and a maximal isometric effort of elbow extension; Second and third trace from the bottom, raw surface flexor and extensor electromyogram in volts; Top 2 traces, flexor and extensor electromyogram rectified and smoothed (time constant 40ms). NOTE. The area under the curve that measures (A) maximal agonist flexor activity, (B) maximal agonist extensor activity, (C) corresponding extensor cocontraction, and (D) corresponding flexor cocontraction. The MRV over each of these areas is used to represent the (A) flexor agonist MRV, (B) flexor antagonist MRV, (C) extensor antagonist MRV, and (D) flexor antagonist MRV. Archives of Physical Medicine and Rehabilitation 2009 90, 9-16.e2DOI: (10.1016/j.apmr.2008.04.030) Copyright © 2009 American Congress of Rehabilitation Medicine Terms and Conditions