Neuroscience Letters 541 (2013) 20–23 Contents lists available at SciVerse ScienceDirect Neuroscience Letters j ourna l ho me p ag e: www.elsevier.com/locate/neulet Intrafusal effects of botulinum toxin injections for spasticity: Revisiting a previous paper Chetan P. Phadke a,b,∗ , Arzu Y. On c , Yesim Kirazli c , Farooq Ismail a,d , Chris Boulias a,d a Upper Motorneuron Spasticity Research Program, West Park Healthcare Centre, Toronto, ON M6M 2J5, Canada b Department of Physical Therapy, University of Toronto, Toronto, ON M5G 1V7, Canada c Ege University Medical School, Department of Physical Therapy and Rehabilitation, 35100 Bornova, Izmir, Turkey d Division of Physiatry, University of Toronto, Canada h i g h l i g h t s  Botulinum toxin induces chemodenervation of extra- and intramuscular muscle fibers.  H-reflex bypasses and stretch reflex activates muscle spindles.  Intrafusal effects can be isolated from extrafusal effects.  Intrafusal effects are change in stretch reflex minus change in H-reflex size. a r t i c l e i n f o Article history: Received 23 June 2012 Received in revised form 6 February 2013 Accepted 13 February 2013 Keywords: Botulinum toxin Muscle spindle Intrafusal fibers Gamma motorneuron Stretch reflex H-reflex Achilles tendon reflex a b s t r a c t Botulinum toxin, frequently used to manage focal limb spasticity, has been reported to affect both extra- fusal and intrafusal fibers of the injected muscle. Since most studies have used spinal reflexes, it is difficult to isolate the intrafusal effects from extrafusal and central effects. In a paper by On et al. [7], both stretch and H-reflexes were used to examine the intrafusal effects of botulinum toxin injections. Revisiting the data from On et al. [7] presented a unique opportunity to describe a novel method of measuring the effect of botulinum toxin-A on muscle spindle activity in patients with spasticity. H-reflex, maximum M-wave, and Achilles tendon reflex were serially assessed in ten patients with stroke pre-, 2, 4, and 12 weeks post-botulinum. In order to assess the intrafusal effects, we subtracted the %change in H- reflex amplitude from baseline (representing extrafusal and central effects) from the %change in Achilles tendon reflex amplitude from baseline (representing intrafusal, extrafusal and central effects). Using this formula, our results suggest that botulinum induces significant chemodenervation of the intrafusal muscle fibers (33% decreases). Intrafusal effects were greatest at 2 weeks, but tapered off by 12 weeks post-botulinum (p < 0.017). We found a significant positive correlation between the intrafusal effects of botulinum toxin and changes in modified Ashworth scale. Our method of assessing the effects of botulinum toxin shows significant effect on intrafusal fibers, which correlates with clinical manifesta- tion of spasticity. Future studies need to investigate ways to maximize intrafusal effects and minimize extrafusal effects of botulinum therapy. © 2013 Elsevier Ireland Ltd. All rights reserved. Abbreviations: BoNTA, botulinum toxin A; Mmax, maximum motor response; Hmax, maximum H-reflex response; ATR, Achilles tendon reflex; MAS, modified Ashworth scale. ∗ Corresponding author at: West Park Healthcare Centre, Research & Evaluation, 82 Buttonwood Avenue, Toronto, ON M6M 2J5, Canada. Tel.: +1 416 243 3600x2716; fax: +1 416 243 3747. E-mail addresses: cphadke@gmail.com, chetan.phadke@westpark.org (C.P. Phadke), arzu.on@ege.edu.tr (A.Y. On), yesim.kirazli@ege.edu.tr (Y. Kirazli), farooq.ismail@westpark.org (F. Ismail), chris.boulias@westpark.org (C. Boulias). 1. Introduction Among other uses, botulinum toxin-A injection therapy (BoNTA) has been shown to be effective in reducing focal limb spasticity by presynaptically inhibiting acetylcholine release resulting in the decreased output from the neuromuscular junction [3]. This inhibition, termed chemodenervation, occurs at neuromuscular junctions in the vicinity of the injection site including neuro- muscular junctions between alpha motorneuron and extrafusal muscle fiber as well as gamma motorneuron and intrafusal muscle fiber (muscle spindle). Intrafusal muscle fiber, apart from being a muscle fiber with contractile properties, is also a sensory organ that senses muscle stretch [11]. The central portion of the muscle 0304-3940/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.neulet.2013.02.025