Botulinum Toxin Modulates Posterior Parietal Cortex Activation in Post-stroke Spasticity of the Upper Limb

You definition of effective is wrong, botox does not cure spasticity, it only supresses the abnormal activation. You still have to get the opposing muscle working. In my case that control area is dead. What the fuck is the solution to that? Where is your solution for dead brain rehab? There are millions of cases every year, so you have lots of participants to choose from. 

Botulinum Toxin Modulates Posterior Parietal Cortex Activation in Post-stroke Spasticity of the Upper Limb

Tomáš Veverka^1*, Pavel Hok¹, Pavel Otruba¹, Jana Zapletalová², Barbora Kukolová³, Zbyněk Tüdös⁴, Alois Krobot⁵, Petr Kaňovský¹ and Petr Hluštík^1,4

• ¹Department of Neurology, Palacký University and University Hospital, Olomouc, Czechia
• ²Department of Biophysics, Biometry and Statistics, Palacký University and University Hospital, Olomouc, Czechia
• ³Rehabilitation Centre, Hrabyně, Czechia
• ⁴Department of Radiology, Palacký University and University Hospital, Olomouc, Czechia
• ⁵Department of Physiotherapy, Palacký University and University Hospital, Olomouc, Czechia

Post-stroke spasticity (PSS) is effectively treated with intramuscular botulinum toxin type A (BoNT-A), although the clinical improvement is likely mediated by changes at the central nervous system level. Using functional magnetic resonance imaging (fMRI) of the brain, this study aims to confirm and locate BoNT-A-related changes during motor imagery with the impaired hand in severe PSS. Temporary alterations in primary and secondary sensorimotor representation of the impaired upper limb were expected. Thirty chronic stroke patients with upper limb PSS undergoing comprehensive treatment including physiotherapy and indicated for BoNT treatment were investigated. A change in PSS of the upper limb was assessed with the modified Ashworth scale (MAS). fMRI and clinical assessments were performed before (W0) and 4 weeks (W4) and 11 weeks (W11) after BoNT-A application. fMRI data were acquired using 1.5-Tesla scanners during imagery of finger-thumb opposition sequences with the impaired hand. At the group level, we separately modeled (1) average activation at each time point with the MAS score and age at W0 as covariates; and (2) within-subject effect of BoNT-A and the effect of time since W0 as independent variables. Comprehensive treatment of PSS with BoNT-A significantly decreased PSS of the upper limb with a maximal effect at W4. Task-related fMRI prior to treatment (W0) showed extensive activation of bilateral frontoparietal sensorimotor cortical areas, bilateral cerebellum, and contralesional basal ganglia and thalamus. After BoNT-A application (W4), the activation extent decreased globally, mostly in the bilateral parietal cortices and cerebellum, but returned close to baseline at W11. The intra-subject contrast revealed a significant BoNT-A effect, manifesting as a transient decrease in the activation of the ipsilesional intraparietal sulcus and superior parietal lobule. We demonstrate that BoNT-A treatment of PSS of the upper limb is associated with transient changes in the ipsilesional posterior parietal cortex, possibly resulting from temporarily altered sensorimotor upper limb representations.

Introduction

Post-stroke spasticity (PSS) is a major sequelae among stroke survivors (1) with an estimated prevalence of 19–42.6% (2, 3). Clinically relevant PSS may interfere with voluntary movement and frequently causes deterioration in manual dexterity, mobility, walking, and hygiene (2). PSS of the upper limbs is currently treated with botulinum toxin type A (BoNT-A), which is an effective and safe therapeutic agent to improve function of the affected limb (4–6). BoNT-A treatment has been shown to relieve pain, enhance the effects of physiotherapy, improve performance in activities of daily living, and decrease the burden of caregivers (2). Over the last decade, there has been growing evidence that besides the well-known neuromuscular junction site of action, BoNT-A acts centrally. Whereas, direct effect on distant central circuits via retrograde transport and transcytosis in humans is still under debate (7), the central effects have been mostly ascribed to indirect changes due to plastic rearrangement subsequent to modulation of sensory input (8). BoNT-A likely relieves focal PSS by promoting dynamic changes at multiple levels of the sensorimotor system, presumably including the cerebral cortex. It has been suggested that BoNT-A acts on intrafusal as well as well as extrafusal fibers, thereby altering abnormal sensory input to the central nervous system via Ia afferent fibers (8, 9), which is likely the mechanism by which intramuscular BoNT-A injection induces cortical reorganization. The theory of central (remote) BoNT-A effects was first reported in electrophysiological studies of focal dystonia (10, 11). In dystonic disorders, one application of BoNT has been reported to be associated with even more pronounced microstructural gray matter changes in the frontal cortex, namely, primary motor cortex and pre-supplementary motor area (12). There have been several reports of the neuroanatomical correlates of BoNT-A-related relief of PSS using functional magnetic resonance imaging (fMRI) (13–16). However, the studies were conducted with small sample sizes; they differ in their activation tasks, and other methodological aspects. This makes direct comparison between the studies difficult. Patients with prominent upper limb spasticity indicated for BoNT-A treatment often have severe hand weakness, precluding the use of real hand movement. Motor imagery is feasible for severely affected patients and the sensorimotor representations may be preserved even in chronic paralysis (17). Motor imagery has been used widely in post-stroke paralysis, both as a functional neuroimaging probe sensitive to motor network abnormalities during stroke recovery (18) and as a motor training strategy (19). To our knowledge, our pilot study is the only one employing motor imagery to investigate cortical activation changes associated with PSS relief due to BoNT-A treatment (20). Using a longitudinal design, we expected that BoNT-A-induced change in afferent drive (8, 9) will be reflected in modulation of somatosensory cortical processing in the parietal areas (20). Even though our results showed several areas of change in the sensorimotor network over time, no regions showed transient effects following the course of dynamic changes in clinical spasticity. Therefore, the aim of the present longitudinal study was to identify BoNT-A-related patterns of cerebral cortex activation during motor imagery in a more representative cohort of patients with moderate to severe PSS of the upper limbs.

Methods

The study protocol is described in our previous report (20). The following text summarizes the methodology and highlights differences particular for the present study.