Meaningful improvement in walking performance after Botulinum Neurotoxin A (BoNT-A) in chronic spastic patients

Cioncoloni, David; Taddei, Sabrina; Bielli, Silvia; Annunziata, Pasquale; Mazzocchio, Riccardo

doi:10.3233/nre-131021

Cited by 10 publications

(8 citation statements)

References 28 publications

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“…This has also been proven by numerous electrophysiological studies indicative of BoNT-related effects within non-injected muscles [19,20,21]. In spastic syndromes, evidence for central effects of BoNT comes from the fact that injection in one muscle may also act at the corresponding antagonist muscle [22,23] or other non-injected muscles with consecutive clinical benefit [18,24]. Interestingly, the time course of pain relief differed from that of muscle relaxation in cervical dystonia (CD) following BoNT injections.…”

Section: Clinical Evidencementioning

confidence: 97%

Central Effects of Botulinum Neurotoxin—Evidence from Human Studies

Weise

Naumann

2019

Toxins

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For more than three decades, Botulinum neurotoxin (BoNT) has been used to treat a variety of clinical conditions such as spastic or dystonic disorders by inducing a temporary paralysis of the injected muscle as the desired clinical effect. BoNT is known to primarily act at the neuromuscular junction resulting in a biochemical denervation of the treated muscle. However, recent evidence suggests that BoNT’s pharmacological properties may not only be limited to local muscular denervation at the injection site but may also include additional central effects. In this review, we report and discuss the current evidence for BoNT’s central effects based on clinical observations, neurophysiological investigations and neuroimaging studies in humans. Collectively, these data strongly point to indirect mechanisms via changes to sensory afferents that may be primarily responsible for the marked plastic effects of BoNT on the central nervous system. Importantly, BoNT-related central effects and consecutive modulation and/or reorganization of the brain may not solely be considered “side-effects” but rather an additional therapeutic impact responsible for a number of clinical observations that cannot be explained by merely peripheral actions.

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Section: Clinical Evidencementioning

confidence: 97%

Central Effects of Botulinum Neurotoxin—Evidence from Human Studies

Weise

Naumann

2019

Toxins

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“…Clinical benefit, that is, a wider range of movement at the ankle joint in spastic patients, is present 1 month after BoNT/A injection into the soleus muscle, in spite of little peripheral blockade (Mazzocchio and others 2007). Reduction in knee extensor spasticity is the relevant factor for improving locomotion in spastics following a multiple-muscle BoNT/A injection protocol where, paradoxically, the quadriceps was rarely treated (Cioncoloni and others 2014). These data suggest that BoNT/A, by interacting with spinal circuits, may affect pathological muscle synergies.…”

Section: Functional Significance Of Central Effectsmentioning

confidence: 99%

“…Current understanding of how to improve the efficacy of BoNT/A clinical treatment relies on strategies aimed at improving motor function through optimization of the peripheral effect. For instance, in the treatment of lower limb spasticity a rapid and persistent functional improvement can be obtained if factors such as (1) selection and number of muscles to be simultaneously injected at multiple joints (Cioncoloni and others 2014), possibly by (2) electromyography guide so as to target motor endplate locations (Lapatki and others 2011), alone or (3) combined with short-term electrical nerve stimulation of the injected muscles (Hesse and others 1995) are taken into account.…”

Section: Modulating Pre-motoneuronal Synapsesmentioning

confidence: 99%

More than at the Neuromuscular Synapse

Mazzocchio

Caleo

2014

Neuroscientist

Self Cite

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Botulinum neurotoxin type A (BoNT/A) is a metalloprotease that produces a sustained yet transitory blockade of transmitter release from peripheral nerve terminals. Local delivery of this neurotoxin is successfully employed in clinical practice to reduce muscle hyperactivity such as in spasticity and dystonia, and to relieve pain with long-lasting therapeutic effects. However, not all BoNT/A effects can be explained by an action at peripheral nerve terminals. Indeed, it appears that BoNT/A is endowed with trafficking properties similar to the parental tetanus neurotoxin and thus be able to directly affect the CNS. In this review, we present and discuss novel compelling evidence for a direct central effect of BoNT/A in both dorsal and ventral horns of the animal and human spinal cord after peripheral injection of the neurotoxin, with important consequences on pain and motor control. This new knowledge is expected to radically change the approach to the use of BoNT/A in the future. As BoNT/A central action appears to also contribute to functional improvement, for instance in human spastic gait, the challenge will be to develop new subtypes or BoNT derivatives with deliberate, cell-specific central effects in order to fully exploit the spectrum of BoNT/A therapeutic activity.

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“…Other studies have reported improvements in walking ability following BoNT‐A injections of the lower limb using a number of assessment techniques, including timed walking tests, Fugl‐Meyer assessments, use of video technology to measure temporospatial parameters, or instrumented insoles, 8,21‐24 with greater improvements in one study when patients underwent an adjunct guided self‐rehabilitation program 25 …”

Section: Discussionmentioning

confidence: 99%

The Effect of Repeated abobotulinumtoxinA (Dysport®) Injections on Walking Velocity in Persons with Spastic Hemiparesis Caused by Stroke or Traumatic Brain Injury

Esquenazi

Brashear

Deltombe

et al. 2020

PM&R

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Background Botulinum toxin (BoNT) injections were shown to improve muscle tone of limbs in patients with spasticity. However, limited data are available regarding the effects of repeated BoNT injections on walking ability. Objective To assess changes in walking velocity (WV), step length, and cadence under different test conditions after repeated treatment with abobotulinumtoxinA (aboBoNT‐A; Dysport) in spastic lower limb muscles. Design Secondary analysis of an open‐label, multiple‐cycle extension (National Clinical Trials number NCT01251367) to a phase III, double‐blind, randomized, placebo‐controlled, single‐treatment cycle study, in adults with chronic hemiparesis (NCT01249404). Setting Fifty‐two centers across Australia, Belgium, the Czech Republic, France, Hungary, Italy, Poland, Portugal, Russia, Slovakia, and the United States. Patients 352 Ambulatory adults (18‐80 years) with spastic hemiparesis and gait dysfunction caused by stroke or traumatic brain injury, with a comfortable barefoot WV of 0.1 to 0.8 m/s. Interventions Up to four aboBoNT‐A treatment cycles, administered to spastic lower limb muscles. Main Outcome Measurements Changes from baseline in comfortable and maximal barefoot and with shoes WV (m/s), step length (m/step), and cadence (steps/minutes). Results At Week 12 after four injections, WV improved by 0.08 to 0.10 m/s, step length by 0.03 to 0.04 m/step, and cadence by 3.9 to 6.2 steps/minutes depending on test condition (all P < .0001 to .0003 vs baseline). More patients (7% to 17%) became unlimited community ambulators (WV ≥0.8 m/s) across test conditions compared with baseline, with 39% of 151 patients classified as unlimited community ambulators in at least one test condition and 17% in all four test conditions. Conclusions Clinically meaningful and statistically significant improvements in WV, step length, and cadence under all four test conditions were observed in patients with spastic hemiparesis after each aboBoNT‐A treatment cycle.

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Meaningful improvement in walking performance after Botulinum Neurotoxin A (BoNT-A) in chronic spastic patients

Cited by 10 publications

References 28 publications

Central Effects of Botulinum Neurotoxin—Evidence from Human Studies

Central Effects of Botulinum Neurotoxin—Evidence from Human Studies

More than at the Neuromuscular Synapse

The Effect of Repeated abobotulinumtoxinA (Dysport®) Injections on Walking Velocity in Persons with Spastic Hemiparesis Caused by Stroke or Traumatic Brain Injury

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