Recent developments in clinical trials of botulinum neurotoxins

Cocco, Antoniangela; Albanese, Alberto

doi:10.1016/j.toxicon.2017.08.014

Cited by 22 publications

(18 citation statements)

References 44 publications

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“…The vast majority of clinical studies in children with CP have been with the various preparations of BoNT-A, principally onabotulinum toxin A (Botox ® ) and abobotulinum toxin A (Dysport ® ) [1–5]. Injection of BoNT-A produces a dose-dependent, partially reversible chemo-denervation of injected muscle by blocking pre-synaptic release of acetylcholine at the neuromuscular junction [18, 80, 81]. Because of rapid and high-affinity binding to receptors at the neuromuscular junction of the target muscle, little systemic spread of toxin occurs.…”

Section: Bont In Cpmentioning

confidence: 99%

“…However, during the past 15 years there has been a growing body of literature describing harmful effects of injection of BoNT-A at the level of the injected muscle [7, 93, 94]. These bodies of literature rarely intersect and the majority of reviews of BoNT-A make no mention of the risks of muscle atrophy and fibrosis [3, 7, 81]. In earlier literature, injection of BoNT-A was thought to be completely reversible and if the injection failed to improve gait and function, at least it would do no harm (Fig.…”

Section: Bont In Cpmentioning

confidence: 99%

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Botulinum Toxin in the Management of Children with Cerebral Palsy

et al. 2019

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During the past 25 years, botulinum toxin type A (BoNT-A) has become the most widely used medical intervention in children with cerebral palsy. In this review we consider the gaps in our knowledge in the use of BoNT-A and reasons why muscle morphology and function in children with cerebral palsy are impaired. We review limitations in our knowledge regarding the mechanisms underlying the development of contractures and the difficulty in preventing them. It is clear from this review that injection of BoNT-A in the large muscles of both the upper and lower limbs of children with cerebral palsy will result in a predictable decrease in muscle activity, which is usually reported as a reduction in spasticity, for between 3 and 6 months. These changes are noted by the use of clinical tools such as the Modified Ashworth Scale and the Modified Tardieu Scale. Decreased muscle over-activity usually results in improved range of motion in distal joints. Injection of the gastrocnemius muscle for toe-walking in a child with hemiplegia or diplegia usually has the effect of increasing the passive range of dorsiflexion at the ankle. In our review, we found that this may result in a measurable improvement in gait by the use of observational gait scales or gait analysis, in some children. However, improvements in gait function are not always achieved and are small in magnitude and short lived. We found that some of the differences in outcomes in clinical trials may relate to the use of adjunctive interventions such as serial casting, orthoses, night splints and intensive therapy. We note that the majority of clinical trials of the use of BoNT-A in children with cerebral palsy have focussed on a single injection cycle and this is insufficient to understand the balance between benefit and harm. Most outcomes were reported in terms of changes in muscle tone and there were fewer studies with robust methodology that reported improvements in function. Changes in the domains of activities and participation have rarely been reported in studies to date. There were no clinical reviews to date that consider the findings of studies in human volunteers and in experimental animals and their relevance to clinical protocols. In this review we found that studies in human volunteers and in experimental animals show muscle atrophy after an injection of BoNT-A for at least 12 months. Muscle atrophy was accompanied by loss of contractile elements in muscle and replacement with fat and connective tissue. It is not currently known if these changes, mediated at a molecular level, are reversible. We conclude that there is a need to revise clinical protocols by using BoNT-A more thoughtfully, less frequently and with greatly enhanced monitoring of the effects on injected muscle for both short-term and long-term benefits and harms.

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Section: Bont In Cpmentioning

confidence: 99%

Section: Bont In Cpmentioning

confidence: 99%

Botulinum Toxin in the Management of Children with Cerebral Palsy

et al. 2019

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“…Potency tests for dependent samples were again calculated including only the 4 subjects with lesions with an evolution within more than 15 years of evolution since onset (3 out of 7) were excluded (Figure 6). The latter were carried out after noting maximal FA differences in subjects within that range on graphs that plotted years of evolution on x-axis and pre and post-injection FA values in all four of them on y-axis, while no such changes were depicted Some authors have reported central changes after peripheral treatments with botulin toxin [30][31][32][33][34][35][36][37]. However, it is unclear why FA changes post injection were identified in the four subjects of our cohort with an evolution that ranged from 5 to 15 years since the initial lesion while the remaining three, with an evolution of less than five years and more than fifteen years, did not show significant changes [38][39][40][41].…”

Section: Resultsmentioning

confidence: 99%

Fractional Anisotropy Brain Changes in Spasticity after Peripheral Injections of Botulin

Angel¹,

Sakel²,

Hojjatoleslami³

2018

Int J Physiatry

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Purpose: To assess central fractional anisotropy changes of the white matter in subjects with spasticity treated with botulin toxin. Materials and Methods:Seven subjects with spasticity that developed 2-22 years after cerebrovascular accidents (CVA) were studied with 3T MRI of the brain including diffusion tractography (DTI) and fractional anisotropy (FA) measurements of the white matter of the corticospinal tracts (CST), corpus callosum (CC) and cerebral lobes of the affected and contralateral sides prior and after the injection of botulin toxin at the contours of peripheral nerves of the affected side.Results: All 7 subjects improved their preexisting spasticity after the injections of botulin toxin. 4 out of 7 showed FA changes post injection in the CST of the affected side. The latter had CVAs occurring 5-15 years prior to the development of spasticity. 3 out of 7 subjects did not show significant FA changes post-treatment. They had CVAs occurring less than 5 years and more than 15 years prior to the development of spasticity. There was regression between 'years of evolution', as a dependent variable, and the square of pre and post injection differences of FA on the contralateral CST, as well as white matter of the parietal and frontal lobes as independent variables. Conclusion:Botulin toxin injections improved spasticity in all the subjects of our cohort. There also were FA changes in the white matter of the CST of the affected side in those subjects with CVAs happened between 5-15 years prior to the development of spasticity, while those with lesions of less than 5 years and more than 15 years did not show statistically significant FA changes post treatment.

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“…They have received individual generic names and are currently considered individual products that are only partly interchangeable . In addition, other BoNT products are available in specific countries and others are under development .…”

Section: Treatment/managementmentioning

confidence: 99%

Dystonia: diagnosis and management

Albanese

Giovanni

Lalli

2018

Euro J of Neurology

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Clinical practice in dystonia has greatly evolved in recent years; a synthetic review on patient management is provided here. Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures or both. A recent classification has innovated clinical practice and serves as guidance for clinical assessment: Axis I describes clinical features, whereas Axis II indicates etiology. Dystonia presents with different syndromic aggregations with varied somatic involvement and some common features. There are five recognizable physical signs of dystonia: two main signs (dystonic postures and movements) and three additional signs (gestes antagonistes or tricks, mirror dystonia and overflow dystonia). There is still no validation of diagnostic criteria for the different dystonia syndromes, and many cases with mild phenomenology remain undiagnosed. Patients with dystonia also present non-motor features that are variably combined with the movement disorder. The features of the most common inherited and acquired dystonia syndromes are reviewed here. There is clear evidence of genetic-environmental interaction in the determinism of dystonia. The diagnostic process is guided by clinical examination and based on specific laboratory examinations. Symptomatic treatments are available for dystonia: botulinum neurotoxin injections are the primary choice for most focal dystonia syndromes; deep brain stimulation is useful in some generalized and non-generalized syndromes. Additional treatment strategies are currently being assessed.

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Recent developments in clinical trials of botulinum neurotoxins

Cited by 22 publications

References 44 publications

Botulinum Toxin in the Management of Children with Cerebral Palsy

Botulinum Toxin in the Management of Children with Cerebral Palsy

Fractional Anisotropy Brain Changes in Spasticity after Peripheral Injections of Botulin

Dystonia: diagnosis and management

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