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1.
Article in English | MEDLINE | ID: mdl-38948014

ABSTRACT

Background: Musician's focal task-specific dystonia is a complex disorder of fine motor control, with incomplete understanding of its etiology. There have been relatively few trials of botulinum toxin in upper limb task-specific dystonia, and prior studies have yielded variable results, leading to skepticism regarding the utility of this approach in elite performers. Methods: We conducted a double-blind, placebo-controlled, randomized, cross-over study of incobotulinum toxin-A in 21 professional musicians with focal upper extremity task-specific dystonia affecting performance on their instrument, using a novel paradigm of initial injections followed by booster injections at two- and four-week intervals. The primary outcome measure was the change in blinded dystonia rating of the active arm by two expert raters using a Clinical Global Impression numeric scale at week 8 compared to enrollment. Findings: 19 men and 2 women with musicians' dystonia were enrolled over a six-year period. Nineteen patients completed the study. Analysis of the primary outcome measure in comparison to baseline revealed a change in dystonia severity of P = 0.04 and an improvement in overall musical performance of P = 0.027. No clinically significant weakness was observed, and neutralizing antibodies to toxin were not found. Interpretation: Despite its small sample size, our study demonstrated a statistically significant benefit of incobotulinum toxin-A injections as a treatment for musicians' task-specific dystonia. Tailoring the use of toxin with booster injections allowed refinement of dosing strategy and outcomes, with benefits that were meaningful to patients clearly visible on videotaped evaluations. In addition to its application to musicians' dystonia, this approach may have relevance to optimize application of botulinum toxin in other forms of focal dystonia such as blepharospasm, cervical dystonia, writer's cramp, and spasmodic dysphonia.


Subject(s)
Botulinum Toxins, Type A , Cross-Over Studies , Dystonic Disorders , Music , Neuromuscular Agents , Humans , Double-Blind Method , Male , Female , Botulinum Toxins, Type A/administration & dosage , Dystonic Disorders/drug therapy , Dystonic Disorders/physiopathology , Adult , Neuromuscular Agents/administration & dosage , Neuromuscular Agents/pharmacology , Middle Aged , Treatment Outcome , Occupational Diseases/drug therapy
2.
Toxins (Basel) ; 16(7)2024 Jul 07.
Article in English | MEDLINE | ID: mdl-39057949

ABSTRACT

OnabotulinumtoxinA (BT-A) is used in different medical fields for its beneficial effects. BT-A, a toxin originally produced by the bacterium Clostridium botulinum, is widely known for its ability to temporarily paralyze muscles by blocking the release of acetylcholine, a neurotransmitter involved in muscle contraction. The literature continually reports new hypotheses regarding potential applications that do not consider blockade of acetylcholine release at the neuromuscular junction as a common pathway. In this opinion article, it is our aim to investigate the different pathway targets of BT-A in different medical applications. First of all, the acetylcholine effect of BT-A is used to reduce wrinkles for cosmetic purposes, in the treatment of urological problems, excessive sweating, temporomandibular joint disorders, obesity, migraine, spasticity in neurological diseases, and in various cases of muscle overactivity such as cervical dystonia, blepharospasm, and essential head tremor. In another potential pathway, glutamate A, CGRP, and substance P are targeted for pain inhibition with BT-A application in conditions such as migraine, trigeminal neuralgia, neuropathic pain, and myofascial pain syndrome. On the other hand, as a mechanism different from acetylcholine and pain mediators, BT-A is used in the treatment of hair loss by increasing oxygenation and targeting transforming growth factor-beta 1 cells. In addition, the effect of BT-A on the apoptosis of cancer cells is also known and is being developed. The benefits of BT-A applied in different doses to different regions for different medical purposes are shown in literature studies, and it is also emphasized in those studies that repeating the applications increases the benefits in the long term. The use of BT-A continues to expand as researchers discover new potential therapeutic uses for this versatile toxin.


Subject(s)
Botulinum Toxins, Type A , Humans , Botulinum Toxins, Type A/therapeutic use , Botulinum Toxins, Type A/pharmacology , Animals , Acetylcholine Release Inhibitors/therapeutic use , Pain/drug therapy , Acetylcholine/metabolism , Neuromuscular Agents/therapeutic use , Neuromuscular Agents/pharmacology
3.
Eur J Neurol ; 31(8): e16367, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38859620

ABSTRACT

BACKGROUND AND PURPOSE: Hereditary spastic paraplegias (HSPs) comprise a group of inherited neurodegenerative disorders characterized by progressive spasticity and weakness. Botulinum toxin has been approved for lower limb spasticity following stroke and cerebral palsy, but its effects in HSPs remain underexplored. We aimed to characterize the effects of botulinum toxin on clinical, gait, and patient-reported outcomes in HSP patients and explore the potential of mobile digital gait analysis to monitor treatment effects and predict treatment response. METHODS: We conducted a prospective, observational, multicenter study involving ambulatory HSP patients treated with botulinum toxin tailored to individual goals. Comparing data at baseline, after 1 month, and after 3 months, treatment response was assessed using clinical parameters, goal attainment scaling, and mobile digital gait analysis. Machine learning algorithms were used for predicting individual goal attainment based on baseline parameters. RESULTS: A total of 56 patients were enrolled. Despite the heterogeneity of treatment goals and targeted muscles, botulinum toxin led to a significant improvement in specific clinical parameters and an improvement in specific gait characteristics, peaking at the 1-month and declining by the 3-month follow-up. Significant correlations were identified between gait parameters and clinical scores. With a mean balanced accuracy of 66%, machine learning algorithms identified important denominators to predict treatment response. CONCLUSIONS: Our study provides evidence supporting the beneficial effects of botulinum toxin in HSP when applied according to individual treatment goals. The use of mobile digital gait analysis and machine learning represents a novel approach for monitoring treatment effects and predicting treatment response.


Subject(s)
Gait Analysis , Spastic Paraplegia, Hereditary , Humans , Male , Female , Spastic Paraplegia, Hereditary/drug therapy , Adult , Middle Aged , Gait Analysis/methods , Prospective Studies , Neuromuscular Agents/pharmacology , Neuromuscular Agents/administration & dosage , Neuromuscular Agents/therapeutic use , Treatment Outcome , Botulinum Toxins, Type A/therapeutic use , Botulinum Toxins, Type A/pharmacology , Young Adult , Aged , Botulinum Toxins/therapeutic use
4.
Headache ; 64(7): 825-837, 2024.
Article in English | MEDLINE | ID: mdl-38837259

ABSTRACT

OBJECTIVE: In this pilot prospective cohort study, we aimed to evaluate, using high-density electroencephalography (HD-EEG), the longitudinal changes in functional connectivity (FC) in patients with chronic migraine (CM) treated with onabotulinumtoxinA (OBTA). BACKGROUND: OBTA is a treatment for CM. Several studies have shown the modulatory action of OBTA on the central nervous system; however, research on migraine is limited. METHODS: This study was conducted at the Neurology Unit of "Policlinico Tor Vergata," Rome, Italy, and included 12 adult patients with CM treated with OBTA and 15 healthy controls (HC). Patients underwent clinical scales at enrollment (T0) and 3 months (T1) from the start of treatment. HD-EEG was recorded using a 64-channel system in patients with CM at T0 and T1. A source reconstruction method was used to identify brain activity. FC in δ-θ-α-ß-low-γ bands was analyzed using the weighted phase-lag index. FC changes between HCs and CM at T0 and T1 were assessed using cross-validation methods to estimate the results' reliability. RESULTS: Compared to HCs at T0, patients with CM showed hyperconnected networks in δ (p = 0.046, area under the receiver operating characteristic curve [AUC: 0.76-0.98], Cohen's κ [0.65-0.93]) and ß (p = 0.031, AUC [0.68-0.95], Cohen's κ [0.51-0.84]), mainly involving orbitofrontal, occipital, temporal pole and orbitofrontal, superior temporal, occipital, cingulate areas, and hypoconnected networks in α band (p = 0.029, AUC [0.80-0.99], Cohen's κ [0.42-0.77]), predominantly involving cingulate, temporal pole, and precuneus. Patients with CM at T1, compared to T0, showed hypoconnected networks in δ band (p = 0.032, AUC [0.73-0.99], Cohen's κ [0.53-0.90]) and hyperconnected networks in α band (p = 0.048, AUC [0.58-0.93], Cohen's κ [0.37-0.78]), involving the sensorimotor, orbitofrontal, cingulate, and temporal cortex. CONCLUSION: These preliminary results showed that patients with CM presented disrupted EEG-FC compared to controls restored by a single session of OBTA treatment, suggesting a primary central modulatory action of OBTA.


Subject(s)
Botulinum Toxins, Type A , Electroencephalography , Migraine Disorders , Humans , Botulinum Toxins, Type A/pharmacology , Botulinum Toxins, Type A/administration & dosage , Pilot Projects , Migraine Disorders/drug therapy , Migraine Disorders/physiopathology , Female , Male , Adult , Electroencephalography/drug effects , Middle Aged , Chronic Disease , Prospective Studies , Neuromuscular Agents/pharmacology , Neuromuscular Agents/administration & dosage , Brain/drug effects , Brain/physiopathology , Brain/diagnostic imaging
5.
Drugs ; 84(7): 779-809, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38900335

ABSTRACT

OBJECTIVE: Temporomandibular disorders (TMDs) encompass several conditions that cause pain and impair function of the masticatory muscles (M-TMDs) and temporomandibular joints. There is a large interest among clinicians and researchers in the use of botulinum toxin-A (BoNT-A) as a treatment for M-TMD. However, due to the lack of consistent evidence regarding the efficacy as well as adverse events of BoNT-A, clinical decision making is challenging. Therefore, this umbrella review aimed to systematically assess systematic reviews (SRs) evaluating BoNT-A treatment effects on pain intensity, mandibular movements, and adverse events in patients with M-TMDs. METHOD: An electronic search was undertaken in the databases MEDLINE, EMBASE, CINAHL, Cochrane Central Registry of Controlled Trials (CENTRAL), Web of Science, Epistemonikos, ClinicalTrials.gov, and ICTRP to identify SRs investigating BoNT-A effects on M-TMDs, published from the inception of each database until 6 December 2023. The quality of evidence was rated according to the critical appraisal checklist developed by the umbrella review methodology working group. Only high-quality SRs were included. RESULTS: In total, 18 SRs were included. BoNT-A was shown to be more effective than placebo to reduce pain intensity, but not compared to standard treatments. Additionally, BoNT-A was not superior to placebo or standard treatments regarding improvement of mandibular movements. BoNT-A was considered to have a higher risk for adverse events on muscle and bony tissue compared with other treatments. CONCLUSION: The synthesis in this umbrella review provides the highest level of evidence present. Taken together, there are indications of effectiveness of BoNT-A for treatment of M-TMDs, supported by moderate evidence. However, considering the risk of causing serious adverse events, treatment with BoNT-A is recommended to be the last treatment alternative.


Subject(s)
Botulinum Toxins, Type A , Systematic Reviews as Topic , Temporomandibular Joint Disorders , Humans , Botulinum Toxins, Type A/therapeutic use , Botulinum Toxins, Type A/adverse effects , Botulinum Toxins, Type A/administration & dosage , Botulinum Toxins, Type A/pharmacology , Temporomandibular Joint Disorders/drug therapy , Masticatory Muscles/drug effects , Neuromuscular Agents/therapeutic use , Neuromuscular Agents/adverse effects , Neuromuscular Agents/administration & dosage , Neuromuscular Agents/pharmacology
6.
Headache ; 64(6): 652-662, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38700141

ABSTRACT

OBJECTIVE: Migraine, a prevalent and debilitating disease, involves complex pathophysiology possibly including inflammation and heightened pain sensitivity. The current study utilized the complete Freund's adjuvant (CFA) model of inflammation, with onabotulinumtoxinA (BoNT/A) as a treatment of interest due to its use in clinical migraine management. Using an animal model, the study sought to investigate the role of BoNT/A in modulating CFA-induced inflammation, alterations in pain sensitivity, and the regulation of calcitonin gene-related peptide (CGRP) release. Further, we aimed to assess the changes in SNAP-25 through western blot analysis to gain insights into the mechanistic action of BoNT/A. METHODS: BoNT/A or control was administered subcutaneously at the periorbital region of rats 3 days before the induction of inflammation using CFA. Periorbital mechanical sensitivity was assessed post-inflammation, and alterations in CGRP release were evaluated. Changes in SNAP-25 levels were determined using western blot analysis. RESULTS: Upon CFA-induced inflammation, there was a marked increase in periorbital mechanical sensitivity, with the inflammation side showing increased sensitivity compared to other periorbital areas. BoNT/A did decrease the withdrawal thresholds in the electronic von Frey test. Despite not being able to observe differences in pain thresholds or CGRP release, BoNT/A reduced baseline release under CFA inflamed conditions. Analysis of SNAP-25 levels in the trigeminal ganglion revealed both intact and cleaved forms that were notably elevated in BoNT/A-treated animals. These findings, derived from western blot analysis, suggest an effect on neurotransmitter release. CONCLUSION: Our investigation highlights the role of BoNT/A in reducing baseline CGRP in the context of inflammation and its involvement in SNAP-25 cleavage. In contrast, BoNT/A did not appear to alter facial pain sensitivity induced by inflammation, suggesting that mechanisms other than baseline CGRP could be implicated in the elevated thresholds in the CFA model.


Subject(s)
Botulinum Toxins, Type A , Calcitonin Gene-Related Peptide , Disease Models, Animal , Inflammation , Migraine Disorders , Rats, Sprague-Dawley , Synaptosomal-Associated Protein 25 , Animals , Botulinum Toxins, Type A/pharmacology , Botulinum Toxins, Type A/administration & dosage , Migraine Disorders/drug therapy , Migraine Disorders/metabolism , Synaptosomal-Associated Protein 25/metabolism , Calcitonin Gene-Related Peptide/metabolism , Inflammation/drug therapy , Rats , Male , Freund's Adjuvant , Pain/drug therapy , Pain Threshold/drug effects , Neuromuscular Agents/pharmacology , Neuromuscular Agents/administration & dosage
7.
Headache ; 64(6): 663-673, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38700250

ABSTRACT

OBJECTIVE: To determine the tolerability and safety of concurrent peripheral nerve blocks and onabotulinumtoxinA treatment during a single outpatient clinic procedure visit. BACKGROUND: Procedural interventions are available for the treatment of headache disorders. OnabotulinumtoxinA and peripheral nerve blocks are used as alternatives or in addition to oral therapies to reduce the frequency and intensity of migraine attacks. There is currently a lack of safety data focusing on the sequential administration of local anesthetic via peripheral nerve blocks and onabotulinumtoxinA during a single clinical encounter for the treatment of headache. The primary aim of the study was to determine the safety and tolerability of concurrent peripheral nerve blockade and onabotulinumtoxinA injections during a single outpatient clinic procedure visit. We hypothesized that the dual intervention would be safe and well tolerated by patients with chronic migraine and other headache disorders. METHODS: A retrospective chart review was performed using clinical data from patients seen by multiple providers over a 16-month timeframe at one outpatient headache clinic. Patients were identified by procedure codes and those receiving peripheral nerve block(s) and onabotulinumtoxinA injections during a single encounter within the study period were eligible for inclusion. Inclusion criteria were (1) patients 18 years and older who were (2) receiving both peripheral nerve blocks and onabotulinumtoxinA injections for the treatment of chronic migraine. Patients were excluded if they were under age 18, received their procedure outside of the clinic (emergency room, inpatient ward), or were receiving sphenopalatine ganglion blocks. Age- and sex-matched patients who received one procedure, either peripheral nerve blocks or onabotulinumtoxinA, were used for control. The primary outcome of this safety study was the number of adverse events that occurred in the dual intervention group compared to the single intervention control arms. Information regarding adverse events was gathered via retrospective chart review. If an adverse event was recorded, it was then graded by the reviewer utilizing the Common Terminology Criteria for Adverse Events ranging from Grade 1 Mild Event to Grade 5 Death. Additionally, it was noted whether the adverse event led to treatment discontinuation. RESULTS: In total, 375 patients were considered eligible for inclusion in the study. After age and sex matching of controls, 131 patients receiving dual intervention were able to be compared to 131 patients receiving onabotulinumtoxinA alone and 104 patients receiving dual intervention were able to be compared to 104 patients receiving peripheral nerve block(s) alone. The primary endpoint analysis showed no significant difference in total adverse events between dual intervention compared to nerve blocks alone or onabotulinumtoxinA alone. The number of adverse events that led to treatment discontinuation approached but did not reach statistical significance for those receiving dual intervention versus onabotulinumtoxinA alone in the number of adverse events that led to treatment termination (4.6%, 6/131 vs. 0.8%, 1/131, p = 0.065); however, the number of patients who discontinued therapy was not significantly different between those groups (2.3%, 3/131 vs. 0.8%, 1/131; p = 0.314; odds ratio 0.3 [0-3.2]; p = 0.338). CONCLUSIONS: In this retrospective chart review, there was no significant difference in adverse events or therapy discontinuation between patients receiving sequential peripheral nerve block(s) and onabotulinumtoxinA injections versus those receiving either peripheral nerve block(s) or onabotulinumtoxinA injections alone. As a result, we concluded that the combination procedure is likely safe and well tolerated in routine clinical practice.


Subject(s)
Botulinum Toxins, Type A , Migraine Disorders , Nerve Block , Humans , Botulinum Toxins, Type A/administration & dosage , Botulinum Toxins, Type A/adverse effects , Botulinum Toxins, Type A/pharmacology , Female , Male , Retrospective Studies , Middle Aged , Adult , Nerve Block/methods , Migraine Disorders/drug therapy , Headache Disorders/drug therapy , Neuromuscular Agents/administration & dosage , Neuromuscular Agents/adverse effects , Neuromuscular Agents/pharmacology , Aged , Anesthetics, Local/administration & dosage , Anesthetics, Local/pharmacology
8.
Urologie ; 63(7): 653-657, 2024 Jul.
Article in German | MEDLINE | ID: mdl-38698262

ABSTRACT

During the last two decades botulinum toxin has also conquered urology. Botulinum toxin reduces the contractility and sensitivity of the detrusor muscle and relieves pain. It is therefore a promising drug whose use in men also appears promising. The following article highlights the practical relevance of botulinum toxin for male lower urinary tract symptoms (LUTS). But first of all, a distinction must be made between use in male LUTS due to benign prostate syndrome (BPS) and use in cases of overactive bladder (OAB) alone. A differentiated diagnosis and treatment of male LUTS is therefore essential.


Subject(s)
Lower Urinary Tract Symptoms , Urinary Bladder, Overactive , Humans , Male , Lower Urinary Tract Symptoms/drug therapy , Urinary Bladder, Overactive/drug therapy , Botulinum Toxins/therapeutic use , Botulinum Toxins, Type A/therapeutic use , Botulinum Toxins, Type A/administration & dosage , Prostatic Hyperplasia/drug therapy , Prostatic Hyperplasia/complications , Neuromuscular Agents/therapeutic use , Neuromuscular Agents/pharmacology
9.
Spinal Cord ; 62(6): 285-294, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38637637

ABSTRACT

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVES: The current study aimed to assess the efficacy and safety of Onabotulinum toxin A (OBTX-A) treatment for neurogenic detrusor overactivity (NDO) in spinal cord injury (SCI) patients. SETTING: Iran. METHODS: All relevant articles of clinical trials and cohort studies indexed in PubMed/MEDLINE, Embase, Scopus, and Web of Science databases up to September 6, 2022, that addressed OBTX-A treatment for NDO following SCI were included. The quality of eligible studies was evaluated using Cochrane criteria. Also, the weighted mean difference (WMD) was measured with a random-effect model. RESULTS: Regarding the overall efficacy after OBTX-A treatment in the short term, volume per void (VV) (WMD = 118.8, 95% CI: 90.9-146.7, p < 0.01), incontinence-quality of life (IQoL) (WMD = 24.3, 95% CI: 15.8-32.8, p < 0.01), and maximum cystometric capacity (MCC) (WMD = 144.5, 95% CI: 132.3 to 156.7, p < 0.01) significantly increased, while maximum detrusor pressure during storage (MDP) (WMD = -30.5, 95% CI: -35.9 to -25.1, p < 0.01) showed a significant decrease. Furthermore, compared to the placebo group at the 200-unit dose, there was a significant increase in MCC (WMD = 113.5, 95% CI: 84.7 to 142.3, p < 0.01) and a significant decrease in MDP (WMD = -27.2, 95% CI: -39.2 to -15.1, p < 0.01). Urinary tract infection (UTI), hematuria, and autonomic dysreflexia were the most common side effects, occurring at rates of 29.6%, 14.8%, and 13.4%, respectively. CONCLUSION: Our findings highlighted the effectiveness and safety of OBTX-A as a promising treatment of NDO following SCI.


Subject(s)
Botulinum Toxins, Type A , Spinal Cord Injuries , Urinary Bladder, Neurogenic , Urinary Bladder, Overactive , Humans , Botulinum Toxins, Type A/administration & dosage , Botulinum Toxins, Type A/pharmacology , Neuromuscular Agents/administration & dosage , Neuromuscular Agents/pharmacology , Spinal Cord Injuries/complications , Spinal Cord Injuries/drug therapy , Urinary Bladder, Neurogenic/drug therapy , Urinary Bladder, Neurogenic/etiology , Urinary Bladder, Overactive/drug therapy , Urinary Bladder, Overactive/etiology
10.
Headache ; 64(5): 589-594, 2024 May.
Article in English | MEDLINE | ID: mdl-38533675

ABSTRACT

OBJECTIVES: To report the efficacy of onabotulinumtoxinA (BoNTA) injections in relieving pain in patients with primary trochlear headache (PRTH). METHODS: Examination of medical records for patients diagnosed with PRTH according to the International Classification of Headache Disorders, 3rd edition criteria and treated with BoNTA. Data were collected for variables related to pain relief, duration of effectiveness, and adverse effects. RESULTS: Six patients were included in the study. All had previously undergone standard care interventions, including infiltrations or oral treatments, yet experienced treatment failure or symptom recurrence. All patients received 20 units of BoNTA, administered in the corrugator and procerus muscles. Subsequent to the BoNTA injections, all six patients reported substantial pain relief, with five achieving complete remission of symptoms. The analgesic effect persisted for a duration of 3 months. No adverse events were reported in any of the cases. CONCLUSIONS: Our case series presents the first evidence of the potential of BoNTA as a safe and effective treatment option for PRTH. From a clinical standpoint, having a safer alternative is of paramount significance for patients with limited treatment options, such as those with PRTH. Further research is warranted to validate these findings and explore the long-term efficacy of BoNTA in PRTH management.


Subject(s)
Botulinum Toxins, Type A , Adult , Aged , Female , Humans , Male , Middle Aged , Acetylcholine Release Inhibitors/administration & dosage , Acetylcholine Release Inhibitors/pharmacology , Botulinum Toxins, Type A/administration & dosage , Botulinum Toxins, Type A/pharmacology , Headache Disorders, Primary/drug therapy , Neuromuscular Agents/administration & dosage , Neuromuscular Agents/pharmacology , Retrospective Studies , Treatment Outcome
11.
Eur J Paediatr Neurol ; 49: 131-140, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38518417

ABSTRACT

AIM: To identify short-term effects of botulinum neurotoxin type A (BoNT) injections on gait and clinical impairments, in children with spastic cerebral palsy (CP), based on baseline gait pattern-specific subgroups. METHOD: Short-term effects of BoNT injections in the medial hamstrings and gastrocnemius were defined in a retrospective convenience sample of 117 children with CP (median age: 6 years 4 months; GMFCS I/II/III: 70/31/16; unilateral/bilateral: 56/61) who had received gait analyses before and 2 months post-BoNT. First, baseline gait patterns were classified. Statistical and meaningful changes were calculated between pre- and post-BoNT lower limb sagittal plane kinematic waveforms, the gait profile score, and non-dimensional spatiotemporal parameters for the entire sample and for pattern-specific subgroups. These gait waveforms per CP subgroup at pre- and post-BoNT were also compared to typically developing gait and composite scores for spasticity, weakness, and selectivity were compared between the two conditions. RESULTS: Kinematic improvements post-BoNT were identified at the ankle and knee for the entire sample, and for subgroups with apparent equinus and jump gait. Limbs with baseline patterns of dropfoot and to a lesser extent true equinus showed clear improvements only at the ankle. In apparent equinus, jump gait, and dropfoot, spasticity improved post-BoNT, without leading to increased weakness or diminished selectivity. Compared to typical gait, knee and hip motion improved in the crouch gait subgroup post-BoNT. CONCLUSION: This comprehensive analysis highlighted the importance of investigating BoNT effects on gait and clinical impairments according to baseline gait patterns. These findings may help identify good treatment responders.


Subject(s)
Botulinum Toxins, Type A , Cerebral Palsy , Neuromuscular Agents , Humans , Cerebral Palsy/drug therapy , Cerebral Palsy/physiopathology , Cerebral Palsy/complications , Botulinum Toxins, Type A/administration & dosage , Botulinum Toxins, Type A/pharmacology , Botulinum Toxins, Type A/therapeutic use , Child , Male , Female , Neuromuscular Agents/administration & dosage , Neuromuscular Agents/pharmacology , Retrospective Studies , Child, Preschool , Biomechanical Phenomena/drug effects , Gait Disorders, Neurologic/drug therapy , Gait Disorders, Neurologic/etiology , Gait Disorders, Neurologic/physiopathology , Muscle, Skeletal/physiopathology , Muscle, Skeletal/drug effects , Adolescent , Treatment Outcome , Muscle Spasticity/drug therapy , Muscle Spasticity/physiopathology , Muscle Spasticity/etiology , Gait/drug effects , Gait/physiology
12.
Eur J Pharmacol ; 962: 176242, 2024 Jan 05.
Article in English | MEDLINE | ID: mdl-38048980

ABSTRACT

Overt muscle activity and impaired spinal locomotor control hampering coordinated movement is a hallmark of spasticity and movement disorders like dystonia. While botulinum toxin A (BoNT-A) standard therapy alleviates mentioned symptoms presumably due to its peripheral neuromuscular actions alone, the aim of present study was to examine for the first time the toxin's trans-synaptic activity within central circuits that govern the skilled movement. The rat hindlimb motor pools were targeted by BoNT-A intrasciatic bilateral injection (2 U per nerve), while its trans-synaptic action on premotor inputs was blocked by intrathecal BoNT-A-neutralising antitoxin (5 i.u.). Effects of BoNT-A on coordinated and high intensity motor tasks (rotarod, beamwalk swimming), and localised muscle weakness (digit abduction, gait ability) were followed until their substantial recovery by day 56 post BoNT-A. Later, (day 62-77) the BoNT-A effects were examined in unilateral calf muscle spasm evoked by tetanus toxin (TeNT, 1.5 ng). In comparison to peripheral effect alone, combined peripheral and central trans-synaptic BoNT-A action induced a more prominent and longer impairment of different motor tasks, as well as the localised muscle weakness. After near-complete recovery of motor functions, the BoNT-A maintained the ability to reduce the experimental calf spasm evoked by tetanus toxin (TeNT 1.5 ng, day 62) without altering the monosynaptic reflex excitability. These results indicate that, in addition to muscle terminals, BoNT-A-mediated control of hyperactive muscle activity in movement disorders and spasticity may involve the spinal premotor inputs and central circuits participating in the skilled locomotor performance.


Subject(s)
Botulinum Toxins, Type A , Movement Disorders , Neuromuscular Agents , Rats , Animals , Botulinum Toxins, Type A/pharmacology , Tetanus Toxin , Movement , Muscle Weakness , Neuromuscular Agents/pharmacology
13.
Dev Med Child Neurol ; 66(7): 919-930, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38140924

ABSTRACT

AIM: To develop robust multivariable prediction models for non-response to (1) submandibular botulinum neurotoxin A (BoNT-A) injections and (2) concurrent submandibular and parotid (four-gland) injections, to guide treatment decisions for drooling in children with neurodevelopmental disabilities, including cerebral palsy. METHOD: This was a retrospective cohort study including 262 children (155 males/107 females, median age 7 years 11 months [IQR 5 years 1 month], range 4 years 0 months - 17 years 11 months) receiving submandibular injections and 74 children (52 males/22 females, median age 7 years 7 months [IQR 4 years 3 months], range 4 years 9 months - 18 years 8 months) receiving four-gland injections. Multivariable logistic regression analyses were used to estimate associations between candidate predictors and non-response 8 weeks after injection. RESULTS: Ninety-six children (37%) were non-responders to submandibular injections, for which developmental age was the strongest predictor (adjusted odds ratio [aOR] 2.13; 95% confidence interval [CI] 1.02-4.45 for developmental age <4 years or 4-6 years with IQ <70). Other characteristics that showed a trend towards an increased risk of non-response were diagnosis, sex, and head position. Thirty-four children (46%) were non-responders to four-gland injections, for which tongue protrusion (aOR 3.10; 95% CI 1.14-8.43) seemed most predictive, whereas multiple preceding submandibular injections (aOR 0.34; 95% CI 0.10-1.16) showed a trend towards being protective. Predictors were, however, unstable across different definitions of non-response and both models (i.e. submandibular and four-gland) had insufficient discriminative ability. INTERPRETATION: Potential predictors of non-response to BoNT-A injections were identified. Nevertheless, the developed prediction models seemed inadequate for guidance of treatment decisions. WHAT THIS PAPER ADDS: Developmental age seemed most predictive of non-response to submandibular botulinum neurotoxin A injections. Non-response to concurrent submandibular and parotid injections was best predicted by tongue protrusion and number of previous injections. Multivariable prediction models including these clinical characteristics were unable to discriminate well. Predictors differed when non-response was defined using alternative outcome measures.


Subject(s)
Botulinum Toxins, Type A , Neurodevelopmental Disorders , Sialorrhea , Submandibular Gland , Humans , Sialorrhea/drug therapy , Sialorrhea/etiology , Male , Female , Botulinum Toxins, Type A/administration & dosage , Botulinum Toxins, Type A/pharmacology , Child , Child, Preschool , Adolescent , Retrospective Studies , Submandibular Gland/drug effects , Neuromuscular Agents/administration & dosage , Neuromuscular Agents/pharmacology , Cerebral Palsy/complications , Cerebral Palsy/drug therapy , Parotid Gland
14.
Parkinsonism Relat Disord ; 114: 105792, 2023 09.
Article in English | MEDLINE | ID: mdl-37540934

ABSTRACT

INTRODUCTION: Anxiety is present in 30-40% of patients with cervical dystonia (CD). It has been ascribed to a direct effect of the state of motor symptoms on related pain, disability, and disfigurement. Accordingly, any reported benefit of botulinum toxin (BoNT) on anxiety is thought to be secondary to its effect on the same. We sought to evaluate the distinctive impact of botulinum toxin (BoNT) on anxiety in cervical dystonia (CD). METHODS: In this prospective observational study, 60 participants with idiopathic isolated CD were recruited from clinic. We assessed motor and anxiety burden using Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) parts I-III and State-Trait Anxiety Inventory (STAI). Assessments were done at time of BoNT (baseline) and at 6 weeks post-injection. RESULTS: STAI and motor severity TWSTRS scores poorly correlated at the baseline visit (rho = -0.30, p = 0.411). Both, motor TWSTRS (Mdifference = -1.46, p < 0.024) and STAI (Mdifference = -10.37, p = 0.007) improved from baseline to 6 weeks (peak effect). The change in motor TWSTRS poorly correlated with change in anxiety scores from baseline visit to 6 weeks (rho = -0.14, p > 0.999). Of these measures of anxiety, improvement in STAI-T had the largest effect size (rank biserial = 0.52). CONCLUSION: BoNT improves both motor severity and anxiety in CD. Poor correlation between motor severity and anxiety at both the time of injection and during the time of peak effect, and improvement in trait anxiety suggests that BoNT has a direct beneficial effect on anxiety.


Subject(s)
Botulinum Toxins, Type A , Neuromuscular Agents , Torticollis , Humans , Botulinum Toxins, Type A/pharmacology , Botulinum Toxins, Type A/therapeutic use , Torticollis/complications , Prospective Studies , Neuromuscular Agents/pharmacology , Neuromuscular Agents/therapeutic use , Anxiety/drug therapy , Anxiety/etiology , Treatment Outcome
15.
Schmerz ; 37(4): 297-307, 2023 Aug.
Article in German | MEDLINE | ID: mdl-37365293

ABSTRACT

Botulinum toxin has been used for decades in the treatment of a variety of painful diseases. Botulinum toxin not only blocks neuromuscular transmission, but also the secretion of neuropeptides, such as substance P, glutamate and calcitonin gene-related peptide (CGRP) and thus inhibits neurogenic inflammation. In addition, it has a modulatory pain-relieving effect via retrograde transport into the central nervous system. In addition to approval for the treatment of dystonia or spasticity, onabotulinum toxin A is also approved for the prophylaxis of chronic migraine if the oral prophylactic migraine medication has had an insufficient effect or has not been tolerated. In addition, botulinum toxin is also recommended in guidelines as a third-line treatment for neuropathic pain, but in Germany this is an off-label application. This article provides an overview of the current clinically relevant areas of application of botulinum toxin in the field of pain medicine.


Subject(s)
Botulinum Toxins, Type A , Migraine Disorders , Neuromuscular Agents , Humans , Botulinum Toxins, Type A/therapeutic use , Neuromuscular Agents/pharmacology , Neuromuscular Agents/therapeutic use , Analgesics/therapeutic use , Pain/drug therapy , Migraine Disorders/prevention & control
16.
J Oral Rehabil ; 50(5): 343-350, 2023 May.
Article in English | MEDLINE | ID: mdl-36810787

ABSTRACT

BACKGROUND: Previous studies concerning the effect of botulinum toxin in masseter muscle have mainly reported effects observed through inspection of facial features or differences in pain levels. One systematic review of studies utilizing objective measurements reported that long-term muscular effect of botulinum neurotoxin injections into masseter muscle was inconclusive. OBJECTIVE: To evaluate the duration of reduced maximal voluntary bite force (MVBF) after botulinum toxin intervention. METHODS: The intervention group was comprised of individuals seeking aesthetic treatment for masseter reduction (n = 20), the reference group (n = 12) comprised of individuals with no intervention. Intervention through 25 units of Xeomin® (Merz Pharma GmbH & Co KGaA, Frankfurt am Main, Germany) botulinum neurotoxin type A injected into the masseter muscles bilaterally (totalling 50 units). A reference group did not receive any intervention. MVBF was measured in Newtons using a strain gauge meter at the incisors and first molars. MVBF was measured at baseline, at 4 weeks, 3 months, 6 months, and after 1 year. RESULTS: Both groups were similar in terms of bite force, sex and age at baseline. MVBF remained similar compared to baseline in the reference group. At 3 months, a significant reduction at all measurement points was observed in the intervention group; at 6 months, this reduction was no longer significant. CONCLUSION: A single intervention of 50 units of botulinum neurotoxin results in a reversible MVBF reduction of at least 3 months, although a visually discernable reduction may be more long-lasting.


Subject(s)
Botulinum Toxins, Type A , Neuromuscular Agents , Humans , Masseter Muscle , Neuromuscular Agents/pharmacology , Neuromuscular Agents/therapeutic use , Bite Force , Injections, Intramuscular , Hypertrophy/drug therapy , Botulinum Toxins, Type A/pharmacology , Botulinum Toxins, Type A/therapeutic use
17.
Acta Chir Belg ; 123(1): 12-18, 2023 Feb.
Article in English | MEDLINE | ID: mdl-33899686

ABSTRACT

OBJECTIVES: There are few published data on the optimized use of botulinum toxin A (BTA) for the treatment of chronic anal fissure (CAF). The aim of this study was to investigate the effect of injection of 100 IU BTA into the internal anal sphincter (IAS) at the side opposite of the fissure, using an anal retractor, sedation, and perianal transcutaneous pudendal nerve block. METHODS: The prospectively maintained data of 132 patients who underwent BTA injection for CAF were retrospectively analyzed. Demographic data, symptom duration, fissure location, post-procedure pain, complications, continence status, response to treatment, and follow-up period were investigated. Postoperative analgesic requirements of patients who did and did not receive pudendal nerve block were compared. RESULTS: Eighty-two patients were male and the median age was 40 (18-74) years. Sixty-six patients required no, 46 required oral, and 20 required parenteral analgesics. No complications were observed. Complete response was observed in 105 patients (79.5%). Symptomatic improvement was observed in 67.4% of patients within 3-7 d. Median follow-up was 24 (18-42) months. The median Wexner's incontinence score was 0 (0-8) at 1 month. In all, 104 patients had no, 22 patients had minor, and 6 patients had non-minor incontinence. All patients with incontinence recovered fully within 4 (2-13) weeks. CONCLUSIONS: BTA injection using an anal retractor under sedation and perianal transcutaneous pudendal nerve block is an effective and safe alternative to partial lateral internal sphincterotomy (LIS) for the treatment of CAF.


Subject(s)
Botulinum Toxins, Type A , Fissure in Ano , Neuromuscular Agents , Humans , Male , Adult , Female , Fissure in Ano/drug therapy , Fissure in Ano/complications , Neuromuscular Agents/pharmacology , Retrospective Studies , Treatment Outcome , Botulinum Toxins, Type A/pharmacology , Anal Canal/surgery , Chronic Disease
18.
Digit J Ophthalmol ; 29(4): 97-1000, 2023.
Article in English | MEDLINE | ID: mdl-38344060

ABSTRACT

Crocodile tear syndrome (CTS) is a late complication of facial nerve palsy characterized by unilateral lacrimation in response to gustatory stimulation. We present 2 cases of patients diagnosed with CTS after recovering from unilateral idiopathic facial nerve palsy. Both patients underwent transconjunctival lacrimal gland incobotulinumtoxinA injection, with doses of 5-16 units. The patients were seen in clinic for post-treatment follow-up at 2 weeks, 3 months, and 6 months. Outcomes were measured by treatment efficacy and adverse drug effects. Following treatment, both patients reported resolution of gustatory lacrimation. The patient treated with 16 U experienced transient ptosis and diplopia following injection, whereas the patient treated with 5-7.5 U experienced no adverse effects.


Subject(s)
Autonomic Nervous System Diseases , Bell Palsy , Blepharoptosis , Botulinum Toxins, Type A , Congenital Cranial Dysinnervation Disorders , Facial Paralysis , Jaw Abnormalities , Lacrimal Apparatus Diseases , Lacrimal Apparatus , Neuromuscular Agents , Reflex, Abnormal , Toxins, Biological , Humans , Lacrimal Apparatus/innervation , Botulinum Toxins, Type A/pharmacology , Botulinum Toxins, Type A/therapeutic use , Neuromuscular Agents/pharmacology , Neuromuscular Agents/therapeutic use , Lacrimal Apparatus Diseases/diagnosis , Lacrimal Apparatus Diseases/drug therapy , Facial Paralysis/complications , Facial Paralysis/drug therapy , Bell Palsy/complications , Bell Palsy/drug therapy , Autonomic Nervous System Diseases/complications , Autonomic Nervous System Diseases/drug therapy , Toxins, Biological/pharmacology , Toxins, Biological/therapeutic use
19.
Toxins (Basel) ; 14(11)2022 11 10.
Article in English | MEDLINE | ID: mdl-36356027

ABSTRACT

Following spinal cord injury (SCI), pathological reflexes develop that result in altered bladder function and sphincter dis-coordination, with accompanying changes in the detrusor. Bladder chemodenervation is known to ablate the pathological reflexes, but the resultant effects on the bladder tissue are poorly defined. In a rodent model of contusion SCI, we examined the effect of early bladder chemodenervation with botulinum toxin A (BoNT-A) on bladder histopathology and collagen deposition. Adult female Long Evans rats were given a severe contusion SCI at spinal level T9. The SCI rats immediately underwent open laparotomy and received detrusor injections of either BoNT-A (10 U/animal) or saline. At eight weeks post injury, the bladders were collected, weighed, and examined histologically. BoNT-A injected bladders of SCI rats (SCI + BoNT-A) weighed significantly less than saline injected bladders of SCI rats (SCI + saline) (241 ± 25 mg vs. 183 ± 42 mg; p < 0.05). Histological analyses showed that SCI resulted in significantly thicker bladder walls due to detrusor hypertrophy and fibrosis compared to bladders from uninjured animals (339 ± 89.0 µm vs. 193 ± 47.9 µm; p < 0.0001). SCI + BoNT-A animals had significantly thinner bladder walls compared to SCI + saline animals (202 ± 55.4 µm vs. 339 ± 89.0 µm; p < 0.0001). SCI + BoNT-A animals had collagen organization in the bladder walls similar to that of uninjured animals. Detrusor chemodenervation soon after SCI appears to preserve bladder tissue integrity by reducing the development of detrusor fibrosis and hypertrophy associated with SCI.


Subject(s)
Botulinum Toxins, Type A , Contusions , Neuromuscular Agents , Spinal Cord Injuries , Urinary Bladder Diseases , Urinary Bladder, Neurogenic , Female , Rats , Animals , Botulinum Toxins, Type A/pharmacology , Botulinum Toxins, Type A/therapeutic use , Neuromuscular Agents/pharmacology , Urinary Bladder , Rodentia , Rats, Long-Evans , Spinal Cord Injuries/complications , Spinal Cord Injuries/drug therapy , Urinary Bladder Diseases/drug therapy , Urinary Bladder Diseases/etiology , Fibrosis , Contusions/complications , Hypertrophy/drug therapy
20.
Toxins (Basel) ; 14(6)2022 05 25.
Article in English | MEDLINE | ID: mdl-35737026

ABSTRACT

Botulinum neurotoxin type A (BoNT/A) causes muscle paralysis by blocking cholinergic signaling at neuromuscular junctions and is widely used to temporarily correct spasticity-related disorders and deformities. The paralytic effects of BoNT/A are time-limited and require repeated injections at regular intervals to achieve long-term therapeutic benefits. Differences in the level and duration of effectivity among various BoNT/A products can be attributed to their unique manufacturing processes, formulation, and noninterchangeable potency units. Herein, we compared the pharmacodynamics of three BoNT/A formulations, i.e., Botox® (onabotulinumtoxinA), Xeomin® (incobotulinumtoxinA), and Coretox®, following repeated intramuscular (IM) injections in mice. Three IM injections of BoNT/A formulations (12 U/kg per dose), 12-weeks apart, were administered at the right gastrocnemius. Local paresis and chemodenervation efficacy were evaluated over 36 weeks using the digit abduction score (DAS) and compound muscle action potential (CMAP), respectively. One week after administration, all three BoNT/A formulations induced peak DAS and maximal reduction of CMAP amplitudes. Among the three BoNT/A formulations, only Coretox® afforded a significant increase in paretic effects and chemodenervation with a prolonged duration of action after repeated injections. These findings suggest that Coretox® may offer a better overall therapeutic performance in clinical settings.


Subject(s)
Botulinum Toxins, Type A , Neuromuscular Agents , Animals , Botulinum Toxins, Type A/toxicity , Injections, Intramuscular , Mice , Muscle Spasticity , Muscle, Skeletal , Neuromuscular Agents/pharmacology , Paresis
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