Botulinum Toxin Therapy Research Articles

Cortical somatosensory processing after botulinum toxin therapy in post-stroke spasticity.

In dystonic and spastic movement disorders, abnormalities of motor control and somatosensory processing as well as cortical modulations associated with clinical improvement after botulinum toxin A (BoNT-A) treatment have been reported, but electrophysiological evidence remains controversial. In the present observational study, we aimed to uncover central correlates of post-stroke spasticity (PSS) and BoNT-A-related changes in the sensorimotor cortex by investigating the cortical components of somatosensory evoked potentials (SEPs). Thirty-one chronic stroke patients with PSS of the upper limb were treated with BoNT-A application into the affected muscles and physiotherapy. Clinical and electrophysiological evaluations were performed just before BoNT-A application (W0), then 4 weeks (W4) and 11 weeks (W11) later. PSS was evaluated with the modified Ashworth scale (MAS). Median nerve SEPs were examined in both upper limbs with subsequent statistical analysis of the peak-to-peak amplitudes of precentral P22/N30 and postcentral N20/P23 components. At baseline (W0), postcentral SEPs were significantly lower over the affected cortex. At follow up, cortical SEPs did not show any significant changes attributable to BoNT-A and/or physiotherapy, despite clear clinical improvement. Our results imply that conventional SEPs are of limited value in evaluating cortical changes after BoNT-A treatment and further studies are needed to elucidate its central actions.

O Uso da Toxina Botulínica no Controlo da Dor na Lombalgia

Introduction : Low back pain is the most prevalent musculoskeletal disorder, affecting 40%-80% of individuals worldwide, representing a major disability factor in quality of life and enormous costs for the society. The present review aims to reflect on scientific evidence that evaluates the role of botulinum toxin (BT) as a treatment of low back pain. Methods : The present study is a systematic review. The authors reviewed the literature indexed in the databases Medline (via PubMed), Web of Science and CENTRAL. To achieve study purposes, only randomized clinical trials (RCT) were included, with at least 2 months of follow-up, appropriate sample size and in line with the standards of the Delphi List. Results : In the evidence contemplated, BT therapy proved to be superior in pain control and in the improvement of functional capacity when compared with placebo. On the other hand, the treatment of BT + physiotherapy showed more effectiveness versus 1) placebo + physiotherapy and versus 2) therapy of infiltrations with corticosteroid and local anesthetic (triamcinolone and lidocaine) + physiotherapy, regarding pain control of low back pain. Conclusion : Even though the approached studies indicate the important role of BT in low back pain management, the consolidation of these conclusions need scientific evidence with higher quality, larger randomized clinical trials, standardization of the evaluated outcomes and detailed intervention protocols. BT therapy, integrated in a multimodal approach, may be a relevant asset in the management of low back pain.

The Role of Ultrasound for the Personalized Botulinum Toxin Treatment of Cervical Dystonia.

The visualization of the human body has frequently been groundbreaking in medicine. In the last few years, the use of ultrasound (US) imaging has become a well-established procedure for botulinum toxin therapy in people with cervical dystonia (CD). It is now undisputed among experts that some of the most relevant muscles in this indication can be safely injected under visual US guidance. This review will explore the method from basic technical considerations, current evidence to conceptual developments of the phenomenology of cervical dystonia. We will review the implications of introducing US to our understanding of muscle function and anatomy of common cervical dystonic patterns. We suggest a flow chart for the use of US to achieve a personalized treatment of people with CD. Thus, we hope to contribute a resource that is useful in clinical practice and that stimulates the ongoing development of this valuable technique.

The effects of COVID-19 pandemic countermeasures on patients receiving botulinum toxin therapy and on their caregivers: a study from an Italian cohort

COVID-19 outbreak had a huge worldwide impact, and several countermeasures to contain its spread have been adopted, such as the interruption of nonurgent outpatient clinics. We wanted to describe the effects of the national lockdown on the well-being of a cohort of Italian patients with cerebral palsy (CP) receiving botulinum toxin (BT) therapy and of their caregivers. Twenty-five patients receiving BT therapy were surveyed using the structuralized questionnaire by Dressler and Adib Saberi, while the caregivers were assessed using the Caregiver Burden Scale. The lockdown delayed BT therapy by 9 ± 2.8 months. Around 44% of the selected patients noticed increased muscle cramps, 24% increased muscle pain, and 32% both of them. Due to the lockdown, the patient’s quality of life was reduced by 68.4 ± 21.1%. After the lockdown, 100% of patients perceived BT therapy as more important than before. Around 76% of the patients perceived the lockdown as inadequate and felt that their rights were not respected. The overall score of the Caregiver Burden Scale, as regarded before the lockdown, was 29.12 ± 11.63, while the overall score as regarded after the lockdown was 37.44 ± 14.85. The overall score increased, from before the lockdown to after the lockdown, for 92% of caregivers. The BT outpatient clinic’s interruption was seen to significantly worsen the psychophysical condition of subjects with CP and the care burden of their caregivers, exposing them to greater stress than before. Therefore, any kind of BT treatment suspension or delay should be avoided.

Neuromuscular Retraining versus BTX-A Injection in Subjects with Chronic Facial Nerve Palsy, A Clinical Trial.

Introduction:Chronic facial nerve palsy has long been known to negatively affect the quality of life in patients. The present study aimed to investigate the efficacy of Botulinum Toxin A (BTX-A) and neuromuscular retraining therapy (NMRT) in the symmetry of chronic facial palsy. Materials and Methods:Two groups, namely experimental and control, were considered each consisting of 13 patients. The study population included a total of 15 female subjects. The BTX-A was injected into the synkinetic muscle in the experimental group; nevertheless, the patients in the second group participated in special neuromuscular retraining. The rate of reducing synkinesis and symmetrical improvement was evaluated using the Facial Grading System (FGS) after 4 months of treatment. The independent t-test was performed to compare the two groups. Results:According to the Sunnybrook FGS, the mean changes in Sunnybrook scores in the experimental and neuromuscular retraining groups were 3% and 24%, respectively. The comparison of the mean scores of the two groups was statistically significant after the interventions (P=0.033). A variable ratio of statistically significant improvement was observed in synkinesis in both groups following the treatment (P=0.041). In addition, by comparing the synkinesis scores between the two groups, the reduction of synkinesis was observed to be greater in the neuromuscular retraining group (P=0.041) after the treatment. Conclusions:The findings of the current study indicated that special neuromuscular retraining leads to significant improvement in the FGS score, compared to botulinum toxin therapy alone. Moreover, it was observed that facial symmetry can be treated with special neuromuscular retraining and the patient can overcome synkinesis.

Apraxia of Lid Opening in Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease-Frequency, Risk Factors and Response to Treatment.

New-onset apraxia of lid opening (ALO) is reported to occur in Parkinson's disease (PD) patients following Deep Brain Stimulation (DBS). There are only few systematic studies on this uncommon disorder of eyelid movements. We aimed to examine the frequency, temporal evolution, predisposing factors and response to treatment, of new-onset ALO in PD patients who underwent bilateral subthalamic nucleus (STN) DBS. We retrospectively reviewed the data of patients who underwent STN DBS at our centre between 1999 and 2017, with a minimum of 2 years of follow up after surgery. New-onset ALO was seen in 17 (9.1%) of the 187 patients after an average of 16.9 months (Range - 6-36 months). Comparison of the groups with and without ALO revealed that ALO occurred more often in older patients, both at the onset of PD symptoms and at surgery and in those with non-tremor dominant subtypes of PD and freezing of gait at baseline. The extent of levodopa dose reduction after surgery and the pre-operative severity of motor symptoms were not risk factors. Response to adjustments of dopaminergic medications and stimulation parameters was ill-sustained or nil. Botulinum toxin therapy resulted in satisfactory improvement in the majority. New-onset ALO is an uncommon phenomenon that manifests months after STN DBS. Development of ALO is likely to be due to the effects of chronic stimulation of basal ganglia-thalamo-cortical or brain stem circuits controlling lid movements in susceptible patients. Botulinum toxin therapy offers relatively better relief of symptoms than other strategies.

Sacral neuromodulation in patients with refractory overactive bladder symptoms after failed Botulinum toxin therapy: Results in a large cohort of patients.

AimsSacral neuromodulation (SNM) and Botulinum toxin A (BoNT‐A) injections are well‐known third‐line treatment options in patients with refractory overactive bladder (OAB). Our aim is to evaluate the success rate of SNM in patients who received prior therapy with BoNT‐A injections.MethodsAll patients with OAB symptoms referred for SNM between 2006 and 2019 were included. History taking and 3‐day voiding diaries assessed the complaints and suitability for SNM. The success rate of SNM in patients who received prior BoNT‐A was compared with BoNT‐A naive patients. Success was defined as an improvement of 50% or greater in voiding diary parameters. Satisfaction was registered at their most recent visit.ResultsA total of 263 patients underwent SNM test stimulation, of which 75 (16 male/57 female) received prior BoNT‐A and 188 (46 male/142 female) were BoNT‐A naive. Success rate for SNM in BoNT‐A naive patients was 72.9% and in BoNT‐A patients 66.7% (p = 0.316). Success rate after ≤2 BoNT‐A injections was 68.5%, compared to 61.1% after ≥3 injections (p > 0.05). Success rate in patients perceiving lack of efficacy of BoNT‐A was 67.4% (p > 0.05), subjected to temporary CISC was 73.7% (p > 0.05) and with temporary effect of BoNT‐A was 50% (p > 0.05). In 86% of BoNT‐A patients the system was still activated and used to their satisfaction at their last follow‐up visit (mean FU, 40.70 months).ConclusionSNM in patients with refractory OAB who failed prior BoNT‐A is an excellent approach. The number of injections nor reason of BoNT‐A discontinuation have predictive value for success with SNM.

Combined Interventional Treatment of Refractory Chronic Migraine

Migraine is one of the main causes of disability in modern world. Treatment of chronic refractory migraine (RCM) would be a challenge even for experienced physician. The aim of this study was to analyze the effect of combination therapy for RCM: greater occipital nerve’s (GON) pulsed radiofrequency (PRF) and botulinum toxin injections. We observed 6 female patients, suffering from RCM according to the European Headache Federation criteria. All patients had long history of migraine (5–44 years) with conservative treatment failure (at least three medication groups). Their migraine could be classified as refractory for long period of time (1–10 years). All of our patients passed a combination of PRF and BTA injection as consecutive 1-day treatments. Botulinum toxin type A injections were done in accordance to the PREEMPT protocol, followed by ultrasound-guided PRF of GONs bilateral. The observation period was 6 months after the procedure. We observed a positive response to treatment in all patients with dramatic reduction of pain intensity (from 7 ± 1 to 2 ± 2 on NRS scale) and significant decrease in the number of headache days (from 22 ± 5 to 4 ± 4) during first month after treatment. Two patients (30%) were pain free after the treatment until the end of the observation. No adverse effects were registered. Bilateral GON’s PRF followed by botulinum toxin therapy as 1-day treatment may be a useful option for the treatment of refractory chronic migraine. These interventional procedures are effective, minimally invasive, inexpensive, safe, and well-tolerated and can be performed on an outpatient basis.

Consensus guidelines for botulinum toxin therapy: general algorithms and dosing tables for dystonia and spasticity

Botulinum toxin (BT) therapy is a complex and highly individualised therapy defined by treatment algorithms and injection schemes describing its target muscles and their dosing. Various consensus guidelines have tried to standardise and to improve BT therapy. We wanted to update and improve consensus guidelines by: (1) Acknowledging recent advances of treatment algorithms. (2) Basing dosing tables on statistical analyses of real-life treatment data of 1831 BT injections in 36 different target muscles in 420 dystonia patients and 1593 BT injections in 31 different target muscles in 240 spasticity patients. (3) Providing more detailed dosing data including typical doses, dose variabilities, and dosing limits. (4) Including total doses and target muscle selections for typical clinical entities thus adapting dosing to different aetiologies and pathophysiologies. (5) In addition, providing a brief and concise review of the clinical entity treated together with general principles of its BT therapy. For this, we collaborated with IAB—Interdisciplinary Working Group for Movement Disorders which invited an international panel of experts for the support.

Treatment outcomes of overactive bladder with combined therapies of botulinum toxin injections and oral agents.

Treatment options for refractory overactive bladder (OAB) following behavioral modifications and oral OAB medications remain limited. Up to 33% of women fail botulinum toxin injections (Amundsen et al. Eur Urol. 74(1):66-73, 7). This study evaluates the effectiveness of combining oral OAB agents with botulinum toxin in subjects who failed botulinum toxin therapy alone. This is a retrospective observational study. Eligible women were those who received botulinum toxin injections for OAB between 2013 and 2018 at one academic institution. Women were given the option of oral medications as add-back therapy following failed treatment with botulinum toxin alone. Treatment response was a subjective outcome, with subjects reporting being satisfied or unsatisfied. The primary outcome was the proportion of subjects who achieved satisfactory treatment response with the combination of oral OAB medications and botulinum toxin injections. A subanalysis was performed to further investigate any risk factors associated with poor response to combination treatment. Variables were analyzed using chi-squared or Fisher's exact test and Student's t-test or Mann-Whitney U when appropriate. A total of 107 charts were reviewed. Forty-five (48%) women failed botulinum toxin alone as a treatment; 26 (29%) elected to try one or more oral OAB medications. Of the 26 women who received the combination treatment, 17 (65%) reported satisfaction and 9 (35%) remained unsatisfied. Risk factors associated with treatment failure were not identified. This is an initial report on adding back oral OAB meds to patients who have failed botulinum toxin injections suggesting there may be a role for add-back oral OAB medications.

Benign essential blepharospasm: epidemiology, clinical manifestations, pathophysiology, botulinum toxin therapy

Blepharospasm (BPS) is a variant of focal dystonia manifested by involuntary eyelid spasms with eye closure and/or increased spontaneous blinking. Along with motor symptoms, this condition is characterized by sensory, affective, and cognitive disorders. Patients with BPS are found to have changes in the basal ganglia, cerebellum, primary/secondary sensorimotor and visual areas according to functional magnetic resonance imaging. This may reflect the involvement of above regions in suppressing defective movement and sensorimotor disintegration. Botulinum toxin therapy is the most effective treatment for BPS. The advantage of Xeomin ® that does not contain complexing proteins, is characterized by a low probability of antibody production, is the ability to vary between-injection intervals. Probably, botulinum toxin therapy has a pathogenetic and modifying impact on BPS.

Botulinum toxin dosing in arm muscles: contextual factors

Botulinum toxin (BT) has been successfully used for many years to treat various muscle hyperactivity disorders including dystonia and spasticity. Its dosing is guided by dosing tables describing target muscles and dose ranges. To refine the BT dosing, we wanted to analyse how contextual factors may influence the injector's final dosing decision.In a retrospective review of real-life data of 1170 BT treatments, we studied the influence of various contextual factors on the BT doses in 21 arm muscles of 252 patients receiving BT therapy for different muscle hyperactivity disorders.We found that BT arm doses are significantly higher in treatment of spasticity than in treatment of dystonia. We also found that spontaneous arm dystonia requires higher BT doses in a proximal application pattern, whereas task specific writer's cramp requires considerably reduced BT doses with a distal application pattern. Injections of non-arm muscles influence the BT dosing in arm muscles only marginally.Our study demonstrates that BT dosing does not only depend on the particularities of the individual target muscle injected, such as its volume and its static or phasic function. BT dosing and its application pattern rather depend on additional contextual factors such as the aetiology and pathophysiology of the muscle hyperactivity treated. These contextual factors need to be included in dosing tables and may improve the outcome of BT therapy.

Botulinum toxin injection into the intrinsic laryngeal muscles to treat spasmodic dysphonia: A multicenter, placebo-controlled, randomized, double-blinded, parallel-group comparison/open-label clinical trial.

Background and purposeBotulinum toxin (BT) injection into the laryngeal muscles has been a standard treatment for spasmodic dysphonia (SD). However, few high‐quality clinical studies have appeared, and BT is used off‐label in most countries.MethodsWe performed a multicenter, placebo‐controlled, randomized, double‐blinded, parallel‐group comparison/open‐label clinical trial to obtain approval for BT (Botox) therapy in Japan. Twenty‐four patients (22 with adductor SD and two with abductor SD) were enrolled. The primary end point was the change in the number of aberrant morae (phonemes) at 4 weeks after drug injection. The secondary end points included the change in the number of aberrant morae, GRBAS scale, Voice Handicap Index (VHI), and visual analog scale (VAS) over the entire study period.ResultsIn the adductor SD group, the number of aberrant morae at 4 weeks after injection was reduced by 7.0 ± 2.30 (mean ± SE) in the BT group and 0.2 ± 0.46 in the placebo group (p = 0.0148). The improvement persisted for 12 weeks following BT injections. The strain element in GRBAS scale significantly reduced at 2 weeks after BT treatment. The VHI and VAS scores as subjective parameters also improved. In the abductor SD group, one patient responded to treatment. Adverse events included breathy hoarseness (77.3%) and aspiration when drinking (40.9%) but were mild and resolved in 4 weeks.ConclusionsBotulinum toxin injection was safe and efficacious for the treatment of SD. Based on these results, BT injection therapy was approved as an SD treatment in Japan.

Bromhidrosis treatment modalities: A literature review

Treatment options for Bromhidrosis include botulinum toxin therapy, microwave-based therapy, laser therapy, and surgical intervention. Limited studies compare their efficacies. The purpose of this literature review is to compare the efficacy and safety of these treatments for bromhidrosis. A PubMed search included terms bromhidrosis and bromhidrosis AND treatment. A total of 25 articles were reviewed. Botulinum toxin therapy shows consistent benefit but requires repeated therapies. Microwave therapies have shown promising results but require larger cohort sizes with bromhidrosis. Similarly, laser therapy has shown promise with biopsy-proven results, but long-lasting effects remain unknown. Surgery has the best long-term prognosis, but the ideal surgical method remains unknown. Each study varied in their treatment interval and method of assessing bromhidrosis, making direct comparisons difficult. Managing bromhidrosis requires shared decision making with the patient. Mild-to-moderate symptoms may be treated initially with botulinum toxin therapy. In cases that are refractory, laser therapy should be considered, as it is better studied than microwave therapy currently. Lastly, if the condition is severe and refractory to other options, surgery can be considered, although the ideal method remains unknown.

Botulinum Toxin Therapy in a Patient with HHH Syndrome with Gait Disturbance: A Case Report

Botulinum Toxin Therapy in a Patient with HHH Syndrome with Gait Disturbance: A Case Report

A new approach to study the influence of the course of cervical dystonia severity before botulinum toxin on long-term outcome after botulinum toxin therapy

A new approach to study the influence of the course of cervical dystonia severity before botulinum toxin on long-term outcome after botulinum toxin therapy

Exoskeleton “ExoAtlet” and botulinum toxin therapy in rehabilitation of stroke patients

Exoskeleton “ExoAtlet” and botulinum toxin therapy in rehabilitation of stroke patients

Хирургическое лечение детей с клапаном задней уретры

Objective. To assess treatment outcomes in children with posterior urethral valve (PUV). Patients and methods. We analyzed treatment outcomes in 60 children with PUV within a non-randomized, retrospective, single-center, pilot study. Sixty patients have undergone PUV ablation; 8 of them required repeated ablation. Endoscopic treatment of vesicoureteral reflux (VUR) was performed in 31 ureters; 5 children had botulinum toxin therapy. Results. Type 1 PUV was diagnosed in 49 patients (81.6%), whereas type 3 PUV was identified in 11 patients (18.3%). VUR was detected in in 65 ureters (54.1%); obstructive ureterohydronephrosis was diagnosed in 40 ureters (33.3%). Ablation of the valve flaps improved lower urinary tract (LUT) urodynamics in 27 children. Thirty-three patients had valve bladder syndrome (VBS). Improvement of the upper urinary tract (UUT) condition was achieved in 54 cases. Fifteen children have undergone nephroureterectomy. There was a significant decrease in the activity of pyelonephritis in children after endoscopic ablation of the PUV. Fifty-three patients (88.3%) demonstrated severe UUT urodynamic disorders. The baseline grade of UUT lesions affected treatment outcome (p = 0.0009). Children with VBS symptoms had progressive UUT pathology and persistent urinary incontinence. Six patients eventually required replacement therapy. Conclusion. The majority of PUV children (88.3%) presented with severe UUT impairments. More than half of the patients (55.0%) had VBS symptoms. Their treatment should be comprehensive and include long-term monitoring of urodynamics and kidney function. Key words: posterior urethral valve, valve bladder syndrome, vesicoureteral reflux

Важные аспекты двигательного восстановления пациента со спастическим парезом верхней конечности и проприоцептивными нарушениями после очагового поражения ЦНС (клиническое наблюдение)

Motor disorders (i.e., spastic paresis of the upper limb) are among the most common complications of a stroke. Motor deficiency (muscle weakness/paresis), increased muscle tone, proprioceptive loss, and lesions of muscles, joints, and surrounding tissues develop in the limb. As a result, its functional rehabilitation is a challenging, long-term, and labor-intensive process. This paper addresses factors that directly affect the functional recovery of the upper limb after stroke. The authors emphasize the importance of timely diagnosis of all lesions using assessment scales, optimal rehabilitation programs, including techniques to recover sensitivity and muscle tone, and current rehabilitation techniques with biofeedback. This rehabilitation allows for adapting patients (particularly younger patients of working age) to society and daily life. This case report describes a 22-year-old man with cerebral infarction in the right temporoparietal in whom relevant diagnostic tools and personalized rehabilitation programs provided an excellent functional outcome. These methods are crucial for motor rehabilitation of patients with spastic paresis of the upper limb and proprioceptive disorders after focal CNS lesion. KEYWORDS: stroke, paresis, spasticity, prognosis, proprioception, rehabilitation, botulinum toxin therapy, biofeedback. FOR CITATION: Khat’kova S.E., Nikolaev E.A., Pogorel’tseva O.A. et al. Motor rehabilitation of the spastic paresis and proprioceptive disorders of the upper limb after focal CNS lesion (case report). Russian Medical Inquiry. 2021;5(10):674–682 (in Russ.). DOI: 10.32364/2587-6821- 2021-5-10-674-682.

Ultrasound and Electromyography as Guidance Tools for the Botulinum Toxin Therapy in Cervical Dystonia

Cervical Dystonia (CD) is the most common type of focal dystonia in the movement disorders units of any specialized hospital around the world. Botulinum Toxin (BT) infiltration is the treatment of choice for CD, according to most of the experts around the world, however the efficacy and tolerance of BT therapy in CD depend on the accuracy when BT is released into the muscles. We reviewed the medical literature in regard to the use of guiding tools for the BT infiltration in CD patients. Results: The use of guiding tools such as Ultrasound or EMG definitely improves the accuracy for releasing the BT into the muscles involved according to some authors. Conclusion: the use of Ultrasound and EMG improves the efficacy and reduce the adverse effects in the BT therapy in CD patients.