Neurotoxin Treatment Research Articles

Effect of muscle selection for botulinum neurotoxin treatment on spasticity in patients with post-stroke elbow flexor muscle over-activity: an observational prospective study

Purpose/Aim To investigate the effect of muscle selection for botulinum neurotoxin A (BoNT-A) treatment on spasticity in patients with post-stroke elbow flexor muscle over-activity. Materials and Methods Chronic stroke patients with a deforming spastic paresis in the upper limb (elbow flexion with forearm pronation) who were injected BoNT-A into at least one of elbow flexor muscles (brachialis, brachioradialis, and biceps brachii) were included in this prospective observational study. The main outcome measure was spasticity angle by Tardieu Scale recorded at pre-treatment and week 4 after treatment. Results Three muscle selection groups with sufficient sample size for statistical analysis were able to be created; brachialis (n = 14), biceps brachii (n = 21), and brachialis plus brachioradialis (n = 11). Although there was a significant improvement in spasticity angle within all groups over time (p < 0.05), the change in spasticity angle was not different between the groups (p > 0.05 for each pairwise comparison). However, the magnitude of the change in spasticity angle was larger in the groups in which brachialis was preferred. Conclusions In stroke patients with a spontaneous spastic posture of elbow flexion and forearm pronation, targeting brachialis for BoNT-A injection seems more effective in reducing the severity of spasticity. Clinical trial registration no NCT04036981

Prevalence, indications and demographic characteristics of Botulinum neurotoxin use in a tertiary oculoplastic centre.

Over the past 40 years, Botulinum Neurotoxin (BoNT) treatment has been used in many presentations to the hospital eye service. There is little published on its practice in an ophthalmology setting. We aim to report on the prevalence of BoNT use, indications for treatment, age, gender, socioeconomic and ethnic variations observed, and dosages used. We performed a retrospective cross sectional observation study on the use of botulinum neurotoxin treatment in the oculoplastic department of a busy tertiary centre in the University Hospitals of Leicester, United Kingdom. The prevalence of BoNT in the service was 13.7 per 100,000 people. Of the 145 cases identified, the commonest indications for treatment were hemifacial spasm (62% of cases) and blepharospasm (29% of cases). Proportionally, twice as many females than males received BoNT (χ2 = 17.3, p < 0.0001). For those >30 years of age, the prevalence increased with age with those >90 years having a seven times higher prevalence than the mean. Overall, no significant differences were found in ethnicity and median index of multiple deprivation rank between those with treatment and the general population although specific district council variations were noted. These findings would assist commissioners in providing adequate resources to meet demand based on the demographics of their local population. Further qualitative and quantitative research is required to enhance our understanding of some of these trends.

Botulinum neurotoxin in cervical dystonia revisited - recent advances and unanswered questions.

Cervical dystonia (CD) usually presents a complex pattern of head/neck movements accompanied by tremor, myoclonic jerks and a wide spectrum of non-motor disturbances such as pain, depression, anxiety, and sleep problems. This is the most challenging indication for botulinum neurotoxin (BoNT) treatment. It can offer significant improvement, but it can be difficult after the first injection. Thorough examination and identification of the proper CD pattern, the identification of the muscles responsible, and adjusting doses given precisely under ultrasound and/or electromyographic guidance seem to be the key success modifiers. Nevertheless, this is a lifelong treatment and should be planned and conducted carefully to avoid failures and drop outs. The aim of this paper was to examine the current concepts in terms of anatomy, physiology and CD patterns (Col-Cap concept) as well as the proper dosages and any possible obstacles impeding successful treatment.

A Randomized, Single-Blind, Crossover Study Evaluating the Impact of OnabotulinumtoxinA Treatment on Mood and Appearance During the COVID-19 Pandemic.

BackgroundThe emergence of Coronavirus disease of 2019 (COVID-19), quickly became one of the most severe disease outbreaks in modern history. This caused many aesthetic practices around the country to close temporarily and led to a unique time period to evaluate the impact neurotoxin has in the setting of an ongoing pandemic.ObjectivesTo examine whether the administration of onabotulinumtoxinA (BOTOX Cosmetic, Allergan plc, Coolock, Ireland), in regular users, synergistically amplifies the elevation in mood/happiness, self-satisfaction with appearance and overall satisfaction, in the context of the ongoing pandemic.MethodsA randomized single-blind cross-over study was designed to evaluate the impact of neurotoxin treatment in the upper third of the face on mood, self-satisfaction with appearance, and overall satisfaction. The placebo group crossed over to treatment after 1 month. Surveys evaluating patient happiness, self-satisfaction with appearance and overall efficacy were completed among both groups, and again to the placebo group again following crossover to treatment.ResultsForty-five subjects were enrolled with 30 in the treatment and 15 in the control/cross-over group. The placebo group demonstrated no change in happiness or self-satisfaction in appearance until cross-over to the treatment group. Both groups, once receiving, onabotulinumtoxinA reported increased happiness, self-satisfaction with appearance and overall treatment satisfaction.ConclusionsOnabotulinumtoxinA treatment to the upper face in the midst of the COVID-19 pandemic was found to increase patient happiness, self-satisfaction with appearance, and overall treatment satisfaction.

Prospective randomized clinical study of a new topical formulation for face wrinkle reduction and dermal regeneration.

A new topical formulation (TF) based on 3 main lifting components has been developed to reduce superficial facial wrinkles. Determine the effectiveness of this new TF in reducing superficial face wrinkles and restructuring the dermal matrix. Women, aged 30-65y.o. with moderate to severe crow's feet wrinkles were included. men; younger than 30 or older than 65years old; smokers. Patients received 15IU of botulinum toxin on crow's feet and 2 creams. Fifty patients (Group 1) applied the TP (Product A) and 50 (Group 2) a placebo (Product B). Assessments were made by digital macro-photography's, Antera 3D, and a patient satisfaction questionnaire. From April to June 2019, 100 women were enrolled in the study and were divided into two homogeneous groups. No major or minor side effects were reported. In group 1, wrinkles, texture, static and dynamic crow's feet wrinkles improved significantly at 3 and 6months. Patients were very satisfied at 3months and satisfied at 6months. In group 2, wrinkles and texture improved significantly at 3months but did not improve at 6months. Static and dynamic crow's feet wrinkles improved significantly at 1 and 3months but did not improve significantly at 6months. Our prospective and randomized study has shown that the new TF is safe and effective in reducing superficial face wrinkles and producing dermal regeneration. It, therefore, prolongs the duration of the botulinum toxin. Further controlled study would be necessary to compare the new TF to neurotoxin treatment, or its action alone.

Subjective versus objective symptom intensities ratings in cervical dystonia and hemifacial spasm across a botulinum neurotoxin cycle.

BackgroundSubjective symptom complaints often do not match the expert’s ratings in focal dystonia. Nonetheless, perceived symptom intensities drive compliance and outcome of botulinum neurotoxin (BoNT) treatment.MethodsPerception of symptom development across a BoNT cycle was obtained in 21 cervical dystonia (CD) and 15 hemifacial spasm (HFS) patients at four time points during a BoNT cycle. Subjective assessments were recorded by means of a quality‐of‐life questionnaire and a patient diary containing items related to subjective severity of disease, mood, pain, social impairment, and quality of life. Medical investigation used the Tsui score and TWSTRS, and a HFS rating score, respectively.ResultsIn both patient groups, subjective intensities were strongly associated with psychological variables. Only in CD did objective assessment moderately correlate with subjective ratings solely at the beginning and the end of the BoNT cycle. Overall, the beneficial effects of BoNT treatment were only loosely associated with subjective experiences in both groups.ConclusionThe emotional situation should be assessed regularly in patients undergoing BoNT therapy.

18272 DaxibotulinumtoxinA for Injection is similarly effective in experienced botulinum neurotoxin patients and in those naïve to treatment

Introduction: Clinical trials for glabellar lines (GL) have classically recruited subjects who are naïve to treatment to maintain population homogeneity. The DaxibotulinumtoxinA for Injection (DAXI) phase 3 GL program did not restrict enrollment in this way and included subjects with previous botulinum neurotoxin (BoNT) treatment experience as well as those naïve to treatment. Comparing these two subgroups will help determine if prior experience is an influential baseline characteristic.

IncobotulinumtoxinA for the Treatment of Blepharospasm in Toxin-Naïve Subjects: A Multi-Center, Double-Blind, Randomized, Placebo-Controlled Trial.

This study aimed to assess the efficacy/safety of incobotulinumtoxinA (Xeomin®, Merz Pharmaceuticals GmbH) in botulinum neurotoxin-naïve subjects with blepharospasm. Botulinum neurotoxin-naïve subjects (≥ 12months without botulinum neurotoxin treatment for blepharospasm) received single-dose incobotulinumtoxinA 50 U, 25U, or placebo. Subjects were followed for 6-20weeks (main period). Qualified subjects entered an open-label extension period and received another incobotulinumtoxinA injection (≤ 70 U). The primary efficacy variable was change from baseline in the Jankovic Rating Scale (JRS) severity subscore at the main period of week 6. Other efficacy variables included changes in the Blepharospasm Disability Index score and JRS frequency subscore and sumscore. Adverse events were monitored. Sixty-one subjects were randomized (main period: incobotulinumtoxinA 50 U, n = 19; incobotulinumtoxinA 25 U, n = 22; placebo, n = 20); 39 entered the open-label extension period (9, 14, and 16 subjects from the incobotulinumtoxinA 50 U, incobotulinumtoxinA 25 U, and placebo groups [main period], respectively, changed to open-label extension period dosing). A statistically significantly greater reduction in JRS severity subscore was reported for subjects receiving incobotulinumtoxinA 50 U versus placebo (ANCOVA, least square mean difference: -1.2, p = 0.0004). Subjects receiving incobotulinumtoxinA experienced improvements in other efficacy variables versus baseline and/or placebo. Sustained clinical improvements and low adverse event rates (22.2-42.1%) were observed. This is the second placebo-controlled, double-blind study that demonstrates favorable efficacy/safety of incobotulinumtoxinA in subjects with blepharospasm. IncobotulinumtoxinA is the first botulinum neurotoxin that could fulfill the American Academy of Neurology criteria for a Level A recommendation for blepharospasm.Trial registration ClinicalTrials.gov identifier, NCT01896895.

Glia-Mediated Regenerative Response Following Acute Excitotoxic Damage in the Postnatal Squamate Retina.

The retina is a complex tissue responsible for both detection and primary processing of visual stimuli. Although all vertebrate retinas share a similar, multi-layered organization, the ability to regenerate individual retinal cells varies tremendously, being extremely limited in mammals and birds when compared to anamniotes such as fish and amphibians. However, little is yet known about damage response and regeneration of retinal tissues in “non-classical” squamate reptiles (lizards, snakes), which occupy a key phylogenetic position within amniotes and exhibit unique regenerative features in many tissues. Here, we address this gap by establishing and characterizing a model of excitotoxic retinal damage in bearded dragon lizard (Pogona vitticeps). We particularly focus on identifying, at the cellular and molecular level, a putative endogenous cellular source for retinal regeneration, as diverse self-repair strategies have been characterized in vertebrates using a variety of retinal injury and transgenic models. Our findings reveal for the first time that squamates hold the potential for postnatal retinal regeneration following acute injury. Although no changes occur in the activity of physiologically active progenitors recently identified at the peripheral retinal margin of bearded dragon, two distinct successive populations of proliferating cells at central retina respond to neurotoxin treatment. Following an initial microglia response, a second source of proliferating cells exhibit common hallmarks of vertebrate Müller glia (MG) activation, including cell cycle re-entry, dedifferentiation into a progenitor-like phenotype, and re-expression of proneural markers. The observed lizard glial responses, although not as substantial as in anamniotes, appear more robust than the absent or neonatal-limited regeneration reported without exogenous stimulation in other amniotes. Altogether, these results help to complete our evolutionary understanding of regenerative potential of the vertebrate retina, and further highlight the major importance of glial cells in retinal regeneration. Furthermore, our work offers a new powerful vertebrate model to elucidate the developmental and evolutionary bases of retinal regeneration within amniotes. Such new understanding of self-repair mechanisms in non-classical species endowed with regenerative properties may help designing therapeutic strategies for vertebrate retinal diseases.

Frequency and risk factors of antibody-induced secondary failure of botulinum neurotoxin therapy.

To investigate the risk factors of neutralizing antibody (NAB)-induced complete secondary treatment failure (cSTF) during long-term botulinum neurotoxin (BoNT) treatment in various neurologic indications. This monocenter retrospective cohort study analyzed the data of 471 patients started on BoNT therapy between 1995 and 2015. Blood samples of 173 patients were investigated for NABs using the mouse hemidiaphragm test (93 with suspected therapy failure, 80 prospective study participants). The frequency of NAB-cSTF was assessed for various indications: hemifacial spasm, blepharospasm, cervical dystonia, other dystonia, and spasticity. A priori defined potential risk factors for NAB-cSTF were evaluated, and a stepwise binary logistic regression analysis was performed to identify independent risk factors. Treatment duration was 9.8 ± 6.2 years (range, 0.5-30 years; adherence, 70.6%) and number of treatment cycles 31.2 ± 22.5 (3-112). Twenty-eight of 471 patients (5.9%) had NAB-cSTF at earliest after 3 and at latest after 103 treatment cycles. None of the 49 patients treated exclusively with incobotulinumtoxinA over 8.4 ± 4.2 (1-14) years developed NAB-cSTF. Independent risk factors for NAB-cSTF were high BoNT dose per treatment, switching between onabotulinumtoxinA and other BoNT formulations (except for switching to incobotulinumtoxinA), and treatment of neck muscles. We present a follow-up study with the longest duration to date on the incidence of NAB-cSTF in patients treated with various BoNT formulations, including incobotulinumtoxinA. Whereas the overall risk of NAB-cSTF is low across indications and BoNT formulations, our findings underpin the recommendations to use the lowest possible dose particularly in cervical dystonia, and to avoid unnecessary switching between different formulations.

Anatomical Considerations When Treating Compensatory Hypertrophy of the Upper Part of the Masseter after Long-Term Botulinum Neurotoxin Type A Injections.

The masseter is the most targeted muscle when treating hypertrophy to produce a smooth face shape. Compensatory hypertrophy is a well known clinical sequela that occurs in botulinum neurotoxin (BoNT) treatments and is limited to the lower part of the masseter. Based on the masseteric hypertrophy procedure, which targets a confined area, we predicted the possibility of compensatory hypertrophy occurring in the upper part of the masseter. If the patient complains about an unexpected result, additional injections must be performed, but the involved anatomical structures have not been revealed yet. The aim of this study was to identify the morphological patterns of the masseter. Deep tendons were observed in most specimens of the upper part of the masseter and mostly appeared in a continuous pattern (69.7%). The superficial and deep tendons could be classified into a simply connected form and forms surrounding part of the muscle. In 45.5% of cases there were tendon capsules that completely enclosed the muscle, which can interfere with how the injected toxin spreads. Interdigitation patterns in which the tendons could be identified independently between the muscles were present in 9.1% of cases. The present findings provide anatomical knowledge for use when injecting BoNT into the masseter.

Assessment of Spontaneous Neuronal Activity In Vitro Using Multi-Well Multi-Electrode Arrays: Implications for Assay Development.

Multi-electrode arrays (MEAs) are being more widely used by researchers as an instrument platform for monitoring prolonged, non-destructive recordings of spontaneously firing neurons in vitro for applications in modeling Alzheimer’s, Parkinson’s, schizophrenia, and many other diseases of the human CNS. With the more widespread use of these instruments, there is a need to examine the prior art of studies utilizing MEAs and delineate best practices for data acquisition and analysis to avoid errors in interpretation of the resultant data. Using a dataset of recordings from primary rat (Rattus norvegicus) cortical cultures, methods and statistical power for discerning changes in neuronal activity on the array level are examined. Further, a method for unsupervised spike sorting is implemented, allowing for the resolution of action potential incidents down to the single neuron level. Following implementation of spike sorting, the dynamics of firing frequency across populations of individual neurons and networks are examined longitudinally. Finally, the ability to detect a frequency independent phenotype, the change in action potential amplitude, is demonstrated through the use of pore-forming neurotoxin treatments. Taken together, this study provides guidance and tools for users wishing to incorporate multi-well MEA usage into their studies.

Botulinum Toxin Type A: Evaluation of Onset and Satisfaction.

With the increasing interest in nonsurgical cosmetic procedures, this research study sought to evaluate the onset of Botulinum toxin Type A (BoNTA) between naive and non-naive consumers and its effect on satisfaction. This single-blinded research study consisted of 15 adults with scheduled appointments for neurotoxin treatment of undesired glabellar lines. Participants completed pretreatment FACE-Q scales. Both the participant and the researcher rated pretreated glabellar lines with the Merz 5-point scale. Daily photographs of the treated area were taken by the participant and submitted to the researcher over a secure electronic system. Photographs were started on the treatment day and continued until both participant- and researcher-reported onset. The day of onset was determined with at least 1-point improvement when observed by both the participant and the researcher on the Merz 5-point scale. Once onset was determined, participants completed posttreatment FACE-Q scales. The average onset of treatment was 2.3 days. The average day of onset was 1.8 days in the naive group and 2.65 days in the non-naive group. Posttreatment, patients reported an average of 47.65% reduction in the appearance of glabellar lines; a 35.65% reduction was reported in the non-naive group, and a 59.67% reduction was reported in the naive group. The average participants perceived themselves 2.07 years younger prior to treatment and 6.47 years younger than their actual age posttreatment. On average, participants perceived themselves 4.4 years younger than at baseline. Both groups reported a high level of satisfaction with decision at an average of 85.73% and an average of 86.20% on satisfaction with outcome. The posttreatment FACE-Q expectation scores on average exceeded the pretreatment expectation scores by 8.25%; in the naive group, the scores were exceeded by 25.54%. The onset of BoNTA treatment in naive and non-naive participants demonstrated differences. The naive group experienced onset, on average, 1 day sooner than the non-naive group. The amount of time for a participant to see a noticeable difference influences patient satisfaction. Improvements in appearance and a reduction in the appraisal of age in relation to actual age enhanced satisfaction with treatment. Findings indicate that satisfaction is not solely based on onset, improvements in appearance, and reports of looking younger. The patient perception is also a key factor affecting satisfaction, which can be improved by setting clear expectations, improving patient communication, and encouraging follow-up assessments. The need for additional research on naive and non-naive patients demonstrating the influence of onset on satisfaction scores is crucial to confirm the evidence of this study.

Magnesium-Induced Cell Survival Is Dependent on TRPM7 Expression and Function

Mg2+ homeostasis is essential for cell survival and the loss of this regulation has been associated with many neurodegenerative diseases, including loss of dopaminergic neurons. Although the neurotoxin-mediated loss of dopaminergic neurons in Parkinson disease models is extensively studied, the ion channel(s) that regulate Mg2+ homeostasis and thus could prevent neuronal cell death is not yet identified. Here, we show that TRPM7 (transient receptor potential melastatin 7) is involved in regulating Mg2+ homeostasis in dopaminergic cells. Importantly, transient loss of TRPM7 decreased intracellular Mg2+ levels and decreased dopaminergic cells/neurons survival. We provide further evidence that both increases in extracellular Mg2+ or transiently increasing TRPM7 levels protected dopaminergic SH-SY5Y cells against neurotoxin-mediated cell death. Neurotoxin treatment significantly decreased TRPM7 levels in both SH-SY5Y cells and the substantia nigra pars compacta region of mice, along with a decrease in Mg2+ influx. Moreover, Mg2+ supplementation showed a concentration-dependent decrease in caspase-3 activity, an increase in cell survival, restored mitochondrial membrane potential, and increase TRPM7 levels in neurotoxin-treated cells. In contrast, transient silencing of TRPM7 inhibited the positive effect of Mg2+ supplementation in protecting against neurotoxins. Whereas, TRPM7 overexpression not only maintained Mg2+ homeostasis but also inhibited caspase 3 activity that induced cell survival. Overall, these results suggest a significant role of TRPM7 channels in Mg2+ homeostasis and the survival of neurotoxin-induced loss of dopaminergic cells.

Patient Satisfaction and Patients' Family or Significant Other Perceptions After OnabotulinumtoxinA Treatment: A Prospective Cross-Sectional Study.

OnabotulinumtoxinA treatment is associated with improved emotional well-being in patients. This study aimed to determine satisfaction with onabotulinumtoxinA treatment in patients naive to neurotoxin treatment and patients with previous experience with the procedure and evaluate treatment impact on patients' partners, "significant others," or close family members. Patients' satisfaction and their family's/significant other's perception to treatment outcome were assessed in a prospective, cross-sectional study using standardized questionnaires. OnabotulinumtoxinA treatment was associated with high patient satisfaction ranging from 80% to 100%. Study patients (61 patients) reported that their faces appeared to be more balanced and symmetrical (mean difference, 1.05) and that they looked much better in photographs (mean difference, 1.43), with their significant others also noting the improvement in appearance. Overall, 98% of patients expressed that they would undergo retreatment, and 100% expressed that they would recommend the procedure to others. The main obstacle for treatment repetition was economic constraints (26%). OnabotulinumtoxinA treatment is one of the most precise and predictable cosmetic treatments available, with high patient satisfaction (97%). A positive outcome of onabotulinumtoxinA treatment, as expressed by patients surveyed using standardized questionnaires, was the appreciation and acceptance by those in close contact with them.

Treatment with Botulinum Neurotoxin Improves Activities of Daily Living and Quality of Life in Patients with Upper Limb Tremor.

BackgroundBotulinum neurotoxin’s degree of effectiveness on upper limb tremor is subject to debate; although this treatment reduces the tremor’s amplitude, a clear functional benefit has not been demonstrated. The objective of this study was to assess the effect of botulinum neurotoxin type A treatment on activities of daily living and quality of life in patients with upper limb tremor.MethodsWe retrospectively examined the medical records of 50 consecutive patients treated with botulinum neurotoxin for upper limb tremor that was refractory to oral medication. One month after the injection, the patient was evaluated according to the Quality of Life in Essential Tremor Questionnaire, and the Essential Tremor Embarrassment Assessment.ResultsFull data sets were available for 38 patients suffering variously from essential tremor (n = 21), Holmes tremor secondary to a focal brain lesion (n = 8), idiopathic dystonic tremor (n = 4), primary writing tremor (n = 4), and Parkinson’s disease (n = 1). The Quality of Life Essential Tremor Questionnaire and the Essential Tremor Embarrassment Assessment scores improved significantly (p < 0.001) in the study population as a whole, and in the essential tremor and Holmes tremor subgroups.DiscussionBotulinum neurotoxin treatment of patients with upper limb tremor is associated with improved quality of life and activities of daily living, irrespective of the tremor’s etiology. Long-term treatment enables the physician to adjust the injection strategy to the patient’s needs. Our study was limited by its retrospective design. The results must therefore be confirmed in a prospective, double-blind, placebo-controlled, randomized clinical trial.

Botulinum neurotoxin treatment in jerky and tremulous functional movement disorders: a double-blind, randomised placebo-controlled trial with an open-label extension

ObjectiveTo study the effect of botulinum neurotoxin (BoNT) treatment in jerky and tremulous functional movement disorders (FMD).MethodsPatients with invalidating, chronic (>1 year) symptoms were randomly assigned to two subsequent treatments...

Validation of the Hemifacial Spasm Grading Scale: a clinical tool for hemifacial spasm.

To create an objective rating tool for hemifacial spasm (HFS) and validate it on a cohort of patients. A panel of movement disorders specialists elaborated, through the Delphi method, the Hemifacial Spasm Grading Scale (HSGS). The validity of the scale was tested in a longitudinal, prospective observational study, with standardized video recording protocol before and after botulinum neurotoxin (BoNT) treatment. The video recordings obtained from each patient were then independently assessed with HSGS by three blinded raters. The scale was compared to patient-reported HFS-7 scale and to the clinical grading of spasm intensity scale. Intra-rater reproducibility ranged between ICC 0.73 (95% CI = 0.54-0.86) and 0.83 (0.68-0.92) and inter-rater reproducibility between 0.62 (95% CI = 0.44-0.77) and 0.82 (0.69-0.90). HSGS scores correlated with clinical grading of spasm intensity scale scores, but not with HFS-7. HSGS confirmed BoNT efficacy, with scores lowering at 1month from treatment. HSGS represents an objective, quick and reliable scale for the assessment of HFS, and might be useful to monitor BoNT treatment efficacy over time.

Pallidal neurostimulation versus botulinum toxin injections in the treatment of cervical dystonia: protocol of a randomized, sham-controlled trial (StimTox-CD)

BackgroundSelective peripheral denervation via botulinum neurotoxin injections into dystonic muscles is the first-line treatment for cervical dystonia. Pallidal neurostimulation is a potent alternative, but currently restricted to patients failing on neurotoxin therapy. As botulinum neurotoxin is partially effective but often unsatisfactory in a relevant proportion of patients, earlier neurostimulation might be advantageous in providing stable symptom control and preventing disability. This trial intends to demonstrate, that pallidal neurostimulation is superior to neurotoxin injections in best clinical practice for controlling the symptoms of cervical dystonia and that it is safe in patients with a partial therapy response to peripheral denervation. We hypothesize a better outcome in everyday functioning and health-related quality of life of neurostimulated patients.MethodsWe aim to recruit 66 cervical dystonia patients into a double-blind comparison of pallidal neurostimulation versus botulinum neurotoxin type A. Eligible patients need ≥25% motor symptom reduction 4 weeks after a neurotoxin test injection, but are willing to undergo DBS surgery due to unsatisfactory symptom control. All participants will be implanted with a DBS system, and randomized into 2 groups: First group will receive effective neurostimulation and saline injections into dystonic muscles. Second group is treated with regular neurotoxin injections and undergoes a sham-stimulation. Primary outcome is the change in TWSTRS total score between baseline and 6 months of therapy. Secondary outcome parameters are corresponding changes in TWSTRS motor score, Tsui score, CDQ-24 and SF-36. Safety will be assessed by frequency and severity of reported adverse events. Statistical analysis includes intention-to-treat and per protocol populations, analysis based on imputation of missing values and analysis adjusting for differences in baseline TWSTRS. After 6 months of blinded treatment all patients will receive open-label neurostimulation and neurotoxin treatment as needed, and are followed up 48 weeks after randomization.PerspectiveWe will assess if pallidal neurostimulation is a safe and effective alternative to selective peripheral denervation by botulinum toxin injections in cervical dystonia, which may be offered earlier in the course of disease based on patient preference. A positive study outcome would influence future treatment guidelines of cervical dystonia.Trial registrationEudraCT registration number: 2016–001378-13

Ultrasonography of the internal architecture of the superficial part of the masseter muscle in vivo.

It is unclear whether the deep inferior tendon (DIT) is equally present in vivo, and little anatomical information is available regarding the existence and morphology of the DIT in healthy young subjects. The aim of this study was to characterize the DIT of the masseter muscle in healthy young subjects using ultrasonography and to compare the morphology of this tendon with previously reported data for healthy young subjects in order to provide the most-effective injection methods for botulinum neurotoxin treatments of masseteric hypertrophy. This study investigated two fresh cadavers and 30 healthy subjects. Ultrasonography scanning in both longitudinal and transverse directions was applied to the masseter muscle. The DIT within the superficial part of the masseter was observed in both the fresh cadavers and the living subjects. The posterior region of the masseter muscle was compartmentalized (entirely covered) by the DIT in 26.7% of the specimens. The superficial part of the masseter muscle was divided by the DIT transversely and longitudinally into the superficial and deep muscle bellies in 35% and 38.3% of the specimens, respectively. The present findings suggest applying a DIT-based injection technique under guidance by ultrasonography prior to treating masseteric hypertrophy. Clin. Anat. 32:446-452, 2019. © 2019 Wiley Periodicals, Inc.