The Use of High Initial Doses of Botulinum Toxin Therapy for Cervical Dystonia Is a Risk Factor for Neutralizing Antibody Formation—A Monocentric Cross-Sectional Pilot Study

Background and Objectives: The present study aims to analyze the complex patient/treating physician interaction at onset of botulinum toxin (BoNT) therapy in patients with idiopathic cervical dystonia (CD) and the influence of high initial doses on long-term outcomes. Materials and Methods: A total of 74 CD patients with well-documented courses of BoNT treatment were consecutively recruited after written informed consent. Patients had to rate the amount of improvement of CD in percent of severity of CD at onset of BoNT therapy. They had to draw the course of disease severity (CoD) of CD from the onset of symptoms until the onset of BoNT therapy and from the onset of BoNT therapy until recruitment. The remaining severity of CD was estimated by the treating physician using the TSUI score. Demographic- and treatment-related data were extracted from the charts of the patients. Seventeen patients with suspected secondary treatment failure (STF) were tested for the presence of antibodies. Results: Depending on the CoD before BoNT therapy, three patient subgroups could be distinguished: rapid onset, continuous onset and delayed onset groups. Time to BoNT therapy, increase in dose and improvement were significantly different between these three groups. In the rapid onset group, with the highest initial doses, the best improvement was reported, but the highest number of patients with an STF and with neutralizing antibodies was also observed. Conclusion: The use of high initial doses in the BoNT therapy of CD is associated with a rapid response and quick success; however, it leads to an elevated risk for the development of a secondary treatment failure and induction of neutralizing antibodies.

Non-Surgical Strategies for Assisting Closure of Pharyngocutaneous Fistula after Total Laryngectomy: A Systematic Review of the Literature

Background: Pharyngocutaneous fistula (PCF) is a frequent complication after total laryngectomy, with an incidence of up to 65%. Many conservative or invasive approaches are available and the choice among them is usually made on a case-by-case basis. The aim of the present review is to critically summarize the available evidence of the effectiveness of the non-surgical management of PCF. Methods: A systematic review and a meta-analysis of the literature were conducted, according to the PRISMA guidelines. Studies investigating botulinum toxin therapy, scopolamine transdermal patch, hyperbaric oxygen therapy (HBOT), and negative pressure wound therapy (NPWT) were assessed. Complete fistula closure after the initiation of non-surgical treatment was the main outcome. Results: After the application of selection criteria, a total of seven articles and 27 patients were included in the present review. All the eligible studies were descriptive case series, while only one article used a standard group as a comparison. The mean age was 63.3 and 14 patients (51.9%) had previously received RT. The reported comorbidities were diabetes, ischemic heart disease, hypertension, dyslipidemia, COPD, and atrial fibrillation. With a mean healing time of 25.0 days, the overall success rate was 92.6%. Conclusions: Non-surgical treatment of PCF is only based on the experience of small series. Although success rates seem promising, the absence of properly designed comparative studies does not allow us, at present, to identify ideal candidates for these non-invasive management strategies for PCF.

Botulinum Toxin Therapy in Writer’s Cramp and Musician’s Dystonia

Task-specific focal dystonia is characterized by muscle contraction(s) during a specific task, resulting in abnormal postures or movements. Specifically, writer’s cramp involves the upper extremity during the act of writing. Musician’s dystonia has a highly variable presentation, and thus makes therapeutic options more limited. Treatments include oral pharmacologic agents, neuromodulation, surgery and, most often, botulinum toxin (BoNT) injection. Selection of target muscles for toxin injection continues to be an area of active research for these task-specific movements. We present a review of the literature selected from a predefined search of the MEDLINE and ClinicalTrials.gov databases. We include six controlled studies of botulinum toxin for the management of writer’s cramp and focal task-specific dystonia (FTSD), including musician’s dystonia. Overall, 139 patients were included across all studies, with 99 individuals injected for writer’s cramp and the remaining 40 individuals with FTSD. The age range of all patients was 18–80 years old. We included studies that utilized only the BoNT-A serotype. These studies utilized various severity scales to quantify response to toxin injection, with ratings of instrument or pen control included as subjective ratings. Of the included 139 patients in this review, pooled data for toxin response show that 73% of patients who received the drug demonstrated improvement. Specific techniques for muscle localization and targeting were difficult to study as variable methods were employed. This remains an area of ongoing exploration.

Botulinum Toxin Therapy: A Series of Clinical Studies on Patients with Spasmodic Dysphonia in Japan

Spasmodic dysphonia (SD) is a rare voice disorder caused by involuntary and intermittent spasms of the laryngeal muscles. Both diagnosis and treatment have been controversial. Therefore, a series of clinical studies has recently been conducted in Japan. A nationwide epidemiological survey revealed that adductor SD predominated (90–95% of all cases; 3.5–7.0/100,000), principally among young women in their 20s and 30s. To facilitate early diagnosis, we created diagnostic criteria for SD and a severity grading system. The diagnostic criteria include the principal and accompanying symptoms, clinical findings during phonation, the treatment response, and the differential diagnoses. The severity grade is determined using a combination of subjective and objective assessments. Botulinum toxin (BT) injection is the treatment of choice; however, there have been few high-quality clinical studies and BT has been used off-label. We conducted a placebo-controlled, randomized, double-blinded clinical trial of BT therapy; this was effective and safe. BT treatment is now funded by the Japanese medical insurance scheme. Studies thus far have facilitated early diagnosis and appropriate therapy; they have fostered patient awareness of SD.

Analysis of Facial Muscle Depths to Guide Botulinum Toxin Therapy of the Periocular Region

Purpose: Botulinum toxin (BTX) injections are used in cosmetic surgery to efface facial wrinkles. Botulinum toxin relaxes the muscle by preventing the release of the neurotransmitter acetylcholine at the neuromuscular junction located at the posterior muscle surface causing local muscle paralysis. The purpose of this study is to provide anatomic knowledge of muscle belly depths of the frontalis, corrugator supercilii, procerus, and orbicularis oculi muscles in an attempt to improve the efficacy of BTX treatment of glabellar, forehead, and lateral eyelid rhytides. Methods: Six-millimeter punch biopsies were obtained from 7 fresh cadavers. Biopsies were taken from the corrugator supercilii, frontalis, procerus, and orbicularis oculi muscles at the sites of routine BTX injection. Specimens were fixed in formalin, and representative H&E-stained sections were used to measure muscle surface depths by light microscopy equipped with digital camera that includes a digital micrometer. One-way analysis of variance test analyses were used to identify statistical differences between measured muscle depths. Results: The measured anterior muscle depth of the corrugator supercilii, frontalis, procerus, and orbicularis oculi was found to be 4.2 ± 0.6, 3.9 ± 0.6, 2.9 ± 0.4, and 2.3 ± 0.7 mm, respectively. The anterior muscle surface of the corrugator supercilii and frontalis was found to be deeper than that of the procerus and orbicularis oculi ( P < .001). The posterior surface depth of the corrugator supercilii, frontalis, procerus, and orbicularis oculi was found to be 6.6 ± 0.8, 5.1 ± 0.7, 4.9 ± 0.7, and 3.8 ± 1.0 mm, respectively. The posterior surface depth of the corrugator supercilii was found to be significantly deeper than that of the frontalis, procerus, and orbicularis oculi ( P < .001); the posterior surface depth of the frontalis and procerus was deeper than that of the orbicularis oculi ( P < .001). The muscle belly width of the corrugator supercilii, frontalis, procerus, and orbicularis oculi measured 2.5 ± 0.9, 1.1 ± 0.4, 2.0 ± 0.6, and 1.5 ± 0.5 mm, respectively. The corrugator supercilii was found to be thicker than the frontalis and orbicularis oculi, while the procerus was found to be thicker than the frontalis ( P < .001). Conclusion: The findings above demonstrate statistical differences in the posterior muscle surface depth of the corrugator supercilii, frontalis, procerus, and orbicularis oculi which can be used clinically to improve BTX injection efficacy when used to efface facial rhytides.

Changes in Cortical Excitability and Parkinson Tremor After Botulinum Toxin Therapy

Background and ObjectivesTo investigate the relationship between botulinum toxin type A (BoNT-A) administration, tremor amplitude, and modulation of intracortical excitability and sensorimotor processing using paired-pulse transcranial magnetic stimulation (pp-TMS) in patients with early, tremor-dominant Parkinson disease (PD).MethodsTwelve de novo (naive to anti-PD medications) and 7 l-dopa (optimized on levodopa) participants with PD with tremor affecting one arm were recruited. All participants received 4 serial BoNT-A treatments for tremor every 12 weeks and peak effect was assessed 6 weeks posttreatment, totaling 8 visits over 42 weeks. Injection measures were based on kinematic tremor analysis. Short interval intracortical inhibition (SICI), intracortical facilitation (ICF), long interval intracortical inhibition (LICI), and measures of sensorimotor interaction (short-latency afferent [SAI] and long-latency afferent [LAI] stimulation) were assessed in both hemispheres using pp-TMS paradigms at each time point. Linear mixed models analyzed the effect of each pp-TMS measure and tremor severity within each cohort and the association between pp-TMS and tremor severity in the de novo cohort over 42 weeks. t Tests compared pp-TMS measures between hemispheres per time point.ResultsBaseline SICI, LICI, and SAI was reduced (higher motor evoked potential [MEP] ratio) on the tremulous/treated side compared to the nontremulous side in de novo participants. On the treated side in the de novo cohort, BoNT-A treatment significantly reduced ICF and increased LICI, SAI, and LAI (lower MEP ratio) at peak BoNT-A time points. The change in tremor severity was significantly associated with changes in SICI, LICI, and LAI.DiscussionOur findings suggest that tremor severity in early PD may be related to impaired intracortical inhibition and defective sensorimotor integration.

Effects of Botulinum Toxin Type A on Pain among Trigeminal Neuralgia, Myofascial Temporomandibular Disorders, and Oromandibular Dystonia

The differences in analgesic effects of botulinum toxin type A were compared in 28 patients with trigeminal neuralgia, 53 patients with myofascial temporomandibular disorders, and 89 patients with the jaw closing oromandibular dystonia. The patients were treated by injection of botulinum toxin type A into the masseter, temporalis, medial pterygoid, and other muscles based on the symptoms of each patient. The pain severity was evaluated using the visual analog scale, pain frequency, and pain scale of the oromandibular dystonia rating scale. Botulinum toxin injection was performed 1068 times in all patients without significant adverse effects. The visual analog, pain frequency, and pain scales at baseline were reduced (p < 0.001) after two, four, eight, and 12 weeks after the first botulinum toxin therapy and at the endpoint. The effects differed significantly (p < 0.001) among the groups (repeated-measures analysis of variance). The mean improvement (0%, no effect; 100%, complete recovery) at the endpoint was 86.8% for trigeminal neuralgia, 80.8% for myofascial pain, and 75.4% for oromandibular dystonia. Injection of the botulinum toxin can be a highly effective and safe method to treat trigeminal neuralgia, myofascial pain, and oromandibular dystonia.

Botulinum Toxin Services for Neurorehabiliation: Recommendations for Challenges and Opportunities during the COVID-19 Pandemic

The COVID-19 pandemic severely impacted the function of medical facilities and rehabilitation services worldwide, including toxin services delivering Botulinum toxin treatments for neuromuscular conditions such as spasticity, dystonia, and sialorrhea. The aim of this paper is to understand how toxin services have dealt with the situation and what strategies have been adopted to continue services. The recommendations are based on a virtual round table held with toxin services experts from different European countries who shared their experiences and discussed the best practices. The challenges for toxin services were reviewed based on the experts’ experiences and on relevant literature from 2020 and 2021. A set of recommendations and best practices were compiled, focusing firstly on guidance for clinical practice, including assessing patients’ health and risk status and the urgency of their treatment. Secondly, it was discussed how patients on botulinum toxin therapy can be cared for and supported during the pandemic, and how modern technology and tele-medicine platforms can be generally used to optimize effectiveness and safety of toxin treatments. The technological advances prompted by the COVID-19 crisis can result in better and more modern patient care in the future.

IncobotulinumtoxinA in the treatment of sialorrhea in patients with infantile cerebral palsy

Sialorrhea is a severe medical problem that is difficult to treat, which can lead to serious complications. In almost all cases, chronic sialorrhea is accompanied by a restriction of the child's contacts with peers, socialization difficulties, and a significant decrease in the quality of life. Nowadays, botulinum therapy can be an effective tool that significantly reduces sialorrhea manifestation.Oblective: to evaluate the effectiveness of Xeomin (incobotulinumtoxinA) in the treatment of sialorrhea in patients with spastic infantile cerebral palsy (ICP).Patients and methods. We enrolled 24 children with ICP (14 (58.3%) females, and 10 (41.7%) males) with various disease forms: 4 (16.6%) — with spastic hemiparesis, 6 (25.0%) — with spastic diplegia, and 14 (58.3%) — with spastic quadriparesis. IncobotulinumtoxinA injections were performed bilaterally in the parotid and submandibular salivary glands under ultrasound control at a total dose of 40-100 U (min 1.3, max 4.5 U/kg of body weight). IncobotulinumtoxinA. The Drooling Impact (DIS) and the Global Impression of Change Scale (GICS) were used 1, 3 and 6 months after IncobotulinumtoxinA injections to assess treatment effectiveness.Results and discussion. Botulinum toxin therapy resulted in a significant decrease in saliva discharge from the oral cavity 1 and 3 months after IncobotulinumtoxinA injections, which was demonstrated by a reduction in mean DIS score from 78.6±9.6 (min 62, max 95 points; 95% CI 74.6—82.7) to 48.7±6.7(min 25, max 61 points; 95% CI45.8—51.6) and 52.7±8.5points (min 22, max 65; 95% CI49.1—56.3), respectively, as well as an increase in delta GICSscore up to +1.3+0.8(min 0, max 3points; 95% CI 1.0—1.6) and +1.0+0.7points (min 0, max 3points; 95% CI 0.8—1.3), respectively. Adverse events were observed in 4patients (16.6%), which were classified as mild in 3 patients (did not require special treatment and completely stopped within six days) and moderate in 1 patient (also did not require special treatment and completely stopped within three weeks).Conclusion. In the majority (79.1%) of patients with ICP, it is possible to achieve high efficiency in reducing sialorrhea and this effect persists for at least 3 months.