Botulinum Toxin in Treatment of Tics

Cerebral palsy (CP) is characterized by aberrant control of movement or posture and appears early in life secondary to central nervous system damage. The symptoms of CP fall into four groups: symptoms due to loss of selective motor control; symptoms due to abnormal muscle tone; symptoms due to imbalance between muscle agonists and antagonists; and symptoms due to impaired balance. The goals of treatment are to maximize function and minimize the development of joint contracture and other secondary problems. Development of a treatment plan begins with the definition of objectives and consideration of the effects of growth and development on the patient's abilities. The role of botulinum toxin in CP treatment has grown in recent years. The patient who could benefit most from botulinum toxin treatment is one who is hypertonic and whose abnormal muscle tone is interfering with function, or who is expected to develop joint contracture with growth because of this abnormal tone. By altering this muscle tone, function can be enhanced or additional therapeutic modalities can be employed. Assessing treatment outcomes for BTX injection involves the same set of questions and measurements as for other types of treatments and depends on the careful definition of treatment objectives beforehand.

The authors consider modern epidemiological and demographic data on morbid obesity. Literature review is devoted to non-surgical treatment of patients with morbid obesity. The authors analyze the results of experimental and clinical studies on endoscopic intragastric injection of botulinum toxin and bariatric efficacy of this approach. The indications for endoscopic intragastric injection of botulinum toxin and advantages of this technique are clearly formulated. The authors identified the most significant criteria for objective assessment of clinical effectiveness of endoscopic intragastral injection of botulinum toxin, as well as scientific and methodological principles necessary for this technique. Clinical efficacy of intragastric injection of botulinum toxin including overweight loss, anorexigenic and gastroparetic effects indicates inconsistent results and certain unresolved problems. Thus, large-scale multiple-center randomized controlled trials and multivariate analysis are required to determine the role of endoscopic intragastric injection of botulinum toxin in complex treatment of patients with morbid obesity.

Promising new techniques in the management of vocal fold nodules have been developed in the past 2 years. Simultaneously, the therapeutic use of botulinum toxin has rapidly expanded. This review explores the use of botulinum toxin in treatment of vocal nodules and summarizes current therapeutic concepts. New microsurgical instruments and techniques, refinements in laser technology, radiosurgical excision and steroid intralesional injections are all promising new techniques in the management of vocal nodules. Botulinum toxin-induced 'voice rest' is a new technique we have employed in patients with recalcitrant nodules. Successful resolution of nodules is possible with this technique, without the risk of vocal fold scarring inherent in dissection/excision techniques. Botulinum toxin usage is exponentially increasing, and large-scale, long-term studies demonstrate its safety profile. Targeted vocal fold temporary paralysis induced by botulinum toxin injection is a new, well tolerated and efficacious treatment in patients with persistent vocal fold nodules.

Aims: Depressive disorders, as defined by the International Classification of Diseases (11th Revision), involve a depressive mood (feeling sad, irritable, or empty) along with other symptoms affecting a person’s ability to function. Botulinum toxin, used for conditions like migraines and muscle spasms, is being researched as a treatment for depression. The theory is based on facial feedback, where paralysing facial muscles could reduce the brain’s ability to process negative emotions, potentially improving mood. This review aims to explore how botulinum toxin might work in depression treatment and summarize the current research and future directions in this field.Methods: We searched PubMed. Inclusion criteria were paper should discuss depression and botulinum. We excluded papers before 2010 and papers which included botulinum toxin in patient comorbid migraine.Results: Magid et al. reviewed 2 case series, 3 randomized controlled trials (RCTs), and one meta-analysis on botulinum toxin for depression. 29\39 U was injected. They concluded that botulinum toxin was not yet an appropriate treatment.Kugar and Wollmer examined studies on botulinum toxin’s effects on depression, especially patients with chronic migraine. 29/39 U was injected. Some improvement but called for further research.Wollmer et al. (2019) analysed 4 RCTs and 3 case series, confirming the efficacy of botulinum toxin in treating depression. They found a lasting effect of about 3 months with a single treatment but recommended further research.Qian et al. (2020) conducted a systematic review of RCTs and concluded that botulinum toxin might offer a new treatment option for major depressive disorder. However, the effects on depression secondary to other conditions remain unclear.Danilo et al. (2021) analysed 5 RCTs, finding botulinum toxin more effective than a placebo in treating depression. They noted low risk of bias, with statistically significant results.Yang Li et al. (2021) reviewed 10 RCTs and confirmed that studies support botulinum toxin as a potential alternative treatment for depression.Wollmer et al. (2022) evaluated 5 studies and found botulinum toxin effective for patients although the exact mechanisms are still under study.Conclusion: While botulinum toxin has shown potential in treatment for depression, particularly for patients who didn’t respond to antidepressants or who experience side effects, the current evidence remains preliminary. Several studies indicate that botulinum toxin may offer symptomatic relief. However, the overall quality of the evidence is limited by small sample sizes, methodological inconsistencies, and the need for more trials.

Salivary fistula is a troublesome complication of parotid surgery. The treatment of this condition requires weeks before effect becomes evident. Botulinum toxin injection is a newer treatment modality. This systematic review sheds light on the efficacy of Botulinum toxin in treatment of post surgical parotid fistula. Studies comparing botulinum toxin with the other available treatment modalities as well as those studies solely using botulinum toxin are taken into consideration in the review. Electronic data search of Pub Med, Google Scholar, EMBASE, Institutional Library, Email to authors and manual search of various journals. Finally, 9 studies were included in qualitative synthesis with a total of 25 estimates. Botulinum toxin type A injections are effective in reducing the flow of saliva in treatment of post operative parotid fistula, thereby aiding in healing of the fistula. The studies had a varying variety of dose, route of administration and cycles of administration per case, making it difficult to evaluate the efficacy of Botulinium toxin in the treatment of parotid fistula. Further research focusing on streamlining the dose and delivery of the toxin must be conducted in order to establish definitive guidelines.

The mainstay of treatment for cervical dystonia (CD) is regular botulinum toxin injections every 3-4 months. Clinical evaluation of response is dependent on the patient's recall of how well symptoms responded to the previous injection. A mobile health app could assist both patients and health care professionals to monitor treatment benefits and side effects to assist with the selection of muscle and toxin dose to be injected at the next visit. The DystoniaDiary is a bespoke electronic health journal for monitoring symptoms of CD and response to treatment. The objective of this study was to assess the acceptability and utility of the DystoniaDiary in patients with CD treated with botulinum toxins as part of their usual care. In this open-label, single-center, single-arm observational study, patients attending a botulinum toxin injection clinic were invited to download the DystoniaDiary app. Patients selected up to 3 of their most troublesome CD symptoms (from a predefined list) and were prompted every 3 days to rate the control of these symptoms on a scale from 0 (very badly) to 100 (very well). Dates of onset and wearing off of response to injected botulinum toxin and responses to the Cervical Dystonia Impact Profile (CDIP-58) questionnaire at baseline and week 6 were also recorded in the app. A total of 34 patients installed DystoniaDiary. Twenty-five patients (25/34, 74%) recorded data for ≥12 weeks and 21 patients (21/34, 62%) for ≥16 weeks. Median time between the first and last data input was 140 days with a median of 13 recordings per patient. User experience questionnaires at weeks 4 and 12 (20 respondents) indicated that the majority of respondents found the DystoniaDiary app easy to install and use, liked using it, would recommend it to others (19/20), and wished to continue using it (16/20). A smaller proportion indicated that the DystoniaDiary gave a greater sense of control in managing their CD (13/20). There was interindividual variation in patients' perceptions of control of their symptoms after botulinum toxin injection. Response to treatment was apparent in the symptom control scores for some patients, whereas the severity of other patients' symptoms did not appear to change after treatment. This observational study demonstrated that the DystoniaDiary app was perceived as useful and acceptable for a large proportion of this sample of patients with CD attending a botulinum toxin clinic. Patients with CD appear to be willing to regularly record symptom severity for at least the duration of a botulinum injection treatment cycle (12-16 weeks). This app may be useful in monitoring and optimizing individual patient responses to botulinum toxin injection.

BackgroundDifferential effects of botulinum toxin (BoNT) treatment in cervical dystonia (CD) and blepharospasm (BSP) treatment satisfaction and emotional responses to a life with a disabling condition were investigated. Special interest was drawn to the course within a BoNT treatment cycle and the effects of subjective well-being vs perceived intensity of motor symptoms and quality of life.MethodsA questionnaire was distributed among 372 CD patients and 125 BSP patients, recruited from 13 BoNT centers throughout Germany. Items were related to dystonic symptoms, BoNT treatment responses and treatment satisfaction, quality of life, working situation, and emotional reactions to a life with dystonia.ResultsCD patients and BSP patients were widely satisfied with BoNT treatment, but treatment satisfaction worsened significantly within the treatment cycle. Especially CD patients reported that both the dystonic symptoms and the effects of BoNT treatment were influenced by emotional factors. Despite good overall treatment effects, patients from both groups perceived marked persistence of motor symptoms, restrictions of everyday life functions, and reduced quality of life. Functional amelioration of motor symptoms and emotional well-being were only moderately correlated. About 22% of patients from both groups reported mental disorders or emotional disturbances prior to the onset of dystonia.ConclusionAs numerous psychological factors determine perceived outcome, BoNT treatment should be further improved by patient’s education strategies enhancing behavioral self-control. From the patient’s perspective, individual intervals, which may avoid exacerbation between injection points, should be considered. Moreover, patients at risk, with reduced adherence and poor BoNT outcome, should be identified and addressed within psychoeducation.

So far, studies addressing the negative psychological effects of crow's feet treatment with botulinum toxin A (BoNTA) have rarely been published. BoNTA causes neuromuscular paralysis through a process of chemical denervation, temporarily preventing muscle contraction. The ability of botulinum toxin to alleviate dynamic wrinkles was coincidentally discovered after treating patients for benign essential blepharospasm in 1987.1 Since then, it has been widely used in cosmetic dermatology to reduce wrinkles and rejuvenate the skin. We report the cases of three female patients who presented with negative emotional complaints following BoNTA treatment for crow's feet. A 34-year-old Caucasian woman presented 14 days after the first BoNTA treatment. She reported having been injected with onabotulinumtoxinA (10 units per side) in the lateral part of the orbicularis oculi muscles on both sides. She reported a history of depression, treated with citalopram. The injection pattern was 3-4-3 U (Figures 1a and 2). A 28-year-old Caucasian woman presented 12 days after the first BoNTA treatment. She was injected 20 units of incobotulinumtoxinA (10 units per side) in the lateral part of the musculus orbicularis oculi. Her medical history was not relevant for previous diseases. The injection pattern was 3-4-3 U (Figure 1a). A 56-year-old Caucasian woman presented 10 days after the first BoNTA treatment. In this case, she was injected 50 units of abobotulinumtoxinA (25 units per side) in the lateral part of the musculus orbicularis oculi. Her medical history was only relevant to smoking. The injection pattern was 10-10-10 U (Figure 1b). All three cases were attended in our specialised outpatient clinic at Erasmus MC for complications of injectables, reporting a non-natural smile after BoNTA treatment. All patients reported a mental impact in the form of sadness, distress and insecurities, and a socio-psychological impact manifested as limitations in their daily functions, such as going to work or even going outside. All patients stated that their emotional status was normal before the treatment. Physical examination revealed complete paralysis of the lateral part of the orbicularis oculi muscles, resulting in a non-smooth transition with a crease between the lower eyelid and the cheek area (Figure 2). After explaining the anatomy of this area, mechanisms of action and temporary effect of BoNTA, the patients were reassured with a biweekly follow-up. Upon smiling, the zygomaticus major muscles contraction lifts a ‘shelf’ of cheek tissue and rhytids that stops abruptly as it transitions into the smooth paralysed lateral orbital area.2 Among older patients, this effect can be accentuated and even visible at rest, due to the excess skin in the lower lid.3 For most people, this muscle is also an accessory upper cheek elevator. When the lower portion of the lateral orbicularis oculi is totally paralysed, a small loss of upper cheek elevation is observed, resulting in a weaker facial feedback effect.3, 4 The injection pattern used in all three cases was similar (Figure 1a,b) and the doses between the different toxins were equivalent, reflecting a standardised practice in many current medical settings. Published guidelines for the use of BoNTA are an excellent starting point and an important tool for clinicians with little experience; however, each practitioner is likely to develop their own algorithm for facial rejuvenation procedures.5 Different injection patterns and new techniques, such as the microdroplet technique for BoNTA treatment on crow's feet, may possibly achieve a smoother transition between treated and non-treated areas for a more harmonious and natural outcome.6 Besides, appreciation for the aesthetic result desired by the patient, clear explanations about the mechanism of action of BoNTA and appropriate management of expectations result in a better doctor–patient communication and higher patient satisfaction. We think that the negative psychological effects of BoNTA treatment are under-reported. Although temporary, these effects can be very distressing and may lead to decreased client retention. The report of these cases should raise awareness about the importance of a personalised treatment plan for each patient, based on a deep understanding of the patient's unique characteristics combined with appropriate doctor-patient communication. The authors declare no conflict of interest. The patients in this manuscript have given written informed consent to the publication of their case details. I had full access to all the data in the study and I take responsibility for the integrity of the data and the accuracy of the data analysis as well as the decision to submit for publication.

Response

Botulinum toxin in treatment of axial dystonia

BackgroundFollowing repeated botulinum toxin (BTX) treatments, patients with hemifacial spasm (HFS) are recommended to undergo microvascular decompression (MVD) for a permanent cure. Intraoperative lateral spread response (LSR) monitoring is important to improve surgical outcomes. However, LSR monitoring during MVD surgery in HFS patients who have previously received BTX is challenging, since the muscles typically used to assess the LSR are paralyzed. Here, we describe our use of the upper part of the orbicularis oculi and mentalis muscles for intraoperative monitoring of the LSR during MVD in HFS patients following BTX treatment.MethodsHFS patients who underwent MVD surgery were divided into two groups based on their history of BTX treatment: BTX+ and BTX- groups. In the BTX+ group, MVD was performed at least 3 months after the last BTX injection. We measured LSR morphology, including the number of spikes, their duration, and maximum amplitude in all patients. We also measured intraoperative LSR disappearance rate, and the cure rate of HFS at the final follow-up (over 1 year after surgery).ResultsAlthough the waveforms showed a trend toward shorter durations with mandibular branch stimulation in the BTX+ group, there was no difference in the number of spikes or maximum amplitude values. There was no increase in LSR dysmetria after BTX treatment (BTX+ group: 32.8% vs. BTX- group: 31.9%). There was also no difference in intraoperative LSR disappearance rate between the two groups (BTX+ group: 68.3% vs. BTX- group: 74.6%).ConclusionIntraoperative LSR monitoring using the upper part of the orbicularis oculi muscle and the mentalis muscle at an interval of at least 3 months after the last BTX treatment might be a feasible monitoring technique during MVD for HFS.

Botulinum toxin(BTX)treatment is the first-line neurological treatment for hemifacial spasm(HFS). In my neurology clinic, Clinique Kita Neurologique(CKN), I have provided a cumulative total of approximately 400 BTX treatments for approximately 50 HFS patients for 23 years. Based on my own practical clinical experience, I have demonstrated the efficacy of BTX treatment. In compressive HFS, BTX treatment is indicated in patients who are not indicated or unwilling to undergo neurodecompression surgery. This is also indicated in the case of a long waiting period before surgery. In postparetic HFS, BTX treatment is indicated in patients with spasm and synkinesia. The amount of each BTX injection in postparetic HFS should be less than that in compressive HFS because of latent facial paresis. Although BTX injections can be easily administered in neurology outpatient clinics, it is important to perform the procedure safely and promptly.

Introduction: Dystonia can present in primary and secondary forms, depending on co-occurring symptoms and syndromic associations. In contrast to primary dystonia, secondary forms of dystonia are often associated with lesions in the putamen or globus pallidus. Such disorders are commonly neurodegenerative or neurometabolic conditions which produce varied neurologic as well as systemic manifestations other than dystonia. Chemo-denervation with botulinum toxin has been successfully used for focal or segmental dystonia. However, studies evaluating the effect of BoNT therapy on patients with secondary dystonia are sparse, given the heterogeneity in etiology and presentation. Methods: We present a series of patients with secondary dystonia who were managed with botulinum toxin therapy. Patients included in this series had a confirmed neurometabolic cause of dystonia. Results: A total of 14 patients, with ages ranging from 17 to 36 years, with disorders including Wilson’s disease, pantothenate kinase-associated neurodegeneration (PKAN), Niemann–Pick disease type C (NPC), glutaric aciduria type 1, Sanfilippo syndrome (Mucopolysaccharidosis Type IIIb), and GM2 gangliosidosis (Sandhoff disease) are presented. Most patients experienced a mild to moderate improvement in treated dystonia with benefits ranging from 6 to 12 weeks, with the median length of the benefits lasting approximately eight weeks, without any significant adverse effects. Conclusion: Although the secondary causes of dystonia are complex and diverse, our presented data and the available reports of the use of botulinum toxin support the conclusion that chemo-denervation plays an important role in symptom alleviation.

Abstracts from the TOXINS 2012

To investigate the effect of botulinum toxin-A (BTX-A) treatment on corneal topography, ocular biometry and keratometry in patients with benign essential blepharospasm (BEB) and hemifacial spasm (HFS). This study comprised 66 eyes of 33 patients with BEB and 5 eyes of 5 patients with HFS who underwent BTX-A injections consecutively. Refractive error values, tear break-up time (TBUT), corneal topography [corneal power of flat axis (K1) and steep axis (K2), mean corneal power (Km), corneal astigmatism (K2-K1)] and ocular optical biometry [axial length (AL), anterior chamber depth (ACD)] were recorded before BTX-A treatment and 1 month after BTX-A treatment. The researchers calculated the expected emmetropic intraocular lens power (emm-IOL) using the SRK-T, Holladay, Hoffer-Q and Haigis formulas at each examination. K1 (43.48 ± 2.02 vs. 43.57 ± 2.08, p = 0.036), Km (43.91 ± 1.99 vs. 43.99 ± 2.06, p = 0.024) and ACD (3.22 (2.77-3.76) vs. 3.41 (2.99-4.02), p < 0.001) values were found to be significantly higher. The expected emm-IOL according to the SRK-T (21.04 ± 1.6 vs. 20.93 ± 1.6, p = 0.048), Holladay (21.05 ± 1.6 vs. 20.91 ± 1.62, p = 0.037) and Hoffer-Q (21.08 ± 1.65 vs. 20.94 ± 1.68, p = 0.038) decreased significantly. The expected emm-IOL according to the Haigis formula slightly decreased, but it was not significant (p = 0.386). Additionally, TBUT was found to be significantly lower (p < 0.001) after BTX-A injection. Other parameters were not statistically significant (p > 0.05). Our study is the first in the literature to compare optic biometry data and intraocular lens power calculation formulas before and after BTX-A injection in eyes with BEB and HFS. BTX-A injection could play an important role in changing the keratometric and ACD values. It should be considered that IOL power calculations that might be unpredictable due to blepharospasm, so repeated measurements and especially measurements after releasing the spasm with BTX-A injections, are necessary in BEB and HFS.