A systematic review of the perspectives of botulinum toxin use on the quality of life of neurological patients with drooling.

OBJECTIVE: To investigate the effectiveness of botulinum toxin in the salivary glands of patients with neurological impairment and drooling and its impact on the quality of life. MATERIALS AND METHODS: This systematic review was registered with the International Prospective Register of Systematic Reviews (CRD 42,023,435,242) and conducted using the Preferred Reporting Items for Systematic Reviews and Meta-analyses. An electronic search was performed in the PubMed/MEDLINE, Embase, Scopus, Cochrane Library, and clinical trial databases until August 2023, no language restriction. Cohort studies and randomized clinical trials of patients diagnosed with drooling and neurological impairment who used botulinum toxin on the salivary gland were included, which evaluated subjective quality of life parameters. The risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist and Risk of Bias 2 tools. The certainty of the evidence was analyzed using the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: Eight studies involving 317 patients were included. All studies, through subjective parameters, suggested the effectiveness of botulinum toxin in reducing drooling, resulting in an improvement in the quality of life. Three studies demonstrated improvements in swallowing and four in cases of respiratory diseases. Two clinical trials had a high risk of bias, whereas one had low risk. The five cohort studies that were evaluated had a high risk of bias. The certainty of the evidence was considered low. CONCLUSIONS: Based on the patient/caregivers' perception of improvement in drooling, dysphagia, and respiratory symptoms, it can be inferred that botulinum toxin application reduces subjective drooling in neurologically compromised patients. Its impact contributes to the general well-being and quality of life. CLINICAL RELEVANCE: Injection of botulinum toxin into the salivary glands can be considered an alternative technique to surgical or medicinal approaches in reducing drooling. It is effective, less invasive and without significant side effects. It promotes a positive impact on the well-being and quality of life of neurological patients.

A systematic review of procedural modalities in the treatment of notalgia paresthetica.

BACKGROUND: Notalgia paresthetica (NP) is a rare condition characterized by localized pain and pruritus of the upper back, associated with a distinct area of hyperpigmentation. Given the lack of standardized treatment and the uncertain efficacy of available options, applying procedural methods is of growing interest in treating NP. AIMS: We sought to comprehensively evaluate the role of procedural treatments for NP. METHODS: We systematically searched PubMed/Medline, Ovid Embase, and Web of Science until November 14th, 2023. We also performed a citation search to detect all relevant studies. Original clinical studies published in the English language were included. RESULTS: Out of 243 articles, sixteen studies have reported various procedural modalities, with or without pharmacological components, in treating NP. Pharmacological procedures, including injections of botulinum toxin, lidocaine, and corticosteroids, led to a level of improvement in case reports and case series. However, botulinum toxin did not show acceptable results in a clinical trial. Moreover, non-pharmacological procedures were as follows: physical therapy, exercise therapy, kinesiotherapy, acupuncture and dry needling, electrical muscle stimulation, surgical decompression, and phototherapy. These treatments result in significant symptom control in refractory cases. Physical therapy can be considered a first-line choice or an alternative in refractory cases. CONCLUSION: Procedural modalities are critical in the multidisciplinary approach to NP, especially for patients who are refractory to topical and oral treatments. Procedural modalities include a spectrum of options that can be applied based on the disease's symptoms and severity.

Combined rehabilitation therapy with botulinum toxin to the upper limbs for acute spinal cord injury: A case report.

INTRODUCTION: Patients with spinal cord injury (SCI) and incomplete paralysis may experience muscle immobilization due to functional impairment of agonist and antagonist muscles. This can induce spasticity and pain, with the risk of contracture increasing as the period of immobilization increases. This could be aggravated by pain, which interferes with rehabilitation. There is no established treatment for pain and joint contractures caused by acute SCI. Botulinum therapy plays a role in relieving muscle tension. Here, we report a case of acute SCI in which botulinum therapy was administered. CASE PRESENTATION: The patient experienced a C5-cervical SCI due to a road traffic accident, with marked paralysis in the upper and lower limbs below the C5 level. The patient had persistent elbow flexion since the SCI and complained of excruciating pain, making adequate rehabilitation difficult. Botulinum toxin was administered to the biceps and brachialis muscles 15 days after the SCI. After administration, the patient experienced a reduction in pain with relaxation of the elbow flexor muscles, and rehabilitation treatment was resumed. This patient's contracture did not worsen, his pain decreased, and he was able to initiate self-feeding training. DISCUSSION: In this case, occupational and physical therapy was administered with botulinum therapy. Together, they successfully reduced pain. Botulinum therapy provides analgesia and muscle relaxation and may lead to functional recovery, and we believe that treatment can be considered even in the acute phase.

Iatrogenic botulism cases after gastric and axillary application of botulinum toxin and review of literature.

INTRODUCTION: Iatrogenic botulism is a rare, serious disease that progresses with descending paralysis and develops after cosmetic or therapeutic botulinum toxin-A (BoNT-A) application. CASE PRESENTATIONS: In this case series; six cases of iatrogenic botulism followed up in our center are presented. Four of these developed after gastric BoNT-A and two after axillary BoNT-A application. RESULTS: The most important cause for the disease was the use of unlicensed products and high-dose toxin applications. The first symptoms were blurred vision, double vision, difficulty in swallowing, and hoarseness. Symptoms appeared within 4-10 days after the application of BoNT-A. Symptoms progressed in the course of descending paralysis in the following days with fatigue, weakness in extremities and respiratory distress. Diagnosis was based on patient history and clinical findings. The main principles of foodborne botulism therapy were applied in the treatment of iatrogenic botulism. If clinical worsening continued, regardless of the time elapsed after BoNT-A application, the use of botulinum antitoxin made a significant contribution to clinical improvement and was recommended. CONCLUSIONS: Routine and new indications for BoNT-A usage are increasing and, as a result, cases of iatrogenic botulism will be encountered more frequently. Physicians should be alert for iatrogenic botulism in the follow-up after BoNT-A applications and in the differential diagnosis of neurological diseases that are presented with similar findings.

Recent Developments in Engineering Non-Paralytic Botulinum Molecules for Therapeutic Applications.

This review discusses the expanding application of botulinum neurotoxin in treating neurological conditions. The article specifically explores novel approaches to using non-paralytic botulinum molecules. These new molecules, such as BiTox or el-iBoNT, offer an alternative for patients who face limitations in using paralytic forms of botulinum neurotoxin due to concerns about muscle function loss. We highlight the research findings that confirm not only the effectiveness of these molecules but also their reduced paralytic effect. We also discuss a potential cause for the diminished paralytic action of these molecules, specifically changes in the spatial parameters of the new botulinum molecules. In summary, this article reviews the current research that enhances our understanding of the application of new botulinum neurotoxins in the context of common conditions and suggests new avenues for developing more efficient molecules.

Sequelae Treatment Needs Following Peripheral Facial Palsy: Retrospective Analysis of 525 Patients.

OBJECTIVE: This study uses retrospective longitudinal data from a large unselected cohort of patients with peripheral facial paralysis to determine the prevalence and patient characteristic predictors of sequelae receiving intervention. STUDY DESIGN: Retrospective case review. SETTING: Karolinska University Hospital in Stockholm Sweden serves as the only tertiary facial palsy center in the region. Here, patients are diagnosed, are followed up, and undergo all major interventions. PATIENTS: All adult patients presenting with peripheral facial palsy due to idiopathic, zoster, or Borrelia origin at Karolinska, January 1, 2010 to December 31, 2011 with follow-up until December 2022. INTERVENTIONS: Patient charts were studied to identify patient characteristics, etiology, initial treatment, severity of palsy, and treatments targeting sequelae. MAIN OUTCOME MEASURES: Types of initial and late treatments were noted. Sunnybrook and/or House-Brackmann scales were used for palsy grading. RESULTS: Five hundred twenty-five patients were included. Thirty-three patients (6.3%) received botulinum toxin injections and/or surgical treatment. In this subgroup, 67% received corticosteroids compared to 85% of all patients ( p = 0.005), cardiovascular disease prevalence was higher (23 and 42%, respectively, p = 0.009). For 81 patients (15%), follow-up was discontinued although the last measurement was Sunnybrook less than 70 or House-Brackmann 3 to 6. CONCLUSIONS: Of patients with peripheral facial palsy, 6.3% underwent injections and/or surgical treatment within 12 years. However, due to a rather large proportion not presenting for follow-up, this might be an underestimation. Patients receiving late injections and/or surgical treatment had more comorbidities and received corticosteroid treatment to a significantly lower extent in the acute phase of disease.

Beyond Wrinkles: A Comprehensive Review of the Uses of Botulinum Toxin.

BACKGROUND: Botulinum neurotoxin (BoNT) exhibits inhibitory effects on the neuromuscular junction, and its use is well established in cosmetic dermatology. Our review aims to analyze the evidence for its use in the treatment of various dermatological, neurological, gastroenterological, ophthalmological, otorhinolaryngological, dental, urological, gynecological, and cardiovascular disorders. METHODS: A systematic review of the literature was performed for studies published between 2012 and 2022 that discussed the therapeutic use of BoNT in human participants. A total of 58 studies were selected for inclusion in this review.  Results: We discovered a large range of therapeutic applications of BoNT toxin beyond aesthetic and US Food and Drug Administration (FDA)-approved non-aesthetic uses.  Conclusions: BoNT is a powerful neurotoxin that has varied FDA-approved indications and has been studied in a wide range of therapeutic applications. Further investigation through higher power studies is needed to assess the potential of BoNT and expand its versatility across other medical specialties.  J Drugs Dermatol. 2024;23(3):173-186. doi:10.36849/JDD.7243e.

The state of the art in therapeutic administration of botulinum toxin in children with cerebral palsy: an integrative review.

OBJECTIVE: To describe the current state of the art in the therapeutic administration of botulinum toxin with indications, efficacy, and safety profile for children and adolescents with cerebral palsy. DATA SOURCE: An integrative review was conducted. The MEDLINE/PubMed database was searched twice within the last decade using distinct terms, and only studies written in the English language were included. The study population was limited to those aged 0-18 years. Articles that were duplicates or lacked sufficient methodology information were excluded. DATA SYNTHESIS: We found 256 articles, of which 105 were included. Among the included studies, most were conducted in developed countries. Botulinum toxin demonstrated good safety and efficacy in reducing spasticity, particularly when administered by a multidisciplinary rehabilitation team. It is primarily utilized to improve gait and upper limb function, facilitate hygiene care, reduce pain, prevent musculoskeletal deformities, and even decrease sialorrhea in patients without a functional prognosis for walking. CONCLUSIONS: The administration of botulinum toxin is safe and efficacious, especially when combined with a multi-professional rehabilitation team approach, which increases the probability of functional improvement. It can also be beneficial for patients with significant functional impairments to help with daily care tasks, such as hygiene, dressing, and reducing sialorrhea. Pediatricians must be familiar with this treatment and its indications to attend to and refer patients promptly when necessary, and to exploit their neuroplasticity. Further research on this topic is required in developing countries.

Musician's dystonia in a percussionist - clinical video analysis and botulinum toxin intervention: a case report.

OBJECTIVE: Musician's focal hand dystonia is a painless task-specific focal dystonia, which presents with involuntary movements, abnormal postures, and loss of fine motor dexterity. We report here the case of a 63-year-old male, percussionist, with african ethnicity, with musician's focal hand dystonia who was treated with botulinum toxin, and describe the results at 4-weeks follow up. METHODS: Clinical examination and video analysis revealed abnormal flexion of the 3rd finger, followed by flexion of the 4th and 5th fingers while playing the congas. Based on these findings, a diagnosis of musician's focal hand dystonia was established. Ten units of botulinum toxin were injected into the muscle fibres of the flexor digitorum superficialis corresponding to the 4th finger using electromyography and ultrasound guidance. Four weeks later, the patient reported a subjective 60% improvement in his performance. He emphasized the effect of botulinum toxin on performance speed and tension over the forearm and hand. CONCLUSION: Botulinum toxin is not a definitive treatment for musician's focal hand dystonia, but it may potentiate other definitive rehabilitation techniques. More research is needed to determine the long-term effects of botulinum toxin on function enhancement in musician's focal hand dystonia.

[Clinical characteristics and prognosis of 8 cases of severe infant botulism].

Objective: To summarize the clinical characteristics and prognosis of severe infant botulism and evaluate the therapeutic effect of botulinum antitoxin in the pediatric intensive care unit (PICU). Methods: The clinical data of 8 cases diagnosed with infantile botulism were retrospectively analyzed in the PICU of Beijing Children's Hospital from October 2019 to August 2023. Data of basic demographic information, clinical manifestations, laboratory tests, treatment and prognosis of each child were collected and analyzed using descriptive statistical methods. Results: Eight laboratory-confirmed cases of infant botulism were included in this study, all of which were male infants with an age of 6.0 (3.3,6.8) months. Three of the children were from Inner Mongolia Autonomous Region, 2 of them were from Hebei, and the other 3 were from Beijing, Shandong and Xinjiang Uyghur Autonomous Region, respectively. All the patients were previously healthy. In 4 of these cases, the possible cause was the ingestion of either honey and its products or sealed pickled food by the mother or child before the onset of the disease. The first symptom was poor milk intake (4 cases), followed by shallow shortness of breath (7 cases), limb weakness (7 cases) and so on. The typical signs were bilateral dilated pupils (8 cases) and decreased limb muscle strength (8 cases). The main subtype was type B (7 cases), and only 1 case was classified as type A. Six of the children were treated with antitoxin therapy for a duration of 24 (19, 49) d. Seven of them had invasive mechanical ventilation. All the patients survived upon discharge with a follow-up period of 29 d to 3 years and 8 months. Six patients had fully recovered, and 2 recently discharged patients were gradually recovering. Conclusions: For infants with suspected contact or ingestion of botulinum and presented with bilateral pupillary paralysis, muscle weakness and clear consciousness, the stool should be collected for diagnostic testing using a mouse bioassay as soon as possible. Type B was the most common type. The antitoxin treatment was effectiveness and the prognosis was well.

The effectiveness of physiotherapy for patients with isolated cervical dystonia: an updated systematic review and meta-analysis.

BACKGROUND: Cervical dystonia is a movement disorder typically characterized by a patterned and twisting movement of sustained or intermittent muscle contractions. Recently, new clinical trials are emerging, highlighting the potential benefit of physiotherapy (PT) on disease outcomes. Thus, the objective of this review is to update the effectiveness of PT on cervical dystonia disease outcomes and subsequently perform a meta-analysis. METHODS: Interventional studies published in English with adult patients with isolated cervical dystonia following a physiotherapy program were included. Relevant articles were searched in PubMed (MEDLINE), Web of Science, and Scopus. Cochrane and Joanna Briggs Institute risk of bias checklists were used for quality reporting. Meta-analysis was done using Review Manager 5.3 statistical software and a pooled mean difference for pain was presented. RESULTS: Fourteen articles were included in the review and two articles were included in the meta-analysis. The meta-analysis revealed that PT intervention had a significant effect on pain reduction scale (-5.00, 95% CI -6.26, -3.74) when used as an additional therapy with botulinum toxin (BoNT) injection. Additionally, findings indicate a possible positive effect of PT disease severity, disability, and quality of life. CONCLUSIONS: Physiotherapy in addition to BoNT is recommended to decrease pain. The findings suggest a reduction of disease severity, disability, and improvement in quality of life. The variety in the type and duration of PT interventions did not allow a clear recommendation of a specific type of PT.

Spatiotemporal Gait Differences before and after Botulinum Toxin in People with Focal Dystonia: A Pilot Study.

BACKGROUND: The impact of focal dystonia on gait has attracted little attention and remains elusive. Considering the importance of both visual and head control in gait, blepharospasm and cervical dystonia should affect gait. Improvement of cervical/eyelid control following botulinum toxin (BTX) injections would translate into gait changes. OBJECTIVES: To assess gait differences in people with focal dystonia before and after BTX treatment. METHODS: Ten patients with blepharospasm, 10 patients with cervical dystonia, and 20 healthy age- and gender-matched controls were included. Gait was assessed before and 1-month after BTX injections using Biodex Gait Trainer™ 3. Gait velocity, cadence, step length, step asymmetry, and variability of step length were compared between patients and controls, and between the two time-points using non-parametric statistics. RESULTS: At baseline, compared to controls, cervical dystonia patients showed reduced gait velocity, step length, and cadence. After BTX injections, while gait velocity and step length were significantly increased and step length variability reduced, gait parameters still differed between patients and controls. In blepharospasm patients, baseline gait velocity and step length were significantly smaller than in controls. After BTX injections, these gait parameters were significantly increased and variability decreased, so that patients no longer differed from controls. CONCLUSION: Gait differences exist between patients with focal dystonia not directly affecting the lower limbs and healthy controls. These gait abnormalities were improved differently by BTX treatment according to the type of dystonia. These disparities suggest different pathophysiological mechanisms and support the need for changes in rehabilitation routines in cervical dystonia.

[Botulinum Toxin Treatment for Hemifacial Spasm:Based on the Practical Clinical Experience in the Neurology Outpatient Clinic].

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.

[Pain and cervical dystonia]. / Schmerzen bei zervikaler Dystonie.

BACKGROUND: Dystonia is a hyperkinetic movement disorder that results in twisting, cramps and tremors due to sustained or intermittent muscle contractions. Cervical dystonia is the most common form of dystonia, in which the head, neck and/or shoulder areas are affected. In addition to these motor symptoms, pain and psychiatric symptoms are frequent in (cervical) dystonia. OBJECTIVE: Description of the incidence and evaluation of pain in cervical dystonia, summary and discussion of treatment options and effects. MATERIAL AND METHODS: In this review article the results in the scientific literature on pain in dystonia are summarized and discussed. RESULTS: Compared to other forms of dystonia, pain occurs most frequently in patients with cervical dystonia. A large proportion of patients with cervical dystonia suffer from pain, which contributes most to impairment of the patient. The motor symptoms of dystonia are usually treated with botulinum toxin injections. These have a muscle relaxing effect and also relieve pain. The study situation on the occurrence and treatment of pain in other forms of dystonia is so far very limited. Pain can dominate the clinical picture in patients with cervical dystonia. Evaluation of pain in cervical dystonia can be performed using standardized questionnaires. CONCLUSION: It is important to ask patients with cervical dystonia about pain and to consider it in treatment planning and evaluation. Vice versa, if pain is present the possibility of a causative dystonia should also be considered. For pain assessment there are some newly developed questionnaires to assess pain in a standardized way in patients with dystonia. Further research is needed to better understand the pathomechanisms of pain in dystonia.

Effects of glabellar botulinum toxin injections on resting-state functional connectivity in borderline personality disorder.

Meta-analyses suggest a sustained alleviation of depressive symptoms through glabellar botulinum toxin (BTX) injections. This can be explained by the disruption of facial feedback loops, which may moderate and reinforce the experience of negative emotions. Borderline personality disorder (BPD) is characterized by excessive negative emotions. Here, a seed-based resting-state functional connectivity (rsFC) analysis following BTX (N = 24) or acupuncture (ACU, N = 21) treatment in BPD is presented on areas related to the motor system and emotion processing. RsFC in BPD using a seed-based approach was analyzed. MRI data were measured before and 4 weeks after treatment. Based on previous research, the rsFC focus was on limbic and motor areas as well as the salience and default mode network. Clinically, after 4 weeks both groups showed a reduction of borderline symptoms. However, the anterior cingulate cortex (ACC) and the face area in the primary motor cortex (M1) displayed aberrant rsFC after BTX compared to ACU treatment. The M1 showed higher rsFC to the ACC after BTX treatment compared to ACU treatment. In addition, the ACC displayed an increased connectivity to the M1 as well as a decrease to the right cerebellum. This study shows first evidence for BTX-specific effects in the motor face region and the ACC. The observed effects of BTX on rsFC to areas are related to motor behavior. Since symptom improvement did not differ between the two groups, a BTX-specific effect seems plausible rather than a general therapeutic effect.

Essential Palatal Myoclonus and Clicking Tinnitus in a Nine-Year-Old Boy-A Case Report.

The work describes a case of palatal myoclonus with distressing tinnitus in a 9-year-old boy and its successful treatment with injections of botulinum toxin. This case report discusses common questions about myoclonic-induced clicking tinnitus and provides answers. Laryngoscope, 134:397-399, 2024.

A practical guide to botulinum neurotoxin treatment of teres major muscle in shoulder spasticity: Intramuscular neural distribution of teres major muscle in cadaver model.

BACKGROUND: Botulinum neurotoxin treatment typically focuses on the teres major muscle as a primary target for addressing shoulder spasticity. The muscle is located deep within a large muscle group and optimal injection locations have not been identified. OBJECTIVE: To identify the preferred location for administering botulinum toxin injections in the teres major muscle. METHODS: Teres major specimens were removed from 18 cadaveric models and stained with Sihler's method to reveal the neural distribution within the muscle. The muscles were systematically divided into equal lengths from origin to insertion. The neural density in each section was evaluated to determine the location that would be likely to increase effectiveness of the injection. RESULTS: The greatest density of intramuscular nerve endings was located in the middle 20% of the muscle. The tendinous portion was observed at the ends of the muscle. CONCLUSIONS: The results suggest that botulinum neurotoxin should be delivered in the middle 20% of the teres major muscle.