Systematic Review and Meta‐Analysis of Secondary Treatment Failure and Immunogenicity With Botulinum Neurotoxin A in Multiple Indications

BackgroundCardiovascular disease (CVD) and CVD risk factors are highly prevalent in rheumatoid arthritis (RA) and associated with morbidity and mortality. We previously reported an association between CVD risk factors and...

Poststroke spasticity (PSS) is a common complication associated with other signs and symptoms of the upper motor neuron syndrome, including agonist/antagonist co-contraction, weakness, and lack of coordination. Together, they result in impairments and functional problems that can predispose to costly complications. The goal of PSS management should take into consideration not only reduction of muscle hypertonia but also the impact of PSS on function and well-being. Therapeutic interventions focus on peripheral and central strategies, such as physical techniques to increase muscle length through stretching and pharmacological modulation. Although there are few comparative studies on the superiority of one method over another, it appears that optimal management of PSS involves a combined and coordinated compendium of therapies that encompass cost-effective pharmacological and surgical interventions, along with rehabilitative efforts. Spasticity, commonly defined as “a motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with exaggerated tendon jerks, resulting from hyperexcitability of the stretch reflex, as one component of the upper motor neuron syndrome,”1 is a common complication of stroke. It contributes to the impairments and disabilities that negatively impact functional recovery. Consequently, PSS, along with weakness and lack of coordination, result in gait abnormalities and problems with arm use. In addition to functional limitations, spasticity, when inappropriately treated, may lead to reduced quality of life, increased pain, and joint contractures. Three community-based studies that followed-up stroke survivors for 3 to 12 months reported an incidence of PSS between 17% and 43%.2–4 Certain factors are recognized as predictors of PSS: stroke lesions in the brain stem; hemorrhagic stroke and younger age;5 and severe paresis and hemihypesthesia at stroke onset.3 To quantify the full impact of PSS, assessment should include a measure of passive stretch, volitional movement, and active/passive function.6,7 The benefit of …

Systematic Review and Meta-Analysis of Secondary Treatment Failure and Immunogenicity with Botulinum Neurotoxin A in Multiple Indications-Comment on Recommending IncobotulinumtoxinA as First-Line to Prevent Secondary Treatment Failure [Letter

Cervical dystonia (CD) is the most common form of focal dystonia with Botulinum neurotoxin (BoNT) being a frequent method of treatment. Dysphagia is a common side effect of BoNT treatment for CD. Instrumental evaluation of swallowing in CD using standardized scoring for the videofluoroscopic swallowing study (VFSS) and validated and reliable patient-reported outcomes measures is lacking in the literature. (1) to determine if BoNT injections change instrumental findings of swallowing function using the Modified Barium Swallow Impairment Profile (MBSImP) in individuals with CD; (2) to determine if BoNT injections change self-perception of the psychosocial handicapping effects of dysphagia in individuals with CD, using the Dysphagia Handicap Index (DHI); (3) to determine the effect of BoNT dosage on instrumental swallowing evaluation and self-reported swallowing outcomes measures. 18 subjects with CD completed a VFSS and the DHI before and after BoNT injection. There was a significant increase in pharyngeal residue for pudding consistency after BoNT injection, p = 0.015. There were significant positive associations between BoNT dosage and self-perception of the physical attributes of the handicapping effect of dysphagia, the grand total score and patient self-reported severity of dysphagia on the DHI; p = 0.022; p = 0.037; p = 0.035 respectively. There were several significant associations between changes in MBSImP scores and BoNT dose. Pharyngeal efficiency of swallowing may be affected by BoNT for thicker consistencies. Individuals with CD perceive greater physical handicapping effects of dysphagia with increased amounts of BoNT units and have greater self-perceptions of dysphagia severity with increased amounts of BoNT units.

Comparison of Botulinum Neurotoxin Preparations for the Treatment of Cervical Dystonia

BackgroundBotulinum toxins are considered first-line therapy for treatment of cervical dystonia (CD) and must be injected on a repeat basis. Understanding the duration of clinical benefit of botulinum toxins and its impact on health care utilization are thus important in the contemporary environment. However, there is currently no overall consensus on the duration of effect of onabotulinumtoxinA in the treatment of CD. We performed a systematic review and meta-analysis to identify the duration of effect of onabotulinumtoxinA in CD and investigate factors that may influence it.MethodsA systematic literature search identified prospective or retrospective studies reporting duration of effect of onabotulinumtoxinA for the treatment of CD. Inclusion criteria included peer-reviewed, non-review, English-language articles published between January 1980 and January 2013. A formal meta-analysis using Comprehensive Meta-Analysis Version 2 was conducted to identify the duration of effect of onabotulinumtoxinA in the treatment of CD; both fixed and random effects models were performed. Subgroup analyses were performed to identify factors that influenced the duration of effect of onabotulinumtoxinA.ResultsA total of 18 studies (including >1,900 patients) met the inclusion criteria and were used for the meta-analysis. The mean duration of effect of onabotulinumtoxinA in CD was found to be 93.2 days (95% CI 91.8-94.6 days) for the fixed effects model and 95.2 days (95% CI 88.9-101.4 days) for the random effects model. A meta-regression found that dose of onabotulinumtoxinA and country of origin influenced the duration of effect of onabotulinumtoxinA, whereas quality score of the article and study type did not. In particular, doses ≥180 Units were associated with longer durations of effect than doses <180 Units (107-109 days vs. 86-88 days, respectively; p < 0.01). Limitations included pooling studies that used discrete definitions of duration and had different designs and study quality.ConclusionsBased on the published literature, the mean duration of effect of onabotulinumtoxinA in CD was 93-95 days (13.2-13.5 weeks). This suggests that, in general, patients with CD treated with onabotulinumtoxinA should require ~4 treatments per year.

Monitorización farmacocinética de adalimumab como marcador precoz de fallo secundario en los pacientes con psoriasis en placa moderada-grave

Cosmetic botulinum toxin type A (BTX-A) injections have been widely used for improving facial aesthetics. Although the procedure is generally safe, immune-mediated adverse events, such as hypersensitivity reactions and secondary treatment failures, may rarely occur. We report the first case in which repeated BTX-A injections resulted in both a delayed-onset cutaneous hypersensitivity reaction and complete secondary treatment failure. A 42-year-old female, with a history of successful BTX-A treatments for glabellar lines and masseter hypertrophy, experienced diminished efficacy following a treatment session. Ten hours after a touch-up injection, she developed facial swelling and edematous erythema localized to the injection sites. These manifestations persisted for over one month without any observable aesthetic improvement, indicating complete secondary treatment failure. The therapeutic effect was not restored even after switching to an alternative BTX-A formulation. We hypothesize that the patient's local hypersensitivity reaction represents a type III immune complex-mediated response (Arthus reaction) driven by IgG antibodies. The repeated BTX-A injections may have induced neutralizing IgG antibodies that, in concert with the cutaneous hypersensitivity reaction, contributed synergistically to both the cutaneous reaction and the complete treatment failure. The short interval between the injections may have facilitated these immunologic events. This case underscores the importance for clinicians to remain vigilant regarding the potential for delayed-onset cutaneous allergic reactions and complete secondary treatment failure following repeated BTX-A injections.

Although botulinum neurotoxin A has been used for many years to treat focal dystonia-like blepharospasm (BLSP), cervical dystonia (CD), and hemifacial spasm (HFS) as vascular compression disorder of the facial nerve, there are few data on its long-term efficacy. We analysed dosages and injection intervals in a group of 130 patients with various focal dystonias treated for 6-16 years. During the observation period from 2000 to 2006, the mean dosage required to obtain appropriate clinical benefit increased only slightly in BLSP and HSF. In CD however, significantly higher doses were necessary for good clinical results. The mean intervals between injection varied highly between individual patients but did not change significantly between 2000 and 2006. Adverse effects, mostly minor, were reported in 4.2% of all treatment cycles in HSF; the frequencies were 3.8 for BLSP and 2.9 for CD, respectively. None of the patients stopped treatment because of resistance due to antibodies. Botulinum neurotoxin A is effective in long-term treatment of focal dystonia when injection intervals and dosages are chosen carefully.

On a group level, satisfaction with botulinum neurotoxin (BoNT) treatment in neurological indications is high. However, it is well known that a relevant amount of patients may not respond as expected. The aim of this study is to evaluate the BoNT treatment outcome on an individual level using a statistical single-case analysis as an adjunct to traditional group statistics. The course of the daily perceived severity of symptoms across a BoNT cycle was analyzed in 20 cervical dystonia (CD) and 15 hemifacial spasm (HFS) patients. A parametric single-case autoregressive integrated moving average (ARIMA) time series analysis was used to detect individual responsiveness to BoNT treatment. Overall, both CD and HFS patients significantly responded to BoNT treatment with a gradual worsening of symptom intensities towards BoNT reinjection. However, only 8/20 CD patients (40%) and 5/15 HFS patients (33.3%) displayed the expected U-shaped curve of BoNT efficacy across a single treatment cycle. CD (but not HFS) patients who followed the expected outcome course had longer BoNT injection intervals, showed a better match to objective symptom assessments, and were characterized by a stronger certainty to control their somatic symptoms (i.e., internal medical locus of control). In addition to standard evaluation procedures, patients should be identified who do not follow the mean course-of-treatment effect. Thus, the ARIMA single-case time series analysis seems to be an appropriate addition to clinical treatment studies in order to detect individual courses of subjective symptom intensities.

Human T-cell responses to botulinum neurotoxin. Responses in vitro of lymphocytes from patients with cervical dystonia and/or other movement disorders treated with BoNT/A or BoNT/B

Introduction and aim: Botulinum neurotoxin (BoNT), a protein naturally produced by bacteria from the Clostridium family, has evolved into a cornerstone therapy in neurology. The aim of this article is to examine the clinical applications, safety profiles and emerging applications of BoTN in neurology. Review methods: This review is based on publicly avalible PubMed, MDPI and Google Scholar databases, targeting studies published between January 2019 and March 2025. Search terms included “botulinum toxin in neurology”, “BoNT-A in spasticity,” “chronic migraine,” “neuropathic pain treatment” “dystonia treatment”, “hemifacial spasm treatment” and “BoNT-A/B”. Brief description of the state of the art: Through its mechanism of action—blocking acetylcholine release by cleaving SNARE proteins—BoNT enables localized and reversible neuromuscular blockade. Upon oral ingestion, BoNT causes the neuroparalytic syndrome botulism, but BoNT injections are used to manage chronic medical conditions across multiple indications. Since its first therapeutic use in the 1980s, BoNT has been widely adopted for medical and cosmetic applications. In addition to its established role in treating hyperkinetic movement disorders such as dystonia and spasticity, BoNT has demonstrated significant effectiveness in managing a range of autonomic nervous system disorders. Especially serotyoes A and B are utilized, showing both safety and efficacy. Summary: Applications of botulinum toxin have demonstrated continued growth in therapeutic scope, reinforcing its value across neurology. With the accumulation of clinical evidence and technological advancements, BoNT’s role is constantly expanding and offering targeted relief with minimal systemic effects.

Introduction Thoracic outlet syndrome (TOS) is a rare, often perplexing disorder caused by compression of neurovascular structures, leading to cervicogenic–brachial pain and other symptoms in neck and upper limb. Thoracic outlet syndrome is a group of disorders, not a single disorder, and patients may present with a wide variety of signs and symptoms. The wide range of symptoms and signs in TOS may confound clinicians unfamiliar with this condition (Sanders et al ., 2008; Ferrante, 2012; Foley et al ., 2012). Again, because TOS is a group of disorders, there is no “gold standard” to establish the diagnosis. This may lead to misdiagnosis or overdiagnosis of TOS in patients who present with symptoms suggesting TOS but who have other causes for their symptoms. It is, therefore, imperative that physicians be familiar with the range of symptoms and signs of TOS and testing that either supports or refutes this diagnosis. It is also critical that the diagnosis be correctly established before proceeding to invasive interventions for a presumed diagnosis of TOS, including botulinum neurotoxin (BoNT) injections. One of the many emerging applications for BoNT therapy is for the treatment of musculoskeletal pain disorders, including TOS. While the efficacy of BoNT on decreasing pain associated with cervical dystonia and chronic migraine is established, the antinocioceptive mechanism of action of BoNT is not fully understood (Mense, 2004; Aoki, 2005). Reports of reduced pain with BoNT have been reported in various musculoskeletal pain disorders, including joint pain, myofascial pain and cerebral palsy (Barwood et al ., 2000; Gobel et al ., 2006; Singh et al ., 2009). Although there are numerous reports in the literature citing the efficacy of BoNT for pain and other symptoms associated with TOS, additional research is needed to establish the role of BoNT in TOS and other pain disorders (Jordan et al ., 2007; Danielson and Odderson, 2008; Torriani et al ., 2010; Foley et al ., 2012). The proposed mechanism of action includes reduced muscle spasm leading to decreased compression of neurovascular structures (Jordan et al ., 2007; Tsao, 2007; Danielson and Odderson, 2008). Injection of BoNT into muscles also leads to denervation atrophy, which may reduce compression and neurogenic or vasogenic symptoms. It has also been reported that BoNT reduces the release of nocioceptive neurotransmitters, which could also be a contributing factor in reduced pain in TOS.

Botulinum neurotoxin A (BoNT) is the first line treatment for cervical dystonia (CD) and treatment outcome significantly depends on the correct identification of the muscles involved. In a case with insufficient response to BoNT treatment further work up with magnetic resonance imaging (MRI) of the neck revealed a hypertrophic spinalis cervicis muscle, that is not commonly involved in CD. This highlights the use of MRI for muscle selection in treatment refractory CD cases.

A 29-year-old man with Kallmann syndrome suddenly developed decreased semen volume, azoospermia, and facial hair loss after 11 years of successful human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG) treatment. Anti-hCG antibody was not detected in the patient's serum. A high serum level of luteinizing hormone (LH) with nasal LH-releasing hormone analogue administration failed to increase serum testosterone to a sufficient level. Testosterone injection after cessation of hCG and hMG therapy was able to improve semen volume, but not azoospermia. Resumption of hCG and hMG therapy after 6 months cessation partially restored spermatogenesis. The secondary failure of hCG and hMG therapy suggests a decrease of testicular sensitivity to LH as well as hCG.