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1.
Cell ; 173(5): 1083-1097.e22, 2018 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-29754819

RESUMO

The nervous system, the immune system, and microbial pathogens interact closely at barrier tissues. Here, we find that a bacterial pathogen, Streptococcus pyogenes, hijacks pain and neuronal regulation of the immune response to promote bacterial survival. Necrotizing fasciitis is a life-threatening soft tissue infection in which "pain is out of proportion" to early physical manifestations. We find that S. pyogenes, the leading cause of necrotizing fasciitis, secretes streptolysin S (SLS) to directly activate nociceptor neurons and produce pain during infection. Nociceptors, in turn, release the neuropeptide calcitonin gene-related peptide (CGRP) into infected tissues, which inhibits the recruitment of neutrophils and opsonophagocytic killing of S. pyogenes. Botulinum neurotoxin A and CGRP antagonism block neuron-mediated suppression of host defense, thereby preventing and treating S. pyogenes necrotizing infection. We conclude that targeting the peripheral nervous system and blocking neuro-immune communication is a promising strategy to treat highly invasive bacterial infections. VIDEO ABSTRACT.


Assuntos
Neurônios/metabolismo , Neutrófilos/metabolismo , Infecções Estreptocócicas/patologia , Streptococcus pyogenes/patogenicidade , Animais , Proteínas de Bactérias/imunologia , Proteínas de Bactérias/metabolismo , Toxinas Botulínicas Tipo A/administração & dosagem , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Caspase 1/deficiência , Caspase 1/genética , Diterpenos/farmacologia , Fasciite Necrosante/etiologia , Fasciite Necrosante/patologia , Fasciite Necrosante/veterinária , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neutrófilos/imunologia , Dor/etiologia , Transdução de Sinais , Pele/metabolismo , Pele/patologia , Infecções Estreptocócicas/complicações , Infecções Estreptocócicas/veterinária , Streptococcus pyogenes/metabolismo , Estreptolisinas/imunologia , Estreptolisinas/metabolismo , Canais de Cátion TRPV/deficiência , Canais de Cátion TRPV/genética
2.
N Engl J Med ; 389(19): 1753-1765, 2023 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-37937777

RESUMO

BACKGROUND: Local injections of botulinum toxin type A have been used to treat essential head tremor but have not been extensively studied in randomized trials. METHODS: In a multicenter, double-blind, randomized trial, we assigned, in a 1:1 ratio, adult patients with essential or isolated head tremor to receive botulinum toxin type A or placebo. Botulinum toxin or placebo was injected under electromyographic guidance into each splenius capitis muscle on the day of randomization (day 0) and during week 12. The primary outcome was improvement by at least 2 points on the Clinical Global Impression of Change (CGI) scale at week 6 after the second injection (week 18 after randomization). The CGI scale was used to record the patient's assessment of the degree of improvement or worsening of head tremor since baseline; scores range from 3 (very much improved) to -3 (very much worse). Secondary outcomes included changes in tremor characteristics from baseline to weeks 6, 12, and 24. RESULTS: A total of 120 patients were enrolled; 3 patients were excluded during screening, and 117 patients were randomly assigned to receive botulinum toxin (62 patients) or placebo (55 patients) and were included in the intention-to-treat analysis. Twelve patients in the botulinum toxin group and 2 patients in the placebo group did not receive injections during week 12. The primary outcome - improvement by at least 2 points on the CGI scale at week 18 - was met by 31% of the patients in the botulinum toxin group as compared with 9% of those in the placebo group (relative risk, 3.37; 95% confidence interval, 1.35 to 8.42; P = 0.009). Analyses of secondary outcomes at 6 and 12 weeks but not at 24 weeks were generally supportive of the primary-outcome analysis. Adverse events occurred in approximately half the patients in the botulinum toxin group and included head and neck pain, posterior cervical weakness, and dysphagia. CONCLUSIONS: Injection of botulinum toxin into each splenius capitis muscle on day 0 and during week 12 was more effective than placebo in reducing the severity of isolated or essential head tremor at 18 weeks but not at 24 weeks, when the effects of injection might be expected to wane, and was associated with adverse events. (Funded by the French Ministry of Health; Btx-HT ClinicalTrials.gov number, NCT02555982.).


Assuntos
Toxinas Botulínicas Tipo A , Tremor Essencial , Fármacos Neuromusculares , Tremor , Adulto , Humanos , Toxinas Botulínicas Tipo A/administração & dosagem , Toxinas Botulínicas Tipo A/efeitos adversos , Toxinas Botulínicas Tipo A/uso terapêutico , Método Duplo-Cego , Tremor Essencial/tratamento farmacológico , Cabeça , Resultado do Tratamento , Tremor/tratamento farmacológico , Eletromiografia/métodos , Injeções Intramusculares/métodos , Cefaleia/induzido quimicamente , Cervicalgia/induzido quimicamente , Fármacos Neuromusculares/administração & dosagem , Fármacos Neuromusculares/efeitos adversos , Fármacos Neuromusculares/uso terapêutico
3.
Exp Dermatol ; 33(6): e15110, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38884423

RESUMO

Botulinum toxin A (BTX) and microwave thermolysis (MWT) are standard axillary hyperhidrosis treatments, but comparison of their subclinical effects is lacking. Line-field confocal optical coherence tomography (LC-OCT) is a promising non-invasive imaging tool for visualizing tissue-interactions. This study aimed to describe subclinical effects of BTX and MWT for axillary hyperhidrosis with LC-OCT-imaging compared to histology. This study derived from an intra-individual, randomized, controlled trial, treating axillary hyperhidrosis with BTX versus MWT. Subclinical effects based on LC-OCT images from baseline and 6-month follow-up (n = 8 patients) were evaluated and compared to corresponding histological samples. At baseline, LC-OCT visualized eccrine pores at the skin surface and ducts in the upper dermis (500 µm), but not deeper-lying sweat glands. Histology identified entire sweat glands. Six months post-treatment, LC-OCT revealed no detectable morphology changes in any BTX-treated axillae (100%), while recognizing obstructed eccrine pores and atrophy of eccrine ducts in most MWT-treated axillae (75%). Histology corroborated LC-OCT findings, while also showing substantial changes to entire sweat glands. LC-OCT enabled visualization of subclinical alterations of superficial eccrine ducts after MWT and unchanged morphology after BTX. LC-OCT is a promising tool for non-invasive assessment of treatment-specific tissue-interactions that can be complementary to histology.


Assuntos
Axila , Toxinas Botulínicas Tipo A , Hiperidrose , Micro-Ondas , Tomografia de Coerência Óptica , Hiperidrose/tratamento farmacológico , Hiperidrose/diagnóstico por imagem , Humanos , Tomografia de Coerência Óptica/métodos , Toxinas Botulínicas Tipo A/administração & dosagem , Adulto , Feminino , Masculino , Glândulas Sudoríparas/diagnóstico por imagem , Glândulas Sudoríparas/efeitos dos fármacos , Adulto Jovem , Pessoa de Meia-Idade , Glândulas Écrinas/diagnóstico por imagem , Glândulas Écrinas/efeitos dos fármacos
4.
Muscle Nerve ; 70(1): 28-35, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38529885

RESUMO

Botulinum toxin (BTX) injections into the musculature surrounding the brachial plexus have been examined as a potential treatment for neurogenic thoracic outlet syndrome (nTOS). This systematic review identified 15 publications, of which one was a randomized controlled trial. BTX injections performed with ultrasound or electromyographic guidance, and with the inclusion of the pectoralis minor muscle, in addition to the anterior and/or middle scalenes, tended to provide greater symptom improvement and may predict response to first rib resection. Importantly, most studies were of low quality; thus, the results should be interpreted with caution. Further high-quality studies are needed to confirm these findings.


Assuntos
Toxinas Botulínicas , Síndrome do Desfiladeiro Torácico , Síndrome do Desfiladeiro Torácico/tratamento farmacológico , Humanos , Toxinas Botulínicas/administração & dosagem , Toxinas Botulínicas/uso terapêutico , Fármacos Neuromusculares/administração & dosagem , Fármacos Neuromusculares/uso terapêutico , Injeções Intramusculares , Resultado do Tratamento , Toxinas Botulínicas Tipo A/administração & dosagem , Toxinas Botulínicas Tipo A/uso terapêutico
5.
Cephalalgia ; 44(6): 3331024241259452, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38870368

RESUMO

BACKGROUND: There is no defined preventive treatment protocol for persistent post-craniotomy headache. In several small case series and individual case reports onabotulinumtoxinA injected into the craniotomy scar has shown possible efficacy. What is lacking is long term follow-up and if focusing on the cranial suture lines along with the craniotomy scar can enhance improvement and provide more sustained benefit. METHODS: Retrospective chart review with case series. RESULTS: Four patients (three women, one man) with ICHD-3 defined persistent post craniotomy headache were treated using a novel onabotulinumtoxinA injection protocol. All the patients presented with continuous head pain of moderate to severe intensity. All had severe allodynia on the side of their craniotomy. All had significant reduction in quality of life. Our application of onabotulinumtoxinA involved injection into both the surgical scar and the transected/irritated cranial suture lines noted on neuroimaging and physical examination. With treatment all patients demonstrated significant benefit including a reduction in daily pain intensity (75%-100%), developing periods of pain freedom (2-7 days per week) and having a dramatic improvement in quality of life (close to 100% in all). The benefit was sustained for at least five years of follow-up. CONCLUSION: From our case series it appears that injection not only along the painful craniotomy scar but into the involved cranial suture lines provides positive efficacy and sustained improvement in patients with persistent post craniotomy headache.


Assuntos
Toxinas Botulínicas Tipo A , Cicatriz , Craniotomia , Humanos , Feminino , Craniotomia/efeitos adversos , Toxinas Botulínicas Tipo A/administração & dosagem , Toxinas Botulínicas Tipo A/uso terapêutico , Masculino , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Seguimentos , Suturas Cranianas/cirurgia , Resultado do Tratamento
6.
Headache ; 64(5): 589-594, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38533675

RESUMO

OBJECTIVES: To report the efficacy of onabotulinumtoxinA (BoNTA) injections in relieving pain in patients with primary trochlear headache (PRTH). METHODS: Examination of medical records for patients diagnosed with PRTH according to the International Classification of Headache Disorders, 3rd edition criteria and treated with BoNTA. Data were collected for variables related to pain relief, duration of effectiveness, and adverse effects. RESULTS: Six patients were included in the study. All had previously undergone standard care interventions, including infiltrations or oral treatments, yet experienced treatment failure or symptom recurrence. All patients received 20 units of BoNTA, administered in the corrugator and procerus muscles. Subsequent to the BoNTA injections, all six patients reported substantial pain relief, with five achieving complete remission of symptoms. The analgesic effect persisted for a duration of 3 months. No adverse events were reported in any of the cases. CONCLUSIONS: Our case series presents the first evidence of the potential of BoNTA as a safe and effective treatment option for PRTH. From a clinical standpoint, having a safer alternative is of paramount significance for patients with limited treatment options, such as those with PRTH. Further research is warranted to validate these findings and explore the long-term efficacy of BoNTA in PRTH management.


Assuntos
Toxinas Botulínicas Tipo A , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Liberação da Acetilcolina/administração & dosagem , Inibidores da Liberação da Acetilcolina/farmacologia , Toxinas Botulínicas Tipo A/administração & dosagem , Toxinas Botulínicas Tipo A/farmacologia , Transtornos da Cefaleia Primários/tratamento farmacológico , Fármacos Neuromusculares/administração & dosagem , Fármacos Neuromusculares/farmacologia , Estudos Retrospectivos , Resultado do Tratamento
7.
Headache ; 64(6): 663-673, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38700250

RESUMO

OBJECTIVE: To determine the tolerability and safety of concurrent peripheral nerve blocks and onabotulinumtoxinA treatment during a single outpatient clinic procedure visit. BACKGROUND: Procedural interventions are available for the treatment of headache disorders. OnabotulinumtoxinA and peripheral nerve blocks are used as alternatives or in addition to oral therapies to reduce the frequency and intensity of migraine attacks. There is currently a lack of safety data focusing on the sequential administration of local anesthetic via peripheral nerve blocks and onabotulinumtoxinA during a single clinical encounter for the treatment of headache. The primary aim of the study was to determine the safety and tolerability of concurrent peripheral nerve blockade and onabotulinumtoxinA injections during a single outpatient clinic procedure visit. We hypothesized that the dual intervention would be safe and well tolerated by patients with chronic migraine and other headache disorders. METHODS: A retrospective chart review was performed using clinical data from patients seen by multiple providers over a 16-month timeframe at one outpatient headache clinic. Patients were identified by procedure codes and those receiving peripheral nerve block(s) and onabotulinumtoxinA injections during a single encounter within the study period were eligible for inclusion. Inclusion criteria were (1) patients 18 years and older who were (2) receiving both peripheral nerve blocks and onabotulinumtoxinA injections for the treatment of chronic migraine. Patients were excluded if they were under age 18, received their procedure outside of the clinic (emergency room, inpatient ward), or were receiving sphenopalatine ganglion blocks. Age- and sex-matched patients who received one procedure, either peripheral nerve blocks or onabotulinumtoxinA, were used for control. The primary outcome of this safety study was the number of adverse events that occurred in the dual intervention group compared to the single intervention control arms. Information regarding adverse events was gathered via retrospective chart review. If an adverse event was recorded, it was then graded by the reviewer utilizing the Common Terminology Criteria for Adverse Events ranging from Grade 1 Mild Event to Grade 5 Death. Additionally, it was noted whether the adverse event led to treatment discontinuation. RESULTS: In total, 375 patients were considered eligible for inclusion in the study. After age and sex matching of controls, 131 patients receiving dual intervention were able to be compared to 131 patients receiving onabotulinumtoxinA alone and 104 patients receiving dual intervention were able to be compared to 104 patients receiving peripheral nerve block(s) alone. The primary endpoint analysis showed no significant difference in total adverse events between dual intervention compared to nerve blocks alone or onabotulinumtoxinA alone. The number of adverse events that led to treatment discontinuation approached but did not reach statistical significance for those receiving dual intervention versus onabotulinumtoxinA alone in the number of adverse events that led to treatment termination (4.6%, 6/131 vs. 0.8%, 1/131, p = 0.065); however, the number of patients who discontinued therapy was not significantly different between those groups (2.3%, 3/131 vs. 0.8%, 1/131; p = 0.314; odds ratio 0.3 [0-3.2]; p = 0.338). CONCLUSIONS: In this retrospective chart review, there was no significant difference in adverse events or therapy discontinuation between patients receiving sequential peripheral nerve block(s) and onabotulinumtoxinA injections versus those receiving either peripheral nerve block(s) or onabotulinumtoxinA injections alone. As a result, we concluded that the combination procedure is likely safe and well tolerated in routine clinical practice.


Assuntos
Toxinas Botulínicas Tipo A , Transtornos de Enxaqueca , Bloqueio Nervoso , Humanos , Toxinas Botulínicas Tipo A/administração & dosagem , Toxinas Botulínicas Tipo A/efeitos adversos , Toxinas Botulínicas Tipo A/farmacologia , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Bloqueio Nervoso/métodos , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos da Cefaleia/tratamento farmacológico , Fármacos Neuromusculares/administração & dosagem , Fármacos Neuromusculares/efeitos adversos , Fármacos Neuromusculares/farmacologia , Idoso , Anestésicos Locais/administração & dosagem , Anestésicos Locais/farmacologia
8.
Headache ; 64(6): 652-662, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38700141

RESUMO

OBJECTIVE: Migraine, a prevalent and debilitating disease, involves complex pathophysiology possibly including inflammation and heightened pain sensitivity. The current study utilized the complete Freund's adjuvant (CFA) model of inflammation, with onabotulinumtoxinA (BoNT/A) as a treatment of interest due to its use in clinical migraine management. Using an animal model, the study sought to investigate the role of BoNT/A in modulating CFA-induced inflammation, alterations in pain sensitivity, and the regulation of calcitonin gene-related peptide (CGRP) release. Further, we aimed to assess the changes in SNAP-25 through western blot analysis to gain insights into the mechanistic action of BoNT/A. METHODS: BoNT/A or control was administered subcutaneously at the periorbital region of rats 3 days before the induction of inflammation using CFA. Periorbital mechanical sensitivity was assessed post-inflammation, and alterations in CGRP release were evaluated. Changes in SNAP-25 levels were determined using western blot analysis. RESULTS: Upon CFA-induced inflammation, there was a marked increase in periorbital mechanical sensitivity, with the inflammation side showing increased sensitivity compared to other periorbital areas. BoNT/A did decrease the withdrawal thresholds in the electronic von Frey test. Despite not being able to observe differences in pain thresholds or CGRP release, BoNT/A reduced baseline release under CFA inflamed conditions. Analysis of SNAP-25 levels in the trigeminal ganglion revealed both intact and cleaved forms that were notably elevated in BoNT/A-treated animals. These findings, derived from western blot analysis, suggest an effect on neurotransmitter release. CONCLUSION: Our investigation highlights the role of BoNT/A in reducing baseline CGRP in the context of inflammation and its involvement in SNAP-25 cleavage. In contrast, BoNT/A did not appear to alter facial pain sensitivity induced by inflammation, suggesting that mechanisms other than baseline CGRP could be implicated in the elevated thresholds in the CFA model.


Assuntos
Toxinas Botulínicas Tipo A , Peptídeo Relacionado com Gene de Calcitonina , Modelos Animais de Doenças , Inflamação , Transtornos de Enxaqueca , Ratos Sprague-Dawley , Proteína 25 Associada a Sinaptossoma , Animais , Toxinas Botulínicas Tipo A/farmacologia , Toxinas Botulínicas Tipo A/administração & dosagem , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/metabolismo , Proteína 25 Associada a Sinaptossoma/metabolismo , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Inflamação/tratamento farmacológico , Ratos , Masculino , Adjuvante de Freund , Dor/tratamento farmacológico , Limiar da Dor/efeitos dos fármacos , Fármacos Neuromusculares/farmacologia , Fármacos Neuromusculares/administração & dosagem
9.
Dev Med Child Neurol ; 66(7): 919-930, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38140924

RESUMO

AIM: To develop robust multivariable prediction models for non-response to (1) submandibular botulinum neurotoxin A (BoNT-A) injections and (2) concurrent submandibular and parotid (four-gland) injections, to guide treatment decisions for drooling in children with neurodevelopmental disabilities, including cerebral palsy. METHOD: This was a retrospective cohort study including 262 children (155 males/107 females, median age 7 years 11 months [IQR 5 years 1 month], range 4 years 0 months - 17 years 11 months) receiving submandibular injections and 74 children (52 males/22 females, median age 7 years 7 months [IQR 4 years 3 months], range 4 years 9 months - 18 years 8 months) receiving four-gland injections. Multivariable logistic regression analyses were used to estimate associations between candidate predictors and non-response 8 weeks after injection. RESULTS: Ninety-six children (37%) were non-responders to submandibular injections, for which developmental age was the strongest predictor (adjusted odds ratio [aOR] 2.13; 95% confidence interval [CI] 1.02-4.45 for developmental age <4 years or 4-6 years with IQ <70). Other characteristics that showed a trend towards an increased risk of non-response were diagnosis, sex, and head position. Thirty-four children (46%) were non-responders to four-gland injections, for which tongue protrusion (aOR 3.10; 95% CI 1.14-8.43) seemed most predictive, whereas multiple preceding submandibular injections (aOR 0.34; 95% CI 0.10-1.16) showed a trend towards being protective. Predictors were, however, unstable across different definitions of non-response and both models (i.e. submandibular and four-gland) had insufficient discriminative ability. INTERPRETATION: Potential predictors of non-response to BoNT-A injections were identified. Nevertheless, the developed prediction models seemed inadequate for guidance of treatment decisions. WHAT THIS PAPER ADDS: Developmental age seemed most predictive of non-response to submandibular botulinum neurotoxin A injections. Non-response to concurrent submandibular and parotid injections was best predicted by tongue protrusion and number of previous injections. Multivariable prediction models including these clinical characteristics were unable to discriminate well. Predictors differed when non-response was defined using alternative outcome measures.


Assuntos
Toxinas Botulínicas Tipo A , Transtornos do Neurodesenvolvimento , Sialorreia , Glândula Submandibular , Humanos , Sialorreia/tratamento farmacológico , Sialorreia/etiologia , Masculino , Feminino , Toxinas Botulínicas Tipo A/administração & dosagem , Toxinas Botulínicas Tipo A/farmacologia , Criança , Pré-Escolar , Adolescente , Estudos Retrospectivos , Glândula Submandibular/efeitos dos fármacos , Fármacos Neuromusculares/administração & dosagem , Fármacos Neuromusculares/farmacologia , Paralisia Cerebral/complicações , Paralisia Cerebral/tratamento farmacológico , Glândula Parótida
10.
Neurol Sci ; 45(7): 3509-3511, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38548894

RESUMO

BACKGROUND: Hemiballism (HB) and hemichorea (HC) are the most frequent secondary movement disorders, usually caused by cerebrovascular diseases. In only a minority of cases, these involuntary movements are not self-limited, and they may severely compromise patients' quality of life, so that symptomatic treatments are required. Typical and atypical neuroleptics as well as tetrabenazine are considered therapies of choice. However, anecdotal reports of antiseizures medications and botulinum neurotoxin injection effectiveness have been described. METHODS: We described a case of severely disabling acute-onset lesional HB/HC, where high dosage of first- and second-line therapies was contraindicated due to patient's comorbidities. RESULTS: After botulin neurotoxin (BoNT) injections in his left upper limb muscles (biceps brachii, triceps brachii, teres major, and deltoid), the patient experienced gradual reduction of hyperkinetic movements. The gradual discontinuation of topiramate (TPM) did not worsen the clinical picture. DISCUSSION: The reduction of hyperkinetic movements led to rhabdomyolysis resolution as well as cutaneous injuries healing with renal function improvement, so that the patient was able to be eligible for rehabilitation, which was prevented by HB/HC itself. The clinical improvement was consistent with BoNT pharmacokinetic. The administration of BoNT early after the onset of lesional HB/HC remarkably modified the clinical management and drove toward comorbidities resolution and rehabilitation. CONCLUSION: The present case highlights the effectiveness of unconventional therapeutic options in disabling acute onset lesional HB/HC when first-line therapies are contraindicated. Particularly, this report may encourage BoNT application in the early stage of movement disorder emergencies.


Assuntos
Discinesias , Humanos , Masculino , Discinesias/tratamento farmacológico , Discinesias/etiologia , Fármacos Neuromusculares/administração & dosagem , Fármacos Neuromusculares/uso terapêutico , Toxinas Botulínicas Tipo A/administração & dosagem , Toxinas Botulínicas Tipo A/uso terapêutico , Coreia/tratamento farmacológico , Pessoa de Meia-Idade
11.
Dermatol Surg ; 50(6): 535-541, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38470985

RESUMO

BACKGROUND: Hyperfunctional glabellar frown lines can transmit facial miscues that adversely affect emotional communication, increase perceptions of age, and diminish self-esteem. OBJECTIVE: To evaluate the efficacy of letibotulinumtoxinA in mitigating the negative psychological impact associated with moderate to severe glabellar lines and to assess subject satisfaction with treatment outcome in the BLESS phase 3 clinical trials. MATERIALS AND METHODS: Baseline and posttreatment assessments were made using validated subject-administered instruments: Modified Skindex-16 Glabellar Line Quality of Life (GL-QoL) Scale, Facial Assessment and Cosmetic Evaluation Questionnaire (FACE-Q) Appraisal of Lines Between Eyebrows Scale, FACE-Q Age Appraisal Visual Analog Scale, and FACE-Q Satisfaction with Outcome Scale. An integrated analysis using pooled BLESS data was conducted on these secondary end points. RESULTS: Among enrolled and treated subjects ( N = 1,272), 85.5% had moderate to severe psychological impact at baseline. LetibotulinumtoxinA subjects experienced significant improvements compared with placebo on all measures. Mean improvement to Week 4 for the Modified Skindex-16 GL-QoL Scale overall score was -33.84 for letibotulinumtoxinA subjects compared with -1.37 for placebo subjects ( p < .001). Attenuation of psychological burden was highly correlated with improvement in glabellar line severity ( p < .0001). CONCLUSION: LetibotulinumtoxinA significantly improved the psychosocial burden associated with glabellar lines across all trials. Treated subjects experienced improved quality of life, younger perceived age, and satisfaction with treatment outcome.


Assuntos
Toxinas Botulínicas Tipo A , Testa , Satisfação do Paciente , Qualidade de Vida , Envelhecimento da Pele , Humanos , Toxinas Botulínicas Tipo A/administração & dosagem , Feminino , Masculino , Pessoa de Meia-Idade , Envelhecimento da Pele/efeitos dos fármacos , Adulto , Resultado do Tratamento , Método Duplo-Cego , Idoso , Inquéritos e Questionários , Técnicas Cosméticas/psicologia , Fármacos Neuromusculares/administração & dosagem
12.
Dermatol Surg ; 50(6): 527-533, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38518110

RESUMO

BACKGROUND: Despite the widespread use of botulinum toxin (BTX) injection for the treatment of masseter muscle hypertrophy (MMH), there is no standard treatment option. OBJECTIVE: We report the efficacy and safety for BTX in MMH over a period of 48 weeks. METHODS: In double-blinded, placebo-controlled phase 3 trials, 180 patients (randomized 1:1) received treatment with placebo (normal saline) or prabotulinumtoxinA (48 units). Masseter muscle thickness (at maximal clenching and resting positions), 3D imaging analysis, and masseter muscle hypertrophy scale grades were analyzed at each time point. After the 24-week CORE study, all patients who met the same criteria of the CORE study at week 24 ( n = 114) received only prabotulinumtoxinA, regardless of previous treatment, for an additional 24 weeks (48 weeks in total) for the open-label extension study. RESULTS: The largest differences in mean and percent changes from baseline in masseter muscle thickness were observed at 12 weeks, and there were significant differences between the 2 groups at all time points (all p < .001). The effect was independent of the number of injections. No serious adverse event was observed. CONCLUSION: PrabotulinumtoxinA could effectively ameliorate MMH without major complications.


Assuntos
Toxinas Botulínicas Tipo A , Hipertrofia , Músculo Masseter , Humanos , Toxinas Botulínicas Tipo A/administração & dosagem , Toxinas Botulínicas Tipo A/efeitos adversos , Método Duplo-Cego , Hipertrofia/tratamento farmacológico , Músculo Masseter/efeitos dos fármacos , Músculo Masseter/patologia , Músculo Masseter/anormalidades , Feminino , Pessoa de Meia-Idade , Adulto , Masculino , Resultado do Tratamento , Fármacos Neuromusculares/administração & dosagem , Fármacos Neuromusculares/efeitos adversos , Injeções Intramusculares
13.
Orthod Craniofac Res ; 27 Suppl 1: 115-121, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38459796

RESUMO

INTRODUCTION: Folinic acid and botulinum toxin A have shown promising results in wound healing in different studies. This study aimed to compare the effects of these approaches on wound healing after simulating cleft lip surgery in rats. METHODS: In this experimental animal study, after creating lip defects, 30 rats were randomly divided into three groups and received normal saline (CTL), botulinum toxin A (BOT), and folinic acid (FOL). Biopsy from the skin wounds was performed after 14- and 28-days. These samples were stained with haematoxylin and eosin and Masson trichrome staining. Finally, each pathological parameter of wound healing was rated in this study. RESULTS: While the inflammatory response was not different among the study groups, fibroblast proliferation and collagen deposition were significantly higher in FOL group compared to BOT group. Moreover, both BOT and FOL facilitated epithelial healing and 14-day angiogenesis as compared with normal saline. CONCLUSIONS: Improved wound healing was observed using both botulinum toxin A and folinic acid in rat animal models. However, the application of botulinum toxin A caused less fibroblast proliferation and collagen deposition which can potentially lead to less scar formation, which can be particularly important in the aesthetic zone.


Assuntos
Toxinas Botulínicas Tipo A , Fenda Labial , Cicatrização , Animais , Toxinas Botulínicas Tipo A/farmacologia , Toxinas Botulínicas Tipo A/administração & dosagem , Cicatrização/efeitos dos fármacos , Ratos , Fenda Labial/cirurgia , Fibroblastos/efeitos dos fármacos , Colágeno , Masculino , Ratos Wistar , Modelos Animais de Doenças , Proliferação de Células/efeitos dos fármacos
14.
Spinal Cord ; 62(6): 285-294, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38637637

RESUMO

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVES: The current study aimed to assess the efficacy and safety of Onabotulinum toxin A (OBTX-A) treatment for neurogenic detrusor overactivity (NDO) in spinal cord injury (SCI) patients. SETTING: Iran. METHODS: All relevant articles of clinical trials and cohort studies indexed in PubMed/MEDLINE, Embase, Scopus, and Web of Science databases up to September 6, 2022, that addressed OBTX-A treatment for NDO following SCI were included. The quality of eligible studies was evaluated using Cochrane criteria. Also, the weighted mean difference (WMD) was measured with a random-effect model. RESULTS: Regarding the overall efficacy after OBTX-A treatment in the short term, volume per void (VV) (WMD = 118.8, 95% CI: 90.9-146.7, p < 0.01), incontinence-quality of life (IQoL) (WMD = 24.3, 95% CI: 15.8-32.8, p < 0.01), and maximum cystometric capacity (MCC) (WMD = 144.5, 95% CI: 132.3 to 156.7, p < 0.01) significantly increased, while maximum detrusor pressure during storage (MDP) (WMD = -30.5, 95% CI: -35.9 to -25.1, p < 0.01) showed a significant decrease. Furthermore, compared to the placebo group at the 200-unit dose, there was a significant increase in MCC (WMD = 113.5, 95% CI: 84.7 to 142.3, p < 0.01) and a significant decrease in MDP (WMD = -27.2, 95% CI: -39.2 to -15.1, p < 0.01). Urinary tract infection (UTI), hematuria, and autonomic dysreflexia were the most common side effects, occurring at rates of 29.6%, 14.8%, and 13.4%, respectively. CONCLUSION: Our findings highlighted the effectiveness and safety of OBTX-A as a promising treatment of NDO following SCI.


Assuntos
Toxinas Botulínicas Tipo A , Traumatismos da Medula Espinal , Bexiga Urinaria Neurogênica , Bexiga Urinária Hiperativa , Humanos , Toxinas Botulínicas Tipo A/administração & dosagem , Toxinas Botulínicas Tipo A/farmacologia , Fármacos Neuromusculares/administração & dosagem , Fármacos Neuromusculares/farmacologia , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/tratamento farmacológico , Bexiga Urinaria Neurogênica/tratamento farmacológico , Bexiga Urinaria Neurogênica/etiologia , Bexiga Urinária Hiperativa/tratamento farmacológico , Bexiga Urinária Hiperativa/etiologia
15.
J Oral Maxillofac Surg ; 82(5): 525-530, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38438110

RESUMO

Botulinum toxin (BTX) injection is a common treatment for bruxism, but there is no literature on potential salivary gland complications. This paper presents a case of acute parotitis in a 60-year-old female following BTX injections to the masseter muscle. This case highlights the possible salivary gland complications after injection of BTX into the masticatory muscles. An electronic search of PubMed and Embase databases was conducted to create a literature review in order to delve into the etiology behind the presented case and suggest potential preventive measures to avoid salivary gland complications. Thirty-one articles are reviewed and discussed. Currently, there is no consensus on the causes of the mentioned complication. However, various factors have been proposed, encompassing anatomical, physiological, biological, and physical aspects. Several methods have been recommended for the safe injection of BTX, which, along with better medical training and knowledge, are warranted to achieve predictable results.


Assuntos
Músculo Masseter , Parotidite , Humanos , Feminino , Pessoa de Meia-Idade , Injeções Intramusculares , Toxinas Botulínicas Tipo A/uso terapêutico , Toxinas Botulínicas Tipo A/efeitos adversos , Toxinas Botulínicas Tipo A/administração & dosagem , Complicações Pós-Operatórias/prevenção & controle , Fármacos Neuromusculares/uso terapêutico , Fármacos Neuromusculares/efeitos adversos , Fármacos Neuromusculares/administração & dosagem , Bruxismo
16.
Am J Otolaryngol ; 45(3): 104210, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38241761

RESUMO

INTRODUCTION: Botox is frequently used for sialorrhea in patients with compromised airways and those with etiologies causing difficulty with secretion management (i.e. strokes, neurologic disorders, etc.). There are no published studies regarding the use of botulinum toxin (BoNT) in the neonate population. We aim to discuss our experience and safety of BoNT use in the neonate population in regards to alleviating secretion management and airway protection. METHODS: Retrospective review of neonates admitted to the neonatal intensive care unit (NICU) ≤12 months of age who received BoNT injection to submandibular (SMG) and parotid (PG) glands for sialorrhea/dysphagia. BoNT was administered under ultrasound (u/s) guidance by interventional radiology. RESULTS: 6 children were examined. 2 (33 %) were male. Avg NICU stay was 87.5 ± 33.1 days. 2 underwent surgical airway intervention prior to injection. Mean age at initial BoNT was 1.5 ± 0.7 months. Avg weight at injection was 4 ± 1.1 kg. Each PG and SMG were injected in 5/6 cases. Bilateral SMG were unidentified on u/s in 1 case and thus not injected. Dose range injected per gland was 5-15u. 100 % required tube feeds, 50 % with tubes distal to stomach (NJT/NDT). 83 % were completely NPO prior to injection and there was no noted clinical improvement in oral skills post injection. All had noted desats/apneas prior to injection and 83 % had reported decreased events post injection. 50 % had reported decrease O2 requirements and frequent suctioning 2wks after injection, however 2 (33 %) required surgical airway intervention after injection (trach, SGP/MDO). 4/6 (67 %) trialed medical therapy, anticholinergics being the most common. 50 % underwent 2nd injection (age = 6.5 ± 0.3 months) avg. 4.7 ± 0.7mo after 1st injection, and the same 3pts underwent 3rd injection (age = 12.5 ± 2.4 months) avg. 6.1 ± 2.5mo after 2nd injection. 1 pt. had a total 6 injections. There were no injection related complications. CONCLUSION: BoNT injection is a safe, non-invasive alterative for management of sialorrhea in neonates. Further extensive study needs to be performed to identify the optimal dose per gland in this population.


Assuntos
Toxinas Botulínicas Tipo A , Transtornos de Deglutição , Sialorreia , Humanos , Sialorreia/tratamento farmacológico , Sialorreia/etiologia , Estudos Retrospectivos , Masculino , Feminino , Recém-Nascido , Toxinas Botulínicas Tipo A/administração & dosagem , Transtornos de Deglutição/tratamento farmacológico , Transtornos de Deglutição/etiologia , Lactente , Resultado do Tratamento , Glândula Submandibular , Glândula Parótida , Unidades de Terapia Intensiva Neonatal
17.
Int J Urol ; 31(7): 772-777, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38693892

RESUMO

INTRODUCTION: Sacral neuromodulation (SNM) and onabotulinumtoxinA (BoNTA) injection are third-line therapies for overactive bladder (OAB). Although the efficacy of each third-line treatment has been well established in clinical trials, there is far less information about performing one third-line therapy after the other. Our aim is thus to investigate the outcomes of post-SNM BoNTA and post-BoNTA SNM as "second" third-line treatments. METHODS: We retrospectively reviewed all OAB patients who had both SNM and BoNTA between 2013 and 2022. The primary endpoint was the response rates (>50% improvements) of the second third-line treatments. Secondary endpoints were the proportion of the patients who achieved total dry, the duration of treatments of patients who had significant responses, and risk factors that are associated with treatment response or duration of treatments. RESULTS: A total of 172 patients had two third-line therapies. There were 104 patients who had post-SNM BoNTA and 68 patients who had post-BoNTA SNM. In the post-SNM BoNTA group, 62.5% (65/104) had significant responses after BoNTA treatment. In the post-BoNTA SNM group, 61.8% (44/68) had significant responses after SNM treatment. The proportions of patients who became dry were 21.2% and 23.5%, respectively. In the post-SNM BoNTA group, spinal pathology is associated with a lower probability of a significant response (48.9% vs. 73.7%, p-value = 0.0105). CONCLUSIONS: BoNTA or SNM remains a viable option for refractory OAB after patients fail from one another. Spinal pathology is associated with a poorer response of post-SNM BoNTA.


Assuntos
Toxinas Botulínicas Tipo A , Bexiga Urinária Hiperativa , Humanos , Bexiga Urinária Hiperativa/terapia , Bexiga Urinária Hiperativa/tratamento farmacológico , Toxinas Botulínicas Tipo A/administração & dosagem , Toxinas Botulínicas Tipo A/uso terapêutico , Estudos Retrospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Idoso , Terapia por Estimulação Elétrica/métodos , Fármacos Neuromusculares/administração & dosagem , Fármacos Neuromusculares/uso terapêutico , Adulto , Plexo Lombossacral
18.
Ann Plast Surg ; 92(5): 508-513, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38685490

RESUMO

BACKGROUND: Botulinum toxin type A is widely used to treat glabellar and forehead wrinkles, but the pain caused by multiple injections often deters patients from receiving long-term treatment. Despite several methods used to alleviate this pain, consistency and effectiveness remain a challenge. Therefore, this study aimed to evaluate the effectiveness and safety of nerve block guided by anatomic landmarks only in reducing pain associated with botulinum toxin type A injections. PATIENTS AND METHODS: Between 2018 and 2022, the study enrolled 90 patients divided into 3 groups: the nerve block group (n = 30), the lidocaine cream group (n = 30), and the control group (n = 30). In the nerve block group, a landmarks-based technique was used to perform the nerve block. The study collected general information and comorbidities, and recorded pain at each point and time spent on preparation and treatment for each patient's forehead and glabellar area on each side. Patient-reported outcomes and complications were followed up at 2, 4, and 12 weeks after the injections. RESULTS: The nerve block group had significantly lower total pain scores in all regions compared to the lidocaine cream and control groups (P < 0.01). There were no significant differences in patient-reported outcomes between the groups at any follow-up point. Additionally, the complication rates related to injection were low and comparable among the 3 groups. CONCLUSIONS: Nerve block guided by anatomic landmarks only is a safe, effective, and consistent approach to reduce pain during botulinum toxin type A treatment for glabellar and forehead lines. This technique may offer advantages over other methods used to alleviate the pain associated with these injections.


Assuntos
Pontos de Referência Anatômicos , Toxinas Botulínicas Tipo A , Testa , Bloqueio Nervoso , Envelhecimento da Pele , Humanos , Toxinas Botulínicas Tipo A/administração & dosagem , Toxinas Botulínicas Tipo A/uso terapêutico , Testa/inervação , Feminino , Bloqueio Nervoso/métodos , Pessoa de Meia-Idade , Masculino , Envelhecimento da Pele/efeitos dos fármacos , Adulto , Fármacos Neuromusculares/administração & dosagem , Fármacos Neuromusculares/uso terapêutico , Medição da Dor , Lidocaína/administração & dosagem , Lidocaína/uso terapêutico , Resultado do Tratamento , Anestésicos Locais/administração & dosagem , Anestésicos Locais/uso terapêutico
19.
ScientificWorldJournal ; 2024: 7446251, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38854678

RESUMO

This paper explores the role of botulinum neurotoxin in aiding fracture recovery through temporary muscle paralysis. Specifically, it investigates the effects of botulinum neurotoxin-induced paralysis of the sternocleidomastoid muscle on clavicle fractures in rats. The research aims to assess safety, effectiveness, and the impact on fracture healing. Healthy male Albino Wistar rats were divided into four groups: clavicle fracture, botulinum neurotoxin injection, both, and control. Surgeries were conducted under anaesthesia, and postoperatively, animals were monitored for 28 days. Euthanasia and radiological assessment followed, examining fracture healing and muscle changes, while tissues were histopathologically evaluated. The modified Lane-Sandhu scoring system was used for the radiographic evaluation of clavicle fractures, and the results varied from complete healing to nonunion. Histopathological examination at 28 days postfracture showed fibrous tissue, mesenchymal cells, and primary callus formation in all groups. Despite varied callus compositions, botulinum neurotoxin administration did not affect clavicle healing, as evidenced by similar scores to the control group. Several studies have explored botulinum neurotoxin applications in fracture recovery. Research suggests its potential to enhance functional recovery in certain types of fractures. Theoretical benefits include managing muscle spasticity, aiding reduction techniques, and preventing nonunion. However, botulinum neurotoxin's transient effect and nonuniversal applications should be considered. The present study found that botulinum toxin had no clear superiority in healing compared to controls, while histological evaluation showed potential adverse effects on muscle tissue. Further research is essential to understand its risk-benefit balance and long-term effects.


Assuntos
Toxinas Botulínicas Tipo A , Consolidação da Fratura , Fraturas Ósseas , Ratos Wistar , Animais , Toxinas Botulínicas Tipo A/farmacologia , Toxinas Botulínicas Tipo A/administração & dosagem , Ratos , Masculino , Consolidação da Fratura/efeitos dos fármacos , Fraturas Ósseas/tratamento farmacológico , Tratamento Conservador/métodos , Clavícula/lesões , Clavícula/efeitos dos fármacos , Modelos Animais de Doenças
20.
J Craniofac Surg ; 35(4): 1089-1091, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38709042

RESUMO

BACKGROUND: This study explores the dynamic changes in plastic surgery practices, focusing on the growth rates across different subcategories, particularly highlighting the trends in the United States. OBJECTIVES: To analyze evolving trends in plastic surgery using statistical methods, providing insights into the changes and growth patterns in various segments over time. MATERIALS AND METHODS: Utilizing data from 2005 to 2019 from the American Society of Plastic Surgeons, the authors, conducted a comprehensive statistical analysis using the SPSS program to investigate trends in plastic surgery procedures. RESULTS: Our analysis revealed no significant differences in year-on-year growth rates between cosmetic and reconstructive surgery. However, in reconstructive surgery subcategories, maxillofacial surgery showed the highest mean growth rate at 11.61%, though this was not statistically significant. In cosmetic minimally invasive procedures, soft tissue filler injections and botulinum toxin A injections experienced notably higher growth trends compared with microdermabrasion. CONCLUSION: The findings suggest that practitioners considering a career in plastic surgery should not focus solely on choosing between reconstructive and cosmetic surgery. Recognizing substantial growth in cosmetic minimally invasive procedures, especially botulinum toxin A injections and fillers, is vital for making informed career decisions.


Assuntos
Técnicas Cosméticas , Procedimentos Cirúrgicos Minimamente Invasivos , Procedimentos de Cirurgia Plástica , Cirurgia Plástica , Humanos , Estados Unidos , Procedimentos de Cirurgia Plástica/tendências , Técnicas Cosméticas/tendências , Procedimentos Cirúrgicos Minimamente Invasivos/tendências , Cirurgia Plástica/tendências , Preenchedores Dérmicos/administração & dosagem , Toxinas Botulínicas Tipo A/administração & dosagem , Padrões de Prática Médica/tendências , Sociedades Médicas
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