RESUMEN
Neuromuscular inhibitors have been quickly advanced from being used only for aesthetic purposes to being used as a treatment for musculoskeletal pain and muscle spasticity. This phenomenon stems from the diminished force exerted by muscles, which are essential for bone remodeling. In this context, it is hypothesized that botulinum toxin (BTX) might exert a direct influence on bone resorption. Although such treatments have the potential to provide patients with significant relief, bone loss occurring due to elective muscle paralysis has yet to be examined in clinical trials. The disuse model resulting from spinal cord injury, characterized by the absence of ground reaction and muscle forces, provides an ideal context for exploring the skeletal ramifications of intramuscular BTX injection. This approach enables an investigation into the intricate interplay between muscle and bone, encompassing the impact of spasticity on bone preservation, the potential positive and negative outcomes of BTX on bone metabolism, and the involvement of the autonomic nervous system in bone remodeling regulation. This paper presents a narrative review of research findings on the disturbance of the typical balance between muscles and bones caused by acute muscle paralysis from BTX, resulting in osteopenia and bone resorption.
Asunto(s)
Toxinas Botulínicas , Espasticidad Muscular , Traumatismos de la Médula Espinal , Humanos , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/tratamiento farmacológico , Espasticidad Muscular/tratamiento farmacológico , Espasticidad Muscular/etiología , Toxinas Botulínicas/administración & dosificación , Toxinas Botulínicas/uso terapéutico , Fármacos Neuromusculares/administración & dosificación , Fármacos Neuromusculares/uso terapéutico , Animales , Huesos/efectos de los fármacos , Remodelación Ósea/efectos de los fármacos , Remodelación Ósea/fisiología , Resorción Ósea , Músculo Esquelético/efectos de los fármacos , Enfermedades Óseas Metabólicas/tratamiento farmacológicoRESUMEN
Gait disorders in neurological diseases are frequently associated with spasticity. Intramuscular injection of Botulinum Toxin Type A (BTX-A) can be used to treat spasticity. Providing optimal treatment with the highest possible benefit-risk ratio is a crucial consideration. This paper presents a novel approach for predicting knee and ankle kinematics after BTX-A treatment based on pre-treatment kinematics and treatment information. The proposed method is based on a Bidirectional Long Short-Term Memory (Bi-LSTM) deep learning architecture. Our study's objective is to investigate this approach's effectiveness in accurately predicting the kinematics of each phase of the gait cycle separately after BTX-A treatment. Two deep learning models are designed to incorporate categorical medical treatment data corresponding to the injected muscles: (1) within the hidden layers of the Bi-LSTM network, (2) through a gating mechanism. Since several muscles can be injected during the same session, the proposed architectures aim to model the interactions between the different treatment combinations. In this study, we conduct a comparative analysis of our prediction results with the current state of the art. The best results are obtained with the incorporation of the gating mechanism. The average prediction root mean squared error is 2.99° (R2 = 0.85) and 2.21° (R2 = 0.84) for the knee and the ankle kinematics, respectively. Our findings indicate that our approach outperforms the existing methods, yielding a significantly improved prediction accuracy.
Asunto(s)
Toxinas Botulínicas Tipo A , Aprendizaje Profundo , Marcha , Humanos , Marcha/efectos de los fármacos , Marcha/fisiología , Toxinas Botulínicas Tipo A/uso terapéutico , Fenómenos Biomecánicos , Espasticidad Muscular/tratamiento farmacológico , Espasticidad Muscular/fisiopatología , Inyecciones Intramusculares , Masculino , FemeninoRESUMEN
BACKGROUND: Spasticity is a common and potentially debilitating symptom of multiple sclerosis (MS) with a highly variable presentation. Understanding, quantifying, and managing MS-associated spasticity (MSS) is a challenge for research and in clinical practice. The tetrahydrocannabinol:cannabidiol oromucosal spray nabiximols has demonstrated beneficial effects in the treatment of MSS in clinical studies as well as real-world observational studies, and is approved for the treatment of MSS in 29 countries globally. Most randomized studies evaluated the efficacy of nabiximols using the change in average daily spasticity scores reported by patients using the spasticity Numeric Rating Scale as a primary endpoint. This study, RELEASE MSS1 (NCT04657666), was conducted using a prespecified primary endpoint of change in spastic muscle tone (Modified Ashworth Scale Lower Limb Muscle Tone-6 [MAS LLMT-6]) to corroborate the efficacy of nabiximols as adjunctive therapy observed with the patient-measured spasticity Numeric Rating Scale primary endpoint in the previous pivotal studies. METHODS: This was a phase 3, multicenter, randomized, double-blind, placebo-controlled, 2-treatment, 2-period, crossover trial. Because of the prevalence and functional impact of lower limb spasticity on the individual patient's overall experience of MS spasticity, the MAS LLMT-6 was derived from the clinician-rated MAS. The MAS LLMT-6 is the average transformed MAS score of 6 muscle groups (knee flexors, knee extensors, and ankle plantar flexors; all assessed bilaterally). Secondary measures included MAS LLMT-4 scores, defined as the average of the 4 individual MAS-transformed scores of knee flexors and knee extensors bilaterally. Patients had a diagnosis of MS and an untransformed MAS score of at least 2 in ≥2 of 6 LLMT-6 muscle groups despite current treatment with ≥1 of the following oral antispasticity agents: baclofen, tizanidine, or dantrolene. Eligible participants were randomly assigned to 1 of 2 treatment sequences. Each treatment sequence consisted of two treatment periods, each consisting of a 14-day dose titration phase followed by a 7-day dose maintenance phase. RESULTS: Of 68 patients enrolled, 33 were assigned to nabiximols followed by placebo and 35 were assigned to placebo followed by nabiximols. Least squares mean changes in MAS LLMT-6 scores from baseline to day 21 were -0.23 for nabiximols and -0.26 for placebo; the least squares mean treatment difference in MAS LLMT-6 scores for nabiximols versus placebo was 0.04, which was not statistically significant (P = 0.7152). Mean changes in MAS LLMT-4 scores from baseline to day 21 also were not significantly different between the nabiximols and placebo groups. Safety results in this study were consistent with the known safety profile of nabiximols in patients with MSS. CONCLUSION: Despite the established efficacy of nabiximols in MSS observed using patient-reported measures, the primary endpoint was not met in this study. The findings from this study reflect and emphasize some of the challenges in the evaluation and treatment of MS spasticity. CLINICAL TRIAL REGISTRATION NUMBER (CLINICALTRIALS.GOV): : NCT04657666.
Asunto(s)
Cannabidiol , Dronabinol , Combinación de Medicamentos , Esclerosis Múltiple , Espasticidad Muscular , Humanos , Espasticidad Muscular/tratamiento farmacológico , Espasticidad Muscular/etiología , Cannabidiol/administración & dosificación , Cannabidiol/farmacología , Dronabinol/administración & dosificación , Dronabinol/farmacología , Método Doble Ciego , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/tratamiento farmacológico , Adulto , Masculino , Vaporizadores Orales , Femenino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de SaludRESUMEN
Upper-limb spasticity, frequent after central nervous system lesions, is typically treated with botulinum neurotoxin type A (BoNT-A) injections to reduce muscle tone and increase range of motion. However, performing adjunct physical therapy post-BoNT-A can be challenging due to residual weakness or spasticity. This study evaluates the feasibility of hand therapy using a robotic hand orthosis (RELab tenoexo) with a mobile phone application as an adjunct to BoNT-A injections. Five chronic spastic patients participated in a two-session pilot study. Functional (Box and Block Test (BBT), Action Research Arm Test (ARAT)), and muscle tone (Modified Ashworth Scale (MAS)) assessments were conducted to assess functional abilities and impairment, along with usability evaluations. In the first session, subjects received BoNT-A injections, and then they performed a simulated unsupervised therapy session with the RELab tenoexo in a second session a month later. Results showed that BoNT-A reduced muscle tone (from 12.2 to 7.4 MAS points). The addition of RELab tenoexo therapy was safe, led to functional improvements in four subjects (two-cube increase in BBT as well as 2.8 points in grasp and 1.3 points in grip on ARAT). Usability results indicate that, with minor improvements, adjunct RELab tenoexo therapy could enhance therapy doses and, potentially, long-term outcomes.
Asunto(s)
Toxinas Botulínicas Tipo A , Estudios de Factibilidad , Mano , Espasticidad Muscular , Fármacos Neuromusculares , Aparatos Ortopédicos , Robótica , Humanos , Proyectos Piloto , Espasticidad Muscular/tratamiento farmacológico , Espasticidad Muscular/terapia , Masculino , Femenino , Toxinas Botulínicas Tipo A/administración & dosificación , Toxinas Botulínicas Tipo A/uso terapéutico , Persona de Mediana Edad , Adulto , Mano/fisiopatología , Fármacos Neuromusculares/administración & dosificación , Fármacos Neuromusculares/uso terapéutico , Anciano , Resultado del TratamientoRESUMEN
We conducted a multicenter and retrospective study to describe the use of botulinum toxin type A (BoNT-A) to treat post-stroke spasticity (PSS). Data were extracted from free-text in electronic health records (EHRs) in five Spanish hospitals. We included adults diagnosed with PSS between January 2015 and December 2019, stratified into BoNT-A-treated and untreated groups. We used EHRead® technology, which incorporates natural language processing and machine learning, as well as SNOMED CT terminology. We analyzed demographic data, stroke characteristics, BoNT-A use patterns, and other treatments. We reviewed the EHRs of 1,233,929 patients and identified 2190 people with PSS with a median age of 69 years; in total, 52.1% were men, 70.7% had cardiovascular risk factors, and 63.2% had suffered an ischemic stroke. Among the PSS patients, 25.5% received BoNT-A at least once. The median time from stroke to spasticity onset was 205 days, and the time from stroke to the first BoNT-A injection was 364 days. The primary goal of BoNT-A treatment was pain control. Among the study cohort, rehabilitation was the most common non-pharmacological treatment (95.5%). Only 3.3% had recorded monitoring scales. In conclusion, a quarter of patients with PSS received BoNT-A mainly for pain relief, typically one year after the stroke. Early treatment, disease monitoring, and better data documentation in EHRs are crucial to improve PSS patients' care.
Asunto(s)
Toxinas Botulínicas Tipo A , Aprendizaje Automático , Espasticidad Muscular , Procesamiento de Lenguaje Natural , Accidente Cerebrovascular , Humanos , Espasticidad Muscular/tratamiento farmacológico , Espasticidad Muscular/etiología , Toxinas Botulínicas Tipo A/uso terapéutico , Masculino , Femenino , Anciano , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/tratamiento farmacológico , Estudios Retrospectivos , Persona de Mediana Edad , Registros Electrónicos de Salud , Fármacos Neuromusculares/uso terapéutico , Anciano de 80 o más AñosRESUMEN
Botulinum neurotoxin-A (BoNT-A) injections are effective for focal spasticity. However, the impact on muscle strength is not established. This study aimed to investigate the effect of BoNT-A injections on muscle strength in adult neurological conditions. Studies were included if they were Randomised Controlled Trials (RCTs), non-RCTs, or cohort studies (n ≥ 10) involving participants ≥18 years old receiving BoNT-A injection for spasticity in their upper and/or lower limbs. Eight databases (CINAHL, Cochrane, EMBASE, Google Scholar, Medline, PEDro, Pubmed, Web of Science) were searched in March 2024. The methodology followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was registered in the Prospective Register of Systematic Reviews (PROSPERO: CRD42022315241). Quality was assessed using the modified Downs and Black checklist and the PEDro scale. Pre-/post-injection agonist, antagonist, and global strength outcomes at short-, medium-, and long-term time points were extracted for analysis. Following duplicate removal, 8536 studies were identified; 54 met the inclusion criteria (3176 participants) and were rated as fair-quality. Twenty studies were analysed as they reported muscle strength specific to the muscle injected. No change in agonist strength after BoNT-A injection was reported in 74% of the results. Most studies' outcomes were within six weeks post-injection, with few long-term results (i.e., >three months). Overall, the impact of BoNT-A on muscle strength remains inconclusive.
Asunto(s)
Toxinas Botulínicas Tipo A , Espasticidad Muscular , Fuerza Muscular , Fármacos Neuromusculares , Humanos , Espasticidad Muscular/tratamiento farmacológico , Espasticidad Muscular/fisiopatología , Toxinas Botulínicas Tipo A/administración & dosificación , Toxinas Botulínicas Tipo A/uso terapéutico , Fuerza Muscular/efectos de los fármacos , Fármacos Neuromusculares/uso terapéutico , Fármacos Neuromusculares/administración & dosificación , Adulto , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Músculo Esquelético/efectos de los fármacosRESUMEN
Our objective was to provide expert consensus on best practices for anatomy teaching and training on ultrasound-guided botulinum neurotoxin type A (BoNT-A) injection for specialists involved in treating spasticity and dystonia. Nine experts (three neurologists; six physical medicine and rehabilitation physicians) participated in a three-round modified Delphi process. Over three rounds, experts reached consensus on 15 of 16 statements describing best practices for anatomy and BoNT-A injection training. They unanimously agreed that knowledge of the target audience, including their needs and current competency, is crucial when designing training programs. Experts also agreed that alignment between instructors is essential to ensure consistency of approach over time and between regions, and that training programs should be simple, adaptable, and "hands-on" to enhance engagement and learning. Consensus was also reached for several other key areas of training program development. The best-practice principles identified by expert consensus could aid in the development of effective, standardized programs for anatomy teaching and BoNT-A injection training for the purposes of treating spasticity and dystonia. This will enhance the exchange of knowledge, skills, and educational approaches between global experts, allowing more specialists to treat important movement disorders and ultimately improving patient outcomes.
Asunto(s)
Toxinas Botulínicas Tipo A , Técnica Delphi , Distonía , Espasticidad Muscular , Humanos , Toxinas Botulínicas Tipo A/administración & dosificación , Toxinas Botulínicas Tipo A/uso terapéutico , Distonía/tratamiento farmacológico , Espasticidad Muscular/tratamiento farmacológico , Ultrasonografía Intervencional , Anatomía/educación , Fármacos Neuromusculares/administración & dosificación , Fármacos Neuromusculares/uso terapéutico , ConsensoRESUMEN
BACKGROUND: Botulinum toxin A (BoNT-A) is widely used in treating dystonia and spasticity to managing chronic migraine and cosmetic applications. However, its immunogenic potential presents challenges, such as the development of neutralizing antibodies that lead to diminished therapeutic efficacy over time, known as secondary nonresponse. OBJECTIVE: This review aims to bridge the knowledge gap regarding the immunogenic mechanisms of BoNT-A and to explore effective management strategies to mitigate these immune responses. MATERIALS AND METHODS: The authors conducted a systematic search in databases including PubMed, Embase, and Web of Science, using keywords related to BoNT-A's immunogenicity. The selection process refined 157 initial articles down to 23 relevant studies, which underwent analysis to investigate the underlying mechanisms of immunogenicity and the factors influencing it. RESULTS: The analysis revealed that both the neurotoxin component and the neurotoxin-associated proteins could elicit an immune response. However, only antibodies against the core toxin influence therapeutic outcomes. Various patient-specific factors such as genetic predispositions and prior immune experiences, along with treatment-related factors such as dosage and frequency, play crucial roles in shaping these responses. CONCLUSION: Understanding the specific immunogenic triggers and responses to BoNT-A is critical for optimizing treatment protocols and improving patient outcomes.
Asunto(s)
Toxinas Botulínicas Tipo A , Humanos , Toxinas Botulínicas Tipo A/inmunología , Fármacos Neuromusculares/inmunología , Fármacos Neuromusculares/administración & dosificación , Anticuerpos Neutralizantes/inmunología , Espasticidad Muscular/tratamiento farmacológico , Espasticidad Muscular/inmunologíaRESUMEN
OBJECTIVE: To compare the effect of rectus femoris diagnostic motor nerve blocks (DNB) with anaesthetics and rectus femoris muscle botulinum toxin (BoNT-A) injection in multiple sclerosis patients with unilateral stiff-knee gait. DESIGN: Prospective observational study Subjects/Patients: Multiple sclerosis patients in stable condition. METHODS: Patients underwent evaluation before and 1 hour after the anaesthetic block, and 1 month after the botulinum injection. Assessment included a 10-m walking test, a 6-minute walking test, a timed-up-and-go (TUG) test, and a Baseline Expanded Disability Status Scale (EDSS). Post-DNB and post-BoNT-A satisfaction was measured with the global assessment of efficacy scale. RESULTS: Fourteen patients with unilateral stiff-knee gait due to multiple sclerosis underwent a DNB, among whom 13 received botulinum injections in the rectus femoris muscle after a satisfying test result. Positive post-DNB results correlated with significant functional improvements after BoNT-A. Higher EDSS and longer time from diagnosis correlated with poorer post-DNB and post-BoNT-A absolute outcomes. CONCLUSION: DNB showed predictive value for BoNT-A outcomes, especially in the case of worse functional status. It effectively predicted endurance and walking speed improvement, while TUG showed greater improvement after botulinum. In cases of uncertain therapeutic benefit, nerve blocks may provide a valuable diagnostic support, particularly in patients with lower functional status.
Asunto(s)
Toxinas Botulínicas Tipo A , Esclerosis Múltiple , Espasticidad Muscular , Bloqueo Nervioso , Fármacos Neuromusculares , Músculo Cuádriceps , Humanos , Espasticidad Muscular/etiología , Espasticidad Muscular/tratamiento farmacológico , Femenino , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/tratamiento farmacológico , Masculino , Estudios Prospectivos , Persona de Mediana Edad , Bloqueo Nervioso/métodos , Toxinas Botulínicas Tipo A/administración & dosificación , Toxinas Botulínicas Tipo A/farmacología , Adulto , Fármacos Neuromusculares/administración & dosificación , Fármacos Neuromusculares/farmacología , Resultado del Tratamiento , Trastornos Neurológicos de la Marcha/etiología , Trastornos Neurológicos de la Marcha/tratamiento farmacológicoRESUMEN
INTRODUCTION: Poststroke spasticity (PSS) affects up to 40% of patients who had a stroke. Botulinum neurotoxin type A (BoNT-A) has been shown to improve spasticity, but the optimal timing of its application remains unclear. While several predictors of upper limb PSS are known, their utility in clinical practice in relation to BoNT-A treatment has yet to be fully elucidated. The COLOSSEO-BoNT study aims to investigate predictors of PSS and the effects of BoNT-A timing on spasticity-related metrics in a real-world setting. METHODS AND ANALYSIS: The recruitment will involve approximately 960 patients who have recently experienced an ischaemic stroke (within 10 days, V0) and will follow them up for 24 months. Parameters will be gathered at specific intervals: (V1) 4, (V2) 8, (V3) 12, (V4) 18 months and (V5) 24 months following enrolment. Patients will be monitored throughout their rehabilitation and outpatient clinic journeys and will be compared based on their BoNT-A treatment status-distinguishing between patients receiving treatment at different timings and those who undergo rehabilitation without treatment. Potential predictors will encompass the Fugl-Meyer assessment, the National Institute of Health Stroke Scale (NIHSS), stroke radiological characteristics, performance status, therapies and access to patient care pathways. Outcomes will evaluate muscle stiffness using the modified Ashworth scale and passive range of motion, along with measures of quality of life, pain, and functionality. ETHICS AND DISSEMINATION: This study underwent review and approval by the Ethics Committee of the Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy. Regardless of the outcome, the findings will be disseminated through publication in peer-reviewed journals and presentations at national and international conferences. TRIAL REGISTRATION NUMBER: NCT05379413.
Asunto(s)
Toxinas Botulínicas Tipo A , Espasticidad Muscular , Fármacos Neuromusculares , Accidente Cerebrovascular , Extremidad Superior , Femenino , Humanos , Masculino , Toxinas Botulínicas Tipo A/uso terapéutico , Toxinas Botulínicas Tipo A/administración & dosificación , Estudios Longitudinales , Espasticidad Muscular/tratamiento farmacológico , Espasticidad Muscular/etiología , Fármacos Neuromusculares/uso terapéutico , Fármacos Neuromusculares/administración & dosificación , Estudios Observacionales como Asunto , Estudios Prospectivos , Accidente Cerebrovascular/complicaciones , Rehabilitación de Accidente Cerebrovascular/métodos , Extremidad Superior/fisiopatologíaRESUMEN
INTRODUCTION: Injections of botulinum toxin type A (BoNT-A) are the first-line treatment for spastic muscle overactivity (MO). Some authors observed that BoNT-A injections lead to changes in muscle structure and muscle elasticity that are probably not completely reversible. This possible effect is critical, as it could lead to negative impacts on the effectiveness of BoNT-A interventions. Our study aimed to evaluate the current literature regarding changes in muscle elasticity and structure after BoNT-A injection, by diagnostic imaging, in neurological populations with MO. Our second objective was to pool all articles published on this topic in order to provide a quantitative synthesis of the data. EVIDENCE ACQUISITION: A systematic search was conducted between October 2021 and April 2023 using different databases in accordance with PRISMA guidelines. Two independent reviewers screened articles for inclusion, extracted data, and evaluated methodological quality of the studies. A meta-analysis was performed to compare muscle elasticity and structure before and after BoNT-A injections. EVIDENCE SYNTHESIS: A sample of 34 studies was selected for qualitative review and 19 studies for quantitative review. Meta-analysis of pre-post studies demonstrated significant improvement with a medium effect size (standardized mean difference=0.74; 95% CI 0.46-1.02; P<0.001) of muscle elasticity assessed by ultrasound elastography (USE) 4 weeks after BoNT-A injection. No statistically significant difference was found for muscle thickness, pennation angle, and muscle echo-intensity assessed by magnetic resonance imaging and/or ultrasonography at short-term. On the other hand, normalized muscle volume decreased with a small effect size (standardized mean difference = -0.17; 95% CI -0.25 - -0.09; P<0.001) 6 months after BoNT-A injection. CONCLUSIONS: Muscle elasticity measured by USE improves with a temporary effect at short-term following BoNT-A injections. Synthesis of studies that assesses muscle structure is hindered by methodological differences between studies. However, based on a small amount of data, normalized muscle volume seems to decrease at long-term after BoNT-A injections in children with CP suggesting that the timing of re-injection should be considered with caution in this population. Further work should focus on the long-term effect of repeated injections on muscle structure and elasticity in neurological populations.
Asunto(s)
Toxinas Botulínicas Tipo A , Elasticidad , Espasticidad Muscular , Fármacos Neuromusculares , Humanos , Toxinas Botulínicas Tipo A/administración & dosificación , Elasticidad/efectos de los fármacos , Inyecciones Intramusculares , Espasticidad Muscular/tratamiento farmacológico , Espasticidad Muscular/fisiopatología , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/fisiopatología , Fármacos Neuromusculares/administración & dosificaciónRESUMEN
BACKGROUND: Cerebral palsy (CP) is the most cause of motor dysfunction in children. Selective dorsal rhizotomy (SDR) plays a major role in long term spasticity control. However, limited data exists on the effect of SDR on postoperative spasticity treatment requirements and supraspinal effects, and the stimulation responses of dorsal nerve roots in those with CP. METHODS: The current study included the outcome for 35 individuals undergoing SDR for motor functional outcome, spasticity, baclofen dose changes, botulinum toxin injection frequency, and spasticity related orthopedic procedures. We also report on the stimulation responses in 112 individuals who underwent SDR at our institution. RESULTS: There was a significant difference in gross motor function measures (GMFM)-66 scores at last follow up that remained present when considering only ambulatory children but not with non-ambulatory children. Ashworth scores were significantly decreased for both upper and lower extremities after SDR at all follow up points. There was a significant decrease in Baclofen dose and botulinum toxin injections requirements after SDR, but no significant difference in the need for orthopedic intervention. A total of 5502 dorsal nerve roots were tested showing a decrease in stimulation intensity and increase in grade on the right side and for descending lumbosacral levels. CONCLUSIONS: SDR improves gross motor scores during short term follow up but has additional benefits in decreasing baclofen dosing and botulinum toxin injections requirements after surgery. They stimulation responses of sectioned dorsal nerve roots adds to the limited available data and our understanding of the pathological changes that occur in CP.
Asunto(s)
Parálisis Cerebral , Espasticidad Muscular , Rizotomía , Raíces Nerviosas Espinales , Parálisis Cerebral/cirugía , Humanos , Rizotomía/métodos , Masculino , Raíces Nerviosas Espinales/cirugía , Niño , Femenino , Espasticidad Muscular/cirugía , Espasticidad Muscular/tratamiento farmacológico , Resultado del Tratamiento , Adolescente , Baclofeno/administración & dosificación , Baclofeno/uso terapéutico , Preescolar , Relajantes Musculares Centrales/uso terapéutico , Relajantes Musculares Centrales/administración & dosificaciónRESUMEN
INTRODUCTION: Spasticity is one of the most common secondary complications following a spinal cord injury (SCI), which can significantly debilitate a patient irrespective of the severity of the injury. Intrathecal baclofen therapy can effectively reduce global spasticity in bilateral lower extremities at lower doses and allows precise dose titration to manage spasticity optimally. In complex patients with spasticity and multiple medical comorbidities, multidisciplinary teamwork is required to assess ITB safety and deliver timely intervention to prevent secondary complications of spasticity and improve quality of life. CASE PRESENTATION: A 61-year-old African American male with multiple comorbidities, including end-stage renal disease (ESRD) requiring dialysis sustained non-traumatic SCI due to epidural abscess resulting in paraplegia and severe debilitating spasticity. Spasticity gradually worsened and interfered with his ability to achieve independence with functional activities appropriate for his neurological level of injury. A multidisciplinary team approach in this complex case resulted in a successful ITB trial and subsequent ITB implantation, resulting in reduced spasticity and improved quality of life. To our knowledge, this is the first case report of the administration of intrathecal baclofen pump therapy in a person with SCI and end-stage renal disease (ESRD) dependent on hemodialysis. DISCUSSION: ITB therapy can be safely delivered in a person with SCI and multiple medical comorbidities, including ESRD, dependent on hemodialysis to manage spasticity. However, a careful evaluation and discussion among the multidisciplinary team managing the patient's morbidities and patient is required to assess the risks and benefits of ITB therapy to allow the patient to make an informed decision.
Asunto(s)
Baclofeno , Inyecciones Espinales , Fallo Renal Crónico , Relajantes Musculares Centrales , Espasticidad Muscular , Diálisis Renal , Traumatismos de la Médula Espinal , Humanos , Baclofeno/administración & dosificación , Espasticidad Muscular/tratamiento farmacológico , Espasticidad Muscular/etiología , Masculino , Persona de Mediana Edad , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Traumatismos de la Médula Espinal/complicaciones , Relajantes Musculares Centrales/administración & dosificaciónRESUMEN
Botulinum neurotoxin (BNT) injection into the cricopharyngeus muscle (CPM) under ultrasound (US) guidance is a minimally invasive technique performed to relieve cricopharyngeal dysphagia by reducing CPM spasticity. This technique is basically accessible only to both lateral sides of the CPM. This cadaveric study aimed to evaluate whether US-guided injection could effectively deliver BNT to abundant areas of gross nerve endings within the CPM. We utilized a newly modified Sihler's staining method to identify regions with abundant neural endings within the CPM while preserving the three-dimensional morphology of the muscle in 10 sides of 5 fresh cadavers. A mixture of 0.2 mL dye was injected into the 16 sides of CPM under US guidance in 8 cadavers. Nerve endings were abundant in posterolateral areas of the CPM; the injected dye was identified at the posterolateral area on 12 sides (12/16 side, 75%) without diffusion into the posterior cricoarytenoid muscle. The injection failed on four sides (two sides of the prevertebral fascia and two sides of the esophagus below the CPM). These results suggest that US-guided injection could be a feasible technique as it can deliver BNT to the most abundant nerve distribution areas within the CPM in most cases.
Asunto(s)
Cadáver , Estudios de Factibilidad , Espasticidad Muscular , Ultrasonografía Intervencional , Humanos , Espasticidad Muscular/tratamiento farmacológico , Masculino , Femenino , Toxinas Botulínicas Tipo A/administración & dosificación , Terminaciones Nerviosas/efectos de los fármacos , Músculos Faríngeos/efectos de los fármacos , Músculos Faríngeos/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Inyecciones Intramusculares , Toxinas Botulínicas/administración & dosificaciónRESUMEN
Numerous studies have established a robust body of evidence for botulinum toxin A (BoNT-A) therapy as a treatment for upper motor neuron syndrome. These studies demonstrated improvements in spasticity, range of joint motion, and pain reduction. However, there are few studies that have focused on improvement of paralysis or functional enhancement as the primary outcome. This paper discusses the multifaceted aspects of spasticity assessment, administration, and rehabilitation with the goal of optimising the effects of BoNT-A on lower-limb spasticity and achieving functional improvement and gait reconstruction. This paper extracts studies on BoNT-A and rehabilitation for the lower limbs and provides new knowledge obtained from them. From these discussion,, key points in a walking reconstruction strategy through the combined use of BoNT-A and rehabilitation include: (1) injection techniques based on the identification of appropriate muscles through proper evaluation; (2) combined with rehabilitation; (3) effective spasticity control; (4) improvement in ankle joint range of motion; (5) promotion of a forward gait pattern; (6) adjustment of orthotics; and (7) maintenance of the effects through frequent BoNT-A administration. Based on these key points, the degree of muscle fibrosis and preintervention walking speed may serve as indicators for treatment strategies. With the accumulation of recent studies, a study focusing on walking functions is needed. As a result, it is suggested that BoNT-A treatment for lower limb spasticity should be established not just as a treatment for spasticity but also as a therapeutic strategy in the field of neurorehabilitation aimed at improving walking function.
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Toxinas Botulínicas Tipo A , Marcha , Espasticidad Muscular , Fármacos Neuromusculares , Humanos , Espasticidad Muscular/tratamiento farmacológico , Espasticidad Muscular/rehabilitación , Marcha/efectos de los fármacos , Toxinas Botulínicas Tipo A/uso terapéutico , Toxinas Botulínicas Tipo A/administración & dosificación , Fármacos Neuromusculares/uso terapéutico , Terapia Combinada , Enfermedad de la Neurona Motora/tratamiento farmacológico , Enfermedad de la Neurona Motora/rehabilitaciónRESUMEN
OBJECTIVE: To evaluate the impact of combining botulinum toxin-A (BoNT-A) injection with robot-assisted gait training (RAGT) on lower limb spasticity and motor function in children with cerebral palsy. METHODS: A prospective study was conducted from January 2020 to January 2023, including 68 patients. Twenty patients received the combination of BoNT-A injection and RAGT, while 48 received BoNT-A injection alone. Assessments were performed before the intervention and at 1, 3, and 6 months post-injection using the Modified Tardieu Scale (MTS), sections D and E of the Gross Motor Function Measure-88 (GMFM-88), 6-minute walk test (6MWT), and 10-meter walk test (10MWT). RESULTS: Compared to the control group receiving BoNT-A alone, the combination of BoNT-A and RAGT did not significantly improve spasticity-related outcomes, including MTS scores, R1, and R2 angles (p > .05). However, the combination group demonstrated significantly improved gross motor function, particularly in walking, running (GMFM-E), short-term walking endurance (6MWT), and walking speed (10MWT) in children with cerebral palsy after the intervention (p < .05). CONCLUSION: While the addition of RAGT did not enhance the anti-spasticity effects of BoNT-A, it significantly improved gross motor function and walking abilities in children with cerebral palsy.
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Toxinas Botulínicas Tipo A , Parálisis Cerebral , Espasticidad Muscular , Fármacos Neuromusculares , Robótica , Humanos , Parálisis Cerebral/rehabilitación , Parálisis Cerebral/fisiopatología , Parálisis Cerebral/tratamiento farmacológico , Masculino , Niño , Femenino , Espasticidad Muscular/tratamiento farmacológico , Espasticidad Muscular/rehabilitación , Espasticidad Muscular/fisiopatología , Toxinas Botulínicas Tipo A/administración & dosificación , Toxinas Botulínicas Tipo A/uso terapéutico , Fármacos Neuromusculares/administración & dosificación , Estudios Prospectivos , Preescolar , Terapia por Ejercicio/métodos , Marcha/fisiología , Terapia CombinadaRESUMEN
BACKGROUND: Around 40% of stroke survivor develop spasticity. Plantar flexors (PF) muscles are often affected, with severe functional impairment. The treatment of choice is botulinum toxin type A (BoNT-A) combined with adjuvant treatments. The temporary pharmacological effect implies periodic reassessment and reinjection. These long-term chronic programs require monitoring the functional impact of each cycle and the clinical evolution in relation to aging and repeated interventions. AIM: Evaluating changes of functional level in patients with post-stroke spasticity treated with BoNT-A by assessing the long-term maintenance of the therapeutic efficacy. DESIGN: Retrospective longitudinal observational study. SETTING: Outpatients. POPULATION: Chronic stroke survivors undergoing BoNT-A treatment and subsequent intensive rehabilitation (10 sessions in a day-hospital regime). METHODS: Medical records of the enrolled patients were consulted. The primary endpoint was the change in PF spasticity by at least 1 point on the Modified Ashworth Scale (MAS) at each cycle. Secondary endpoints were the assessment of possible trends in gait parameters (Six Minute Walking Test [6MWT]; Timed Up and Go [TUG], and 10 Meters Walking Test [10mWT]) pre- and post-injection and at each cycle. RESULTS: Thirty-six patients were enrolled. A reduction of at least one MAS point for PF was recorded after each cycle in all subjects. A time-dependent reduction in the proportion of patients reporting an improvement higher than the minimal clinically important difference (MCID) in 6MWT and 10mWT was observed. In the case of TUG, this data kept stable at all cycles. A one-point increase in the basal functional ambulation classification (FAC) score resulted in a reduction in the probability of having a TUG improvement greater than the MCID. The opposite correlation was found for 6MWT and 10mWT. CONCLUSIONS: With the proposed treatment, the clinical significance TUG improvement remains constant throughout repeated cycles and the proportion of patients with improvement in 6MWT and 10mWT tends to decline over time. The predictive value of basal FAC on the functional variables expected improvement may provide a potential treatment targeting tool. CLINICAL REHABILITATION IMPACT: These results may deliver prognostic indication allowing an optimized integration of different post-BoNT-A rehabilitation approaches, agreeing with current evidence. Adequate monitoring and treatment protocols are crucial for the stability of functional level and may prevent excessive fluctuations.
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Toxinas Botulínicas Tipo A , Espasticidad Muscular , Fármacos Neuromusculares , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Humanos , Espasticidad Muscular/tratamiento farmacológico , Espasticidad Muscular/etiología , Espasticidad Muscular/fisiopatología , Femenino , Toxinas Botulínicas Tipo A/administración & dosificación , Toxinas Botulínicas Tipo A/uso terapéutico , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Accidente Cerebrovascular/complicaciones , Anciano , Rehabilitación de Accidente Cerebrovascular/métodos , Fármacos Neuromusculares/uso terapéutico , Fármacos Neuromusculares/administración & dosificación , Estudios Longitudinales , Resultado del Tratamiento , Estudios de SeguimientoRESUMEN
BACKGROUND: The first pump for intrathecal administration of baclofen was implanted in 1984. Over thirty years, intrathecal prolonged infusion of muscle relaxants has occupied a worthy niche among all methods for correction of non-focal drug-resistant disabling muscle spasticity. However, this method has not become routine despite high awareness of specialists in Russia and abroad, as well as undeniable advantages for restoring the daily activity, improving the walking pattern and providing care and quality of life in people with limited mobility. This is due to scrupulous analysis of adverse events and accurate attitude towards its use.The purpose of this review was to systematize data on indications, selection criteria, pump implantation technique, subsequent patient management and treatment outcomes over a 30-year history. METHOD: A review of national and foreign literature was performed. RESULTS AND CONCLUSION: Prolonged intrathecal baclofen therapy is perspective for long-term treatment of severe spasticity interfering with quality of life and self-care if oral muscle relaxants are contraindicated or ineffective. This procedure is effective for impaired articulation, chewing and spastic pain syndrome. One can reduce the incidence of side effects via correct dosage of the drug, and tolerance to therapy can be reduced by timely elimination of problems with catheter.
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Baclofeno , Inyecciones Espinales , Relajantes Musculares Centrales , Espasticidad Muscular , Baclofeno/administración & dosificación , Baclofeno/uso terapéutico , Humanos , Espasticidad Muscular/tratamiento farmacológico , Inyecciones Espinales/métodos , Relajantes Musculares Centrales/administración & dosificación , Bombas de Infusión Implantables , Calidad de VidaRESUMEN
OBJECTIVE: The aim of this study was 1) to describe the rate of intrathecal baclofen (ITB)-associated complications at a large tertiary center, and 2) to evaluate the impact of patient-related factors on the likelihood of developing such complications. METHODS: A retrospective single-center study was carried out. A total of 301 eligible patients were included in the analysis. Univariate regression models were used to evaluate the impact of age, sex, diagnosis, ambulation status, modified Ashworth scale score, body mass index, diabetes status, and pain level on the likelihood of developing a device-related infection, pump malfunction, catheter malfunction, and other clinically significant complications. RESULTS: Overall, 27% of patients experienced an ITB-related complication. The most common complications included infection (6%, 18/301), pump malfunction (7.3%, 22/301), and catheter malfunction (14%, 42/301). The univariate analyses revealed that the patient's ambulatory status had a significant impact on the likelihood of developing a catheter-related malfunction. Furthermore, a trend toward significance was identified between patients' preoperative body mass index and device-related infection. Finally, the risk of suffering any ITB-related complications was statistically correlated with the number of years that had passed since the initial pump implantation. CONCLUSIONS: The authors' analysis reveals a previously underrecognized association between ambulatory status at the time of ITB pump implantation and the incidence of catheter-related complications, and confirms the impact of time since surgery on the risk of developing any ITB-related complication. The patient's age, sex, diagnosis, diabetes status, or pain level at baseline were not associated with the risk of complications. Collectively, these insights contribute novel information to the existing literature, providing practical value for physicians in guiding patient selection for ITB therapy.
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Baclofeno , Bombas de Infusión Implantables , Inyecciones Espinales , Relajantes Musculares Centrales , Humanos , Baclofeno/administración & dosificación , Baclofeno/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto , Factores de Riesgo , Bombas de Infusión Implantables/efectos adversos , Relajantes Musculares Centrales/administración & dosificación , Relajantes Musculares Centrales/efectos adversos , Inyecciones Espinales/efectos adversos , Anciano , Adulto Joven , Espasticidad Muscular/tratamiento farmacológico , Falla de Equipo/estadística & datos numéricos , AdolescenteRESUMEN
OBJECTIVE: Intrathecal baclofen (ITB) pumps are commonly used in pediatric patients with cerebral palsy (CP) and medically refractory spasticity. However, catheter malfunction and associated risk factors are not well understood. The aim of this study was to examine potential risk factors for spinal catheter malfunction and characterize postoperative follow-up to understand the clinical consequences. METHODS: Patients who received ITB pump replacement or revision at Boston Children's Hospital between 2010 and 2023 were retrospectively reviewed. The spinal catheter revision cohort (SCRC) included patients whose spinal catheter was occluded requiring lumbar catheter revision. The second cohort included abdominal pump replacements only (APRC). Between-group comparisons and multivariable regression identified factors associated with catheter revision and postoperative outcomes. RESULTS: Forty-one (33.6%) patients underwent spinal catheter revision and were compared with 81 patients (66.4%) who underwent abdominal pump replacement only. Younger age at surgery and an elevated preoperative lower-extremity modified Ashworth scale grade were associated with spinal catheter revision (p < 0.05). Catheter model type, tip location, and history of spinal fusion were not associated with obstruction. Postoperatively, SCRC patients experienced a higher rate of infection (17.1%) relative to APRC patients (0%) within 30 days from their ITB pump replacement procedure (p < 0.05) and greater likelihood of subsequent ITB system removal compared with the APRC (24.4% vs 7.4%, p < 0.05). Although not differing preoperatively, SCRC patients had lower postoperative ITB doses when compared with the APRC group (median dose 143 vs 350 µg/day, p < 0.05) at hospital discharge and remained statistically different at the 6-month and 1-year follow-ups (p < 0.05). There were no postoperative differences in baclofen overdose, withdrawal, or median number of hospital readmissions within 30 days. Overall, 31.7% of spinal catheter revisions were unanticipated by the clinical team at time of surgery. CONCLUSIONS: Younger age at surgery and increased preoperative lower-extremity tone may be risk factors for catheter obstruction, resulting in a higher rate of postoperative infection and subsequent ITB pump removal compared with pump replacement alone. Spinal catheter occlusion can complicate revision or replacement procedures, especially when unanticipated. Routine clinical assessment may be inadequate for diagnosing insidious catheter malfunction. Catheter occlusion deserves further study, and routine assessment of catheter patency may be warranted to prevent suboptimal tone therapy.