Real-world differences in dosing and clinical utilization of OnabotulinumtoxinA and AbobotulinumtoxinA in the treatment of upper limb spasticity.

According to prescribing information, potency units are not interchangeable between botulinum toxin A products. This exploratory study compared real-world dosing and utilization of onabotulinumtoxinA and abobotulinumtoxinA in adults with upper limb spasticity. In this retrospective study, 101 clinicians provided chart data via online surveys for 215 US post-stroke patients treated for upper limb spasticity with ≥3 onabotulinumtoxinA or abobotulinumtoxinA doses (phase 1: 9/18/2020-12/10/2020; phase 2: 9/30/2021-12/7/2021). Most participating clinicians were physicians (70.3%) specializing in neurology (71.3%) or physiatry (20.8%). In the onabotulinumtoxinA (n = 107) and abobotulinumtoxinA (n = 108) groups, ∼75% of patients had moderate-to-severe spasticity. A range of onabotulinumtoxinA:abobotulinumtoxinA dose ratios (1:2.2 [95% CI: 1.8, 2.6] to 1:4.1 [95% CI: 3.0, 6.0]) was observed across muscles. For the most recent dose, mean number of muscles injected was greater for onabotulinumtoxinA (4.3) versus abobotulinumtoxinA (3.1; P = 0.0003). For onabotulinumtoxinA versus abobotulinumtoxinA, the proportion of injections was 81.3% versus 63.9% (P = 0.0067) in forearm muscles and 23.4% versus 3.7% (P = 0.0001) in hand muscles. Mean injection intervals were similar (onabotulinumtoxinA: 102.0 days; abobotulinumtoxinA: 99.1 days). Differences in real-world dosing and utilization of onabotulinumtoxinA and abobotulinumtoxinA for upper limb spasticity were observed. There was no standard dose-conversion ratio, consistent with each product's prescribing information.

Exploring the sexual experiences and challenges of individuals with cerebral palsy.

PURPOSE: Cerebral palsy (CP) is a prevalent motor disorder affecting children, with evolving demographics indicating an increasing survival into adulthood. This shift necessitates a broader perspective on CP care, particularly in addressing the often overlooked aspect of sexuality. The purpose of this study was to investigate experiences of, challenges with, and related factors of sexuality and intimacy that people with CP are facing. METHODS: This was a descriptive and cross-sectional single institution survey among individuals with CP, ages 18 to 65, who had the ability to independently complete an online survey. RESULTS: A total of 40 respondents participated in the survey (Gross Motor Function Classification System [GMFCS] level I/II, 32.5%; III, 35%; IV, 32.5%). Of those, 45% were partnered, 60% had past sexual experience, 47.5% were currently sexually active at the time of submitting the survey, 80% had masturbation experience, and 45.8% believed it had positive effect on their self-esteem. Only 10% received sex education tailored for people with disability, whereas school (72.5%) and internet (35%) were the most common sources of sex education. Muscle spasms, positioning difficulty, and pain/discomfort were the most common physical challenges experienced during intimate activity amongst all function stratifications. Stratification analysis showed that, compared to higher functioning respondents, a smaller proportion of lower functioning respondents were partnered (GMFCS IV, 23.1%; quadriplegic, 31.6%), had past or current sexual experience (GMFCS IV, 44.4%, 36.4%; quadriplegic, 42.1%, 26.3%, respectively), and had masturbation experience (GMFCS IV, 61.5%); Also, they had worse Quality of Life Scale scores on average (GMFCS IV, 88.4; quadriplegic, 88.3) and a higher rate of reported positive effects of sexual experiences on self-esteem than negative (GMFCS IV, 38.5%; quadriplegic, 35%).

Improvement in a post-stroke pediatric patient with hemiplegia: Use of a hand-arm bimanual intensive therapy with hybrid assistive limb.

BACKGROUND: Pediatric stroke is a rare medical condition that often leads to long-lasting motor and cognitive impairments. Although therapies for adults after a stroke are well described, treatments for motor deficits following a pediatric stroke are yet to be investigated. We report a case of pediatric stroke in the chronic phase, in which a combination of novel treatments resulted in a significant improvement in physical function. CASE REPORT: A seven-year-old girl with a left hemispheric cerebral infarction lost almost all right upper extremity motor function. Following onabotulinumtoxinA treatment, she underwent hand-arm bimanual intensive therapy augmented with a hybrid assistive limb for 90 h over 15 days. Evaluation after the training revealed significant improvements in physical function, daily activities, and occupational performance. CONCLUSIONS: This report highlights the importance of innovative combinations of techniques in the treatment of pediatric stroke.

A call for action: Increasing the pediatric rehabilitation medicine workforce.

Pediatric Rehabilitation Medicine (PRM) is a unique blend of traditional medical rehabilitation knowledge and skills primarily focused on temporary and/or permanent disability conditions of childhood onset throughout the age continuum, with an emphasis on promoting function and participation. Although there are two established pathways to enhance knowledge and skills in PRM, one a combined residency with Pediatrics and the other a PRM fellowship, there has been a relative decline in participants in this training, as has been seen across other subspecialties in Physical Medicine and Rehabilitation (PM&R) and other medical specialties. Based on pediatric rehabilitation physician surveys and the increasing prevalence of children with disabilities, there has been a call to consider opening PRM fellowships to physicians not trained in PM&R. This commentary proposes establishing a commission to lead a transparent and inclusive process to assure that all options to address issues related to optimizing PRM care are considered and provide a course of action to address the needs of children and adults with childhood onset disabilities.

Treatment of oromandibular dystonia with botulinum toxin A improves apnea in a teenager with quadriplegic cerebral palsy: A case report.

This report describes a 15-year-old female with known spastic and dystonic quadriplegic cerebral palsy (CP), Gross Motor Function Classification System IV, and obstructive sleep apnea (OSA). She experienced decreased apneic episodes after receiving onabotulinumtoxin A (BoNT-A) injections for the treatment of oromandibular dystonia (OMD). After her OSA diagnosis, she initially received injections to the bilateral masseter and temporalis muscles with no effect on the frequency of nightly apneic episodes. Subsequently, the bilateral lateral pterygoid muscles were added and she was later noted to have fewer apneic episodes overnight. This case report describes the use of BoNT-A in the muscles of mastication for management of OMD and the ensuing improvement in OSA in a teenager with CP.

Treatment of pediatric spasticity, including children with cerebral palsy, with Botox (onabotulinumtoxinA): Development, insights, and impact.

Spasticity is a velocity-dependent increase in muscle tone that has a negative effect on quality of life and hinders the ability of others to provide care. In children, most cases are caused by cerebral palsy. Traditionally, many children are treated with surgery, sometimes performed before their limbs had grown sufficiently to permit long-term success. Nonsurgical treatment comprises oral pharmacological options, but their efficacy is limited and side effects such as drowsiness and decreased short-term memory are common; nerve block procedures can cause painful dysesthesias and muscle scarring. OnabotulinumtoxinA was first approved for the treatment of pediatric lower limb spasticity in Europe in the 1990s and is now licensed for use in pediatric patients in over 80 countries worldwide, based on a large body of clinical evidence demonstrating its efficacy and safety. In 2019 the U.S. Food and Drug Administration approved onabotulinumtoxinA for the treatment of pediatric patients with upper or lower limb spasticity. This approval represents 3 decades of work to refine the dose, measurements, patient selection, and muscle selection. The availability of onabotulinumtoxinA as a treatment for pediatric spasticity can have a substantial impact on a patient's quality of life. The use of onabotulinumtoxinA in combination with orthoses and occupational/physical therapy can postpone corrective surgery until growth is nearly complete and minimize the number of corrective surgeries.

Effects of Timed Frontal Plane Pelvic Moments During Overground Walking With a Mobile TPAD System.

Robotic gait training may improve overground ambulation for individuals with poor control over pelvic motion. However, there is a need for an overground gait training robotic device that allows full control of pelvic movement and synchronizes applied forces to the user's gait. This work evaluates an overground robotic gait trainer that applies synchronized forces on the user's pelvis, the mobile Tethered Pelvic Assist Device. To illustrate one possible control scheme, we apply assistive frontal plane pelvic moments synchronized with the user's continuous gait in real-time. Ten healthy adults walked with the robotic device, with and without frontal plane moments. The frontal plane moments corresponded to 10% of the user's body weight with a moment arm of half their pelvic width. The frontal plane moments significantly increased the range of frontal plane pelvic angles from 2.6° to 9.9° and the sagittal and transverse planes from 4.6° to 10.1° and 3.0° to 8.3°, respectively. The frontal plane moments also significantly increased the activation of the left gluteus medius muscle, which assists in regulating pelvic obliquity. The right gluteus medius muscle activation did not significantly differ when frontal plane moments were applied. This work highlights the ability of the mobile Tethered Pelvic Assist Device to apply a continuous pelvic moment that is synchronized with the user's gait cycle. This capability could change how overground robotic gait training strategies are designed and applied. The potential for gait training interventions that target gait deficits or muscle weakness can now be explored with the mobile Tethered Pelvic Assist Device.

Ultrasound-Guided OnabotulinumtoxinA Injections to Treat Oromandibular Dystonia in Cerebral Palsy.

Cerebral palsy (CP) is a group of non-progressive disorders of motor function in children resulting from an injury to an immature brain. In addition to abnormal limb and trunk movement, individuals with CP can experience involuntary muscle contractions of the lower facial muscle groups, causing oromandibular dystonia (OMD). Contraction of the lateral pterygoids and submandibular muscles depresses the mandible. OMD involving the lateral pterygoids can therefore lead to involuntary jaw opening posture, affecting the ability to feed and speak effectively. We present a case series of five patients with CP and OMD that received novel ultrasound-guided onabotulinumtoxinA to the lateral pterygoid muscles. Our goal was to determine if chemodenervation would improve the mouth-closing ability, thus in turn improving the ability to swallow, chew, manage secretions, and communicate. We describe this unique injection method and report a subjective improvement in eating abilities and communication, in addition to a positive upward trend in most patients' weights, with no significant adverse side effects.

A pediatric physiatrist's approach to neuromuscular hip dysplasia in cerebral palsy.

Cerebral palsy (CP) encompasses a group of disorders pertaining to abnormalities in movement, tone, and/or posture due to a nonprogressive lesion to an immature brain. Hip dysplasia is the second most common orthopedic deformity seen in CP, and its severity can range from a hip at risk for subluxation to full hip dislocation with degenerative changes. The purpose of this article is to review the hip pathologies that occur in CP focusing on their pathogenesis, physical exam findings, impact on function, and conservative treatment. Through a review of the medical literature, it is demonstrated that early, aggressive, and comprehensive care led by a pediatric physiatrist is essential to mitigate progression to complete hip dislocation and preserve range of motion, prevent contracture, and promote maximum functional ability in all children with CP.

Efficacy and safety of onabotulinumtoxinA with standardized physiotherapy for the treatment of pediatric lower limb spasticity: A randomized, placebo-controlled, phase III clinical trial.

BACKGROUND: Spasticity is common in cerebral palsy and can result in pain and diminished health-related quality of life. OBJECTIVE: To evaluate the safety and efficacy of onabotulinumtoxinA for lower limb spasticity treatment in children with cerebral palsy. METHODS: In this registrational phase 3, multinational, randomized, double-blind, placebo-controlled trial (NCT01603628), children (2-< 17 years) with cerebral palsy and ankle spasticity (Modified Ashworth Scale-Bohannon [MAS] score≥2) were randomized 1 : 1 : 1 to standardized physical therapy and onabotulinumtoxinA (4 or 8 U/kg), or placebo. Primary endpoint was average change from baseline at weeks 4 and 6 in MAS ankle score. Secondary endpoints included the Modified Tardieu Scale (MTS) and Global Attainment Scale (GAS). RESULTS: 381 participants were randomized. MAS scores averaged at weeks 4 and 6 were significantly reduced with both onabotulinumtoxinA doses (8 U/kg: -1.06, p = 0.010; 4 U/kg: -1.01, p = 0.033) versus placebo (-0.8). Significant improvements in average dynamic component of spasticity, measured by MTS, and in function, measured by GAS, were observed at several time points with both onabotulinumtoxinA doses versus placebo. Most adverse events were mild or moderate. CONCLUSIONS: OnabotulinumtoxinA was well tolerated and effective in reducing lower limb spasticity and improving functional outcomes versus placebo in children.

Is botulinum toxin type A more effective and safer than other treatments for the management of lower limb spasticity in children with cerebral palsy? A Cochrane Review summary with commentary.

BACKGROUND: Botulinum toxin A (BoNT-A) is a well-accepted treatment for the medical management of spasticity in children with cerebral palsy (CP). OBJECTIVE: To assess the efficacy and safety of BoNT-A compared with other treatment options in managing lower limb spasticity in children with CP. METHODS: A summary of the Cochrane Review update by Blumetti et al. (2019), with comments. RESULTS: This review included 31 randomized controlled trials (1508 participants). Compared with usual care/physiotherapy, the evidence is very uncertain about the effect of BoNT-A on gait, function, ankle joint range of motion (ROM), satisfaction, and ankle spasticity in children with CP. Compared with placebo/sham, BoNT-A probably benefits these same outcomes, although the results for function are contradictory. BoNT-A may not be more effective than serial casting at improving gait, function, ankle ROM and spasticity at any time point. However, it may be more effective than an orthosis at medium-term follow-up for hip ROM and adductor spasticity, but not function. The rate of adverse events with BoNT-A is similar to placebo/sham and serial casting. CONCLUSIONS: Evidence for the effectiveness and safety of BoNT-A for the management of lower limb spasticity in children with CP is uncertain, with better quality evidence available from studies of placebo/sham than non-placebo controls. To produce high-quality evidence, future studies need to improve their methodological quality and increase sample sizes.

Placebo-Controlled Clinical Trial of IncobotulinumtoxinA for Sialorrhea in Children: SIPEXI.

BACKGROUND AND OBJECTIVES: This prospective phase III study (SIPEXI) investigated efficacy and safety of repeated injections of incobotulinumtoxinA (incoBoNT/A) for treatment of chronic sialorrhea (drooling) associated with neurological disorders (e.g., cerebral palsy, traumatic brain injury) and/or intellectual disability in children/adolescents. METHODS: The study enrolled 2-17-year-olds with sialorrhea due to neurological disorders and/or intellectual disability. Patients received body weight-dependent doses of incoBoNT/A (20 U to 75 U). A main period with 1 injection cycle (placebo-controlled, double-blind, 6-17-year-olds) was followed by an open-label extension with up to 3 further cycles. An additional cohort of 2-5-year-olds received active treatment throughout the study. Co-primary endpoints were the change in unstimulated salivary flow rate (uSFR) from baseline to week 4, and the carers' global impression of change scale (GICS) rating at week 4. Adverse events were recorded. RESULTS: In the main period, 220 patients aged 6-17 years were randomized and treated (148 patients in incoBoNT/A group, 72 patients in placebo group). 35 patients aged 2-5 years received incoBoNT/A (no placebo). 214 patients aged 6-17 years and 33 patients aged 2-5 years continued treatment in the open-label extension period. For the 6-17-year-olds, a significant difference between incoBoNT/A and placebo was seen in the mean uSFR decrease (difference: -0.06 g/min; p = 0.0012) and the carers' GICS rating (difference: 0.28 points; p = 0.032) at week 4, in favor of active treatment. The secondary endpoints consistently supported these results. A sustained benefit was observed during the extension. Incidences of adverse events were comparable between incoBoNT/A and placebo and did not increase notably with repeated injections. The most common adverse events were respiratory infections. Efficacy and safety were also favorable in the uncontrolled cohort of 2-5-year-olds. DISCUSSION: Both co-primary efficacy endpoints were reached and superiority of incoBoNT/A over placebo was confirmed. IncoBoNT/A (up to 75 U, up to 4 cycles) is an effective and well-tolerated treatment for sialorrhea associated with neurological disorders in children. STUDY REGISTRATIONS: Clinicaltrials.gov: NCT02270736 (www.clinicaltrials.gov/ct2/show/results/NCT02270736); EU Clinical Trials Register: 2013-004532-30 (www.clinicaltrialsregister.eu/ctr-search/search?query=2013-004532-30). CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that injection of incobotulinumtoxinA decreases drooling in children aged 6-17 years with neurological disorders.

Cumulative Efficacy of Longitudinal Repeat Salivary Gland OnabotulinumtoxinA Injection: A Retrospective Study.

AIM: We hypothesized that repeat onabotulinumtoxinA (BTX-A) injections to salivary glands would have a cumulative effect on drooling, leading to prolonged efficacy duration. METHODS: We retrospectively reviewed medical records and conducted a telephone survey of individuals treated with BTX-A to the salivary glands to investigate ongoing efficacy or adverse effects. Outcome measures were duration of decrease in drooling and adverse events. The main independent variable was the number of injections. We identified 52 consecutive individuals (26 females) with cerebral palsy with an average age of 9 yrs, 3 mos ± 5 yrs 2 mos, who had received BTX-A for sialorrhea. RESULTS: Linear regression analysis showed that each additional injection resulted in the duration of efficacy being 0.68 mos longer (P < 0.001, R2 = 0.47). Age, sex, Gross Motor Function Classification System level, presence of tube feeding, presence of tracheostomy, gastroesophageal reflex, seizures, and concurrent intramuscular injections seizures were not significant contributors to the association between injection number and efficacy duration (F (6, 45) = 1.01, P = 0.431). INTERPRETATION: There may be a cumulative effect of BTX-A injections to the salivary glands, resulting in longer periods of efficacy with consecutive injection.

Capsular distention for adhesive capsulitis in a pediatric patient with acute flaccid myelitis: A case report.

INTRODUCTION: Acute Flaccid Myelitis (AFM) is a recently recognized pediatric condition characterized by flaccid paralysis that can cause lifelong deficits. Adhesive Capsulitis (AC) is a chronic condition that causes loss of passive range of motion in the shoulder due to joint contracture. CASE REPORT: This is a case report of a 15-year-old male who suffered from shoulder pain with progressive loss of passive range of motion after AFM, diagnosed with AC based on exam and radiology. After failing conservative management, the patient was successfully treated with ultrasound guided corticosteroid injection. DISCUSSION/CONCLUSION: AC is uncommonly reported in pediatric patients. However, secondary adhesive capsulitis is frequently associated with disorders of shoulder immobility in adults. This case contributes to the body of literature regarding pediatric frozen shoulder, highlights the successful use of ultrasound guided injections for management, and suggests a relationship between AFM and AC which may be beneficial for pediatric physiatrists in treating patients with shoulder pain or immobility related to this condition.

Evaluation of assessment of caregiver experience with neuromuscular disease: reliability and responsiveness of a new caregiver-reported outcome measure in patients with cerebral palsy.

BACKGROUND: Cerebral palsy (CP) is the most common cause of chronic childhood disability. Caregivers often provide prolonged care over patients' life span, thus measuring the impact of the disease and its treatments on caregivers has become a recent focus in research. The current study aims to present an evaluation of the reliability and responsiveness of assessment of caregiver experience with neuromuscular disease (ACEND) following botulinum toxin injection to relieve spasticity in children with CP. METHODS: Patients with baseline ACEND scores and at least one assessment following botulinum toxin injection were enrolled. Data on their gender, age, diagnoses, and functional levels (according to The Gross Motor Function Classification System, GMFCS), and ACEND scores were analyzed. Statistical analyses performed included paired t-test and linear regression. RESULTS: Baseline ACEND scores (117.7±47.7) were strongly correlated with follow-up scores (120.4±49.5) with a coefficient of 0.929 (P<0.001), suggesting the high reliability of the questionnaire. Paired-sample t-test revealed an insignificant average improvement in ACEND of 2.7 (P=0.352). The ICD-10 code and the GMFCS level were found to be significant predictors for baseline (P=0.043, P<0.001) and follow-up ACEND scores (P=0.025, P<0.001). Male gender was a significant predictor for improvement in ACEND scores. CONCLUSIONS: We demonstrated the reliability of ACEND through strong correlations of scores before and after botulinum toxin injection. In terms of responsiveness, while the burden of care is largely determined by ICD-10 diagnosis and the GMFCS level, changes in care burden are only related to the gender of the patient and the follow-up time interval.

Symptomatic cervical spinal stenosis in spastic cerebral palsy.

AIM: To describe the prevalence of symptomatic cervical spinal stenosis (CSS) in spastic cerebral palsy (CP) and associated characteristics. METHOD: This cross-sectional study of adults (>18y) with CP (2006-2016) at a single institution compared the patient characteristics (demographics, comorbidities, surgical history, medications, Gross Motor Function Classification System [GMFCS] level, and CP type) of patients with and without CSS. RESULTS: Of 424 patients (mean age 33y 4mo, SD 13y 6mo, range 18-78y; 225 females, 199 males), 32 patients (7.5%) had symptomatic CSS. GMFCS levels in the study cohort were distributed as follows: level I, 25%; level II, 25%; level III, 22%; level IV, 19%; level V, 9%. Twenty-five out of 32 (78.1%) patients had spastic CP, two (6.3%) had dystonic CP, and one (3.1%) had mixed characteristics. Individuals with CSS were older (mean age 54y 6mo, SD 10y 5mo vs mean age 31y 7mo, SD 12y 1mo, p<0.05) and had a higher body mass index (26.1, SD 4.8 vs 23.4, SD 6.2, p<0.05) than those without CSS. Presentations included upper-extremity symptoms (73%), ambulation decline (70%), neck pain (53%), and incontinence (30%). Common stenosis levels were C5-C6 (59%), C4-C5 (56%), and C6-C7 (53%). INTERPRETATION: Symptomatic CSS was identified in 7.5% of this adult cohort during the 2006 to 2016 period. Diagnosis in CP is difficult due to impaired communication and pre-existing gait abnormalities and spasticity. Given the high prevalence of symptomatic CSS in adults, we propose developing screening guidelines. Physicians must maintain a high level of suspicion for CSS if patients present with changes in gait or spasticity.

Facts and de facto treatment of spasticity.

Recent studies have generally shown favorable outcomes for the use of botulinum toxin (BoNT) injections for the treatment of lower extremity spasticity in children with cerebral palsy. The randomized controlled trials and placebo trials are well described although even those and other studies show high variability in methodology for use of BoNT. This raises questions about which strategies are the most effective. In order to hone the technique, the aim of this review is to discuss these specific parameters: toxin type, dosing, series of injections, localization method, age, number of muscles, and troubleshooting poor outcomes.