Relationship of anthropometric measurements and percent body fat mass to cardiovascular disease risk factors in adults with cerebral palsy.

INTRODUCTION: Adults with cerebral palsy (CP) face high morbidity from cardiovascular disease (CVD). Of concern, classic screening parameters are inconsistent in identifying CVD risk in this population. Dual-energy x-ray absorptiometry (DEXA), which provides direct measurements of fat mass (FM), may be an alternative screening method. OBJECTIVE: To evaluate whether FM measurement with DEXA is feasible in screening adults with CP and compare FM and anthropometric measures to CVD risk factors. DESIGN: Cross-sectional study. SETTING: Outpatient rehabilitation hospital. PARTICIPANTS: Forty-seven adults with CP. MAIN OUTCOME MEASURES: Weight, height, waist circumference (WC), and hip circumference (HC) were measured; waist-to-hip ratio (WHR) and body mass index (BMI) were calculated. Blood pressure (BP), FM by DEXA, hemoglobin A1c (HbA1c), and lipid measurements were obtained. Logistic regression models investigated odds ratios (ORs) and 95% confidence intervals (CIs) between anthropometric measurements/FM and CVD risk factors; correlations were assessed using Pearson correlation coefficients. RESULTS: Elevated BP or hypertension diagnosis was present in 47.8%; HbA1c ≥5.7% in 22.2%; and high-density lipoprotein (HDL) level below optimal for 33.3%. DEXA FM was obtained in 29 of 47 participants, as surgical metal and positioning limited many studies. Excess FM was noted in 75.9% versus 41.3% overweight/obese by BMI. WC correlated with HbA1c (r = 0.46, p = .002), HDL (r = -0.36, p = .018), and triglyceride (TG) levels (r = 0.30, p = .045); however at-risk WC values were associated only with odds of elevated HbA1c (OR 8.53, 95% CI 1.46-50.05; p = .018). HC correlated with HbA1c levels (r = 0.38, p = .011) and systolic BPs (r = 0.35, p = .019); similarly, ORs for elevated HC were weakly associated with elevated HbA1c and BPs (OR 1.08, 95% CI 1.01-1.16; p = .024 and OR 1.07, 95% CI 1.01-1.14; p = .024, respectively). WHR correlated with TGs; however few TG levels were elevated. FM measures were not associated with at-risk lab values or BPs. CONCLUSIONS: DEXA FM measurements may not be feasible for CVD screening in many adults with CP. Although CVD risk factors are frequently present, anthropometric measurements commonly used for general population screening may not translate well to adults with CP.

Do Muscle Changes Contribute to the Neurological Disorder in Spastic Paresis?

Background: At the onset of stroke-induced hemiparesis, muscle tissue is normal and motoneurones are not overactive. Muscle contracture and motoneuronal overactivity then develop. Motor command impairments are classically attributed to the neurological lesion, but the role played by muscle changes has not been investigated. Methods: Interaction between muscle and command disorders was explored using quantified clinical methodology-the Five Step Assessment. Six key muscles of each of the lower and upper limbs in adults with chronic poststroke hemiparesis were examined by a single investigator, measuring the angle of arrest with slow muscle stretch (XV1) and the maximal active range of motion against the resistance of the tested muscle (XA). The coefficient of shortening CSH = (XN-XV1)/XN (XN, normally expected amplitude) and of weakness CW = (XV1-XA)/XV1) were calculated to estimate the muscle and command disorders, respectively. Composite CSH (CCSH) and CW (CCW) were then derived for each limb by averaging the six corresponding coefficients. For the shortened muscles of each limb (mean CSH > 0.10), linear regressions explored the relationships between coefficients of shortening and weakness below and above their median coefficient of shortening. Results: A total of 80 persons with chronic hemiparesis with complete lower limb assessments [27 women, mean age 47 (SD 17), time since lesion 8.8 (7.2) years], and 32 with upper limb assessments [18 women, age 32 (15), time since lesion 6.4 (9.3) years] were identified. The composite coefficient of shortening was greater in the lower than in the upper limb (0.12 ± 0.04 vs. 0.08 ± 0.04; p = 0.0002, while the composite coefficient of weakness was greater in the upper limb (0.28 ± 0.12 vs. 0.15 ± 0.06, lower limb; p < 0.0001). In the lower limb shortened muscles, the coefficient of weakness correlated with the composite coefficient of shortening above the 0.15 median CSH (R = 0.43, p = 0.004) but not below (R = 0.14, p = 0.40). Conclusion: In chronic hemiparesis, muscle shortening affects the lower limb particularly, and, beyond a threshold of severity, may alter descending commands. The latter might occur through chronically increased intramuscular tension, and thereby increased muscle afferent firing and activity-dependent synaptic sensitization at the spinal level.

Association Between Daily Physical Activity and Clinical Anthropomorphic Measures in Adults With Cerebral Palsy.

OBJECTIVE: To describe the relationship between activity level and cardiovascular risk measures as well as describe general activity patterns of adults with cerebral palsy. DESIGN: Cross-sectional. SETTING: Academic outpatient rehabilitation clinic. PARTICIPANTS: Adults with cerebral palsy (N=47). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Gross Motor Functional Classification System (GMFCS) level was determined by validated self-report questionnaire. Activity (daily step count, walk time, sitting time, standing time, and transitional movements) over 6 days recorded using an activPAL. Weight, body mass index (BMI), and waist-to-hip ratio were measured. Bivariate relationships between anthropomorphic and activity measures were assessed. RESULTS: Thirty-eight participants completed all measurements. Nine were excluded because of incomplete activPAL data. The median age was 28.50 years (interquartile range [IQR]=24.25-47.00), range 18-77 years. Participants' GMFCS levels were I: 13%; II: 16%; III: 21%; IV: 34%; and V: 16%. Median steps/day for GMFCS I/II participants were 5258.3 (IQR=3606.8-6634.7), and median steps/day were 1681.3 (IQR=657.2-2751.8) and 30.0 (IQR=6.8-54.2) for GMFCS level III and IV/V participants, respectively. Significantly greater steps/day were found for GMFCS I/II or III participants compared to those GMFCS IV/V (P<.001 and P=.0074, respectively). In addition, 60.5% of the subjects had a BMI in the normal range, 10.5% were obese, 23.6% were overweight, and 5.3% were underweight. For subjects with GMFCS I/II, the Spearman's rank correlation coefficient for time standing and waist circumference was -0.73 (0.01). GMFCS III and GMFCS IV/V participants had respective correlations of -0.16 (0.71) and -0.01 (0.98). For subjects with GMFCS I/II, the Spearman's rank correlation coefficient for standing time and BMI was -0.55 (P=.08). For the GMFCS III and GMFCS IV/V groups the respective correlations were -0.19 (0.67) and 0.00 (1.00). CONCLUSIONS: Subjects with GMFCS level I or II who engaged in more activity tended to have more favorable anthropometric profiles. Subjects with GMFCS level III, IV, or V did not have a similar trend. Our findings suggest factors beyond activity patterns affect anthropometrics to a greater degree in those with higher GMFCS levels.

Breast Health Experiences in Women with Cerebral Palsy: A Qualitative Approach.

Background: All women, regardless of disability status, should receive screening for breast cancer. In 2010, only 61.4% of women with disabilities (WWD) received a mammogram in the past 2 years compared to 75% of women without disabilities. The purpose of this study is to explore breast cancer screening experiences of women with cerebral palsy (CP) with the aim of identifying factors that could improve screening rates for WWD. Methods: Thirty women with CP, 22-72 years of age, residing in New York, Chicago, or Los Angeles areas participated in individual or group interviews about breast health. Twenty-five of the participants identified themselves as white, and one self-identified as Hispanic or Latina. Facilitators used a semistructured guide across the three sites. Qualitative analysis utilized an iterative coding process to generate themes related to breast health. Results: We identified six predominant themes in these interviews, which revolved around physical, environmental, and emotional barriers and facilitators. Within each theme, we identified subthemes. Physical barriers included the most highly identified subthemes of age, pain, holding breath, holding still, spasticity, standing, fatigue, and positioning. Self-advocacy and communication between the health care professional and the patient were the most common subthemes identified among the emotional facilitators. Conclusion: Women with CP perceive a variety of issues impacting breast health. These findings are multifaceted and suggest that improving screening rates for women with CP should address these barriers and facilitators.

Women with cerebral palsy: A qualitative study about their experiences with sexual and reproductive health education and services.

PURPOSE: To explore the recalled experiences of women with CP regarding sexual health education and services they received. METHODS: Semi-structured interviews and focus groups were conducted at four academic tertiary hospitals with 33 adult women with CP. Templates were used to ask about four key content domains: appointment planning (including planning for a gynecologic exam), accessibility of services, experiences with providers, and recommendations for improvement. Sessions were transcribed verbatim and analyzed to generate a coding dictionary. Blinded coding was carried out for each transcript, with duplicate coding used to confirm identified themes. Iterative analysis was used to identify and consolidate coding and key themes. RESULTS: Similar barriers were discussed at the four sites, including lack of accessible exam tables, hospital staff unfamiliar with physical disabilities, and assumptions that women with CP are not sexually active. Many described the sexual education they received as brief, omitted, or mistimed. Self-advocacy was crucial, and recommended strategies ranged from pre-gynecologic exam medication to visit checklists. CONCLUSION: Reproductive health education for young women with CP is frequently inadequate. Medical professionals lack relevant knowledge and awareness; medical facilities lack necessary infrastructure. Recommendations for improvements are made.

Blood pressure in adults with cerebral palsy: a systematic review and meta-analysis of individual participant data.

OBJECTIVES: This systematic review and meta-analysis was designed to determine the overall mean blood pressure and prevalence of hypertension among a representative sample of adults living with cerebral palsy by combining individual participant data. Additional objectives included estimating variations between subgroups and investigating potential risk factors for hypertension. METHODS: Potential datasets were identified by literature searches for studies published between January 2000 and November 2017 and by experts in the field. Samples of adults with cerebral palsy (n ≥ 10, age ≥ 18 years) were included if blood pressure data, cerebral palsy-related factors (e.g. cerebral palsy subtype), and sociodemographic variables (e.g. age, sex) were available. Hypertension was defined as at least 140/90 mmHg and/or use of antihypertensive medication. RESULTS: We included data from 11 international cohorts representing 444 adults with cerebral palsy [median (IQR) age of the sample was 29.0 (23.0-38.0); 51% men; 89% spastic type; Gross Motor Function Classification System levels I-V]. Overall mean SBP was 124.9 mmHg [95% confidence interval (CI) 121.7-128.1] and overall mean DBP was 79.9 mmHg (95% CI 77.2-82.5). Overall prevalence of hypertension was 28.7% (95% CI 18.8-39.8%). Subgroup analysis indicated higher blood pressure levels or higher prevalence of hypertension in adults with cerebral palsy above 40 years of age, men, those with spastic cerebral palsy or those who lived in Africa. BMI, resting heart rate and alcohol consumption were risk factors that were associated with blood pressure or hypertension. CONCLUSION: Our findings underscore the importance of clinical screening for blood pressure in individuals with cerebral palsy beginning in young adulthood.

Diet quality in adults with cerebral palsy: a modifiable risk factor for cardiovascular disease prevention.

AIM: To assess diet quality and its relationship with cardiovascular health measures for adults with cerebral palsy (CP). METHOD: A convenience sample of 45 adults with CP (26 females, 19 males; mean age 35y 10mo [SD 14y 9mo]). were recruited for this cross-sectional study. Demographic, medical, and Gross Motor Function Classification System (GMFCS) information were obtained through in-person visits. Participants completed two 24-hour dietary recalls using the Automated Self-Administered 24-hour Dietary Assessment Tool. Specific macronutrient intake was compared to 2015 to 2020 US Department of Agriculture (USDA) guidelines. Other data included body mass index (BMI), waist-to-hip ratio (WHR), blood pressure, and hemoglobin A1c (HgA1c;n=43). RESULTS: Adults across GMFCS levels I to V were enrolled, 20 participants were in GMFCS levels IV or V. Mean calorie intake was 1777.91/day (SD 610.54), while sodium intake was 3261.75mg/day (SD 1484.92). Five participants met USDA vegetable and seven fruit guidelines. None met whole grain targets. Sixteen were overweight/obese by BMI. Sixteen participants without hypertension diagnoses had elevated blood pressure and nine had abnormal HgA1c without prediabetes/diabetes history. Percent calories from saturated fat was inversely associated with WHR in unadjusted and adjusted models (p=0.002 and p=0.003 respectively); all other dietary recommendations assessed (total calories, sodium, and sugar) were non-significant. Post hoc analyses were unchanged using 2020 to 2025 USDA guidelines. INTERPRETATION: Assessment of nutrient intake and diet quality is feasible and warrants further study in adults with CP, as USDA guidelines are largely unmet. What this paper adds Adults with cerebral palsy (CP) do not meet US Department of Agriculture dietary quality recommendations. Prediabetes and hypertension may be common, but unrecognized, in adults with CP. Screening for nutrient intake and diet quality should be performed to facilitate nutritional counseling.

Sustained efficacy of incobotulinumtoxina repeated injections for upper-limb post-stroke spasticity: A post hoc analysis.

OBJECTIVE: This post hoc analysis assessed the impact of repeated incobotulinumtoxinA injections on muscle tone, disability, and caregiver burden in adults with upper-limb post-stroke spasticity. DESIGN: Data from the double-blind, placebo-controlled main period and three open-label extension cycles of two Phase 3, randomized, multicentre trials were pooled. METHODS: Subjects received incobotulinumtoxinA 400 Units at 12-week intervals (±3 days) (study 3001, NCT01392300) or ≤ 400 Units at ≥12-week intervals based on clinical need (study 0410, NCT00432666). Ashworth Scale (AS) arm sumscore (sum of elbow, wrist, finger and thumb flexor, and forearm pronator AS scores), Disability Assessment Scale (DAS), and Carer Burden Scale (CBS) scores were assessed. RESULTS: Among 465 subjects, from study baseline to 4 weeks post-injection, mean (standard deviation) AS arm sumscore improved continuously: main period, -3.23 (2.55) (placebo, -1.49 (2.09)); extension cycles 1, 2, and 3, -4.38 (2.85), -4.87 (3.05), and -5.03 (3.02), respectively. DAS principal target domain responder rate increased from 47.4% in the main period (placebo 27.2%) to 66.6% in extension cycle 3. Significant improvements in CBS scores 4 weeks post-injection accompanied improved functional disability in all cycles. CONCLUSION: IncobotulinumtoxinA conferred sustained improvements in muscle tone, disability, and caregiver burden in subjects with upper-limb post-stroke spasticity.

Duration of Treatment Effect Using IncobotulinumtoxinA for Upper-limb Spasticity: A Post-hoc Analysis.

The efficacy and safety of incobotulinumtoxinA ≤400 U was demonstrated in subjects with post-stroke upper-limb spasticity in a randomized, double-blind Phase 3 study with an open-label extension (OLEX; EudraCT number 2005-003951-11, NCT00432666). We report a post-hoc analysis of the duration of the treatment effect. Subjects completing the placebo-controlled main period (single injection cycle with 12-20-week observation) entered the OLEX and received a maximum of five further treatments (maximum duration 69 weeks) with incobotulinumtoxinA ≤400 U at flexible intervals with a minimum duration of 12 weeks, based on clinical need. Intervals between two consecutive incobotulinumtoxinA injections, excluding treatment intervals prior to the end-of-study visit, were evaluated. Of 437 incobotulinumtoxinA treatment intervals, 415 received by 136 subjects were included in the post-hoc analysis. More than half (52.3%; 217/415) of all incobotulinumtoxinA reinjections were administered at Week ≥14, 31.1% (129/415) at Week ≥16, 19.0% (79/415) at Week ≥18, and 11.6% (48/415) at Week ≥20. The duration of effect may vary and can exceed 20 weeks or more, which was observed in at least one injection cycle in 29.4% (40/136) subjects over the course of their treatment. Data show that incobotulinumtoxinA retreatment for upper-limb spasticity may not be required at 12-week intervals and provides evidence for flexible treatment intervals beyond this time frame.

IncobotulinumtoxinA Treatment in Upper-Limb Poststroke Spasticity in the Open-Label Extension Period of PURE: Efficacy in Passive Function, Caregiver Burden, and Quality of Life.

BACKGROUND: Poststroke spasticity affects motor function and the ability to perform activities of daily living, with the potential to affect quality of life (QoL) and increase caregiver burden. OBJECTIVE: To investigate the effect of repeated incobotulinumtoxinA treatment on spasticity-associated functional disability, caregiver burden, and QoL in the 36-week open-label extension of the phase 3 PURE study (NCT01392300). DESIGN: Open-label extension period of a prospective, double-blind, placebo-controlled, randomized, multicenter study. SETTING: Forty-six investigation sites in seven countries (Czech Republic, Germany, Hungary, India, Poland, Russia, United States). PARTICIPANTS: Adults, aged 18-80 years, ≥12 months since last botulinum neurotoxin injection or entirely toxin naïve, with median poststroke upper-limb spasticity of >2 years' duration. METHODS: Participants who completed the 12-week, double-blind main period could enter the open-label extension and receive up to three additional incobotulinumtoxinA treatments (fixed total dose 400 U at 12-week intervals) into the affected muscles of one upper limb. MAIN OUTCOME MEASURES: Functional disability (Disability Assessment Scale; DAS), caregiver burden (Carer Burden Scale), and quality of life (QoL; EuroQol [EQ] 5-dimensions three-level [EQ-5D-3L]). RESULTS: The open-label extension included 296 treated patients. Mean DAS score for the principal target domain improved significantly from the main period baseline to the end-of-study visit (P < .0001). Carer Burden Scale scores also significantly improved from the main period baseline to the end-of-study visit (P < .05 for all caregiving activities except "applying a splint"). At the end-of-study visit, versus the main period baseline, 19.7%-33.3% of patients experienced improvements for each parameter on the EQ-5D-3L, except "mobility," with significant improvement in EQ-5D visual analog scale scores (P < .001). CONCLUSIONS: Repeated incobotulinumtoxinA treatments at 12-week intervals in participants with chronic poststroke upper-limb spasticity resulted in significant improvements in QoL, as well as significant reductions in upper-limb functional disability and caregiver burden.

Spasticity and pain in adults with cerebral palsy.

AIM: To evaluate whether spasticity measures are related to pain in adults with cerebral palsy (CP). METHOD: This cross-sectional study recruited individuals aged 16 to 89 years with a diagnosis of CP. Participants completed the Penn Spasm Frequency Scale (PSFS), Brief Pain Inventory (BPI), and PROMIS Pain Interference measures. The Modified Ashworth Scale (MAS) and Tardieu spasticity angles of six joints were rated and summed to composite MAS and Tardieu scores for each participant. Associations between spasticity and pain measures were evaluated. RESULTS: Forty-seven participants (27 females, 20 males) with a mean age of 35 years 7 months (range 18-77y) spanning all Gross Motor Function Classification System (GMFCS) levels were included. Twenty-six participants reported their average pain level on BPI as greater than 0 over the past week (median pain level 4.0). Median PSFS was 1.0 (range 0.0-1.0) and this correlated with average BPI and Pain Interference T scores (median 40.7; ρ=0.33 and ρ=0.31 respectively [both p=0.01]). When adjusted for pain medication use and age, MAS correlated with BPI (ρ=0.30; p=0.04). Other pain and spasticity measures, or GMFCS level, were not significantly related with pain interference or BPI rating. Age was weakly associated with BPI (slope=0.10; p<0.01). INTERPRETATION: PROMIS Pain Interference was lower than population-based norms. Patient-rated spasm frequency demonstrated better association with pain levels and interference than physician-rated MAS and Tardieu. WHAT THIS PAPER ADDS: Pain was not associated with Gross Motor Function Classification System level. Pain increased with age, as anticipated. Self-reported spasm scores were associated with increased pain in contrast to clinical examination scales. Adjusted, summed spasticity on the Modified Ashworth Scale was associated with pain scores on the Brief Pain Inventory. Although pain is experienced by adults with cerebral palsy, pain did not interfere with activities.

Using Implementation Frameworks to Provide Proactive Physical Therapy for People With Parkinson Disease: Case Report.

BACKGROUND AND PURPOSE: European clinical practice guidelines recommend physical therapy for people with Parkinson disease (PD) soon after diagnosis to provide education, physical activity advice, and individualized interventions when needed. However, therapy is frequently not used until after gait and balance problems occur. The purpose of this administrative case study is to present the application of a proactive physical therapy (PAPT) approach at 1 rehabilitation center using implementation frameworks to support the (1) implementation process, (2) determinants of implementation success, and (3) implementation evaluation. CASE DESCRIPTION: The PAPT program targeted people with PD before the onset of significant mobility dysfunction. It was initiated in 1 outpatient neurological rehabilitation center. The program used shared decision-making to promote long-term maintenance of independent exercise. The Knowledge-to-Action Framework was used by champions to plan implementation processes. Implementation barriers were addressed using the Consolidated Framework for Implementation Research. The program was evaluated using the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework with mixed methods. OUTCOMES: In the program's first year, 38 people were referred, 28 were evaluated, and 20 participated in the 6-month program evaluation. Following PAPT, the number of participants reporting regular participation in aerobic, strengthening, and flexibility exercise approximately doubled, while those engaging in balance activities increased from 1 to 8. They reported a median of 140 minutes of aerobic exercise per week. Implementation barriers included location, insurance coverage, and difficulty scheduling long-term follow-up visits. Participants reported physical and emotional benefits of the program. DISCUSSION: Implementation frameworks assisted with the implementation and evaluation of a PAPT delivery model that helped people with PD to increase and maintain independent exercise participation.

Ultrasound Structural Changes in Triceps Surae After a 1-Year Daily Self-stretch Program: A Prospective Randomized Controlled Trial in Chronic Hemiparesis.

INTRODUCTION: The effects of long-term stretching (>6 months) in hemiparesis are unknown. This prospective, randomized, single-blind controlled trial compared changes in architectural and clinical parameters in plantar flexors of individuals with chronic hemiparesis following a 1-year guided self-stretch program, compared with conventional rehabilitation alone. METHODS: Adults with chronic stroke-induced hemiparesis (time since lesion >1 year) were randomized into 1 of 2, 1-year rehabilitation programs: conventional therapy (CONV) supplemented with the Guided Self-rehabilitation Contract (GSC) program, or CONV alone. In the GSC group, specific lower limb muscles, including plantar flexors, were identified for a diary-based treatment utilizing daily, high-load, home self-stretching. Blinded assessments included (1) ultrasonographic measurements of soleus and medial gastrocnemius (MG) fascicle length and thickness, with change in soleus fascicle length as primary outcome; (2) maximum passive muscle extensibility (XV1, Tardieu Scale); (3) 10-m maximal barefoot ambulation speed. RESULTS: In all, 23 individuals (10 women; mean age [SD], 56 [±12] years; time since lesion, 9 [±8] years) were randomized into either the CONV (n = 11) or GSC (n = 12) group. After 1 year, all significant between-group differences favored the GSC group: soleus fascicle length, +18.1mm [9.3; 29.9]; MG fascicle length, +6.3mm [3.5; 9.1]; soleus thickness, +4.8mm [3.0; 7.7]; XV1 soleus, +4.1° [3.1; 7.2]; XV1 gastrocnemius, +7.0° [2.1; 11.9]; and ambulation speed, +0.07m/s [+0.02; +0.16]. CONCLUSIONS: In chronic hemiparesis, daily self-stretch of the soleus and gastrocnemius over 1 year using GSC combined with conventional rehabilitation increased muscle fascicle length, extensibility, and ambulation speed more than conventional rehabilitation alone.

IncobotulinumtoxinA Efficacy and Safety in Adults with Upper-Limb Spasticity Following Stroke: Results from the Open-Label Extension Period of a Phase 3 Study.

INTRODUCTION: The objective of the study was to investigate the efficacy and safety of repeated incobotulinumtoxinA injections for the treatment of upper-limb post-stroke spasticity in adults. METHODS: Adults 18-80 years of age with post-stroke upper-limb spasticity who completed the 12-week randomized, double-blind, placebo-controlled main period (MP) of a phase 3 trial (NCT01392300) were eligible to enrol in the 36-week open-label extension period (OLEX). The OLEX included three treatment cycles at fixed 12-week injection intervals; subjects were injected with 400 U incobotulinumtoxinA into the affected upper limb. Efficacy assessments included evaluation of muscle tone using the Ashworth Scale (AS) and the Global Impression of Change Scale (GICS) assessed by the investigator, subject, and caregiver. The incidence of adverse events (AEs) was monitored throughout the OLEX. RESULTS: A total of 296 of 299 subjects (99.0%) who completed the MP received incobotulinumtoxinA in the OLEX, and 248 subjects completed the 36-week OLEX. The proportion of subjects with at least a 1-point improvement in AS score from each incobotulinumtoxinA treatment to the respective 4-week post-injection visit ranged by cycle from 52.3% to 59.2% for wrist flexors, 49.1% to 52.3% for elbow flexors, 59.8% to 64.5% for finger flexors, 35.5% to 41.2% for thumb flexors, and 37.4% to 39.9% for forearm pronators (P < 0.0001 for all). Over 90% of subjects were assessed by the investigator to be at least minimally improved (4 weeks post-injection) on the GICS during each injection cycle; 61.0% in the 1st cycle, 58.2% in the 2nd cycle, and 57.4% in the 3rd cycle were considered much improved or very much improved on the GICS. Three percent of subjects (9/296) reported treatment-related AEs; the most frequently reported were pain in the extremity (n = 2, 0.7%) and constipation (n = 2, 0.7%). Serious AEs were reported by 22 subjects (7.4%); however, none were considered treatment-related. CONCLUSIONS: Repeated injections of incobotulinumtoxinA for the treatment of post-stroke upper-limb spasticity led to significant improvements in muscle tone and investigator's global impression of change. Treatment was well tolerated, with no serious treatment-related AEs. FUNDING: Merz Pharmaceuticals GmbH.

Effect on Passive Range of Motion and Functional Correlates After a Long-Term Lower Limb Self-Stretch Program in Patients With Chronic Spastic Paresis.

BACKGROUND: In current health care systems, long-duration stretching, performed daily, cannot be obtained through prescriptions of physical therapy. In addition, the short-term efficacy of the various stretching techniques is disputed, and their long-term effects remain undocumented. OBJECTIVE: To evaluate changes in extensibility in 6 lower limb muscles and in ambulation speed after a ≥1-year self-stretch program, the Guided Self-rehabilitation Contract (GSC), in individuals with chronic spastic paresis. DESIGN: Retrospective study. SETTING: Neurorehabilitation clinic. PARTICIPANTS: Patients diagnosed with hemiparesis or paraparesis at least 1 year before the initiation of a GSC and who were then involved in the GSC program for at least 1 year. INTERVENTIONS: For each patient, specific muscles were identified for intervention among the following: gluteus maximus, hamstrings, vastus, rectus femoris, soleus, and gastrocnemius. Prescriptions and training for a daily, high-load, prolonged, home self-stretching program were primarily based on the baseline coefficient of shortening, defined as CSH = [(XN -XV1)/XN] (XV1 = PROM, passive range of motion; XN = normally expected amplitude). MAIN OUTCOME MEASUREMENTS: Six assessments were performed per year, measuring the Tardieu XV1 or maximal slow stretch range of motion angle (PROM), CSH, 10-m ambulation speed, and its functional ambulation category (Perry's classification: household, limited, or full). Changes from baseline in self-stretched and nonself-stretched muscles were compared, with meaningful XV1 change defined as ΔXV1 >5° for plantar flexors and >10° for proximal muscles. Correlation between the composite XV1 (mean PROM for the 6 muscles) and ambulation speed also was evaluated. RESULTS: Twenty-seven GSC participants were identified (14 women, mean age 44 years, range 29-59): 18 with hemiparesis and 9 with paraparesis. After 1 year, 47% of self-stretched muscles showed meaningful change in PROM (ΔXV1) versus 14% in nonself-stretched muscles (P < .0001, χ2). ΔCSH was -31% (95% confidence interval [95% CI] -41.5 to -15.2) in self-stretched versus -7% (95% CI -11.9 to -2.1) in nonself-stretched muscles (P < .0001, t-test). Ambulation speed increased by 41% (P < .0001) from 0.81 m/s (95% CI 0.67-0.95) to 1.15 m/s (95% CI 1.01-1.29). Eight of the 12 patients (67%) who were in limited or household categories at baseline moved to a higher functional ambulation category. There was a trend for a correlation between composite XV1 and ambulation speed (r = 0.44, P = .09) in hemiparetic patients. CONCLUSION: Therapists should consider prescribing and monitoring a long-term lower limb self-stretch program using GSC, as this may increase muscle extensibility in adult-onset chronic paresis. LEVEL OF EVIDENCE: III.

Breast cancer screening in women with cerebral palsy: Could care delivery be improved?

BACKGROUND: Women with disabilities (WWD) have reported lower mammography rates than the general population, however rates for women with cerebral palsy (CP) have not been specifically studied. OBJECTIVE: To evaluate mammography rates in women with CP and to identify strengths and barriers with their screening experience. METHODS: Women with CP 40 years or older (n = 118) participating in a prospective cross-sectional survey were queried regarding screening status, imaging modality, and accommodation needs and availability. Categorical variables were summarized and Chi-square testing used to assess factors contributing to screening compliance. The effect of functional factors on screening was evaluated using logistic regression. RESULTS: 77 women (65.3%) had mammograms within the past two years; 56 (47.5%) were screening mammograms. Severity of fine motor deficits was associated with lack of screening (OR 0.559, p = 0.019). 85 (72.0%) experienced positive staff attitudes. Facilities most often met needs for ramps, elevators, and/or wide doorways (92.9%), exam explanations (84.4%), and accessible parking (82.5%). Needs least often met included accommodations for standing (59.3%) or for difficulties with arm/shoulder positioning (57.1%), and wheelchair-accessible mammogram machines (59.1%). CONCLUSIONS: The screening compliance rate for women with CP is low, although the 2-year mammography rate is comparable to that reported for WWD and the general female U.S. POPULATION: Women were usually offered respectful care. Adequate physical accommodations during the procedure were reported less often than overall facility environmental accommodations. These findings demonstrate the need for improved screening rates in women with CP, and highlight areas for improving their screening experience.

Efficacy and Safety of AbobotulinumtoxinA (Dysport) for the Treatment of Hemiparesis in Adults With Upper Limb Spasticity Previously Treated With Botulinum Toxin: Subanalysis From a Phase 3 Randomized Controlled Trial.

OBJECTIVE: To assess the efficacy and safety of abobotulinumtoxinA in adults with upper limb spasticity previously treated with botulinum toxin A (BoNT-A). DESIGN: A post hoc analysis from a Phase 3, prospective, double-blind, randomized, placebo-controlled study (NCT01313299). SETTING: A total of 34 neurology or rehabilitation clinics in 9 countries. PARTICIPANTS: Adults aged 18-80 years with hemiparesis, ≥6 months after stroke or traumatic brain injury. This analysis focused on a subgroup of subjects with previous onabotulinumtoxinA or incobotulinumtoxinA treatment (n = 105 of 243 in the total trial population) in the affected limb. The mean age was 52 years, and 62% were male. INTERVENTION: Study subjects were randomized 1:1:1 to receive a single injection session with abobotulinumtoxinA 500 or 1000 U or with placebo in the most hypertonic muscle group among the elbow, wrist, or finger flexors (primary target muscle group [PTMG]), and ≥2 additional muscle groups from the upper limb. MAIN OUTCOME MEASUREMENTS: Efficacy and safety measures were assessed, including muscle tone (Modified Ashworth Scale [MAS] in the PTMG), Physician Global Assessment (PGA), perceived function, spasticity, active movement, and treatment-emergent adverse events. RESULTS: At week 4, more subjects had ≥1 grade improvement in MAS for the PTMG with abobotulinumtoxinA versus placebo (abobotulinumtoxinA 500 U, 81.1%; abobotulinumtoxinA 1000 U, 75.0%; placebo, 25.0%). PGA scores ≥1 were achieved by 75.7% and 87.5% of abobotulinumtoxinA 500 and 1000 U subjects versus 41.7% with placebo. Perceived function (Disability Assessment Scale), spasticity angle (Tardieu Scale), and active movement were also improved with abobotulinumtoxinA. There were no treatment-related deaths or serious adverse events. CONCLUSIONS: The efficacy and safety of abobotulinumtoxinA in subjects previously treated with BoNT-A were consistent with those in the total trial population. Hence, abobotulinumtoxinA is a treatment option in these patients, and no difference in initial dosing appears to be required compared to that in individuals not treated previously. LEVEL OF EVIDENCE: III.

Safety, Tolerability, and Sensorimotor Effects of Extended-release Dalfampridine in Adults With Cerebral Palsy: A Pilot Study.

PURPOSE: The goal of this study was to evaluate the safety and tolerability of dalfampridine extended release (D-ER) in a pilot study of adults with cerebral palsy (CP) and limited ambulatory ability, and to explore drug effects on sensorimotor function. METHODS: An initial double-blind, single-dose crossover study was performed in 11 individuals randomized 1:1 to receive D-ER (10 mg) or placebo, followed by a 2-day washout period and the opposite treatment, with evaluation for safety and tolerability. A twice daily dosing, double-blind, placebo-controlled, crossover study was then performed. Participants were randomized in a 1:1 ratio to 1 of 2 sequences: 1 week of D-ER (10 mg BID) or placebo, followed by a 1-week washout and 1 week of the opposite treatment. Key inclusion criteria were age 18 to 70 years, body mass index 18.0 to 30.0 kg/m2, diagnosis of CP, and ability to perform all study procedures. Key exclusion criteria were severe CP, moderate or severe renal impairment, history of nonfebrile seizures, and prior dalfampridine use. Primary outcomes were safety profile and tolerability. Exploratory functional outcomes comprised changes in upper and lower extremity sensorimotor function (grip and pinch strength tests), manual dexterity (Box and Block Tests), and walking speed (Timed 25-Foot Walk). The most pronounced measured functional deficit in each individual was defined as the exploratory primary functional end point. Full crossover data were analyzed by using a mixed effects model. FINDINGS: Among the 24 total participants who were randomized to treatment and completed the twice daily dosing phase study, their mean age was 38.6 years (range, 20-62 years), 54% were women, and 83% had spastic CP. Adverse events were consistent with previous D-ER trials, most commonly headache (13% D-ER, 4% placebo), fatigue (13% D-ER, 0% placebo), insomnia (8% D-ER, 4% placebo), diarrhea (4% D-ER, 4% placebo), and nausea (4% D-ER, 4% placebo). The mixed model analysis of full crossover data identified no significant difference between D-ER and placebo in the primary functional analysis (the most pronounced deficit; P = 0.70) or in the secondary analyses (hand strength [P = 0.48], manual dexterity [P = 0.13], or walking speed [P = 0.42]). IMPLICATIONS: In this preliminary study of adults with CP, a BID dose of 10-mg D-ER was generally safe and well tolerated. The exploratory functional assessments for upper and lower sensorimotor deficits did not establish that the study population was markedly responsive to D-ER relative to placebo. These findings do not provide the proof-of-concept that would support further evaluation of D-ER as a potential intervention to improve function in adults with CP. ClinicalTrials.gov identifier: NCT01468350.

Long-Term Dosing of Intrathecal Baclofen in the Treatment of Spasticity After Acquired Brain Injury.

BACKGROUND: Intrathecal baclofen (ITB) often is used to treat severe spasticity of cerebral origin. Although literature exists regarding the efficacy of ITB, there has been minimal investigation related to dosing in the adult-acquired brain injury population, particularly at long-term duration. OBJECTIVE: To investigate long-term dosing of ITB in adult patients with spasticity of cerebral origin due traumatic brain injury (TBI), stroke, and hypoxic-ischemic encephalopathy (HIE). DESIGN: Retrospective cohort study. SETTING: An academic outpatient rehabilitation clinic. PATIENTS: Forty-two adult patients with spasticity secondary to TBI, stroke, or HIE treated with ITB for greater than 3 years. METHODS: Medical records and device manufacturer records of included patients were reviewed to obtain demographic data, dosing information, dates of pump and catheter placements, and revisions. MAIN OUTCOME MEASURE: Average daily ITB doses and mean change in ITB dose over 1, 2, and 3 years. Goal of ITB treatment (active function versus comfort/care/positioning) also was compared. RESULTS: Of 42 total patients, spasticity was attributed to either TBI (n = 19), stroke (n = 11), or HIE (n = 12). The mean (standard deviation) age was 35.21 (10.17), 56.7 (13.1), and 35.1 (12.4) years for the TBI, stroke, and HIE groups, respectively (P < .001). There was a significant difference in the goal of therapy with "improving functional independence," accounting for 27.8%, 72.8%, and 0% in the TBI, stroke, and HIE groups, respectively (P = .002). The mean duration of ITB therapy was 8.5 (5.0), 7.8 (3.4), and 9.1 (4.6) years in the TBI, stroke, and HIE groups, respectively (P = .79). The mean daily ITB dose was 596.9 (322.8) µg/d, 513.2 (405.7) µg/d, and 705.2 (271.7) µg/d for the TBI, stroke, and HIE groups, respectively (P = .39). In the subset of the cohort with ITB therapy for more than 5 years, the mean percent change in daily ITB dose between time of chart review and 1, 2, and 3 years previously was 7.3% (13.6), 12.7% (16), and 24.7% (50.3), respectively. A complex dosing pattern was used more frequently in those with stroke (36.4%) compared with the TBI and HIE (9.7%) groups (P = .04). CONCLUSION: Despite the long-term use of ITB therapy in this cohort, the mean daily dose of ITB continued to require adjustments. There was no significant difference in the mean daily dose between patients with a diagnosis of TBI, stroke, or HIE. A complex dosing pattern was used more frequently in patients with stroke. LEVEL OF EVIDENCE: III.