Savary Om

Factors influencing secondary non-response to botulinum toxin type A injections in cervical dystonia

BACKGROUND The development of secondary non-response (SNR) to botulinum neurotoxin type-A (BoNT-A) is considered a key issue in the management of cervical dystonia (CD). This case-controlled study was performed to systematically identify factors influencing SNR during BoNT-A therapy. METHODS This was a retrospective, international, non-interventional study of CD patients. Patients with SNR were matched with up to three responder patients (control) on the basis of duration of therapy and number of injection cycles. Factors influencing the development of SNR were screened using a univariate logistic regression model and confirmed using a multivariate conditional logistic regression model. RESULTS 216 patients were enrolled, and 201 (SNR = 52; responder = 149) were matched and subdivided into blocks (doublets, triplets or quadruplets). At baseline, a significantly higher proportion of SNR patients had received previous or concomitant therapies (p = 0.038) and surgery for CD (p = 0.007) compared with controls. Although disease severity at onset was similar between groups, a significantly higher proportion of SNR patients experienced severe CD at the time of SNR compared with controls at the last documented visit. Multivariate analyses identified five factors that were significantly associated in predicting SNR (odds ratio [OR] > 1 indicated higher chances for being SNR): previous surgical procedure for CD (OR 9.8, p = 0.013), previous BoNT-A related severe adverse event (AE) (OR 5.6 p = 0.027), physical therapy (OR 4.6, p = 0.028), neuroleptic use (OR 3.3, p = 0.019) and average BoNT-A dose (OR 2.7, p = 0.010). CONCLUSIONS These findings suggest that SNR may not reflect true pharmacological resistance to BoNT-A therapy, but may be related to underlying disease severity.

Spectrum of practice in the routine management of cervical dystonia with abobotulinumtoxinA: findings from three prospective open-label observational studies

BackgroundCervical dystonia is a heterogeneous disorder with several possible presentations, for which first-line therapy is often botulinum toxin (BoNT). In routine clinical practice the success of each BoNT injection is dependent on several variables, including individual presentation and injection technique. Large multicenter, observational studies provide important information on individualized administration strategies that cannot be otherwise ascertained from controlled clinical trials. In this meta-analysis of patient level data, we aimed to evaluate the clinical characteristics of patients with cervical dystonia undergoing routine treatment with botulinum toxin, specifically abobotulinumtoxinA. We also aimed to characterize current abobotulinumtoxinA injection techniques and parameters and to explore international differences in patient presentation and treatment.MethodsThis was a meta-analysis of baseline data from three prospective, international, multicenter, observational studies (NCT01314365, NCT00833196 and NCT01753349) of botulinum toxin treatment for the routine management of adult cervical dystonia.ResultsData presented illustrate the significant heterogeneity of CD presentation in routine practice. Most subjects presented with a complex pattern of dystonic movements and the majority had additional components of shoulder elevation, tremor and/or jerk. Dosing was generally in accordance with that recommended in the abobotulinumtoxinA prescribing information, although the range of dosing also indicates that injections are tailored to individual presentation. Sub-group analyses at the country level revealed distinct differences in injection practice.ConclusionsThis meta-analysis is based on the largest dataset of subjects with cervical dystonia studied to date. The heterogeneity revealed in our baseline findings support the need to develop consistent, practical and comprehensive best practice guidelines.

Poster 182 Baseline Characteristics of Cervical Dystonia Subjects in Observational Routine-Practice Studies are Different to Those from Randomized Controlled Trials

peritendinous FCR steroid injection, but pain recurred within 6 months. Next, partial thickness Triangular Fibrocartilage tear with wrist effusion was diagnosed with MRI. Wrist arthroscopy with debridement did not result in lasting relief either. The patient was then offered FCR tenotomy versus surgical excision, which she declined. Setting: At 2 years, this patient was evaluated by Rehabilitation medicine in an outpatient setting. Results: The patient was diagnosed with focal dystonia of FCR with Writer’s cramp. 50U of intramuscular Botulinum toxin A was injected into the FCR, Flexor-Pollicis-Longus, and Flexor-Digitorum-Superficialis, followed by rehabilitation with specialized hand therapy. The patient reported gradual improvement, with resolution of symptoms in 4 weeks. Discussion: Focal dystonia should be sought out early in the course of persistent wrist pain, especially in the setting of failed conservative management for common conditions such as flexor tendinitis, and definitely before surgical intervention. Botulinum toxin can be used as an early non-invasive diagnostic tool for focal dystonia, and should improve pain intensity and frequency in case this is the diagnosis, thus avoiding expensive investigations such as MRI, as well as surgical management such as joint arthroscopy or tenotomy. Conclusions: A high index of suspicion for FCR focal dystonia should exist for persistent wrist pain that has failed conservative and surgical management for other diagnoses. Botox has merit for use as both a diagnostic and therapeutic tool for FCR dystonia. Further study can help in establishing evidence for this treatment method. Level of Evidence: Level V

Poster 498 Geographic Differences in the Characteristics of Cervical Dystonia Patients

Design: Cross-sectional survey. Setting: A major academic-medical and trauma center in West Africa. Participants: Residents and medical students completing training in 7 medical and surgical specialties (N1⁄4253). Interventions: Not applicable. Main Outcome Measures: Responses to a 25-item survey organized into four domains: 1. General attitudes towards persons with disability (PWDs); 2. Perceived adequacy of disability education; 3. Importance of disability training and education to current and future practice; and 4. General perceived value of caring for PWDs. Results: Of all respondents, 51% were female, 94 were residents, 159 were medical students and the mean age was 24.0 3.85 years old. Majority of respondents were in a surgical (41%) or medical specialty (21%). Residents had limited experience with PWDs (12% had some experience and 13% had little experience) whereas medical students had very limited experience (a total of 50% had little to no experience with PWDs) and more negative responses towards PWDs. Overall, residents demonstrated significantly higher mean composite scores than medical students for general perceived value of care for PWD (P 1⁄4 .0001), importance of disability education (P 1⁄4 .0001), and perceived adequacy of disability education score (P 1⁄4 .006). There was no statistically significant difference between the 2 groups for general attitudes composite score (P 1⁄4 .08). The mean composite scores of West-African trainees in each of the survey domains were comparable to the scores of physiatry residents in the United states, with the highest positive attitudes demonstrated for importance of disability education and perceived adequacy of disability education. Conclusions: The study highlights attitudinal health challenges towards disabled persons in a milieu devoid of rehabilitation-trained physicians and identifies areas of opportunity for strategic interventions. Level of Evidence: Level III

Poster 187 Is There a Correlation Between Tremor and Other Symptoms of Cervical Dystonia? An Analysis of Data from the Ongoing INTEREST IN CD2 Study

Case/Program Description: Thirty-one-year-old woman with chronic right lateral elbow pain for three years was referred to our hospital for surgical treatment after previous standard conservative managements and extracorporeal shock-wave therapy (ESWT) had failed. Tenderness was prominent over the right lateral epicondyle and the pain was aggravated by resisted wrist extension. Laboratory findings were normal. Plain x-ray and T2-weighted fat-suppressed magnetic resonance imaging (MRI) showed the curvilinear calcification around lateral epicondyle of elbow. Numeric rating scale (NRS) was 7 and Roles-Maudsley score (RMS) “poor” grade. The patient received USguided barbotage and additional 3 sessions of ESWT (0.15 mJ/mm, 600 shocks, weekly). Setting: Tertiary care hospital. Results: After US-guided barbotage combined ESWT, pain and tenderness started to dramatically decrease. Two months after, additional three sessions of ESWT were given to reduce residual pain (NRS 3). At 8 months and 12 months follow-up, pain scores were NRS 1 and NRS 0, and RMSs were good and excellent, respectively. Calcific deposits nearly disappeared on X-ray at 8 months follow-up. Discussion: This is the first reported case, to our knowledge, of chronic intractable calcific tendinitis of the common extensor tendon which was successfully treated with US-guided barbotage combined with ESWT. Conclusions: US-guided barbotage combined with ESWT may be a good non-surgical therapeutic option for managements of chronic intractable calcific tendinitis of the common extensor tendon. Level of Evidence: Level V

Poster 306 Clinical Characteristics of Cervical Dystonia: Differences between Patients Previously Treated with Botulinum Neurotoxin Type A and Naïve Patients

Twenty-one muscles were selected for injection at Visit 1; of these the 5 most commonly injected were splenius capitis (93% of patients), sternocleidomastoid (SCM) (91%), trapezius (63%), levator scapulae (42%), and the semispinalis capitis (27%). Other muscles were injected with a frequency between 0.4e6%. The mean total injected volumes were 1.05 1.16 mL for splenius capitis, 0.68 0.78 mL for SCM, 0.67 0.58 mL for trapezius, 0.42 0.26 mL for levator scapulae and 0.56 0.33 mL for semispinalis capitis. Mean number of injection points were: splenius capitis (2.7 1.5), SCM (2.2 1.2), trapezius (2.7 1.6), levator scapulae (1.5 0.7), and semispinalis capitis (2.0 1.3). At Visit 2 the frequency of muscles injected, the injected volume, and injection points were similar to Visit 1. Injection guidance techniques were used in 37% (SCM) to 57% (levator scapulae) of Visit 1 injections, and this did not change at Visit 2. Analyses by study center revealed that when an injector uses guidance for one muscle, they generally use it for all muscles. Conclusion: In these interim analyses, 5 muscles were identified as being most frequently injected for CD, with other muscles being injected at much lower rates. The muscles and injection method (volume and number of injection points) are in line with recommendations in the literature and did not change between visits.

Poster 305 Patterns of Cervical Dystonia of Patients Receiving BoNT-A Treatment

Twenty-one muscles were selected for injection at Visit 1; of these the 5 most commonly injected were splenius capitis (93% of patients), sternocleidomastoid (SCM) (91%), trapezius (63%), levator scapulae (42%), and the semispinalis capitis (27%). Other muscles were injected with a frequency between 0.4e6%. The mean total injected volumes were 1.05 1.16 mL for splenius capitis, 0.68 0.78 mL for SCM, 0.67 0.58 mL for trapezius, 0.42 0.26 mL for levator scapulae and 0.56 0.33 mL for semispinalis capitis. Mean number of injection points were: splenius capitis (2.7 1.5), SCM (2.2 1.2), trapezius (2.7 1.6), levator scapulae (1.5 0.7), and semispinalis capitis (2.0 1.3). At Visit 2 the frequency of muscles injected, the injected volume, and injection points were similar to Visit 1. Injection guidance techniques were used in 37% (SCM) to 57% (levator scapulae) of Visit 1 injections, and this did not change at Visit 2. Analyses by study center revealed that when an injector uses guidance for one muscle, they generally use it for all muscles. Conclusion: In these interim analyses, 5 muscles were identified as being most frequently injected for CD, with other muscles being injected at much lower rates. The muscles and injection method (volume and number of injection points) are in line with recommendations in the literature and did not change between visits.

Poster 304 Evolution of Injection Technique with Repeat Botulinum Therapy in Patients with Cervical Dystonia

Results or Clinical Course: During all types of simulated rehabilitation exercises following both partial and complete LCL injury, vertical overhead positioning enhanced elbow stability as compared to other arm positions (P<.05). However, during elbow extension in the vertical overhead position following complete LCL injury, simulated active motion did not significantly improve stability as compared to passive motion (P 1⁄4 .071). Conclusion: There is a biomechanical basis for doing exercises in the vertical overhead position following LCL injury. Previous studies show that muscle activation improves elbow stability when the arm is dependently positioned. This investigation found, however, that the impact of active versus passive motion may be less significant when exercises are done with the arm overhead. Initiating earlier range of motion in the “safer” overhead position may prevent the development of elbow flexion contracture, a common occurrence post-ligamentous injury. Cadaveric studies can be used to elicit optimal rehabilitation strategies without causing patient discomfort.

Poster 303 Correlation between Tsui Tremor Scores and the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) in Clinical Practice

Results or Clinical Course: During all types of simulated rehabilitation exercises following both partial and complete LCL injury, vertical overhead positioning enhanced elbow stability as compared to other arm positions (P<.05). However, during elbow extension in the vertical overhead position following complete LCL injury, simulated active motion did not significantly improve stability as compared to passive motion (P 1⁄4 .071). Conclusion: There is a biomechanical basis for doing exercises in the vertical overhead position following LCL injury. Previous studies show that muscle activation improves elbow stability when the arm is dependently positioned. This investigation found, however, that the impact of active versus passive motion may be less significant when exercises are done with the arm overhead. Initiating earlier range of motion in the “safer” overhead position may prevent the development of elbow flexion contracture, a common occurrence post-ligamentous injury. Cadaveric studies can be used to elicit optimal rehabilitation strategies without causing patient discomfort.

Poster 179 Evolution of Cervical Dystonia and Patient Satisfaction with Repeat Botulinum Toxin Therapy in Clinical Practice

Participants: A total of 721 medical records were reviewed in Seoul National University Hospital Healthcare System Gangnam Center and data of 165 older subjects (> 65 years, 81 men and 84 women) were retrospectively analyzed. Main Outcome Measures: Subjects were categorized into either CLBP (back pain for 6 months; 35 men and 36 women) or control groups (46 men and 48 women). The Modified Skeletal Muscle Mass Index (MSMI), lumbar lordotic angles (LLA), and prevalence of sarcopenia were evaluated. Results or Clinical Course: The LLA of men and women in the CLBP group (29.8 10.6 degrees, 32.1 11.2 degrees, respectively) were significantly lower (P 1⁄4 .001 and .006, respectively) than those the control group (37.1 8.5 degrees and 38.3 9.2 degrees, respectively). Additionally, MSMI was decreased in the CLBP group compared to the control group; it was 31.2 1.7% vs. 32.3 1.9% (P 1⁄4 .008) in men, 26.1 1.9% vs. 27.1 2.1% (P 1⁄4 .02) in women. For both sexes, positive correlations were also observed between MSMI and LLA (r 1⁄4 0.220, P 1⁄4 .048 in men, r 1⁄4 0.225, P 1⁄4.040 in women). Conclusion: A close cross-sectional relationship was observed between sarcopenia and CLBP suggesting potential interactions between decreased muscle mass, altered lumbar spine sagittal alignment, and CLBP.