Adaptive functioning and neurodevelopment in patients with Dravet syndrome: 12-month interim analysis of the BUTTERFLY observational study.

OBJECTIVE: The BUTTERFLY observational study aims to elucidate the natural trajectory of Dravet syndrome (DS) and associated comorbidities in order to establish a baseline for clinical therapies. We present the 12-month interim analysis of the study. MATERIALS AND METHODS: Patients with a genetically confirmed diagnosis of DS were enrolled in the study. Adaptive functioning and neurodevelopmental status were measured using the Vineland Adaptive Behavior Scale, Third Edition (Vineland-III), Bayley Scales of Infant Development, Third Edition (BSID-III), and Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV). Executive function, ambulatory function and locomotor activities, and overall clinical status were measured using the Behavior Rating Inventory of Executive Function - Preschool Version (BRIEF-P) scale, Gillette Functional Assessment Questionnaire (Gillette FAQ), and Clinician or Caregiver Global Impression of Change scales (CGI-C or CaGI-C) respectively. RESULTS: Overall, 36 patients were enrolled across three age groups, with 35 patients completing at least part or all of one post-baseline visit through Month 12. Significant improvements in receptive communication, as assessed by Vineland-III and BSID-III raw scores, and in verbal comprehension subtests, as assessed by WPPSI-IV raw scores, were observed in BUTTERFLY patients for the all-patient group. Many patients performed on the impaired end of the BRIEF-P Global Executive Composite scale at baseline suggesting difficulties in executive function, and no significant change was observed in BRIEF-P scores for the all-patient group. Most patients performed in the dynamic range of the Gillette FAQ at baseline, and no significant change was observed in Gillette FAQ scores for the all-patient group. Lastly, there was significant improvement observed in the CaGI-C scores for the all-patient group. SIGNIFICANCE: This BUTTERFLY interim analysis shows small improvements in communication skills along with stability in other developmental abilities across patients with DS enrolled in the study from baseline to Month 12.

Interim results of adaptive functioning and neurodevelopment in BUTTERFLY - An observational study of children and adolescents with Dravet syndrome.

PURPOSE: The purpose of this study is to evaluate adaptive functioning and neurodevelopment study assessments in a prospective study of patients with Dravet syndrome (DS). We present 3-month interim adaptive functioning and neurodevelopment data from the prospective, observational BUTTERFLY study in patients with DS aged 2-18 years. RESULTS: BUTTERFLY enrolled thirty-six patients divided 1:1:1 across three age groups (2-7: 8-12: and 13-18 years). Most enrolled patients were female (61.1%), white (94.4%), and non-Latino (83.3%) with a mean (standard deviation; SD) age of 10.8 (5.2) years and a mean (range) age of seizure onset of 0.4 (0.2-1.0) years. Patients used a mean (SD) of 3.5 (1.63) anti-seizure therapies at baseline. Regression analysis of the baseline Vineland Adaptive Behavior Scale - third edition (VABS-III) composite score indicated that the gap in adaptive function between patients with DS (n = 33) and neurotypical children widens with age. Similarly, developmental quotients calculated for patients who completed all Bayley Scales of Infant Development - third edition (BSID-III) subtests at baseline (n = 15) highlighted a gap in intellectual functioning between patients with DS and neurotypical children that widens with age. More patients in the two older age groups were able to validly complete the Wechsler Preschool and Primary Scale of Intelligence - fourth edition (WPPSI-IV) at baseline compared with the youngest age group. There were trends towards higher raw scores, albeit of low magnitude, in the oldest age group compared with the younger age two groups across multiple VABS-III domains and WPPSI-IV subtests. All three measures showed no significant change in the all-patients analyses and demonstrated relatively low intra-patient variability from baseline to Month 3. CONCLUSIONS: Three-month interim data from BUTTERFLY demonstrated the feasibility of utilizing the VABS-III, BSID-III, and WPPSI-IV for the assessment of adaptive function and neurodevelopment in future clinical studies of DS. Moreover, many patients with DS appear to gain neurodevelopmental and adaptive function skills over time, although at a slower rate and lower magnitude than that seen in the neurotypical population.

Ex vivo biomechanical comparison of 2.7 mm string-of-pearl plate versus screw/wire/Polymethylmethacrylate composite fixation and 2.7 mm veterinary acetabular plate for repair of simulated canine acetabular fractures.

BACKGROUND: Acetabular fractures comprise 12-30% of canine pelvic fractures and require accurate anatomic reduction and rigid stability to ensure proper healing and minimize future osteoarthritis. Many techniques have been used to repair these fractures, with common techniques including veterinary acetabular plates or use of screw/wire/polymethylmethacrylate constructs. String-of-Pearl™ plating systems have also been used clinically but there is a lack of research supporting their use for these fractures. The purpose of this study was to compare fracture reduction accuracy, biomechanical characteristics, and mode of failure between String-of-Pearls™, veterinary acetabular plates, screw/wire/polymethylmethacrylate constructs in a simulated, ex-vivo acetabular fracture model. We hypothesized that the String-of-Pearls™ constructs would have equivalent or greater mechanical properties and reduction compared to the other constructs. RESULTS: The mean craniocaudal acetabular diameter before fixation (mean 25.2 mm; range 20 mm - 30.1 mm) was not significantly different from after fixation (mean 23.9 mm; range 20 mm - 28.3 mm) for any fixation method. Comparison of reduction scores between groups revealed no significant differences. No significant differences were noted for cyclical displacement or stiffness. There was significant difference with superior failure load of String-of-Pearls™ compared to screw/wire/polymethylmethacrylate in the 75th percentile of animal weight (P = 0.0021), and superior failure load of String-of-Pearls™ compared to veterinary acetabular plates in the 50th (P = 0.0232) and 75th percentiles (P = 0.0058). Stiffness of the String-of-Pearls™ construct was significantly greater than the veterinary acetabular plate construct (P = 0.0417). For ultimate load, String-of-Pearls™ constructs were significantly greater than screw/wire/polymethylmethacrylate (P = 0.0331) and veterinary acetabular plates (P = 0.0218). CONCLUSION: Although the ease of application for the String-of-Pearls™ implant was subjectively better than other implants, no significant differences were found in fracture reduction scores. The String-of-Pearls™ constructs were stiffer than veterinary acetabular plates and exhibited greater failure and ultimate loads compared to veterinary acetabular plates and screw/wire/polymethylmethacrylate fixations. The String-of-Pearls™ implant appears to be a suitable fixation choice for simple canine acetabular fractures.

Ground reaction forces, temporospatial parameters, range of motion, and limb characteristics were analyzed for small and medium size sound dogs with the use of pressure sensitive walkway.

OBJECTIVE: To study ground reaction forces (GRF) and temporospatial parameters for small and medium size dogs using a pressure sensitive walkway (PSW). We hypothesized that, at a given speed, small dogs would have shorter stance time than medium dogs and that dog height (DH) would influence GRF. ANIMALS: 30 healthy, sound dogs were divided into 2 groups, small < 15 kg and medium dog group weighing 15 to 25 kg. PROCEDURES: GRFs were measured for both groups at walk and trot using PSW. Muscle mass and joint angles were measured. Data were analyzed using SAS version 9.4. Two groups were compared using 2-sample t test, Wilcoxon rank sum test, and Fisher exact test. RESULTS: GRFs were successfully measured in both dog groups for walk and trot. Medium dogs had larger limb girth, more peak pressure, max force, increased stance, swing time, and larger stride length compared with small dogs. Stance time increased as DH increased at walk and trot (r = 0.854, P < .001; r = 0.876, P < .001). Stance time increased as BW (body weight) increased at walk and trot (r = 0.887, P < .001; r = 0.858 P < .001). Inconclusive data was obtained for stride acceleration and velocity. The handler side did not influence results (P > .05). Range of motion (ROM) did not differ among groups. CLINICAL RELEVANCE: Results suggested that PSW is a reliable device for small and medium dogs. At walk and at a trot, GRF are smaller in small dogs compared with medium dogs, suggesting that normal reference data for PSW need to take BW and DH into account.

Development and initial validation of a disease specific outcome measure for early onset scoliosis.

INTRODUCTION: Treatment of children with early onset scoliosis (EOS) seeks to improve natural history and health related quality of life (QOL). QOL measurement presents a significant challenge given the young age, comorbidities, and heterogeneity of this population. OBJECTIVE: To develop a disease specific measure reflecting issues of importance to EOS patients and caretakers. MATERIALS AND METHODS: Review of the literature and relevant measures informed development of semi-structured qualitative interviews. Interviews of caregivers of EOS patients were interpreted through the framework technique. A master-list of 75-items was created and responses were scaled on a 5-point Likert-scale. Psychometric analysis was performed to group items into domains, to maintain score distribution, to create a responsive instrument, and to identify question redundancy. RESULTS: Content validation revealed 8-items with low content validity indices. Item distribution analysis demonstrated 19-items with skewed distribution. Item reliability demonstrated redundant items within domains (r> or =0.5). Construct validity demonstrated unique domains measuring intended issues of interest. The resulting Early Onset Scoliosis Questionnaire (EOSQ) includes 33-items in 13-domains: General Health, Pain, Physical Function, Pulmonary Function, Daily Living, Fatigue, Emotion, Surgical Concerns, Satisfaction, Transfer, Financial Burden, Parental Burden, and Treatment Outcomes. CONCLUSION: The EOSQ reflects QOL and caregiver burden in the EOS population. The EOSQ will expand options for outcome assessment in this unique population.

Adult cerebellar glioblastoma: understanding survival and prognostic factors using a population-based database from 1973 to 2009.

OBJECTIVE: Glioblastoma (GB) is rarely found in the cerebellum. Because of its rarity, it is poorly understood if cerebellar GB (CGB) behaves similarly to supratentorial GB. Studies have been limited to case reports and small case series. A better understanding of CGB may help guide treatment strategies. METHODS: Surveillance, Epidemiology and End Results database was analyzed from 1973 to 2009 for all adult patients with GB located in the cerebellum. Stepwise multivariate proportional hazards regression analyses were used to identify factors independently associated with survival. RESULTS: Two hundred eight (0.9%) patients with CGB were identified from 23,329 GB patients with known locality. The mean age was 58 years. Median survival was 8 months, with 1-, 2- and 5-year survival rates of 21%, 13%, and 2%. When compared to supratentorial GB, CGB occurred in younger patients (58 ± 16 vs. 61 ± 13 years, P = 0.001), less commonly in Whites (85.6% vs. 91.3%, P = 0.005), and were smaller (3.7 ± 1.1 vs. 4.5 ± 1.7 cm, P = 0.001). A cerebellar location independently predicted poorer survival when compared to other GB locations (P = 0.048). In multivariate analysis for patients with CGB, younger age (P < 0.001), Asian or Pacific Islander race (P = 0.046), and radiation therapy (P < 0.001) were independently associated with prolonged survival. CONCLUSION: CGBs are difficult to analyze using institutional series because of their rarity. This study shows they are clinically different from supratentorial GB. Among patients with CGB, radiation therapy may prolong survival. This may help guide treatment strategies aimed at prolonging survival for patients with these extremely rare lesions.

Plasma taurine as a predictor of poor outcome in patients with mild neurological deficits after aneurysmal subarachnoid hemorrhage.

OBJECT: The object of this study was to determine the relationship between plasma taurine and subarachnoid hemorrhage (SAH) outcome. METHODS: Forty patients with SAH and mild neurological deficits were included in this prospective, blinded cohort study. Plasma taurine levels were measured using high-performance liquid chromatography on admission and were correlated with patient outcomes at discharge. RESULTS: Twenty-five percent of the patients ultimately had a poor outcome. Plasma taurine concentrations at admission were increased (2-fold) in SAH patients with a favorable outcome and were further increased (6-fold) in those who had a poor outcome. Increased taurine levels identified patients who would be discharged with a poor outcome, with sensitivity and specificity values of approximately 80% and 100%, respectively, and positive and negative predictive values of approximately 90%. Delayed cerebral vasospasm showed an OR of 27.9 (95% CI 1.090-714.9) for a poor outcome, whereas an increased taurine concentration had an OR of 105 for a poor outcome (95% CI 8.3-1328.0, p < 0.001). CONCLUSIONS: Increased plasma taurine concentrations on admission predict a poor outcome in SAH.

Prognostic factors and survival in primary malignant astrocytomas of the spinal cord: a population-based analysis from 1973 to 2007.

STUDY DESIGN: Observational cross-sectional study. OBJECTIVE: Using data from the population-based cancer registries of the Surveillance, Epidemiology and End Results (SEER) program, we analyzed demographic features, tumor and treatment characteristics, as well as survival rates in patients with primary malignant astrocytomas of the spinal cord (PMASC). SUMMARY OF BACKGROUND DATA: PMASC is a rare neoplasm and is considered to carry the same dismal outcome as their cerebral counterparts. Our current knowledge is incomplete, and understanding the epidemiology, diagnosis, and optimal treatment still poses challenges. METHODS: The SEER data from 1973 to 2007 were reviewed for pathologically confirmed primary anaplastic astrocytomas (AA) and glioblastomas of the spinal cord (C72.0). We compared the clinical features and outcomes of the cohort in uni- and multivariate fashion. Survival was calculated and compared using Kaplan-Meier curves and log-rank analysis. RESULTS: Our search criteria retrieved 135 patients diagnosed with PMASC. The median survival for PMASC was 13 months with 1-, 2-, and 5-year survival rates of 51.8%, 32.2%, and 18.7%. Patient diagnosed with AA had a median survival time of 17 months versus 10 months in patients diagnosed with glioblastomas. Adult patients observed markedly prolonged survival compared with the pediatric group, with a 16-month versus 9-month median survival, respectively. Multivariate analysis revealed age at diagnosis, pediatric and adult age groups, sex, tumor histology, and extent of resection as significant predictors of survival. Interestingly, outcomes did not significantly change throughout the last decades or by receiving radiotherapy. CONCLUSION: Outcome for patients diagnosed with PMASC remains poor and presents an ongoing challenge for professionals in the field of neurospinal medicine and surgery. In our analyses of AA, adult patients, males, and patients undergoing radical resections were associated with increased survival. However, incidence of these lesions is low; hence, building strong collaborative, interdisciplinary, and multi-institutional study groups is necessary to define the optimal treatment of PMASC.

Electronic monitoring improves brace-wearing compliance in patients with adolescent idiopathic scoliosis: a randomized clinical trial.

STUDY DESIGN: Randomized controlled trial. OBJECTIVE: To assess whether monitoring increases brace-wearing compliance in patients with adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: Noncompliance is a barrier to brace treatment of AIS. Studies have demonstrated that monitoring improves medication compliance; however, this has not been investigated in spinal braces. METHODS: Twenty-one patients (mean age = 12.4 ± 2.0 years) with AIS were prescribed treatment with a custom-made Thoraco-Lumbo-Sacral-Orthosis for 18 hours a day using a standardized script. Before beginning treatment, 10 patients were randomized to be informed that their compliance was monitored, whereas 11 patients were unaware. Compliance was measured via a temperature probe embedded within the Thoraco-Lumbo-Sacral-Orthosis hidden from view. RESULTS: Patients who were notified that they had a monitor in their brace demonstrated significantly increased compliance during the first 14 weeks of treatment compared with those who were uninformed (85.7% vs. 56.5%, P = 0.029), corresponding to a mean difference of 5.24 hours of daily brace wear. CONCLUSION: Electronic monitoring can improve compliance with orthoses in patients with spinal deformity during a short observation period.