Faculty Bibliography
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248
The effectiveness of computerized screening in detecting cognitive deficits in people with multiple sclerosis [Meeting Abstract]
ISI:000413730203096
ISSN: 1352-4585
CID: 5343572
Multiple sclerosis: brain atrophy and computerized cognitive testing - a cross-sectional pilot investigation [Meeting Abstract]
ISI:000413730203235
ISSN: 1352-4585
CID: 5343582
A preliminary investigation into the relationship between Visual Evoked Potential Latency (VEP-L) and outcome parameters from Optical Coherence Tomography (OCT) in people with multiple sclerosis [Meeting Abstract]
ISI:000413730203253
ISSN: 1352-4585
CID: 5343592
Switching to natalizumab is associated with improvements in cognitive function as measured by NeuroTrax [Meeting Abstract]
ISI:000413730204112
ISSN: 1352-4585
CID: 5343602
Multiple sclerosis and cognition: the impact of psychotropic medications [Meeting Abstract]
ISI:000413730204240
ISSN: 1352-4585
CID: 5343612
Multiple sclerosis treatment decisions: EDSS independent disease impact/reserve and the use of additional economically impactful milestones that matter [Meeting Abstract]
ISI:000413730204275
ISSN: 1352-4585
CID: 5343622
An investigation into the relationship between the multiple sclerosis Impact Scale (MSIS-29) and Predicted Medication Adherence as measured by the Morisky Medication Adherence Scale (MMAS-8) [Meeting Abstract]
ISI:000413730205204
ISSN: 1352-4585
CID: 5343632
Alemtuzumab improves preexisting disability in active relapsing-remitting MS patients
OBJECTIVE:To characterize effects of alemtuzumab treatment on measures of disability improvement in patients with relapsing-remitting multiple sclerosis (RRMS) with inadequate response (≥1 relapse) to prior therapy. METHODS:Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) II, a 2-year randomized, rater-blinded, active-controlled, head-to-head, phase 3 trial, compared efficacy and safety of alemtuzumab 12 mg with subcutaneous interferon-β-1a (SC IFN-β-1a) 44 μg in patients with RRMS. Prespecified and post hoc disability outcomes based on Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), and Sloan low-contrast letter acuity (SLCLA) are reported, focusing on improvement of preexisting disability in addition to slowing of disability accumulation. RESULTS:Alemtuzumab-treated patients were more likely than SC IFN-β-1a-treated patients to show improvement in EDSS scores (p < 0.0001) on all 7 functional systems. Significantly more alemtuzumab patients demonstrated 6-month confirmed disability improvement. The likelihood of improved vs stable/worsening MSFC scores was greater with alemtuzumab than SC IFN-β-1a (p = 0.0300); improvement in MSFC scores with alemtuzumab was primarily driven by the upper limb coordination and dexterity domain. Alemtuzumab-treated patients had more favorable changes from baseline in SLCLA (2.5% contrast) scores (p = 0.0014) and MSFC + SLCLA composite scores (p = 0.0097) than SC IFN-β-1a-treated patients. CONCLUSIONS:In patients with RRMS and inadequate response to prior disease-modifying therapies, alemtuzumab provides greater benefits than SC IFN-β-1a across several disability outcomes, reflecting improvement of preexisting disabilities. CLASSIFICATION OF EVIDENCE/METHODS:This study provides Class I evidence (based on rater blinding and a balance in baseline characteristics between arms) that alemtuzumab modifies disability measures favorably compared with SC IFN-β-1a.
PMCID:5109953
PMID: 27733571
ISSN: 1526-632x
CID: 5348132
Best Practices for Intrathecal Baclofen Therapy: Screening Test
INTRODUCTION/BACKGROUND:Intrathecal baclofen (ITB) screening assesses response to a test dose of ITB on spasticity and function and identifies adverse reactions. METHOD/METHODS:An expert panel consulted on best practices after conducting an extensive literature search and conducting an online survey. RESULTS:A successful trial may confirm predetermined goals, which may include improved mobility/positioning, decreased time/improved independence for activities, less home exercise, better wheelchair tolerance, decreased caregiver time, improved sleep, and reduced pain, or may modify goals and expectations. Individuals should not be tested in the presence of active medical issues (e.g., MS exacerbations, active urinary tract infection, nonhealing wounds). Oral antispasmodics can be weaned before trial if a goal is to eliminate them. The standard baclofen test dose is a 50-mcg bolus, 25 mcg in very small children or patients who rely on spasticity for mobility. Patients unresponsive to the standard dose may require 75 mcg or 100 mcg; 24 hours should elapse between bolus doses. Cardiopulmonary parameters should be checked frequently during the first two hours postinjection, and spasticity measures assessed at least twice within four hours. Observation continues until the patient is stable and recovers from hypertonia. Adverse events include spinal headaches, nausea/vomiting, urinary retention, hypotension, seizures, drowsiness/sedation, respiratory depression, and coma. Before implantation, team members must discuss starting dose, drug concentration, delivery mode, pump size and location, and catheter tip placement. Patients/caregivers should understand the commitment necessary for ITB therapy. CONCLUSIONS:Screening helps identify appropriate candidates for ITB.
PMID: 27434115
ISSN: 1525-1403
CID: 5342182
Effect of Deutetrabenazine on Chorea Among Patients With Huntington Disease: A Randomized Clinical Trial
IMPORTANCE/OBJECTIVE:Deutetrabenazine is a novel molecule containing deuterium, which attenuates CYP2D6 metabolism and increases active metabolite half-lives and may therefore lead to stable systemic exposure while preserving key pharmacological activity. OBJECTIVE:To evaluate efficacy and safety of deutetrabenazine treatment to control chorea associated with Huntington disease. DESIGN, SETTING, AND PARTICIPANTS/METHODS:Ninety ambulatory adults diagnosed with manifest Huntington disease and a baseline total maximal chorea score of 8 or higher (range, 0-28; lower score indicates less chorea) were enrolled from August 2013 to August 2014 and randomized to receive deutetrabenazine (n = 45) or placebo (n = 45) in a double-blind fashion at 34 Huntington Study Group sites. INTERVENTIONS/METHODS:Deutetrabenazine or placebo was titrated to optimal dose level over 8 weeks and maintained for 4 weeks, followed by a 1-week washout. MAIN OUTCOMES AND MEASURES/METHODS:Primary end point was the total maximal chorea score change from baseline (the average of values from the screening and day-0 visits) to maintenance therapy (the average of values from the week 9 and 12 visits) obtained by in-person visits. This study was designed to detect a 2.7-unit treatment difference in scores. The secondary end points, assessed hierarchically, were the proportion of patients who achieved treatment success on the Patient Global Impression of Change (PGIC) and on the Clinical Global Impression of Change (CGIC), the change in 36-Item Short Form- physical functioning subscale score (SF-36), and the change in the Berg Balance Test. RESULTS:Ninety patients with Huntington disease (mean age, 53.7 years; 40 women [44.4%]) were enrolled. In the deutetrabenazine group, the mean total maximal chorea scores improved from 12.1 (95% CI, 11.2-12.9) to 7.7 (95% CI, 6.5-8.9), whereas in the placebo group, scores improved from 13.2 (95% CI, 12.2-14.3) to 11.3 (95% CI, 10.0-12.5); the mean between-group difference was -2.5 units (95% CI, -3.7 to -1.3) (P < .001). Treatment success, as measured by the PGIC, occurred in 23 patients (51%) in the deutetrabenazine group vs 9 (20%) in the placebo group (P = .002). As measured by the CGIC, treatment success occurred in 19 patients (42%) in the deutetrabenazine group vs 6 (13%) in the placebo group (P = .002). In the deutetrabenazine group, the mean SF-36 physical functioning subscale scores decreased from 47.5 (95% CI, 44.3-50.8) to 47.4 (44.3-50.5), whereas in the placebo group, scores decreased from 43.2 (95% CI, 40.2-46.3) to 39.9 (95% CI, 36.2-43.6), for a treatment benefit of 4.3 (95% CI, 0.4 to 8.3) (P = .03). There was no difference between groups (mean difference of 1.0 unit; 95% CI, -0.3 to 2.3; P = .14), for improvement in the Berg Balance Test, which improved by 2.2 units (95% CI, 1.3-3.1) in the deutetrabenazine group and by 1.3 units (95% CI, 0.4-2.2) in the placebo group. Adverse event rates were similar for deutetrabenazine and placebo, including depression, anxiety, and akathisia. CONCLUSIONS AND RELEVANCE/CONCLUSIONS:Among patients with chorea associated with Huntington disease, the use of deutetrabenazine compared with placebo resulted in improved motor signs at 12 weeks. Further research is needed to assess the clinical importance of the effect size and to determine longer-term efficacy and safety. TRIAL REGISTRATION/BACKGROUND:clinicaltrials.gov Identifier: NCT01795859.
PMID: 27380342
ISSN: 1538-3598
CID: 5342172
