Objectives Phase I (PhI): assess the safety of Polyphenon E in people with multiple sclerosis (MS) and determine the futility of Polyphenon E as a neuroprotective agent. Correlate plasma levels of EGCG with neuroprotective effects. Phase II (PhII): Further assess safety and confirm the neuroprotective effects of Polyphenon E. Design PhI: single group futility study. PhII: parallel group randomized double-blind placebo-controlled study. Participants Recruitment area (both studies) LSU MS Center, New Orleans, LA and general public from surrounding areas. Inclusion criteria (both studies) 1) MS per 2005 McDonald criteria; 2) relapsing remitting or secondary progressive MS; 3) stable for six months prior to enrollment on either no therapy or glatiramer acetate (GA) for the PhI study and on either on GA or Interferon β for the PhII study. Exclusion criteria (both studies) 1) complete bone marrow ablation or alentuzumab use at any time; 2) mitoxantrone, cyclophosphamide, natalizumab or fingolimod use in the prior nine months; 3) liver problems or significant medical problems. Interventions PhI: Polyphenon E, a green tea extract containing 50% of the antioxidant Epigallocatechin-gallate (EGCG), two capsules twice daily (200 mg of EGCG per capsule; total daily dose 800mg) for six months. PhII: Polyphenon E or matching placebo capsules, same dose for one year. Only the research pharmacist knew treatment assignment and she randomized participants (one-to-one, stratified by GA or Interferon β, blocks of 4 or 6). Outcome evaluators did not discuss side effects with participants. Outcome measures PhI: 1) adverse events (AE); 2) futility: decrease in N-acetyl aspartate (NAA) from baseline to six months of 10% or more; 3) association between EGCG plasma levels and change in NAA. PhII: 1) AEs; 2) difference in the rate of change of NAA-levels over twelve months. We measured NAA using a point resolved magnetic resonance spectroscopic imaging sequence (TE30/TR2000) on a 10cm × 10cm × 1cm volume of interest (VOI) located just superior to the lateral ventricles. The field of view was 16×16 resulting in 1cm3 voxels. We quantified NAA and creatine/phosphocreatine (Cr) levels using LCModel for post-processing. Results PhI: Ten participants enrolled and completed all assessments with no serious AEs. One discontinued therapy due to grade (G) I abnormal liver function tests (LFTs). We included all participants in the analysis. NAA adjusted for creatine increased by 10% [95% CI(3.4%,16.2%), p<0.01] rejecting the futility endpoint. PhII: Thirteen participants enrolled and twelve started treatment. The DSMB stopped the study because 5/7 participants on Polyphenon E had abnormal LFTs (2 G I, 1 G II and 1 G IV). Median time to onset of abnormal LFTs was 20 weeks [Inter-Quartile Range (IQR) (10,23)]. Only two participants completed the six-month visit, so we could not analyze the NAA levels. PhI participants took capsules from lot 189I1107 while 6/7 PhII participants took capsules from a new lot (L0206306). Both lots had simil...

In the experimental autoimmune encephalitis model of multiple sclerosis, the effects of stress on disease severity depend on multiple factors, including the animal's genetics and the type of stressor. The studies in humans relating stress to the risk of developing multiple sclerosis have found discordant results. The studies looking at the association of stress with relapses show a fairly consistent association, where higher stress is associated with a higher risk of relapse. Higher stress levels also appear to increase the risk of development of gadolinium-enhancing lesions. A recent randomized trial shows that reducing stress using stress management therapy (SMT), a cognitive-behavioral therapy approach, results in a statistically significant reduction in new magnetic resonance imaging lesions. The magnitude of this effect is large and comparable to the effects of existent disease-modifying therapies, but no data exist yet proving that SMT reduces relapses or clinical progression; the effect of SMT appears to be short-lived. Additional work is needed to improve the duration of this effect and make this therapy more widely accessible.

Study Design Systematic review and meta-analysis. Objective The goal of this study was to (i) assess the risk of neurological injury after anterior cervical spine surgery (ACSS) with and without intraoperative neuromonitoring (ION) and (ii) evaluate differences in the sensitivity and specificity of ION for ACSS. Summary of Background Data Although ION is used to detect impending neurological injuries in deformity surgery, it’s utility in ACSS remains controversial. Methods A systematic search of multiple medical reference databases was conducted for studies on ION use for ACSS. Studies that included posterior cervical surgery were excluded. Meta-analysis was performed using the random-effects model for heterogeneity. Outcome measure was postoperative neurological injury. Results The search yielded 10 studies totaling 26,357 patients. The weighted risk of neurological injury after ACSS was 0.64% (0.23–1.25). The weighted risk of neurological injury was 0.20% (0.05–0.47) for ACDFs compared with 1.02% (0.10–2.88) for corpectomies. For ACDFs, there was no difference in the risk of neurological injury with or without ION (odds ratio, 0.726; confidence interval, CI, 0.287–1.833; P = 0.498). The pooled sensitivities and specificities of ION for ACSS are 71% (CI: 48%–87%) and 98% (CI: 92%–100%), respectively. Unimodal ION has a higher specificity than multimodal ION [unimodal: 99% (CI: 97%–100%), multimodal: 92% (CI: 81%–96%), P = 0.0218]. There was no statistically significant difference in sensitivities between unimodal and multimodal [68% vs. 88%, respectively, P = 0.949]. Conclusion The risk of neurological injury after ACSS is low although procedures involving a corpectomy may carry a higher risk. For ACDFs, there is no difference in the risk of neurological injury with or without ION use. Unimodal ION has a higher specificity than multimodal ION and may minimize “subclinical” intraoperative alerts in ACSS.

Background: Patient-reported outcome measures are important to determine outcomes after orthopaedic procedures. There is currently no standard for outcome measures in the evaluation of patient outcomes after proximal hamstring repair. Purpose: To identify and evaluate outcome measures used after proximal hamstring repair. Study Design: Systematic review; Level of evidence, 4. Methods: A systematic review was performed to identify all English-language articles assessing outcomes after proximal hamstring repair in PubMed, Embase, CINAHL via EBSCOhost, MEDLINE via OvidSP, and Web of Science between 2000 and 2019. After duplicates were removed, studies were selected using eligibility criteria established by the authors. Image reviews, anatomic/histology studies, literature reviews, surgical technique reports, systematic reviews, narrative reviews, case studies, and studies with <5 patients were excluded. Extraction, synthesis, and analysis of outcome measure data were performed using Microsoft Excel. Quality assessment of included studies was performed using Methodological Index for Non-Randomized Studies criteria. Results: After duplicate articles were removed, a total of 304 unique articles were identified and 27 met the inclusion criteria. The mean number of patients with proximal hamstring repairs per study was 40. The most frequently reported outcome measures were return to sport (14/27; 51.9%), custom survey/questionnaire (13/27; 48.1%), and isokinetic hamstring strength testing (13/27; 48.1%). Six of the 10 most commonly used outcome measures were validated and included Lower Extremity Functional Scale, 12-Item Short Form Health Survey, visual analog scale for pain, Perth Hamstring Assessment Tool (PHAT), Single Assessment Numeric Evaluation, and Tegner Activity Scale. Of those, PHAT was the only validated outcome measure designed for proximal hamstring repair. Conclusion: There is currently no consensus on the best outcome measurements for the evaluation of patients after proximal hamstring repair. We recommend an increased commitment to the use of return to sport, isokinetic strength testing, Lower Extremity Functional Scale, and PHAT when assessing such injuries. Future studies should aim to define the most reliable methods of outcome measurement in this patient population through consistent use of tools that are clinically relevant and important to patients and can easily be employed in a variety of clinical scenarios.