ContributionsMagdy Selim --organized the trial hypotheses, designed the trial, provided guidance about the data analysis and interpretation and presentation of the data, and drafted most of the sections of the manuscript. Lydia Foster --involved in the statistical analysis and data interpretation, and Contributed to the development and revisions to the manuscript. Claudia Moy --involved in the oversight of the trial conduct and progress Guohua Xi --organized the trial hypotheses, and provided critical revisions to the manuscript. MH, MJ, VS, and WC contributed to recruitment and randomization of trial participants, and provided critical revisions to the manuscript. LM and SG were involved in the design of the trial and provided critical revisions to the manuscript. Casey Norton --provided volumetric measurements of imaging data. Yuko Palesch --involved in the design of the study, statistical analysis and data interpretation, and provided critical revisions to the manuscript. Sharon yeatts --involved in the design of the study, statistical analysis and data interpretation, and contributed to the development and revisions to the manuscript. The idef investigators (see appendix) --contributed to the identification and, when eligible, randomization of trial participants. DECLARATION OF INTERESTSThis was an investigator-initiated study, funded by the NINDS (U01 NS074425). Deferoxamine Mesylate is a generic drug, and there was no commercial or industrial support for the trial. None of the authors has any competing interests related to the submitted work. MS reports grants from the NIH/NINDS (i-DEF) and the American Heart Association (outside the submitted work), and personal fees for serving on the advisory board of CSL Behring (outside the submitted work) during the conduct of the trial. SDY reports grant support from the NINDS, personal fees from Genentech and other fees from CR Bard Inc. (outside the submitted work) during the conduct of the study. SG, LDF, YP, and GX report grants from the NIH/NINDS. MDH reports personal fees from Merck, nonfinancial support from Hoffmann-La Roche Canada Ltd, grants from Covidien (Medtronic), grants from Boehringer-Ingleheim, grants from Stryker Inc., grants from Medtronic LLC, grants from NoNO Inc., (outside the submitted work); In addition, MDH has a patent Systems and Methods for Assisting in Decision-Making and Triaging for Acute Stroke Patients pending to US Patent office Number: 62/086,077 and owns stock in Calgary Scientific Incorporated, a company that focuses on medical imaging software, is a director of the Canadian Federation of Neurological Sciences, a not-for-profit group and has received grant support from Alberta Innovates Health Solutions, CIHR, Heart & Stroke Foundation of Canada, and NINDS. LM, VS, WC, MJ, CM, and CN have nothing to disclose.

A 4-Year Randomized Controlled Trial The Parkinson Study Group* Background: The best way to initiate dopaminergic therapy for early Parkinson disease remains unclear. Objective: To compare initial treatment with pramipexole vs levodopa in early Parkinson disease, followed by levodopa supplementation, with respect to the development of dopaminergic motor complications, other adverse events, and functional and quality-of-life outcomes. Design: Multicenter, parallel-group, double-blind, randomized controlled trial. Setting: Academic movement disorders clinics at 22 sites in the United States and Canada. Patients: Patients with early Parkinson disease (N=301) who required dopaminergic therapy to treat emerging disability, enrolled between October 1996 and August 1997 and observed until August 2001. Intervention: Subjects were randomly assigned to receive 0.5 mg of pramipexole 3 times per day with levodopa placebo (n = 151) or 25/100 mg of carbidopa/ levodopa 3 times per day with pramipexole placebo (n=150). Dosage was escalated during the first 10 weeks for patients with ongoing disability. Thereafter, investigators were permitted to add open-label levodopa or other antiparkinsonian medications to treat ongoing or emerging disability. Main Outcome Measures: Time to the first occurrence of dopaminergic complications: wearing off, dyskinesias, on-off fluctuations, and freezing; changes in the Unified Parkinson's Disease Rating Scale and quality-oflife scales; and adverse events. Results: Initial pramipexole treatment resulted in a significant reduction in the risk of developing dyskinesias (24.5% vs 54%; hazard ratio, 0.37; 95% confidence interval [CI], 0.25-0.56; PϽ.001) and wearing off (47% vs 62.7%; hazard ratio, 0.68; 95% CI, 0.49-0.63; P=.02). Initial levodopa treatment resulted in a significant reduction in the risk of freezing (25.3% vs 37.1%; hazard ratio, 1.7; 95% CI, 1.11-2.59; P =.01). By 48 months, the occurrence of disabling dyskinesias was uncommon and did not significantly differ between the 2 groups. The mean improvement in the total Unified Parkinson's Disease Rating Scale score from baseline to 48 months was greater in the levodopa group than in the pramipexole group (2 ± 15.4 points vs-3.2 ± 17.3 points, P = .003). Somnolence (36% vs 21%, P = .005) and edema (42% vs 15%, PϽ.001) were more common in pramipexole-treated subjects than in levodopa-treated subjects. Mean changes in quality-of-life scores did not differ between the groups. Conclusions: Initial treatment with pramipexole resulted in lower incidences of dyskinesias and wearing off compared with initial treatment with levodopa. Initial treatment with levodopa resulted in lower incidences of freezing, somnolence, and edema and provided for better symptomatic control, as measured by the Unified Parkinson's Disease Rating Scale, compared with initial treatment with pramipexole. Both options resulted in similar quality of life. Levodopa and pramipexole both appear to be reasonable options as initial dopaminergic therapy for Parkinson disease, but...

Object In a double-blind randomized study, platelet concentrate was used to treat 50 patients who underwent anterior cervical fusion with allograft bone and internal fixation, predominantly for degenerative disc disease or soft herniated cervical disc. The goal in this study was to compare the outcomes in patients treated with and without the platelet gel. Methods Patients were assessed radiographically at 6, 12, and 52 weeks and at 2 years if needed. Clinically, patients were evaluated with the visual analog scale, Neck Disability Index, Short Form–36, and a modified Prolo Scale. Results Follow-up included 90% of the patients at 1 year and 84% at 2 years. The overall fusion rate was 84%. Conclusions Whereas patients with degenerative discs treated with platelet gel demonstrated early fusion at the 12-week follow-up interval, no consistent early fusion was obtained with the use of the platelet gel preparation in patients with a soft disc herniation.

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Background: Patient-reported quality of life (QoL) using standardized tools have been proposed as outcome measures in clinical trials. The NeuroQoL scale has been evaluated in patients with common neurological disorders (e.g., ischemic stroke, epilepsy, ALS, and Parkinson’s), but has not been applied to familial cerebral cavernous malformation (FCCM). FCCM is typically characterized by multiple brain lesions that can cause clinical symptoms (hemorrhages, seizures, headaches, neurological deficits) and affect QoL. The purpose of this study was to summarize NeuroQoL domain scores in FCCM patients. Methods: NeuroQoL short forms covering 12 QoL domains (Figure) were completed by 50 FCCM adults enrolled in the Brain Vascular Malformation Consortium CCM Project. Raw scores summing responses in each domain were converted to T-scores, which are standardized to general (8 domains) or clinical (4 domains) reference populations with mean of 50 and standard deviation of 10. One-sample t-tests were used to determine whether mean T-scores were significantly different from 50 (p<0.05). Results: We observed significant differences between FCCM and the reference populations on several domains (Figure). Compared to the general reference population, FCCM patients were more likely to have higher positive affect (56, p<0.001) and less depression (55, p<0.001), but lower social satisfaction (48, p=0.032). Compared to the clinical reference population, FCCM patients reported significantly less stigma (61, p<0.001) and less fatigue (54, p=0.018). Conclusion: FCCM patients differed from the reference populations on several NeuroQoL domains, including positive affect, depression, stigma, fatigue and social satisfaction. Further studies are needed to understand the effect of clinical symptoms on NeuroQoL domains in FCCM.