Acorda Therapeutics Research Articles

Effect of Cognitive Demand on Functional Mobility in Ambulatory Individuals with Multiple Sclerosis.

As disease progresses, cognitive demands may affect functional mobility in individuals with multiple sclerosis (MS). The Timed Up and Go (TUG) test assesses functional mobilityin populationssuch as MS. A cognitive-demanding task can be added to the TUG test to assess its effect on functional mobility. People with MS (n = 52) and controls (n = 57) performed three versions of the TUG test: TUG alone (TUG-alone), TUG plus reciting the alphabet (TUG-alpha), and TUG plus subtracting numbers by 3s (TUG-3s). Times to complete the TUG tests were compared among controls and three groups of participants with MS created using Expanded Disability Status Scale (EDSS) scores 0 to 3.5, 4.0 to 5.5, and 6. Differences among groups were analyzed using split-plot analysis of variance. Group and TUG type were significant (P < .001 for both), with no interaction effect of group × TUG type (P = .21). Mean times were 8.7, 9.4, and 11.1 seconds to perform the TUG-alone, TUG-alpha, and TUG-3s, respectively. Mean times for groups were 8.0, 8.2, 11.1, and 11.6 seconds for controls and individuals with MS and EDSS 0 to 3.5, 4.0 to 5.5, and 6, respectively. People with MS with an EDSS score greater than 3.5 had a statistically significant reduction in performance of the TUG test even with the addition of a simple cognitive task, which might have implications for a person's more complex everyday activities.

Spinal Cord as an Adjunct to Brain Magnetic Resonance Imaging in Defining "No Evidence of Disease Activity" in Multiple Sclerosis.

Monitoring patients with multiple sclerosis (MS) for “no evidence of disease activity” (NEDA) may help guide disease-modifying therapy (DMT) management decisions. Whereas surveillance brain magnetic resonance imaging (MRI) is common, the role of spinal cord monitoring for NEDA is unknown. To evaluate the role of brain and spinal cord 3T MRI in the 1-year evaluation of NEDA. Of 61 study patients (3 clinically isolated syndrome, 56 relapsing-remitting, 2 secondary progressive), 56 (91.8%) were receiving DMT. The MRI included brain fluid-attenuated inversion recovery and cervical/thoracic T2-weighted fast spin echo images. On MRI, NEDA was defined as the absence of new or enlarging T2 lesions at 1 year. Thirty-nine patients (63.9%) achieved NEDA by brain MRI, only one of whom had spinal cord activity. This translates to a false-positive rate for NEDA based on the brain of 2.6% (95% CI, 0.1%–13.5%). Thirty-eight patients (62.3%) had NEDA by brain and spinal cord MRI. Fifty-five patients (90.2%) had NEDA by spinal cord MRI, 17 of whom had brain activity. Of the 22 patients (36.1%) with brain changes, 5 had spinal cord changes. No evidence of disease activity was sustained in 48.3% of patients at 1 year and was the same with the addition of spinal cord MRI. Patients with MRI activity in either the brain or the spinal cord only were more likely to have activity in the brain (P = .0001). Spinal cord MRI had a low diagnostic yield as an adjunct to brain MRI at 3T in monitoring patients with MS for NEDA over 1 year. Studies with larger data sets are needed to confirm these findings.

ErbB Receptors Signaling Promote Endothelial Phenotype of Human Left Ventricular Epicardial Highly Proliferative Cells

Despite a long history of heart‐specific ErbB signaling research, the role of ErbB receptors in cardiac non‐myocyte cells is largely unknown. We recently have shown that neuregulin‐1b (NRG‐1b) prevented transition of CD105posCD31neg cells obtained from mouse heart into myfibroblasts. These cells can form single‐cell derived colonies with high proliferative potential and capability to differentiate into different cell types. The present study examines the expression of ErbB receptors on highly proliferative cells (HiPC) obtained from human LV epicardium and the role of ErbB receptor subtypes in the regulation of CD31, VEGFR2 and Tie2 endothelial markers expression. Left ventricular free wall epicardial biopsies from human subjects undergoing open heart surgery were used to obtain myocytes‐depleted cardiac cell suspension. These cells were seeded at low cell density to produce colonies of HiPC. We found that human HiPC are characterized by expression of all four ErbB receptors. The level of ErbB receptors varied among HiPC obtained from different subjects. ErbB2 and ErbB3 showed highest level of inter‐individual variability compared to ErbB1 and ErbB4. Flow cytometric analysis revealed strong expression of CD105 (endoglin), CD73 (ecto‐5′‐nucleotidase) and CD29 (integrin β1), and lack of CD34, CD117 (c‐kit), CD11b, and CD45 on HiPC. In addition, we detected expression of CD49f (integrin alpha 6), CD90 (Thy‐1) and CD31 (PECAM‐1) on cell surface of HiPC. A strong positive correlation was found between CD31/PECAM‐1 and ErbB2 but not ErbB1, 3 or 4. To determine the role of ErbB receptors, we incubated HiPC in the absence or presence of EGF to stimulate ErbB1, and NRG‐1b to stimulate ErbB3 and ErbB4 receptor activation. We found that both EGF and NRG‐1b ligands promoted CD31 cell surface expression on HiPC which express high level of ErbB2 (ErbB2hi). In contrast, no effects of ErbB ligands were seen in ErbB2low/− HiPC. Only EGF but not NRG‐1b increased VEGFR2 expression on HiPC. No difference was found between ErbB2hi and ErbB2low/− HiPC, indicating that ErbB1 receptors are solely responsible for the upregulation of cell surface expression of VEGFR2. In addition, both EGF and NRG‐1b induced up‐regulation of Tie2 on HiPC to a similar degree, irrespective of the level of ErbB2 expression. Thus our data identified a novel role of ErbB signaling in promotion of endothelial phenotype of human HiPC.Support or Funding InformationSupported in part by Acorda therapeutics, Inc, U01 HL100398, and the Osher Cardiovascular Research Fund at Maine Medical Center

Is Exercise Training Beneficial in Progressive Multiple Sclerosis?

There is substantial evidence for the benefits of exercise training in people with multiple sclerosis (MS). These benefits, however, have primarily been established in the early, relapsing disease phase or are derived from heterogeneous MS samples (ie, relapsing and progressive MS). This makes it challenging to determine whether the consequences of exercise training are similar in the relapsing and progressive disease courses. The role of exercise training in progressive MS is far less clear. This study examined the potential role of exercise training in people with progressive MS. We review the current evidence from studies examining conventional exercise training modalities (eg, cycle ergometry) as well as specialized exercise training approaches (eg, functional electrical stimulation cycling) in samples involving exclusively individuals with progressive MS. The evidence reviewed from nine trials provides preliminary support for the benefits of exercise training with regard to fitness, symptom, and quality of life outcomes in progressive MS, although these data are currently limited and at times conflicting. Considering the prevalence of progressive MS (ie, 1 million people worldwide), the lack of effective treatment options, and the considerable frustration of researchers, clinicians, and patients, we believe that exercise training represents a viable therapeutic option worthy of further consideration. Future research should involve well-designed, randomized clinical trials with appropriate sample sizes and control conditions to establish the safety, feasibility, and therapeutic efficacy of exercise training in progressive MS.

A Framework of Care in Multiple Sclerosis, Part 2: Symptomatic Care and Beyond.

The Consortium of Multiple Sclerosis Centers (CMSC) convened a Framework Taskforce composed of a multidisciplinary group of clinicians and researchers to examine and evaluate the current models of care in multiple sclerosis (MS). The methodology of this project included analysis of a needs assessment survey and an extensive literature review. The outcome of this work is a two-part continuing education series of articles. Part 1, published previously, covered the updated disease phenotypes of MS along with recommendations for the use of disease-modifying therapies. Part 2, presented herein, reviews the variety of symptoms and potential complications of MS. Mobility impairment, spasticity, pain, fatigue, bladder/bowel/sexual dysfunction, cognitive dysfunction, and neuropsychiatric issues are examined, and both pharmacologic and nonpharmacologic interventions are described. Because bladder and bowel symptoms substantially affect health-related quality of life, detailed information about elimination dysfunction is provided. In addition, a detailed discussion about mental health and cognitive dysfunction in people with MS is presented. Part 2 concludes with a focus on the role of rehabilitation in MS. The goal of this work is to facilitate the highest levels of independence or interdependence, function, and quality of life for people with MS.

CME/CNE Article: A Framework of Care in Multiple Sclerosis, Part 1: Updated Disease Classification and Disease-Modifying Therapy Use in Specific Circumstances.

CME/CNE Article: A Framework of Care in Multiple Sclerosis, Part 1: Updated Disease Classification and Disease-Modifying Therapy Use in Specific Circumstances.

Letter to the Editor: The Emerging Role of Pharmacists in the Multidisciplinary Care of Patients with Multiple Sclerosis.

Letter to the Editor: The Emerging Role of Pharmacists in the Multidisciplinary Care of Patients with Multiple Sclerosis.

The Evaluation of Magnesium Chloride within a Polyethylene Glycol Formulation in a Porcine Model of Acute Spinal Cord Injury.

A porcine model of spinal cord injury (SCI) was used to evaluate the neuroprotective effects of magnesium chloride (MgCl2) within a polyethylene glycol (PEG) formulation, called "AC105" (Acorda Therapeutics Inc., Ardsley, NY). Specifically, we tested the hypothesis that AC105 would lead to greater tissue sparing at the injury site and improved behavioral outcome when delivered in a clinically realistic time window post-injury. Four hours after contusion/compression injury, Yucatan minipigs were randomized to receive a 30-min intravenous infusion of AC105, magnesium sulfate (MgSO4), or saline. Animals received 4 additional infusions of the same dose at 6-h intervals. Behavioral recovery was tested for 12 weeks using two-dimensional (2D) kinematics during weight-supported treadmill walking and the Porcine Injury Behavior Scale (PTIBS), a 10-point locomotion scale. Spinal cords were evaluated ex vivo by diffusion-weighted magnetic resonance imaging (MRI) and subjected to histological analysis. Treatment with AC105 or MgSO4 did not result in improvements in locomotor recovery on the PTIBS or in 2D kinematics on weight-supported treadmill walking. Diffusion weighted imaging (DWI) showed severe loss of tissue integrity at the impact site, with decreased fractional anisotropy and increased mean diffusivity; this was not improved with AC105 or MgSO4 treatment. Histological analysis revealed no significant increase in gray or white matter sparing with AC105 or MgSO4 treatment. Finally, AC105 did not result in higher Mg2+ levels in CSF than with the use of standard MgSO4. In summary, when testing AC105 in a porcine model of SCI, we were unable to reproduce the promising therapeutic benefits observed previously in less-severe rodent models of SCI.

Acorda Buys CNS Drug Firm Biotie

Acorda Therapeutics will pay $363 million in cash to acquire Finland’s Biotie Therapies, a developer of central nervous system drugs. Acorda will gain tozadenant, a small-molecule adenosine A2A receptor antagonist in Phase III clinical trials for treating Parkinson’s disease, and SYN120, a small-molecule 5-HT6/5-HT2A dual receptor antagonist for Parkinson’s-related dementia in Phase II trials. Ardsley, N.Y.-based Acorda plans to keep Biotie’s South San Francisco location and staff but is considering the future of the firm’s Finnish headquarters.

Acorda Therapeutics awarded grant to study ARCUS technology in respiratory distress syndrome

Acorda Therapeutics awarded grant to study ARCUS technology in respiratory distress syndrome

High-Dose Capsaicin for the Treatment of Neuropathic Pain: What We Know and What We Need to Know.

Neuropathic pain is a frequent and disabling condition with diverse underlying etiologies and is often difficult to treat. Systemic drug treatment is often limited in efficacy. Furthermore, adverse effects may be a limiting factor when trying to reach the necessary dose. Analgesics that can be applied topically have the potential to largely overcome this problem. They may be of particular advantage in localized neuropathic pain syndromes such as postherpetic neuralgia or small fiber neuropathy. Capsaicin, the pungent component of chili peppers, is a natural ligand of the transient receptor potential vanilloid 1 channel and has long been used as topically applicable cream with concentrations of 0.025 to 0.075%. In 2009, a high-concentration transdermal capsaicin 8% patch (Qutenza®; Acorda Therapeutics, Inc., Ardsley, NY, USA; Astellas Pharma Europe Ltd., Chertsey, Surrey, UK) was introduced for the treatment of peripheral neuropathic pain syndromes other than of diabetic origin in adults. It has since been widely used in diverse neuropathic pain disorders. In this review article, we summarize current knowledge on Qutenza, its advantages and problems, and expose unmet needs.Electronic supplementary materialThe online version of this article (doi:10.1007/s40122-014-0027-1) contains supplementary material, which is available to authorized users.

Robot Therapy Tipping Point

From the Departments of Neurology and Epidemiology, Brown University, Providence, RI; VARRD Center of Excellence for Neurorestoration and Neurotechnology, Providence VA Medical Center, Providence, RI; Neuroscience Research, Mandell Multiple Sclerosis Center, Saint Francis Hospital, Hartford CT (ACL); and VA Cooperative Studies Program, VA Connecticut Healthcare System, West Haven, Yale University (PDG). All correspondence and requests for reprints should be addressed to: Albert C. Lo, MD, PhD, Providence VA Medical Center, Building 32, 830 Chalkstone Ave, Providence, RI 02908-4799. Dr Albert Lo has received travel expense reimbursement from Hocoma. He has no other relevant disclosures. For all other disclosures, Dr Lo has received grants and travel reimbursement from the Department of Veterans Affairs and the National Multiple Sclerosis Society. He has received travel reimbursement from Novartis, the Department of Defense, and the University of Pennsylvania. He has received funding from Acorda Therapeutics for an investigator-initiated project. He has received honorarium from Scripps, Braintree, and Los Rancho Amigos. Albert Lo and Peter Guarino are federal government employees. Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article.

RESTORE Study: Effects of a 24-Week Natalizumab Treatment Interruption on Immune Parameters and Multiple Sclerosis Magnetic Resonance Imaging Disease Activity (P06.168)

RESTORE Study: Effects of a 24-Week Natalizumab Treatment Interruption on Immune Parameters and Multiple Sclerosis Magnetic Resonance Imaging Disease Activity (P06.168)

Subtle Lesion Appearance on MRI May Precede Development of Progressive Multifocal Leukoencephalopathy in Multiple Sclerosis Patients Treated with Natalizumab (P07.059)

Objective: To report MRI features of 3 cases with confirmed progressive multifocal leukoencephalopathy (PML) in multiple sclerosis (MS) patients treated with natalizumab that presented with subtle new lesions on MRI several months prior to diagnosis. Background Clinical vigilance and early recognition of specific MRI changes are considered caveats for early diagnoses of PML in natalizumab treated patients. Design/Methods: Retrospective clinical and MRI evaluation of 3 patients with confirmed PML (by detection of JC virus in cerebrospinal fluid), who had several serial scans prior to the PML diagnosis. Results: Case 1: 41 year old man who received 29 monthly natalizumab infusions. A small new T2 hyperintense/T1 enhancing lesion in the subcortical white matter of the left frontal lobe was detected. No clinical symptoms were associated and he tested negative for prior JC virus exposure 6 months previous. Seven months later, a large T2 hyperintense/T1 enhancing lesion, indicative of PML was detected in the same location. He tested positive for JC virus exposure on repeat analysis, one month prior to diagnosis. Case 2: 47 year old woman on natalizumab for 31 months complained of new onset double vision. A small T2 hyperintense, T1 non-enhancing lesion was detected in pons. Two months later, a large T2 hyperintense lesion consistent with PML was detected in the same location, in addition to multiple other lesions. Case 3: 54 year old woman on natalizumab for 61 months presented with mild vertigo. A small new T2 hyperintense lesion in pons was seen retrospectively. Four months later a large T2 hyperintense lesion consistent with PML was detected in the same location, in addition to multiple other lesions. Conclusions: The appearance of subtle new T2 hyperintense lesions may suggest PML in patients treated with natalizumab for more than two years. Disclosure: Dr. Hojnacki has received personal compensation for activities with Biogen Idec, Serono, Inc., Pfizer Inc, and Teva Neuroscience as a speaker and/or participant on scientific advisory boards. Dr. Zivadinov has received personal compensation for activities with Teva Neuroscience, Biogen Idec, EMD Serono, and Questcor Pharmaceuticals as a speaker and/or consultant. Dr. Zivadinov has received research support from Biogen Idec, Teva Neuroscience, Genzyme Corporation, Bracco, Questcor Pharmaceuticals and EMD Serono. Dr. Weinstock-Guttman has received personal compensation for activities with Acorda Therapeutics, Biogen Idec, Serono, Inc., Novartis, Pfizer Inc, Teva Neuroscience as a speaker and/or participant on an advisory board. Dr. Weinstock-Guttman has received research support from Acorda Therapeutics, Biogen Idec, Serono Inc., Novartis, Pfizer Inc, Teva Neuroscience, National Multiple Sclerosis Society, the National Institutes of Health, ITN, Teva Neuroscience, Aspreva-Roche, Acorda Therapeutics and Shire Pharmaceuticals.

Successful Treatment of Natalizumab Induced PML with CMX001 and the Side Effects Associated with Its Use (P07.060)

Objective: To describe a case of natalizumab induced Progressive Multifocal Leukoencephalopathy (PML) in a multiple sclerosis (MS) patient that was successfully treated with CMX001 and to report the adverse events associated with its use. Background Natalizumab is an effective treatment for MS that has been associated with the risk of developing PML. CMX001 is an oral analogue of cidofovir which selectively inhibits viral DNA polymerase. Design/Methods: Retrospective clinical and laboratory evaluation of a patient with confirmed PML that was treated with CMX001. Results: 45 year old woman with MS on natalizumab 54 months diagnosed with PML on routine brain MRI. CSF revealed 783 copies/ml of JC virus. Five plasma exchanges were performed. Repeat CSF (day 8) revealed 9,511 copies/ml of JC virus. CMX001 was initiated on day 9 (200mg orally twice a week). After four doses, she experienced severe nausea, vomiting and diarrhea. The drug was held one week and restarted at 200mg twice a week. After two doses nausea, vomiting and diarrhea again became severe. Colonoscopy revealed eosinophilic colitis. She was started on mesalamine, cholestyramine and diphenoxylate/atropine. CMX001 was held one week and restarted at 150mg twice a week. Over the next three weeks she continued to have diarrhea and decreased appetite but less than at the higher dose. After six weeks on CMX001 150mg twice a week, she presented confused and had two observed seizures. Multiple electrolyte abnormalities were seen. CMX001 was discontinued and not restarted. JC virus in the CSF dropped while on CMX001 to 3133, 428, 140, and 78copies/ml at week 6, 9, 14, and 16 weeks respectively. Conclusions: CMX001 may have been effective for treatment of natalizumab induced PML but had significant gastrointestinal side effects at 200mg twice a week and may have contributed to two seizures. Disclosure: Dr. Hojnacki has received personal compensation for activities with Biogen Idec, Serono, Inc., Pfizer Inc, and Teva Neuroscience as a speaker and/or participant on scientific advisory boards. Dr. Zivadinov has received personal compensation for activities with Teva Neuroscience, Biogen Idec, EMD Serono, and Questcor Pharmaceuticals as a speaker and/or consultant. Dr. Zivadinov has received research support from Biogen Idec, Teva Neuroscience, Genzyme Corporation, Bracco, Questcor Pharmaceuticals and EMD Serono. Dr. Weinstock-Guttman has received personal compensation for activities with Acorda Therapeutics, Biogen Idec, Serono, Inc., Novartis, Pfizer Inc, Teva Neuroscience as a speaker and/or participant on an advisory board. Dr. Weinstock-Guttman has received research support from Acorda Therapeutics, Biogen Idec, Serono Inc., Novartis, Pfizer Inc, Teva Neuroscience, National Multiple Sclerosis Society, the National Institutes of Health, ITN, Teva Neuroscience, Aspreva-Roche, Acorda Therapeutics and Shire Pharmaceuticals.

EBV, CMV, and HSV IgG Titers Are Not Predictive of Subsequent Relapse Risk in Pediatric Multiple Sclerosis (P02.096)

Objective: We evaluated whether antibody response against Epstein-Barr virus (EBV), cytomegalovirus (CMV), and herpes simplex virus 1 and 2 (HSV) are associated with relapse rate in pediatric patients with multiple sclerosis (MS). Background Elevated EBV titers have been shown to be associated with having MS. Data conflict as to whether EBV response predicts disease activity or disease subtype. It is not known if viral antibody levels are associated with relapse rate. Design/Methods: Sera were collected early during disease course in patients who subsequently received prospective clinical follow-up to document relapses at 6 pediatric MS clinics. Antibodies against EBV early antigen (EBVEA, a marker of viral reactivation), Epstein-Barr nuclear antigen-1 (EBNA1), HSV, and CMV were measured by ELISA. A repeated events analysis was employed to determine if viral antibody response or status (positive vs. negative) predicted subsequent relapses. Proportional hazards models adjusted for the time-varying covariate of disease-modifying therapy usage and fixed demographic variables. Results: 111 participants had serum from initial visit and subsequent relapse data. The prevalence of positive status for EBVEA, EBNA1, CMV, HSV1, and HSV2 were, respectively, 44.1%, 89.2%, 24.3%, 38.7%, and 21.6%. There was no statistically significant association in the relapse hazard rate for EBVEA (hazard ratio (HR) 0.97, 95%CI:0.78 to 1.22, p=0.81) or for EBNA1 antibody response (HR 1.08, 95%CI: 0.71 to 1.65, p=0.7). Adjustment for disease-modifying therapy, race, ethnicity, gender and HLA-DRB1 status did not substantially affect HRs. Similarly, HRs for EBV status, CMV titer or status and HSV-1 or 2 titers or status, did not show an association with subsequent relapse rate. Conclusions: Although previous studies have shown an association between prior infection with EBV and risk of MS, we did not detect an association between EBV, CMV or HSV antibody response and subsequent relapse rate in pediatric MS patients. Supported by: Dr. Graves is supported by the National Multiple Sclerosis Society Sylvia Lawry Award. The work was funded by the Nancy Davis Foundation and the NMSS. Disclosure: Dr. Graves has nothing to disclose. Dr. Krupp has received personal compensation for activities with Teva Neuroscience, BiogenIdec, Serono, Inc., Bayer Pharmaceuticals Corporation, Guidepoint Global, Pfizer Inc, Axon Advisors, Sanofi-Aventis Pharmaceuticals, Inc., as a speaker, consultant and/or participant on an advisory board. Dr. Krupp has received (royalty or license fee or contractual rights) payments from Genzyme Corporation, Bristol-Myers Squibb Company, MedImmune, and Novartis. Dr. Krupp has received research support from Serono Inc. and Biogen Idec. Dr. Weinstock-Guttman has received personal compensation for activities with Acorda Therapeutics, Biogen Idec, Serono, Inc., Novartis, Pfizer Inc, Teva Neuroscience as a speaker and/or participant on an advisory board. Dr. Weinstock-Guttman has received research support from Acorda Therapeutics, Biogen Idec, Serono Inc., Novartis, Pfizer Inc, Teva Neuroscience, National Multiple Sclerosis Society, the National Institutes of Health, ITN, Teva Neuroscience, Aspreva-Roche, Acorda Therapeutics and Shire Pharmaceuticals. Dr. Strober has nothing to disclose. Dr. Belman has nothing to disclose. Dr. Yeh has nothing to disclose. Dr. Ness has received research support from EMD Serono. Dr. Gorman has nothing to disclose. Dr. Rodriguez has nothing to disclose. Dr. Chitnis has received personal compensation for activities with Teva Neuroscience, Biogen Idec, Sanofi-Aventis Pharmaceuticals, Inc., and Novartis. Dr. Chitnis has received research support from Merck Serono. Dr. Waubant has received personal compensation for activities with Teva Neuroscience, Actelion, Sanofi-Aventis Pharmaceuticals, Roche Diagnostics Corporation and Biogen Idec as a speaker and/or consultant. Dr. Waubant has received research support from Biogen Idec and Sanofi-Aventis Pharmaceuticals.

Comparison of a 1.5T Standard vs. 3T Optimized Protocols in Multiple Sclerosis Patients (P03.053)

Objective: To investigate the superiority of the 3T optimized vs. the 1.5T standardized protocols in detecting gadolinium enhancing (GD-E) lesions in patients with multiple sclerosis (MS). Background Use of post-contrast T1-weighted imaging (WI) is an important tool in diagnosing and predicting the course of MS. Application of optimized imaging strategies has the potential to increase detection of MRI disease activity. Design/Methods: A standard protocol was defined as a 1.5T scan with a single-dose of Gd and a 5-minute scanning delay after injection. An optimized protocol was defined as a 3T MRI scan, using a triple dose of Gd, 20 min scan delay, and using an off-resonance saturated magnetization transfer pulse to reduce the background signal. Fourteen relapsing-remitting MS patients and 3 healthy controls (HC) were scanned with 1.5T standardized and a 3T optimized protocols in random order over 72 hours. Results: There were 47 Gd-E lesions in the MS patients on 3T optimized and 34 on 1.5T standard protocols, a 38.2% increase. There was a significant increase in Gd-enhanced lesion volume (LV) detected with the optimized protocol (179.6%, p Conclusions: The 3T optimized protocol is a useful technique for increasing sensitivity of MRI to detect Gd-E lesions. Disclosure: Dr. Livshits has nothing to disclose. Dr. Hussein has nothing to disclose. Dr. Kennedy has nothing to disclose. Dr. Weinstock-Guttman has received personal compensation for activities with Acorda Therapeutics, Biogen Idec, Serono, Inc., Novartis, Pfizer Inc, Teva Neuroscience as a speaker and/or participant on an advisory board. Dr. Weinstock-Guttman has received research support from Acorda Therapeutics, Biogen Idec, Serono Inc., Novartis, Pfizer Inc, Teva Neuroscience, National Multiple Sclerosis Society, the National Institutes of Health, ITN, Teva Neuroscience, Aspreva-Roche, Acorda Therapeutics and Shire Pharmaceuticals. Dr. Hojnacki has received personal compensation for activities with Biogen Idec, Serono, Inc., Pfizer Inc, and Teva Neuroscience as a speaker and/or participant on scientific advisory boards. Dr. Zivadinov has received personal compensation for activities with Teva Neuroscience, Biogen Idec, EMD Serono, and Questcor Pharmaceuticals as a speaker and/or consultant. Dr. Zivadinov has received research support from Biogen Idec, Teva Neuroscience, Genzyme Corporation, Bracco, Questcor Pharmaceuticals and EMD Serono.

Two-Year Relapse Rate in the TOP MS Study: Completer Cohort (P01.132)

Objective: To evaluate characteristics related to 2-year relapse rate for the TOP MS study completer cohort. Background The Therapy Optimization in MS Study (TOP MS) is a prospective, open-label parallel group study of patients who are being treated with disease-modifying therapies (DMT). All of the DMT have been shown to effectively reduce relapse rates. Design/Methods: Potential participants for TOP MS were identified at specialty pharmacies with medication therapy management programs. Signed informed consent forms were returned to the pharmacies, and study enrollment produced log-on instructions for the study website. At baseline and monthly intervals over 24 months, enrolled participants receive reminders to respond to surveys. Self-reported responses are entered directly into the study database. Results: The TOP MS completer cohort consists of 531 subjects with a mean duration of disease of 11.1+9.2 years. Nearly 90% of participants met the criteria for relapsing forms of MS. The 2-year relapse rate for this cohort was 35.3%. Glatiramer acetate was being used by 50.8%, and 49.2% were using interferon-beta at study enrollment. Over two years therapy change occurred for 50 patients (9.4%) and was significantly associated with the number of confirmed relapses (chi 2 = 13.9, df = 2, p = .001). While mean duration of current DMT treatment was 4.3+4.1 years, shorter duration was correlated with more confirmed relapses (p = .004). One-third of the completer cohort had used other DMT prior to starting their current therapy (mean number of previous therapies: 1.3) and number of previous DMT was positively correlated with number of confirmed relapses (p = .001). Disease duration and enrollment DMT were not associated with relapses. Conclusions: The two-year relapse rate in the completer cohort of the TOP MS Study was influenced by change in DMT therapy, time on DMT treatment, and number of previous DMT treatments. Supported by: Teva Pharmaceuticals. Disclosure: Dr. Coyle has received personal compensation for activities with Acorda Therapeutics, Avanir Pharmaceuticals, Bayer Pharmaceuticals Corporation, Biogen Idec, Genzyme Corporation, Novartis, Questcor, Roche Diagnostics Corporation, Sanofi-Aventis Pharmaceuticals, Inc., and Teva Neuroscience. Dr. Coyle has received personal compensation in an editorial capacity for NEURA. Dr. Coyle has received research support from Serono, Inc., Novartis, and Sanofi-Aventis Pharmaceuticals, Inc. Dr. Zwibel has received personal compensation for activities with Serono, Inc., and Teva Neuroscience. Dr. Zwibel has received research support from Teva Neuroscience. Dr. Cohen has received research support from Biogen Idec. Dr. Leist has received personal compensation for activities with EMD Serono, Teva Neuroscience and Bayer.Dr. Leist has received research support from Bayer, EMD Serono and Teva Neuroscience. Dr. Tullman has received personal compensation for activities with Acorda Therapeutics, Biogen Idec, Serono Inc., Novartis, Pfizer Inc., Teva Neuroscience, Sanofi-Aventis Pharmaceuticals, Abbott Labortories, Inc. and Vaccinex as a consultant and/or speaker. Dr. Tullman has received research support from Acorda Therapeutics, BioMS, Novartis, and Genentech, Inc. Dr. Markowitz has received personal compensation for activities with Bayer, Teva, EMD-Serono, Biogen Idec, and Eli Lilly. Dr. Hughes has received research support from Teva Neuroscience, Berlex Labratories and Genentech, Inc..

Risk Factors for Chronic Cerebrospinal Venous Insufficiency (CCSVI) (P05.127)

Objective: To investigate the association between presence of a newly proposed vascular condition called chronic cerebrospinal venous insufficiency (CCSVI) and environmental factors in a large volunteer control group without a known central nervous system pathology. Background The role of intra- and extra-cranial venous system impairment in the pathogenesis of various vascular, inflammatory and neurodegenerative neurological disorders, as well as in aging, has not been studied in detail. Design/Methods: The data were collected in a prospective study from 252 subjects who were screened for medical history as part of the entry criteria and participated in the case-control study of CCSVI prevalence in multiple sclerosis (MS) patients and were analyzed post hoc. All participants underwent physical and Doppler sonography examinations, and were assessed with a structured environmental questionnaire. Fullfilment of ≥ 2 positive venous hemodynamic (VH) criteria on Doppler sonography was considered indicative of CCSVI diagnosis. Risk and protective factors associated with CCSVI were analyzed using logistic regression analysis. Results: Seventy (27.8%) subjects presented with CCSVI diagnosis and 153 (60.7%) presented with one or more VH criteria. The presence of heart disease (p=.001), especially heart murmurs (p=.007), a history of infectious mononucleosis (p=.002), and irritable bowel syndrome (p=.005) were associated with more frequent CCSVI diagnosis. Current or previous smoking (p=.029) showed a trend for association with more frequent CCSVI diagnosis, while use of dietary supplements (p=.018) showed a trend for association with less frequent CCSVI diagnosis. Conclusions: Risk factors for CCSVI differ from established risk factors for peripheral venous diseases. Vascular, infectious and inflammatory factors were associated with higher CCSVI frequency. Supported by: Funded with internal resources of the Buffalo Neuroimaging Analysis Center and Baird MS Center, the Jacobs Neurological Institute, University of Buffalo. In addition, we received support from the Direct MS Foundation and the Jacquemin Foundation. Disclosure: Dr. Dolic has nothing to disclose. Dr. Weinstock-Guttman has received personal compensation for activities with Acorda Therapeutics, Biogen Idec, Serono, Inc., Novartis, Pfizer Inc, Teva Neuroscience as a speaker and/or participant on an advisory board. Dr. Weinstock-Guttman has received research support from Acorda Therapeutics, Biogen Idec, Serono Inc., Novartis, Pfizer Inc, Teva Neuroscience, National Multiple Sclerosis Society, the National Institutes of Health, ITN, Teva Neuroscience, Aspreva-Roche, Acorda Therapeutics and Shire Pharmaceuticals. Dr. Marr has nothing to disclose. Dr. Valnarov has nothing to disclose. Dr. Carl has nothing to disclose. Dr. Hagemeier has nothing to disclose. Dr. Brooks has nothing to disclose. Dr. Kilanowski has nothing to disclose. Dr. Ramanathan has received personal compensation for activities with EMD Serono, Biogen Idec, Allergan, Netezza, Pfizer, Novartis, The National Multiple Sclerosis Society, The Department of Defense, Jog for the Jake Foundation, and The National Institutes of H as a consultant.Dr. Ramanathan has received personal compensation in an editorial capacity for The American Association of Pharmaceutical Scientists.Dr. Ramanathan has received research support from EMD Serono, Biogen Idec, Allergan, Netezza, Pfizer, Novartis, The National Multiple Sclerosis Society, The Department of Defense, Jog for the Jake Foundation, and The National Institutes of H. Dr. Zivadinov has received personal compensation for activities with Teva Neuroscience, Biogen Idec, EMD Serono, and Questcor Pharmaceuticals as a speaker and/or consultant. Dr. Zivadinov has received research support from Biogen Idec, Teva Neuroscience, Genzyme Corporation, Bracco, Questcor Pharmaceuticals and EMD Serono.

Pain in Neuromyelitis Optica Is More Common, Disabling, and Refractory Compared to MS (P07.070)

Objective: Determine whether pain frequency, use of pain-relief medications, and pain level control differed between subjects with NMO versus MS. Background Pain is a frequent and disabling symptom among demyelinating diseases. Neuromyelitis optica (NMO) is associated with severe inflammatory lesions of the spinal cord and optic nerve, with potential for chronic pain. Design/Methods: Cross-sectional study (NMO=29, MS=66) included McGill Pain Score (MPS), Short Form 36 Scale (SF36), Center for Epidemiologic Studies Depression Scale (CES-D), Expanded Disability Status Score (EDSS), Multiple Sclerosis Functional Composite (MSFC). Involved T2 spinal segments were counted. CNS pain medications use was quantified. Results: Current pain was noted in 86% in NMO subjects, compared to 41% in MS. Severe current pain was present in 52% with NMO vs. 11% with MS. Painful tonic spasms were present in 90% with NMO vs. 39% with MS. McGill Pain Score had a positive correlation with involved spinal cord segments for NMO (r=0.45, p=0.02). Current pain on a 10 point scale was correlated with the physical component of the SF36 (r= -0.49, p Conclusions: Pain is very common in NMO, and is severe in the majority. Pain magnitude has a deleterious effect on quality of life. Although medications are often used to help relieve pain, many patients continue to suffer. Our pain medications may be contributing to side effects such as slowed cognition and fatigue. Supported by: NIH funding T32NS007205 to PQ. NIH funding K23NS052430 to RTN. Disclosure: Dr. Qian has received personal compensation for activities with Teva Neuroscience as an employee. Dr. Cross has received personal compensation for activities with Bayer Healthcare, Biogen Idec, Teva Neuroscience, Eli Lilly & Company, Hoffman-La Roche, and Genentech, Inc. Dr. Naismith has received personal compensation for activities with Acorda Therapeutics, Bayer Pharmaceuticals Corporation, and Biogen Idec as a consultant and/or speaker. Dr. Naismith has received personal compensation in an editorial capacity for Journal Watch Neurology. Dr. Naismith has received research from Acorda Therapeutics.