Personal Compensation For Activities Research Articles

Responder Analyses from a 78-Week Phase 2 Placebo-Controlled Study of ELND005 (Scyllo-Inositol) in Mild to Moderate (MM) Alzheimer's Disease (AD) (P04.195)

Objective: To evaluate responder proportions in Mild AD using new responder criteria, to inform selection of optimal definitions in future studies of this candidate oral disease modifying agent. Background This study enrolled 353 M/M patients (MMSE 16-26) to placebo or ELND005 (250mg, 1000mg, or 2000mg, all BID). Safety findings led to discontinuation of the 2 highest doses, efficacy analyses were based on placebo and 250mg arms. Treatment effects were not significant in M/M population for NTB, ADCS-ADL (cognitive, functional co-primary outcomes). In pre-specified Mild AD analyses, NTB showed significant effects in study completers (Salloway et al., Neurology 2011). The CDR-SB will likely be the co-primary global outcome in future studies, thus responder analyses focused on NTB and CDR-SB. Design/Methods: Responder definitions explored in m-ITT population were: 1. NTB responders: NTB change from baseline ≥ 0; 2. CDR-SB responder: CDR-SB ≤ 0; 3. Response on either NTB or CDR-SB. Responder proportions were analyzed in M/M and Mild group (MMSE 22-26), with no adjustments for multiplicity testing. Results: In M/M group, there were 15.7 and 32.7% NTB responders (N=51/52, p= 0.07), NTB or CDR responders were 23.5 and 38.5% in placebo/250mg groups (NS); while in Mild group, there were 15.6% and 50.0% NTB responders (N=32/32, p or CDR responders were 25.0% and 56.3% (p= 0.02) in placebo/250mg groups. In both M/M and Mild groups CDR-SB responder proportions to ELND005 were small (15.4%, 21.9%) and differences from placebo (13.7%, 18.8%) were NS. Conclusions: Responder proportions with ELND005 were consistently higher in Mild than in M/M AD. Using the “either NTB or CDR-SB” responder definition, responsder proportion was significantly higher on ELND005 than placebo in Mild patients, where 56% improved or remained stable at week 78. These responder analyses support the positive NTB trends in pre-specified analyses of Mild AD, and will be included in future studies. Supported by: Elan Pharmaceuticals, South San Francisco, CA. Disclosure: Dr. Salloway has received personal compensation for activities with Elan Corporation, Sanofi-Aventis Pharmaceuticals, Inc., Pfizer Inc, Eisai Inc., Bristol-Myers Squibb, Novartis, Forest, and Athena Diagnostics. Dr. Salloway has received research support from Eisai Inc., Pfizer Inc, Forest Laboratories, Inc., Janssen Pharmaceutica, Medivation, GlaxoSmithKline, Inc., Myriad Pharmaceuticals, Elan Corporation, Neurochem, Wyeth, Bristol-Myers Squibb, Voyager, and Cephalon, Inc. Dr. Sperling has received personal compensation for activities with Pfizer Inc, Bristol-Myers Squibb, Janssen, and Elan as a consultant. Dr. Sperling has received research support from Bristol-Myers Squibb and Elan. Dr. Porsteinsson has received personal compensation for activities with Medivation, Elan, Janssen Immunotherapy, Pfizer, Transition Therapeutics, and Forest LaboratoriesDr Porsteinsson has received research support from BMS, Baxter, Elan, Janssen Immunotherapy, Medivation, Pfizer, Toyama, and Wyeth. Dr. Crans has received personal compensation for activities with Elan Pharmaceuticals and JANSSEN Alzheimer Immunotherapy Research and Development, LLC. Dr. Hernandez has received personal compensation for activities with Elan Pharmaceuticals as an employee. Dr. Abu-Shakra has receievd personal compensation for activities with Allergan, Inc as an employee.

Responders to ELND005 (Scyllo-Inositol) Demonstrate Clinical and Biomarker Characteristics Consistent with Mild Alzheimer's Disease (AD): Data from a 78-Week Phase 2 Study in Mild to Moderate (M/M) AD (P04.194)

Objective: To describe the clinical and biomarker characteristics (v-MRI and CSF) of patients who demonstrated cognitive benefit on ELND005, a candidate disease modifying agent. Background Post-hoc analyses were from a Phase 2, placebo-controlled, 78 week study in 353 M/M AD patients (MMSE 16-26), which included 3 active arms (250, 1000 and 2000mg all BID). The 2 highest doses were discontinued due to safety findings (Salloway et al. Neurology 2011). Design/Methods: Clinical response was defined as improved or stable Neuropsychological Test Battery scores (NTB, co-primary outcome) assessed in all 3 doses at 78 weeks. Baseline parameters and percent changes from baseline were compared using t-tests. Correlation analyses were performed on response rate, defined as number of times a patient9s NTB remained ≥0 at any visit divided by time on study. Results: Clinical responders compared to non-responders (n= 39/109), had significantly higher baseline MMSE (mean 23.3 versus 20.6, p Conclusions: Patients who improved or remained stable at 78 weeks had mild disease at baseline, by MMSE and CSF tau pararmeters. Clinical responders developed significantly less brain atrophy and ventricular enlargement than non-responders over 78 weeks. Correlations of CSF biomarkers and clinical outcome changes were limited by the small CSF sample size at study endpoint (N=34). These data support the potential benefit of ELND005 when treatment is initiated at the Mild AD stage, and help define the population for future studies. Supported by: Elan Pharmaceuticals, South San Francisco, CA. Disclosure: Dr. Porsteinsson has received personal compensation for activities with Medivation, Elan, Janssen Immunotherapy, Pfizer, Transition Therapeutics, and Forest LaboratoriesDr Porsteinsson has received research support from BMS, Baxter, Elan, Janssen Immunotherapy, Medivation, Pfizer, Toyama, and Wyeth. Dr. Sperling has received personal compensation for activities with Pfizer Inc, Bristol-Myers Squibb, Janssen, and Elan as a consultant. Dr. Sperling has received research support from Bristol-Myers Squibb and Elan. Dr. Salloway has received personal compensation for activities with Elan Corporation, Sanofi-Aventis Pharmaceuticals, Inc., Pfizer Inc, Eisai Inc., Bristol-Myers Squibb, Novartis, Forest, and Athena Diagnostics. Dr. Salloway has received research support from Eisai Inc., Pfizer Inc, Forest Laboratories, Inc., Janssen Pharmaceutica, Medivation, GlaxoSmithKline, Inc., Myriad Pharmaceuticals, Elan Corporation, Neurochem, Wyeth, Bristol-Myers Squibb, Voyager, and Cephalon, Inc. Dr. Crans has received personal compensation for activities with Elan Pharmaceuticals and JANSSEN Alzheimer Immunotherapy Research and Development, LLC. Dr. Hernandez has received personal compensation for activities with Elan Pharmaceuticals as an employee. Dr. Abu-Shakra has receievd personal compensation for activities with Allergan, Inc as an employee.

Neuromyelitis Optica Relapse Associated with Pregnancy: Similarities to Multiple Sclerosis (P06.184)

Objective: To determine whether relapses of neuromyelitis optica (NMO) are associated with pregnancy. Background The risk of multiple sclerosis (MS) relapse is known to decrease markedly during pregnancy, particularly in the third trimester, and increase again in the first 3 months postpartum. However, little is known about the influence of pregnancy on the clinical course of NMO. Design/Methods: We retrospectively studied pregnant patients with NMO seen at Tokyo Women9s University Hospital, Tohoku University Hospital, or Juntendo University Hospital and diagnosed according to AQP4 antibody-positive findings and the revised criteria. We analyzed disease onset and/or relapse associated with pregnancy and investigated each trimester during pregnancy (1st, DP1; 2nd, DP2; 3rd, DP3) and each trimester postpartum (1st, PP1; 2nd, PP2; 3rd, PP3; 4th and over, PP4). Results: Among total 51 pregnant women diagnosed with NMO, we extracted 14 NMO patients (mean age at disease onset, 30.4±8.5 years; mean age at pregnancy, 32.6±6.6 years; these mean ages were lower than those of the general age at onset for NMO [39 years]). Total number of relapses was 17 among our patients. For each period, the number of relapses was 3 for DP1, 2 for DP2, 1 for DP3, 5 for PP1, 3 for PP2, 1 for PP3, 1 for PP4, and 1 immediately after elective abortion. NMO appeared to be associated with pregnancy in 6 patients, and the time of disease onset was more frequently postpartum (n=6) than during pregnancy (n=2) in these patients. Almost all of these patients delivered healthy babies. Conclusions: Our results suggest that NMO patients of childbearing age need to be aware of the potential for disease exacerbation and may be at a higher risk of relapse/disease onset postpartum compared to during pregnancy. The influence of pregnancy on NMO might bear some resemblance to MS. Supported by: A Health and Labour Sciences Research Grant on Intractable Diseases (Neuroimmunological Diseases) from the Ministry of Health, Labour and Welfare of Japan. Disclosure: Dr. Shimizu has received personal compensation for activities with Bayer Yakuhin, Biogen Idec Japan, Teijin Pharma, and Novartis. Dr. Shimizu has received royalty payments for the Quick Reference Guide for Management. Dr. Ohashi has received personal compensation for activities with Bayer Yakuhin, Biogen Idec Japan, Teijin Pharma, and Novartis Pharma. Dr. Maruyama has nothing to disclose. Dr. Nakashima has received personal compensation for activities with Bayer Schering, Novartis, and Biogen Idec. Dr. Nakashima has received research support from Mitsubishi Chemical Medience Corporation and the Ministry of Education, Science, and Technology of Japan. Dr. Yokoyama has personal compensation for activities with Bayer Yakuhin, Biogen Idec Japan, Mitsubishi Tanabe Pharma, Teijin Pharma, Asteras Pharma, Daiichi Sankyo, Cosmic Corporation, Takeda Pharma, and AstraZeneca Pharmaceuticals. Dr. Fujihara has received personal compensation for Bayer Schering Pharma, Biogen Idec, Merck Serono, Biogen Idec, Eisai Inc., Mitsubishi Tanabe Pharma Corporation, Astellas Pharma Inc., Takeda Pharmaceutical Company Limited, and Asahi Kasei Kuraray Medical Co., Ltd. Dr. Fujihara has received personal compensation in an editorial capacity for Clinical and Experimental Neuroimmunology. Dr. Fujihara has received research support from Bayer Schering Pharma, Biogen Idec Japan, Asahi Kasei Kuraray Medical Co., The Chemo-Sero-Therapeutic Research Institute, Teva Pharmaceutical K.K., Mitsubishi Tanabe Pharma Corporation, Teijin Pharma, Eisai Inc., and Kyowa Pharmaceuticals America, Inc. Dr. Uchiyama has received personal compensation for activities with Sanofi-Aventis Pharmaceuticals, Inc., Otsuka, Novartis, Boehringer Ingelheim Pharmaceuticals, Inc., and Daiichi Sankyo.

Association of Markers for Urinary Tract Infection with Neurologic Impairment and Function Following Stroke (P01.017)

Objective: We compared the importance of the following Urine Analysis (UA) markers on neurologic impairment and function following stroke: Urinary nitrites, Leukocyte Esterase, Pyuria, and Bacteuria. Background Urinary Tract Infection (UTI) adversely affects functional outcomes and increases neurologic impairment following stroke. Design/Methods: UAs for 785 admissions to an acute inpatient stroke rehabilitation unit were used to determine the presence of markers for UTI, their association with age, interval post stroke, admission and discharge Functional Independence Measure (FIM), Fugl Meyer Motor Impairment (FMMI) and 2 and 6 minute walk tests (2MWT)(6MWT). ANOVA was used to correct for multiple comparisons. Spearman9s Rho correlation coefficient was used to assess associations between the number (0-4) of UTI markers present (UTITOT) and the above dependent variables. Results: ANOVA showed that the presence of bacteuria identified patients with significantly lower admission scores for each of the 4 dependent variables: FIM motor score 25 vs 31 (p= 0.000); FMMI Lower Extremity score 16 vs 19 (0.000); 2MWT 57 ft vs 76 (0.002); 6MWT 130 ft vs 176 (0.007). Urinary Nitrites were associated with significantly lower admission scores for 3 of 4 variables, Pyuria with lower scores for 2 of 4 variables, and Leukocyte Esterase with 1 of 4 variables. Spearman9s Rho for number of UTI markers present and age was 0.13 (0.000); interval post stroke 0.18 (0.00); admission FIM motor score –0.16 (0.000); FMMI Lower Extremity Score –0.11 (0.006); 2MWT –0.09 (0.02); 6MWT –0.08 (0.05). Presence of UTI markers at the time of admission were not associated with change in the above scores from admission to discharge. Conclusions: Patients with stroke and Rehabilitation Hospital admission UA markers for UTI have significantly lower admission FIM, FMMI, and walking scores. Admission UTI markers did not affect change in outcome scores implying that, with adequate treatment, patients with/without evidence of UTI show equal functional improvement. Supported by: Weill Medical College of Cornell University at Burke Rehabilitation Hospital, White Plains, NY 10605. Disclosure: Dr. Desai has nothing to disclose. Dr. Elashvili has nothing to disclose. Dr. Reding has received personal compensation for activities with Accorda Pharmaceuticals as a consultant.

Relapse Outcomes with Alemtuzumab vs. Rebif(R) in Treatment-Naive Relapsing-Remitting Multiple Sclerosis (CARE-MS I): Secondary and Tertiary Endpoints (PD5.004)

Objective: Compare alemtuzumab and subcutaneous interferon beta-1a (IFNB-1a) on relapse outcomes from a phase 3 trial in patients with relapsing-remitting multiple sclerosis (RRMS). Background Over 2 years, alemtuzumab reduced the rate of relapse by 55% compared with IFNB-1a (p Design/Methods: CARE-MS I was a 2-year, randomized, rater-blinded, global trial comparing the efficacy and safety of alemtuzumab to subcutaneous IFNB-1a in active, treatment-naive RRMS patients. Alemtuzumab treatment was 12mg/day intravenously for 5 days at study start and 3 days one year later. IFNB-1a treatment was 44mcg SC 3-times weekly for 24 months. Relapse rate was a co-primary endpoint. Relapse events were required to last at least 48 hours, required objective signs on exam as assessed by blinded raters, and were adjudicated by an independent relapse adjudication committee. Results: Annualized relapse rate was 0.18 (95% CI: 0.13, 0.23) for alemtuzumab-treated patients compared with 0.39 (95% CI: 0.29, 0.53) for IFNB-1a-treated patients (55% reduction, p Conclusions: Alemtuzumab significantly reduces relapses in RRMS patients compared with high-dose, high-frequency IFNB-1a. These results suggest the potential for alemtuzumab to be a meaningful addition to treatment options for RRMS, if approved. Supported by: Genzyme, a Sanofi company and Bayer Healthcare Pharmaceuticals. Disclosure: Dr. Fox has received personal compensation for activities with Bayer Pharmaceuticals Corporation, Biogen Idec, EMD Serono, Genzyme Corporation, Novartis, Opexa Therapeutics, Pfizer Inc, and Teva Neuroscience. Dr. Fox has received personal compensation in an editorial capacity for Neura. Dr. Fox has received research support from Biogen Idec, Eli Lilly & Company, EMD Serono, Genzyme Corporation, Novartis, Ono Pharmaceutical, Roche Diagnostics Corporation, Sanofi-Aventis Pharmaceuticals, Inc., and Teva Neuroscience. Dr. Arnold has received personal compensation for activities with Bayer Healthcare, Biogen Idec, Genentech, Inc., NeuroRx Research, Roche Diagnostics Corporation, Schering, Serono, Inc., and Teva Neuroscience. Dr. Arnold Dr. Arnold has received research support from Bayer Healthcare, Biogen Idec, Genentech, Inc., NeuroRx Research, Roche Diagnostics Corporation, Schering, Serono, Inc., and Teva Neuroscience. Dr. Brinar has nothing to disclose. Dr. Cohen has received personal compensation for activities with Biogen Idec, Eli Lilly & Company, Novartis, and Vaccinex. Dr. Cohen has received research support for activities with Biogen Idec, BioMS, Genzyme Corporation, Novartis, Synthon, and Teva Neuroscience. Dr. Coles has received personal compensation for activities with Genzyme Corporation, GlaxoSmithKline, Inc., and Merck Serono as a consultant and/or speaker. Dr. Coles has received research support from Genzyme Corportation. Dr. Confavruex has received personal compensation for activities with Biogen Dompe, Biogen Idec, Gemacbio, Genzyme Corporation, Hertie Foundation, Novartis, Sanofi-Aventis Pharmaceuticals, Inc., Teva Neuroscience, UCB Pharma, Bayer Schering, and Merck Serono. Dr. Confavruex has received research support from Bayer Schering, Biogen Idec, Merck Serono, Novartis, Sanofi-Aventis Pharmaceuticals, and Teva Neuroscience. Dr. Giovannoni has received personal compensation for activities with Bayer-Pharmaceuticals Corporation, Biogen Idec, Five Prime Therapeutics, Inc, Genzyme Corporation, Ironwood Pharmaceuticals, Merck Serono, Novartis, Teva Neuroscience, Sanofi-Aventis Pharmaceuticals and Vertex Pharmaceuticals as a speaker, consultant and/or serving on data monitoring boards. Dr. Hartung has received personal compensation for activities with Bayer Pharmaceuticals Corporation, Biogen Idec, BioMS, Genzyme Corporation, Merck Serono, Novartis, Sanofi-Aventis and Teva as a speaker and/or consultant. Dr. Havrodova has received personal compensation for activities with Bayer Pharmaceuticals Corporation, Biogen Idec, Genzyme Corporation, GlaxoSmithKline, Inc., Novartis, Merck, Sanofi-Aventis Pharmaceuticals, Serono, Inc., and Teva as consultant, speaker and/or advisory board participant. Dr. Selmaj has received personal compensation for activities with Genzyme, Ono, and Biogen Idec. Dr. Stojanovic has nothing to disclose. Dr. Weiner has received personal compensation for activities with Biogen Idec, Novartis, Serono, Inc., Teva Neurosciences, GlaxoSmithKline, Nasvax, Xenoport and Genzyme Corporation as consulting and/or speaking activities. Dr. Weiner has received research support from Merck Serono. Dr. Lake has received personal compensation for activities with Genzyme as an employee. Dr. Margolin has received personal compensation for activities with Genzyme Corporation as an employee. Dr. Panzara has received personal compensation for activities with Biogen Idec as an employee.Dr. Panzara holds stock and/or stock options in Biogen Idec. Dr. Compston has received personal compensation for activities with Genzyme Corporation as a speaker. Dr. Compston has received research support from Genzyme Corporation.

Efficacy of Rituximab in Patients with Secondary Progressive Multiple Sclerosis, Primary Progressive Multiple Sclerosis and Neuromyelitis Optica with Individual Treatment Cycles According to Peripheral B-Cell Return (P04.145)

Objective: To evaluate a standardised treatment protocol (375mg/m2 iv) given once according to the individual B-cell return. Background Rituximab, a monoclonal antibody, selectively depleting CD20+ B cells, has demonstrated efficacy in reducing disease activity in relapsing remitting MS, in subgroups of primary progressive MS and Neuromyelitis optica. Case studies suggest that the recurrence of B-lymphocytes can be correlated with the reactivation of inflammatory activity. Design/Methods: 15 patients (11 SPMS, 1 PPMS, 3 NMO) who failed first line therapy received 375 mg/m2 rituximab iv. Blood samples were taken before, after 4 months, then every 2 months. Patients received next course as soon as B-lymphocyte counts increased. Primary endpoints were confirmed disease progression measured by EDSS-increase and paraclinical MRI progression. Secondary endpoints were annualized relapse rate and safety parameters. Results: 11 patients received three doses of rituximab, the remaining patients two, four, five and six courses. Time between the courses varied according to B-cell count between month four and twelve. EDSS was registered before the first course and every following (from 2.5 to 8.0). Patients showed a decreased mean annualized relapse rate (from 1.67 to 0.73) and stabilization in mean EDSS score (from 5.6 to 5.66). Gadolinium enhancing lesions were registered in 5 patients before initiating therapy, after the first two courses of Rituximab, one patient showed inflammatory MRI lesions. Three patients showed paraclinical progression on MRI. Adverse effects occured as mild infections, no severe adverse effects. Conclusions: In all 15 patients Rituximab reduced inflammatory brain lesions, clinical relapses and showed a stabilizing of EDSS and paraclinical progression. No severe side effects occurred, observation phase up to 224 weeks. Although the patient population is small and heterogenous the positive results of previous studies regarding efficacy can be confirmed. This is to our knowledge the first report showing that the standard dosing protocol according to peripheral B-cell return might be effective and safe. Disclosure: Dr. Bernsen has nothing to disclose. Dr. Sorgalla has nothing to disclose. Dr. Gerbershagen has received personal compensation for activities with Merck Serono, Sanofi-Aventis Pharmaceuticals, Inc., Bayer Pharmaceuticals Corporation, Biogen Idec and Bionorica AG as a speaker. Dr. Limmroth has received personal compensation for activities with Bayer, Biogen Idec, Novartis, Roche, Sanofi-ventis, Serono, and Teva.Dr. Limmroth has received research support from Bayer, Biogen Idec, Novartis, Roche, Sanofi-Aventis, Serono, and Teva.

Differences between Familial and Non-Familial Early Onset Alzheimer's Disease (P05.045)

Objective: To investigate neurological differences between Non-familial EAD and PSEN1, the most common FAD, as markers for FAD. Background Although familial Alzheimer9s disease (FAD) is an Early onset AD (EAD), most patients with EAD do not have a familial disorder. Recent guidelines recommend obtaining genetic testing only in those EAD patients with 2 first-degree relatives. However, some patients with FAD may lack a known family history or other indications for suspecting FAD but might nonetheless be FAD mutation carriers and the results of such testing helpful to clinicians and families. Design/Methods: Retrospective chart review of a large University-based cohort of patients with non-familial early-onset AD (n=75) and with PSEN1-related AD (n=31). Results: There were group differences in age of onset, with PSEN1 mutation carriers being significantly younger, and in disease severity/duration (p Conclusions: In addition to a much younger age of onset, clinicians may be able to recognize FAD patients with PSEN1 mutations by specific abnormalities on the neurological history and examination. In some contexts, these findings should lead to genetic counseling and appropriate recommendations for obtaining PSEN1 testing or other genetic tests for FAD. Supported by: PHS K08 AG-22228, California DHS #04-35522, Alzheimer9s Disease Research Center Grant P50 AG-16570 from the National Institute on Aging, the Easton Consortium for Alzheimer9s Disease Drug Discovery and Biomarkers, the Sidell Kagan Foundation, the Shirley and Jack Goldberg Trust and Veteran9s Affairs Merit award. Disclosure: Dr. Joshi has nothing to disclose. Dr. Lee has nothing to disclose. Dr. Ringman has received personal compensation for activities with Takeda Pharmaceuticals as a scientific advisory board member.Dr. Ringman has received research support from Wyeth, Elan, Janssen, Bristol-Myers Squibb, Medivation, and Pfizer Pharmaceuticals. Dr. Juarez has nothing to disclose. Dr. Mendez has nothing to disclose.

Fingolimod Treatment Increases the Proportion of Patients Who Are Free from Disease Activity in Multiple Sclerosis Compared to IFN-b1a: Results from a Phase 3, Active-Controlled Study (TRANSFORMS) (PD5.006)

Objective: To examine the proportions of patients with multiple sclerosis (MS) free from disease activity with fingolimod (Gilenya TM ) therapy compared with interferon beta-1a IM (IFN beta-1a). Background Fingolimod has demonstrated superior efficacy to placebo and IFN beta-1a in MS. Absence of disease activity is an important objective of treatment and was assessed post hoc via the composite endpoint 9disease-free status9. Design/Methods: Patients with relapsing-remitting MS were randomized to fingolimod 0.5mg or 1.25mg, or to 30mcg IFN beta-1a IM in a 12-month, double-blind, double-dummy study (TRANSFORMS). Disease-free status was defined as absence of gadolinium-enhancing (Gd+) lesions, new/enlarging T2 lesions, confirmed relapses and 3-month confirmed disability progression. Results: Among 1292 patients 1153 (89%) completed the study. Fingolimod resulted in more disease-free patients vs. IFN beta-1a over 12 months (0.5mg, 46%, p vs. 69% of IFN beta-1a patients were free of relapses (p vs. 92% were free of disability progression (p=0.498). For MRI measures 56% vs. 49% were free of new/enlarging T2 lesions (p=0.058) and 90% vs. 81% were free of Gd-enhancingT1 lesions (p Conclusions: Fingolimod therapy significantly increased the proportion of patients with MS who were free of disease activity compared with IFN beta-1a IM over 12 months. Supported by: Novartis Pharma AG, Basel, Switzerland. Disclosure: Dr. Khatri has received personal compensation for activities with Teva Neuroscience, Bayer Pharmaceuticals Corporation, Pfizer Inc, Medtronics, Biogen Idec, Serono, Inc., and Caridian. Dr. Khatri has received research support from Biogen Idec. Dr. Barkhof has received personal compensation for activities with Novartis, Biogen Idec, Merck-Serono, and Bayer-Schering as a consultant. Dr. Comi has received personal compensation for activities with Novartis, Teva Neuroscience, Sanofi-Aventis Pharmaceuticals, Inc., Merck Serono, Bayer Schering, and Biogen Dompe. Dr. Jin has received personal compensation for activities with Novartis Pharma AG. Dr. Francis has received personal compensation for activities with Novartis as an employee. Dr. Francis holds stock and/or stock options in Novartis, which sponsored research in which Dr. Francis was involved as an investigator. Dr. Cohen has received personal compensation for activities with Biogen Idec, Eli Lilly & Company, Novartis, and Vaccinex. Dr. Cohen has received research support for activities with Biogen Idec, BioMS, Genzyme Corporation, Novartis, Synthon, and Teva Neuroscience.

Increasing Awareness in the Diagnosis and Treatment of NMDA Encephalitis (P05.212)

Objective: To report the definitive diagnosis of anti-NMDA receptor (NMDAR) encephalitis in a 19-year old male with no known malignancy. Background Anti-NMDA receptor (NMDAR) encephalitis is a rare form of autoimmune disease mostly affecting young women with known ovarian malignancy. In this case report, we present a case of a 19 year old male with NMDAR encephalitis with no known malignancy. Although the clinical features of the acute disease are well characterized, the search for malignancy in this young male yielded negative results. Design/Methods: This is a case report where extensive review of history and laboratory evaluation including testing for NMDAR in serum and CSF was determined. Results: This is a case of a 19 year old male who initially presented with generalized tonic-clonic seizure with no evidence of epileptiform discharge on his EEG. His neurologic status has deteriorated and eventually presented with bizarre symptoms including alternating tachycardia and bradycardia, asystole, orofacial dyskinesias, hypoventilation and episodes of apnea. Initial tests were unrevealing, including a brain MRI, nonspecific CSF pleocytosis with lymphocytic predominance with negative bacterial, viral and fungal studies in the CSF. Work-up for malignancy has yielded negative results. Patient9s CSF was found positive for NMDA antibody. Conclusions: Although NMDAR encephalitis usually present in females with known ovarian teratoma. Our patient9s clinical presentation emphasizes that anti-NMDAR encephalitis can present in males with no known malignancy. When diagnosed early on, it is potentially reversible with immuno-modulatory treatment and often have good prognosis. Disclosure: Dr. Valenzuela has nothing to disclose. Dr. Zallek has nothing to disclose. Dr. Nersesyan has nothing to disclose. Dr. Kattah has received personal compensation for activities with Biogen Idec as a consultant. Dr. Kattah has received personal compensation in an editorial capacity for Bayer Pharmaceuticals Corporation. Dr. Blume has nothing to disclose. Dr. Patel has nothing to disclose. Dr. Pula has received personal compensation for activities with Bayer, Teva, Lundbeck, and Novartis as a speaker.

Acceleration of White Matter Hyperintensity Burden Preceding Onset of Mild Cognitive Impairment (S24.006)

Objective: Determine the timing of white matter hyperintensity (WMH) burden acceleration in relation to mild cognitive impairment (MCI) onset. Background Cerebral white matter change, observed as hyperintensities on T2 MRI, are very common in cognitively intact elderly. Those with greater baseline and rates of WMH accumulation are at increased risk of MCI, a likely precursor of progressive dementia. The timing of acceleration of WMH increase relative to clinical transition to MCI has not been established. Design/Methods: 189 cognitively intact older volunteers from the Oregon Brain Aging Study underwent yearly evaluations, including brain MRI, and cognitive testing. MCI was defined as being the first of two consecutive Clinical Dementia Rating scores of 0.5 or higher. The time before MCI, when the change in WMH burden accelerates, was assessed using a mixed-effects model with a change point for subjects who developed MCI during follow up. Results: During a follow up duration of up to 22.2 years, 135 subjects developed MCI. Acceleration in %WMH volume increase occurred 10.6 years before MCI onset. On average, the annual rate of change in %WMH increased an additional 3.3% after the change point. Acceleration in %ventricular CSF volume increase and total brain volume decrease occurred 3.7 and 5.0 years before the onset of MCI, respectively. Out of 63 volunteers who converted to MCI and had autopsy, only 28.5% had Alzheimer9s disease (AD) as the sole etiology of their dementia, while almost just as many had both AD and significant ischemic cerebrovascular disease present. Conclusions: Acceleration in WMH burden, a common indicator of cerebrovascular disease in the elderly, is a pathological change that emerges early in the pre-symptomatic phase leading to MCI. Monitoring longitudinal WMH change may thus be useful in determining those at risk for cognitive impairment and for planning strategies for introducing disease specific modifying therapies prior to dementia onset. Supported by: NIH (P30 AG08017, M01 RR000334, R01 AG024059), Department of Veterans Affairs, Storms Family Fund at the Oregon Community Foundation, T&J Meyer Foundation. Disclosure: Dr. Silbert has nothing to disclose. Dr. Dodge has nothing to disclose. Dr. Perkins has nothing to disclose. Dr. Lahna has nothing to disclose. Dr. Kaye has received personal compensation for activities with Eli Lilly & Company as a participant on a data safety and monitoring board. Dr. Kaye has received research support from Elan Corporation, Danone Medical, Bristol-Myers Squibb Company, Satoris, and Intel.

Evaluating the Safety and Success of Bedside Lumbar Puncture in a Changing Academic Environment (P06.021)

Objective: To determine the impact on resident training and patient safety of a dedicated lumbar puncture (LP) service utilizing mid-level practitioners (MLP). Background LP is a common bedside procedure. An unsuccessful LP may lead to repeated procedures or fluoroscopy guided LP, increasing patient risks associated with radiation exposure. With reduction in resident work hours by the ACGME, many academic institutions are using MLPs to supplement the provision of patient care, including performing LPs. To our knowledge, the impact of the utilization of specialized MLPs on resident training and patient safety specific to LPs has not been studied. Design/Methods: We conducted a retrospective chart review of inpatients undergoing bedside LP by either a neurology resident physician or neurology MLP from July 2009 through August 2011. Results: A total of 97 LPs were reviewed, 40 performed by a MLP and 57 by a resident physician. Successful bedside LP was documented in 70% and 71.9% of cases by the MLP and residents, respectively (p=0.1815). The average number of skin punctures required to obtain CSF was 1.53 by the MLP vs. 1.67 by residents (p=0.252). There was a numerical but non-significant trend toward improvement when comparing success rate and number of puncture attempts of the MLP in the first six months compared to the second six months of clinical practice (70% vs 77%, p=0.252 and 1.57 to 1.47, p=0.659, respectively). There was insufficient recorded data to make similar comparisons for residents. Conclusions: This study demonstrates no difference between a trained neurology MLP and neurology resident physicians in success rates or safety of performing bedside LP. Nor did we find evidence for negative impact on resident training or proficiency. Specifically there was no evidence for decreased LP success rates in the resident group following introduction of a specialized MLP. Disclosure: Dr. Jordan has nothing to disclose. Dr. Greenberg has received personal compensation for activities with DioGenix, Greater Good Foundation, Biogen Idec, Serono, Inc., Sanofi-Aventis Pharmaceuticals, Inc., the Multiple Sclerosis Association of America and Teva Neuroscience as a consultant and/or speaker. Dr. Greenberg holds stock and/or stock options in Diogeix. Dr. Greenberg has received research support from Guthy-Jackson Charitable Foundation, Amplimmune, Inc. and the Accelerated Cure Project. Dr. Lee has received personal compensation for activities with Boehringer Ingelheim as a speaker.

Degeneration and Regeneration of Peripheral Motor Axons Is Impaired in Mice Heterozygously Deficient for the Myelin Protein P0 Gene (IN1-2.001)

Objective: The aim of this study was to compare degeneration and regeneration of peripheral motor axons in early symptomatic P 0 +/- and age matched WT. Background Mice with a heterozyogous knock-out of the myelin protein P 0 gene (P 0 +/-) are models of Charcot-Marie-Tooth disease. The mice are indistinguishable from wild-types (WT) at birth; however, from about 7 months of age, they develop a slowly progressing demyelinating neuropathy. Although conduction slowing is known to be associated with a reduction of compound muscle action potential (CMAP) amplitude, the relationship between demyelination and axonal loss remains poorly understood. Design/Methods: Right sciatic nerves were lesioned at the thigh. Changes of the tibial nerve at ankle were investigated by electrophysiological, histological and molecular methods. In vivo motor nerve electrophysiology was carried out by conventional conduction studies and axon excitability studies using threshold tracking. The overall motor performance was investigated using Rotor-Rod. To map differences in degeneration, we compared gene expression profiles in the distal stump of degenerated nerves using Affymetrix genechips. To evaluate regeneration we monitored the recovery of motor function after crush, and then compared the fiber distribution by histology. Results: In both P 0 +/- and WT axonal degeneration triggered a change of gene expression related to axon guidance and neuroinflammation. At 7 days after lesion we found that on the lesioned side, a series of genes (Dnm3, Paxip1, Aspa, Tmod1, Frzb, Slitrk6, Thy1, Met, Sytl2, Sema3e, Fbn2, Akap6, Snord52 and Gnb4) were up-regulated less in P 0 +/- as compared to WT, whereas on the unlesioned side the expression of these genes did not differ. CMAP recovery during regeneration appeared delayed in P 0 +/-, in agreement with reduced excitability and poor performance at Rotor-Rod after one month. Conclusions: Together, these data suggest that both axonal degeneration and regeneration are impaired in the presence of mutant Schwann cells heterozygously deficient in the P 0 gene. Supported by: The Lunbeck Foundation. Disclosure: Dr. Krarup has received personal compensation for activities with Integra LifeSciences as a speaker. Dr. Krarup has received research support from Integra LifeSciences and Shire. Dr. Rosberg has nothing to disclose. Dr. Vikesa has nothing to disclose. Dr. Cilius Nielsen has nothing to disclose. Dr. Moldovan has nothing to disclose.

Efficacy and Safety Results from Comparison of Alemtuzumab and Rebif(R) Efficacy in Multiple Sclerosis II (CARE-MS II): A Phase 3 Study in Relapsing-Remitting Multiple Sclerosis Patients Who Relapsed on Prior Therapy (S01.004)

Objective: Evaluate the effect of alemtuzumab on relapse and disability versus subcutaneous interferon beta-1a (SC IFNB-1a) in relapsing-remitting multiple sclerosis (RRMS) patients who have relapsed on prior therapy. Background Alemtuzumab was significantly more effective than SC IFNB-1a in two clinical trials with treatment-naive RRMS patients. Treatment options are limited for RRMS patients experiencing disease activity during therapy, and few controlled studies have been conducted to determine their appropriate management. Design/Methods: CARE-MS II is a 2-year rater-blinded trial with RRMS patients who have relapsed during prior therapy. Alemtuzumab treatment was 12 mg/day (or 24 mg/day in an exploratory cohort) by intravenous administration for 5 days at study start and 3 days one year later. IFNB-1a treatment was 44 mcg SC 3-times weekly throughout the study. Entry criteria included 18-55 years of age, MS symptom onset within 10 years, and Expanded Disability Status Scale (EDSS) score ≤5. Primary endpoints include relapses adjudicated by an independent panel and time to sustained accumulation of disability assessed by blinded evaluators. Results: 840 patients from 180 centers in 23 countries were randomized. Baseline characteristics (mean) were: age 35 years; disease duration 3.9 years; EDSS 2.7; with 1.6 and 2.7 relapses in 1 and 2 years prior to study entry, respectively. The most common prior MS therapies were interferon-beta (78.6%) or glatiramer acetate (32.5%); less than 5% of patients had received other prior MS therapy (some patients received more than one therapy). Conclusions: Database lock and study analysis will occur in late 2011. The principal efficacy and safety results will be presented. ®Rebif is a registered trademark of EMD Serono, Inc. Supported by: Genzyme, a Sanofi company and Bayer Healthcare Pharmaceuticals. Disclosure: Dr. Cohen has received personal compensation for activities with Biogen Idec, Eli Lilly & Company, Novartis, and Vaccinex. Dr. Cohen has received research support for activities with Biogen Idec, BioMS, Genzyme Corporation, Novartis, Synthon, and Teva Neuroscience. Dr. Twyman has received personal compensation for activities with Genzyme Corporation as a consultant, speaker and participant on advisory boards. Dr. Twyman has received research support from Genzyme Corporation. Dr. Arnold has received personal compensation for activities with Bayer Healthcare, Biogen Idec, Genentech, Inc., NeuroRx Research, Roche Diagnostics Corporation, Schering, Serono, Inc., and Teva Neuroscience. Dr. Arnold Dr. Arnold has received research support from Bayer Healthcare, Biogen Idec, Genentech, Inc., NeuroRx Research, Roche Diagnostics Corporation, Schering, Serono, Inc., and Teva Neuroscience. Dr. Coles has received personal compensation for activities with Genzyme Corporation, GlaxoSmithKline, Inc., and Merck Serono as a consultant and/or speaker. Dr. Coles has received research support from Genzyme Corportation. Dr. Confavruex has received personal compensation for activities with Biogen Dompe, Biogen Idec, Gemacbio, Genzyme Corporation, Hertie Foundation, Novartis, Sanofi-Aventis Pharmaceuticals, Inc., Teva Neuroscience, UCB Pharma, Bayer Schering, and Merck Serono. Dr. Confavruex has received research support from Bayer Schering, Biogen Idec, Merck Serono, Novartis, Sanofi-Aventis Pharmaceuticals, and Teva Neuroscience. Dr. Fox has received personal compensation for activities with Bayer Pharmaceuticals Corporation, Biogen Idec, EMD Serono, Genzyme Corporation, Novartis, Opexa Therapeutics, Pfizer Inc, and Teva Neuroscience. Dr. Fox has received personal compensation in an editorial capacity for Neura. Dr. Fox has received research support from Biogen Idec, Eli Lilly & Company, EMD Serono, Genzyme Corporation, Novartis, Ono Pharmaceutical, Roche Diagnostics Corporation, Sanofi-Aventis Pharmaceuticals, Inc., and Teva Neuroscience. Dr. Hartung has received personal compensation for activities with Bayer Pharmaceuticals Corporation, Biogen Idec, BioMS, Genzyme Corporation, Merck Serono, Novartis, Sanofi-Aventis and Teva as a speaker and/or consultant. Dr. Havrodova has received personal compensation for activities with Bayer Pharmaceuticals Corporation, Biogen Idec, Genzyme Corporation, GlaxoSmithKline, Inc., Novartis, Merck, Sanofi-Aventis Pharmaceuticals, Serono, Inc., and Teva as consultant, speaker and/or advisory board participant. Dr. Selmaj has received personal compensation for activities with Genzyme, Ono, and Biogen Idec. Dr. Weiner has received personal compensation for activities with Biogen Idec, Novartis, Serono, Inc., Teva Neurosciences, GlaxoSmithKline, Nasvax, Xenoport and Genzyme Corporation as consulting and/or speaking activities. Dr. Weiner has received research support from Merck Serono. Dr. Miller has received personal compensation for activities with Allergan, Bayer, Biogen Idec, Eli Lilly, EMD Serono, Forest, Novartis, Sanofi Aventis, and Teva as a speaker. Dr. Miller has received research support from Allergan, Biogen Idec, Genzyme, Elan, Teva, Novartis, Ono, Sanofi Aventis, EMD Serono, and Roche-Genetech. Dr. Lake has received personal compensation for activities with Genzyme as an employee. Dr. Margolin has received personal compensation for activities with Genzyme Corporation as an employee. Dr. Panzara has received personal compensation for activities with Biogen Idec as an employee.Dr. Panzara holds stock and/or stock options in Biogen Idec. Dr. Compston has received personal compensation for activities with Genzyme Corporation as a speaker. Dr. Compston has received research support from Genzyme Corporation.

MK2-Deficiency Fails To Protect Mice from Experimental Autoimmune Encephalomyelitis (P05.114)

Objective: Investigation of the role of the mitogen-activated proteinkinase activated proteinkinase 2 in experimental autoimmune encephalomyelitis. Background The p38 mitogen-activated protein kinase pathway mediates cellular responses to injurious stress and immune signaling. The downstream targets of p38 MAPK include the mitogen-activated proteinkinase activated proteinkinase (MK) 2. Recently, the role of MK2 has been studied in models of inflammatory or degenerative diseases. The findings suggest that a lack of MK2 reduces inflammation and protects against destruction of the brain and other tissues. Thus, we investigated the role of MK2 in experimental autoimmune encephalomyelitis (EAE). Design/Methods: EAE was induced in MK2 knockout mice (MK2-/-) and wildtype controls by immunization with MOG35-55 in CFA. Animals were observed over a period of 24 days. The inflammation and demyelination was estimated by histology and immunohistochemistry in the acute phase of the disease. Moreover, cells isolated from the CNS were counted and TNFα serum level was assigned by ELISA in different stages of EAE. Results: Contrary to expectance, MK2-/- had more severe disease signs correlating with an increased number of cells in the CNS. There was no difference in the onset of EAE and both groups developed paresis in the early phase of the disease. From day 18 post immunization wildtype controls showed significantly improved locomotor recovery compared to MK2-/-. The histological examination of CNS sections in the acute phase showed that there was no difference in demyelination but MK2-/- had more CD4 and CD8 positive cells in the CNS. Moreover, we found a reduced level of the inflammation mediator TNFα. Conclusions: In contrast to the expectations, the MK2-/- aggravated the disease course and was associated with more inflammation. The reason for these findings may partially be explained by differences in TNFα biosynthesis and therefore a changed apoptosis characteristic in autoreactive cells in the CNS of MK2-/- mice. Disclosure: Dr. Tietz has nothing to disclose. Dr. Viard has nothing to disclose. Dr. Thomas has nothing to disclose. Dr. Gaestel has nothing to disclose. Dr. Berghoff has received personal compensation for activities with Bayer Vital GmbH, Merck Serono, TEVA Neuroscience and Biogen Idec as a speaker. Dr. Berghoff has received research support from Bayer Vital GmhB, TEVA Neuroscience, Merck Serono and Biogen Idec.

Case of Infantile-Onset SCA-5 and a Novel SPTBN2 Mutation (P02.174)

Objective: To describe a girl with infantile onset of Spinocerebellar Ataxia Type 5 and novel SPTBN2 mutation. Background Dominant spinocerebellar ataxias (SCA) are a rare clinically and genetically heterogeneous group of neurodegenerative disorders. They are characterized by progressive cerebellar ataxia resulting in unsteady gait, clumsiness, dysarthria and swallowing difficulty. The onset usually occurs during the third or fourth decade of life; however, manifestations may start as early as late infancy or childhood. Design/Methods: Clinical and genetic description of neurological and developmental symptoms and signs in 12 year-old with mutation of SPTBN2 identified on Spinocerebellar Ataxia Panel. Results: Spinocerebellar Ataxia Panel identified a SPTBN2 gene mutation (transition C>T) at nucleotide position 1438. Further analysis of this variant found that this change has not been seen in normals, the position is highly conserved, and computer protein analysis predicted the change to be pathogenic. Conclusions: A novel SPTBN2 mutation (transition C>T) at nucleotide position 1438 leads to a more severe phenotype of Spinocerebellar Ataxia Type. Disclosure: Dr. Ho has nothing to disclose. Dr. Jacob has nothing to disclose. Dr. Darras has received personal compensation for activities with UpToDate, Inc., Isis Pharmaceuticals, Inc, and Athena Diagnostics as a consultant.Dr. Darras has received research support from PTC Therapeutics, Inc. Dr. Martinez-Ojeda has nothing to disclose. Dr. Torres has nothing to disclose. Dr. Khwaja has nothing to disclose.

Use of Rasagiline or Selegiline and Hospitalizations among Patients with Parkinson's Disease (P06.087)

Objective: To compare hospitalizations among patients with Parkinson9s disease (PD) who were treated with either rasagiline or selegiline. Background Resource utilization study. Design/Methods: Data for this study was obtained from the i3 LabRx database over the time period from January 1, 2006 through June 30, 2010. Patients who were diagnosed with PD, initiated therapy with either rasagiline or selegiline, and had continuous insurance coverage from 6 months prior through 12 months after medication initiation were included in the study. Logistic models were used to examine the odds of being hospitalized and generalized linear models with a negative binomial distribution were used to examine the number of inpatient stays and total hospital length of stay (LOS). Models controlled for patient age, sex, region of residence, type of insurance coverage, prior hospitalization, and general health using the Charlson comorbidity index. Results: There were 1,242 individuals who fit the study criteria (926 initiated on rasagiline and 316 on selegiline). The likelihood of having at least one hospitalization, after controlling for patient characteristics, general health, and prior hospitalization, did not differ between patients who initiated on rasagiline, compared to those who initiated on selegiline,(Odds Ratio = 0.774; 95% Confidence Interval 0.638 - 1.197). However, patients who initiated therapy with rasagiline, compared to those who initiated therapy on selegiline were found to have significantly fewer total hospitalizations (1.119 v 2.113; P=0.0127) as well as a significantly shorter overall hospital LOS (2.762 days v 5.556 days; P=0.0136). Conclusions: Results from this retrospective study indicate no difference in the odds of having at least one hospitalization among PD patients who initiate therapy on rasagiline or selegiline. However, rasagiline use was associated with a significantly lower total number of hospitalizations as well as shorter LOS compared to selegiline use. Future work will focus on identifying the main reasons associated with such hospitalizations. Supported by: Teva Pharmaceuticals. Disclosure: Dr. Grubb has received personal compensation for activities with Teva Pharmaceuticals as an employee. Dr. Lage has received personal compensation for activities with Teva Pharmaceuticals. Dr. Lage has received research support from Teva Pharmaceuticals. Ms. Castelli-Haley has received personal compensation for activities with Teva Neuroscience as an employee.

Bilateral Cervical-Artery Dissection Associated with Leri-Weill Dyschondrosteosis. A Case Report and Literature Review (P01.022)

Objective: To report the first case of spontaneous cervical-artery dissection (sCAD) associated with Leri-Weill dyschondrosteosis (LWD) and a comprehensive review of the literature. Background CAD is a major cause of cerebral ischemia in young adults. Skin biopsies from many patients with sCAD show mild connective tissue alterations. An underlying arteriopathy, which could be in part genetically determined, is believed to have a role in the development of sCAD. There are few case reports of sCAD in patients with inherited connective tissue disorders like Ehlers-Danlos syndrome, Marfan syndrome or Osteogenesis Imperfecta. LWD is an osteochondrodysplasia whith mesomelic short stature and Madelung deformity of the wrist. Expression of LWD is variable but the clinical features are generally more severe in females. In around 70% of cases, LWD is caused by haploinsufficiency of the short stature homeobox (SHOX) gene and remains unknown in the remaining 30%. Design/Methods: Case report followed by a literature review. Results: A 36-years-old woman was admitted in July 2009 for sudden-onset right hemiplegia and Wernicke aphasia. Her NIHSS was 9. Her past medical history consisted in LWD and hypothyroidism treated with levothyroxine sodium. She had had no injuries during the previous days or weeks. The diffusion-weighted MRI showed a left carotid infarct. Laboratory test results and cardiac explorations were normal. Magnetic resonance angiography combined with T1-weighted with the fat-saturation technique confirmed bilateral carotid artery dissection. Anticoagulation was conducted for 6 months then was relayed by antiplatelet. When last seen in April, 2011, the patient had only minor aphasia and the MRI was back to normal. Conclusions: Even though this association is rare, screening patients with sCAD for clinical signs that are suggestive of connective tissue seems important. In such cases, a longer and closer follow-up is recommended because of the heightened risk of recurrence. Disclosure: Dr. Bonnet has nothing to disclose. Dr. Cogez has nothing to disclose. Dr. Bataille has nothing to disclose. Dr. Defer has received personal compensation for activities with BiogenIdec, Novartis, Teva Pharmaceutical Industries Ltd, Merck Serono, and Guerbet. Dr. Viader has nothing to disclose.

Validation of the NINDS-CSN 5-Minute Battery for Vascular Cognitive Impairment (P04.200)

Objective: To validate the National Institute of Neurological Disorders and Stroke-Canadian Stroke Network (NINDS-CSN) 5-minute cognitive battery using other measures of cognitive function and measures of vascular risk. Background The recent NINDS-CSN Vascular Cognitive Impairment Harmonization Standards recommended a 5-minute neuropsychological battery as a brief screening instrument sensitive to deficits commonly seen in vascular cognitive impairment (VCI). Design/Methods: Cross-sectional study involving 7,199 stroke-free US adults enrolled in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study from January 2003 to October 2007. We examined effects of demographics on the NINDS-CSN 5-minute battery score at first assessment (in 2009 and later), and correlation of 5-minute battery scores with other cognitive tests and with measures of cerebrovascular risk. Results: Total scores on the NINDS-CSN 5-minute battery were highly related to age (Spearman9s ρ = -0.305, p Conclusions: The NINDS-CSN 5-minute battery is a brief, easily administered screening measure of cognition that is sensitive to increasing levels of cerebrovascular risk. The NINDS-CSN 5-minute battery offers a valid method of screening for cognitive correlates in VCI. Supported by: A cooperative agreement U01 NS041588 from the National Institute of Neurological Disorders and Stroke and grant T32 HL072757 from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Service. Disclosure: Dr. Kennedy has nothing to disclose. Dr. Wadley has nothing to disclose. Dr. McClure has nothing to disclose. Dr. Unverzagt has received personal compensation for activities with Eli Lilly & Company as a consultant. Dr. Unverzagt has received research support from Posit Science Inc. Dr. Crowe has nothing to disclose. Dr. Kelley has received personal compensation for activities with Eli Lilly & Company as a consultant. Dr. Nyenhuis has received personal compensation for activities with Pfizer Inc and Eisai Inc., as a speaker. Dr. Kana has nothing to disclose. Dr. Marceaux has nothing to disclose. Dr. Tamura has nothing to disclose. Dr. Howard has nothing to disclose. Dr. Howard has received personal compensation for activities with Bayer Healthcare and Abbott Labratories as a consultant. Dr. Howard has received research support from Amgen Inc. and Bayer Healthcare.

ADVANCE Phase 3 Study of PEGylated Interferon Beta-1a for Relapsing Multiple Sclerosis: Patient Baseline Characteristics (P01.133)

Objective: The ongoing phase 3 ADVANCE trial is evaluating the efficacy and safety of polyethylene glycol (PEG)–conjugated (PEGylated) interferon beta-1a (PEG-IFN beta-1a) in patients with relapsing multiple sclerosis (RMS). Background PEGylation extends the half-life of IFN beta-1a, potentially allowing dosing every 2 or 4 weeks instead of the once-weekly dosing of intramuscular IFN beta-1a. PEG-IFN beta-1a is expected to offer efficacy at least equivalent to that of intramuscular IFN beta-1a 30 μg. Recognizing that PEG-IFN beta-1a may help address unmet patient needs, the US FDA has granted this drug Fast Track designation. Design/Methods: The ADVANCE phase 3 trial is a global, 2-year, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of subcutaneous PEG-IFN beta-1a 125 μg. Eligible patients must be 18–65 years old and have confirmed RMS (McDonald criteria), a baseline Expanded Disability Status Scale (EDSS) score ≤5.0, ≥2 relapses within 3 years of randomization, and ≥1 relapse within 12 months of randomization. Approximately 1500 patients will be randomized 1:1:1 to placebo, PEG-IFN beta-1a every 2 weeks, or PEG-IFN beta-1a every 4 weeks. After 1 year, patients randomized to placebo will be re-randomized to PEG-IFN beta-1a either every 2 weeks or every 4 weeks. Dosing will remain unchanged for the remaining patients. An open-label extension study (ATTAIN) will be available after 2 years for patients participating in the ADVANCE trial. Results: . Patient baseline characteristics will be presented. Conclusions: PEG-IFN beta-1a is being developed to reduce dosing frequency and improve patient convenience while maintaining the proven efficacy, safety, and tolerability of IFN beta-1a. As such, PEG-IFN beta-1a may be an important new addition to the therapeutic armamentarium for MS. Supported by: Biogen Idec Inc. Disclosure: Dr. Calabresi has received personal compensation for activities with Teva, Biogen Idec, Novartis, Genzyme, Johnson & Johnson, and Vertex. Dr. Calabresi has received research support from Biogen Idec, Teva, EMD Serono, Vertex, Genentech, Abbott, and Bayer. Dr. Kieseier has received personal compensation for activities with Bayer Pharmaceuticals Corporation, Biogen Idec, Merck Serono, Novartis, Roche Diagnostics, Sanofi-Aventis Pharmaceuticals, and TEVA Neurosciences as speaker. Dr. Kieseier has received research support from Bayer Pharmaceuticals, Biogen Idec, Merck Serono and Teva Neurosciences. Dr. Arnold has received personal compensation for activities with Bayer Healthcare, Biogen Idec, Genentech, Inc., NeuroRx Research, Roche Diagnostics Corporation, Schering, Serono, Inc., and Teva Neuroscience. Dr. Arnold Dr. Arnold has received research support from Bayer Healthcare, Biogen Idec, Genentech, Inc., NeuroRx Research, Roche Diagnostics Corporation, Schering, Serono, Inc., and Teva Neuroscience. Dr. Balcer has received personal compensation for activities with Biogen Idec, Vaccinex and Bayer as a consultant and has received honoraria from Biogen Idec and Novartis. Dr. Boyko has received personal compensation for activities with Novartis, Merck Serono, TEVA, Gensyme, Biogen Idec, Nicomed as a member of advisory boards, a speaker and a participant of clinical trials. Dr. Pelletier has received research support from Sanofi-Aventis, Pharmaceuticals, Inc., Bayer Schering, Biogen Idec, Merck Serono, Novartis, and Teva Neuroscience. Dr. Zhu has received personal compensation for activities with Biogen Idec as an employee. Dr. Zhu holds stock and/or stock options in Biogen Idec, which sponsored research in which Dr. Zhu was involved as an investigator. Dr. Deykin has received personal compensation for activities with Biogen Idec as an employee.

Dexpramipexole Effects on Functional Decline in ALS Patients in a Phase II Study: Subgroup Analysis of Demographic and Clinical Characteristics (P04.149)

Objective: We conducted post hoc analyses of data from a two-part, Phase II study of oral dexpramipexole to explore potential differential treatment effects in a variety of patient subgroups. Background In the study, dexpramipexole was well tolerated for up to 9 months and showed dose-dependent trends in abating functional decline and improving survival in ALS patients. Design/Methods: Post-hoc analyses were performed on data from Part 2 of the study. After a study drug washout, ALS patients (n=92) were randomized to high- (300 mg) or low-dose (50 mg) dexpramipexole for 24 weeks. We evaluated the effects of dexpramipexole on the slope of the revised ALS Functional Rating Score (ALSFRS-R) in various patient subgroups. Subgroup variables included: riluzole use vs no riluzole use, gender, and site of symptom onset (bulbar vs limb). Other subgroups were formed using continuous variables dichotomized on mean baseline values: age ( Results: Overall, there was a 21% reduction in the ALSFRS-R decline favoring the 300-mg vs 50-mg dexpramipexole group (p=0.177). This statistical trend was recapitulated in all subgroups analyzed. For example, patients taking riluzole who received 300-mg vs 50-mg dexpramipexole showed reduced ALSFRS-R declines (−1.08 vs −1.30) as did men taking 300-mg vs 50-mg dexpramipexole (−1.08 vs −1.22). Likewise, patients with a baseline ALSFRS-R Conclusions: These results suggest that the slightly larger benefit of 300-mg vs 50-mg dexpramipexole on functional decline is uniform across a diverse study population regardless of baseline demographic and clinical characteristics. Supported by: Sponsored by Biogen Idec. Medical writing assistance, funded by Biogen Idec, was provided by Linda Goldstein at UBC Scientific Solutions. Disclosure: Dr. Rudnicki has received research support from Biogen Idec. Dr. Berry has nothing to disclose. Dr. Ingersoll has received personal compensation for activities with Knopp Biosciences LLC as an employee. Dr. Ingersoll holds stock and/or stock options in Knopp Biosciences LLC, which sponsored research in which Dr. Ingersoll was involved as an investigator. Dr. Archibald has received personal compensation for activities with Knopp Biosciences LLC as an employee. Dr. Archibald holds stock and/stock options in Knopp Biosciences LLC, which sponsored research in which Dr. Archibald was involved as an investigator. Dr. Cudkowicz has received personal compensation for activities with Synapse, Trophos, and Acclerson as a data safety monitoring board chair or an advisory board member. Dr. Kerr has received personal compensation for activities with Teva Neuroscience, Biogen Idec, and Pfizer Inc as a speaker. Dr. Kerr has received compensation for serving as a co-founder of Nerveda Inc. Dr. Kerr has received research support from Nerveda Inc. Dr. Dong has received personal compensation for activities with Biogen Idec as an employee.