Background It is unclear if all patients with RRMS ultimately develop progressive MS. Onset of progressive disease course seems to be age- rather than disease duration dependent. Some forms of progressive MS (e.g. PPMS) are uncommon in population-based studies. Ascertainment of patients with PPMS from clinic-based populations can facilitate a powerful comparison of age-of-progression-onset between SPMS and PPMS but may introduce unclear biases. Objective To confirm that onset of progressive disease course is more relevant to patient's age than the presence or duration of a pre-progression relapsing disease course in MS. Methods We studied a population-based MS cohort (n=210, relapsing-remitting MS n=109, progressive MS n=101) and a clinic-based progressive MS cohort (n=754). Progressive course was classified as primary- (PPMS; n=322), single attack- (SAPMS; n=112) and secondary-progressive (SPMS; n=421). We studied demographics (chi2 or t-test), age-of-progression-onset (t-test) and time-to-EDSS6 (Kaplan-Meier analyses). Results Sex-ratio (p=0.58), age-of-progression-onset (p=0.37) and time-to-EDSS6 (p=0.16) did not differ between the cohorts. Progression had developed before age 75 in 99% of patients with known progressive disease course; 38% with RRMS did not develop progression by age 75. Age-of-progression-onset did not differ between SPMS (44.9±9.6), SAPMS (45.5±9.6) and PPMS (45.7±10.8). In either cohort, only 2% of patients had reached EDSS6 before onset of progression. Conclusions Patients with RRMS do not inevitably develop progressive disease course. Onset of progression is more dependent on age than the presence or duration of a pre-progression symptomatic disease course. Moderate disability is sustained predominantly after the onset of a progressive disease course in MS.

Objective: We examined the effect of relapses-before and after progression onset-on the rate of postprogression disability accrual in a progressive multiple sclerosis (MS) cohort. Methods:We studied patients with primary progressive MS (n 5 322) and bout-onset progressive MS (BOPMS) including single-attack progressive MS (n 5 112) and secondary progressive MS (n 5 421). The effect of relapses on time to Expanded Disability Status Scale (EDSS) score of 6 was studied using multivariate Cox regression analysis (sex, age at progression, and immunomodulation modeled as covariates). Kaplan-Meier analysis was performed using EDSS 6 as endpoint. Conclusions: Pre-and postprogression relapses accelerate time to severe disability in progressive MS. Continuing immunomodulation for 5 years after the onset of progressive disease or until 55 years of age may be reasonable to consider in patients with BOPMS who have ongoing relapses. Results: Preprogression relapses (hazard ratioNeurology ® 2015;84:81-88 GLOSSARY BOPMS 5 bout-onset progressive multiple sclerosis; CI 5 confidence interval; EDSS 5 Expanded Disability Status Scale; HR 5 hazard ratio; MS 5 multiple sclerosis; PPMS 5 primary progressive multiple sclerosis; RRMS 5 relapsing-remitting multiple sclerosis; SAPMS 5 single-attack progressive multiple sclerosis; SPMS 5 secondary progressive multiple sclerosis.

Patients with MS with poor recovery from early relapses will develop progressive disease course earlier than those with good recovery.

In ring-enhancing lesions, peripheral diffusion restriction is more common in IDD than in tumors/abscesses, whereas central restriction is more common among abscesses. Rapid ADC pattern changes in IDD probably reflect dynamic lesion evolution and may distinguish IDD from tumors.

ON is the best studied CIS. The visual prognosis is excellent in most cases regardless of whether the patient is treated with corticosteroids or not. Three recently completed prospective, randomized, double-blinded, placebo-controlled studies have shown that starting a disease-modifying drug at the time of a CIS can reduce the rate of development of MS. However, better diagnostic tools are needed to precisely predict the conversion to MS and the factors influencing disease severity to determine the most appropriate therapeutic paradigm and avoid unnecessary treatment.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) that affects at least 400,000 people in the US alone. Estimates of the prevalence of MS were made in the early 1990s and may vastly underestimate the true prevalence of the disease.1,2 The cause of MS remains unknown, but it is clear that inflammatory demyelination and axonal damage lead to considerable disability in both early-and late-stage disease. The rate and extent of disability progression are highly variable.The mainstay of MS treatment over the past 17 years has primarily been treatment with interferons (IFNs) and glatiramer acetate. IFNβ-1b AbstractLaquinimod is a novel oral immunomodulatory agent in development for the treatment of relapsing-remitting multiple sclerosis (RRMS). It is a derivative of roquinimex that was structurally altered to maximize safety and efficacy. In animal models laquinimod was far more potent than its parent compound with no apparent propensity to induce inflammatory reactions. Laquinimod is a broad-spectrum immunomodulatory agent with a multitude of effects on the immune system but no effect on the ability of animals to mount a cellular or humoral immune response. In phase II trials selected for highly active RRMS patients, laquinimod reduced the frequency of gadolinium-enhancing lesions by 55%, significantly reduced the number of new T 2 lesions, and had a trend toward an effect on reducing brain volume loss. Laquinimod was well tolerated in phase II trials and had a favorable safety profile with a paucity of adverse events. It is metabolized by the cytochrome P-450 system (CYP-3A4) and may interact with some compounds used in symptomatic therapy. With a favorable efficacy and safety profile, laquinimod is a potential first-line agent in the future treatment of RRMS. KeywordsMultiple sclerosis, laquinimod, immunomodulatory, safety, efficacy Disclosure: Douglas R Jeffery, MD, PhD, has received honoraria for speaking and consulting from Teva, Bayer, Biogen-Idec, Novartis, Serono, Pfizer, Acorda, and GSK, and has received research support from Teva, Bayer, Biogen-Idec, Serono, Novartis, and Pfizer. The remaining authors have no conflicts of interest to declare.

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