SPMS Group Research Articles

Utilization of the multiple sclerosis functional composite in follow-up: relationship to disease phenotype, disability and treatment strategies

As multiple sclerosis (MS) has a dynamic process, monitoring of the disability is important in the remission period. The main aim of the present study was to investigate the usefulness of MSFC instead of EDSS in the follow-up period of MS. In addition, evaluation of the effect of immunomodulatory therapy, and the difference among the type of MS in follow-up was purposed. One hundred and eighty-three patients with definite MS were enrolled in the present study. Patients were diagnosed as having relapsing–remitting (RR) MS ( n=149) or secondary progressive (SP) MS ( n=34). Fifty-eight out of 149 RRMS patients who had at least two relapses in the last 2 years have received any of the immunomodulator agents. The Multiple Sclerosis Functional Composite (MSFC) and Expanded Disability Status Scale (EDSS) were performed at baseline and after 2 years to assess disability. Patients who were under disease modifying therapy were assessed before the treatment and 2 years after starting the treatment. Cross-sectional correlations between MSFC and EDSS score at baseline and follow-up were studied. Patients were divided into three subgroups: (1) RRMS patients who did not receive disease modifying therapy (DMT)—non-DMT group, (2) RRMS patients who received DMT—DMT group, (3) SPMS patients who did not receive DMT—SPMS group. EDSS and MSFC scores got worsened significantly at the end of the second year. Decreases in either EDSS or MSFC scores were more prominent in SPMS group. The most significant worsening was found in T25WT. The most prominent and significant decrease was in PASAT of SPMS group. Moderately strong cross-sectional correlations were found between MSFC and EDSS scores at baseline and follow-up. The most prominent correlation was between EDSS and T25WT scores with an excellent correlation. We concluded that the MSFC assesses aspects of neurological function not measured by the EDSS, suggesting that it is more sensitive to detect change over time and better able to demonstrate a therapeutic effect. The pattern of correlations among the MSFC, its components, and the EDSS supported the validity of MSFC.

Dissociating perceptual and conceptual implicit memory in multiple sclerosis patients

Previous studies indicate that Multiple Sclerosis (MS) patients exhibit deficits in tests of explicit memory such as free recall, but show normal priming on implicit tests of memory such as word stem completion. However, the memory performance of patients with different MS disease subtypes has not been fully examined. In the current study, memory was assessed in Primary Progressive (PPMS), Relapsing Remitting (RRMS), and Secondary Progressive (SPMS) MS subgroups. Explicit memory as well as perceptual and conceptual implicit memory were examined using free recall, word fragment completion, and exemplar generation tests, respectively. All three groups of MS patients exhibited free recall deficits and normal priming on the exemplar generation test. However, the PPMS group exhibited a deficit in word fragment completion priming, whereas the RRMS and SPMS groups exhibited normal levels of priming on this task. Lesion load was assessed using magnetic resonance imaging and was negatively correlated with explicit memory performance, but it did not account for the observed deficits in perceptual implicit memory. The results indicate that PPMS patients exhibit a pattern of memory impairment that is distinct from that of the RRMS and SPMS groups. Moreover, the results indicate that perceptual implicit memory can be neurologically dissociated from conceptual implicit memory.

The use of magnetic resonance imaging in multiple sclerosis treatment trials: power calculations for annual lesion load measurement.

Phase III definitive treatment trials of new multiple sclerosis (MS) therapies now routinely incorporate an annual magnetic resonance imaging protocol, with change in T2-weighted brain lesion load providing an important outcome measure. To date the accepted strategy has been to perform a core imaging protocol on all patients in such studies. The aim of this study was to provide power calculations based on this MRI endpoint. Serial MRI data from 128 patients with either relapsing remitting (RR) or secondary progressive (SP) MS were used to calculate sample size requirements using a repeated measures analysis of variance design. We provide sample size calculations based on various follow-up intervals and effect sizes. Sample sizes for the SPMS cohort were substantially larger than for the RRMS group, reflecting the greater variance in lesion load changes between patients in the SPMS group. With a follow-up of 3 years, we estimate that only 12 and 33 patients per arm are needed to show stabilisation of MRI lesion load in the RRMS and SPMS groups, respectively. Our results suggest that ongoing phase III treatment trials are more than adequately powered to detect even subtle treatment effects, and indicate that incorporating measurements from longer follow-up durations increases power substantially. We conclude that an annual imaging protocol provides a robust and powerful tool for assessing effects on the radiological appearance of the disease process.

Exploratory treatment trials in multiple sclerosis using MRI: sample size calculations for relapsing-remitting and secondary progressive subgroups using placebo controlled parallel groups

OBJECTIVESSerial brain MRI is widely used in pilot studies of new agents to monitor treatment efficacy in relapsing-remitting (RR) and secondary progressive (SP) multiple sclerosis (MS). For pilot trials, sample...