MBI was common in memory clinic patients without dementia and was associated with greater caregiver burden. These data show that MBI is a common and clinically relevant syndrome.

We report a trial of minocycline in people with relapsingremitting multiple sclerosis (RRMS) that evaluates safety and estimates its effect on magnetic resonance imaging (MRI). Ten subjects with active RRMS received oral minocycline 100mg twice daily for 6 months after a 3-month run-in period. A 30-month treatment extension is ongoing. Clinical and laboratory assessments were completed at enrollment and then at 3-month intervals. MRI was performed at enrolment and then every 4 weeks. Patients without MRI activity during the run-in phase continued in the study, including completion of all MRI scans, to confirm lack of MRI worsening. The primary outcome was change in the mean number of gadolinium-enhancing lesions per scan during the first 6 months of treatment compared with the run-in period (Wilcoxon signed rank test, two-sided alpha of 0.05).Eighty percent of participants were women. Mean age was 42.8 years (SD 4.0). Mean MS duration was 11.8 years (SD 6.3). Median baseline extended disability status score (EDSS) was 2.5 (range 1.5-5.5). Mean relapse number in the two prior years was 2.6 (range 2-4). During the trial, there were no serious adverse events or laboratory abnormalities and no change in EDSS. Three relapses occurred during the run-in phase, five during the first 6-month treatment phase, and none during the following 6 months. On-treatment relapses included one associated with MRI enhancement (during month 1), two without enhancement (one scan was a postrelapse scan, and one scan was missed because the patient was taking steroids), and two mild truncal sensory attacks unassociated with MRI enhancement (both at 5 months).Mean total enhancing lesion number decreased from 1.38 lesions per scan during the run-in phase to 0.22 during the treatment phase (z ϭ 2.204, p ϭ 0.0276), representing a relative reduction of greater than 84%. During the run-in phase, 47.5% of MRI scans (19/40) were active, whereas 9.3% (5/54) were active during the minocycline phase. There were no active scans after month 2 (Fig) and no new active lesions after month 1. Although five patients accounted for all MRI activity before and after treatment, all patient data were included in all analyses.This study provides preliminary evidence that minocycline may be useful in MS and supports its safety. The MRI results are consistent with the ability of minocycline to inhibit matrix metalloproteinases, 1,2 thus reducing lymphocyte access to the central nervous system. In addition, minocycline may have other beneficial properties including neuroprotection.3 Small sample size and short trial duration limit conclusions, but reduced MRI activity is encouraging and calls for definitive studies to establish minocycline efficacy in MS. Departments of

This study provides Class 1 evidence that MBP8298 is not effective in patients with SPMS who are HLA DR2(+) or DR4(+).

The treatment of multiple sclerosis has finally become possible with the advent of the current disease-modifying therapies (DMTs) that have had a significant impact on those living with this disease. Though demonstrating clear efficacy on a number of short-term outcome measures, unfortunately, these agents are not “cures” and many patients with multiple sclerosis continue to experience disease activity in spite of treatment. Clinicians are becoming more comfortable initiating therapy with DMTs, but it is now important to focus attention on monitoring the results of the chosen therapy and deciding whether or not a patient is responding well to treatment. At present, however, clinicians lack criteria for defining optimal versus suboptimal responses to DMTs as well as evidence-based guidelines on how to improve treatment outcomes. Using a recently published model as a framework, The Canadian Multiple Sclerosis Working Group developed practical recommendations on how neurologists can assess the status of patients on DMTs and decide when it may be necessary to modify treatment in order to optimize outcomes. The Canadian Multiple Sclerosis Working Group's recommendations are based on monitoring relapses, neurological progression and MRI activity. Other possible causes of suboptimal treatment responses or treatment failure are also considered.

Minocycline has immunomodulatory and neuroprotective activities in vitro and in an animal model of multiple sclerosis (MS). We have previously reported that minocycline decreased gadolinium-enhancing activity over six months in a small trial of patients with active relapsing-remitting MS (RRMS). Here we report the impact of oral minocycline on clinical and magnetic resonance imaging (MRI) outcomes and serum immune molecules in this cohort over 24 months of open-label minocycline treatment. Despite a moderately high pretreatment annualized relapse rate (1.3/year pre-enrolment; 1.2/year during a three-month baseline period) prior to treatment, no relapses occurred between months 6 and 24. Also, despite very active MRI activity pretreatment (19/40 scans had gadolinium-enhancing activity during a three-month run-in), the only patient with gadolinium-enhancing lesions on MRI at 12 and 24 months was on half-dose minocycline. Levels of the p40 subunit of interleukin (IL)-12, which at high levels might antagonize the proinflammatory IL-12 receptor, were elevated over 18 months of treatment, as were levels of soluble vascular cell adhesion molecule-1. The activity of matrix metalloproteinase-9 was decreased by treatment. Thus, clinical and MRI outcomes are supported by systemic immunological changes and call for further investigation of minocycline in MS.