[i] The median is frequently used to report results in epidemiological studies rather than an average value because it is not significantly changed by a small number of high or low values (outliers) in the sample and thus may give a better idea of a typical value for the group. The average value, on the other hand may be pulled to one side or another by a few very high or very low values

[ii] The four specific areas of the CNS are next to the fluid filled spaces in the brain (periventricular); on or near the surface of the brain (cortical or juxtacortical); in the brainstem or lower part of the brain (infratentorial); and, the spinal cord.

[iii] These blood tests look for diseases that mimic MS. The thyroid profile evaluates the function of your thyroid gland; erythrocyte sedimentation rate screens for evidence of inflammation in your body aside from possible MS. The antinuclear antibody, SS-A and SS-B antibody, Lyme Antibody, and ACE, rule out systemic lupus erythematosus, Sjogren’s syndrome, Lyme disease and sarcoidosis, respectively.

[iv] Nevertheless, even some patients with sustained disability over 6 months may improve in relapsing-remitting MS if the patient is followed long enough (Cordeaux).

[v] By the slope of a patient’s decline

[vi] A typical dosing regimen for plasma exchange would be 1.1 to 1.4 plasma volumes exchanged every other day for a total of 7 exchanges. Of note, in addition to harboring all of the risks typically associated with central line placement, plasma exchange poses the additional risks of myocardial infarction, arrhythmia, hemolysis, and death in small percentages of patients (Jacqueline F. Marcus 2013 ).

[vii] Belk, O er al. retrospectively analyzed RRMS and PMS patients initially diagnosed and registered in the Swedish MS Registry between January 1995 and December 2010. By 2017 there were a total of 12,512 MS patients in the Swedish MS registry. Of these, 7331 had at least two recorded EDSS scores and thus could be included in this study. Median duration of follow up of the patients was 8.5 years (interquartile range 4.7-13.8 years). Patients were followed from the date of onset of their MS to when they attained EDSS scores of 3,4, and 6. They looked at the change in the risk of attaining EDSS Scores of 3,4,and 6 depending upon the onset date of MS. Over the 15 years studied, the risk for relapsing-onset MS of achieving an EDSS score of 3 decreased by an average of 3% per year; for an EDSS of 4 by 6% and for an EDSS of 6 by 7%. These trends were not significant for progressive-onset MS. Using these results, a person diagnosed with RMS in 2010 had a 14%, 26%, and 30% lower risk of achieving an EDSS of 3, 4, and 6 compared with someone who was diagnosed with rms in 2005.

 [ix] Markers in the cerebrospinal fluid (the fluid that surrounds the brain and spinal cord) include: neurofilaments which are a protein which is a major component of the axonal cytoskeleton which is released following neuronal injury; actin; tubulin; sphingolipids; glial fibrillary acidic protein; and, S100B. Biomarkers in the blood include neurofilaments and myxovirus-resistant protein A micro RNA. (Outcome measures will be discussed in more detail in a future post.)

[x] This procedure is called enrichment. Enrichment is the use of any patient characteristic to select a study population in which detection of a drug effect (if one is in fact present) is more likely than it would be in an unselected population.

[xi] A future post will discuss whether disease modifying therapy will mitigate your risk for long-term disability if you have a progressive form of MS.

[xii] Data collection began in January 1999 and ended in December 2016. Of the 592 MS patients, 104 were treated initially with a higher efficacy therapy (70 received alemtuzumab and 34 natalizumab);488 were started on a lower efficacy therapy; and 58 patients initially started on a lower efficacy therapy and subsequently switched to a higher efficacy therapy when they had clinical or radiological evidence of disease activity.

[xiii] The annualized relapse rate was 0 in the high efficacy disease modifying therapy group. 0.16 in lower efficacy group and 0.9 in the lower group that escalated to high efficiency disease modifying therapy. Only 179 of the 592 patients had EDSS scores available at baseline and follow up; 41 in the high efficacy group and 138 in lower efficacy group. On average, the baseline disability was higher in the high efficacy group than in the lower efficacy group. The mean EDSS in the high efficacy group was 4.2 versus 3.5 in the ME group.

[xiv] The average change in the EDSS was 0.3 in the high efficacy group compared to 1.2 in the lower efficacy group.