Are you a glass-half-full or a glass-half-empty person?
J Neurol Sci. 2018 May 15;388:12-18. doi: 10.1016/j.jns.2018.02.036. Epub 2018 Feb 22.
Natural history of benign multiple sclerosis: Clinical and HLA correlates in a Western Australian cohort.
Fabis-Pedrini MJ, James I, Seewann A, Yau WY, van de Bovenkamp AA, Sanders FRK, Qiu W, Burton J, Mastaglia FL, Carroll WM, Kermode AG.
Benign multiple sclerosis (BMS) is a controversial term that has been used for MS patients with minimal disability decades after disease onset. Herein, we evaluated disease status after 20 years in a Western Australian cohort defined as BMS based on an Expanded Disability Status Scale (EDSS) score ≤ 3.0 at 10 years from onset.
MS patients with an EDSS score ≤ 3.0 at 10 years from onset and minimum of 20 years follow up were included in the study. The 20-year EDSS score was considered the primary outcome. Associations with demographic and clinical characteristics and HLA-DRB1 genotype were investigated.
Among 120 patients with a benign course at 10 years, 78 (65%) remained benign at the 20-year follow up, but patients with an EDSS ≥ 2.5 were more likely to go on to develop more severe disability in the next decade. When considering factors associated with an increase in EDSS score ≤ 1 from 10 to 20 years, indicating limited progression, apart from the EDSS score at 10 years, poly-symptomatic presentation (p = 0.004) and cerebellar/brainstem mono-symptomatic presentation (p = 0.016) were independently associated with more rapid progression compared with other mono-symptomatic presentations. Carriage of the high risk HLA-DRB1*1501 allele was marginally associated with slower progression.
In this geographically isolated MS cohort of predominantly Anglo-Celtic origin clinical progression in the benign MS group was similar to that in other published series from Western countries. These results are in keeping with the view that patients labeled as benign MS are part of a heterogeneous continuum of disease progression and do not possess unique clinical characteristics. Possible genetic determinants of a benign course warrant further investigation.
The brittle subject of "benign MS" was discussed at the Stornoway meeting over this weekend. Someone pointed out that in the days of no treatment, it was justifiable to offer the security buffer of benign MS in mild cases of MS so as not to unduly distress the person; which, rightly or wrongly seemed a good thing at the time. Whether this applies to hear and now is questionable; we are definitely not as helpless at managing MS as we were back then. Our most effective strategies for treating MS are 1) early treatment, 2) the achievement of "No Evidence of Disease Activity (NEDA)". And yet we still talk of "benign MS".
Is the new untruth better than the old truth?
Here, Australian neurologists see whether there is a case to be made for benign MS in their region?They looked at 120 PwMS with a benign course (as defined as an EDSS score </= 3.0 at 10 years) after a 20 year follow-up period.
They found that 65% PwMS remained benign at year 20; of those who had progressed (EDSS >3.0), 57% were significantly disabled with an EDSS >6.0 (i.e. requiring at least one unilateral assistance). They also found that whilst disability increased steadily in those with EDSS </= 2.0, there was a more rapid increase in those with an initial EDSS >/= 2.5.
The bottom line is that an initial benign course in the first 10 years of the disease did not guarantee a similar outcome at 20 years. It wouldn't surprise me if the percentage of benign MS cases lessened further when the study population is pushed to 30 years.
In terms of risk factors for progression they found that women derived a marginal benefit over men, as did those who presented initially with sensory or optic symptoms as opposed to motor or cerebellar or polysymptomatic presentations, HLA-DRB1*13 allele carriage was also associated with a lower chance of remaining benign, while the carriage of the high risk allele HLA-DRB1*15 was associated with a marginal, though not significant chance of remaining benign. The latter is not an isolated finding and has been reported in other studies.
Overall, despite majority of benign cases at the first decade remaining benign through to the second decade; in one-third there was progression. The latter cannot be ignored. Moreover, the current definition of motor disability using the EDSS score ignores hidden disability, such as cognitive dysfunction, employability, depression, and social problems.
Labels: Benign MS and progression, Genetic Risk