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European Committee for Treatment and Research in MS (ECTRIMS), London UK, 14-17 September 2016
MS pathogenesis
Clinical course
Genetics
MS pathogenesis
Two decades ago, dopamine D2 receptor agonism was observed to reduce the severity and duration of neurological symptoms in EAE (Dijkstra et al. Psychoneuroendocrinology 1994;19:135-42), which was attributed to dopamine-mediated prolactin suppression. Recent studies have suggested a more direct role. Boyko and colleagues have reported serum dopamine levels are lower during MS relapses (Melnikov et al. J Neuroimmunol 2016;292:97-101). Dopamine suppressed production of IL-17 and interferon-gamma, an effect that was abolished by sulpiride, a dopamine D2 receptor antagonist (Boyko et al. ECTRIMS 2016; abstract P426). Conversely, the antipsychotic agent risperidone, which blocks dopamine D2/5-HT2a receptors, reduced disease severity in EAE, in part through D2 receptor blockade as well as by reducing microglia/macrophage activation (O’Sullivan et al. PLoS One 2014;9:e104430). Dopamine receptor mRNA levels in lymphocytes have also been proposed as a biomarker for interferon-beta response (Cosentino et al. J Neuroimmunol 2014;277:193-6).
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Clinical course
Prodrome: MS patients appear to be less well for several years prior to diagnosis, according to an analysis of the Swedish national databases (Beiki et al. ECTRIMS 2016; abstract P311). The databases included >10,000 MS patients and >200,000 controls. The mean number of sick days increased over a 7-year period prior to MS onset in patients diagnosed at age 30-39 years; the greatest increase coincided with the age of onset. Further studies are needed to investigate the causes of sick days to determine if they indicate an etiologic or triggering event.
Prognosis: Adolescent obesity has been reported to be an MS risk factor. Increased BMI and dyslipidemia at first demyelinating event (FDE) are now proposed as risk factors for disease progression. The Ausimmune study examined a cohort of 279 FDE patients followed for five years (van der Mei et al. ECTRIMS 2016; abstract P317). Higher BMI (hazard ratio 1.04) and triglycerides (HR 1.20) at entry were associated with an increased risk of relapse. BMI and total cholesterol/HDL cholesterol ratio were associated with a higher annual change in disability.
Hormones and pregnancy: An analysis of data from the New York State MS Consortium found that worsening symptoms during menstruation may be associated with greater disease severity (Kavak et al. ECTRIMS 2016; abstract P323). A total of 16.3% of 443 survey respondents reported worse MS symptoms during menstruation. They had earlier onset of MS compared to women without MS symptoms during menstruation (mean age 25.4 vs. 30.5 years), were more likely to use a cane (47.2% vs. 36.0%), and younger when they first used a cane (mean age 40.0 vs. 46.4 years). Relapse rates were non-significantly lower in current oral contraceptive (OC) users vs. non-users.
In the CLIMB study, annualized relapse rates were lower in past OC users vs. never-users (0.27 vs. 0.46); the trend held when adjusted for age and BMI (0.70 vs. 1.19) (Bove et al. ECTRIMS 2016; abstract P320). Past/current OCs users had a lower risk of reaching a higher EDSS score vs. never-users at 8-year follow-up, but differences were not significant. A prior study found that OC use was associated with less disease severity but only in patients with past/current DMT use (Gava et al. Fertil Steril 2014;102:116-22).
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Genetics: Two studies reported on subclinical MS in relatives of persons with MS. In the Genes and Environment in Multiple Sclerosis (GEMS) study of first-degree relatives, 8% in the female cohort had MRI findings that met McDonald 2010 criteria for dissemination in space (Xia et al. ECTRIMS 2016; abstract P537). Female relatives were asymptomatic but demonstrated impaired vibration sensitivity suggestive of myelitis or neurodegeneration. A German study of 53 monozygotic twin pairs reported that radiologically isolated syndrome was detectable in 34% using 3T MRI; 12 of 15 twins with RIS were OCB+ (Gerdes et al. ECTRIMS 2016; abstract 169). Non-specific white-matter changes were detected in 18%.