Characterising aggressive multiple sclerosis

Journal of Clinical Medicine, 2020

Background: Compared to the adult onset of multiple sclerosis (AOMS), both early-onset (EOMS) and late-onset (LOMS) are much less frequent, but are often under- or misdiagnosed. The aims of the present study were: 1. To compare demographic and clinical features of individuals with EOMS, AOMS and LOMS, and 2. To identify predictors for disability progression from relapsing remitting MS (RRMS) to secondary progressive MS (SPMS). Method: Data were taken from the Isfahan Hakim MS database. Cases were classified as EOMS (MS onset ≤ 18 years), LOMS (MS onset >50 years) and AOMS (MS >18 and ≤ 50 years). Patients’ demographic and clinical (initial symptoms; course of disease; disease patterns from MRI; disease progress) information were gathered and assessed. Kaplan–Meier and Cox proportional hazard regressions were conducted to determine differences between the three groups in the time lapse in conversion from relapsing remitting MS to secondary progressive MS. Results: A total of 26...

BMC neurology, 2016

This retrospective analysis explored prognostic factors associated with a benign multiple sclerosis (BMS) disease course at baseline and over the 4-year follow-up. Patients from the centralized New York State Multiple Sclerosis Consortium registry were classified as having BMS according to 3 different criteria centered on disease duration and disability. Additional analyses explored prognostic factors associated with BMS using the most conservative disability criteria (Expanded Disability Status Scale ≤2 and disease duration ≥10 years). Among 6258 patients who fulfilled eligibility criteria, 19.8 % to 33.3 % were characterized as having BMS, at baseline depending on classification criteria used. Positive prognostic factors for BMS at baseline included female sex (p < 0.0001) and younger age at onset (p < 0.0001); negative prognostic factors included progressive-onset type of MS and African-American race. Of the 1237 BMS patients (per most conservative criteria), 742 were follo...

Neurology, 1996

Accurate clinical course descriptions (phenotypes) of multiple sclerosis (MS) are important for communication, prognostication, design and recruitment of clinical trials, and treatment decision-making. Standardized descriptions published in 1996 based on a survey of international MS experts provided purely clinical phenotypes based on data and consensus at that time, but imaging and biological correlates were lacking. Increased understanding of MS and its pathology, coupled with general concern that the original descriptors may not adequately reflect more recently identified clinical aspects of the disease, prompted a re-examination of MS disease phenotypes by the International Advisory Committee on Clinical Trials of MS. While imaging and biological markers that might provide objective criteria for separating clinical phenotypes are lacking, we propose refined descriptors that include consideration of disease activity (based on clinical relapse rate and imaging findings) and disease progression. Strategies for future research to better define phenotypes are also outlined.

Multiple Sclerosis Journal

While the major phenotypes of multiple sclerosis (MS) and relapsing–remitting, primary and secondary progressive MS have been well characterized, a subgroup of patients with an active, aggressive disease course and rapid disability accumulation remains difficult to define and there is no consensus about their management and treatment. The current lack of an accepted definition and treatment guidelines for aggressive MS triggered a 2018 focused workshop of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) on aggressive MS. The aim of the workshop was to discuss approaches on how to describe and define the disease phenotype and its treatments. Unfortunately, it was not possible to come to consensus on a definition because of unavailable data correlating severe disease with imaging and molecular biomarkers. However, the workshop highlighted the need for future research needed to define this disease subtype while also focusing on its treatment and managem...

Brain, 2012

Multiple sclerosis may have a non-progressive symptomatology for decades; however, it is not clear whether the disease activity may abate completely. We identified a cohort of patients, resident in Gothenburg at the time of disease onset, between the years 1950-64 (n = 307). These geographical and temporal restrictions, along with favourable conditions for a 'spider' epidemiological study, were optimal for an unbiased selection; this 15-year incidence cohort was essentially followed prospectively for 37-59 years after onset. The shortest follow-up time for patients without primary or secondary progression was 45 years. For patients with an initial relapsing-remitting course and multiple sclerosis diagnosis according to the Poser criteria (n = 202), the probability of non-progressive disease after 40 years was 22% (standard error 3.0%), and after 50 years it was 14% (standard error 3.2%). For attack onset including patients with possible multiple sclerosis, the corresponding probabilities after 40 and 50 years were 35% (standard error 3.3%) and 28% (standard error 3.5%), respectively. At the last follow-up in 2009-10, when patients reached the average age of the Swedish population life expectancy, only 13 patients from the multiple sclerosis diagnosis cohort, according to the Poser criteria, remained alive and non-progressive. Their annualized attack frequency diminished with time from 0.29 to 0.015. These patients had been functioning well socially. Nine patients had an Expanded Disability Status Scale score of 0-2.5, and four patients had a score of 3 or 3.5, with deficits dating back to attacks decades ago. Eight patients participated in a complete neuropsychological examination, which showed a slight difference (P 5 0.01) concerning verbal memory and executive function compared to an age and socially matched reference group, whereas results for five other cognitive domains were within the normal range. Magnetic resonance images fulfilled the Barkhof-Tintoré criteria for multiple sclerosis in 10 of 11 patients, with conspicuously few subcortical lesions relative to extensive periventricular lesions and lesions extending from the inferior midline aspect of the corpus callosum. Prediction of the non-progressive stage was possible with moderate hazard ratios and low sensitivity. Early features that predicted a non-progressive course were complete remission of the onset attack, low or moderate initial relapse frequency and-when the patients with possible multiple sclerosis were included-dominating afferent symptoms. The clinical disease activity had abated in these 13 patients, with the caveat that transition to secondary progression continued to occur after four decades, albeit with decreasing risk.

Multiple Sclerosis, 2005

Journal of the Neurological Sciences, 2008

Background: Multiple sclerosis (MS) has a low prevalence in Hong Kong. Objective: To reassess MS prevalence in Hong Kong and to examine associated risk factors for relapsing-remitting type MS patients to reach Kurtzke's Extended Disability Status Scale (EDSS) of 6.0, i.e. when walking aid was needed. Design: Retrospective observational study on MS patients over 11 years. Setting: Three tertiary hospitals in Hong Kong. Results: A hundred and six patients were recruited. Female to male ratio was 3.2:1 and the prevalence was 4.8 per 100,000. 95 were relapsing-remitting (RR) type. The mean disease duration was 12.7 years (range: 1-45 years) and the duration of follow up was 11.0 +/− 0.8 (mean +/− SE) years. The initial mean EDSS was 1.59 and the latest mean EDSS was 4.26. 38 (40%) RR type MS patients progressed to EDSS 6.0 after a mean duration of 6.0 years. With Cox regression analysis, patients with older age (N 35y) of onset (HR 2.57; 95% CI:1.29-5.11), higher EDSS of 2.0 or more upon presentation (HR 2.19; 95%CI: 1.12-4.26) were associated with progression to EDSS of 6.0, while there was a tendency towards slower disease progression for patients initially presenting with optic symptoms (HR 0.52; 95%CI: 0.23-1.16). The number of relapses and use of interferon could not be shown to have significant effect on disease progression. Conclusions: The local period prevalence ratio of MS was 4.8 per 100,000. Older age of onset and higher EDSS upon initial presentation were independent predictors for progression to EDSS of 6.0.

Journal of …, 2006

Acta Neurologica Scandinavica, 2011

Background-Comorbidity may be associated with the clinical phenotype of disease, and may affect prognostication and treatment decisions. Using the North American Research Committee on Multiple Sclerosis Registry, we described comorbidities present at onset and diagnosis of multiple sclerosis (MS); and examined whether comorbidities present at onset were associated with clinical course or age of MS symptom onset. Methods-In 2006, 8983 participants reported their physical and mental comorbidities; smoking status; height; and past and present weight. We compared clinical course at onset and age of symptom onset by comorbidity status. Results-At MS onset a substantial proportion of participants had physical (24%), or mental (8.4%) comorbidities. The mean (SD) age of MS onset was 31.2 (9.0) years. Vascular, autoimmune, cancer, visual, and musculoskeletal comorbidities were associated with a later age of symptom onset. Among men and women the odds of a relapsing course at onset were increased if mental comorbidities (OR 1.48; 1.08-2.01) were present at symptom onset. In women, gastrointestinal comorbidities (OR 1.78; 1.25-2.52) and obesity (OR 2.08 1.53-2.82) at MS onset were also associated with a relapsing course at onset. Conclusions-Comorbidity is frequently present at onset of MS and is associated with differences in clinical characteristics.

Archives of Iranian medicine, 2012

Multiple sclerosis (MS) typically affects young adults; however, the first symptoms can occur after age 50 and is classified as late-onset MS (LOMS). In this retrospective study, we extracted the records of 3522 MS patients (2716 females and 806 males) registered in the Isfahan MS Society (IMSS) from 2003 to 2010. Next, we searched for LOMS cases. We aimed to compare these cases with 1698 non-LOMS subjects also extracted from the IMSS database. We found 48 LOMS patients (28 females and 20 males), which gave a crude frequency of 1.36%. The frequency by sex of LOMS in males (2.4%) was significantly greater than in females (1.0%, P = 0.002). The mean age at onset was 55.1 ± 4.3 years. The female to male ratio of 1.4:1 in these patients was significantly lower than in non-LOMS subjects (3.37:1, P = 0.003). The leading pattern of MS was relapsing-remitting (RR) in 62.5%, followed by primary progressive (PP) in 27.1%, and secondary progressive (SP) in 10.4%. Predominant presenting sympto...