Determinants of disability development in patients with multiple sclerosis

Aim: Multiple sclerosis (MS) is the most frequently seen autoimmune, chronic inflammatory and degenerative disease in young population and it is characterized with demyelinization and axonal degeneration in central nervous system (CNS). The prognosis of MS is quite variable. It has been found that some demographical and clinical variables at the early stage of the disease have effects on prognosis of the disease. The aim of the current study is to investigate the clinical and the demographical factors that are associated with development of irreversible disability at the early stages of the disease in patients with relapsing remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS) which has onset characterized with attacks. Material and Method: The current study is a study which retrospectively evaluated demographical and clinical variables of 741 patients who were registered in MSBase database of MS polyclinics of Karadeniz Technical University and who had been diagnosed as RRMS and SPMS according to McDonald 2010 criterias. The gender of patients, the age at disease onset, the disease onset pattern as presence of clinical symptoms in one or more than one region (monosymptomatic or polysmptomatic), types of first attack, the number of attacks in first five years following the onset of disease, the interval between the first two attacks, the time of beginning of immunomodulatory or immunosuppressive therapy, cigarette use and the amount of daily cigarette consumption were evaluated. Kaplan Meier analysis was used in analysis of the period up to development of disability according to demographical and clinical characteristics. Three EDSS endpoints such as reaching EDSS 4 (limitation in walking without any need of help), EDSS 6 (walking with a unilateral support) and from EDSS 4 to EDSS 6 were evaluated with Kaplan Meier analysis. Furthermore chi-square test was used in comparison of endpoints such as reaching EDSS 4, EDSS 6, from EDSS 4 to EDSS 6 and secondary progressive phase according to the demographical and clinical variables. Findings: Eighty-seven percent of the patients (n=645) included to the current study had the diagnosis of RRMS and 13% (n=96) had the diagnosis of SPMS. 65.3% (n=421) of the patients with RRMS were female and 34.7% (n=224) were male. 67.7% of the patients with SPMS (n=65) were female and 32.3% (n=31) were male. It has been found that out of 741 MS patients, 228 patients (30.8%) has reached to EDSS 4 and 131 patients (17.7%) has reached to EDSS 6. Out of the patients reaching EDSS 4, 123 patients (53.9%) has reached to EDSS 6. According to the results of the current study, the factors which affect the long-term progress of the disease in MS patients who had a disease onset with attacks are; having a disease onset at age above 40, presence of urinary bladder-intestinal type of first attack, presence of polysymptomatic disease onset, presence of an interval shorter than 2 years between the first two attacks, presence of 4 or more attacks within the first five years after the disease onset. In the current study it has been found that cigarette smoking and beginning the disease modifying therapies after two years have no effect on the time to reach EDSS 4 and EDSS 6, however they significantly shorten the time from EDSS 4 to EDSS 6. It has been found that gender and daily amount of cigarette consumption had no effect on the time to reach EDSS 4, EDSS 6 and the time from EDSS 4 to EDSS 6. Results: The current retrospective study demonstrates that some demographical and clinical variables at the early stage of MS disease are strong determinants of developing disability. These variables are disease onset at age above 40, presence of urinary bladder-intestinal type of first attack, a polysymptomatic disease onset, an interval shorter than two years between the first two attacks and presence of 4 or more than 4 attacks within the first five years after the disease onset. Keywords: Multiple Sclerosis (MS), Expanded Disability Status Scale (EDSS), disability, clinical and demographic determinants, prognosis.