Prognostic factors for conversion to multiple sclerosis in clinically isolated syndrome: A controlled, prospective study

ABSTRACTIntroduction: Clinically isolated syndrome (CIS) is an inflammatory and demyelinating process of the central nervous system that suggests multiple sclerosis (MS) in the absences of the other alternative diagnosis. About 85% of patients with MS presents with CIS. MS is a chronic disease and has high potential for progression so the identification of prognostic factors that determine the development of MS in CIS gains importance. Identification of prognostic factors such as the age of onset, gender, initial symptoms, site of involvement, presence of polyregional onset, baseline Expanded Disability Status Scale (EDSS) score and the clinical response to attacks, presence of cognitive symptoms, Cerebrospinal Fluid (CSF) and Manyetik Resonans Imaging (MRI) findings provide the prediction of conversion to MS. This approach may provide intervention possibilities for the natural history of disease such as early immunomodulating therapy. Assessment of the quality of life which has been known as subjective perception of signs and symptoms by the patients, fatigue, depression, cognition in attack and remission periods may contribute to the determine the risk of conversion to MS. Comparing therapeutic properties of the first event with MS patients may help to predict conversion to MS from CIS and is an area that will contribute to understand the relationship between CIS and MS. In addition, evaluating the common effects of clinical, neuro-imaging and CSF findings that potentially affect conversion to MS are candidates to strengthen the data. 5Materials and Methods: The EDSS, Multiple Sclerosis Functional Composite (MSFC), Auditory Consanat Trigram (ACT), Faces Symbol Test (FST), Fatigue Impact Scale (FIS), Fatigue Severity Scale (FSS), Multiple Sclerosis International Quality of Life (MUSIQoL), Beck Depression Scales (BDS) are used for evaluating the severity of attacks at initially and after treatment period. In addition, cognition of CIS patients was also evaluated at the same period, and repeated at first month and and every 3 months interval. 9-Hole Peg Test (9-NHPT) and Timed 25-Foot Walk Test (T25WT) performed and EDSS were calculated every day during treatment. MS patients who met criteria as control group were included in the study. Lumbar puncture was performed in all patients before treatment. CSF IgG index, presence of CSF oligoclonal IgG bands were studied. In addition, brain and spinal MRI was performed in first visit in both groups. All CIS patients were observed at least 24 months. Endpoint for the study group was determined definite diagnosis of MS according to Poser or McDonald criteria of 2005. Results:Initial physical disability parameters (EDSS, 9-HPT, T25WT) were compared with the time point of end of the pulse therapy and the first month. First month values were significantly better in CIS group than end of treatment values in all three parameters. The ratio of sufficiency with five days pulse therapy was significantly higher in MS group. PASAT score were significantly elevated in CIS group at the end of pulse therapy. ACT and FST scores showed significant improvement after treatment period compared to baseline in both CIS and MS groups. The average ACT test scores significantly increased in CIS group after the first month of treatment compared to the end of pulse therapy. However, a similar increase was not detected in the MS group. 35 of 41 patients (85%) converted to MS at the end of study. 6 patients remained CIS. Polysymptomatic involvement was found to be a prognostic factor for conversion to MS. Sensory involvement is also found to be significant. Cases who respond to pulse therapy completely in first clinical event had higher rates of conversion to MS than patients who partial responded or did not respond. Presence of lesions in periventricular, juxtacortical, brainstem and corpus callosum in initial MRI were found to be a factor in conversion. Detection of black holes and presence of Gadolinium enhancing lesions in the initial MRI were found as a significant factor for conversion. The presence of oligoclonal band was detected as a predictive value in terms of conversion to MS. Patients without sensory symptoms converted to MS earlier. Patients having black holes in the initial brain 6MRI converted to MS at an earlier stage. We found that all CIS cases presenting with optic neuritis, transverse myelitis, supratentorial or polysymptomatic involvement,having positive CSF and MRI definitely converted to MS within 2 years. Discussion: Clinically isolated syndrome is a significant precursor of MS. Our study demonstrated the similarities of clinical, radiological and CSF findings between CIS and MS. In addition, conversion of 85% of CIS cases within 2 years are shown as yet another proof of this close relationship between CIS and MS. This is the first study being used the ACT and FST in CIS. Because of the first results in this field, these data obtained in this study is the reference feature. Fatigue was studied and compared to MS for the first time in CIS attacks. Fatigue was more common in CIS group but was found to occur more severe in MS group. For the first time, in a prospective study, clinical, MRI and CSF findings were used together to evaluate the conversion to MS in CIS patients. Although clinically sensory involvement is a risk factor for conversion to MS, the longest time period for transformation to MS occurred in this group. This result is shown for the first time in the literature. Our result showed that risk of conversion to MS increased if MRI met the Barkhof-Tintore criteria or CSF was positive for MS. These factors were found to be stronger important predictive factors for converting to MS if they were found together. Key words: Clinically isolated syndrome, multiple sclerosis, attack, prognosis, treatment