An Observational Study on the Progression of Clinically Isolated Syndrome to Multiple Sclerosis Over a 2-year Period
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Sclerosis
Study type: Observational

Summary: 
      This is a prospective, multicentric, observational study with a 2 years recruitment period.
      The purpose of the study is to observe the multiple sclerosis (MS) progression of subjects
      since their first episode of neurological event and secondly, to determine status of
      anti-AQP4 immunoglobulin (IgG) antibody in MS subjects.
    

Detailed description: 
      Multiple sclerosis is chronic, inflammatory disease of the central nervous system (CNS)
      characterised by areas of demyelination, or plaques, in the CNS. In 85% of subjects who later
      develop MS, clinical onset is with an acute or subacute episode of neurological disturbance
      due to a single white-matter lesion (e.g. optic neuritis, or an isolated brainstem or partial
      spinal-cord syndrome). This presentation is known as a Clinically Isolated Syndrome (CIS).
      Because a CIS is typically the earliest clinical expression of MS, research on subjects with
      a CIS may provide new insights into early pathological changes and pathogenetic mechanisms
      that might affect the course of the disorder.

      In the group of subjects with optic-spinal MS (OSMS), the main lesions are typically confined
      to the optic nerve and spinal cord. In Asians, OSMS has similar features to the relapsing
      remitting form of neuromyelitis optica (NMO) seen in Westerners. It is still a matter of
      debate whether NMO represents a disease entity in itself or whether it is a subform of MS.
      Early differentiation of NMO from MS is highly desirable, as treatment options and prognoses
      differ widely. Recently, a new serum autoantibody (NMO-IgG) has been detected in NMO
      subjects. The binding sites of this autoantibody were reported to colocalize with aquaporin 4
      (AQP4) water channels. Optic-spinal MS is sometime suggested to be NMO based on the frequent
      detection of the anti-AQP4 IgG antibody. In Taiwan, study has shown that 56% of MS subjects
      were of the optic-spinal type.

      OBJECTIVES

      The study is designed firstly, to observe the MS progression of subjects since their first
      episode of neurological event and secondly, to determine status of anti-AQP4 IgG antibody in
      MS subjects.

      Primary objective:

        -  To describe the progression of subjects who have experienced a CIS to MS over a 2-year
           period

      Secondary objectives:

        -  To assess the relationship between CIS and MS including optic-spinal MS (OSMS)

        -  To determine the status of anti-AQP4 IgG antibody in subjects who convert to MS

      Each subject shall be followed up for 2 years after enrolment. At baseline, routine
      examinations shall be performed to confirm subject's neurological episode. After the baseline
      visit, the subject shall be instructed to return for further examination if he/she
      experiences a relapse. During the follow-up examinations, the treating physician shall
      determine whether the subject fulfil the diagnostic criteria for MS.

      If subject is being diagnosed with MS, he/she shall be considered as reaching the end of
      his/her study participation. Further management of the MS condition will be at the discretion
      of the treating physician. During 2-year follow-up period, telephone calls to the subject
      shall be made quarterly to assess subject's neurological and/or visual status and to remind
      subject that he/she need to return for evaluation in the event of a relapse. All data will be
      collected using a standardised case report form (CRF).
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Subjects who have experienced a single, first clinical event potentially suggestive of MS
        within the last 2 years from study entry.
      
Biospecimen description: 
      Whole blood
    
Keywords: Multiple Sclerosis; Clinical isolated syndrome; Demyelination