An Observational Study on the Progression of Clinically Isolated Syndrome to Multiple Sclerosis Over a 2-year Period
An Observational Study on the Progression of Clinically Isolated Syndrome to Multiple Sclerosis Over a 2-year Period
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.
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).
Inclusion Criteria:

 -  Subjects aged between 6-60 years, both inclusive

 -  Subjects who have experienced a single, first clinical event potentially suggestive of
 MS within the last 2 years from study entry. The event must be a new neurological
 abnormality present for at least 24 hours, either mono- or polysymptomatic, other than
 paresthesia or vegetative dysfunction

 -  Subjects who have given written informed consent.

 Exclusion Criteria:

 -  Subjects with the diagnosis of MS

 -  Subjects with other disease that could better explain the subject's signs and symptoms

 -  Subjects who are scheduled to participate in any interventional treatment trial

 -  Subjects who have any condition that could interfere with MRI evaluation