Clinically and Radiological isolated syndrome (MS risk)

The easy and wide availability of brain MRI in the last decades has led to its increasing use in evaluation of a variety of neurological symptoms. Given its widespread use, it is common to detect some incidental indings in patients undergoing brain MRI for unrelated medical indications, such as head trauma or headache. The most common of these incidental abnormalities are white matter lesions that based on their appearance, location, and distribution are consistent with demyelination or MS (multiple sclerosis) but are not associated with any clinical symptoms suggesting MS [1]. Diagnosis of MS is based on demonstrating dissemination in space and time on MRI and excluding other neurological disorders that can clinically and radiologically mimic MS [2]. MRI criteria for MS are based on the presence of focal lesions in the white and /or gray matter of the CNS, which are considered typical for this condition in terms of distribution, morphology, evolution, and signal abnormalities on conventional MRI sequences (T2weighted, FLAIR, preand post-contrast T1-weighted scans) [3]. According to the 2017 revision of McDonald criteria, including two major changes, irst is the early diagnosis of MS in patients with CIS with dissemination in space and +ve OCBs, without waiting for dissemination in time, second is, symptomatic or asymptomatic MRI lesions (except those in the optic nerve) can be considered as dissemination in space or time [4]. Incidental MR imaging indings resembling MS without typical MS symptoms are termed RIS, it was introduced in 2009 by Okuda to categorize incidental WM lesions Abstract


Introduction
The easy and wide availability of brain MRI in the last decades has led to its increasing use in evaluation of a variety of neurological symptoms. Given its widespread use, it is common to detect some incidental indings in patients undergoing brain MRI for unrelated medical indications, such as head trauma or headache. The most common of these incidental abnormalities are white matter lesions that based on their appearance, location, and distribution are consistent with demyelination or MS (multiple sclerosis) but are not associated with any clinical symptoms suggesting MS [1]. Diagnosis of MS is based on demonstrating dissemination in space and time on MRI and excluding other neurological disorders that can clinically and radiologically mimic MS [2]. MRI criteria for MS are based on the presence of focal lesions in the white and /or gray matter of the CNS, which are considered typical for this condition in terms of distribution, morphology, evolution, and signal abnormalities on conventional MRI sequences (T2weighted, FLAIR, pre-and post-contrast T1-weighted scans) [3]. According to the 2017 revision of McDonald criteria, including two major changes, irst is the early diagnosis of MS in patients with CIS with dissemination in space and +ve OCBs, without waiting for dissemination in time, second is, symptomatic or asymptomatic MRI lesions (except those in the optic nerve) can be considered as dissemination in space or time [4]. Incidental MR imaging indings resembling MS without typical MS symptoms are termed RIS, it was introduced in 2009 by Okuda to categorize incidental WM lesions suggestive of demyelinating disease in patients without typical MS symptoms and no better explanation for the MR imaging anomalies [5]. CSF analysis was one of the main paraclinical diagnostic criteria for MS (it is mandatory in the 2017 revision of McDonald criteria for MS); nowadays, it is of great importance in differential diagnosis of MS [4]. The presence of ≥2 OCBs in the CSF have a positive predictive value of 97%, negative predictive value of 84%, sensitivity of 91%, and speci icity of 94% for developing (relapsing remitting MS) RRMS after a CIS [5] (Tables 1,2).
The condition to be termed CIS, the episode should last for at least 24 hour, and occur in the absence of fever or infection, with no clinical features of encephalopathy [7]. A retrospective review of brain MRI showed that 58% had white matter T2 hyperintensities and that the prevalence of MRI indings meeting the Barkhof criteria for dissemination in space in a consecutive series of patients imaged for headaches ranged from 2.4% to 7.1% [8]. Several risk factors of conversion from RIS to MS have been discussed ( Table 3).

Aim of the study
This study was prospective study that aimed to con irm the diagnosis of MS in patient presenting with neurological disorder and MRI brain inding suggestive MS.

Patients and methods
The study was carried out on sixty one patient aged ≥ 15 years and less than 58 years of both sex attended the outpatient clinic or admitted at Neurology Department of Al-Jadaani and Bugshan Hospitals, Jeddah, KSA during the period from irst January 2017 to the end of March 2018. Based on the digital radiological information system and digital patient charts, all patients undergoing a brain MRI and had radiological inding ful illing the criteria of CIS or RIS during this period were included in the study. All MRI examinations were performed in the regular clinical setting in one of two 1.5 T MRI machines (gadolinium enhanced T1, T2, FLAIR and Diffusion sequences were done for all patients), MRI was interpreted by radiologist. This study had been approved by ethical committee of Al-Jadaani and Bugshan Hospitals. Patients who diagnosed MS, Table 1: Proposed diagnostic criteria for radiologically isolated syndrome [5].
A-The presence of incidentally identifi ed CNS white matter anomalies meeting the following MRI criteria 1. Ovoid, well-circumscribed and homogeneous foci with or without involvement of the corpus callosum 2. T2 hyperintensities measuring >3 mm and fulfi lling Barkhof criteria (at least three out of four; table 2) for dissemination in space 3. CNS white matter lesions not consistent with a vascular pattern B-No historical accounts of remitting clinical symptoms consistent with neurological dysfunction C-The MRI fi ndings do not account for clinically apparent impairments in social, occupational or generalized areas of functioning D-The MRI fi ndings are not due to the direct physiological effects of substances (recreational drug abuse, toxic exposure) or a medical condition E-Exclusion of individuals with MRI phenotypes suggestive of leukoaraiosis or extensive white matter pathology lacking involvement of the corpus callosum F-The CNS MRI anomalies are not better accounted for by another disease process  Table 3: Clinical and radiological predictors which increase the risk of clinical progression in radiologically isolated syndrome [9].
Asymptomatic spinal cord lesions (especially cervical cord lesions) Infratentorial lesions A higher number of T2 lesions in MRI Pathological visual evoked potential Younger age Oligoclonal bands and/or a pathological IgG index in combination with more than nine T2-lesions on the initial MRI examination acute disseminated encephalomyelitis, autoimmune disease, cerebrovascular stroke, or patients who refused to participate in the study were excluded from the study. All patients included in the study were subjected to complete neurological history and examination. Detailed history of neurological symptoms (onset, duration, course and aggravating factors) and complete neurological examination including mental state, cranial nerves, motor, sensory systems and cerebellum were done for all patients. CSF and blood samples (in parallel) for oligoclonal bands and IgG index were done for all patients. Appropriate statistical methods were applied and the results were tabulated accordingly. P <0.05 was considered signi icant.

Discussion
The diagnosis of MS is primary clinical and is dependent on the demonstration of neurologic signs and symptoms subsequent to white matter lesions on MRI. It depends largely on the results of MRI examination. Incidental MRI indings suggestive of MS without typical MS symptoms de ined as RIS [10].
The association of RIS and MS is also strengthened in that both patient groups show similarities in both qualitative and quantitative MRI measurements [11,12]. Patients should not be diagnosed with MS on the basis of MRI indings alone, and at least one clinical event consistent with acute demyelination should remain a cornerstone for diagnosis [13]. Our study was included 61 patients, 40 females and 21 males. After clinical, MRI inding and laboratory results, 44 patients were diagnosed as CIS and 17 patient were diagnosed as RIS. Male to female ratio was 1:1.9 among studied patients and 1:2.14 among patients diagnosed CIS. These results were agree with [14,15] they reported that MS is more common in women than in men, and has increased over the last decades from a female-to-male ratio of 1.4 in 1955 to 2.3 in 2000. This corresponds to a lifetime risk of 2.5% in women compared to 1.4% in men. The mean age of patients was 31ys and for patients with CIS 30.5. It was higher among male than female with signi icant difference especially among patients with CIS that consistent with [16] he reported that the incidence of MS is low in childhood and increases after the age of 18, reaching a peak between 20 and 40 years (mean age of 30 years) with women being affected approximately 2-5 years earlier than men [17].
Reported that, the onset of MS in 85% of young adults (aged 20-45 years). Regarding results of OCB, 75% of patients with CIS have positive OCB in CSF while in RIS only 23% has positive results. These results was partially agreed with [18][19][20][21][22][23][24][25] they mentioned that, Sixty to seventy percent of patients with CIS have positive OCBs and with [26] he reported that the positive OCB were detected in 61% of patients with CIS [27]. Found CSF oligoclonal banding having sensitivity between 69-91% for diagnosis of MS. Regarding the clinical presentation, optic neuritis was most common presentation for CIS patients (31%) and headache was most common presentation for RIS patients (41%) [28]. Reported that, acute demyelinating optic neuritis is the presenting symptom in about 20% of MS patients and affects about half of MS patients at some point in the disease course and also [16] reported that, typical clinical presentations of RRMS are optic neuritis (in about 20% of cases this is the initial symptom). Headache is the most common reason for performing the initial MRI unveiling RIS, but it is unclear if there is a causative relationship between the incidental MRI indings and the headaches [29]. A study by Liu et al., showed that among patients undergoing MRI of the brain due to headaches, MRI indings ful illing the Barkhof criteria are common [8].

Conclusion
The diagnosis of MS not depend only on MRI inding but need clinical presentation consistent with diagnosis of MS and CSF analysis for oligoclonal bands to con irm diagnosis.