Radiologically Isolated Syndrome Research Articles

The diagnostic workup of children with the radiologically isolated syndrome differs by age and by sex.

Cerebrospinal fluid (CSF) and spinal MRIs are often obtained in children with the radiologically isolated syndrome (RIS) for diagnosis and prognosis. Factors affecting the frequency and timing of these tests are unknown. To determine whether age or sex were associated with (1) having CSF or spinal MRI obtained or (2) the timing of these tests. We analyzed children (≤ 18y) with RIS enrolled in an international longitudinal study. Index scans met 2010/2017 multiple sclerosis (MS) MRI criteria for dissemination in space (DIS). We used Fisher's exact test and multivariable logistic regression (covariates = age, sex, MRI date, MRI indication, 2005 MRI DIS criteria met, and race). We included 103 children with RIS (67% girls, median age = 14.9y). Children ≥ 12y were more likely than children < 12y to have CSF obtained (58% vs. 21%, adjusted odds ratio [AOR] = 4.9, p = 0.03). Pre-2017, girls were more likely than boys to have CSF obtained (n = 70, 79% vs. 52%, AOR = 4.6, p = 0.01), but not more recently (n = 30, 75% vs. 80%, AOR = 0.2, p = 0.1; p = 0.004 for interaction). Spinal MRIs were obtained sooner in children ≥ 12y (median 11d vs. 159d, p = 0.03). Younger children with RIS may be at continued risk for misdiagnosis and misclassification of MS risk. Consensus guidelines are needed.

The Time Trajectory of Choroid Plexus Enlargement in Multiple Sclerosis.

Choroid plexus (CP) can be seen as a watchtower of the central nervous system (CNS) that actively regulates CNS homeostasis. A growing body of literature suggests that CP alterations are involved in the pathogenesis of multiple sclerosis (MS) but the underlying mechanisms remain elusive. CPs are enlarged and inflamed in relapsing-remitting (RRMS) but also in clinically isolated syndrome (CIS) and radiologically isolated syndrome (RIS) stages, far beyond MS diagnosis. Increases in the choroid plexus/total intracranial volume (CP/TIV) ratio have been robustly associated with increased lesion load, higher translocator protein (TSPO) uptake in normal-appearing white matter (NAWM) and thalami, as well as with higher annual relapse rate and disability progression in highly active RRMS individuals, but not in progressive MS. The CP/TIV ratio has only slightly been correlated with magnetic resonance imaging (MRI) findings (cortical or whole brain atrophy) and clinical outcomes (EDSS score) in progressive MS. Therefore, we suggest that plexus volumetric assessments should be mainly applied to the early disease stages of MS, whereas it should be taken into consideration with caution in progressive MS. In this review, we attempt to clarify the pathological significance of the temporal CP volume (CPV) changes in MS and highlight the pitfalls and limitations of CP volumetric analysis.

Shifting our attention earlier in the multiple sclerosis disease course.

Revisions of multiple sclerosis (MS) diagnostic criteria enable clinicians to diagnose patients earlier in the biologic disease course. Prompt initiation of therapy correlates with improved clinical outcomes. This has led to increased attention on the earliest stages of MS, including the MS prodrome and radiologically isolated syndrome (RIS). Here, we review current understanding and approach to patients with preclinical MS. MS disease biology often begins well before the onset of typical MS symptoms, and we are increasingly able to recognize preclinical and prodromal stages of MS. RIS represents the best characterized aspect of preclinical MS, and its diagnostic criteria were recently revised to better capture patients at highest risk of conversion to clinical MS. The first two randomized control trials evaluating disease modifying therapy use in RIS also found that treatment could delay or prevent onset of clinical disease. Despite progress in our understanding of the earliest stages of the MS disease course, additional research is needed to systematically identify patients with preclinical MS as well as capture those at risk for developing clinical disease. Recent data suggests that preventive immunomodulatory therapies may be beneficial for high-risk patients with RIS; though management remains controversial.

Emerging imaging markers in radiologically isolated syndrome: implications for earlier treatment initiation.

The presence of central nervous system lesions fulfilling the criteria of dissemination in space and time on MRI leads to the diagnosis of a radiologically isolated syndrome (RIS), which may be an early sign of multiple sclerosis (MS). However, some patients who do not fulfill the necessary criteria for RIS still evolve to MS, and some T2 hyperintensities that resemble demyelinating lesions may originate from mimics. In light of the recent recognition of the efficacy of disease-modifying therapy (DMT) in RIS, it is relevant to consider additional imaging features that are more specific of MS. We performed a narrative review on cortical lesions (CL), the central vein sign (CVS), and paramagnetic rim lesions (PRL) in patients with RIS. In previous RIS studies, the reported prevalence of CLs ranges between 20.0 and 40.0%, CVS + white matter lesions (WMLs) between 87.0 and 93.0% and PRLs between 26.7 and 63.0%. Overall, these imaging findings appear to be frequent in RIS cohorts, although not consistently taken into account in previous studies. The search for CLs, CVS + WML and PRLs in RIS patients could lead to earlier identification of patients who will evolve to MS and benefit from DMTs.

Retinal and Choroidal Vascularity Evaluation in Pediatric Radiologically Isolated Syndrome and Multiple Sclerosis

BackgroundTo assess vessel density (VD) and flow of retinal plexuses and peripapillary region related with the pediatric radiologically isolated syndrome (RIS) and multiple sclerosis (MS). MethodsWe analyzed 24 eyes of 12 participants with the diagnosis of RIS, 24 eyes of 12 participants with the diagnosis of MS, and 26 eyes of 13 age- and sex-matched healthy controls in this prospective, cross-sectional study. The superficial capillary plexus (SCP) and deep capillary plexus, foveal avascular zone, and the flow of choriocapillaris were investigated using optical coherence tomography angiography. ResultsParafoveal VD and all subregion parameters in SCP were significantly decreased in the MS group compared with the controls, whereas only nasal and inferior VD were significantly decreased in the pediatric RIS group compared with the controls. Ganglion cell layer (GCL) thickness of all subregions of the inner ring was significantly decreased in the pediatric MS group compared with the control group. No significant difference was observed between the pediatric RIS group and the control group regarding thickness. ConclusionsWe showed lower parafoveal VD in all subregions of SCP in pediatric MS, whereas only parafoveal nasal and inferior VD were decreased in pediatric RIS. GCL thickness of inner ring was significantly decreased in the pediatric MS, whereas GCL thickness did not change in pediatric RIS. Therefore, a decrease of parafoveal nasal and inferior VD without a decrease in thickness implies an early impairment of microvasculature in the RIS before impairment of thickness and that microvascular alterations begin from highly vascular superficial parafovea.

The diagnostic value of the central vein sign in radiologically isolated syndrome.

The radiologically isolated syndrome (RIS) represents the earliest detectable preclinical phase of multiple sclerosis (MS). Increasing evidence suggests that the central vein sign (CVS) enhances lesion specificity, allowing for greater MS diagnostic accuracy. This study evaluated the diagnostic performance of the CVS in RIS. Patients were prospectively recruited in a single tertiary center for MS care. Participants with RIS were included and compared to a control group of sex and age-matched subjects. All participants underwent 3 Tesla magnetic resonance imaging, including postcontrast susceptibility-based sequences, and the presence of CVS was analyzed. Sensitivity and specificity were assessed for different CVS lesion criteria, defined by proportions of lesions positive for CVS (CVS+) or by the absolute number of CVS+ lesions. 180 participants (45 RIS, 45 MS, 90 non-MS) were included, representing 5285 white matter lesions. Among them, 4608 were eligible for the CVS assessment (970 in RIS, 1378 in MS, and 2260 in non-MS). According to independent ROC comparisons, the proportion of CVS+ lesions performed similarly in diagnosing RIS from non-MS than MS from non-MS (p = 0.837). When a 6-lesion CVS+ threshold was applied, RIS lesions could be diagnosed with an accuracy of 87%. MS could be diagnosed with a sensitivity of 98% and a specificity of 83%. Adding OCBs or Kappa index to CVS biomarker increased the specificity to 100% for RIS diagnosis. This study shows evidence that CVS is an effective imaging biomarker in differentiating RIS from non-MS, with similar performances to those in MS.

How Early Is Early Multiple Sclerosis?

The development and further optimization of the diagnostic criteria for multiple sclerosis (MS) emphasize the establishment of an early and accurate diagnosis. So far, numerous studies have revealed the significance of early treatment administration for MS and its association with slower disease progression and better late outcomes of the disease with regards to disability accumulation. However, according to current research results, both neuroinflammatory and neurodegenerative processes may exist prior to symptom initiation. Despite the fact that a significant proportion of individuals with radiologically isolated syndrome (RIS) progress to MS, currently, there is no available treatment approved for RIS. Therefore, our idea of "early treatment administration" might be already late in some cases. In order to detect the individuals who will progress to MS, we need accurate biomarkers. In this review, we present notable research results regarding the underlying pathology of MS, as well as several potentially useful laboratory and neuroimaging biomarkers for the identification of high-risk individuals with RIS for developing MS. This review aims to raise clinicians' awareness regarding "subclinical" MS, enrich their understanding of MS pathology, and familiarize them with several potential biomarkers that are currently under investigation and might be used in clinical practice in the future for the identification of individuals with RIS at high risk for conversion to definite MS.

A multicenter study of radiologically isolated syndrome in children and adolescents: Can we predict the course?

To evaluate clinical characteristics, imaging features and etiological profile of Radiologically Isolated Syndrome (RIS) along with clinical and radiological follow-up. Demographic, clinical and radiological data of patients younger than 18 years fulfilling the criteria for RIS were retrospectively analyzed. RIS was defined by the detection of lesions meeting the revised 2010 McDonald Criteria for dissemination in space on magnetic resonance imaging (MRI) in the absence of any symptoms of demyelinating disease or an alternative cause for the MRI findings. There were total 69 patients (38 girls, 31 boys). The median age at index MRI was 15.7 years, and median follow-up time was 28 months. The most common reason for neuroimaging was headache (60.9%). A first clinical event occurred with median 11 months in 14/69 (20%) of cases. Those with oligoclonal bands (OCB) in cerebrospinal fluid (CSF) and follow-up longer than 3 years were more likely to experience a clinical event (p<0.05): 25% of those with OCB manifested clinical symptoms within the first year and 33.3% within the first two years compared to 6.3% and 9.4%, respectively in those without OCB. Radiological evolution was not associated with any variables: age, sex, reason for neuroimaging, serum 25-hydroxyvitamin D level, elevated IgG index, OCB positivity, total number and localization of lesions, presence of gadolinium enhancement, achievement of 2005 criteria for DIS and duration of follow-up. Children and adolescents with RIS and CSF OCB should be followed-up for at least 3 years in order to detect any clinical symptoms suggestive of a demyelinating event. Because disease-modifying treatments are not approved in RIS and no consensus report justifies their use especially in pediatric RIS, close follow-up of OCB-positive patients is needed for early recognition of any clinical event and timely initiation of specific treatment.

Abnormal functional connectivity in radiologically isolated syndrome: A resting-state fMRI study

Background: Radiologically isolated syndrome (RIS) patients might have psychiatric and cognitive deficits, which suggests an involvement of major resting-state functional networks. Notwithstanding, very little is known about the neural networks involved in RIS. Objective: To examine functional connectivity differences between RIS and healthy controls using resting-state functional magnetic resonance imaging (fMRI). Methods: Resting-state fMRI data in 25 RIS patients and 28 healthy controls were analyzed using an independent component analysis; in addition, seed-based correlation analysis was used to obtain more information about specific differences in the functional connectivity of resting-state networks. Participants also underwent neuropsychological testing. Results: RIS patients did not differ from the healthy controls regarding age, sex, and years of education. However, in memory (verbal and visuospatial) and executive functions, RIS patients’ cognitive performance was significantly worse than the healthy controls. In addition, fluid intelligence was also affected. Twelve out of 25 (48%) RIS patients failed at least one cognitive test, and six (24.0%) had cognitive impairment. Compared to healthy controls, RIS patients showed higher functional connectivity between the default mode network and the right middle and superior frontal gyri and between the central executive network and the right thalamus (pFDR < 0.05; corrected). In addition, the seed-based correlation analysis revealed that RIS patients presented higher functional connectivity between the posterior cingulate cortex, an important hub in neural networks, and the right precuneus. Conclusion: RIS patients had abnormal brain connectivity in major resting-state neural networks and worse performance in neurocognitive tests. This entity should be considered not an “incidental finding” but an exclusively non-motor (neurocognitive) variant of multiple sclerosis.

Kappa Free Light Chain Index Predicts Disease Course in Clinically and Radiologically Isolated Syndromes.

To evaluate whether the kappa free light chain index (K-index) can predict the occurrence of new T2-weighted MRI lesions (T2L) and clinical events in clinically isolated syndrome (CIS) and radiologically isolated syndrome (RIS). All consecutive patients presenting for the diagnostic workup, including CSF analysis, of clinical and/or MRI suspicion of multiple sclerosis (MS) since May 1, 2018, were evaluated. All patients diagnosed with CIS and RIS with at least 1-year follow-up were included. Clinical events and new T2L were collected during follow-up. The K-index performances in predicting new T2L and a clinical event were evaluated using time-dependent ROC analyses. The time to clinical event or new T2L was estimated using survival analysis according to the binarized K-index using an independent cutoff of 8.9, and the ability of each variable to predict outcomes was compared using the Harrell c-index. One hundred and eighty two patients (146 CIS and 36 RIS, median age 39 [30; 48] y-o, 70% females) were included with a median follow-up of 21 [13, 33] months. One hundred five (58%) patients (85 CIS and 20 RIS) experienced new T2L, and 28 (15%; 21 CIS and 7 RIS) experienced a clinical event. The K-index could predict new T2L over time in CIS (area under the curve [AUC] ranging from 0.86 to 0.96) and in RIS (AUC ranging from 0.84 to 0.54) but also a clinical event in CIS (AUC ranging from 0.75 to 0.87). Compared with oligoclonal bands (OCBs), the K-index had a better sensitivity and a slight lower specificity in predicting new T2L and clinical events in both populations. In the predictive model, the K-index was the variable that best predict new T2L in both CIS and RIS but also clinical events in CIS (c-index ranging from 0.70 to 0.77), better than the other variables, including OCB. This study provides evidence that the K-index predicts new T2L in CIS and RIS but also clinical attack in patients with CIS. We suggest adding the K-index in the further MS diagnosis criteria revisions as a dissemination-in-time biomarker.

Teriflunomide and Time to Clinical Multiple Sclerosis in Patients With Radiologically Isolated Syndrome

Radiologically isolated syndrome (RIS) represents the earliest detectable preclinical phase of multiple sclerosis (MS) punctuated by incidental magnetic resonance imaging (MRI) white matter anomalies within the central nervous system. To determine the time to onset of symptoms consistent with MS. From September 2017 to October 2022, this multicenter, double-blind, phase 3, randomized clinical trial investigated the efficacy of teriflunomide in delaying MS in individuals with RIS, with a 3-year follow-up. The setting included referral centers in France, Switzerland, and Turkey. Participants older than 18 years meeting 2009 RIS criteria were randomly assigned (1:1) to oral teriflunomide, 14 mg daily, or placebo up to week 96 or, optionally, to week 144. Clinical, MRI, and patient-reported outcomes (PROs) were collected at baseline and yearly until week 96, with an optional third year in the allocated arm if no symptoms have occurred. Primary analysis was performed in the intention-to-treat population, and safety was assessed accordingly. Secondary end points included MRI outcomes and PROs. Among 124 individuals assessed for eligibility, 35 were excluded for declining to participate, not meeting inclusion criteria, or loss of follow-up. Eighty-nine participants (mean [SD] age, 37.8 [12.1] years; 63 female [70.8%]) were enrolled (placebo, 45 [50.6%]; teriflunomide, 44 [49.4%]). Eighteen participants (placebo, 9 [50.0%]; teriflunomide, 9 [50.0%]) discontinued the study, resulting in a dropout rate of 20% for adverse events (3 [16.7%]), consent withdrawal (4 [22.2%]), loss to follow-up (5 [27.8%]), voluntary withdrawal (4 [22.2%]), pregnancy (1 [5.6%]), and study termination (1 [5.6%]). The time to the first clinical event was significantly extended in the teriflunomide arm compared with placebo, in both the unadjusted (hazard ratio [HR], 0.37; 95% CI, 0.16-0.84; P = .02) and adjusted (HR, 0.28; 95% CI, 0.11-0.71; P = .007) analysis. Secondary imaging end point outcomes including the comparison of the cumulative number of new or newly enlarging T2 lesions (rate ratio [RR], 0.57; 95% CI, 0.27-1.20; P = .14), new gadolinium-enhancing lesions (RR, 0.33; 95% CI, 0.09-1.17; P = .09), and the proportion of participants with new lesions (odds ratio, 0.72; 95% CI, 0.25-2.06; P = .54) were not significant. Treatment with teriflunomide resulted in an unadjusted risk reduction of 63% and an adjusted risk reduction of 72%, relative to placebo, in preventing a first clinical demyelinating event. These data suggest a benefit to early treatment in the MS disease spectrum. ClinicalTrials.gov Identifier: NCT03122652.

Conversion from Radiologically Isolated Syndrome to Multiple Sclerosis: Single Center Retrospective Study

Objective: The study aimed to investigate the conversion duration from Radiologically Isolated Syndrome (RIS) to multiple sclerosis (MS) and identify factors associated with an increased risk of progression. Materials and Methods: The study involved a meticulous review of the medical records of 18 patients diagnosed with RIS, who presented without demyelinating clinic in the first applying. Data on patient demographics, laboratory findings, and clinical outcomes were collected. Those who converted from RIS to MS and their conversion duration were recorded. Patients were categorized into two groups; group 1 who progressed to clinically definite MS, and group 2  who remained asymptomatic without clinical progression. The duration of conversion from RIS to MS was also recorded. Results: The study population had a mean age of 39.8 ± 11.5 years, with 15 females and 3 males. All male patients belonged to Group 1. Although the ages between the two groups did not significantly differ, it was noteworthy that all RIS patients were female. No significant difference between the two groups was observed in the presence of oligoclonal bands or the IgG index. Additionally, the evaluation of spinal lesions did not reveal a statistically significant disparity. The median conversion duration for patients progressing from RIS to MS was 19.5 (interquartile range: 29.25) months. Conclusion: The study provides valuable insights into the conversion from RIS to MS. The study did not identify spinal lesions, oligoclonal bands, or age as prominent indicators for predicting RIS conversion to MS. Early identification of RIS patients at higher risk of progression may enable timely intervention and improve long-term outcomes.

Sociodemographic and Neuroimaging Evaluation of Patients with Multiple Sclerosis and Radiologically Isolated Syndrome in Isfahan, Iran

Background: Multiple sclerosis (MS) is categorized into four subtypes, including clinically-isolated syndrome (CIS), primary progressive multiple sclerosis (PPMS), secondary progressive multiple sclerosis (SPMS), and relapsing-remitting multiple sclerosis (RRMS). On the other hand, radiologically-isolated syndrome (RIS) is characterized by the imaging manifestations of MS rather than its clinical symptoms. Objectives: This study aimed to compare the sociodemographic and neuroimaging findings of different MS phenotypes and RIS. Methods: The current cross-sectional study was conducted on 3716 patients at the Multiple Sclerosis Clinic of Kashani Hospital, Isfahan, Iran, from June 2018 to April 2019. Patients presenting with RIS, CIS, and MS were included in this study. Results: The age of disease onset was remarkably lower in patients with RRMS, while the body mass index was significantly higher in RIS (P-value &lt; 0.05). Other factors, including gender, occupation, marital status, smoking, and family history of MS, showed no significant difference (P-value &gt; 0.05). Neuroimaging assessments revealed significant differences in terms of the location of the plaques, the activity of the plaques, brain atrophy, lesion load, the number of cervical plaques, and the presence of longitudinally-extended transverse myelitis (P-value &lt; 0.05), but not regarding the activity of cervical and thoracolumbar plaques and the number of thoracolumbar lesions (P-value &gt; 0.05). Conclusions: Different MS phenotypes showed variations in terms of sociodemographic and neuroimaging characteristics. Follow-up studies are recommended to determine the risk factors predicting the conversion of RIS and CIS to other MS phenotypes.

The CXCL13 Index as a Predictive Biomarker for Activity in Clinically Isolated Syndrome.

Multiple sclerosis (MS) is a clinically heterogenous disease. Currently, we cannot identify patients with more active disease who may potentially benefit from earlier interventions. Previous data from our lab identified the CXCL13 index (ICXCL13), a measure of intrathecal production of CXCL13, as a potential biomarker to predict future disease activity in MS patients two years after diagnosis. Patients with clinically isolated syndrome (CIS) or radiologically isolated syndrome (RIS) underwent a lumbar puncture and blood draw, and the ICXCL13 was determined. They were then followed for at least 5 years for MS activity. Patients with high ICXCL13 were more likely to convert to clinically definite MS (82.4%) compared to those with low ICXCL13 (10.0%). The data presented below demonstrate that this predictive ability holds true in CIS and RIS patients, and for at least five years compared to our initial two-year follow-up study. These data support the concept that ICXCL13 has the potential to be used to guide immunomodulatory therapy in MS.

Central vein sign and paramagnetic rim sign: From radiologically isolated syndrome to multiple sclerosis.

The widespread use of magnetic resonance imaging (MRI) has led to an increase in incidental findings in the central nervous system. Radiologically isolated syndrome (RIS) is a condition where imaging reveals lesions suggestive of demyelinating disease without any clinical episodes consistent with multiple sclerosis (MS). The prognosis for RIS patients is uncertain, with some remaining asymptomatic while others progress to MS. Several risk factors for disease progression have been identified, including male sex, younger age at diagnosis, and spinal cord lesions. This article reviews two promising biomarkers, the central vein sign (CVS) and the paramagnetic rim sign (PRS), and their potential role in the diagnosis and prognosis of MS and RIS. Both CVS and PRS have been shown to be accurate diagnostic markers in MS, with high sensitivity and specificity, and have been useful in distinguishing MS from other disorders. Further research is needed to validate these findings and determine the clinical utility of these biomarkers in routine practice.

Impact of COVID-19 vaccination or infection on disease activity in a radiologically isolated syndrome cohort: The VaxiRIS study

Background: Vaccination in patients with multiple sclerosis (MS) treated with immunosuppressive drugs is highly recommended. Regarding COVID-19 vaccination, no specific concern has been raised. Objectives: We aimed to evaluate if COVID-19 vaccination or infection increased the risk of disease activity, either radiological or clinical, with conversion to MS in a cohort of people with a radiologically isolated syndrome (RIS). Methods: This multicentric observational study analyzed patients in the RIS Consortium cohort during the pandemic between January 2020 and December 2022. We compared the occurrence of disease activity in patients according to their vaccination status. The same analysis was conducted by comparing patients’ history of COVID-19 infection. Results: No difference was found concerning clinical conversion to MS in the vaccinated versus unvaccinated group (6.7% vs 8.5%, p > 0.9). The rate of disease activity was not statistically different (13.6% and 7.4%, respectively, p = 0.54). The clinical conversion rate to MS was not significantly different in patients with a documented COVID-19 infection versus non-infected patients. Conclusion: Our study suggests that COVID-19 infection or immunization in RIS individuals does not increase the risk of disease activity. Our results support that COVID-19 vaccination can be safely proposed and repeated for these subjects.

Presymptomatic MS or radiologically isolated syndrome (RIS) should be actively monitored and treated – NO

Presymptomatic MS or radiologically isolated syndrome (RIS) should be actively monitored and treated – NO

Incidental demyelination in magnetic resonance imaging and 10-year risk of multiple sclerosis: A data lake cohort study.

There is an absence of data from large population-based cohort studies on the incidence of radiologically isolated syndrome (RIS). The incidence of RIS and the subsequent risk for multiple sclerosis (MS) were investigated. A population-based, retrospective cohort study was conducted using a data-lake-based analysis of digitalized radiology reports. All brain and spinal cord magnetic resonance imaging (MRI) in people aged 16-70 during the years 2005-2010 (n = 102,224) were screened using optimized search terms to detect cases with RIS. The subjects with RIS were followed up until January 2022. The cumulative incidence of RIS was 0.03% when all MRI modalities were included and 0.06% when only brain MRI was included according to MAGNIMS 2018 recommendation criteria. With the Okuda 2009 criteria, the respective figures were 0.03% and 0.05% (86% concordance). The overall risk for MS after RIS was similar, 32% by using the MAGNIMS and 32% by using the Okuda definition of RIS. Individuals aged <35.5 years exhibited the most significant predisposition to MS (80%), whilst those >35.5 years had less than 10% risk of MS. MS diagnosed after RIS constituted 0.8% of the incident MS cases in the population during 2005-2010. A population-wide context was provided for the incidence of RIS and its relationship to MS. MAGNIMS recommendations were only slightly more sensitive to detect RIS compared to the Okuda criteria. RIS has a subtle effect on the overall incidence of MS, yet the risk for MS in individuals under the age of 35.5 years is substantial.

Abstract #1401381: Rare Case of Asymptomatic Multiple Sclerosis Lesions in Hyperprolactinemia

Hyperprolactinemia is associated with established multiple sclerosis (MS) and MS progression/relapse. An association between hyperprolactinemia and asymptomatic MS lesions, also known as radiologically isolated syndrome (RIS), has not been reported. A 29-year-old African American man presented with gynecomastia during a primary care visit. Medical history included prediabetes, hypertension, and obesity. He denied galactorrhea, decrease in libido, blurred vision, fatigue, enlarged hands/feet, hyperpigmentation, depression, easy bruising, skin changes, polyuria, and any neurological symptoms. His physical exam was unremarkable except for bilateral gynecomastia and obesity. Laboratory results revealed elevated prolactin 30.6 ng/mL. Thyroid function test was normal. Magnetic resonance imaging (MRI) brain showed normal pituitary gland size with a 0.3-cm rounded hypo-enhancing region, enhancement of the left optic nerve, and areas of abnormal T2/FLAIR lesion involving the juxtacortical and subcortical white matter in the left temporal region. Enhancements in the right occipitotemporal region and a small juxtacortical lesion in the medial inferior left frontoparietal region were also observed. The patient was referred to endocrinology. His only complaint was fatigue, and physical exam was unremarkable. Repeat prolactin was higher than before at 78 ng/mL. TSH was elevated at 6.44 mIU/mL with a free T4 of 1.03 ng/dL. Labs including ANA, AQP 4, Lyme, HIV, JC virus, and syphilis panel were negative. He was started on cabergoline 0.5 mg twice weekly for treatment of hyperprolactinemia. He was also started on levothyroxine for fatigue, which was attributed to subclinical hypothyroidism. Neurology initiated treatment for MS with diroximel fumarate. Follow-up in 2 months showed a prolactin level of 1 ng/mL and a normal TSH and free T4. The patient will be followed with MRI pituitary surveillance at 1 year and 5 years. This is a very rare case of hyperprolactinemia associated with RIS. The decision to treat the patient for MS was made to prevent or delay potential clinical symptoms or progression to overt disease. One study has noted a 34% risk of conversion of RIS lesions to the first clinical event of MS in 5 years, especially with risk factors like young age and male gender. However, it is still debatable whether RIS lesions progress and should be treated, given that medications used to treat MS are associated with possible side effects including allergic reaction. Follow-up will focus on presence of new neurological symptoms concerning for MS and change in the size of the pituitary lesion.

Comparative Analysis of Diagnostic Criteria for Radiologically Isolated Syndrome (S31.009)

<h3>Objective:</h3> This study aimed to analyze the factors that predict the conversion of radiologically isolated syndrome (RIS) patients to multiple sclerosis (MS), and the validity of the two RIS diagnostic criteria. <h3>Background:</h3> Okuda et al. introduced the RIS criteria for the first time in 2009. In 2018, the MAGNIMS group proposed less stringent criteria. There are no studies comparing these two criteria. <h3>Design/Methods:</h3> All participants with suspected demyelinating brain MRI lesions were included in this study. Patient data was collected including demographics, clinical and cerebrospinal fluid (CSF) parameters, and MRI lesion characteristics. All MRI images were reevaluated by two MS specialists and a neuroradiologist. Multi-parameter Cox-regression method was used during the analyses. <h3>Results:</h3> A total of 130 patients (30 mRIS, 65 Okuda and mRIS, 35 nonRIS) from seven centers were included into the study. Fifty percent of the patients converted into MS after 8.59 years (95% CI: 3.95–13.22). The conversion rate of the three groups were comparable (p=0.18). Presence of oligoclonal bands in the CSF (OCB) (HR=0.09, p=0.02), elevated IgG index (HR=0.08, p=0.02), and presence of spinal MRI lesion (HR= 0.23, p=0.001) predicted conversion to MS. Male gender (HR=1.05, p=0.89) and age less than 37 (HR=0.56, p=0.21) were not predictive of conversion to MS. <h3>Conclusions:</h3> Our findings indicates that baseline spinal lesions, an elevated IgG index, and OCB are the best predictors of conversion to MS. Considering conversion to MS, we found no difference between patients who fulfilled the Okuda or modified RIS criteria. It is necessary to explore new parameters that will improve the sensitivity and specificity of the present diagnostic criteria for RIS. <b>Disclosure:</b> Tuncay Gunduz has nothing to disclose. Dr. Ciftci has nothing to disclose. Bilge Piri Cinar has nothing to disclose. Mr. Baba has nothing to disclose. MERAL SEFEROGLU has nothing to disclose. Dr. SIVACI has nothing to disclose. Dr. Cilingir has nothing to disclose.ÖZLEM ETHEMOGLU has nothing to disclose. LEVENT OCEK, 4284 has nothing to disclose. Dr. Barburoglu has nothing to disclose. Dr. Ozakbas has nothing to disclose. Dr. Eraksoy has nothing to disclose. Dr. Kurtuncu has nothing to disclose.