Radiologically Isolated Syndrome Patients Research Articles

Dimethyl fumarate preserves brainstem and cervical spinal cord integrity in radiologically isolated syndrome.

The first randomized placebo-controlled therapeutic trial in radiologically isolated syndrome (RIS), ARISE, demonstrated that treatment with dimethyl fumarate (DMF) delayed the onset of a first clinical event related to CNS demyelination and was associated with a significant reduction in new and/or newly enlarging T2-weighted hyperintense lesions. The purpose of this study was to explore the effect of DMF on volumetric measures, including whole brain, thalamic, and subcortical gray matter volumes, brainstem and upper cervical spine three-dimensional (3D) volumes, and brainstem and upper cervical spine surface characteristics. Standardized 3T MRIs including 3D isotropicT1-weighted gradient echo images were acquired at baseline and end-of-study according to the ARISE study protocol. The acquired datawere analyzed using Structural Image Evaluation Using Normalization of Atrophy (SIENA), FreeSurfer v7.3, and an in-house pipeline for 3D conformational metrics. Multivariate mixed models for repeated measures were used to analyze rates of change in whole brain, thalamic, subcortical gray matter, as well as change in the 3D surface curvature of the dorsal pons and dorsal medulla and 3D volume change at the medulla-upper cervical spinal cord. The study population consisted of 64 RIS subjects (DMF:30, placebo:34). No significant difference was seen in whole brain, thalamic, or subcortical gray matter volumes in treated vs. untreated RIS patients. A significant difference was observed in dorsal pons curvature with the DMF group having a lower least squares mean change of -4.46 (standard estimate (SE): 3.77) when compared to placebo [6.94 (3.71)] (p = 0.036). In individuals that experienced a first clinical event,a greater reduction in medulla-upper cervical spinal cord volume (p = 0.044) and a decrease in surface curvature was observed at the dorsal medulla (p = 0.009) but not at the dorsal pons (p = 0.443). The benefit of disease-modifying therapy in RIS may extend to CNS structures impacted by neurodegeneration that is below the resolution of conventional volumetric measures.

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.

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.

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.

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.

Assessment of Retinal Nerve Fiber Layer (RNFL) and Retinal Ganglion Cell Layer (RGCL) Thickness in Radiologically Isolated Syndrome (RIS)

Background: Three-thirds of people with radiologically isolated syndrome (RIS) develop multiple sclerosis (MS) within five years following their first brain magnetic resonance imaging (MRI). Subclinical applications of optical coherence tomography (OCT) include measuring the thickness of different retinal layers and monitoring the progression of visual pathway atrophy and neurodegeneration in relation to the progress of the entire brain. Objectives: Our OCT study was conducted in individuals with RIS to evaluate the thickness of the macular retinal nerve fiber layer (mRNFL) and the retinal ganglion cell layer (RGCL). Methods: In this study, 22 patients with RIS and 23 healthy individuals healthy control (HC) were enrolled. The control group and the RIS subjects underwent retinal imaging with OCT. Results: Total mRNFL thickness was 110.34 ± 13.71 μm in the RIS patients and 112.10 ± 11.23 μm in the HC group. Regional analysis of the mRNFL showed that the difference in thickness was more prominent in the superior quadrant. In regards to ganglion cell layer (GCL)++ thickness, the RIS and HCs population showed statistically significant differences in the nasal (P = 0.041), inferior (P = 0.040), and superior (P = 0.045) quadrants. The nasal (P = 0.041) quadrant showed the highest reduction in thickness compared to other regions of the GCL++. Meanwhile, no significant reduction was seen in GCL+ thickness (P-value &gt; 0.05). When the thickness of the retinal layer of the right eye was compared to that of the left eye of the RIS group, no statistically significant differences were found (P-value &gt; 0.05). Conclusions: Compared to the control group, the RIS group had a lower mean thickness of mRNFL and GCL++, indicating retinal neuroaxonal loss.

Biological Markers in Early Multiple Sclerosis: the Paved Way for Radiologically Isolated Syndrome.

Radiologically Isolated Syndrome (RIS) is characterized by MRI-typical brain lesions fulfilling the 2009 Okuda criteria, detected in patients without clinical conditions suggestive of MS. Half of all RIS patients convert to MS within 10 years. The individual course of the disease, however, is highly variable with 12% of RIS converting directly to progressive MS. Demographic and imaging markers have been associated with the risk of clinical MS in RIS: male sex, younger age, infra-tentorial, and spinal cord lesions on the index scan and gadolinium-enhancing lesions on index or follow-up scans. Although not considered as a distinct MS phenotype, RIS certainly shares common pathological features with early active and progressive MS. In this review, we specifically focus on biological markers that may help refine the risk stratification of clinical MS and disability for early treatment. Intrathecal B-cell activation with cerebrospinal fluid (CSF) oligoclonal bands, elevated kappa free light chains, and cytokine production is specific to MS, whereas neurofilament light chain (NfL) levels reflect disease activity associated with neuroaxonal injury. Specific microRNA profiles have been identified in RIS converters in both CSF and blood. CSF levels of chitinases and glial acidic fibrillary protein (GFAP) reflecting astrogliosis might help predict the evolution of RIS to progressive MS. Innovative genomic, proteomic, and metabolomic approaches have provided several new candidate biomarkers to be explored in RIS. Leveraging data from randomized controlled trials and large prospective RIS cohorts with extended follow-up to identify, as early as possible, biomarkers for predicting greater disease severity would be invaluable for counseling patients, managing treatment, and monitoring.

Olfactory Dysfunction and Cognition in Radiologically Isolated Syndrome and Relapsing-Remitting Multiple Sclerosis

Background: Multiple Sclerosis (MS) is a neuroinflammatory, neurodegenerative, demyelinating disease that causes cognitive, olfactory, and other neurological dysfunctions. Radiologically Isolated Syndrome (RIS), in which only radiological findings are monitored, is accepted as the preclinical stage of demyelinating disease and is considered an important period for disease pathology. Therefore, in this study, we aimed to evaluate the olfactory and cognitive functions and their clinical correlation in RIS and Relapsing-Remitting MS (RRMS) patients and a healthy control group. Methods: Our study included 10 RRMS patients, 10 RIS patients, and 10 healthy controls. We conducted an olfactor evaluation via the “Sniffin’ Sticks” test. The subjects underwent a neuropsychometric test battery to evaluate cognitive functions, including memory, visuospatial, and executive functions. Depression was evaluated using the Beck depression scale. Fatigue and daily life activity were evaluated using the Fatigue Severity Scale (FSS) and the 36-Item Short Form Survey (SF-36), respectively. Disability assessment was done with the Expanded Disability Status Scale (EDSS). Results: RRMS and RIS patients’ olfactory test scores were significantly different from those in the control group (p < 0.05). There was a significant difference between the odor threshold scores of patients in the RRMS and RIS groups. There was a significant correlation between memory-oriented cognitive tests and olfactory tests in the RRMS and RIS groups. Conclusion: Olfactory dysfunction can be seen in RIS patients, like in RRMS patients. Cognitive and olfactory dysfunction may be together a sign of degeneration in demyelinating diseases.

Using advanced analysis of multifocal visual-evoked potentials to evaluate the risk of clinical progression in patients with radiologically isolated syndrome

This study aimed to assess the role of multifocal visual-evoked potentials (mfVEPs) as a guiding factor for clinical conversion of radiologically isolated syndrome (RIS). We longitudinally followed a cohort of 15 patients diagnosed with RIS. All subjects underwent thorough ophthalmological, neurological and imaging examinations. The mfVEP signals were analysed to obtain features in the time domain (SNRmin: amplitude, Latmax: monocular latency) and in the continuous wavelet transform (CWT) domain (bmax: instant in which the CWT function maximum appears, Nmax: number of CWT function maximums). The best features were used as inputs to a RUSBoost boosting-based sampling algorithm to improve the mfVEP diagnostic performance. Five of the 15 patients developed an objective clinical symptom consistent with an inflammatory demyelinating central nervous system syndrome during follow-up (mean time: 13.40 months). The (SNRmin) variable decreased significantly in the group that converted (2.74 ± 0.92 vs. 4.07 ± 0.95, p = 0.01). Similarly, the (bmax) feature increased significantly in RIS patients who converted (169.44 ± 24.81 vs. 139.03 ± 11.95 (ms), p = 0.02). The area under the curve analysis produced SNRmin and bmax values of 0.92 and 0.88, respectively. These results provide a set of new mfVEP features that can be potentially useful for predicting prognosis in RIS patients.

Predicting conversion to multiple sclerosis in patients with radiologically isolated syndrome: a retrospective study.

Aims:To retrospectively analyse the Bernese radiologically isolated syndrome (RIS) cohort with the goal of developing a prediction score for conversion to multiple sclerosis (MS).Methods:A total of 31 patients with RIS were identified by screening medical records of neurological patients seen at the University Hospital of Bern between 2004 and 2017 for the diagnoses ‘radiologically isolated syndrome’ and ‘RIS’ adhering to 2009 Okuda recommendations. We analysed clinical, paraclinical and magnetic resonance imaging data during a maximum follow-up period of 3 years and identified significant predictors of conversion to MS.Results:Data were available for 31 patients meeting 2009 Okuda RIS criteria. During the 3 years of follow up, 5/31 RIS patients converted to relapsing-remitting (RR) MS. In our univariate analysis, gadolinium (Gd) enhancement, brainstem and cerebellar hemisphere lesions, immune cell count and albumin concentration in cerebrospinal fluid (CSF), and anti-nuclear antibody (ANA) positivity in serum were identified as significant predictors of conversion to MS. Integrating these factors into our ‘RIS–MS prediction score’ enabled us to calculate a cut-off for prediction of conversion to MS within 3 years with high specificity [1.0, 95% confidence interval (CI) 0.84–1.00) and acceptable sensitivity (0.6, 95% CI 0.17–0.93)].Conclusion:Our RIS–MS prediction score, if validated in an independent cohort, integrating radiological (Gd enhancement, brainstem and cerebellar hemisphere lesions) and paraclinical factors (ANA in serum, cell count and albumin in CSF) could be a useful prognostic tool for early recognition of RIS patients with a high risk of clinical progression to MS.

Radiologically isolated syndrome: targeting miRNAs as prognostic biomarkers.

Aim: Some clinical and biological characteristics have been described as prognostic factors for clinical conversion into clinically definite multiple sclerosis in radiologically isolated syndrome (RIS) population. The aim of this study was to assess signatures of circulating miRNAs in those patients according to their conversion status after 5years of follow-up. Patients & methods: OpenArray plates assessing 216 miRNA candidates were run in 15 RIS patients, and their relative abundances were analyzed. Results: A specific profile of deregulated circulating miRNAs (miR-144-3p, miR-448 and miR-653-3p in cerebrospinal fluid and miR-142-3p, miR-338-3p, miR-363-3p, miR-374b-5p, miR-424-5p, miR-483-3p in plasma) differentiated individuals who remained as RIS after 5years of follow-up. Conclusion: Circulating miRNAs might be used as prognostic biomarkers for RIS patients.

The importance of follow-up and re-diagnosis of patients with demyelinating syndrome suspicion - a case study of a conversion from radiologically isolated syndrome to clinically definite multiple sclerosis

Introduction. Radiologically isolated syndrome (RIS) is a term to describe criteria of diagnosis for the individuals, who underwent brain MRI because of other reasons than multiple sclerosis (MS) suspicion, but turned out to have white matter lesions similar to those present in patients with diagnosed MS. RIS is a separate entity with the presence of MR detected lesions strongly suggestive of MS in patients with no neurological manifestations. Although RIS is not the first stage of MS in every individual, 30-45% of them will present clinical symptoms later. There is a consensus, that about 1/3 of RIS patients will convert to clinically definite MS (CDMS) within 5 years of follow-up. There are some significant predictors of conversion, such as: age (&lt; 37 when diagnosed), male sex and presence of lesions in spinal cord.Case report. We describe a case of a 35-year-old female patient who was initially diagnosed with RIS after MRI performed due to migraine. After about year and a half of follow-up she presented first clinical manifestation (temporary left eye blindness) followed by second episode (in the second eye), a progression in MRI and appearance of oligoclonal bands in cerebrospinal fluid.Discussion. Among individuals with incidentally found lesions in MRI, only few happen to have white matter findings similar to demyelinating lesions in patients with CDMS. Non-specific MRI white matter lesions are much more often than than those fulfilling 2017 MAGNIMS criteria.There is more research needed to determine significant risk factors for conversion from RIS to CDMS. In RIS patients watchful neurological supervision is indispensable.

CSF-Progranulin and Neurofilament Light Chain Levels in Patients With Radiologically Isolated Syndrome-Sign of Inflammation.

Background: Cerebrospinal fluid (CSF) markers of disease in patients with radiologically isolated syndrome (RIS) are the subject of intense investigation, because they have the potential to enhance our understanding of the natural disease course and provide insights into similarities and differences between RIS and other multiple sclerosis (MS) disease identities.Methods: Here we compared neurofilament light chain (NFL) and progranulin (PGRN) levels in the CSF in RIS patients with levels in patients with different subtypes of MS and healthy controls (HC) using Kruskal–Wallis one-way analysis of variance.Results: Median CSF NFL concentrations in RIS patients did not differ to those in HC and clinically isolated syndrome (CIS) patients, but were significantly lower than in relapsing remitting (RRMS) and primary progressive (PPMS) MS patients. In contrast, RIS patients exhibited higher median CSF PGRN levels than HC and showed no significant differences compared with CIS, RRMS, and PPMS cases.Conclusion: We postulate that elevated PGRN values in the CSF of RIS patients might indicate inflammatory and repair activity prior to axonal disintegration.

Should Spinal MRI Be Routinely Performed in Patients With Clinically Isolated Optic Neuritis?

Should Spinal MRI Be Routinely Performed in Patients With Clinically Isolated Optic Neuritis?

Decision-making on radiologically isolated syndrome among Argentinean neurologists: A survey based on clinical experience

BackgroundAlthough management of radiologically isolated syndrome (RIS) is still a challenge in clinical practice, in the absence of evidence-based guidelines, the report of survey results might give neurologists some guidance to optimize clinical decision-making. Our aim was to investigate the current RIS management approach of Argentinean neurologists based on their clinical experience. MethodsAn anonymous voluntary cross-sectional web-based survey was performed by Argentinean neurologists. We developed questions based on a hypothetical patient with RIS. General agreement was defined as at least 75% of concordance in the answer to each particular question. ResultsSixty-six out of 91 (72%) neurologists completed the survey. There was general agreement on following up patients, performing further examinations and not treating RIS patients at presentation. In addition, participants agreed to perform a lumbar puncture to evaluate the presence of oligoclonal bands (OCB, 82%) and to order a spinal cord MRI (75.4%). During follow-up, there was agreement to perform brain (100%) and spinal (80%) MRI. A few participants would prescribe treatment to RIS patients with both Gd-negative and Gd-positive lesions on spinal MRI. In addition, if a brain Gd-positive lesion is observed at onset, 43.6% would prescribe treatment. During the follow-up, only 15.4% would initiate treatment in the absence of clinical symptoms, regardless of the examinations’ results. In those cases in which a treatment was prescribed, there was agreement in using injectable drugs (78.7%). ConclusionThese findings give us a first idea about Argentinean neurologists’ decision-making on this entity and may help in the development of a practice guideline.

Should we treat patients with radiologically isolated syndrome (RIS)? Comments

The presence of brain/spinal white matter lesions typical for multiple sclerosis (MS) in asymptomatic individuals is known as ‘radiologically isolated syndrome’ (RIS). Taking into account that RIS patients are at high risk of MS development, the understanding of mechanisms underlying its pathogenesis is of great importance. In order to investigate RIS-specific transcription signature we performed high-throughput RNA-sequencing in peripheral blood mononuclear cells (PBMCs) of 8 RIS patients and 8 age- and sex-matched healthy controls. We identified 57 differentially expressed genes (DEGs), which levels differed by more than 2 times when comparing RIS patients to healthy controls (FDR p value < 0.05). Gene ontology enrichment analysis in the "biological process" category revealed 16 signaling pathways significantly overrepresented by identified DEGs. The most significant changes in gene expression in PBMCs of RIS patients occur in pathways involved in regulation of the immune response, cytokine and chemokine signaling, cytokine production, and leukocyte migration. In general, analyzing the global transcriptome we demonstrated the dysregulation of immune processes in PBMCs of RIS patients, confirming the current assumption that RIS represents the preclinical stage and/or subclinical form of MS.

Cerebrospinal fluid chitinase-3-like protein 1 level is not an independent predictive factor for the risk of clinical conversion in radiologically isolated syndrome

Background: Younger age, male sex and presence of spinal cord lesion(s) increase the risk of conversion from radiologically isolated syndrome (RIS) to relapsing-remitting multiple sclerosis (RRMS). Elevated cerebrospinal fluid (CSF) chitinase-3-like protein 1 (CHI3L1) levels predict conversion from clinically isolated syndrome (CIS) to RRMS. Objective: To evaluate the prognostic value of CSF CHI3L1 in RIS patients for conversion to RRMS. Methods: We compared CSF CHI3L1 concentrations in RIS, CIS, RRMS and symptomatic controls (SCs). We analysed the influence of epidemiological, radiological and CSF parameters on the risk of clinical event. Results: A total of 211 patients (71 RIS, 48 CIS, 50 RRMS and 42 SC) were included. CSF CHI3L1 levels were lower in RIS than in RRMS and higher in RIS with positive CSF versus negative CSF and SC. The presence of at least one spinal cord lesion was the only independent predictor of faster conversion to RRMS. Association of high CSF CHI3L1 levels, positive CSF (presence of oligoclonal bands and/or an elevated IgG index) or four Barkhof criteria with any spinal cord lesion showed a tendency for reduced mean conversion time. Conclusion: CSF CHI3L1 correlates with positive CSF but is not an independent predictor of the risk of conversion from RIS to RRMS.

Evoked potentials and other guiding factors of conversion from radiologically isolated syndrome to definite multiple sclerosis

Objective: Radiologically Isolated Syndrome (RIS) has become a popular subject recently with quite a number of follow-up and other clinical studies being done. A consensus on the approach to the patient with RIS is being tried to be established. The aim of our study was to assess the role of visual evoked potential (VEP) and somatosensory evoked potential (SEP) as a guiding factor for the conversion from Radiologically Isolated Syndrome (RIS) to definite Multiple Sclerosis (MS). Material and methods: 49 RIS patients who were referred to GATA Haydarpasa Training Hospital Neurology Department between 2011-2015. All of the patients fullfillied the 2009 Okuda criteria for RIS and other differential diagnosis were excluded accordingly. VEP and SEP examinations made during the pre-MS RIS period were scanned retrospectively. For the VEP examination, the P100 latency and amplitudes, for the SEP examination, the P40 latency and amplitude was analysed. Results: 49 patients were included in this study, the mean time of follow-up was 21,8 months. 63% of patients were female, while 37% were male. The mean age was 31,2 years. Among the four patients with abnormal SEPs, MS developed in three of them (75%) over time. This is statistically significant (p = 0.011). VEP and/or SEP was abnormal in 8 patients and MS developed in 4 (50%) of those (p=0.017). The following factors have a positive statistically significant correlation with conversion to MS: Presence of active plaques (r=0.461, p<0.001), presence of more than 9 plaques (r=0.287, p=0.046), VEP and/or SEP pathologies (r=0.402, p=0.004) and number of plaques (r=0.309, p=0.031). The most important factor for the transformation is the presence of active plaque which increases the risk 8.1-fold. The second important factor seems to be the presence of VEP and/or SEP abnormality, but this factor does not reach statistical significance. Conclusion: In the conversion to MS risk from RIS, VEP- SEP examinations are important and should take its place in the follow-up of these patients.

Normal-appearing brain tissue analysis in radiologically isolated syndrome using 3 T MRI.

To date, it remains largely unknown whether there is in radiologically isolated syndrome (RIS) brain damage beyond visible T2 white matter lesions. We used single- voxel proton magnetic resonance spectroscopy and diffusion tensor imaging (3 T MRI) to analyze normal-appearing brain tissue regions in 18 RIS patients and 18 matched healthy controls. T2-hyperintense lesion volumes and structural brain volumes were also measured. The absolute metabolite concentrations and ratios of total N-acetylaspartate+N-acetylaspartyl glutamate (NAA), choline-containing compounds, myoinositol, and glutamine-glutamate complex to creatine were calculated. Spectral analysis was performed by LCModel. Voxelwise morphometry analysis was performed to localize regions of brain tissue showing significant changes of fractional anisotropy or mean diffusivity. Compared with healthy controls, RIS patients did not show any significant differences in either the absolute concentration of NAA or NAA/Cr ratio in mid-parietal gray matter. A trend toward lower NAA concentrations (–3.35%) was observed among RIS patients with high risk for conversion to multiple sclerosis. No differences in the other metabolites or their ratios were observed. RIS patients showed lower fractional anisotropy only in clusters overlapping lesional areas, namely in the cingulate gyrus bilaterally and the frontal lobe subgyral bilaterally (P < 0.001). Normalized brain and cortical volumes were significantly lower in RIS patients than in controls (P = 0.01 and P = 0.03, respectively). Our results suggest that in RIS, global brain and cortical atrophy are not primarily driven by significant occult microstructural normal appearing brain damage. Longitudinal MRI studies are needed to better understand the pathological processes underlying this novel entity.