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Objective: To explore the long-term outcomes of patients with clinically isolated syndromes from the Barcelona cohort. Methods: We selected patients with a follow-up longer than 10 years to (1) estimate the risks of multiple sclerosis (MS) and disability accumulation according to the baseline number of T2 lesions and to compare treated versus untreated patients and early versus delayed treatment, and (2) to study baseline features of patients with aggressive MS (Expanded Disability Status Scale (EDSS) ⩾6.0 at 10 years). Results: In all, 401 patients were included (mean follow-up of 14.4 (standard deviation of 2.9) years). A higher number of T2 lesions was associated with an earlier MS diagnosis and an earlier risk of irreversible disability. Early treatment was associated with a decreased risk of EDSS of 3.0: adjusted hazard ratio = 0.4, 95% confidence interval = (0.2, 0.7). Patients with aggressive MS differed in their baseline brain magnetic resonance images: The median (interquartile range) number of T2 lesions and contrast-enhancing lesions (CEL) was 71 (28–95) versus 7 (1–19) and 3 (1–24) versus 0 (0–1), respectively. The cut-offs that better classified patients with aggressive MS were 20 for T2 lesions and 2 for CEL. Conclusion: Although MS natural history is changing, a high lesion load at onset is helpful to identify patients at risk of presenting an aggressive MS. [ABSTRACT FROM AUTHOR]

Background: Brain atrophy is a known marker of irreversible tissue damage in multiple sclerosis (MS). Cerebrospinal fluid (CSF) osteopontin (OPN) and neurofilament light chain (NF-L) have been proposed as candidate surrogate markers of inflammatory and neurodegenerative processes in MS. Objective: To evaluate the relationship between CSF NF-L and OPN levels and brain grey and white matter volumes in patients with clinically isolated syndrome (CIS) suggestive of MS. Methods: A total of 41 CIS patients and 30 neurological controls (NCs) were included. CSF NF-L and OPN were measured by commercial ELISA. Measures of brain volume (normalized brain volume (NBV), normalized grey matter volume (NGV), peripheral grey matter volume (PGV), normalized white matter volume (WMV), and ventricular volume) were obtained by SIENAX. Corpus callosum index (CCI) was calculated. Brain volumes were categorized into ‘high’ and ‘low’ according to the median value. Results: CSF NF-L and OPN levels were higher in CIS patients in comparison with NCs. CIS patients with ‘low’ TGV, PGV, and TBV showed higher CSF NF-L levels than CIS patients with ‘high’ brain volumes. TGV and PGV correlated inversely with NF-L levels, whereas CCI was inversely related to OPN levels. CSF NF-L was the only independent predictor of TGV and PGV. Conclusion: CSF NF-L tracks mainly grey matter damage in patients with CIS suggestive of MS. [ABSTRACT FROM AUTHOR]

This study used quantitative MRI to study normal appearing white matter (NAWM) in patients with clinically isolated syndromes suggestive of multiple sclerosis and relapsing-remitting multiple sclerosis (RRMS). This was done at ultrahigh field (7 T) for greater spatial resolution and sensitivity. 17 CIS patients, 11 RRMS patients, and 20 age-matched healthy controls were recruited. They were scanned using a 3D inversion recovery turbo field echo sequence to measure the longitudinal relaxation time ( T1). A 3D magnetization transfer prepared turbo field echo (MT-TFE) sequence was also acquired, first without a presaturation pulse and then with the MT presaturation pulse applied at −1.05 kHz and +1.05 kHz off resonance from water to produce two magnetization transfer ratio maps (MTR(−) and MTR(+)). Histogram analysis was performed on the signal from the voxels in the NAWM mask. The upper quartile cut-off of the T1 histogram was significantly higher in RRMS patients than in controls ( p < 0.05), but there was no difference in CIS. In contrast, MTR was significantly different between CIS or RRMS patients and controls ( p < 0.05) for most histogram measures considered. The difference between MTR(+) and MTR(−) signals showed that NOE contributions dominated the changes found. There was a weak negative correlation ( r = −0.46, p < 0.05) between the mode of T1 distributions and healthy controls' age; this was not significant for MTR(+) ( r = −0.34, p > 0.05) or MTR(−) ( r = 0.13, p > 0.05). There was no significant correlation between the median of T1, MTR(−), or MTR(+) and the age of healthy controls. Furthermore, no significant correlation was observed between EDSS or disease duration and T1, MTR(−), or MTR(+) for either CIS or RRMS patients. In conclusion, MTR was found to be more sensitive to early changes in MS disease than T1. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Natural history studies have identified factors that predict evolution to multiple sclerosis or risk of disability accumulation over time. Although these studies are based on large multicentre cohorts with long follow-ups, they have limitations such as lack of standardized protocols, a retrospective data collection or lack of a systematic magnetic resonance imaging acquisition and analysis protocol, often resulting in failure to take magnetic resonance and oligoclonal bands into account as joint covariates in the prediction models. To overcome some of these limitations, the aim of our study was to identify and stratify baseline demographic, clinical, radiological and biological characteristics that might predict multiple sclerosis development and disability accumulation using a multivariate approach based on a large prospective cohort of patients with clinically isolated syndromes. From 1995 to 2013, 1058 patients with clinically isolated syndromes were included. We evaluated the influence of baseline prognostic factors on the risk for developing clinically definite multiple sclerosis, McDonald multiple sclerosis, and disability accumulation (Expanded Disability Status Scale score of 3.0) based on univariate (hazard ratio with 95% confidence intervals) and multivariate (adjusted hazard ratio with 95% confidence intervals) Cox regression models. We ultimately included 1015 patients followed for a mean of 81 (standard deviation = 57) months. Female/male ratio was 2.1. Females exhibited a similar risk of conversion to multiple sclerosis and of disability accumulation compared to males. Each younger decade at onset was associated with a greater risk of conversion to multiple sclerosis and with a protective effect on disability. Patients with optic neuritis had a lower risk of clinically definite multiple sclerosis [hazard ratio 0.6 (0.5-0.8)] and disability progression [hazard ratio 0.5 (0.3-0.8)]; however, this protective effect remained marginal only for disability [adjusted hazard ratio 0.6 (0.4-1.0)] in adjusted models. The presence of oligoclonal bands increased the risk of clinically definite multiple sclerosis [adjusted hazard ratio 1.3 (1.0-1.8)] and of disability [adjusted hazard ratio 2.0 (1.2-3.6)] independently of other factors. The presence of 10 or more brain lesions on magnetic resonance increased the risk of clinically definite multiple sclerosis [adjusted hazard ratio 11.3 (6.7-19.3)] and disability [adjusted hazard ratio 2.9 (1.4-6.0)]. Disease-modifying treatment before the second attack reduced the risk of McDonald multiple sclerosis [adjusted hazard ratio 0.6 (0.4-0.9)] and disability accumulation [adjusted hazard ratio 0.5 (0.3-0.9)]. We conclude that the demographic and topographic characteristics are low-impact prognostic factors, the presence of oligoclonal bands is a mediumimpact prognostic factor, and the number of lesions on brain magnetic resonance is a high-impact prognostic factor. [ABSTRACT FROM AUTHOR]

Beta-interferon use in definite multiple sclerosis (MS) has been proven to modify clinical and magnetic resonance imaging outcome. We review and summarize the data of published double-blind, randomized clinical trials to assess, with a meta-analysis the safety and efficacy of beta-interferon on the occurrence of relapses in patients with a first clinical event suggestive of MS. After two years of follow-up, interferon beta decreased the risk of conversion to clinically definite MS 0.51[0.39-0.65], and delayed the time to diagnosis up to 367 days. Side-effects were mild and self limited. Our findings support the efficacy of early treatment with beta-interferon in reducing conversion to clinically defined MS in patients with clinically isolated syndromes.Já é suficientemente conhecido que a utilização de interferon beta modifica o prognóstico clínico e de ressonância magnética em pacientes com esclerose múltipla (EM). Revisamos e sumarizamos os dados dos ensaios clínicos, duplo-cegos, randomizados e controlados com placebos para analisar, através de meta-análise, a segurança e eficácia dos interferons-beta sobre a ocorrência de recidivas em pacientes com um primeiro evento clínico sugestivo de EM. Após dois anos de seguimento, os interferons-beta diminuíram o risco de conversão para EM clinicamente definida 0,51[0,39-0,65] e retardaram o tempo para diagnóstico em 367 dias. Os efeitos colaterais foram leves e auto limitados. Nossos dados comprovam a eficácia e segurança do interferon-beta em reduzir a conversão para EM clinicamente definida de pacientes com síndromes clínicas isoladas.

Background: Some patients with Guillain-Barré syndrome (GBS) also have acquired demyelination of the central nervous system (CNS) (i.e. acquired demyelinating syndrome, ADS). Often, the overlap of GBS and ADS is overlooked. Therefore, we evaluated case reports of GBS/ADS overlap syndrome. Methods: We mainly performed website-based research based on articles in cases presented with GBS/ADS overlap syndrome. A total of 66 cases were included. Clinical and prognosis data were analyzed. Results: A total of 85% of patients with simultaneous or consecutive occurrence of GBS and ADS were identified within 4 weeks of the initial diagnosis. Transverse myelitis (TM) (32%) was the most common ADS found in GBS/ADS. Patients with Miller Fisher syndrome (MFS)/ADS overlap syndrome had greater female predominance, mean age, frequency of onset at the same time period, or within a short period, and percentage of sole involvement of the subtentorial region. The outcome was favorable based on the functional status in 74% of patients. The sensory level (OR = 0.182, 95% CI = 0.055-0.598; P = 0.005) was the best predictor of a poor outcome, while visual deficit (OR = 4.667, 95% CI = 1.187-18.352; P = 0.027) predicted a favorable outcome. Conclusion: The ADS in GBS are diverse, CNS demyelinating may occur at any time, but early in the GBS course (and vice versa). MFS/ADS overlap syndromes is more common. The prognosis is generally good, but patients with sensory level deficit are likely to have a poor prognosis. The features of MFS/other CIS may better reflect involvement of the brainstem in MFS itself, rather than ADS in autoimmune peripheral neuropathies. [ABSTRACT FROM AUTHOR]

Context High serum cholesterol is adversely associated with clinical and imaging disease progression outcomes in multiple sclerosis (MS) and in clinically isolated syndrome (CIS), the earliest stage of MS. Low vitamin D levels are associated with an increased risk of disease progression. Objectives To investigate the mechanisms mediating the adverse effects of cholesterol in CIS and to determine the role of the nexus between the vitamin D 3 (D 3 ) and cholesterol pathways. Design Multi-center, prospective, longitudinal prospective study. Setting University hospital multiple sclerosis centers. Intervention Serum samples were obtained prior to any treatment from study subjects. Methods Serum obtained prior to any treatment from 172 CIS patients enrolled in a multi-center, prospective, longitudinal study (119 females: 53 males, age: 28.1 ± SD 8.1 years) were analyzed for high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein AI (ApoAI), ApoAII, ApoB, ApoE, and lipoprotein-a. Levels of 25-hydroxy vitamin D 3 (25(OH)D 3 ), 1,25-dihydroxy D 3 , and 24,25-dihydroxy D 3 were measured using liquid chromatography–mass spectrometry. Results Greater levels of HDL-C biomarkers (e.g., HDL-C itself, ApoAI, ApoAII and paroxonase arylesterase activity) and LDL-C biomarkers (e.g., LDL-C itself, Apo B) were associated with greater 25(OH)D 3 . The effects of HDL-C biomarkers were stronger than those of LDL-C. Free cholesterol and cholesteryl ester levels were positively associated with higher 25(OH)D 3 levels. Cholesterol palmitate was particularly potent. The nexus between the D 3 and cholesterol pathways was proximal to, or in linkage disequilibrium with, 7-dehydrocholesterol reductase DHCR7 rs1790349, endothelial lipase LIPG rs4939883 and proprotein convertase subtilisin/kexin type 9 PCSK9 rs11206510. Conclusions The associations between cholesterol biomarkers and vitamin D metabolite levels in CIS are consistent with the biochemical inter-dependence between the two pathways. Cholesterol biomarkers should be considered for inclusion as covariates when assessing vitamin D levels in CIS. [ABSTRACT FROM AUTHOR]

Background and purpose This study aims to explore the effectiveness of a brief, computerized battery of tests in detecting cognitive differences between clinically isolated syndromes ( CIS), relapsing−remitting multiple sclerosis ( RRMS), primary progressive multiple sclerosis ( PPMS) and secondary progressive multiple sclerosis ( SPMS) patients. Methods Four groups of patients between the ages of 18 and 63 were enrolled from two hospital-based multiple sclerosis clinics: CIS ( n = 42), RRMS ( n = 44), PPMS ( n = 15) and SPMS ( n = 37). All subjects were administered a validated battery of five computerized cognitive tests: the STROOP Color-Word Test, the Computerized Symbol Digit Modalities Test, the Paced Visual Serial Addition Test ( PVSAT) 4 s and 2 s trials, and a speed of cognition index obtained by subtracting simple reaction time from choice reaction time. Results were recorded by the test administrator. Results Significant between-group differences in cognition were evident on all tests ( P < 0.01) with the exception of the PVSAT 2 s trial. CIS patients were the least impaired, SPMS the most. RRMS and PPMS patients generally had a similar cognitive profile, more impaired than the CIS patients but less so than the SPMS patients. These differences persisted after controlling for the effects of age and education. Conclusions The ability of this computerized cognitive battery to distinguish the progression of cognitive deficits across the entire multiple sclerosis disease spectrum from CIS through to SPMS enhances its construct validity. This finding, coupled with the battery's brevity (20 min) and ease of administration, highlights its potential utility in a busy clinic setting. [ABSTRACT FROM AUTHOR]

MRI is highly sensitive in detecting focal white matter lesions in multiple sclerosis (MS). For this reason, it has been formally included in the diagnostic workup of patients with clinically isolated syndromes suggestive of MS, through the definition of ad hoc sets of criteria to show disease dissemination in space and time. MRI is used in virtually all clinical trials of the disease as a surrogate measure of treatment response. Several guidelines have been published to help characterizing the imaging features on conventional MR sequences of “typical” MS lesions and work has also been performed to identify “red flags” which should alert the clinicians to exclude possible alternative conditions. Despite this, the application of the available guidelines and criteria in daily life clinical practice is still limited and varies among and within countries (including Italy) due to regulatory issues and heterogeneity of MRI facilities. It is crucial for neurologists and neuroradiologists to become familiar with these criteria to improve the quality of their diagnostic assessment. In patients with established MS, the main problem is to define standard procedures for monitoring the course of the disease and treatment response. This review aims at providing daily life guidelines to clinicians for a correct application of MRI in the workup of patients suspected of having MS as well as in the monitoring of disease evolution in those with established MS. It also offers clues for the standardization of MRI studies and relative reporting to be applied at a national level. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To investigate whether anti-herpesvirus antibodies are associated with serum cholesterol profiles in clinically isolated syndromes (CIS). Methods: Pre-treatment serum samples from 118 high-risk CIS patients were analyzed for IgG antibodies against cytomegalovirus (anti-CMV), Epstein Barr virus (EBV) viral capsid antigen (VCA) and EBV nuclear antigen-1 (EBNA-1). A lipid profile consisting of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) was obtained. Clinical and MRI assessments were obtained at baseline, 6, 12, and 24months after start of interferon-beta treatment. Results: The study included 118 CIS patients (77 females, 41 males, 65.3% female; mean age: 28.1±SD 8.1years). Anti-EBV EBNA-1 antibody levels were associated with LDL-C (p =0.009) and TC (p =0.008) levels. Anti-CMV positivity status was associated with reduced time to relapse (p =0.006) and the greater number of relapses (p =0.009) in patients with high HDL-C. Anti-EBV VCA antibody levels were associated with greater number of new T2 lesions (p =0.002) and with increased brain atrophy (p <0.001) in patients with high LDL-C. Conclusions: Our results indicate that higher levels of anti-EBV EBNA-1 antibodies are associated with higher LDL-C and TC levels. Anti-CMV positive individuals have greater disease progression in the presence of higher HDL-C levels. Individuals with higher levels of anti-EBV VCA antibodies have greater progression on MRI measures in the presence of higher LDL-C. [Copyright &y& Elsevier]

The article presents a study which evaluated the new magnetic resonance imaging (MRI) criteria for multiple sclerosis (MS) diagnosis in patients having clinically isolated syndrome (CIS) in Buenos Aires, Argentina. New criteria accuracy, negative predictive value (NPV), positive predictive value (PPV), specificity and sensitivity were determined. The sub-analysis applied just to non-European descendants revealed a high level of accuracy for the new MRI criteria.

Abstract: Background: A clinically isolated syndrome (CIS) may be the initial presentation of multiple sclerosis (MS). However, some CIS never develop MS. The identification of patients at risk of MS conversion is crucial as early treatment may improve their outcome. Free kappa chains (FKC) are increased in cerebrospinal fluid (CSF) of MS patients. We studied the accuracy of CSF FKC level measurement, using a new nephelometric test, to predict conversion of CIS patients to MS. Methods: We calculated linearity and inter-assay variability of the FKC test for CSF values and quantified this protein in CSF from 25 patients with non-inflammatory neurological diseases (NIND) and 78 consecutive CIS patients. We assessed whether high CSF FKC levels associate with CIS conversion to clinically definite MS, defined as the onset of new relapses during follow-up. Results: Between 0.1 and 5mg/l the FKC test showed linearity of 0.98 and inter-assay correlation coefficient of =0.99. A cut-off value of 0.53mg/l (mean+2SD of NIND group CSF FKC values) was calculated. CIS patients with CSF FKC above this value showed earlier conversion to MS in univariate and multivariate Cox analysis (HR=6.41; 95% CI=1.88–21.78, p=0.003). Conclusion: High CSF FKC levels accurately predict CIS patient conversion to MS. [Copyright &y& Elsevier]

The purpose of this study was to determine the value of spinal cord lesions as a predictive factor for conversion in clinically isolated syndrome (CIS) patients. Patients with CIS and without immunomodulatory treatment were prospectively included. Age at onset, sex, clinical syndrome at onset, oligoclonal bands, and presence, number and location of lesions on brain and spinal MRI were analyzed. Conversion to multiple sclerosis (MS) was the primary endpoint. Cox regression was used to compare outcomes between groups. A total of 75 patients were included: 53 (71%) women, mean age at onset 32.7 years (SD ± 7.5), mean follow-up time 72.5 months (SD ± 9; range 17-104 months). There were 11 (14.6%) patients with one focal spinal cord lesion, while 13 (17%) patients had two or more spinal cord lesions at the first scan during the onset of the disease. Of the 23 patients (30.6%) who converted to clinically definite MS (CDMS), 2 had a normal spinal cord MRI, 8 patients had one spinal cord lesion, and 13 had more than one lesion on MRI ( p < 0.001). In multivariable analyses, one focal spinal cord lesion was significantly associated with increased risk of conversion to MS ( p = 0.01, HR 3.5, CI 95% 2.1-6.9), while the presence of two or more focal spinal cord lesions was independently associated with a higher risk of conversion to MS ( p < 0.001, HR 5.9, CI 95% 3.2-10.8). CIS patients with an abnormal baseline spinal cord MRI have a higher risk for developing clinically definite MS, independent of brain lesions as well as the presence of cerebrospinal fluid oligoclonal banding (OSF-OB) . [ABSTRACT FROM AUTHOR]

Background: Recently the International Panel on Diagnosis of Multiple Sclerosis (MS) has proposed new magnetic resonance imaging (MRI) criteria for the diagnosis of MS in patients with clinically isolated syndromes (CIS). We aimed to evaluate the accuracy of these new criteria for lesions dissemination in space (DIS) and time (DIT), from a single MRI scan, to predict conversion from CIS to clinically definite MS.Methods: We studied 67 CIS patients with baseline MRI performed within the first 3 months after onset. The follow-up was of at least 24 months. The sensitivity, specificity and accuracy of Barkhof–Tintoré criteria and the new proposed MRI criteria for DIS and DIT were calculated with SPSS v.15.0.Results: The mean age for clinical onset was 30 years and 64% of patients were female. The overall conversion rate was 74%. In our cohort, Barkhof–Tintoré criteria showed a sensitivity of 71.43%, a specificity of 66.67%, with an accuracy of 73.1%. New DIS criteria showed a sensitivity of 85.71%, a specificity of 64.71% and an accuracy of 80.30%. We also evaluated the new DIT criteria with a single MRI scan in 54 patients with baseline scans that included gadolinium-enhanced images. The sensitivity of the test was 52.63% with a specificity of 75.00% and an accuracy of 59.26%.Conclusion: New DIS criteria are simpler and more sensitive than previous criteria. The sensitivity of DIT criterion using a single MRI scan was rather low, as other previous studies showed, reflecting its stringency, but it could improve the accuracy of early MS diagnosis in that group of patients with typical CIS and gadolinium-enhancing and non-enhancing lesions on their baseline scans. These results reinforce their use in MS diagnosis. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: The presence of MRI lesions at the first demyelinating event increases the risk of developing clinically definite multiple sclerosis (MS). The HLA DRB1*1501 genotype is linked to MS susceptibility but its relationship to quantitative MRI parameters at the first demyelinating event has not been assessed. The objectives were to assess the associations between HLA DRB1*1501 status and magnetic resonance imaging (MRI) measures in clinically isolated syndromes (CIS) at the first demyelinating event. Methods: We genotyped 205 CIS patients (age: 29.0±7.7years) enrolled in the Observational Study of Early Interferon beta 1-a Treatment in High Risk Subjects after CIS (SET study), a multi-center, clinical study of CIS for rs3135005, a single nucleotide polymorphism associated with HLA DRB1*1501 status. The inclusion criteria required 2 or more brain MRI lesions and the presence of two or more oligoclonal bands in cerebrospinal fluid. Clinical and MRI assessments were obtained within 4months of the initial demyelinating event. Results: The frequency of HLA DRB1*1501 positivity was 102/205 (49.7%). HLA DRB1*1501 positivity was associated with higher contrast-enhancing (CE) lesion number (p =0.002), higher CE-lesion volume (LV) (p <0.001) and exhibited a trend with higher T2-LV (p =0.012). There was no evidence for significant associations of HLA DRB1*1501 positivity with disability, symptoms at CIS presentation, whole brain, white and gray matter atrophy. Conclusions: HLA DRB1*1501 positivity is associated with increased brain inflammatory processes at first clinical onset. However, the effect sizes of the HLA DRB1*1501 associations with MRI are modest, which potentially limits the clinical usefulness. [Copyright &y& Elsevier]

Object: While occurrence of motor cortical reorganization has been clearly demonstrated in patients with multiple sclerosis (MS), it is not yet clear whether this cortical reorganization constitutes a response to cortico-spinal lesions or to more diffuse damage affecting the neuronal network involved in motor act preparation, or both. We proposed to investigate the changes in the activation pattern during a simple motor task devoid of cortico-spinal dysfunction occurring in patients with clinically isolated syndrome (CIS) suggestive of MS. Materials and methods: Among 15 right-handed CIS patients, we selected eight patients with a preserved central motor pathway established by motor evoked potentials. Ten healthy right-handed gender- and age-matched volunteers were also included. After morphological MRI, subjects performed calibrated conjugated finger flexion and extension movements during fMRI acquision. Results: In CIS patients, simple movements of the non-dominant hand induced recruitment of the anterior cingulate cortex (BA32) usually involved in complex motor movements. This reorganization was correlated with the diffuse brain tissue damage (brain T lesion load). Conclusion: These results suggest that at least part of the cortical reorganization observed during very simple tasks in the earliest stage of MS occurs whether or not the efferent pathways are intact. [ABSTRACT FROM AUTHOR]

Background: Radiologically isolated syndrome (RIS) is characterized by patients with asymptomatic T2 hypersignals detected by brain MRI fulfilling dissemination in space criteria and is suggestive of subclinical multiple sclerosis (MS). In previous studies, it was demonstrated that visual evoked potential and cerebrospinal fluid help to identify pejorative markers in converting to MS. Objective: To date the cognitive function has never been investigated in a cohort of RIS. The objective of this study was to investigate cognitive function in a cohort of 26 RIS patients. Methods: We prospectively assessed the BCcogSEP (a French adaptation of the Brief Repeatable Battery (BRB) including eight cognitive tests) of 26 patients with RIS, compared with 26 MS patients and 26 healthy subjects matched for age, sex and level of education. Results: When comparing the three groups, the cognitive performance was significantly lower in the RIS and MS groups compared with healthy subjects for the Paced Auditory Serial Addition Test (PASAT) 3 seconds (p=0.002), phonemic fluencies (p=0.02), the code of the WAIS (p=0.05), the direct (p=0.002) or indirect (p=0.007) digit span test, the cross-taping test (p=0.019) and Go-No-Go (p=0.001). When we compared RIS and MS, the cognitive performance was significantly lower in MS patients for the direct span number (p=0.003) and cross-tapping test (p=0.05). We did not find significant differences between the three groups for the other tests. We did not find a correlation between clinical, biological and MRI results and cognitive dysfunctions. Conclusions: This study confirms the recently developed concept of RIS patients who present similar features to MS patients. Further studies are necessary to confirm these initial results and to correlate cognitive disorders with MRI surrogate markers. [ABSTRACT FROM AUTHOR]

The objective of the study was to evaluate whether the presence of oligoclonal bands (OB) adds information in predicting CIS conversion to clinical definite multiple sclerosis (CDMS) and conversion time to CDMS. From 1998 to 2006, CIS patients were included in a prospective study. Patients underwent brain MRI and OB determination within 2 months of the first demyelinating event. We analyzed conversion to CDMS and time to conversion to CDMS according to abnormal MRI and the presence of OB. Forty patients were included. Fifteen patients (37%) converted to CDMS; 14 of them (93.3%) had abnormal baseline MRI ( P = 0.01, RR = 5.9; 95% CI 1.3–10.1) and 13 (86.7%) had positive OB in CSF ( P = <0.01, RR = 5.3; 95% CI 1.6–9.5). The risk of conversion to CDMS in patients with positive OB and abnormal baseline MRI was significantly higher compared to patients negative for both tests or with only one positive (RR = 9.1; 95% CI 3.5–14.6). Time to conversion to CDMS was 6.8 ± 3.5 months for patients with OB and abnormal baseline MRI and 19 ± 14 months for patients with only one abnormal test. CIS patients with abnormal baseline OB in CSF have a higher risk for developing CDMS. Regarding conversion time to CDMS, when abnormal MRI was added to positive OB, patients converted faster (mean time, 6 vs. 19 months). This information may be useful when considering treatment in CIS patients. [ABSTRACT FROM AUTHOR]

Recognition of multiple sclerosis (MS) attacks relies mostly on clinical assessment. However, their definition based on McDonald criteria refers mostly to timing and when dealing with clinical features is rather ambiguous: “...of the kind seen in multiple sclerosis.” This is heightened in clinically isolated syndromes of the brainstem/cerebellum (CISB), where clinical manifestations can be manifold. This study aimed to describe the clinical features of patients with CISB to improve clinical recognition of patients with brainstem manifestations at the onset of their MS. To this end, we conducted a retrospective analysis of case notes of consecutively recruited patients with CISB assessed within 3 months of symptoms onset. Seventy-five patients were included. Most common brainstem-specific symptoms were: diplopia (68%), facial sensory symptoms (32%) and gait disturbance (31%). Adjusting for follow-up times, total number of symptoms and presence of other brainstem-specific symptoms, only the presence of facial sensory symptoms was predictive of (a lower risk of) conversion to clinically definite (CD) MS (Odds ratio: 0.086; p = 0.007). Neither the total number of brainstem-specific, non brainstem-specific nor the sum of both predicted conversion to CDMS. Results indicate that diplopia, facial sensory symptoms and gait disturbance occur in more than 30% of patients with CISB. Facial sensory symptoms are less associated with conversion to CDMS. [ABSTRACT FROM AUTHOR]

The MRI Barkhof-Tintoré criteria have proved to be highly specific for predicting conversion to clinically definite multiple sclerosis in patients with clinically isolated syndromes (CIS), but lacked an optimal sensitivity. In order to improve the accuracy of early multiple sclerosis diagnosis, new imaging criteria have been proposed by Swanton et al. We aimed to evaluate the accuracy of both MRI criteria for dissemination in space to predict conversion from CIS to clinically definite multiple sclerosis. We studied 79 CIS patients with baseline MRI performed within the first 3 months after onset. The sensitivity and specificity of both MRI criteria to predict conversion to clinically definite multiple sclerosis were analysed. The time to develop clinically definite multiple sclerosis from CIS onset, according to each imaging criteria, was studied by Kaplan-Meier survival curves. The overall conversion rate was 75.7% with a median follow-up of 57 months. Barkhof- Tintoré's criteria showed a sensitivity of 71.9% and a specificity of 77.2%. Swanton's criteria had a sensitivity of 91.2% and a specificity of 68.1%. Both MRI criteria identified CIS patients with higher risk and faster conversion to clinically definite multiple sclerosis. Swanton's criteria are simpler and more sensitive than Barkhof-Tintoré's criteria, with a slight decrease in specificity. These results reinforce their use in multiple sclerosis diagnosis. [ABSTRACT FROM AUTHOR]

Significant cognitive impairment has been found in 20-30% of patients with clinically isolated syndromes suggestive of multiple sclerosis. In this study we aimed to assess the prognostic value of the presence of cognitive impairment for the conversion to multiple sclerosis in patients with clinically isolated syndromes. All patients with clinically isolated syndromes consecutively referred to our centre since 2002 and who had been followed-up for at least one year underwent cognitive assessment through the Rao's Battery and the Stroop test. Possible predictors of conversion to clinically definite multiple sclerosis were evaluated through the Kaplan Meier curves and Cox regression analysis. A total of 56 patients (41 women; age 33.2±8.5 years; expanded disability scale score 1.2±0.7) were recruited. At baseline, 32 patients (57%) fulfilled McDonald's criteria for dissemination in space. During the follow-up (3.5±2.3 years), 26 patients (46%) converted to a diagnosis of multiple sclerosis. In particular, 64% of patients failing ≥2 tests and 88% of patients failing ≥3 tests converted to multiple sclerosis. In the Cox regression model, the failure of at least three tests (HR 3.3; 95% CI 1.4-8.1; p=0.003) and the presence of McDonald's dissemination in space at baseline (HR 3.8; 95% CI 1.5-9.7; p=0.005), were found to be predictors for conversion to multiple sclerosis. We conclude that cognitive impairment is detectable in a sizable proportion of patients with clinically isolated syndromes. In these subjects cognitive impairment has a prognostic value in predicting conversion to multiple sclerosis and may therefore play a role in therapeutic decision making. [ABSTRACT FROM AUTHOR]

Gray matter (GM) magnetic resonance imaging (MRI) T2 hypointensity, a putative marker of iron deposition, is a frequent finding in patients with clinically definite (CD) multiple sclerosis (MS). The objective of this study was to assess: (a) how early deep GM T2 hypointensity occurs in MS, by studying patients with clinically isolated syndromes (CIS) suggestive of MS, and (b) whether they contribute to predict subsequent evolution to CDMS. Dual-echo scans using two different acquisition protocols were acquired from 47 CIS patients and 13 healthy controls (HC). Normalized T2-intensity of the basal ganglia and thalamus was quantified. Patients were assessed clinically at the time of MRI acquisition and after three years. During the observation period, 18 patients (38%) evolved to CDMS. At the baseline, only the GM T2-intensity of the left caudate nucleus was significantly reduced in CIS patients in comparison with the HC (p=0.04). At the baseline, the T2 intensity of the left caudate nucleus was significantly lower (p=0.01) in CIS patients with disease dissemination in space (DIS), but not in those without DIS, compared to the HC. The baseline T2 lesion volume, but not GM T2 hypointensity, was associated with evolution to CDMS (hazard ratio=1.60, 95% confidence interval (CI)=1.05-2.42; p=0.02). In CIS patients, deep GM is not spared, suggesting that iron-related changes and neurodegeneration occurs early. The magnitude of such damage is only minor and not associated with an increased risk of evolution to CDMS. [ABSTRACT FROM AUTHOR]

Patients with clinically isolated syndrome (CIS) by definition do not have multiple sclerosis (MS) but are at risk of developing it. While studies show earlier immunomodulating drug use is effective, treatment must consider likely patient prognosis. In this paper we review current diagnosis, prognosis, and treatment literature for patients with CIS within Latin American clinical settings. Latin American MS experts, convened by ACINDES (The Civil Association for Research and Development in Health), reviewed current CIS (and early MS) literature and drew consensus conclusions. Three subgroups addressed separate questionnaires on CIS issues: prognosis, diagnosis, and treatment. MRI can contribute to predicting MS risk in patients with CIS; in Latin America, investigation of haplotype presence associated with CIS would be appropriate. McDonald's criteria and subsequent revisions enable earlier, more accurate MS diagnosis. Type A evidence exists supporting all leading immunomodulating MS drugs for effective treatment of CIS with a high risk of conversion to MS. In conclusion, patients with CIS are usually young, with often-limited symptomatic manifestations, and must be adequately prepared to receive preventive treatment. This consensus review should contribute to the dialogue between physicians and patients. [ABSTRACT FROM AUTHOR]

Abstract: In multiple sclerosis (MS) it is emerging that the most visible element of pathology, white matter (WM) lesions, represents only a fraction of the disease burden borne by the brain; non-lesional WM is also damaged, as is the grey matter (GM). Evidence is also accruing that GM damage may be a major determinant of longer-term outcomes in MS, and that such damage occurs from the earliest clinical stages of the disease. In this review, we focus on the early stages of relapse onset MS, considering the nature, extent and evolution of GM pathology, as determined using magnetic resonance imaging. [Copyright &y& Elsevier]

The prevalence of pathological laughing and crying in multiple sclerosis (MS) is 10%. It has been speculated that the anatomical lesion responsible for the pathological laughing is located in the pontine base, prefrontal cortex, and cerebellum. We report an 18-year-old male patient presenting with pathological laughing and hypomania. In his neurological examination, he had a euphoric effect with ataxic walking and dysarthria speech. He had a bilateral conjugated gaze limitation, with a prominent bilateral horizontal nystagmus on left gaze, dysmetria, dysdiadokokinesia, and remarkable dysfunction in a heel-to-shin test on the left. The IgG index in cerebrospinal fluid was normal with an oligoclonal band was present. In cranial MRI, there was a lesion on central pons which was hypointense in T1 images with contrast enhancement and hyperintense in T2 and flair images. Also another lesion in right brachium pontis which did not contrast enhancement but was hyperintense on T2 and flair images was present. There was an elevation of myoinositol/creatine ratio and choline and a reduction of NAA in proton MR spectroscopy. MR spectroscopic evaluation of the patient demonstrated the demyelination process. There has been no report of patients in whom pathological laughter was the presenting symptom of clinically isolated brainstem syndrome. [ABSTRACT FROM AUTHOR]

Background In multiple sclerosis, grey matter (GM) damage appears more clinically relevant than either white matter damage or lesion load. Objective We investigated if normal-appearing white matter (NAWM) and grey matter tissue changes assessed by magnetization transfer ratio were associated with long-term disability. Methods Sixty-nine people were assessed 20 years after presentation with a clinically isolated syndrome (CIS) [28 still CIS, 31 relapsing-remitting multiple sclerosis, 10 secondary progressive multiple sclerosis], along with 19 healthy subjects. Mean magnetization transfer ratio, peak height (PH) and peak location of the normalized magnetization transfer ratio histograms were determined in NAWM and grey matter, as well as, white matter and GM Fraction (GMF) and T2-weighted lesion load. Results Median expanded disability status scale for multiple sclerosis patients was 2.5 (range 1-8). GM-PH, and less so, NAWM mean and peak location, were lower in multiple sclerosis patients (P = 0.009) versus controls, relapsing-remitting multiple sclerosis versus CIS (P = 0.008) and secondary progressive multiple sclerosis versus relapsing-remitting multiple sclerosis (P = 0.002). GM-PH (as well as GMF) correlated with expanded disability status scale (rs = -0.49; P = 0.001) and multiple sclerosis functional score (rs = 0.51; P = 0.001). GM-PH independently predicted disability with similar strength to the associations of GMF with clinical measures. Conclusion Grey matter damage was related to long-term disability in multiple sclerosis cohort with a relatively low median expanded disability status scale. Markers of intrinsic grey matter damage (magnetization transfer ratio) and tissue loss offer clinically relevant information in multiple sclerosis. [ABSTRACT FROM AUTHOR]

This study investigated the presence of sub-clinical cognitive dysfunction in patients with clinically isolated syndrome (CIS) and the abnormalities of cognitive event-related potentials (ERPs). Subclinical cognitive dysfunction was assessed in 20 patients with CIS and in 20 healthy controls. Patients had impairments in verbal learning and long-term memory, evaluating attention, executive function and visuospatial skills, in decreasing order of frequency. SDLT and SIT were the most, and COWAT and BNT were the least affected tests. The N200 and P200 latencies were prolonged, and N100, N200 and P200 amplitudes were reduced in the patients relative to the controls, from the Fz, Cz and Pz electrode positions ( p<0.05). Detailed cognitive testing is valuable in determining subclinical cognitive dysfunction in CIS patients. ERP abnormalities as well as abnormalities in detailed cognitivetesting in patients with CIS are helpful in the diagnosis of sub-clinical cognitive dysfunction. [ABSTRACT FROM AUTHOR]

Basic disease-modifying treatment for relapsing forms of active multiple sclerosis (MS) is now available in many countries with high prevalence rates, for this chronic inflammatory disease of the central nervous system. Several lines of evidence support early immunomodulatory treatment with either recombinant interferon-beta or glatiramer acetate, and positive results from phase III trials encourage start of treatment even in patients with clinically isolated syndromes (CIS). However, currently available drugs for basic therapy are only partially effective and patients may still encounter relapses or disease progression. As treatment-refractory, clinically active MS can quickly lead to irreversible neurological disability there is an urgent need for effective escalating strategies. Patients with suboptimal treatment response to basic therapy have been treated with combination therapies, cytotoxic drugs (such as mitoxantrone and cyclophosphamide) or autologous hematopoietic stem cell transplantation. Recently, the monoclonal antibody, natalizumab, was added to this armamentarium. None of these strategies have been vigorously evaluated in large randomized, controlled phase III trials with patients who failed basic therapy. Therefore, the decision to escalate immunotherapy is still based on limited evidence. This article will review potential candidates for intensified immunosuppression and call for innovative study designs to better evaluate escalating immunotherapy in MS. [ABSTRACT FROM PUBLISHER]

High field magnetic resonance imaging (MRI) provides higher lesion load measurements in patients presenting with clinically isolated syndromes (CIS) suggestive of demyelination and has impact upon the classification of these syndromes and potentially, the diagnosis of multiple sclerosis (MS). To investigate whether high field MRI can provide an earlier diagnosis of definite MS within the International Panel (IP) and Swanton criteria. Forty patients presenting with CIS suggestive of MS were included. All patients received multi-sequence MRI at 1.5 Tesla (T) and 3T as well as a neurological assessment at baseline. Follow-up visits including MRI at both field strengths and neurological examinations were scheduled 3–4 and 6–7 months after the first clinical event. Based on MRI and clinical findings, fulfilled IP criteria as well as Swanton criteria were analysed. At baseline, the higher detection rate of inflammatory lesions using high field MRI leads to higher classifications according to the Swanton criteria in 15 % of the patients. One additional patient was diagnosed with dissemination in space according to Swanton and IP criteria. During follow-up, an earlier diagnosis of definite MS could not be accomplished, neither according to the IP nor to the Swanton criteria. Although high field MRI shows a higher detection rate of inflammatory brain lesion in CIS and MS patients with an influence according to MRI criteria, this influence does not lead to an earlier diagnosis of lesion dissemination in time and therefore definite MS. [ABSTRACT FROM AUTHOR]

Abstract: Demonstration of lesion dissemination in space (DIS) and time (DIT) is necessary for the diagnosis of multiple sclerosis (MS) in clinically isolated syndromes (CIS). The McDonald criteria accepted two methods to demonstrate DIS. The fulfillment of at least three of four MRI Barkhof criteria (MRI-BC) or, alternatively, the finding of at least two MRI lesions on T2-weighted images (T2 lesions) plus the presence of oligoclonal IgG bands (OCGB) in cerebrospinal fluid (CSF). We aimed to evaluate the accuracy of both methods for DIS demonstration to predict conversion of CIS to MS using a new OCGB test. We studied fifty-eight CIS patients with OCGB detection and brain MRI, and followed them up during 6 years. Twenty-eight patients fulfilled MRI-BC. Twenty-five of them converted to MS during follow-up (sensitivity 73.53%, specificity 87.50%, accuracy 79.31%). Thirty-four patients had at least two T2 lesions plus oligoclonal bands. Thirty-three converted to MS during follow-up (sensitivity 94.29%, specificity 95.65%, accuracy 94.82%). The presence of oligoclonal IgG bands plus two T2 lesions accurately predicts CIS conversion to MS. MRI-BC criteria have a high specificity but less sensitivity and accuracy. These results reinforce the role of CSF study in MS diagnosis. [Copyright &y& Elsevier]

The aim of this study was to determine the prognostic value of metabolic alterations in the normal-appearing white matter (NAWM) of patients presenting with clinically isolated syndromes (CIS) suggestive of multiple sclerosis (MS) with special regard to the prediction of conversion to definite MS. Using a 3T whole-body MR system, a multisequence conventional MRI protocol and single-voxel proton MR spectroscopy (PRESS, repetition time 2000 ms, echo times 38 ms and 140 ms) of the parietal NAWM were performed in 25 patients presenting with CIS at baseline and in 20 controls. Absolute concentrations of N-acetyl-aspartate (tNAA), myo-inositol (Ins), choline (Cho) and creatine (tCr) as well as metabolite ratios were determined. Follow-up including neurological assessment and conventional MRI was performed 3–4 and 6–7 months after the initial event. Nine patients converted to definite MS during the follow-up period. Compared to controls, those patients who converted to MS also showed significantly lower tNAA concentrations in the NAWM (−13.4%, P = 0.002) whereas nonconverters (−6.5%, P = 0.052) did not. The Ins concentration was 20.2% higher in the converter group and 1.9% higher in the nonconverter group, but these differences did not reach significance. No significant differences could be observed for tCr and Cho in either patient group. Axonal damage at baseline in patients presenting with CIS was more prominent in those who subsequently converted to definite MS in the short term follow-up, indicating that tNAA might be a sufficient prognostic marker for patients with a higher risk of conversion to early definite MS. [ABSTRACT FROM AUTHOR]

To prospectively investigate metabolic changes in the normal-appearing white matter (NAWM) of patients presenting with clinically isolated syndromes (CIS) suggestive of multiple sclerosis (MS) and to correlate these changes to conventional MR imaging findings in terms of MR imaging criteria. Multisequence MR imaging of the brain and 1H-MR spectroscopy of the parietal NAWM were performed in 31 patients presenting with CIS and in 20 controls using a 3. 0 T MR system. MR imaging criteria and International Panel criteria were assessed based on imaging, clinical and paraclinical results. Metabolite ratios and absolute concentrations of N-acetyl-aspartate (tNAA), myoinositol (Ins), choline (Cho), and total creatine (tCr) were determined. The metabolite concentrations were correlated with the fulfilled MR imaging criteria. In comparison to the control group, the CIS group showed significantly decreased mean tNAA concentrations (–8. 1%, p = 0. 012). Significant changes could not be detected regarding Ins, tCr and Cho. No significant correlations between absolute metabolite concentrations and MR imaging criteria were observed. Patients with and without a lesion dissemination in space showed no significant differences of their metabolite concentrations. As assessed by 1H-MRS a significant axonal damage already occurs during the first demyelinating episode in patients with CIS. Conventional MR imaging in terms of diagnostic imaging criteria does not significantly reflect NAWM disease activity in terms of metabolic alterations detected by 1H-MR spectroscopy. [ABSTRACT FROM AUTHOR]

Clinically isolated syndromes (CIS) classically refer to optic neuritis (ON), brainstem or spinal cord syndromes. Less common first episodes suggestive of central nervous system (CNS) demyelination, such as hemispheric or clinically polyregional syndromes, have been only slightly studied. The aim of this study was to describe these CIS topographies in our cohort of patient with a CIS. We evaluated 320 patients with a CIS, and classified the topographies of the attacks according to clinical symptoms only into CIS of the optic nerve (123), brainstem (78), spinal cord (89), hemispheric (6), polyregional (12) or undetermined (12) topographies. Patients underwent brain MRI within three months of their first attack, and again 12 months later. Conversion to multiple sclerosis (MS), determined either clinically or by magnetic resonance imaging (MRI), was evaluated according to topography. Hemispheric and polyregional syndromes were closer to brainstem or spinal cord syndromes than ON in clinical and MRI conversion terms, although a statistical analysis was not performed because of the small number of patients. There are differences between several studies in the definition, and, therefore, the prevalence of these so-called atypical CIS. Consensus on the denomination and definition of these syndromes must be reached. [ABSTRACT FROM AUTHOR]

Thirty patients with clinically isolated syndromes (CIS) were evaluated at the onset of neurological symptoms and when they developed clinically definite MS (CDMS). Surface expression of LFA-1α, VLA-4 and intercellular adhesion molecule-1 (ICAM-1) on PBMC and CSF cells was evaluated using flow cytometry. Serum and CSF concentrations of soluble vascular cell adhesion molecules-1 (VCAM-1), ICAM-1 and E-Selectin, as well as MMP-9 and MMP-2 serum concentrations were assayed using ELISA. Surface expression of LFA-1α and VLA-4 molecules on peripheral blood and CSF T cells and monocytes from CIS and CDMS was significantly increased compared with control subjects. Moreover, LFA-1α and VLA-4 expression was significantly higher in patients who developed CDMS compared with those with CIS. Similar changes were observed in the serum levels of MMP-9. Furthermore, patients with CIS and CDMS had significantly higher levels of CSF sVCAM and s-E-Selectin than control subjects. These data suggest that VLA-4, LFA-1α and MMP-9 play a leading role in the evolution of inflammatory demyelinating lesions in patients with CIS who develop CDMS. [Copyright &y& Elsevier]

CD4+ T-cell lines (TCLs) from patients with clinically isolated syndromes (CIS) were selected with purified human myelin basic protein (MBP) and recombinant human myelin oligodendrocyte glycoprotein (rhMOG), at onset of neurological symptoms and when patients developed clinically definite multiple sclerosis (CDMS). The epitope specificity of each TCL was mapped with overlapping synthetic peptides. TCLs were assessed for their ability to secrete IFN-γ, IL-4, and IL-6.Diverse patterns of epitope recognition were observed: (a) recognition of a broad spectrum of MBP peptide epitopes with evidence of shifts over time; (b) an initial T-cell response focused to a restricted segment of the MBP molecule (83–102) that broadened over the course of disease; and (c) persistence of a focused anti-MOG T-cell response. CIS patients who failed to develop CDMS maintained a focused epitope response against two to six MBP epitopes. Most MBP peptide-specific TCLs secreted considerable amounts of IFN-γ and low amounts of IL-4 and IL-6, whereas anti rhMOGIgd peptide-specific TCLs secreted preferentially IL-4 and IL-6. These data raise important issues for the pathogenesis and treatment of multiple sclerosis (MS). [Copyright &y& Elsevier]

Background and aim: Conversion to multiple sclerosis (MS) after optic neuritis and myelitis has been thoroughly studied; however, limited data are available regarding conversion to MS after a clinically isolated syndrome of the brainstem (CISB). The aim of this study was to investigate conversion to MS in patients with CISB. Methods: Fifty-one patients with CISB were prospectively studied. Cranial magnetic resonance imaging (MRI), determination of oligoclonal bands (OBs) in the cerebrospinal fluid (CSF) and evoked potentials (EPs) were performed. Based on conversion to MS at follow-up, the sensitivity, specificity, accuracy and positive and negative predictive values of these tests were calculated. Results: Clinically definite MS developed in 18 (35%) patients after a mean follow-up of 37 months. Paty's MRI criteria showed a sensitivity of 89%, a specificity of 52% and an accuracy of 65%; Fazekas' criteria showed a sensitivity of 89%, a specificity of 48% and an accuracy of 63%; Barkhof's criteria showed a sensitivity of 78%, a specificity of 61% and an accuracy of 67%. The presence of OBs in the CSF showed a sensitivity of 100%, a specificity of 42% and an accuracy of 63%. No differences for neurophysiological parameters were found between patients who did and those who did not convert to MS. Conclusion: Fulfilling Paty's, Fazekas' or Barkhof's MRI criteria and the presence of OBs in the CSF are associated with a higher risk of conversion to MS in patients with CISB. Determination of OBs in the CSF has the greatest sensitivity of all tests. Barkhof's MRI criteria have greater specificity (although less than previously published for mixed cohorts of clinically isolated syndromes) in predicting conversion to MS for CISB than either Paty's or Fazekas' criteria. [ABSTRACT FROM AUTHOR]

Aim of the study: To evaluate and compare the capacity of oligoclonal bands (OB) and three sets of MR imaging criteria to predict the conversion of clinically isolated syndromes (CIS) to clinically definite multiple sclerosis (CDMS). Patients and methods: One hundred and twelve patients with CIS were prospectively studied with MR imaging and determination of OB. Based on the clinical follow-up (conversion or not conversion to CDMS), we calculated the sensitivity, specificity accuracy, positive and negative predictive value of the OB, and MR imaging criteria proposed by Paty et al, Fazekas et al and Barkhof et al. Results: CDMS developed in 26 (23.2%) patients after a mean follow-up of 31 months (range 12 – 62). OB were positive in 70 (62.5%) patients and were associated with a higher risk of developing CDMS. OB showed a sensitivity of 81%, specificity of 43%, accuracy of 52%, positive predictive value (PPV) of 30% and negative predictive value (NPV) of 88%. Paty and Fazekas criteria showed the same results with a sensitivity of 77%, specificity of 51%, accuracy of 57%, positive predictive value of 32% and negative predictive value of 88%. Barkhof criteria showed a sensitivity of 65%, specificity of 70%, accuracy of 69%, PPV of 40% and NPV of 87%. The greatest accuracy was achieved when patients with positive OB and three or four Barkhof's criteria were selected. Conclusions: We observed a high prevalence of OB in CIS. OB and MR imaging (Paty's and Fazekas' criteria) have high sensitivity. Barkhof's criteria have a higher specificity. Both OB and MR imaging criteria have a high negative predictive value. [ABSTRACT FROM AUTHOR]

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