Clinically Isolated Syndrome Research Articles

Association between dietary inflammatory index and risk of demyelinating autoimmune diseases.

Background: Considering limited data on the association between dietary inflammatory index (DII) and demyelinating autoimmune diseases, here, we studied this issue in the early diagnosed patients [e.g., preceding Multiple Sclerosis (MS) diagnosing level (Clinically Isolated Syndrome (CIS), and Radiologically Isolated Syndrome (RIS), MS, and Neuromyelitis Optica Spectrum Disorder (NMOSD)] using a case-control study among the Iranian population. Methods: A total of 291 subjects were selected as the cases (Patients with demyelinating autoimmune diseases including CIS, RIS, MS, and NMOSD, who were diagnosed less than six months before recruitment) and 297 others as controls. A 117-item semi-quantitative food frequency questionnaire (FFQ) was obtained from all of the participants and DII was calculated. Results: After controlling for potential confounders, adherence to a pro-inflammatory diet was associated with a higher risk of demyelinating autoimmune diseases (OR=2.05, 95% CI: 0.51, 3.58), EDSS (OR=2.02, 95% CI: 0.51, 3.53), active plaque (OR=1.90, 95% CI: 0.08, 3.71), higher lesion load (OR=2.11, 95% CI: 0.58, 3.64), LETM (OR=2.19, 95% CI: 0.27, 4.11), higher number of plaques (OR=2.11, 95% CI: 0.58, 3.64), and brain atrophy (OR=2.12, 95% CI: 0.57, 3.67). Conclusion: Our study suggests a possible link between the inflammatory potential of the diet and demyelinating autoimmune disease; however, further prospective cohort studies are needed to draw a causal link on this issue.

Therapeutic Plasma Exchange (TPE) Complications in Patients With Multiple Sclerosis (MS) and Clinically Isolated Syndrome (CIS): A Report From a Tertiary Center.

Therapeutic plasma exchange (TPE) is a conventional second-line treatment for patients with multiple sclerosis (MS) or clinically isolated syndrome with steroid-refractory relapses. MS and clinically isolated syndrome patients with a steroid-refractory relapse, who fulfilled the indications for TPE were enrolled in this study. An expert nurse recorded the data comprising age, sex, type of MS, disease modifying therapy, disease duration, relapse rate, vital signs at the beginning, during and at the end of each plasma exchange session, plasma exchange volume, normal saline volume, and TPE complications. Ultimately, the statistical association was estimated amongst the variables. A total of 122 cases were assessed. Twelve cases (9.8%) received plasmapheresis for the second time. The mean age was 32.2±8.7 years and 107 (87.7%) were female. In total, 609 plasma exchange sessions were completed. Hypotension and skin reaction were the most clinical complications. Hemoglobin loss and hypokalemia were the most laboratory complications. Fifty-four cases (44.3%) had no complications, 40 (32.8%) had 1 complication, 21 (17.2%) 2 complications, 6 (4.9%) had 3 complications, and 1 (0.8%) disclosed 4 complications. The relapse rate in the past 12 months and the mean plasma volume exchange were significantly different between the groups. We revealed that TPE could be considered as a safe second-line therapy in MS relapses. Hypotension, skin reaction, hemoglobin loss, and hypokalemia were the most complications of TPE in our patients.

Secondary Prevention in Radiologically Isolated Syndromes and Prodromal Stages of Multiple Sclerosis.

Following the extraordinary progress in the treatment of multiple sclerosis (MS), two major unmet needs remain: understanding the etiology of the disease and, hence, designing definitive cures (this perspective is neither at hand, nor it can be taken for granted that the etiologic targets will be readily treatable); the prevention of an overt and disabling disease, which seems to be a more realistic and pragmatic perspective, as the integration of genetic data with endophenotypes, MRI, and other biomarkers ameliorates our ability to identify early neuroinflammation. Radiologically isolated syndrome (RIS; diagnosed when the unanticipated MRI finding of brain spatial dissemination of focal white matter lesions highly suggestive of MS occurs in subjects without symptoms of MS, and with normal neurological examinations) and the recently focused “prodromal MS” are conditions at risk of conversion toward overt disease. Here, we explore the possibility of secondary prevention approaches in these early stages of neuroinflammation. RIS and prodromal MS are rare conditions, which suggest the importance of Study Groups and Disease Registry to implement informative clinical trials. We summarize ongoing preventive approaches in the early stages of the demyelinating process, especially in RIS conditions. Moreover, we highlight the importance of the biomarkers and the predictors of evolution to overt disease, which may be useful to select the individuals at risk of conversion to clinically isolated syndrome (CIS) and/or clinically definite MS. Finally, we illustrate the importance of the endophenotypes to test the frontline immunomodulatory approach for preventive strategies. Future investigations, especially in relatives of patients, based on MRI techniques and biological studies (better with integrated approaches) may provide opportunities to understand the MS early causal cascade and may help to identify a “therapeutic window” to potentially reverse early disease processes.

Multimodal Evoked Potentials as Potential Biomarkers of Disease Activity in Patients With Clinically Isolated Syndrome.

ObjectiveThere is an ongoing search for markers useful in monitoring and predicting disease activity at the early stage of multiple sclerosis (MS). The goals of this study were to prospectively evaluate the changes in parameters of multimodal evoked potentials (EP) and cognition within a 3-year follow-up period in patients with clinically isolated syndrome (CIS), and to assess the prognostic value of baseline findings with regard to the disease outcomes.MethodsIn 29 patients (20 women, nine men, mean age 31.1) multimodal (visual, brainstem auditory, somatosensory, event-related) EP and neuropsychological tests (NT) were performed at baseline (T0) and after 1 (T1) and 3 (T3) years. Their results were compared longitudinally between baseline, T1, and T3. Baseline results confirmed conversion of CIS into multiple sclerosis (MS) and disability level at T1 and T3 using multiple comparisons and a logistic regression model.ResultsApart from mean N13/P16 SEP (somatosensory evoked potentials) amplitude (lower at T1 and T3 than at baseline (T0 1.02 ± 0.37 μV, T1 0.90 ± 0.26 μV, T3 0.74 ± 0.32 μV, p < 0.05 for both comparisons), no significant changes of EP or NT parameters were found in longitudinal assessment. Baseline P300 Pz latency was longer for the patients with MS than for those with CIS at T1 (352.69 vs. 325.56 ms). No predictive value was shown for any of the analyzed baseline variables with regard to conversion from CIS into MS.SignificanceBaseline ERP abnormalities were associated with their short-term conversion into MS. ERP are worth considering in multimodal EP evaluation at the early stage of MS.

Changes in serum neurofilament light chain levels following narrowband ultraviolet B phototherapy in clinically isolated syndrome.

ObjectiveTo determine whether serum neurofilament light chain (sNfL) levels are suppressed in patients with the clinically isolated syndrome (CIS) following narrowband ultraviolet B phototherapy (UVB‐PT).MethodssNfL levels were measured using a sensitive single‐molecule array assay at baseline and up to 12 months in 17 patients with CIS, 10 of whom received UVB‐PT, and were compared with healthy control (HC) and early relapsing remitting multiple sclerosis (RRMS) group. sNfL levels were correlated with magnetic resonance imaging total lesion volume (LV) determined using icobrain version 4.4.1 and with clinical outcomes.ResultsBaseline median sNfL levels were significantly higher in the CIS (20.6 pg/mL, interquartile range [IQR] 13.7–161.4) and RRMS groups (36.6 pg/ml [IQR] 16.2–212.2) than in HC (10.7 pg/ml [IQR] 4.9–21.5) (p = .012 and p = .0002, respectively), and were strongly correlated with T2 and T1 LV at 12 months (r = .800; p = .014 and r = .833; p = .008, respectively) in the CIS group. Analysis of changes in sNfL levels over time in the CIS group showed a significant cumulative suppressive effect of UVB‐PT in the first 3 months (UVB‐PT −10.6% vs non‐UVB‐PT +58.3%; p = .04) following which the levels in the two groups converged and continued to fall.ConclusionsOur findings provide the basis for further studies to determine the utility of sNfL levels as a marker of neuro‐axonal damage in CIS and early MS and for assessing the efficacy of new therapeutic interventions such as UVB‐PT.

Evaluating Magnetic Resonance Diffusion Properties Together with Brain Volumetry May Predict Progression to Multiple Sclerosis

Although the gold standard in predicting future progression from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) consists in the McDonald criteria, efforts are being made to employ various advanced MRI techniques for predicting clinical progression. This study's main aim was to evaluate the predictive power of diffusion tensor imaging (DTI) of the brain and brain volumetry to distinguish between patients having CIS with future progression to CDMS from those without progression during the following 2 years and to compare those parameters with conventional MRI evaluation. All participants underwent an MRI scan of the brain. DTI and volumetric data were processed and various parameters were compared between the study groups. We found significant differences between the subgroups of patients differing by future progression to CDMS in most of those DTI and volumetric parameters measured. Fractional anisotropy of water diffusion proved to be the strongest predictor of clinical conversion among all parameters evaluated, demonstrating also higher specificity compared to evaluation of conventional MRI images according to McDonald criteria. Conclusion: Our results provide evidence that the evaluation of DTI parameters together with brain volumetry in patients with early-stage CIS may be useful in predicting conversion to CDMS within the following 2 years of the disease course.

Body mass index as a predictor of MS activity and progression among participants in BENEFIT

Background: There is a lack of studies on the association between obesity and conversion from a clinically isolated syndrome (CIS) to multiple sclerosis (MS). Objective: The aim of this study was to determine whether obesity predicts disease activity and prognosis in patients with CIS. Methods: Body mass index (BMI) at baseline was available for 464 patients with CIS in BENEFIT. Obesity was defined as BMI ⩾ 30 kg/m2 and normal weight as 18.5 ⩽ BMI < 25. Patients were followed up for 5 years clinically and by magnetic resonance imaging. Hazard of conversion to clinically definite (CDMS) or to 2001 McDonald criteria (MDMS) MS, annual rate of relapse, sustained progression on Expanded Disability Status Scale (EDSS), change in brain and lesion volume, and development of new brain lesions were evaluated. Results: Obese individuals were 39% more likely to convert to MDMS (95% CI: 1.02–1.91, p = 0.04) and had a 59% (95% CI: 1.01–2.31, p = 0.03) higher rate of relapse than individuals with normal weight. No associations were observed between obesity and conversion to CDMS, sustained progression on EDSS or magnetic resonance imaging (MRI) outcomes, except for a larger reduction of brain volume in obese smokers as compared to normal weight smokers (−0.82%; 95% CI: −1.51 to −0.12, p = 0.02). Conclusion: Obesity was associated with faster conversion to MS (MDMS) and a higher relapse rate.

T1/T2-weighted ratio in multiple sclerosis: A longitudinal study with clinical associations

BackgroundT1w/T2-w ratio has been proposed as a clinically feasible MRI biomarker to assess tissue integrity in multiple sclerosis. However, no data is available in the earliest stages of the disease and longitudinal studies analysing clinical associations are scarce. ObjectiveTo describe longitudinal changes in T1-w/T2-w in patients with clinically isolated syndrome (CIS) and multiple sclerosis, and to investigate their clinical associations. MethodsT1-w/T2-w images were generated and the mean value obtained in the corresponding lesion, normal-appearing grey (NAGM) and white matter (NAWM) masks. By co-registering baseline to follow-up MRI, evolved lesions were assessed; and by placing the mask of new lesions to the baseline study, the pre-lesional tissue integrity was measured. ResultsWe included 171 CIS patients and 22 established multiple sclerosis patients. In CIS, evolved lesions showed significant T1-w/T2-w increases compared to baseline (+7.6%, P < 0.001). T1-w/T2-w values in new lesions were lower than in pre-lesional tissue (-28.2%, P < 0.001), and pre-lesional tissue was already lower than baseline NAWM (-7.8%, P < 0.001). In CIS at baseline, higher NAGM T1-w/T2-w was associated with multiple sclerosis diagnosis, and longitudinal decreases in NAGM and NAWM T1-w/T2-w were associated with disease activity. In established multiple sclerosis, T1-w/T2-w was inversely correlated with clinical disability and disease duration. ConclusionA decrease in T1-w/T2-w ratio precedes lesion formation. In CIS, higher T1-w/T2-w was associated with multiple sclerosis diagnosis. In established multiple sclerosis, lower T1-w/T2-w values were associated with clinical disability. The possible differential impact of chronic inflammation, iron deposition and demyelination should be considered to interpret these findings.

Periventricular magnetisation transfer abnormalities in early multiple sclerosis

ObjectiveRecent studies suggested that CSF-mediated factors contribute to periventricular (PV) T2-hyperintense lesion formation in multiple sclerosis (MS) and this in turn correlates with cortical damage. We thus investigated if such PV-changes are observable microstructurally in early-MS and if they correlate with cortical damage. MethodsWe assessed the magnetisation transfer ratio (MTR) in PV normal-appearing white matter (NAWM) and in MS lesions in 44 patients with a clinically isolated syndrome (CIS) suggestive of MS and 73 relapsing-remitting MS (RRMS) patients. Band-wise MTR values were related to cortical mean thickness (CMT) and compared with 49 healthy controls (HCs). For each band, MTR changes were assessed relative to the average MTR values of all HCs. ResultsRelative to HCs, PV-MTR was significantly reduced up to 2.63% in CIS and 5.37% in RRMS (p < 0.0001). The MTR decreased towards the lateral ventricles with 0.18%/mm in CIS and 0.31%/mm in RRMS patients, relative to HCs. In RRMS, MTR-values adjacent to the ventricle and in PV-lesions correlated positively with CMT and negatively with EDSS. ConclusionPV-MTR gradients are present from the earliest stage of MS, consistent with more pronounced microstructural WM-damage closer to the ventricles. The positive association between reduced CMT and lower MTR in PV-NAWM suggests a common pathophysiologic mechanism. Together, these findings indicate the potential use of multimodal MRI as refined marker for MS-related tissue changes.

Oral contraceptives do not modify the risk of a second attack and disability accrual in a prospective cohort of women with a clinically isolated syndrome and early multiple sclerosis

Objective: To evaluate whether oral contraceptive (OC) use is associated with the risk of a second attack and disability accrual in women with a clinically isolated syndrome (CIS) and early multiple sclerosis (MS). Methods: Reproductive information from women included in the Barcelona CIS prospective cohort was collected through a self-reported cross-sectional survey. We examined the relationship of OC exposure with the risk of a second attack and confirmed Expanded Disability Status Scale of 3.0 using multivariate Cox regression models, adjusted by age, topography of CIS, oligoclonal bands, baseline brain T2 lesions, body size at menarche, smoking, and disease-modifying treatment (DMT). OC and DMT exposures were considered as time-varying variables. Findings were confirmed with sensitivity analyses using propensity score models. Results: A total of 495 women were included, 389 (78.6%) referred to ever use OC and 341 (68.9%) started OC before the CIS. Exposure to OC was not associated with a second attack (adjusted hazard ratio (aHR) = 0.73, 95% confidence interval (CI) = 0.33–1.61) or disability accrual (aHR = 0.81, 95% CI = 0.17–3.76). Sensitivity analyses confirmed these results. Conclusion: OC use does not modify the risk of second attack or disability accrual in patients with CIS and early MS, once considered as a time-dependent exposure and adjusted by other potential confounders.

The effects of HMG-CoA reductase inhibitors on disease activity in multiple sclerosis: A systematic review and meta-analysis

ObjectiveTo assess whether statins (3‑hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) exert disease-modifying effects in multiple sclerosis (MS). ApproachA systematic review and meta-analysis was performed including randomized-controlled clinical trials (RCTs) on statin use in MS. A random-effects model was applied to calculate pooled estimates and odds ratios (ORs) with corresponding 95% confidence intervals (CIs), when comparing patients treated with statins alone or adjunct to disease modifying treatment (DMT) to non-statin-treated patients. ResultsWe identified 7 RCTs including 789 patients with relapsing-remitting MS (RRMS), all of whom received additional DMT with IFN-β. Single identified RCTs in secondary-progressive MS (SPMS), clinically isolated syndrome (CIS) and optic neuritis (ON) were not meta-analyzed. In RRMS, add-on statin use was not associated with the risk of clinical relapse (OR=1.30, 95%CI: 0.901.87) or EDSS-progression from baseline, neither appeared related to the risk of new contrast-enhancing or T2 lesions (OR=1.28, 95%CI: 0.364.58), and the risk of whole-brain volume reduction on MRI. Add-on statins to IFN-β were safe and well-tolerated. In SPMS, stand-alone simvastatin led to significantly reduced annualized rate of whole-brain volume reduction. In CIS and ON, statins were associated with reduced risk for new T2 lesions and improved visual recovery, respectively. ConclusionsWe detected no benefit from statin treatment as add-on to IFN-β in RRMS. However, a potential beneficial effect in SPMS, CIS and ON deserves independent confirmation and further evaluation within adequately powered RCTs.

Antibodies to neurofilament light as potential biomarkers in multiple sclerosis

Background and objectiveThe concentration of neurofilament light (NfL) protein in cerebrospinal fluid (CSF) and blood is widely considered as a quantitative measure of neuro-axonal injury. Immune reactivity to NfL released...

Performance of the 2017 and 2010 Revised McDonald Criteria in Predicting MS Diagnosis After a Clinically Isolated Syndrome: A MAGNIMS Study.

To compare the performance of the 2017 revisions to the McDonald criteria with the 2010 McDonald criteria in establishing multiple sclerosis (MS) diagnosis and predicting prognosis in patients with clinically isolated syndrome (CIS) suggestive of MS. CSF examination and brain and spinal cord MRI obtained ≤5 months from CIS onset and a follow-up brain MRI acquired within 15 months from CIS onset were evaluated in 785 patients with CIS from 9 European centers. Date of second clinical attack and of reaching Expanded Disability Status Scale score (EDSS) ≥3.0, if they occurred, were also collected. Performance of the 2017 and 2010 McDonald criteria for dissemination in space (DIS), dissemination in time (DIT) (including oligoclonal bands assessment), and DIS plus DIT for predicting a second clinical attack (clinically definite MS [CDMS]) and EDSS ≥3.0 at follow-up was evaluated. Time to MS diagnosis for the different criteria was also estimated. At follow-up (median 69.1 months), 406/785 patients with CIS developed CDMS. At 36 months, the 2017 DIS plus DIT criteria had higher sensitivity (0.83 vs 0.66), lower specificity (0.39 vs 0.60), and similar area under the curve values (0.61 vs 0.63). Median time to MS diagnosis was shorter with the 2017 vs the 2010 or CDMS criteria (2017 revision, 3.2; 2010 revision, 13.0; CDMS, 58.5 months). The 2 sets of criteria similarly predicted EDSS ≥3.0 milestone. Three periventricular lesions improved specificity in patients ≥45 years. The 2017 McDonald criteria showed higher sensitivity, lower specificity, and similar accuracy in predicting CDMS compared to 2010 McDonald criteria, while shortening time to diagnosis of MS. This study provides Class II evidence that the 2017 McDonald Criteria more accurately distinguish CDMS in patients early after a CIS when compared to the 2010 McDonald criteria.

Cerebrospinal Fluid IgM and Oligoclonal IgG Bands in Multiple Sclerosis: A Meta-Analysis of Prevalence and Prognosis.

The presence of intrathecal IgM synthesis (ITMS) has been associated with an aggressive multiple sclerosis (MS) clinical course. In the present systematic review, we aimed at assessing the prevalence of ITMS among different MS phenotypes. Moreover, we aimed at quantifying the risk of a second relapse in ITMS positive and oligoclonal IgG bands (OCGBs)-positive patients. We selected clinical studies reporting the ITMS prevalence assessed as oligoclonal IgM Bands (OCMBs), lipid-specific OCMBs (LS-OCMBs), and/or as an intrathecal IgM production > 0% (IgMLoc, Reiber formula). The overall prevalence of ITMS was higher in relapsing-remitting (RR) than clinically isolated syndrome (CIS) patients (40.1% versus 23.8%, p < 0.00001), while was in line with that detected in primary progressive MS (PPMS, 26.7%). Almost all patients (98%) with ITMS had also OCGBs. The risk of having a second relapse was higher in OCGBs positive patients (HR = 2.18, p = 0.007) but much higher in ITMS positive patients (HR = 3.62, p = 0.0005). This study revealed that the prevalence of ITMS is higher in RRMS patients. It suggests that the risk of having a second relapse, previously ascribed to OCGBs, may, to a certain extent, be related to the presence of intrathecal IgM.

Activation of NLRP1 and NLRP3 Inflammasomes in Multiple Sclerosis and Clinically Isolated Syndrome

Objective: Multiple sclerosis (MS) is a chronic, inflammatory and neurodegenerative disease characterized with demyelination and axonal damage in central nervous system (CNS). Inflamasomes, which are important part of this inflammatory process, regulate maturation of proinflammatory cytokines. Infamazom complexes are thought to increase in MS attacks. We investigated role of inflammasome complexes (nod-like receptor protein 1 and 3) in serum and cerebrospinal fluid (CSF) levels for MS development.&#x0D; Methods: Eighteen clinically isolated syndrome (CIS), 19 relapsing remitting multiple sclerosis (RRMS) and 20 healthy control cases were included in the study. Nod-like receptor protein 1 and 3 (NLRP1, NLRP3), inflammasome complex levels and oligoclonal band (OCB) patterns of all the groups were measured in serum and CSF samples using Enzyme-Linked Immuno Sorbent Assay (ELISA) method.&#x0D; Results: Although NLRP1 and NLRP3 levels in both RRMS and CIS patients measured in serum and CSF were significantly higher than healthy control group, there was no statistically significant difference between RRMS and CIS patients. On the other hand, the levels of NLRP1 and NLRP3 in CSF were significantly higher in OCB pattern positive patients compared to the OCB pattern negative patients.&#x0D; Conclusion: In this pilot study, it is shown that NLRP1 and NLRP3 inflammasome complexes increased in CSF samples of MS cases and that this tendency occurred during or maybe before the first MS attack. As a result, it was thought that these complexes may have an effect on the formation of the OCB band.

Type I interferon therapies of multiple sclerosis and hepatitis C virus infection

Abstract Interferons type I (IFN-I), activated following a bacterial or viral infection, play a major role in the induction and regulation of the immune system. The immune response results in viral RNA and binds to receptors such as RIG-I-like receptors (RLRs) or Toll-like receptors, leading to the IFN-I signaling cascade. Thanks to its cellular function, IFN-I is widely used in therapies for such diseases as multiple sclerosis (MS) and hepatitis C disease (HCD). MS is a neurological, autoimmune, chronic inflammatory disease of the central nervous system (CNS). During MS, nerve cell demyelination is observed due to the myelin heaths and oligodendrocyte damage. As a result, neuronal signal and neuron communication are attenuated. The mechanism of MS is still unknown. MS therapy applies interferon-β (IFN-β). IFN-β therapy has been used since the last century, but the therapeutic mechanism of IFN-β has not been completely understood. MS can lead to four syndromes: clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), primary progressive MS (PPMS), and secondary progressive MS (SPMS). HCD occurs as a result of infection with the hepatitis C virus (HCV), belonging to the Flaviviridae family. HCV is a blood-borne virus with a positive single-stranded RNA. A vaccine for HCV is not available yet. HCD can lead to liver damage or cancer. In HCD interferon-α therapy (IFN-α) is applied. As with MS, the mechanism of IFN-α therapy is not completely known.

Quality of life in individuals newly diagnosed with multiple sclerosis or clinically isolated syndrome.

Little is known about quality of life (QOL) at the time of multiple sclerosis (MS) or clinically isolated syndrome (CIS) diagnosis and how it evolves in the critical adjustment period immediately following a new diagnosis. To (1) describe QOL trajectory in the first year post-MS/CIS diagnosis and (2) examine associations of demographic and biopsychosocial factors with QOL at baseline and as it evolves over the first year post-MS/CIS diagnosis. Participants were N = 250 individuals newly diagnosed with MS or CIS. Participants completed self-report assessments of QOL, demographics, and biopsychosocial factors at 1, 2, 3, 6, 9, and 12months post-diagnosis using validated measures. At 1-month post-diagnosis, QOL M = 75.2/100 with subsequent assessments revealing consistent ratings on average. Modelling revealed a small number of variables that were predictive of QOL at baseline and/or change in QOL over time. QOL in the first year post-MS/CIS diagnosis was, on average, high and stable. A subset of modifiable factors across the biopsychosocial spectrum was associated with baseline level of QOL and change in QOL over time. The stability in QOL suggests that patients can be assessed early after diagnosis for key variables that are predictive of both current and future QOL.

Characterizing 1-year development of cervical cord atrophy across different MS phenotypes: A voxel-wise, multicentre analysis

Background: Spatio-temporal evolution of cord atrophy in multiple sclerosis (MS) has not been investigated yet. Objective: To evaluate voxel-wise distribution and 1-year changes of cervical cord atrophy in a multicentre MS cohort. Methods: Baseline and 1-year 3D T1-weighted cervical cord scans and clinical evaluations of 54 healthy controls (HC) and 113 MS patients (14 clinically isolated syndromes (CIS), 77 relapsing-remitting (RR), 22 progressive (P)) were used to investigate voxel-wise cord volume loss in patients versus HC, 1-year volume changes and clinical correlations (SPM12). Results: MS patients exhibited baseline cord atrophy versus HC at anterior and posterior/lateral C1/C2 and C4–C6 (p < 0.05, corrected). While CIS patients showed baseline volume increase at C4 versus HC (p < 0.001, uncorrected), RRMS exhibited posterior/lateral C1/C2 atrophy versus CIS, and PMS showed widespread cord atrophy versus RRMS (p < 0.05, corrected). At 1 year, 13 patients had clinically worsened. Cord atrophy progressed in MS, driven by RRMS, at posterior/lateral C2 and C3–C6 (p < 0.05, corrected). CIS patients showed no volume changes, while PMS showed circumscribed atrophy progression. Baseline cord atrophy at posterior/lateral C1/C2 and C3–C6 correlated with concomitant and 1-year disability (r = −0.40/–0.62, p < 0.05, corrected). Conclusions: Voxel-wise analysis characterized spinal cord neurodegeneration over 1 year across MS phenotypes and helped to explain baseline and 1-year disability.

CSF inflammatory profile in clinically isolated syndrome and definite multiple sclerosis patients

Clinically isolated syndrome (CIS) characterizes the first episode of multiple sclerosis (MS). IgG oligoclonal bands (OCBs) and high levels of inflammatory factors in CSF represent promising biochemical markers of CIS and MS. Here we evaluated the levels of a complex panel of CSF inflammatory mediators in CIS and relapsing-remitting MS (RRMS) patients at time of diagnosis, both with and without OCB, compared with a control group.

Progression independent of relapse activity in early multiple sclerosis patients

Disability accrual in multiple sclerosis (MS) may occur as relapse-associated worsening (RAW) or progression independent of relapse activity (PIRA). We investigated the contribution of RAW and PIRA to confirmed disability accumulation (CDA) in patients with clinically isolated syndrome (CIS) and early relapsing-remitting (RR) MS.