Clinically Definite Multiple Sclerosis Research Articles

Diagnostic value of visual evoked potentials for clinical diagnosis of multiple sclerosis.

Prolonged latency of visual evoked potentials (VEP) has been used to identify clinically silent lesions in multiple sclerosis (MS) suspects. The objective of this study was to determine the reliability of VEP to predict the development of MS in MS suspects. Retrospective hospital records of MS suspects were evaluated. VEP was analyzed together with subsequent diagnostic confirmation of MS by McDonald diagnostic criteria for MS-2005. MS developed in 12 of 35 patients (34 %) and 23 (66 %) failed to exhibit diagnostic characteristics. P100 latencies and interocular latency differences were longer in clinically definite multiple sclerosis (CDMS) than non-CDMS patients (p = 0.002, 0.001, respectively). All patients in the subsequent MS group had P100 latencies longer than102 ms, a mean of our MS-free subjects thus providing 100 % of sensitivity. No patient developed MS with a P100 latency <102 ms. Brain MRI lesions associated significantly with developing CDMS (p = 0.001). Predictability of developing CDMS was highest when criteria for P100 latency, interocular latency difference, and brain MRI lesions were combined. MS suspects with a P100 latency longer than mean of MS-free subjects are more likely to develop MS than those with lower values. VEP latency combined with MRI could improve the accuracy of MS prediction.

Early MRI activity predicts treatment nonresponse with intramuscular interferon beta-1a in clinically isolated syndrome

ObjectiveDetermine whether MRI activity 6 months after treatment initiation in the Controlled High-Risk Subjects Avonex® Multiple Sclerosis Prevention Study (CHAMPS) predicted progression to clinically definite multiple sclerosis (CDMS) over the subsequent 30 months in intramuscular interferon beta-1a (IM IFNβ-1a)-treated patients vs placebo-treated patients. MethodsCHAMPS patients were randomized to once-weekly IM IFNβ-1a 30μg or placebo for up to 36 months. MRI was performed every 6 months until CDMS confirmation. Patient groups were defined based on new T2 and/or Gd+ lesions at 6 months. ResultsThirteen IM IFNβ-1a patients (6.7%) and 24 placebo patients (12.6%) developed CDMS prior to month 6 and did not undergo the 6-month MRI. At 6 months, 29.7% of IM IFNβ-1a-treated patients vs 40.9% of placebo-treated patients were defined as having high MRI activity levels (≥2 new T2 and/or ≥2 Gd+ lesions). In this subgroup, estimated cumulative probabilities of CDMS were similar between groups (HR=0.88 [0.44–1.77], p=0.7227). A significant treatment response was seen for patients with <2 new T2 and <2 Gd+ lesions at 6 months (HR=0.39 [0.19–0.82], p=0.0120). ConclusionMRI scans 6 months after IM IFNβ-1a initiation in CIS patients predict early treatment non-response. Standardized scanning and monitoring may facilitate early disease management.

Fatigue at time of CIS is an independent predictor of a subsequent diagnosis of multiple sclerosis

ObjectiveFatigue is a common, disabling symptom of multiple sclerosis (MS), but little is known about fatigue in patients with clinically isolated syndrome (CIS), often the presenting symptom of MS. We...

Longitudinal MRI and neuropsychological assessment of patients with clinically isolated syndrome.

Cognitive impairment (CI) may occur in clinically isolated syndrome (CIS) patients. While the relationship between CI and magnetic resonance imaging (MRI) has been investigated extensively in multiple sclerosis (MS), MRI correlates of CI in CIS patients are unknown. To investigate the evolution of CI and to determine brain MRI structural correlates associated with CI in CIS patients. This prospective 24-month observational study examined 81 CIS patients treated with 30µg of intramuscular interferon beta 1a once a week. MRI acquisition and neuropsychological (NP) assessment were performed at baseline, 6, 12 and 24months. Participants were tested with Czech-validated version of Minimal Assessment of Cognitive Function in MS battery and MRI measures of lesion activity and burden, and global, tissue-specific and regional brain atrophy were performed. Over 24months, 36 CIS patients developed clinically definite MS (CDMS). CI was observed in 10 (12.3%) CIS patients at baseline and at the 24months follow-up. Eight CIS patients changed their CI status over the follow-up (four improved and four worsened). No significant difference in development of CI was detected between stable CIS patients and those who developed CDMS. In multivariate regression and mixed-effect model analyses, no significant relationship was found between NP and MRI parameters. The lack of significant relationship between MRI metrics and cognition in this group of CIS patients could be attributed to several factors including the cognitive reserve, effect of disease-modifying therapy and relatively short follow-up period.

An adverse lipid profile is associated with disability and progression in disability, in people with MS

Background: There is accumulating data suggesting an association between serum lipids, apolipoproteins and disability in multiple sclerosis (MS). Objectives: To investigate the associations between serum lipids, apolipoproteins and disability in MS. Methods: A cohort of 178 participants with clinically-definite MS in southern Tasmania, Australia were prospectively followed from 2002 – 2005, and serum samples were obtained at study entry and at each biannual review, to measure lipid profile and apolipoprotein levels. Associations with disability and annual change in disability were evaluated using linear regression and multilevel mixed-effects linear regression. Results: In the unadjusted analyses, nearly all lipid-related variables were positively associated with Expanded Disability Status Scale (EDSS). After adjustment for confounders, total cholesterol (TC) (p = 0.037), apolipoprotein B (ApoB) (p = 0.003), and the apolipoprotein B to apolipoprotein A-I ratio (ApoB/ApoA-I ratio) (p = 0.018) were independently associated with a higher EDSS. Higher body mass index (BMI) was also independently associated with higher EDSS (p = 0.013). With the progression analysis, the total cholesterol to high density lipoprotein (HDL) ratio (TC/HDL ratio) (p = 0.029) was prospectively associated with subsequent change in EDSS. Conclusion: In this prospective population-based cohort study, an adverse lipid profile was associated with high levels of MS disability and disease progression. Improving serum lipids may be beneficial for MS patients, to potentially improve clinical outcomes and vascular comorbidities.

Diagnostic value of brain chronic black holes on T1-weighted MR images in clinically isolated syndromes

Background: Non-enhancing black holes (neBHs) are more common in multiple sclerosis (MS) patients with longer disease durations and progressive disease subtypes. Objective: Our aim was to analyse the added value of neBHs in patients with clinically isolated syndromes (CISs) for predicting conversion to clinically definite MS (CDMS). Methods: Patients were classified based on the presence or absence of neBHs and on the number of Barkhof–Tintoré (B-T) criteria fulfilled. Dissemination in space (DIS) was defined as the presence of at least three of the four B-T criteria. Dissemination in time (DIT)1 was defined by simultaneous presence of enhancing and non-enhancing lesions. DIT2 was defined by simultaneous presence of neBHs and T2 lesions not apparent on T1-weighted images. Results: Focal T2-hyperintense brain lesions were identified in 87.7% of the 520 CIS patients, and 41.4% of them presented at least one neBH. Patients meeting DIS, DIT1, and DIT2 had a significantly higher rate of conversion to CDMS. After adjusting for DIS, only patients who fulfilled DIT1 preserved a significant increase in CDMS conversion. Conclusions: Non-enhancing black holes in CIS patients are associated with a higher risk of conversion to CDMS. However, the predictive value of this finding is lost when added to the DIS criteria.

Patient subgroup analyses of the treatment effect of subcutaneous interferon β-1a on development of multiple sclerosis in the randomized controlled REFLEX study

The REFLEX study (NCT00404352) established that subcutaneous (sc) interferon (IFN) β-1a reduced the risks of McDonald MS (2005 criteria) and clinically definite multiple sclerosis (CDMS) in patients with a first clinical demyelinating event suggestive of MS. The aim of this subgroup analysis was to assess the treatment effect of sc IFN β-1a in patient subgroups defined by baseline disease and demographic characteristics (age, sex, use of steroids at the first event, classification of first event as mono- or multifocal, presence/absence of gadolinium-enhancing lesions, count of <9 or ≥9 T2 lesions), and by diagnosis of MS using the revised McDonald 2010 MS criteria. Patients were randomized to the serum-free formulation of IFN β-1a, 44 μg sc three times weekly or once weekly, or placebo, for 24 months or until diagnosis of CDMS. Treatment effects of sc IFN β-1a on McDonald 2005 MS and CDMS in the predefined subgroups were similar to effects found in the intent-to-treat population. McDonald 2010 MS was retrospectively diagnosed in 37.7 % of patients at baseline. Both regimens of sc IFN β-1a significantly reduced the risk versus placebo of McDonald 2005 MS and CDMS, irrespective of McDonald 2010 status at baseline (risk reductions between 29 and 51 %). The effect of sc IFN β-1a was not substantially influenced by baseline patient demographic and disease characteristics, or baseline presence/absence of McDonald 2010 MS.

MRI correlates of disability progression in patients with CIS over 48 months.

BackgroundGray matter (GM) and white matter (WM) pathology has an important role in disease progression of multiple sclerosis (MS).ObjectivesTo investigate the association between the development of GM and WM pathology and clinical disease progression in patients with clinically isolated syndrome (CIS).MethodsThis prospective, observational, 48-month follow-up study examined 210 CIS patients treated with 30 µg of intramuscular interferon beta-1a once a week. MRI and clinical assessments were performed at baseline, 6, 12, 24, 36 and 48 months. Associations between clinical worsening [24-weeks sustained disability progression (SDP) and occurrence of a second clinical attack] and longitudinal changes in lesion accumulation and brain atrophy progression were investigated by a mixed-effect model analysis after correction for multiple comparisons.ResultsSDP was observed in 32 (15.2%) CIS patients, while 146 (69.5%) were stable and 32 (15.2%) showed sustained disability improvement. 112 CIS patients (53.3%) developed clinically definite MS (CDMS). CIS patients who developed SDP showed increased lateral ventricle volume (p < .001), and decreased GM (p = .011) and cortical (p = .001) volumes compared to patients who remained stable or improved in disability. Converters to CDMS showed an increased rate of accumulation of number of new/enlarging T2 lesions (p < .001), decreased whole brain (p = .007) and increased lateral ventricle (p = .025) volumes.ConclusionsDevelopment of GM pathology and LVV enlargement are associated with SDP. Conversion to CDMS in patients with CIS over 48 months is dependent on the accumulation of new lesions, LVV enlargement and whole brain atrophy progression.

The Prevalence of Familial Multiple Sclerosis in Saskatoon, Saskatchewan

Background. A population-based prevalent cohort of 150 clinical definite multiple sclerosis (MS) cases (102 women; 48 men) ascertained on January 1, 1977, Saskatoon, Saskatchewan, was found to have a familial rate of MS as 17.3%. Objectives. To determine the occurrence of familial MS cases and the frequency of MS among the biological relatives of the study cohort. Methods. The search for new familial cases MS affected relatives continued for 35 years until 2012. The natural history of the disease of sporadic cases is compared with that of the familial cases. SPSS V19 and Kaplan-Meier survival analysis were used for data analysis. Results. Of the 150 unrelated MS patients, 49 cases (32.7%) (36 women and 13 men) were reported of having at least one family member with MS. There were a total of 86 affected relatives, 26 (30.2%) first-degree relatives, 15 (17.4%) second-degree relatives, 20 (23.3%) third-degree relatives, and 25 (29.1%) distant relatives. The average age of MS onset for men with sporadic MS was 33.9 (SD = 10) years and 27.6 (SD = 8.4) years for familial cases and 29.3 (SD = 8.3) years and 26.8 (SD = 8.5) years for women. Conclusion. This 35-year longitudinal natural history study reveals a high frequency of cases with family members developing MS and supports a genetic influence in the etiology of MS.

Prospective, Longitudinal, Multicenter Observational Study of Long-term Treatment with Intramuscular Interferon β-1a of Patients with Clinically Isolated Syndrome at High Risk of Conversion

Introduction: Early initiation of treatment with intramuscular (IM) interferon (IFN) β-1a in patients with a single demyelinating event suggestive of multiple sclerosis (MS) has been shown to reduce the risk of a second event. This study investigated the characteristics of patients with clinically isolated syndrome (CIS), conversion to clinically definite MS and quality of life (QoL) in clinical practice. Methods: Patients eligible for IM IFNβ-1a for CIS were followed for 4 years (1 visit every 6 months, 9 visits in total). Disease progression was assessed using the Expanded Disability Status Scale (EDSS). The rate of conversion, adverse events and laboratory parameters were reported. Patients were administered QoL questionnaires (Functional Assessment of Multiple Sclerosis [FAMS] and EuroQol 5D [EQ-5D]). Results: Thirty-four patients from 15 Spanish hospitals were included and 18 completed the study. The mean ± SD age of the patients was 32.1 ± 9.08 years and 64% were women. At baseline, the mean EDSS was 0.94 ± 0.85. During follow-up, mean EDSS ranged from 0.89-1.25 and 15 patients (45.5%) converted to CIS. The most common adverse reaction was flu-like syndrome (55%). One patient discontinued treatment due to flu-like syndrome. The mean score on the visual analogue scale of the FAMS and the EQ-5D remained constant throughout the study (p>0.05 with respect to baseline). Conclusions: The conversion rate was higher than in the immediate-treatment arm of CHAMPIONS study, which could be expected due to differences in the patient population and delays in treatment initiation. The added value of the present study lies in the prospective collection of data from the clinical practice in highrisk CIS patients treated with IM IFNβ-1a in Spain. To our knowledge, this is the first study published with these characteristics.

Radiologically Definite Multiple Sclerosis (RDMS) as a New Terminology in Demyelinating Disease

Dear editor &#x0D; Multiple sclerosis (MS) is the most common inflammatory demyelinating disease of the central nervous system. MS is characterized by dissemination in time and place. Dissemination can be clinically (clinically definite multiple sclerosis) or radiologically by magnetic resonance imaging (MRI). Correct diagnosis of MS needs dissemination both in time and in place and also exclusion of all other neurological diseases that can mimic MS. Clinically, dissemination in time is defined as two episodes of neurological symptoms occurrence, separated at least one month apart, and dissemination in place is characterized as the presence of symptoms or signs in at least two different parts of central nervous system (CNS) (e.g. visual, sensory, motor, etc.). Radiologically dissemination in space (DIS) was defined as the presence of clinically silent lesions in T2-weighted MRI in two of four locations including juxtacortical, preventricular, infratentorial, and spinal cord and dissemination in time (DIT) as the presence of simultaneous gadolinium enhancing and non enhancing lesions in MRI [1,2].&#x0D;  There are some terminologies which are frequently used in patients with demyelinating disorders including clinically definite MS (CDMS), clinically isolated syndrome (CIS) and radiologically isolated syndrome (RIS) [1-3]. CDMS is defined as two attacks of neurological symptoms in two different neurological systems (e.g. optic neuritis and myelitis) separated and apart for at least one month [1]. Radiologically isolated syndrome (RIS) was used in persons with MRI findings suggestive of MS without typical symptoms and signs [3].&#x0D; CIS is defined as the first episode of neurological symptoms and signs suggestive of MS. The onset of MS in 85% of patients presents as CIS. This terminology is widely used in clinical practice. By definition, CIS is always clinically isolated in time. Around 50-70% of patients with CIS have white matter lesions in brain or spinal MRI. On the other hand, CIS usually represents a wide clinical spectrum of diseases of CNS and can be present in a multitude of clinical manifestation [1, 2].&#x0D; At present time, MRI is the most important tool for diagnosis of MS in patients with CIS and the application of MRI for diagnosis of MS has been increased during the past few years [4]. Today, the diagnosis of MS is possible very earlier than before due to the wide integration of MRI in McDonalds’ criteria (2010). MacDonald’s criteria mostly rely on MRI findings to facilitate the early diagnosis of MS [1, 4]. By using the new MacDonald’s criteria some patients who presented with CIS can be diagnosed as MS if MRI fulfills dissemination in time and space. For patients who fulfill the criteria of both DIT and DIS, the term of CDMS is used; but for patients who have had one attack of neurological symptoms and fulfill DIT and DIS radiologically (by MRI) there is no appropriate terminology and all of them are classified as CIS [2, 4]. We know that this terminology is somewhat ambiguous, because CIS may be the first presentation of many neurological diseases including demyelinating diseases, inflammatory diseases such as vasculitis or non-inflammatory non-demyelinating diseases like vascular lesions [2].&#x0D; We recommend the term of radiologically definite MS (RDMS) for patients who have had one attack of neurological symptoms and fulfill DIT and DIS radiologically by MRI. Because many neurologists are not completely familiar with the term CIS and some are confused about it, we need an appropriate terminology to use in every day’s clinical practice. Also, early diagnosis of MS in patients with CIS is very important. Because early treatment of patients with CIS by disease modifying drugs including Beta-Interferon can delay turning into CDMS and also decreases brain atrophy and new brain lesions. All current disease modifying drugs have been shown to be effective in treating CIS [5]. But it is clear that all patients with CIS do not require these treatments and only those patients who show dissemination in time and space by MRI should be treated by these agents [2, 6].&#x0D; In conclusion, radiologicaly definite MS (RDMS) is the recommended terminology for patients who have one attack of neurological symptoms and radiologically fulfill DIT and DIS criteria and these patients should be treated by disease modifying agents as well.

Long-term impact of interferon beta-1b in patients with CIS: 8-year follow-up of BENEFIT

ObjectiveTo examine the long-term impact of early treatment initiation of interferon beta-1b (IFNB1b, Betaferon/Betaseron) in patients with a first event suggestive of multiple sclerosis (MS).MethodsIn the original placebo-controlled phase of...

Glatiramer Acetate: A Review of Its Use in Patients with Relapsing-Remitting Multiple Sclerosis and in Delaying the Onset of Clinically Definite Multiple Sclerosis

Glatiramer acetate (Copaxone(®)) is a synthetic analogue of the multiple sclerosis (MS)-associated antigen, myelin basic protein. Although its exact mechanisms of action in MS remain to be fully elucidated, the key mechanisms of action of glatiramer acetate appear to be modulation of the inflammatory response and neuroprotective and/or neuroregenerative effects. Subcutaneous glatiramer acetate is indicated for the treatment of adult patients with relapsing-remitting MS (RRMS) and the treatment of patients who have experienced a well-defined first clinical episode and have magnetic resonance imaging (MRI) features consistent with MS or have been determined to be at high risk of developing clinically definite MS (CDMS). In clinical trials in patients with RRMS, glatiramer acetate reduced the frequency of relapses and reduced the burden and activity of disease on MRI, was more effective than placebo and showed generally similar efficacy to subcutaneous interferon (IFN) β-1a and IFNβ-1b. Furthermore, the beneficial effects of glatiramer acetate were sustained during up to 15 years of treatment in an extension study. In patients with clinically isolated syndrome (CIS), glatiramer acetate significantly delayed the onset of CDMS compared with placebo. The drug was generally well tolerated in these patient populations, with injection-site reactions being the most commonly occurring adverse events. Therefore, glatiramer acetate remains a valuable first-line option in the treatment of RRMS and is an option for delaying the onset of CDMS in patients with CIS.

Memory impairment in patients with clinically isolated syndrome

Background: Multiple sclerosis (MS) is a chronic disease affecting young adults, manifesting beside motor and visual deficits also by cognitive impairment, including memory. Recent studies indicated that cognitive impairment can be present already in patients with clinically isolated syndrome (CIS), who are at higher risk of developing CDMS (clinically definite MS) but specific studies focused on memory in CIS patients are lacking.

Application of the 2010 revised criteria for the diagnosis of multiple sclerosis to patients with clinically isolated syndromes

Recently, the McDonald criteria for the diagnosis of multiple sclerosis (MS) have been revised, with the aims to diagnose earlier and to simplify the use of brain MRI. To validate the 2010 revised criteria they were applied to a cohort of patients with clinically isolated syndromes (CIS). In all, 178 CIS patients were followed from onset. Test characteristics were calculated after 1, 3 and 5 years and compared between the 2005 and 2010 revised criteria. The time to diagnosis of the 2005 and 2010 criteria was compared using survival analysis and the log-rank test. Clinical evidence for dissemination in space and time was the gold standard for clinically definite MS (CDMS). During follow-up, 76 patients converted to CDMS (mean time to conversion 23.9 months). At 1 year, the specificity and accuracy of the 2005 criteria were a little higher than those of the 2010 criteria (98.0% and 98.4% vs. 86.3% and 88.5%). However, at 5 years, differences completely disappeared (specificity 85.7% and accuracy 93.3% for both criteria). MS diagnosis could be made significantly faster with the 2010 criteria (P = 0.007). Using the 2010 criteria, in 19% of patients the diagnosis could already be made at baseline. By applying the 2010 revised criteria a diagnosis of MS can be made earlier, whilst prediction of disease progression is maintained. This validation brings along great advantages, for treatment possibilities as well as patient counselling.

Evaluation of McDonald MRI criteria for dissemination in space in Korean patients with clinically isolated syndromes

We investigated the validity of the 2005 and 2010 McDonald magnetic resonance imaging (MRI) criteria for dissemination in space (DIS) to predict the conversion of clinically definite multiple sclerosis (CDMS) in 94 Korean patients with clinically isolated syndromes (CIS). The sensitivity, specificity, accuracy, positive and negative predictive values of the 2005, 2010 McDonald DIS criteria were comparable to those observed in the Caucasian population. This finding suggests that after careful exclusion of alternative explanations, particularly neuromyelitis optica (NMO) and NMO spectrum disorder (NMOSD), both the 2005 and 2010 McDonald DIS criteria are also useful to predict conversion to CDMS in Korean patients with CIS.

Interferon beta-1b reduces black holes in a randomised trial of clinically isolated syndrome

Background: Multiple sclerosis (MS) is characterised by inflammatory lesions of the central nervous system. Interferon beta-1b (IFNB-1b) has been shown to improve clinical and magnetic resonance imaging (MRI) measures for patients with MS. Objective: To evaluate whether IFNB-1b in patients presenting with clinically isolated syndromes (CIS) prevented persisting T1 hypointensities on MRI (persistent black holes (PBHs)). Methods: In the placebo-controlled phase, patients (n = 468) were initially randomised to IFNB-1b (n = 292) or placebo (n = 176) for two years or clinically definite MS (CDMS). In the open-label phase (n = 418), both groups were offered IFNB-1b for up to five years. Lesions were classified as PBHs if T1 hypointensity persisted throughout the last available scan (minimum time one year). Results: A total of 435 patients were evaluable for analysis. The number of PBHs/patient was lower in the early rather than the delayed treatment arm during both phases (.42 vs .71, p = .0102 and .70 vs 1.17, p = .0121). Exploratory analyses identified baseline characteristics that affected rate of conversion. Conclusions: Although the rate of lesions that converted to PBH showed no significant differences between groups, the numbers of PBHs per patient out of new lesions was significantly lower in IFNB-1b patients compared to patients on placebo. Trial registration number: NCT00544037.

Vitamin D levels and risk of multiple sclerosis in patients with clinically isolated syndromes

Background: Growing evidence suggests that vitamin D deficiency may be one of the most important environmental factors for the development of multiple sclerosis (MS). Objectives: The objectives of this paper are to evaluate serum 25-hydroxyvitamin D (25(OH)D) levels in patients with clinically isolated syndromes (CIS) and to examine whether they are related to MS risk. Methods: This is a retrospective study of 100 CIS patients hospitalized from 2000 to 2009 at San Raffaele Hospital, Milan, Italy. We evaluated baseline 25(OH)D level as well as clinical, brain magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) data. Results: A total of 52% of CIS patients had vitamin D deficiency (25(OH)D < 50 nmol/l). During follow-up (median: 7.17 years), 55 patients developed clinically definite MS (CDMS). Patients with very low (< 10th percentile) and low (< 25th percentile) 25(OH)D levels were particularly at risk of CDMS (HRs (95% CIs): 2.12 (0.91–4.96) and 1.61 (0.85–3.03), respectively), while no further reduction in the HRs of disease was observed at high levels of 25(OH)D. This association was even stronger after adjustment for additional risk factors for CDMS development (HRs (95% CIs) for 25(OH)D levels < 10th and 25th percentiles: 3.34 (1.32–8.45) and 2.04 (0.96–4.36), respectively). Conclusion: Low serum vitamin D is associated with increased MS risk in patients with CIS.

Limited utility of current MRI criteria for distinguishing multiple sclerosis from common mimickers: primary and secondary CNS vasculitis, lupus and Sjogren’s syndrome

Background: Magnetic resonance imaging (MRI) criteria play an important role in making an earlier diagnosis of multiple sclerosis (MS) in patients presenting with clinically isolated syndrome. Objective: The objective of this paper is to determine whether MRI criteria may be used to distinguish MS from primary and secondary central nervous system (CNS) vasculitis, lupus, and Sjogren’s syndrome. Methods: MRI criteria were applied retrospectively to images for patients with clinically definite MS (CDMS), primary CNS vasculitis, secondary CNS vasculitis, and autoimmune disorders including systemic lupus erythematosus (SLE) and Sjogren’s syndrome. Classical statistics and Bayesian analyses were performed. Results: Overall modified Barkhof’s MRI criteria were statistically significant in distinguishing CDMS (60%) from SLE/Sjogren’s syndrome (17%, p = 0.0173) but not in distinguishing CDMS from primary CNS vasculitis (50%, p = 0.7376) or secondary CNS vasculitis (58%, p = 1.0000). Four of the five other MRI criteria tested were demonstrated to be superior to modified Barkhof’s criteria in predicting MS: nine or more T2 lesions (a component of Barkhof’s criteria), one or more ovoid periventricular T2 lesions, one or more perpendicular periventricular T2 lesions, and one or more T2 lesions larger than 6 mm. Conclusions: MRI criteria, including the modified Barkhof’s criteria, were unsuccessful in distinguishing MS from primary CNS vasculitis or secondary CNS vasculitis and mildly successful in distinguishing MS from SLE/Sjogren’s syndrome.

Thalamic Atrophy Is Associated with Development of Clinically Definite Multiple Sclerosis

To investigate the association between the development of thalamic and cortical atrophy and the conversion to clinically definite multiple sclerosis (CDMS) in patients with clinically isolated syndrome (CIS). This prospective study was approved by the institutional review board. Informed consent was given by 216 CIS patients, and patients were treated with 30 µg of intramuscular interferon β1a once a week. They were assessed with a magnetic resonance (MR) imaging examination at baseline, 6 months, 1 year, and 2 years. Patients were evaluated within 4 months of an initial demyelinating event, had two or more brain lesions on MR images, and had two or more oligoclonal bands in cerebrospinal fluid. MR imaging measures of progression included cumulative number and volume of contrast agent-enhanced (CE) new and enlarged T2 lesions, and changes in whole-brain, tissue-specific global, and regional gray matter volumes. Regression and mixed-effect model analyses were used. Over 2 years, 92 of 216 patients (42.6%) converted to CDMS; 122 (56.5%) CIS patients fulfilled McDonald 2005 criteria and 153 (70.8%) fulfilled McDonald 2010 criteria for MR imaging dissemination in time and space. The mean time to first relapse was 3.1 months, and mean annual relapse rate was 0.46. In mixed-effect model analysis, the lateral ventricle volume (P = .005), accumulation of CE (P = .007), new total T2 (P = .009) and new enlarging T2 lesions (P = .01) increase, and thalamic (P = .009) and whole-brain (P = .019) volume decrease were associated with development of CDMS. In multivariate regression analysis, decrease in thalamic volumes and increase in lateral ventricle volumes (P = .009) were MR imaging variables associated with the development of CDMS. Measurement of thalamic atrophy and increase in ventricular size in CIS is associated with CDMS development and should be used in addition to the assessment of new T2 and CE lesions.