Josephine Swanton

MRI criteria for multiple sclerosis in patients presenting with clinically isolated syndromes: a multicentre retrospective study.

BACKGROUND The 2001 and 2005 McDonald criteria allow MRI evidence for dissemination in space (DIS) and dissemination in time (DIT) to be used to diagnose multiple sclerosis in patients who present with clinically isolated syndromes (CIS). In 2006, new criteria were proposed in which DIS requires at least one T2 lesion in at least two of four locations (juxtacortical, periventricular, infratentorial, and spinal-cord) and DIT requires a new T2 lesion on a follow-up scan. We applied all three criteria in a large cohort of CIS patients to assess their performance by use of conversion to clinically definite multiple sclerosis (CDMS) as the outcome. METHODS Patients who had two MRI scans within 12 months of CIS onset were identified in four centres in the Magnims European research network. The specificity and sensitivity of MRI criteria for CDMS after 3 years was assessed in 208 patients. A Cox proportional hazards model was applied in a larger cohort of 282 patients that included all patients irrespective of length of follow-up. FINDINGS The specificity of all criteria for CDMS was high (2001 McDonald, 91%; 2005 McDonald, 88%; new, 87%). Sensitivity of the new (72%) and 2005 McDonald (60%) criteria were higher than the 2001 McDonald criteria (47%). The Cox proportional hazards model showed a higher conversion risk for all three criteria in those with both DIS and DIT than those with either DIS or DIT alone. When all three criteria were included in the model, only the new criteria had an independent significant effect on conversion risk. INTERPRETATION The new criteria are simpler than the McDonald criteria without compromising specificity and accuracy. The presence of both DIS and DIT from two MRI scans has a higher specificity and risk for CDMS than either DIS or DIT alone.

MRI criteria for MS in patients with clinically isolated syndromes

In recent years, criteria for the diagnosis of multiple sclerosis (MS) have changed, mainly due to the incorporation of new MRI criteria. While the new criteria are a logical step forward, they are complex and—not surprisingly—a good working knowledge of them is not always evident among neurologists and neuroradiologists. In some circumstances, several MRI examinations are needed to achieve an accurate and prompt diagnosis. This provides an incentive for continued efforts to refine the incorporation of MRI-derived information into the diagnostic workup of patients presenting with a clinically isolated syndrome. Within the European multicenter collaborative research network that studies MRI in MS (MAGNIMS), a workshop was held in London in November 2007 to review information that may simplify the existing MS diagnostic criteria, while maintaining a high specificity that is essential to minimize false positive diagnoses. New data that are now published were reviewed and discussed and together with a new proposal are integrated in this position paper.

Modification of MRI criteria for multiple sclerosis in patients with clinically isolated syndromes

Background: The McDonald criteria include MRI evidence for dissemination in space and dissemination in time for the diagnosis of multiple sclerosis in young adult patients who present with clinically isolated syndromes (CIS) typical of the disease. Although a major advance, the criteria have limited sensitivity for making an early diagnosis. Objective: To compare the performance of McDonald criteria and modified McDonald criteria for dissemination in space and time for assessing the development of clinically definite multiple sclerosis. Methods: McDonald criteria were modified using the combination of a less stringent definition for dissemination in space and allowing a new T2 lesion per se after three months as evidence for dissemination in time. Modified and McDonald criteria were applied in 90 CIS patients at baseline and at three month follow up scans. Results: Both criteria were highly specific (>90%) but the modified criteria were more sensitive (77% v 46%) and more accurate (86% v 73%). Conclusions: These modified criteria should be evaluated in other CIS cohorts.

A Single, Early Magnetic Resonance Imaging Study in the Diagnosis of Multiple Sclerosis

BACKGROUND A diagnosis of multiple sclerosis in patients who present for the first time with a clinically isolated syndrome (CIS) can be established with brain magnetic resonance imaging (MRI) if the MRI demonstrates demyelinating lesions with dissemination in space (DIS) and dissemination in time (DIT). OBJECTIVE To investigate the diagnostic performance of a single MRI study obtained within the first 3 months after symptom onset in a cohort of patients with a CIS suggestive of multiple sclerosis at presentation. DESIGN Multicenter inception cohort with a follow-up of at least 24 months. SETTING Referral hospitals. Patients Patients with CIS onset between April 1, 1995, and September 30, 2004, who fulfilled the following criteria were included: (1) age of 14 to 50 years and (2) clinical follow-up for at least 24 months after CIS onset or until development of clinically definite multiple sclerosis (CDMS), if this occurred within 2 years. Main Outcome Measure All patients underwent 2 comparable brain MRI examinations, the first within 3 months (early) and the second between 3 and 12 months (delayed) after CIS onset. We defined DIS using several existing MRI criteria, and DIT was inferred when there were simultaneous gadolinium-enhancing and nonenhancing lesions on a single MRI. RESULTS Two hundred fifty patients were included in the study. The comparison of the diagnostic performance of various MRI criteria for identifying early converters to CDMS showed similar sensitivity and specificity between early and delayed MRIs. In addition, the use of less stringent criteria for DIS yielded better sensitivity and similar specificity, particularly when assessed in the first weeks after CIS onset. CONCLUSION A single brain MRI study that demonstrates DIS and shows both gadolinium-enhancing and nonenhancing lesions that suggest DIT is highly specific for predicting the early development of CDMS, even when the MRI is performed within the first 3 months after the onset of a CIS.

Cognitive impairment in multiple sclerosis can be predicted by imaging early in the disease

Background: Cognitive impairment is common in multiple sclerosis (MS) and adds significantly to the burden of the disease. The ability to predict future cognitive impairment from imaging obtained at disease onset has not been investigated. Methods: 62 patients imaged within 3 months of a clinically isolated syndrome were assessed neuropsychologically 7 years later. Baseline and periodic MRI measures of lesions, atrophy and normal-appearing white and grey matter were regressed against neuropsychological scores to explore the best predictors of cognitive outcome. Results: 28 patients had developed clinically definite MS at follow-up and a further nine met revised McDonald criteria for MS. Deficits in speed of information processing and executive function were the most common abnormalities. Poor performance correlated with high anxiety ratings. Baseline T1 lesion metrics predicted executive deficits, and new T2 lesions at the 3-month follow-up predicted slowed information processing. An increase in myo-inositol concentration in normal-appearing white matter over the first 3 years was associated with poor executive function. Conclusions: MRI variables obtained at the onset of a clinically isolated syndrome can predict future development of cognitive abnormalities. Our findings may have implications in monitoring and treating patients.

Brain atrophy and lesion load measures over 1 year relate to clinical status after 6 years in patients with clinically isolated syndromes

Background Conventional MRI lesion measures modestly predict long term disability in some clinically isolated syndrome (CIS) studies. Brain atrophy suggests neuroaxonal loss in multiple sclerosis (MS) with the potential to reflect disease progression to a greater extent than lesion measures. Objective To investigate whether brain atrophy and lesion load, during the first year in patients presenting with CIS, independently predict clinical outcome (development of MS and disability at 6 years). Methods 99 patients presenting with CIS were included in the study. T1 gadolinium enhanced and T2 weighted brain MRI was acquired at baseline and approximately 1 year later. Percentage brain atrophy rate between baseline and follow-up scans was analysed using SIENA. Results Mean annual brain atrophy rates were −0.38% for all patients, −0.50% in patients who had developed MS at 6 years and −0.26% in those who had not. Brain atrophy rate (p = 0.005) and baseline T2 lesion load (p<0.001) were independent predictors of clinically definite MS. While brain atrophy rate was a predictor of Expanded Disability Status Scale (EDSS) score in a univariate analysis, only 1 year T2 lesion load change (p = 0.007) and baseline gadolinium enhancing lesion number (p = 0.03) were independent predictors of EDSS score at the 6 year follow-up. T1 lesion load was the only MRI parameter which predicted Multiple Sclerosis Functional Composite score at the 6 year follow-up. Conclusions The findings confirm that brain atrophy occurs during the earliest phases of MS and suggest that 1 year longitudinal measures of MRI change, if considered together with baseline MRI variables, might help to predict clinical status 6 years after the first demyelinating event in CIS patients, better than measurements such as lesion or brain volumes on baseline MRI alone.

Early MRI in optic neuritis: the risk for disability.

Background: MRI findings influence the risk of patients with optic neuritis (ON) developing clinically definite (CD) multiple sclerosis (MS) but their influence on future disability is less clear. Objective: To investigate in patients with ON the influence of lesion number, location and activity, and non-lesion MRI measures obtained on early scans on disability. Methods: A total of 106 of 143 prospectively recruited patients with ON had reached a scheduled 5-year follow-up, of whom 100 were evaluated clinically. Lesion number, location, and activity measures were analyzed at baseline (within 3 months of onset) and lesion activity measures were studied at 3-month follow-up. Brain atrophy, magnetization transfer ratio, and spectroscopy measures were also analyzed. Ordinal logistic regression assessed the association between early MRI findings and subsequent disability. Results: At median 6 years follow-up, 48% had converted to CDMS and 52% remained with clinically isolated syndrome (median Expanded Disability Status Scale 2 and 1). In the final models, both the presence and the number of spinal cord lesions at baseline (odds ratios [OR] 3.30, 1.94) and new T2 lesions at follow-up (OR 7.12, 2.06) were significant independent predictors of higher disability. Disability was also predicted by the presence at baseline of gadolinium-enhancing lesions (OR 2.78) and number of infratentorial lesions (OR 1.82). Only spinal cord lesions predicted disability in patients converting to CDMS. Conclusion: Spinal cord, infratentorial, and gadolinium lesions within 3 months of optic neuritis onset and new T2 lesions after 3 months predicted disability after 6 years; only spinal cord lesions were predictive of disability in those developing clinically definite multiple sclerosis. BPF = brain parenchymal fraction; CD = clinically definite; CI = confidence interval; CIS = clinically isolated syndrome; EDSS = Expanded Disability Status Scale; FOV = field of view; Gd = gadolinium; GM = gray matter; GMF = gray matter parenchymal fraction; IQR = interquartile range; LR = likelihood ratio; MS = multiple sclerosis; MTI = magnetization transfer imaging; MTR = MT ratio; NAGM = normal-appearing gray matter; NAWM = normal-appearing white matter; ON = optic neuritis; OR = odds ratio; PRESS = point resolved spectroscopy; RRMS = relapsing remitting MS; SPMS = secondary progressive MS; TE = echo time; TR = repetition time; WM = white matter; WMF = white matter parenchymal fraction.

Early MRI in optic neuritis: the risk for clinically definite multiple sclerosis.

MRI brain lesions at presentation with optic neuritis (ON) increase the risk for developing clinically definite (CD) multiple sclerosis (MS). More detailed early MRI findings may improve prediction of conversion. The objectives of this study were to investigate the influence of number, location and activity of lesions at presentation, new lesions at early follow-up and non-lesion MRI measures on conversion from optic neuritis (ON) to CDMS. 142/143 ON patients, prospectively recruited into a serial MRI and clinical follow-up study, were followed-up at least once. Cox regression analysis determined independent early MRI predictors of time to CDMS from: (i) baseline lesion number, location and activity measures, (ii) three-month lesion activity measures and (iii) brain atrophy, magnetization transfer ratio and spectroscopy measures. 114/142 (80%) had abnormal baseline brain or cord MRI. 57 (40%) developed CDMS (median of 16 months from clinically isolated syndrome onset). Median follow-up of the non-converters was 62 months. Multivariate analysis of baseline parameters revealed gender, periventricular and gadolinium-enhancing lesions as independent predictors of CDMS. Considering both scans together, gender, baseline periventricular and new T2 lesions at follow-up remained significant (hazard ratios 2.1, 2.4 and 4.9, respectively). No non-conventional measure predicted CDMS. It was concluded that new T2 lesions on an early follow-up scan were the strongest independent predictor of CDMS.

MRI only conversion to multiple sclerosis following a clinically isolated syndrome

Objectives Using current diagnostic criteria, patients who present with a clinically isolated syndrome (CIS) may develop multiple sclerosis (MS) by subsequently exhibiting dissemination in space and time on clinical (clinically definite (CD) MS) or radiological (MRI) grounds. This study investigated the frequency of radiological without clinical conversion to MS after long term follow-up as this has not previously been defined. Methods Two cohorts who underwent serial clinical and MRI studies from presentation with a CIS and who were followed-up over a mean of 6 and 20 years were investigated. The distribution and formation of lesions visible on brain MRI were assessed using the revised McDonald criteria (2005). Radiologically defined (RD) MS was determined by fulfilment of the MRI but not the CDMS criteria. Results 105 people were followed-up for 6 years after a CIS, of whom 51% developed CDMS, 15% RDMS and the remainder were classified as still having had a CIS. 70 people were followed-up at 20 years, of whom 61% and 11% had developed CDMS and RDMS, respectively. Conclusion About 10–15% of CIS patients may develop MS on MRI criteria only, without further clinical events for up to two decades.

Association of asymptomatic spinal cord lesions and atrophy with disability 5 years after a clinically isolated syndrome.

Background: Spinal cord pathology is an important substrate for long-term disability in multiple sclerosis (MS). Objective: To investigate longitudinal changes in spinal cord lesions and atrophy in patients with a non-spinal clinically isolated syndrome (CIS), and how they relate to the development of disability. Methods: In all, 131 patients with a non-spinal CIS had brain and spinal cord imaging at the time of CIS and approximately 5 years later (median: 5.2 years, range: 3.0–7.9 years). Brain magnetic resonance imaging (MRI) measures consisted of T2-hyperintense and T1-hypointense lesion loads plus brain atrophy. Spinal cord MRI measures consisted of lesion number and the upper cervical cord cross-sectional area (UCCA). Disability was measured using the Expanded Disability Status Scale (EDSS). Multiple linear regression was used to identify independent predictors of disability after 5 years. Results: During follow-up, 93 (71%) patients were diagnosed with MS. Baseline spinal cord lesion number, change in cord lesion number and change in UCCA were independently associated with EDSS (R2 = 0.53) at follow-up. Including brain T2 lesion load and brain atrophy only modestly increased the predictive power of the model (R2 = 0.64). Conclusion: Asymptomatic spinal cord lesions and spinal cord atrophy contribute to the development of MS-related disability over the first 5 years after a non-spinal CIS.