Improving the Characterization of Radiologically Isolated Syndrome Suggestive of Multiple Sclerosis

OBJECTIVE: To improve the characterization of asymptomatic subjects with brain magnetic resonance imaging (MRI) abnormalities highly suggestive of multiple sclerosis (MS), a condition named as "radiologically isolated syndrome" (RIS). METHODS: Quantitative MRI metrics such as brain volumes and magnetization transfer (MT) were assessed in 19 subjects previously classified as RIS, 20 demographically-matched relapsing-remitting MS (RRMS) patients and 20 healthy controls (HC). Specific measures were: white matter (WM) lesion volumes (LV), total and regional brain volumes, and MT ratio (MTr) in lesions, normal-appearing WM (NAWM) and cortex. RESULTS: LV was similar in RIS and RRMS, without differences in distribution and frequency at lesion mapping. Brain volumes were similarly lower in RRMS and RIS than in HC (p<0.001). Lesional-MTr was lower in RRMS than in RIS (p = 0.048); NAWM-MTr and cortical-MTr were similar in RIS and HC and lower (p<0.01) in RRMS. These values were particularly lower in RRMS than in RIS in the sensorimotor and memory networks. A multivariate logistic regression analysis showed that 13/19 RIS had ≥70% probability of being classified as RRMS on the basis of their brain volume and lesional-MTr values. CONCLUSIONS: Macroscopic brain damage was similar in RIS and RRMS. However, the subtle tissue damage detected by MTr was milder in RIS than in RRMS in clinically relevant brain regions, suggesting an explanation for the lack of clinical manifestations of subjects with RIS. This new approach could be useful for narrowing down the RIS individuals with a high risk of progression to MS

Relevance of cognitive deterioration in early relapsing-remitting MS: a 3-year follow-up study

Objective: To assess longitudinally cognitive functioning in relapsing-remitting multiple sclerosis (RRMS) patients and its relationship with clinical and MRI variables. Methods: Early RRMS patients and matched healthy controls were assessed in parallel in three testing sessions over 3 years, using the Rao's Brief Repeatable Battery of Neuropsychological Tests. Patients also underwent an MRI analysis of T2-weighted lesion volume (T2LV), number of gadolinium-enhanced lesions and whole brain atrophy. Forty-nine RRMS patients (mean age 36.9 ± 8.9 years; mean disease duration 2.9 ± 1.7 years, mean Expanded Disability Status Scale, 1.7 ± 0.7) and 56 healthy controls were recruited. Results: At baseline, cognitive impairment was detected in 15 patients (30.6%). After 3 years, cognitive functioning worsened in the 29.3% of patients, whereas Expanded Disability Status Scale progression was observed in only three patients. The most sensitive test to detect cognitive deterioration over time was the Symbol Digit Modalities Test (SDMT). Only the presence of moderate cognitive impairment at baseline predicted further cognitive deterioration (p = 0.03). Among MRI variables, T2LV showed a weak to moderate relationship with some cognitive tasks. Conclusions: Over a 3-year period cognitive deterioration can be expected in approximately one-third of MS patients with relatively short disease duration. The SDMT is particularly suitable for longitudinal assessment of MS-related cognitive changes. © The Author(s) 2010

Brain volumes in HC, RIS and RRMS.

<p>Box plots comparing the brain volumes of HC (left), RIS subjects (center) and RRMS patients (right). Values are relative to NBV (left), NWMV (center) and NCV (right). Note the presence of similarly low values of brain volume in RIS subjects and RRMS patients with respect to HC. See text for abbreviations.</p

MTr in HC, RIS and RRMS.

<p>Box plots comparing the MTr measures of HC (left), RIS subjects (center) and RRMS patients (right). Values are relative to whole brain-MTr (top left), lesional-MTr (top right), NAWM-MTr (bottom left) and cortical-MTr (bottom right). Note the differences between the three groups, with generally higher MTr values in RIS subjects than in RRMS patients. See text for abbreviations.</p

Brain regions of the grey and white matter where RIS showed higher MTr than RRMS.

<p>Statistically significant regions (p<0.05, cluster-corrected for multiple comparisons) are ordered by decreasing values of the highest local maxima (Z-max). L = left, R = right, M = middle. MNI coordinates are expressed in mm.</p

Logistic regression analysis: probability for RIS to be HC or RRMS.

<p>Panel A shows the distribution of subjects according to their NBV and lesional-WM MTr. HC are in blu, RIS subjects in red, and RRMS patients in green. Lesional-MTr values were calculated in RIS subjects and RRMS patients from T₂-W lesional WM regions. MTr values in the WM of HC were calculated from areas homologous to those of the WM lesions of the RIS and RRMS. The black line separates the subjects with a probability of being a RRMS patient below and above 50%, according to the coefficients estimated by the penalized logistic model. The histogram of probability to be RRMS, as estimated according to the penalized logistic model including NBV and lesional-MTr as independent predictors, is reported in panel B. See text for further details.</p

Demographic and clinical characteristics of subjects with RIS.

<p>n.p. =  not performed.</p><p>DIT =  dissemination in time.</p><p>CSF =  cerebrospinal fluid.</p><p>See text for other abbreviations.</p>∧<p>+: presence of cervical spine lesion; -: absence of signal abnormalities.</p><p>*+: presence of oligoclonal bands and/or abnormal IgG Index; -: normal pattern.</p>#<p>+: presence of abnormal P100 in at least one of the eyes; -: normal pattern.</p>$<p>+: failure of ≥2 tests at the Rao Brief Repeatable Battery; -: failure of ≤1 test.</p