Does the radiologically isolated syndrome exist? A dual-task cost pilot study.

Simultaneous performance of motor and cognitive tasks may compete for common brain network resources in aging or patients with some neurological diseases, suggesting the occurrence of a cognitive-motor interference. While this phenomenon has been well described for multiple sclerosis (MS) patients, it never has been tested on asymptomatic subject with magnetic resonance imaging (MRI) findings suggestive of demyelinating disease (i.e., radiologically isolated syndrome: RIS). In this pilot study, 10 RIS subjects and 10 sex/age-matched healthy controls were tested by means of static posturography under eyes opened (single-task trial) and while performing two different cognitive tasks (semantic modified word list generation for first dual-task trial and phonemic semantic modified word list generation for second dual-task trial), to estimate the dual-task cost (DTC) of standing balance. In our sample, under cognitive interference (without any substantial differences between semantic and phonemic modified word list generation), the RIS group showed significance differences in CoP (center of pressure) total sway area, ellipse eccentricity, CoP sway path length, CoP median sway velocity along the AP (anteroposterior) axis and along the ML (mediolateral) axis, reflecting a higher negative DTC respect to healthy subjects (which have simply shown a statistical trend, failing to reach a significance, in some trials). The phenomenon of cognitive-motor interference might be unmasked by a dual-task posturography in RIS subjects, too. We hypothesize that this approach could be useful to early reveal the presence of a demyelinating disease and to reach a MS diagnosis in subjects otherwise classified as RIS.

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 30 µg of intramuscular interferon beta 1a once a week. MRI acquisition and neuropsychological (NP) assessment were performed at baseline, 6, 12 and 24 months. 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 24 months, 36 CIS patients developed clinically definite MS (CDMS). CI was observed in 10 (12.3 %) CIS patients at baseline and at the 24 months 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.

Low cerebrospinal fluid sulfatide predicts progression of white matter lesions: The LADIS study.

BACKGROUND/AIMS: Demyelination and axonal degeneration are the hallmarks of established white matter lesions (WML). The neurochemistry of ongoing WML is only partially known. We explored cerebrospinal fluid (CSF) substances as markers of brain tissue damage in relation to progression of WML rated on magnetic resonance imaging. METHODS: CSF from elderly individuals with WML was analyzed for amyloid markers, total τ, hyperphosphorylated τ, neurofilament protein light subunit, sulfatide and CSF/serum-albumin ratio. After 3 years, a follow-up magnetic resonance imaging was performed. Progression of WML was rated using the Rotterdam Progression Scale (RPS). RESULTS: 37 subjects (age 73.6 ± 4.6 years) were included. Subjects with more pronounced progression (RPS > 2; n = 15) had lower mean sulfatide concentration at baseline as compared to subjects with no or minimal progression (RPS 0-2; n = 22) according to univariate analyses (p = 0.009). Sulfatide was the only biomarker that predicted the RPS score according to regression analysis, explaining 18.9% of the total variance (r = 0.38, p = 0.015). CONCLUSION: The correlation of CSF sulfatide levels and RPS scores may reflect a remyelination response to the demyelination process associated with WML. Furthermore, the results strengthen the notion that WML pathology is different from that of Alzheimer's disease.