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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.

Cohort study; Oral contraceptives; Second relapse Estudio de cohorte; Anticonceptivos orales; Segunda recaída Estudi de cohorts; Anticonceptius orals; Segona recaiguda 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 author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This project was supported by FIS PI15/0070 from Ministry of Economy and Competitiveness of Spain.

Background and objectives: Treatment of spasticity poses a major challenge given the complex clinical presentation and variable efficacy and safety profiles of available drugs. We present a systematic review of the pharmacological treatment of spasticity in multiple sclerosis (MS) patients. Methods: Controlled trials and observational studies were identified. Scientific evidence was evaluated according to pre-specified levels of certainty. Results: The evidence supports the use of baclofen, tizanidine and gabapentin as first-line options. Diazepam or dantrolene could be considered if no clinical improvement is seen with the previous drugs. Nabiximols has a positive effect when used as add-on therapy in patients with poor response and/or tolerance to first-line oral treatments. Despite limited evidence, intrathecal baclofen and intrathecal phenol show a positive effect in severe spasticity and suboptimal response to oral drugs. Conclusion: The available studies on spasticity treatment offer some insight to guide clinical practice but are of variable methodological quality. Large, well-designed trials are needed to confirm the effectiveness of antispasticity agents and to produce evidence-based treatment algorithms.

The diagnostic criteria used in primary progressive (PP) and relapsing—remitting (RR) multiple sclerosis (MS) show substantial differences. This introduces complexity in the diagnosis of MS which could be resolved if these criteria could be unified in terms of the requirements for dissemination in space (DIS). The aim of this study was to assess whether a single algorithm may be used to demonstrate DIS in all forms of MS. Five sets of RRMS criteria for DIS were applied to a cohort of 145 patients with established PPMS (mean disease duration: 11 years — PPMS-1): C1: Barkhof—Tintoré (as in 2005 McDonald’s criteria); C2: Swanton et al. (as in JNNP 2006); C3: presence of oligoclonal bands plus two lesions (as in McDonald’s criteria); C4 and C5: a two-step approach was also followed (patients not fulfilling C1 or C2 were then assessed for C3). Two sets of PPMS criteria for DIS were applied: C6: Thompson et al. (as in 2001 McDonald’s criteria); C7: 2005 McDonald criteria. A second sample of 55 patients with less than 5 years of disease duration (PPMS-2) was also analysed using an identical approach. For PPMS-1/PPMS-2, fulfilment was: C1:73.8%/66.7%; C2:72.1%/59.3%; C3:89%/79.2%; C4:96%/92.3%; C5:96%/85.7%; C6:85.8%/78.7%; C7:91%/80.4%. Levels of fulfilment suggest that the use of a single set of criteria for DIS in RRMS and PPMS might be feasible, and reinforce the added value of cerebrospinal fluid (CSF) findings to increase fulfilment in PPMS. Unification of the DIS criteria for both RRMS and PPMS could be considered in further revisions of the MS diagnostic criteria.

Although the mechanisms underlying the accumulation of disability in primary progressive (PP) multiple sclerosis (MS) are still unclear, a major role seems to be played by `occult' tissue damage. We investigated whether conventional and magnetization transfer (MT) MRI may provide complementary information for the assessment of PPMS severity. Conventional and MT MRI scans from 226 PPMS patients and 84 healthy controls were collected for centralized analysis. The expanded disability status scale (EDSS) score was rated at the time of MRI acquisition. T2 lesion volume, normalized brain volume (NBV) and cervical cord cross-sectional area (CSA) were measured. Magnetization transfer ratio (MTR) histograms from whole brain tissue, normal-appearing white matter and grey matter (NAGM) were also obtained. Mean NBV, CSA and MTR histogram-derived metrics showed significant inter-centre heterogeneity. After correcting for the acquisition centre, pooled average MTR and histogram peak height values were different between PPMS patients and controls for all tissue classes ( P-values between 0.03 and 0.0001). More severe brain and cord atrophy and MT MRI-detectable NAGM damage were found in patients who required walking aids than in those who did not ( P-values: 0.03, 0.001 and 0.016). A composite score of NBV, CSA, whole brain and NAGM MTR histogram peak height z-scores was correlated with patients' EDSS ( r = 0.37, P 0.001). Magnetization transfer MRI might provide information complementary to that given by conventional MRI when assessing PPMS severity. Sequence-related variability of measurements makes the standardization of MT MRI acquisition essential for the design of multicentre studies. Multiple Sclerosis 2008; 14: 455—464. http://msj.sagepub.com