Improved Assessment of Longitudinal Spinal Cord Atrophy in Multiple Sclerosis Using a Registration-Based Approach: Relevance for Clinical Studies.

BACKGROUND: Reliable measurements of cervical cord atrophy progression may be useful for monitoring neurodegeneration in multiple sclerosis (MS). PURPOSE: To compare a new, registration-based (Reg) method with two existing methods (active surface [AS] and propagation segmentation [PropSeg]) to measure cord atrophy changes over time in MS. STUDY TYPE: Retrospective. SUBJECTS: Cohort I: Eight healthy controls (HC) and 28 MS patients enrolled at a single institution, and cohort II: 25 HC and 63 MS patients enrolled at three European sites. FIELD STRENGTH/SEQUENCE: 3D T1-weighted gradient echo sequence, acquired at 1.5 T (cohort I) and 3.0 T (cohort II). ASSESSMENT: Percentage cord area changes (PCACs) between baseline and follow-up (cohort I: 2.34 years [interquartile range = 2.00-2.55 years], cohort II: 1.05 years [interquartile range = 1.01-1.18 years]) were evaluated for all subjects using Reg, AS, and PropSeg. Reg included an accurate registration of baseline and follow-up straightened cord images, followed by AS-based optimized cord segmentation. A subset of studies was analyzed twice by two observers. STATISTICAL TESTS: Linear regression models were used to estimate annualized PCAC, and effect sizes expressed as the ratio between the estimated differences and HC error term (P < 0.05). Reproducibility was assessed by linear mixed-effect models. Annualized PCACs were used for sample size calculations (significance: α = 0.05, power: 1 - ß = 0.80). RESULTS: Annualized PCACs and related standard errors (SEs) were lower with Reg than with other methods: PCAC in MS patients at 1.5 T was -1.12% (SE = 0.22) with Reg, -1.32% (SE = 0.30) with AS, and -1.40% (SE = 0.33) with PropSeg, while at 3.0 T PCAC was -0.83% (SE = 0.25) with Reg, -0.92% (SE = 0.32) with AS, and -1.18 (SE = 0.53) with PropSeg. This was reflected in larger effect sizes and lower sample sizes. Intra- and inter-observer agreement range was 0.72-0.91 with AS, and it was >0.96 with Reg. DATA CONCLUSION: The results support the use of the registration method to measure cervical cord atrophy progression in future MS clinical studies. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

Patterns of care for Multiple Sclerosis in a setting of universal care access: A cross-sectional study.

BACKGROUND: Current guidelines recommend regular neurological MS care in persons diagnosed with MS, but little is known about implementation of this recommendation or potential access barriers. This study examined disease-specific and sociodemographic differences between MS patients in Neurological Care (NeC), General Practitioner Care (GPC), or no Physician Care (NoPC) to identify group differences and characteristics that may suggest care access barriers. METHODS: Patient-reported data were analyzed from 1038 Swiss Multiple Sclerosis Registry participants by means of multivariable regression to identify systematic differences across the three care groups. Assessments included comprehensive data on clinical, sociodemographic, and geographic factors. RESULTS: 89% reported being in regular care by a neurologist (56% in private practices, 44% in hospitals), 5% were in GPC, and 6% reported No Physician Care (NoPC). Compared with the NeC group, patients not seeing a neurologist included two subgroups, one consisting of persons with a primary progressive MS (PPMS) and/or an extended MS history. The second subgroup included persons with a recent MS diagnosis within the last 2 years. Within the NeC group, the patients seen in private practices were of older age and more frequently female compared to those at clinics, but no differences were detected with regard to disability status, MS type, or treatment patterns. CONCLUSIONS: Access to neurological care is high in Switzerland. Given the emerging paradigm for early treatment and new drugs for progressive MS, regular neurology visits should be promoted among patient groups currently less in neurological care such as persons with PPMS or recently diagnosed.

Treatment satisfaction, adherence and behavioral assessment in patients de-escalating from natalizumab to interferon ß.

BACKGROUND: De-escalating natalizumab (NTZ) to interferon beta 1b (IFN B 1B) is a possible treatment option in multiple sclerosis (MS) patients interrupting NTZ because of increased risk of progressive multifocal leukoencephalopathy (PML). The aim of this study was to evaluate satisfaction and adherence to treatment, behavioral and fatigue changes in patients switched to IFN B 1B compared to continued NTZ treatment. METHODS: A 1 year, prospective, randomized, rater-blinded, parallel-group study. Nineteen relapsing remitting (RR) MS patients, randomly assigned to undergo either NTZ (n = 10) or IFN B 1B (n = 9) treatment, who had previously received NTZ for at least 12 months with disease stability and fearing or at risk for PML were included. Patients underwent behavioral and treatment assessments at baseline, after 24-week and 1 year follow-up. Behavioral assessment included measures of cognition, fatigue and quality of life. Treatment assessment included measures of satisfaction, persistence and adherence to treatment. Clinical-radiological disease activity and safety were also assessed. RESULTS: Baseline characteristics of patients were similar between groups except for Euro Quality Visual Analogue Scale, being higher in the NTZ group (p = 0.04). Within-group comparisons at the three time points, as well as interaction analysis of treatment effect over time did not show any statistically significant differences in behavioral or treatment assessments, but a coherent trend favoring NTZ over IFN B 1B. CONCLUSIONS: De-escalating NTZ to IFN B 1B is feasible and associated with overall good patient related outcome and persistently stable behavioral measures.