Stratification and monitoring of natalizumab-associated progressive multifocal leukoencephalopathy risk: recommendations from an expert group.

The use of natalizumab for highly active relapsing-remitting multiple sclerosis (MS) is influenced by the occurrence of progressive multifocal leukoencephalopathy (PML). Through measurement of the anti-JCV antibody index, and in combination with the presence or absence of other known risk factors, it may be possible to stratify patients with MS according to their risk of developing PML during treatment with natalizumab and detect early suspected PML using MRI including a diffusion-weighted imaging sequence. This paper describes a practical consensus guideline for treating neurologists, based on current evidence, for the introduction into routine clinical practice of anti-JCV antibody index testing of immunosuppressant-naïve patients with MS, either currently being treated with, or initiating, natalizumab, based on their anti-JCV antibody status. Recommendations for the frequency and type of MRI screening in patients with varying index-associated PML risks are also discussed. This consensus paper presents a simple and pragmatic algorithm to support the introduction of anti-JCV antibody index testing and MRI monitoring into standard PML safety protocols, in order to allow some JCV positive patients who wish to begin or continue natalizumab treatment to be managed with a more individualised analysis of their PML risk.

Alemtuzumab for multiple sclerosis: Long term follow-up in a multi-centre cohort.

BACKGROUND: Alemtuzumab has recently been approved for treatment of relapsing MS, but concerns remain about its use since long-term studies of adverse events remain limited. Furthermore, a clear understanding of its application and durability of effect in clinical practice has yet to evolve. OBJECTIVES: To investigate long-term efficacy and safety outcomes in a multicentre cohort of patients treated with alemtuzumab. METHODS: Patients treated from 2000 and followed-up at three regional centres were identified. Baseline and prospective data were obtained and validated by clinical record review. RESULTS: One hundred patients were identified with a mean follow-up of 6.1 years (range 1-13). Forty patients were retreated with at least one further treatment cycle. Annualized relapse rates fell from 2.1 to 0.2 (p<0.0001) post-treatment and were sustained for up to eight years of follow-up. Mean change in EDSS score was +0.14. Forty-seven patients developed secondary autoimmunity. CONCLUSION: Observed reduction in relapse rates reflected those reported in clinical trials, but we were unable to corroborate previous observations of disability reversal. 40% of patients required additional treatment cycles. Autoimmune adverse events were common, occurring at a higher rate than previously reported, but were largely predictable, and could be managed effectively within a rigorous monitoring regime.

Quantified measurement of activity provides insight into motor function and recovery in neurological disease.

BACKGROUND: A direct quantitative measurement of locomotor activity in an individual's own environment over an extended period may help in evaluating the impact of impairments in neurological disorders. OBJECTIVE: To investigate the reliability and validity of activity monitoring in neurological patients and healthy subjects. METHODS: Initial reliability studies were completed on 10 healthy subjects and 10 mobility restricted neurological patients. Validity was investigated using 7 days of ambulatory monitoring with the Step Watch( step activity monitor, laboratory based measures of gait and the Rivermead Mobility Index (RMI) in 10 patients with multiple sclerosis, 10 with Parkinson's disease, and 10 with a primary muscle disorder. Additionally, 30 healthy subjects participated in the study. Two clinical illustrations of ambulatory monitoring are provided. RESULTS: The mean (range) right step count of 7 days of monitoring in both healthy and neurological patients proved a reliable measure of activity (intra-class correlations 0.89 and 0.86 respectively). The 7 day mean (range) right step count was 5951 (2886-9955) in healthy subjects, 3818 (1611-5391) in patients with Parkinson's disease, 3003 (716-5302) in those with muscular disorders, and 2985 (689-5340) in those with multiple sclerosis. A moderate correlation was noted between 7 day mean step count and gait speed (r = 0.45, p = 0.01) in the grouped neurological patients but not the RMI (r(s) = 0.3, p = 0.11). CONCLUSION: Ambulatory monitoring provides a reliable and valid measure of activity levels. Neurological patients, living independently, demonstrate lower activity levels than healthy matched controls. Ambulatory monitoring as an outcome measure has potential for improving the evaluation of ambulation and providing insight into participation.