The Multiple Sclerosis Data Alliance Catalogue: Enabling Web-Based Discovery of Metadata from Real-World Multiple Sclerosis Data Sources.

BACKGROUND: One of the major objectives of the Multiple Sclerosis Data Alliance (MSDA) is to enable better discovery of multiple sclerosis (MS) real-world data (RWD). METHODS: We implemented the MSDA Catalogue, which is available worldwide. The current version of the MSDA Catalogue collects descriptive information on governance, purpose, inclusion criteria, procedures for data quality control, and how and which data are collected, including the use of e-health technologies and data on collection of COVID-19 variables. The current cataloguing procedure is performed in several manual steps, securing an effective catalogue. RESULTS: Herein we summarize the status of the MSDA Catalogue as of January 6, 2021. To date, 38 data sources across five continents are included in the MSDA Catalogue. These data sources differ in purpose, maturity, and variables collected, but this landscaping effort shows that there is substantial alignment on some domains. The MSDA Catalogue shows that personal data and basic disease data are the most collected categories of variables, whereas data on fatigue measurements and cognition scales are the least collected in MS registries/cohorts. CONCLUSIONS: The Web-based MSDA Catalogue provides strategic overview and allows authorized end users to browse metadata profiles of data cohorts and data sources. There are many existing and arising RWD sources in MS. Detailed cataloguing of MS RWD is a first and useful step toward reducing the time needed to discover MS RWD sets and promoting collaboration.

Thyroid disorders in alemtuzumab-treated multiple sclerosis patients: a Belgian consensus on diagnosis and management.

This paper deals with thyroid disease that can occur after treatment with alemtuzumab (humanized monoclonal anti-CD52) for relapsing-remitting multiple sclerosis (MS). The 5-year incidence of thyroid adverse events in phase 3 clinical trials is up to 40.7%. In most cases, the thyroid dysfunction is mild and easily manageable and only few serious thyroid adverse events have been reported. The need for patient education on the risk of thyroid dysfunction, as well as regular clinical and biochemical thyroid function screening is well described. However, practical clinical guidance in case of abnormal thyroid-related findings prior to or after alemtuzumab treatment is currently lacking. Therefore, a Belgian taskforce consisting of MS and thyroid experts was created in 2016, with the objective of issuing a clinical thyroid management algorithm based on available scientific evidence and personal experience with regard to alemtuzumab treatment-related thyroid adverse events.

Does including the full CVLT-II and BVMT-R improve BICAMS? Evidence from a Belgian (Dutch) validation study.

BACKGROUND: The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) is a fast, easy-to-administer and already widely validated neuropsychological battery for cognition in multiple sclerosis. OBJECTIVE: The goals of our study were to validate the BICAMS in a Belgian Dutch-speaking population and to investigate to what extent including extensive versions of two of the three BICAMS subtests improved its psychometric qualities. METHODS: Ninety-seven persons with MS and ninety-seven healthy controls were included and group-matched on age, education level and gender. All participants performed the BICAMS with an extensive version of the CVLT-II and BVMT-R. RESULTS: The SDMT and BVMT-R were able to dissociate between the MS and healthy control group, while the CVLT-II was not. Distributions of CVLT-II scores suggest learning effects in the MS group, indicating the need for alternative word lists or the construction of an adapted version fitted for repeated administration. Including the full CVLT-II and BVMT-R did not markedly improve the psychometric qualities of the BICAMS. CONCLUSION: This study validates the BICAMS in a Belgian Dutch-speaking population and facilitates the use of it in clinical practice, while providing evidence that including full versions of the CVLT-II and BVMT-R does not increase its psychometric qualities markedly.

Is the Nociception Coma Scale-Revised a Useful Clinical Tool for Managing Pain in Patients With Disorders of Consciousness?

OBJECTIVES: Our objective was to assess the clinical usefulness of the Nociception Coma Scale-revised (NCS-R) in pain management of patients with disorders of consciousness. MATERIALS AND METHODS: Thirty-nine patients with potential painful conditions (eg, due to fractures, decubitus ulcers, or spasticity) were assessed during nursing cares before and after the administration of an analgesic treatment tailored to each patient's clinical status. In addition to the NCS-R, the Glasgow Coma Scale (GCS) was used before and during treatment to observe fluctuations in consciousness. Twenty-three of them had no analgesic treatment before the assessment, whereas the analgesic treatment has been adapted in the other 16 patients. We performed nonparametric Wilcoxon tests to investigate the difference in the NCS-R and GCS total scores but also in the NCS-R subscores before versus during treatment. The effect of the level of consciousness and the etiology were assessed using a Mann-Whitney U test. RESULTS: NCS-R total scores were statistically lower during treatment when compared with the scores obtained before treatment. We also found that the motor, verbal, and facial expression subscores were lower during treatment than before treatment. In contrast, we found no difference between the GCS total scores obtained before versus during treatment. DISCUSSION: Our results suggest that the NCS-R is an interesting clinical tool for pain management. Besides, this tool seems useful when a balance is needed between reduced pain and preserved level of consciousness in patients with disorders of consciousness.

Safety and efficacy of natalizumab in Belgian multiple sclerosis patients: subgroup analysis of the natalizumab observational program.

Natalizumab (Tysabri(®)) is highly efficacious in controlling disease activity in relapsing multiple sclerosis (MS) patients. As it is one of the more recent therapies for MS, there remains a need for long-term safety and efficacy data of natalizumab in a clinical practice setting. The Tysabri observational program (TOP) is an open-label, multicenter, multinational, prospective observational study, aiming to recruit up to 6,000 patients with relapsing-remitting MS from Europe, Canada and Australia. The objectives of this study are to collect long-term safety and efficacy data on disease activity and disability progression. We report here the interim results of the 563 patients included in TOP between December 2007 and 2012 from Belgium. This patient cohort was older at baseline, had longer disease duration, higher neurological impairment, and a higher baseline annualized relapse rate, when compared to patients included in the pivotal phase III AFFIRM trial. Nevertheless, the efficacy of natalizumab was comparable. The annualized relapse rate on treatment was reduced by 90.70 % (p < 0.0001) with a cumulative probability of relapse of 26.87 % at 24 months. The cumulative probabilities of sustained disability improvement and progression at 24 months were 25.68 and 9.01 %, respectively. There were no new safety concerns over the follow-up period. Two cases of progressive multifocal leukoencephalopathy were diagnosed. Our results are consistent with other observational studies in the post-marketing setting.

Consensus guidelines on the neurologist's role in the management of neurogenic lower urinary tract dysfunction in multiple sclerosis.

OBJECTIVE: To review current management of neurogenic lower urinary tract dysfunction (NLUTD) in MS patients and give recommendations on the joint role of the neurologist and urologist in NLUTD management. METHODS: An algorithm for evaluation and referral of MS patients to urologists was created. It is an outcome of discussions about current knowledge, existing guidelines, and key issues during two Belgian consensus meetings attended by neurologists, urologists and other stakeholders involved in MS management. At these meetings, updated information on management of NLUTD in MS was exchanged and the neurologists' opinion on how to integrate this in the other aspects of care in MS patients was explored. RESULTS: Short evaluation of NLUTD in MS patients by neurologists and appropriate referral to urologists could accelerate proper diagnosis and treatment. Neurologists can play a central role in the inter-disciplinary communication on interactions between disease manifestations of MS and their treatments. CONCLUSION: The coordinating role of neurologists in NLUTD management may considerably improve QoL in MS patients. More research is needed to evaluate outcomes of urological assessments and treatment.

Boosting endogenous neuroprotection in multiple sclerosis: the ASsociation of Inosine and Interferon beta in relapsing- remitting Multiple Sclerosis (ASIIMS) trial.

Anti-inflammatory drugs are effective on relapses, but neuroprotective agents to prevent disability are still unavailable. Uric acid has neuroprotective effects in experimental models including encephalomyelitis and appears to be involved in multiple sclerosis. Oral administration of inosine, a precursor of uric acid, increases serum uric acid levels and is well tolerated. Our objective was to test the possibility that a combination therapy associating an anti-inflammatory drug (interferon beta) and an endogenous neuroprotective molecule (uric acid) would be more effective than interferon beta alone on the accumulation of disability. Patients with relapsing-remitting multiple sclerosis on interferon beta for at least 6 months were randomized to interferon beta + inosine or interferon beta + placebo for 2 years. The dose of inosine was adjusted to maintain serum uric acid levels in the range of asymptomatic hyperuricaemia (

Associations of apolipoprotein E gene with ischemic stroke and intracranial atherosclerosis.

The apolipoprotein E (APOE) epsilon4 allele is associated with elevated cholesterol and risk of atherosclerosis. However, its role in ischemic stroke (IS) remains controversial. We investigated a possible link between IS or the severity of intracranial atherosclerosis and the APOE promoter polymorphisms -219G/T and +113G/C, involved in regulating APOE transcription. We genotyped subjects from a multicentric Belgian case-control study, including 237 middle-aged patients with IS due to small- or large-vessel atherosclerotic stroke and 326 ethnicity- and gender-matched controls and a Finnish autopsy series of 1004 non-stroke cases, who had received a quantitative score of atherosclerosis in the circle of Willis. The APOE epsilon4+ genotype did not associate with IS, but was related to more severe intracranial atherosclerosis score in men (5.4 vs 4.6, P=0.044). Within the most common APOE epsilon3/epsilon3 genotype group, the risk of IS associated with the G-allele of the tightly linked -219G/T (OR=6.2; 95% CI: 1.6-24.3, P=0.009) and +113G/C (OR=7.1; 95% CI: 1.7-29.9, P=0.007) promoter polymorphisms. There was no difference in the severity of intracranial atherosclerosis between -219G/G genotype carriers and non-carriers. This study suggests a multifaceted role of apoE on the risk of cerebrovascular diseases. The APOE epsilon4+ genotype did not predict the risk of IS but was associated with severity of subclinical intracranial atherosclerosis in men on the autopsy study. In contrast, the promoter variants were significant predictors of IS, suggesting that quantitative rather than qualitative variation of apoE is related to IS.

A unique episode of REM sleep behavior disorder triggered during surgery for Parkinson's disease.

REM sleep behavior disorder (RBD) is characterized by vigorous movements during REM sleep. Here, the authors report the case of a patient who presented such a disorder immediately after the implantation of the definitive electrode for left subthalamic stimulation. Interestingly, this was and has remained a unique episode in his medical history. It was found that a microlesion in or near the upper part of the pars compacta of the substantia nigra was very likely responsible for this phenomenon.