Sensor-Derived Measures of Motor and Cognitive Functions in People With Multiple Sclerosis Using Unsupervised Smartphone-Based Assessments: Proof-of-Concept Study.

Background: Smartphones and wearables are revolutionizing the assessment of cognitive and motor function in neurological disorders, allowing for objective, frequent, and remote data collection. However, these assessments typically provide a plethora of sensor-derived measures (SDMs), and selecting the most suitable measure for a given context of use is a challenging, often overlooked problem.

Objective: This analysis aims to develop and apply an SDM selection framework, including automated data quality checks and the evaluation of statistical properties, to identify robust SDMs that describe the cognitive and motor function of people with multiple sclerosis (MS).

DISPEL: A Python Framework for Developing Measures From Digital Health Technologies.

: This paper introduces DISPEL, a Python framework to facilitate development of sensor-derived measures (SDMs) from data collected with digital health technologies in the context of therapeutic development for neurodegenerative diseases. : Modularity, integrability and flexibility were achieved adopting an object-oriented architecture for data modelling and SDM extraction, which also allowed standardizing SDM generation, naming, storage, and documentation. Additionally, a functionality was designed to implement systematic flagging of missing data and unexpected user behaviors, both frequent in unsupervised monitoring.

Konectom™ cognitive processing speed test enables reliable remote, unsupervised cognitive assessment in people with multiple sclerosis: Exploring the use of substitution time as a novel digital outcome measure.

Background: The Konectom™ smartphone-based cognitive processing speed (CPS) test is designed to assess processing speed and account for impact of visuomotor function on performance.

Objective: Evaluate reliability and validity of Konectom CPS Test, performed in clinic and remotely.

Methods: Data were collected from people with multiple sclerosis (PwMS) aged 18-64 years and healthy control participants (HC) matched for age, sex, and education.

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%.

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.

Treatment effect of natalizumab on relapse outcomes in multiple sclerosis patients despite ongoing MRI activity.

Natalizumab treatment significantly reduced the annualised relapse rate and MRI activity over 2 years compared with placebo in phase III trials when administered as monotherapy in AFFIRM or in combination with interferon β-1a (IFNβ) in SENTINEL. The post hoc analyses reported here sought to determine the effect of natalizumab treatment on relapse activity in the minority of patients who continued to show MRI activity (ie, ≥ 1 gadolinium enhancing (Gd+) lesions or new or enlarging T2 hyperintense lesions) over 2 years in these trials. These analyses demonstrated that natalizumab treatment, both alone (AFFIRM) and in combination with IFNβ (SENTINEL), resulted in a reduced annualised relapse rate despite the presence of Gd+ lesions (p=0.

Symptomatic therapy in multiple sclerosis: a review for a multimodal approach in clinical practice.

As more investigations into factors affecting the quality of life of patients with multiple sclerosis (MS) are undertaken, it is becoming increasingly apparent that certain comorbidities and associated symptoms commonly found in these patients differ in incidence, pathophysiology and other factors compared with the general population. Many of these MS-related symptoms are frequently ignored in assessments of disease status and are often not considered to be associated with the disease. Research into how such comorbidities and symptoms can be diagnosed and treated within the MS population is lacking.

Natalizumab induces a rapid improvement of disability status and ambulation after failure of previous therapy in relapsing-remitting multiple sclerosis.

Background: Natalizumab (Tysabri) is a monoclonal antibody that was recently approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). Our primary objective was to analyse the efficacy of natalizumab on disability status and ambulation after switching patients with RRMS from other disease-modifying treatments (DMTs).

Methods: A retrospective, observational study was carried out.

Methylprednisolone in combination with interferon beta-1a for relapsing-remitting multiple sclerosis (MECOMBIN study): a multicentre, double-blind, randomised, placebo-controlled, parallel-group trial.

Background: Interferon beta is commonly used to treat patients with relapsing-remitting multiple sclerosis; however, the treatment is only partially effective in reducing relapses and progression of disability. Corticosteroids are used to treat relapses in patients with multiple sclerosis. We therefore aimed to investigate the combination of cyclic methylprednisolone and interferon beta for the treatment of relapsing-remitting multiple sclerosis.

Stroke presentation and outcome in developing countries: a prospective study in the Gambia.

Background And Purpose: Despite increasing burden of stroke in Africa, prospective descriptive data are rare. Our objective was to describe, in The Gambia, the clinical outcome of stroke patients admitted to the Royal Victoria Teaching Hospital in the capital Banjul, to assess mortality and morbidity, and propose preventive and therapeutic measures.

Methods: Prospective data were collected on consecutive patients older than 15 years old admitted between February 2000 and February 2001 with the diagnosis of nonsubarachnoid stroke.

Could visual neglect induce amblyopia?

Oculomotor nerve disease is a common cause of diplopia. When strabismus is present, absence of diplopia has to induce the research of either uncovering of visual fields or monocular suppression, amblyopia or blindness. We describe the case of a 41-year-old woman presenting with right oculomotor paresis and left object-centred visual neglect due to a right fronto-parietal haemorrhage expanding to the right peri-mesencephalic cisterna caused by the rupture of a right middle cerebral artery aneurysm.

The idiopathic hypereosinophilic syndrome: clinical presentation, pathogenesis and therapeutic strategies.

The idiopathic hypereosinophilic syndrome (HES) is a heterogenous disease entity characterized by persistent unexplained hypereosinophilia generally complicated by end-organ damage. Correct diagnosis and management are important in order to prevent long-term complications. Furthermore, it appears that HES represents a premalignant state in some patients, and close follow-up is necessary to detect early signs of malignant transformation.

Antiphospholipid antibodies and ischemic neuropathy following cardiac surgery.

Sciatic nerve palsy is an uncommon complication of cardiac surgery and is thought to be induced by a combination of reduced femoral artery blood flow, small vessel vascular disease or prolonged hypoxia. We here describe a new case which is the first described with transient elevation of antiphospholipid antibodies. Although transient elevation of lupus coagulation inhibitor is known to occur frequently in patients treated in an intensive care unit, there are very few data about the possible role of antiphospholipid antibodies in the generation of ischemic neuropathies.

The cerebellum may be directly involved in cognitive functions.

Neuropsychological deficits may occur in infratentorial strokes. Only minor cognitive disturbances are reported in unilateral anterior cerebellar lesions. Here, the authors describe a patient with bilateral anterior ponto-cerebellar ischemic lesions associated with major neuropsychological deficits.

Interleukin-3 and interferon beta cooperate to induce differentiation of monocytes into dendritic cells with potent helper T-cell stimulatory properties.

It was observed that interferon beta (IFN-beta) prevents the down-regulation of the interleukin-3 receptor alpha chain (IL-3Ralpha), which spontaneously occurs during culture of human monocytes. The functionality of IL-3R was demonstrated by the fact that IL-3 rescued IFN-beta-treated monocytes from apoptosis. Monocytes cultured in the presence of IFN-beta and IL-3 acquire a dendritic morphology and express high levels of HLA antigen class I and class II and costimulatory molecules.

[Anti-tumor immunotherapy based on dendritic cells].

In cancer immunotherapy, the use of dendritic cells (DC) loaded with tumor-associated antigens (TAA) emerged as a promising strategy. We initiated 3 pilot clinical trials with immunological endpoints using TAA loaded autologous DC. These trials showed that this approach was safe and associated with the induction of potent TAA specific IFN-gamma responses, which were transient despite the providing a further help through KLH presentation.

Human monocyte-derived dendritic cells produce bioactive gelatinase B: inhibition by IFN-beta.

We studied the secretion of gelatinase B by dendritic cells (DC) generated by culturing human peripheral blood monocytes in granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). First, we found the intracellular expression of gelatinase B on sections of fixed DC pellets. Zymography analysis of the supernatants of DC cultured for 72 h demonstrated the presence of gelatinase B.

IFN-beta interferes with the differentiation of dendritic cells from peripheral blood mononuclear cells: selective inhibition of CD40-dependent interleukin-12 secretion.

We studied the effects of interferon-beta (IFN-beta) on the differentiation of dendritic cells (DC) obtained by culturing plastic-adherent peripheral blood mononuclear cells (PBMC) from a total of 30 healthy volunteers in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). First, we found that the addition of IFN-beta at the initiation of the culture did not modify DC morphology but caused a reproducible and statistically significant upregulation of HLA-DR, CD86, and CD80 surface expression. CD1a expression was significantly reduced, and CD40 expression was unchanged.

Interferon-beta inhibits Th1 responses at the dendritic cell level. Relevance to multiple sclerosis.

Clinical studies have demonstrated beneficial effects of interferon-beta (IFN-beta) therapy in multiple sclerosis (MS) patients. However, the mechanism of action of IFN-beta in MS remains unknown. IFN-beta has even been demonstrated to enhance isolated T cell secretion of IFN-gamma, a cytokine proven to be deleterious in MS.

Analysis of ballistic movements in ataxic hemiparesis following a pontine stroke.

Although cerebellar-like ataxia is a well known component of the ataxic hemiparesis (AH), the mechanism of hypermetria in AH has not been established. We describe a patient presenting a left AH following a right pontine infarction. We investigated the ballistic flexion movements of both wrists and the associated agonist and antagonist electromyographic (EMG) activities, before and after addition of inertial loads.