Progressive multifocal leukoencephalopathy associated with sphingosine-1-phosphate receptor modulators: A large case series.

Background: Risk factors for progressive multifocal leukoencephalopathy (PML) associated with sphingosine-1-phosphate receptor (S1PR) modulators are not as well-characterized as for natalizumab. We characterized S1PR modulator-associated PML cases and risk factors for PML using spontaneous adverse event reports.

Methods: We reviewed case reports from the FDA Adverse Event Reporting System database and the medical literature.

Immune-mediated colitis associated with ocrelizumab: A new safety risk.

Background: An association between certain immunomodulatory therapies (rituximab, ipilimumab, and other immune checkpoint inhibitors) and inflammatory (non-ischemic and non-infectious) colitis in oncologic and non-oncologic patient populations is well documented in the medical literature.

Objective: The purpose of this case series is to describe adverse event reports of new onset, inflammatory colitis in association with ocrelizumab in patients with multiple sclerosis submitted to U.S.

The neuroradiology of progressive multifocal leukoencephalopathy: a clinical trial perspective.

Progressive multifocal leukoencephalopathy (PML) is an opportunistic infection of the CNS caused by the JC virus, which infects white and grey matter cells and leads to irreversible demyelination and neuroaxonal damage. Brain MRI, in addition to the clinical presentation and demonstration of JC virus DNA either in the CSF or by histopathology, is an important tool in the detection of PML. In clinical practice, standard MRI pulse sequences are utilized for screening, diagnosis and monitoring of PML, but validated imaging-based outcome measures for use in prospective, interventional clinical trials for PML have yet to be established.

Technology-enabled assessments to enhance multiple sclerosis clinical care and research.

Background: Comprehensive and efficient assessments are necessary for clinical care and research in chronic diseases. Our objective was to assess the implementation of a technology-enabled tool in MS practice.

Method: We analyzed prospectively collected longitudinal data from routine multiple sclerosis (MS) visits between September 2015 and May 2018.

Technology-enabled comprehensive characterization of multiple sclerosis in clinical practice.

Background: Objective and longitudinal measurements of disability in patients with multiple sclerosis (MS) are desired in order to monitor disease status and response to disease-modifying and symptomatic therapies. Technology-enabled comprehensive assessment of MS patients, including neuroperformance tests (NPTs), patient-reported outcome measures (PROMs), and MRI, is incorporated into clinical care at our center. The relationships of each NPT with PROMs and MRI measures in a real-world setting are incompletely studied, particularly in larger datasets.

Serum neurofilament light chain concentration in a phase 1/2 trial of autologous mesenchymal stem cell transplantation.

Background: Serum neurofilament light chain concentration is a proposed biomarker of axonal injury in multiple sclerosis. Mesenchymal stem cells have anti-inflammatory and repair-promoting activities, making them of interest for potential multiple sclerosis treatment.

Objectives: The purpose of this study was to assess correlation of serum neurofilament light chain concentration and measures of multiple sclerosis disease activity/severity, longitudinal stability of serum neurofilament light chain concentration, and treatment effect of mesenchymal stem cell transplantation on serum neurofilament light chain concentration.

Tuberculosis screening in multiple sclerosis: effect of disease-modifying therapies and lymphopenia on the prevalence of indeterminate TB screening results in the clinical setting.

Background: Tuberculosis screening is recommended in multiple sclerosis patients starting certain disease-modifying therapies. Disease-modifying therapies may affect interferon-gamma release assay results.

Objective: To determine the effects of multiple sclerosis disease-modifying therapies on interferon-gamma release assay results.

Developing therapeutic strategies to promote myelin repair in multiple sclerosis.

: Approved disease-modifying therapies for multiple sclerosis (MS) lessen inflammatory disease activity that causes relapses and MRI lesions. However, chronic inflammation and demyelination lead to axonal degeneration and neuronal loss, for which there currently is no effective treatment. There has been increasing interest in developing repair-promoting strategies, but there are important unanswered questions regarding the mechanisms and appropriate methods to evaluate these treatments.

Autologous Hematopoietic Cell Transplantation for Treatment-Refractory Relapsing Multiple Sclerosis: Position Statement from the American Society for Blood and Marrow Transplantation.

Multiple sclerosis (MS) is a chronic, disabling, immune-mediated, demyelinating and degenerative disease of the central nervous system. Approved disease-modifying therapies may be incompletely effective in some patients with highly active relapsing disease and high risk of disability. The use of immunoablative or myeloablative therapy followed by autologous hematopoietic cell transplantation (AHCT) has been investigated in retrospective studies, clinical trials, and meta-analyses/systematic reviews as an approach to address this unmet clinical need.

Therapeutic Advances and Challenges in the Treatment of Progressive Multiple Sclerosis.

Despite the fact that majority of patients with multiple sclerosis (MS) have relapsing-remitting disease, many transition to secondary progressive disease (SPMS) over time. This transition is thought to be related to neurodegenerative processes increasingly predominating over inflammatory processes as the driving forces of disability. However, some patients initially present with primary progressive disease (PPMS) that is characterized by a gradual accumulation of neurological symptoms and subsequent disability accumulation.

Streamlined EDSS for use in multiple sclerosis clinical practice: Development and cross-sectional comparison to EDSS.

Background: The Expanded Disability Status Scale (EDSS) is the standard measure of disability in multiple sclerosis clinical trials. The EDSS has limited application in the clinical setting due to required completion time and scoring complexity. Systematically recording an objective, simplified, less time-intensive, and neurologist-derived disability score would be beneficial for patient care.

Daclizumab: Development, Clinical Trials, and Practical Aspects of Use in Multiple Sclerosis.

Daclizumab is a humanized monoclonal antibody directed towards CD25, the alpha subunit of the high-affinity interleukin (IL)-2 receptor. Daclizumab exerts its effects via multiple mechanisms, including reduction of IL-2-mediated lymphocyte activation and upregulation of CD56-bright natural killer cells. Intravenous daclizumab (Zenapax™) was initially approved for prevention of rejection in renal transplant.

Predicting abdominal closure after component separation for complex ventral hernias: maximizing the use of preoperative computed tomography.

Background: Component separation techniques (CSTs) have allowed for midline fascial reapproximation in large midline ventral hernias. In certain cases, however, fascial apposition is not feasible, resulting in a bridged repair that is suboptimal. Previous estimates on myofascial advancement are based on hernia location and do not take into account variability between patients.

A case-control study of wicket spikes using video-EEG monitoring.

Purpose: To investigate clinical characteristics associated with wicket spikes in patients undergoing long-term video-EEG monitoring.

Methods: A case-control study was performed in 479 patients undergoing video-EEG monitoring, with 3 age- (±3 years) and gender-matched controls per patient with wicket spikes. Logistic regression was utilized to investigate the association between wicket spikes and other factors, including conditions that have been previously associated with wicket spikes.

Validation of an incremental motor unit number estimation technique in rabbits.

Motor unit number estimation (MUNE) allows for quantitative assessment of functional motor units in a nerve. Several techniques have been applied to human studies. Although MUNE has been performed in animals to study neurological disorders, reproducibility has not been addressed.

Added sampling improves reproducibility of multipoint motor unit estimates.

Motor unit number estimation (MUNE) has been used to track motor unit attrition. Studies have used the modified multiple-point stimulation (MPS) technique, collecting three surface motor unit action potentials (sMUAPs) from 3 sites to calculate MUNE. Factoring additional sMUAPs should theoretically improve reproducibility, but the optimal number has not been defined.