Sphingosine 1-phosphate receptor modulators in multiple sclerosis treatment: A practical review.

Four sphingosine 1-phosphate (S1P) receptor modulators (fingolimod, ozanimod, ponesimod, and siponimod) are approved by the US Food and Drug Administration for the treatment of multiple sclerosis. This review summarizes efficacy and safety data on these S1P receptor modulators, with an emphasis on similarities and differences. Efficacy data from the pivotal clinical trials are generally similar for the four agents.

Differential Diagnosis of Tumor-like Brain Lesions.

Purpose Of Review: Tumor-like brain lesions are rare and commonly suggest a neoplastic etiology. Failure to rapidly identify non-neoplastic causes can lead to increased morbidity and mortality. In this review, we describe 10 patients who presented with atypical, non-neoplastic tumor-like brain lesions in which brain biopsy was essential for a correct diagnosis and treatment.

Autologous Hematopoietic Stem Cell Transplant in Multiple Sclerosis: Recommendations of the National Multiple Sclerosis Society.

Importance: Autologous hematopoietic stem cell transplant (AHSCT) for multiple sclerosis has gained increasing interest in recent years. Despite the availability of many US Food and Drug Administration-approved disease-modifying therapies, some patients do not respond adequately and others may have very early aggressive disease that prompts consideration of alternative, highly effective, long-lasting therapy. The National Medical Advisory Committee of the National Multiple Sclerosis Society has reviewed recent literature on AHSCT for the purpose of making recommendations about its use based on current knowledge, as well as pointing out areas of controversy and issues requiring further research.

Clinical and MRI efficacy of sc IFN β-1a tiw in patients with relapsing MS appearing to transition to secondary progressive MS: post hoc analyses of PRISMS and SPECTRIMS.

This study evaluated efficacy of subcutaneous (sc) interferon beta-1a (IFN β-1a) 44 µg 3 × weekly (tiw) in patients appearing to transition from relapsing-remitting multiple sclerosis (RRMS) to secondary progressive MS (SPMS). The PRISMS study included 560 patients with RRMS (EDSS 0-5.0; ≥ 2 relapses in previous 2 years), and the SPECTRIMS study included 618 patients with SPMS (EDSS 3.

Acute Exertional Upper-Extremity Rhabdomyolysis as a Result of a Single Training Event: Report of 3 Female Trainees.

Early diagnosis and comprehensive management of exertional rhabdomyolysis are crucial to ensure full recovery and avoidance of complications.

Phase 2 Trial of Ibudilast in Progressive Multiple Sclerosis.

Background: There are limited treatments for progressive multiple sclerosis. Ibudilast inhibits several cyclic nucleotide phosphodiesterases, macrophage migration inhibitory factor, and toll-like receptor 4 and can cross the blood-brain barrier, with potential salutary effects in progressive multiple sclerosis.

Methods: We enrolled patients with primary or secondary progressive multiple sclerosis in a phase 2 randomized trial of oral ibudilast (≤100 mg daily) or placebo for 96 weeks.

Cladribine tablets added to IFN-β in active relapsing MS: The ONWARD study.

Objective: To evaluate the safety and efficacy of cladribine tablets in patients still experiencing active relapsing MS despite interferon (IFN)-β treatment.

Methods: A 96-week phase II study, randomizing patients treated with IFN-β to cladribine tablets 3.5 mg/kg/IFN-β or placebo/IFN-β.

Robot-guided ankle sensorimotor rehabilitation of patients with multiple sclerosis.

Background: People with multiple sclerosis (MS) often develop symptoms including muscle weakness, spasticity, imbalance, and sensory loss in the lower limbs, especially at the ankle, which result in impaired balance and locomotion and increased risk of falls. Rehabilitation strategies that improve ankle function may improve mobility and safety of ambulation in patients with MS. This pilot study investigated effectiveness of a robot-guided ankle passive-active movement training in reducing motor and sensory impairments and improving balance and gait functions.

Demonstration of equivalence of a generic glatiramer acetate (Glatopa™).

Glatiramer acetate (GA) has been available under the brand name Copaxone® for nearly two decades. Recently, the US Food and Drug Administration (FDA) approved the first generic GA, Glatopa™, as fully substitutable for all indications for which Copaxone 20mg is approved; Glatopa also represents the first FDA-approved "AP-rated," substitutable generic for treating patients with MS. Glatiramer acetate is a complex mixture of polypeptides and, consequently, its characterization presented challenges not generally encountered in drug development.

Diagnostic utility of aquaporin-4 in the analysis of active demyelinating lesions.

Objective: To assess, in a surgical biopsy cohort of active demyelinating lesions, the diagnostic utility of aquaporin-4 (AQP4) immunohistochemistry in identifying neuromyelitis optica (NMO) or NMO spectrum disorder (NMOSD) and describe pathologic features that should prompt AQP4 immunohistochemical analysis and AQP4-immunoglobulin G (IgG) serologic testing.

Methods: This was a neuropathologic cohort study of 20 surgical biopsies (19 patients; 11 cord/9 brain), performed because of diagnostic uncertainty, interpreted as active demyelinating disease and containing 2 or more of the following additional features: tissue vacuolation, granulocytic infiltrates, or astrocyte injury.

Results: AQP4 immunoreactivity was lost in 18 biopsies and increased in 2.

Therapy optimization in multiple sclerosis: a prospective observational study of therapy compliance and outcomes.

Background: Data sources for MS research are numerous but rarely provide an objective measure of drug therapy compliance coupled with patient-reported health outcomes. The objective of this paper is to describe the methods and baseline characteristics of the Therapy Optimization in MS (TOP MS) study designed to investigate the relationship between disease-modifying therapy compliance and health outcomes.

Methods: TOP MS was designed as a prospective, observational, nationwide patient-focused study using an internet portal for data entry.

Characterizations of reflex and nonreflex changes in spastic multiple sclerosis.

Background: Spasticity, an increased resistance of a limb to movement, is associated with functional limitations and a major source of disability in neurological disorders, including multiple sclerosis (MS) and stroke. Despite the clinical significance of spasticity in brain and spinal cord injuries, it is often not clear whether the spasticity is due to reflex or non-reflex changes.

New Method: Reflex and nonreflex properties of the human knee joint were studied in eight MS patients with spasticity and ten healthy subjects.

Constructing an adaptive care model for the management of disease-related symptoms throughout the course of multiple sclerosis--performance improvement CME.

Background: Symptom management remains a challenging clinical aspect of MS.

Objective: To design a performance improvement continuing medical education (PI CME) activity for better clinical management of multiple sclerosis (MS)-related depression, fatigue, mobility impairment/falls, and spasticity.

Methods: Ten volunteer MS centers participated in a three-stage PI CME model: A) baseline assessment; B) practice improvement CME intervention; C) reassessment.

Opportunistic infections of the central nervous system in the transplant patient.

Therapeutic advances in transplantation medicine have resulted in ever expanding patient populations that receive organ or stem cell transplantation. Modern potent immunomodulatory therapies have resulted in improvements in allograft and patient survival, but, consequently, as a result of the immunosuppressive state, transplant recipients are highly vulnerable to infection, including those that affect the central nervous system (CNS). CNS infections present a diagnostic and therapeutic challenge for clinicians involved in the care of the transplant patient, with a propensity to result in profound morbidity and often high mortality in this patient population.

Enhancing the quality of care for patients with multiple sclerosis through performance improvement CME.

Multiple sclerosis (MS) is an inflammatory neurodegenerative disease marked by a heterogeneous clinical presentation and disease course. Although improvements in the recognition and management of MS have been made in recent years, challenges remain due to the complex nature of the disease. Clinicians must remain current with their skills as knowledge surrounding MS care continues to advance.

Presentation of neuromyelitis optica spectrum disorder after more than twenty years of systemic sclerosis.

Neuromyelitis optica is an autoimmune disorder characterized by optic neuritis, transverse myelitis, and aquaporin-4 autoantibodies. The term "neuromyelitis optica spectrum disorder" refers neuromyelitis optica features occurring in association with other systemic rheumatologic conditions. We present a case of a 51-year-old woman with long-standing systemic sclerosis who developed transverse myelitis in association with the presence aquaporin-4 autoantibodies.

Biomarkers of neurological status in HIV infection: a 3-year study.

Purpose: To evaluate circulating cytokines and chemokines as correlates of the degree of brain injury in individuals with advanced human immunodeficiency virus (HIV) infection.

Experimental Design: Study participants included ten well-characterized subjects in advanced stage HIV infection. High-throughput multiplexed analysis was used to quantify markers of interest at baseline and 3 years later in the clinical course.

PRISMS: the story of a pivotal clinical trial series in multiple sclerosis.

Background: The PRISMS (Prevention of Relapses and disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) study was initiated in 1994, at which time there were few disease-modifying drugs for multiple sclerosis (MS). The PRISMS series of studies has since provided up to 8 years of clinical, magnetic resonance imaging (MRI), safety, and immunogenicity data on the use of subcutaneous (sc) interferon (IFN) beta-1a in patients with relapsing-remitting MS. This review is the first collation of all these data in one article, with a look ahead to the next generation of studies involving the new formulation of sc IFN beta-1a.

Serum matrix metalloproteinase levels correlate with brain injury in human immunodeficiency virus infection.

Circulating levels of specific matrix metalloproteinases (MMPs; 1 and 7) were evaluated as correlates of brain injury in eight individuals in advanced human immunodeficiency virus (HIV) infection. Neurological status was quantified in vivo with automated segmentation algorithms and with diffusion tensor imaging. Both metalloproteinases correlated with microstructural brain alterations and the degree of atrophy.

Identification, causation, alleviation, and prevention of complications (ICAP): an approach to symptom and disability management in multiple sclerosis.

Comprehensive management of patients with multiple sclerosis (MS) includes treatment to modify the disease course and interventions to address the persistent symptoms and consequences of this chronic illness, which can affect patients for decades. Although much excitement and attention accompanies new therapeutic initiatives for disease management, symptomatic issues are often overshadowed despite their impact on patients' daily lives. This article describes the application of an organizational scheme of identification, causation, alleviation, and prevention of complications as a tool for identifying and managing symptomatic issues in patients with MS.

The implications of immunogenicity for protein-based multiple sclerosis therapies.

Administered proteins are inherently immunogenic, which may influence their efficacy or safety when used therapeutically. A review of the published literature was performed to compare and evaluate the development and consequences of antibodies against therapeutic protein agents for the treatment of multiple sclerosis (MS). Interferon beta (IFNbeta), glatiramer acetate (GA), and natalizumab are all protein-based therapeutic agents approved to treat MS and are associated with the development of antibodies.

Platelet decline: an avenue for investigation into the pathogenesis of human immunodeficiency virus -associated dementia.

Background: The identification of biomarkers identifying onset of human immunodeficiency virus-associated dementia (HIV-D) is critical for diagnosis and the elucidation of pathophysiologic pathways.

Objective: To examine the association between platelet decline from baseline and HIV-D.

Design: Prospective cohort study within the North-East AIDS Dementia cohort.