Natalizumab in Early Relapsing-Remitting Multiple Sclerosis: A 4-Year, Open-Label Study.

Introduction: STRIVE was a 4-year, multicenter, observational, open-label, single-arm study of natalizumab treatment in anti-JC virus antibody-negative (JCV-negative) relapsing-remitting multiple sclerosis (RRMS) patients with disease duration ≤ 3 years. The objective of STRIVE was to examine no evidence of disease activity (NEDA) status and predictors of NEDA in natalizumab-treated patients with early RRMS.

Methods: Proportions of patients with NEDA were evaluated along with baseline predictors of NEDA, annualized relapse rate, 24-week confirmed disability worsening (CDW), magnetic resonance imaging assessments (T2 and gadolinium-enhancing lesions), and serious adverse events.

APOE ε4 is associated with exacerbation of cognitive decline in patients with multiple sclerosis.

Background: : In previous studies we and others have demonstrated an association with apolipoprotein (APOE) ε4 genotype and the presence of cognitive deficits in multiple sclerosis (MS). In this follow-up study, we have assessed whether APOE ε4 status exacerbates progression of cognitive deficits in MS.

Methods: : A total of 197 patients with MS were assessed for APOE genotype, and baseline cognitive performance was measured using a standardized battery of tests.

Central nervous system (CNS)-resident natural killer cells suppress Th17 responses and CNS autoimmune pathology.

Natural killer (NK) cells of the innate immune system can profoundly impact the development of adaptive immune responses. Inflammatory and autoimmune responses in anatomical locations such as the central nervous system (CNS) differ substantially from those found in peripheral organs. We show in a mouse model of multiple sclerosis that NK cell enrichment results in disease amelioration, whereas selective blockade of NK cell homing to the CNS results in disease exacerbation.

Expansion of regulatory T cells via IL-2/anti-IL-2 mAb complexes suppresses experimental myasthenia.

Human autoimmune diseases are often characterized by a relative deficiency in CD4(+)CD25(+) regulatory T cells (Treg). We therefore hypothesized that expansion of Treg can ameliorate autoimmune pathology. We tested this hypothesis in an experimental model for autoimmune myasthenia gravis (MG), a B-cell-mediated disease characterized by auto-Ab directed against the acetylcholine receptor within neuromuscular junctions.

B cells from glatiramer acetate-treated mice suppress experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) thought to be primarily mediated by T cells. However, emerging evidence supports an important role for B cells in the pathogenesis and inhibition of MS. Glatiramer acetate (GA), a Food and Drug Administration-approved drug for the treatment of MS, has a good safety profile.

T-bet deficiency decreases susceptibility to experimental myasthenia gravis.

T-bet, a tissue-specific transcription factor, controls T helper 1 (Th1) cell differentiation and IFN-production. Given the reciprocal relationship between Th1 and other types of helper T cells, we hypothesized that T-bet impacts multiple helper and regulatory T (Treg) cells, thereby influencing the magnitude of autoimmune disease. We tested this hypothesis in an experimental model of autoimmune myasthenia gravis (EAMG) of mice.

Nicotinic attenuation of central nervous system inflammation and autoimmunity.

The expression of nicotinic acetylcholine receptors by neurons, microglia, and astrocytes suggests possibly diverse mechanisms by which natural nicotinic cholinergic signaling and exposure to nicotine could modulate immune responses within the CNS. In this study, we show that nicotine exposure significantly delays and attenuates inflammatory and autoimmune responses to myelin Ags in the mouse experimental autoimmune encephalomyelitis model. In the periphery, nicotine exposure inhibits the proliferation of autoreactive T cells and alters the cytokine profile of helper T cells.

CCL2 recruitment of IL-6-producing CD11b+ monocytes to the draining lymph nodes during the initiation of Th17-dependent B cell-mediated autoimmunity.

The development and function of Th17 cells are influenced in part by the cytokines TGF-beta, IL-23 and IL-6, but the mechanisms that govern recruitment and activity of Th17 cells during initiation of autoimmunity remain poorly defined. We show here that the development of autoreactive Th17 cells in secondary lymphoid organs in experimental autoimmune myasthenia gravis--an animal model of human myasthenia gravis--is modulated by IL-6-producing CD11b(+) cells via the CC chemokine ligand 2 (CCL2). Notably, acetylcholine receptor (AChR)-reactive Th17 cells provide help for the B cells to produce anti-AChR antibodies, which are responsible for the impairment of the neuromuscular transmission that contributes to the clinical manifestations of autoimmunity, as indicated by a lack of disease induction in IL-17-deficient mice.

IL-21 receptor expression determines the temporal phases of experimental autoimmune encephalomyelitis.

The IL-21 receptor (IL-21R) consists of a unique subunit and a common gamma chain (gamma(c)) that is shared with other cytokines including IL-2, IL-4, IL-7, and IL-15. The interaction between IL-21 and IL-21R results in significant effects on both innate and adaptive immune responses. In this study we examined the influence of IL-21R deficiency (IL-21R(-/-)) on the development of experimental autoimmune encephalomyelitis (EAE), an animal model of human multiple sclerosis (MS).

Therapeutic effect of anthracene-based anticancer agent ethonafide in an animal model of multiple sclerosis.

The side effects of cancer chemotherapeutic agents such as mitoxantrone (MIT) in multiple sclerosis (MS) patients justify the search for less toxic drugs. Ethonafide is an anthracene-based antineoplastic drug similar to MIT. With reference to MIT, we examined the effect of ethonafide on experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice, an animal model of human MS.

Autoreactive T cells mediate NK cell degeneration in autoimmune disease.

Emerging evidence indicates that NK cells play an important and complex role in autoimmune disease. Humans with autoimmune diseases often have reduced NK cell numbers and compromised NK cell functions. Mechanisms underlying this NK cell degeneration and its biological significance are not known.

Do Th2 cells mediate the effects of glatiramer acetate in experimental autoimmune encephalomyelitis?

Mechanisms underlying the clinical benefits of glatiramer acetate (GA) for patients with multiple sclerosis (MS) remain elusive. A prevailing hypothesis is that GA can induce Th2-polarized T cells, which cross-recognize myelin-specific epitopes and can inhibit myelin-reactive autoaggression in Th1 T cells, a process referred to as 'bystander suppression.' To test whether the efficacy of GA is indeed mediated by Th2 T cells, we have utilized an animal model for MS: experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice.

Cooperation of invariant NKT cells and CD4+CD25+ T regulatory cells in the prevention of autoimmune myasthenia.

CD1d-restricted NKT cells and CD4+CD25+ regulatory T (Treg) cells are thymus-derived subsets of regulatory T cells that have an important role in the maintenance of self-tolerance. Whether NKT cells and Treg cells cooperate functionally in the regulation of autoimmunity is not known. We have explored this possibility in experimental autoimmune myasthenia gravis (EAMG), an animal model of human myasthenia gravis, induced by immunization of C57BL/6 mice with the autoantigen acetylcholine receptor.

Improving resident research in physical medicine and rehabilitation: impact of a structured training program.

Objective: This study describes a research training program that implemented several processes and structures with the aim of increasing the quality and quantity of resident research in physical medicine and rehabilitation. Another aim of the program was to address the Accreditation Council for Graduate Medical Education (ACGME) Practice-Based Learning and Improvement competency.

Design: Educational program.

Critical review of prolotherapy for osteoarthritis, low back pain, and other musculoskeletal conditions: a physiatric perspective.

The current scientific literature relevant to the use of prolotherapy for osteoarthritis, low back pain, and other musculoskeletal conditions was reviewed and critically analyzed to determine a clinical effect. Three randomized, controlled studies were found studying the use of dextrose/glycerine/phenol prolotherapy for chronic low back pain; however, they were inconclusive due to the lack of adequate controls, heterogeneity in patient diagnoses, and variations in solutions injected. Two randomized, controlled studies were found that provide some evidence supporting the use of 10% dextrose prolotherapy for osteoarthritis.

Autonomic dysreflexia: one more way EMS can positively affect patient survival.

Autonomic dysreflexia is a life-threatening medical condition that affects people with spinal cord injuries above T6. Caused by the division of the autonomic nervous system, it can result in disastrous hypertension. Although complicated in nature, AD can be quickly treated and reversed by prehospital providers.

Spinal cord injury computer-assisted instruction for medical students.

Objective: To determine if a computer-assisted instruction program would improve fourth-year medical students' knowledge base related to spinal cord injury, as determined by pretest and posttest scores.

Design: A multimedia computer-assisted instruction program was developed and offered on a volunteer basis to an entire class of fourth-year medical students (n = 168). Effectiveness of the instructional content was evaluated with pretests and posttests, and overall user satisfaction with the module was assessed with the courseware evaluation.

Appropriateness of the Ilfeld Psychiatric Symptom Index as a screening tool for depressive symptomatology in persons with spinal cord injury.

Background: Depressive symptomatology is seen in some persons with spinal cord injury (SCI). Identification of a depressed mood can assist clinicians in early treatment. The Ilfeld Psychiatric Symptom Index (Ilfeld PSI) is a screening tool that assesses a range of symptoms: depression, cognitive disturbance, anxiety, and anger.