Multiple sclerosis: Frequency, cost, and economic burden in the United States

Chen, Alex Y.; Chonghasawat, Amy O.; Leadholm, Kevin L.

doi:10.1016/j.jocn.2017.06.005

Cited by 30 publications

(20 citation statements)

References 11 publications

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“…Multiple sclerosis (MS) is a chronic inflammatory disease of central nervous system (CNS) that affects more than 2.5 million people worldwide. 1 In MS, inflammation, demyelination and neurodegeneration are considered to contribute to disease development. 2 , 3 It is assumed that in MS, a misguided immune response against the CNS is initiated and orchestrated by autoreactive T cells, leading to progressive demyelination, oligodendrocyte injury and axonal loss, 4 , 5 that affect not only the white but also the grey matter.…”

Section: Introductionmentioning

confidence: 99%

Teriflunomide preserves peripheral nerve mitochondria from oxidative stress-mediated alterations

Malla

Cotten

Ulshoefer

et al. 2020

Therapeutic Advances in Chronic Disease

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Mitochondrial dysfunction is a common pathological hallmark in various inflammatory and degenerative diseases of the central nervous system, including multiple sclerosis (MS). We previously showed that oxidative stress alters axonal mitochondria, limiting their transport and inducing conformational changes that lead to axonal damage. Teriflunomide (TFN), an oral immunomodulatory drug approved for the treatment of relapsing forms of MS, reversibly inhibits dihydroorotate dehydrogenase (DHODH). DHODH is crucial for de novo pyrimidine biosynthesis and is the only mitochondrial enzyme in this pathway, thus conferring a link between inflammation, mitochondrial activity and axonal integrity. Here, we investigated how DHODH inhibition may affect mitochondrial behavior in the context of oxidative stress. We employed a model of transected murine spinal roots, previously developed in our laboratory. Using confocal live imaging of axonal mitochondria, we showed that in unmanipulated axons, TFN increased significantly the mitochondria length without altering their transport features. In mitochondria challenged with 50 µM hydrogen peroxide (H2O2) to induce oxidative stress, the presence of TFN at 1 µM concentration was able to restore mitochondrial shape, motility, as well as mitochondrial oxidation potential to control levels. No effects were observed at 5 µM TFN, while some shape and motility parameters were restored to control levels at 50 µM TFN. Thus, our data demonstrate an undescribed link between DHODH and mitochondrial dynamics and point to a potential neuroprotective effect of DHODH inhibition in the context of oxidative stress-induced damage of axonal mitochondria.

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Section: Introductionmentioning

confidence: 99%

Teriflunomide preserves peripheral nerve mitochondria from oxidative stress-mediated alterations

Malla

Cotten

Ulshoefer

et al. 2020

Therapeutic Advances in Chronic Disease

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“…MS is associated with high social and economic burden and increases over time. The economic burden associated with MS in Europe was estimated to be approximately 14.6 billion euros in 2010, and the United States bore the associated costs of approximately $4.3 billion in 2013 ( 99 ). Although the etiology of MS is currently unknown, many disease-related risk factors have been identified.…”

Section: Gene Polymorphisms and Autoimmune Diseasesmentioning

confidence: 99%

Toll-Like Receptors Gene Polymorphisms in Autoimmune Disease

et al. 2021

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Toll-like receptors (TLRs) are important initiators of the immune response, both innate and acquired. Evidence suggests that gene polymorphisms within TLRs cause malfunctions of certain key TLR-related signaling pathways, which subsequently increases the risk of autoimmune diseases. We illustrate and discuss the current findings on the role of Toll-like receptor gene polymorphisms in numerous autoimmune diseases in this review, such as type 1 diabetes mellitus, Graves’ disease, rheumatoid arthritis, systemic lupus erythematosus and multiple sclerosis. The study of genetic variation in TLRs in different populations has shown a complex interaction between immunity and environmental factors. This interaction suggests that TLR polymorphisms affect the susceptibility to autoimmune diseases differently in various populations. The identification of Toll-like receptor gene polymorphisms can expand our understanding of the pathogenesis of autoimmune diseases, which will subsequently guide effective medical management and provide insight into prognosis and advanced treatments.

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“…It results in a heterogeneous array of outcomes that can compromise quality of life. 1 One of the most common and impactful results of MS is cognitive dysfunction, affecting nearly two-thirds of persons with MS. 2 Cognitive dysfunction typically manifests as impaired information processing speed, learning and memory, and/or executive function. 2,3 Although there may be multiple mechanisms contributing to cognitive dysfunction in MS, cerebrovascular dysfunction may play an underappreciated role in this setting.…”

Section: O N L I N E F I R S Tmentioning

confidence: 99%

Assessment of Cerebrovascular Dynamics and Cognitive Function with Acute Aerobic Exercise in Persons with Multiple Sclerosis

Lefferts¹,

Rosenberg²,

Schroeder³

et al. 2021

International Journal of MS Care

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Background: Cognitive dysfunction in multiple sclerosis (MS) may partially stem from inadequate cerebral blood flow. Cerebral blood flow and cognitive function improve with aerobic exercise in healthy adults. The effect of aerobic exercise on cerebrovascular hemodynamics and cognitive performance in persons with MS is unclear. The acute effect of aerobic exercise versus quiet rest on cerebrovascular hemodynamics and cognitive performance in relapsing-remitting MS was examined. Methods: Sixteen adults with relapsing-remitting MS underwent cerebrovascular hemodynamics and cognitive performance testing before, 2 minutes after, and 30 minutes after aerobic exercise (20-minute treadmill walking, 60% peak oxygen consumption) and a time-matched seated control. Brachial blood pressure was obtained via an oscillometric cuff. Right middle cerebral artery (MCA) blood velocity was measured via transcranial Doppler and used to calculate mean velocity, pulsatility index (PI), and conductance. Carotid artery stiffness was measured via ultrasonography and tonometry. Cognitive performance (accuracy, reaction time) was assessed using a modified flanker task. Results: Exercise elicited significant increases in mean pressure and carotid artery stiffness and decreases in MCA conductance at 2 minutes after exercise, which subsided by 30 minutes (P < .05). Exercise did not significantly alter MCA PI. Flanker reaction time decreased during posttesting in both conditions (P < .05). There were no condition × time interactions for cognitive performance. Conclusions: Persons with MS seem resilient to exercise-induced acute changes in MCA PI despite transient carotid stiffening, potentially via reductions in MCA conductance. These data suggest that changes in cognitive performance after acute aerobic exercise are not directly related to transient cerebrovascular responses in persons with MS.

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Multiple sclerosis: Frequency, cost, and economic burden in the United States

Cited by 30 publications

References 11 publications

Teriflunomide preserves peripheral nerve mitochondria from oxidative stress-mediated alterations

Teriflunomide preserves peripheral nerve mitochondria from oxidative stress-mediated alterations

Toll-Like Receptors Gene Polymorphisms in Autoimmune Disease

Assessment of Cerebrovascular Dynamics and Cognitive Function with Acute Aerobic Exercise in Persons with Multiple Sclerosis

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