Progressive multiple sclerosis exhibits decreasing glutamate and glutamine over two years

El, MacMillan; Tam, Roger; Zhao, Yinshan; Vavasour, Irene M; Li, Dkb; Oger, Joël; Kolind, SH; Al, Traboulsee

doi:10.1177/1352458515586086

Cited by 41 publications

(47 citation statements)

References 14 publications

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“…Several MRI techniques may provide improved pathologic specificity and, thus, better correlation with clinical disability: diffusion tensor imaging (DTI, which quantifies the threedimensional diffusion of water), 34 magnetization transfer imaging (MTI, which quantifies tissue integrity through the interaction of protons bound to molecular structures and free water), 35 magnetic resonance spectroscopy (which quantifies tissue metabolites), 36 and techniques such as magnetic resonance fingerprinting. 37 These techniques can be applied to the whole brain, or selectively to gray or white matter lesions, or regions that appear normal on standard MRI.…”

Section: "Advanced" Mri Techniquesmentioning

confidence: 99%

Progressive multiple sclerosis: prospects for disease therapy, repair, and restoration of function

et al. 2017

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Multiple sclerosis is a major cause of neurological disability, which accrues predominantly during progressive forms of the disease. Although development of multifocal inflammatory lesions is the underlying pathological process in relapsing-remitting multiple sclerosis, the gradual accumulation of disability that characterises progressive multiple sclerosis seems to result more from diffuse immune mechanisms and neurodegeneration. As a result, the 14 anti-inflammatory drugs that have regulatory approval for treatment of relapsing-remitting multiple sclerosis have little or no efficacy in progressive multiple sclerosis without inflammatory lesion activity. Effective therapies for progressive multiple sclerosis that prevent worsening, reverse damage, and restore function are a major unmet need. In this Series paper we summarise the current status of therapy for progressive multiple sclerosis and outline prospects for the future.

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Section: "Advanced" Mri Techniquesmentioning

confidence: 99%

Progressive multiple sclerosis: prospects for disease therapy, repair, and restoration of function

et al. 2017

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“…MacMillan et al found early and consistent alterations in the Glu and glutamine levels in CNS over two years in SPMS patients with MR spectroscopy. This method might be competent to measure disease progression over years, using the appropriate imaging techniques suggested by the authors [160]. …”

Section: Biomarkers In Tissue Damage Of Msmentioning

confidence: 99%

Excitotoxins, Mitochondrial and Redox Disturbances in Multiple Sclerosis

Rajda

Pukoli

Bende

et al. 2017

IJMS

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Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). There is increasing evidence that MS is not only characterized by immune mediated inflammatory reactions, but also by neurodegenerative processes. There is cumulating evidence that neurodegenerative processes, for example mitochondrial dysfunction, oxidative stress, and glutamate (Glu) excitotoxicity, seem to play an important role in the pathogenesis of MS. The alteration of mitochondrial homeostasis leads to the formation of excitotoxins and redox disturbances. Mitochondrial dysfunction (energy disposal failure, apoptosis, etc.), redox disturbances (oxidative stress and enhanced reactive oxygen and nitrogen species production), and excitotoxicity (Glu mediated toxicity) may play an important role in the progression of the disease, causing axonal and neuronal damage. This review focuses on the mechanisms of mitochondrial dysfunction (including mitochondrial DNA (mtDNA) defects and mitochondrial structural/functional changes), oxidative stress (including reactive oxygen and nitric species), and excitotoxicity that are involved in MS and also discusses the potential targets and tools for therapeutic approaches in the future.

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“…More recently, however, research has begun to indicate that changes in glutamate levels and glutamate receptor expression may be significant earlier in the disease process than originally thought [10]. In one two-year study [11], the levels of both glutamate and glutamine were shown to change markedly over time in the white matter of MS patients with large decreases seen over the course of the study. Overall, the expression of those enzymes responsible for the production and degradation of glutamate is imbalanced in MS [12], potentially causing a type of positive-feedback loop in which glutamate excitotoxicity induces axonal apoptosis, releasing more glutamate [13].…”

Section: Introductionmentioning

confidence: 99%

Serum Glutamate Is a Predictor for the Diagnosis of Multiple Sclerosis

Gawwam

Sharquie

2017

The Scientific World Journal

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One neurotransmitter, glutamate, has been implicated in the autoimmune demyelination seen in multiple sclerosis (MS). Glutamate is present in many tissues in the body, so consideration should be given to whether the serum level of glutamate is likely well correlated with the activity of the disease. This research aimed to compare the serum glutamate levels from patients diagnosed with MS with those from an age-matched control population. A review of this data could shed light upon whether the serum testing of glutamate using Enzyme-Linked Immunosorbent Assay (ELISA) is a reliable indicator of MS activity. Serum samples were obtained from 55 patients with different patterns of MS and from 25 healthy adults as a control group. The ELISA technique was used to determine the glutamate levels in the serum samples. The mean serum glutamate level for patients with MS was 1.318 ± 0.543 nmol/ml and that of the controls was 0.873 ± 0.341 nmol/ml. The serum glutamate levels showed an area under the curve via the receiver operating characteristics (ROC) of 0.738, which was significant (p value = 0.001). The present study is the first to establish a strong connection between the serum glutamate levels and MS patients, where there was statistically significant elevation of serum glutamate in MS patients; hence this elevation might be used as a monitor to help in the diagnosis of MS patients.

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Progressive multiple sclerosis exhibits decreasing glutamate and glutamine over two years

Abstract: The high rates of change of both glutamate and glutamine over two years suggest they are promising new biomarkers of MS disease progression.

Cited by 41 publications

References 14 publications

Progressive multiple sclerosis: prospects for disease therapy, repair, and restoration of function

Progressive multiple sclerosis: prospects for disease therapy, repair, and restoration of function

Excitotoxins, Mitochondrial and Redox Disturbances in Multiple Sclerosis

Serum Glutamate Is a Predictor for the Diagnosis of Multiple Sclerosis

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