Brain iron MRI: A biomarker for amyotrophic lateral sclerosis

Ignjatović, Aleksandar; Stević, Zorica; Lavrnić, Slobodan; Daković, Marko; Bačić, Goran

doi:10.1002/jmri.24121

Cited by 72 publications

(74 citation statements)

References 50 publications

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“…Third, until now, MR imaging studies investigated, individually, cortical atrophy [8][9][10]18,19 or hypointensity. 7,22 To the best of our knowledge, this is the first study assessing the combination of both parameters, thus improving the radiologic evaluation of M1. Compared with the assessment of a single parameter (SH or Thk), the use of the SH/Thk gives us 3 main advantages: 1) to assess simultaneously 2 different radiologic features related to the cortical neurodegeneration; 2) to find a radiologic tool that correlates with clinical UMN impairment; and 3) to reduce the false-positive ratio related to the increase in T2* hypointensity of M1 in the elderly.…”

Section: Results Of Visual Assessment Of 3t and 7t Imagesmentioning

confidence: 99%

Semiautomated Evaluation of the Primary Motor Cortex in Patients with Amyotrophic Lateral Sclerosis at 3T

Donatelli¹,

Retico

Ienco

et al. 2017

AJNR Am J Neuroradiol

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BACKGROUND AND PURPOSE:Amyotrophic lateral sclerosis is a neurodegenerative disease involving the upper and lower motor neurons. In amyotrophic lateral sclerosis, pathologic changes in the primary motor cortex include Betz cell depletion and the presence of reactive iron-loaded microglia, detectable on 7T MR images as atrophy and T2*-hypointensity. Our purposes were the following: 1) to investigate the signal hypointensity-to-thickness ratio of the primary motor cortex as a radiologic marker of upper motor neuron involvement in amyotrophic lateral sclerosis with a semiautomated method at 3T, 2) to compare 3T and 7T results, and 3) to evaluate whether semiautomated measurement outperforms visual image assessment.

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Section: Results Of Visual Assessment Of 3t and 7t Imagesmentioning

confidence: 99%

Semiautomated Evaluation of the Primary Motor Cortex in Patients with Amyotrophic Lateral Sclerosis at 3T

Donatelli¹,

Retico

Ienco

et al. 2017

AJNR Am J Neuroradiol

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“…Signs of iron accumulation and high levels of iron import have been observed in the central nervous system of ALS patients [5–7] and in a mouse model of ALS [8]. Several clinical reports showed higher serum ferritin and lower serum transferrin levels in ALS patients [9–12].…”

Section: Introductionmentioning

confidence: 99%

Iron Metabolism Disturbance in a French Cohort of ALS Patients

Veyrat-Durebex

Corcia

Mucha

et al. 2014

BioMed Research International

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Objective. The aim of this study was to assess iron status in a cohort of amyotrophic lateral sclerosis (ALS) patients compared to controls in order to evaluate these parameters as a risk factor or a modifying factor of ALS. Methods. We collected serum iron, ferritin, transferrin, total iron-binding capacity, and transferrin saturation coefficient (TSC) from 104 ALS patients at the time of diagnosis and from 145 controls. We reported phenotypic characteristics and evolution parameters such as ALSFRS-R and forced vital capacity at diagnosis and after one year of follow-up. In a first step we compared iron status between ALS patients and controls, and then we evaluated the relation between iron status and disease evolution of ALS patients using univariate and multivariate analysis. Results. We observed increased concentrations of serum iron (P = 0.002) and ferritin (P < 0.0001) and increased TSC (P = 0.017) in ALS patients. We also showed an association between markers of iron status and high body weight loss in ALS patients. The multivariate analysis of survival highlighted a significant relation between ferritin level and disease duration (P = 0.038). Conclusion. This is the first study showing a higher concentration of serum iron in ALS patients, strengthening the involvement of a deregulation of iron metabolism in ALS.

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“…ALS is associated with elevated iron, with increased iron and iron-related proteins in the serum of ALS patients [108], and elevated iron www.futuremedicine.com in motor cortex of ALS patients as detected by MRI [109][110][111]. Evidence from SOD1 mice indicates this includes elevated mitochondrial iron [112].…”

Section: Amyotrophic Lateral Sclerosismentioning

confidence: 92%

Targeting Mitochondrial Metal Dyshomeostasis for the Treatment of Neurodegeneration

Liddell

2015

Neurodegener. Dis. Manag.

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Mitochondrial impairment and metal dyshomeostasis are suggested to be associated with many neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis and Friedreich's ataxia. Treatments aimed at restoring metal homeostasis are highly effective in models of these diseases, and clinical trials hold promise. However, in general, the effect of these treatments on mitochondrial metal homeostasis is unclear, and the contribution of mitochondrial metal dyshomeostasis to disease pathogenesis requires further investigation. This review describes the role of metals in mitochondria in health, how mitochondrial metals are disrupted in neurodegenerative diseases, and potential therapeutics aimed at restoring mitochondrial metal homeostasis and function.

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Brain iron MRI: A biomarker for amyotrophic lateral sclerosis

Abstract: The detection of hypointensities in PGGM appears to be a very promising surrogate MRI biomarker for ALS due to its simplicity, high sensitivity and specificity, suitability for longitudinal studies, and relationship with the pathogenesis of the disease.

Cited by 72 publications

References 50 publications

Semiautomated Evaluation of the Primary Motor Cortex in Patients with Amyotrophic Lateral Sclerosis at 3T

Semiautomated Evaluation of the Primary Motor Cortex in Patients with Amyotrophic Lateral Sclerosis at 3T

Iron Metabolism Disturbance in a French Cohort of ALS Patients

Targeting Mitochondrial Metal Dyshomeostasis for the Treatment of Neurodegeneration

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