Brain metabolites in definite amyotrophic lateral sclerosis

Unrath, Alexander; Ludolph, Albert C.; Kassubek, Jan

doi:10.1007/s00415-006-0495-2

Cited by 56 publications

(26 citation statements)

References 29 publications

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“…Whereas conventional brain MRI is unremarkable in ALS [4], 1 H-MRS has revealed various neurochemical abnormalities that may indicate underlying disease processes, including gliosis, glutamate excitotoxicity, and oxidative stress. 1 H-MRS studies over the years in humans with ALS have suggested abnormal levels of the following brain metabolites: N -acetylaspartate (NAA, marker of neuronal integrity) [5–7]; myo -inositol (mIns, putative marker of glial cells) [8,9]; glutamate (Glu, excitatory neurotransmitter) [10]; γ-aminobutyric acid (GABA, inhibitory neurotransmitter) [5]; and glutathione (GSH, thiol antioxidant) [11]. Nearly all of these studies included the primary motor cortex and its underlying white matter as a region of investigation.…”

Section: Introductionmentioning

confidence: 99%

Ultra-High Field Proton MR Spectroscopy in Early-Stage Amyotrophic Lateral Sclerosis

et al. 2017

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A major hurdle in the development of effective treatments for amyotrophic lateral sclerosis (ALS) has been the lack of robust biomarkers for use as clinical trial endpoints. Neurochemical profiles obtained in vivo by high field proton magnetic resonance spectroscopy (1H-MRS) can potentially provide biomarkers of cerebral pathology in ALS. However, previous 1H-MRS studies in ALS have produced conflicting findings regarding alterations in the levels of neurochemical markers such as glutamate (Glu) and myo-inositol (mIns). Furthermore, very few studies have investigated the neurochemical abnormalities associated with ALS early in its course. In this study, we measured neurochemical profiles using single-voxel 1H-MRS at 7 tesla (T) and glutathione (GSH) levels using edited MRS at 3 T in 19 subjects with ALS who had relatively high functional status (ALS Functional Rating Scale-Revised mean ± SD = 39.8 ± 5.6) and 17 healthy controls. We observed significantly lower total N-acetylaspartate over mIns (tNAA/mIns) ratio in the motor cortex and pons of subjects with ALS versus healthy controls. No group differences were detected in GSH at 3 and 7 T. In subjects with ALS, the levels of tNAA, mIns, and Glu in the motor cortex were dependent on the extent of disease represented by El Escorial diagnostic subcategories. Specifically, combined probable/definite ALS had lower tNAA than possible ALS and controls (both p = 0.03), higher mIns than controls (p < 0.01), and lower Glu than possible ALS (p < 0.01). The effect of disease stage on MRS-measured metabolite levels may account for dissimilar findings among previous 1H-MRS studies in ALS.

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Section: Introductionmentioning

confidence: 99%

Ultra-High Field Proton MR Spectroscopy in Early-Stage Amyotrophic Lateral Sclerosis

et al. 2017

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“…Follow-up studies have shown a decrease in the NAA peak in the precentral cortex (with no differences for other metabolites) [96], a decrease in the NAA/Cho peak and an increase in the Cho/Cr peak [91]. …”

Section: Resultsmentioning

confidence: 99%

The value of magnetic resonance imaging as a biomarker for amyotrophic lateral sclerosis: a systematic review

et al. 2016

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BackgroundAmyotrophic lateral sclerosis (ALS) is a fatal, rapidly progressive neurodegenerative disease that mainly affects the motor system. A number of potentially neuroprotective and neurorestorative disease-modifying drugs are currently in clinical development. At present, the evaluation of a drug’s clinical efficacy in ALS is based on the ALS Functional Rating Scale Revised, motor tests and survival. However, these endpoints are general, variable and late-stage measures of the ALS disease process and thus require the long-term assessment of large cohorts. Hence, there is a need for more sensitive radiological biomarkers. Various sequences for magnetic resonance imaging (MRI) of the brain and spinal cord have may have value as surrogate biomarkers for use in future clinical trials. Here, we review the MRI findings in ALS, their clinical correlations, and their limitations and potential role as biomarkers.MethodsThe PubMed database was screened to identify studies using MRI in ALS. We included general MRI studies with a control group and an ALS group and longitudinal studies even if a control group was lacking.ResultsA total of 116 studies were analysed with MRI data and clinical correlations. The most disease-sensitive MRI patterns are in motor regions but the brain is more broadly affected.ConclusionDespite the existing MRI biomarkers, there is a need for large cohorts with long term MRI and clinical follow-up. MRI assessment could be improved by standardized MRI protocols with multicentre studies.

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“…MRI can also demonstrate subtle changes in ALS patients such as T2 hypointensity in the precentral gyrus (52) and T2 hyperintensity in the corticospinal tract (53,54). However, these findings are nonspecific and lack diagnostic validity (55–58).…”

Section: Discussionmentioning

confidence: 99%

Diagnostic Accuracy Using Diffusion Tensor Imaging in the Diagnosis of ALS

Foerster¹,

Dwamena²,

Petrou³

et al. 2012

Academic Radiology

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Rationale and Objectives A number of studies have reported decreases in fractional anistropy (FA) in amyotrophic lateral sclerosis using diffusion tensor imaging (DTI). The purpose of this study was to perform a meta-analysis in order to estimate the diagnostic test accuracy measures of DTI for the diagnosis of amyotrophic lateral sclerosis (ALS). Materials and Methods We searched MEDLINE (1966–April 2011), EMBASE (1999–April 2011), CINAHL (1999–April 2011), and Cochrane (2005–April 2011) databases to identify studies that measured FA in ALS subjects. Human, single-center studies using a DTI region of interest (ROI) or tractography techniques were used to compare FA values along the brain corticospinal tracts between ALS subjects and healthy controls. There were no language restrictions. Independent extraction of articles by 2 authors using predefined data fields including study quality indicators. We identified 30 case-control studies that used region of interest or tractography DTI techniques. We applied binormal receiver operative characteristic (ROC) curve analysis to assign specificity and sensitivity for each study. We applied the bivariate mixed-effects regression model using the Markov Chain Monte Carlo Simulation to calculate summary estimates for the sensitivity and specificity. We used the metan module in Stata, version 11.0, to calculate the area under the ROC curve, diagnostic odds ratio and the test effectiveness summary estimates. Results The pooled sensitivity was 0.65 (95% CI 0.61–0.69); the pooled specificity, 0.67 (95% CI 0.63–0.72); the pooled diagnostic odds ratio, 1.88 (95% CI 1.46–2.30); the pooled test effectiveness, 1.04 (95% CI 0.81–1.27); and the pooled area under the ROC curve, 0.76 (95% CI 0.71–0.81). Subanalyses comparing magnetic resonance imaging (MRI) field strength (1.5T vs. 3.0T) and brain location (corticospinal tract average vs. internal capsule) revealed no significant differences in the test accuracy measures. Reference standard used for the diagnosis of ALS was the El Escorial criteria. There was at least moderate heterogeneity between the studies. True study quality is uncertain. Conclusion The discriminatory capability of DTI to make a diagnosis of ALS is only modest. There were no significant differences in the diagnostic test accuracy summary estimates with respect to MRI field strength or brain location.

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Brain metabolites in definite amyotrophic lateral sclerosis

Cited by 56 publications

References 29 publications

Ultra-High Field Proton MR Spectroscopy in Early-Stage Amyotrophic Lateral Sclerosis

Ultra-High Field Proton MR Spectroscopy in Early-Stage Amyotrophic Lateral Sclerosis

The value of magnetic resonance imaging as a biomarker for amyotrophic lateral sclerosis: a systematic review

Diagnostic Accuracy Using Diffusion Tensor Imaging in the Diagnosis of ALS

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