A Potential Biomarker in Amyotrophic Lateral Sclerosis: Can Assessment of Brain Iron Deposition with SWI and Corticospinal Tract Degeneration with DTI Help?
Sheelakumari R1, Madhusoodanan M1, Radhakrishnan A1, Ranjith G1, Thomas B2. AJNR Am J Neuroradiol. 2015 Oct 22.

Abstract
BACKGROUND AND PURPOSE:
Iron-mediated oxidative stress plays a pivotal role in the pathogenesis of amyotrophic lateral sclerosis. This study aimed to assess iron deposition qualitatively and quantitatively by using SWI and microstructural changes in the corticospinal tract by
using DTI in patients with amyotrophic lateral sclerosis.
MATERIALS AND METHODS:
Seventeen patients with amyotrophic lateral sclerosis and 15 age- and sex-matched controls underwent brain MR imaging with SWI and DTI. SWI was analyzed for both signal-intensity scoring and quantitative estimation of iron deposition in the anterior and
posterior banks of the motor and sensory cortices and deep gray nuclei. The diffusion measurements along the corticospinal tract at the level of pons and medulla were obtained by ROI analysis.
RESULTS:
Patients with amyotrophic lateral sclerosis showed reduced signal-intensity grades in the posterior bank of the motor cortex bilaterally. Quantitative analysis confirmed significantly higher iron content in the posterior bank of the motor cortex in
patients with amyotrophic lateral sclerosis. In contrast, no significant differences were noted for the anterior bank of the motor cortex, anterior and posterior banks of the sensory cortex, and deep nuclei. Receiver operating characteristic comparison
showed a cutoff of 35μg Fe/g of tissue with an area under the curve of 0.78 (P = .008) for the posterior bank of the motor cortex in discriminating patients with amyotrophic lateral sclerosis from controls. Fractional anisotropy was lower in the
pyramidal tracts of patients with amyotrophic lateral sclerosis at the pons and medulla on either side, along with higher directionally averaged mean diffusivity values. The combination of SWI and DTI revealed an area under the curve of 0.784 for
differentiating patients with amyotrophic lateral sclerosis from controls. CONCLUSIONS:
Measurements of motor cortex iron deposition and diffusion tensor parameters of the corticospinal tract may be useful biomarkers for the diagnosis of clinically suspected amyotrophic lateral sclerosis.

© 2016 American Society of Neuroradiology.

PMID: 26494694

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Brain signal intensity changes as biomarkers in amyotrophic lateral sclerosis Acta Neurologica Scandinavica
Juan F. Vázquez-Costa, Miguel Mazón, Joan Carreres-Polo, David Hervás, Jordi Pérez-Tur, Luis Martí-Bonmatí, Teresa Sevilla
First published: 29 October 2017Full publication history
DOI: 10.1111/ane.12863
Abstract
Objectives
To evaluate the contribution of the demographical, clinical, analytical and genetic factors to brain signal intensity changes in T2-weighted MR images in amyotrophic lateral sclerosis (ALS) patients and controls.
Methods
Susceptibility-weighted and FLAIR sequences were obtained in a 3T MR scanner. Iron-related hypointensities in the motor cortex (IRhMC) and hyperintensities of the corticospinal tract (HCT) were qualitatively scored. Age, gender, family history and
clinical variables were recorded. Baseline levels of ferritin were measured. C9orf72 was tested in all patients and SOD1 only in familial ALS patients not carrying a C9orf72 expansion. Patients who carried a mutation were categorized as genetic.
Associations of these variables with visual scores were assessed with multivariable analysis.
Results
A total of 102 ALS patients (92 non-genetic and 10 genetic) and 48 controls (28 ALS mimics and 20 healthy controls) were recruited. In controls, IRhMC associated with age, but HCT did not. In ALS patients, both HTC and IRhMC strongly associated with
clinical UMN impairment and bulbar onset. The intensity/extent of IRhMC in the different motor homunculus regions (lower limbs, upper limbs and bulbar) were linked to the symptoms onset site. Between genetic and sporadic patients, no difference in IRhMC
and HCT was found.
Conclusions
IRhMC and HCT are reliable markers of UMN degeneration in ALS patients and are more frequent in bulbar onset patients, independently of the mutation status. Age should be considered when evaluating IRhMC. The regional measurement of IRhMC following the
motor homunculus could be used as a measure of disease progression.

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