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Updated: Feb 19, 2026
Utility of Dissociated Intrinsic Hand Muscle Atrophy in the Diagnosis of Amyotrophic Lateral Sclerosis
Published on: March 4, 2014
Brain signal intensity changes as biomarkers in amyotrophic lateral sclerosis
Juan F Vázquez-Costa1,2,3, Miguel Mazón4, Joan Carreres-Polo4
1Neuromuscular Research Unit, Instituto de Investigación Sanitaria la Fe, Valencia, Spain.
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.
Insights
Iron-related hypointensities in the motor cortex and hyperintensities of the corticospinal tract are reliable markers of neurodegeneration in amyotrophic lateral sclerosis (ALS). These MRI findings are more common in bulbar onset patients and can indicate disease progression.
Area of Science:
- Neurology
- Radiology
- Genetics
Background:
- Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease.
- Brain MRI signal intensity changes may reflect underlying pathology.
Purpose of the Study:
- To evaluate demographic, clinical, analytical, and genetic factors influencing T2-weighted MRI signal intensity changes in ALS patients and controls.
- To determine the utility of specific MRI markers in ALS.
Main Methods:
- Susceptibility-weighted and FLAIR MRI sequences were acquired.
- Iron-related hypointensities in the motor cortex (IRhMC) and hyperintensities of the corticospinal tract (HCT) were scored.
- Genetic testing (C9orf72, SOD1) and clinical data were analyzed.
Main Results:
- In ALS patients, both IRhMC and HCT correlated with upper motor neuron (UMN) impairment and bulbar onset.
- The extent of IRhMC mapped to the motor homunculus corresponded to symptom onset location.
- No significant differences in IRhMC and HCT were observed between genetic and sporadic ALS patients.
Conclusions:
- IRhMC and HCT are dependable indicators of UMN degeneration in ALS, irrespective of genetic status.
- Bulbar onset ALS patients exhibit these MRI changes more frequently.
- Regional IRhMC measurements may serve as a biomarker for ALS disease progression.
