Quantitative susceptibility mapping may help diagnose amyotrophic lateral sclerosis

1. Quantitative susceptibility mapping is both a sensitive and specific imaging technique for the degree of iron deposition in the motor cortex, a useful biomarker in the diagnosis of amyotrophic lateral sclerosis and primary lateral sclerosis.  

Evidence Rating: 3 (Average)

Study Rundown: Amyotrophic lateral sclerosis (ALS) is currently a diagnosis of exclusion without a reliable biomarker for early detection, and diagnosis often requires documentation of progressive upper and lower motor neuron signs over long periods of time. Similarly, primary lateral sclerosis (PLS) remains difficult to diagnose as it is less common, has a more indolent course and only affects the upper motor neurons, but may be physiologically related to ALS. False positive diagnostic rates remain high and imaging has played a limited role in these diagnoses of exclusion. The current study utilized quantitative susceptibility mapping (QSM) to assess the magnetic susceptibility of tissues, a technique which highlights the paramagnetic effects of metal deposition well while differentiating from the diamagnetic effects of calcium deposits. The rationale was based upon prior studies reporting increased microglial iron deposition in the motor cortex of patients suffering from ALS.

QSM was found to be both a sensitive and specific technique in assessing the level of iron deposition in patients with upper motor neuron disease consistent with ALS or PLS. These patients were matched to control patients and evaluated by 2 neuroradiologists who were blinded to diagnosis. The ability of QSM to aid in the diagnosis of ALS or PLS was compared against the diagnostic accuracy of T2 and T2 weighted fluid attenuated inversion recovery (FLAIR) sequences, on which hypointensity had previously been shown to correlate with disease severity. This study is among the first to identify QSM as a viable technique to quantify iron deposition in the motor cortex, one of the first biomarkers that have been identified to possibly aid in the early diagnosis of patients with ALS or PLS. Limitations in the study included the small sample size and case-series nature. Additionally, the exclusion of high risk patients from the study due to the technical difficulty in evaluating them through MRI, posed a significant limitation by potentially excluding evidence that would further support the use of QSM in the diagnosis of ALS or PLS in those patients with the most advanced disease, and presumably, a proportional increase in biomarker deposition.

Click to read the study in American Journal of Roentgenology

Relevant reading: Brain iron MRI: a biomarker for amyotrophic lateral sclerosis.

In-Depth [case-control study]: Patients that had previously been identified as having possible, probable or definite ALS/PLS were identified through institutional chart review, using the El Escorial criteria for ALS and clinical criteria for PLS. Of these patients, 16 were identified for study inclusion and matched to 23 control patients based on age and sex. Two neuroradiologists, blinded to the diagnosis, evaluated QSM, T2-weighted, T2-FLAIR and T2*-weighted images for the presence of motor neuron disease in both case and control patients. Findings were graded for motor cortex T2 hypointensity, motor cortex T2* hypointensity, motor cortex QSM hyperintensity, and corticospinal tract T2 hyperintensity. Relative susceptibility was quantified by segmentation of the motor cortex, with pixel intensity values thresholded against control white matter and cerebrospinal fluid. When evaluated against each other, QSM had the greatest diagnostic accuracy among imaging modalities in the diagnosis of ALS and PLS. Motor cortex susceptibility was found to be significantly greater in patients with motor neuron disease than in control patients (46.0 and 35.0 parts per billion; p < 0.001), with a receiver operating characteristic analysis showing an area under curve of 0.88 (p < 0.0001) for differentiating control patients from patients with ALS or PLS. Overall, the sensitivity and specificity of QSM in the diagnosis of ALS and PLS was 87.5% and 87%, respectively.

Image: CC/Wikimedia Commons/Jurii

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