We read with interest the study by Cooper et al. in this issue of the journal evaluating the diagnostic utility of MRI brain imaging findings in the diagnosis of amyotrophic lateral sclerosis (ALS) as well as its relationship to functional disability. ^{Reference Cooper, Lu and Chan1} This was a prospective study using participants enrolled in the Canadian ALS Neuroimaging Consortium 1 study. The qualitative assessment of hypointensity in the motor cortex on susceptibility-weighted echo planar imaging and unilateral and/or bilateral corticospinal tract FLAIR hyperintensity by both a neuroradiologist and neurologist were determined to have specificities of 95% and 85%, respectively, for a diagnosis of ALS. The inter-rater reliability of these signs between the reading neuroradiologist and neurologist was not strong, and there was no any association between the presence of these neuroimaging findings and ALS Functional Rating Scale-Revised scores.

The prevalence of susceptibility-weighted imaging (SWI) hypointensity in the motor cortex, often referred to as the “motor band sign,” has been observed by prior studies. ^{Reference Chakraborty, Gupta, Nguyen and Bourque2–Reference Conte, Contarino and Casale5} A recent retrospective study of 47 ALS patients, 15 disease mimics and 23 healthy controls identified that SWI hypointensity in the motor cortex was significantly higher in patients with upper motor neuron (UMN)–predominant ALS compared to lower motor neuron–predominant ALS, ALS without clinically defined predominance, disease mimics and healthy controls. ^{Reference Conte, Sbaraini and Morelli6} Taken together, these neuroimaging signs may aid clinicians in suspecting a diagnosis of ALS, particularly early in the disease course, in which UMN signs may be subtle.

The study highlights an enduring tension in ALS care where clinicians face pressure to diagnose earlier while avoiding misdiagnosis. This is important in an era of potential disease-modifying therapies, access to multidisciplinary care and genetic testing and enrollment in clinical trials. In this setting, biomarkers for UMN degeneration specific to the diagnosis of ALS are attractive.

In Cooper et al., ^{Reference Cooper, Lu and Chan1} the authors acknowledge study limitations such as the small sample size, lack of disease control and the limited axial slices available for review. The specificity of these neuroimaging findings is limited to a degree as it is present in disease mimics such as primary lateral sclerosis. ^{Reference Chung, Melkus, Bourque and Chakraborty4} As such, the clinical context remains paramount; these neuroimaging findings are most helpful in a patient with suspected ALS with clinical signs of UMN dysfunction. We look forward to larger prospective studies with disease controls that can further clarify its diagnostic role in this challenging clinical scenario.