Motor band sign is specific for amyotrophic lateral sclerosis and corresponds to motor symptoms

Abstract

Objective: Magnetic resonance imaging can detect neurodegenerative iron accumulation in the motor cortex, called the motor band sign. This study aims to evaluate its sensitivity/specificity and correlations to symptomatology, biomarkers, and clinical outcome in amyotrophic lateral sclerosis.

Methods: This prospective study consecutively enrolled 114 persons with amyotrophic lateral sclerosis and 79 mimics referred to Karolinska University Hospital, and also 31 healthy controls. All underwent 3-Tesla brain susceptibility-weighted imaging. Three raters independently assessed motor cortex susceptibility with total and regional motor band scores. Survival was evaluated at a median of 34.2 months after the imaging.

Results: The motor band sign identified amyotrophic lateral sclerosis with a sensitivity of 59.6% and a specificity of 91.1% versus mimics and 96.8% versus controls. Higher motor band scores were more common with genetic risk factors (p = 0.032), especially with C9orf72 mutation, and were associated with higher neurofilament light levels (std. β 0.22, p = 0.019). Regional scores correlated strongly with focal symptoms (medial region vs. gross motor dysfunction, std. β -0.64, p = 0.001; intermediate region vs. fine motor dysfunction, std. β -0.51, p = 0.031; lateral region vs. bulbar symptoms std. β -0.71, p < 0.001). There were no associations with cognition, progression rate, or survival.

Interpretation: In a real-life clinical setting, the motor band sign has high specificity but relatively low sensitivity for identifying amyotrophic lateral sclerosis. Associations with genetic risk factors, neurofilament levels and somatotopic correspondence to focal motor weakness suggest that the motor band sign could be a suitable biomarker for diagnostics and clinical trials in amyotrophic lateral sclerosis.

Figure 1

Motor band sign grading. Different grades (0–2) of primary motor cortex hypointensities, the motor band sign, on axial susceptibility‐weighted brain MRI in the intermediate region. D–F showing magnifications of A–C, respectively. A 74‐year‐old male with isointense (Grade 0) motor cortex (D); a 73‐year‐old male with mildly hypointense (Grade 1) motor cortex (B and E), and a 70‐year‐old male with marked hypointense (Grade 2) motor cortex (C and F).

Figure 2

Motor band sign topographical classification. Anatomical distribution of primary motor cortex hypointensities, the motor band sign, on axial susceptibility‐weighted brain MRI in a 72‐year‐old female patient with dysarthria and mild motor weakness in the upper and lower extremities. D–F showing magnifications of A–C, respectively. There was marked hypointensities in the medial (A and D), intermediate (B and E), and lateral (C and F) regions of the motor cortex.

Figure 3

Distribution of the total motor band sign score in 114 ALS patients, 79 ALS mimics, and 31 controls.

Figure 4

Regional motor band sign (MBS) score distribution by total score subgroup. Illustrations of the distribution in three different regions of the primary motor cortex (M1) (lateral, intermediate, and medial) shown separately for patients with low (1–3, A), moderate (4–5, B), and high (≥6, C) total MBS scores. The distribution is reported on group level: total regional MBS scores and the proportion of the maximum regional score (calculated as two times the number of patients as each region is rated on a scale of 0–2).