MRI cortical feature of bulbar impairment in patients with amyotrophic lateral sclerosis

Abstract

The decline of voluntary bulbar functions such as speech and swallowing are among the clinical manifestations of amyotrophic lateral sclerosis (ALS) influencing a worst prognosis. Differential diagnosis between the contribution of upper motor neuron (UMN) and lower motor neuron degeneration to the bulbar impairment is often hard. Thinning and T2* hypointensity of the primary motor cortex have been recently suggested as possible MRI markers of UMN impairment in ALS patients, but little research has purposely targeted the orofacial region of the primary motor cortex (fM1). With the aim of finding an MRI marker of UMN impairment responsible for bulbar dysfunction, we investigated the T2* signal intensity of fM1 and the relationship with bulbar impairment in ALS patients. Fifty-five ALS patients were examined with 3 T MRI. Their fM1 was evaluated both qualitatively in terms of T2* signal intensity and quantitatively by measuring its magnetic susceptibility with Quantitative Susceptibility Mapping (QSM). Bulbar functions were assessed clinically, by neurological examination and using the items 1–3 of the ALSFRS-R, and with neurophysiological tests. The marked hypointensity of fM1 was detected in 25% of ALS patients, including all patients with bulbar onset, and was 74% sensitive, 100% specific and 91% accurate in diagnosing functional bulbar impairment. Such hypointensity involved the middle and ventral part of fM1 and was usually visible in both hemispheres. The magnetic susceptibility was significantly higher in patients with marked fM1 hypointensity than in the other patients ( p ≤ .001). The relationship with clinical and neurophysiological data suggests that such feature could be a marker of UMN degeneration for voluntary bulbar functions.

Combining structural and metabolic markers in a quantitative MRI study of motor neuron diseases

“…Two previous QSM studies, using either a voxel‐based approach or a regional analysis along the posterior and precentral gyri, found an increase of iron deposition levels within the motor cortex of ALS patients, in comparison to either HCs 8 or patients with ASL mimics and non‐motor neuron symptoms 13 . In addition, the study of Donatelli et al., 14 which specifically targeted the orofacial portion of the primary motor cortex, also reported that the hypointensity of T2* signal and the corresponding higher susceptibility values, albeit non‐quantitatively, had significant discriminative power in diagnosing ALS with functional bulbar impairment. Similarly, the recent study of Conte et al 11 .…”

“…The development of advanced MRI techniques has allowed the proliferation of quantitative MRI (qMRI) markers, MRI‐derived measures that can be calibrated to standard physical units, whose diagnostic potential is yet to be fully investigated in the context of clinical MRI studies on the ALS pathology. For example, the involvement of gray matter (GM) structures in ALS neurodegeneration has been extensively studied using quantitative MRI markers, not only as morphometric indices of GM atrophy, but also as biophysical surrogates of structural and metabolic tissue properties, such as iron deposition 8–18 and cerebral perfusion 19–21 …”

Systematic Review: Quantitative Susceptibility Mapping (QSM) of Brain Iron Profile in Neurodegenerative Diseases

“…In a recent study, the orofacial region of the primary motor cortex was investigated in relation to bulbar onset of ALS presentation. Magnetic susceptibility was significantly higher in those with marked T2 * hypointensity in the deep layer of orofacial region of the motor cortex, which was predominantly observed in patients with bulbar-onset disease (Donatelli et al, 2019 ).…”

An Automated Tongue Tracker for Quantifying Bulbar Function in ALS

“…To test for these assumptions, one could perform longitudinal sampling with our tool to track tongue kinematic features with disease progression. Accurately quantifying bulbar dysfunction is further necessary to identify corresponding brain changes to the bulbar area of M1 by using neuroimaging methods (7,28). In addition, our measure could be used to track tongue movement training success to improve outcomes in dysphagia, as previously demonstrated with specialized equipment to measure tongue pressure in patients following acquired brain injury and stroke (4).…”