Genetic and constitutional factors are major contributors to substantia nigra hyperechogenicity

Abstract

Hyperechogenicity of substantia nigra (SNh) is a frequent finding in amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD) and other movement disorders (MD) patients, but its meaning is unclear. To ascertain the contribution of different factors to SNh area, we measured it in 108 ALS, 102 PD, 91 other MD patients and 91 healthy controls. Demographical data were collected in all patients and controls. In ALS patients, we also recorded clinical variables, performed genetic analysis and measured baseline levels of ferritin. After family history and genetic testing, ALS patients were classified as familial (15) or sporadic (93). ALS, PD and other MD patients had a larger SNh area than controls. Left SNh and male gender, but not age, associated with larger SNh area in both patients and controls. Familial ALS patients showed larger SNh area than sporadic ones and familial ALS was the only clinical variable in the multivariate analysis to be associated with larger SNh area in ALS patients. Our results suggest that SNh associates with genetic and constitutional factors (male gender, handedness), some of which predispose to certain neurodegenerative diseases. This evidence supports the idea of SNh as an inborn marker of unspecific neuronal vulnerability.

The width of the third ventricle associates with cognition and behaviour in motor neuron disease

“…As a progression's biomarker would be especially suitable for ALS patients, since it can be easily obtained in advanced disease stages (even in patients requiring ventilation support) at bedside and does not require post-processing, unlike MRI-based biomarkers.Finally, unlike the hyperechogenicity of the substantia nigra,23 our study was unable to find differences in sporadic vs genetic MND patients. FRSBE values correspond to Z-scores.…”

“…A longitudinal assessment of the WTV would account for these interindividual differences and might allow the prediction or monitoring of a progressive cognitive impairment. As a progression's biomarker would be especially suitable for ALS patients, since it can be easily obtained in advanced disease stages (even in patients requiring ventilation support) at bedside and does not require post-processing, unlike MRI-based biomarkers.Finally, unlike the hyperechogenicity of the substantia nigra,23 our study was unable to find differences in sporadic vs genetic MND patients. This result should be considered with caution due to the low number of gMND patients and the heterogeneity of the causal mutations.…”

“…20 Patients presenting with a progressive isolated LMN impairment, affecting at least two regions, were diagnosed with PMA after appropriately excluding other LMN syndromes. 23 For comparison purposes, a cohort of controls without neurological diseases was also recruited. 22 Patients with stroke history were excluded.…”

“…The hyperechogenicity of the substantia nigra was also assessed in a subgroup of these population and the results have been published elsewhere. 23 For comparison purposes, a cohort of controls without neurological diseases was also recruited.…”

Brain signal intensity changes as biomarkers in amyotrophic lateral sclerosis

“…We found no differences in iron deposits between genetic ALS and non‐genetic ALS, which suggests that, unlike substantia nigra hyperechogenicity, genetic factors do not influence IRhMC. Previous multiparametric MRI studies consistently show larger involvement of frontotemporal and subcortical structures in C9orf72‐positive vs negative patients.…”