Progressive brainstem pathology in motor neuron diseases: Imaging data from amyotrophic lateral sclerosis and primary lateral sclerosis

Abstract

A standardised, single-centre, longitudinal imaging protocol was used to evaluate longitudinal brainstem alterations in 100 patients with amyotrophic lateral sclerosis (ALS) with reference to 33 patients with primary lateral sclerosis (PLS), 30 patients with frontotemporal dementia (FTD) and 100 healthy controls. "Brainstem pathology in amyotrophic lateral sclerosis and primary lateral sclerosis: A longitudinal neuroimaging study" [1] ALS patients were scanned twice; 4 months apart. T1-weighted imaging data were acquired on a 3 T Philips Achieva MRI system, using a 3D Inversion Recovery prepared Spoiled Gradient Recalled echo (IR-SPGR) sequence. Raw MRI data underwent meticulous quality control before pre-processing. A Bayesian segmentation algorithm was utilised to parcellate the brainstem into the medulla oblongata, pons and mesencephalon before estimating the volume of each segment. Vertex-based shape analyses were carried out to characterise anatomical patterns of atrophy. Brainstem volume loss in ALS was dominated by medulla oblongata atrophy, but significant pontine pathology was also detected. Brainstem volume reductions were more significant in PLS than in ALS after correcting for demographic variables and total intracranial volume. Shape analyses revealed bilateral 'flattening' of the medullary pyramids in ALS compared to healthy controls. Our data demonstrate that computational neuroimaging readily detects brainstem pathology in vivo in both amyotrophic lateral sclerosis and primary lateral sclerosis.

Keywords: Amyotrophic lateral sclerosis; Brainstem; Frontotemporal dementia; Magnetic resonance imaging; Medulla oblongata; Mesencephalon; Pons; Primary lateral sclerosis.

Fig. 1

The comparative volumetric brainstem profile of patients with amyotrophic lateral sclerosis at time-point 1 (ALST1), patients with amyotrophic lateral sclerosis at time-point 2 (ALST2), frontotemporal dementia (FTD), healthy controls (HC) and patients with primary lateral sclerosis (PLS).

Fig. 2

The segmental brainstem profile of ALS, PLS and FTD with reference to healthy controls. 100% represents the estimated marginal mean of healthy controls for each structure. Estimated marginal means of volumes were calculated with the following values Age = 59.59, Gender = 1.43, Education = 13.63, TIV = 1435355.28.

Fig. 3

Anatomical patterns of atrophy in ALS compared to healthy controls based on vertex-analyses after corrections for demographic variables. Top: Vertex analyses; brainstem mesh is shown in blue and shape deformations are highlighted in orange at p < 0.05 FWE Bottom: Surface-based vertex analyses; the brainstem mesh template is shown in red.