Medullary, pontine and mesencephalic pathology in ALS and PLS: the segmental brainstem profile of motor neuron disease

Published: 22 January 2020| Version 3 | DOI: 10.17632/4t8c4bmw5p.3
Peter Bede,
Rangariroyashe Chipika,
Eoin Finegan,
Stacey Li Hi Shing,
Kai Ming Chang,
Orla Hardiman


Brainstem pathology is a pathognomonic feature of ALS encompassing lower cranial nerve and descending corticospinal tract degeneration. Post mortem studies have highlighted macroscopic brainstem atrophy in ALS since the earliest descriptions of the disease, and brainstem involvement is a stage-defining feature of pathological TDP-43 burden. Despite the plethora of recent imaging studies in ALS, brainstem alterations are poorly characterised radiologically. The majority of imaging papers in ALS and PLS focus on cortical atrophy patterns, telencephalic white matter degeneration, basal ganglia and spinal cord pathology. The quantitative assessment of brainstem changes in vivo offers the opportunity to assess longitudinal changes, explore correlations with clinical metrics, and define the imaging signatures of specific motor neuron disease phenotypes. In a prospective, single-centre imaging study, we have acquired high-resolution imaging data for 100 patients with amyotrophic lateral sclerosis (ALS), 33 patients with primary lateral sclerosis (PLS), 30 patients with frontotemporal dementia (FTD) and 100 healthy controls (HC) using a standardised imaging protocol. ALS patients were scanned longitudinally 4 months apart. T1-weighted imaging data were acquired with a 3D Inversion Recovery prepared Spoiled Gradient Recalled echo (IR-SPGR) pulse sequence on a 3 Tesla MRI system. Following quality control and standard pre-processing steps, a Bayesian parcellation algorithm was utilised to segment the brainstem into the medulla oblongata, pons and mesencephalon. Raw volumetric data are presented for each brainstem segment, stratified by study-group membership as supplementary information to our recent research paper (Reference 1). Our data demonstrate that segmental and progressive brainstem pathology can be readily detected in vivo in ALS and our findings also confirm considerable brainstem atrophy in PLS. The interpretation of our volumetric data is aided by the availability of reference data sets from healthy- and disease-controls. Reference 1 - the original research paper with methodological details: Bede P, Chipika RH, Finegan E, Li Hi Shing S, Doherty MA, Hengeveld JC, Vajda A, Hutchinson S, Donaghy C, McLaughlin RL, Hardiman O, Brainstem pathology in amyotrophic lateral sclerosis and primary lateral sclerosis: A longitudinal neuroimaging study. NeuroImage Clinical. 24 (2019):102054. Epub 2019/11/12.



Radiology, Neurology