Voxel-based mapping of grey matter volume and glucose metabolism profiles in amyotrophic lateral sclerosis

Abstract

BackgroundAmyotrophic lateral sclerosis (ALS) is a rapidly progressive disease of the nervous system involving both upper and lower motor neurons. The patterns of structural and metabolic brain alterations are still unclear. Several studies using anatomical MRI yielded a number of discrepancies in their results, and a few PET studies investigated the effect of ALS on cerebral glucose metabolism. The aim of this study was threefold: to highlight the patterns of grey matter (GM) atrophy, hypometabolism and hypermetabolism in patients with ALS, then to understand the neurobehavioral significance of hypermetabolism and, finally, to investigate the regional differences between the morphologic and functional changes in ALS patients, using a specially designed voxel-based method.Thirty-seven patients with ALS and 37 age- and sex-matched healthy individuals underwent both structural MRI and 18[F]-fluorodeoxyglucose (FDG) PET examinations. PET data were corrected for partial volume effects. Structural and metabolic abnormalities were examined in ALS patients compared with control subjects using two-sample t tests in statistical parametric mapping (SPM). Then, we extracted the metabolic values of clusters presenting hypermetabolism to correlate with selected cognitive scores. Finally, GM atrophy and hypometabolism patterns were directly compared with a one-paired t test in SPM.ResultsWe found GM atrophy as well as hypometabolism in motor and extra motor regions and hypermetabolism in medial temporal lobe and cerebellum. We observed negative correlations between the metabolism of the right and left parahippocampal gyri and episodic memory and between the metabolism of right temporal pole and cognitive theory of mind. GM atrophy predominated in the temporal pole, left hippocampus and right thalamus, while hypometabolism predominated in a single cluster in the left frontal superior medial cortex.ConclusionsOur findings provide direct evidence of regional variations in the hierarchy and relationships between GM atrophy and hypometabolism in ALS. Moreover, the 18FDG-PET investigation suggests that cerebral hypermetabolism is deleterious to cognitive function in ALS.

Regional thalamic MRI as a marker of widespread cortical pathology and progressive frontotemporal involvement in amyotrophic lateral sclerosis

“…Diffusion MRI studies in ALS consistently report markers of reduced thalamic cellular integrity 28 29. Thalamic abnormalities extend beyond conventional grey matter and diffusion change to altered functional connectivity,28 increased iron deposition,30 altered metabolism,31 decreased texture features,32 altered cerebral blood flow,33 reduced motor task-related activation34 and increased microglial activation 35. Thus, despite the variability of detectable grey matter atrophy, thalamic abnormalities are a very robust finding consistent across a wider range of neuroimaging modalities (table 4).…”

Regional Dynamics of the Resting Brain in Amyotrophic Lateral Sclerosis Using Fractional Amplitude of Low-Frequency Fluctuations and Regional Homogeneity Analyses

“…This structure is proved to participate in motor as well as in cognitive and behavioural functions and plays an important role in neurodegenerative diseases, including ALS (Strick ete al., 2009; for a review see Gellersen et al, 2017). Functional abnormalities and hypometabolism in the cerebellum are well documented in ALS (Ferrer et al, 2016;Buhour et al, 2017) as well as gray and white matter changes, and proven to correlate with cognitive and behavioural symptoms (Tan et al, 2014;Christidi et al, 2017;Thivard et al, 2007). Clinical motor characteristics and possibly cognitive symptoms could be further explained by the involvement of these fALFF and ReHo changes found in the cerebellum.…”

Hypermetabolism is a deleterious prognostic factor in patients with amyotrophic lateral sclerosis

“…This hyperexcitability could increase glucose metabolism. Indeed, an increase of metabolism of glucose, which is the main energy substrate in neurons, was found with 18 fluorodeoxyglucose–positron emission tomography in brains of patients with ALS . This increase of brain glucose consumption could lead to an increase of metabolic rate in these patients.…”