Diffusion tensor MRI changes in gray structures of the frontal-subcortical circuits in amyotrophic lateral sclerosis

Abstract

In this study, we used an automated segmentation of regions of interest and co-registration to diffusion tensor imaging (DTI) images to investigate whether microstructural abnormalities occur in gray structures of the frontal-subcortical circuits in patients with amyotrophic lateral sclerosis (ALS). Twenty-four patients with probable or definite sporadic ALS and 22 healthy controls were enrolled in the study. Thirteen out of 24 ALS patients and all of the control subjects underwent a detailed neuropsychological evaluation. DTI was performed to measure mean diffusivity (MD) and fractional anisotropy in the frontal cortex, caudate, putamen, globus pallidus, thalamus, amygdala and hippocampus. MD values of ALS patients were significantly higher in the frontal cortex (P = 0.023), caudate (P = 0.01), thalamus (P = 0.019), amygdala (P = 0.012) and hippocampus (P = 0.002) compared to controls. MD of these structures significantly correlated to a variable degree with neurological disability and neuropsychological dysfunctions. The increased MD values in several cortical and subcortical gray structures and their correlations with neuropsychological variables substantiate a multisystemic degeneration in ALS and suggest that dysfunctions of frontal-subcortical circuits could play a pivotal role in frontal impairment and behavioral symptoms in ALS patients.

Measuring the progression of upper motor neuron disease using diffusion MRI and its correlation with Clinical phenotype

“…In the parahippocampal tract and the left thalamic radiation, increased FA correlated with increased apathy score on Frontal Systems Behavior Scale (FrSBe) . MD in the thalamus correlated positively with disease duration and negatively with ALSFRS-R (Barbagallo, Nicoletti et al 2014). …”

“…The average FA of the fornix was also reported to be reduced (Trojsi, Corbo et al 2013). The amygdala was found by one group to have increased MD, which was negatively correlated with ALSFRS-R (Barbagallo, Nicoletti et al 2014). ROI analysis showed significant changes in FA and MD in the thalamic radiation in the frontal region (Pettit, Bastin et al 2012).…”

“…There was reduced FA in the thalamus (Pettit, Bastin et al 2012, Heimrath, Gorges et al 2014, more significant on the right side (Sach, Winkler et al 2004) and anteriorly (Trojsi, Corbo et al 2013, Sarica, Cerasa et al 2014). The hippocampus, thalamus and anterior cingulum were found to have increased RD (Cardenas-Blanco, ) and MD (Barbagallo, Nicoletti et al 2014) in ALS specifically when using ROI-based methods , which was found to be correlated with reverse digital span (Pettit, Bastin et al 2012). The average FA of the fornix was also reported to be reduced (Trojsi, Corbo et al 2013).…”

“…When comparing ALS with their counterparts who had cognitive impairment, increased RD and MD were seen in ThR and Cg in ALSci ). (Barbagallo, Nicoletti et al 2014). FA and MD in the fornix correlated with verbal learning and memory test scores (Filippi, ).…”

“…There have been reports of abnormalities of extra-motor pathways in ALS (Sato, Aoki et al 2010, Barbagallo, Nicoletti et al 2014, Sarica, Cerasa et al 2014 and FTD (Avants, Cook et al 2010, 167 Alruwaili thesis 2016 Whitwell, Avula et al 2010. The majority of studies involving ALS subjects did not test cognition; it is therefore possible that the extramotor abnormalities found on DTI in ALS are due to a subset of patients with clinical features of extra-motor disease such as cognitive impairment, which is found in some patients with ALS (Lillo, Savage et al 2012).…”