Motor and extramotor neurodegeneration in amyotrophic lateral sclerosis: A 3T high angular resolution diffusion imaging (HARDI) study

Abstract

In amyotrophic lateral sclerosis (ALS), diffusion weighted magnetic resonance imaging (DW-MRI) has produced mounting evidence of a widespread white matter (WM) damage within motor and extramotor pathways. To provide novel information about the degenerative process in ALS, overcoming some of the limitations imposed by diffusion tensor imaging (DTI), we performed a high angular resolution diffusion imaging (HARDI) analysis of DW-MRI data. Generalized fractional anisotropy (GFA) was evaluated in 19 patients with ALS and 19 matched control subjects, and was correlated with clinical scores of disability, pyramidal impairment by upper motor neuron (UMN) score and frontal dysfunction by the Frontal Systems Behaviour (FrSBe) scale. Results demonstrated that ALS patients showed a significant decrease of GFA in the WM tracts underneath the left and right precentral gyri and the body of the corpus callosum (p < 0.05, corrected), where GFA was significantly related to UMN scores (p < 0.001, uncorrected); and in the left superior longitudinal fasciculus (p < 0.05, corrected), where GFA was significantly related to FrSBe scale scores (p < 0.01, uncorrected). In conclusion, this study revealed a pattern of motor and extramotor frontal diffusivity abnormalities (probably related to behavioural and cognitive dysfunctions) showing a spatial distribution similar to what was previously described in ALS - frontotemporal dementia continuum.

Finding Markers in Amyotrophic Lateral Sclerosis Diagnosis

“…The most pronounced decreased FA and increased have been shown in the posterior limb of internal capsule [34,35].…”

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

“…Apart from the study of Grapperon et al who reported an increase in FA (Grapperon, Verschueren et al 2014), all other studies found reduction of the average FA over the entire CST(Abe, Yamada et al 2004, Karlsborg, Rosenbaum et al 2004, Iwata, Aoki et al 2008, Pettit, Bastin et al 2012, Prudlo, Bissbort et al 2012, Agosta, Caso et al 2013, Bastin, Pettit et al 2013, Rajagopalan, Yue et al 2013, Trojsi, Corbo et al 2013, Crespi, Cerami et al 2014, Floeter, Katipally et al 2014 as well as at different levels along the tract , Karlsborg, Rosenbaum et al 2004, Mitsumoto, Ulug et al 2007, Rajagopalan, Yue et al 2013, Hübers, Müller et al 2015. This was more apparent in the right CST (Sarica, Cerasa et al 2014) with RD increase (Zhang, Schuff et al 2009), superiorly (Bede, Bokde et al 2013) caudally (Zhang, Yin et al 2014, Hübers, Müller et al 2015 and rostrally (Filippini, Douaud et al 2010) and with MD increases , Prudlo, Bissbort et al 2012, Floeter, Katipally et al 2014 at the level of the internal capsule (Sach, Winkler et al 2004).…”

“…The latter study found that there was a trend towards significant correlation between ALSFRS-R scores and FA (Sarica, Cerasa et al 2014). Other studies found no correlation between FA and ALSFRS-R and disease duration (Furtula, Johnsen et al 2013, Woo, Wang et al 2014 or disease progression (Trojsi, Corbo et al 2013). …”

“…In ALS, increased AD , MD and RD ) and decreased FA along the CST were associated with higher UMN scores (Abe, Yamada et al 2004, Iwata, Aoki et al 2008, Filippini, Douaud et al 2010, Trojsi, Corbo et al 2013, Woo, Wang et al 2014. Longer disease duration correlated with increased FA (Filippini, Douaud et al 2010) and AD (Rajagopalan, Yue et al 2013).…”

“…When using cognitive examination, it was found that reduced FA correlated with reduced letter fluency (Pettit, Bastin et al 2012) and negatively with frontal system behavior scale (FrSBe) score at the level of pontomesencephalic junction (Trojsi, Corbo et al 2013). Reduced FA along CST correlated with Trail-making test scores and Stroop test scores ).…”