Table 1.

Main results of most significant studies.

Conventional brain MR imaging and qualitative MR imaging biomarkers
Hyperintensity of the corticospinal tract on FLAIR/T2	Hecht et al., 2001; Agosta et al., 2010a; Foerster et al., 2013b; Huynh et al., 2016; Jin et al., 2016
Hypontensity of the motor cortex on SWI	Adachi et al., 2015; Sheelakumari et al., 2016; Vázquez-Costa et al., 2018b
Structural magnetic resonance imaging
Atrophy in the precentral gyri (VBM)	Ellis et al., 2001; Chang et al., 2005; Kassubek et al., 2005; Grosskreutz et al., 2006; Agosta et al., 2007; Mezzapesa et al., 2007; Thivard et al., 2007; Menke et al., 2014; Zhang et al., 2014; Devine et al., 2015
No atrophy in the precentral gyri (VBM)	Kiernan and Hudson, 1994; Ellis et al., 2001; Mezzapesa et al., 2007; Raaphorst et al., 2015
Atrophy in extra-motor regions (VBM)	Chang et al., 2005; Kassubek et al., 2005; Agosta et al., 2007, 2012; Mezzapesa et al., 2007; Thivard et al., 2007; Bede et al., 2013; Abdulla et al., 2014; Zhang et al., 2014; Christidi et al., 2018
Cortical thinning of the primary motor cortex (SBM)	Roccatagliata et al., 2009; Verstraete et al., 2010, 2012; Agosta et al., 2012; Walhout et al., 2015; Al-Chalabi et al., 2016
Cortical thinning of extra-motor regions (SBM)	Verstraete et al., 2012; Mioshi et al., 2013; d’Ambrosio et al., 2014; Schuster et al., 2014a; Walhout et al., 2015
Diffusion tensor imaging
Decreased FA and increased ADC of the corticospinal tract	Ellis et al., 1999; Sage et al., 2007, 2009; Schimrigk et al., 2007; Iwata et al., 2008, 2011; Yin et al., 2008; Ciccarelli et al., 2009; Nickerson et al., 2009; Filippini et al., 2010; Stagg et al., 2013; Foerster et al., 2014; Sarica et al., 2014; Rosskopf et al., 2015; Tang et al., 2015
Decreased FA in the corpus callosum	Sach et al., 2004; Agosta et al., 2007; Sage et al., 2007, 2009; Ciccarelli et al., 2009; Senda et al., 2009; Filippini et al., 2010; Zhang et al., 2011; Rose et al., 2012; Shen et al., 2016
Decreased FA in extra-motor regions	Abe et al., 2004; Sach et al., 2004; Agosta et al., 2007; Sage et al., 2007, 2009; Thivard et al., 2007; Ciccarelli et al., 2009; Filippini et al., 2010; Keil et al., 2012; Prell et al., 2013; Rosskopf et al., 2015
Magnetic resonance spectroscopy
Decrease in absolute NAA concentrations in the motor cortex.	Gredal et al., 1997; Rooney et al., 1998; Bradley et al., 1999; Pohl et al., 2001b; Sarchielli et al., 2001; Schuff et al., 2001; Block et al., 2002; Suhy et al., 2002; Kalra et al., 2006a,c; Mitsumoto et al., 2007; Han and Ma, 2010; Cervo et al., 2015; Liu et al., 2015
Decrease NAA/Cr in the motor cortex.	Pioro et al., 1994; Jones et al., 1995; Block et al., 1998, 2002; Rooney et al., 1998; Abe et al., 2001; Rule et al., 2004; Yin et al., 2004; Kalra et al., 2006a,b; Mitsumoto et al., 2007; Charil et al., 2009; Lombardo et al., 2009; Han and Ma, 2010; Pyra et al., 2010; Sivák et al., 2010
Decrease in NAA/Cho in the motor cortex.	Pioro et al., 1994; Jones et al., 1995; Giroud et al., 1996; Block et al., 1998, 2002; Rooney et al., 1998; Pohl et al., 2001a; Suhy et al., 2002; Rule et al., 2004; Kalra et al., 2006a; Pyra et al., 2010
Decrease in NAA/(Cr+Cho) in the motor cortex.	Rooney et al., 1998; Suhy et al., 2002; Rule et al., 2004
Other altered metabolites in the motor cortex.	Block et al., 1998; Bowen et al., 2000; Kalra et al., 2006a; Lombardo et al., 2009; Han and Ma, 2010; Foerster et al., 2012a, 2014
Altered metabolites in the CST and extra-motor regions	Rooney et al., 1998; Bowen et al., 2000; Abe et al., 2001; Schuff et al., 2001; Rule et al., 2004; Yin et al., 2004; Han and Ma, 2010; Pyra et al., 2010; Sivák et al., 2010; Sharma et al., 2011; Sudharshan et al., 2011; Govind et al., 2012; Foerster et al., 2014
Quantitative iron imaging
Iron deposition in motor cortex	Costagli et al., 2016; Donatelli et al., 2018a
Iron deposition in CST and extra-motor regions	Minnerop et al., 2009; Langkammer et al., 2010a; Prell et al., 2015
Functional magnetic resonance (fMR) imaging
Cerebral activation alterations during motor tasks (task-based fMRI)	Konrad et al., 2002, 2006; Schoenfeld et al., 2005; Han and Ma, 2006; Lulé et al., 2007b; Stanton et al., 2007; Kollewe et al., 2011; Mohammadi et al., 2011, 2015; Cosottini et al., 2012
Cerebral activation alterations with other tasks (task-based fMRI)	Abrahams et al., 2004; Lulé et al., 2007a, 2010; Palmieri et al., 2010; Passamonti et al., 2013
Decreased functional connectivity within the sensorimotor network (Resting State fMRI)	Mohammadi et al., 2009a; Jelsone-Swain et al., 2010; Tedeschi et al., 2012; Fekete et al., 2013; Zhou et al., 2013
Abnormalities in other networks (Resting State fMRI)	Mohammadi et al., 2009a; Jelsone-Swain et al., 2010; Luo et al., 2012; Zhou et al., 2013
Increased network coherence in the somatosensory and extra-motor areas (Resting State fMRI)	Agosta et al., 2011, 2013, 2014; Douaud et al., 2011; Luo et al., 2012; Tedeschi et al., 2012; Fekete et al., 2013; Zhou et al., 2013