Table 1 The main results of volumetric studies

Abdulla et al., [39, 80]

58/29

Low volume in the right hippocampus

Verbal memory test performance is correlated with the left hippocampal volume.

Agosta et al., [21]

25/18

GM volume reduction in right precentral, left inferior frontal cortex and temporal superior cortex.

Negative with ALSFRS-R and DD.

Agosta et al., [35]

44/26

Reduction in cortical thickness in the precentral, frontal, limbic, parietal, temporal and occipital lobes.

DPR is correlated with the mean cortical thickeness of left sensorimotor cortex.

Bede et al., [37]

39/44

GM volume reduction in the thalamus, caudate nucleus, hippocampus, left putamen.

Not available.

Canu et al., [23]

23/24

GM volume reduction in the precentral, right opercular and angular cortex, WM volume reduction in the frontal lobe (especially the subcortical motor areas) and the temporal lobe.

Not available.

Cerami et al., [36]

14/20

Low GM density in the anterior cingulate and right inferior frontal gyri.

Not available.

Chang et al., [22]

20 (10 ALS and 10 ALS-FTD)/22

GM volume reduction in the precentral, frontal and temporal cortex and left posterior thalamus.

Not available.

Chapman et al., [40]

25/22

No intergroup difference in the corpus callosum area

Not available.

Devine et al., [27]

30/17

GM volume reduction in the left precentral cortex, left frontal gyrus, medial frontal gyri and anterior cingulate gyri.

Increased GM volume reduction in the dominant (left) motor cortex irrespective to the side of limb onset. Asymmetric GM reduction of the left somatosensory cortex and the temporal gyri in in right limb onset ALS

Ellis et al., [26]

16 (8 bulbar onset and 8 limb onset)/8

GM volume reduction in the superior, middle and medial frontal cortex. WM volume reduction in the right frontal cortex.

Compared to limb onset ALS, bulbar onset ALS showed GM volume reduction in the brainstem, the cerebellum and in the fusiform gyri (BA 34) and WM volume reduction along the left corticospinal tract.

Grosskreutz et al., [18]

17/17

GM volume reduction in the precentral, frontal and parietal cortex. No WM atrophy.

ALSFRS-R correlated positively with GM volume reduction in the right medial frontal gyrus (BA 10).

Kassubek et al., [32]

22/22

GM volume reduction in the right primary motor cortex and the left medial gyrus and bilateral inferior temporal gyrus.

Negative with ALSFRS-R and DD.

Meadcroft et al., 2014

8/6

Post mortem study; loss of signal difference between WM and GM (mainly in the primary motor cortex).

Not available.

Mezzapesa et al., [19]

16/9

GM volume reduction in the precentral, frontal and parietal cortex.

Not available.

Mezzapesa et al., [20]

29/20

GM volume reduction in the precentral, frontal, right temporal and right occipital cortex.

Different patterns of volume reduction in ALS group, high UMN burden, spinal onset and faster progression compared to controls.

Sach et al., [33]

15/12

No difference -study not designed to voxel-based morphometry.

Not available.

Sage et al., [34]

28/26

No difference -study not designed to voxel-based morphometry.

Not available.

Schuster et al., [25]

93 (60 ALS, 17 with dominant UMN, 16 with dominant LMN)/67

Correlations between the site of onset and upper vs. lower motor neuron involvement, with focal reductions in cortical thickness in the precentral cortex.

Different patterns of volume reduction in ALS subgroups: bulbar and spinal UMN signs, only spinal UMN signs, classical ALS, UMN ALS-variants, LMN ALS-variants or sites of onset compared to controls. GM reduction is most important in the left precentral cortex in bulbar onset vs. limb onset. No correlations of MRI with DPR, DD and ALSFRS-R.

Thivard et al., [24]

15/25

GM volume reduction in the precentral, frontal and temporal cortex (especially the hippocampus), the parietal and occipital cortex, the thalamus and the cerebellum. No difference in WM.

Not available.

Verstraete et al., [30]

12/12

GM reduction in the right and left precentral cortex.

Not available.

Walhout et al., [29]

153 (112 ALS, 19 UMN, 19 LMN)/60

GM reduction in the right and (predominantly) left precentral cortex and the right paracentral cortex.

Bulbar and arms ALSFRS-R subscores are correlated with cortical thickness of corresponding precentral cortex areas of the motor homunculus. DPR is correlated with the thickness of the right inferior temporal cortex, the postcentral cortex and the right paracentral cortex.

Westenberg et al., 2014

112/60

GM volume reduction in the hippocampus and left subiculum.

Larger ventricles are correlated to a lower ALSFRS-R score. Smaller basal ganglia, smaller limbic structures and larger ventricles are associated with shorter survival.

Zhang et al., [28]

43/43

GM reduction in the left precentral cortex, left supplemental area and left postcentral gyrus. Reduction in neocortex volume, GM and WM volume and brain parenchymal fraction.

GM volume reduction is most important in the motor cortex of the contralateral hemisphere of the limb of onset. ALSFRS is positively correlated with GM density in the left postcentral cortex and DPR is negatively correlated with GM density in the right precentral cortex

Zhu et al., [31, 87]

22/22

GM reduction in the right and left precentral cortex.

Negative with DD, DPR and all other clinical parameters.