Table 3.
Studies investigating asymptomatic C9orf72 mutation vs. controls.
| No. | Author | Year | Study design | No. of subjects | Techniques | Findings |
|---|---|---|---|---|---|---|
| 1 | Rohrer et al. (19) | 2015 | Cross-sectional | 18 aC9+ | sMRI | Atrophy in subcortical areas (the thalamus, insula, and posterior cortical areas) at 25 years before EO, followed by the frontal and temporal lobes at 20 years before EO, and the cerebellum at 10 years before EO |
| 2 | Walhout et al. (29) | 2015 | Cross-sectional | 16 aC9+ vs. 23 NC | sMRI DTI |
Cortical thinning in the temporal, parietal and occipital regions, and smaller volume in the left caudate and putamen. No difference |
| 3 | Floeter et al. (68) | 2016 | Longitudinal | 7 aC9+ vs. 28 HC | sMRI | Baseline: no difference |
| 5 aC9+ vs. 23 HC | Longitudinal: no difference | |||||
| 4 | Lee et al. (30) | 2017 | Cross-sectional | 15 aC9+ vs. 67 HC | sMRI | Lower GM intensity in the bilateral posterior mid-cingulate, left medial pulvinar thalamus, and small, scattered regions in the bilateral dorsolateral prefrontal cortex |
| 12 aC9+ vs. 29 HC | DTI | Reduced FA in the corpus callosum, cingulum bundles, corticospinal tracts, uncinate fasciculi and inferior longitudinal fasciculi. | ||||
| 13 aC9+ vs. 30 HC | rfMRI | Intrinsic connectivity deficits in DMN, sensorimotor, but most prominent in SN and medial pulvinar thalamus-seeded networks | ||||
| 5 | Papma et al. (69) | 2017 | Cross-sectional | 18 aC9+ vs. 15 NC | sMRI | No difference for whole group; in a subgroup >40 years, lower gray matter volume in the right inferior temporal gyrus, right cerebellum, left postcentral and precentral gyrus, the left superior parietal lobe and the left thalamus |
| DTI | Lower FA and higher RD within the right superior corona radiata, inferior longitudinal fasciculus, uncinate fasciculus, internal and external capsule, bilateral anterior thalamic radiation and corticospinal tract | |||||
| 6 | Bertrand et al. (31) | 2018 | Cross-sectional | 41 aC9+ vs. 39 NC | sMRI | Atrophy in the frontal, inferior temporal and parietal cortex and bilateral thalamus |
| DTI | Lower FA, higher diffusivity in the frontal regions and bilateral corticospinal tracts | |||||
| 7 | Cash et al. (6) | 2018 | Cross-sectional | 40 aC9+ vs. 144 NC | sMRI | GM loss bilaterally in the thalamus, right superior posterior cerebellum, superior temporal and inferior frontal regions |
| 8 | Jiskoot et al. (36) | 2018 | Cross-sectional | 35 aC9+ vs. 115 NC | DTI | Posteriorly located WM tracts (posterior thalamic radiation, splenium of the corpus callosum, posterior corona radiata) |
| 9 | Fumagalli et al. (20) | 2018 | Cross-sectional | 24 a C9+ vs. 148 NC | sMRI | No difference |
| 10 | Popuri et al. (32) | 2018 | Cross-sectional | 15 aC9+ vs. 37 NC | sMRI | Cortical thinning in the temporal, parietal and frontal regions; reduced volumes of bilateral thalamus and left caudate |
| 11 | Panman et al. (22) | 2019 | Longitudinal | 11 aC9+ vs. 53 NC | sMRI | Baseline: GM volume loss in the cerebellum, insula, left fronto-temporal lobes; cortical thinning in the right postcentral gyrus |
| Follow-up: GM volume loss in the thalamus, cerebellum, and several bilateral orbitofrontal and insular cortices, and the postcentral gyrus; Cortical thinning in bilateral precentral gyrus and right superior parietal lobule |
||||||
| Longitudinal: no difference | ||||||
| 12 aC9+ vs. 50 NC | DTI | Baseline and follow-up: lower FA in frontotemporal tracts and higher MD in the entire skeleton | ||||
| Longitudinal: no difference |