Table 1.
Selection of original neuroimaging research articles in ALS since 2015 with more than 30 patients.
| References | Study design |
Sample size
Study participants |
Raw imaging data/Imaging technique | Assessment tools | Follow-up interval (months) | Key study findings |
|---|---|---|---|---|---|---|
| Agosta et al. (1) | Cross-sectional, Prospective, Multi-center, Case-control |
ALS n = 56 UMN phenotype n = 31 LMN phenotype n = 14 |
MRI Cortical thickness DTI |
ALSFRS-R MMSE RCPM CET WCST WCFST RAVLT BADA HDRS FBI ALS-FTD questionnaire Phonemic and semantic fluency Digit span forwards and backwards |
N/A | - Cortical thinning of the bilateral precentral gyrus, insular and cingulate cortices, and frontotemporal regions was detected in all groups. - There was involvement of the extra-motor WM tracts in the corpus callosum and frontotemporal regions. - These findings were more marked in those with cognitive or behavioral impairment. |
| Alshikho et al. (2) | Longitudinal, Prospective, Single-center, Case-control |
ALS n = 53 PLS n = 11 |
MRI Cortical thickness DTI ROI analysis [11C]-PBR28 PET |
ALSFRS-R UMNB |
6-months | - In ALS, increased glia activation was detected in the precentral and paracentral gryi that correlated with areas of cortical thinning. |
| Alruwaili et al. (3) | Cross-sectional, Prospective, Single-center, Case-control |
ALS n = 30 | MRI VBM DTI TBSS |
ALSFRS-R ACE-III FAB ALS-FTD questionnaire |
N/A | - GM and WM degeneration was detected in the motor and extra motor regions in those with and without cognitive impairment. The WM alterations were more extensive in those with cognitive impairment. |
| Basaia et al. (4) | Cross-sectional, Prospective, Multi-center, Case-control |
ALS n = 173 PLS n = 38 PMA n = 28 |
MRI DTI Resting-state fMRI Global brain network analysis Functional connectivity analysis |
MMSE RAVLT Digit span forward and backward Stroop test CET WCFST WCST RCPM Phonemic and semantic fluency Italian battery for the assessment of aphasic disorders. HDRS Beck depression inventory FBI ALS-FTD Questionnaire |
N/A | - In ALS, there was widespread motor and extra-motor network degeneration. |
| Bede et al. (5) | Cross-sectional, Prospective, Single-center, Case-control |
ALS n = 36 | MRI DTI TBSS ROI analysis |
ALSFRS-R Neuropsychological assessment |
N/A | - In patients with ALS without cognitive impairment, WM degeneration was detected in the cerebellum, brain stem, occipital lobes, operculum, and insula. |
| Bede et al. (6) | Cross-sectional, Prospective, Single-center, Case-control |
ALS n = 70 | MRI Cortical gray matter morphometry Basal ganglia morphometry DTI |
ALSFRS-R | - There is GM degeneration of the anterior cingulate, orbitofrontal cortex, and mesial temporal lobes. There is also WM degeneration involving the fornix. - There is subcortical involvement of the thalamus, caudate, nucleus accumbens and hippocampus. |
|
| Bede et al. (7) | Longitudinal, Prospective, Single-center, Case-control |
ALS n = 32 | MRI VBM Cortical thickness DTI ROI analysis |
ALSFRS-R | 4-months 8-months | - WM degeneration was detected early with limited interval progression; GM degeneration was limited at baseline with continued progression. |
| Bede et al. (8) | Longitudinal, Prospective, Single-center, Case-control |
ALS n = 100 PLS n = 33 FTD n = 30 |
MRI Volumetry, vertex and morphometry analyses |
ALSFRS-R | 4-months | - In ALS, there was progressive brainstem atrophy predominantly in medulla oblongata. |
| Bede et al. (9) | Longitudinal, Prospective, Single-center, Case-control |
ALS n = 100 PLS n = 33 FTD n = 30 |
MRI Volumetry analyses |
ALSFRS-R | 4-months | - In ALS, there was progressive brainstem atrophy in the medulla oblongata and the pons. |
| Chipika et al. (10) | Cross-sectional, Prospective, Single-center, Case-control |
ALS n = 100 PLS n = 33 |
MRI Volumetry analyses ROI morphometry |
ALSFRS-R ECAS |
N/A | - In ALS, there was involvement of the motor and sensory regions of the thalamus. |
| Christidi et al. (11) | Cross-sectional, Prospective, Single-center, Case-control |
ALS n = 42 | MRI DTI |
ALSFRS-R RAVLT BSRT RCFT |
N/A | - The involvement of WM in the frontotemporal and hippocampal regions was associated with verbal and non-verbal episodic memory test results. |
| Christidi et al. (12) | Cross-sectional, Prospective, Single-center, Case-control |
ALS n = 50 | MRI VBM DTI TBSS |
ALSFRS-R MMSE TMT WCST RAVLT BSRT RCFT WAIS Stroop test Phonemic fluency Digit span forward and backwards |
N/A | - There were motor and extra-motor GM and WM changes in non-demented cognitively-impaired ALS patients. Some of these findings were also observed in those with ALS without cognitive impairment. |
| Christidi et al. (13) | Cross-sectional, Prospective, Single-center, Case-control |
ALS n = 50 AD n = 18 |
MRI Hippocampal volumetry DTI |
ALSFRS-R RAVLT BSRT RCFT ALS Depression Inventory |
N/A | - Patients with ALS and Alzheimer's disease have divergent hippocampal imaging signatures. - The cornu/ammonis 2/3 subfield and the hippocampus-amygdala transition area are the most affected regions in ALS. |
| Consonni et al. (14) | Cross-sectional, Prospective, Single-center, Case-control |
ALS n = 48 | MRI Cortical thickness |
ALSFRS-R MMSE RAVLT BADA FBI Recognition memory test Neuropsychological examination of aphasia Visual object and space perception battery Digit span forward and backwards Letter fluency test Stroop test Brixton spatial anticipation test Ekman 60-faces test Story-based empathy task Dysexecutive questionnaire |
N/A | - There was cortical thinning in the frontoparietal region independent of cognitive and behavioral status. - Cortical thinning involving the following regions were associated with the specific deficits: ° The Inferior frontal, temporal, cingular, and insular regions were associated with cognitive or behavioral impairments. ° The left temporal pole and insular regions were associated with language deficits. |
| Illán-Gala et al. (15) | Cross-sectional, Prospective, Single-center, Case-control |
ALS n = 31 bvFTD n = 20 |
MRI Cortical thickness Cortical mean diffusivity |
ALSFRS-R MMSE ECAS |
N/A | - In ALS without cognitive impairment, cortical thinning was restricted to the dorsal motor cortex. In ALS with cognitive impairment, cortical thinning involved the frontoinsular and temporal regions bilaterally. |
| Machts et al. (16) | Cross-sectional, Prospective, Multi-center, Case-control |
ALS n = 67 | MRI Subcortical volumetry, shape, density analyses |
ALSFRS-R Letter and semantic fluency test TMT Stroop test Digit span backwards FrSBe |
N/A | - In ALS with or without cognitive impairment there were distinctive patterns of basal ganglia atrophy. There were structure specific correlations between imaging and neuropsychological measures. |
| Masuda et al. (17) | Cross-sectional, Prospective, Single-center, Case-control |
ALS n = 51 | MRI VBM DTI TBSS |
MMSE FAB RCPM Alzheimer's disease assessment scale Stroop test Digit span forward and backwards Letter and semantic fluency |
N/A | - In ALS with and without cognitive impairment, there were disrupted networks between the caudate and medial prefrontal or lateral orbitofrontal cortex. |
| Rosskopf et al. (18) | Cross-sectional, Prospective, Single-center, Case-control |
ALS n = 140 PLS n = 30 |
MRI DTI WBSS ROI analysis |
N/A | N/A | - WM degeneration involving the corticospinal tracts, corpus callosum, frontal, and brainstem regions. |
| Srivastava et al. (19) | Cross-sectional, Prospective, Multi-center, Case-control |
ALS n = 65 | MRS | ALSFRS-R Verbal fluency Semantic fluency Digit span forward and backwards |
N/A | - There was reduced tNAA/Cr and tNAA/Cho in the prefrontal cortex. Verbal fluency, semantic fluency, and digit span forwards and backwards were associated with prefrontal tNNA/Cr. |
| Digit ordering Finger and foot tapping |
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| Shen et al. (20) | Cross-sectional, Prospective, Multi-center, Case-control |
ALS n = 638 | MRI VBM |
N/A | N/A | - There was reduction in extra-motor GM volume involving the left Rolandic operculum, inferior frontal gyrus, and superior temporal gyrus. |
| Westeneng et al. (21) | Longitudinal, Prospective, Single-center, Case-control |
ALS n = 112 | MRI Subcortical volumetry Subcortical shape analysis |
ALSFRS-R | 5.5 months | - In ALS, progressive subcortical degeneration correlated with clinical parameters. |
ACE-III, Addenbrooke's cognitive examination III; AD, Alzheimer's disease; ALS, amyotrophic lateral sclerosis; ALSFRS-R, amyotrophic lateral sclerosis functional rating scale revised; BADA, battery for the aphasic deficit analysis; bvFTD, behavioral variant frontotemporal dementia; BSRT, Babcock story recall test; CET, cognitive estimation task; DTI, diffusion tensor imaging; ECAS, Edinburgh cognitive and behavioral ALS screen; FAB, frontal assessment battery; FBI, frontal behavioral inventory; FrSBe, Frontal systems behavior scale; FTD, frontotemporal dementia; GM, gray matter; HDRS, Hamilton depression rating scale; LMN, lower motor neuron; MMSE, mini-mental state examination; MRI, magnetic resonance imaging; tNAA/Cho, total N-acetylaspartate/choline; tNAA/Cr, total N-acetylaspartate/creatine; PET, Positron emission tomography; PLS, Primary lateral sclerosis; RAVLT, Rey auditory verbal learning test; RCFT, Rey's complex figure test; ROI, region of interest; RCPM, Raven's colored progressive matrices; TBSS, tract-based spatial statistics; TMT, Trail making test; UMN, upper motor neuron; UMNB, upper motor neuron burden; VBM, voxel-based morphometry; WAIS, Wechsler adult intelligence scale; WBSS, whole brain spatial statistics; WCFST, Weigl color-form sorting test; WCST, Wisconsin card sorting test; WM, white matter.