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Microstructural changes across different clinical milestones of disease in amyotrophic lateral sclerosis.

Trojsi F, Caiazzo G, Corbo D, Piccirillo G, Cristillo V, Femiano C, Ferrantino T, Cirillo M, MonsurrĂ² MR, Esposito F, Tedeschi G - PLoS ONE (2015)

Bottom Line: ALS patients in clinical stage 2B (with impairment of two functional regions) exhibited decreased fractional anisotropy (FA) (p<0.001, uncorrected) and increased mean (MD) and radial diffusivity (RD) (p<0.001, uncorrected) in the left cerebellar hemisphere and brainstem precerebellar nuclei, as well as in motor areas, while GM atrophy (p<0.001, uncorrected) was detected only in the left inferior frontal gyrus and right cuneus.Finally, ALS patients in stage 3 (with impairment of three functional regions) exhibited decreased FA and increased MD and RD (p<0.05, corrected) within WM underneath bilateral pre and postcentral gyri, corpus callosum midbody, long associative tracts and midbrain, while no significant clusters of GM atrophy were observed.Our findings reinforce the hypothesis that the neurodegenerative process propagates along the axonal pathways and develops beyond motor areas from early stages, involving progressively several frontotemporal regions and their afferents and efferents, while the detection of GM atrophy in earlier stages and its disappearance in later stages may be the result of reactive gliosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy; MRI Research Center SUN-FISM-Second University of Naples, 80138 Naples, Italy.

ABSTRACT
Neurodegenerative process in amyotrophic lateral sclerosis (ALS) has been proven to involve several cortical and subcortical brain regions within and beyond motor areas. However, how ALS pathology spreads progressively during disease evolution is still unknown. In this cross-sectional study we investigated 54 ALS patients, divided into 3 subsets according to the clinical stage, and 18 age and sex-matched healthy controls, by using tract-based spatial statistics (TBSS) diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) analyses. We aimed to identify white (WM) and gray matter (GM) patterns of disease distinctive of each clinical stage, corresponding to specific clinical milestones. ALS cases in stage 2A (i.e., at diagnosis) were characterized by GM and WM impairment of left motor and premotor cortices and brainstem at ponto-mesenchephalic junction. ALS patients in clinical stage 2B (with impairment of two functional regions) exhibited decreased fractional anisotropy (FA) (p<0.001, uncorrected) and increased mean (MD) and radial diffusivity (RD) (p<0.001, uncorrected) in the left cerebellar hemisphere and brainstem precerebellar nuclei, as well as in motor areas, while GM atrophy (p<0.001, uncorrected) was detected only in the left inferior frontal gyrus and right cuneus. Finally, ALS patients in stage 3 (with impairment of three functional regions) exhibited decreased FA and increased MD and RD (p<0.05, corrected) within WM underneath bilateral pre and postcentral gyri, corpus callosum midbody, long associative tracts and midbrain, while no significant clusters of GM atrophy were observed. Our findings reinforce the hypothesis that the neurodegenerative process propagates along the axonal pathways and develops beyond motor areas from early stages, involving progressively several frontotemporal regions and their afferents and efferents, while the detection of GM atrophy in earlier stages and its disappearance in later stages may be the result of reactive gliosis.

No MeSH data available.


Related in: MedlinePlus

Voxel-wise correlation analyses between ALSFRS-R and ACE-R scores and FA in the three groups of patients.Widespread patterns of positive correlations (p<0.05, corrected) between both disability scores and FA in all clinical stages examined, with overlaps between the three patients groups.
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pone.0119045.g002: Voxel-wise correlation analyses between ALSFRS-R and ACE-R scores and FA in the three groups of patients.Widespread patterns of positive correlations (p<0.05, corrected) between both disability scores and FA in all clinical stages examined, with overlaps between the three patients groups.

Mentions: In each clinical stage examined, we detected significant positive correlations between FA and ALSFRS-R and ACE-R scores (p<0.05, corrected for multiple comparisons) in the midpart of CC, superior and inferior longitudinal and fronto-occipital fasciculi and within WM underneath primary motor and premotor cortices, inferior frontal and temporal gyri, supramarginal gyri, visual cortices and brainstem at the ponto-mesenchephalic junction (Fig. 2). Moreover, these widespread patterns of correlation were observed in all clinical stages considered, with an overlapping pattern between the three patients groups. Conversely, no significant correlations were observed between DTI metrics and disease duration in the three subsets of patients evaluated. RD and MD showed positive correlations with FrSBe scale T-scores in all the clinical stages considered in the midpart of CC, superior and inferior longitudinal and fronto-occipital fasciculi and within WM underneath primary motor and premotor cortices, inferior frontal and temporal gyri and brainstem at the ponto-mesenchephalic junction (S1 Fig.).


Microstructural changes across different clinical milestones of disease in amyotrophic lateral sclerosis.

Trojsi F, Caiazzo G, Corbo D, Piccirillo G, Cristillo V, Femiano C, Ferrantino T, Cirillo M, MonsurrĂ² MR, Esposito F, Tedeschi G - PLoS ONE (2015)

Voxel-wise correlation analyses between ALSFRS-R and ACE-R scores and FA in the three groups of patients.Widespread patterns of positive correlations (p<0.05, corrected) between both disability scores and FA in all clinical stages examined, with overlaps between the three patients groups.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4368555&req=5

pone.0119045.g002: Voxel-wise correlation analyses between ALSFRS-R and ACE-R scores and FA in the three groups of patients.Widespread patterns of positive correlations (p<0.05, corrected) between both disability scores and FA in all clinical stages examined, with overlaps between the three patients groups.
Mentions: In each clinical stage examined, we detected significant positive correlations between FA and ALSFRS-R and ACE-R scores (p<0.05, corrected for multiple comparisons) in the midpart of CC, superior and inferior longitudinal and fronto-occipital fasciculi and within WM underneath primary motor and premotor cortices, inferior frontal and temporal gyri, supramarginal gyri, visual cortices and brainstem at the ponto-mesenchephalic junction (Fig. 2). Moreover, these widespread patterns of correlation were observed in all clinical stages considered, with an overlapping pattern between the three patients groups. Conversely, no significant correlations were observed between DTI metrics and disease duration in the three subsets of patients evaluated. RD and MD showed positive correlations with FrSBe scale T-scores in all the clinical stages considered in the midpart of CC, superior and inferior longitudinal and fronto-occipital fasciculi and within WM underneath primary motor and premotor cortices, inferior frontal and temporal gyri and brainstem at the ponto-mesenchephalic junction (S1 Fig.).

Bottom Line: ALS patients in clinical stage 2B (with impairment of two functional regions) exhibited decreased fractional anisotropy (FA) (p<0.001, uncorrected) and increased mean (MD) and radial diffusivity (RD) (p<0.001, uncorrected) in the left cerebellar hemisphere and brainstem precerebellar nuclei, as well as in motor areas, while GM atrophy (p<0.001, uncorrected) was detected only in the left inferior frontal gyrus and right cuneus.Finally, ALS patients in stage 3 (with impairment of three functional regions) exhibited decreased FA and increased MD and RD (p<0.05, corrected) within WM underneath bilateral pre and postcentral gyri, corpus callosum midbody, long associative tracts and midbrain, while no significant clusters of GM atrophy were observed.Our findings reinforce the hypothesis that the neurodegenerative process propagates along the axonal pathways and develops beyond motor areas from early stages, involving progressively several frontotemporal regions and their afferents and efferents, while the detection of GM atrophy in earlier stages and its disappearance in later stages may be the result of reactive gliosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy; MRI Research Center SUN-FISM-Second University of Naples, 80138 Naples, Italy.

ABSTRACT
Neurodegenerative process in amyotrophic lateral sclerosis (ALS) has been proven to involve several cortical and subcortical brain regions within and beyond motor areas. However, how ALS pathology spreads progressively during disease evolution is still unknown. In this cross-sectional study we investigated 54 ALS patients, divided into 3 subsets according to the clinical stage, and 18 age and sex-matched healthy controls, by using tract-based spatial statistics (TBSS) diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) analyses. We aimed to identify white (WM) and gray matter (GM) patterns of disease distinctive of each clinical stage, corresponding to specific clinical milestones. ALS cases in stage 2A (i.e., at diagnosis) were characterized by GM and WM impairment of left motor and premotor cortices and brainstem at ponto-mesenchephalic junction. ALS patients in clinical stage 2B (with impairment of two functional regions) exhibited decreased fractional anisotropy (FA) (p<0.001, uncorrected) and increased mean (MD) and radial diffusivity (RD) (p<0.001, uncorrected) in the left cerebellar hemisphere and brainstem precerebellar nuclei, as well as in motor areas, while GM atrophy (p<0.001, uncorrected) was detected only in the left inferior frontal gyrus and right cuneus. Finally, ALS patients in stage 3 (with impairment of three functional regions) exhibited decreased FA and increased MD and RD (p<0.05, corrected) within WM underneath bilateral pre and postcentral gyri, corpus callosum midbody, long associative tracts and midbrain, while no significant clusters of GM atrophy were observed. Our findings reinforce the hypothesis that the neurodegenerative process propagates along the axonal pathways and develops beyond motor areas from early stages, involving progressively several frontotemporal regions and their afferents and efferents, while the detection of GM atrophy in earlier stages and its disappearance in later stages may be the result of reactive gliosis.

No MeSH data available.


Related in: MedlinePlus