Distinct white matter alterations following severe stroke: Longitudinal DTI study in neglect.
OBJECTIVE
To distinguish white matter remodeling directly induced by stroke lesion from that evoked by remote network dysfunction, using spatial neglect as a model.


METHODS
We examined 24 visual neglect/extinction patients and 17 control patients combining comprehensive analyses of diffusion tensor metrics and global fiber tracking with neuropsychological testing in the acute (6.3 ± 0.5 days poststroke) and chronic (134 ± 7 days poststroke) stroke phases.


RESULTS
Compared to stroke controls, patients with spatial neglect/extinction displayed longitudinal white matter alterations with 2 defining signatures: (1) perilesional degenerative changes characterized by congruently reduced fractional anisotropy and increased radial diffusivity (RD), axial diffusivity, and mean diffusivity, all suggestive of direct axonal damage by lesion and therefore nonspecific for impaired attention network and (2) transneuronal changes characterized by an increased RD in contralesional frontoparietal and bilateral occipital connections, suggestive of primary periaxonal involvement; these changes were distinctly related to the degree of unrecovered neglect symptoms in chronic stroke, hence emerging as network-specific alterations.


CONCLUSIONS
The present data show how stroke entails global alterations of lesion-spared network architecture over time. Sufficiently large lesions of widely interconnected association cortex induce distinct, large-scale structural reorganization in domain-specific network connections. Besides their relevance to unrecovered domain-specific symptoms, these effects might also explain mechanisms of domain-general deficits in stroke patients, pointing to potential targets for therapeutic intervention.
From the Department of Neurology (R.M.U., L.B., C.P.K., V.G., C.W.), Freiburg Brain Imaging (R.M.U., L.B., C.P.K., S.K., I.M., V.G., C.W.), BrainLinks-BrainTools Cluster of Excellence (R.M.U., L.B., C.P.K., S.K., C.W.), Department of Psychiatry and Psychotherapy (R.M.U., S.K.), Medical Physics, Department of Radiology (M.R., V.G.K.), and Department of Neuroradiology (I.M.), Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Germany; University Hospital of Old Age Psychiatry (S.K.), University of Bern, Switzerland; and NatBrainLab (M.C.), Institute of Psychiatry, King's College London, UK. roza.umarova@uniklinik-freiburg.de.
Roza M
RM
Umarova
From the Department of Neurology (R.M.U., L.B., C.P.K., V.G., C.W.), Freiburg Brain Imaging (R.M.U., L.B., C.P.K., S.K., I.M., V.G., C.W.), BrainLinks-BrainTools Cluster of Excellence (R.M.U., L.B., C.P.K., S.K., C.W.), Department of Psychiatry and Psychotherapy (R.M.U., S.K.), Medical Physics, Department of Radiology (M.R., V.G.K.), and Department of Neuroradiology (I.M.), Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Germany; University Hospital of Old Age Psychiatry (S.K.), University of Bern, Switzerland; and NatBrainLab (M.C.), Institute of Psychiatry, King's College London, UK.
Lena
L
Beume
From the Department of Neurology (R.M.U., L.B., C.P.K., V.G., C.W.), Freiburg Brain Imaging (R.M.U., L.B., C.P.K., S.K., I.M., V.G., C.W.), BrainLinks-BrainTools Cluster of Excellence (R.M.U., L.B., C.P.K., S.K., C.W.), Department of Psychiatry and Psychotherapy (R.M.U., S.K.), Medical Physics, Department of Radiology (M.R., V.G.K.), and Department of Neuroradiology (I.M.), Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Germany; University Hospital of Old Age Psychiatry (S.K.), University of Bern, Switzerland; and NatBrainLab (M.C.), Institute of Psychiatry, King's College London, UK.
Marco
M
Reisert
From the Department of Neurology (R.M.U., L.B., C.P.K., V.G., C.W.), Freiburg Brain Imaging (R.M.U., L.B., C.P.K., S.K., I.M., V.G., C.W.), BrainLinks-BrainTools Cluster of Excellence (R.M.U., L.B., C.P.K., S.K., C.W.), Department of Psychiatry and Psychotherapy (R.M.U., S.K.), Medical Physics, Department of Radiology (M.R., V.G.K.), and Department of Neuroradiology (I.M.), Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Germany; University Hospital of Old Age Psychiatry (S.K.), University of Bern, Switzerland; and NatBrainLab (M.C.), Institute of Psychiatry, King's College London, UK.
Christoph P
CP
Kaller
From the Department of Neurology (R.M.U., L.B., C.P.K., V.G., C.W.), Freiburg Brain Imaging (R.M.U., L.B., C.P.K., S.K., I.M., V.G., C.W.), BrainLinks-BrainTools Cluster of Excellence (R.M.U., L.B., C.P.K., S.K., C.W.), Department of Psychiatry and Psychotherapy (R.M.U., S.K.), Medical Physics, Department of Radiology (M.R., V.G.K.), and Department of Neuroradiology (I.M.), Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Germany; University Hospital of Old Age Psychiatry (S.K.), University of Bern, Switzerland; and NatBrainLab (M.C.), Institute of Psychiatry, King's College London, UK.
Stefan
S
Klöppel
From the Department of Neurology (R.M.U., L.B., C.P.K., V.G., C.W.), Freiburg Brain Imaging (R.M.U., L.B., C.P.K., S.K., I.M., V.G., C.W.), BrainLinks-BrainTools Cluster of Excellence (R.M.U., L.B., C.P.K., S.K., C.W.), Department of Psychiatry and Psychotherapy (R.M.U., S.K.), Medical Physics, Department of Radiology (M.R., V.G.K.), and Department of Neuroradiology (I.M.), Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Germany; University Hospital of Old Age Psychiatry (S.K.), University of Bern, Switzerland; and NatBrainLab (M.C.), Institute of Psychiatry, King's College London, UK.
Irina
I
Mader
From the Department of Neurology (R.M.U., L.B., C.P.K., V.G., C.W.), Freiburg Brain Imaging (R.M.U., L.B., C.P.K., S.K., I.M., V.G., C.W.), BrainLinks-BrainTools Cluster of Excellence (R.M.U., L.B., C.P.K., S.K., C.W.), Department of Psychiatry and Psychotherapy (R.M.U., S.K.), Medical Physics, Department of Radiology (M.R., V.G.K.), and Department of Neuroradiology (I.M.), Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Germany; University Hospital of Old Age Psychiatry (S.K.), University of Bern, Switzerland; and NatBrainLab (M.C.), Institute of Psychiatry, King's College London, UK.
Volkmar
V
Glauche
From the Department of Neurology (R.M.U., L.B., C.P.K., V.G., C.W.), Freiburg Brain Imaging (R.M.U., L.B., C.P.K., S.K., I.M., V.G., C.W.), BrainLinks-BrainTools Cluster of Excellence (R.M.U., L.B., C.P.K., S.K., C.W.), Department of Psychiatry and Psychotherapy (R.M.U., S.K.), Medical Physics, Department of Radiology (M.R., V.G.K.), and Department of Neuroradiology (I.M.), Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Germany; University Hospital of Old Age Psychiatry (S.K.), University of Bern, Switzerland; and NatBrainLab (M.C.), Institute of Psychiatry, King's College London, UK.
Valerij G
VG
Kiselev
From the Department of Neurology (R.M.U., L.B., C.P.K., V.G., C.W.), Freiburg Brain Imaging (R.M.U., L.B., C.P.K., S.K., I.M., V.G., C.W.), BrainLinks-BrainTools Cluster of Excellence (R.M.U., L.B., C.P.K., S.K., C.W.), Department of Psychiatry and Psychotherapy (R.M.U., S.K.), Medical Physics, Department of Radiology (M.R., V.G.K.), and Department of Neuroradiology (I.M.), Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Germany; University Hospital of Old Age Psychiatry (S.K.), University of Bern, Switzerland; and NatBrainLab (M.C.), Institute of Psychiatry, King's College London, UK.
Marco
M
Catani
From the Department of Neurology (R.M.U., L.B., C.P.K., V.G., C.W.), Freiburg Brain Imaging (R.M.U., L.B., C.P.K., S.K., I.M., V.G., C.W.), BrainLinks-BrainTools Cluster of Excellence (R.M.U., L.B., C.P.K., S.K., C.W.), Department of Psychiatry and Psychotherapy (R.M.U., S.K.), Medical Physics, Department of Radiology (M.R., V.G.K.), and Department of Neuroradiology (I.M.), Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Germany; University Hospital of Old Age Psychiatry (S.K.), University of Bern, Switzerland; and NatBrainLab (M.C.), Institute of Psychiatry, King's College London, UK.
Cornelius
C
Weiller
D000208:Acute Disease; D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging*; D002908:Chronic Disease; D038524:Diffusion Magnetic Resonance Imaging; D056324:Diffusion Tensor Imaging; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000000981:diagnostic imaging; D009483:Neuropsychological Tests; D010468:Perceptual Disorders / Q000000981:diagnostic imaging* / Q000209:etiology*; D012720:Severity of Illness Index; D020521:Stroke / Q000150:complications* / Q000000981:diagnostic imaging* / Q000523:psychology; D066127:White Matter / Q000000981:diagnostic imaging*