Intrinsic and Extrinsic Mechanisms of Thalamic Pathology in Multiple Sclerosis

Objective Thalamic atrophy is among the earliest brain changes detected in patients with multiple sclerosis (MS) and the degree of thalamic atrophy is a strong predictor of disability progression. The causes of thalamic atrophy are not fully understood. Here, we investigate the contributions of thal...

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Published inAnnals of neurology Vol. 88; no. 1; pp. 81 - 92
Main Authors Mahajan, Kedar R., Nakamura, Kunio, Cohen, Jeffrey A., Trapp, Bruce D., Ontaneda, Daniel
Format Journal Article
LanguageEnglish
Published Hoboken, USA John Wiley & Sons, Inc 01.07.2020
Wiley Subscription Services, Inc
Subjects
Aged
Atrophy
Atrophy - diagnostic imaging
Atrophy - pathology
Autopsy
Axons
Brain
Brain slice preparation
Cell activation
Change detection
Correlation
Degeneration
Demyelination
Discoloration
Disease Progression
Female
Humans
Lesions
Macrophages
Magnetic Resonance Imaging
Male
Middle Aged
Multiple sclerosis
Multiple Sclerosis - diagnostic imaging
Multiple Sclerosis - pathology
Neurodegeneration
Neuroimaging
Neurons - pathology
Pathology
Pulvinar
Pulvinar - diagnostic imaging
Pulvinar - pathology
Sensory neurons
Sex
Substantia alba
Thalamus
Thalamus - diagnostic imaging
Thalamus - pathology
White Matter - diagnostic imaging
White Matter - pathology
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Abstract Objective Thalamic atrophy is among the earliest brain changes detected in patients with multiple sclerosis (MS) and the degree of thalamic atrophy is a strong predictor of disability progression. The causes of thalamic atrophy are not fully understood. Here, we investigate the contributions of thalamic demyelinated lesions, thalamic neuronal loss, and cerebral white matter (WM) lesions to thalamic volume. Methods We used postmortem in situ magnetic resonance imaging (MRI) scans of 95 subjects with MS to correlate thalamic lesion volumes with global MRI metrics. We histologically characterized thalamic demyelination patterns and compared neuronal loss and neuritic pathology in the thalami with the extremes of volume. Results Grossly apparent thalamic discolorations in cm‐thick brain slices were T2/fluid‐attenuated inversion recovery (FLAIR) hyperintense, T1‐hypointense, and appeared as perivascular demyelinated lesions with dystrophic neurons/axons. Subependymal demyelinated lesions with axonal loss and microglial/macrophage activation were also observed. The 12 subjects with the least thalamic volume had a 17.6% reduction of median neuronal density in the dorsomedial/ventrolateral and pulvinar nuclei compared with the 14 subjects with the greatest thalamic volume (p = 0.03). After correcting for age, disease duration, sex, and T2 lesion volume, the total (p = 0.20), ovoid (p = 0.31), or subependymal (p = 0.44) MRI thalamic lesion volumes correlated with thalamic volume. Thalamic volume correlated with cerebral T2 lesion volume (Spearman’s rho = −0.65, p < 0.001; p < 0.0001 after correcting for age, disease duration, and sex). Interpretation Our findings suggest the degeneration of efferent/afferent thalamic projections and/or a neurodegenerative process as greater contributors to thalamic atrophy than thalamic demyelinating lesions. ANN NEUROL 2020 ANN NEUROL 2020;88:81–92
AbstractList Thalamic atrophy is among the earliest brain changes detected in patients with multiple sclerosis (MS) and the degree of thalamic atrophy is a strong predictor of disability progression. The causes of thalamic atrophy are not fully understood. Here, we investigate the contributions of thalamic demyelinated lesions, thalamic neuronal loss, and cerebral white matter (WM) lesions to thalamic volume. We used postmortem in situ magnetic resonance imaging (MRI) scans of 95 subjects with MS to correlate thalamic lesion volumes with global MRI metrics. We histologically characterized thalamic demyelination patterns and compared neuronal loss and neuritic pathology in the thalami with the extremes of volume. Grossly apparent thalamic discolorations in cm-thick brain slices were T2/fluid-attenuated inversion recovery (FLAIR) hyperintense, T1-hypointense, and appeared as perivascular demyelinated lesions with dystrophic neurons/axons. Subependymal demyelinated lesions with axonal loss and microglial/macrophage activation were also observed. The 12 subjects with the least thalamic volume had a 17.6% reduction of median neuronal density in the dorsomedial/ventrolateral and pulvinar nuclei compared with the 14 subjects with the greatest thalamic volume (p = 0.03). After correcting for age, disease duration, sex, and T2 lesion volume, the total (p = 0.20), ovoid (p = 0.31), or subependymal (p = 0.44) MRI thalamic lesion volumes correlated with thalamic volume. Thalamic volume correlated with cerebral T2 lesion volume (Spearman's rho = -0.65, p < 0.001; p < 0.0001 after correcting for age, disease duration, and sex). Our findings suggest the degeneration of efferent/afferent thalamic projections and/or a neurodegenerative process as greater contributors to thalamic atrophy than thalamic demyelinating lesions. ANN NEUROL 2020 ANN NEUROL 2020;88:81-92.
Thalamic atrophy is among the earliest brain changes detected in patients with multiple sclerosis (MS) and the degree of thalamic atrophy is a strong predictor of disability progression. The causes of thalamic atrophy are not fully understood. Here, we investigate the contributions of thalamic demyelinated lesions, thalamic neuronal loss, and cerebral white matter (WM) lesions to thalamic volume.OBJECTIVEThalamic atrophy is among the earliest brain changes detected in patients with multiple sclerosis (MS) and the degree of thalamic atrophy is a strong predictor of disability progression. The causes of thalamic atrophy are not fully understood. Here, we investigate the contributions of thalamic demyelinated lesions, thalamic neuronal loss, and cerebral white matter (WM) lesions to thalamic volume.We used postmortem in situ magnetic resonance imaging (MRI) scans of 95 subjects with MS to correlate thalamic lesion volumes with global MRI metrics. We histologically characterized thalamic demyelination patterns and compared neuronal loss and neuritic pathology in the thalami with the extremes of volume.METHODSWe used postmortem in situ magnetic resonance imaging (MRI) scans of 95 subjects with MS to correlate thalamic lesion volumes with global MRI metrics. We histologically characterized thalamic demyelination patterns and compared neuronal loss and neuritic pathology in the thalami with the extremes of volume.Grossly apparent thalamic discolorations in cm-thick brain slices were T2/fluid-attenuated inversion recovery (FLAIR) hyperintense, T1-hypointense, and appeared as perivascular demyelinated lesions with dystrophic neurons/axons. Subependymal demyelinated lesions with axonal loss and microglial/macrophage activation were also observed. The 12 subjects with the least thalamic volume had a 17.6% reduction of median neuronal density in the dorsomedial/ventrolateral and pulvinar nuclei compared with the 14 subjects with the greatest thalamic volume (p = 0.03). After correcting for age, disease duration, sex, and T2 lesion volume, the total (p = 0.20), ovoid (p = 0.31), or subependymal (p = 0.44) MRI thalamic lesion volumes correlated with thalamic volume. Thalamic volume correlated with cerebral T2 lesion volume (Spearman's rho = -0.65, p < 0.001; p < 0.0001 after correcting for age, disease duration, and sex).RESULTSGrossly apparent thalamic discolorations in cm-thick brain slices were T2/fluid-attenuated inversion recovery (FLAIR) hyperintense, T1-hypointense, and appeared as perivascular demyelinated lesions with dystrophic neurons/axons. Subependymal demyelinated lesions with axonal loss and microglial/macrophage activation were also observed. The 12 subjects with the least thalamic volume had a 17.6% reduction of median neuronal density in the dorsomedial/ventrolateral and pulvinar nuclei compared with the 14 subjects with the greatest thalamic volume (p = 0.03). After correcting for age, disease duration, sex, and T2 lesion volume, the total (p = 0.20), ovoid (p = 0.31), or subependymal (p = 0.44) MRI thalamic lesion volumes correlated with thalamic volume. Thalamic volume correlated with cerebral T2 lesion volume (Spearman's rho = -0.65, p < 0.001; p < 0.0001 after correcting for age, disease duration, and sex).Our findings suggest the degeneration of efferent/afferent thalamic projections and/or a neurodegenerative process as greater contributors to thalamic atrophy than thalamic demyelinating lesions. ANN NEUROL 2020 ANN NEUROL 2020;88:81-92.INTERPRETATIONOur findings suggest the degeneration of efferent/afferent thalamic projections and/or a neurodegenerative process as greater contributors to thalamic atrophy than thalamic demyelinating lesions. ANN NEUROL 2020 ANN NEUROL 2020;88:81-92.
ObjectiveThalamic atrophy is among the earliest brain changes detected in patients with multiple sclerosis (MS) and the degree of thalamic atrophy is a strong predictor of disability progression. The causes of thalamic atrophy are not fully understood. Here, we investigate the contributions of thalamic demyelinated lesions, thalamic neuronal loss, and cerebral white matter (WM) lesions to thalamic volume.MethodsWe used postmortem in situ magnetic resonance imaging (MRI) scans of 95 subjects with MS to correlate thalamic lesion volumes with global MRI metrics. We histologically characterized thalamic demyelination patterns and compared neuronal loss and neuritic pathology in the thalami with the extremes of volume.ResultsGrossly apparent thalamic discolorations in cm‐thick brain slices were T2/fluid‐attenuated inversion recovery (FLAIR) hyperintense, T1‐hypointense, and appeared as perivascular demyelinated lesions with dystrophic neurons/axons. Subependymal demyelinated lesions with axonal loss and microglial/macrophage activation were also observed. The 12 subjects with the least thalamic volume had a 17.6% reduction of median neuronal density in the dorsomedial/ventrolateral and pulvinar nuclei compared with the 14 subjects with the greatest thalamic volume (p = 0.03). After correcting for age, disease duration, sex, and T2 lesion volume, the total (p = 0.20), ovoid (p = 0.31), or subependymal (p = 0.44) MRI thalamic lesion volumes correlated with thalamic volume. Thalamic volume correlated with cerebral T2 lesion volume (Spearman’s rho = −0.65, p < 0.001; p < 0.0001 after correcting for age, disease duration, and sex).InterpretationOur findings suggest the degeneration of efferent/afferent thalamic projections and/or a neurodegenerative process as greater contributors to thalamic atrophy than thalamic demyelinating lesions. ANN NEUROL 2020 ANN NEUROL 2020;88:81–92
Objective Thalamic atrophy is among the earliest brain changes detected in patients with multiple sclerosis (MS) and the degree of thalamic atrophy is a strong predictor of disability progression. The causes of thalamic atrophy are not fully understood. Here, we investigate the contributions of thalamic demyelinated lesions, thalamic neuronal loss, and cerebral white matter (WM) lesions to thalamic volume. Methods We used postmortem in situ magnetic resonance imaging (MRI) scans of 95 subjects with MS to correlate thalamic lesion volumes with global MRI metrics. We histologically characterized thalamic demyelination patterns and compared neuronal loss and neuritic pathology in the thalami with the extremes of volume. Results Grossly apparent thalamic discolorations in cm‐thick brain slices were T2/fluid‐attenuated inversion recovery (FLAIR) hyperintense, T1‐hypointense, and appeared as perivascular demyelinated lesions with dystrophic neurons/axons. Subependymal demyelinated lesions with axonal loss and microglial/macrophage activation were also observed. The 12 subjects with the least thalamic volume had a 17.6% reduction of median neuronal density in the dorsomedial/ventrolateral and pulvinar nuclei compared with the 14 subjects with the greatest thalamic volume (p = 0.03). After correcting for age, disease duration, sex, and T2 lesion volume, the total (p = 0.20), ovoid (p = 0.31), or subependymal (p = 0.44) MRI thalamic lesion volumes correlated with thalamic volume. Thalamic volume correlated with cerebral T2 lesion volume (Spearman’s rho = −0.65, p < 0.001; p < 0.0001 after correcting for age, disease duration, and sex). Interpretation Our findings suggest the degeneration of efferent/afferent thalamic projections and/or a neurodegenerative process as greater contributors to thalamic atrophy than thalamic demyelinating lesions. ANN NEUROL 2020 ANN NEUROL 2020;88:81–92
Author Trapp, Bruce D.
Cohen, Jeffrey A.
Mahajan, Kedar R.
Nakamura, Kunio
Ontaneda, Daniel
AuthorAffiliation 3 Department of Biomedical Engineering, Lerner Research Institute, Neurologic Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
1 Mellen Center for MS Treatment and Research, Neurologic Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
2 Department of Neuroscience, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
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  surname: Mahajan
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  givenname: Kunio
  surname: Nakamura
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Cites_doi 10.1212/WNL.0000000000005292
10.1016/j.msard.2015.10.006
10.1002/ana.25019
10.1177/1352458514558134
10.1056/NEJM199801293380502
10.1007/s00415-016-8368-9
10.3389/fneur.2019.00459
10.1177/2055217319827618
10.1136/jnnp-2014-310142
10.1212/NXI.0000000000000102
10.1097/NEN.0b013e3181a19a5a
10.1038/nmeth.2019
10.1016/j.jns.2016.09.020
10.1016/j.jns.2014.04.026
10.1002/ana.21113
10.1002/ana.25145
10.1016/0165-5728(94)90075-2
10.1002/ana.10326
10.1016/j.neuroimage.2010.07.052
10.1093/brain/123.9.1845
10.1007/BF00389441
10.1016/j.jns.2016.04.054
10.1016/S1474-4422(16)00018-1
10.1212/WNL.0000000000007450
10.1016/S1474-4422(18)30245-X
10.1212/01.wnl.0000291010.54692.85
10.1093/brain/122.1.17
10.1097/01.jnen.0000190067.20935.42
10.1177/1352458510376405
10.1155/2015/482536
10.1148/radiol.13122424
10.1038/s41586-019-1404-z
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K.R.M., K.N., J.A.C., B.D.T., and D.O. contributed to study conception, design of the study, and analysis of the data. K.R.M. and K.N. contributed to the acquisition and processing of the data. K.R.M. drafted the text and prepared the figures.
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PublicationTitle Annals of neurology
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PublicationYear 2020
Publisher John Wiley & Sons, Inc
Wiley Subscription Services, Inc
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References 2015; 2
2009; 68
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2017; 82
2019; 5
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2019; 11
2019; 10
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2016; 5
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2020
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2015; 2015
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2018; 90
2017
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2017; 264
2000; 123
2014; 342
2019; 573
1994; 51
2012; 9
2016; 370
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References_xml – volume: 264
  start-page: 482
  year: 2017
  end-page: 493
  article-title: Cognitive impairment and structural brain changes in patients with clinically isolated syndrome at high risk for multiple sclerosis
  publication-title: J Neurol
– volume: 370
  start-page: 88
  year: 2016
  end-page: 93
  article-title: MRI venous architecture of the thalamus
  publication-title: J Neurol Sci
– volume: 64
  start-page: 1101
  year: 2005
  end-page: 1107
  article-title: Grey matter pathology in multiple sclerosis
  publication-title: J Neuropathol Exp Neurol
– volume: 52
  start-page: 650
  year: 2002
  end-page: 653
  article-title: Thalamic neurodegeneration in multiple sclerosis
  publication-title: Ann Neurol
– volume: 17
  start-page: 870
  year: 2018
  end-page: 884
  article-title: Cortical neuronal densities and cerebral white matter demyelination in multiple sclerosis: a retrospective study
  publication-title: Lancet Neurol
– volume: 87
  start-page: 461
  year: 2016
  end-page: 467
  article-title: DIR‐visible grey matter lesions and atrophy in multiple sclerosis: partners in crime?
  publication-title: J Neurol Neurosurg Psychiatry
– volume: 122
  start-page: 17
  year: 1999
  end-page: 26
  article-title: Cortical lesions in multiple sclerosis
  publication-title: Brain
– volume: 21
  start-page: 1139
  year: 2015
  end-page: 1150
  article-title: Thalamic lesions in multiple sclerosis by 7T MRI: clinical implications and relationship to cortical pathology
  publication-title: Mult Scler
– volume: 15
  start-page: 373
  year: 2016
  end-page: 381
  article-title: Safety and efficacy of the selective sphingosine 1‐phosphate receptor modulator ozanimod in relapsing multiple sclerosis (RADIANCE): a randomised, placebo‐controlled, phase 2 trial
  publication-title: Lancet Neurol
– volume: 268
  start-page: 831
  year: 2013
  end-page: 841
  article-title: Thalamic atrophy is associated with development of clinically definite multiple sclerosis
  publication-title: Radiology
– volume: 5
  year: 2019
  article-title: Subjective cognitive concern in multiple sclerosis is associated with reduced thalamic and cortical gray matter volumes
  publication-title: Mult Scler J Exp Transl Clin
– volume: 9
  start-page: 676
  year: 2012
  end-page: 682
  article-title: Fiji: an open‐source platform for biological‐image analysis
  publication-title: Nat Methods
– volume: 92
  start-page: e2240
  year: 2019
  end-page: e2249
  article-title: Damage of the lateral geniculate nucleus in MS: assessing the missing node of the visual pathway
  publication-title: Neurology
– volume: 54
  start-page: 278
  year: 2011
  end-page: 289
  article-title: CLADA: cortical longitudinal atrophy detection algorithm
  publication-title: Neuroimage
– volume: 1
  start-page: 92
  year: 1970
  end-page: 98
  article-title: The veins of the thalamus
  publication-title: Neuroradiology
– volume: 5
  start-page: 29
  year: 2016
  end-page: 33
  article-title: Longitudinal associations between brain structural changes and fatigue in early MS
  publication-title: Mult Scler Relat Disord
– volume: 68
  start-page: 489
  year: 2009
  end-page: 502
  article-title: Demyelination, inflammation, and neurodegeneration in multiple sclerosis deep gray matter
  publication-title: J Neuropathol Exp Neurol
– volume: 82
  start-page: 635
  year: 2017
  end-page: 639
  article-title: T1−/T2‐weighted ratio differs in demyelinated cortex in multiple sclerosis
  publication-title: Ann Neurol
– volume: 83
  start-page: 210
  year: 2018
  end-page: 222
  article-title: Deep gray matter volume loss drives disability worsening in multiple sclerosis
  publication-title: Ann Neurol
– volume: 90
  start-page: e1324
  year: 2018
  end-page: e1332
  article-title: Fingolimod effect on gray matter, thalamus, and white matter in patients with multiple sclerosis
  publication-title: Neurology
– volume: 1
  year: 2017
  article-title: Heterogeneous pathological processes account for thalamic degeneration in multiple sclerosis: insights from 7 T imaging
  publication-title: Mult Scler
– volume: 10
  start-page: 459
  year: 2019
  article-title: Thalamic atrophy without whole brain atrophy is associated with absence of 2‐year NEDA in multiple sclerosis
  publication-title: Front Neurol
– volume: 11
  year: 2019
  article-title: Effect of disease‐modifying therapies on subcortical gray matter atrophy in multiple sclerosis
  publication-title: Mult Scler
– volume: 2
  year: 2015
  article-title: Early CNS neurodegeneration in radiologically isolated syndrome
  publication-title: Neurol Neuroimmunol Neuroinflamm
– volume: 573
  start-page: 75
  year: 2019
  end-page: 82
  article-title: Neuronal vulnerability and multilineage diversity in multiple sclerosis
  publication-title: Nature
– volume: 123
  start-page: 1845
  year: 2000
  end-page: 1849
  article-title: Regional axonal loss in the corpus callosum correlates with cerebral white matter lesion volume and distribution in multiple sclerosis
  publication-title: Brain
– volume: 366
  start-page: 229
  year: 2016
  end-page: 233
  article-title: Subcortical grey matter volumes predict subsequent walking function in early multiple sclerosis
  publication-title: J Neurol Sci
– volume: 16
  start-page: 1220
  year: 2010
  end-page: 1228
  article-title: Basal ganglia and frontal/parietal cortical atrophy is associated with fatigue in relapsing‐remitting multiple sclerosis
  publication-title: Mult Scler
– volume: 342
  start-page: 62
  year: 2014
  end-page: 68
  article-title: Thalamic atrophy and cognitive impairment in clinically isolated syndrome and multiple sclerosis
  publication-title: J Neurol Sci
– volume: 149
  year: 2019
  article-title: Comprehensive autopsy program for individuals with multiple sclerosis
  publication-title: JoVE
– volume: 338
  start-page: 278
  year: 1998
  end-page: 285
  article-title: Axonal transection in the lesions of multiple sclerosis
  publication-title: N Engl J Med
– volume: 51
  start-page: 135
  year: 1994
  end-page: 146
  article-title: Detection of MHC class II‐antigens on macrophages and microglia, but not on astrocytes and endothelia in active multiple sclerosis lesions
  publication-title: J Neuroimmunol
– year: 2020
– volume: 62
  start-page: 219
  year: 2007
  end-page: 228
  article-title: Imaging correlates of axonal swelling in chronic multiple sclerosis brains
  publication-title: Ann Neurol
– volume: 70
  start-page: 1107
  year: 2008
  end-page: 1112
  article-title: Evidence of thalamic gray matter loss in pediatric multiple sclerosis
  publication-title: Neurology
– year: 2017
– volume: 2015
  start-page: 482536
  year: 2015
  article-title: Objectively measured physical activity is associated with brain volumetric measurements in multiple sclerosis
  publication-title: Behav Neurol
– ident: e_1_2_8_18_1
  doi: 10.1212/WNL.0000000000005292
– ident: e_1_2_8_6_1
  doi: 10.1016/j.msard.2015.10.006
– ident: e_1_2_8_27_1
  doi: 10.1002/ana.25019
– ident: e_1_2_8_19_1
  doi: 10.1177/1352458514558134
– ident: e_1_2_8_3_1
  doi: 10.1056/NEJM199801293380502
– ident: e_1_2_8_7_1
  doi: 10.1007/s00415-016-8368-9
– ident: e_1_2_8_12_1
  doi: 10.3389/fneur.2019.00459
– ident: e_1_2_8_14_1
  doi: 10.1177/2055217319827618
– ident: e_1_2_8_24_1
  doi: 10.1136/jnnp-2014-310142
– ident: e_1_2_8_5_1
  doi: 10.1212/NXI.0000000000000102
– ident: e_1_2_8_22_1
  doi: 10.1097/NEN.0b013e3181a19a5a
– ident: e_1_2_8_29_1
  doi: 10.1038/nmeth.2019
– ident: e_1_2_8_33_1
  doi: 10.1016/j.jns.2016.09.020
– ident: e_1_2_8_8_1
  doi: 10.1016/j.jns.2014.04.026
– ident: e_1_2_8_30_1
  doi: 10.1002/ana.21113
– ident: e_1_2_8_11_1
  doi: 10.1002/ana.25145
– ident: e_1_2_8_28_1
  doi: 10.1016/0165-5728(94)90075-2
– ident: e_1_2_8_2_1
– ident: e_1_2_8_21_1
  doi: 10.1002/ana.10326
– ident: e_1_2_8_31_1
  doi: 10.1016/j.neuroimage.2010.07.052
– volume: 149
  start-page: e59511
  year: 2019
  ident: e_1_2_8_25_1
  article-title: Comprehensive autopsy program for individuals with multiple sclerosis
  publication-title: JoVE
– ident: e_1_2_8_38_1
  doi: 10.1093/brain/123.9.1845
– ident: e_1_2_8_34_1
  doi: 10.1007/BF00389441
– ident: e_1_2_8_4_1
  doi: 10.1016/j.jns.2016.04.054
– ident: e_1_2_8_17_1
  doi: 10.1016/S1474-4422(16)00018-1
– volume-title: R: a language and environment for statistical computing
  year: 2020
  ident: e_1_2_8_32_1
– ident: e_1_2_8_37_1
  doi: 10.1212/WNL.0000000000007450
– volume: 1
  start-page: 135245851772638
  year: 2017
  ident: e_1_2_8_20_1
  article-title: Heterogeneous pathological processes account for thalamic degeneration in multiple sclerosis: insights from 7 T imaging
  publication-title: Mult Scler
– ident: e_1_2_8_26_1
  doi: 10.1016/S1474-4422(18)30245-X
– ident: e_1_2_8_10_1
  doi: 10.1212/01.wnl.0000291010.54692.85
– ident: e_1_2_8_36_1
  doi: 10.1093/brain/122.1.17
– ident: e_1_2_8_23_1
  doi: 10.1097/01.jnen.0000190067.20935.42
– ident: e_1_2_8_13_1
  doi: 10.1177/1352458510376405
– volume: 11
  start-page: 135245851982636
  year: 2019
  ident: e_1_2_8_16_1
  article-title: Effect of disease‐modifying therapies on subcortical gray matter atrophy in multiple sclerosis
  publication-title: Mult Scler
– ident: e_1_2_8_15_1
  doi: 10.1155/2015/482536
– ident: e_1_2_8_9_1
  doi: 10.1148/radiol.13122424
– ident: e_1_2_8_35_1
  doi: 10.1038/s41586-019-1404-z
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Snippet Objective Thalamic atrophy is among the earliest brain changes detected in patients with multiple sclerosis (MS) and the degree of thalamic atrophy is a strong...
Thalamic atrophy is among the earliest brain changes detected in patients with multiple sclerosis (MS) and the degree of thalamic atrophy is a strong predictor...
ObjectiveThalamic atrophy is among the earliest brain changes detected in patients with multiple sclerosis (MS) and the degree of thalamic atrophy is a strong...
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StartPage 81
SubjectTerms Aged
Atrophy
Atrophy - diagnostic imaging
Atrophy - pathology
Autopsy
Axons
Brain
Brain slice preparation
Cell activation
Change detection
Correlation
Degeneration
Demyelination
Discoloration
Disease Progression
Female
Humans
Lesions
Macrophages
Magnetic Resonance Imaging
Male
Middle Aged
Multiple sclerosis
Multiple Sclerosis - diagnostic imaging
Multiple Sclerosis - pathology
Neurodegeneration
Neuroimaging
Neurons - pathology
Pathology
Pulvinar
Pulvinar - diagnostic imaging
Pulvinar - pathology
Sensory neurons
Sex
Substantia alba
Thalamus
Thalamus - diagnostic imaging
Thalamus - pathology
White Matter - diagnostic imaging
White Matter - pathology
Title Intrinsic and Extrinsic Mechanisms of Thalamic Pathology in Multiple Sclerosis
URI https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fana.25743
https://www.ncbi.nlm.nih.gov/pubmed/32286701
https://www.proquest.com/docview/2415801266
https://www.proquest.com/docview/2389674317
https://pubmed.ncbi.nlm.nih.gov/PMC8291218
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