Structural remodeling of white matter in the contralesional hemisphere is correlated with early motor recovery in patients with subcortical infarction

Introduction: Cerebral microvascular disease and Alzheimer’s disease (AD) account for the majority of dementia diagnoses with 50% of patients having mixed dementia with features of both microvascular stroke in the white matter and AD pathology. This significant co-morbidity indicates an interactive neurobiologic relationship yet it is unclear if these two pathologies synergize or simply co-exist. Methods: To determine the synergistic effect of subcortical stroke on amyloid deposition, focal subcortical white matter ischemic lesion underneath left sensorimotor cortex or sham procedures were introduced at 2 months of age into E4FAD transgenic mice that express the human ApoE4 knock-in allele together with the 5xFAD transgene or littermate controls. Animals underwent behavioral assessment, brain metabolism analysis by PET/CT, and histologic tissue analysis. Results: In E4FAD-positive mice, subcortical stroke vs. sham resulted in a greater inter-hemispheric difference in amyloid burden in the ipsilateral hemisphere (-0.291 vs. -0.078, p=0.08). This was associated with improved motor recovery on rotarod testing in the E4FAD-positive plus stroke group compared to E4FAD-negative stroke group (53.8 sec vs. 45.23 sec, p=0.016). In E4FAD-positive mice, subcortical stroke vs. sham also resulted in improved hippocampal memory function on fear conditioning (17.6+/-5.0 vs. 32.9+/-5.0, p=0.082) while hippocampal plaque number was not significantly different in this cohort. 18 F-FDG PET/CT imaging demonstrated reduced frontal cortex metabolism in the mixed dementia cohort. Conclusions: This novel mouse model of mixed subcortical stroke and Alzheimer’s disease in E4FAD mice illustrates the value of studying the overlap between vascular and Alzheimer’s pathology in the biology of these two common disorders. The combined pathologies demonstrate a potentially paradoxical enhancement in motor recovery and memory impairment compared to stroke or Alzheimer’s disease alone, suggesting that activation of unique molecular pathways in each pathology may partially temper the natural course of each disorder.

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Motor Recovery Prediction With Clinical Assessment and Local Diffusion Homogeneity After Acute Subcortical Infarction

Stroke ◽

10.1161/strokeaha.117.017060 ◽

2017 ◽

Vol 48 (8) ◽

pp. 2121-2128 ◽

Cited By ~ 10

Author(s):

Gang Liu ◽

Shuangquan Tan ◽

Chao Dang ◽

Kangqiang Peng ◽

Chuanmiao Xie ◽

...

Keyword(s):

Clinical Assessment ◽

Motor Recovery ◽

Local Diffusion ◽

Subcortical Infarction

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Whole Brain White Matter Microstructure and Upper Limb Function: Longitudinal Changes in Fractional Anisotropy and Axial Diffusivity in Post-Stroke Patients

Journal of Central Nervous System Disease ◽

10.1177/1179573519863428 ◽

2019 ◽

Vol 11 ◽

pp. 117957351986342

Author(s):

Nicodemus Edrick Oey ◽

Geoffrey Sithamparapillai Samuel ◽

Joseph Kai Wei Lim ◽

Antonius MJ VanDongen ◽

Yee Sien Ng ◽

...

Keyword(s):

White Matter ◽

Fractional Anisotropy ◽

Upper Limb ◽

Case Series ◽

Elbow Flexion ◽

Motor Recovery ◽

Stroke Patients ◽

Axial Diffusivity ◽

Post Stroke ◽

Kinematic Measures

Background: Diffusion tensor imaging (DTI) magnetic resonance imaging (MRI) measuring fractional anisotropy (FA) and axial diffusivity (AD) may be a useful biomarker for monitoring changes in white matter after stroke, but its associations with upper-limb motor recovery have not been well studied. We aim to describe changes in the whole-brain FA and AD in five post-stroke patients in relation to kinematic measures of elbow flexion to better understand the relationship between FA and AD changes and clinico-kinematic measures of upper limb motor recovery. Methods: We performed DTI MRI at two timepoints during the acute phase of stroke, measuring FA and AD across 48 different white matter tract regions in the brains of five hemiparetic patients with infarcts in the cortex, pons, basal ganglia, thalamus, and corona radiata. We tracked the progress of these patients using clinical Fugl-Meyer Assessments and kinematic measures of elbow flexion at the acute phase within 14 (mean: 9.4 ± 2.49) days of stroke symptom onset and at a follow-up appointment 2 weeks later (mean: 16 ± 1.54) days. Results: Changes in FA and AD in 48 brain regions occurring during stroke rehabilitation are described in relation to motor recovery. In this case series, one patient with a hemipontine infarct showed an increase in FA of the ipsilateral and contralateral corticospinal tract, whereas other patients with lesions involving the corona radiata and middle cerebral artery showed widespread decreases in perilesional FA. On the whole, FA and AD seemed to behave inversely to each other. Conclusions: This case series describes longitudinal changes in perilesional and remote FA and AD in relation to kinematic parameters of elbow flexion at the subacute post-stroke period. Although studies with larger sample sizes are needed, our findings indicate that longitudinally measured changes in DTI-based measurements of white matter microstructural integrity may aid in the prognostication of patients affected by motor stroke.

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White Matter Medullary Infarcts: Acute Subcortical Infarction in the Centrum ovale

Cerebrovascular Diseases ◽

10.1159/000015868 ◽

1998 ◽

Vol 8 (5) ◽

pp. 289-295 ◽

Cited By ~ 25

Author(s):

Stephen J. Read ◽

Louise Pettigrew ◽

Laetitia Schimmel ◽

Christopher R. Levi ◽

Christopher F. Bladin ◽

...

Keyword(s):

White Matter ◽

Subcortical Infarction

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Differential Relationship between Microstructural Integrity in White Matter Tracts and Motor Recovery following Stroke Based on Brain-Derived Neurotrophic Factor Genotype

Neural Plasticity ◽

10.1155/2020/5742421 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Eunhee Park ◽

Jungsoo Lee ◽

Won Hyuk Chang ◽

Ahee Lee ◽

Friedhelm C. Hummel ◽

...

Keyword(s):

White Matter ◽

Neurotrophic Factor ◽

Primary Motor Cortex ◽

Diffusion Tensor ◽

Premotor Cortex ◽

Brain Derived Neurotrophic Factor ◽

Motor Recovery ◽

Link Type ◽

Interhemispheric Connection ◽

Microstructural Integrity

Objective. The relationship between white matter integrity and the brain-derived neurotrophic factor (BDNF) genotype and its effects on motor recovery after stroke are poorly understood. We investigated the values of fractional anisotropy (FA) in the corticospinal tract (CST), the intrahemispheric connection from the primary motor cortex to the ventral premotor cortex (M1PMv), and the interhemispheric connection via the corpus callosum (CC) in patients with the BDNF genotype from the acute to the subacute phase after stroke. Methods. The Fugl-Meyer assessment, upper extremity (FMA-UE), and tract-related FA were assessed at 2 weeks (T1) and 3 months (T2) after stroke using diffusion tensor imaging (DTI). Fifty-eight patients diagnosed with ischemic stroke were classified according to the BDNF genotype into a Val (valine homozygotes) or Met (methionine heterozygotes and homozygotes) group. Results. The Val group exhibited a larger reduction of FA values in the ipsilesional M1PMv than the Met group from T1 to T2. The FMA-UE at T2 was negatively correlated with FA of the contralesional M1PMv at T2 in the Val group but was positively correlated with FA of the ipsilesional CST and CC at T2 in the Met group. Conclusions. The integrity of the intra- and interhemispheric connections might be related to different processes of motor recovery dependent on the BDNF genotype. Thus, the BDNF genotype may need to be considered as a factor influencing neuroplasticity and functional recovery in patients with stroke. This trial is registered with http://www.clinicaltrials.gov: NCT03647787.

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Both projection and commissural pathways are disrupted in individuals with chronic stroke: investigating microstructural white matter correlates of motor recovery

BMC Neuroscience ◽

10.1186/1471-2202-13-107 ◽

2012 ◽

Vol 13 (1) ◽

pp. 107 ◽

Cited By ~ 44

Author(s):

Michael R Borich ◽

Cameron Mang ◽

Lara A Boyd

Keyword(s):

White Matter ◽

Chronic Stroke ◽

Motor Recovery ◽

Commissural Pathways

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Sensory-parietal cortical stimulation improves motor recovery in severe capsular infarct

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x15606136 ◽

2016 ◽

Vol 36 (12) ◽

pp. 2211-2222 ◽

Cited By ~ 4

Author(s):

Ra Gyung Kim ◽

Jongwook Cho ◽

Jinkyue Ree ◽

Hyung-Sun Kim ◽

Pedro Rosa-Neto ◽

...

Keyword(s):

White Matter ◽

Parietal Cortex ◽

Subcortical White Matter ◽

Motor Recovery ◽

Mapping Study ◽

Motor Impairments ◽

Micropet Imaging ◽

Severe Motor ◽

Cortical Electrical Stimulation ◽

Stimulation Group

The prevalence of subcortical white matter strokes in elderly patients is on the rise, but these patients show mixed responses to conventional rehabilitative interventions. To examine whether cortical electrical stimulation can promote motor recovery after white matter stroke, we delivered stimulation to a small or wide region of sensory-parietal cortex for two weeks in a rodent model of circumscribed subcortical capsular infarct. The sham-operated group (SOG) showed persistent and severe motor impairments together with decreased activation in bilateral sensorimotor cortices and striatum. In contrast, sensory-parietal cortex stimulation significantly improved motor recovery: final recovery levels were 72.9% of prelesion levels in the wide stimulation group (WSG) and 37% of prelesion levels in the small stimulation group (SSG). The microPET imaging showed reversal of cortical diaschisis in both groups: in both hemispheres for the WSG, and in the hemisphere ipsilateral to stimulation in the SSG. In addition, we observed activation of the corpus callosum and subcortical corticostriatal structures after stimulation. The results from the c-Fos mapping study were grossly consistent with the microPET imaging. Sensory-parietal cortex stimulation may therefore be a useful strategy for overcoming the limits of rehabilitative training in patients with severe forms of subcortical capsular infarct.

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Longitudinal Structural and Functional Differences Between Proportional and Poor Motor Recovery After Stroke

Neurorehabilitation and Neural Repair ◽

10.1177/1545968317740634 ◽

2017 ◽

Vol 31 (12) ◽

pp. 1029-1041 ◽

Cited By ~ 21

Author(s):

Adrian G. Guggisberg ◽

Pierre Nicolo ◽

Leonardo G. Cohen ◽

Armin Schnider ◽

Ethan R. Buch

Keyword(s):

White Matter ◽

Structural Changes ◽

Primary Motor Cortex ◽

Diffusion Tensor ◽

Motor Recovery ◽

Brain Organization ◽

Fiber Tracts ◽

Functional Differences ◽

Eeg Functional Connectivity ◽

The Brain

Background. Evolution of motor function during the first months after stroke is stereotypically bifurcated, consisting of either recovery to about 70% of maximum possible improvement (“proportional recovery, PROP”) or in little to no improvement (“poor recovery, POOR”). There is currently no evidence that any rehabilitation treatment will prevent POOR and favor PROP. Objective. To perform a longitudinal and multimodal assessment of functional and structural changes in brain organization associated with PROP. Methods. Fugl-Meyer Assessments of the upper extremity and high-density electroencephalography (EEG) were obtained from 63 patients, diffusion tensor imaging from 46 patients, at 2 and 4 weeks (T0) and at 3 months (T1) after stroke onset. Results. We confirmed the presence of 2 distinct recovery patterns (PROP and POOR) in our sample. At T0, PROP patients had greater integrity of the corticospinal tract (CST) and greater EEG functional connectivity (FC) between the affected hemisphere and rest of the brain, in particular between the ventral premotor and the primary motor cortex. POOR patients suffered from degradation of corticocortical and corticofugal fiber tracts in the affected hemisphere between T0 and T1, which was not observed in PROP patients. Better initial CST integrity correlated with greater initial global FC, which was in turn associated with less white matter degradation between T0 and T1. Conclusions. These findings suggest links between initial CST integrity, systems-level cortical network plasticity, reduction of white matter atrophy, and clinical motor recovery after stroke. This identifies candidate treatment targets.

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The Relationship Between ADAMTS13 Activity and Overall Cerebral Small Vessel Disease Burden: A Cross-Sectional Study Based on CSVD

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.738359 ◽

2021 ◽

Vol 13 ◽

Author(s):

Wenbo Sun ◽

Yufan Luo ◽

Shufan Zhang ◽

Wenmei Lu ◽

Luqiong Liu ◽

...

Keyword(s):

White Matter ◽

Confidence Interval ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

White Matter Hyperintensity ◽

Adamts13 Activity ◽

Vessel Disease ◽

The Mean ◽

Subcortical Infarction

Objectives: This study aimed to investigate the association between plasma von Willebrand factor (VWF) level, ADAMTS13 activity, and neuroimaging features of cerebral small vessel disease (CSVD), including the CSVD neuroimaging markers and the overall CSVD burden.Methods: CSVD patients admitted to our hospital from 2016 to 2020 were recruited. Plasma VWF level and ADAMTS13 activity were measured. The overall effect of CSVD on the brain was described as a validated CSVD score. We evaluated the association between VWF levels, ADAMTS13 activity, and the increasing severity of CSVD score by the logistic regression model.Results: We enrolled 296 patients into this study. The mean age of the sample was 69.0 years (SD 7.0). The mean VWF level was 1.31 IU/mL, and the ADAMTS13 activity was 88.01 (SD 10.57). In multivariate regression analysis, lower ADAMTS13 activity and higher VWF level was related to white matter hyperintensity (WMH) [β = −7.31; 95% confidence interval (CI) (−9.40, −4.93); p<0.01; β = 0.17; 95% confidence interval (0.11, 0.23); p<0.01], subcortical infarction (SI) [(β = −9.22; 95% CI (−11.37, −7.06); p<0.01); β = 0.21; 95% confidence interval (0.15, 0.27); p<0.01] independently, but not cerebral microbleed (CMB) [(β = −2.3; 95% CI (−4.95, 0.05); p = 0.22); β = 0.02; 95% confidence interval (−0.05, 0.08); p = 0.63]. Furthermore, ADAMTS13 activity was independently negatively correlated with the overall CSVD burden (odd ratio = 21.33; 95% CI (17.46, 54.60); p < 0.01) after adjustment for age, history of hypertension, and current smoking.Conclusions: Reducing ADAMTS13 activity change is related to white matter hyperintensity, subcortical infarction, but not with cerebral microhemorrhage. In addition, ADAMTS13 may have played an essential role in the progression of CSVD.

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