Predicting Future Brain Tissue Loss From White Matter Connectivity Disruption in Ischemic Stroke

Kuceyeski, Amy; Kamel, Hooman; Navi, Babak B.; Raj, Ashish; Iadecola, Costantino

doi:10.1161/strokeaha.113.003645

Cited by 44 publications

(44 citation statements)

References 36 publications

(30 reference statements)

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“…In the case of focal ischemia, functionally connected (but distal) sites from the stroke may also suffer from diaschesis in the short term, followed by more prolonged degeneration due to the loss of afferent synaptic input from distally connected regions (Kuceyeski et al, 2014). Databases of tractograms from healthy individuals can be used to predict the sites of distal degeneration in patients with focal ischemia (Kuceyeski et al, 2014) and may open the door for therapeutic interventions aimed at preventing distal degeneration.…”

Section: Major Themes Of Circuit Disruption and Recovery: Diaschisis mentioning

confidence: 99%

Stroke and the Connectome: How Connectivity Guides Therapeutic Intervention

Silasi

Murphy

2014

Neuron

188

146

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Connections between neurons are affected within 3 min of stroke onset by massive ischemic depolarization and then delayed cell death. Some connections can recover with prompt reperfusion; others associated with the dying infarct do not. Disruption in functional connectivity is due to direct tissue loss and indirect disconnections of remote areas known as diaschisis. Stroke is devastating, yet given the brain's redundant design, collateral surviving networks and their connections are well-positioned to compensate. Our perspective is that new treatments for stroke may involve a rational functional and structural connections-based approach. Surviving, affected, and at-risk networks can be identified and targeted with scenario-specific treatments. Strategies for recovery may include functional inhibition of the intact hemisphere, rerouting of connections, or setpoint-mediated network plasticity. These approaches may be guided by brain imaging and enabled by patient- and injury-specific brain stimulation, rehabilitation, and potential molecule-based strategies to enable new connections.

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Section: Major Themes Of Circuit Disruption and Recovery: Diaschisis mentioning

confidence: 99%

Stroke and the Connectome: How Connectivity Guides Therapeutic Intervention

Silasi

Murphy

2014

Neuron

188

146

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“…Cytotoxic edema occurrence provokes both a reduction in the extracellular volume fraction and changes in membrane permeability. These events eventually reduce WM integrity locally, at the primary lesion location, because of tissue damage or remotely as a consequence of the loss of afferent synaptic input from distally connected regions or retrograde axonal degeneration 9,12 In sum, these above-mentioned studies may provide a reasonable explanation why SLI people have a lower structural integrity. But recent evidence suggests that elements of the immune system are intimately involved in all stages of ischemic cascade, contributing to the pathophysiology of cerebrovascular diseases.…”

Section: Discussionmentioning

confidence: 99%

Association of White Matter Integrity and Cognitive Functions in Patients With Subcortical Silent Lacunar Infarcts

Chen

Wang

Tang

et al. 2015

Stroke

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Background and Purpose-Silent lacunar infarct (SLI) is a risk factor for dementia. This study investigated the white matter integrity abnormality and its relationship to the cognition impairments in SLI patients. Methods-Between 27 patients with SLI in basal ganglia and 30 healthy controls, we assessed the difference in a batter of neuropsychological tests and in white matter integrity measurements, fractional anisotropy, and mean diffusivity, using tract-based spatial statistics. Results-Compared with healthy controls, SLI patients performed worse in general mental status, memory, executive function, and language ability. They also had reduced fractional anisotropy and increase mean diffusivity in brain regions such as the body and genu of corpus callosum, the forceps minor, the bilateral superior and bilateral anterior corona radiate, and the left external capsule. Furthermore, we found that in SLI patients, fractional anisotropy measure in left external capsule was positively correlated to the performance in memory and language ability. Conclusions-SLI in basal ganglia leads to local and remote white matter integrity damages and to the cognition impairments.

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“…Microstructural alterations in connecting fiber tracts were analyzed by measuring mean diffusivity (MD). MD is a sensitive and robust measure of microstructural white matter alterations after stroke 14,15 and is preferred over other diffusion tensor imaging measures because it is less affected by the directionality of different tracts.…”

Section: Methods Study Cohortmentioning

confidence: 99%

Acute infarcts cause focal thinning in remote cortex via degeneration of connecting fiber tracts

et al. 2015

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Objective: To study remote effects distant from acute ischemic infarcts by measuring longitudinal changes of cortical thickness in connected brain regions as well as changes in microstructural integrity in connecting fiber tracts.Methods: Thirty-two patients (mean age 71 years) underwent a standardized protocol including multimodal MRI and clinical assessment both at stroke onset and 6 months after the event. Cortex connected to acute infarcts was identified by probabilistic diffusion tensor tractography starting from the acute lesion. Changes of cortical thickness were measured using the longitudinal stream of FreeSurfer. Microstructural damage in white matter tracts was assessed by changes of mean diffusivity. Results:We found focal cortical thinning specifically in areas connected to acute infarcts (p , 0.001). Thinning was more pronounced in regions showing a high probability of connectivity to infarcts. Microstructural damage in white matter tracts connecting acute infarcts with distant cortex significantly correlated with thickness changes in that region (r 5 20.39, p 5 0.028). There was no indication of an influence of cavitation status or infarct etiology on the observed changes in cortex and white matter.Conclusions: These findings identify secondary degeneration of connected white matter tracts and remote cortex as key features of acute ischemic infarcts. Our observations may have implications for the understanding of structural and functional reorganization after stroke. Remote cortical effects of acute infarcts critically contribute to functional reorganization after stroke and influence clinical outcome.1,2 We recently identified focal cortical thinning as a potential structural correlate of remote effects after ischemic lesions. In a small retrospective study on 9 patients with inherited small vessel disease, we showed that incident subcortical lacunes are associated with focal thinning in cortex connected to the infarct. 3,4 We attributed these findings to secondary cortical neurodegeneration following damage to the connecting subcortical fiber tracts. However, the study protocol and small sample size precluded a detailed assessment of these tracts and how changes in these tracts relate to changes in the connected cortex. Also, the results were obtained in a rare hereditary condition and were limited to a single infarct mechanism and to chronic, cavitating infarcts.In the current prospective, longitudinal study, we investigated the processes driving secondary neurodegeneration after acute infarcts. We measured changes of cortical thickness and microstructural integrity of connecting white matter tracts over a 6-month interval starting from stroke onset. We tested the following hypotheses: (1) cortical thinning in connected cortical regions is detectable within a few months after an acute infarct; (2) cortical thinning relates to *These authors contributed equally to this work.

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Predicting Future Brain Tissue Loss From White Matter Connectivity Disruption in Ischemic Stroke

Cited by 44 publications

References 36 publications

Stroke and the Connectome: How Connectivity Guides Therapeutic Intervention

Stroke and the Connectome: How Connectivity Guides Therapeutic Intervention

Association of White Matter Integrity and Cognitive Functions in Patients With Subcortical Silent Lacunar Infarcts

Acute infarcts cause focal thinning in remote cortex via degeneration of connecting fiber tracts

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