The impact of structural and functional dysconnections on stroke recovery in patients who received mechanical thrombectomy

• Applicant: Dr. Philipp Koch
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology ; Experimental and Theoretical Network Neuroscience
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 469959208

Stroke is the worldwide third leading cause of long-term disability (Johnson et al. 2016). This is due to a high incidence of stroke and a poor functional outcome in many patients. This is despite a growing infrastructure holding acute treatment options such as intraarterial mechanical thrombectomy (MT), as well as post-acute treatment with intensive rehabilitation in the subacute and chronic stage. Thus, there is a strong need for i) optimizing acute intervention strategies and ii) the efficiency of neuro-rehabilitative treatments to reduce the stroke-related long-term disability. Hereby, the heterogeneity of stroke patients, with regards to the brain lesion and recovery potential, poses a challenge but it may also offer chances. Stratifying patients into different phenotypes based on novel diagnostic markers could help to identify those who are most likely to respond to a specific therapy in acute recanalization therapy or neurorehabilitation. Stroke is a network disease, in which a focal lesion affects a widely distributed network by disrupted white matter tracts and disconnected neurons. Describing the initial pathology as a lesion-network relationship led to the concept of dysconnectomics introduced for functional (Fox 2018) as well as structural imaging (Foulon et al. 2018), which shows reproducibility, patient specificity as well as functional relevance (de Schotten et al. 2020). Thus, the individual dysconnectivity profile has high potential to reflect heterogeneity in stroke and might serve as a diagnostic marker to identify stroke phenotypes.In the hyperacute phase of stroke, around the ischemic core with irreversibly tissue damage there is tissue at risk (‘penumbra’) in which the homeostasis can be maintained for a certain amount of time and which is the targeted salvageable tissue in acute treatment options like MT. Still, the potential functional benefit from acute recanalization must be evaluated critically while considering a risk of periinterventional complications, which might worsen the outcome. Penumbra associated dysconnectivity might serve as predictive marker for good clinical outcome after MT and support decision making.Long-term recovery following stroke is accompanied by intrinsic mechanisms of neuroplasticity and adaption in functional as well as structural connectivity that compensate for lost function from acute to chronic phase (Guggisberg et al. 2019). There is evidence, that those network adaptions are not shared between all stroke survivors but specific to certain subgroups of patients (Koch et al. 2021, in press). The open question is if the initial pathology, described by means of lesion dysconnectivity, determines specific network alterations in individual patients? In summary, we intend to investigate how individual patterns of penumbra and stroke lesions-related dysconnectivity determine specific functional outcome after stroke as well as patient specific network plasticity supporting long-term recovery.

• DFG Programme: WBP Position