Investigation of the impact of intensive neurorehabilitation on reticulospinal tract activity in chronic stroke patients

• Applicant: Dr. David Baur
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 539064619

Stroke is a leading course of acquired permanent disability worldwide, warranting great need for improved therapies. To attain motor recovery, chronic stroke patients suffering from severe motor impairment appear to rely on upregulation of their reticulospinal tract (RST). Previous findings indicate the existence of two distinct RST-defined phenotypes in this patient group, one with low and the other with high RST upregulation. However, the reasons for this bimodal distribution as well as the precise role of the RST in stroke recovery remain poorly explored. With this proposal, I aim to address these questions by investigating 1) whether the two RST subtypes exhibit differential characteristics in their paresis presentation and 2) whether they respond distinctly to intensive neurorehabilitation. Different motor stroke phenotypes are expected to show dissimilar reactions to therapeutic interventions. Therefore, an individually tailored approach will be needed for effective treatment and to increase overall therapy success, which is the ultimate purpose of this proposal. In a cross-sectional experiment utilizing state-of-the-art kinematic assessments, I first intend to characterize different components of arm paresis in the two RST phenotypes, which will be defined by their startle reflex response using the StartReact protocol. Further, transcranial magnetic stimulation will be employed to elicit ipsilateral motor evoked potentials (iMEPs). It will be tested whether iMEP modulation through brain stem reflexes can distinguish between the two RST phenotypes, because biomarkers like paresis components and iMEP modulation obtained by this multi-modal approach promise improved and more comprehensive differentiation of the two subtypes and will eventually facilitate allocation of patients to targeted therapy interventions. A second longitudinal experiment will investigate whether intensive neurorehabilitation can increase RST activity in the low-upregulated but severely impaired patient group. Given that a possible explanation for lacking RST upregulation in these patients is the so far insufficient amount of rehabilitation therapy, the proposal assesses whether intensive rehabilitation will enhance RST activity exclusively in this group and result in clinical improvement. If correct, the findings will enable the identification of patients who would profit most from intensive rehabilitation training. After all, this proposal seeks to characterize and subsequently pinpoint stroke patients who are likely to respond positively to intensive neurorehabilitation. The implementation of such an individualized approach holds considerable potential for augmenting the effectiveness of motor rehabilitation, thereby improving quality of life in severely impaired chronic stroke survivors.

• DFG Programme: WBP Fellowship
• International Connection: United Kingdom
• Host: Professor Dr. Nick Ward