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Functional Neuroimaging Guided Active Rehabilitation for PCS: A Retrospective Comparative Study of an NVC-Targeting Therapeutic Approach

Caleb T Epps, Marci L Johnson, Alina K Fong, Mark D Allen*

Background: Recent work has demonstrated several advancements in therapeutic options for patients with postconcussion syndrome (PCS). Specifically, active rehabilitation has emerged as a promising direction for the best treatment outcomes. Enhanced Performance in Cognition (EPIC) is one form of active rehabilitation for PCS that uses a multi-disciplinary clinical approach focusing on two primary aims: the objective diagnosis of PCS using a quantitative, biomarker-based form of fMRI, and targeted neurorehabilitation. The targeting and rehabilitation of the neurovascular coupling (NVC) unit is an essential and novel component of this approach. This study seeks to contribute to the current field of active PCS therapy by demonstrating the usefulness of targeting NVC dysfunction. Further, we compare the EPIC protocol to treatment as usual using a retrospective comparative study design.

Methods: The principal cohort was designated as all patients who received EPIC treatment from the time original pilot data was published to the time of retrospective data analysis and chart review (June 2016-October 2017) (N=375). Pre- and post-EPIC post-concussion symptom scales (PCSS) and severity index scores (SIS) were measured and compared. Then, based on pre-specified inclusion criteria for chart review, two patient cohorts were retrospectively assigned to treatment order 1 (TO1: N=15) and treatment order 2 (TO2: N=28). SIS was measured at pre-/post-EPIC and pre-/post-treatment as usual (TAU) functional neurocognitive imaging scans. SIS results from the treatment periods were compared and reported.

Results: For the principal cohort (N=375), there was a statistically significant reduction in post-EPIC SIS and PCSS. Concerning the treatment cohorts, there was a highly significant (p<0.0001) overall effect of treatment type on SIS but no such effect of treatment order. However, analysis of TO2 alone revealed a significant effect on SIS reduction (p<0.001) if TAU occurs after EPIC therapy.

Conclusion: The findings in this study appear to agree with the current body of research that demonstrates the effectiveness of active rehabilitation strategies compared to standard symptom-modulating and rest-based PCS therapies. Further, EPIC-style therapies contribute to the field of active PCS treatment by addressing NVC disruption in addition to the autoregulatory/vasoreactive aspects of PCS pathophysiology.