Investigating the Association of Wallerian Degeneration and Diaschisis After Ischemic Stroke With BOLD Cerebrovascular Reactivity.

C H B Van Niftrik,C Stippich,G Muscas,M Sebök,J Fierstra,S Wegener,A R Luft,L Regli

doi:10.3389/fphys.2021.645157

Abstract

IntroductionWallerian degeneration and diaschisis are considered separate remote entities following ischemic stroke. They may, however, share common neurophysiological denominators, since they are both related to disruption of fiber tracts and brain atrophy over time. Therefore, with advanced multimodal neuroimaging, we investigate Wallerian degeneration and its association with diaschisis.MethodsIn order to determine different characteristics of Wallerian degeneration, we conducted examinations on seventeen patients with chronic unilateral ischemic stroke and persisting large vessel occlusion, conducting high-resolution anatomical magnetic resonance imaging (MRI) and blood oxygenation-level dependent cerebrovascular reactivity (BOLD-CVR) tests, as well as Diamox 15(O)–H2O–PET hemodynamic examinations. Wallerian degeneration was determined using a cerebral peduncle asymmetry index (% difference of volume of ipsilateral and contralateral cerebral peduncle) of more than two standard deviations away from the average of age-matched, healthy subjects (Here a cerebral peduncle asymmetry index > 11%). Diaschisis was derived from BOLD-CVR to assess the presence of ipsilateral thalamus diaschisis and/or crossed cerebellar diaschisis.ResultsWallerian degeneration, found in 8 (47%) subjects, had a strong association with ipsilateral thalamic volume reduction (r2 = 0.60) and corticospinal-tract involvement of stroke (p < 0.001). It was also associated with ipsilateral thalamic diaschisis (p = 0.021), No cerebral peduncular hemodynamic differences were found in patients with Wallerian degeneration. In particular, no CBF decrease or BOLD-CVR impairment was found.ConclusionWe show a strong association between Wallerian degeneration and ipsilateral thalamic diaschisis, indicating a structural pathophysiological relationship.

Highlights

Wallerian degeneration and diaschisis are considered separate remote entities following ischemic stroke
Wallerian degeneration, found in 8 (47%) subjects, had a strong association with ipsilateral thalamic volume reduction (r2 = 0.60) and corticospinal-tract involvement of stroke (p < 0.001). It was associated with ipsilateral thalamic diaschisis (p = 0.021), No cerebral peduncular hemodynamic differences were found in patients with Wallerian degeneration
We show a strong association between Wallerian degeneration and ipsilateral thalamic diaschisis, indicating a structural pathophysiological relationship

Summary

Introduction

Wallerian degeneration and diaschisis are considered separate remote entities following ischemic stroke. Ischemic stroke can lead to neurophysiological and structural brain tissue changes, distant from the acute, primary focal lesion These changes can be seen as post-stroke phenomena, known as Wallerian degeneration and diaschisis (i.e., crossed cerebellar diaschisis and ipsilateral thalamic diaschisis). Diaschisis on the other hand, encompasses remote neurophysiological changes, caused by neuronal deactivation, due to a supratentorial lesion (e.g., ischemic stroke) Both have a similar pathophysiological origin (i.e., disruption of fiber tracts), the main imaging feature of Wallerian degeneration is structural change (i.e., atrophy), whereas diaschisis displays functional–i.e., neurophysiological–changes, such as a local reduction in cerebral blood flow and hypometabolism (Baron et al, 1981; Pantano et al, 1986; Sebök et al, 2018; van Niftrik et al, 2019). Ipsilateral thalamic diaschisis exhibited impaired BOLD-CVR in and thalamic atrophy whereas presence of crossed cerebellar diaschisis detected with BOLD-CVR showed an association with hemodynamic impairment, thereby further supporting the concept of a vascular component (Sebök et al, 2018; van Niftrik et al, 2019; von Bieberstein et al, 2020)

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