Non-Ischemic Cerebral Energy Dysfunction at the Early Brain Injury Phase following Aneurysmal Subarachnoid Hemorrhage.

Laurent Carteron,Daria Solari,Roy T Daniel,Reto Meuli,Mahmoud Messerer,Mauro Oddo,Camille Patet,Philippe Eckert

doi:10.3389/fneur.2017.00325

Abstract

The pathophysiology of early brain injury following aneurysmal subarachnoid hemorrhage (SAH) is still not completely understood. Using brain perfusion CT (PCT) and cerebral microdialysis (CMD), we examined whether non-ischemic cerebral energy dysfunction may be a pathogenic determinant of EBI. A total of 21 PCTs were performed (a median of 41 h from ictus onset) among a cohort of 18 comatose mechanically ventilated SAH patients (mean age 58 years, median admission WFNS score 4) who underwent CMD and brain tissue PO2 (PbtO2) monitoring. Cerebral energy dysfunction was defined as CMD episodes with lactate/pyruvate ratio (LPR) >40 and/or lactate >4 mmol/L. PCT-derived global CBF was categorized as oligemic (CBF < 28 mL/100 g/min), normal (CBF 28-65 mL/100 g/min), or hyperemic (CBF 69-85 mL/100 g/min), and was matched to CMD/PbtO2 data. Global CBF (57 ± 14 mL/100 g/min) and PbtO2 (25 ± 9 mm Hg) were within normal ranges. Episodes with cerebral energy dysfunction (n = 103 h of CMD samples, average duration 7.4 h) were frequent (66% of CMD samples) and were associated with normal or hyperemic CBF. CMD abnormalities were more pronounced in conditions of hyperemic vs. normal CBF (LPR 54 ± 12 vs. 42 ± 7, glycerol 157 ± 76 vs. 95 ± 41 µmol/L; both p < 0.01). Elevated brain LPR correlated with higher CBF (r = 0.47, p < 0.0001). Cerebral energy dysfunction is frequent at the early phase following poor-grade SAH and is associated with normal or hyperemic brain perfusion. Our data support the notion that mechanisms alternative to ischemia/hypoxia are implicated in the pathogenesis of early brain injury after SAH.

Highlights

Increasing evidence suggests that early events occurring during the first 72 h following ictus onset, before the occurrence of secondary delayed neurological deterioration, substantially contribute to the pathophysiology and outcome of aneurysmal subarachnoid hemorrhage (SAH)
While research efforts have predominantly focused on cerebral hemodynamics and perfusion, and the comprehension of mechanisms involved in brain ischemia, it is increasingly recognized that a number of alternative “non-ischemic” mechanisms are implicated in the pathogenesis of early brain injury [7]
cerebral blood flow (CBF) was calculated with brain perfusion CT (n = 21, performed a median of 41 h from ictus onset) in four different regions of interest (ROIs); global CBF was defined as the average of CBF from the four different ROIs

Summary

Introduction

Increasing evidence suggests that early events occurring during the first 72 h following ictus onset, before the occurrence of secondary delayed neurological deterioration, substantially contribute to the pathophysiology and outcome of aneurysmal subarachnoid hemorrhage (SAH). This so-called early brain injury phase includes multiple physiological derangements that exacerbates the primary cerebral insult and may eventually worsen patient prognosis [1,2,3,4,5,6]. Whether cerebral energy dysfunction contributes to early brain injury following SAH has not been extensively studied; its exact nature and potential cerebral blood flow (CBF) correlates have not been precisely characterized. The pathophysiology of early brain injury following aneurysmal subarachnoid hemorrhage (SAH) is still not completely understood

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