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

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

Abstract

Background: The pathophysiology of early brain injury following aneurysmal subarachnoid hemorrhage (SAH) is still not completely understood.

Objective: Using brain perfusion CT (PCT) and cerebral microdialysis (CMD), we examined whether non-ischemic cerebral energy dysfunction may be a pathogenic determinant of EBI.

Methods: 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.

Results: 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).

Conclusion: 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.

Keywords: cerebral microdialysis; early brain injury; hyperemia; neuroenergetics; subarachnoid hemorrhage.

Figures

Figure 1
Figure 1
Cerebral energy dysfunction is associated with normal or hyperemic CBF in the early brain injury phase of aneurysmal subarachnoid hemorrhage. Illustrative examples of two patients in whom cerebral energy dysfunction was associated with brain perfusion CT (PCT) showing normal (A) or hyperemic (B) CBF. Time from PCT to subarachnoid hemorrhage was 16 h in patient (A) and 38 h in patient (B). Brain extracellular concentrations of lactate/pyruvate (LP) ratio, glutamate, and glycerol were measured with a 20 kDa cerebral microdialysis catheter that was located in the subcortical white matter, adjacent to a brain tissue PO2 (PbtO2) probe. Abbreviations: CBF, cerebral blood flow; CBV, cerebral blood volume; MTT, mean transit time.
Figure 2
Figure 2
Hyperemic cerebral blood flow (CBF) is positively correlated with cerebral metabolic and cellular distress. Graphs illustrate Spearman’s linear correlations of global CBF, measured with perfusion CT, with brain extracellular concentrations of lactate/pyruvate (LP) ratio and glycerol.

References

    1. Budohoski KP, Guilfoyle M, Helmy A, Huuskonen T, Czosnyka M, Kirollos R, et al. The pathophysiology and treatment of delayed cerebral ischaemia following subarachnoid haemorrhage. J Neurol Neurosurg Psychiatry (2014) 85(12):1343–53.10.1136/jnnp-2014-307711
    1. Cossu G, Messerer M, Oddo M, Daniel RT. To look beyond vasospasm in aneurysmal subarachnoid haemorrhage. Biomed Res Int (2014) 2014:628597.10.1155/2014/628597
    1. Fujii M, Yan J, Rolland WB, Soejima Y, Caner B, Zhang JH. Early brain injury, an evolving frontier in subarachnoid hemorrhage research. Transl Stroke Res (2013) 4(4):432–46.10.1007/s12975-013-0257-2
    1. Macdonald RL. Delayed neurological deterioration after subarachnoid haemorrhage. Nat Rev Neurol (2014) 10(1):44–58.10.1038/nrneurol.2013.246
    1. Tso MK, Macdonald RL. Subarachnoid hemorrhage: a review of experimental studies on the microcirculation and the neurovascular unit. Transl Stroke Res (2014) 5(2):174–89.10.1007/s12975-014-0323-4
    1. Zheng VZ, Wong GK. Neuroinflammation responses after subarachnoid hemorrhage: a review. J Clin Neurosci (2017) 42:7–11.10.1016/j.jocn.2017.02.001
    1. Etminan N, Vergouwen MD, Ilodigwe D, Macdonald RL. Effect of pharmaceutical treatment on vasospasm, delayed cerebral ischemia, and clinical outcome in patients with aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis. J Cereb Blood Flow Metab (2011) 31(6):1443–51.10.1038/jcbfm.2011.7
    1. Bergsneider M, Hovda DA, Lee SM, Kelly DF, McArthur DL, Vespa PM, et al. Dissociation of cerebral glucose metabolism and level of consciousness during the period of metabolic depression following human traumatic brain injury. J Neurotrauma (2000) 17(5):389–401.10.1089/neu.2000.17.389
    1. Bergsneider M, Hovda DA, McArthur DL, Etchepare M, Huang SC, Sehati N, et al. Metabolic recovery following human traumatic brain injury based on FDG-PET: time course and relationship to neurological disability. J Head Trauma Rehabil (2001) 16(2):135–48.10.1097/00001199-200104000-00004
    1. Bergsneider M, Hovda DA, Shalmon E, Kelly DF, Vespa PM, Martin NA, et al. Cerebral hyperglycolysis following severe traumatic brain injury in humans: a positron emission tomography study. J Neurosurg (1997) 86(2):241–51.10.3171/jns.1997.86.2.0241
    1. Bouzat P, Sala N, Payen JF, Oddo M. Beyond intracranial pressure: optimization of cerebral blood flow, oxygen, and substrate delivery after traumatic brain injury. Ann Intensive Care (2013) 3(1):23.10.1186/2110-5820-3-23
    1. Brooks GA, Martin NA. Cerebral metabolism following traumatic brain injury: new discoveries with implications for treatment. Front Neurosci (2015) 8:408.10.3389/fnins.2014.00408
    1. Carpenter KL, Jalloh I, Hutchinson PJ. Glycolysis and the significance of lactate in traumatic brain injury. Front Neurosci (2015) 9:112.10.3389/fnins.2015.00112
    1. Jalloh I, Carpenter KL, Grice P, Howe DJ, Mason A, Gallagher CN, et al. Glycolysis and the pentose phosphate pathway after human traumatic brain injury: microdialysis studies using 1,2-(13)C2 glucose. J Cereb Blood Flow Metab (2015) 35(1):111–20.10.1038/jcbfm.2014.177
    1. Jalloh I, Carpenter KL, Helmy A, Carpenter TA, Menon DK, Hutchinson PJ. Glucose metabolism following human traumatic brain injury: methods of assessment and pathophysiological findings. Metab Brain Dis (2015) 30(3):615–32.10.1007/s11011-014-9628-y
    1. Sala N, Suys T, Zerlauth JB, Bouzat P, Messerer M, Bloch J, et al. Cerebral extracellular lactate increase is predominantly nonischemic in patients with severe traumatic brain injury. J Cereb Blood Flow Metab (2013) 33(11):1815–22.10.1038/jcbfm.2013.142
    1. Vespa P, Bergsneider M, Hattori N, Wu HM, Huang SC, Martin NA, et al. Metabolic crisis without brain ischemia is common after traumatic brain injury: a combined microdialysis and positron emission tomography study. J Cereb Blood Flow Metab (2005) 25(6):763–74.10.1038/sj.jcbfm.9600073
    1. Vespa P, Tubi M, Claassen J, Buitrago-Blanco M, McArthur D, Velazquez AG, et al. Metabolic crisis occurs with seizures and periodic discharges after brain trauma. Ann Neurol (2016) 79(4):579–90.10.1002/ana.24606
    1. Xu Y, McArthur DL, Alger JR, Etchepare M, Hovda DA, Glenn TC, et al. Early nonischemic oxidative metabolic dysfunction leads to chronic brain atrophy in traumatic brain injury. J Cereb Blood Flow Metab (2010) 30(4):883–94.10.1038/jcbfm.2009.263
    1. Connolly ES, Jr, Rabinstein AA, Carhuapoma JR, Derdeyn CP, Dion J, Higashida RT, et al. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke (2012) 43(6):1711–37.10.1161/STR.0b013e3182587839
    1. Cremers CH, van der Schaaf IC, Wensink E, Greving JP, Rinkel GJ, Velthuis BK, et al. CT perfusion and delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis. J Cereb Blood Flow Metab (2014) 34(2):200–7.10.1038/jcbfm.2013.208
    1. Huang AP, Tsai JC, Kuo LT, Lee CW, Lai HS, Tsai LK, et al. Clinical application of perfusion computed tomography in neurosurgery. J Neurosurg (2014) 120(2):473–88.10.3171/2013.10.JNS13103
    1. Hutchinson PJ, Jalloh I, Helmy A, Carpenter KL, Rostami E, Bellander BM, et al. Consensus statement from the 2014 International Microdialysis Forum. Intensive Care Med (2015) 41(9):1517–28.10.1007/s00134-015-3930-y
    1. Lagares A, Cicuendez M, Ramos A, Salvador E, Alén JF, Kaen A, et al. Acute perfusion changes after spontaneous SAH: a perfusion CT study. Acta Neurochir (Wien) (2012) 154(3):405–11; discussion 411–2.10.1007/s00701-011-1267-z
    1. van der Schaaf I, Wermer MJ, van der Graaf Y, Hoff RG, Rinkel GJ, Velthuis BK. CT after subarachnoid hemorrhage: relation of cerebral perfusion to delayed cerebral ischemia. Neurology (2006) 66(10):1533–8.10.1212/01.wnl.0000216272.67895.d3
    1. Oddo M, Schmidt JM, Carrera E, Badjatia N, Connolly ES, Presciutti M, et al. Impact of tight glycemic control on cerebral glucose metabolism after severe brain injury: a microdialysis study. Crit Care Med (2008) 36(12):3233–8.10.1097/CCM.0b013e31818f4026
    1. Asgari S, Vespa P, Hu X. Is there any association between cerebral vasoconstriction/vasodilatation and microdialysis lactate to pyruvate ratio increase? Neurocrit Care (2013) 19(1):56–64.10.1007/s12028-013-9821-6
    1. Vespa PM, O’Phelan K, McArthur D, Miller C, Eliseo M, Hirt D, et al. Pericontusional brain tissue exhibits persistent elevation of lactate/pyruvate ratio independent of cerebral perfusion pressure. Crit Care Med (2007) 35(4):1153–60.10.1097/01.CCM.0000259466.66310.4F
    1. Oddo M, Levine JM, Frangos S, Maloney-Wilensky E, Carrera E, Daniel RT, et al. Brain lactate metabolism in humans with subarachnoid hemorrhage. Stroke (2012) 43(5):1418–21.10.1161/STROKEAHA.111.648568
    1. Samuelsson C, Hillered L, Zetterling M, Enblad P, Hesselager G, Ryttlefors M, et al. Cerebral glutamine and glutamate levels in relation to compromised energy metabolism: a microdialysis study in subarachnoid hemorrhage patients. J Cereb Blood Flow Metab (2007) 27(7):1309–17.10.1038/sj.jcbfm.9600433
    1. Jacobsen A, Nielsen TH, Nilsson O, Schalen W, Nordstrom CH. Bedside diagnosis of mitochondrial dysfunction in aneurysmal subarachnoid hemorrhage. Acta Neurol Scand (2014) 130(3):156–63.10.1111/ane.12258
    1. Hinzman JM, Wilson JA, Mazzeo AT, Bullock MR, Hartings JA. Excitotoxicity and metabolic crisis are associated with spreading depolarizations in severe traumatic brain injury patients. J Neurotrauma (2016) 33(19):1775–83.10.1089/neu.2015.4226
    1. Glenn TC, Kelly DF, Boscardin WJ, McArthur DL, Vespa P, Oertel M, et al. Energy dysfunction as a predictor of outcome after moderate or severe head injury: indices of oxygen, glucose, and lactate metabolism. J Cereb Blood Flow Metab (2003) 23(10):1239–50.10.1097/01.WCB.0000089833.23606.7F
    1. Dreier JP. The role of spreading depression, spreading depolarization and spreading ischemia in neurological disease. Nat Med (2011) 17(4):439–47.10.1038/nm.2333
    1. Sakowitz OW, Santos E, Nagel A, Krajewski KL, Hertle DN, Vajkoczy P, et al. Clusters of spreading depolarizations are associated with disturbed cerebral metabolism in patients with aneurysmal subarachnoid hemorrhage. Stroke (2013) 44(1):220–3.10.1161/STROKEAHA.112.672352
    1. Hashemi P, Bhatia R, Nakamura H, Dreier JP, Graf R, Strong AJ, et al. Persisting depletion of brain glucose following cortical spreading depression, despite apparent hyperaemia: evidence for risk of an adverse effect of Leao’s spreading depression. J Cereb Blood Flow Metab (2009) 29(1):166–75.10.1038/jcbfm.2008.108
    1. Chen HI, Stiefel MF, Oddo M, Milby AH, Maloney-Wilensky E, Frangos S, et al. Detection of cerebral compromise with multimodality monitoring in patients with subarachnoid hemorrhage. Neurosurgery (2011) 69(1):53–63; discussion 63.10.1227/NEU.0b013e3182191451
    1. Bouzat P, Oddo M. Lactate and the injured brain: friend or foe? Curr Opin Crit Care (2014) 20(2):133–40.10.1097/MCC.0000000000000072
    1. Bouzat P, Sala N, Suys T, Zerlauth JB, Marques-Vidal P, Feihl F, et al. Cerebral metabolic effects of exogenous lactate supplementation on the injured human brain. Intensive Care Med (2014) 40(3):412–21.10.1007/s00134-013-3203-6
    1. Quintard H, Patet C, Zerlauth JB, Suys T, Bouzat P, Pellerin L, et al. Improvement of neuroenergetics by hypertonic lactate therapy in patients with traumatic brain injury is dependent on baseline cerebral lactate/pyruvate ratio. J Neurotrauma (2016) 33(7):681–7.10.1089/neu.2015.4057
    1. Schubert GA, Seiz M, Hegewald AA, Manville J, Thome C. Acute hypoperfusion immediately after subarachnoid hemorrhage: a xenon contrast-enhanced CT study. J Neurotrauma (2009) 26(12):2225–31.10.1089/neu.2009.0924
    1. Nordstrom CH, Reinstrup P, Xu W, Gärdenfors A, Ungerstedt U. Assessment of the lower limit for cerebral perfusion pressure in severe head injuries by bedside monitoring of regional energy metabolism. Anesthesiology (2003) 98(4):809–14.10.1097/00000542-200304000-00004

Source: PubMed

Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

3
Předplatit