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Correspondence

An editorial on markers of cerebral damage

GAO, F.; HARRIS, D. N. F.

Author Information
European Journal of Anaesthesiology: January 1998 - Volume 15 - Issue 1 - p 125-126

Sir:

Thank you for referring me to the letter from Dr Mats Enlund concerning the enzyme adenylate kinase (AK), a well validated marker of brain damage measured in cerebrospinal fluid(CSF).

We thank Dr Mats Enlund for his comments after reading our paper [1]. We agree that AK has been used as a marker of brain damage in a great number of different pathological situations. Brain tissue AK activities have been used to assess the degree of brain injury and the protective effects of hypothermia and antioxidant [2,3]. However, as Dr Enlund mentions in his letter, almost all publications available are from CSF-AK analysis. To our knowledge, there are no publications on plasma AK analysis. Ideally, for clinical purposes, it is necessary to have a biochemical marker that can be measured in blood.

Cerebrospinal fluid (CSF) concentration of adenylate kinase

Following cardiopulmonary bypass (CPB) surgery

A significant increase in CSF-AK was correlated with changes in an index of intellectual function [4] and psychometric performance [5]. Its measurement might therefore be useful in research to improve the quality of open-heart surgery. Magnetic resonance imaging (MRI) is a sensitive measure of subclinical cerebral ischaemia after CPB. CSF neurone-specific enolase (NSE) and lactic dehydrogenase may be less sensitive than MRI, but appear to be more sensitive than CSF-AK [6]. When CSF-AK was used to assess cerebral ischaemia of gaseous microembolic origin, there was no significant difference in AK as marker of ischaemia between nitrous oxide and control groups following CPB [7].

Following stroke and global cerebral ischaemia

CSF-AK levels were correlated with clinically neurological signs and sizes of infarction from computed tomography (CT) [8-10] following acute cerebral ischaemic infarction. However, the results were unrepeatable because of difficulties in sampling and handling CSF material [11]. The contamination of AK from erythrocytes and serum [12] is a significant limiting factor for AK to fulfil the criteria for an ideal CSF marker. Nevertheless, this limiting factor could be ruled out by using the specific light absorbency for oxyhaemoglobin [13].

Following cardiac arrest

The CSF-AK activity at 24 h after cardiac arrest showed predictive prognosis in 12 patients[14], however, CSF-AK did not show any prognostic value in neurological outcome after cardiac arrest in 32 patients in Edgren's study[15].

In summary, CSF-AK is an interesting and important biochemical marker of cerebral damage. However, serum AK levels may be difficult to interpret because of contamination by erythrocyte-derived AK.

F. GAO

D. N. F. HARRIS

Department of Anaesthesia and Intensive Care

Birmingham Heartlands Hospital; Birmingham, UK

Hammersmith Hospital; London, UK

References

1 Gao F, Harris DNF. Biochemical markers of cerebral damage (editorial). Eur J Anaesthesiol 1997; 14: 113-117.
2Tokuda Y, Uozumi T, Kawasaki T. The superoxide dismutase activities of cerebral tissues, assessed by the chemiluminescence methods, in the gerbil focal ischemia/reperfusion and global ischemia models. Neurochem Int 1993; 23: 107-114.
3 Welsh FA, Sims RE, Harris VA. Mild hypothermia prevents ischemic injury in gerbil hippocampus. J Cereb Blood Flow Metab 1990; 10: 557-563.
4 Aberg T, Ronquist G, Tyden H, Ahlund P, Bergstrom K. Release of adenylate kinase into cerebrospinal fluid during open-heart surgery and its relation to postoperative intellectual function. Lancet 1982;1: 1139-1142.
5 Aberg T, Ronquist G, Tyden H, Brunnkvist S, Bergstrom K. Cerebral damage during open-heart surgery. Clinical, psychometric, biochemical and CT data. Scand J Thorac Cardiovasc Surg 1987; 21: 159-163.
6 Steinberg GK, De-La-Paz R, Mitchell RS, Bell TE, Albers GW. MR and cerebrospinal fluid enzymes as sensitive indicators of subclinical cerebral injury after open-heart valve replacement surgery. AJNR Am J Neuroradiol 1996; 17: 205-212.
7Wells DG, Podolakin W, Mohr M, Buxton B, Bray H. Nitrous oxide and cerebrospinal fluid markers of ischaemia following cardiopulmonary bypass. Anaesth Intensive Care 1987; 15: 431-435.
8 Buttner T, Hornig CR, Busse O, Dorndorf W. CSF cyclic AMP and CSF adenylate kinase in cerebral ischaemic infarction. J Neurol 1986; 233: 297-303.
9 Terent A, Ronquist G, Bergstrom K, Hallgren R, Aberg H. Ischemic edema in stroke. A parallel study with computed tomography and cerebrospinal fluid markers of disturbed brain cell metabolism. Stroke 1981; 12: 33-40.
10 Frithz G, Ronquist G, Hugosson R. Perspectives of adenylate kinase activity and glutathione concentration in cerebrospinal fluid of patients ischemic and neoplastic brain lesions. Eur Neurol 1982; 21: 41-47.
11 Frithz G, Ronquist G, Hugosson R. Perspectives of adenylate kinase activity and glutathione concentration in cerebrospinal fluid of patients ischemic and neoplastic brain lesions. Eur Neurol 1982;21: 41-47.
12 Ronquist G, Terent A. Cerebrospinal fluid markers of disturbed brain cell metabolism. Prog Neurobiol 1982;18: 167-180.
13 Terent A, Ronquist G. Cerebrospinal fluid markers of disturbed brain cell metabolism in patients with stroke and global cerebral ischemia. Acta Neurol Scand 1980; 62: 327-335.
14 Edgren E, Terent A, Hedstrand U, Ronquist G. Cerebrospinal fluid markers in relation to outcome in patients with global cerebral ischaemia. Crit Care Med 1983; 11: 4-6.
15 Edgren E, Hedstrand U, Nordin M, Rydin E, Ronquist G. Prediction of outcome after cardiac arrest. Crit Care Med 1987; 15: 820-825.
© 1998 European Academy of Anaesthesiology