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Anaesthesia and Intensive Care, Vol. 40, No. 3, May 2012
Serum lactate dehydrogenase as early marker of posterior reversible encephalopathy syndrome:
keep your eyes open
Posterior reversible encephalopathy syndrome (PRES) is associated with many clinical conditions including pre-eclampsia/eclampsia. So far, this association has been explained mainly in terms of blood pressure variation, failure of cerebral vasculature autoregulatory mechanism and brain
oedema1,2. However, it is well known the main
mechanism in pre-eclampsia is the endothelial activation and injury with systemic consequences, i.e. vasoconstriction, instable blood pressure and
abnormal response to vasopressors3.
L-lactate dehydrogenase (LDH) is an intra- cellular enzyme that converts lactic acid to pyruvic acid, elevated levels indicating cellular
death or damage4. LDH isoenzymes are present
in many body tissues such as brain, kidney, liver, lung, myocardium, spleen, erythrocytes, leucocytes
and platelets5. Tissue levels of these isoenzymes
are about 500 fold higher than those normally found in serum; leakage of the enzymes from a damaged tissue can increase the serum LDH
levels5. Endothelial injuries or irregularities of
the endothelial walls lead to a disruption or a morphological disturbance of red blood cells and to an increased release of LDH into the
serum6,7. Moreover in eclampsia, overwhelming
inflammatory response, placental-maternal immune reaction and anti-endothelial cell antibodies are responsible for the endothelial activation/ injury, resulting in platelet adhesion/degranulation, haemolysis and LDH elevation, protein/fluid
leakage and systemic oedema3.
Schwartz et al first reported the correlation between increased LDH levels and risk of PRES in individuals with pre-eclampsia/eclampsia. Indeed, in some cases, increased LDH value was the only abnormal laboratory parameter before the
onset of symptoms6. Demirtas et al also reported
raised LDH levels in pre-eclamptic/eclamptic patients with abnormal magnetic resonance
imaging findings suggestive of PRES7. Finally,
Finocchi et al showed abnormally high LDH levels in eclamptic subjects who developed PRES,
even before the onset of the symptoms8.
We reviewed the clinical charts of the obstetric patients with PRES admitted at our intensive care unit during a period of 12 months. Analysis of the data (Table 1) revealed overall increased LDH levels (995.6±440.6 IU/l; n.v.227 to 450 IU/l) at presentation, including patients with normal
T able 1 Summary of patients’ clinical data Pt Age Headache Seizures Impaired consciousness V isual abnormalities BP at presentation, mmHg Distribution of MRI abnormalities
Brain oedema severity*
LDH level** O P F T BG Onset 1 2 3 1 29 -+ + + 130/70 + + + + + 3 1842 639 609 653 2 28 + -+ + 135/80 -+ + -2 1025 624 812 805 3 22 + + + + 150/80 -+ + -2 976 1100 800 710 4 41 -+ + -140/70 + + -+ + 3 656 646 544 560 5 22 + + -140/100 + + + + + 3 689 968 640 635 6 32 -+ + -150/95 + + -2 786 654 556 523 * A ccording to Liman et al
9. ** Days before onset of PRES. LDH normal
values: 227 to 450 IU/l. BP=blood
pressure, MRI=magnetic resonance imaging, LDH=L -lactate dehydrogenase,
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CorrespondenCe
Anaesthesia and Intensive Care, Vol. 40, No. 3, May 2012
blood pressure values. Although we failed to find a clear association between LDH values and severity of brain oedema, all subjects showed abnormally high LDH levels already three (628.6±95.8 IU/l) or two (660.16±118.3 IU/l) days before the onset of PRES. Notably, the peak of LDH increase did not necessarily correspond to the symptoms presentation. In fact LDH increase already even some days before PRES would further support the role of asymptomatic or subclinical endothelial dysfunction/ injury as the primum movens in both hyper- tensive and normotensive patients. The endothelial damage probably impairs the mechanism of vasorelaxation, which depends on normal endo-thelium function and that is responsible for a zone of vasoconstriction/vasodilatation also in the cerebral capillary bed, thus resulting in a
blood-brain barrier breakdown10. The next step
of this breakdown mechanism is the extravasation of fluid in resulting in vasogenic brain oedema. The pathogenetic mechanisms of PRES remain controversial. Opposing theories are the hypertension/hyperperfusion and vasoconstriction/
hypoperfusion3. We believe that behind these
two opposing theories there is a common denominator, i.e. endothelial damage that can explain both hypotheses.
M. Vargas
g.serVillo
p. sTriano
Naples and Genoa, Italy
References
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2. Servillo G, Striano P, Striano S, Tortora F, Boccella P, De Robertis E et al. Posterior reversible encephalopathy syndrome (PRES) in critically ill obstetric patients. Intensive Care Medicine 2003; 29: 2323-2326.
3. Bartynski WS. Posterior reversible encephalopathy syndrome, part 2: controversies surrounding pathophysiology of vasogenic edema. Am J Neuroradiol 2008; 29:1043.
4. Qublan HS, Ammarin V, Bataineh O, Al Shraideh Z, Tahat Y, Awamleh I et al. lactic dehydrogenase as a biochemical marker of adverse pregnancy outcome in severe pre-eclampsia. Med Sci Monit 2005; 11: 393-397.
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8. Finocchi V, Bozzao A, Bonamini M, Ferrante M, Romano A, Colonnese C et al. Magnetic resonance imaging in Posterior Reversible Encephalopathy Syndrome: report of three cases and review of literature. Arch Gynecol Obstet 2005; 71:79-85. 9. Liman TG, Bohner G, Heuschmann PU, Scheel M, Endres
M, Siebert E. Clinical and radiological differences in posterior reversible encephalopathy syndrome between patients with preeclampsia-eclampsia and other predisposing diseases. Eur J Neurol 2012; [Epub ahead of print].
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