Clinica Chimica Acta 397 (2008) 27–31

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Clinica Chimica Acta

j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / c l i n c h i m

Evaluation of lactate as a marker of metabolic stress and cause of secondary damage

in acute ischemic stroke or TIA
Raf Brouns a,b, Rishi Sheorajpanday a,b, Annick Wauters c, Didier De Surgeloose d,
Peter Mariën a,b,e, Peter P. De Deyn a,b,⁎
a
Department of Neurology and Memory Clinic, ZNA Middelheim Hospital, Antwerp, Belgium
b
Laboratory for Neurochemistry and Behaviour, Institute Born-Bunge, Department of Biomedical Sciences, University of Antwerp, Belgium
c
Department of Clinical Biology, ZNA Middelheim Hospital, Antwerp, Belgium
d
Department of Radiology, ZNA Middelheim Hospital, Antwerp, Belgium
e
Department of Linguistics, Vrije Universiteit Brussel, Belgium

a r t i c l e i n f o a b s t r a c t

Article history: Background: Accumulation of lactate in ischemic regions has been documented in acute stroke. We evaluated
Received 25 June 2008 the relation between lactate levels in blood and cerebrospinal fluid (CSF) and ischemic stroke evolution and
Received in revised form 10 July 2008 outcome.
Accepted 10 July 2008
Methods: Lactate was measured in blood of 187 acute ischemic stroke and TIA patients at admission, 24 h, 72 h and
Available online 19 July 2008
7 days after stroke onset. In a subpopulation of 85 stroke patients and in 51 controls, lactate was measured in CSF.
Keywords:
Stroke evolution was evaluated by change in the NIHSS score within the first 72 h and by occurrence of
Lactate progressing stroke. At 3 months after stroke, outcome was assessed on the basis of mortality rate and the modified
Stroke Rankin Scale.
Stroke evolution Results: We found no relation between lactate levels in blood and stroke evolution or outcome. Lactate in CSF was
Stroke outcome higher in stroke patients than in controls and correlated with stroke evolution and outcome. Multivariate
Cerebrospinal fluid regression analyses showed that CSF lactate levels, age and stroke severity are independent predictors for stroke
Metabolic stress evolution and outcome.
Secondary ischemia
Conclusions: Lactate levels in CSF, but not in blood, are a reliable marker for metabolic crisis in acute ischemic
stroke and correlate with the stroke evolution in the subacute phase and with long-term outcome.
© 2008 Elsevier B.V. All rights reserved.

1. Introduction Since cerebrospinal fluid (CSF) is considered to be equivalent to

Most glucose in the brain is ultimately oxidized to carbon dioxide
and water, but reduced oxygen availability due to perfusion deficit
results in anaerobic glycolysis and production of lactate [1].
Accumulation of lactate in ischemic regions has been documented
by magnetic resonance spectrometry (MRS) and microdialysis studies
in acute stroke, both in animal models [2–4] and in patients [5–8].
Moreover, elevated levels of lactate are thought to cause secondary
damage with infarct expansion and poor outcome as a result [9].
Indirect evidence from the literature indicates that lactate may be
detrimental in cortical infarction but not in lacunar stroke [10].
extracellular fluid of the brain [11], it seems plausible that the findings
from MRS and microdialysis are reflected in CSF. Lumbar puncture is a
relatively straightforward procedure that does not require advanced,
costly and time consuming imaging techniques and is less invasive
than cerebral microdialysis. Nevertheless, reports on analysis of
lactate in CSF of acute ischemic stroke patients are rare and essentially
limited to one study dating from the early 1980s [12].
The aim of this study is to evaluate lactate levels in CSF of acute
ischemic stroke patients as a marker for metabolic crisis and as a
possible cause of secondary damage leading to infarct expansion and
poor outcome.

2. Materials and methods

Abbreviations: ΔNIHSS72, change in NIHSS score from admission to 72 h after stroke
onset; CSF, cerebrospinal fluid; CT, computed tomography; Exp(β), exponential β; mRS,
modified Rankin Scale; MRI, magnetic resonance imaging; MRS, magnetic resonance
spectrometry; NA, not applicable; NIHSS, National Institutes of Health Stroke Scale;
ROC, receiver operating characteristic curve.
⁎ Corresponding author. Laboratory of Neurochemistry and Behaviour, Institute Born-
Bunge, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium. Tel.: +32 3
820 26 20; fax: +32 3 820 26 18.
E-mail address: peter.dedeyn@ua.ac.be (P.P. De Deyn).
2.1. Study population
Ischemic stroke or TIA patients were included after informed consent, if clinical
evaluation, computed tomography (CT) of the brain and venous and arterial blood
sampling were performed within twenty-four hours after onset of stroke symptoms.
From October 2005 until December 2007, 190 patients were included of whom 3 in
retrospect appeared to suffer from other conditions, mimicking stroke (sepsis, non-
convulsive status epilepticus). Lumbar puncture was performed within twenty-four

0009-8981/$ – see front matter © 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.cca.2008.07.016
28 R. Brouns et al. / Clinica Chimica Acta 397 (2008) 27–31

hours after onset of stroke symptoms in 85 patients without contra-indication for this
procedure. The baseline characteristics and vascular risk factors of the 187 patients who
underwent blood sampling and the 85 patients who underwent lumbar puncture are
shown in Table 1. On admission, neurological deficits were quantified using the National
Institutes of Health Stroke Scale (NIHSS) [13] by trained stroke physicians (R.B. and R.S.)
and a CT or magnetic resonance imaging (MRI) study of the brain was performed to rule
out hemorrhagic stroke or other intracerebral pathology. Blood gasses and pH-metry
were performed on the arterial blood samples to exclude lactate acidosis. During
hospitalization, the underlying mechanism of the ischemic event was assessed
according to the European Stroke Initiative recommendations [14] and stroke etiology
was classified according to the TOAST criteria [15]. In addition to the neuroimaging on
admission, 166 patients underwent MRI of the brain on average 3.2 days after onset of
stroke symptoms. In 12 patients with a contra-indication for MRI (5 hemodynamically
instable patients, pacemaker in 5 patients and claustrophobia in 2 patients), repeat CT
of the brain was obtained on average 3.7 days after stroke onset. Nine patients deceased
before repeat neuroimaging was performed. Laboratory studies including complete
blood count, prothrombin time with international normalised ratio, activated partial
thromboplastin time, serum electrolytes, blood glucose, inflammatory markers, hepatic
and renal chemical analyses, lipid profile, thyroid function and arterial blood gas
analysis were performed in all patients. In patients subjected to lumbar puncture,
glycorachia, proteinorachia and CSF cell count were obtained. Clinical evaluation and
venous blood sampling with analysis of lactate was repeated at 24 h, 72 h and 7 days
after onset of stroke symptoms. The study was conducted according to the revised
Declaration of Helsinki (1998) and in agreement with the guidelines of the Ethics
Committees of ZNA Antwerp and the University of Antwerp.
2.2. Control population
Since data on normal concentrations of lactate in CSF are scanty, we included a
control population consisting of patients who were hospitalized in the department of
neurology of our hospital from October 2005 until December 2007 for evaluation of
neurodegenerative disease (progressive cognitive deterioration (n = 16), progressive
cerebellar syndrome (n = 3), amyotrophic lateral sclerosis (n = 3)), headache (negative
investigation for subarachnoid hemorrhage (n = 9) and meningitis (n = 8)) or peripheral
nervous system disorders (polyneuropathy (n = 9) and myasthenia gravis (n = 3)). In all
patients, stroke was excluded by neuroimaging and CSF samples of controls with N 5
white blood cells/mm3 were excluded from the study as well. The characteristics of the
control group are listed in Table 1.
2.3. Blood sampling and lumbar puncture
Venous blood samples were collected in 2.6-mL tubes containing Fluoride EDTA
and arterial blood samples in 2.0-mL tubes containing calcium-balanced Lithium
Heparin (Sarstedt Monovette®, Nümbrecht, Germany). CSF samples were collected in
dry tubes. All samples were immediately sent to the hospital laboratory, promptly
centrifuged and analysed instantly after centrifugation. Measurement of lactate in
venous blood and CSF samples was done on a Vitros 5.1FS analyser (Ortho Clinical
Diagnostics, Rochester, NY) by means of a lactate oxidase/peroxidase coupled reaction.
Table 1
Baseline characteristics and risk factors of the study corpus of 187 patients with acute
ischemic stroke or TIA and 51 controls
Value
Characteristic Patients with blood Patients with cerebrospinal Controls
sample (n = 187) fluid sample (n = 85) (n = 51)
Patient characteristics
Age (years) 71.9 ± 12.4 71.8 ± 13.2 70.6 ± 13.8
Female gender 90 (48.1) 37 (43.5) 23 (45.1)
Time to sampling 5.1 ± 5.8 8.3 ± 5.9 NA
(hours)
The measurable range for lactate in blood and CSF is 0.5 to 12 mmol/L. The between-run
imprecision was less than 1.5%.
2.4. Evaluation of stroke evolution, outcome and subtype
The evolution of the clinical condition of the patients in the first 72 h after onset of
stroke symptoms was assessed by means of the NIHSS score obtained at the time of
admission and 72 h post stroke (ΔNIHSS72) and calculated by subtracting the NIHSS score
at 72 h from the score on admission. ΔNIHSS72 values of − 2 and higher were regarded to
represent a stable or favourable evolution in the subacute phase, whereas values lower
than − 2 represent an unfavourable evolution. In the same time window, patients were
evaluated for progressing stroke as defined by the European Progressing Stroke Study
criteria [16]. At 3 months after stroke, outcome was assessed by means of mortality and the
modified Rankin Scale (mRS, 0 indicates full recovery and 6 indicates death) [17]. In
agreement with literature data, poor outcome was defined as mRS score N3 [18].
Patients were classified as subjects with lacunar or cortical stroke, based on clinical
and neuroimaging findings. Thirty-two patients were diagnosed with lacunar stroke
and in 110 patients evidence of cortical infarction was present on neuroimaging. In 45
patients, there was no proof of acute cortical ischemia or lacunar stroke (Table 1).
2.5. Infarct volumetry
Infarct volume was assessed on diffusion weighted MRI or on CT in patients with a
contra-indication for MRI. Proof of an acute ischemic lesion was found in 130 of 187
patients (70%) who underwent neuroimaging in the subacute phase. Using the public
domain software Image J (National Institutes of Health, Bethesda, Md, http://rsb.info.
nih.gov/ij), all lesion areas were manually outlined on a slice-by-slice basis and volumes
were automatically produced by the multiplication of the total lesion area times the
sum of slice thickness and interslice gap. Measurements of lesion volume were
performed independently by 2 observers (R.B. and D.D.), one of whom was blinded to all
other data (D.D.). Intra-observer analysis was obtained by measurement of the volume
of each lesion on two occasions separated by at least one month (R.B.). The mean ± SD
infarct volume at the first rating was 62.3 ± 123.0 mL and 63.0 ± 124.3 mL at the second
rating. The single-measure intraclass correlation coefficient for the intraobserver
measurements was 0.99 (95% confidence interval, 0.97–0.99; Cronbach α = .99). The
mean ± SD infarct volume obtained by the blinded rater was 64.5 ± 125.1 mL and the
interobserver agreement revealed a single-measure intraclass correlation coefficient of
0.99 (95% confidence interval, 0.97–0.99; Cronbach α = .99). The final infarct volume
was achieved as the mean of the individually obtained infarct volumes.
2.6. Statistical analyses
Data were analyzed using Microsoft Excel (version 2003 SP2; Microsoft Corp. 2003)
and the SPSS 13.0 software package for Windows (SPSS Inc, Chicago, Ill). First, we calculated
bivariate correlations between stroke evolution in the subacute phase and outcome at
month 3 and lactate levels in blood and CSF. Student's t-test for independent samples was
applied to evaluate the differences between two groups. Using receiver operating
characteristic curve (ROC) analysis, we calculated cut-points that provided optimal
sensitivities and specificities. Based on these cut-points, accuracy measures predicting
stroke evolution and outcome were derived from cross-tabulations. The Fisher exact test
was used to indicate significant findings and α adjustment according to the modified
Bonferroni procedure was applied. For four tests with an average correlation of 0.43, α was
lowered to.023. In order to estimate whether CSF lactate is independently predictive of
stroke evolution and outcome, we constructed a multivariate stepwise logistic regression
model that included age, gender, time between onset of stroke symptoms and lumbar
puncture, number of red blood cells in CSF (as marker of traumatic lumbar puncture),
diagnosis of TIA or ischemic stroke, NIHSS at admission, infarct volume at 72 h, stroke
etiology and history of diabetes mellitus.
3. Results
3.1. Lactate levels in blood and CSF

Stroke characteristics Lactate blood levels were available in 183 patients on admission
TIA/ischemic stroke 42/142 (22.5/77.5) 20/65 (23.5/76.5) NA (mean ± SD; 1.5 mmol/L ± 1.1), in 173 patients at 24 h (mean ± SD;
NIHSS at admission 9±9 8±9 NA 1.4 mmol/L ± 0.6), in 171 patients at 72 h (mean ± SD; 1.4 mmol/L ± 0.6)
Infarct volume (mL) 62.3 ± 123.0 60.4 ± 112.1 NA and in 160 patients at 7 days after onset of stroke (mean ± SD;
Stroke etiology
1.5 mmol/L ± 0.5). CSF lactate concentrations were measured in 85
Cardioembolic 84 (44.9) 37 (43.5) NA
Lacunar 32 (17.1) 16 (18.8) NA stroke or TIA patients (mean ± SD; 1.5 mmol/L ± 0.4) and 51 control
Atherothrombotic 29 (15.5) 10 (11.8) NA patients (mean ± SD; 1.3 mmol/L ± 0.2). Lactate levels in venous blood
Specific 14 (7.5) 3 (3.5) NA and CSF obtained simultaneously from stroke patients at admission
Undetermined 28 (15.0) 19 (22.4) NA
showed only a moderate correlation (Pearson's R = 0.34; P b .001).
Stroke subtype
Cortical 110 (58.8) 46 (54.1) NA
Lacunar 32 (17.1) 16 (18.8) NA 3.2. Lactate levels and stroke evolution in the subacute phase
Unclassified 45 (24.1) 23 (27.1) NA

Data given as mean ± SD or as number (percentage). No correlation was found between lactate levels in blood taken at
Abbreviations: NA, not applicable; NIHSS, National Institutes of Health Stroke Scale. admission, 24 h, 72 h or 7 days after stroke onset and ΔNIHSS72 or
 R. Brouns et al. / Clinica Chimica Acta 397 (2008) 27–31 29

Mean lactate concentration in CSF of the 75 patients who remained

stable or improved in the first 72 h was 1.5 ± 0.3 mmol/L, compared to
1.9 ± 0.9 mmol/L in the 10 patients who deteriorated (t-test; P = .001).
Similar findings were found in patients without progressing stroke
(n = 71; mean lactate concentration in CSF, 1.4 ± 0.3 mmol/L) compared
to patients who developed progressing stroke (n = 14; mean lactate
concentration in CSF, 1.9 ± 0.7 mmol/L) (t-test; P = .001) (Fig. 1A). ROC-
curve analysis yielded an area under the curve of 0.78 (95% CI, 0.51–
0.91) for ΔNIHSS72 and 0.77 (95% CI, 0.64–0.91) for progressing stroke.
As cut-point for differentiation between the favourable and unfavour-
able evolution, 2.0 mmol/L was set. Correlations and accuracy
measures for stroke evolution are listed in Table 2. The results of the
multivariate regression analyses show that lactate levels in CSF and
infarct volume at 72 h are independent predictors for stroke evolution
(Table 3).

3.3. Lactate levels and stroke outcome

No correlation was found between lactate levels in blood taken at

Fig. 1. Bar graphs demonstrating mean lactate levels in cerebrospinal fluid in relation to
stroke evolution (A) and outcome (B). White boxes represent controls, gray boxes patients
with favourable evolution or outcome, and black boxes patients with poor evolution or
outcome. The black vertical line in each bar represents the 95% confidence interval.
admission, 24 h, 72 h or 7 days after stroke onset and mortality or mRS
score at 3 months, but lactate concentrations in CSF correlated with
mortality (Spearman's ρ = 0.33; P = .002) and mRS score (Spearman's
ρ = 0.42; P b.001). Mean lactate concentration in CSF of survivors
(n = 78) is 1.5 ± 0.3 mmol/L, compared to 2.2 ± 0.9 mmol/L in the 7
patients who deceased (t-test; P = .001). Patients with poor outcome
(mRS N 3, n = 50) on average had higher lactate concentrations in CSF
than patients with mRS 0–3 (n = 35) (1.8 ± 0.7 vs. 1.4 ± 0.3 mmol/L
respectively; t-test P = .003) (Fig. 1B). ROC-curve analysis yielded an
area under the curve of 0.84 (95% CI, 0.63–1.0) for mortality and 0.66
(95% CI, 0.52–0.81) for functional outcome based on the mRS. As cut-
point for differentiation between favourable and unfavourable out-
come, 2.0 mmol/L was set. Correlations and accuracy measures for
stroke evolution are listed in Table 2. The results of the multivariate
regression analyses show that lactate levels in CSF are independent
predictors for stroke evolution in the first 72 h and for outcome at
3 months after stroke onset (Table 3). Other relevant predictors for
evolution and outcome were infarct volume on neuroimaging, NIHSS
score at admission and age. Multicollinearity between the indepen-
dent variables was checked by bivariate correlations, but was not
present.
3.4. Lactate levels and stroke subtype

In patients with lacunar stroke, lactate levels in blood or CSF did

not correlate with stroke evolution (ΔNIHSS72, progressing stroke) or
progressing stroke. Lactate concentrations in CSF on the other hand with stroke outcome (mortality, mRS score at 3 months). In patients
inversely correlated with ΔNIHSS72 (Pearson's R = − 0.61; P b .001) and with cortical infarction, no relation between blood lactate levels and
correlated with progressing stroke (Spearman's ρ = 0.36; P b .001). stroke evolution or outcome was found, but CSF lactate levels

Table 2
Lactate levels in CSF in relation to stroke evolution and outcome

Correlation Correlation

Variable Spearman ρ Pearson R P valuea Sensitivity Specificity Positive predictive value Negative predictive value Overall accuracy Odds ratio P valuea,b
Stroke evolution
ΔNIHSS72 −0.61 b .001 0.30 0.95 0.43 0.91 0.88 7.6 .022
Progressing stroke 0.36 b .001 0.29 0.97 0.67 0.87 0.86 13.6 .006

Stroke outcome
Mortality 0.33 .002 0.57 0.97 0.67 0.96 0.94 50.0 b .001
mRS 0.42 b.001 0.20 0.97 0.67 0.80 0.79 7.8 .017

Accuracy measures for prediction of unfavourable evolution and outcome using 2.0 mmol/L as cut-point for lactate concentration.
Stroke evolution based on dichotomization of ΔNIHSS72 and progressing stroke; Stroke outcome based on mortality and dichotomized mRS score at month 3.
Abbreviations: ΔNIHSS72, change in NIHSS score from admission to 72 h after onset of stroke symptoms; mRS, modified Rankin Scale.
a
P b.023 indicates significant findings.
b
Fisher Exact Test.
30 R. Brouns et al. / Clinica Chimica Acta 397 (2008) 27–31
Table 3
Logistic regression models of independent predictors of stroke evolution (Model 1) and
outcome (Model 2)
Variable Exp(β)
Model 1: Stroke evolution in first 72 h
ΔNIHSS72
Lactate in CSF 6.3
Infarct volume 1.0
Progressing stroke
Lactate in CSF 62.0
NIHSS at admission 1.2
Model 2: Stroke outcome at month 3
Mortality
Lactate in CSF 9558.4
Age 54.9
Functional outcome
Lactate in CSF 98.9
Age 1.2
NIHSS at admission 1.2
Infarct volume 1.1
Stroke evolution represents dichotomization between patients with favourable
evolution (ΔNIHSS72 N − 2 and non progressing stroke) vs. unfavourable evolution
(ΔNIHSS72 b − 2 and progressing stroke). Stroke outcome represents dichotomization
between favourable outcome (survivors and mRS 0–3) vs. unfavourable outcome
(patients who deceased and mRS 4–6).
Abbreviations: Exp(β), exponential β; ΔNIHSS72, change in NIHSS score from admission
to 72 h after stroke onset; CSF, cerebrospinal fluid; NIHSS, National Institutes of Health
Stroke Scale.
correlated strongly with ΔNIHSS72 (Pearson's R = − 0.67; P b.001),
progressing stroke (Spearman's ρ = 0.51; P b.001), mortality (Spear-
man's ρ = 0.52; P b.001) and mRS score (Spearman's ρ = 0.39; P = .008).
4. Discussion
Elevated lactate levels in CSF have been described in bacterial
meningitis [19], perinatal cerebral hypoxia [20], status epilepticus
[21], and inborn errors of metabolism such as pyruvate dehydro-
genase deficiency [22] and respiratory chain disorders [23]. In
animal models of hyperacute stroke, regional increase in lactate has
been documented by microdialysis [2], MRS [3,4], and post-mortem
studies [24]. In concordance with these findings, MRS in ischemic
stroke patients has shown elevated levels of lactate in ischemic
regions, as defined by abnormal diffusion weighted imaging [5,6]. In
addition, in limited series of patients with severe ischemic stroke
investigated by microdialysis, increased concentrations of lactate in
the extracellular fluid of the infarcted core and to a lesser extent in
the ischemic penumbra, but not in non-infarcted brain tissue have
been described [7,8]. The lactate production is thought to be the
consequence of anaerobic glycolysis in brain regions that suffer from
severe hypoperfusion [1] and it is hypothesized that lactate can
spread from the infarcted brain tissue into peri-infarct tissue, where
it exerts detrimental effects on neuronal cells and impairs cere-
brovascular autoregulation leading to edema and secondary ische-
mia with infarct expansion as a result [9]. These pathophysiological
processes are reflected by an unfavourable clinical evolution and
poor outcome. Indeed, microdialysis studies in patients with large
medial cerebral artery infarction show that lactate levels are higher
and increase sharply in patients who develop malignant brain
infarction, in contrast to patients with favourable evolution [7,8].
Based on these findings, it seems that lactate not only is a useful
marker of anaerobic metabolism in stroke [25], but also a possible
cause of secondary damage leading to unfavourable evolution of
stroke in the subacute phase and eventually to poor outcome. Our
results are concordant with the findings in the literature suggesting
that lactate is detrimental in cortical stroke but not in lacunar stroke
[10]. In contrast to cortical ischemia, lacunar strokes preferentially
damage axons and glial cells. Lactate production by astrocytes is an
important rescue source of energy for axons [26] and perhaps also
for oligodendrocytes [27]. Therefore, increased lactate levels may be
P value protective rather than the cause of secondary damage in acute
lacunar stroke.
Since cerebrospinal fluid is considered to be equivalent to
.048
extracellular fluid of the brain [11], it is plausible that the findings
.012
from MRS and microdialysis are reflected in the CSF as well. Due to the
.005 relatively simple and cheap procedure, lumbar puncture seems to be
.009 more suitable for evaluation of larger patient cohorts than costly and
time consuming MRI or invasive microdialysis. However, data on
lactate in CSF of acute ischemic stroke patients are limited. Busse et al.
.020 found a linear relation between CSF lactate levels and infarct edema
.014 on CT in patients with middle cerebral artery ischemia, especially at
three days after stroke when lactate levels were maximal [12]. Patients
.019
with more than 4.0 mmol/L lactate in CSF had more severe edema,
.001
.012 compared to patients with lactate levels under 2.5 mmol/L who had
.024 less edema and better chances of survival [12]. A more anecdotal
report on lactate levels in CSF of a patient who suffered from ischemic
stroke as a complication of aortic aneurysm surgery confirms the time
linked increase of lactate in CSF with occurrence of cerebral ischemia.
In this patient, the lactate concentration peaked at 48 h after stroke
onset and was in the range of 4.0 mmol/L [28]. The lactate levels in CSF
in our study population are lower than the levels reported in the
previous studies. This may be due to the fact that we performed CSF
analysis in a heterogeneous cohort of hyperacute stroke and TIA
patients of variable severity. The mean interval between stroke onset
and lumbar puncture was 8.3 h, which is much earlier than the time
points for maximal lactate concentrations in CSF as reported by Busse
et al. and Andersson et al. [12,28].
Normative data on lactate concentrations in CSF are scarce. In a study
based on adult cisternal puncture samples, the normal range was
defined as 0.68–2.10 mmol/L[29] and the median lactate concentration
in CSF of a pediatric population was 1.5 mmol/L [30]. This is in range with
the mean lactate concentration found in our control population.
To the best of our knowledge, no data on lactate levels in blood of
stroke patients are available. Blood and CSF lactate equilibrate slowly
[31], probably due to the fact that lactic acid dissociates almost entirely
to lactate anion at physiologic pH. This charged species cannot cross
plasma membranes by free diffusion but requires transport by
monocarboxylate transporters [32]. Thus in acute disorders, CSF lactate
is a better indicator of local metabolism than blood lactate [30]. This is in
line with our findings revealing a weak correlation between lactate
levels in CSF and blood and no correlation between lactate levels in
blood at admission, at 24 h, at 72 h or at day 7 and stroke evolution or
outcome.
This study's main drawback probably lies in the limited number of
patients in the subgroups with unfavourable evolution or outcome,
which results in large confidence intervals. Nevertheless, the accuracy
measures and odds ratios for poor evolution and outcome are
indicative of a relevant predictive value of CSF lactate concentration
in hyperacute stroke.
In conclusion, the results of this study indicate that lactate in CSF,
but not in blood, is a reliable marker for the metabolic crisis in acute
ischemic stroke and a possible cause of secondary neuronal damage in
cortical infarction resulting in unfavourable evolution in the subacute
phase of stroke and poor long-term outcome.
Author contributions
Study concept and design: Brouns and De Deyn. Acquisition of
clinical data: Brouns and Sheorajpanday. Blood and CSF sampling:
Brouns and Sheorajpanday. Analysis of lactate in blood and cere-
brospinal fluid: Wauters. Acquisition of neuroimaging data: Brouns
and De Surgeloose. Analysis and interpretation of data: Brouns,
Sheorajpanday, Wauters, Marien, De Surgeloose and De Deyn. Drafting
 R. Brouns et al. / Clinica Chimica Acta 397 (2008) 27–31 31

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