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The cerebrospinal fluid lactate is decreased in early stages of multiple sclerosis


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The purpose of this study was to investigate if the concentration of lactate can provide additional information for pathologies that need examination of the cerebrospinal fluid (CSF) in their diagnostic controls or protocols. A prospective study carried out in the year 2001 at the University Hospital of Bellvitge (Barcelona), on 92 samples of CSF from patients who needed this examination. The concentration of lactate, glucose, and the cell count was determined. One year later, the diagnosis revealed from the previous analyzed samples were sorted into groups according to the diagnosis. In the group with multiple sclerosis (MS) (n = 30), there was a significant decrease in lactate concentration (1.52 +/- 0.19 mmol/L) compared to the control group (1.89 +/- 0.11 mmol/L) (p < 0.001). The glucose concentration remained within the normal range and the cell count was < 4 cell/microL even in the relapses. In the early stages of MS, the lactate concentration in CSF is decreased and this could be related to alterations in sensitivity observed in those patients. Further studies are needed to evaluate if this lactate concentration is a prognostic indicator of the disease.
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PRHSJ Vol. 27 No. 2
June, 2008 Multiple Sclerosis and Lactate
Fonalledas, M. A., et al.
The cerebrospinal fluid lactate is decreased in early stages of multiple
*Departament de Ciències Fisiològiques II. Facultat de Medicina. Universitat de
Barcelona. L’Hospitalet de Llobregat. Barcelona, Laboratori Clínic. Hospital
Universitari de Bellvitge. L’Hospitalet de Llobregat. Barcelona.
Address correspondence to: M. Assumpta Fonalledas, MD, Departament
Ciències Fisiològiques II. Facultat de Medicina.Campus de Bellvitge.
Universitat de Barcelona. 08907 L’Hospitalet de Llobregat. Barcelona.Spain, Tel:
034934024517, FAX: 034934024268, E-mail:
Background: The purpose of this study was to
investigate if the concentration of lactate can provide
additional information for pathologies that need
examination of the cerebrospinal fluid (CSF) in their
diagnostic controls or protocols.
Methods: A prospective study carried out in the year
2001 at the University Hospital of Bellvitge (Barcelona),
on 92 samples of CSF from patients who needed this
examination. The concentration of lactate, glucose, and
the cell count was determined. One year later, the
diagnosis revealed from the previous analyzed samples
were sorted into groups according to the diagnosis.
Results: In the group with multiple sclerosis (MS)
(n=30), there was a significant decrease in lactate
concentration (1.52 ± 0.19 mmol/L) compared to the
control group (1.89 ± 0.11 mmol/L) (p<0.001). The
glucose concentration remained within the normal
range and the cell count was < 4 cell/μL even in the
Conclusions: In the early stages of MS, the lactate
concentration in CSF is decreased and this could be
related to alterations in sensitivity observed in those
patients. Further studies are needed to evaluate if this
lactate concentration is a prognostic indicator of the
Key words: Cerebrospinal fluid; Lactate; Multiple
In recent years, knowledge of lactic acid
physiopathology has increased its usefulness as a
biological indicator outside the limits of anaerobic
metabolism. The ionization potential (pK) of lactic acid at
37ºC (3.87) (1), assures the dissociation to the anion lactate
in the cerebrospinal fluid (CSF) within its physiological
pH levels (7.35-7.40). Lactate is a more reliable indicator in
CSF than in blood, owing to less variation in cerebral pH.
In some infectious processes, such as meningitis, the
determination of CSF lactate has been used to establish the
differential diagnosis between a viral or a bacterial aetiology
(2) but, as far as we know, there is not much information
about these questions, and therefore, the use of lactate as a
biological indicator, is still practically unknown.
The objective of this study is to determine if the
concentration of lactate can provide additional information
in those pathologies that need examination of CSF in their
diagnostic protocols or controls.
Materials and Methods
The prospective study was carried out for 4 months in
2001. The samples of CSF were from 92 patients from the
clinical laboratory at the University Hospital of Bellvitge
One hour after collecting the samples obtained by
lumbar puncture, the glucose values were determined
using the glucose-oxidase method (Roche Diagnostics /
Hitachi 911, Mannheim, Germany) and the cell count was
obtained in a Fuchs-Rosenthal chamber. The samples were
then centrifuged and stored at -80ºC to prevent
degradation of the lactate (3).
The lactate concentration was determined in an YSI 1500
analyser (YSI Inc., EUA) by an enzymatic method that
uses lactate-oxidase to transform the lactate into hydrogen
peroxide, which in turn is oxidised on a platinum anode
that produces electrons until it reaches equilibrium.
Two of the samples were discarded due to haematic
A year later, the clinical histories were consulted and
the 90 diagnoses were checked. The cases were grouped
according to generic diagnosis that included a minimum
of 5 samples (Table 1).
The control group (C) consisted of 8 samples of CSF
corresponding to 8 patients that showed normality in the
PRHSJ Vol. 27 No. 2
June, 2008
Multiple Sclerosis and Lactate
Fonalledas, M. A., et al.
analysis and a slight clinical diagnosis. The clinical
diagnoses were: Slight cognitive deterioration; slight
traffic accident control; cortical dysfunction; subacute
dementia; radiculopathy L5-S1; discopathy L4-L5;
psychotic disorder and migraine. Prior to the group
distribution, 5 samples with an associated diagnosis that
could mask results were excluded
Statistical analysis: The differences between groups
were analysed using the Mann-Whitney U test and in all
the contrasts, statistical significance was established as
p<0.05. The data obtained was analysed using the
statistical program “SPSS for Windows”, version 14.0
The data from the 85 CSF samples finally included in the
study are shown in Tables 1 and 2.
A) All groups (Table 1)
In the multiple sclerosis (MS) group, statistically
significant differences were observed with respect to group
C for lactate concentration values of 19.6 % lower (p<0.001),
and for glucose concentration values of 15.6 % lower
(p=0.003). For cell counts, higher values were observed
In the demyelinating diseases group other than MS
(DM), statistically significant differences were observed
with respect to group C for lactate concentration values
of 20.6% lower (p<0.01).
In the subacute inflammatory diseases (SI) group, no
statistically significant differences were observed with
respect to group C.
In the acute infections (AI) group, statistically
significant differences were observed with respect to group
C for lactate concentration values of 33.3% higher (p<0.05),
and for glucose concentration values of 48.1% lower
In the neoformations (NEO)group, statistically
significant differences were observed with respect to group
C for lactate concentration values of 121% higher (p<0.01).
B) MS groups (Table 2)
In the relapsing remitting multiple sclerosis (RRMS)
subgroup, statistically significant differences were
observed with respect to the primary progressive multiple
sclerosis (PPMS) subgroup for lactate concentration
values of 11.1% lower (p<0.05).
In the clinically isolated syndrome (CIS) subgroup,
statistically significant differences were observed with
respect to the PPMS subgroup, for lactate concentration
values of 11.6 % lower (p<0.05).
In the present study, we observed that a substantial
percentage of the samples had a diagnosis of demyelinating
diseases, especially MS, as their diagnostic protocol
included the presence of oligoclonal bands of Ig G and/or
the index of Ig G in CSF (4).
In the MS group, 93% of the CSF samples collected in
clinical early stages to analyse and establish the definite
diagnosis show a significantly reduced lactate
concentration (1.52 ± 0.19 mmol/L) as compared to group
C (1.89 ± 0.11 mmol/L). The values in group C are
comparable with the normal values obtained in other similar
studies (2). Within the MS group, the decrease in lactate
Table 1. Clinical and CSF data in patients with various diseases.
Groups Diagnoses No. of Sex Age Lactate Glucose Cells
cases (M/F) years mmol/L mmol/L no/μμ
Range (M±SD) (M±SD) Range
C Controls 8 5/3 23-75 1.89 ± 0.11 3.78 ± 0.50 0-3
MS Multiple sclerosis 30 10/20 21-72 1.52 ± 0.19 3.19 ± 0.38 0-4
DM Demyelinating diseases 5 4/1 31-70 1.50 ± 0.10 3.18 ± 0.59 0-4
SI Subacute inflammations 6 4/2 31-68 1.87 ± 0.27 3.43 ± 0.54 0-20
AI Acute infections 5 3/2 20-66 2.52 ± 0.48 1.96 ± 1.03 35-850
NEO Neoformations 8 7/1 22-68 4.18 ± 2.06 3.17 ± 2.02 0-250
OD Other diseases 23 11/12 21-79 1.59 ± 0.76 3.59 ± 2.01 0-7
M ± SD: Mean ± Standard Deviation
Mann-Whitney test:
Comparison C vs MS: p<0.001 and p=0.003 for lactate and glucose concentration.
Comparison C vs DM: p<0.01 for lactate concentration.
Comparison C vs AI: p<0.05, p<0.01 and p<0.01 for lactate and glucose concentration, and cell count.
Comparison C vs NEO: p<0.01 for lactate concentration.
The other comparisons are not significants.
PRHSJ Vol. 27 No. 2
June, 2008 Multiple Sclerosis and Lactate
Fonalledas, M. A., et al.
concentration is more marked in RRMS and CIS, which
show values lower than those obtained in PPMS (Table
2), in agreement with other publications (5), suggesting
that PPMS constitutes a separate disease entity different
from RRMS.
The decrease in lactate concentration in the CSF of
patients with MS, may explain the alterations in sensitivity
in some of these patients. In the present study, the lowest
values in the lactate concentration (mean 1.25 mmol/L)
range corresponded to 3 patients from the group of other
diseases (OD), with isolated symptoms of deficient
sensitivity (lower limb paraesthesias; hemibody
hypoesthesia; neurosensorial hypoacusia), similar
symptoms to those seen in some patients with early stages
of MS, suggesting alterations in the ionic acid-sensitive
channels, because of the increased resistance of these
channels to opening and depolarisation when the effect
of lactate is reduced. This facilitates the opening of the
channels (pores) due to their capacity of removing Ca²+
cations that block them (6).
The decrease in lactate concentration in the CSF of
patients with MS may be due to an increase in the
consumption of lactate satisfying a double need:
maintaining myelination as well as a minimum level of
glucose. In fact, it has been noted that, on one hand, the
oligodendrocytes prefer lactate for synthesizing myelin
(7) and, on the other hand, that, experimentally, in cases of
glucose depletion, the lactate is used as the energy source
of first choice (8). In these conditions, thermodynamically,
the step from lactate to pyruvate (when entering into the
tricarboxilic acid cycle) is preferred over the conversion of
glucose to pyruvate, which does not require the previous
investment of adenosine triphosphate (ATP).
These observations concur with other results in the
present study showing glucose concentration values in
the CSF of patients with MS (3.19 ± 0.38 mmol/L) 15.6%
lower with respect to group C (3.78 ± 0.50 mmol/L).
Although these values remain within the normality of the
method used here (interval reference: 2.8-4.2 mmol/L), they
are at the lower range limit. According to our knowledge,
low levels of CSF glucose in patients with MS have not
been described, although reduced levels of the cerebral
metabolism of glucose have been observed in the frontal
cortex and the basal ganglia, using functional techniques
such as positron emission tomography (PET) in patients
with MS and fatigue (9).
The results of the present study are in agreement with a
published article (10) whose authors have observed a
decrease in lactate concentration and other gluconeogenic
metabolites, such as glutamine in the CSF of patients with
MS, by means of a proton magnetic resonance
spectroscopy (1H-RMS).
Other authors (11) are in apparent disagreement with
our results. In 1H-RMS, they have observed increases in
lactate concentration and, correlatively, in the cell count
of CSF of patients with RRMS during relapses. But, this
study was done in patients who had been previously
diagnosed with MS. It is known, that the diagnosis of MS
always involves a certain waiting time, generally over a
year. However, in our present study, the CSF samples and
their subsequent analysis were done in the early clinical
stages with the objective of establishing a definite
diagnosis: In 65 % of the patients who were subsequently
diagnosed with MS, a lumbar puncture was performed
within a week of the relapse and, in not later than a month.
Therefore, chronologically, the results of preceding authors
are not comparable with those shown here. But, it needs
to be pointed out that the low cell count levels in the CSF
of patients with MS studied here, that are within the normal
range (0-4 cells/ML) (12), are not in disagreement with the
positive correlation between lactate and the cell count
observed by these authors.
Finally, in the present study, it is important to note that,
although the number of CSF samples used as controls is
Table 2. Values of parameters in the CSF of patients with multiple sclerosis.
Subgroups MS Clinical forms No. of Lactate Glucose Cells
cases mmol/L mmol/L n.o/μμ
(M + SD) (M + SD) Range
CIS Clinically isolated syndrome 7 1.44 ± 0.23 3.09 ± 0.29 0-4
RRMS Relapsing-remitting 20 1.53 ± 0.17 3.17 ± 0.38 0-4
PPMS Primary progressive 3 1.71 ± 0.06 3.57 ± 0.46 0-1
M + SD: Mean + Standard Deviation.
Mann-Whitney test:
Comparison CIS vs PPMS: p<0.05 for lactate concentration.
Comparison RRMS vs PPMS: p<0.05 for lactate concentration.
The other comparisons are not significants.
PRHSJ Vol. 27 No. 2
June, 2008
Multiple Sclerosis and Lactate
Fonalledas, M. A., et al.
small, this limitation has been corrected accepting as
completely valid those results in the MS group, taking
into consideration the values already known and confirmed
by the parameters studied in the remaining groups that
were analysed (Table 1) that contributed to verification of
the results. Thus, for example, the confirmation of the high
values in the lactate concentration already described from
samples with a diagnosis of IA (13), or the high values in
the lactate concentration from samples with a diagnosis
of NEO correspond with the poly-medicated patients.
To summarise, the results of the present study show a
decrease in CSF lactate concentration in the early stages
of MS that may explain some alterations in the sensitivity
of these patients, and also suggest a greater consumption
of lactate as an alternative energy source, in order to
preserve a minimum level of glucose. However, further
studies are necessary to confirm these results and evaluate
if the lactate concentration is a prognostic indicator of the
La propuesta de este estudio era investigar si la
concentración de lactato puede aportar información
adicional en aquellas patologías que precisan el examen
del liquido cefalorraquídeo (LCR) en sus protocolos de
diagnóstico o control. Estudio prospectivo realizado en el
año 2001 en el Hospital Universitario de Bellvitge
(Barcelona), sobre 92 muestras de LCR de pacientes que
precisaban este examen, determinándose la concentración
de lactato, de glucosa y el recuento de células. Un año
después se develaron los diagnósticos de las muestras
previamente analizadas, y se clasificaron en grupos según
los diagnósticos. En el grupo con esclerosis múltiple (EM)
(n=30), se halló una concentración de lactato (1.52 ± 0.19
mmol/L) significativamente disminuida en comparación con
el grupo control (1.89 ± 0.11 mmol/L) (p<0.001). La
concentración de glucosa permaneció dentro de los límites
de la normalidad y el recuento de células fue < 4 cel/µL,
incluso en los brotes. En las fases tempranas de la EM, la
concentración de lactato en el LCR se haya disminuida,
pudiendo estar relacionada con alteraciones de la
sensibilidad observadas en estos pacientes. Serán
necesarios más estudios para valorar si esta concentración
de lactato es un indicador pronóstico de la enfermedad.
To Prof. Dr.Txomin Arbizu, Unidad de Esclerosis
Múltiple, Hospital Universitari de Bellvitge, Barcelona,
Spain, for reviewing the manuscript and the Fonalledas
Foundation of Puerto Rico for the financial support.
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... In contrary, other data showed a diminished CSF lactate level or comparable levels. Those results were mainly in the initial phases of MS [21][22][23]. ...
... The overproduced lactate in MS stay in the CSF transiently and quickly passes into the circulation. This step of the transients overproduction of lactate in CSF clarify the controversial data of literature, and explain why the increment in CSF lactate level was not showed to be linked to EDSS or the subtypes of MS [17][18][19][20][21][22][23]. ...
... MS is characterized by metabolic disturbance caused by impaired mitochondrial functions, so it is expected that MS may lead to overproduction of the neuronal lactate. Information related to conceivable alterations in lactate level in MS patients are conflicting due to either increment [17,20] or no alter [23] in serum lactate levels has been determined. Also, information accessible in literature has basically been gotten in generally limited cohorts of MS patients and no relationship with the progression of MS or with the disease subtype (RR MS, SP MS, and PP MS) has been illustrated (19,17,20]. ...
Objective: To study the serum lactate level in MS and to explore its correlation with the progression and disability in multiple sclerosis (MS), and the important role of mitochondrial dysfunction in the pathogenesis of MS. Methods: This case-control study included 80 participants, involved 50 MS patients and 30 normal healthy controls. Detailed history taking, complete neurological examination, and clinical evaluation of the disability using the Expanded Disability Status Scale (EDSS) were done for all patients. Level of serum lactate was measured in both groups and was correlated with EDSS, MS subtypes, MRI brain, and MRS findings. Results: Serum lactate in MS patients was about three and half times higher than serum lactate levels of healthy controls (22.87 ± 5.92 mg/dl versus 6.39 ± 0.9 6.39 ± 0.91, p < 0.001). Importantly, serum lactate values were increased in MS cases with a progressive course compared with MS cases with RR course. Also, there were linearly correlations linking serum lactate levels and the duration of MS (r = 0.342, P = 0.015), relapses numbers (r = 0.335, P = 0.022), and EDSS (r = 0.483, P < 0.001). Also, there were strong positive correlations between serum lactate and Lipid/Lactate (r = 0.461, P = 0.001), periventricular lesion (r = 0.453, P = 0.005), and moderate positive correlations between serum lactate and juxtacortical lesion (r = 0.351, P = 0.02), and infratentorial lesion (r = 0.355, P = 0.02). Conclusion: Measurement of serum lactate may be helpful in MS and this supports the hypothesis of the critical role of mitochondrial dysfunction and axonal damage in MS.
... It can be concluded that there is an elevation in extra-mitochondrial glucose metabolism in MS patients, which could also be associated with impaired mitochondrial function [117]. Taking into account the aforementioned data, the fluctuations in lactate levels have the potential to serve as diagnostic criteria as they could indicate the progression of the disease [118]. ...
Full-text available
Multiple sclerosis (MS) is a complex autoimmune disease of the central nervous system (CNS), characterized by demyelination and neurodegeneration. Oligodendrocytes play a vital role in maintaining the integrity of myelin, the protective sheath around nerve fibres essential for efficient signal transmission. However, in MS, oligodendrocytes become dysfunctional, leading to myelin damage and axonal degeneration. Emerging evidence suggests that metabolic changes, including mitochondrial dysfunction and alterations in glucose and lipid metabolism, contribute significantly to the pathogenesis of MS. Mitochondrial dysfunction is observed in both immune cells and oligodendrocytes within the CNS of MS patients. Impaired mitochondrial function leads to energy deficits, affecting crucial processes such as impulse transmission and axonal transport, ultimately contributing to neurodegeneration. Moreover, mitochondrial dysfunction is linked to the generation of reactive oxygen species (ROS), exacerbating myelin damage and inflammation. Altered glucose metabolism affects the energy supply required for oligodendrocyte function and myelin synthesis. Dysregulated lipid metabolism results in changes to the composition of myelin, affecting its stability and integrity. Importantly, low levels of polyunsaturated fatty acids in MS are associated with upregulated lipid metabolism and enhanced glucose catabolism. Understanding the intricate relationship between these mechanisms is crucial for developing targeted therapies to preserve myelin and promote neurological recovery in individuals with MS. Addressing these metabolic aspects may offer new insights into potential therapeutic strategies to halt disease progression and improve the quality of life for MS patients.
... Nonetheless, a study by Amorini el al. has reported a threefold elevation in serum lactate levels in MS patients [24]. Although this study supports evidence of mitochondrial dysfunction in MS, previous studies assessing both serum [25] and CSF (cerebral spinal fluid) [26] lactate levels in this disorder have failed to show any evidence of an increase in the level of this metabolite. Importantly, lactate levels may not necessarily be raised as a consequence of MRC dysfunction as evidenced in patients with primary mitochondrial disorders [27]. ...
Full-text available
Objectives: Evidence of mitochondrial respiratory chain (MRC) dysfunction and oxidative stress has been implicated in the pathophysiology of multiple sclerosis (MS). However, at present, there is no reliable low invasive surrogate available to evaluate mitochondrial function in these patients. In view of the particular sensitivity of MRC complex IV to oxidative stress, the aim of this study was to assess blood mononuclear cell (BMNC) MRC complex IV activity in MS patients and compare these results to age matched controls and MS patients on β-interferon treatment. Methods: Spectrophotometric enzyme assay was employed to measure MRC complex IV activity in blood mononuclear cell obtained multiple sclerosis patients and aged matched controls. Results: MRC Complex IV activity was found to be significantly decreased (p< 0.05) in MS patients (2.1 ± 0.8 k/nmol × 10-3; mean ± SD] when compared to the controls (7.2 ± 2.3 k/nmol × 10-3). Complex IV activity in MS patients on β-interferon (4.9 ± 1.5 k/nmol × 10-3) was not found to be significantly different from that of the controls. Conclusions: This study has indicated evidence of peripheral MRC complex IV deficiency in MS patients and has highlighted the potential utility of BMNCs as a potential means to evaluate mitochondrial function in this disorder. Furthermore, the reported improvement of complex IV activity may provide novel insights into the mode(s) of action of β-interferon.
... In another study performed by Albanese et al., the oxidative stress-induced mitochondrial abnormality has been reported to raise CSF lactate levels as a result of impaired energy metabolism (anaerobic metabolism) as well as disrupted neuro-axonal homeostasis (Albanese et al., 2016). Contrarily, some other studies suggest, however, that CSF lactate levels fell in the early stages of MS or that no significant difference was found in the serum lactate levels compared to the control group (Aasly et al., 1997;Fonalledas-Perelló et al., 2008). However, it should be noted that contradictory results of the aforementioned studies may be due to the fact that the present study's sample size was restricted (Mähler et al., 2012). ...
... reported lower levels. 16 Lactate is the final cytoplasmic product of the glycolysis pathway and represents quantitatively the most important monocarboxylate. Indeed, during glycolysis in the Krebs cycle, glucose breaks down to pyruvate, which is subsequently reversibly converted to lactate by the enzyme lactate dehydrogenase. ...
Full-text available
Melatonin has a beneficial role in adult rat models of multiple sclerosis (MS). In this study, melatonin treatment (10 mg/kg/d) was investigated in young age (5-6 weeks old) Lewis rat model of acute experimental autoimmune encephalomyelitis (EAE) followed by assessing serum levels of lactate and melatonin. Results showed that clinical outcomes were exacerbated in melatonin- (neurological score=6) versus PBS-treated EAE rats (score=5). Melatonin caused a significant increase in serum IFN-γ, in comparison to PBS-treated EAE rats whereas no considerable change in IL-4 levels were found, although they were significantly lower than those of controls. The ratio of IFN-γ/IL-4, an indicator of Th-1/Th-2, was significantly higher in PBS- and melatonin- treated EAE rats, in comparison to controls. Moreover, results showed increased lymphocyte infiltration, activated astrocytes (GFAP+ cells) but also higher demyelinated plaques (MBP-deficient areas) in the lumbar spinal cord of melatonin-treated EAE rats. Finally, serum levels of lactate, but not melatonin, significantly increased in the melatonin group, compared to untreated EAE and normal rats. In conclusion, our results indicated a relationship between age and the development of EAE since a negative impact was found for melatonin on EAE recovery of young rats by enhancing IFN-γ, the ratio of Th1/Th2 cells, and astrocyte activation, which seems to delay the remyelination process. While melatonin levels decline in MS patients, lactate might be a potential diagnostic biomarker for prediction of disease progression. Early administration of melatonin in the acute phase of MS might be harmful and needs further investigations.
... MRI studies showed a correlation between CSF lactate concentration and the number of inflammatory plaques [8,11]. In contrast, data reporting decreased CSF lactate levels in the early stages of MS or comparable concentration have also been published [9,10,25]. In our study, carried out in a large cohort of RRMS patients, we noted a significant increase of CSF lactate levels, possibly due to the deranged use of energetic substrates caused by the impairment of oxidative phosphorylation cycle. ...
Full-text available
Altered cerebrospinal fluid (CSF) levels of lactate have been described in neurodegenerative diseases and related to mitochondrial dysfunction and neuronal degeneration. We investigated the relationship between CSF lactate levels, disease severity, and biomarkers associated with neuroaxonal damage in patients with multiple sclerosis (MS). One-hundred eighteen subjects with relapsing-remitting multiple sclerosis (RRMS) were included, along with one-hundred fifty seven matched controls. CSF levels of lactate, tau protein, and neurofilament light were detected at the time of diagnosis. Patients were followed-up for a mean of 5 years. Progression index (PI), multiple sclerosis severity scale (MSSS), and Bayesian risk estimate for multiple sclerosis (BREMS) were assessed as clinical measures of disease severity and progression. Differences between groups and correlation between CSF lactate, disease severity and CSF biomarkers of neuronal damage were explored. CSF lactate was higher in RRMS patients compared to controls. A negative correlation was found between lactate levels and disease duration. Patients with higher CSF lactate concentration had significantly higher PI, MSSS, and BREMS scores at long-term follow-up. Furthermore, CSF lactate correlated positively and significantly with CSF levels of both tau protein and neurofilament light protein. Measurement of CSF lactate may be helpful, in conjunction with other biomarkers of tissue damage, as an early predictor of disease severity in RRMS patients. A better understanding of the alterations of mitochondrial metabolic pathways associated to RRMS severity may pave the way to new therapeutic targets to contrast axonal damage and disease severity.
Multiple sclerosis (MS) is a complicated autoimmune disease characterized by inflammatory and demyelinating events in the central nervous system. The exact etiology and pathogenesis of MS have not been elucidated. However, a set of metabolic changes and their effects on immune cells and neural functions have been explained. This review highlights the contribution of carbohydrates and lipids metabolism to the etiology and pathogenesis of MS. Then, we have proposed a hypothetical relationship between such metabolic changes and the immune system in patients with MS. Finally, the potential clinical implications of these metabolic changes in diagnosis, prognosis, and discovering therapeutic targets have been discussed. It is concluded that research on the pathophysiological alterations of carbohydrate and lipid metabolism may be a potential strategy for paving the way toward MS treatment.
Background Some studies have demonstrated elevated concentrations of lactate both in the cerebrospinal fluid (CSF) and blood samples of multiple sclerosis (MS) patients as a pathological condition. We designed an experimental study first to investigate the serum level of lactate as a biomarker of MS progression and also to investigate the effect of methylprednisolone on serum lactate. Methods Experimental autoimmune encephalomyelitis (EAE) was inducted in Lewis rats, and then rats were treated intraperitoneally with methylprednisolone (30 mg/kg/d), at the disease onset, and the clinical scores were recorded. After seven days of treatment, the serum levels of lactate were determined using high performance liquid chromatography (HPLC). Moreover, lymphocyte infiltration and the demyelinated area was analysed in spinal cord. Results Compared to the untreated-EAE rats, methylprednisolone remarkably improved the clinical score of EAE and ameliorated the spinal cord inflammation and demyelination. In addition, the marked decline in IFN-γ and the increase in IL-4 confirmed improvement in the rats treated with methylprednisolone. Measurement of lactate using HPLC indicated enhancement in the serum level of lactate in the untreated-EAE rats; the lactate level significantly decreased after methylprednisolone therapy. Moreover, serum lactates and disease severity were correlated positively and significantly. Conclusion These data confirmed for the first time, that methylprednisolone can decreases the enhanced level of serum lactate in EAE model. In addition, it was shown that measurement of serum lactate could be an inexpensive and accurate laboratory test to determine the response to treatment and to assess disease severity in MS patients.
Multiple Sclerosis is the most common autoimmune disorder affecting the central nervous system. The heterogeneity of pathophysiological processes in MS contributes to the highly variable course of the disease and unpredictable response to therapies. The major focus of the research on MS is the identification of biomarkers in biological fluids, such as cerebrospinal fluid or blood, to guide patient management reliably. Because of the difficulties in obtaining spinal fluid samples and the necessity for lumbar puncture to make a diagnosis has reduced, the research of blood-based biomarkers may provide increasingly important tools for clinical practice. However, currently there are no clearly established MS blood-based biomarkers. The availability of reliable biomarkers could radically alter the management of MS at critical phases of the disease spectrum, allowing for intervention strategies that may prevent evolution to long-term neurological disability. This article provides an overview of this research field and focuses on recent advances in blood-based biomarker research. Copyright © 2015. Published by Elsevier B.V.
A new MCE method for the determination of oxalic, citric, glycolic, lactic, and 2‐ and 3‐hydroxybutyric acids, indicators of some metabolic and neurological diseases, in cerebrospinal fluid (CSF) was developed. MCE separations were performed on a PMMA microchip with coupled channels at lower pH (5.5) to prevent proteins interference. A double charged counter‐ion, BIS‐TRIS propane, was very effective in resolving the studied organic acids. The limits of detection (S/N = 3) ranging from 0.1 to 1.6 μM were obtained with the aid of contact conductivity detector implemented directly on the microchip. RSDs for migration time and peak area of organic acids in artificial and CSF samples were Keywords: Cerebrospinal fluid; MCE; Micro‐SPE; Organic acids Document Type: Research Article DOI: Publication date: August 1, 2014 $(document).ready(function() { var shortdescription = $(".originaldescription").text().replace(/\\&/g, '&').replace(/\\, '<').replace(/\\>/g, '>').replace(/\\t/g, ' ').replace(/\\n/g, ''); if (shortdescription.length > 350){ shortdescription = "" + shortdescription.substring(0,250) + "... more"; } $(".descriptionitem").prepend(shortdescription); $(".shortdescription a").click(function() { $(".shortdescription").hide(); $(".originaldescription").slideDown(); return false; }); }); Related content In this: publication By this: publisher By this author: Danč, Ladislav ; Bodor, Róbert ; Troška, Peter ; Horčičiak, Michal ; Masár, Marián GA_googleFillSlot("Horizontal_banner_bottom");
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The Committee of the European Concerted Action for Multiple Sclerosis (Charcot Foundation) organised five workshops to discuss CSF analytical standards in the diagnosis of multiple sclerosis. This consensus report from 12 European countries summarises the results of those workshops. It is hoped that neurologists willconfer with their colleagues in clinical chemistry to arrange the best possible local practice. The most sensitive method for the detection of oligoclonal immunoglobulin bands is isoelectric focusing. The same amounts of IgG in parallel CSF and serum samples are used and oligoclonal bands are revealed with IgG specific antibody staining. All laboratories performing isoelectric focusing should check their technique at least annually using "blind" standards for the five different CSF and serum patterns. Quantitative measurements of IgG production in the CNS are less sensitive than isoelectric focusing. The preferred method for detection of blood-CSF barrier dysfunction is the albumin quotient. The CSFalbumin or total protein concentrations are less satisfactory. These results must be interpreted with reference to the age of the patient and the local method of determination. Cells should be counted. The normal value is no more than 4 cells/pl. Among evolving optional tests, measurement of the combined localsynthesis of antibodies against measles, rubella, and/or varicella zoster could represent a significant advance if it offers higher specificity (not sensitivity) for identifying chronic rather than acuteinflammation. Other tests that may have useful correlations with clinical indices include those for oligoclonal free lightchains, IgM, IgA, or myelin basic protein concentrations.
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Proton magnetic spectroscopy (1H-MRS) investigation was performed on CSF samples of patients with neurological inflammatory diseases including 52 cases of multiple sclerosis (MS). 12 acute idiopathic polyneuropathies, 20 acute meningitides (10 viral and 10 bacterial). Spectra were compared with those acquired in 18 neurological controls. High CSF lactate levels were found in MS patients during clinical exacerbation of relapsing-remitting course (p = 0.036 vs neurological controls). In MS patients with MRI evidence of Gd-enhanced plaques CSF lactate was higher than in patients with MRI inactive plaques (p = 0.017). CSF lactate positivity correlated with number of CSF mononuclear cells in MS patients with clinical activity (p = 0.05) as well as in MS patients with MRI enhancement (p = 0.003). A comparative 1H-MRS investigation in vivo on localized demyelinating areas confirmed an elevated lactate signal in Gd-enhanced (61%) more frequently than in unenhanced (22%) plaques (p = 0.03). MS patients with high lactate signal in active plaques showed high lactate levels in CSF. Increased CSF lactate was found also in patients with acute meningitis and idiopathic polyneuropathy. These data suggest that changes in lactate levels may depend on anaerobic glycolytic metabolism in activated leukocytes during inflammatory diseases. A decrease of CSF formulate levels was found in MS patients during active and inactive clinical phase (p = 0.037, p=0.05 vs neurological controls respectively). Formate changes might be related to a disorder of choline-glycine cycle in MS. 1H-MRS in vivo showed significant increase of choline in acute plaques, whereas a decrease of N-acetyl aspartate was found in chronic plaques; these metabolites are undetectable in CSF. CSF glucose levels were lower in bacterial than in viral meningitis (p = 0.014) and in neurological controls (p = 0.05). These observations suggest that 1H-MRS may be able to detect CSF metabolic impairment in neurological inflammatory diseases. In MS some CSF findings reflect metabolic changes occurring in brain demyelinating areas, and they could be useful foe evaluation of disease activity in different stages of disease evolution.
In a retrospective study of 78 cases of adult meningitis, the CSF lactate was measured on the first spinal tap (ST); 25 had a bacterial meningitis, 28 a viral meningitis; 22 other cases had been on antibiotics prior to admission; 3 cases had meningitis of rare aetiology. The median CSF lactate level among the 25 bacterial cases amounted to 13.6 mmol/l (range: 3.5-24.5) whereas it remained low in the 28 viral cases: 2.7 mmol/l (range: 1.4-4.2). These differences are highly significant. The comparison of the CSF lactate level with the other tests routinely performed showed that the CSF lactate level had the highest sensitivity, specificity and predictive values. The CSF lactate level on the first ST had no prognostic value, but a rapid decrease of the CSF lactate during the treatment is indicative of good prognosis. Among the pretreated cases, a high lactate level could be an indication that bacteria were the causal agents. In conclusion, the measurement of the CSF lactate, quickly performed and inexpensive, is worth performing when a meningitis is suspected, as it appears to be the best way of distinguishing bacterial from non-bacterial meningitis.
The present study was undertaken to examine the possibility that cerebral energy metabolism can be fueled by lactate. As a sole energy substrate, lactate supported normal synaptic function in rat hippocampal slices for hours without any sign of deterioration. Slices that were synaptically silent as a result of glucose depletion could be reactivated with lactate to show normal synaptic function. When slices were exposed to the glycolytic inhibitor iodoacetic acid, lactate-supported synaptic function was unaffected, whereas that supported by glucose was completely abolished. This indicated that lactate was metabolized directly via pyruvate to enter the tricarboxylic acid cycle. Thus, under conditions that lead to lactate accumulation (cerebral ischemia) this "end product" may be a useful alternative as a substrate for energy metabolism.
The stability of lactic acid in cerebrospinal fluid specimens from children with or without infections of the central nervous system was determined. Twenty-six patients were studied. These were ten children with bacterial meningitis, nine with aseptic meningitis and seven without any inflammation of the central nervous system. The specimens were left at room temperature and lactic acid concentration was measured at sequential intervals: 15 minutes, and two, six and 24 hours following their collection. A decline in the concentration was noticed in all specimens. However, the most marked total reduction in lactic acid concentration was noted in specimens obtained from patients with bacterial meningitis. The average reduction in that group was 5 mg/dl after two hours, 11 mg/dl after six hours and 18 mg/dl following 24 hours. Lactic acid concentration remained unchanged up to 72 hours in specimens frozen at -20 degrees C. To prevent misleading results, it is recommended that cerebrospinal fluid specimens not be left at room temperature for prolonged periods of time prior to lactic acid determination.
To analyse various metabolites in human cerebrospinal fluid from healthy controls and patients with multiple sclerosis. Cerebrospinal fluid was obtained from patients by lumbar puncture, frozen, redissolved, and analysed for metabolites by proton nuclear magnetic resonance spectroscopy. Significantly lower values for lactate and glutamine were found in patients with multiple sclerosis in comparison with controls. No significant differences were found between patients with the relapsing-remitting and chronic progressive forms of the disease for any of the metabolites measured. There is a concomitant reduction in both lactate and glutamine in the cerebrospinal fluid of patients with multiple sclerosis compared to controls. This may be related to altered astrocytic metabolism during the disease. The results clearly show the diagnostic potential of magnetic resonance spectroscopy in diseases such as multiple sclerosis.