Developmental adaptations of γδ T cells and B cells in blood and intestinal mucosa from birth until weaning in Holstein bull calves.

This study aimed to characterize the development of systemic and colon tissue resident B and γδ T cells in newborn calves from birth until weaning. At birth, calves have limited capacity to initiate immune responses, and the immune system gradually matures over time. Gamma delta (γδ) T cells are an important lymphocyte subset in neonatal calves that confer protection and promote immune tolerance. A total of 36 newborn calves were enrolled in a longitudinal study to characterize how systemic and colon tissue resident B and γδ T cells develop from birth until weaning. Blood and colon biopsy samples were collected on d 2, 28, and 42 to determine the proportions of various B and γδ T cell subsets by flow cytometry. We classified γδ T cells into different functional subsets according to the level of expression intensity of the coreceptors WC1.1 (effector function) and WC1.2 (regulatory function). Furthermore, naive B cells were classified based on the expression IgM receptor, and activation state was determined based on expression of CD21 and CD32, 2 receptors with opposing signals involved in B cell activation in early life. Additional colon biopsy samples were used for 16S sequencing, and microbial diversity data are reported. At birth, γδ T cells were the most abundant lymphocyte population in blood, accounting for 58.5% of the lymphocyte pool, after which the proportions of these cells declined to 38.2% after weaning. The proportion of γδ T cells expressing WC1.1 decreased by 50% from d 2 to d 28, whereas no change was observed in the expression of WC1.2. In the colon, there was a 50% increase of γδ T cells after weaning and the proportion of WC1.2+ γδ T cells doubled from d 28 to 42. The proportion of IgM+ B lymphocytes in blood increased from 23.6% at birth to 30% after weaning, were the proportion of B cells expressing CD21 increased by 25%, while the proportion of B cells expressing CD32 decreased by 30%. While no changes were observed for the overall proportion of IgM+ B lymphocytes in the colon, there was a 6-fold increase in the proportion of CD21+ B cells from pre- (d 28) to postweaning (d 42). Microbial diversity increased from d 2 of life to 28 and declined abruptly after weaning. The reduction in microbial diversity during weaning was negatively correlated with the increase in all γδ T cell subsets and CD21+ B cells. These data suggest that developmental adaptations after birth coordinate expansion of γδ T cells to provide early systemic protection, as well as to steer immune tolerance, while B cells mature over time. Additionally, the increase of colonic γδ T cells on d 42 suggests a protective role of these cells during weaning.

A novel method for isolation and flow cytometry analysis of intraepithelial lymphocytes from colon biopsies.

Investigating the immune responses of the intestine in response to different insults is predominantly limited to indirect methods such as circulating markers of intestinal health or gene expression from dissections. We describe here a validated protocol for the isolation and subsequent flow cytometry analysis of intestinal intraepithelial lymphocytes (IEL) from colonic biopsy samples. Colon biopsy samples were collected with endoscopy forceps from Holstein dairy bull calves at d 2, 28, and 42 of life. The biopsies were put into an isolation solution of Hanks' balanced salt solution, and fetal bovine serum followed by digestion solution. The solution was filtered and the flow-through, containing IEL, was stained with fluorescent antibodies for flow cytometry analysis. Density gradient separation of the isolate yielded higher viability and cleaner samples for flow cytometry analysis. Anti-bovine γ chain of the T cell receptor was used to identify populations of gamma delta (γδ) T cells via flow cytometry. In addition, γδ T cell subsets were identified using an anti-bovine antibody against the coreceptor workshop cluster 1. This method allowed for the precise identification of lymphocyte populations and evaluation of the proportion of different subsets of γδ T cells from intestinal IEL over time. The technique described here will allow the research community to characterize intestinal immune function over time and improve our understanding of how different management and nutritional strategies affect intestinal health.

Value of prolonged scrotal drainage after penile prosthesis implantation: a multicenter prospective nonrandomized pilot study.

We aimed to understand the risks and benefits of post-inflatable penile prosthesis (IPP) implantation drainage and optimal duration. Our patients were divided into 3 groups: Group 1 (n = 114) had no drain placed, Group 2 had a drain placed for 24 h (n = 114) and Group 3 had a drain placed for 72 h (n = 117). Postoperative scrotal hematoma and prosthesis infection rates were compared between the groups. The patients from Group 3 demonstrated a statistically significant lower incidence of hematoma on the 10th postoperative day: (n = 1, 0.9%) compared to Group 2: (n = 11, 9.6%) and Group 1: (n = 8, 7%), (p = 0.013). However, on the 3rd postoperative day, there was a statistically significant lower incidence of hematoma in both Groups 3 and 2: (0.9% and 6.1%, respectively) vs. Group 1: (11.4%), (p = 0.004). Hematoma rates followed the same group order after the first day of surgery: 1.7% (n = 2), 5.3% (n = 6), and 8.8% (n = 10), respectively, (p = 0.05). Five patients (4.4%) in Group 1 and four patients (3.5%) in Group 2 developed an IPP associated infection, opposed to only a single patient (0.85%) in Group 3, (p = 0.210). We concluded that prolonged scrotal drainage for 72 h after virgin IPP implantation significantly reduces hematoma and infection rates.

Immunotolerance of dairy heifers in response to repeated exposure to bacterial lipopolysaccharide endotoxin.

Dairy cattle face a variety of stressful events on a daily basis. More specifically, climate change has resulted in more frequent heat stress events that increase the incidence of chronic bacterial infections by inducing conditions like leaky gut syndrome, whereby the integrity of the intestinal epithelium is compromised allowing for luminal bacterial lipopolysaccharide (LPS) endotoxin to infiltrate the host's bloodstream resulting in acute or chronic systemic stimulation of the innate immune system. Repeated exposure to LPS over a short period of time is reported to induce immunotolerance within the host. This LPS tolerance is an essential immunohomeostatic response that can protect against over activation of the inflammatory response during subsequent exposure to LPS. In the present study, Holstein calves (n = 20) were initially stress challenged with either saline, or 100, 200 or 400 ng/kg of LPS administered intramuscular, and again re-challenged with 200 ng/kg of LPS 2-weeks later. Serum was collected every 2 hr for 6 hr to profile changes in circulatory stress biomarkers after the repeated LPS exposures. Heifers that were initially challenged with 100, 200 and 400 ng/kg of LPS demonstrated significantly attenuated cortisol responses in the second challenge (p < 0.01, 0.01 and 0.05, respectively), whereas control animals who previously received saline demonstrated a strong cortisol response at 2 hr after receiving 200 ng/kg of LPS (p < 0.05). The cytokine/chemokine (IL-6, CCL2, CCL3 and CCL4) responses were also attenuated during the LPS rechallenge (p < 0.05). Finally, microRNA expression profiles were determined to assess the epigenetic response to repeated LPS exposure. Interestingly, miR-31 and miR-223 were downregulated in response to the second LPS challenge. The present study demonstrates the dynamic nature of the stress response in dairy cattle as it relates to the development of LPS tolerance. Understanding the roles of various stress biomarkers in the context of innate immune cell tolerance is essential for evaluating their impact on immune system homeostasis.

Dynamic changes in Holstein heifer circulatory stress biomarkers in response to lipopolysaccharide immune challenge.

Dairy cattle routinely face a variety of stressors. For example, climate change has resulted in more frequent heat stress events that increase the incidence of bacterial infections by inducing conditions like leaky gut syndrome, whereby the integrity of the intestinal epithelium is compromised allowing for luminal bacteria and their membrane components to infiltrate the host's bloodstream resulting in systemic inflammation. Lipopolysaccharide (LPS) is a well-characterized and biologically relevant microbe-associated molecular pattern (MAMP) that makes up the outer membrane of pathogenic and commensal Gram-negative bacteria and is known to contribute to inflammatory disorders including mastitis, acidosis and septicemia. In the present study, Holstein heifers (n = 20) were randomly allocated into different treatment groups receiving saline, 100, 200 or 400 ng/kg of LPS intramuscularly to create an experimentally induced endotoxemic state. Serum was collected hourly for 8 hr and then again at 24 hr to profile changes in circulatory stress biomarkers. All LPS -challenged animals demonstrated distinct cortisol responses 2 hr post-LPS challenge, and in the 200 ng/kg and 400 ng/kg of LPS treatments cortisol concentrations remained significantly induced for up to 4 hr. Rectal temperature was significantly increased for heifers challenged with 100 and 200 ng/kg of LPS at 2 and 4 hr as compared to their pre-challenge temperature. All LPS-challenged animals demonstrated marked leukopenia and thrombocytopenia as compared to the saline control animals. A total of 8 cytokines, including TNFα, and IL-10, were found to be induced between 2 and 4 hr. Finally, we report that miR-1246, miR-223, miR-29 and miR-31 were significantly induced in animals challenged with LPS as compared to the saline controls. The present study demonstrated that the stress response in dairy heifers is dynamic and there are peak windows of time when cortisol, cytokines and also miRNA are induced, and blood cells are sequestered as part of the systemic inflammatory response. Variability in the response to LPS warrants further investigation in dairy cattle to better understand the contribution of genetics and associations between LPS-induced stress and health and performance.

GFAP and S100B are biomarkers of traumatic brain injury: an observational cohort study.

BACKGROUND: Biomarker levels in blood after traumatic brain injury (TBI) may offer diagnostic and prognostic tools in addition to clinical indices. This study aims to validate glial fibrillary acidic protein (GFAP) and S100B concentrations in blood as outcome predictors of TBI using cutoff levels of 1.5 µg/L for GFAP and 1.13 µg/L for S100B from a previous study. METHODS: In 79 patients with TBI (Glasgow Coma Scale score [GCS] ≤12), serum, taken at hospital admission, was analyzed for GFAP and S100B. Data collected included injury mechanism, age, gender, mass lesion on CT, GCS, pupillary reactions, Injury Severity Score (ISS), presence of hypoxia, and hypotension. Outcome was assessed, using the Glasgow Outcome Scale Extended (dichotomized in death vs alive and unfavorable vs favorable), 6 months post injury. RESULTS: In patients who died compared to alive patients, median serum levels were increased: GFAP 33.4-fold and S100B 2.1-fold. In unfavorable compared to favorable outcome, GFAP was increased 19.8-fold and S100B 2.1-fold. Univariate logistic regression analysis revealed that mass lesion, GFAP, absent pupils, age, and ISS, but not GCS, hypotension, or hypoxia, predicted death and unfavorable outcome. Multivariable analysis showed that models containing mass lesion, pupils, GFAP, and S100B were the strongest in predicting death and unfavorable outcome. S100B was the strongest single predictor of unfavorable outcome with 100% discrimination. CONCLUSION: This study confirms that GFAP and S100B levels in serum are adjuncts to the assessment of brain damage after TBI and may enhance prognostication when combined with clinical variables.

A mathematical model gives insights into the effects of vitamin B-6 deficiency on 1-carbon and glutathione metabolism.

We experimented with a mathematical model for 1-carbon metabolism and glutathione (GSH) synthesis to investigate the effects of vitamin B-6 deficiency on the reaction velocities and metabolite concentrations in this metabolic network. The mathematical model enabled us to independently alter the activities of each of the 5 vitamin B-6-dependent enzymes and thus determine which inhibitions were responsible for the experimentally observed consequences of a vitamin B-6 deficiency. The effect of vitamin B-6 deficiency on serine and glycine concentrations in tissues and plasma was almost entirely due to its effects on the activity of glycine decarboxylase. The effect of vitamin B-6 restriction on GSH concentrations appeared to be indirect, arising from the fact that vitamin B-6 restriction increases oxidative stress, which, in turn, affects several enzymes in 1-carbon metabolism as well as the GSH transporter. Vitamin B-6 restriction causes an abnormally high and prolonged homocysteine response to a methionine load test. This effect appeared to be mediated solely by its effects on cystathionine beta-synthase. Reduction of the enzymatic activity of serine hydroxymethyltransferase (SHMT) had negligible effects on most metabolite concentrations and reaction velocities. Reduction or total elimination of cytoplasmic SHMT had a surprisingly moderate effect on metabolite concentrations and reaction velocities. This corresponds to the experimental findings that a reduction in the enzymatic activity of SHMT has little effect on 1-carbon metabolism. Our simulations showed that the primary function of SHMT was to increase the rate by which the glycine-serine balance was reequilibrated after a perturbation.

Glial and neuronal proteins in serum predict outcome after severe traumatic brain injury.

OBJECTIVE: To study the ability of glial (glial fibrillary acidic protein [GFAP] and S100b) and neuronal (neuron specific enolase [NSE]) protein levels in peripheral blood to predict outcome after severe traumatic brain injury. METHODS: Eighty-five patients with severe traumatic brain injury (admission Glasgow Coma Score [GCS] < or = 8) were included. Blood samples taken at the time of hospital admission were analyzed for S100b, GFAP, and NSE. Data collected included demographic and clinical variables. Outcome was assessed using the Glasgow Outcome Scale (GOS) at 6 months post injury. RESULTS: The median serum levels of S100b, GFAP, and NSE were raised 18.3 fold (S100b), 4.6 fold (GFAP), and twofold (NSE) compared to normal reference values. S100b, GFAP, and NSE serum levels correlated significantly with the injury severity score and CT findings but not with age, sex, or GCS. S100b, GFAP, and NSE levels were significantly higher in patients who died or had a poor outcome 6 months post injury than in those who were alive or had good outcome. S100b level >1.13 microg/L was the strongest predictor of death with 100% discrimination, but GFAP (>1.5 microg/L) and NSE (>21.7 microg/L) levels also strongly predicted death (adjusted odds ratios 5.82 [for GFAP] and 3.91 [for NSE]). S100b, GFAP, and NSE all strongly predicted poor outcome (adjusted odds ratios 5.12 [S100b], 8.82 [GFAP], and 3.95 [NSE]). CONCLUSIONS: These results suggest that determination of serum levels of glial and neuronal proteins may add to the clinical assessment of the primary damage and prediction of outcome after severe traumatic brain injury.

Protein S-100B, neuron-specific enolase (NSE), myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP) in cerebrospinal fluid (CSF) and blood of neurological patients.

In this study, data about protein S-100B, neuron-specific enolase, myelin basic protein and glial fibrillary acidic protein in cerebrospinal fluid and blood of patients with an acute or chronic progressive neurological disorder with brain damage are reviewed. Especially in disorders with acute brain damage, determination of these proteins in CSF and blood can be helpful to establish structural and/or functional brain damage to determine severity and prognosis of the disease process and to monitor treatment effects.

Peri-operative levels of s-100 protein in serum: marker for surgical manipulation and postoperative complications.

Although minimally invasive neurosurgical techniques are highly sophisticated nowadays, almost any operative procedure causes an inevitable surgical trauma to the brain. As a consequence unfavorable functional outcomes are not rare. Intraoperative biochemical monitoring can be helpful first to detect but also to prevent brain damage. We investigated if serum S-100 protein (S-100) levels are a reliable marker for the extent of acute cerebral damage caused by surgical trauma or postoperative complication. S-100 is present in the cytosol of glial cells. This protein leaks into the extracellular space after cell damage and can be detected both in the cerebrospinal fluid (CSF) and serum. To determine S-100 protein levels, serum samples from 20 patients with various intracranial tumors were collected before surgery, and at one day, as well as at seven days after surgery. It was hypothesised that the size of the tumor-brain contact surface (TBCS) was closely related to the dimension of the surgical trauma. TBCS was measured from radiological imaging. The pre- and postoperative (day 1 and day 7) clinical condition of each patient was assessed. The S-100 levels were correlated with the TBCS and the clinical condition. Levels of S-100 on day 1 and day 7 were significantly higher as compared with levels on day 0 ( p = 0.02, respectively p = 0.01). There was a significant relationship between rise of S-100 level and worsening of clinical condition between day 0 and day 1 ( p = 0.001). Also a significant positive relationship between TBCS and the level of S-100 could be found on day 1 and on day 7 ( R = 0.71, p = 0.0009, respectively R = 0.73, p = 0.004). Furthermore, a significant relationship between the rise of S-100 level between day 0 and day 1, as well as between day 0 and day 7, and TBCS could be documented ( R = 0.61, p = 0.01, respectively R = 0.64, p = 0.005). In conclusion, serum S-100 levels are a reliable marker for acute or recent CNS damage caused by neurosurgical manipulation or as a result of secondary postoperative complications. Therefore, intraoperative monitoring of serum S-100 levels seems very promising. In such a setting the negative effects of surgical manipulation can be measured instantaneously, which should bring the neurosurgeon to change his strategy. As a consequence the surgical trauma can be minimized and functional outcome can be optimized.

Intraoperative values of S-100 protein, myelin basic protein, lactate, and albumin in the CSF and serum of neurosurgical patients.

OBJECTIVES: To assess the concentrations of S-100 protein, myelin basic protein (MBP), and lactate, and the (CSF)/serum albumin ratio (Qalb) during intracranial neurosurgical procedures. METHODS: Samples of CSF from 91 patients with various CNS diseases were obtained by aspiration of cisternal CSF at the beginning of surgery (before starting surgical manipulation of the brain) and concentrations of S-100 protein, MBP, and lactate, and Qalb were determined. At the same time blood was sampled for determination of serum S-100 protein concentration. Patients were divided into three groups according to the aetiology of their CNS disease (intracranial haemorrhage, n=11; benign intracranial mass lesion, n=52; malignant neoplastic disease, n=28). Radiological and intraoperative characteristics were documented. RESULTS: In each of these three groups median values of all four CSF variables measured were raised. The occurrence of brain oedema and a midline shift correlated significantly with raised concentrations of MBP and Qalb. Breaching of the arachnoid layer, documented at surgery for benign lesions, correlated with higher concentrations of MBP, lactate, CSF S-100 protein, and Qalb. CONCLUSIONS: Intraoperative values of S-100 protein, MBP, lactate, and Qalb are increased in patients with intracranial haemorrhage, benign intracranial mass lesion, and malignant neoplastic disease. Breaching of the arachnoid layer and oedema is associated with higher concentrations of some of the aforementioned proteins. These biochemical data can serve as a basis for further research into CSF specific proteins.

S100B protein, glia and Gilles de la Tourette syndrome.

Activated glial cells play an important role in a variety of neurological disorders. This study examines S100B protein levels in the serum of patients with Gilles de la Tourette syndrome, as potential marker for glial cell function. Two groups of children were examined: 61 reference patients and 33 patients with Gilles de la Tourette syndrome. It was found that S100B serum concentrations in the reference group decrease with increasing age. Furthermore it was found that the mean S100B concentration in serum of children with Gilles de la Tourette syndrome is significantly higher than in the reference group. These preliminary results suggest that glial tissue might be involved in the pathophysiology of the syndrome.

Release of glial tissue-specific proteins after acute stroke: A comparative analysis of serum concentrations of protein S-100B and glial fibrillary acidic protein.

BACKGROUND AND PURPOSE: This study was aimed at the comparative analysis of serum concentrations of glial fibrillary acidic protein (GFAP) and protein S-100B in patients with acute stroke. METHODS: We investigated 32 patients with stroke symptoms consistent with cerebral ischemia in the anterior territory of vascular supply. Serial venous blood samples were taken after admission to the hospital and during the first 4 days after onset of stroke. Evaluation of lesion topography and volume of infarcted brain area was based on cranial CT data. The patients' clinical status was consecutively evaluated by the National Institutes of Health Stroke Scale (NIHSS) and the Barthel Index score at discharge from the hospital. RESULTS: Protein S-100B and GFAP release was found to be significantly correlated (r=0.96; P:<0.001). The release of both biochemical markers was associated with the volume of brain lesions (S-100B: r=0.957, P:<0.0001; GFAP: r=0.955, P:<0.0001) and the neurological status at discharge from the hospital (S-100B: r=0.821, P:=0.0002; GFAP: r=0.717, P:=0.0003). The highest correlation between both S-100B and GFAP serum concentration and Barthel score was calculated at the last time of blood sampling, 4 days after stroke onset (S-100B: r=0.621, P:<0.001; GFAP: r=0.655, P:<0.001). The release of both astroglia derived proteins differed between different subtypes of stroke. GFAP was found to be a more sensitive marker of brain damage in patients with smaller lacunar lesions or minor strokes. CONCLUSIONS: Our results indicate that postischemic release patterns of GFAP and S-100B protein may allow insight into the underlying pathophysiology of acute cerebral infarcts and may be used as a valuable tool of clinical stroke treatment.

Cerebrospinal fluid C3 and C4 indexes in immunological disorders of the central nervous system.

OBJECTIVES: Validation of cerebrospinal fluid (CSF) indexes as a measure for intrathecal C3 and C4 production. Examination of their role in differential diagnosis of immunological disorders of the central nervous system (CNS). MATERIAL AND METHODS: Correlative study in controls (low back pain without disk herniation) between the CSF/serum ratio (Q) for albumin, and Q C3 and Q C4. Comparative study of C3 and C4 indexes in patients with CNS dysfunction due to relapsing-remitting (RR) multiple sclerosis (MS), secondary progressive (SP) MS, systemic lupus erythematosus (SLE), and human immunodeficiency virus (HIV) infection. RESULTS: Strong and statistically highly significant correlations between Q albumin and Q C3 (r=0.89, P=0.0001), and Q C4 (r=0.68, P= 0.0001). In MS patients decreased mean values for serum (RR, SP) and CSF (RR) C3, and increased C3 index mean value (RR, SP). In CNS SLE increase of mean C3 and C4 index values. In CNS HIV increase of mean C3 and C4 index values, and CSF C3 and C4 concentrations. Most individual index values were within the reference range. CONCLUSION: CSF index is a valid tool to detect intrathecal C3 or C4 production. C3 or C4 index contributes little to the differential diagnosis of immunological CNS disorders. C3 might play a pathogenic role in various immunological CNS disorders.

Composite cerebrospinal fluid score in relapsing-remitting and secondary progressive multiple sclerosis.

We investigated whether cerebrospinal fluid (CSF) analysis may differentiate between relapsing-remitting (RR) and secondary progressive (SP) multiple sclerosis (MS). In 17 RR and 16 SP patients we determined: albumine CSF/PB ratio; mononuclear cell (MNC) number, CD4+, CD8+, and B1+ subsets, CD4+/CD8+ ratio; IgG, IgG index, IgM, IgM index, complement components C3 and C4, and C3 and C4 indexes; myelin basic protein; neuron-specific enolase (NSE); S100; and lactate. For each parameter the statistical distance was calculated. Then, using linear discriminant analysis, we computed a discriminant score, including only variables with a P value less than or equal to 0.15: albumin CSF/PB ratio, MNC number, IgM, IgM index, C3, C4, NSE, S100, and lactate. The discriminant score allocated all 17 RR patients to the RR group and 15 of 16 SP patients to the SP group. We conclude that RR and SP MS patients differ with respect to CSF profile and that in individual patients a composite CSF score may differentiate between RR and SP MS.

Myelin basic protein in CSF as indicator of disease activity in multiple sclerosis.

There is an evident need for a quantitative laboratory marker for ascertaining disease activity and treatment effects in multiple sclerosis (MS) patients. Activity of the disease process in MS is accompanied by myelin breakdown and appearance of myelin basic protein (MBP) in cerebrospinal fluid (CSF). In this paper MBP in CSF of relapsing-remitting (RR) MS patients is reviewed. MBP in CSF is a fragment containing an epitope corresponding to amino acid residues 45-89 of the native molecule. From several relevant studies about CSF MBP in RR MS the following relations can be concluded: CSF MBP levels in active MS patients are frequently increased (45-100%), remain increased until 5 to 6 weeks after onset symptoms and are higher in polysymptomatic exacerbations and correlate with number of gadolinium-enhanced (Gd) lesions on MRI, severity of relapses, EDSS score and CSF intrathecal IgM synthesis. After an intravenous methylprednisolone treatment the increased CSF MBP levels return to normal values and reduction in CSF MBP is related to reduction in EDSS score, number of Gd lesions and CSF intrathecal IgM synthesis.

Abnormalities of biogenic amines affecting the metabolism of serotonin and catecholamines.

This paper describes the relevance of measuring biogenic amine metabolites in cerebrospinal fluid in order to detect inborn errors affecting catecholamines and serotonin biosynthesis. Defects in tetrahydrobiopterin and a deficiency of aromatic L-amino acid decarboxylase, tyrosine hydroxylase or dopamine-beta-hydroxylase are candidate inborn errors for neurotransmitter metabolites screening. This investigation has to be considered in any child with motor retardation and extrapyramidal signs.

Cerebrospinal fluid analysis differentiates between relapsing-remitting and secondary progressive multiple sclerosis.

OBJECTIVES: To find whether CSF analysis may differentiate between relapsing-remitting and secondary progressive multiple sclerosis. METHODS: In 17 patients with relapsing-remitting and 16 patients with secondary progressive multiple sclerosis, all without current or recent relapses, albumin CSF: peripheral blood ratio, mononuclear cell number, CD4+, CD8+, and B1+ subsets, CD4+:CD8+ ratio, IgG, IgG index, IgM, IgM index, complement components C3 and C4, and C3 and C4 indices, myelin basic protein, neuron specific enolase, S100, and lactate were determined. For each measure the statistical distance measure D2 was calculated. For computation of a discriminant score variables with a P value< or =0.15 were included (two sided univariate t test). These were albumin CSF: peripheral blood ratio, mononuclear cell number, IgM, IgM index, C3, C4, neuron specific enolase, S100, and lactate. Simultaneous distributions of the variables were compared between both groups (multivariate t test) and a discriminant score was computed (linear discriminant analysis). RESULTS: The discriminant score allocated all 14 relapsing-remitting patients to the relapsing-remitting group (positive score) and 12 of 13 secondary progressive patients to the secondary progressive group (negative score). One secondary progressive patient was allocated to the relapsing-remitting group. CONCLUSIONS: Patients with relapsing-remitting or secondary progressive multiple sclerosis differ in CSF profile and CSF analysis may help to differentiate between relapsing-remitting and secondary progressive multiple sclerosis.

Neuron-specific enolase, S-100 protein, myelin basic protein and lactate in CSF in dementia.

The pattern of injury of the specific cell structures of the central nervous system (CNS) is different in the various types of the dementia syndrome. We challenged the hypothesis that this could be reflected in specific patterns of brain-specific proteins in the cerebrospinal fluid (CSF). The neuron-specific enolase (NSE), S-100, myelin basic protein (MBP) and lactate levels were retrospectively analyzed in the CSF of 159 patients with various types of dementia. A previous study from our department demonstrated age-related reference values for the brain-specific proteins in the CSF. The present study affirmed the strikingly high NSE and S-100 values in the CSF of patients with autopsydiagnosed Creutzfeld-Jacob disease: NSE, S-100 and MBP levels in the CSF of patients with various other types of dementia, and controls, did not differ significantly. Therefore we concluded that a single determination of CSF concentrations of these brain-specific proteins were of little value in the differential diagnosis of the dementia syndrome. In the diagnosis of normal pressure hydrocephalus increased levels of CSF lactate may be helpful.