Does thrombopoiesis in multiple myeloma patients depend on the stage of the disease?

PURPOSE: Infiltration of the bone marrow by neoplastic plasmocytes in multiple myeloma (MM) patients might impair megakaryocytopoiesis. The aim of the study was to evaluate stage-dependent platelet count (PLT) and thrombopoietin (TPO) concentration in comparison to the control group. We also wanted to establish whether TPO might be recognized as a marker of the stage of the disease. MATERIAL/METHODS: The study group consisted of 41 patients (mean age 67.7) with newly diagnosed MM prior to treatment and categorized according to the Durie and Salmon diagnostic classification. The control group consisted of 30 healthy subjects (mean age 65.5). PLT, WBC, RBC and Hb were measured with the use of the haematological analyser. TPO was assayed with the use of ELISA and albumin with the use of the immunonephelometry method. The number of plasma cells in the bone marrow was evaluated in bone marrow smears under light microscopy. RESULTS: PLT was not statistically different as compared the control groups, but was stage-dependent. Thrombocytopenia was observed in the III stage of MM. TPO median was significantly higher in study group than in healthy subjects and it was increasing considerably with the stage of the disease. TPO concentration was negatively correlated with albumin and PLT. AUC for TPO was 0.9764. The number of plasma cells in the bone marrow was considerably increasing with the stage of the disease. CONCLUSIONS: PLT and TPO in MM patients were stage-dependent. Elevated TPO concentration in MM patients might be an unfavourable marker of the stage of the disease.

Bone marrow megakaryocytes, soluble P-selectin and thrombopoietic cytokines in multiple myeloma patients.

The expression of adhesion molecules and other cell-surface molecules is substantial in the communication between plasma cells and bone marrow microenvironment, and may lead to increased proliferation of myeloma cells. Many of the cytokines involved in multiple myeloma (MM) pathogenesis, e.g. thrombopoietin (TPO) and interleukin-6 (IL-6), play a pivotal role in different developmental stages of megakaryocytopoiesis and thrombopoiesis. The principal aim of our study was to explore the relationship between thrombopoietic cytokines, megakaryocytes (MKs) and soluble P-selectin (sP-selectin) levels in MM patients before and after anti-angiogenic treatment. Forty-four patients (20 female and 24 male) with a newly diagnosed MM were examined in three groups, following a division based on the International Staging System, ISS. Plasma levels of TPO, IL-6 and soluble P-selectin (human sP-selectin) were measured by means of ELISA. Bone marrow specimens were studied to determine the number of MKs and the so-called "naked nuclei" (NN), as well as the expression of platelet-derived growth factor (PDGF). The comparison revealed a significantly higher concentration of cytokines and sP-selectin in newly diagnosed MM patients compared to healthy volunteers: for TPO, p=0.01, IL-6, p=0.0005 and sP-selectin, p=0.00008, respectively. Marked differences were observed in the concentration of sP-selectin, expression of PDGF and MKs counts between patients with MM stage I and MM stage III. Statistically meaningful correspondences were also found between MKs versus TPO, NN versus TPO, as well as MKs versus MPV, p=0.009, p=0.004 and p=0.0005, respectively. Furthermore, the analysis exhibited some statistically meaningful divergences between initial concentrations of sP-selectin in subgroups with different response after chemotherapy. The initial concentration of sP-selectin in the group of MM patients with complete or partial remission stood at 31.86 ± 6.13 ng/ml. In the remaining patients (stable disease), the concentration of sP-selectin amounted to 35.15 ± 7.23 ng/ml (p=0.048). We found a correlation between sP-selectin and IL-6 (ρ=0.57, p=0.0004), TPO and IL-6 (ρ=0.46, p=0.001) as well as sP-selectin and TPO (ρ=0.36, p=0.043), and sP-selectin and PDGF (ρ=0.36, p=0.03). Our study has eventually demonstrated that sP-selectin, as a marker of platelet activation, could be a useful marker of maximum response to therapy. Its strong association with another marker like PDGF-AB could further lead to the development of new combinational therapeutic strategies of anti-angiogenic therapy in MM patients.

Expression of P-selectin (CD62P) on platelets after thrombin and ADP in hypotrophic and healthy, full-term newborns.

BACKGROUND: Hypotrophic newborns in comparison with eutrophic newborns demonstrate a reduced blood platelet count and therefore may have haemostasis disorders. Expression of P-selectin (CD62P) on the surface of platelets is a marker of stimulated, activated blood platelets. The ability of platelets to react can be determined after the addition of the following activators: strong (thrombin) and weak (ADP). MATERIALS AND METHODS: We studied 48 hypotrophic newborns, 25 females and 23 males, weighing less than the 10th centile and 55 healthy, full-term newborns, 25 females and 30 males. Expression of CD62P on the surface of platelets was examined in the native state, after the addition of thrombin or ADP. RESULTS: Hypotrophic newborns exhibited almost double the percentage of platelets expressing CD62P compared with the control group, 4.21% versus 2.88%. After the addition of thrombin, the percentage was 31.5% versus 12.5%, p < 0.001, whereas after the addition of ADP, the percentage was 9.54% versus 4.5%, p = 0.002. CONCLUSIONS: Hypotrophic newborns are capable of greater platelet activation in comparison with healthy term newborns. However, gender does not affect the expression of P-selectin.

Multiplexing analysis of the polyspecific intrathecal immune response in multiple sclerosis.

Intrathecal synthesis of the antibodies specific to neurotrofic viruses: measles (M), rubella (R), Varicella-Zoster (Z), and/or H. simplex (H), known as "MRZH-reaction" plays important diagnostic role in multiple sclerosis (MS). Whereas the analysis of the oligoclonal IgG bands provides high sensitivity, the MRZH-reaction shows high specificity, and hence these methods complement each other. For the first time we applied multiplexing bead-based technology to simultaneously analyze cerebrospinal fluid (CSF) and serum concentrations of antibodies against these viruses, and to calculate the antibody specific indices (ASI's). The method shows reasonable precision: intra-assay, 2.9-6.7%, and inter-assay, 2.0-3.2%. The results are comparable with these obtained with other methods (ELISAs), including two runs of the certified external quality control schemes. Eighty-one percent of the MS cases (n=27) and none of the sex- and age-matched controls (n=14), except one subject with "borderline" anti-measles ASI of 1.5, showed intrathecal synthesis of IgG against at least one of the viruses discussed. The ratios of the MRZH-positive cases in the MS group were: 12/22 for M, 12/19 for R, 13/26 for Z, and 7/26 for H. We conclude that the multiplexing technology can be applied as a tool to study the intrathecal immune response in the diagnosis of MS.

Platelet expression of CD62P in hypotrophic newborns.

BACKGROUND: Hypotrophic newborns demonstrate a reduced blood platelet count and therefore may have haemostasis disorders. The antigen density of CD62P on the surface of platelets may indicate the activation of blood platelets. MATERIALS AND METHODS: We have studied 31 hypotrophic newborns, and have divided these into two groups: weighing less than the 5th centile and between the 5th and 10th centiles. The antigen density of CD62P was calculated according to the procedure recommended by DAKO QIFIKIT. RESULTS: Hypotrophic newborns exhibited a median 22 000 of CD62P per platelet. There is a distinct gender difference (female median 29 768, male median 19 044 of CD62P per platelet, p = 0.001). Newborns below the 5th centile demonstrated a median 30 000 of CD62P per platelet, whereas between the 5th and 10th centiles - a median 18 700. A negative correlation (R = -0.53, p = 0.002) was found between the antigen density of CD62P and birth weight. CONCLUSION: Hypotrophy affects the expression of CD62P. There is a negative correlation between the antigen density of CD62P and birth weight.

Study of the mechanisms of aldosterone prothrombotic effect in rats.

INTRODUCTION: We investigated the role of primary haemostasis, fibrinolysis, nitric oxide (NO) and oxidative stress as well as mineralocorticoid receptors (MR) in acute aldosterone prothrombotic action. MATERIALS AND METHODS: Venous thrombosis was induced by stasis in Wistar rats. Aldosterone (ALDO; 10, 30, 100 µg/kg/h) was infused for 1 h. Eplerenone (EPL; 100 mg/kg, p.o.), a selective MR antagonist, was administered before ALDO infusion. Bleeding time (BT) and platelet adhesion to collagen were evaluated. The expression of nitric oxide synthase (NOS), NADPH oxidase, superoxide dismutase (SOD) and plasminogen activator inhibitor (PAI-1) was measured. NO, malonyl dialdehyde (MDA) and hydrogen peroxide (H(2)O(2)) plasma levels were assayed. RESULTS: Significant enhancement of venous thrombosis was observed after ALDO infusion. ALDO shortened BT and increased platelet adhesion. Marked increases were observed in PAI-1, NADPH oxidase and SOD mRNA levels. MDA and H(2)O(2) levels were augmented in ALDO-treated groups, and NOS expression and NO level were decreased. EPL reduced ALDO effects on thrombus formation, primary haemostasis, PAI-1 expression and MDA level. CONCLUSION: Short-term ALDO infusion enhances experimental venous thrombosis in the mechanism involving primary haemostasis, fibrinolysis, NO and oxidative stress-dependent pathways. The MR antagonist only partially diminished the ALDO effects, suggesting the involvement of additional mechanisms.

Cerebrospinal fluid leakage--reliable diagnostic methods.

Prompt diagnosis and early treatment of cerebrospinal fluid (CSF) leakage minimizes the risk of severe complications. In patients presenting with clear fluid nasal discharge it is important to identify the nature of the rhinorrhea. The CSF leakage may occur as post-traumatic, iatrogenic, spontaneous or idiopathic rhinorrhea. The differential diagnosis of CSF rhinorrhea often presents a challenging problem. The confirmation of CSF rhinorrhea and localization of the leakage may be diagnosed by CT, MRI cisternography and MRI cisternography in combination with single photon emission tomography or radioisotopic imaging. Although these methods allow estimation of the CSF leakage with high accuracy, they are expensive and invasive procedures. Therefore, biochemical methods are still used in the differentiation. Although the most common diagnostic method for screening CSF leakage is glucose oxidase, its diagnostic sensitivity and specificity is generally unsatisfactory. False negative results may occur with bacterial contamination and false positive results are common in diabetic patients. Glucose detection is not recommended as a confirmatory test. As such, other biomarkers of the CSF leakage, such as beta-2-transferrin (beta-2 trf) and beta-trace protein (betaTP) are necessary to identify and confirm of this condition.

[Prothrombotic aldosterone action--a new side of the hormone]. / Prozakrzepowe dzialanie aldosteronu--nowe oblicze hormonu.

Recent studies have focused on a new wave of interest in aldosterone due mainly to its growing profile as a local messenger in pathology of the cardiovascular system, rather than its hormonal action. In the last few years strong evidence for a correlation between raised aldosterone level and haemostasis disturbances leading to increased risk of cardiovascular events has been provided. It has been demonstrated that aldosterone contributes to endothelial dysfunction, fibrinolytic disorders and oxidative stress augmentation. It was also shown that chronic aldosterone treatment results in enhanced experimental arterial thrombosis. Our study in a venous model of thrombosis in normotensive rats confirmed that even a short-lasting increase in aldosterone level intensified thrombus formation. One-hour aldosterone infusion shortened bleeding time; increased platelet adhesion to collagen; reduced tissue factor, thrombin activatable fibrinolysis inhibitor, and plasminogen activator inhibitor; and increased plasminogen activator plasma level. A fall in plasma nitric oxide metabolite concentration with a decrease in aortic nitric oxide synthase mRNA level was also observed. Moreover, aldosterone increased hydrogen peroxide and malonyl dialdehyde plasma concentration and augmented NADPH oxidase and superoxide dismutase aortic expression. Therefore, the mechanism of aldosterone prothrombotic action is multiple and involves primary haemostasis activation, procoagulative and antifibrinolytic action, NO bioavailability impairment and oxidative stress augmentation. The effects of aldosterone were not fully abolished by mineralocorticoid receptor blockade, suggesting the involvement of alternative mechanisms in the prothrombotic aldosterone action.

[Platelets haemostatic in patients with multiple myeloma]. / Hemostaza plytkowa u chorych na szpiczaka mnogiego.

Multiple myeloma (MM) is a type of disseminated cancer which derive plasma cells that are immune system cells in bone marrow and produce monoclonal protein. It represents approximately 1% of all cancers, but recent statistics indicate both increasing incidence and earlier age of onset. Haemostatic disorders are an important clinical problem in patients with MM. The most common disturbances symptoms are bleeding and deep-vein thrombosis can due to platelet dysfunction, inhibition of fibrin and increased clearance of coagulation factors connected with monoclonal protein presence. The aim of study is a presentation of disturbances haemostatic in patients with MM, which make up important clinical and diagnostic problems.

Thrombopoiesis in small for gestational age newborns.

Thrombocytopenia in small for gestational age (SGA) newborns may be due to placental vascular pathology, fetal consumptive coagulopathy and platelet destruction, local imbalance of thromboxane A2 causing placental vasoconstriction and platelet aggregation. Thrombopoiesis in SGA newborns is poorly recognized. In 61 SGA newborns we evaluated thrombocytopoiesis in relation to gender and the rate maturity expressed as <5th percentile and <10th percentile. Female newborns demonstrated higher thrombopoietin (TPO) level at 92.06 pg/ml than male newborns at 79.81 pg/ml. Newborns less developed <5th percentile, showed increased TPO level of 92.0 pg/ml in comparison to <10th percentile of 78.0 pg/ml. This observation is more pronounced in female newborns. Contrary to our expectations we did not find any statistically significant differences in the percentage of reticulated platelets (PLRET) and platelets count in relation to gender and <5th percentile or <10th percentile. We can postulate intrauterine hypoxia is responsible for the increase of erythropoietin and impairment of thrombopoiesis in SGA newborns.

[A new look at platelets and microparticles, including their role in haemostatic disorders and progression of neoplastic disease]. / Nowe spojrzenie na plytki krwi i mikroplytki z uwzglednieniem ich roli w zaburzeniach krzepniecia i progresji choroby nowotworowej.

Platelets (PLT) are the smallest yet highly reactive components of the circulatory system. Microvesicles (platelet-derived microvesicles - PMV), also known as microparticles or microplatelets (platelet-derived microparticles - PMP), are released from platelets upon stimulation by thrombin, collagen or others platelet agonists. Both PLT and PMP play a role in haemostasis and mediate signal transmission between cells, especially cancer cells, thus modulating their functions. Moreover, these two platelet populations participate in transcellular exchange of information, affect immune responses and angiogenesis, which may facilitate tumour growth and development of distant metastases. Their role in tumour progression has been recognized, but the mechanism of their action remains still unclear. Assessment of PMP as a diagnostic and prognostic marker in various disorders is currently a subject of intense investigation.

Evaluation of PDGF-AB and sP-selectin concentrations in relation to platelet count in patients with colorectal cancer before and after surgical treatment.

INTRODUCTION: Platelet-derived growth factor (PDGF) and P-selectin, the low-molecular weight proteins located mainly in the platelet alpha-granules, are considered to be biologically active markers of platelet (PLT) activation. OBJECTIVES: The study objective was to assess levels of PDGF-AB and sP-selectin in relation to PLT blood count in patients with colorectal cancer (CRC) who were examined before and after radical surgical treatment of the cancer. PATIENTS AND METHODS: The study involved 38 CRC patients including B1 - 20 patients (T(2-3)N(1)M(0)), B2 -18 patients (T(2-3)N2M0) and 24 age and sex-matched healthy subjects (the control group). Blood samples were collected from the antecubital vein prior to and 3 months after the radical surgery. PDGF-AB and souble (s)P-selectin, the markers of PLT activation, were determined by the immunoenzymatic methods. RESULTS: In CRC patients, the levels of PDGF-AB and sP-selectin were a few times higher, whereas the PLT count was lower as compared to the control group. Moreover, these levels were statistically much higher before, compared to those after the surgery, in patients with a higher grade of clinical and histological differentiation (p <0.05) as well. However, no positive correlation was found between the PLT count and the PDGF-AB and sP-selectin levels. CONCLUSIONS: High levels of PDGF-AB and sP-selectin, the sensitive markers of PLT activation prior to surgical treatment seem to indicate cancer tissue as the source of both PDGF and sP-selectin. For this reason, PDGF-AB and sP-selectin determination may help in early non-invasive CRC evaluation in the future.

[Platelet- derived growth factor--the construction, role and it's receptors]. / Plytkopochodny czynnik wzrostu--budowa, rola i jego receptory.

CONSTRUCTION: The platelet- derived growth factor (PDGF) is a small protein which is produced by many cells. PDGF was originally identified in platelets and in serum. It is a dimeric molecule consisting of disulfide- bonded, structurally similar A- and B- polypeptide chains. There are four isoforms of PDGF: PDGF A, PDGF B, PDFG C and PDGF D. There are purified from the alpha-granules of the platelets. ROLE: PDGF is a critical regulator of mesenchymal cell migration and proliferation. It is essential for angiogenesis, embryogenesis and cancer development and progression. Clinical studies reveal that aberrant expression of PDGF and its receptors is often associated with a variety of disorders including atherosclerosis, fibroproliferative diseases of lungs and kidneys. RECEPTORS: There are two structurally related PDGF- receptors, each with its own variation in signaling mechanism. Each subunit of PDGF binds one receptor subunit, leading to receptor dimerization. The receptors are tyrosine kinases. PDGFR alpha binds all types of isoforms. PDGFR beta can bind only polypeptide B.

[Cell adhesion molecules and their participation in the process of inflammation and cancerogenesis]. / Czasteczki adhezyjne oraz ich udzial w procesie zapalnym i nowotworowym.

Cell adhesion molecules (CAMs) determine the integral part of protein of cell membranes. CAMs mediate in the reception and the transformation of the information from the external environment. Then CAMs mediate in the transfer of the information in the from of the signal to each fine structure. The inflammation process, in which the whole family of cell adhesion molecules takes place, is a state which leads to cancer or tumor metastasis. We observe in the cancerogenesis process a disturbance of the cell adhesion and proliferation, as well as scaled-down integrality between cell and intercellular matrix. CAMs function suggests that they play a very important role in inflammation the neoplasia process. It use can be found in the early pathogenesis cancer disease.

Megakaryocytes and platelets in experimentally induced renovascular hypertension (2K1C) in rats.

INTRODUCTION: Hypertension is one of the most frequently occurring diseases worldwide. Approximately 10% of the population with hypertension reveals the secondary type of the disease. The aim of the study was to evaluate the megakaryocyte-platelet system in the course of renovascular hypertension. MATERIAL/METHODS: An experimental model of hypertension in rats according to Goldblatt was used in the study. The experimental material (blood, bone marrow) was collected in the 4th, 8th, and 16th weeks of the study. Bone marrow megakaryocytes (MKs) were evaluated using immunohistochemical and morphometric methods. Blood platelets were analyzed based on their count (PLT) and mean volume (MPV). Plasma thrombopoietin (TPO) concentration was also assessed. RESULTS: The investigation showed increased numbers of MKs 16 weeks after partial unilateral ligation of the renal artery. Statistically significant increase in platelet count, platelet mass, and the number of MK naked nuclei (NKs) as well as elevation of the circular deviation of the nuclei (CDN) of MKs accompanied the changes. MPV and TPO concentration did not change during the experiment. There was significant positive correlation between the increase in blood pressure and the numbers of MKs and NKs. The number of MKs correlated positively with PLT and CDN. Although TPO plasma level did not change significantly, there was marked negative correlation between plasma TPO concentration and PLT. CONCLUSIONS: Although features of intensified platelet turnover were not observed, on the basis of the study it can be assumed that the megakaryocytic system undergoes changes in the course of renovascular hypertension. This can contribute to blood platelet production and the development of possible hypertension complications.

The effect of gestational age on platelet surface expression of CD62P in preterm newborns.

Hemostasis in preterm newborns is characterized by low reserve functional capacity with special reference to the presence of such risk factors as asphyxia or infection. Platelets play vitally important role in hemostasis. Expression of CD62P is a marker of stimulated or activated blood platelets. The study involved a group of 16 preterm newborns, five girls and 11 boys. DAKO QIFIKIT was applied to calculate the number of these antigens. The mean CD 62P expression was found to be 23,792 per platelet. Correlation was found between antigen density and gestational age r = 0.954, p = 0.01. Evident deficit of P-selectin on the surface of platelets in preterm newborns may be at least in part responsible for platelet dysfunction, with special reference to interaction between circulating leukocytes and combating infection.

Platelet-derived microparticles and platelet count in preterm newborns.

OBJECTIVE: Does formation of platelet-derived microparticles correspond to platelet activation? METHODS: The study was performed in 51 preterm newborns, 25 girls and 26 boys. The control group consisted of 55 term newborns, 25 girls and 30 boys. Blood samples were collected from the umbilical artery. The percentage of platelet-derived microparticles and platelet count were determined using flow cytometric analysis based on the CD61-positive antigen. RESULTS: The percentage of platelet-derived microparticles was higher in preterm newborns (5.46) in comparison to term newborns (4.22, p < 0.01). We found 4.61% of platelet-derived microparticles in preterm female newborns and 6.28% in preterm boys (p < 0.0070). The platelet count was 256 x 10(3) microl in girls and 238 x 10(3) microl in boys. Female healthy term newborns presented higher values of platelet-derived microparticles (4.4%) than male newborns (4.07%, p = 0.4725, table 1). The platelet count in girls was found to be 308 x 10(3) microl and in boys 270 x 10(3) microl. CONCLUSIONS: Higher percentage of platelet-derived microparticles in preterm newborns may provide a compensatory mechanism for the hemostatic system.

Does prematurity affect thrombocytopoiesis?

Data concerning thrombocytopoiesis in newborns are poorly recognized. Platelets have a crucial role in hemostatic physiology, which is deficient in newborns, especially in preterm newborns. A total of 51 preterm newborns (PTN), 25 girls and 26 boys, were recruited for the study. The control group consisted of 25 female and 30 male healthy term newborns (HTN). Plasma thrombopoietin (TPO) was measured using Quantikine human TPO system. Reticulated platelets (PLRET) was estimated by means of Retic-Count Kit. Platelet count (PLT) was determined using Advia(TU) 120 Hematology System. TPO was evidently higher in PTN (110.9 pg/ml) than in HTN (71.5 pg/ml), (p < 0.001). The percentage of reticulated platelets (PLRET) was also twice as high in PTN (3.49%) in comparison to HTN (1.7%), (p < 0.001). The PLT count was lower in PTN (246.7 x 10(3) microL) than in HTN (287.2 x 10(3) microL), (p < 0.01). Increased TPO levels and the percentage of PLRET indicate that thrombocytopoiesis is more active in prematurity. Our finding may be useful in therapeutic strategies.

[SP-selectin and beta-TG as serum markers of platelet activation in menopausal women with depression]. / SP-selektyna i beta-tromboglobulina jako osoczowe markery aktywacji plytek krwi u kobiet z depresja w okresie menopauzy.

UNLABELLED: During activation, blood platelets (PLT) release a number of micromolecular compounds, of which P-selectin and beta-thromboglobulin (beta-TG) are considered the major markers of the activation. The activated platelets and the released micromolecular compounds actively participate in thromboembolic disorders frequently observed in menopause. Low estrogen level in menopausal women is a common cause of depressive disorders. The aim of the study was to compare the state of PLT activation in menopausal women with and without depression. The assessment of PLT activation was based on the concentration of sP-selectin and beta-TG as serum markers of the activation. MATERIAL AND METHODS: Among 65 menopausal women examined, 16 (approx. 25%) had depression. PLT activation was assessed on the basis of sP-selectin and beta-TG levels. The investigation was performed in the low-platelet citrate serum obtained from venous blood collected onto anticoagulant. The levels of beta-TG and sP-selectin were determined using the immunoenzymatic method, with ELISA Kit reagents. RESULTS: In all the women, both with and without depression, the levels of beta-TG and sP-selectin several times exceeded the accepted norms. The concentration of beta-TG was statistically significantly higher (p < 0.05) in women with depression as compared to those with no depressive disorders. CONCLUSIONS: Menopausal women suffering from depression show enhanced intravascular platelet activation. High beta-TG level in women with depression indicates higher risk of thromboembolic disorders in comparison with depression-free women in menopause.

[Cerebrospinal rhinorrhea--etiology, clinical signs and laboratory diagnosis]. / Plynotok nosowy--etiologia, objawy kliniczne oraz postepowanie diagnostyczne.

Last studies have shown unsatisfactory diagnosis of cerebrospinal rhinorrhea. Although the majority of cerebrospinal (CSF) fistulas in the anterior skuli base are traumatic in nature, the minority is non-traumatic or primary. The authors have made an attempt of presenting on the basis of scientific reports of the physiopathology, imagin and diagnosis of cerebrospinal fluid leaks. This article introduces rapid, accurate and non-invasive biochemical methods for detection of cerebrospinal fluid leakage using combined determination of glucose, beta-trace-protein and beta-2-transferrin in secretion and serum. There are presented new invasive techniques for detection and localization of the cerebrospinal fluid leaks: CT and CT with contrast, MR cisternography and MRI cisternography in combination with single photon emission tomography. Finally, discusses different opinion in the management of the problem once it occurs.