The Experts below are selected from a list of 96 Experts worldwide ranked by ideXlab platform
Bibiana Bielekova - One of the best experts on this subject based on the ideXlab platform.
-
intrathecal not systemic inflammation is correlated with multiple sclerosis severity especially in progressive multiple sclerosis
Frontiers in Neurology, 2019Co-Authors: Joshua L Milstein, Christopher Barbour, Kayla Jackson, Peter Kosa, Bibiana BielekovaAbstract:Objective: To test the hypothesis that Multiple Sclerosis (MS) patients have increased peripheral inflammation compared to healthy donors and that this systemic activation of the immune system, reflected by acute phase reactants (APRs) measured in the blood, contributes to intrathecal inflammation, which in turn contributes to the development of disability in MS. Methods: Eight serum APRs measured in a prospectively-collected cross-sectional cohort with a total of 51 healthy donors and 291 untreated MS patients were standardized and assembled into related biomarker clusters to derive global measures of systemic inflammation. The resulting APR clusters were compared between diagnostic categories and correlated to equivalently-derived cerebrospinal fluid (CSF) biomarkers of innate and adaptive immunity. Finally, correlations were calculated between biomarkers of systemic and intrathecal inflammation and MS severity measures, which predict future rates of disability progression. Results: While two blood APR clusters were elevated in MS patients, only one exhibited a weak correlation with MS severity. All CSF inflammation clusters, except CSF Albumin, correlated with at least one measure of MS severity, with biomarkers of humoral adaptive immunity exhibiting the strongest correlations, especially in Progressive MS. Conclusion: Systemic inflammation does not appear to be strongly associated with intrathecal inflammation in MS. Positive correlations between markers of intrathecal inflammation, especially of humoral immunity, with MS severity measures support a pathogenic role of intrathecal (compartmentalized) inflammation in central nervous system tissue destruction, including in Progressive MS.
M Gronning - One of the best experts on this subject based on the ideXlab platform.
-
cerebrospinal fluid in the diagnosis of multiple sclerosis a consensus report
Journal of Neurology Neurosurgery and Psychiatry, 1994Co-Authors: Magnus Andersson, Jose C Alvarezcermeno, Giorgio Bernardi, I Cogato, Pam Fredman, J L Frederiksen, S Fredrikson, Paolo Gallo, Lm Grimaldi, M GronningAbstract: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 will confer 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 CSF Albumin 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/microliters. Among evolving optional tests, measurement of the combined local synthesis 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 acute inflammation. Other tests that may have useful correlations with clinical indices include those for oligoclonal free light chains, IgM, IgA, or myelin basic protein concentrations.
Joshua L Milstein - One of the best experts on this subject based on the ideXlab platform.
-
intrathecal not systemic inflammation is correlated with multiple sclerosis severity especially in progressive multiple sclerosis
Frontiers in Neurology, 2019Co-Authors: Joshua L Milstein, Christopher Barbour, Kayla Jackson, Peter Kosa, Bibiana BielekovaAbstract:Objective: To test the hypothesis that Multiple Sclerosis (MS) patients have increased peripheral inflammation compared to healthy donors and that this systemic activation of the immune system, reflected by acute phase reactants (APRs) measured in the blood, contributes to intrathecal inflammation, which in turn contributes to the development of disability in MS. Methods: Eight serum APRs measured in a prospectively-collected cross-sectional cohort with a total of 51 healthy donors and 291 untreated MS patients were standardized and assembled into related biomarker clusters to derive global measures of systemic inflammation. The resulting APR clusters were compared between diagnostic categories and correlated to equivalently-derived cerebrospinal fluid (CSF) biomarkers of innate and adaptive immunity. Finally, correlations were calculated between biomarkers of systemic and intrathecal inflammation and MS severity measures, which predict future rates of disability progression. Results: While two blood APR clusters were elevated in MS patients, only one exhibited a weak correlation with MS severity. All CSF inflammation clusters, except CSF Albumin, correlated with at least one measure of MS severity, with biomarkers of humoral adaptive immunity exhibiting the strongest correlations, especially in Progressive MS. Conclusion: Systemic inflammation does not appear to be strongly associated with intrathecal inflammation in MS. Positive correlations between markers of intrathecal inflammation, especially of humoral immunity, with MS severity measures support a pathogenic role of intrathecal (compartmentalized) inflammation in central nervous system tissue destruction, including in Progressive MS.
Elisabeth Bech Skriver - One of the best experts on this subject based on the ideXlab platform.
-
blood brain barrier integrity in patients with cerebral infarction investigated by computed tomography and serum CSF Albumin
Acta Neurologica Scandinavica, 2009Co-Authors: Suad Alkassab, Tom Skyhoj Olsen, Elisabeth Bech SkriverAbstract:Measurements of CSF-Albumin, and S/CSF-Albumin in two groups of patients with small and large infarcts failed to show BBB damage to Albumin in about one half of the patients. No significant difference was found between the two groups of patients in regard to the above-mentioned parameters. The localization of the infarcts (close to the CSF or deep in the brain) did not influence the S/CSF-Albumin. No correlation was found between the S/CSF-Albumin and the time interval between the onset of the stroke and the lumbar puncture within 96 h. Some suggestions are put forward to explain the discrepancies between the CT-scan and S/CSF-Albumin in the assessment of BBB damage.
Kaj Blennow - One of the best experts on this subject based on the ideXlab platform.
-
CSF evidence of pericyte damage in alzheimer s disease is associated with markers of blood brain barrier dysfunction and disease pathology
Alzheimer's Research & Therapy, 2019Co-Authors: James Scott Miners, Kaj Blennow, Patrick G Kehoe, Seth Love, Henrik ZetterbergAbstract:We aimed to assess the relationship between levels of a cerebrospinal fluid (CSF) marker of pericyte damage, soluble platelet-derived growth factor receptor β (sPDGFRβ) and CSF markers of blood-brain barrier (BBB) integrity (CSF Albumin and CSF/serum Albumin ratio) and disease pathology (reduced CSF Aβ42 and elevated CSF total and phosphorylated tau) in Alzheimer’s disease (AD). sPDGFRβ and Albumin were measured by sandwich ELISA in ante-mortem CSF from 39 AD and 39 age-matched controls that were grouped according to their biomarker profile (i.e. AD cases t-tau > 400 pg/mL, p-tau > 60 pg/mL and Aβ42 < 550 pg/mL). sPDGFRβ was also measured in matched serum and CSF samples (n = 23) in a separate neurologically normal group for which the CSF/serum Albumin ratio had been determined. CSF sPDGFRβ level was significantly increased in AD (p = 0.0038) and correlated positively with Albumin (r = 0.45, p = 0.007), total tau (r = 0.50, p = 0.0017) and phosphorylated tau (r = 0.41, p = 0.013) in AD but not in controls. CSF sPDGFRβ did not correlate with Aβ42. Serum and CSF sPDGFRβ were positively correlated (r = 0.547, p = 0.0085) in the independent neurologically normal CSF/serum matched samples. We provide further evidence of an association between pericyte injury and BBB breakdown in AD and novel evidence that a CSF marker of pericyte injury is related to the severity of AD pathology.
-
evidence for sex difference in the CSF plasma Albumin ratio in 20 000 patients and 335 healthy volunteers
Journal of Cellular and Molecular Medicine, 2018Co-Authors: Cristina Parradofernandez, Kaj Blennow, M Hansson, Valerio Leoni, Angel Cedazominguez, Ingemar BjorkhemAbstract:Given sex-related differences in brain disorders, it is of interest to study if there is a sex difference in the permeability of the blood-cerebrospinal fluid barrier (BCSFB) and the blood-brain barrier (BBB). The CSF/serum Albumin ratio (QAlb ) is a standardized biomarker that evaluates the function of these barriers. In previous studies, contradictory results have been reported with respect to sex difference using this quotient, possibly because of small population sizes and heterogeneity with respect to ages. QAlb measurements in more than 20 000 patients between 1 and 90 years visiting our hospitals revealed a significant sex difference in all age groups also when excluding patients with pathologically high CSF Albumin > 400 mg/L. Similar pattern was found in 335 healthy volunteers in similar age intervals. Although also other factors are likely important, our observation is consistent with lower integrity of the brain barriers in males. If the difference in QAlb is caused mainly by a difference in barrier function, this may require different drug doses and strategies for efficient central nervous system (CNS) delivery in males and females, as well as it may indicate differences in brain metabolism. Moreover, our study emphasizes that different reference values should be used both for different ages and sexes.
-
cerebrospinal fluid markers of brain injury inflammation and blood brain barrier dysfunction in cardiac surgery
The Annals of Thoracic Surgery, 2012Co-Authors: Bjorn Reinsfelt, Kaj Blennow, Henrik Zetterberg, Svenerik Ricksten, Johan Fredenlindqvist, Anne WesterlindAbstract:Background Neurocognitive dysfunction occurs frequently after open-heart surgery. Cerebral microembolization, inflammation, blood-brain barrier (BBB) dysfunction, and impaired cerebral oxygenation are considered among possible etiologies. The relationships between intraoperative microembolic signals and the release of cerebrospinal fluid (CSF) markers of inflammation, neuronal and glial cell injuries, and BBB function were evaluated after cardiac surgery with cardiopulmonary bypass. Methods Ten patients undergoing aortic valve replacement were included. The CSF was obtained the day before and 24 hours after surgery for assessment of neuronal damage (neuron-specific enolase, total tau, and neurofilament light chain protein), glial cell injury (S-100B, glial fibrillary acidic protein), BBB integrity (CSF to serum Albumin ratio) and cytokines (interleukin-6, interleukin-8). Intraoperative extent of microemboli and their occurrence were described using the transcranial Doppler technique. Results Intraoperatively, 354 ± 79 microemboli were detected; 81% after release of the aortic cross clamp. The S-100B and glial fibrillary acidic protein increased by 35% ( p p = 0.055), respectively. Neuron-specific enolase, total tau, and neurofilament light chain protein, were not significantly affected by the surgery. The CSF Albumin increased by 13% ( p p p = 0.011). There was a 3.5- and 12-fold increase in interleukin-6 ( p p Conclusions Cardiac surgery with cardiopulmonary bypass causes cerebral inflammation, glial cell injury, and BBB dysfunction without biochemical signs of neuronal damage. These changes are not associated with intraoperative microembolization.