Individual blood-brain barrier phenylalanine transport determines clinical outcome in phenylketonuria

2001 ◽  
Vol 50 (4) ◽  
pp. 463-467 ◽  
Author(s):  
Josef Weglage ◽  
Dirk Wiedermann ◽  
Jonas Denecke ◽  
Reinhold Feldmann ◽  
Hans-Georg Koch ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain ◽  
Phenylalanine Transport

No evidence for individual blood-brain barrier phenylalanine transport to influence clinical outcome in typical phenylketonuria patients

2002 ◽  
Vol 52 (3) ◽  
pp. 382-383 ◽  
Author(s):  
Joachim Pietz ◽  
Andr� Rupp ◽  
Peter Burgard ◽  
Chris Boesch ◽  
Roland Kreis
Keyword(s):  
Clinical Outcome ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain ◽  
Phenylalanine Transport

scholarly journals Combined Perfusion and Permeability Imaging Reveals Different Pathophysiologic Tissue Responses After Successful Thrombectomy

2021 ◽  
Author(s):  
Arne Potreck ◽  
Matthias A. Mutke ◽  
Charlotte S. Weyland ◽  
Johannes A. R. Pfaff ◽  
Peter A. Ringleb ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Blood Brain Barrier ◽  
Hemorrhagic Transformation ◽  
Brain Barrier ◽  
Dynamic Susceptibility ◽  
Blood Brain Barrier Disruption ◽  
Flow Maps ◽  
Blood Brain ◽  
Patients At Risk ◽  
Brain Barrier Disruption

AbstractDespite successful recanalization of large-vessel occlusions in acute ischemic stroke, individual patients profit to a varying degree. Dynamic susceptibility-weighted perfusion and dynamic T1-weighted contrast-enhanced blood-brain barrier permeability imaging may help to determine secondary stroke injury and predict clinical outcome. We prospectively performed perfusion and permeability imaging in 38 patients within 24 h after successful mechanical thrombectomy of an occlusion of the middle cerebral artery M1 segment. Perfusion alterations were evaluated on cerebral blood flow maps, blood-brain barrier disruption (BBBD) visually and quantitatively on ktrans maps and hemorrhagic transformation on susceptibility-weighted images. Visual BBBD within the DWI lesion corresponded to a median ktrans elevation (IQR) of 0.77 (0.41–1.4) min−1 and was found in all 7 cases of hypoperfusion (100%), in 10 of 16 cases of hyperperfusion (63%), and in only three of 13 cases with unaffected perfusion (23%). BBBD was significantly associated with hemorrhagic transformation (p < 0.001). While BBBD alone was not a predictor of clinical outcome at 3 months (positive predictive value (PPV) = 0.8 [0.56–0.94]), hypoperfusion occurred more often in patients with unfavorable clinical outcome (PPV = 0.43 [0.10–0.82]) compared to hyperperfusion (PPV = 0.93 [0.68–1.0]) or unaffected perfusion (PPV = 1.0 [0.75–1.0]). We show that combined perfusion and permeability imaging reveals distinct infarct signatures after recanalization, indicating the severity of prior ischemic damage. It assists in predicting clinical outcome and may identify patients at risk of stroke progression.

scholarly journals Individual blood-brain barrier phenylalanine transport in siblings with classical phenylketonuria

2002 ◽  
Vol 25 (6) ◽  
pp. 431-436 ◽  
Author(s):  
J. Weglage ◽  
D. Wiedermann ◽  
J. Denecke ◽  
R. Feldmann ◽  
H.-G. Koch ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain ◽  
Classical Phenylketonuria ◽  
Phenylalanine Transport

Abstract 1122‐000167: Hyperintense Acute Reperfusion Marker and Hemorrhagic Conversion in Stroke Patients Undergoing Mechanical Reperfusion

2021 ◽  
Vol 1 (S1) ◽  
Author(s):  
Pouria Moshayedi ◽  
Hamidreza Saber ◽  
David S Liebeskind ◽  
Jeffrey Gornbein ◽  
Bryan Yoo ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
White Matter ◽  
Clinical Outcome ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Periventricular White Matter ◽  
Vessel Occlusion ◽  
Blood Brain ◽  
Ischemic Core ◽  
Core Volume

Introduction : Endovascular thrombectomy (EVT) is a highly effective treatment to improve clinical outcome in patients with acute ischemic stroke due to large vessel occlusion (AIS‐LVO). However, blood‐brain barrier (BBB) disruption causing hemorrhagic transformation and reperfusion injury can potentially negate the beneficial effect of reperfusion. Studying determinants, frequency, and outcomes of the hyperintense acute reperfusion marker (HARM) sign, a biomarker of BBB disruption, would help to identify individual patients at increased risk, as well as developing therapies to prevent BBB breakdown. Methods : In consecutive AIS‐LVO patients with AIS‐LVO who underwent EVT followed by MRI within the next 24 hours, we evaluated frequency, determinants, and outcomes of HARM sign. Results : Among 81 patients meeting study criteria, age was 71.0 (SD 19.7), 58% female, mean NIHSS was 14.5 (SD 6.8), and time from last known well to treatment was 355 min (IQR 206.5 ‐ 664). HARM sign was observed in 64% (52/81) of patients. On multivariate logistic analysis, presence of HARM sign was independently associated with greater periventricular white matter hyperintensity, higher pre‐EVT ischemic core volume, more proximal target vessel occlusion, and achievement of successful reperfusion or better. Hemorrhagic conversion was seen in 31.8% of patients with HARM sign and 26.7% of patients without HARM sign. Multivariate analysis identified higher blood glucose, lower ASPECT, score and greater post‐EVT ischemic core volume as independent predictors of hemorrhagic conversion. HARM sign was identified to correlate with poor clinical outcome in bivariate analysis, but multivariate analysis only identified less neurological deficits, lower baseline systolic BP, lower degree of periventricular white matter hyperintensities, shorter time to device deployment and reduced post EVT ischemic core volume as independent predictors of good clinical outcome (mRS 0–2) upon discharge. Conclusions : The HARM sign indicating disruption of the blood‐brain barrier following EVT is common, present in about 6 of every 10 treated patients. Independent risk factors for HARM sign are chronic ischemic microangiopathy, greater acute ischemic core, and successful reperfusion. HARM sign presence is associated with worse functional outcome.

scholarly journals Permeability of the blood-brain barrier through the phases of ischaemic stroke and relation with clinical outcome: protocol for a systematic review

BMJ Open ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. e039280
Author(s):  
Sara Bernardo-Castro ◽  
Helena Donato ◽  
Lino Ferreira ◽  
João Sargento-Freitas
Keyword(s):  
Systematic Review ◽  
Clinical Outcome ◽  
Ischaemic Stroke ◽  
Blood Brain Barrier ◽  
Grey Literature ◽  
Arterial Occlusion ◽  
Brain Barrier ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Blood Brain

IntroductionIschaemic stroke is the most prevalent type of stroke and is characterised by a myriad of pathological events triggered by a vascular arterial occlusion. Disruption of the blood-brain barrier (BBB) is a key pathological event that may lead to fatal outcomes. However, it seems to follow a multiphasic pattern that has been associated with distinct biological substrates and possibly contrasting outcomes. Addressing the BBB permeability (BBBP) along the different phases of stroke through imaging techniques could lead to a better understanding of the disease, improved patient selection for specific treatments and development of new therapeutic modalities and delivery methods. This systematic review will aim to comprehensively summarise the existing evidence regarding the evolution of the BBBP values during the different phases of an acute ischaemic stroke and correlate this event with the clinical outcome of the patient.Methods and analysisWe will conduct a computerised search on Medline, EMBASE, Cochrane Central Register of Controlled Trials, Scopus and Web of Science. In addition, grey literature and ClinicalTrials.gov will be scanned. We will include randomised controlled trials, cohort, cross-sectional and case-controlled studies on humans that quantitatively assess the BBBP in stroke. Retrieved studies will be independently reviewed by two authors and any discrepancies will be resolved by consensus or with a third reviewer. Reviewers will extract the data and assess the risk of bias of the selected studies. If possible, data will be combined in a quantitative meta-analysis following the guidelines provided by Cochrane Handbook for Systematic Reviews of Interventions. We will assess cumulative evidence using the Grading of Recommendations, Assessment, Development and Evaluation approach.Ethics and disseminationEthical approval is not needed. All data used for this work are publicly available. The result obtained from this work will be published in a peer-reviewed journal and disseminated in relevant conferences.PROSPERO registration numberCRD42019147314.

Blood Brain Barrier Disruption in Diabetic Stroke Related to Unfavorable Outcome

2016 ◽  
Vol 42 (1-2) ◽  
pp. 49-56 ◽  
Author(s):  
Xinfeng Yu ◽  
Xiaojun Xu ◽  
Alan Jackson ◽  
Jianzhong Sun ◽  
Peiyu Huang ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Blood Brain Barrier ◽  
Unfavorable Outcome ◽  
Brain Barrier ◽  
Diabetic Patients ◽  
Stroke Outcome ◽  
Ischemic Lesion ◽  
Post Contrast ◽  
Blood Brain ◽  
Wide Range

Background: Diabetes mellitus (DM) is associated with a wide range of microvascular abnormalities in the brain. These include the dysfunction of the blood brain barrier (BBB). In this study, we test the hypotheses that disruption of the BBB in patients presenting with acute stroke is common in patients with DM and is related to outcome. Methods: Sixty-two consecutive patients with ischemic stroke in the middle cerebral artery territory were enrolled within 3-7 days after onset. In ischemic lesion, BBB disruption was detected by parenchymal enhancement (PE) on 5 min delayed post-contrast T1 weighted imaging. National Institute of Health Stroke Score (NIHSS) assessed neurologic impairment on admission. Clinical outcome at 3 months was classified as unfavorable if the modified Rankin scale was >1. The independent factors associated with clinical outcome were analyzed using multivariate logistic regression analysis and OR with its 95% CIs were estimated. Results: An unfavorable stroke outcome was found in 19 diabetic patients and 21 non-diabetic patients. Diabetic patients had a significantly higher frequency of PE than non-diabetic patients (58.6 vs. 27.3%, p = 0.013) and DM was independently associated with PE (OR 4.40; 95% CI 1.22-15.83; p = 0.023). PE was significantly more common in diabetic patients with unfavorable stroke outcome (73.7%) than in other 3 subgroups: diabetic patients with favorable stroke outcome (30.0%), non-diabetic patients with favorable stroke outcome (38.1%) and unfavorable stroke outcome (8.3%; p = 0.002). PE was independently associated with unfavorable outcome (UO) in diabetic stroke (DS; OR 7.04; 95% CI 1.20-41.52; p = 0.031). Admission NIHSS score was associated with UO in non-DS (NDS) (OR 1.71; 95% CI 1.10-2.66; p = 0.017). Conclusions: Compared with NDS, DS had increased BBB disruption defined by the presence of PE. A different form of the relationship between admission NIHSS and UO in NDS, BBB disruption was related with UO in diabetic patients after stroke.

scholarly journals Death Is Associated with Complement C3 Depletion in Cerebrospinal Fluid of Patients with Pneumococcal Meningitis

mBio ◽  
2012 ◽  
Vol 3 (2) ◽  
Author(s):  
U. R. Goonetilleke ◽  
M. Scarborough ◽  
S. A. Ward ◽  
S. Hussain ◽  
A. Kadioglu ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Clinical Outcome ◽  
Blood Brain Barrier ◽  
Pneumococcal Meningitis ◽  
Brain Barrier ◽  
Complement C3 ◽  
Neuronal Necrosis ◽  
Beneficial Effects ◽  
Blood Brain ◽  
Specific Proteins

ABSTRACTPneumococcal meningitis can lead to death or serious neurological sequelae as a result of the host inflammatory response. We investigated the association between host response protein expression and outcome in patients with pneumococcal meningitis. Cerebrospinal fluid (CSF) was obtained from 80 patients with pneumococcal meningitis (40 nonsurvivors and 40 survivors) and 10 normal controls. Candidate proteins were analyzed for an association with survival. Complement C3 levels were 5-fold lower in nonsurvivors than in survivors (P< 0.05). This C3 reduction was not associated with lower levels in serum, indicating a compartmentalized CSF response. Transferrin levels were significantly higher in CSF (but not serum) from nonsurvivors than in CSF from survivors, suggestive of blood-brain barrier damage. Classical apoptosis proteins caspase 3 and apoptosis-inducing factor were not present in CSF. Expression of creatine kinase BB in clinically infected CSF suggested neuronal necrosis, but there was no clear association between level of expression and clinical outcome. Increased blood-brain barrier permeability and complement C3 depletion may have a role in determining outcome from bacterial meningitis. Therapeutic use of citicoline or caspase inhibitors is unlikely to have beneficial effects in patients with meningitis.IMPORTANCEWe previously identified proteins associated with clinical outcome in patients diagnosed with pneumococcal meningitis in a pilot proteomics study of cerebrospinal fluid (CSF). In this article, we have quantitatively assayed specific proteins identified from this previous proteomics analysis along with proteins associated with cell death by using Western blotting.

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