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Brain microdialysate tau dynamics predict functional and neurocognitive recovery after poor-grade subarachnoid haemorrhage

Subarachnoid haemorrhage is a devastating disease that results in neurocognitive deficits and a poor functional outcome in a considerable proportion of patients. In this study, we investigated the prognostic value of microtubule-associated tau protein measured in the cerebral microdialysate for long...

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Autores principales: Heilig, Marina, Rass, Verena, Lindner, Anna, Kofler, Mario, Ianosi, Bogdan-Andrei, Gaasch, Maxime, Putnina, Lauma, Humpel, Christian, Scherfler, Christoph, Zamarian, Laura, Bodner, Thomas, Djamshidian, Atbin, Schiefecker, Alois, Thomé, Claudius, Beer, Ronny, Pfausler, Bettina, Helbok, Raimund
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9851418/
https://www.ncbi.nlm.nih.gov/pubmed/36687392
http://dx.doi.org/10.1093/braincomms/fcac342
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author Heilig, Marina
Rass, Verena
Lindner, Anna
Kofler, Mario
Ianosi, Bogdan-Andrei
Gaasch, Maxime
Putnina, Lauma
Humpel, Christian
Scherfler, Christoph
Zamarian, Laura
Bodner, Thomas
Djamshidian, Atbin
Schiefecker, Alois
Thomé, Claudius
Beer, Ronny
Pfausler, Bettina
Helbok, Raimund
author_facet Heilig, Marina
Rass, Verena
Lindner, Anna
Kofler, Mario
Ianosi, Bogdan-Andrei
Gaasch, Maxime
Putnina, Lauma
Humpel, Christian
Scherfler, Christoph
Zamarian, Laura
Bodner, Thomas
Djamshidian, Atbin
Schiefecker, Alois
Thomé, Claudius
Beer, Ronny
Pfausler, Bettina
Helbok, Raimund
author_sort Heilig, Marina
collection PubMed
description Subarachnoid haemorrhage is a devastating disease that results in neurocognitive deficits and a poor functional outcome in a considerable proportion of patients. In this study, we investigated the prognostic value of microtubule-associated tau protein measured in the cerebral microdialysate for long-term functional and neuropsychological outcomes in poor-grade subarachnoid haemorrhage patients. We recruited 55 consecutive non-traumatic subarachnoid haemorrhage patients who underwent multimodal neuromonitoring, including cerebral microdialysis. Mitochondrial dysfunction was defined as lactate-to-pyruvate ratio >30 together with pyruvate >70 mmol/L and metabolic distress as lactate-to-pyruvate ratio >40. The multidimensional 12-month outcome was assessed by means of the modified Rankin scale (poor outcome: modified Rankin scale ≥4) and a standardized neuropsychological test battery. We used multivariable generalized estimating equation models to assess associations between total microdialysate-tau levels of the first 10 days after admission and hospital complications and outcomes. Patients were 56 ± 12 years old and presented with a median Hunt & Hess score of 5 (interquartile range: 3–5). Overall mean total microdialysate-tau concentrations were highest within the first 24 h (5585 ± 6291 pg/mL), decreased to a minimum of 2347 ± 4175 pg/mL on Day 4 (P < 0.001) and remained stable thereafter (P = 0.613). Higher total microdialysate-tau levels were associated with the occurrence of delayed cerebral ischaemia (P = 0.001), episodes of metabolic distress (P = 0.002) and mitochondrial dysfunction (P = 0.034). Patients with higher tau levels had higher odds for a poor 12-month functional outcome (adjusted odds ratio: 2.61; 95% confidence interval: 1.32–5.17; P = 0.006) and impaired results in the trail making test-B (adjusted odds ratio: 3.35; 95% confidence interval: 1.16–9.68; P = 0.026) indicative of cognitive flexibility. Total microdialysate-tau levels significantly decreased over the first 10 days (P < 0.05) in patients without delayed cerebral ischaemia or good functional outcomes and remained high in those with delayed cerebral ischaemia and poor 12-month outcomes, respectively. Dynamic changes of total tau in the cerebral microdialysate may be a useful biomarker for axonal damage associated with functional and neurocognitive recovery in poor-grade subarachnoid haemorrhage patients. In contrast, ongoing axonal damage beyond Day 3 after bleeding indicates a higher risk for delayed cerebral ischaemia as well as a poor functional outcome.
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spelling pubmed-98514182023-01-20 Brain microdialysate tau dynamics predict functional and neurocognitive recovery after poor-grade subarachnoid haemorrhage Heilig, Marina Rass, Verena Lindner, Anna Kofler, Mario Ianosi, Bogdan-Andrei Gaasch, Maxime Putnina, Lauma Humpel, Christian Scherfler, Christoph Zamarian, Laura Bodner, Thomas Djamshidian, Atbin Schiefecker, Alois Thomé, Claudius Beer, Ronny Pfausler, Bettina Helbok, Raimund Brain Commun Original Article Subarachnoid haemorrhage is a devastating disease that results in neurocognitive deficits and a poor functional outcome in a considerable proportion of patients. In this study, we investigated the prognostic value of microtubule-associated tau protein measured in the cerebral microdialysate for long-term functional and neuropsychological outcomes in poor-grade subarachnoid haemorrhage patients. We recruited 55 consecutive non-traumatic subarachnoid haemorrhage patients who underwent multimodal neuromonitoring, including cerebral microdialysis. Mitochondrial dysfunction was defined as lactate-to-pyruvate ratio >30 together with pyruvate >70 mmol/L and metabolic distress as lactate-to-pyruvate ratio >40. The multidimensional 12-month outcome was assessed by means of the modified Rankin scale (poor outcome: modified Rankin scale ≥4) and a standardized neuropsychological test battery. We used multivariable generalized estimating equation models to assess associations between total microdialysate-tau levels of the first 10 days after admission and hospital complications and outcomes. Patients were 56 ± 12 years old and presented with a median Hunt & Hess score of 5 (interquartile range: 3–5). Overall mean total microdialysate-tau concentrations were highest within the first 24 h (5585 ± 6291 pg/mL), decreased to a minimum of 2347 ± 4175 pg/mL on Day 4 (P < 0.001) and remained stable thereafter (P = 0.613). Higher total microdialysate-tau levels were associated with the occurrence of delayed cerebral ischaemia (P = 0.001), episodes of metabolic distress (P = 0.002) and mitochondrial dysfunction (P = 0.034). Patients with higher tau levels had higher odds for a poor 12-month functional outcome (adjusted odds ratio: 2.61; 95% confidence interval: 1.32–5.17; P = 0.006) and impaired results in the trail making test-B (adjusted odds ratio: 3.35; 95% confidence interval: 1.16–9.68; P = 0.026) indicative of cognitive flexibility. Total microdialysate-tau levels significantly decreased over the first 10 days (P < 0.05) in patients without delayed cerebral ischaemia or good functional outcomes and remained high in those with delayed cerebral ischaemia and poor 12-month outcomes, respectively. Dynamic changes of total tau in the cerebral microdialysate may be a useful biomarker for axonal damage associated with functional and neurocognitive recovery in poor-grade subarachnoid haemorrhage patients. In contrast, ongoing axonal damage beyond Day 3 after bleeding indicates a higher risk for delayed cerebral ischaemia as well as a poor functional outcome. Oxford University Press 2023-01-02 /pmc/articles/PMC9851418/ /pubmed/36687392 http://dx.doi.org/10.1093/braincomms/fcac342 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Heilig, Marina
Rass, Verena
Lindner, Anna
Kofler, Mario
Ianosi, Bogdan-Andrei
Gaasch, Maxime
Putnina, Lauma
Humpel, Christian
Scherfler, Christoph
Zamarian, Laura
Bodner, Thomas
Djamshidian, Atbin
Schiefecker, Alois
Thomé, Claudius
Beer, Ronny
Pfausler, Bettina
Helbok, Raimund
Brain microdialysate tau dynamics predict functional and neurocognitive recovery after poor-grade subarachnoid haemorrhage
title Brain microdialysate tau dynamics predict functional and neurocognitive recovery after poor-grade subarachnoid haemorrhage
title_full Brain microdialysate tau dynamics predict functional and neurocognitive recovery after poor-grade subarachnoid haemorrhage
title_fullStr Brain microdialysate tau dynamics predict functional and neurocognitive recovery after poor-grade subarachnoid haemorrhage
title_full_unstemmed Brain microdialysate tau dynamics predict functional and neurocognitive recovery after poor-grade subarachnoid haemorrhage
title_short Brain microdialysate tau dynamics predict functional and neurocognitive recovery after poor-grade subarachnoid haemorrhage
title_sort brain microdialysate tau dynamics predict functional and neurocognitive recovery after poor-grade subarachnoid haemorrhage
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9851418/
https://www.ncbi.nlm.nih.gov/pubmed/36687392
http://dx.doi.org/10.1093/braincomms/fcac342
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