scholarly journals Neuronal and Glia-Related Biomarkers in Cerebrospinal Fluid of Patients with Acute Ischemic Stroke

2014 ◽  
Vol 6 ◽  
pp. JCNSD.S13821 ◽  
Author(s):  
Clara Hjalmarsson ◽  
Maria Bjerke ◽  
Björn Andersson ◽  
Kaj Blennow ◽  
Henrik Zetterberg ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Ischemic Stroke ◽  
White Matter ◽  
Acute Ischemic Stroke ◽  
Experimental Studies ◽  
Csf Biomarkers ◽  
Stroke Severity ◽  
Neurofilament Light ◽  
Age Related ◽  
T Tau

Background Cerebral ischemia promotes morphological reactions of the neurons, astrocytes, oligodendrocytes, and microglia in experimental studies. Our aim was to examine the profile of CSF (cerebrospinal fluid) biomarkers and their relation to stroke severity and degree of white matter lesions (WML). Methods A total of 20 patients (mean age 76 years) were included within 5–10 days after acute ischemic stroke (AIS) onset. Stroke severity was assessed using NIHSS (National Institute of Health stroke scale). The age-related white matter changes (ARWMC) scale was used to evaluate the extent of WML on CT-scans. The concentrations of specific CSF biomarkers were analyzed. Results Patients with AIS had significantly higher levels of NFL (neurofilament, light), T-tau, myelin basic protein (MBP), YKL-40, and glial fibrillary acidic protein (GFAP) compared with controls; T-Tau, MBP, GFAP, and YKL-40 correlated with clinical stroke severity, whereas NFL correlated with severity of WML (tested by Mann–Whitney test). Conclusions Several CSF biomarkers increase in AIS, and they correlate to clinical stroke severity. However, only NFL was found to be a marker of degree of WML.

Structural integrity of white matter tracts as a predictor of acute ischemic stroke outcome

2020 ◽  
Vol 15 (9) ◽  
pp. 965-972
Author(s):  
Deepthi Rajashekar ◽  
Pauline Mouchès ◽  
Jens Fiehler ◽  
Bijoy K Menon ◽  
Mayank Goyal ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Acute Ischemic Stroke ◽  
Support Vector Regression ◽  
Support Vector ◽  
Stroke Severity ◽  
Lesion Volume ◽  
White Matter Tract ◽  
Support Vector Regression Model ◽  
White Matter Tracts

Background and purpose Clinical assessment scores in acute ischemic stroke are only moderately correlated with lesion volume since lesion location is an important confounding factor. Many studies have investigated gray matter indicators of stroke severity, but the understanding of white matter tract involvement is limited in the early phase after stroke. This study aimed to measure and model the involvement of white matter tracts with respect to 24-h post-stroke National Institutes of Health Stroke Scale (NIHSS). Material and methods A total of 96 patients (50 females, mean age 66.4 ± 14.0 years, median NIHSS 5, interquartile range: 2–9.5) with follow-up fluid-attenuated inversion recovery magnetic resonance imaging data sets acquired one to seven days after acute ischemic stroke onset due to proximal anterior circulation occlusion were included. Lesions were semi-automatically segmented and non-linearly registered to a common reference atlas. The lesion overlap and tract integrity were determined for each white matter tract in the AALCAT atlas and used to model NIHSS outcomes using a supervised linear-kernel support vector regression method, which was evaluated using leave-one-patient-out cross validation. Results The support vector regression model using the tract integrity and tract lesion overlap measurements predicted the 24-h NIHSS score with a high correlation value of r = 0.7. Using the tract overlap and tract integrity feature improved the modeling accuracy of NIHSS significantly by 6% (p < 0.05) compared to using overlap measures only. Conclusion White matter tract integrity and lesion load are important predictors for clinical outcome after an acute ischemic stroke as measured by the NIHSS and should be integrated for predictive modeling.

Abstract P317: White Matter Hyperintensity Lesion Burden Modulates Functional Outcome After Acute Ischemic Stroke

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Anna K Bonkhoff ◽  
Sungmin Hong ◽  
Markus Schirmer ◽  
Martin Bretzner ◽  
Anne-Katrin Giese ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Acute Ischemic Stroke ◽  
Functional Outcome ◽  
White Matter Hyperintensity ◽  
Study Cohort ◽  
Stroke Severity ◽  
Ischemic Lesion ◽  
Long Term Outcome ◽  
Index Stroke

Introduction: As a radiographic signature of end-stage small vessel disease, white matter hyperintensity (WMH) burden impacts recovery and outcomes after acute ischemic stroke (AIS). In this study, we sought to investigate the effect of WMH volume (WMHv) on stroke severity and functional outcomes independent of the infarct size and topography. Methods: We analyzed 503 AIS patients with MRI data obtained on admission for index stroke enrolled in the multi-center MRI-GENIE study (cohort 1), followed by validation of the findings in an independent single-site study of 555 AIS patients (cohort 2). Stroke severity (NIHSS score) at index stroke and the long-term outcome (3-6 months mRS score) were modeled via Bayesian linear regression. Models included WMHv, age, sex, a 10-dimensional spatial ischemic lesion representation, acute infarct (DWI) volume, and common vascular risk factors (hypertension, diabetes mellitus, atrial fibrillation, coronary artery disease). Results: Cohorts did not differ significantly in major clinical characteristics [cohort 1: age: 65.0±14.6, 41% female, NIHSS: 5.5±5.4, mRS: 1(iqr 2); cohort 2: age: 65.0±14.8, 38% female, NIHSS: 5.0±6.0, mRS: 1(iqr 3), p >0.05 for all comparisons]. WMHv did not substantially affect AIS severity ( Fig A ); in contrast, it emerged as an independent predictor of functional outcome in both datasets ( Fig B ). Conclusions: When accounted for AIS lesion topography and stroke volume, total WMH lesion burden did not appear to modulate initial stroke severity but was associated with worse functional post-stroke outcomes. Future studies are needed to explore potential origins of these detrimental effects of pre-existing WMH burden on recovery after AIS.

Abstract TP286: The Use Of Benzodiazepines In Patients With Acute Ischemic Stroke

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Monique B Alves ◽  
Andrea M Pereira ◽  
Paula S Nogueira ◽  
Renata C Miranda ◽  
Fernando M Coelho ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Cumulative Dose ◽  
Negative Impact ◽  
Neuronal Damage ◽  
Focal Cerebral Ischemia ◽  
Smoking Status ◽  
Experimental Studies ◽  
Stroke Severity ◽  
Benzodiazepine Use

Background and Purpose: The effect of benzodiazepines in patients with acute ischemic stroke is controversial. In experimental studies, benzodiazepines can reduce neuronal damage and improve neurological outcome after focal cerebral ischemia. Conversely, patients whose initial stroke syndrome had substantially improved clinically can show transient reemergence of their initial focal syndrome after benzodiazepine use. We assessed the hypothesis that benzodiazepine use can have a negative impact upon functional outcome and increase the risks of complication in patients with acute ischemic stroke. Patients and methods: We performed a post-hoc analysis of prospectively collected data of consecutive patients admitted to a Brazilian tertiary hospital with acute ischemic stroke from February 2009 to April 2012. The use of benzodiazepines including drugs, doses, and frequencies were obtained from the electronic pharmacy records. A benzodiazepine equivalence table was used to calculate the equivalent doses to 10mg of diazepam. Results: We evaluated 424 patients with acute ischemic stroke (mean age: 72.5 +/-15.2 yo, 58.7% males). Of those, 102 patients (24.1%) received at least one dose of benzodiazepine during hospital admission. The median cumulative dose of benzodiazepine used was 4 [2,11] (1 equivalent=10mg of diazepam). Patients who received benzodiazepines were similar to those who did not receive in age, gender and stroke severity measured by the NIHSS. The cumulative dose of benzodiazepine was an independent predictor of in-hospital pneumonia (OR= 1.03, 95% CI 1.02-1.06, p=0.03 for each unit of diazepam equivalent (1 equivalent=10mg of diazepam) when adjusted for age, gender, stroke severity (NIHSS) and smoking status. The modified Rankin scale at discharge was not different in patients who received or not benzodiazepines. Conclusions: In conclusion, exposure to benzodiazepine is associated with in-hospital pneumonia in patients with acute ischemic stroke. Alternative approaches to treat anxiety, insomnia and agitation in such patients are warranted.

scholarly journals Integrity of normal-appearing white matter and functional outcomes after acute ischemic stroke

Neurology ◽  
2017 ◽  
Vol 88 (18) ◽  
pp. 1701-1708 ◽  
Author(s):  
Mark R. Etherton ◽  
Ona Wu ◽  
Pedro Cougo ◽  
Anne-Katrin Giese ◽  
Lisa Cloonan ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Acute Ischemic Stroke ◽  
Functional Outcomes ◽  
Stroke Severity ◽  
Cerebral Tissue ◽  
Nihss Score ◽  
Normal Appearing White Matter ◽  
Acute Infarct

Objective:To characterize the effect of white matter microstructural integrity on cerebral tissue and long-term functional outcomes after acute ischemic stroke (AIS).Methods:Consecutive AIS patients with brain MRI acquired within 48 hours of symptom onset and 90-day modified Rankin Scale (mRS) score were included. Acute infarct volume on diffusion-weighted imaging (DWIv) and white matter hyperintensity volume (WMHv) on T2 fluid-attenuated inversion recovery MRI were measured. Median fractional anisotropy (FA), mean diffusivity, radial diffusivity, and axial diffusivity values were calculated within normal-appearing white matter (NAWM) in the hemisphere contralateral to the acute lesion. Regression models were used to assess the association between diffusivity metrics and acute cerebral tissue and long-term functional outcomes in AIS. Level of significance was set at p < 0.05 for all analyses.Results:Among 305 AIS patients with DWIv and mRS score, mean age was 64.4 ± 15.9 years, and 183 participants (60%) were male. Median NIH Stroke Scale (NIHSS) score was 3 (interquartile range [IQR] 1–8), and median normalized WMHv was 6.19 cm3 (IQR 3.0–12.6 cm3). Admission stroke severity (β = 0.16, p < 0.0001) and small vessel stroke subtype (β = −1.53, p < 0.0001), but not diffusivity metrics, were independently associated with DWIv. However, median FA in contralesional NAWM was independently associated with mRS score (β = −9.74, p = 0.02), along with age, female sex, NIHSS score, and DWIv.Conclusions:FA decrease in NAWM contralateral to the acute infarct is associated with worse mRS category at 90 days after stroke. These data suggest that white matter integrity may contribute to functional recovery after stroke.

Comparison between plasma and cerebrospinal fluid biomarkers for the early diagnosis and association with survival in prion disease

2020 ◽  
Vol 91 (11) ◽  
pp. 1181-1188 ◽  
Author(s):  
Samir Abu-Rumeileh ◽  
Simone Baiardi ◽  
Anna Ladogana ◽  
Corrado Zenesini ◽  
Anna Bartoletti-Stella ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Diagnostic Accuracy ◽  
Prion Disease ◽  
Single Molecule ◽  
Clinical Care ◽  
Csf Biomarkers ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Lower Accuracy ◽  
T Tau

ObjectiveTo compare the diagnostic accuracy and the prognostic value of blood and cerebrospinal fluid (CSF) tests across prion disease subtypes.MethodsWe used a single-molecule immunoassay to measure tau and neurofilament light chain (NfL) protein levels in the plasma and assessed CSF total(t)-tau, NfL and protein 14-3-3 levels in patients with prion disease (n=336), non-prion rapidly progressive dementias (n=106) and non-neurodegenerative controls (n=37). We then evaluated each plasma and CSF marker for diagnosis and their association with survival, taking into account the disease subtype, which is a strong independent prognostic factor in prion disease.ResultsPlasma tau and NfL concentrations were higher in patients with prion disease than in non-neurodegenerative controls and non-prion rapidly progressive dementias. Plasma tau showed higher diagnostic value than plasma NfL, but a lower accuracy than the CSF proteins t-tau and 14-3-3. In the whole prion cohort, both plasma (tau and NfL) and CSF (t-tau, 14-3-3 and NfL) markers were significantly associated with survival and showed similar prognostic values. However, the intrasubtype analysis revealed that only CSF t-tau in sporadic Creutzfeldt-Jakob disease (sCJD) MM(V)1, plasma tau and CSF t-tau in sCJD VV2, and plasma NfL in slowly progressive prion diseases were significantly associated with survival after accounting for covariates.ConclusionsPlasma markers have lower diagnostic accuracy than CSF biomarkers. Plasma tau and NfL and CSF t-tau are significantly associated with survival in prion disease in a subtype-specific manner and can be used to improve clinical trial stratification and clinical care.

scholarly journals Excessive White Matter Hyperintensity Increases Susceptibility to Poor Functional Outcomes After Acute Ischemic Stroke

2021 ◽  
Vol 12 ◽  
Author(s):  
Sungmin Hong ◽  
Anne-Katrin Giese ◽  
Markus D. Schirmer ◽  
Anna K. Bonkhoff ◽  
Martin Bretzner ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Acute Ischemic Stroke ◽  
Functional Outcomes ◽  
Linear Regression Analysis ◽  
Functional Independence ◽  
White Matter Hyperintensity ◽  
Stroke Severity ◽  
Post Stroke

Objective: To personalize the prognostication of post-stroke outcome using MRI-detected cerebrovascular pathology, we sought to investigate the association between the excessive white matter hyperintensity (WMH) burden unaccounted for by the traditional stroke risk profile of individual patients and their long-term functional outcomes after a stroke.Methods: We included 890 patients who survived after an acute ischemic stroke from the MRI-Genetics Interface Exploration (MRI-GENIE) study, for whom data on vascular risk factors (VRFs), including age, sex, atrial fibrillation, diabetes mellitus, hypertension, coronary artery disease, smoking, prior stroke history, as well as acute stroke severity, 3- to−6-month modified Rankin Scale score (mRS), WMH, and brain volumes, were available. We defined the unaccounted WMH (uWMH) burden via modeling of expected WMH burden based on the VRF profile of each individual patient. The association of uWMH and mRS score was analyzed by linear regression analysis. The odds ratios of patients who achieved full functional independence (mRS &lt; 2) in between trichotomized uWMH burden groups were calculated by pair-wise comparisons.Results: The expected WMH volume was estimated with respect to known VRFs. The uWMH burden was associated with a long-term functional outcome (β = 0.104, p &lt; 0.01). Excessive uWMH burden significantly reduced the odds of achieving full functional independence after a stroke compared to the low and average uWMH burden [OR = 0.4, 95% CI: (0.25, 0.63), p &lt; 0.01 and OR = 0.61, 95% CI: (0.42, 0.87), p &lt; 0.01, respectively].Conclusion: The excessive amount of uWMH burden unaccounted for by the traditional VRF profile was associated with worse post-stroke functional outcomes. Further studies are needed to evaluate a lifetime brain injury reflected in WMH unrelated to the VRF profile of a patient as an important factor for stroke recovery and a plausible indicator of brain health.

scholarly journals Neurobiochemical Markers of Brain Damage in Cerebrospinal Fluid of Acute Ischemic Stroke Patients

2010 ◽  
Vol 56 (3) ◽  
pp. 451-458 ◽  
Author(s):  
Raf Brouns ◽  
Bart De Vil ◽  
Patrick Cras ◽  
Didier De Surgeloose ◽  
Peter Mariën ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Calcium Binding ◽  
Infarct Volume ◽  
Neuron Specific Enolase ◽  
Stroke Severity ◽  
Stroke Outcome ◽  
Stroke Patients ◽  
Nihss Score

Abstract Background: Ischemic injury to the central nervous system causes cellular activation and disintegration, leading to release of cell-type–specific proteins into the cerebrospinal fluid (CSF). We investigated CSF concentrations of myelin basic protein (MBP), glial fibrillary astrocytic protein (GFAP), the calcium-binding protein S100B, and neuron-specific enolase (NSE) in acute ischemic stroke patients and their relation to initial stroke severity, stroke location, and long-term stroke outcome. Methods: CSF concentrations of MBP, GFAP, S100B, and NSE were assessed in 89 stroke patients on admission (mean 8.7 h after stroke onset) and in 35 controls. We evaluated the relation between CSF concentrations and (a) stroke severity (NIH Stroke Scale [NIHSS] score on admission, infarct volume), (b) stroke location, and (c) stroke outcome (modified Rankin Scale [mRS] score at month 3). Results: MBP concentration was significantly higher in subcortical than in cortical infarcts (median MBP, 1.18 vs 0.66 μg/L, P &lt; 0.001). GFAP and S100B concentrations correlated with the NIHSS score on admission (GFAP, R = 0.35, P = 0.001; S100B, R = 0.29, P = 0.006), infarct volume (GFAP, R = 0.34, P = 0.001; S100B, R = 0.28, P = 0.008), and mRS score at month 3 (R = 0.42, P &lt; 0.001 and R = 0.28, P = 0.007). Concentrations of NSE did not correlate with stroke characteristics. Conclusions: MBP, GFAP, S100B, and NSE display relevant differences in cellular and subcellular origins, which are reflected in their relation to stroke characteristics. MBP is a marker for infarct location. GFAP and S100B correlate with stroke severity and outcome.

scholarly journals Diffuse microvascular dysfunction and loss of white matter integrity predict poor outcomes in patients with acute ischemic stroke

2017 ◽  
Vol 38 (1) ◽  
pp. 75-86 ◽  
Author(s):  
Natalia S Rost ◽  
Pedro Cougo ◽  
Svetlana Lorenzano ◽  
Hua Li ◽  
Lisa Cloonan ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Acute Ischemic Stroke ◽  
Mean Transit Time ◽  
Microvascular Dysfunction ◽  
White Matter Integrity ◽  
Matrix Metalloproteinase 2 ◽  
Stroke Severity ◽  
Post Stroke ◽  
Bbb Permeability

We sought to investigate the relationship between blood–brain barrier (BBB) permeability and microstructural white matter integrity, and their potential impact on long-term functional outcomes in patients with acute ischemic stroke (AIS). We studied 184 AIS subjects with perfusion-weighted MRI (PWI) performed <9 h from last known well time. White matter hyperintensity (WMH), acute infarct, and PWI-derived mean transit time lesion volumes were calculated. Mean BBB leakage rates (K2 coefficient) and mean diffusivity values were measured in contralesional normal-appearing white matter (NAWM). Plasma matrix metalloproteinase-2 (MMP-2) levels were studied at baseline and 48 h. Admission stroke severity was evaluated using the NIH Stroke Scale (NIHSS). Modified Rankin Scale (mRS) was obtained at 90-days post-stroke. We found that higher mean K2 and diffusivity values correlated with age, elevated baseline MMP-2 levels, greater NIHSS and worse 90-day mRS (all p < 0.05). In multivariable analysis, WMH volume was associated with mean K2 ( p = 0.0007) and diffusivity ( p = 0.006) values in contralesional NAWM. In summary, WMH severity measured on brain MRI of AIS patients is associated with metrics of increased BBB permeability and abnormal white matter microstructural integrity. In future studies, these MRI markers of diffuse cerebral microvascular dysfunction may improve prediction of cerebral tissue infarction and functional post-stroke outcomes.

scholarly journals White Matter Hyperintensities Are No Major Confounder for Alzheimer’s Disease Cerebrospinal Fluid Biomarkers

2021 ◽  
Vol 79 (1) ◽  
pp. 163-175
Author(s):  
Linda J.C. van Waalwijk van Doorn ◽  
Mohsen Ghafoorian ◽  
Esther M.C. van Leijsen ◽  
Jurgen A.H.R. Claassen ◽  
Andrea Arighi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
White Matter ◽  
White Matter Hyperintensities ◽  
Linear Regression Analysis ◽  
Amyloid Β ◽  
Csf Biomarkers ◽  
Csf Biomarker ◽  
T Tau

Background: The cerebrospinal fluid (CSF) biomarkers amyloid-β 1–42 (Aβ42), total and phosphorylated tau (t-tau, p-tau) are increasingly used to assist in the clinical diagnosis of Alzheimer’s disease (AD). However, CSF biomarker levels can be affected by confounding factors. Objective: To investigate the association of white matter hyperintensities (WMHs) present in the brain with AD CSF biomarker levels. Methods: We included CSF biomarker and magnetic resonance imaging (MRI) data of 172 subjects (52 controls, 72 mild cognitive impairment (MCI), and 48 AD patients) from 9 European Memory Clinics. A computer aided detection system for standardized automated segmentation of WMHs was used on MRI scans to determine WMH volumes. Association of WMH volume with AD CSF biomarkers was determined using linear regression analysis. Results: A small, negative association of CSF Aβ42, but not p-tau and t-tau, levels with WMH volume was observed in the AD (r2 = 0.084, p = 0.046), but not the MCI and control groups, which was slightly increased when including the distance of WMHs to the ventricles in the analysis (r2 = 0.105, p = 0.025). Three global patterns of WMH distribution, either with 1) a low, 2) a peak close to the ventricles, or 3) a high, broadly-distributed WMH volume could be observed in brains of subjects in each diagnostic group. Conclusion: Despite an association of WMH volume with CSF Aβ42 levels in AD patients, the occurrence of WMHs is not accompanied by excess release of cellular proteins in the CSF, suggesting that WMHs are no major confounder for AD CSF biomarker assessment.

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