Additional value of CTP maps in occlusion detection on CTP angiographic reconstructions for ischemic stroke.

BACKGROUND: CT perfusion angiographic reconstructions (CTP-AR), derived at the peak arterial inflow, have demonstrated similar diagnostic accuracy to CTA for occlusion detection in the anterior circulation. Colour-coded CTP maps may aid in localizing an occlusion. This study aim to assess the additional value of CTP maps for occlusion detection in ischemic stroke patients assessed with CTA or CTP-AR. METHODS: In this single center retrospective study, ischemic stroke patients who underwent both CTA and CTP from September 2020 up to and including September 2021 were included. The 1 mm CTP series at peak arterial inflow corresponds to the CTP-AR. Following the initial assessment of CTA and CTP-AR for occlusion detection, three readers with varying levels of experienced, reassessed the CTA and CTP-AR with access to the color-coded CTP maps. Each CTA and CTP-AR was reviewed by two readers, and certainty of assessment was recorded. The reference standard was determined through a consensus meeting. Differences in certainty were assessed using a t-test for paired samples. RESULTS: Out of 210 patients, 107 patients had an occlusion based on our reference standard. The addition of CTP maps resulted in the finding of 11 (2.6%) additional occlusions out of 420 CTA readings and 9 (2.1%) out of 420 CTP-AR readings, primarily involving distal occlusions. After addition of CTP maps, 7 (1.6%) initial assessments on CTA and 3 (0.7%) initial assessments on CTP-AR were deemed false positive. The overall certainty of all readers significantly (P < 0.001) increased after addition of CTP maps. CONCLUSION: The usage of CTP maps improved occlusion detection on both CTA and CTP-AR, especially for distal occlusions, and resulted in the increase of the overall level of certainty among readers with varying levels of experience.

Procedural blood pressure and contrast extravasation on dual energy computed tomography after endovascular stroke treatment.

BACKGROUND: Blood brain barrier disruption (BBBD) can be visualized by contrast extravasation (CE) after endovascular treatment (EVT) in patients with acute ischemic stroke. Elevated blood pressure is a risk factor for BBBD. However, the association between procedural blood pressure and CE post-EVT is unknown. METHODS: In this single-center retrospective study, we analyzed 501 eligible patients who received a dual energy CT (DECT) immediately post-EVT for acute ischemic stroke. Procedural blood pressure values (SBPmean, SBPmax, SBPmax-min, and MAPmean) were collected. CE was quantified by measuring the maximum parenchymal iodine concentration on DECT iodine overlay map reconstructions. As a measure for the extent of BBBD, we created CE-ASPECTS by deducting one point per hyperdense ASPECTS region on iodine overlay maps. The association between blood pressure and CE was assessed using multivariable linear regression. RESULTS: The procedural SBPmean, SBPmax, and MAPmean were 150 ± 26 mmHg, 173 ± 29 mmHg, and 101 ± 17 mmHg, respectively. The median maximum iodine concentration on post-EVT DECT was 1.2 mg/ml (IQR 0.7-2.0), and median CE-ASPECTS was 8 (IQR 5-11). The maximum iodine concentration was not associated with blood pressure. SBPmean, SBPmax, and MAPmean were significantly associated with CE-ASPECTS (per 10 mmHg, ß = -0.2, 95 % CI -0.31 to -0.09, ß = -0.15, 95 % CI -0.25 to -0.06, ß = -0.33, 95 % CI -0.49 to -0.17, respectively). CONCLUSION: In acute ischemic stroke patients undergoing EVT, particularly in patients achieving successful recanalization, SBPmean, SBPmax, and MAPmean are associated with the extent of BBBD on immediate post-EVT DECT, but not with maximum iodine concentration.

Procedural Blood Pressure and Intracranial Hemorrhage on Dual-Energy Computed Tomography After Endovascular Stroke Treatment.

PURPOSE: Optimal systolic blood pressure (SBP) management during endovascular treatment (EVT) for acute ischemic stroke remains a topic of debate. Though BP is associated with worse functional outcome, the relationship between BP and post-procedural intracranial hemorrhage (ICH) is less well-known. We aimed to investigate the association between BP during EVT and post-procedural ICH on dual-energy CT (DECT). METHODS: We included all patients who underwent EVT for an anterior circulation large vessel occlusion between 2010 and 2019, and received DECT < 3 h post-EVT. All BP measurements during the EVT procedure were used to calculate mean arterial pressure (MAPmean), mean SBP (SBPmean), and SBPmax-min (highest minus lowest). ICH was assessed using virtual post-procedural unenhanced DECT reconstructions and classified as intraparenchymal or extraparenchymal. Symptomatic ICH was scored according to the Heidelberg criteria. The association between different BP parameters and ICH was assessed using multivariable logistic regression. RESULTS: We included 478 patients. Seventy-six patients (16%) demonstrated ICH on DECT, of which 26 (34%) were intraparenchymal. Symptomatic intraparenchymal and extraparenchymal ICH occurred in 10 (38%) and 4 (8%) patients. SBPmax, SBPmean, and MAPmean were associated with intraparenchymal ICH with an adjusted odds ratio of 1.19 (95%CI, 1.02-1.39), 1.22 (95%CI, 1.03-1.46), and 1.40 (95%CI, 1.09-1.81) per 10 mmHg, while BP was not significantly associated with extraparenchymal ICH. BP did not differ between asymptomatic and symptomatic ICH. CONCLUSION: Procedural BP is associated with intraparenchymal ICH on post-EVT DECT but not with extraparenchymal ICH. Future studies should evaluate whether individual procedural BP management reduces post-EVT ICH and improves clinical outcome.

Characterization of cerebral small vessel disease by neutrophil and platelet activation markers using artificial intelligence.

Cerebral small vessel disease (cSVD) accounts for 25% of ischemic strokes and is a major cause of cognitive decline. Inflammatory processes, involving immune cells and platelets might drive development and progression of cSVD. The aim of the study was to identify potential novel biomarkers for cSVD, gaining new insights into its pathophysiology. We measured inflammation and platelet and neutrophil activation markers in patients with cSVD and age-matched controls. It was hypothesized that cSVD is accompanied by altered levels of these markers. The levels of interleukin 1ß, CX3CL1, CXCL4, CXCL7, myeloperoxidase (MPO), MPO-DNA complex and S100A8/A9 were measured by ELISA in plasma samples of patients with cSVD presenting with mild vascular cognitive impairment (mVCI, n = 36) or lacunar stroke (Laci, n = 44), and controls (n = 38). To determine the relevance of these ELISA markers compared with patient- and MRI-based characteristics, all characteristics were entered into three machine learning models. Among the ELISA markers measured, MPO levels were significantly elevated in patients with cSVD (48.3 (27.8-80.1, interquartile range) ng/mL) compared with controls (32.2 (19.6-47.4) ng/mL, P = 0.023), particularly in the Laci group (56.8 (33.3-84.7) ng/mL, P = 0.004). Regularized logistic regression and random forest algorithms returned MPO levels as an important feature in the detection and prediction of cSVD. Of note, logistic regression and random forest analysis also highlighted levels of CXCL4, CXCL7, MPO-DNA and S100A8/A9 as features associated with cSVD. Taken together, the neutrophil activation marker MPO is elevated in patients with Laci and machine learning indicates platelet and neutrophil markers as interesting molecules for future investigation. SHORTENED ABSTRACT: Cerebral small vessel disease (cSVD) is a major cause of cognitive decline and stroke. We aimed to identify potential novel biomarkers for cSVD and to obtain new insights into its pathophysiology. Levels of markers reflecting neutrophil activation, neutrophil extracellular trap (NET) formation, platelet activation and vascular inflammation were measured in plasma samples of patients with cSVD, and controls. Only myeloperoxidase (MPO) levels were significantly altered. Regularized logistic regression and random forest algorithms returned MPO levels as an important feature in the detection and prediction of cSVD and highlighted platelet- and NET markers as cSVD associated.

Nurse-led stroke aftercare addressing long-term psychosocial outcome: a comparison to care-as-usual.

PURPOSE: To examine whether nurse-led stroke aftercare is beneficial for long-term psychosocial outcome of community-dwelling persons with stroke. MATERIALS AND METHODS: Comparative effectiveness research design in which a prospective stroke aftercare cohort (n = 87) was compared to care-as-usual (n = 363) at six- and 12-months post stroke. Changes over time in cognitive and emotional problems experienced in daily life, fatigue and stroke impact on daily life were examined for stroke aftercare only. Multilevel modelling was used to compare stroke aftercare to care-as-usual concerning anxiety and depression symptoms, social participation and quality of life, over time. RESULTS: Sample characteristics did not differ between cohorts except for stroke type and on average, more severe stroke in the stroke aftercare cohort (p < 0.05). Following stroke aftercare, anxiety and emotional problems decreased significantly (p < 0.05), whereas care-as-usual remained stable over time in terms of anxiety. No significant changes over time were observed on the other outcome domains. CONCLUSIONS: Nurse-led stroke aftercare showed to be beneficial for emotional well-being in comparison to care-as-usual. Providing psychoeducation and emotional support seem effective elements but adding other therapeutic elements such as self-management strategies might increase the effectiveness of nurse-led stroke aftercare.Implications for rehabilitationRoutine stroke follow-up care should pay attention to psychosocial and emotional outcome in a systematic manner, in addition to secondary prevention.Healthcare professionals such as (specialized) nurses are needed to appropriately address the hidden cognitive and emotional consequences of stroke.Providing psychoeducation and emotional support in stroke aftercare diminish insecurities and worries in community-dwelling persons with stroke, leading to better outcomes.

Reliability of the intracerebral hemorrhage score for predicting outcome in patients with intracerebral hemorrhage using oral anticoagulants.

BACKGROUND AND PURPOSE: The intracerebral hemorrhage (ICH) score is the most widely used and validated prognostic model for estimating 30-day mortality in ICH. However, the score was developed and validated in an ICH population probably not using oral anticoagulants (OACs). The aim of this study was to determine the performance of the ICH score for predicting the 30-day mortality rate in the full range of ICH scores in patients using OACs. METHODS: Data from admitted patients with ICH were collected retrospectively in two Dutch comprehensive stroke centers. The validity of the ICH score was evaluated by assessing both discrimination and calibration in OAC and OAC-naive patient groups. RESULTS: A total of 1752 patients were included of which 462 (26%) patients were on OAC. The 30-day mortality was 54% for the OAC cohort and 34% for the OAC-naive cohort. The 30-day mortality was higher in the OAC cohort for ICH score 1 (33% vs. 12.5%; odds ratio, 3.4; 95% confidence intervals, 1.1-10.4) and ICH score 2 (53% vs. 26%; odds ratio, 3.2; 95% confidence intervals, 1.2-8.2) compared with the predicted mortality rate of the original ICH score. Overall, the discriminative ability of the ICH score was equally good in both cohorts (area under the curve 0.83 vs. 0.87, respectively). CONCLUSIONS: The ICH score underestimated the 30-day mortality rate for lower ICH scores in OAC-ICH. When estimating the prognosis of ICH in patients using OAC, this underestimation of mortality must be taken into account.

On the Reproducibility of Inversion Recovery Intravoxel Incoherent Motion Imaging in Cerebrovascular Disease.

BACKGROUND AND PURPOSE: Intravoxel incoherent motion imaging can measure both microvascular and parenchymal abnormalities simultaneously. The contamination of CSF signal can be suppressed using inversion recovery preparation. The clinical feasibility of inversion recovery-intravoxel incoherent motion imaging was investigated in patients with cerebrovascular disease by studying its reproducibility. MATERIALS AND METHODS: Sixteen patients with cerebrovascular disease (66 ± 8 years of age) underwent inversion recovery-intravoxel incoherent motion imaging twice. The reproducibility of the perfusion volume fraction and parenchymal diffusivity was calculated with the coefficient of variation, intraclass correlation coefficient, and the repeatability coefficient. ROIs included the normal-appearing white matter, cortex, deep gray matter, white matter hyperintensities, and vascular lesions. RESULTS: Values for the perfusion volume fraction ranged from 2.42 to 3.97 ×10-2 and for parenchymal diffusivity from 7.20 to 9.11 × 10-4 mm2/s, with higher values found in the white matter hyperintensities and vascular lesions. Coefficients of variation were <3.70% in normal-appearing tissue and <9.15% for lesions. Intraclass correlation coefficients were good to excellent, showing values ranging from 0.82 to 0.99 in all ROIs, except the deep gray matter and cortex, with intraclass correlation coefficients of 0.66 and 0.54, respectively. The repeatability coefficients ranged from 0.15 to 0.96 × 10-2 and 0.10 to 0.37 × 10-4 mm2/s for perfusion volume fraction and parenchymal diffusivity, respectively. CONCLUSIONS: Good reproducibility of inversion recovery-intravoxel incoherent motion imaging was observed with low coefficients of variation and high intraclass correlation coefficients in normal-appearing tissue and lesion areas in cerebrovascular disease. Good reproducibility of inversion recovery-intravoxel incoherent motion imaging in cerebrovascular disease is feasible in monitoring disease progression or treatment responses in the clinic.

Protocol for intraoperative assessment of the human cerebrovascular glycocalyx.

INTRODUCTION: Adequate functioning of the blood-brain barrier (BBB) is important for brain homoeostasis and normal neuronal function. Disruption of the BBB has been described in several neurological diseases. Recent reports suggest that an increased permeability of the BBB also contributes to increased seizure susceptibility in patients with epilepsy. The endothelial glycocalyx is coating the luminal side of the endothelium and can be considered as the first barrier of the BBB. We hypothesise that an altered glycocalyx thickness plays a role in the aetiology of temporal lobe epilepsy (TLE), the most common type of epilepsy. Here, we propose a protocol that allows intraoperative assessment of the cerebrovascular glycocalyx thickness in patients with TLE and assess whether its thickness is decreased in patients with TLE when compared with controls. METHODS AND ANALYSIS: This protocol is designed as a prospective observational case-control study in patients who undergo resective brain surgery as treatment for TLE. Control subjects are patients without a history of epileptic seizures, who undergo a craniotomy or burr hole surgery for other indications. Intraoperative glycocalyx thickness measurements of sublingual, cortical and hippocampal microcirculation are performed by video microscopy using sidestream dark-field imaging. Demographic details, seizure characteristics, epilepsy risk factors, intraoperative haemodynamic parameters and histopathological evaluation are additionally recorded. ETHICS AND DISSEMINATION: This protocol has been ethically approved by the local medical ethical committee (ID: NL51594.068.14) and complies with the Declaration of Helsinki and principles of Good Clinical Practice. Informed consent is obtained before study enrolment and only coded data will be stored in a secured database, enabling an audit trail. Results will be submitted to international peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER: NTR5568.

Association between eye position on brain scan and hospital mortality in acute intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Conjugate eye deviation (CED) and horizontal skew deviation are often seen in patients with intracerebral hemorrhage (ICH), but its prognostic significance is unclear. In this study, the association between brain scan assessed eye position and hospital mortality in patients with supratentorial ICH was tested. METHODS: A retrospective analysis was performed in 316 patients with supratentorial ICH. Eye position was measured on first brain computed tomography or magnetic resonance imaging. Patients with CED, horizontal skew deviation or no deviation were distinguished. The association between eye position and hospital mortality was assessed using logistic regression analysis. RESULTS: Conjugate eye deviation was present in 96 (30.4%), skew deviation in 44 (13.9%) and no deviation in 176 (55.7%) patients. In patients with CED, 81.3% had an eye position to the ipsilateral side of the hemorrhage. In univariable regression analysis, skew deviation was associated with mortality (odds ratio 3.10, 95% confidence interval 1.57-6.11; P = 0.001). In multivariable regression analysis, adjusting for age, ICH volume, intraventricular extension and Glasgow Coma Scale, eye position was not independently associated with mortality. CONCLUSION: Horizontal skew eyes were found to be an unfavorable prognostic factor. However, this was not independent of other important predictors of ICH mortality and is most probably explained by its association with worse initial clinical presentation.

Levels of heparin-releasable TFPI are increased in first-ever lacunar stroke patients.

OBJECTIVES: New insights in the pathophysiology of lacunar stroke (LS) suggest that it is caused by increased permeability of the blood-brain barrier due to endothelial activation. Because endothelial cells are the major production and storage site of tissue factor pathway inhibitor (TFPI), this protein can be used as marker of endothelial activation. In this observational study we measured the different pools of TFPI, as a marker of endothelial function, in first-ever lacunar stroke patients. METHODS: We determined antigen levels of total and free full-length (FL) TFPI using ELISA in 149 patients and 42 controls. Heparin-releasable free FL TFPI was determined in a random subset of 17 patients and 15 controls. By brain MRI, we classified LS patients as having isolated lacunar infarct (ILA) or silent ischemic lesions (SILs). RESULTS: Plasma levels of total TFPI were highest in patients with SILs compared with those with ILA, but this association disappeared after correction for age and levels of low-density lipoprotein cholesterol. However, levels of heparin-releasable free FL TFPI were higher in patients than in controls. CONCLUSIONS: Although ambient plasma levels of total TFPI were not different in subtypes of LS, the increased levels of heparin-releasable TFPI in patients suggest a role of endothelial activation in the pathogenesis of LS.

Metabolic syndrome relates to lacunar stroke without white matter lesions: a study in first-ever lacunar stroke patients.

BACKGROUND: Metabolic syndrome (MetS) is a cluster of three or more of the following risk factors: obesity, elevated blood pressure, elevated triglyceride level, elevated glucose level, and low high-density lipoprotein level. Lacunar infarcts (LS) account for 25% of all ischemic strokes and are small, deeply located brain infarcts. Two different subtypes exist, which are distinguished by the presence of concomitant white matter lesions (WML) on brain imaging. We determined the prevalence of MetS in LS and the association between MetS with LS subtypes in a series of first-ever LS patients. METHODS: We included 92 patients with a first-ever LS, and 92 patients with a first-ever atheroslerotic cortical stroke (CS) matched for age and sex. LS subtypes were defined according to presence of concomitant WML. We defined MetS retrospectively according to previously defined standards. RESULTS: 35.9% of LS patients and 45.7% of CS patients had MetS (OR 0.67; 95% CI 0.37-1.20). MetS was more prevalent in LS without WML than in LS with WML (44.4 and 23.7%, respectively; OR 2.98; 95% CI 1.04-8.47). Similarly, MetS related more to CS compared to LS with WML (OR 2.56; 95% CI 1.03-6.37). CONCLUSION: MetS relates more strongly to LS without WML and to CS, than to LS with WML. Our results suggest a different underlying mechanism between LS without WML and CS, and lacunar stroke with WML.

Haptoglobin phenotype may alter endothelial progenitor cell cluster formation in cerebral small vessel disease.

Cerebral small vessel disease results in silent ischemic lesions (SIL) among which is leukoaraiosis. In this process, endothelial damage is probably involved. Endothelial progenitor cells (EPC), are involved in endothelial repair. By restoring the damaged endothelium, EPC could mitigate SIL and cerebral small vessel disease. Haptoglobin 1-1, one of three phenotypes of haptoglobin, relates to SIL and may therefore attenuate the endothelial repair by EPC. Our aim was to quantify EPC number and function and to assess haptoglobin phenotype and its effect on EPC function in patients with a high prevalence of SIL: lacunar stroke patients. We assessed EPC In 42 lacunar stroke patients and 18 controls by flow cytometry and culture with fetal calf serum, patient and control serum. We determined haptoglobin phenotype and cultured EPC with the three different haptoglobin phenotypes. We found that EPC cluster counts were lower in patients (96.9 clusters/well +/- 83.4 (mean +/- SD)), especially in those with SIL (85.0 +/- 64.3), than in controls (174.4 +/- 112.2). Cluster formation was inhibited by patient serum, especially by SIL patient serum, but not by control serum. Patients with haptoglobin 1-1 had less clusters in culture, and when haptoglobin 1-1 was added to EPC cultures, cluster numbers were lower than with the other haptoglobin phenotypes. We conclude that lacunar stroke patients, especially those with SIL, have impaired EPC cluster formation, which may point at decreased endothelial repair potential. The haptoglobin 1-1 phenotype is likely a causative factor in this impairment.

Dynamic cerebral autoregulation and cerebrovascular reactivity: a comparative study in lacunar infarct patients.

The major purpose of this study was to simultaneously evaluate dCA before and shortly after cerebral vasodilatation evoked by infusion of acetazolamide (ACZ). It was questioned if and to what degree dCA was changed after ACZ infusion. Using 15 mg kg(-1) ACZ infusion cerebrovascular reactivity (CVR) was assessed in 29 first ever lacunar stroke patients (19 M/10 F). During the CVR-test, the electrocardiogram, non-invasive finger arterial blood pressure (ABP) and middle cerebral artery blood flow velocity (CBFV) were recorded. DCA based on spontaneous blood pressure variations was evaluated in 24 subjects by linear transfer function analysis. Squared coherence, gain and phase angle in the frequency range of autoregulation (0.04-0.16 Hz) were compared before and after ACZ infusion. After ACZ infusion, median phase angle decreased significantly (p < 0.005 Wilcoxon) to 0.77 rad compared to a pre-test baseline value of 1.05 rad, indicating less efficient dCA due to ACZ. However, post-test phase values are still mostly within the normal range. Poor and statistically non-significant correlations were found between CVR and absolute dCA phase angle. It can be concluded that CVR testing with body weight adjusted infusion of ACZ lowers dCA performance but by no means exhausts dCA, suggesting that in this way maximal CVR is not determined. Characterizing dCA based on transfer function analysis of ABP to CBFV needs no provocation and adverse patient effects are minimal. The poor correlation between CVR and dCA phase angle supports an interpretation that CVR and dCA study different mechanisms of cerebrovascular control.

Virchow-Robin spaces relate to cerebral small vessel disease severity.

BACKGROUND AND PURPOSE: Virchow-Robin spaces (VRs) are perivascular spaces surrounding the deep perforating brain arteries. VRs dilatation is pathologic, and it could be a manifestation of cerebral small vessel disease. In the present study we assessed the relation between VRs and silent ischemic lesions in a cohort of patients with cerebral small vessel disease. METHODS: We divided dilated VRs on MRI (1.5 Tesla) into three semi-quantitative categories in 165 first ever lacunar stroke patients. We counted asymptomatic lacunar infarcts and graded white matter lesions, and compared the prevalence of vascular risk factors in different categories of VRs. We also determined independent predictors of silent ischemic lesions. RESULTS: VRs at basal ganglia level related to age, hypertension, asymptomatic lacunar infarcts, and white matter lesions. VRs at basal ganglia level predicted silent ischemic lesions (odds ratio 10.58 per higher VRs category; 95 %- confidence interval 3.40 - 32.92). CONCLUSION: Dilated VRs in the basal ganglia relate to the severity of cerebral small vessel disease and might be a manifestation of the same small vessel abnormality that causes silent ischemic lesions. This adds a role for VRs as a potential marker for small vessel disease.

[The hot summer of 2003: heat stroke in Maastricht]. / De hete zomer van 2003: hitteberoerte in Maastricht.

Two male patients, 46 and 62 years of age, were brought to the emergency department on a hot summer's day. Both wore excessive clothing. The first patient had a temperature of 43 degrees C and was comatose. Heteroanamnesis indicated that he was suffering from schizophrenia. Although the prognosis seemed to be poor, his condition improved after treatment in intensive care, consisting of cooling and supportive treatment, but the patient had considerable permanent neurological impairment. The second patient had a temperature of 40.3 degrees C, was confused and had an atactic gait. He was cooled immediately and recovered swiftly without complications. Heat stroke is a life-threatening illness, which is defined as a body temperature above 40 degrees C and central nervous-system dysfunction. Heat stroke may be attended by many serious complications, including multi-organ failure and residual brain damage. Prompt recognition and rapid treatment, consisting of adequate cooling, are required.

Prenatal diagnosis of trisomy 12 mosaicism: normal development of a 3 years old female child.

Trisomy 12 mosaicism is a rare chromosomal mosaicism in prenatal diagnosis by amniocentesis. In the literature we found at least 27 cases. 13 Pregnancies were terminated, with multiple congenital anomalies (MCA) in 2 out of 13. Of the 12 liveborns with follow-up ranging from 0 to 5 years, 5 presented MCA and died within the first weeks. 2 Fetus died during pregnancy and further data are lacking. A normal outcome, with limited follow up however, was reported in 7/12 liveborns without congenital anomalies and is well demonstrated in the presently reported girl. We describe the 3-years follow up in a girl with trisomy 12 mosaicism, detected by amniocentesis for advanced maternal age. She is a healthy girl with normal physical and psychomotor development.