Diffusion-weighted magnetic resonance imaging in early central retinal artery occlusion.

INTRODUCTION: Restricted retinal diffusion (RDR) has recently been recognized as a frequent finding on standard diffusion-weighted imaging (DWI) in central retinal artery occlusion (CRAO). However, data on early DWI signal evolution are missing. PATIENTS AND METHODS: Consecutive CRAO patients with DWI performed within 24 h after onset of visual impairment were included in a bicentric, retrospective cross-sectional study. Two blinded neuroradiologists assessed randomized DWI scans for the presence of retinal ischemia. RDR detection rates, false positive ratings, and interrater agreement were evaluated for predefined time groups. RESULTS: Sixty eight CRAO patients (68.4 ± 16.8 years; 25 female) with 72 DWI scans (76.4% 3 T, 23.6% 1.5 T) were included. Mean time-delay between onset of CRAO and DWI acquisition was 13.4 ± 7.0 h. Overall RDR detection rates ranged from 52.8% to 62.5% with false positive ratings in 4.2%-8.3% of cases. RDR detection rates were higher in DWI performed 12-24 h after onset, when compared with DWI acquired within the first 12 h (79.5%vs 39.3%, p < 0.001). The share of false positive ratings was highest for DWI performed within the first 6 h of symptom onset (up to 14.3%). Interrater reliability was "moderate" for DWI performed within the first 18 h (κ = 0.57-0.58), but improved for DWI acquired between 18 and 24 h (κ = 0.94). CONCLUSION: DWI-based detection of retinal ischemia in early CRAO is likely to be time-dependent with superior diagnostic accuracy for DWI performed 12-24 h after onset of visual impairment.

Automated acute ischemic stroke lesion delineation based on apparent diffusion coefficient thresholds.

Purpose: Automated lesion segmentation is increasingly used in acute ischemic stroke magnetic resonance imaging (MRI). We explored in detail the performance of apparent diffusion coefficient (ADC) thresholding for delineating baseline diffusion-weighted imaging (DWI) lesions. Methods: Retrospective, exploratory analysis of the prospective observational single-center 1000Plus study from September 2008 to June 2013 (clinicaltrials.org; NCT00715533). We built a fully automated lesion segmentation algorithm using a fixed ADC threshold (≤620 × 10-6 mm2/s) to delineate the baseline DWI lesion and analyzed its performance compared to manual assessments. Diagnostic capabilities of best possible ADC thresholds were investigated using receiver operating characteristic curves. Influential patient factors on ADC thresholding techniques' performance were studied by conducting multiple linear regression. Results: 108 acute ischemic stroke patients were selected for analysis. The median Dice coefficient for the algorithm was 0.43 (IQR 0.20-0.64). Mean ADC values in the DWI lesion (ß = -0.68, p < 0.001) and DWI lesion volumes (ß = 0.29, p < 0.001) predicted performance. Optimal individual ADC thresholds differed between subjects with a median of ≤691 × 10-6 mm2/s (IQR ≤660-750 × 10-6 mm2/s). Mean ADC values in the DWI lesion (ß = -0.96, p < 0.001) and mean ADC values in the brain parenchyma (ß = 0.24, p < 0.001) were associated with the performance of individual thresholds. Conclusion: The performance of ADC thresholds for delineating acute stroke lesions varies substantially between patients. It is influenced by factors such as lesion size as well as lesion and parenchymal ADC values. Considering the inherent noisiness of ADC maps, ADC threshold-based automated delineation of very small lesions is not reliable.

Deep learning-based segmentation of brain parenchyma and ventricular system in CT scans in the presence of anomalies.

Introduction: The automatic segmentation of brain parenchyma and cerebrospinal fluid-filled spaces such as the ventricular system is the first step for quantitative and qualitative analysis of brain CT data. For clinical practice and especially for diagnostics, it is crucial that such a method is robust to anatomical variability and pathological changes such as (hemorrhagic or neoplastic) lesions and chronic defects. This study investigates the increase in overall robustness of a deep learning algorithm that is gained by adding hemorrhage training data to an otherwise normal training cohort. Methods: A 2D U-Net is trained on subjects with normal appearing brain anatomy. In a second experiment the training data includes additional subjects with brain hemorrhage on image data of the RSNA Brain CT Hemorrhage Challenge with custom reference segmentations. The resulting networks are evaluated on normal and hemorrhage test casesseparately, and on an independent test set of patients with brain tumors of the publicly available GLIS-RT dataset. Results: Adding data with hemorrhage to the training set significantly improves the segmentation performance over an algorithm trained exclusively on normally appearing data, not only in the hemorrhage test set but also in the tumor test set. The performance on normally appearing data is stable. Overall, the improved algorithm achieves median Dice scores of 0.98 (parenchyma), 0.91 (left ventricle), 0.90 (right ventricle), 0.81 (third ventricle), and 0.80 (fourth ventricle) on the hemorrhage test set. On the tumor test set, the median Dice scores are 0.96 (parenchyma), 0.90 (left ventricle), 0.90 (right ventricle), 0.75 (third ventricle), and 0.73 (fourth ventricle). Conclusion: Training on an extended data set that includes pathologies is crucial and significantly increases the overall robustness of a segmentation algorithm for brain parenchyma and ventricular system in CT data, also for anomalies completely unseen during training. Extension of the training set to include other diseases may further improve the generalizability of the algorithm.

Machine learning-based prediction of clinical outcomes after first-ever ischemic stroke.

Background: Accurate prediction of clinical outcomes in individual patients following acute stroke is vital for healthcare providers to optimize treatment strategies and plan further patient care. Here, we use advanced machine learning (ML) techniques to systematically compare the prediction of functional recovery, cognitive function, depression, and mortality of first-ever ischemic stroke patients and to identify the leading prognostic factors. Methods: We predicted clinical outcomes for 307 patients (151 females, 156 males; 68 ± 14 years) from the PROSpective Cohort with Incident Stroke Berlin study using 43 baseline features. Outcomes included modified Rankin Scale (mRS), Barthel Index (BI), Mini-Mental State Examination (MMSE), Modified Telephone Interview for Cognitive Status (TICS-M), Center for Epidemiologic Studies Depression Scale (CES-D) and survival. The ML models included a Support Vector Machine with a linear kernel and a radial basis function kernel as well as a Gradient Boosting Classifier based on repeated 5-fold nested cross-validation. The leading prognostic features were identified using Shapley additive explanations. Results: The ML models achieved significant prediction performance for mRS at patient discharge and after 1 year, BI and MMSE at patient discharge, TICS-M after 1 and 3 years and CES-D after 1 year. Additionally, we showed that National Institutes of Health Stroke Scale (NIHSS) was the top predictor for most functional recovery outcomes as well as education for cognitive function and depression. Conclusion: Our machine learning analysis successfully demonstrated the ability to predict clinical outcomes after first-ever ischemic stroke and identified the leading prognostic factors that contribute to this prediction.

Exploring the ATN classification system using brain morphology.

BACKGROUND: The NIA-AA proposed amyloid-tau-neurodegeneration (ATN) as a classification system for AD biomarkers. The amyloid cascade hypothesis (ACH) implies a sequence across ATN groups that patients might undergo during transition from healthy towards AD: A-T-N-➔A+T-N-➔A+T+N-➔A+T+N+. Here we assess the evidence for monotonic brain volume decline for this particular (amyloid-conversion first, tau-conversion second, N-conversion last) and alternative progressions using voxel-based morphometry (VBM) in a large cross-sectional MRI cohort. METHODS: We used baseline data of the DELCODE cohort of 437 subjects (127 controls, 168 SCD, 87 MCI, 55 AD patients) which underwent lumbar puncture, MRI scanning, and neuropsychological assessment. ATN classification was performed using CSF-Aß42/Aß40 (A+/-), CSF phospho-tau (T+/-), and adjusted hippocampal volume or CSF total-tau (N+/-). We compared voxel-wise model evidence for monotonic decline of gray matter volume across various sequences over ATN groups using the Bayesian Information Criterion (including also ROIs of Braak stages). First, face validity of the ACH transition sequence A-T-N-➔A+T-N-➔A+T+N-➔A+T+N+ was compared against biologically less plausible (permuted) sequences among AD continuum ATN groups. Second, we evaluated evidence for 6 monotonic brain volume progressions from A-T-N- towards A+T+N+ including also non-AD continuum ATN groups. RESULTS: The ACH-based progression A-T-N-➔A+T-N-➔A+T+N-➔A+T+N+ was consistent with cognitive decline and clinical diagnosis. Using hippocampal volume for operationalization of neurodegeneration (N), ACH was most evident in 9% of gray matter predominantly in the medial temporal lobe. Many cortical regions suggested alternative non-monotonic volume progressions over ACH progression groups, which is compatible with an early amyloid-related tissue expansion or sampling effects, e.g., due to brain reserve. Volume decline in 65% of gray matter was consistent with a progression where A status converts before T or N status (i.e., ACH/ANT) when compared to alternative sequences (TAN/TNA/NAT/NTA). Brain regions earlier affected by tau tangle deposition (Braak stage I-IV, MTL, limbic system) present stronger evidence for volume decline than late Braak stage ROIs (V/VI, cortical regions). Similar findings were observed when using CSF total-tau for N instead. CONCLUSION: Using the ATN classification system, early amyloid status conversion (before tau and neurodegeneration) is associated with brain volume loss observed during AD progression. The ATN system and the ACH are compatible with monotonic progression of MTL atrophy. TRIAL REGISTRATION: DRKS00007966, 04/05/2015, retrospectively registered.

New Cerebral Microbleeds After Catheter-Based Structural Heart Interventions: An Exploratory Analysis.

Background Cerebral microbleeds (CMBs) are increasingly recognized as "covert" brain lesions indicating increased risk of future neurological events. However, data on CMBs in patients undergoing catheter-based structural heart interventions are scarce. Therefore, we assessed occurrence and predictors of new CMBs in patients undergoing catheter-based left atrial appendage closure and percutaneous mitral valve repair using the MitraClip System. Methods and Results We conducted an exploratory analysis using data derived from 2 prospective, observational studies. Eligible patients underwent cerebral magnetic resonance imaging (3 Tesla) examinations and cognitive tests (using the Montreal Cognitive Assessment) before and after catheter-based left atrial appendage closure and percutaneous mitral valve repair. Forty-seven patients (53% men; median age, 77 years) were included. New CMBs occurred in 17 of 47 patients (36%) following catheter-based structural heart interventions. Occurrences of new CMBs did not differ significantly between patients undergoing catheter-based left atrial appendage closure and percutaneous mitral valve repair (7/25 versus 10/22; P=0.348). In univariable analysis, longer procedure time was significantly associated with new CMBs. Adjustment for heparin attenuated this association (adjusted odds ratio [per 30 minutes]: 1.77 [95% CI, 0.92-3.83]; P=0.090). Conclusions New CMBs occur in approximately one-third of patients after catheter-based left atrial appendage closure and percutaneous mitral valve repair using the MitraClip System. Our data suggest that longer duration of the procedure may be a risk factor for new CMBs. Future studies in larger populations are needed to further investigate their clinical relevance. Clinical Trial Registration German Clinical Trials Register: DRKS00010300 (https://drks.de/search/en/trial/DRKS00010300); ClinicalTrials.gov : NCT03104556 (https://clinicaltrials.gov/ct2/show/NCT03104556?term=NCT03104556&draw=2&rank=1).

White matter hyperintensities are an independent predictor of cognitive decline 3 years following first-ever stroke-results from the PROSCIS-B study.

BACKGROUND: White matter hyperintensities (WMH) are the result of cerebral small vessel disease and may increase the risk of cognitive impairment (CI), recurrent stroke, and depression. We aimed to explore the association between selected cerebrovascular risk factors (CVRF) and WMH load as well as the effect of increased WMH burden on recurrent vascular events, CI, and depression in first-ever ischemic stroke patients. METHODS: 431 from the PROSpective Cohort with Incident Stroke (PROSCIS) were included; Age-Related White Matter Changes (ARWMC) score was used to assess WMH burden on FLAIR. The presence of CVRF (defined via blood pressure, body-mass-index, and serological markers of kidney dysfunction, diabetes mellitus, and hyperlipoproteinemia) was categorized into normal, borderline, and pathological profiles based on commonly used clinical definitions. The primary outcomes included recurrent vascular events (combined endpoint of recurrent stroke, myocardial infarction and/or death), CI 3 years post-stroke, and depression 1-year post-stroke. RESULTS: There was no clear association between CVRF profiles and WMH burden. High WMH lesion load (ARWMC score ≥ 10) was found to be associated with CI (adjusted OR 1.05 [95% CI 1.00-1.11]; p < 0.02) in a mixed-model analysis. Kaplan-Meier survival analysis showed a visible increase in the risk of recurrent vascular events following stroke; however, after adjustment, the risk was non-significant (HR 1.5 [95% CI 0.76-3]; p = 0.18). WMH burden was not associated with depression 1-year post stroke (adjusted OR 0.72 [95% CI 0.31-1.64]; p = 0.44). CONCLUSION: Higher WMH burden was associated with a significant decline in cognition 3 years post-stroke in this cohort of first-ever stroke patients.

Reclassifications of ischemic stroke patterns due to variants of the Circle of Willis.

BACKGROUND: Variants of the Circle of Willis (vCoW) may impede correct identification of ischemic lesion patterns and stroke etiology. We assessed reclassifications of ischemic lesion patterns due to vCoW. METHODS: We analyzed vCoW in patients with acute ischemic stroke from the 1000+ study using time-of-flight magnetic resonance angiography (TOF MRA) of intracranial arteries. We assessed A1 segment agenesis or hypoplasia in the anterior circulation and fetal posterior cerebral artery in the posterior circulation. Stroke patterns were classified as one or more-than-one territory stroke pattern. We examined associations between vCoW and stroke patterns and the frequency of reclassifications of stroke patterns due to vCoW. RESULTS: Of 1000 patients, 991 had evaluable magnetic resonance angiography. At least one vCoW was present in 37.1%. VCoW were more common in the posterior than in the anterior circulation (33.3% vs. 6.7%). Of 238 patients initially thought to have a more-than-one territory stroke pattern, 20 (8.4%) had to be reclassified to a one territory stroke pattern after considering vCoW. All these patients had fetal posterior cerebral artery and six (30%) additionally had carotid artery disease. Of 753 patients initially presumed to have a one-territory stroke pattern, four (0.5%) were reclassified as having more-than-one territory pattern. CONCLUSIONS: VCoW are present in about one in three stroke patients and more common in the posterior circulation. Reclassifications of stroke lesion patterns due to vCoW occurred predominantly in the posterior circulation with fetal posterior cerebral artery mimicking multiple territory stroke pattern. Considering vCoW in these cases may uncover symptomatic carotid disease.

Frequency of silent brain infarction in transient global amnesia.

BACKGROUND AND PURPOSE: To determine the frequency and distribution pattern of acute DWI lesions outside the hippocampus in patients clinically presenting with Transient Global Amnesia (TGA). METHODS: Consecutive patients clinically presenting with TGA between January 2010 and January 2017 admitted to our hospital were retrospectively evaluated. All patients fulfilled diagnostic criteria of TGA. We analyzed imaging and clinical data of all patients undergoing MRI with high-resolution diffusion-weighted imaging within 72 h from symptom onset. RESULTS: A total of 126 cases were included into the study. Fifty-three percent (n = 71/126) presented with one or more acute lesions in hippocampal CA1-area. Additional acute DWI lesions in other cortical regions were found in 11% (n = 14/126). All patients with DWI lesions outside the hippocampus presented with neurological symptoms typical for TGA (without additional symptoms.) CONCLUSIONS: In a relevant proportion of clinical TGA patients, MRI reveals acute ischemic cerebral lesions. Therefore, cerebral MRI should be performed in patients with TGA to identify a possible cardiac involvement and to detect stroke chameleons.

Can intracranial time-of-flight-MR angiography predict extracranial carotid artery stenosis?

OBJECTIVES: Extracranial stenosis of the internal carotid artery (ICA) is an important cause of ischemic stroke and transient ischemic attack (TIA). It can be diagnosed using contrast-enhanced CT or MR angiography (MRA) as well as Doppler ultrasound. In this study, we assessed the diagnostic value of intracranial time-of-flight (TOF) MRA to predict extracranial ICA stenosis (ICAS). METHODS: We retrospectively analyzed consecutive patients with acute ischemic stroke or TIA and middle- (50-69%) or high-grade (70-99%) unilateral extracranial ICAS according to NASCET criteria assessed by ultrasound between January 2016 and August 2018. The control group consisted of patients without extracranial ICAS. Intraluminal signal intensities (SI) of the intracranial ICA on the side of the extracranial stenosis were compared to the contralesional side on TOF-MRA source images. SI ratios (SIR) of contralesional:lesional side were compared between groups. RESULTS: In total, 151 patients were included in the main analysis. Contralesional:lesional SIR in the intracranial C4-segment was significantly higher in patients with ipsilateral extracranial ICA stenosis (n = 51, median 74 years, 57% male) compared to the control group (n = 100, median 68 years, 48% male). Mean SIR was 1.463 vs. 1.035 (p < 0.001) for right-sided stenosis and 1.362 vs. 1.000 (p < 0.001) for left-sided stenosis. Receiver-operating characteristic curve demonstrated a cut-off value of 1.086 for right-sided [sensitivity/specificity 75%/81%; area under the curve (AUC) 0.81] and 1.104 for left-sided stenosis (sensitivity/specificity 70%/84%; AUC 0.80) in C4 as a good predictor for high-grade extracranial ICAS. CONCLUSIONS: SIR on TOF-MRA can be a marker of extracranial ICAS.

Cerebral embolisation during transcatheter edge-to-edge repair of the mitral valve with the MitraClip system: a prospective, observational study.

BACKGROUND: New ischaemic brain lesions on magnetic resonance imaging (MRI) are reported in up to 86% of patients after transcatheter edge-to-edge repair of the mitral valve (TEER-MV). Knowledge of the exact procedural step(s) that carry the highest risk for cerebral embolisation may help to further improve the procedure. AIMS: The aim of this study was to identify the procedural step(s) that are associated with an increased risk of cerebral embolisation during TEER-MV with the MitraClip system. Furthermore, the risk of overt stroke and silent brain ischaemia after TEER-MV was assessed. METHODS: In this prospective, pre-specified observational study, all patients underwent continuous transcranial Doppler examination during TEER-MV to detect microembolic signals (MES). MES were assigned to specific procedural steps: (1) transseptal puncture and placement of the guide, (2) advancing and adjustment of the clip in the left atrium, (3) device interaction with the MV, and (4) removal of the clip delivery system and the guide. Neurological examination using the National Institutes of Health Stroke Scale (NIHSS) and cerebral MRI were performed before and after TEER-MV. RESULTS: Fifty-four patients were included. The number of MES differed significantly between the procedural steps with the highest numbers observed during device interaction with the MV. Mild neurological deterioration (NIHSS ≤3) occurred in 9/54 patients. New ischaemic lesions were detected in 21/24 patients who underwent MRI. Larger infarct volume was significantly associated with neurological deterioration. CONCLUSIONS: Cerebral embolisation is immanent to TEER-MV and predominantly occurs during device interaction with the MV. Improvements to the procedure may focus on this procedural step.

Evolution of Blood-Brain Barrier Permeability in Subacute Ischemic Stroke and Associations With Serum Biomarkers and Functional Outcome.

Background and Purpose: In the setting of acute ischemic stroke, increased blood-brain barrier permeability (BBBP) as a sign of injury is believed to be associated with increased risk of poor outcome. Pre-clinical studies show that selected serum biomarkers including C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNFα), matrix metallopeptidases (MMP), and vascular endothelial growth factors (VEGFs) may play a role in BBBP post-stroke. In the subacute phase of stroke, increased BBBP may also be caused by regenerative mechanisms such as vascular remodeling and therefore may improve functional recovery. Our aim was to investigate the evolution of BBBP in ischemic stroke using contrast-enhanced (CE) magnetic resonance imaging (MRI) and to analyze potential associations with blood-derived biomarkers as well as functional recovery in subacute ischemic stroke patients. Methods: This is an exploratory analysis of subacute ischemic stroke patients enrolled in the BAPTISe study nested within the randomized controlled PHYS-STROKE trial (interventions: 4 weeks of aerobic fitness training vs. relaxation). Patients with at least one CE-MRI before (v1) or after (v2) the intervention were eligible for this analysis. The prevalence of increased BBBP was visually assessed on T1-weighted MR-images based on extent of contrast-agent enhancement within the ischemic lesion. The intensity of increased BBBP was assessed semi-quantitatively by normalizing the mean voxel intensity within the region of interest (ROI) to the contralateral hemisphere ("normalized CE-ROI"). Selected serum biomarkers (high-sensitive CRP, IL-6, TNF-α, MMP-9, and VEGF) at v1 (before intervention) were analyzed as continuous and dichotomized variables defined by laboratory cut-off levels. Functional outcome was assessed at 6 months after stroke using the modified Rankin Scale (mRS). Results: Ninety-three patients with a median baseline NIHSS of 9 [IQR 6-12] were included into the analysis. The median time to v1 MRI was 30 days [IQR 18-37], and the median lesion volume on v1 MRI was 4 ml [IQR 1.2-23.4]. Seventy patients (80%) had increased BBBP visible on v1 MRI. After the trial intervention, increased BBBP was still detectable in 52 patients (74%) on v2 MRI. The median time to v2 MRI was 56 days [IQR 46-67]. The presence of increased BBBP on v1 MRI was associated with larger lesion volumes and more severe strokes. Aerobic fitness training did not influence the increase of BBBP evaluated at v2. In linear mixed models, the time from stroke onset to MRI was inversely associated with normalized CE-ROI (coefficient -0.002, Standard Error 0.007, p < 0.01). Selected serum biomarkers were not associated with the presence or evolution of increased BBBP. Multivariable regression analysis did not identify the occurrence or evolution of increased BBBP as an independent predictor of favorable functional outcome post-stroke. Conclusion: In patients with moderate-to-severe subacute stroke, three out of four patients demonstrated increased BBB permeability, which decreased over time. The presence of increased BBBP was associated with larger lesion volumes and more severe strokes. We could not detect an association between selected serum biomarkers of inflammation and an increased BBBP in this cohort. No clear association with favorable functional outcome was observed. Trial registration: NCT01954797.

A novel approach for assessing hypoperfusion in stroke using spatial independent component analysis of resting-state fMRI.

Individualized treatment of acute stroke depends on the timely detection of ischemia and potentially salvageable tissue in the brain. Using functional MRI (fMRI), it is possible to characterize cerebral blood flow from blood-oxygen-level-dependent (BOLD) signals without the administration of exogenous contrast agents. In this study, we applied spatial independent component analysis to resting-state fMRI data of 37 stroke patients scanned within 24 hr of symptom onset, 17 of whom received follow-up scans the next day. Our analysis revealed "Hypoperfusion spatially-Independent Components" (HICs) whose spatial patterns of BOLD signal resembled regions of delayed perfusion depicted by dynamic susceptibility contrast MRI. These HICs were detected even in the presence of excessive patient motion, and disappeared following successful tissue reperfusion. The unique spatial and temporal features of HICs allowed them to be distinguished with high accuracy from other components in a user-independent manner (area under the curve = 0.93, balanced accuracy = 0.90, sensitivity = 1.00, and specificity = 0.85). Our study therefore presents a new, noninvasive method for assessing blood flow in acute stroke that minimizes interpretative subjectivity and is robust to severe patient motion.

Cognition-Related Functional Topographies in Parkinson's Disease: Localized Loss of the Ventral Default Mode Network.

Cognitive dysfunction in Parkinson's disease (PD) is associated with increased expression of the PD cognition-related pattern (PDCP), which overlaps with the normal default mode network (DMN). Here, we sought to determine the degree to which the former network represents loss of the latter as a manifestation of the disease process. To address this, we first analyzed metabolic images (fluorodeoxyglucose positron emission tomography [PET]) from a large PD sample with varying cognitive performance. Cognitive impairment in these patients correlated with increased PDCP expression as well as DMN loss. We next determined the spatial relationship of the 2 topographies at the subnetwork level. To this end, we analyzed resting-state functional magnetic resonance imaging (rs-fMRI) data from an independent population. This approach uncovered a significant PD cognition-related network that resembled previously identified PET- and rs-fMRI-based PDCP topographies. Further analysis revealed selective loss of the ventral DMN subnetwork (precuneus and posterior cingulate cortex) in PD, whereas the anterior and posterior components were not affected by the disease. Importantly, the PDCP also included a number of non-DMN regions such as the dorsolateral prefrontal and medial temporal cortex. The findings show that the PDCP is a reproducible cognition-related network that is topographically distinct from the normal DMN.

Frequency, clinical presentation and outcome of vigilance impairment in patients with uni- and bilateral ischemic infarction of the paramedian thalamus.

Ischemic stroke of the paramedian thalamus is a rare differential diagnosis in sudden altered vigilance states. While efforts to describe clinical symptomatology exist, data on the frequency of paramedian thalamic stroke as a cause of sudden impaired vigilance and on accompanying clinical signs and outcome are scarce. We retrospectively analyzed consecutive patients admitted to a tertiary stroke center between 2010 and 2019 diagnosed with paramedian thalamic stroke. We evaluated frequency of vigilance impairment (VI) due to paramedian thalamic stroke, accompanying clinical signs and short-term outcome in uni- versus bilateral paramedian lesion location. Of 3896 ischemic stroke patients, 53 showed a paramedian thalamic stroke location (1.4%). VI was seen in 29/53 patients with paramedian thalamic stroke and in 414/3896 with any stroke (10.6%). Paramedian thalamic stroke was identified as causal to VI in 3.4% of all patients with initial VI in the emergency department and in 0.7% of all ischemic stroke patients treated in our center. Accompanying clinical signs were detected in 21 of these 29 patients (72.4%) and facilitated a timely diagnosis. VI was significantly more common after bilateral than unilateral lesions (92.0% vs. 21.4%; p < 0.001). Patients with bilateral paramedian lesions were more severely affected, had longer hospital stays and more frequently required in-patient rehabilitation. Paramedian thalamic lesions account for about 1 in 15 stroke patients presenting with impaired vigilance. Bilateral paramedian lesion location is associated with worse stroke severity and short-term outcome. Paying attention to accompanying clinical signs is of importance as they may facilitate a timely diagnosis.

The Effect of Scan Length on the Assessment of BOLD Delay in Ischemic Stroke.

Objectives: To evaluate the impact of resting-state functional MRI scan length on the diagnostic accuracy, image quality and lesion volume estimation of BOLD delay maps used for brain perfusion assessment in acute ischemic stroke. Methods: Sixty-three acute ischemic stroke patients received a 340 s resting-state functional MRI within 24 h of stroke symptom onset. BOLD delay maps were calculated from the full scan and four shortened versions (68 s, 136 s, 204 s, 272 s). The BOLD delay lesions on these maps were compared in terms of spatial overlap and volumetric agreement with the lesions derived from the full scans and with time-to-maximum (Tmax) lesions derived from DSC-MRI in a subset of patients (n = 10). In addition, the interpretability and quality of these maps were compared across different scan lengths using mixed models. Results: Shortened BOLD delay scans showed a small volumetric bias (ranging from 0.05 to 5.3 mL; between a 0.13% volumetric underestimation and a 7.7% overestimation relative to the mean of the volumes, depending on scan length) compared to the full scan. Decreased scan length was associated with decreased spatial overlap with both the BOLD delay lesions derived from the full scans and with Tmax lesions. Only the two shortest scan lengths (68 and 136 s) were associated with substantially decreased interpretability, decreased structure clarity, and increased noisiness of BOLD delay maps. Conclusions: BOLD delay maps derived from resting-state fMRI scans lasting 272 and 204 s provide sufficient diagnostic quality and adequate assessment of perfusion lesion volumes. Such shortened scans may be helpful in situations where quick clinical decisions need to be made.

"Thalamic aphasia" after stroke is associated with left anterior lesion location.

BACKGROUND: Aphasic symptoms are typically associated with lesions of the left fronto-temporal cortex. Interestingly, aphasic symptoms have also been described in patients with thalamic strokes in anterior, paramedian or posterolateral location. So far, systematic analyses are missing. METHODS: We conducted a retrospective analysis of consecutive patients admitted to our tertiary stroke care center between January 2016 and July 2017 with image-based (MRI) proven ischemic stroke. We evaluated stroke lesion location, using 3-T MRI, and presence of aphasic symptoms. RESULTS: Out of 1064 patients, 104 (9.8%) presented with a thalamic stroke, 52 of which (4.9%) had an isolated lesion in the thalamus (ILT). In patients with ILT, 6/52 had aphasic symptoms. Aphasic symptoms after ILT were only present in patients with left anterior lesion location (n = 6, 100% left anterior vs. 0% other thalamic location, p < 0.001). CONCLUSIONS: Aphasic symptoms in thalamic stroke are strongly associated with left anterior lesion location. In thalamo-cortical language networks, specifically the nuclei in the left anterior thalamus could play an important role in integration of left cortical information with disconnection leading to aphasic symptoms.

Elevated brain oxygen extraction fraction measured by MRI susceptibility relates to perfusion status in acute ischemic stroke.

Recent clinical trials of new revascularization therapies in acute ischemic stroke have highlighted the importance of physiological imaging to identify optimal treatments for patients. Oxygen extraction fraction (OEF) is a hallmark of at-risk tissue in stroke, and can be quantified from the susceptibility effect of deoxyhemoglobin molecules in venous blood on MRI phase scans. We measured OEF within cerebral veins using advanced quantitative susceptibility mapping (QSM) MRI reconstructions in 20 acute stroke patients. Absolute OEF was elevated in the affected (29.3 ± 3.4%) versus the contralateral hemisphere (25.5 ± 3.1%) of patients with large diffusion-perfusion lesion mismatch (P = 0.032). In these patients, OEF negatively correlated with relative CBF measured by dynamic susceptibility contrast MRI (P = 0.004), suggesting compensation for reduced flow. Patients with perfusion-diffusion match or no hypo-perfusion showed less OEF difference between hemispheres. Nine patients received longitudinal assessment and showed OEF ratio (affected to contralateral) of 1.2 ± 0.1 at baseline that normalized (decreased) to 1.0 ± 0.1 at follow-up three days later (P = 0.03). Our feasibility study demonstrates that QSM MRI can non-invasively quantify OEF in stroke patients, relates to perfusion status, and is sensitive to OEF changes over time. Clinical trial registration: Longitudinal MRI examinations of patients with brain ischemia and blood brain barrier permeability; clinicaltrials.org :NCT02077582.

Non-invasive monitoring of longitudinal changes in cerebral hemodynamics in acute ischemic stroke using BOLD signal delay.

Relative delays in blood-oxygen-level-dependent (BOLD) signal oscillations can be used to assess cerebral perfusion without using contrast agents. However, little is currently known about the utility of this method in detecting clinically relevant perfusion changes over time. We investigated the relationship between longitudinal BOLD delay changes, vessel recanalization, and reperfusion in 15 acute stroke patients with vessel occlusion examined within 24 h of symptom onset (D0) and one day later (D1). We created BOLD delay maps using time shift analysis of resting-state functional MRI data and quantified perfusion lesion volume changes (using the D1/D0 volume ratio) and severity changes (using a linear mixed model) over time. Between baseline and follow-up, BOLD delay lesions shrank (median D1/D0 ratio = 0.2, IQR = 0.03-0.7) and BOLD delay severity decreased (b = -4.4 s) in patients with recanalization, whereas they grew (median D1/D0 ratio = 1.47, IQR = 1.1-1.7) and became more severe (b = 4.3 s) in patients with persistent vessel occlusion. Clinically relevant changes in cerebral perfusion in early stroke can be detected using BOLD delay, making this non-invasive method a promising option for detecting tissue at risk of infarction and monitoring stroke patients following recanalization therapy.

The Association Between Recanalization, Collateral Flow, and Reperfusion in Acute Stroke Patients: A Dynamic Susceptibility Contrast MRI Study.

Background: Collateral circulation in ischemic stroke patients plays an important role in infarct evolution und assessing patients' eligibility for endovascular treatment. By means of dynamic susceptibility contrast MRI, we aimed to investigate the effects of reperfusion, recanalization, and collateral flow on clinical and imaging outcomes after stroke. Methods: Retrospective analysis of 184 patients enrolled into the prospective observational 1000Plus study (clinicaltrials.org NCT00715533). Inclusion criteria were vessel occlusion on baseline MR-angiography, imaging within 24 h after stroke onset and follow-up perfusion imaging. Baseline Higashida score using subtracted dynamic MR perfusion source images was used to quantify collateral flow. The influence of these variables, and their interaction with vessel recanalization, on clinical and imaging outcomes was assessed using robust linear regression. Results: Ninety-eight patients (53.3%) showed vessel recanalization. Higashida score (p = 0.002), and recanalization (p = 0.0004) were independently associated with reperfusion. However, we found no evidence that the association between Higashida score and reperfusion relied on recanalization status (p = 0.2). NIHSS on admission (p < 0.0001) and recanalization (p = 0.001) were independently associated with long-term outcome at 3 months, however, Higashida score (p = 0.228) was not. Conclusion: Higashida score and recanalization were independently associated with reperfusion, but the association between recanalization and reperfusion was similar regardless of collateral flow quality. Recanalization was associated with long-term outcome. DSC-based measures of collateral flow were not associated with long-term outcome, possibly due to the complex dynamic nature of collateral recruitment, timing of imaging and the employed post-processing.