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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 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.

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.

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

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 p Conclusions SIR on TOF-MRA can be a marker of extracranial ICAS.

Aphasie ist ein typisches Symptom links fronto-temporaler Lasionen. Nicht selten werden aphasische Symptome jedoch auch nach subkortikalen Lasionen z. B. im Thalamus beschrieben. Als Ursache fur aphasische Symptome bei Thalamusschadigungen vermutet man die Storung eines thalamo-kortikalen Sprachnetzwerkes. Die Rolle des Thalamus in Sprachfunktionen wird in einer Rekrutierung sprachrelevanter, kortikaler Areale im Sinne einer Monitorfunktion vermutet. Wir berichten uber einen 72-jahrigen Patienten, der nach einem isolierten, links-anterioren Thalamusinfarkt eine expressiv betonte Aphasie gezeigt hat, und geben einen Uberblick zu pathophysiologischen Konzepten. Aphasia is a language disturbance typically associated with left fronto-temporal lesions. However, aphasic symptoms can also be seen after subcortical lesions, for example in the thalamus. Thalamic aphasia is thought to occur after disruption of a thalamo-cortical language networks. The thalamus is considered to act as a monitor, engaging specific cortical areas need for language functions. We report on a 72-year old male patient who presented with aphasia following a left-anterior ischemic stroke of the thalamus and present a review of the relevant literature.

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.

Neurological diseases such as ischemic stroke and dementia are associated with compromised blood-brain barrier (BBB) permeability. Knowledge about the time course of BBB leakage may have impact on therapeutic interventions and diagnostic measures such as testing for blood biomarkers. However, reports on the timeline and pattern of this leakage are contradictory. Therefore, we aimed to assess the time course of BBB permeability in ischemic stroke patients during the first 24 hours after symptom onset using dynamic contrast enhanced (DCE) MRI at 3 Tesla. We categorized time from stroke symptom onset to imaging into the following groups 1) 0-6 hours (n=10), 2) 6-16 hours (n=14) and 3) 16-24 hours (n=29). BBB permeability differed significantly between stroke lesions and the contralesional tissue for groups 2 and 3 (p=0.006, p

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.

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. 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. 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

Background and Purpose— Many patients with acute ischemic stroke are not eligible for thrombolysis or mechanical reperfusion therapies due to contraindications, inaccessible vascular occlusions, late presentation, or large infarct core. Sphenopalatine ganglion (SPG) stimulation to enhance collateral flow and stabilize the blood-brain barrier offers an alternative, potentially more widely deliverable, therapy. Methods— In a randomized, sham-controlled, double-masked trial at 41 centers in 7 countries, patients with anterior circulation ischemic stroke not treated with reperfusion therapies within 24 hours of onset were randomly allocated to active SPG stimulation or sham control. The primary efficacy outcome was improvement beyond expectations on the modified Rankin Scale of global disability at 90 days (sliding dichotomy), assessed in the modified intention-to-treat population. The initial planned sample size was 660 patients, but the trial was stopped early when technical improvements in device placement occurred, so that analysis of accumulated experience could be conducted to inform a successor trial. Results— Among 303 enrolled patients, 253 received at least one active SPG or sham stimulation, constituting the modified intention-to-treat population (153 SPG stimulation and 100 sham control). Age was median 73 years (interquartile range, 64–79), 52.6% were female, deficit severity on the National Institutes of Health Stroke Scale was median 11 (interquartile range, 9–15), and time from last known well median 18.6 hours (interquartile range, 14.5–22.5). For the primary outcome, improved 3-month disability beyond expectations, rates in the SPG versus sham treatment groups were 49.7% versus 40.0%; odds ratio, 1.48 (95% CI, 0.89–2.47); P =0.13. A significant treatment interaction with stroke location (cortical versus noncortical) was noted, P =0.04. In the 87 patients with confirmed cortical involvement, rates of improvement beyond expectations were 50.0% versus 27.0%; odds ratio, 2.70 (95% CI, 1.08–6.73); P =0.03. Similar response patterns were observed for all prespecified secondary efficacy outcomes. No differences in mortality or serious adverse event safety end points were observed. Conclusions— SPG stimulation within 24 hours of onset is safe in acute ischemic stroke. SPG stimulation was not shown to statistically significantly improve 3-month disability above expectations, though favorable outcomes were nominally higher with SPG stimulation. Beneficial effects may distinctively be conferred in patients with confirmed cortical involvement. The results of this study need to be confirmed in a larger pivotal study. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT03767192.

To determine the frequency and distribution pattern of acute DWI lesions outside the hippocampus in patients clinically presenting with Transient Global Amnesia (TGA).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.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.

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.

International audience; BACKGROUND: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers. METHODS: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0-1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0-2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4-6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903. FINDINGS: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10-2·03]; p=0·011), with low heterogeneity across studies (I(2)=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05-1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06-2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4-6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52-1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03-4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [\textless1%], adjusted OR 5·58 [1·22-25·50]; p=0·024). INTERPRETATION: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death. FUNDING: None.

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., This article presents a new, noninvasive method for assessing blood flow in acute stroke that minimizes interpretative subjectivity and is robust to patient motion.

ObjectiveTo identify, characterize, and automatically classify hypoperfusion-related changes in the blood oxygenation level dependent (BOLD) signal in acute stroke using spatial independent component analysis of resting-state functional MRI data. MethodsWe applied spatial independent component analysis to resting-state functional MRI data of 37 stroke patients scanned within 24 hours of symptom onset, 17 of whom received follow-up scans the next day. All patients also received dynamic susceptibility contrast MRI. After denoising and manually classifying the components, we extracted a set of temporal and spatial features from each independent component and used a generalized linear model to automatically identify components related to tissue hypoperfusion. ResultsOur analysis revealed "Hypoperfusion spatially-Independent Components" (HICs) whose BOLD signal spatial patterns 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 (AUC = 0.95, accuracy = 0.96, sensitivity = 1.00, specificity = 0.96). InterpretationOur study presents a new, non-invasive method for assessing blood flow in acute stroke that minimizes interpretative subjectivity and is robust to severe patient motion.

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

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.

Background and Purpose— Data on effects of intravenous thrombolysis on outcome of patients with ischemic stroke who are dependent on assistance in activities of daily living prestroke are scarce. Recent registry based analyses in activities of daily –independent patients suggest that earlier start of intravenous thrombolysis in the prehospital setting leads to better outcomes when compared with the treatment start in hospital. We evaluated whether these observations can be corroborated in patients with prestroke dependency. Methods— This observational, retrospective analysis included all patients with acute ischemic stroke depending on assistance before stroke who received intravenous thrombolysis either on the Stroke Emergency Mobile (STEMO) or through conventional in-hospital care (CC) in a tertiary stroke center (Charité, Campus Benjamin Franklin, Berlin) during routine care. Prespecified outcomes were modified Rankin Scale scores of 0 to 3 and survival at 3 months, as well as symptomatic intracranial hemorrhage. Outcomes were adjusted in multivariable logistic regression. Results— Between February 2011 and March 2015, 122 of 427 patients (28%) treated on STEMO and 142 of 505 patients (28%) treated via CC needed assistance before stroke. Median onset-to-treatment times were 97 (interquartile range, 69–159; STEMO) and 135 (interquartile range, 98–184; CC; P P =0.01) and 86 (70%, STEMO) versus 85 (60%, CC) patients were alive ( P =0.07). After adjustment, STEMO care was favorable with respect to modified Rankin Scale scores of 0 to 3 (odds ratio, 1.99; 95% confidence interval, 1.02–3.87; P =0.042) with a nonsignificant result for survival (odds ratio, 1.73; 95% confidence interval, 0.95–3.16; P =0.07). Symptomatic intracranial hemorrhage occurred in 5 STEMO versus 12 CC patients (4.2% versus 8.5%; P =0.167). Conclusions— The results of this study suggest that earlier, prehospital (as compared with in-hospital) start of intravenous thrombolysis in acute ischemic stroke may translate into better clinical outcome in patients with prestroke dependency. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT02358772.

ObjectivesPost-contrast magnetic resonance angiography (PC-MRA) enables visualization of vessel segments distal to an intra-arterial thrombus in acute ischemic stroke. We hypothesized that PC-MRA also allows clot length measurement in different intracranial vessels.MethodsPatients with MRI-confirmed ischemic stroke and intracranial artery occlusion within 24 hours of symptom onset were prospectively evaluated. PC-MRA was added to a standard stroke MRI protocol. Thrombus length was measured on thick slab maximum intensity projection images. Clinical outcome at hospital discharge was assessed by modified Rankin Scale (mRS).ResultsThirty-four patients (median age 72 years) presenting with a median National Institutes of Health Stroke Scale score of 11 and a median onset to imaging time of 116 min were included. PC-MRA enabled precise depiction of proximal and distal terminus of the thrombus in 31 patients (91%), whereas in three patients (9%) PC-MRA presented a partial occlusion. Median thrombus length in patients with complete occlusion was 9.9 mm. In patients with poor outcome (mRS ≥3) median thrombus length was significantly longer than in those with good outcome (mRS ≤2;P=0.011).ConclusionsPC-MRA demonstrates intra-arterial thrombus length at different vessel occlusion sites. Longer thrombus length is associated with poor clinical outcome.Clinical trial registrationNCT02077582; Results.

Objective Elevated levels of cardiac troponin, and especially their relative changes over time, indicate acute myocardial injury. They are also frequently observed after acute ischemic stroke (AIS), indicating poor functional outcome and increased mortality. However, recent evidence showed that, in most AIS patients, myocardial injury is not caused by coronary ischemia. Instead, stroke lesion location has been suggested to precipitate myocardial injury. Methods Voxel-based lesion-symptom mapping (VLSM) was used in 299 patients who had a magnetic resonance imaging–confirmed acute ischemic stroke within the anterior circulation and a high-sensitivity cardiac troponin T (hs-cTnT) acquired on the day of admission. Of these, 228 had a second troponin measurement during the acute phase. The absolute hs-cTnT levels above the 99th percentile of a healthy reference population (≥14ng/l) as well as their relative temporal changes were used as continuous variables of interest in the VLSM model, including a multiple regression analysis adjusted for confounding variables. Results The anterior insular cortex of the right hemisphere, in particular its dorsal subregion, was significantly associated with the relative temporal changes of hs-cTnT (p

Objective:To quantitatively evaluate blood–brain barrier changes in ischemic stroke patients using dynamic contrast-enhanced (DCE) MRI.Methods:We examined 54 stroke patients (clinicaltrials.govNCT00715533, NCT02077582) in a 3T MRI scanner within 48 hours after symptom onset. Twenty-eight patients had a follow-up examination on day 5–7. DCE T1 mapping and Patlak analysis were employed to assess BBB permeability changes.Results:Median stroke Ktrans values (0.7 × 10−3 min−1 [interquartile range (IQR) 0.4–1.8] × 10−3 min−1) were more than 3-fold higher compared to median mirror Ktrans values (0.2 × 10−3 min−1, IQR 0.1–0.7 × 10−3 min−1, p < 0.001) and further increased at follow-up (n = 28, 2.3 × 10−3 min−1, IQR 0.8–4.6 × 10−3 min−1, p < 0.001). By contrast, mirror Ktrans values decreased over time with a clear interaction of timepoint and stroke/mirror side (p < 0.001). Median stroke Ktrans values were 2.5 times lower than in hemorrhagic transformed regions (0.7 vs 1.8 × 10−3 min−1; p = 0.055). There was no association between stroke Ktrans values and the delay from symptom onset to baseline examination, age, and presence of hyperintense acute reperfusion marker.Conclusion:BBB in acute stroke patients can be successfully assessed quantitatively. The decrease of BBB permeability in unaffected regions at follow-up may be an indicator of global BBB leakage even in vessel territories remote from the index infarct.

Objective To identify possible gray matter alterations in patients with chronic migraine using voxel-based morphometry (VBM). Background VBM studies demonstrate structural alterations of gray matter (GM) in episodic migraine (EM) patients. Some of these alterations correlate with disease duration and headache frequency. We assessed GM alterations in chronic migraine (CM) and EM to evaluate the concept of migraine as a progressive disorder of the brain. Methods Individually age and sex-matched subjects with CM or EM (both without aura) and healthy controls (n = 21 per group) underwent magnetic resonance imaging-based VBM. Results We found an increase of GM volume (GMV) in amygdala and putamen, in CM compared to controls. GMV of EM compared to controls did not differ statistically significantly. Headache frequency in all migraineurs (EM and CM) correlated positively with GMV in putamen, frontal and temporal gyrus and negatively in left cuneus. Conclusion CM is associated with structural changes in brain regions involved in pain processing but also in affective and cognitive aspects of pain. Some GM alterations are correlated with headache frequency assessed in EM and CM. The findings support the assumption that chronic pain alters brain plasticity. GMV increase may reflect a remodeling of the central nervous system due to repetitive headache attacks leading to chronic sensitization and a continuous ictal-like state of the brain in chronic migraineurs.

Background and purpose Several studies have described an association between insular infarction and mortality. Large infarcts often include the insula and lesion size is associated with mortality. We hypothesized that there is an association between insular infarction and mortality independent of lesion volume. Methods We included consecutive stroke patients between 1 September 2008 and 11 November 2012 from the 1000Plus database with an acute ischaemic lesion on diffusion-weighted imaging on day 1 and a completed 90-day follow-up. Insular infarct location was determined using the in-house software Stroke Lesion Atlas. In multiple Cox regression analysis (dependent variable: mortality), we adjusted for insular infarcts, age, lesion volume, history of atrial fibrillation, National Institutes of Health Stroke Scale and previous stroke. Results We included 736 patients, of whom 168 had an insular infarction. Within a medium follow-up time of 107 days, cumulative survival was 90% in patients with insular infarction and 99% in patients without insular infarction (P < 0.001). Right insular infarction was independently associated with mortality (hazard ratio, 2.60; confidence interval, 1.3–5.4; P = 0.010). Conclusions In our study, right insular involvement was a prognostic marker for mortality after ischaemic stroke. A selection bias towards patients able to give informed consent warrants further studies.

Perfusion imaging (PI) is susceptible to confounding factors such as motion artefacts as well as delay and dispersion (D/D). We evaluate the influence of different post-processing algorithms on hypoperfusion assessment in PI analysis software packages to improve the clinical accuracy of stroke PI. Fifty patients with acute ischaemic stroke underwent MRI imaging in the first 24 h after onset. Diverging approaches to motion and D/D correction were applied. The calculated MTT and CBF perfusion maps were assessed by volumetry of lesions and tested for agreement with a standard approach and with the final lesion volume (FLV) on day 6 in patients with persisting vessel occlusion. MTT map lesion volumes were significantly smaller throughout the software packages with correction of motion and D/D when compared to the commonly used approach with no correction (p = 0.001–0.022). Volumes on CBF maps did not differ significantly (p = 0.207–0.925). All packages with advanced post-processing algorithms showed a high level of agreement with FLV (ICC = 0.704–0.879). Correction of D/D had a significant influence on estimated lesion volumes and leads to significantly smaller lesion volumes on MTT maps. This may improve patient selection. • Assessment on hypoperfusion using advanced post-processing with correction for motion and D/D. • CBF appears to be more robust regarding differences in post-processing. • Tissue at risk is estimated more accurately by correcting software algorithms. • Advanced post-processing algorithms show a higher agreement with the final lesion volume.

Background and Purpose— In computed tomographic imaging of acute intracerebral hemorrhage spot sign on computed tomographic angiography has been established as a marker for hematoma expansion and poor clinical outcome. Although, magnetic resonance imaging (MRI) can accurately visualize acute intracerebral hemorrhage, a corresponding MRI marker is lacking to date. Methods— We prospectively examined 50 consecutive patients with acute intracerebral hemorrhage within 24 hours of symptom onset. The MRI protocol consisted of a standard stroke protocol and dynamic contrast-enhanced T1-weighted imaging with a time resolution of 7.07 s/batch. Stroke scores were assessed at admission and at time of discharge. Volume measurements of hematoma size and spot sign were performed with MRIcron. Results— Contrast extravasation within sites of the hemorrhage (MRI spot sign) was seen in 46% of the patients. Patients with an MRI spot sign had a significantly shorter time to imaging than those without ( P P ≤0.001). Hematoma expansion was observed in the spot sign group compared with the nonspot sign group, although the differences were not significant. Conclusions— Spot sign can be detected using MRI on postcontrast T1-weighted and dynamic T1-weighted images. It is associated with worse clinical outcome. The time course of contrast extravasation in dynamic T1 images indicates that these spots represent ongoing bleeding.

Cardiac troponin (hs-cTnT) is a sensitive marker of myocardial injury and has been linked to incident dementia. The underlying mechanism of that observation is still unknown. Given that severity of cerebral small vessel disease is a predictor of cognitive decline, we aimed to explore whether there is an association between hs-cTnT and severity of white matter lesions (WML) as a marker of cerebral small vessel disease in patients with ischemic stroke. We analyzed consecutive acute ischemic stroke patients admitted to Charite-University Hospital, Berlin from 2011 to 2013. Severity of WML was graded on 3T-MRI using the age-related white matter severity score (ARWMS). Patients with hs-cTnT elevation suggestive of acute coronary syndrome (ACS) were excluded (hs-cTnT > 52 ng/l or dynamic change of hs-cTnT > 50%, ESC guideline). We performed unadjusted and adjusted quantile regression models to assess the association between increased hs-cTnT (dichotomized at the 99th percentile, 14 ng/l) and severity of WML. A total of 860 patients was analyzed (median age 73 years, 44.8% female, median ARWMS 6). Patients with elevated hs-cTnT had more extensive WML than those without (median ARWMS 8 vs. 5, adjusted beta for 50th percentile 1.12, 95% CI 0.41–1.84). The association between WML and hs-cTnT elevation was strongest in patients with severe WML (adjusted beta 1.77, 95% CI 0.26–3.27 for 80th WML percentile). Elevated hs-cTnT levels were associated with extent of WML in acute stroke patients. Further studies are needed to assess whether hs-cTnT can be used to identify stroke patients at risk for cognitive decline.

The functional organization of the brain can be represented as a low-dimensional space that reflects its macroscale hierarchy. The dimensions of this space, described as connectivity gradients, capture the similarity of areas' connections along a continuous space. Studying how pathological perturbations with known effects on functional connectivity affect these connectivity gradients provides support for their biological relevance. Previous work has shown that localized lesions cause widespread functional connectivity alterations in structurally intact areas, affecting a network of interconnected regions. By using acute stroke as a model of the effects of focal lesions on the connectome, we apply the connectivity gradient framework to depict how functional reorganization occurs throughout the brain, unrestricted by traditional definitions of functional network boundaries. We define a three-dimensional connectivity space template based on functional connectivity data from healthy controls. By projecting lesion locations into this space, we demonstrate that ischemic strokes result in dimension-specific alterations in functional connectivity over the first week after symptom onset. Specifically, changes in functional connectivity were captured along connectivity Gradients 1 and 3. The degree of functional connectivity change was associated with the distance from the lesion along these connectivity gradients (a measure of functional similarity) regardless of the anatomical distance from the lesion. Together, these results provide support for the biological validity of connectivity gradients and suggest a novel framework to characterize connectivity alterations after stroke., Highlights • Impact of stroke follows continuous architecture of connectivity gradients. • The widespread effects of stroke can be detected at the connectome level. • Distance from lesion within connectivity space captures changes during recovery. • Connectivity gradients offer template to capture reorganization at connectome level.