Long-Term Outcomes in Patients With Spontaneous Cerebellar Hemorrhage: An International Cohort Study.

BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) in the cerebellum has a poor short-term prognosis, whereas data on the long-term case fatality and recurrent vascular events are sparse. Herewith, we aimed to assess the long-term case fatality and recurrence rate of vascular events after a first cerebellar ICH. METHODS: In this international cohort study, we included patients from 10 hospitals (the United States and Europe from 1997 to 2017) aged ≥18 years with a first spontaneous cerebellar ICH who were discharged alive. Data on long-term case fatality and recurrence of vascular events (recurrent ICH [supratentoria or infratentorial], ischemic stroke, myocardial infarction, or major vascular surgery) were collected for survival analysis and absolute event rate calculation. RESULTS: We included 405 patients with cerebellar ICH (mean age [SD], 72 [13] years, 49% female). The median survival time was 67 months (interquartile range, 23-100 months), with a cumulative survival rate of 34% at 10-year follow-up (median follow-up time per center ranged: 15-80 months). In the 347 patients with data on vascular events 92 events occurred in 78 patients, after initial cerebellar ICH: 31 (8.9%) patients had a recurrent ICH (absolute event rate, 1.8 per 100 patient-years [95% CI, 1.2-2.6]), 39 (11%) had an ischemic stroke (absolute event rate, 2.3 [95% CI, 1.6-3.2]), 13 (3.7%) had a myocardial infarction (absolute event rate, 0.8 [95% CI, 0.4-1.3]), and 5 (1.4%) underwent major vascular surgery (absolute event rate, 0.3 [95% CI, 0.1-0.7]). The median time to a first vascular event during follow-up was 27 months (interquartile range, 8.7-50 months), with a cumulative hazard of 47% at 10 years. CONCLUSIONS: The long-term prognosis of patients who survive a first spontaneous cerebellar ICH is poor and comparable to that of patients who survive a first supratentorial ICH. Further identification of patients at high risk of vascular events following the initial cerebellar ICH is needed. Including patients with cerebellar ICH in randomized controlled trials on secondary prevention of patients with ICH is warranted.

Signal intensity and volume of carotid intraplaque hemorrhage on magnetic resonance imaging and the risk of ipsilateral cerebrovascular events: The Plaque At RISK (PARISK) study.

BACKGROUND: The Plaque At RISK (PARISK) study demonstrated that patients with a carotid plaque with intraplaque hemorrhage (IPH) have an increased risk of recurrent ipsilateral ischemic cerebrovascular events. It was previously reported that symptomatic carotid plaques with IPH showed higher IPH signal intensity ratios (SIR) and larger IPH volumes than asymptomatic plaques. We explored whether IPH SIR and IPH volume are associated with future ipsilateral ischemic cerebrovascular events beyond the presence of IPH. METHODS: Transient ischemic attack and ischemic stroke patients with mild-to-moderate carotid stenosis and an ipsilateral IPH-positive carotid plaque (n = 89) from the PARISK study were included. The clinical endpoint was a new ipsilateral ischemic cerebrovascular event during 5 years of follow-up, while the imaging-based endpoint was a new ipsilateral brain infarct on brain magnetic resonance imaging (MRI) after 2 years (n = 69). Trained observers delineated IPH, a hyperintense region compared to surrounding muscle tissue on hyper T1-weighted magnetic resonance images. The IPH SIR was the maximal signal intensity in the IPH region divided by the mean signal intensity of adjacent muscle tissue. The associations between IPH SIR or volume and the clinical and imaging-based endpoint were investigated using Cox proportional hazard models and logistic regression, respectively. RESULTS: During 5.1 (interquartile range: 3.1-5.6) years of follow-up, 21 ipsilateral cerebrovascular ischemic events were identified. Twelve new ipsilateral brain infarcts were identified on the 2-year neuro MRI. There was no association for IPH SIR or IPH volume with the clinical endpoint (hazard ratio (HR): 0.89 [95% confidence interval: 0.67-1.10] and HR: 0.91 [0.69-1.19] per 100-µL increase, respectively) nor with the imaging-based endpoint (odds ratio (OR): 1.04 [0.75-1.45] and OR: 1.21 [0.87-1.68] per 100-µL increase, respectively). CONCLUSION: IPH SIR and IPH volume were not associated with future ipsilateral ischemic cerebrovascular events. Therefore, quantitative assessment of IPH of SIR and volume does not seem to provide additional value beyond the presence of IPH for stroke risk assessment. TRIAL REGISTRATION: The PARISK study was registered on ClinicalTrials.gov with ID NCT01208025 on September 21, 2010 (https://clinicaltrials.gov/study/NCT01208025).

Improvements in Endovascular Treatment for Acute Ischemic Stroke: A Longitudinal Study in the MR CLEAN Registry.

BACKGROUND: We evaluated data from all patients in the Netherlands who underwent endovascular treatment for acute ischemic stroke in the past 3.5 years, to identify nationwide trends in time to treatment and procedural success, and assess their effect on clinical outcomes. METHODS: We included patients with proximal occlusions of the anterior circulation from the second and first cohorts of the MR CLEAN (Multicenter Randomized Clinical trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry (March 2014 to June 2016; June 2016 to November 2017, respectively). We compared workflow times and rates of successful reperfusion (defined as an extended Thrombolysis in Cerebral Infarction score of 2B-3) between cohorts and chronological quartiles (all included patients stratified in chronological quartiles of intervention dates to create equally sized groups over the study period). Multivariable ordinal logistic regression was used to assess differences in the primary outcome (ordinal modified Rankin Scale at 90 days). RESULTS: Baseline characteristics were similar between cohorts (second cohort n=1692, first cohort n=1488) except for higher age, poorer collaterals, and less signs of early ischemia on computed tomography in the second cohort. Time from stroke onset to groin puncture and reperfusion were shorter in the second cohort (median 185 versus 210 minutes; P<0.001 and 236 versus 270 minutes; P<0.001, respectively). Successful reperfusion was achieved more often in the second than in the first cohort (72% versus 66%; P<0.001). Functional outcome significantly improved (adjusted common odds ratio 1.23 [95% CI, 1.07-1.40]). This effect was attenuated by adjustment for time from onset to reperfusion (adjusted common odds ratio, 1.12 [95% CI, 0.98-1.28]) and successful reperfusion (adjusted common odds ratio, 1.13 [95% CI, 0.99-1.30]). Outcomes were consistent in the analysis per chronological quartile. CONCLUSIONS: Clinical outcomes after endovascular treatment for acute ischemic stroke in routine clinical practice have improved over the past years, likely resulting from improved workflow times and higher successful reperfusion rates.

Blood Pressure in the First 6 Hours Following Endovascular Treatment for Ischemic Stroke Is Associated With Outcome.

Background and Purpose: Optimal blood pressure (BP) management in the acute phase of ischemic stroke remains an unresolved issue. It is uncertain whether guidelines for BP management during and after intravenous alteplase can be extrapolated to endovascular treatment (EVT) for stroke due to large artery occlusion in the anterior circulation. We evaluated the associations between systolic BP (SBP) in the first 6 hours following EVT and functional outcome as well as symptomatic intracranial hemorrhage. Methods: Patients of 8 MR CLEAN (Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry centers, with available data on SBP in the 6 hours following EVT, were analyzed. We evaluated maximum, minimum, and mean SBP. Study outcomes were functional outcome (modified Rankin Scale) at 90 days and symptomatic intracranial hemorrhage. We used multivariable ordinal and binary regression analysis to adjust for important prognostic factors and studied possible effect modification by successful reperfusion. Results: Post-EVT SBP data were available for 1161/1796 patients. Higher maximum SBP (per 10 mm Hg increments) was associated with worse functional outcome (adjusted common odds ratio, 0.93 [95% CI, 0.88­0.98]) and a higher rate of symptomatic intracranial hemorrhage (adjusted odds ratio, 1.17 [95% CI, 1.02­1.36]). The association between minimum SBP and functional outcome was nonlinear with an inflection point at 124 mm Hg. Minimum SBP lower and higher than the inflection point were associated with worse functional outcomes (adjusted common odds ratio, 0.85 per 10 mm Hg decrements [95% CI, 0.76­0.95] and adjusted common odds ratio, 0.81 per 10 mm Hg increments [95% CI, 0.71­0.92]). No association between mean SBP and functional outcome was observed. Successful reperfusion did not modify the relation of SBP with any of the outcomes. Conclusions: Maximum SBP in the first 6 hours following EVT is positively associated with worse functional outcome and an increased risk of symptomatic intracranial hemorrhage. Both lower and higher minimum SBP are associated with worse outcomes. A randomized trial to evaluate whether modifying post-intervention SBP results in better outcomes after EVT for ischemic stroke seems justified.

In situ decompression vs conservative treatment for mild ulnar neuropathy at the elbow.

INTRODUCTION: The best treatment strategy for mild ulnar neuropathy at the elbow (UNE) is not known, due to lack of trials comparing surgery vs conservative treatment. METHODS: We recruited patients with clinical symptoms and signs of mild UNE and an electrophysiologically or sonographically confirmed diagnosis. Patients were randomly allocated to either in situ decompression or conservative treatment. The primary outcome was the proportion of patients with subjective symptom improvement at short-term (3 months) and long-term (6-12 months) follow-up. RESULTS: One hundred seventeen patients were included: 56 and 61 patients were allocated to surgery and conservative treatment, respectively. A larger proportion of surgically treated patients showed improvement at short-term follow-up (85% vs 50%; odds ratio, 5.6; P < .001), but no differences were observed at long-term follow-up. DISCUSSION: In situ decompression for mild UNE may result in faster relief of symptoms when compared with conservative treatment, but at long-term follow-up no differences were observed.

A randomized trial of intraarterial treatment for acute ischemic stroke.

BACKGROUND: In patients with acute ischemic stroke caused by a proximal intracranial arterial occlusion, intraarterial treatment is highly effective for emergency revascularization. However, proof of a beneficial effect on functional outcome is lacking. METHODS: We randomly assigned eligible patients to either intraarterial treatment plus usual care or usual care alone. Eligible patients had a proximal arterial occlusion in the anterior cerebral circulation that was confirmed on vessel imaging and that could be treated intraarterially within 6 hours after symptom onset. The primary outcome was the modified Rankin scale score at 90 days; this categorical scale measures functional outcome, with scores ranging from 0 (no symptoms) to 6 (death). The treatment effect was estimated with ordinal logistic regression as a common odds ratio, adjusted for prespecified prognostic factors. The adjusted common odds ratio measured the likelihood that intraarterial treatment would lead to lower modified Rankin scores, as compared with usual care alone (shift analysis). RESULTS: We enrolled 500 patients at 16 medical centers in The Netherlands (233 assigned to intraarterial treatment and 267 to usual care alone). The mean age was 65 years (range, 23 to 96), and 445 patients (89.0%) were treated with intravenous alteplase before randomization. Retrievable stents were used in 190 of the 233 patients (81.5%) assigned to intraarterial treatment. The adjusted common odds ratio was 1.67 (95% confidence interval [CI], 1.21 to 2.30). There was an absolute difference of 13.5 percentage points (95% CI, 5.9 to 21.2) in the rate of functional independence (modified Rankin score, 0 to 2) in favor of the intervention (32.6% vs. 19.1%). There were no significant differences in mortality or the occurrence of symptomatic intracerebral hemorrhage. CONCLUSIONS: In patients with acute ischemic stroke caused by a proximal intracranial occlusion of the anterior circulation, intraarterial treatment administered within 6 hours after stroke onset was effective and safe. (Funded by the Dutch Heart Foundation and others; MR CLEAN Netherlands Trial Registry number, NTR1804, and Current Controlled Trials number, ISRCTN10888758.).

Intravoxel Incoherent Motion Imaging in Small Vessel Disease: Microstructural Integrity and Microvascular Perfusion Related to Cognition.

BACKGROUND AND PURPOSE: Cerebral small vessel disease (SVD) is associated with cognitive impairment. This may be because of decreased microstructural integrity and microvascular perfusion, but data on these relationships are scarce. We determined the relationship between cognition and microvascular perfusion and microstructural integrity in SVD patients, using intravoxel incoherent motion imaging-a diffusion-weighted magnetic resonance imaging technique designed to determine microvascular perfusion and microstructural integrity simultaneously. METHODS: Seventy-three patients with SVD and 39 controls underwent intravoxel incoherent motion imaging and neuropsychological assessment. Parenchymal diffusivity D (a surrogate measure of microstructural integrity) and perfusion-related measure fD* were calculated for the normal appearing white matter, white matter hyperintensities, and cortical gray matter. The associations between cognitive performance and D and fD* were determined. RESULTS: In SVD patients, multivariable analysis showed that lower fD* in the normal appearing white matter and cortical gray matter was associated with lower overall cognition (P=0.03 and P=0.002, respectively), lower executive function (P=0.04 and P=0.01, respectively), and lower information-processing speed (P=0.04 and P=0.01, respectively). D was not associated with cognitive function. In controls, no association was found between D, fD*, and cognition. CONCLUSIONS: In SVD patients, lower cognitive performance is associated with lower microvascular perfusion in the normal appearing white matter and cortical gray matter. Our results support recent findings that both cortical gray matter and normal appearing white matter perfusion may play a role in the pathophysiology of cognitive dysfunction in SVD. CLINICAL TRIAL REGISTRATION: URL: http://www.trialregister.nl. Unique identifier: NTR3786.

Ischemic Stroke Patients Demonstrate Increased Carotid Plaque Microvasculature Compared to (Ocular) Transient Ischemic Attack Patients.

BACKGROUND: Patients with a recent ischemic stroke have a higher risk of recurrent stroke compared to (ocular) transient ischemic attack (TIA) patients. Plaque microvasculature is considered as a feature of plaque vulnerability and can be quantified with carotid dynamic contrast-enhanced MRI (DCE-MRI). The purpose of this cross-sectional study was to explore the association between plaque microvasculature and the type of recent cerebrovascular events in symptomatic patients with mild-to-moderate carotid stenosis. METHODS: A total of 87 symptomatic patients with a recent stroke (n = 35) or (ocular) TIA (n = 52) underwent carotid DCE-MRI examination. Plaque microvasculature was studied in the vessel wall and adventitia using DCE-MRI and the pharmacokinetic modeling parameter Ktrans. Statistical analysis was performed with logistic regression, correcting for associated clinical risk factors. RESULTS: The 75th percentile adventitial (OR 1.97, 95% CI 1.18-3.29) Ktrans was significantly associated with a recent ischemic stroke compared to (ocular) TIA in multivariate analysis, while clinical risk factors were not significantly associated with the type of event. CONCLUSIONS: This study indicates a positive association of leaky plaque microvasculature with a recent ischemic stroke compared to (ocular) TIA. Prospective longitudinal studies are needed to investigate whether Ktrans or other plaque characteristics may serve as an imaging marker for predicting (the type of) future cerebrovascular events.

Incidence of oral anticoagulant-associated intracerebral hemorrhage in the Netherlands.

BACKGROUND AND PURPOSE: The aim of this study was to estimate the annual adult incidence and risk of intracerebral hemorrhage (ICH) and oral anticoagulant-associated ICH (OAC-ICH) in the Netherlands. METHODS: We retrospectively selected all consecutive adult patients with a nontraumatic ICH seen in 1 of 3 hospitals in the region South-Limburg, the Netherlands, from 2007 to 2009. Crude incidences were age-adjusted to Dutch and European population. RESULTS: We identified 652 ICH cases, of which 168 (25.8%) were OAC associated. The adult Dutch age-adjusted annual incidence of ICH and OAC-ICH was 34.8 (95% confidence interval, 32.0-37.8) and 8.7 (95% confidence interval, 7.3-10.3) per 100 000 person-years, respectively. The absolute risk of OAC-ICH was estimated at 0.46% per patient-year of OAC treatment. CONCLUSIONS: The annual incidences of ICH and OAC-ICH are relatively high in the Netherlands when compared with international literature.

Persistent migraine aura: new cases, a literature review, and ideas about pathophysiology.

BACKGROUND: Persistent migraine aura without infarction (PMA) is a rare condition that is defined as an aura that lasts longer than 1 week in absence of infarction. Two types of PMA have been distinguished, notably persistent primary visual disturbance (PPVD) and typical aura (TA). OBJECTIVES: This case-based review article describes four new cases of PMA as well as reviews all cases reported, trying to identify relevant associations, in particular with respect to functional investigations. METHODS: We performed a systematic literature search, extending from the period when it was first described (1991) to March 2014. We included all case descriptions of which criteria for PMA formulated in the International Classification of Headache Disorders, second edition, were met. In addition, we described four new cases. RESULTS: We identified 47 cases of PMA, 27 PMA-PPVD and 19 PMA-TA. In one case, there was not enough information to define the type of PMA. The mean age of onset was 30 years, varying from 7 to 74 years. The duration of symptoms varied from 9 days to 28 years. Besides a longer duration in symptoms in the PMA-PPVD group, we could not identify any differences between these groups. Some authors report occipital hypoactivity on Tc99m-hexamethylpropylene amine oxime -single-photon emission computed tomography (Tc99m-HMPAO-SPECT) or fluorodeoxyglucose-positron emission tomography (FDG-PET) in PMA cases, but data are inconsistent. Multiple drugs have been used for the treatment of PMA, usually with little effect. Lamotrigine seems to be the most effective drug. CONCLUSION: Despite the fact that 47 cases of PMA have been reviewed in this paper, many questions remain. The cases that have been described so far show inconsistent data with respect to the results of functional studies as well as treatment effects. The pathophysiology of PMA is still largely a matter of conjecture.

Safety and efficacy of active blood-pressure reduction to the recommended thresholds for intravenous thrombolysis in patients with acute ischaemic stroke in the Netherlands (TRUTH): a prospective, observational, cluster-based, parallel-group study.

BACKGROUND: Intravenous thrombolysis is contraindicated in patients with ischaemic stroke with blood pressure higher than 185/110 mm Hg. Prevailing guidelines recommend to actively lower blood pressure with intravenous antihypertensive agents to allow for thrombolysis; however, there is no robust evidence for this strategy. Because rapid declines in blood pressure can also adversely affect clinical outcomes, several Dutch stroke centres use a conservative strategy that does not involve the reduction of blood pressure. We aimed to compare the clinical outcomes of both strategies. METHODS: Thrombolysis and Uncontrolled Hypertension (TRUTH) was a prospective, observational, cluster-based, parallel-group study conducted across 37 stroke centres in the Netherlands. Participating centres had to strictly adhere to an active blood-pressure-lowering strategy or to a non-lowering strategy. Eligible participants were adults (≥18 years) with ischaemic stroke who had blood pressure higher than 185/110 mm Hg but were otherwise eligible for intravenous thrombolysis. The primary outcome was functional status at 90 days, measured using the modified Rankin Scale and assessed through telephone interviews by trained research nurses. Secondary outcomes were symptomatic intracranial haemorrhage, the proportion of patients treated with intravenous thrombolysis, and door-to-needle time. All ordinal logistic regression analyses were adjusted for age, sex, stroke severity, endovascular thrombectomy, and baseline imbalances as fixed-effect variables and centre as a random-effect variable to account for the clustered design. Analyses were done according to the intention-to-treat principle, whereby all patients were analysed according to the treatment strategy of the participating centre at which they were treated. FINDINGS: Recruitment began on Jan 1, 2015, and was prematurely halted because of a declining inclusion rate and insufficient funding on Jan 5, 2022. Between these dates, we recruited 853 patients from 27 centres that followed an active blood-pressure-lowering strategy and 199 patients from ten centres that followed a non-lowering strategy. Baseline characteristics of participants from the two groups were similar. The 90-day mRS score was missing for 15 patients. The adjusted odds ratio (aOR) for a shift towards a worse 90-day functional outcome was 1·27 (95% CI 0·96-1·68) for active blood-pressure reduction compared with no active blood-pressure reduction. 798 (94%) of 853 patients in the active blood-pressure-lowering group were treated with intravenous thrombolysis, with a median door-to-needle time of 35 min (IQR 25-52), compared with 104 (52%) of 199 patients treated in the non-lowering group with a median time of 47 min (29-78). 42 (5%) of 852 patients in the active blood-pressure-lowering group had a symptomatic intracranial haemorrhage compared with six (3%) of 199 of those in the non-lowering group (aOR 1·28 [95% CI 0·62-2·62]). INTERPRETATION: Insufficient evidence was available to establish a difference between an active blood-pressure-lowering strategy-in which antihypertensive agents were administered to reduce blood pressure below 185/110 mm Hg-and a non-lowering strategy for the functional outcomes of patients with ischaemic stroke, despite higher intravenous thrombolysis rates and shorter door-to-needle times among those in the active blood-pressure-lowering group. Randomised controlled trials are needed to inform the use of an active blood-pressure-lowering strategy. FUNDING: Fonds NutsOhra.

Association between type of intervention center and outcomes after endovascular treatment for acute ischemic stroke: Results from the MR CLEAN Registry.

Background: Endovascular treatment (EVT) for acute ischemic stroke (AIS) is performed in intervention centers that provide the full range of neuro(endo)vascular care (level 1) and centers that only perform EVT for AIS (level 2). We compared outcomes between these center types and assessed whether differences in outcomes could be explained by center volume (CV). Patients and methods: We analyzed patients included in the MR CLEAN Registry (2014-2018), a registry of all EVT-treated patients in the Netherlands. Our primary outcome was the shift on the modified Rankin scale (mRS) after 90 days (ordinal regression). Secondary outcomes were the NIHSS 24-48 h post-EVT, door-to-groin time (DTGT), procedure time (linear regression), and recanalization (binary logistic regression). We compared outcomes between level 1 and 2 centers using multilevel regression models, with center as random intercept. We adjusted for relevant baseline factors, and in case of observed differences, we additionally adjusted for CV. Results: Of the 5144 patients 62% were treated in level 1 centers. We observed no significant differences between center types in mRS (adjusted(a)cOR: 0.79, 95% CI: 0.40 to 1.54), NIHSS (aß: 0.31, 95% CI: -0.52 to 1.14), procedure duration (aß: 0.88, 95% CI: -5.21 to 6.97), or DTGT (aß: 4.24, 95% CI: -7.09 to 15.57). The probability for recanalization was higher in level 1 centers compared to level 2 centers (aOR 1.60, 95% CI: 1.10 to 2.33), and this difference probably depended on CV. Conclusions: We found no significant differences, that were independent of CV, in the outcomes of EVT for AIS between level 1 and level 2 intervention centers.

Decrease in incidence of oral anticoagulant-related intracerebral hemorrhage over the past decade in the Netherlands.

Background: Data on oral anticoagulant-related (OAC) intracerebral hemorrhage (ICH) incidence are scarce. Most studies on incidence time trends were performed before the introduction of Direct Oral Anticoagulants (DOACs). Between 2008 and 2018, the number of OAC-users in the Netherlands increased by 63%, with the number of DOAC-users almost equaling that of Vitamin K Antagonists (VKA)-users. We aimed to determine the recent total and OAC-related ICH incidence and assess changes over the last decade, including the effect of DOAC introduction. Methods: All adult non-traumatic ICH patients presenting in any of three hospitals in the enclosed region of South-Limburg, the Netherlands, were retrospectively included, during two 3-year time periods: 2007-2009 and 2017-2019. OAC-related ICH was defined as ICH in patients using VKAs or DOACs. We calculated the incidence rate ratio (IRR) between the two study periods. Results: In the 2007-2009 period, we registered 652 ICHs of whom 168 (25.8%) were OAC-related (all VKA). In the 2017-2019 period, we registered 522 ICHs, 121 (23.2%) were OAC-related (70 VKA and 51 DOAC). In 2007-2009, the annual incidence of total ICH and OAC-related ICH was 40.9 and 10.5 per 100,000 person-years, respectively, which decreased to 32.4 and 7.5 per 100,000 person-years in 2017-2019. The IRR for total ICH and OAC-related ICH was 0.67 (95%-CI: 0.60-0.75) and 0.58 (0.46-0.73), respectively. Conclusion: Both total ICH and OAC-related ICH incidence decreased over the past decade in South-Limburg, the Netherlands, despite the aging population and increasing number of OAC-users. The introduction of DOACs, and possibly an improved cardiovascular risk management and change in OAC prescription pattern, could explain these findings.

Peripheral Artery Disease in Acute Ischemic Stroke Patients Treated With Endovascular Thrombectomy; Results From the MR CLEAN Registry.

Background and Purpose: Though peripheral artery disease (PAD) is a well-known risk factor for ischemic events, better outcomes have been described in acute ischemic stroke patients with co-existing PAD. This paradoxical association has been attributed to remote ischemic preconditioning (RIPC) and might be related to better collateral blood flow. The aim of this study is to compare outcomes after endovascular thrombectomy (EVT) in acute stroke patients with and without PAD and to assess the relation between PAD and collateral grades. Methods: We analyzed acute ischemic stroke patients treated with EVT for an anterior circulation large artery occlusion, included in the Dutch, prospective, multicenter MR CLEAN Registry between March 2014 and November 2017. Collaterals were scored on CT angiography, using a 4-point collateral score. We used logistic regression analysis to estimate the association of PAD with collateral grades and functional outcome, assessed with the modified Rankin Scale (mRS) at 90 days. Safety outcomes included mortality at 90 days, symptomatic intracranial hemorrhage, and stroke progression. Results: We included 2,765 patients for analysis, of whom 254 (9.2%) had PAD. After adjustment for potential confounders, multivariable regression analysis showed no association of PAD with functional outcome [mRS cOR 0.90 (95% CI, 0.7-1.2)], collateral grades (cOR 0.85, 95% CI 0.7-1.1), or safety outcomes. Conclusion: In the absence of an association between the presence of PAD and collateral scores or outcomes after EVT, it may be questioned whether PAD leads to RIPC in patients with acute ischemic stroke due to large vessel occlusion.

Symptomatic Carotid Plaques Demonstrate Less Leaky Plaque Microvasculature Compared With the Contralateral Side: A Dynamic Contrast-Enhanced Magnetic Resonance Imaging Study.

Background Rupture of a vulnerable carotid atherosclerotic plaque is an important underlying cause of ischemic stroke. Increased leaky plaque microvasculature may contribute to plaque vulnerability. These immature microvessels may facilitate entrance of inflammatory cells into the plaque. The objective of the present study is to investigate whether there is a difference in plaque microvasculature (the volume transfer coefficient Ktrans) between the ipsilateral symptomatic and contralateral asymptomatic carotid plaque using noninvasive dynamic contrast-enhanced magnetic resonance imaging. Methods and Results Eighty-eight patients with recent transient ischemic attack or ischemic stroke and ipsilateral >2 mm carotid plaque underwent 3 T magnetic resonance imaging to identify plaque components and to determine characteristics of plaque microvasculature. The volume transfer coefficient Ktrans, indicative for microvascular density, flow, and permeability, was calculated for the ipsilateral and asymptomatic plaque, using a pharmacokinetic model (Patlak). Presence of a lipid-rich necrotic core, intraplaque hemorrhage, and a thin and/or ruptured fibrous cap was assessed on multisequence magnetic resonance imaging . We found significantly lower Ktrans in the symptomatic carotid plaque compared with the asymptomatic side (0.057±0.002 min-1 versus 0.062±0.002 min-1; P=0.033). There was an increased number of slices with intraplaque hemorrhage (0.9±1.6 versus 0.3±0.8, P=0.002) and lipid-rich necrotic core (1.4±1.9 versus 0.8±1.4, P=0.016) and a higher prevalence of plaques with a thin and/or ruptured fibrous cap (32% versus 17%, P=0.023) at the symptomatic side. Conclusions Ktrans was significantly lower in symptomatic carotid plaques, indicative for a decrease of plaque microvasculature in symptomatic plaques. This could be related to a larger amount of necrotic tissue in symptomatic plaques. Clinical Trial Registration URL : http://www.clinicaltrials.gov.uk . Unique identifier: NCT 01208025.

Time to Reperfusion and Treatment Effect for Acute Ischemic Stroke: A Randomized Clinical Trial.

IMPORTANCE: Intra-arterial treatment (IAT) for acute ischemic stroke caused by intracranial arterial occlusion leads to improved functional outcome in patients treated within 6 hours after onset. The influence of treatment delay on treatment effect is not yet known. OBJECTIVE: To evaluate the influence of time from stroke onset to the start of treatment and from stroke onset to reperfusion on the effect of IAT. DESIGN, SETTING, AND PARTICIPANTS: The Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands (MR CLEAN) was a multicenter, randomized clinical open-label trial of IAT vs no IAT in 500 patients. The time to the start of treatment was defined as the time from onset of symptoms to groin puncture (TOG). The time from onset of treatment to reperfusion (TOR) was defined as the time to reopening the vessel occlusion or the end of the procedure in cases for which reperfusion was not achieved. Data were collected from December 3, 2010, to June 3, 2014, and analyzed (intention to treat) from July 1, 2014, to September 19, 2015. MAIN OUTCOMES AND MEASURES: Main outcome was the modified Rankin Scale (mRS) score for functional outcome (range, 0 [no symptoms] to 6 [death]). Multiple ordinal logistic regression analysis estimated the effect of treatment and tested for the interaction of time to randomization, TOG, and TOR with treatment. The effect of treatment as a risk difference on reaching independence (mRS score, 0-2) was computed as a function of TOG and TOR. Calculations were adjusted for age, National Institutes of Health Stroke Scale score, previous stroke, atrial fibrillation, diabetes mellitus, and intracranial arterial terminus occlusion. RESULTS: Among 500 patients (58% male; median age, 67 years), the median TOG was 260 (interquartile range [IQR], 210-311) minutes; median TOR, 340 (IQR, 274-395) minutes. An interaction between TOR and treatment (P = .04) existed, but not between TOG and treatment (P = .26). The adjusted risk difference (95% CI) was 25.9% (8.3%-44.4%) when reperfusion was reached at 3 hours, 18.8% (6.6%-32.6%) at 4 hours, and 6.7% (0.4%-14.5%) at 6 hours. CONCLUSION AND RELEVANCE: For every hour of reperfusion delay, the initially large benefit of IAT decreases; the absolute risk difference for a good outcome is reduced by 6% per hour of delay. Patients with acute ischemic stroke require immediate diagnostic workup and IAT in case of intracranial arterial vessel occlusion. TRIAL REGISTRATION: trialregister.nl Identifier: NTR1804.

CT within 6 hours of headache onset to rule out subarachnoid hemorrhage in nonacademic hospitals.

OBJECTIVE: To investigate whether staff radiologists working in nonacademic hospitals can adequately rule out subarachnoid hemorrhage (SAH) on head CT <6 hours after headache onset. METHODS: In a multicenter, retrospective study, we studied a consecutive series of patients presenting with acute headache to 11 nonacademic hospitals. Inclusion criteria were (1) normal level of consciousness without focal deficits, (2) head CT <6 hours after headache onset and reported negative for the presence of SAH by a staff radiologist, and (3) subsequent CSF spectrophotometry. Two neuroradiologists and one stroke neurologist from 2 academic tertiary care centers independently reviewed admission CTs of patients with CSF results that were considered positive for presence of bilirubin according to local criteria. We investigated the negative predictive value for detection of SAH by staff radiologists in nonacademic hospitals on head CT in patients scanned <6 hours after onset of acute headache. RESULTS: Of 760 included patients, CSF analysis was considered positive for bilirubin in 52 patients (7%). Independent review of these patients' CTs identified one patient (1/52; 2%) with a perimesencephalic nonaneurysmal SAH. Negative predictive value for detection of subarachnoid blood by staff radiologists working in a nonacademic hospital was 99.9% (95% confidence interval 99.3%-100.0%). CONCLUSIONS: Our results support a change of practice wherein a lumbar puncture can be withheld in patients with a head CT scan performed <6 hours after headache onset and reported negative for the presence of SAH by a staff radiologist in the described nonacademic setting.

Is isolated aphasia associated with atrial fibrillation? A prospective study.

BACKGROUND: A cardioembolic source, usually atrial fibrillation (AF), is detected in 14-30% of strokes. If AF is found, anticoagulation therapy provides a substantial decrease of the risk of recurrent cerebrovascular ischemic events. AF is often paroxysmal, and extensive diagnostic procedures may be necessary to detect it in patients. Considering cost-effectiveness and patient burden, however, not every suspected patient can be thoroughly screened. Therefore, the identification of risk factors for AF may be helpful. Previous studies have identified isolated aphasia as a risk factor for AF as the cause of the stroke. These studies, however, were performed with small population samples, in a retrospective setting or focused on a specific subtype of aphasia. The aim of this observational study is to prospectively evaluate whether there is a relation between isolated aphasia and AF as the cause of cerebrovascular ischemia. METHODS: All patients admitted to the Atrium Medical Centre, Heerlen, the Netherlands, with cerebrovascular ischemia or transient ischemic attack in the period of August 2009 to March 2010 or October 2013 to January 2014 were included. The patients were evaluated by a neurologist and admitted to the Brain Care Unit for 24-48 h. Medical history, physical examination and diagnostic results were entered in a database. A diagnosis of isolated aphasia was assigned at admission using the National Institutes of Health Stroke Scale (NIHSS). Presence of AF was determined using a 12-lead electrocardiogram (ECG) on admission and continuous ECG monitoring for 1-2 days. During admission, aphasia tests were done, notably the ScreeLing Test and the Boston Naming Test. Data were analyzed using Pearson's χ(2) test, Fisher's exact test, the Mann-Whitney U test and univariate and multivariate logistic regression analyses. RESULTS: A total of 347 patients were included, of which 115 (33.1%) met the criteria for aphasia, with 26 (7.5%) meeting the criteria for isolated aphasia. Of all patients, 90 had a history of AF (66.7%) or AF was found during hospitalization (33.3%). Patients with AF, in contrast to those without, tended to present more often with any type of aphasia (41.1 vs. 30.4%) and isolated aphasia (10.0 vs. 6.6%), but these differences were not significant. A significant relation was found between global aphasia and AF (p = 0.011). Patients with AF scored significantly lower on the ScreeLing Test alone and on both aphasia tests together (p = 0.034). A history of transient ischemic attack significantly increased the risk for isolated aphasia (OR 2.66, 95% CI 1.09-6.47). CONCLUSIONS: A statistically significant relation between isolated aphasia and AF could not be established in this study. However, our results showed a tendency towards significance. Further studies, in which rhythm is observed for a longer period of time, may be required to confirm this hypothesis.

Anaplastic oligo-astrocytoma occurring after resection of a cerebral cavernous malformation; malignant transformation? Case report and review on etiology.

We report a 71-year-old woman who presented with a cerebral cavernous malformation in the right frontal lobe for which she underwent total resection. Three years later, she was admitted with seizures and neuroimaging revealed a partially calcified lesion in the area of the earlier cavernous malformation, consistent with a residual malformation. A few months later she presented with cognitive decline and neuroimaging now revealed a large mass lesion in the same area as the cavernous malformation, irregularly enhancing, spreading through the corpus callosum to the left frontal lobe. Histological examination showed an anaplastic oligo-astrocytoma. These findings suggest that cerebral cavernous malformations, or at least a subgroup, have the potential for oligodendrocytic and astrocytic transformation. Various hypotheses to explain the etiology of these rare cases are discussed.