Early ischemic recurrence in acute spontaneous cervical artery dissection.

BACKGROUND AND PURPOSE: Early ischemic recurrence (EIR) following the diagnosis of acute spontaneous cervical artery dissection (CeAD) has been little investigated. We aimed to determine the prevalence and determinants on admission of EIR in a large single-center retrospective cohort study of patients with CeAD. METHODS: EIR was defined as any ipsilateral clinical or radiological cerebral ischemia or intracranial artery occlusion, not present on admission and occurring within 2 weeks. CeAD location, degree of stenosis, circle of Willis support, presence of intraluminal thrombus, intracranial extension, and intracranial embolism were analyzed on initial imaging by 2 independent observers. Uni- and multivariate logistic regression was used to determine their association with EIR. RESULTS: Two hundred thirty-three consecutive patients with 286 CeAD were included. EIR was observed in 21 patients (9%,95%CI=5-13%) with a median time from diagnosis of 1.5 days (range:0.1-14.0 days). No EIR was observed in CeAD without ischemic presentation or with less than 70% stenosis. In the remaining cases, poor circle of Willis (OR=8.5, CI95%=2.0-35.4, p = 0.003), CeAD extending to other intracranial arteries than just V4 (OR=6.8, CI95%=1.4-32.6, p = 0.017), cervical artery occlusion (OR=9.5, CI95%=1.2- 39.0, p = 0.031), and cervical intraluminal thrombus (OR=17.5, CI95%=3.0-101.7, p = 0.001) were independently associated with EIR. CONCLUSIONS: Our results suggests that EIR is more frequent than previously reported, and that its risk might be stratified on admission with a standard workup. In particular, the presence of a poor circle of Willis, intracranial extension (other than just V4), cervical occlusion, or cervical intraluminal thrombus are associated with high risk of EIR, for which specific management should be further evaluated.

Endovascular treatment of infectious intracranial aneurysms complicating infective endocarditis: a series of 31 patients with 55 aneurysms.

PURPOSE: Endovascular treatment (EVT) has become a major option in management of infectious intracranial aneurysms (IIAs) complicating infective endocarditis. We report a retrospective, single-center series of consecutive patients with IIAs treated by EVT. METHODS: Patients were included from January 2009 to July 2020. IIAs were diagnosed on DSA. Each patient underwent a neurological assessment before and after EVT and was followed up by imaging within 15 days of EVT. Safety was assessed on the evolution of NIHSS score. A minor stroke was defined as a worsening of NIHSS < 4 points. Efficacy was defined as the absence of hemorrhagic event during cardiac surgery and the exclusion of the IIA on control imaging. RESULTS: Sixty-two IIAs (30 ruptured) were diagnosed in 31 patients. Fifty-six IIAs were diagnosed on the first DSA and 6 on the early control exploration. EVT was achieved in 55 IIAs by parent artery occlusion with glue in 52 distal IIAs and coils in 3 proximal IIAs. IIAs were located in 90.9% of cases on a fourth-division branch of a cerebral artery. The neurological examination remained unchanged in 29 patients (93.5%), and 2 patients suffered minor stroke. EVT was performed before cardiac surgery in 20/22 patients. All treated IIAs were excluded on follow-up imaging. No hemorrhage was observed during cardiac surgery or in the aftermath. Seven (11.3%) unruptured IIAs were not embolized. CONCLUSION: EVT of IIAs by occlusion of the parent artery is effective in preventing rupture and carries no significant neurological risk.

Venous sinus stenting after repair of skull base spontaneous cerebrospinal fluid leaks: A single-center retrospective cohort series with case-control analysis.

BACKGROUND: Management of idiopathic intracranial hypertension (IIH) is recommended after surgical repair of spontaneous cerebrospinal fluid leaks (sCSF-leaks) of the skull base for prevention of recurrence. PURPOSE: To assess the feasibility of venous sinus stenting, a treatment commonly used for the treatment of IIH associated with intracranial venous sinus stenosis (VSS), after sCSF-leaks closure. MATERIALS AND METHODS: A single-center cohort series of consecutive patients who underwent sCSF-leak closure was retrospectively analyzed. Stenting was considered either for leak recurrence or in prophylactic manner after repair in patients with VSS as confirmed by cerebral venous imaging. Leak recurrence, need for new repair or adjunctive treatment of IIH, meningitis, and stenting complications were determined at the last follow-up. Cases who had prophylactic stenting were compared to historical controls before stenting option. RESULTS: Twenty-two patients had intracranial venous stenting after sCSF-leak closure. Their median age was 58 years (Q1=45; Q3=68), BMI=31 kg.m-2 (Q1=27; Q3=36), and female rate=85%. The overall rate of successful repair after stenting was 95% (95% CI = 87-100%) at a median follow-up of 2.4 years (Q1=1.2; Q3=3.3). Adjunctive treatment for IIH was needed in 4 patients (4/22, 18%) including 2 patients without leak recurrence. No meningitis, permanent morbidity or mortality was observed after stenting. Compared to 18 controls, cases had significantly less recurrence (P = 0.03), and a trend for less adjunctive treatment for IIH (P = 0.06). CONCLUSIONS: Our study suggests that stenting might be a valid option for prevention of sCSF-leak recurrences after repair in patients with intracranial venous sinus stenosis.

Navigability of a long sheath in the lateral dural sinuses facilitated by the pilot balloon technique: technical note.

Dural sinus stenting is an increasingly recognized intervention for the treatment of lateral sinus stenosis. This procedure can be challenging in tortuous anatomy and in the presence of intraluminal septa because of poor trackability and crossability of long sheath commonly used for stenting. We report a technique using a pilot angioplasty balloon positioned at the distal end of the long sheath that improves its navigability in dural sinuses and facilitated the intervention.

Intensive therapies of delayed cerebral ischemia after subarachnoid hemorrhage: a propensity-matched comparison of different center-driven strategies.

BACKGROUND: Intensive therapies of delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH) have still controversial and unproven benefit. We aimed to compare the overall efficacy of two different center-driven strategies for the treatment of DCI respectively with and without vasospasm angioplasty. METHODS: Two hundred consecutive patients with aSAH were enrolled in each of two northern European centers. In an interventional center, vasospasm angioplasty was indicated as first line rather than rescue treatment of DCI using distal percutaneous balloon angioplasty technique combined with intravenous milrinone. In non-interventional center, induced hypertension was the only intensive therapy of DCI. Radiological DCI (new cerebral infarcts not visible on immediate post-treatment imaging), death at 1 month, and favorable outcome at 6 months (modified Rankin scale score ≤ 2) were retrospectively analyzed by independent observers and compared between two centers before and after propensity score (PS) matching for baseline characteristics. RESULTS: Baseline characteristics only differed between centers for age and rate of smokers and patients with chronic high blood pressure. In the interventional center, vasospasm angioplasty was performed in 38% of patients with median time from bleeding of 8 days (Q1 = 6.5;Q3 = 10). There was no significant difference of incidence of radiological DCI (9% vs.14%, P = 0.11), death (8% vs. 9%, P = 0.4), and favorable outcome 74% vs. 72% (P = 0.4) between interventional and non-interventional centers before and after PS matching. CONCLUSIONS: Our results suggest either that there is no benefit, or might be minimal, of one between two different center-driven strategies for intensive treatment of DCI. Despite potential lack of power or unknown confounders in our study, these results question the use of such intensive therapies in daily practice without further optimization and validation.

Evaluation of glomerular filtration rate using iohexol plasma clearance in critically ill patients with augmented renal creatinine clearance: A single-centre retrospective study.

BACKGROUND: Augmented renal creatinine clearance (ARC) (≥130 ml min-1 1.73 m-2) is frequent in intensive care unit (ICU) patients and may impact patient outcome. OBJECTIVES: To compare glomerular filtration rate (GFR) measured with iohexol plasma clearance and creatinine clearance in critically ill patients with augmented renal clearance. DESIGN: Single-centre, retrospective study. SETTING: French University Hospital ICU from November 2016 to May 2019. PATIENTS: Adult patients with augmented renal clearance who had a measurement of iohexol plasma clearance. MAIN OUTCOME MEASURE: Agreement between 6 h creatinine clearance (6 h CrCl) and iohexol plasma clearance (GFRio). RESULTS: Twenty-nine patients were included. The median 6 h creatinine clearance was 195 [interquartile range (IQR) 162 to 251] ml min-1 1.73 m-2 and iohexol clearance was 133 [117 to 153] ml min-1 1.73 m-2. Sixteen patients (55%) had hyperfiltration (clearance >130 ml min-1 1.73 m-2) measured with iohexol clearance. Mean bias between iohexol and creatinine clearance was -80 [limits of agreement (LoA) -216 to 56 ml min-1 1.73 m-2]. For Cockcroft and Gault Modification of Diet in Renal Disease equation (MDRD), Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) formulae, mean biases were, respectively -27 (LoA -99 to 45), -14 (LoA -86 to 59) and 15 (LoA -33 to 64) ml min-1 1.73 m-2. CONCLUSION: In the present study, we found that in patients with augmented renal creatinine clearance, half of the patients do not have hyperfiltration using iohexol clearance measurements. We observed an important bias between 6 h CrCl and GFRio with large LoA. In critically patients with ARC, 6 h CrCl does not reliably estimate GFR and 6 h CrCl nearly systematically overestimates renal function. Comparison of creatinine-based GFR estimations and GFRio show acceptable bias but wide LoA.

Impact of Antiplatelet Therapy During Endovascular Therapy for Tandem Occlusions: A Collaborative Pooled Analysis.

Background and Purpose- Antiplatelet agents could be used in the setting of endovascular therapy for tandem occlusions to reduce the risk of de novo intracranial embolic migration, reocclusion of the extracranial internal carotid artery lesion, or in-stent thrombosis in case of carotid stent placement but have to be balanced with the intracerebral hemorrhagic transformation risk. In this study, we aim to investigate the impact of acute antiplatelet therapy administration on outcomes during endovascular therapy for anterior circulation tandem occlusions. Methods- This is a retrospective analysis of a collaborative pooled analysis of 11 prospective databases from the multicenter observational TITAN registry (Thrombectomy in Tandem Lesions). Patients were divided into groups based on the number of antiplatelet administered during endovascular therapy. The primary outcome was favorable outcome, defined as a modified Rankin Scale score of 0 to 2 at 90 days. Results- This study included a total of 369 patients; 145 (39.3%) did not receive any antiplatelet agent and 224 (60.7%) received at least 1 antiplatelet agent during the procedure. Rate of favorable outcome was nonsignificantly higher in patients treated with antiplatelet therapy (58.3%) compared with those treated without antiplatelet (46.0%; adjusted odds ratio, 1.38 [95% CI, 0.78-2.43]; P=0.26). Rate of 90-day mortality was significantly lower in patients treated with antiplatelet therapy (11.2% versus 18.7%; adjusted odds ratio, 0.47 [95% CI, 0.22-0.98]; P=0.042), without increasing the risk of any intracerebral hemorrhage. Successful reperfusion (modified Thrombolysis in Cerebral Ischemia score 2b-3) rate was significantly better in the antiplatelet therapy group (83.9% versus 71.0%; adjusted odds ratio, 1.89 [95% CI, 1.01-3.64]; P=0.045). Conclusions- Administration of antiplatelet therapy during endovascular therapy for anterior circulation tandem occlusions was safe and was associated with a lower 90-day mortality. Optimal antiplatelet therapy remains to be assessed, especially when emergent carotid artery stenting is performed. Further randomized controlled trials are needed.

High frequency of ophthalmic origin of the middle meningeal artery in chronic subdural hematoma.

PURPOSE: Embolization of middle meningeal artery (MMA) has been proposed for postoperative recurrences and primary treatment of chronic subdural hematoma (CSDH). This endovascular intervention is safe only when MMA originates from the internal maxillary artery. The aim of this study was to report an unusual high frequency of MMA originating from the ophthalmic artery, which prohibits this treatment. METHODS: In this retrospective study, we reviewed the anatomical origin of the MMA in patients with CSDH who were referred to our center for endovascular treatment between January 2017 and May 2019 (42 patients with 58 CSDH). We compared the prevalence of this variant in a control group of 66 patients who underwent embolization for epistaxis during the same period. RESULTS: In CSDH group, MMA originated from the ophthalmic artery in 8 out of 58 internal carotid arteries (13.8%). In the control group, this variant was observed in only 1 case out of 131 internal carotid arteries (0.7%) (OR = 20; 95% CI 2.6 to 925.2, p = 0.0003). CONCLUSION: In this study, we report an extremely high prevalence of MMA originating from the ophthalmic artery in CSDH. In the hypothesis of prospective studies, a priori recognition of this variant will be necessary in order to exclude patients in whom endovascular treatment will not be feasible.

Intracranial Extension of Extracranial Vertebral Dissection Is Associated With an Increased Risk of Ischemic Events.

Background and Purpose- Intracranial artery dissection can eventually lead to subarachnoid or intracerebral hemorrhage. Little is known about the clinical features and risks associated with extracranial vertebral artery dissection that extends intracranially. The clinical and imaging characteristics of extracranial vertebral artery dissection (eVAD) with (e+iVAD) or without (eVAD) intracranial extension were analyzed. Methods- The frequency of ischemic events, including ischemic strokes and transient ischemic attacks, was compared between e+iVAD and eVAD patients from a monocentric cohort study. Results- Among 328 patients with cervical artery dissection, vertebral artery dissection was diagnosed in 153 individuals. Twenty-nine patients had e+iVAD (19%) and 124 patients had only eVAD (81%). Cardiovascular risk factors did not differ between these 2 groups, but ischemic events were more frequent in patients with e+iVAD than in patients with eVAD (86% versus 48%, P=0.0002). Subarachnoid hemorrhage occurred in 1 patient with e+iVAD and in 9 with eVAD (6% versus 3%, P=0.53). Intracranial extension was an independent factor associated with ischemic stroke at admission (odds ratio, 6.43; 95% CI, -1.96 to 21.08; P=0.002) after adjustment for cardiovascular risk factors and imaging findings. Conclusions- In a large cohort of patients with vertebral artery dissection, intracranial extension of the vessel dissection appears associated with an increased risk of ischemic stroke.

Emergent Carotid Stenting Plus Thrombectomy After Thrombolysis in Tandem Strokes: Analysis of the TITAN Registry.

Background and Purpose: Emergent carotid artery stenting plus mechanical thrombectomy is an effective treatment for acute ischemic stroke patients with tandem occlusion of the anterior circulation. However, there is limited data supporting the safety of this approach in patients treated with prior intravenous thrombolysis (IVT). We aimed to investigate the safety of emergent carotid artery stenting-mechanical thrombectomy approach in stroke patient population treated with prior IVT Methods: ­We assessed patients with acute ischemic stroke because of atherosclerotic tandem occlusion that were treated with emergent carotid artery stenting-mechanical thrombectomy approach from the multicenter observational Thrombectomy in Tandem Lesions registry. Patients were divided into 2 groups based on pretreatment IVT (IVT versus no-IVT). Intracerebral hemorrhages were classified according to the European Cooperative Acute Stroke Study II criteria. Results: Among 205 patients included in the present study, 125 (60%) received prior IVT. Time from symptoms onsetto-groin puncture was shorter (234±100 versus 256±234 minutes; P=0.002), and heparin use was less in the IVT group (14% versus 35%; P<0.001); otherwise, there was no difference in the baseline characteristics. There was no significant difference between the IVT and no-IVT groups in the rate of symptomatic intracerebral hemorrhage (5% versus 8%; P=0.544), parenchymal hematoma type 1 to 2 (15% versus 18%; P=0.647), successful reperfusion (modified Thrombolysis in Cerebral Ischemia 2b­3), or 90-day favorable outcome (modified Rankin Scale score of 0­2 at 90 days). The 90-day all-cause mortality rate was significantly lower in the IVT group (8% versus 20%; P=0.017). After adjusting for covariates, IVT was not associated with symptomatic intracerebral hemorrhage or 90-day mortality Conclusions: Emergent carotid artery stenting-mechanical thrombectomy approach was not associated with an increased risk of hemorrhagic complications in tandem occlusion patients who received IVT before the intervention.

Propofol/Remifentanil Anesthesia Might Not Alter the Middle Cerebral Artery Diameter by Digital Subtraction Angiography.

INTRODUCTION: Transcranial Doppler (TCD) of the middle cerebral artery (MCA) enables the measurement of the mean blood velocity (MCAVm) and the estimation of the cerebral blood flow (CBF), provided that no significant changes occur in the MCA diameter (MCADiam). Previous studies described a decrease in the MCAVm associated with the induction of total intravenous anesthesia (TIVA) by propofol and remifentanil. This decrease in blood velocity might be interpreted as a decrease in the CBF only where the MCADiam is not modified across TCD examinations. METHODS: In this observational study, we measured the MCADiam of 24 subjects (almost exclusively females) on digital subtraction angiography under awake and TIVA conditions. RESULTS: Across the two phases, we observed a decrease in the mean arterial blood pressure (from 84 ± 9 to 71 ± 6 mmHg; p < 0.001) and heart rate (76 ± 10 vs. 65 ± 8 beats/min; p < 0.001), and a concomitant decrease in the MCAVm (61 vs. 42 cm/s; p < 0.001). In contrast, the MCADiam did not vary in association with TIVA (2.3 ± 0.2 vs. 2.3 ± 0.2 mm; p = 0.52). CONCLUSIONS: Those results suggested that in this population, no significant changes in the MCADiam are associated with TIVA.

Efficacy of Endovascular Therapy in Acute Ischemic Stroke Depends on Age and Clinical Severity.

BACKGROUND AND PURPOSE: Efficacy of endovascular treatment (EVT) for ischemic stroke because of large vessel occlusion may depend on patients' age and stroke severity; we, therefore, developed a prognosis score based on these variables and examined whether EVT efficacy differs between patients with good, intermediate, or poor prognostic score. METHODS: A total of 4079 patients with an acute ischemic stroke were identified from the Paris Stroke Consortium registry. We developed the stroke checkerboard (SC) score (SC score=1 point per decade ≥50 years of age and 2 points per 5 points on the National Institutes of Health Stroke Scale) to predict spontaneous outcome. The primary outcome was the adjusted common odds ratio for an improvement in the modified Rankin Scale at 90 days after EVT, in patients with low, intermediate, or high SC scores. To rule out potential selection biases, a nested case-control analysis, with individual matching for all major prognostic factors, was also performed, to compare patients with large vessel occlusion in the anterior circulation treated or not with EVT. RESULTS: In patients untreated with EVT, SC scores <8 were predictive of good outcomes (modified Rankin Scale score, 0-2; area under the curve, 0.87), whereas SC scores >12 were predictive of poor outcomes (modified Rankin Scale score, 4-6; area under the curve, 0.88). In the overall population, there was an interaction between EVT and prognosis group (P<0.001). EVT was associated with improved outcome in patients with SC scores >12 (common odds ratio, 1.70; 95% confidence interval, 1.13-2.56) and SC scores 8 to 12 (odds ratio, 1.37; 95% confidence interval, 1.11-1.69) but not in patients with SC scores <8 (odds ratio, 0.72; 95% confidence interval, 0.56-0.93). Similar results were obtained in the case-control analysis among 449 patients treated with EVT and 449 matched patients untreated with EVT. CONCLUSIONS: In patients stratified with the SC score, EVT was associated with improved functional outcome in older and more severe patients but not in younger and less severe patients.

Treatment of cerebral vasospasm following aneurysmal subarachnoid haemorrhage: a systematic review and meta-analysis.

OBJECTIVES: To examine the clinical outcome of aneurysmal subarachnoid haemorrhage (aSAH) patients exposed to cerebral vasospasm (CVS)-targeted treatments in a meta-analysis and to evaluate the efficacy of intra-arterial (IA) approaches in patients with severe/refractory vasospasm. METHODS: Randomised controlled trials, prospective and retrospective observational studies reporting clinical outcomes of aSAH patients exposed to CVS targeted treatments, published between 2006-2016 were searched using PubMed, EMBASE and the Cochrane Library. The main endpoint was the proportion of unfavourable outcomes, defined as a modified Rankin score of 3-6 at last follow-up. RESULTS: Sixty-two studies, including 26 randomised controlled trials, were included (8,976 patients). At last follow-up 2,490 of the 8,976 patients had an unfavourable outcome, including death (random-effect weighted-average, 33.7%; 99% confidence interval [CI], 28.1-39.7%; Q value, 806.0; I 2 = 92.7%). The RR of unfavourable outcome was lower in patients treated with Cilostazol (RR = 0.46; 95% CI, 0.25-0.85; P = 0.001; Q value, 1.5; I 2 = 0); and in refractory CVS patients treated by IA intervention (RR = 0.68; 95% CI, 0.57-0.80; P < 0.0001; number needed to treat with IA intervention, 6.2; 95% CI, 4.3-11.2) when compared with the best available medical treatment. CONCLUSIONS: Endovascular treatment may improve the outcome of patients with severe-refractory vasospasm. Further studies are needed to confirm this result. KEY POINTS: • 33.7% of patients with cerebral Vasospasm following aneurysmal subarachnoid-hemorrhage have an unfavorable outcome. • Refractory vasospasm patients treated using endovascular interventions have lower relative risk of unfavourable outcome. • Subarachnoid haemorrhage patients with severe vasospasm may benefit from endovascular interventions. • The relative risk of unfavourable outcome is lower in patients treated with Cilostazol.

Reasoning by analogy requires the left frontal pole: lesion-deficit mapping and clinical implications.

SEE BURGESS DOI101093/BRAIN/AWW092 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE : Analogical reasoning is at the core of the generalization and abstraction processes that enable concept formation and creativity. The impact of neurological diseases on analogical reasoning is poorly known, despite its importance in everyday life and in society. Neuroimaging studies of healthy subjects and the few studies that have been performed on patients have highlighted the importance of the prefrontal cortex in analogical reasoning. However, the critical cerebral bases for analogical reasoning deficits remain elusive. In the current study, we examined analogical reasoning abilities in 27 patients with focal damage in the frontal lobes and performed voxel-based lesion-behaviour mapping and tractography analyses to investigate the structures critical for analogical reasoning. The findings revealed that damage to the left rostrolateral prefrontal region (or some of its long-range connections) specifically impaired the ability to reason by analogies. A short version of the analogy task predicted the existence of a left rostrolateral prefrontal lesion with good accuracy. Experimental manipulations of the analogy tasks suggested that this region plays a role in relational matching or integration. The current lesion approach demonstrated that the left rostrolateral prefrontal region is a critical node in the analogy network. Our results also suggested that analogy tasks should be translated to clinical practice to refine the neuropsychological assessment of patients with frontal lobe lesions.

How sustained is 24-hour diffusion-weighted imaging lesion reversal? Serial magnetic resonance imaging in a patient cohort thrombolyzed within 4.5 hours of stroke onset.

BACKGROUND AND PURPOSE: Here, we assessed how sustained is reversal of the acute diffusion lesion (RAD) observed 24 hours after intravenous thrombolysis, and the relationships between RAD fate and early neurological improvement. METHODS: We analyzed 155 consecutive patients thrombolyzed intravenously 152 minutes (median) after stroke onset and who underwent 3 MR sessions: 1 before and 2 after treatment (median times from onset, 25.6 and 54.3 hours, respectively). Using voxel-based analysis of diffusion-weighted imaging (DWI)1, DWI2, and DWI3 lesions on coregistered image data sets, we assessed the outcome of RAD voxels (hyperintense on DWI1 but not on DWI2) as transient or sustained on DWI3, and their relationships with early neurological improvement, defined as ΔNational Institutes of Health Stroke Scale ≥8 or National Institutes of Health Stroke Scale ≤1 at 24 hours. Tmax and apparent diffusion coefficient values were compared between sustained and transient RAD voxels. RESULTS: The median (interquartile range) baseline National Institutes of Health Stroke Scale and DWI1 lesion volume were 11 (7-18) mL and 15.6 (6.0-50.9) mL, respectively. The median (interquartile range) RAD volume on DWI2 was 2.8 (1.1-6.6) mL, of which 70% was sustained on DWI3. Sixteen (10.3%) patients had sustained RAD ≥10 mL. As compared with transient RAD voxels, sustained RAD voxels had nonsignificantly higher baseline apparent diffusion coefficient values (median [interquartile range], 793 [717-887] versus 777 [705-869]×10(-6) mm(2)·s (-1), respectively; P=0.08) and significantly better perfusion (Tmax, mean±SD, 6.3±3.2 versus 7.8±4.0 s; P<0.001). At variance with transient RAD, the volume of sustained RAD was associated with early neurological improvement in multivariate analysis (odds ratio, 1.08; 95% confidence interval, [1.01-1.17], per 1-mL increase; P=0.03). CONCLUSIONS: After thrombolysis, over two-thirds of the DWI lesion reversal captured on 24-hour follow-up MR is sustained. Sustained DWI lesion reversal volume is a strong imaging correlate of early neurological improvement.

Mechanisms of unexplained neurological deterioration after intravenous thrombolysis.

BACKGROUND AND PURPOSE: Unstable clinical course characterizes the first 24 hours after thrombolysis for anterior circulation stroke, including early neurological deterioration (END), a secondary complication consistently predictive of poor outcome. Apart from straightforward causes, such as intracerebral hemorrhage and malignant edema, the mechanism of END remains unclear in the majority of cases (ENDunexplained). Based on the core/penumbra model, we tested the hypothesis that ENDunexplained is caused by infarct growth beyond the initial penumbra and assessed the associated vascular patterns. METHODS: From our database of consecutive thrombolyzed patients (n=309), we identified 10 ENDunexplained cases who had undergone both admission and 24-hour MRI. Diffusion-weighted imaging lesion growth both within and beyond the acute penumbra (Tmax>6 seconds) was mapped voxelwise. These 10 cases were compared with 30 no-END controls extracted from the database blinded to 24-hour diffusion-weighted imaging to individually match cases (3/case) according to 4 previously identified clinical and imaging variables. RESULTS: As predicted, lesion growth beyond initial penumbra was present in 9 of 10 ENDunexplained patients (substantial in 8) and its volume was significantly larger in cases than controls (2P=0.047). All ENDunexplained cases had proximal arterial occlusion initially, of which only 2 had recanalized at 24 hours. CONCLUSIONS: In this exploratory study, most instances of ENDunexplained were related to diffusion-weighted imaging growth beyond acute penumbra. Consistent presence of proximal occlusion at admission and lack of recanalization at 24 hours in most cases suggest that hemodynamic factors played a key role, via for instance systemic instability/collateral failure or secondary thromboembolic processes. Preventing END after tissue-type plasminogen activator using, eg, early antithrombotics may therefore be feasible.

Unexplained early neurological deterioration after intravenous thrombolysis: incidence, predictors, and associated factors.

BACKGROUND AND PURPOSE: Early neurological deterioration (END) after anterior circulation stroke is a serious clinical event strongly associated with poor outcome. Regarding specifically END occurring within 24 hours of intravenous recombinant tissue-type plasminogen activator, apart from definite causes such as symptomatic intracranial hemorrhage and malignant edema whose incidence, predictors, and clinical management are well established, little is known about END without clear mechanism (ENDunexplained). METHODS: We analyzed 309 consecutive patients thrombolysed intravenously ≤4.5 hours from onset of anterior circulation stroke. ENDunexplained was defined as a ≥4-point deterioration on 24-hour National Institutes of Health Stroke Scale, without definite mechanism on concomitant imaging. ENDunexplained and no-END patients were compared for pretreatment clinical and imaging (including magnetic resonance diffusion and diffusion/perfusion mismatch volumes) data and 24-hour post-treatment clinical (including blood pressure and glycemic changes) and imaging (24-hour recanalization) data, using univariate logistic regression. Exploratory multivariate analysis was also performed after variable reduction, with bootstrap analysis for internal validation. RESULTS: Among 33 END patients, 23 (7% of whole sample) had ENDunexplained. ENDunexplained was associated with poor 3-month outcome (P<0.01). In univariate analysis, admission predictors of ENDunexplained included no prior use of antiplatelets (P=0.02), lower National Institutes of Health Stroke Scale score (P<0.01), higher glycemia (P=0.03), larger mismatch volume (P=0.03), and proximal occlusion (P=0.01), with consistent results from the multivariate analysis. Among factors recorded during the first 24 hours, only no recanalization was associated with ENDunexplained in multivariate analysis (P=0.02). CONCLUSIONS: ENDunexplained affected 7% of patients and accounted for most cases of END. Several predictors and associated factors were identified, with important implications regarding underlying mechanisms and potential prevention of this ominous event.

Is white matter more prone to diffusion lesion reversal after thrombolysis?

BACKGROUND AND PURPOSE: In acute ischemic stroke, white matter (WM) is considered more resistant to infarction than gray matter (GM). To test this hypothesis, we compared the fate of WM and GM voxels belonging to the acute diffusion-weighted imaging (DWI) lesion, expecting WM voxels to be more prone to reversal after thrombolysis. METHODS: Reversible acute DWI (RAD) lesion was defined voxel-wise as an acute lesion on initial DWI (DWI1) with no visible lesion on 24-hour DWI (DWI2). Only patients with RAD lesions >10 mL and >10% of DWI1 from our previously reported cohort were eligible. The core was defined as voxels hyperintense on DWI1 and DWI2. Semiautomated segmentation of DWI1, core, and RAD lesions, normalization into standard space, and WM/GM segmentation allowed calculations of WM/GM proportions in each region of interest using a voxel-counting algorithm. RESULTS: Thirty patients were eligible (RAD lesion median volume [interquartile range], 23.3 mL [19.1-35.0 mL]; onset-to-treatment time, 134 minutes [105-185 minutes]). WM voxels fraction was greater in RAD lesions than in the core (59.4% [52.8%-68.9%] versus 49.6% [43.0%-57.5%]; P=0.011). The proportion of reversibility was greater for WM than for GM voxels (60.8% [25.5%-88.7%] versus 53.5% [21.1%-77.3%]; P=0.02). The percentage of RAD lesions increased with the proportion of WM present in the acute DWI lesion (P<0.0001; R=0.67). CONCLUSIONS: Acute DWI lesions predominantly involving WM may be more prone to reversal and, hence, to respond to therapy than their GM counterparts.