Impact of intravenous thrombolysis on recanalization rates in patients with stroke treated with bridging therapy.

BACKGROUND AND PURPOSE: Randomized controlled trials have shown that bridging endovascular therapy (EVT) after intravenous thrombolysis (IVT) therapy improves outcome in patients with stroke with large-artery anterior circulation stroke compared with IVT alone. It remains unknown whether IVT adds any benefit to EVT in these patients. The aim of this study was to assess recanalization rates and thrombus dislocation before initiation of EVT in patients receiving bridging therapy. METHODS: All patients in the Bernese stroke registry (2008-2015) in whom bridging therapy was considered were included in this analysis. Relevant recanalization before EVT, thrombus dislocation and increase in thrombus load between initial and control imaging were assessed retrospectively. RESULTS: A total of 319 patients were included. Relevant recanalization before EVT occurred in 8.8% and thrombus dislocation in 7.2% of patients before EVT. Recanalization rates were significantly higher in distal compared with large and more proximal vessel occlusions of the anterior circulation (occlusion of internal carotid artery, 5.4%; middle cerebral artery segment M1, 8.1%; middle cerebral artery segment M2, 17.6%) and in drip-and-ship patients compared with mother-ship patients. In multivariable regression analysis the occlusion site was the only independent predictor of relevant recanalization before EVT (P = 0.046). CONCLUSIONS: Relevant recanalization after IVT and prior to EVT in patients receiving bridging therapy was highly dependent on the occlusion site. These findings suggest that future randomized controlled trials should consider occlusion site and treatment paradigm to specify patients who benefit most from bridging therapy in comparison to EVT or IVT alone.

Clinical Significance of Pretransplant Donor-Specific Antibodies in the Setting of Negative Cell-Based Flow Cytometry Crossmatching in Kidney Transplant Recipients.

Antibodies to donor-specific HLA antigens (donor-specific antibodies [DSA]) detected by single-antigen bead (SAB) analysis prior to kidney transplant have been associated with inferior graft outcomes. However, studies of pretransplant DSA, specifically in the setting of a negative flow cytometry crossmatch (FCXM) without desensitization therapy, are limited. Six hundred and sixty kidney and kidney-pancreas recipients with a negative pretransplant FCXM from September 2007 to August 2012 without desensitization therapy were analyzed with a median follow-up of 4.2 years. All patients underwent cell-based FCXM and SAB analysis on current and historic sera prior to transplantation. One hundred and sixty-two patients (24.5%) had DSA detected prior to transplant. One-year acute rejection rates were similar in DSA-positive versus DSA-negative patients (15.4% vs. 11.4%, respectively; p = 0.18) and were higher in those with DSA mean fluorescence intensity (MFI) greater than or equal to 3000 in multivariable analysis (p = 0.046). The estimated glomerular filtration rate (eGFR) at 3 and 4 years was lower in the DSA(+) versus the DSA(-) group (p = 0.050 at 3 years) without an impact on 5-year death-censored graft survival (89.0% vs. 90.6%, respectively; p = 0.53). Timing (current or historic) of DSA detection did not alter these findings. In conclusion, pretransplant DSA in the setting of a negative FCXM confers minimal immunologic risk in the intermediate term, does not necessitate desensitization therapy and should not represent a barrier to renal transplant.

New ischaemic brain lesions in cervical artery dissection stratified to antiplatelets or anticoagulants.

BACKGROUND AND PURPOSE: To determine the frequency of new ischaemic or hemorrhagic brain lesions on early follow-up magnetic resonance imaging (MRI) in patients with cervical artery dissection (CAD) and to investigate the relationship with antithrombotic treatment. METHODS: This prospective observational study included consecutive CAD patients with ischaemic or non-ischaemic symptoms within the preceding 4 weeks. All patients had baseline brain MRI scans at the time of CAD diagnosis and follow-up MRI scans within 30 days thereafter. Ischaemic lesions were detected by diffusion-weighted imaging (DWI), intracerebral bleeds (ICBs) by paramagnetic-susceptible sequences. Outcome measures were any new DWI lesions or ICBs on follow-up MRI scans. Kaplan-Meier statistics and calculated odds ratios with 95% confidence intervals were used for lesion occurrence, baseline characteristics and type of antithrombotic treatment (antiplatelet versus anticoagulant). RESULTS: Sixty-eight of 74 (92%) CAD patients were eligible for analysis. Median (interquartile range) time interval between baseline and follow-up MRI scans was 5 (3-10) days. New DWI lesions occurred in 17 (25%) patients with a cumulative 30-day incidence of 41.3% (standard error 8.6%). Occurrence of new DWI lesions was associated with stroke or transient ischaemic attack at presentation [7.86 (2.01-30.93)], occlusion of the dissected vessel [4.09 (1.24-13.55)] and presence of DWI lesions on baseline MRI [6.67 (1.70-26.13)]. The type of antithrombotic treatment had no impact either on occurrence of new DWI lesions [1.00 (0.32-3.15)] or on functional 6-month outcome [1.27 (0.41-3.94)]. No new ICBs were observed. CONCLUSION: New ischaemic brain lesions occurred in a quarter of CAD patients, independently of the type of antithrombotic treatment. MRI findings could potentially serve as surrogate outcomes in pilot treatment trials.

Survival benefit of repeat liver transplantation in the United States: a serial MELD analysis by hepatitis C status and donor risk index.

Survival benefit (SB) for first liver transplantation (LT) is favorable at Model for End-Stage Liver Disease (MELD)≥15. Herein, we identify the MELD threshold for SB from repeat liver transplantation (ReLT) by recipient hepatitis C virus (HCV) status and donor risk index (DRI). We analyzed lab MELD scores in new United Network for Organ Sharing registrants for ReLT from March 2002 to January 2010. Risk of ReLT graft failure≤1 year versus waitlist mortality was calculated using Cox regression, adjusting for recipient characteristics. Of 3057 ReLT candidates, 54% had HCV and 606 died while listed. There were 1985 ReLT recipients, 52% had HCV and 567 ReLT graft failures by 1 year. Unadjusted waitlist mortality and post-ReLT graft failure rates were 416 (95% confidence interval [CI] 384-450) and 375 (95% CI 345-407) per 1000 patient-years, respectively. Waitlist mortality was higher with increasing waitlist MELD (p<0.001). The MELD for SB from ReLT overall was 21 (21 in non-HCV and 24 in HCV patients). MELD for SB varied by DRI in HCV patients (MELD 21, 24 and 27 for low, medium and high DRI, respectively) but did not vary for non-HCV patients. Compared to first LT, ReLT requires a higher MELD threshold to achieve an SB resulting in a narrower therapeutic window to optimize the utility of scarce liver grafts.

Thrombolysis in patients with prior stroke within the last 3 months.

BACKGROUND AND PURPOSE: Patients with prior stroke within 3 months have been mostly excluded from randomized thrombolysis trials mainly because of the fear of an increased rate of symptomatic intracerebral hemorrhage (sICH). The aim of this study was to compare baseline characteristics and clinical outcome of thrombolyzed patients who had a previous stroke within the last 3 months with those not fulfilling this criterion (comparison group). METHODS: In all, 1217 patients were included in our analysis (42.2% women, mean age 68.8 ± 14.4 years). RESULTS: Patients with previous stroke within the last 3 months (17/1.4%) had more often a basilar artery occlusion (41.2% vs. 10.8%) and less frequently a modified Rankin scale (mRS) score 0-1 prior to index stroke (88.2% vs. 97.3%) and a higher mean time lapse from symptom onset to thrombolysis (321 min vs. 262 min) than those in the comparison group. Stroke severity was not different between the two groups. Rates of sICH were 11.8% vs. 6%. None of the sICHs and only one asymptomatic intracerebral hemorrhage occurred in the region of the former infarct. At 3 months, favorable outcome (mRS ≤ 2) in patients with previous stroke within 3 months was 29.4% (vs. 48.9%) and mortality 41.2% (vs. 22.7%). CONCLUSIONS: In patients with prior stroke within the last 3 months, none of the sICHs and only one asymptomatic intracerebral hemorrhage occurred in the region of the former infarct. The high mortality was influenced by four patients, who died until discharge due to acute major index stroke. It is reasonable to include these patients in randomized clinical trials and registries to assess further their thrombolysis benefit-risk ratio.

Endovascular therapy in 201 patients with acute symptomatic occlusion of the internal carotid artery.

BACKGROUND AND PURPOSE: Endovascular therapy is used increasingly for treatment of acute symptomatic internal carotid artery (ICA) occlusion, although randomized trials are lacking. Predictors of outcome are therefore of special interest. METHODS: From 1992 to 2010 we treated 201 patients with acute ICA occlusion with intra-arterial pharmacological thrombolysis (32), endovascular mechanical therapy (78) or a combination of both (91). All data were assessed prospectively. RESULTS: There were 76/38% patients with tandem occlusions [ICA plus middle (MCA) or anterior cerebral arteries (ACA)], 18/9% without concomitant occlusions of major intracranial arteries (ICA plus branch occlusion) and 107/53% with functional ICA-T occlusions (ICA plus MCA and ACA). Median baseline National Institute of Health Stroke Scale (NIHSS) score was 17. Good recanalization (Thrombolysis in Myocardial Infarction 2-3) was achieved in (157/201) 78% patients and good reperfusion (Thrombolysis in Cerebral Infarction 2-3) in (151/182) 83%. Better recanalization rates were obtained with mechanical approaches, with/without thrombolytics (78/91 = 86% and 64/78 = 82%) compared with pharmacological thrombolysis only (15/32 = 47%; P < 0.001). Twelve patients (6%) suffered symptomatic intracranial haemorrhages. The 3-month outcome was favourable [modified Rankin score (mRS) 0-2] in 54/28% patients and moderate (mRS 0-3) in 90/46%; 60/31% patients died. Only 17/16% patients with functional ICA-T occlusions had favourable outcomes compared with 32/44% with tandem occlusions and 5/31% with ICA plus cerebral branch occlusions (P = 0.001). In multivariate analysis age [odds ratio (OR) = 0.96, 95% confidence interval (CI) = 0.93-0.98], NIHSS on admission (OR = 0.9, 95% CI = 0.83-0.98) and functional ICA-T occlusion (OR = 0.35, 95% CI = 0.16-0.77) were non-modifiable predictors, and vessel recanalization was the only modifiable predictor of outcome (OR = 9.30, 95% CI = 2.03-42.63). CONCLUSIONS: The outcome of acute symptomatic ICA occlusion is poor. However, recanalization is associated with better outcome, and recanalization rates with mechanical techniques were superior to merely pharmacological recanalization attempts.

Safety of endovascular treatment beyond the 6-h time window in 205 patients.

BACKGROUND AND PURPOSE: Intra-arterial treatment (IAT) is effective when performed within 6 h of symptom onset in selected stroke patients ('T < 6H'). Its safety and efficacy is unclear when the patient has had symptoms for more than 6 h ('T > 6H') or for an unknown time (unclear-onset stroke, UOS), or woke up with a stroke (wake-up stroke, WUS). In this study we compared the safety of IAT in these four patient groups. METHODS: Eight-hundred and fifty-nine patients treated with IAT were enrolled. The main outcome parameters were clinical outcome [excellent: modified Rankin Scale (mRS) 0 or 1; or favorable: mRS 0-2] or mortality 3 months after treatment. Further outcome parameters were the rates of vessel recanalization, and cerebral and systemic hemorrhage. RESULTS: Six-hundred and fifty-four patients were treated before (T < 6H) and 205 after 6 h or an unknown time (128 T > 6H, 55 WUS and 22 UOS). NIHSS scores were higher in UOS patients than in T < 6H patients, vertebrobasilar occlusion was more common in T > 6H and UOS patients, and middle cerebral artery occlusions less common in T > 6H than in T < 6H patients. Other baseline characteristics were similar. There was no significant difference in clinical outcome and the rate of hemorrhage in multivariable regression analysis. CONCLUSIONS: Clinical outcome of our four groups of patients was similar with no increase of hemorrhage rates in patients treated after awakening, after an unknown time or more than 6 h. Our preliminary data suggest that treatment of such patients may be performed safely. If confirmed in randomized trials, this would have major clinical implications.

Intra-Arterial Thrombolysis is Associated with Delayed Reperfusion of Remaining Vessel Occlusions following Incomplete Thrombectomy.

BACKGROUND AND PURPOSE: Intra-arterial thrombolytics may be used to treat distal vessel occlusions, which cause incomplete reperfusion following mechanical thrombectomy. Because immediate reperfusion after intra-arterial thrombolytics occurs rarely, the aim of this study was to assess the delayed effect of intra-arterial thrombolytics using follow-up perfusion imaging. MATERIALS AND METHODS: We included patients from a prospective stroke registry (February 2015 to September 2022) who had undergone mechanical thrombectomy and had incomplete reperfusion (expanded TICI 2a-2c) and available 24 hour perfusion imaging. Perfusion imaging was rated as delayed reperfusion if time-sensitive perfusion maps did not show wedge-shaped delays suggestive of persisting occlusions corresponding to the post-mechanical thrombectomy angiographic deficit. Patients treated with intra-arterial thrombolytics were compared with controls using multivariable logistic regression and inverse probability of treatment weighting matching for baseline differences and factors associated with delayed reperfusion. RESULTS: The median age of the final study population (n = 459) was 74 years (interquartile range, 63-81 years), and delayed reperfusion occurred in 61% of cases. Patients treated with additional intra-arterial thrombolytics (n = 40) were younger and had worse expanded TICI scores. After matching was performed, intra-arterial thrombolytics was associated with higher rates of delayed reperfusion (adjusted OR = 2.7; 95% CI, 1.1-6.4) and lower rates of new infarction in the residually hypoperfused territory after mechanical thrombectomy (adjusted OR = 0.3; 95% CI, 0.1-0.7). No difference was found in the rates of functional independence (90-day mRS, 0-2; adjusted OR = 1.4; 95% CI, 0.4-4.1). CONCLUSIONS: Rescue intra-arterial thrombolytics is associated with delayed reperfusion of remaining vessel occlusions following incomplete mechanical thrombectomy. The value of intra-arterial thrombolytics as a potential therapy for incomplete reperfusions after mechanical thrombectomy should be assessed in the setting of randomized controlled trials.

[Acute occlusions of cerebral arterial vessels - intravenous versus intraarterial thrombolysis]. / Akute Verschlüsse der Hirnarterien - intravenöse oder intraarterielle Thrombolyse.

In selected stroke patients intravenous thrombolysis and/or endovascular therapies lead to a significant reduction of long term disabilities. In case of no contraindications, patients with acute ischemic stroke, which arrive within the time window on the emergency unit, should receive thrombolysis consequently and current data indicate that patients with a severe acute ischemic stroke and a proximal cerebral arterial vessel occlusion (i. e. main stem of the arteria cerebri media, posterior, maybe also anterior, arteria carotis interna and basilaris) should preferentially be treated endovascularly, patients with a peripheral cerebral arterial vessel occlusion (i. e. main branch of the arteria cerebri media, anterior and posterior) and mild symptoms with intravenous thrombolysis.

Correlation of Collateral Scores Derived from Whole-Brain Time-Resolved Flat Panel Detector Imaging in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Flat panel detector CT imaging allows simultaneous acquisition of multiphase flat panel CTA and flat panel CTP imaging directly in the angio suite. We compared collateral assessment derived from multiphase flat panel CTA and flat panel CTP with collateral assessment derived from DSA as the gold-standard. MATERIALS AND METHODS: We performed a retrospective analysis of patients with occlusion of the first or second segment of the MCA who underwent pre-interventional flat panel detector CT. The hypoperfusion intensity ratio as a correlate of collateral status was calculated from flat panel CTP (time-to-maximum > 10 seconds volume/time-to-maximum > 6 seconds volume). Intraclass correlation coefficients were calculated for interrater reliability for the Calgary/Menon score for multiphase flat panel CTA and for the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) score for DSA collateral scores. Correlations of the hypoperfusion intensity ratio, multiphase flat panel CTA score, and the ASITN/SIR score were calculated using the Spearman correlation. RESULTS: From November 2019 to February 2020, thirty patients were included. Moderate interrater reliability was achieved for the ASITN/SIR DSA score (0.68; 95% CI, 0.50-0.82) as well as for the Calgary/Menon multiphase flat panel CTA score (0.53; 95% CI, 0.29-0.72). We found a strong correlation between the ASITN/SIR DSA and Calgary/Menon multiphase flat panel CTA score (ρ = 0.54, P = .002) and between the hypoperfusion intensity ratio and the Calgary/Menon multiphase flat panel CTA score (ρ = -0.57, P < .001). The correlation was moderate between the hypoperfusion intensity ratio and the ASITN/SIR DSA score (ρ = -0.49, P = .006). The infarct core volume correlated strongly with the Calgary/Menon multiphase flat panel CTA score (ρ = -0.66, P < .001) and the hypoperfusion intensity ratio (ρ = 0.76, P < .001) and correlated moderately with the ASITN/SIR DSA score (ρ = -0.46, P = .01). CONCLUSIONS: The Calgary/Menon multiphase flat panel CTA score and the hypoperfusion intensity ratio correlated with each other and with the ASITN/SIR DSA score as the gold-standard. In our cohort, the collateral scoring derived from flat panel detector CT was clinically reliable.

Risks of Undersizing Stent Retriever Length Relative to Thrombus Length in Patients with Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Results regarding the association of thrombus length, stent retriever length, and recanalization success in patients with acute ischemic stroke are inconsistent. We hypothesized that the ratio of thrombus length to stent retriever length may be of particular relevance. MATERIALS AND METHODS: Patients with acute ischemic stroke undergoing stent retriever thrombectomy at our institution between January 2010 and December 2018 were reviewed retrospectively. Thrombus length was assessed by measuring the susceptibility vessel sign on SWI using a 1.5T or 3T MR imaging scanner. Multivariable logistic regression models were used to determine the association between thrombus length, stent retriever length, and thrombus length/stent retriever length ratio with first-pass recanalization, overall recanalization, and embolization in new territories. Results are shown as adjusted ORs with 95% CIs. Additional mediation analyses were performed to test for indirect effects on first-pass recanalization and overall recanalization success. RESULTS: The main analysis included 418 patients (mean age, 74.9 years). Increasing stent retriever length was associated with first-pass recanalization. Decreasing thrombus length and lower thrombus length/stent retriever length ratios were associated with first-pass recanalization and overall recanalization. Thrombus length and stent retriever length showed no association with first-pass recanalization or overall recanalization once thrombus length/stent retriever length ratio was factored in, while thrombus length/stent retriever length ratio remained a significant factor in both models (adjusted OR, 0.316 [95% CI, 0.112-0.892]; P = .030 and adjusted OR, = 0.366 [95% CI, 0.194-0.689]; P = .002). Mediation analyses showed that decreasing thrombus length and increasing stent retriever length had a significant indirect effect on first-pass recanalization mediated through thrombus length/stent retriever length ratio. The only parameter associated with embolization in new territories was an increasing thrombus length/stent retriever length ratio (adjusted OR, 5.079 [95% CI, 1.332-19.362]; P = .017). CONCLUSIONS: Information about thrombus and stent length is more valuable when combined. High thrombus length/stent retriever length ratios, which may raise the risk of unsuccessful recanalization and embolization in new territories, should be avoided by adapting stent retriever selection to thrombus length whenever possible.

SWI Susceptibility Vessel Sign in Patients Undergoing Mechanical Thrombectomy for Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: The frequency and clinical significance of the susceptibility vessel sign in patients with acute ischemic stroke remains unclear. We aimed to assess its prevalence in patients with acute ischemic stroke undergoing mechanical thrombectomy and to analyze its association with interventional and clinical outcome parameters in that group. MATERIALS AND METHODS: Six hundred seventy-six patients with acute ischemic stroke and admission MR imaging were reviewed retrospectively. Of those, 577 met the eligibility criteria for further analysis. Imaging was performed using a 1.5T or 3T MR imaging scanner. Associations between baseline variables, interventional and clinical outcome parameters, and susceptibility vessel sign were determined with multivariable logistic regression models. Results are shown as adjusted ORs with 95% CIs. RESULTS: The susceptibility vessel sign was present in 87.5% (n = 505) of patients and associated with tandem occlusion (adjusted OR, 3.3; 95% CI, 1.1-10.0; P = .032) as well as successful reperfusion, defined as an expanded TICI score of ≥2b (adjusted OR, 2.4; 95% CI, 1.28-4.6; P = .007). The susceptibility vessel sign was independently associated with functional independence (mRS ≤ 2: adjusted OR, 2.1; 95% CI, 1.1-4.0; P = .028) and lower mortality (adjusted OR, 0.4; 95% CI, 0.2-0.7; P = .003) at 90 days, even after adjusting for successful reperfusion. The susceptibility vessel sign did not influence the number of passes performed during mechanical thrombectomy, the first-pass reperfusion, or the risk of peri- or postinterventional complications. CONCLUSIONS: The susceptibility vessel sign is an MR imaging phenomenon frequently observed in patients with acute ischemic stroke and is associated with successful reperfusion after mechanical thrombectomy. However, superior clinical functional outcome and lower mortality noted in patients showing the susceptibility vessel sign could not be entirely attributed to higher reperfusion rates.

Evolution of MRI Findings in Patients with Idiopathic Intracranial Hypertension after Venous Sinus Stenting.

BACKGROUND AND PURPOSE: The correlation between imaging findings and clinical status in patients with idiopathic intracranial hypertension is unclear. We aimed to examine the evolution of idiopathic intracranial hypertension-related MR imaging findings in patients treated with venous sinus stent placement. MATERIALS AND METHODS: Thirteen patients with idiopathic intracranial hypertension (median age, 26.9 years) were assessed for changes in the CSF opening pressure, transstenotic pressure gradient, and symptoms after venous sinus stent placement. Optic nerve sheath diameter, posterior globe flattening and/or optic nerve protrusion, empty sella, the Meckel cave, tonsillar ectopia, the ventricles, the occipital emissary vein, and subcutaneous fat were evaluated on MR imaging before and 6 months after venous sinus stent placement. Data are expressed as percentages, medians, or correlation coefficients (r) with P values. RESULTS: Although all patients showed significant reductions of the CSF opening pressure (31 versus 21 cm H2O; P = .005) and transstenotic pressure gradient (22.5 versus 1.5 mm Hg; P = .002) and substantial improvement of clinical symptoms 6 months after venous sinus stent placement, a concomitant reduction was observed only for posterior globe involvement (61.5% versus 15.4%; P = .001), optic nerve sheath diameter (6.8 versus 6.1 mm; P < .001), and subcutaneous neck fat (8.9 versus 7.4 mm; P = .001). Strong correlations were observed between decreasing optic nerve sheath diameters and improving nausea/emesis (right optic nerve sheath diameter, r = 0.592, P = .033; left optic nerve sheath diameter, r = 0.718, P = .006), improvement of posterior globe involvement and decreasing papilledema (r = 0.775, P = .003), and decreasing occipital emissary vein diameter and decreasing headache frequency (r = 0.74, P = .035). Decreasing transstenotic pressure gradient at 6 months strongly correlated with decreasing empty sella (r = 0.625, P = .022) and regressing cerebellar ectopia (r = 0.662, P = .019). CONCLUSIONS: Most imaging findings persist long after normalization of intracranial pressure and clinical improvement. However, MR imaging findings related to the optic nerve may reflect treatment success.

Monro-Kellie Hypothesis: Increase of Ventricular CSF Volume after Surgical Closure of a Spinal Dural Leak in Patients with Spontaneous Intracranial Hypotension.

BACKGROUND AND PURPOSE: CSF loss in spontaneous intracranial hypotension disrupts a well-regulated equilibrium. We aimed to evaluate the volume shift between intracranial compartments in patients with spontaneous intracranial hypotension before and after surgical closure of the underlying spinal dural breach. MATERIALS AND METHODS: In total, 19 patients with spontaneous intracranial hypotension with a proved spinal CSF leak investigated at our institution between July 2014 and March 2017 (mean age, 41.8 years; 13 women) were included. Brain MR imaging-based volumetry at baseline and after surgery was performed with FreeSurfer. In addition, the spontaneous intracranial hypotension score, ranging from 0 to 9, with 0 indicating very low and 9 very high probability of spinal CSF loss, was calculated. RESULTS: Total mean ventricular CSF volume significantly increased from baseline (15.3 mL) to posttreatment MR imaging (18.0 mL), resulting in a mean absolute and relative difference, +2.7 mL and +18.8% (95% CI, +1.2 to +3.9 mL; P < .001). The change was apparent in the early follow-up (mean, 4 days). No significant change in mean total brain volume was observed (1136.9 versus 1133.1 mL, P = .58). The mean spontaneous intracranial hypotension score decreased from 6.9 ± 1.5 at baseline to 2.9 ± 1.5 postoperatively. CONCLUSIONS: Our study demonstrated a substantial increase in ventricular CSF volume in the early follow-up after surgical closure of the underlying spinal dural breach and may provide a causal link between spinal CSF loss and spontaneous intracranial hypotension. The concomitant decrease in the spontaneous intracranial hypotension score postoperatively implies the restoration of an equilibrium within the CSF compartment.

Endovascular Thrombectomy of Calcified Emboli in Acute Ischemic Stroke: A Multicenter Study.

BACKGROUND AND PURPOSE: Large intracranial vessel occlusion due to calcified emboli is a rare cause of major stroke. We assessed the prevalence, imaging appearance, the effectiveness of mechanical thrombectomy, and clinical outcome of patients with large-vessel occlusion due to calcified emboli. MATERIALS AND METHODS: We performed a retrospective analysis of clinical and procedural data of consecutive patients who underwent mechanical thrombectomy due to calcified emboli in 7 European stroke centers. RESULTS: We screened 2969 patients, and 40 patients matched the inclusion criteria, accounting for a prevalence of 1.3%. The mean maximal density of the thrombus was 327 HU (range, 150-1200 HU), and the mean thrombus length was 9.2 mm (range, 4-20 mm). Four patients had multiple calcified emboli, and 2 patients had an embolic event during an endovascular intervention. A modified TICI score of ≥2b was achieved in 57.5% (23/40), with minimal-to-no reperfusion (modified TICI 0-1) in 32.5% (13/40) and incomplete reperfusion (modified TICI 2a) in 10% (4/40). Excellent outcome (mRS 0-1) was achieved in only 20.6%, functional independence (mRS 0-2) in 26.5% and 90-day mortality was 55.9%. CONCLUSIONS: Acute ischemic stroke with large-vessel occlusion due to calcified emboli is a rare entity in patients undergoing thrombectomy, with considerably worse angiographic outcome and a higher mortality compared with patients with noncalcified thrombi. Good functional recovery at 3 months can still be achieved in about a quarter of patients.

Spine MRI in Spontaneous Intracranial Hypotension for CSF Leak Detection: Nonsuperiority of Intrathecal Gadolinium to Heavily T2-Weighted Fat-Saturated Sequences.

BACKGROUND AND PURPOSE: Spine MR imaging plays a pivotal role in the diagnostic work-up of spontaneous intracranial hypotension. The aim of this study was to compare the diagnostic accuracy of unenhanced spine MR imaging and intrathecal gadolinium-enhanced spine MR imaging for identification and localization of CSF leaks in patients with spontaneous intracranial hypotension. MATERIALS AND METHODS: A retrospective study of patients with spontaneous intracranial hypotension examined from February 2013 to October 2017 was conducted. Their spine MR imaging was reviewed by 3 blinded readers for the presence of epidural CSF using 3 different sequences (T2WI, 3D T2WI fat-saturated, T1WI gadolinium). In patients with leaks, the presumed level of the leak was reported. RESULTS: In total, 103 patients with spontaneous intracranial hypotension (63/103 [61%] women; mean age, 50 years) were evaluated. Seventy had a confirmed CSF leak (57/70 [81%] proved intraoperatively), and 33 showed no epidural CSF on multimodal imaging. Intrathecal gadolinium-enhanced spine MR imaging was nonsuperior to unenhanced spine MR imaging for the detection of epidural CSF (P = .24 and .97). All MR imaging sequences had a low accuracy for leak localization. In all patients, only 1 leakage point was present, albeit multiple suspicious lesions were reported in all sequences (mean, 5.0). CONCLUSIONS: Intrathecal gadolinium-enhanced spine MR imaging does not improve the diagnostic accuracy for the detection of epidural CSF. Thus, it lacks a rationale to be included in the routine spontaneous intracranial hypotension work-up. Heavily T2-weighted images with fat saturation provide high accuracy for the detection of an epidural CSF collection. Low accuracy for leak localization is due to an extensive CSF collection spanning several vertebrae (false localizing sign), lack of temporal resolution, and a multiplicity of suspicious lesions, albeit only a single leakage site is present. Thus, dynamic examination is mandatory before targeted treatment is initiated.

Polymerase II promoter activation: closed complex formation and ATP-driven start site opening.

Studies on bacterial RNA polymerases have divided the initiation pathway into three steps, namely (i) promoter binding to form the closed complex; (ii) DNA melting to form an open complex, and (iii) messenger RNA initiation. Potassium permanganate was used to detect DNA melting by mammalian RNA polymerase II in vitro. Closed complexes formed in a rate-limiting step that was stimulated by the activator GAL4-VP16. Adenosine triphosphate was then hydrolyzed to rapidly melt the DNA within the closed complex to form an open complex. Addition of nucleoside triphosphates resulted in the melted bubble moving away from the start site, completing initiation.

Converting Escherichia coli RNA polymerase into an enhancer-responsive enzyme: role of an NH2-terminal leucine patch in sigma 54.

The protein sigma 54 associates with Escherichia coli core RNA polymerase to form a holoenzyme that binds promoters but is inactive in the absence of enhancer activation. Here, mutants of sigma 54 enabled polymerases to transcribe without enhancer protein and adenosine triphosphate. The mutations are in leucines within the NH2-terminal glutamine-rich domain of sigma 54. Multiple leucine substitutions mimicked the effect of enhancer protein, which suggests that the enhancer protein functions to disrupt a leucine patch. The results indicate that sigma 54 acts both as an inhibitor of polymerase activity and as a receptor that interacts with enhancer protein to overcome this inhibition, and that these two activities jointly confer enhancer responsiveness.