Impact of high-resolution intracranial vessel wall magnetic resonance imaging on diagnosis in patients with embolic stroke of unknown source.

BACKGROUND: The mechanism responsible for stroke in patients with embolic stroke of unknown source (ESUS) often remains unknown despite extensive investigations. We aimed to test whether high-resolution intracranial vessel wall MR imaging (icVWI) can add to the diagnostic yield in these patients. PATIENTS AND METHODS: Patients with ESUS were prospectively included into an ongoing registry. Patients that underwent icVWI as part of their diagnostic workup were compared to those that did not have an icVWI. Patients with icVWI positive for intracranial vulnerable plaques were than compared to those without evidence of plaque vulnerability on VWI. RESULTS: A total of 179 patients with ESUS were included and 48 of them (27%) underwent icVWI. Patients that had an icVWI scan were significantly younger, had lower rates of ischemic heart disease and prior disability as well as significantly lower stroke severity. On regression analysis the only factor that remained associated with not obtaining an icVWI scan was increasing age (Odds ratio [OR] 0.97/year, 95% confidence intervals [CI] 0.95-0.97). Among patients that had an icVWI scan 28 (58%) had evidence of plaque enhancement on VWI in the same distribution of the stroke and the remaining 20 studies were negative. The relative proportion of stroke presumed to be secondary to intracranial non-stenotic atheromatous disease increased from 15% in patients without icVWI scans to 58% among patients with icVWI scans (p = 0.001). On regression analysis the only factor that was associated with vulnerable plaques on icVWI was smoking (OR 11.05 95% CI 1.88-65.17). CONCLUSIONS: icVWI can add significant information relevant to stroke pathogenesis and treatment in patients with ESUS and a negative initial exhaustive diagnostic workup.

Does Malignancy Status Effect Outcomes in Patients With Large Vessel Occlusion Stroke and Cancer Who Underwent Endovascular Thrombectomy?

Background Cancer is associated with an increased risk of acute ischemic stroke, including large vessel occlusions. Whether cancer status affects outcomes in patients with large vessel occlusions that undergo endovascular thrombectomy remains unknown. Methods and Results All consecutive patients undergoing endovascular thrombectomy for large vessel occlusions were recruited into a prospective ongoing multicenter database, and the data were retrospectively analyzed. Patients with active cancer were compared with patients with cancer in remission. Association of cancer status with 90-day functional outcome and mortality were calculated in multivariable analyses. We identified 154 patients with cancer and large vessel occlusions that underwent endovascular thrombectomy (mean age, 74±11; 43% men; median National Institutes of Health Stroke Scale 15). Of the included patients, 70 (46%) had a remote history of cancer or cancer in remission, and 84 (54%) had active disease. Outcome data at 90 days poststroke were available for 138 patients (90%) and was classified as favorable in 53 (38%). Patients with active cancer were younger and more often smoked but did not significantly differ from those without malignancy in other risk factors, stroke severity, stroke subtype, or procedural variables. Favorable outcome rates among patients with active cancer did not significantly differ compared with those seen in patients without active cancer, but mortality rates were significantly higher among patients with active cancer on univariate and multivariable analyses. Conclusions Our study suggests that endovascular thrombectomy is safe and efficacious in patients with history of malignancy as well as in those with active cancer at the time of stroke onset, although mortality rates are higher among patients with active cancer.

Diagnostic Yield of High-Resolution Vessel Wall Magnetic Resonance Imaging in the Evaluation of Young Stroke Patients.

(1) Background: The mechanism responsible for stroke in patients younger than 50 often remains unknown. This study was designed to assess whether high-resolution intracranial vessel wall MR imaging (icVWI) may be instrumental in determining stroke cause. (2) Methods: Young stroke patients with and without an identified cause of stroke despite an exhaustive investigation were prospectively included. Patients who underwent icVWI were compared to those who did not. We next compared patients with and without intracranial vulnerable plaques on icVWI. (3) Results: Overall, 47 young stroke patients were identified over the span of 2 years and included in this study. Of those, 20 (42%) underwent intracranial icVWI. Cancer prevalence was higher among patients who did not have an icVWI study (19% vs. 0% p = 0.042) but there were no other significant differences between patients who had an icVWI study and those who did not have an icVWI. Among patients who had an icVWI, 11 (55%) had vulnerable plaques and the remaining nine studies were negative. Patients with positive icVWI scans had significantly higher stroke severity at admission (mean ± SD NIHSS score 5.5 ± 3.5 vs. 1.7 ± 2.3, p = 0.012). Patients with positive icVWI scans were more often treated with antiplatelets upon discharge (100% vs. 67%, p = 0.038). (4) Conclusions: icVWI can add significant information relevant to stroke pathogenesis and secondary prevention among young stroke patients with a negative exhaustive diagnostic workup.

Overestimation of carotid stenosis on CTA - Real world experience.

BACKGROUND: Symptomatic carotid stenosis is responsible for 10% of all strokes. Currently, CT angiography (CTA) is the main diagnostic tool for carotid stenosis. It is frequently the only diagnostic test preceding recommendations for carotid angioplasty and stenting (CAS) or carotid endarterectomy (CEA). However, the specificity of CTA, especially in patients with 50-70% stenosis, was previously reported to be relatively low. Most studies testing the diagnostic accuracy of CTA were published more than a decade ago. Therefore, we aimed to test the diagnostic accuracy of CTA, performed with current available technology, compared with digital subtraction angiography (DSA) in patients with carotid stenosis. This study aims to characterize patients who were candidates for CAS/CEA based on CTA, but may not require it based on DSA. METHODS: Consecutive candidates for carotid interventions (CAS or CEA) following CTA were identified from prospectively maintained stroke center registries at two large academic centers. As part of our institutional practice all patients had a routine pre-procedural diagnostic DSA. In each patient, degree of carotid stenosis was compared between CTA and DSA. Patients with concordant degree of stenosis on DSA and CTA (true positive group) were compared to patients with a discordant degree of stenosis with less than 50% on DSA (false positive group). RESULTS: Out of 90 patients with significant stenosis on CTA, only 70 (78%) were found to have a significant stenosis on DSA. Severe plaque calcification was significantly more common in the false-positive group. In those patients whose CTA reported stenosis of ≥90%, we found a strong agreement between CTA and DSA (positive predictive value [PPV] - 0.9) for a significant stenosis (≥50%). Conversely, the correlation between CTA and DSA in patients with CTA reported 50-70% stenosis was poor (PPV - 0.29) (p < 0.001). CONCLUSIONS: Our results suggest that despite ongoing radiological progress, the specificity of CTA in accurately assessing carotid stenosis remains relatively low in patients with both moderate stenosis and heavily calcified plaques. Consequently, patients could possibly be referred for unnecessary CEA surgery and may become exposed to associated potential complications.

Post-stroke ASPECTS predicts outcome after thrombectomy.

PURPOSE: Infarct growth and final infarct volume are established outcome modifiers following endovascular thrombectomy (EVT) for patients with large vessel occlusion stroke (LVO). Simple techniques for final infarct volume measurement are lacking, and therefore, we tested whether post-EVT ASPECTS can be used for prognostic evaluation after EVT. METHODS: Infarct size at baseline was measured in a prospective cohort of patients with LVO that underwent EVT with the ASPECTS score on admission non-contrast CT. Final infarct size was assessed with a post-EVT ASPECTS (ASPECTS-POST) obtained from a follow-up CT 24-72 h post-EVT. The best performing ASPECTS-POST was chosen based on comparisons of different thresholds. Outcome measures included survival rates and modified Rankin Score at 90 days. RESULTS: A total of 272 patients were included and 166 of them had an ASPECTS-POST ≥ 7. ASPECTS-POST ≥ 7 was associated with increased likelihood of favorable outcome at 90 days (67% vs. 21%, p < 0.001) with sensitivity, specificity, and positive and negative predictive values of 86%, 58%, 61%, and 85%, respectively. On multivariate analysis, ASPECTS-POST ≥ 7 was found to be a significant modifier of favorable outcome (Odds Ratio [OR] 6.2, 95% confidence intervals [CI] 3.1-12.4) and survival (OR 5.8 95% CI 2.4-14.3). CONCLUSION: ASPECTS can be rapidly and easily obtained from the post-EVT NCCT and ASPECTS-POST ≥ 7 correlates with good outcome.

Impact of carotid tortuosity on outcome after endovascular thrombectomy.

BACKGROUND AND OBJECTIVES: Endovascular thrombectomy (EVT) is efficacious in patients with large vessel occlusion stroke (LVO). We explored whether internal carotid (ICA) tortuosity increases the technical difficulty of EVT thereby lowering the chances of successful recanalization and favorable outcomes. PATIENTS AND METHODS: Consecutive patients with LVO and patent ICAs who underwent EVT were included. Carotid tortuosity was determined on pre-EVT CTA and classified by raters blinded to outcomes into: type 1-straight ICA trunk and type 2-severe tortuosity potentially impeding adequate catheter placement. Thrombolysis in cerebral infarction (TICI) 2b-3 was considered successful recanalization, and 90-day-modified Rankin Scale ≤ 2 was considered favorable functional outcome. RESULTS: Among 302 patients (mean age 70 ± 15, median NIHSS 17), 53% had type 1, and 47% type 2 tortuosity. Overall, 85% had successful recanalization. Patients with type 2 tortuosity were significantly older (p < 0.0001) and less frequently achieved successful recanalization (80% vs. 90%; p = 0.019) but had similar outcomes compared with those without tortuosity. On regression analysis, marked tortuosity was associated with lower chances of successful recanalization (OR 0.43 95% CI 0.20-0.92) but had no effect on clinical outcomes. CONCLUSIONS: Carotid tortuosity does not appear to impact the likelihood of favorable functional outcome but may influence recanalization.

Intravenous Line Phase-Wrap Artifact at Bilateral Axial 3-T Breast MRI: Identification, Analysis, and Solution.

Purpose: To understand and remove the source of a phase-wrap artifact produced by residual contrast agent in the intravenous line during acquisition of bilateral axial 3-T dynamic contrast material-enhanced (DCE) breast MRI. Materials and Methods: A two-part study involved a phantom experiment, followed by an institutional review board approved clinical intervention, to evaluate the phase-wrap artifact at MRI. A phantom model evaluated artifact production by using an intravenous line filled with fluids with varying concentrations of gadolinium-based contrast agent (0, 0.4, 0.8, 1.2, 1.6, and 2 mmol/mL) and by positioning the simulated intravenous line within several fields of view (FOV) at 3-T MRI in breast coils. Next, a clinical assessment was performed with a total of 400 patients (control group:interventional group, 200:200) to determine the effect of taping the intravenous line to the patients' backs. Breast MR images were assessed blindly for the presence of the artifact. Software was used for statistical analysis with a P value of less than .05 considered a significant difference. Results: In the phantom model, the artifact was produced only with a 0.4 mmol/mL gadolinium concentration and when the tubing was either close to the edge or within a FOV of 350-450 mm. In the clinical experiment, the artifact was more prevalent in the retrospective control group than in the prospective intervention group (52.5% [105 of 200] vs 22% [44 of 200]; P < .005). Conclusion: The presence of phase-wrap artifacts can be reduced by moving the contrast agent intravenous line out of the FOV during acquisition by taping it to a patient's back during bilateral axial 3-T DCE breast MRI.Keywords: Breast, MR-Imaging, Phantom Studies© RSNA, 2020.

Number of stentriever passes and outcome after thrombectomy in stroke.

BACKGROUND AND PURPOSES: Stroke secondary to emergent large vessel occlusions (ELVO) involving the anterior circulation can be treated with intravenous tissue plasminogen activator (IV-tPA) or thrombectomy. Data regarding the influence of the number of stentriever passes needed for vessel recanalization on outcome is lacking. PATIENTS AND METHODS: We prospectively accrued data on consecutive patients with ELVO that were treated with thrombectomy. Procedural details including the number of stentriever passes needed to achieve vessel recanalization and clot length were collected. Functional outcome was determined with the modified Rankin Scale (mRS) at 90 days post stroke with mRS ≤ 2 considered favorable outcome. Data on demographics, risk factors, stroke severity, survival, and occurrence of symptomatic intracranial hemorrhage (sICH) was also collected. RESULTS: On univariate analysis more than one pass needed to achieve recanalization impacted survival and functional outcome after 90 days as did age, stroke severity and collateral and reperfusion status. On multivariate logistic regression the number of passes needed to achieve revascularization (OR: 10.0, 95% CI: 2.28-43.94, P = 0.002), age (OR: 0.90, 95% CI: 0.84-0.96, P = 0.001) and collateral status (OR: 7.90, 95% CI: 1.87-33.35, P = 0.005) remained significant modifiers for favorable outcome. On logistic regression the only variable associated with the need to perform more than a single stentriever pass was time from symptom onset to target vessel recanalization (OR: 1.007, 95% CI: 1.002-1.012). CONCLUSIONS: The number of passes needed to achieve target vessel recanalization modifies outcome after thrombectomy and successful recanalization after a single pass is associated with favorable outcome.

Increased Risk for Unfavorable Outcome in Patients with Pre-Existing Disability Undergoing Endovascular Therapy.

INTRODUCTION: Most studies evaluating endovascular therapy (EVT) for stroke only included patients without pre-existing disabilities. However, in real life many patients have pre-existing disabilities, and whether they can benefit from EVT remains unknown. METHODS: Patients with emergent large vessel occlusions undergoing EVT were prospectively enrolled. Patients with no or mild pre-existing disabilities (modified Rankin Scale [mRS], 0-2) were compared with patients presenting with pre-existing moderate disability (mRS ≥ 3). Baseline demographics and risk factors, stroke severity (studied with the National Institutes of Health Stroke Scale [NIHSS]), imaging data including pretreatment Alberta Stroke Program Early Computerized Tomography Score (ASPECTS) and ASPECTS collateral scores, as well as procedure-related variables were accrued. Unfavorable outcome was defined as mRS ≥ 4 at day 90. RESULTS: Of 131 enrolled patients, 108 had a baseline mRS of 2 or lower, and 23 had a prestroke mRS score of 3 or higher. Patients with pre-existing mRS scores of 3 or higher were significantly older (80.3 ± 10 versus 66.9 ± 13.7; P = .001) and more often had previous strokes (39% versus 16%; P = .02). Patients with mRS scores of 3 or higher were more likely to have poor outcomes or death (odds ratio [OR], 4.4; 95% confidence interval [CI], 1.3-15.0). Of the 23 patients with pre-existing moderate disability, 8 (35%) maintained their previous degree of disability. On multivariate analysis, age (OR, .92; 95% CI, .88-.97; P = .001), admission NIHSS (OR, .92; 95% CI, .85-.99; P = .042) and pretreatment ASPECTS (OR, 6.4; 95% CI, 1.4-29.5; P = .017) remained significant modifiers of favorable outcome. DISCUSSION AND CONCLUSIONS: Patients with pre-existing moderate disabilities have higher chances of sustaining unfavorable outcomes despite EVT. Nevertheless, some patients maintain the same level of moderate disabilities, and therefore, patients with pre-existing moderate disabilities should not be excluded from EVT.

Wire escalation in emergent revascularization procedures of internal carotid artery occlusions: the use of high tip stiffness microguidewires.

OBJECTIVE: We examined the usefulness and safety of high tip stiffness cardiac microguidewires in the endovascular revascularization of selected cases of internal carotid artery (ICA) occlusion. METHODS: Files of patients with acute ischemic symptoms due to ICA occlusions managed from August 2010 to August 2016 by urgent endovascular revascularization were retrospectively reviewed with a waiver of informed consent. Cases where there was escalation to stiff tipped cardiovascular microguidewires after at least two failed attempts to cross the carotid occlusion with standard neuro-microguidewires were included. Radiological and interventional data were recorded. RESULTS: 63 patients with acute carotid occlusions underwent emergent endovascular revascularization in the study period; 5/63 patients met the inclusion criteria. In 4/5 patients, there was no angiographic evidence of the remnant origin of the ICA; in 1/5 there was a wide round shaped proximal calcified cap that precluded soft guidewire entry. In all cases, antegrade wiring was achieved only after switching to stiffer guidewires designed for the management of chronic cardiac occlusions. The use of these stiffer tip wires was considered of critical importance in achieving the successful performance of the ICA revascularization procedure. In all patients, revascularization was achieved, and 90 day modified Rankin Scale score ranged from 0 to 2. CONCLUSIONS: When regular neuro-guidewires do not allow antegrade wiring in cases of ICA occlusion, wire escalation to high tip stiffness guidewires may improve success. These wires, designed to deal with chronic total coronary occlusions, can serve as a platform for new neuro-guidewires to be used in the challenging field of resistant supra-aortic occlusions.

Stent Retriever-Based Thrombectomy in Octogenarians.

BACKGROUND AND AIMS: Stent retriever-based thrombectomy (SRT) may be beneficial in patients with large hemispheric stroke. Previous studies concluded that favorable outcomes are far less frequent after endovascular therapy in older patients but have not explored outcomes in the era of newer-generation stent retrievers. MATERIALS AND METHODS: Consecutive patients with large hemispheric stroke treated with SRT were included. We compared neurological and functional outcomes between patients younger and older than 80. RESULTS: We included 16 patients older than 80 (22.5%, mean age 84.1 ± 4.4, 56% females) and compared them to 55 patients that were younger than 80 (77.5%, mean age 63.1 ± 12.5, 51% females). Risk factor profile, admission neurological severity, stroke etiology and procedure-related variables including excellent target vessel recanalization did not differ between the groups. Favorable outcome at 90 days (modified Rankin score ≤2) was more common in younger patients (77 vs. 23%; p = 0.031). In contrast, mortality rates were higher in octogenarians (40 vs. 7%; p = 0.01). Logistic regression analysis adjusting for neurological severity and collateral state identified age over 80 (odds ratio, OR 0.15, 95% CI 0.03-0.75; p = 0.02) and reperfusion state (OR 7.4, 95% CI 1.1-49.9; p = 0.04) as significant modifiers of favorable outcome. Similarly, age over 80 was identified as a positive predictor of mortality (OR 8.1, 95% CI 1.8-36.7; p = 0.007). CONCLUSIONS: Octogenarians have higher chances of mortality and lower probability of achieving functional independence even after SRT. Nevertheless, because some elderly patients do achieve favorable outcomes, the cost-effectiveness of SRT in this population needs to be further studied.

Vertebral artery pseudoaneurysms secondary to blunt trauma: Endovascular management by means of neurostents and flow diverters.

Extracranial vertebral pseudoaneurysms that develop following blunt trauma to the cervical area may have a benign course; however, embolic or ischemic stroke and progressive pseudoaneurysm enlargement may occur. We review the presentation and endovascular management of pseudoaneurysms of the cervical vertebral artery (VA) due to blunt trauma in nine patients (eight male, mean age 27years). Pseudoaneurysms occurred in dominant vessels in seven patients and coexisted with segmental narrowing in six. We favored endovascular intervention during the acute phase only in cases with significant narrowing of a dominant VA, especially when anticoagulation was contraindicated. Four patients were treated during the acute stage (contraindication to anticoagulation, mass effect, severely injured dominant VA/impending stroke); five during the chronic phase (pseudoaneurysm growth, ischemic stroke on aspirin prophylaxis, patient preference). Reconstructive techniques were favored over deliberate endovascular occlusion when dominant vessels were involved. Arterial reconstruction was performed in eight of nine patients using a flow-diverter implant (5 patients), stent-assisted coiling (1), overlapping stent implant (1), or implantation of a balloon-expandable stent (1). Deliberate VA occlusion with coils was performed in one of nine patients due to suboptimal expansion of the stented artery after flow-diverter implant. No neurological complications occurred during follow-up. All cases treated by reconstructive techniques showed complete, persistent pseudoaneurysm occlusion and full arterial patency. Endovascular therapy of traumatic VA pseudoaneurysms using neurostents and flow-diverters resulted in occlusion of the pseudoaneurysms, preservation of the parent vessel, and no periprocedural or delayed clinical complications, supporting the feasibility and safety of the approach.

Emergency revascularization of acute internal carotid artery occlusion: Follow the spike, it guides you.

The present study sought to examine the incidence of the angiographic "spike sign" and to assess its predictive significance for achieving carotid revascularization in 54 patients with acute internal carotid artery (ICA) occlusions that required urgent endovascular revascularization. Clinical and imaging files of consecutive patients with ICA occlusion who were treated in a tertiary care academic medical center from 2011-2015 were retrospectively examined under Institutional Review Board approval with a waiver of the requirement for informed consent. All proximal ICA occlusions were treated by stent-assisted carotid angioplasty, and all distal embolic occlusions were managed with stent-assisted mechanical thrombectomy. The study included 24 patients with acute ICA occlusion (group 1) and 30 patients with tandem ICA-intracranial occlusions (group 2). The spike sign was seen in 16/24 patients in group 1 (67%), and successful ICA revascularization was achieved in 14/16 (88%). The sign was seen in 26/30 patients in group 2 (87%), and ICA revascularization was successful in all 26 (100%). The remaining 12 patients had no spike sign, and ICA revascularization was successful in only 7/12 (58%). The spike sign is a transient finding that represents the proximal patent remnant of the stenotic corridor in fresh clot. Acute ICA occlusion frequently leaves the spike sign as a marker of the recent thrombotic event. The spike vertex points to the "path of least resistance" for the guidewire to cross the occlusion and engage the true arterial lumen, a critical step during ICA endovascular revascularization.

Myelin-associated glycoprotein gene mutation causes Pelizaeus-Merzbacher disease-like disorder.

Pelizaeus-Merzbacher disease is an X-linked hypomyelinating leukodystrophy caused by mutations or rearrangements in PLP1. It presents in infancy with nystagmus, jerky head movements, hypotonia and developmental delay evolving into spastic tetraplegia with optic atrophy and variable movement disorders. A clinically similar phenotype caused by recessive mutations in GJC2 is known as Pelizaeus-Merzbacher-like disease. Both genes encode proteins associated with myelin. We describe three siblings of a consanguineous family manifesting the typical infantile-onset Pelizaeus-Merzbacher disease-like phenotype slowly evolving into a form of complicated hereditary spastic paraplegia with mental retardation, dysarthria, optic atrophy and peripheral neuropathy in adulthood. Magnetic resonance imaging and spectroscopy were consistent with a demyelinating leukodystrophy. Using genetic linkage and exome sequencing, we identified a homozygous missense c.399C>G; p.S133R mutation in MAG. This gene, previously associated with hereditary spastic paraplegia, encodes myelin-associated glycoprotein, which is involved in myelin maintenance and glia-axon interaction. This mutation is predicted to destabilize the protein and affect its tertiary structure. Examination of the sural nerve biopsy sample obtained in childhood in the oldest sibling revealed complete absence of myelin-associated glycoprotein accompanied by ill-formed onion-bulb structures and a relatively thin myelin sheath of the affected axons. Immunofluorescence, cell surface labelling, biochemical analysis and mass spectrometry-based proteomics studies in a variety of cell types demonstrated a devastating effect of the mutation on post-translational processing, steady state expression and subcellular localization of myelin-associated glycoprotein. In contrast to the wild-type protein, the p.S133R mutant was retained in the endoplasmic reticulum and was subjected to endoplasmic reticulum-associated protein degradation by the proteasome. Our findings identify involvement of myelin-associated glycoprotein in this family with a disorder affecting the central and peripheral nervous system, and suggest that loss of the protein function is responsible for the unique clinical phenotype.

Is Bridging Necessary? A Pilot Study of Bridging versus Primary Stentriever-Based Endovascular Reperfusion in Large Anterior Circulation Strokes.

BACKGROUND: We aimed to determine whether bridging provides additional benefits over primary stentriever-based endovascular reperfusion (SER) in patients with proximal middle cerebral artery (pMCA) strokes. METHODS: Clinical and radiologic data from consecutive stroke patients with large anterior circulation infarcts involving the pMCA were analyzed. Stroke subtypes were categorized according to Trial of ORG 10172 in Acute Stroke Treatment criteria. Neurologic deficits were assessed with the National Institutes of Health Stroke Scale (NIHSS), and vessel recanalization was determined using the Thrombolysis in Cerebral Infarction scale at the end of SER. Good outcome was defined as a modified Rankin Scale (mRS) score of 2 or lesser. RESULTS: Fifty-seven patients with a median age of 66 years were included. Of those, 24 received prior systemic tissue plasminogen activator and 33 received primary SER. Atrial fibrillation was more common in patients who underwent SER but there were no other between-group differences in baseline variables, procedure-related variables, or outcome parameters. Six patients died and 27 patients achieved an mRS of 2 or less at 90 days. Patients who were treated with tPA before SER needed less stentriever passes to recanalize the occluded vessel, but bridging did not impact the chances for either survival or favorable outcome. Age (odds ratio [OR], .92; 95% confidence interval [CI], .85-.98) and NIHSS score (OR, .12; 95% CI, .02-.78) were the only variables associated with outcome on multivariate analysis. CONCLUSIONS: Primary SER and bridging resulted in equally high survival and good outcome rates. Our results suggest that the benefits of primary SER in such critically ill patients may bypass the need for bridging therapy and merit further study.

Fe/S protein assembly gene IBA57 mutation causes hereditary spastic paraplegia.

OBJECTIVE: To present the clinical, molecular, and cell biological findings in a family with an autosomal recessive form of hereditary spastic paraplegia characterized by a combination of spastic paraplegia, optic atrophy, and peripheral neuropathy (SPOAN). METHODS: We used a combination of whole-genome linkage analysis and exome sequencing to map the disease locus and to identify the responsible gene. To analyze the physiologic consequences of the disease, we used biochemical and cell biological methods. RESULTS: Ten members of a highly consanguineous family manifested a childhood-onset SPOAN-like phenotype with slow progression into late adulthood. We mapped this disorder to a locus on chromosome 1q and identified a homozygous donor splice-site mutation in the IBA57 gene, previously implicated in 2 infants with lethal perinatal encephalomyopathy. This gene encodes the mitochondrial iron-sulfur (Fe/S) protein assembly factor IBA57. In addition to a severely decreased amount of normal IBA57 messenger RNA, a patient's cells expressed an aberrantly spliced messenger RNA with a premature stop codon. Lymphoblasts contained 10-fold-lower levels of wild-type, but no signs of truncated IBA57 protein. The decrease in functional IBA57 resulted in reduced levels and activities of several mitochondrial [4Fe-4S] proteins, including complexes I and II, while mitochondrial [2Fe-2S] proteins remained normal. CONCLUSIONS: Our findings reinforce the suggested specific function of IBA57 in mitochondrial [4Fe-4S] protein maturation and provide additional evidence for its role in human disease. The less decreased IBA57 protein level in this family explains phenotypic differences compared with the previously described lethal encephalomyopathy with no functional IBA57.

Occlusion site does not impact outcome in patients with carotid stroke undergoing endovascular reperfusion.

BACKGROUND: It remains unclear whether occlusion site impacts outcome in patients with acute carotid artery occlusions. METHODS: Patients with acute carotid artery occlusion that underwent endovascular reperfusion treatments were prospectively enrolled. Patients with extracranial carotid bifurcation occlusions were compared with those with intracranial carotid-T-occlusions. Collected data included demographics, risk factor profile, and procedure-related variables. Neurological deficits were studied with the National Institutes of Health Stroke Scale and outcome was studied with the modified Rankin Score at day 90 after stroke and dichotomized into favorable (≤2) or unfavorable (>3). Recanalization status was studied with the thrombolysis in cerebral infarction scale. RESULTS: We included 51 patients (33 with extracranial bifurcation occlusion and 18 with intracranial T-occlusion). Patients with T lesions were significantly older (median 74 versus 56 years, P = 0.02), more frequently had atrial fibrillation (61% versus 18%; P = 0.005) and cardioembolism (78% versus 21% P = 0.001), smoked less often (6% versus 42%; P = 0.01), and less often required stent implantation (11% versus 48%; P = 0.015). However, neurological severity, other procedure and peri-procedure-related variables including recanalization rates and percentages of symptomatic hemorrhages did not differ between the groups. Mortality rates (24% versus 23%) and chances for favorable outcomes (33% versus 24%) did not significantly differ. On multivariate logistic regression analysis, occlusion location was not a significant modifier of outcome. CONCLUSIONS: Despite differences in stroke risk factors and treatments used between patients with extracranial bifurcation and intracranial T-occlusions, lesion location in itself does not influence outcome in patients with acute carotid artery occlusion treated with endovascular reperfusion.

Should DWI MRI be the primary screening test for stroke?

Patients presenting with focal neurological symptoms may suffer from ischemic stroke, intracerebral hemorrhage, or stroke mimics. Such patients are usually screened with a noncontrast-enhanced computed tomography to rule out hemorrhage and to detect early signs of ischemia. However, the sensitivity of noncontrast-enhanced computed tomography for acute stroke is far inferior to that of diffusion-weighted magnetic resonance imaging and the latter is also very sensitive for identifying acute intracerebral hemorrhage. Most centers perform a magnetic resonance imaging stroke protocol that takes long to accomplish and may therefore delay therapy. Herein, we propose that a short diffusion-weighted imaging-only magnetic resonance imaging protocol can effectively differentiate ischemic stroke from intracerebral hemorrhage and stroke mimics and could therefore be used as the first line screening test for stroke. Adopting such a screening strategy will result in increased diagnostic accuracy and avoidance of unnecessary treatment of stroke mimics with thrombolysis but may come at the increased cost of performing a magnetic resonance imaging at the emergency department. Whether such a strategy will be cost effective or not remains to be tested in future studies.