Comparison of Quantitative and Qualitative Oxygen Extraction Fraction (OEF) in Acute Stroke Patients with Large Vessel Occlusion.

The superficial temporal artery-middle cerebral artery bypass (STA-MCA) bypass surgery developed by Donaghy and Yarsagil in 1967 provided relief for patients with acute stroke and large vessel occlusive vascular disease. Early reports showed low morbidity and good outcomes. However, a large clinical trial in 1985 reported a failure of extracranial-intracranial (EC/IC) bypass to show benefit in reducing the risk of stroke compared to best medical treatment. Problems with the study included cross overs to surgery from best medical treatment, patients unwilling to be randomized and chose EC/IC surgery, and loss of patients to follow-up. Most egregious is the fact that the study did not attempt to identify and select the patients at high risk for a second stroke. Based on these shortcomings of the EC/IC bypass study, a carotid occlusion surgery study (COSS) was proposed by Dr. William Powers and colleagues using qualitative hemispheric oxygen extraction fraction (OEF) by positron emission tomography (PET) between the contralateral and ipsilateral hemispheres with a ratio of 1.16 indicative of hemodynamic compromise. To increase patient enrollment, several compromises were made mid study. First. The ratio threshold was lowered to 1.12 and the level of occlusion in the carotid reduced from 70% to 60%. Despite these compromises the study was closed for futility, apparently because the stroke rate in the medically treated group was too low. Thus, the question as to the benefit of EC/IC bypass surgery remains unresolved. In our NIH funded study Quantitative Occlusive Vascular Disease Study (QUOVADIS), we used quantitative OEF to evaluate stroke risk and compared it to the qualitative count-rate ratio method used in the COSS study and found that these two methods did not identify the same patients at increased risk for stroke, which may explain the reason for the failure of the COSS study as our results show that qualitative OEF ratios do not identify the same patients as quantitative OEF.

Predictors and clinical relevance of hemorrhagic transformation after endovascular therapy for anterior circulation large vessel occlusion strokes: a multicenter retrospective analysis of 1122 patients.

BACKGROUND AND PURPOSE: Endovascular techniques are frequently employed to treat large artery occlusion in acute ischemic stroke (AIS). We sought to determine the predictors and clinical impact of intracranial hemorrhage (ICH) after endovascular therapy. METHODS: Retrospective analysis of consecutive patients presenting to 13 high volume stroke centers with AIS due to proximal occlusion in the anterior circulation who underwent endovascular treatment within 8 h from symptom onset. Logistic regression was performed to determine the variables associated with ICH, hemorrhagic infarction (HI), and parenchymal hematomas (PHs), as well as 90 day poor outcome (modified Rankin Scale score ≥3) and mortality. RESULTS: There were a total of 363 ICHs (overall rate 32.3%; HI=267, 24%; PH=96, 8.5%) among the 1122 study patients (mean age 67±15 years; median National Institutes of Health Stroke Scale score 17 (IQR 13-20)). Independent predictors for HI included diabetes mellitus (OR 2.27, 95% CI (1.58 to 3.26), p<0.0001), preprocedure IV tissue plasminogen activator (tPA) (1.43 (1.03 to 2.08), p<0.037), Merci thrombectomy (1.47 (1.02 to 2.12), p<0.032), and longer time to puncture (1.001 (1.00 to 1.002), p<0.026). Patients with atrial fibrillation (1.61 (1.01 to 2.55), p<0.045) had a higher risk of PH while the use of IA tPA (0.57 (0.35 to 0.90), p<0.008) was associated with lower chances of PH. Both the presence of HI (2.23 (1.53 to 3.25), p<0.0001) and PH (6.24 (3.06 to 12.75), p<0.0001) were associated with poor functional outcomes; however, only PH was associated with higher mortality (3.53 (2.19 to 5.68), p<0.0001). CONCLUSIONS: Greater understanding about the predictors and consequences of ICH post endovascular stroke therapy is essential to improve risk assessment, patient selection/clinical outcomes, and early prognostication. Our data suggest that patients with atrial fibrillation are particularly prone to severe ICH and question the 'benign' nature of HI suggested by earlier studies.

Multicenter analysis of stenting in symptomatic intracranial atherosclerosis.

BACKGROUND: Stenting for symptomatic intracranial atherosclerotic disease is a therapeutic option in patients in whom medical therapy fails. OBJECTIVE: To determine the periprocedural complication rates and mid-term restenosis rates in patients treated with balloon-expandable stents (BESs) compared with self-expanding stents (SESs). METHODS: A retrospective review of consecutive patients treated with intracranial stents at 5 institutions was performed. Predictors of 30-day stroke and death as well as mid-term restenosis rates were analyzed. RESULTS: A total of 670 lesions were treated in 637 patients with a mean age of 57 ± 13 years. A total of 454 lesions (68%) were treated with BESs and 216 lesions (32%) with SESs. The overall 30-day periprocedural complication rate was 6.1%, without any difference noted between the 2 groups. Patients treated within 24 hours of the index event were significantly more likely to have experienced a periprocedural complication (odds ratio [OR], 4.0; 95% confidence interval [CI]: 1.7-6.7; P < .007), whereas focal lesions were less likely to have a complication (OR, 0.31; 95% CI: 0.13-0.72; P < .001). Midterm restenosis was less likely in patients with a lower percentage of posttreatment stenosis (OR, 0.97; 95% CI: 0.95-0.99; P < .006), which was more common in BES-treated patients and focal concentric lesions (OR, 0.33; 95% CI: 0.23-0.55; P < .0001). CONCLUSION: BESs have periprocedural complication rates similar to those of SESs. Less posttreatment stenosis was associated with lower rates of mid-term restenosis. Future randomized trials comparing BESs and SESs may help to identify the stent type that is safest and most durable.

Endovascular revascularization of chronic symptomatic vertebrobasilar occlusion.

BACKGROUND AND PURPOSE: Acute basilar artery occlusion is associated with a high risk of stroke, mortality, and poor outcome in survivors. Timely vessel revascularization is critical to improve the clinical outcome in this condition. A subset of patients survives acute occlusion with mild or no disability and some of these individuals develop recurrent ischemic events despite optimal medical therapy. The strategy for management of these patients is unknown. CASE SUMMARY: We described 3 patients with chronic intracranial vertebrobasilar occlusions who presented with recurrent ischemic symptoms and progressive disability. All 3 patients were treated successfully with angioplasty and stenting. One patient experienced headache postprocedure and was found to have subarachnoid hemorrhage, which was self-limiting without need for intervention or result in permanent neurological sequela. All 3 patients have been free of recurrent symptoms for up to 30 months. CONCLUSIONS: Revascularization of chronic vertebrobasilar occlusions is technically feasible. Due to the high-risk nature, it should be reserved as an option only for selected group of patients with recurrent ischemic symptoms and progressive disability despite maximal medical therapy. Further prospective study is helpful to clarify the role of this intervention.

Repair of intracranial vessel perforation with Onyx-18 using an exovascular retreating catheter technique.

Numerous techniques have been described to treat intracranial vessel perforation during endovascular interventions. We describe a novel application of Onyx-18 for the treatment of intracranial catheter perforations by sealing the vessel from the outside while retracting the catheter into the arterial lumen.

Telestroke-guided intravenous tissue-type plasminogen activator treatment achieves a similar clinical outcome as thrombolysis at a comprehensive stroke center.

BACKGROUND AND PURPOSE: Telestroke networks offer an opportunity to increase tissue-type plasminogen activator use in community hospitals. METHODS: We compared 83 patients treated with intravenous tissue-type plasminogen activator by telestroke to 59 patients treated after in-person evaluation by the same neurologists at a tertiary care stroke center. Onset and door-to-treatment times and functional outcome at 90 days were obtained prospectively. Favorable outcome was defined as modified Rankin Scale score ≤2. RESULTS: Favorable outcome rates were comparable between the groups (42.1% versus 37.5%, P=0.7). There was no significant difference in the rate of symptomatic hemorrhage. CONCLUSIONS: Telestroke is a viable alternative to in-person evaluation when stroke expertise is not readily available.

Endovascular treatment of tandem extracranial/intracranial anterior circulation occlusions: preliminary single-center experience.

BACKGROUND AND PURPOSE: Acute ischemic stroke due to tandem occlusions of the extracranial internal carotid artery and intracranial arteries has a poor natural history. We aimed to evaluate our single-center experience with endovascular treatment of this unique stroke population. METHODS: Consecutive patients with tandem occlusions of the internal carotid artery origin and an intracranial artery (ie, internal carotid artery terminus, M1 middle cerebral artery, or M2 middle cerebral artery) were studied retrospectively. Treatment consisted of proximal revascularization with angioplasty and stenting followed by intracranial intervention. Endpoints were recanalization of both extracranial and intracranial vessels (Thrombolysis In Myocardial Ischemia ≥2), parenchymal hematoma, and good clinical outcome (modified Rankin Scale ≤2) at 3 months. RESULTS: We identified 77 patients with tandem occlusions. Recanalization occurred in 58 cases (75.3%) and parenchymal hematoma occurred in 8 cases (10.4%). Distal embolization occurred in 3 cases (3.9%). In 18 of 77 patients (23.4%), distal (ie, intracranial) recanalization was observed after proximal recanalization, obviating the need for distal intervention. Good clinical outcomes were achieved in 32 patients (41.6%). In multivariate analysis, Thrombolysis In Myocardial Ischemia ≥2 recanalization, baseline National Institutes of Health Stroke Scale score, baseline Alberta Stroke Programme Early CT score, and age were significantly associated with good outcome. CONCLUSIONS: Endovascular therapy of tandem occlusions using extracranial internal carotid artery revascularization as the first step is technically feasible, has a high recanalization rate, and results in an acceptable rate of good clinical outcome. Future randomized, prospective studies should clarify the role of this approach.

Intra-arterial thrombolysis or stent placement during endovascular treatment for acute ischemic stroke leads to the highest recanalization rate: results of a multicenter retrospective study.

BACKGROUND: Reperfusion therapy for acute ischemic stroke (AIS) is rapidly evolving, with the development of multiple endovascular modalities that can be used alone or in combination. OBJECTIVE: To determine which pharmacologic or mechanical modality may be associated with increased rates of recanalization. METHODS: A cohort of 1122 patients with AIS involving the anterior circulation treated at 13 stroke centers underwent intra-arterial (IA) therapy within 8 hours of symptom onset. Demographic information, admission National Institutes of Health Stroke Scale (NIHSS), mechanical and pharmacologic treatments used, recanalization grade, and hemorrhagic complications were recorded. RESULTS: The mean age was 67 ± 16 years and the median NIHSS was 17. The sites of arterial occlusion before treatment were M1 middle cerebral artery (MCA) in 561 (50%) patients, carotid terminus in 214 (19%) patients, M2 MCA in 171 (15%) patients, tandem occlusions in 141 (13%) patients, and isolated extracranial internal carotid artery occlusion in 35 (3%) patients. Therapeutic interventions included multimodal therapy in 584 (52%) patients, pharmacologic therapy only in 264 (24%) patients, and mechanical therapy only in 274 (24%) patients. Patients treated with multimodal therapy had a significantly higher Thrombolysis in Myocardial Infarction 2 or 3 recanalization rate (435 patients [74%]) compared with pharmacologic therapy only (160 patients, [61%]) or mechanical only therapy (173 patients [63%]), P<.001. In binary logistic regression modeling, independent predictors of Thrombolysis in Myocardial Infarction 2 or 3 recanalization were use of IA thrombolytic OR 1.58 (1.21-2.08), P<.001 and stent deployment 1.91 (1.23-2.96), P<.001. CONCLUSION: Multimodal therapy has significantly higher recanalization rates compared with pharmacologic or mechanical therapy. Among the individual treatment modalities, stent deployment or IA thrombolytics increase the chance of recanalization.

Endovascular therapy for cardiac catheterization associated strokes.

BACKGROUND: Stroke is one of the most feared complications after cardiac catheterization. Endovascular treatment combining mechanical and pharmacological therapy has been reported as an effective treatment option in selected patients with acute stroke due to large-vessel occlusion. Little is known about safety and clinical outcome when this approach is utilized in cardiac catheterization associated strokes. METHODS AND RESULTS: We analyzed clinical and radiological characteristics and outcomes in the endovascular acute stroke treatment databases from two University Hospitals from July 2006 to December 2008 (Cleveland Clinic Foundation) and September 1999 and December 2008 (UPMC Presbyterian hospital), respectively. Of a total of 419 acute stroke interventions, 14 (3.34%) were identified as strokes during or immediately after cardiac catheterization. The mean age was 71 ± 7 years; eight were women (57.1%). Mean National Institute of Health Stroke Scale was 17 (±7.6). Four patients underwent intravenous thrombolysis followed by intraarterial intervention. Median time to treatment was 240 minutes from last time seen normal (range 66-1,365 minutes). Seven patients (50%) had a favorable outcome (modified Rankin Scale [mRS]≤ 2). In-patient mortality was 42%. CONCLUSION: In acute strokes following cardiac catheterization, multimodal endovascular therapy is safe and feasible and despite a high mortality is associated with a higher than expected rate of favorable outcomes compared to the natural history of the disease. Despite a significant proportion of patients developing symptoms in hospitals where neurointerventions are available, the median time to treatment was longer than expected. Future efforts should focus on faster implementation of recanalization therapies for this form of acute stroke.

PICA origin aneurysm diagnosed 27 years after microvascular decompression of cranial nerve VII.

The authors report a case of a posterior inferior cerebellar artery origin aneurysm causing brainstem compression and swallowing difficulty. The patient had an ipsilateral microvascular decompression of cranial nerve VII for hemifacial spasm 27 years prior to the discovery of the aneurysm. The aneurysm was successfully treated endovascularly. A discussion of possible etiologies of the aneurysm's formation is presented.

Endovascular treatment of atypical posterior circulation aneurysms: technical results and review of the literature.

BACKGROUND: we report our technical success and complication rates in treating posterior circulation aneurysms at sites other than the basilar apex, superior cerebellar artery origin, or the posterior inferior cerebellar artery origin via endovascular embolization or sacrifice. MATERIALS AND METHODS: we retrospectively reviewed case records for patients undergoing coil embolization of atypical posterior circulation aneurysms from January 2003 to December 2007. RESULTS: thirty-two aneurysms in 32 patients were treated. Twenty-one patients (65%) presented with a subarachnoid hemorrhage. Twenty-two aneurysms were treated with coiling alone, 9 with stent-assisted coiling, and 1 with a combination of Onyx plus stent-assisted coiling. Twelve aneurysms were treated with vessel sacrifice. Immediately post procedure, 27/32 aneurysms (84%) were considered successfully treated, resulting in either vessel sacrifice, complete obliteration, or minimal neck remnant. Sixteen of 19 patients (84%) were considered successfully treated at a mean angiographic follow up of 8 months. The procedural morbidity and mortality was 15% and 6% respectively. CONCLUSION: endovascular embolization remains a viable and durable method of treatment for atypical posterior circulation aneurysms.

In-stent thrombosis and stenosis after neck-remodeling device-assisted coil embolization of intracranial aneurysms.

BACKGROUND: Intrinsic thrombosis and stenosis are complications associated with the use of neck-remodeling devices in the treatment of intracranial aneurysms. OBJECTIVE: To examine the technical and anatomic factors that predict short- and long-term stent patency. METHODS: We undertook a retrospective review of 161 patients who underwent coil embolization of 168 ruptured and unruptured aneurysms assisted by the use of a neck-remodeling device. One hundred twenty-seven patients had catheter-based angiographic follow-up to evaluate 133 stent-coil constructs (mean, 15.4 months; median, 12.7 months). The technique of microcatheter jailing was used in a majority of patients; nonstandard stent configurations were also used. RESULTS: Clinical follow-up for all patients who had catheter-based angiograms demonstrated that among 133 stent constructs, a total of 9 (6.8%) had an in-stent event: 6 acute or subacute thrombosis (4.5%) and 3 delayed stenosis or occlusion (2.3%). Seven of these constructs were associated with a symptomatic event (5.3%). A significantly higher rate of in-stent events was seen with the use of constructs to treat anterior communicating artery aneurysms. When all patients are considered, including those who did not receive catheter-based follow-up imaging, 2 of 168 procedures (1.2%) resulted in the death of a patient, and procedural morbidity was 14.9%. CONCLUSION: From these results and those in the published literature, in-stent complication rates are low in carefully selected patients. The use of dual antiplatelet therapy, sensitivity assays, and glycoprotein IIb/IIIa inhibitors may decrease the rate of acute and chronic in-stent complications.

Comparison of safety and clinical and radiographic outcomes in endovascular acute stroke therapy for proximal middle cerebral artery occlusion with intubation and general anesthesia versus the nonintubated state.

BACKGROUND AND PURPOSE: There is considerable heterogeneity in practice patterns between sedation in the intubated state vs nonintubated state during endovascular acute stroke therapy. We sought to compare clinical and radiographic outcomes between these 2 sedation modalities. METHODS: Consecutive patients with acute stroke due to middle cerebral artery-M1 segment occlusion treated with endovascular therapy between January 2006 and July 2009 were identified in our interventional acute stroke database. Level of sedation was determined as intubated (IS) vs nonintubated (NIS) state. Final infarct volumes on follow-up imaging and clinical outcomes at 3 to 6 months were obtained. RESULTS: A total of 126 patients were included (73 [58%] NIS vs 53 [42%] IS). In IS patients, intensive care unit length of stay was longer (6.5 vs 3.2 days, P=0.0008). Intraprocedural complications were lower in NIS patients compared with IS patients (5/73 [6%] vs 8/53 [15%], respectively), but the difference was not significant (P=0.13). In univariate and multivariate analyses, NIS was significantly associated with in-hospital mortality (odds ratio=0.32, P=0.011), good clinical outcome (odds ratio=3.06, P=0.042), and final infarct volume (odds ratio=0.25, P=0.004). CONCLUSIONS: In endovascular acute stroke therapy, treatment of patients in NIS appears to be as safe as treatment in IS and may result in more favorable clinical and radiographic outcomes. Our preliminary observations derived from this retrospective study await confirmation from prospective trials.

Conscious sedation versus general anesthesia during endovascular therapy for acute anterior circulation stroke: preliminary results from a retrospective, multicenter study.

BACKGROUND AND PURPOSE: Patients undergoing intra-arterial therapy (IAT) for acute ischemic stroke receive either general anesthesia (GA) or conscious sedation. GA may delay time to treatment, whereas conscious sedation may result in patient movement and compromise the safety of the procedure. We sought to determine whether there were differences in safety and outcomes in GA patients before initiation of IAT. METHODS: A cohort of 980 patients at 12 stroke centers underwent IAT for acute stroke between 2005 and 2009. Only patients with anterior circulation strokes due to large-vessel occlusion were included in the study. A binary logistic-regression model was used to determine independent predictors of good outcome and death. RESULTS: The mean age was 66+/-15 years and median National Institutes of Health Stroke Scale score was 17 (interquartile range, 13-20). The overall recanalization rate was 68% and the symptomatic hemorrhage rate was 9.2%. GA was used in 44% of patients with no differences in intracranial hemorrhage rates when compared with the conscious sedation group. The use of GA was associated with poorer neurologic outcome at 90 days (odds ratio=2.33; 95% CI, 1.63-3.44; P<0.0001) and higher mortality (odds ratio=1.68; 95% CI, 1.23-2.30; P<0.0001) compared with conscious sedation. CONCLUSIONS: Patients placed under GA during IAT for anterior circulation stroke appear to have a higher chance of poor neurologic outcome and mortality. There do not appear to be differences in hemorrhagic complications between the 2 groups. Future clinical trials with IAT can help elucidate the etiology of the differences in outcomes.

Symptomatic delayed reocclusion after initial successful revascularization in acute ischemic stroke.

BACKGROUND: Endovascular stroke therapy is used for patients with ischemic stroke after failed intravenous thrombolysis or in patients not eligible for thrombolytics. With increasing experience, acute reocclusion has been described and likely worsens clinical outcomes. We assessed the rates and outcomes of delayed symptomatic reocclusion after endovascular therapy for acute ischemic stroke. METHODS: Patients with acute ischemic stroke undergoing endovascular procedures at out institutions from January 2008 to August 2008 were reviewed. In all, 107 consecutive acute stroke interventions were performed. Four patients (3.5%) experienced delayed symptomatic reocclusion detectable by the National Institutes of Health Stroke Scale (NIHSS). RESULTS: The 4 patients (age 45-79 years) had baseline NIHSS score ranging from 8 to 24. Three had right middle cerebral artery occlusions and one had a left middle cerebral artery occlusion. Successful recanalization (thrombolysis in myocardial infarction score 2-3) occurred in all cases after initial treatment. All patients improved postprocedure (NIHSS score 5-10). Clinical deterioration (NIHSS score 14-22) occurred 12 to 18 hours postprocedure. Successful recanalization was achieved in each patient, with improvement in NIHSS score (range 6-13) but not to a lower level compared with after the initial intervention. CONCLUSIONS: Delayed symptomatic reocclusion after initial endovascular stroke therapy can lead to sudden clinical deterioration and impact outcomes. The entity may be missed as many patients present with large clinical deficits at presentation thus requiring careful assessments of patients treated via endovascular methods.

Endovascular treatment of basilar artery occlusion by manual aspiration thrombectomy.

BACKGROUND AND PURPOSE: Basilar artery occlusion remains one of the most devastating subtypes of stroke. Intravenous and intra-arterial therapy have altered the natural history of this disease; however, clinical results remain poor. Therefore, exploring more aggressive and innovative management is warranted. METHODS: Six consecutive patients presenting with a basilar artery occlusion were treated with the same general algorithm of intra-arterial tissue plasminogen activator and mechanical thrombectomy with the Merci retrieval system. If complete recanalization was not achieved after two passes, manual syringe aspiration through a 4.3F catheter was employed. RESULTS: All interventions utilizing aspiration thrombectomy resulted in recanalization, with five out of six cases displaying TIMI3/TICI3 flow and one patient resulting in complete recanalization of the basilar artery with persistent thrombus in one P2 segment (TIMI2/TICI2B). All patients survived, with five out of six independent in activities of daily living at 3 months (mRS 0-2). CONCLUSIONS: Our small case series indicates that aspiration thrombectomy performed manually through a 4.3F catheter can facilitate recanalization of basilar artery occlusion with acceptable clinical outcomes.

Increased cerebral oxygen metabolism and ischemic stress in subjects with metabolic syndrome-associated risk factors: preliminary observations.

Hypertension, diabetes, obesity, and dyslipidemia are risk factors that characterize metabolic syndrome (MetS), which increases the risk for stroke by 40%. In a preliminary study, our aim was to evaluate cerebrovascular reactivity and oxygen metabolism in subjects free of vascular disease but with one or more of these risk factors. Volunteers (n=15) 59±15 (mean±SD)years of age clear of cerebrovascular disease by magnetic resonance angiography but with one or more risk factors were studied by quantitative positron emission tomography for measure ment of cerebral blood flow, oxygen consumption, oxygen extraction fraction (OEF), and acetazolamide cerebrovascular reactivity. Eight of ten subjects with MetS risk factors had OEF >50%. None of the five without risk factors had OEF >50%. The presence of MetS risk factors was highly correlated with OEF >50% by Fisher's exact test (p<0.007). The increase in OEF was significantly (P<0.001) correlated with cerebral metabolic rate for oxygen. Increased OEF was not associated with compromised acetazolamide cerebrovascular reactivity. Subjects with one or more MetS risk factors are characterized by increased cerebral oxygen consumption and ischemic stress, which may be related to increased risk of cerebrovascular disease and stroke.

Mechanical approaches combined with intra-arterial pharmacological therapy are associated with higher recanalization rates than either intervention alone in revascularization of acute carotid terminus occlusion.

BACKGROUND AND PURPOSE: Acute stroke attributable to internal carotid artery terminus occlusion carries a poor prognosis. Vessel recanalization is crucial to improve clinical outcome. Historically, pharmacological thrombolysis alone has low recanalization rates. We sought to determine whether adjunctive mechanical approaches achieve better vessel recanalization and functional outcome. METHODS: We retrospectively reviewed 75 consecutive endovascular cases of acute internal carotid artery terminus occlusions treated at our center between 1998 and 2008. Mechanical approaches (MERCI retrieval/angioplasty/stent) with and without adjunctive intra-arterial pharmacological therapy (urokinase or tissue plasminogen activator) was compared to intra-arterial lytics alone. Univariate and multivariate analyses were performed to determine predictors of recanalization (thrombolysis in myocardial infarction grades 2 to 3) and favorable functional outcome (modified Rankin score

Chronic ischemic cerebral white matter disease is a risk factor for nonfocal neurologic injury after total aortic arch replacement.

OBJECTIVE: Leukoaraiosis (chronic ischemic white matter changes) on preoperative brain magnetic resonance imaging is common in patients having aortic arch surgery. This study sought to determine whether it is associated with adverse neurologic outcome in the postoperative period. METHODS: Data were collected from a retrospective chart review of 142 patients in whom total aortic arch replacement was planned at the Cleveland Clinic between April 2000 and December 2004. All patients had preoperative brain magnetic resonance imaging evaluation. Leukoaraiosis severity was rated semiquantitatively using the Schelten's scale. Postoperative neurologic injuries were investigated by clinical examination and appropriate neuroimaging. They were stratified as type 1 (focal ischemic stroke) and type 2 (nonfocal neurocognitive changes, generalized seizures) injuries. RESULTS: The following were independent predictors of type 1 neurologic injury: age (odds ratio 1.06 [1.01-1.13], P = .02) and moderate to severe aortic atheroma (odds ratio 4.4 [1.4-9.7], P = .012). Total white matter scores (odds ratio 1.16 [1.06-1.27], P = .002) and higher preoperative hemoglobin A1c levels (odds ratio 1.8 [1.00-3.50], P = .05) were significantly associated with type 2 neurologic injuries. Survival was 96%, and 4.2% had persistent focal neurologic deficits at the time of hospital discharge. CONCLUSIONS: Leukoaraiosis is a significant independent predictor of nonfocal postoperative neurologic morbidity following aortic arch replacement surgery. Preoperative evaluation with magnetic resonance imaging allows identification of a patient subgroup at risk and implementation of strategies aimed at improving neurologic outcome.

Paralemmin interacts with D3 dopamine receptors: implications for membrane localization and cAMP signaling.

Paralemmin is a novel lipid-anchored protein, which is highly expressed in neuronal plasma membranes. In this study, we demonstrate that paralemmin specifically interacts with the third intracellular loop of the D3 dopamine receptor. Utilizing co-immunoprecipitation and glutathione-S-transferase (GST) pulldown strategies, we demonstrate that paralemmin interacts exclusively with D3, but not D2 or D4 dopamine receptors or beta-adrenergic receptors. Immunocytochemistry demonstrated co-localization of paralemmin and D3 receptor in vivo in hippocampus and cerebellum and in vitro in glial and neuronal cultures. Deletion mutational analysis indicates that amino acids 154-230 of paralemmin strongly interacted with amino acids 211-227 and 281-330 of the third intracellular loop of D3 receptor. The consequences of these interactions were investigated by co-expression in HEK293 cells. Cell surface biotinylation experiments demonstrate that paralemmin decreased D3 receptor concentration at the plasma membrane. Consistent with this observation, paralemmin expression decreased dopamine-stimulated adenylate cyclase activity. However, paralemmin also decreased basal, isoproterenol and forskolin-stimulated adenylate cyclase activity, suggesting a more general cellular function for paralemmin. Taken together, paralemmin has been implicated as a potent modulator of cellular cAMP signaling within the brain.