Search

Background and Purpose: Although most strokes present with mild symptoms, these have been poorly represented in clinical trials. The objective of this study is to describe multidimensional outcomes, identify predictors of worse outcomes, and explore the effect of thrombolysis in this population. Methods: This prospective observational study included patients with ischemic stroke or transient ischemic attack, a baseline National Institutes of Health Stroke Scale (NIHSS) score 0 to 5, presenting within 4.5 hours from symptom onset. The primary outcome was a 90-day modified Rankin Scale score of 0 to 1; secondary outcomes included good outcomes in the Barthel Index, Stroke Impact Scale-16, and European Quality of Life. Multivariable models were created to determine predictors of outcomes and the effect of alteplase. Results: A total of 1765 participants were included from 100 Get With The Guidelines-Stroke participating hospitals (age, 65±14; 42% women; final diagnosis of ischemic stroke, 90%; transient ischemic attack, 10%; 57% received alteplase). At 90 days, 37% were disabled and 25% not independent. Worse outcomes were noted for older individuals, women, non-Hispanic Blacks and Hispanics, Medicaid recipients, smokers, those with diabetes, atrial fibrillation, prior stroke, higher baseline NIHSS, visual field defects, and extremity weakness. Similar outcomes were noted for the alteplase-treated and untreated groups. Alteplase-treated patients were younger (64±13 versus 67±1.4) with higher NIHSS (2.9±1.4 versus 1.7±1.4). After adjusting for age, sex, race/ethnicity, and baseline NIHSS, we did not identify an effect of alteplase on the primary outcome but did find an association with Stroke Impact Scale-16 in the restricted sample of baseline NIHSS score 3–5. Few symptomatic intracerebral hemorrhages were recorded ( Conclusions: A large proportion of stroke patients presenting with low NIHSS have a disabled outcome. Baseline predictors of worse outcomes are described. An effect of alteplase on outcomes was not identified in the overall cohort, but a suggestion of efficacy was noted in the NIHSS 3–5 subgroup. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02072681.

Introduction: Initial clinical evidence has shown that coiling with the SMART COIL System (Penumbra, Inc.) is a safe and durable treatment option for intracranial aneurysms. The SURF study is a post-market, prospective, multicenter, single-arm, observational study to assess the utility of the WAVE Extra Soft Coil (WAVE) as fill and finishing coil to support adequate occlusion of intracranial aneurysms. Methods: Enrollment began November 5, 2019; this analysis includes data as of July 20, 2021. Patients undergoing embolization of intracranial aneurysms with WAVE as the final finishing coil and Penumbra SMART COIL System accounting for at least 75% of the total number of coils implanted were enrolled consecutively at 34 centers globally. Post-procedure Raymond Roy Occlusion Classification (RROC) was assessed by a core lab. The estimated enrollment will be 800 patients. Results: This analysis includes 346 patients, mean age 60.1 (SD 13.03), 73.1% female. Of the target aneurysms, 39.8% (135/339) were ruptured, and 80.5% (269/334) were saccular, and 11.5% (39/338) were previously treated. Post-procedure, 89.2% (206/231, 95% CI 85.2%, 93.2%) of aneurysms were RROC I or II. Device-related SAEs occurred in 1.5% (5/346, 95% CI 0.2%, 2.7%) of patients up to 7 days or discharge. The rate of major ipsilateral stroke was 0.6% (2/346), and the intra-procedural rupture rate was 0.6% (2/346). Conclusions: We report interim outcomes from the SURF study. This post-market registry evaluates the safety and performance of the Penumbra SMART COIL System, including WAVE as fill and finishing coil, in the treatment of intracranial aneurysms.

This meeting abstract was removed due to the OA licensing requirements of this journal. The full abstract is listed here : https://www.svin.org/files/SVIN_2021_Abstracts_for_Web.pdf

Background and Purpose: Clinical fluctuations in ischemic stroke symptoms are common, but fluctuations before hospital arrival have not been previously characterized. Methods: A standardized qualitative assessment of fluctuations before hospital arrival was obtained in an observational study that enrolled patients with mild ischemic stroke symptoms (National Institutes of Health Stroke Scale [NIHSS] score of 0–5) present on arrival to hospital within 4.5 hours of onset, in a subset of 100 hospitals participating in the Get With The Guidelines–Stroke quality improvement program. The number of fluctuations, direction, and the overall improvement or worsening was recorded based on reports from the patient, family, or paramedics. Baseline NIHSS on arrival and at 72 hours (or discharge if before) and final diagnosis and stroke subtype were collected. Outcomes at 90 days included the modified Rankin Scale, Barthel Index, Stroke Impact Scale 16, and European Quality of Life. Prehospital fluctuations were examined in relation to hospital NIHSS change (admission to 72 hours or discharge) and 90-day outcomes. Results: Among 1588 participants, prehospital fluctuations, consisting of improvement, worsening, or both were observed in 35.5%: 25.1% improved once, 5.3% worsened once, and 5.1% had more than 1 fluctuation. Those who improved were less likely and those who worsened were more likely to receive alteplase. Those who improved before hospital arrival had lower change in the hospital NIHSS than those who did not fluctuate. Better adjusted 90-day outcomes were noted in those with prehospital improvement compared to those without any fluctuations. Conclusions: Fluctuations in neurological symptoms and signs are common in the prehospital setting. Prehospital improvement was associated with better 90-day outcomes, controlling for admission NIHSS and alteplase treatment. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT 02072681.

In patients with COVID-19, acute stroke management may need to be limited to patients with viable outcomes, perhaps younger population with fewer comorbidities, and patients without respiratory failure requiring mechanical ventilation. Protecting healthcare professionals must be kept at the forefront if aggressive stroke treatment is used.

Background and Purpose— It remains unclear how experience influences outcomes after the advent of stent retriever technology. We studied the relationship between site experience and outcomes in the Trevo Acute Ischemic Stroke multicenter registry. Methods— The 24 sites that enrolled patients in the Trevo Acute Ischemic Stroke registry were trichotomized into low-volume (4 cases/month). Baseline features, imaging, and clinical outcomes were compared across the 3 volume strata. A multivariable analysis was performed to assess whether outcomes were influenced by site volumes. Results— A total of 624 patients were included and distributed as low- (n=188 patients, 30.1%), medium- (n=175, 28.1%), and high-volume (n=261, 41.8%) centers. There were no significant differences in terms of age (mean, 66±16 versus 67±14 versus 65±15; P =0.2), baseline National Institutes of Health Stroke Scale (mean, 17.6±6.5 versus 16.8±6.5 versus 17.6±6.9; P =0.43), or occlusion site across the 3 groups. Median (interquartile range) times from stroke onset to groin puncture were 266 (181.8–442.5), 239 (175–389), and 336.5 (221.3–466.5) minutes in low-, medium-, and high-volume centers, respectively ( P =0.004). Higher efficiency and better outcomes were seen in higher volume sites as demonstrated by shorter procedural times (median, 97 versus 67 versus 69 minutes; P P ≤0.0001), and higher rates of good outcome (90-day modified Rankin Scale [mRS], ≤2; 39% versus 50% versus 53.4%; P =0.02). There were no appreciable differences in symptomatic intracranial hemorrhage or 90-day mortality. After adjustments in the multivariable analysis, there were significantly higher chances of achieving a good outcome in high- versus low-volume (odds ratio, 1.67; 95% CI, 1.03–2.7; P =0.04) and medium- versus low-volume (odds ratio, 1.75; 95% CI, 1.1–2.9; P =0.03) centers, but there were no significant differences between high- and medium-volume centers ( P =0.86). Conclusions— Stroke center volumes significantly influence efficiency and outcomes in mechanical thrombectomy.

Purpose: We assess the impact of retrievable stent (RS) compared to first-generation devices on in-hospital mortality and disability in patients with acute ischemic stroke (AIS). Methods: Using the National Inpatient Sample, data were obtained for patients with a primary diagnosis of AIS who underwent mechanical thrombectomy (MT) and were admitted to US hospitals between 2010 and 2014. Two time periods were compared: 2010–2012 (pre-RS Food and Drug Administration [FDA] approval) and 2013–2014 (post-RS FDA approval). Disability level was used to classify outcomes as minimal disability, moderate to severe disability, or in-hospital mortality. Weighted, multivariable logistic regression was used to assess the association between MT device type and disability. Results: A total of 2,443,713 weighted patients admitted with AIS were identified; 148,923 (4.9%) of these received intravenous tissue plasminogen activator; and 23,719 (0.8%) underwent MT. In multivariable logistic regression analysis, the odds of in-hospital mortality decreased (OR 0.69, 95% CI 0.59–0.82) in the post-RS time-period compared with pre-RS time. The odds of moderate-to-severe disability decreased (OR 0.88, 95% CI 0.73–1.06) compared with minimal disability. In-hospital mortality rates decreased successively over the 4 years in the MT-treated patients (p < 0.001). Conclusions: The FDA approval of RS technology after 2012 was associated with decreased in-hospital mortality when compared with the 3-year interval prior. These findings provide an indication that the RCT data on the efficacy of RS technology are translating into improved real-world outcomes.

BackgroundPrior studies evaluating the Wingspan stent for treatment of symptomatic intracranial atherosclerotic disease have included patients with a spectrum of both on-label and off-label indications for the stent. The WEAVE trial assessed 152 patients stented with the Wingspan stent strictly by its current on-label indication and found a 2.6% periprocedural stroke and death rate.ObjectiveThis WOVEN study assesses the 1-year follow-up from this cohort.MethodsTwelve of the original 24 sites enrolling patients in the WEAVE trial performed follow-up chart review and imaging analysis up to 1 year after stenting. Assessment of delayed stroke and death was made in 129 patients, as well as vascular imaging follow-up to assess for in-stent re-stenosis.ResultsIn the 1-year follow-up period, seven patients had a stroke (six minor, one major). Subsequent to the periprocedural period, no deaths were recorded in the cohort. Including the four patients who had periprocedural events in the WEAVE study, there were 11 strokes or deaths of the 129 patients (8.5%) at the 1-year follow-up.ConclusionsThe WOVEN study provides the 1-year follow-up on a cohort of 129 patients who were stented according to the current on-label use. It provides a more homogeneous patient group for analysis than prior studies, and demonstrates a relatively low 8.5% 1-year stroke and death rate in stented patients.

Introduction/Purpose Initial clinical evidence has shown that coiling with the SMART COIL® System (Penumbra, Inc.) is a safe and durable treatment option for intracranial aneurysms.1–5 The WAVE™ Extra Soft Coil (WAVE) is part of the SMART Coil System and is specifically designed as a fill and finish coil. The primary objective of the SURF study, a post-market registry, is to assess the utility of WAVE as a fill and finish coil to support adequate occlusion at one year follow-up. A secondary objective is to compare the ability of digital subtraction angiography (DSA) and magnetic resonance angiography (MRA) to detect incomplete occlusion in the coiled aneurysms. Materials and Methods SURF is a post-market, prospective, multicenter, single-arm, observational study that will enroll approximately 800 consecutive patients at up to 50 centers in North America. Patients age ≥ 18 years, having embolization of intracranial aneurysms, with WAVE as the final finishing coil and Penumbra SMART COIL System accounting for at least 75% of total number of coils implanted, will be included. All subjects will be followed for approximately 1 year. The primary efficacy endpoint is adequate occlusion defined as Raymond-Roy Occlusion Class I and II at final follow-up. The primary safety endpoints are serious adverse events (SAE) within 24 hours post-procedure and device-related SAE up to 7 days or discharge. Imaging will be analyzed by an independent core lab to assess aneurysm occlusion rates at follow-up. Imaging modalities include DSA, computed tomography angiography (CTA), and/or MRA. A comparative analysis between imaging modalities will be performed for patients with DSA and MRA. Results The trial is currently recruiting. Enrollment began November 2019 and the estimated date for study completion is June 2023. Imaging and clinical data collection and core laboratory review are ongoing. Conclusion We report the design of the SURF study, a post-market registry that evaluates the safety and performance of the Penumbra SMART COIL System, including WAVE as a fill and finish coil, in the treatment of intracranial aneurysms. References Daniel B, Henrik S, Ioannis T, Veit R, Marios-Nikos P. SMART coils for intracranial aneurysm repair - a single center experience. BMC Neurol. 2020 Jan 29;20(1):38. Sokolowski JD, Ilyas A, Buell TJ, Taylor DG, Chen CJ, Ding D, Raper DMS, Liu KC. SMART coils for intracranial aneurysm embolization: Follow-up outcomes. J Clin Neurosci 2019 Jan;59:93–97. Ilyas A, Buell TJ, Chen CJ, Ding D, Raper DMS, Taylor DG, Sokolowski JD, Liu KC. SMART coils for intracranial aneurysm embolization: Initial outcomes. Clin Neurol Neurosurg 2018 Jan;164:87–91. Spiotta AM, Fargen KM, Lena J, Chaudry I, Turner RD, Turk AS, Huddle D, Loy D, Bellon R, Frei D. Initial Technical Experience with the SMART Coil for the Embolization of Intracranial Aneurysms. World Neurosurg 2017 Jan;97:80–85. Stapleton CJ, Torok CM, Patel AB. Early experience with the Penumbra SMART coil in the endovascular treatment of intracranial aneurysms: Safety and efficacy. Interv Neuroradiol 2016 Dec;22(6):654–658. Disclosures C. Schirmer: None. I. Kaminsky: None. M. Chaudry: None. O. Zaidat: None. A. Alshekhlee: None. P. Ramakrishnan: None. M. Taqi: None.

Supplemental Digital Content is available in the text., Background and Purpose: Stent-assisted coil embolization using the new generation Neuroform Atlas Stent System has shown promising safety and efficacy. The primary study results of the anterior circulation aneurysm cohort of the treatment of wide-neck, saccular, intracranial, aneurysms with the Neuroform Atlas Stent System (ATLAS trial [Safety and Effectiveness of the Treatment of Wide Neck, Saccular Intracranial Aneurysms With the Neuroform Atlas Stent System]) are presented. Methods: ATLAS IDE trial (Investigational Device Exemption) is a prospective, multicenter, single-arm, open-label study of wide-neck (neck ≥4 mm or dome-to-neck ratio 50%) at the target location. The primary safety end point was any major stroke or ipsilateral stroke or neurological death within 12 months. Adjudication of the primary end points was performed by an independent Imaging Core Laboratory and the Clinical Events Committee. Results: A total of 182 patients with wide-neck anterior circulation aneurysms at 25 US centers were enrolled. The mean age was 60.3±11.4 years, 73.1% (133/182) women, and 80.8% (147/182) white. Mean aneurysm size was 6.1±2.2 mm, mean neck width was 4.1±1.2 mm, and mean dome-to-neck ratio was 1.2±0.3. The most frequent aneurysm locations were the anterior communicating artery (64/182, 35.2%), internal carotid artery ophthalmic artery segment (29/182, 15.9%), and middle cerebral artery bifurcation (27/182, 14.8%). Stents were placed in the anticipated anatomic location in all patients. The study met both primary safety and efficacy end points. The composite primary efficacy end point of complete aneurysm occlusion (Raymond-Roy 1) without parent artery stenosis or aneurysm retreatment was achieved in 84.7% (95% CI, 78.6%–90.9%) of patients. Overall, 4.4% (8/182, 95% CI, 1.9%–8.5%) of patients experienced a primary safety end point of major ipsilateral stroke or neurological death. Conclusions: In the ATLAS IDE anterior circulation aneurysm cohort premarket approval study, the Neuroform Atlas stent with adjunctive coiling met the primary end points and demonstrated high rates of long-term complete aneurysm occlusion at 12 months, with 100% technical success and

BackgroundRecent randomized clinical trials (RCTs) demonstrated the efficacy of mechanical thrombectomy using stent-retrievers in patients with acute ischemic stroke (AIS) with large vessel occlusions; however, it remains unclear if these results translate to a real-world setting. The TREVO Stent-Retriever Acute Stroke (TRACK) multicenter Registry aimed to evaluate the use of the Trevo device in everyday clinical practice.MethodsTwenty-three centers enrolled consecutive AIS patients treated from March 2013 through August 2015 with the Trevo device. The primary outcome was defined as achieving a Thrombolysis in Cerebral Infarction (TICI) score of ≥2b. Secondary outcomes included 90-day modified Rankin Scale (mRS), mortality, and symptomatic intracranial hemorrhage (sICH).ResultsA total of 634patients were included. Mean age was 66.1±14.8 years and mean baseline NIH Stroke Scale (NIHSS) score was 17.4±6.7; 86.7% had an anterior circulation occlusion. Mean time from symptom onset to puncture and time to revascularization were 363.1±264.5 min and 78.8±49.6 min, respectively. 80.3% achieved TICI ≥2b. 90-day mRS ≤2 was achieved in 47.9%, compared with 51.4% when restricting the analysis to the anterior circulation and within 6 hours (similar to recent AHA/ASA guidelines), and 54.3% for those who achieved complete revascularization. The 90-day mortality rate was 19.8%. Independent predictors of clinical outcome included age, baseline NIHSS, use of balloon guide catheter, revascularization, and sICH.ConclusionThe TRACK Registry results demonstrate the generalizability of the recent thrombectomy RCTs in real-world clinical practice. No differences in clinical and angiographic outcomes were shown between patients treated within the AHA/ASA guidelines and those treated outside the recommendations.

Background and Objective: The first pass effect (FPE; achieving complete recanalization with a single thrombectomy device pass) has been shown to be associated with higher rates of good clinical outcomes in patients with acute ischemic stroke. Here, we investigate clinical and radiographic factors associated with FPE in a large U.S. post-marketing registry (TRACK, Trevo Stent-Retriever Acute Stroke). Methods: We analyzed the TRACK database (multicenter registry of 634 patients from 23 centers from March 2013 through August 2015), which 609 patients were included in the final analysis. FPE was defined as a single pass/use of device, TICI 2c/3 recanalization, and no use of rescue therapy. Analysis of individual patient data from TRACK were performed to analyze clinical and radiographic characteristics associated with FPE as well-compared clinical outcomes defined as modified Rankin Scale (mRS) score at 30 and 90 days from hospital discharge to the non-FPE group. Results: The rate of FPE in TRACK was 23% (140/609). There was no association between patient demographics and FPE, including age (p = 0.36), sex (p = 0.50), race (p = 0.50), location of occlusion (p = 0.26), baseline NIHSS (p = 0.62), or past medical history. There was no difference in the use of a balloon-guide catheter or general anesthesia (49 and 57% with FPE vs. 47 and 64%, p = 0.63 and p = 0.14, respectively). Clinical outcomes were significantly associated with FPE; 63 vs. 44% in non-FPE patients achieved mRS 0-2 at 90 days (p = 0.0004). Conclusion: Our study showed that achieving complete recanalization with a single thrombectomy pass using the Trevo device was highly beneficial. The most common clinical factors that are used to determine eligibility for endovascular therapy, such as NIHSS severity, location of occlusion or patient age were not predictive of the ability to achieve FPE.

Background and Purpose- It remains unclear how experience influences outcomes after the advent of stent retriever technology. We studied the relationship between site experience and outcomes in the Trevo Acute Ischemic Stroke multicenter registry. Methods- The 24 sites that enrolled patients in the Trevo Acute Ischemic Stroke registry were trichotomized into low-volume (2 cases/month), medium-volume (2-4 cases/month), and high-volume centers (4 cases/month). Baseline features, imaging, and clinical outcomes were compared across the 3 volume strata. A multivariable analysis was performed to assess whether outcomes were influenced by site volumes. Results- A total of 624 patients were included and distributed as low- (n=188 patients, 30.1%), medium- (n=175, 28.1%), and high-volume (n=261, 41.8%) centers. There were no significant differences in terms of age (mean, 66±16 versus 67±14 versus 65±15; P=0.2), baseline National Institutes of Health Stroke Scale (mean, 17.6±6.5 versus 16.8±6.5 versus 17.6±6.9; P=0.43), or occlusion site across the 3 groups. Median (interquartile range) times from stroke onset to groin puncture were 266 (181.8-442.5), 239 (175-389), and 336.5 (221.3-466.5) minutes in low-, medium-, and high-volume centers, respectively (P=0.004). Higher efficiency and better outcomes were seen in higher volume sites as demonstrated by shorter procedural times (median, 97 versus 67 versus 69 minutes; P0.001), higher balloon guide catheter use (40% versus 36% versus 59%; P≤0.0001), and higher rates of good outcome (90-day modified Rankin Scale [mRS], ≤2; 39% versus 50% versus 53.4%; P=0.02). There were no appreciable differences in symptomatic intracranial hemorrhage or 90-day mortality. After adjustments in the multivariable analysis, there were significantly higher chances of achieving a good outcome in high- versus low-volume (odds ratio, 1.67; 95% CI, 1.03-2.7; P=0.04) and medium- versus low-volume (odds ratio, 1.75; 95% CI, 1.1-2.9; P=0.03) centers, but there were no significant differences between high- and medium-volume centers (P=0.86). Conclusions- Stroke center volumes significantly influence efficiency and outcomes in mechanical thrombectomy.

Background and objective The first pass effect (FPE) has become a novel measure for neurointerventionalists, achieving a complete recanalization with a single thrombectomy device pass, which has been shown to be associated with higher rates of good clinical outcomes. We describe and expand the FPE to one of a large US post-marketing registry (TRACK, Trevo Stent-Retriever Acute Stroke) to elucidate the effect of a single device pass and clinical outcome. Methods TRACK was a core-laboratory adjudicated multicenter registry of 634 patients from 23 centers aimed to evaluate the use of the Trevo device in everyday clinical practice. The TRACK registry was utilized to identify an FPE subgroup (n=140). Baseline features including demographics and clinical data were compared with the non-FPE patients (n=469). Clinical outcome measures included modified Rankin Scale score (mRS) at 30 and 90 days, National Institutes of Health Stroke Scale (NIHSS) score, symptomatic intracranial hemorrhage (sICH), and mortality. FPE was defined as a single pass/use of a device with TICI 2c/3 recanalization, and no use of rescue therapy. Results 609 patients were included in the FPE (140/609, 23%) vs non-FPE (469/609, 77%) subgroup analysis from the TRACK registry. There was no association between patient demographics and FPE group, including age (p=0.36), sex (p=0.50), race (p=0.49), location of occlusion (p=0.26), baseline NIHSS (p=0.61) past medical history including hypertension (p=0.57), atrial fibrillation (p=0.55), diabetes mellitus (p=0.74), hyperlipidemia (p=0.28), coronary artery disease (p=0.27), or history of smoking (p=0.12). The non-FPE group was associated with higher use of intraarterial tPA (FPE: 11% vs non-FPE: 23%). The onset to puncture time in minutes was not significantly different between groups (p=0.31); however, the total procedural time, total fluoroscopic time, and puncture to reperfusion time had significantly shorter mean time in FPE group (p Conclusion The achievement of complete revascularization from a single Trevo Stent-Retriever device pass is associated with higher rates of good clinical outcomes. Additionally, FPE in our subgroup registry analysis was associated with shorter procedural times, lower NIHSS at discharge, and significantly lower rates of EDT. Our analysis was not able to identify any patient demographics that would be associated to achieve first pass effect. Further research is warranted to confirm findings and identify additional factors achieving good clinical outcome after thrombectomy. Disclosures M. Mokin: 2; C; Claret Medical, Nogueira-Stryker Neurovascular (Trevo-2 Trial Principal Investigator; DAWN Trial Principal Investigator, TREVO Registry Steering Committee), Medtronic (SWIFT Trial Steering Committee; SWIFT-Prime Trial Steering Committee ; STAR Trial Angiographic Core Lab), Penumbra (3D Separator Trial Executive Committee), Neuravi (ARISE-2 Steering Committee), Genentech (Physician Advisory Board), Allm Inc (Physician Advisory Board). C. Primiani: None. A. Castonguay: None. R. Nogueira: None. D. Haussen: None. J. English: None. S. Satti: 2; C; Stryker Neurovascular. J. Chen: None. H. Farid: None. C. Borders: None. E. Veznedaroglu: None. M. Binning: None. A. Puri: None. N. Vora: None. R. Budzik: None. G. Dabus: None. I. Linfante: 2; C; Metronic, Stryker, Penumbra, and Cordis. V. Janardhan: None. A. Alshekhlee: None. M. Abraham: None. R. Edgell: None. M. Taqi: None. R. El Khoury: None. A. Majjhoo: None. M. Kabbani: None. M. Froehler: None. I. Finch: None. S. Ansari: None. R. Novakovic: None. T. Nguyen: None. O. Zaidat: 6; C; overall PI for TRACK, Arise II, Co-PI Therapy Trial, Steering committee STRATIS registry.

Background and Purpose: To describe the final results of the TARGET Registry, a multicenter, real-world study of patients with intracranial aneurysms treated with new generation TARGET Coils. Methods: The TARGET Registry is a prospective, single-arm study with independent medical event monitoring and core-lab adjudication. Patients with de novo intracranial aneurysms were embolized with either TARGET-360° or helical coils in 12 US centers. The primary outcome was aneurysm packing density (PD), which was assessed immediately post-procedure. The secondary outcomes were immediate and long-term aneurysm occlusion rate using the Raymond Scale, and independent functional outcome using the modified Rankin Scale (mRS). A secondary analysis investigated the influence of the use of 100% 360-complex coils on clinical and angiographic outcomes. Results: 148 patients with 157 aneurysms met the inclusion and exclusion criteria. 58 (39.2%) patients with ruptured and 90 (61.8%) with unruptured aneurysms were treated using TARGET 360°, helical Coils, or both. Median age was 58.3 (IQR 48.1-67.4), 73% female, and 71.6% were Caucasian. Median follow-up time was 5.9 (IQR 4.0-6.9) months. The majority were treated with TARGET 360-coils (63.7%), followed by mixed and helical coils only. Peri-procedural morbidity and mortality was seen in 2.7% of patients. A good outcome at discharge (mRS 0-2) was seen in 89.9% of the full cohort, and in 84.5 and 93.3% in the ruptured and unruptured patients, respectively. The median packing density was 28.8% (IQR 20.3-41.1). Long-term complete and near complete occlusion rate was seen in 90.4% of aneurysms and complete obliteration was seen in 66.2% of the aneurysms. No significant difference in clinical and angiographic outcomes were noted between the pure 360-complex coiling vs. mixed 360-complex/Helical coiling strategies. In a multivariate analysis, predictors for long-term aneurysm occlusion were aneurysm location, immediate occlusion grade, and aneurysm size. The long-term independent functional outcome was achieved in 128/135 (94.8%) patients and all-cause mortality was seen in 3/148 (2%) patients. Conclusion: In the multicenter TARGET Registry, two-thirds of aneurysms achieved long-term complete occlusion and 91.0% achieved complete or near complete occlusion with excellent independent functional outcome. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT01748903.

Summary Background The Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone (MGTX) showed that thymectomy combined with prednisone was superior to prednisone alone in improving clinical status as measured by the Quantitative Myasthenia Gravis (QMG) score in patients with generalised non-thymomatous myasthenia gravis at 3 years. We investigated the long-term effects of thymectomy up to 5 years on clinical status, medication requirements, and adverse events. Methods We did a rater-blinded 2-year extension study at 36 centres in 15 countries for all patients who completed the randomised controlled MGTX and were willing to participate. MGTX patients were aged 18 to 65 years at enrolment, had generalised non-thymomatous myasthenia gravis of less than 5 years' duration, had acetylcholine receptor antibody titres of 1·00 nmol/L or higher (or concentrations of 0·50–0·99 nmol/L if diagnosis was confirmed by positive edrophonium or abnormal repetitive nerve stimulation, or abnormal single fibre electromyography), had Myasthenia Gravis Foundation of America Clinical Classification Class II–IV disease, and were on optimal anticholinesterase therapy with or without oral corticosteroids. In MGTX, patients were randomly assigned (1:1) to either thymectomy plus prednisone or prednisone alone. All patients in both groups received oral prednisone at doses titrated up to 100 mg on alternate days until they achieved minimal manifestation status. The primary endpoints of the extension phase were the time-weighted means of the QMG score and alternate-day prednisone dose from month 0 to month 60. Analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00294658. It is closed to new participants, with follow-up completed. Findings Of the 111 patients who completed the 3-year MGTX, 68 (61%) entered the extension study between Sept 1, 2009, and Aug 26, 2015 (33 in the prednisone alone group and 35 in the prednisone plus thymectomy group). 50 (74%) patients completed the 60-month assessment, 24 in the prednisone alone group and 26 in the prednisone plus thymectomy group. At 5 years, patients in the thymectomy plus prednisone group had significantly lower time-weighted mean QMG scores (5·47 [SD 3·87] vs 9·34 [5·08]; p=0·0007) and mean alternate-day prednisone doses (24 mg [SD 21] vs 48 mg [29]; p=0·0002) than did those in the prednisone alone group. 14 (42%) of 33 patients in the prednisone group, and 12 (34%) of 35 in the thymectomy plus prednisone group, had at least one adverse event by month 60. No treatment-related deaths were reported during the extension phase. Interpretation At 5 years, thymectomy plus prednisone continues to confer benefits in patients with generalised non-thymomatous myasthenia gravis compared with prednisone alone. Although caution is appropriate when generalising our findings because of the small sample size of our study, they nevertheless provide further support for the benefits of thymectomy in patients with generalised non-thymomatous myasthenia gravis. Funding National Institutes of Health, National Institute of Neurological Disorders and Stroke.

IntroductionThe Solitaire stent retriever registry showed improved reperfusion, faster procedure times, and better outcome in acute stroke patients with large vessel occlusion treated with a balloon guide catheter (BGC) and Solitaire stent retriever compared with a conventional guide catheter. The goal of this study was to evaluate whether use of a BGC with the Trevo stent retriever improves outcomes compared with a conventional guide catheter.MethodsThe TRACK registry recruited 23 sites to submit demographic, clinical, and site adjudicated angiographic and outcome data on consecutive patients treated with the Trevo stent retriever. BGC use was at the discretion of the physician.Results536 anterior circulation patients (of whom 279 (52.1%) had BGC placement) were included in this analysis. Baseline characteristics were notable for younger patients in the BGC group (65.4±15.3 vs 68.1±13.6, P=0.03) and lower rate of hypertension (72% vs 79%, P=0.06). Mean time from symptom onset to groin puncture was longer in the BGC group (357 vs 319 min, P=0.06).Thrombolysis in Cerebral Infarction 2b/3 scores were higher in the BGC cohort (84% vs 75.5%, P=0.01). There was no difference in reperfusion time, first pass effect, number of passes, or rescue therapy. Good clinical outcome at 3 months was superior in patients with BGC (57% vs 40%; P=0.0004) with a lower mortality rate (13% vs 23%, P=0.008). Multivariate analysis demonstrated that BGC use was an independent predictor of good clinical outcome (OR 2; 95% CI 1.3 to 3.1, P=0.001).ConclusionsIn acute stroke patients presenting with anterior circulation large vessel occlusion, use of a BGC with the Trevo stent retriever resulted in improved reperfusion, improved clinical outcome, and lower mortality.

Background: Time to mechanical thrombectomy is a significant driver of outcomes in acute ischemic stroke (AIS) patients presenting with large vessel occlusion (LVO). We aimed to evaluate predictors of onset to groin puncture (OTG), groin puncture to reperfusion (GTR), and onset to reperfusion (OTR) times in AIS patients treated with the Trevo stent-retriever. Methods: The investigator-initiated TRACK registry recruited 23 clinical sites to submit demographic, clinical, site-adjudicated angiographic, and outcome data on consecutive patients treated with the Trevo device. We included patients treated Results: Among 433 patients analyzed (mean age 66.8 +/- 14.6 years; median NIHSS score 18; 88% anterior circulation), the median times were: OTG 240, GTR 64, and OTR 321 minutes. In multivariable analysis (Table), the independent predictors were: 1) OTG: transfer status and general anesthesia (GA) use; 2) GTR: 1 pass attempt only, use of rescue therapy, GA use, and baseline mRS >1; and 3) OTR: transfer status, use of perfusion imaging, anterior circulation LVO, use of rescue therapy, and 1 pass attempt only. Conclusions: Major pre-treatment contributors to delays to reperfusion in AIS patients treated

Background: Patients with minor acute ischemic stroke or transient ischemic attack are at high risk for subsequent stroke, and more potent antiplatelet therapy in the acute setting is needed. However, the potential benefit of more intense antiplatelet therapy must be assessed in relation to the risk for major bleeding. The SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes) was the first trial with ticagrelor in patients with acute ischemic stroke or transient ischemic attack in which the efficacy and safety of ticagrelor were compared with those of aspirin. The main safety objective was assessment of PLATO (Platelet Inhibition and Patient Outcomes)–defined major bleeds on treatment, with special focus on intracranial hemorrhage (ICrH). Methods: An independent adjudication committee blinded to study treatment classified bleeds according to the PLATO, TIMI (Thrombolysis in Myocardial Infarction), and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) definitions. The definitions of ICrH and major bleeding excluded cerebral microbleeds and asymptomatic hemorrhagic transformations of cerebral infarctions so that the definitions better discriminated important events in the acute stroke population. Results: A total of 13 130 of 13 199 randomized patients received at least 1 dose of study drug and were included in the safety analysis set. PLATO major bleeds occurred in 31 patients (0.5%) on ticagrelor and 38 patients (0.6%) on aspirin (hazard ratio, 0.83; 95% confidence interval, 0.52–1.34). The most common locations of major bleeds were intracranial and gastrointestinal. ICrH was reported in 12 patients (0.2%) on ticagrelor and 18 patients (0.3%) on aspirin. Thirteen of all 30 ICrHs (4 on ticagrelor and 9 on aspirin) were hemorrhagic strokes, and 4 (2 in each group) were symptomatic hemorrhagic transformations of brain infarctions. The ICrHs were spontaneous in 6 and 13, traumatic in 3 and 3, and procedural in 3 and 2 patients on ticagrelor and aspirin, respectively. In total, 9 fatal bleeds occurred on ticagrelor and 4 on aspirin. The composite of ICrH or fatal bleeding included 15 patients on ticagrelor and 18 on aspirin. Independently of bleeding classification, PLATO, TIMI, or GUSTO, the relative difference between treatments for major/severe bleeds was similar. Nonmajor bleeds were more common on ticagrelor. Conclusions: Antiplatelet therapy with ticagrelor in patients with acute ischemic stroke or transient ischemic attack showed a bleeding profile similar to that of aspirin for major bleeds. There were few ICrHs. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01994720.

Background: Elevated blood glucose levels following acute ischemic stroke have been associated with adverse clinical outcomes in thrombolytic and nonthrombolytic treated patients. The current study examined multiple blood glucose parameters and their association with modified Rankin Scale (mRS) score at 3 months following mechanical thrombectomy and hospital discharge. Methods: Acute ischemic stroke patients undergoing mechanical thrombectomy with a retrievable stent at two stroke centers were studied. Admission blood glucose level, maximum blood glucose during the hospital stay, and serial blood glucose measurements within the first 24 h of hospital admission were recorded. Variability in blood glucose level was represented by the standard deviation of the serial measurements within the first 24 h. The following demographic and clinical data was also collected: age, sex, baseline NIHSS score, onset-to-reperfusion times, hemoglobin A1c, and stroke mechanism. Results: 79 patients were identified; at 3 months, 35 patients had an mRS score of 0–2 and 44 had had an mRS of 3–6. Among the blood glucose variables, standard deviation of blood glucose in the first 24 h following admission and maximum blood glucose during hospital stay were significantly higher in the mRS 3–6 group. In multivariate logistic regression analysis, only the standard deviation of blood glucose remained significant (OR = 1.07, 95% CI = 1.02–1.11, p = 0.003) in a model that adjusted for admission NIHSS score (p = 0.016) and number of stent retriever passes (p = 0.042). Conclusions: Greater blood glucose variability following acute ischemic stroke is associated with worse clinical outcome in patients undergoing mechanical thrombectomy.

Background: Elevated blood glucose (BG) levels at admission following acute ischemic stroke (AIS) have been associated with adverse clinical outcomes in thrombolytic and non-thrombolytic treated patients. This association has been inconsistent and has not been studied after mechanical thrombectomy (MT). The current study looks at multiple BG parameters and their association with outcome following MT in AIS. Methods: AIS patients undergoing MT with a retrievable stent between 2012 and 2016 at two stroke centers were studied. Favorable clinical outcome was defined as having a modified Rankin Scale score (mRS) of 0-2 at three months. Admission BG, maximum BG during the hospital stay, and serial measurements every 4-6 hours in the first 24 hours were recorded. The following demographic and clinical data was also collected: age, sex, baseline NIHSS score, onset-to-reperfusion times, HgA1c, and stroke mechanism. Results: Seventy-nine patients were identified (mean age 69, 49% male, SEM= 1.56); thirty-three patients had a favorable clinical outcome at three months and 46 had unfavorable outcomes. In univariate analysis, BG variability (standard deviation of BG, SD) in the first 24 hours following admission and maximum BG during hospital stay was associated with unfavorable outcomes (Table 1). The association between admission BG and favorable outcome was not statistically significant. In multivariate logistic regression analysis the SD of BG (OR= 1.08, 95% CI= 1.02-1.13, P= .005) had the highest predictive value for favorable outcome. Conclusions: Greater BG variability is associated with worse clinical outcome in patients with AIS undergoing MT. Using SD and/or serial measurements of BG appear better than single BG measurements at predicting clinical outcome in this population.

Background: In 2005, the Center for Medicare Services (CMS) approved the reimbursement for carotid artery stenting for high-risk carotid stenosis; leaving carotid endarterectomy (CEA) to be performed primarily for a low-risk population. In this study, we assess trends of outcomes associated with CEA over the period of CMS regulation. Methods: A cohort of patients with CEA was identified from the National Inpatient Sample database using the procedure codes (38.12) for the years 2001 through 2009. Patients under age 18, missing information on the death status, transfer between hospitals, and urgent or emergent admissions were eliminated. Trend analysis for the following outcomes (post procedure stroke, myocardial infarction ‘MI’, and death) was performed over the year included in the study. Two periods encompass the implementation of the guideline (first period: 2001 through 2004 and second period: 2006 through 2009) were compared. Results: Over 9 years, 152 051 CEA procedures were performed; 63375 performed during the first period and 70886 in the second period. The mean age (71.02 ± 9.2) and male preponderance (57.4%) were similar in both treatment periods (P > 0.05). Ninety six percent of this population was asymptomatic by the time CEA was performed. Overall poor outcome risk of post-procedure stroke, MI and death was 1.97%; being lower in the second compared to the first period (2.05% versus 1.88%; P =0.02; unadjusted odds ratio “OR’ 0.91; 95% CI, 0.84, 0.98; and adjusted OR 0.88; 95% CI, 0.82, 0.96). The risk of post-procedure stroke was similar in both periods (0.94% versus 0.97%; P = 0.56); however, the risks of MI (0.91% versus 0.76%; P = 0.002) and death (0.46% versus 0.33%; P < 0.0001) declined over time. Conclusion: Following the CMS reimbursement guideline, CEA is associated with lesser risks of poor outcomes (MI and death).

Background: The CREST trial showed that risk of stroke, MI, death, and composite of the any of the 3 adverse events during the periprocedural period of carotid artery stent (CAS) is 4.1%, 1.1%. 0.7%, and 7.2% respectively. We aim to assess trends of periprocedural outcomes after CAS based on different age strata. Methods: A cohort of patients with CAS is identified from the National In patient Sample database using the procedure codes (00.63) for the years 2001 through 2009. We only included elective admissions for CAS. Missing observations on the death status are eliminated. Age was stratified as follows: < 60, 61-70, 71-80, and > 80. Trend analysis for the following periprocedural outcomes: peri-procedure stroke, myocardial infarction ‘MI’, and death; was performed across different age strata. The Cochrane-Armitage test was used for trend analysis. Results: Over 9 years, 10,655 CAS procedures were performed; 1818 (17.1%) were performed in the octogenarians. Race and gender distribution was similar across the age strata; men and Whites were predominant. In addition to age, co-morbid high risk factors were documented in 91% of the octogenarians compared to 83.2% of those < 60. The overall periprocedural outcome of stroke, MI and death across all ages is 2.37%, (stroke 1.6%, MI 0.66% and death 0.37%). Unfavorable periprocedural outcomes in different age strata are as follows: < 60 (1.1%), 61-70 (1.9%), 71-80 (3%), and > 80 (2.75%); trend P value < 0.0001. The risk of stroke is as follows: < 60 (0.72%), 61-70 (1.3%), 71-80 (2.0%), and > 80 (1.9%), P value < 0.0003; and MI < 60 (0.33%), 61-70 (0.52%), 71-80 (0.85%), and > 80 (0.77%), P value < 0.03. Mortality remained between 0.27 and 0.44 in different age strata; P = 0.54. Conclusion: In this study, periprocedural risks of stroke and MI are lower than what was reported in the CREST trial. A slight increase in these risks is noted with age, though appeared to plateau after age of 70 years.

Introduction: In 2015, mechanical thrombectomy (MT) with stent-retrievers became a standard of care treatment for acute ischemic stroke (AIS). Data on the impact of stent-retrievers on clinical outcomes in non-trial settings is limited. This study examines the association between the transition from first generation devices to stent-retrievers and clinical outcomes in a large inpatient sample. Methods: We used data from the 2010 - 2013 National Inpatient Sample for patients (n=3553) with a diagnosis of AIS using the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9 CM) diagnosis codes who underwent MT using ICD-9-CM procedure code of 39.74. Patients in the 2010-2011 time period (Period 1) were categorized as first generation device patients and patients in the 2012-2013 time period (Period 2) were categorized as second generation device patients. Outcomes were in-hospital mortality (alive/dead), discharge disposition (favorable/unfavorable), and length of stay (normal/prolonged). Weighted binary logistic regression models adjusting for patient and hospital level factors were developed. Results: The number of procedures increases from 679 in 2010 to 1128 in 2013. In Period 1, 1443 patients were treated with MT and in Period 2, 2110 patients were treated with MT. In the adjusted model, compared to patients in Period 1, patients in Period 2 were 31% less likely to be deceased (aOR = 0.69; 95% CI = 0.58-0.83) and 22% less likely to be discharged to an unfavorable location (aOR = 0.78; 95% CI = 0.64-0.95). There was no statistically significant association between treatment period and length of stay (aOR = 0.95; 95% CI = 0.82-1.10). Conclusion: Patients that had an MT performed during the stent-retrievers years were less likely to expire and be discharged to an unfavorable location than patients in the first generation device years. This confirms the past literature on the beneficial effects of a second generation of stent-retrievers in the treatment of acute ischemic stroke in a real world setting.

Background Thrombolysis for acute ischemic stroke (AIS) in children is yet to be proven efficacious, and there is limited information about its safety in large pediatric samples. Here we evaluate the safety outcomes associated with thrombolysis in children as well as the trend of hospital utilization over the past decade in the United States. Methods A cohort of children with acute ischemic stroke was identified from the Kids' Inpatient Database for the years 1998-2009. Acute ischemic stroke was identified by the International Classification of Diseases-9 clinical classification software codes (109 and 110). Multivariate logistic regression analyses were used to assess covariates associated with outcomes of hospital mortality and intracerebral hemorrhage. The Cochran-Armitage test was employed for linear trend of discrete variables. Results In this analysis, 9257 children were admitted with the diagnosis of acute ischemic stroke; only 67 (0.7%) received thrombolysis. Thrombolysis-treated children were older than the rest of the cohort (13.1 ± 7.3 vs 8.18 ± 7.5; P P P = 0.06) and intracerebral hemorrhage (2.99% vs 0.77%; P = 0.08) in the thrombolysis group. Adjusted analysis showed that intracerebral hemorrhage is predictive of a higher hospital mortality (odds ratio 3.43; 95% confidence interval 1.89-6.22), whereas thrombolysis was not (odds ratio 1.78; 95% confidence interval 0.86-3.64). The overall rate of thrombolysis per 3 years intervals had increased from 5.2 to 9.7 per 1000 children with acute ischemic stroke ( P = 0.02). This increase was mainly seen in non-children hospitals ( P = 0.01). Conclusion Thrombolysis for acute ischemic stroke is infrequently used in children. There is a trend toward higher risks of intracerebral hemorrhage and hospital mortality, although these risks are as low as those reported in adult population. The hospitals' utilization of thrombolysis in children has increased during the study period.

The relationship between age and vasospasm caused by subarachnoid hemorrhage (SAH) is controversial. We evaluated this relationship in a contemporary sample from a single institution. In a retrospective study design, we included patients with SAH caused by ruptured intracranial aneurysms. All patients underwent an evaluation that included head imaging, cerebral angiography, and treatment for the underlying aneurysm. Vasospasm was classified as absent, any vasospasm, or symptomatic vasospasm. Age was classified into 2 categories with a cutoff of 50 years, and also was stratified by decade. All patients had received preventative and therapeutic measures for vasospasm. Logistic regression analysis was used to assess the association between age and the occurrence of vasospasm. A total of 108 patients were included in this analysis, 67 of whom were age ≥50 years. The older patients had a higher incidence of vascular risk factors, and the younger patients had a higher incidence of smoking and illicit substance abuse. The mean age of the patients with any vasospasm (n = 41) was 48.51 ± 11.23 years, compared with 59.67 ± 13.30 years in those without vasospasm (P.0001). Adjusted analysis found a greater risk of vasospasm in the younger patients compared with the older patients (odds ratio, 5.83; 95% confidence interval, 2.41-14.12 for any vasospasm; odds ratio, 2.66; 95% confidence interval, 1.008-7.052 for symptomatic vasospasm). This risk of vasospasm decreased with advanced age (P.0001). Our findings suggest that patients age50 years are at 5-fold greater risk of any vasospasm compared with older patients, and that age-adjusted prevention protocols may need to be considered.

Background and Purpose: It remains unclear how experience influences outcomes after the advent of stent-retriever technology. We studied the relationship between site experience and outcomes in the TRevo ACute Ischemic StroKe (TRACK) multicenter registry. Methods: The 24 sites that enrolled patients in the TRACK registry were trichotomized into: low volume (enrolling 1-23 cases, less than 2 cases/ month), medium volume (24-47 cases, 2-4 cases/ month), and high volume sites (> 48 cases, > 4 cases/ month). Demographics, baseline features, and key prognostic presentation characteristics were compared across the three volume strata. Results: The 624 TRACK registry patients were divided into three sub groups: low (n=188 patients, 30.1%), medium (n=175, 28.1%), and high (n=261, 41.8%) volume centers. There were no significant differences in terms of age (mean, 66±16 vs. 67±14 vs. 65±15, p=0.2), baseline NIHSS (mean, 17.6±6.5 vs. 16.8±6.5 vs. 17.6±6.9, p=0.43) or site of occlusion across the 3 groups. Times from stroke onset to groin puncture were shorter in the medium volume sites (310 min) but similar in the low vs. high volumes sites (397 vs. 378 min). Higher efficiency and better outcomes were seen in higher volumes sites as demonstrated by faster times from groin puncture to reperfusion (mean, 89 vs. 82 vs. 65 min, p Conclusions: Clinical volumes have a significant influence in terms of efficiency and outcomes across stroke centers.

PURPOSE To assess the safety and efficacy of vertebral artery origin angioplasty and stenting for stroke prevention in a multicenter clinical experience. METHODS Patients with symptomatic vertebral artery origin stenosis (VAOS) were gathered from the Society of Vascular and Interventional Neurology Research Consortium. Demographic, clinical, and procedural data were collected. The main outcome measure was procedural and peri-procedural risks of stroke, transient ischemic attack (TIA), or death at 1 and 3 months. Logistic regression analysis was used to assess covariates associated with future restenosis. RESULTS A total of 148 patients were included with mean age of 66.2 ± 11.5; 74% men and 77% Caucasian. One patient (.8%) had a stroke at 1 month and 5 of 96 (5.2%) patients had TIA at 3 months. There were no immediate procedural events or deaths. The mean angiographic pre-treatment stenosis was 80.5 ± 12.7%, which was reduced to 5.3 ± 9.1% after stent deployment. Follow-up angiography showed 15.5% of patients had significant restenosis (≥50%). Predictors of restenosis included age (OR 3.08; 95% CI 1.01, 9.41) and smoking (OR 3.10; 95% CI 1.12, 8.64). CONCLUSIONS Endovascular intervention of VAOS is associated with low peri-procedural complication rates. Restenosis remains a concern; age and smoking predicted future restenosis.

Hemicraniectomy is a surgical procedure performed to prevent cerebral herniation and death in patients who have sustained a massive ischemic stroke in the anterior circulation territory. Information on in-hospital mortality in patients with large ischemic stroke treated with hemicraniectomy outside randomized trials is lacking. We sought to identify in-hospital mortality associated with hemicraniectomy in a large US sample. We selected our cohort from the National Inpatient Sample database for the years 2000 through 2006 using the clinical classification software codes for acute ischemic stroke (AIS) and arterial occlusion, and identified those patients treated with thrombolysis or hemicraniectomy by the procedure codes. A multivariate logistic regression model was used for adjusted analysis. Among 502,231 patients with AIS, 252 (0.05%) underwent hemicraniectomy, and 7526 (1.5%) were treated with thrombolysis. Compared with the nonsurgical group, patients treated with hemicraniectomy were younger (mean age, 55.6 vs 71.5 years) and had lower Charlson Comorbidity Index scores (92.8% vs 76.0%). The mortality rate was higher in the hemicraniectomy group (32.1% vs 10.8%; adjusted odds ratio [OR] = 3.91; 95% confidence interval [CI] = 2.97-5.16). In patients treated with thrombolysis, mortality was higher in the hemicraniectomy group compared with the nonsurgical group (35.3% vs 13.1%; P = .01). The rate of hospital utilization of hemicraniectomy varied between 0.04% and 0.06% among all stroke admissions; the trend did not change significantly over the 7-year study period ( P = .06). The mortality rate in hemicraniectomy-treated patients was significantly lower than in historical cohorts however, hemicraniectomy remains associated with high in-hospital mortality. The rate of utilization of hemicraniectomy for AIS in US hospitals has remained essentially unchanged.

Introduction: The purpose of this study was to compare the in-hospital mortality and complication rates after early and delayed initiation of plasma exchange (PLEX) in patients with myasthenia gravis (MG). Methods: Our cohort was identified from the Nationwide Inpatient Sample database for the years 2000 through 2005. Early treatment was defined as therapy with PLEX administered within the first 2 days from hospital admission. Univariate and multivariate analyses were employed. Results: One thousand fifty-three patients were treated and included in the analysis. A delay in receiving PLEX was associated with higher mortality (6.56% vs. 1.15%, P < 0.001) and increased complications (29.51% vs. 15.29%, P < 0.001). Adjusted analysis showed increased mortality (odds ra- tio (OR) 2.812; 95% confidence interval (CI) 1.119-7.069) and complications (OR 1.672; 95% CI 1.118-2.501) with delayed PLEX therapy. Conclusions: Delaying PLEX therapy for MG by more than 2 days after admission may lead to higher mortality and complication rates, and thus prompt therapy is warranted. Muscle Nerve 43: 578-584, 2011

To compare clinical and economic outcomes following plasma exchange (PLEX) and intravenous immunoglobulin (IVIG) in U.S. patients with primary diagnoses of myasthenia gravis (MG).Our cohort was identified from the Nationwide Inpatient Sample database for years 2000-2005 using codes from the International Classification of Diseases, 9th edition. Multivariate regression analyses were used to identify predictors of mortality, complications, length of stay, and total inpatient cost.Among 1,606 hospitalized patients, the unadjusted mortality rate of MG crisis remained higher than those without crisis (0.44% vs 4.44%, p0.001), as well as the unadjusted complication rate (26.36% vs 11.23%, p0.001). MG crisis patients receiving PLEX had significantly more complications than those receiving IVIG (30.06% vs 14.79%, p0.001). Among the whole cohort, adjusted mortality and complication rates were not significantly different between the treatment groups (p0.05). Acute respiratory failure, major cardiac complications, and acute renal failure were associated with an increased mortality rate (p0.001). Age and respiratory failure were associated with an increased complication rate (p0.001). Length of stay was significantly longer for MG (6 vs 4 days, p0.001) and MG crisis (10 vs 5 days, p0.001) patients receiving PLEX. Inpatient costs were higher for MG ($26,662 vs $21,124, p0.01) and MG crisis ($53,801 vs $33,924, p0.001) patients receiving PLEX.Compared to PLEX, IVIG appears of similar clinical (mortality and complications) and perhaps of superior economic (length of stay and total inpatient charges) outcomes in the treatment of MG. Elderly and those with complex comorbid diseases including acute respiratory failure may be better treated with IVIG.

Percutaneous endoscopic gastrostomy (PEG) tubes are commonly needed for early nutrition in patients with acute ischemic stroke. We evaluated the relationship between the NIH Stroke Scale (NIHSS) score and the need for PEG tube placement. Patients with acute ischemic stroke were included in this study. We collected information on patient demographics, stroke severity as indicated by the NIHSS, and risk factors for vascular disease. We ascertained the swallowing evaluation and PEG tube placement during the same hospitalization. A hierarchical optimal classification tree was determined for the best predictors. A total of 187 patients (mean age, 67.2 years) were included, only 33 (17.6%) of whom had a PEG tube placed during the course of hospitalization. Those who had the PEG were slightly older (73.8 vs 65.8 years), had severe stroke (median NIHSS score, 18 vs 4), and a longer hospital stay (median 12 vs 4 days). Independent predictors for PEG placement included bulbar symptoms at onset, higher NIHSS score, stroke in the middle cerebral artery distribution, and aspiration pneumonia. Hierarchical analysis showed that patients with aspiration pneumonia and NIHSS scoreor=12 had the highest likelihood (relative risk [RR] = 4.67; P.0001) of requiring a PEG tube. In the absence of pneumonia, NIHSS scoreor=16 yielded a moderate likelihood of requiring PEG (RR = 1.80; P.0001). Our findings indicate that the presence of pneumonia and high NIHSS score are the best predictors for requiring PEG tube insertion in patients with ischemic stroke. These findings may have benefits in terms of early decision making, shorter hospitalization, and possible cost savings.

Peroxisome proliferator-activated receptor gamma (PPARγ) agonists have antineoplastic effects on gliomas in cell lines and animal models. In a retrospective chart review, we assessed the influence of PPARγ agonists on the odds of having a high grade glioma. We reviewed patients with a diagnosis of anaplastic astrocytoma and glioblastoma multiforme (GBM) between 1999 and 2008. Patients with hip fractures served as the control group. Multivariable unconditional logistic regression models were used to calculate the odds of diabetic hip fracture patients using a PPARγ agonist at time of diagnosis as compared to diabetic glioma patients. In addition, survival analysis was performed for all GBM patients. We identified 1602 hip fracture patients and 302 high grade glioma patients, 15 and 16% were diabetics, respectively. PPARγ agonists were used by 20% of diabetic hip fracture patients and by 6% of high grade glioma patients (chi-square P-value = 0.02) with an odds ratio of 4.081 (95% CI: 1.119-14.881). In addition, there was no difference in survival for diabetic patients with GBM compared to non-diabetic patients with GBM. The prevalence of PPARγ agonist use was lower in the diabetic high grade glioma group when compared to diabetic hip fracture patients. These findings suggest that diabetic high grade glioma patients are not given PPARγ agonists as often as diabetic hip fracture patients even though these drugs are considered standard of care and should be equally distributed throughout both groups. This indicates a possible anti-neoplastic effect of PPARγ agonists in gliomas.

Biologic therapy with tumor necrosis factor (TNF)-alpha antagonists for rheumatoid arthritis has been well established. We describe two patients with rheumatoid arthritis who developed chronic inflammatory demyelinating polyneuropathy (CIDP) during their course of therapy with TNF-alpha antagonists. A 45-year-old woman and a 49-year-old man, both with a history of rheumatoid arthritis, were treated with etanercept and infliximab, respectively. Clinical signs of peripheral neuropathy developed 2 weeks and 12 months after the initiation of TNF-alpha antagonists. Electrodiagnostic studies at variable points during the disease course showed signs of acquired demyelination consistent with CIDP. Cerebrospinal fluid examination showed albuminocytologic dissociation (total protein concentration 118 mg/dl and 152 mg/dl, respectively). Both patients failed to improve after discontinuation of the offending agent, and they responded poorly to corticosteroids. However, there was clinical and electrophysiologic recovery after initiation of intravenous immunoglobulin (IVIg) therapy. CIDP may occur early or late during the treatment course with TNF-alpha antagonists. IVIg may reverse and stabilize the inflammatory process.

There are conflicting opinions on whether postural tachycardia syndrome predisposes to syncope. We investigated this relationship by comparing the frequency of syncope in postural tachycardia syndrome and orthostatic hypotension.We queried our autonomic laboratory database of 3700 patients. Orthostatic hypotension and postural tachycardia syndrome were defined in standard fashion, except that postural tachycardia syndrome required the presence of orthostatic symptoms and a further increase in heart rate beyond 10 minutes. Syncope was defined as an abrupt decrease in blood pressure and often, heart rate, requiring termination of the tilt study. Statistical analysis utilized Fisher's exact test and Student's t test, as appropriate.Of 810 patients referred for postural tachycardia syndrome, 185 met criteria while another 328 patients had orthostatic hypotension. Of the postural tachycardia syndrome patients, 38% had syncope on head-up tilt, compared with only 22% of those with orthostatic hypotension (P.0001). In the postural tachycardia group, syncope on head-up tilt was associated with a clinical history of syncope in 90%, whereas absence of syncope on head-up tilt was associated with a clinical history of syncope in 30% (P.0001). In contrast, syncope on head-up tilt did not bear any relationship to clinical history of syncope in the orthostatic hypotension group (41% vs 36%; P=.49).Our results demonstrate that syncope (both tilt table and clinical) occurs far more commonly in patients who have postural tachycardia syndrome than in patients with orthostatic hypotension. These findings suggest that one should be clinically aware of the high risk of syncope in patients with postural tachycardia syndrome, and the low-pressure baroreceptor system that is implicated in postural tachycardia syndrome might confer more sensitivity to syncope than the high pressure system implicated in orthostatic hypotension.

Background Clinicians depend on history given by the patients when considering the diagnosis of orthostatic hypotension. Methods Patients with a decrease in systolic blood pressure more than 60 mm Hg from baseline during a head-up tilt table test were included. They were classified according to their symptoms during the head-up tilt table test. Localization of the cause of orthostatic hypotension was sought in each of these groups. Results Eighty-eight (43%) patients had typical symptoms, 49 (24%) had atypical symptoms, and 68 (33%) were asymptomatic. The average decrease in systolic blood pressure was 88 mm Hg, 87.5 mm Hg, and 89.8 mm Hg in the typical, atypical, and asymptomatic groups, respectively ( P =.81). Patients reported severe dizziness with a similar frequency as lower extremity discomfort. Backache and headache also were common atypical complaints. Patients with peripheral cause of dysautonomia were able to sustain the longest upright position during the head-up tilt table test (21 minutes, compared with central dysautonomia [15 minutes]) ( P =.005). There was no correlation between the cause of dysautonomia and the occurrence of symptoms during the head-up tilt table test ( P =.58). Conclusion A third of the patients with severe orthostatic hypotension are completely asymptomatic during the head-up tilt table test, and another quarter have atypical complaints that would not lead physicians toward the diagnosis of orthostatic hypotension. These findings suggest that they might not provide adequate information in diagnosing profound orthostatic hypotension in a subset of patients with this disorder.

Objective: To determine the incidence and mortality rates and predictors of death in myasthenia gravis (MG) and MG crisis in a large US cohort. Methods: Our cohort was identified from the Nationwide Inpatient Sample database for the years 2000 through 2005 using ICD-9-CM codes. MG crisis was identified by the principal diagnosis code or by the presence of respiratory failure. The incidence of MG was stratified by age, ethnicity, and gender. Multivariate logistic regression analysis was used to identify predictors of mortality in MG. For trend analyses of immune intervention, we used the Cochrane-Armitage test. Results: After data cleansing, 5,502 patients with MG were included. In women, the incidence of admission was two to three times higher during the first 5 decades. In men, the incidence of admission was higher during the sixth, seventh, and eighth decades. The annual incidence rate of MG was higher in black women (0.01 per 1,000 persons/year) compared to white women and white and black men (0.009, 0.008, and 0.007 per 1,000 persons/year). The overall in-hospital mortality rate was 2.2%, being higher in MG crisis (4.47%). Older age and respiratory failure were the predictors of death, with adjusted odds ratios of 9.28 (95% confidence interval [CI], 3.31, 26.0) and 3.58 (95% CI, 2.01, 6.38). The trend of IV immunoglobulin utilization has increased compared to plasma exchange and thymectomy ( p Conclusion: Myasthenia gravis (MG) is still a disease of young women and old men, as reflected by the hospital admission rates. In-hospital mortality of MG is low. Hospital utilization of IV immunoglobulin has significantly increased compared to plasma exchange and thymectomy.

Background Acute ischemic stroke (AIS) is common cause of hospital admission. The objective of this study was to determine the impact of the new Accreditation Council for Graduate Medical Education (ACGME) duty hour regulations on AIS outcomes including inhospital mortality. Methods Hospitalized patients with AIS were selected from the National Inpatient Sample database. Patients with AIS with a known mortality and hospital teaching status were included for the years 2000 through 2005. Inhospital mortality and predictors of mortality were stratified by the hospital teaching status. To determine the variability of mortality around the month of July (July phenomenon) the trend of mortality was determined in teaching hospitals stratified by the calendar month of each year. Results In all, 377,266 patients were included in this analysis; 43.0% were admitted to teaching hospitals. Overall inhospital mortality was 10.8%, slightly higher in teaching hospitals (11.4% v 10.3%, P < .0001). The trend in AIS mortality showed a decline during the 6 years included in this study in both hospital types (P < .0001). Adjusted analysis showed decline in mortality in both hospital types after July 1, 2003: odds ratio (OR) 0.91 (95% confidence interval [CI] 0.87, 0.94) in teaching hospitals and OR 0.81 (95% CI 0.78, 0.84) in nonteaching hospitals. Predictors of AIS-associated hospital mortality were similar in both hospital types except for sepsis, which was another independent predictor of death in nonteaching hospitals (OR 1.58, 95% CI 1.30, 1.94). There was no significant change in AIS mortality when stratified by each calendar month within the years included in this study (P value = .25-.93). Conclusion There was no difference in AIS mortality after the implementation of the new ACGME duty hour standards. In addition, data support the lack of July phenomenon in neurology residency programs in regard to AIS mortality.

Five phenotypically distinct subtypes have been identified in sporadic Creutzfeldt-Jakob disease (sCJD), based on the methionine/valine polymorphic genotype of codon 129 of the prion protein (PrP) gene and the presence of either one of the two protease K-resistant scrapie prion protein (PrP(Sc)) types identified as 1 and 2. The infrequent co-existence of both PrP(Sc) types in the same case has been known for a long time. Recently, it has been reported, using type-specific antibodies, that the PrP(Sc) type 1 is present in all cases of sCJD carrying PrP(Sc) type 2. The consistent co-occurrence of both PrP(Sc) types complicates the diagnosis and the current classification of sCJD, and has implications for the pathogenesis of naturally occurring prion diseases. In the present study, we investigated the prevalence of PrP(Sc) types 1 and 2 co-occurrence, along with its effects on the disease phenotype and PrP(Sc) strain characteristics, comparatively analysing 34 cases of sCJD, all methionine homozygous at codon 129 of the PrP gene (sCJDMM). To minimize overestimating the prevalence of the sCJDMM cases carrying PrP(Sc) types 1 and 2 (sCJDMM1-2), we used proteinase K concentrations designed to hydrolyse all fragments resulting from an incomplete digestion, while preserving the protease-resistant PrP(Sc) core. Furthermore, we used several antibodies to maximize the detection of both PrP(Sc) types. Our data show that sCJDMM cases associated exclusively with either PrP(Sc) type 1 (sCJDMM1) or PrP(Sc) type 2 (sCJDMM2) do exist; we estimate that they account for approximately 56% and 5% of all the sCJDMM cases, respectively; while in 39% of the cases, both PrP(Sc) types 1 and 2 are present together (sCJDMM1-2) either mixed in the same anatomical region or separate in different regions. Clinically, sCJDMM1-2 had an average disease duration intermediate between the other two sCJDMM subtypes. The histopathology was also intermediate, except for the cerebellum where it resembled that of sCJDMM1. These features, along with the PrP immunostaining pattern, offer a diagnostic clue. We also observed a correlation between the disease duration and the prevalence of PrP(Sc) type 2 and sCJDMM2 phenotypes. The use of different antibodies and of the conformational stability immunoassay indicated that the co-existence of types 1 and 2 in the same anatomical region may confer special conformational characteristics to PrP(Sc) types 1 and 2. All of these findings indicate that sCJDMM1-2 should be considered as a separate entity at this time.

Lobectomy for intractable complex partial epilepsy (iCPE) continues to be underutilized despite numerous reports showing low mortality and complications. Our objective was to evaluate patient demographics and in-hospital complications of intracranial electrode (IE) implantation and lobectomy for evaluation and treatment of iCPE in a nationwide cohort in recent years. We queried the Nationwide Inpatient Sample for patients admitted with iCPE in the years 2000-2005. We excluded patients with brain tumors, vascular malformations, and other diagnoses that might cause alteration of awareness or necessitate brain surgery. Patient demographics and in-hospital complications of patients who underwent surgery (lobectomy, IE implantation, or both) were compared to non-surgical patients. In total, 3,005 patients (mean age 31 +/- 16 years, female 51.3%) were included in the analysis. Teaching hospitals admitted the majority (93%), with a median length of stay of 5 days (quartiles 3, 7). Of all iCPE admissions, 484 (16.1%) underwent surgery; 234 patients were evaluated with IE implantation, 182 (6.06%) had lobectomy, and 68 (2.26%) had both procedures in the same hospitalization. We found an increased risk of intracerebral hemorrhage (ICH) in the IE group (OR 14.1, 95% CI 5.22, 38.3), but not in the lobectomy group (OR 1.98, 95% CI 0.24, 16.2). A similar pattern was seen for status epilepticus (SE) between IE implantation (OR 5.12, 95% CI 1.53, 17.3), and lobectomy (OR 1.95, 95% CI 0.24, 15.8). Procedure utilization insignificantly increased over the 6 years studied (p = 0.06). Invasive monitoring is associated with increased risks of ICH and SE. Although the risks of invasive monitoring and lobectomy are low, epilepsy surgery continues to be underutilized in iCPE.

The diaphragm pacing system (DPS) is a minimally invasive alternative to mechanical ventilation in patients with quadriplegia due to cervical myelopathy primarily caused by high cervical spinal cord injury. We evaluated 36 patients, 29 of whom had traumatic spinal cord injury, two who had a history of remote meningitis and demyelinating disease, and five who had cervical myelopathies of unknown etiology. Phrenic nerve conduction studies were performed with simultaneous fluoroscopic observation of diaphragm excursion to assess diaphragm viability. In the preoperative evaluation, diaphragm compound muscle action potentials (CMAPs) were recorded only when the diaphragm moved on fluoroscopy with ipsilateral stimulation. Twenty-six patients who were determined to have a viable diaphragm underwent DPS. Following DPS the primary outcome was the time (hours per day) that patients were able to pace and stay off the ventilator. Of 26 implanted patients, 96% (25 patients) were able to pace and tolerate being off the ventilator for more than 4 h per day. This study demonstrates that the presence of a diaphragm CMAP is associated with diaphragm movement observed by fluoroscopy in cervical myelopathy. In addition, DPS can help patients with cervical spinal cord injury to breathe unassisted by a ventilator.

To evaluate the in-hospital mortality associated with generalized convulsive status epilepticus (GCSE), and predictors of death in a large US cohort.We identified our cohort from the National Inpatient Sample for the years 2000 through 2004 by searching the International Classification of Diseases, Ninth Revision, code for GCSE. We excluded patients with partial status epilepticus, and assessed whether associated diagnoses including brain tumors, CNS infections, stroke, hypoxic-ischemic brain injury, metabolic derangements, and respiratory failure predicted mortality. We used logistic regression models to identify predictors of death.Eleven thousand five hundred eighty patients were included in this analysis. The mean age of the patients was 39 +/- 25.6 years, and the median duration of stay was 3 days. Male sex (53.4%) and white race (42.4%) were predominant. Overall in-hospital mortality was 399 in 11,580 (3.45%). Age was a significant predictor of death. Mortality tripled in those who received mechanical ventilation compared with those who did not (7.43% vs 2.22%, odds ratio [OR] 2.79, 95% CI 2.18 to 3.59). Other predictors of mortality included hypoxic-ischemic brain injury (OR 9.85, 95% CI 6.63 to 14.6), cerebrovascular diseases (OR 2.08, 95% CI 1.13 to 3.82), female sex (OR 1.34, 95% CI 1.04 to 1.73), and higher comorbidity index (OR 6.79, 95% CI 4.27 to 10.8).Overall in-hospital mortality from generalized convulsive status epilepticus is low, but remarkably increases in those treated with mechanical ventilation. Other predictors of mortality include older age, female sex, hypoxic-ischemic brain injury, and higher comorbidity index.