Publications by authors named "Brian-Fred Fitzsimmons"

39 Publications

Consecutive Endovascular Treatment of 20 Ruptured Very Small (<3 mm) Anterior Communicating Artery Aneurysms.

Interv Neurol 2016 Jun 22;5(1-2):57-64. Epub 2016 Mar 22.

Departments of Neurology, Medical College of Wisconsin and Froedtert Hospital, Milwaukee, Wis., USA; Neuroscience and Stroke Center, Mercy Health St Vz Medical Center, Toledo, Ohio, USA.

Background: Small aneurysms located at the anterior communicating artery carry significant procedural challenges due to a complex anatomy. Recent advances in endovascular technologies have expanded the use of coil embolization for small aneurysm treatment. However, limited reports describe their safety and efficacy profiles in very small anterior communicating artery aneurysms.

Objective: We sought to review and report the immediate and long-term clinical as well as radiographic outcomes of consecutive patients with ruptured very small anterior communicating artery aneurysms treated with current endovascular coil embolization techniques.

Methods: A prospectively maintained single-institution neuroendovascular database was accessed to identify consecutive cases of very small (<3 mm) ruptured anterior communicating artery aneurysms treated endovascularly between 2006 and 2013.

Results: A total of 20 patients with ruptured very small (<3 mm) anterior communicating artery aneurysms were consecutively treated with coil embolization. The average maximum diameter was 2.66 ± 0.41 mm. Complete aneurysm occlusion was achieved for 17 (85%) aneurysms and near-complete aneurysm occlusion for 3 (15%) aneurysms. Intraoperative perforation was seen in 2 (10%) patients without any clinical worsening or need for an external ventricular drain. A thromboembolic event occurred in 1 (5 %) patient without clinical worsening or radiologic infarct. Median clinical follow-up was 12 (±14.1) months and median imaging follow-up was 12 (±18.4) months.

Conclusion: This report describes the largest series of consecutive endovascular treatments of ruptured very small anterior communicating artery aneurysms. These findings suggest that coil embolization of very small aneurysms in this location can be performed with acceptable rates of complications and recanalization.
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June 2016

Aspiration Thrombectomy After Intravenous Alteplase Versus Intravenous Alteplase Alone.

Stroke 2016 09 2;47(9):2331-8. Epub 2016 Aug 2.

From the Mount Sinai Health System, New York, NY (J.M.); St. Vincent Mercy Medical Center, Toledo, OH (O.O.Z.); Universitätsklinikum Carl Gustav Carus, Dresden, Germany (R.v.K.); Texas Stroke Institute, Plano (A.J.Y.); WellStar Health System, Marietta, GA (R.G.); Rush University, Chicago, IL (D.L.); Swedish Medical Center, Denver, CO (D.F.); Central DuPage Hospital, Winfield, IL (H.S.); Riverside Methodist Hospital, Columbus, OH (R.B.); Kaiser Los Angeles, CA (Z.A.A.); St. Joseph's Regional Medical Center, Paterson, NJ (A.G., D.A.); St. Joseph's BNI, Phoenix, AZ (C.M.); Sunrise Hospital and Medical Center, Las Vegas, NV (L.B.); Medical College of Wisconsin, Milwaukee (B.-F.F.); University of Miami Health System, FL (D.Y.); Premier Clinical Neuroscience Institute, Dayton, OH (J.T.); Lutheran Medical Center, Brooklyn, NY (J.F.); University of Chicago Medical Center, IL (S.K.L.); Erlanger Health System, Chattanooga, TN (B.B.); Universitätsklinikum Aachen, Germany (M.W.); Universitätsmedizin Göttingen, Germany (M.K.); Forsyth Medical Center, Winston-Salem, NC (D.H.); Sparrow Hospital, Lansing, MI (S.H.); Houston Methodist Hospital, TX (D.C.); Cedars-Sinai Medical Center, Los Angeles, CA (M.J.A.); Alexian Brothers, Elk Grove, IL (T.M.); The Valley Hospital, Ridgewood, NJ (D.A.); JFK Medical Center, Edison, NJ (J.K.); Holy Cross, Fort Lauderdale, FL (L.M.); and University of Cincinnati, OH (P.K.).

Background And Purpose: Thrombectomy, primarily with stent retrievers with or without adjunctive aspiration, provided clinical benefit across multiple prospective randomized trials. Whether this benefit is exclusive to stent retrievers is unclear.

Methods: THERAPY (The Randomized, Concurrent Controlled Trial to Assess the Penumbra System's Safety and Effectiveness in the Treatment of Acute Stroke; NCT01429350) was an international, multicenter, prospective, randomized (1:1), open label, blinded end point evaluation, concurrent controlled clinical trial of aspiration thrombectomy after intravenous alteplase (IAT) administration compared with intravenous-alteplase alone in patients with large vessel ischemic stroke because of a thrombus length of ≥8 mm. The primary efficacy end point was the percent of patients achieving independence at 90 days (modified Rankin Scale score, 0-2; intention-to-treat analysis). The primary safety end point was the rate of severe adverse events (SAEs) by 90 days (as treated analysis). Patients were randomized 1:1 across 36 centers in 2 countries (United States and Germany).

Results: Enrollment was halted after 108 (55 IAT and 53 intravenous) patients (of 692 planned) because of external evidence of the added benefit of endovascular therapy to intravenous-alteplase alone. Functional independence was achieved in 38% IAT and 30% intravenous intention-to-treat groups (P=0.52). Intention-to-treat ordinal modified Rankin Scale odds ratio was 1.76 (95% confidence interval, 0.86-3.59; P=0.12) in favor of IAT. Secondary efficacy analyses all demonstrated a consistent direction of effect toward benefit of IAT. No differences in symptomatic intracranial hemorrhage rates (9.3% IAT versus 9.7% intravenous, P=1.0) or 90-day mortality (IAT: 12% versus intravenous: 23.9%, P=0.18) were observed.

Conclusions: THERAPY did not achieve its primary end point in this underpowered sample. Directions of effect for all prespecified outcomes were both internally and externally consistent toward benefit. It is possible that an alternate method of thrombectomy, primary aspiration, will benefit selected patients harboring large vessel occlusions. Further study on this topic is indicated.

Clinical Trial Registration: URL: Unique identifier: NCT01429350.
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September 2016

Effect of a balloon-expandable intracranial stent vs medical therapy on risk of stroke in patients with symptomatic intracranial stenosis: the VISSIT randomized clinical trial.

JAMA 2015 Mar 24-31;313(12):1240-8

Department of Neurology, University of Virginia, Charlottesville.

Importance: Intracranial stenosis is one of the most common etiologies of stroke. To our knowledge, no randomized clinical trials have compared balloon-expandable stent treatment with medical therapy in symptomatic intracranial arterial stenosis.

Objective: To evaluate the efficacy and safety of the balloon-expandable stent plus medical therapy vs medical therapy alone in patients with symptomatic intracranial stenosis (≥70%).

Design, Setting, And Patients: VISSIT (the Vitesse Intracranial Stent Study for Ischemic Stroke Therapy) trial is an international, multicenter, 1:1 randomized, parallel group trial that enrolled patients from 27 sites (January 2009-June 2012) with last follow-up in May 2013.

Interventions: Patients (N = 112) were randomized to receive balloon-expandable stent plus medical therapy (stent group; n = 59) or medical therapy alone (medical group; n = 53).

Main Outcomes And Measures:

Primary Outcome Measure: a composite of stroke in the same territory within 12 months of randomization or hard transient ischemic attack (TIA) in the same territory day 2 through month 12 postrandomization. A hard TIA was defined as a transient episode of neurological dysfunction caused by focal brain or retinal ischemia lasting at least 10 minutes but resolving within 24 hours. Primary safety measure: a composite of any stroke, death, or intracranial hemorrhage within 30 days of randomization and any hard TIA between days 2 and 30 of randomization. Disability was measured with the modified Rankin Scale and general health status with the EuroQol-5D, both through month 12.

Results: Enrollment was halted by the sponsor after negative results from another trial prompted an early analysis of outcomes, which suggested futility after 112 patients of a planned sample size of 250 were enrolled. The 30-day primary safety end point occurred in more patients in the stent group (14/58; 24.1% [95% CI, 13.9%-37.2%]) vs the medical group (5/53; 9.4% [95% CI, 3.1%-20.7%]) (P = .05). Intracranial hemorrhage within 30 days occurred in more patients in the stent group (5/58; 8.6% [95% CI, 2.9%-19.0%]) vs none in the medical group (95% CI, 0%-5.5%) (P = .06). The 1-year primary outcome of stroke or hard TIA occurred in more patients in the stent group (21/58; 36.2% [95% CI, 24.0-49.9]) vs the medical group (8/53; 15.1% [95% CI, 6.7-27.6]) (P = .02). Worsening of baseline disability score (modified Rankin Scale) occurred in more patients in the stent group (14/58; 24.1% [95% CI, 13.9%-37.2%]) vs the medical group (6/53; 11.3% [95% CI, 4.3%-23.0%]) (P = .09).The EuroQol-5D showed no difference in any of the 5 dimensions between groups at 12-month follow-up.

Conclusions And Relevance: Among patients with symptomatic intracranial arterial stenosis, the use of a balloon-expandable stent compared with medical therapy resulted in an increased 12-month risk of added stroke or TIA in the same territory, and increased 30-day risk of any stroke or TIA. These findings do not support the use of a balloon-expandable stent for patients with symptomatic intracranial arterial stenosis.

Trial Registration: Identifier: NCT00816166.
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April 2015

Stenting and angioplasty for idiopathic intracranial hypertension: a case series with clinical, angiographic, ophthalmological, complication, and pressure reporting.

J Neuroimaging 2015 Jan-Feb;25(1):72-80

Background: Previous studies have demonstrated that cerebral dural sinus stenosis (DSS) may be a potential patho-physiological cause of idiopathic intracranial hypertension (IIH). Endovascular therapy for DSS is emerging as a potential alternative to treat IIH. Here, we present the results of our case series.

Method: We prospectively collected angiographic and manometric data on patients that underwent angioplasty/stenting for IIH. All patients had failed maximal medical therapy (MMT) and had confirmed sinus stenosis. Demographic, clinical and radiological presentation, and outcomes were collected retrospectively.

Results: A total of 18 patients underwent 25 procedures. Demographics revealed a mean age of 30 (range 15-59), 83% (15/18) were female, 72% (13/18) were white, and mean body mass index of 36 (range 23-59.2). All patients presented with classic IIH. Symptom improvement or resolution was reported in 94% (17/18) of patients. All patients had resolution and/or stabilization/improvement of their papilledema. Headaches related to increased pressure improved in 56% (10/18). Re-stenosis and retreatment occurred in 33% (6/18). No procedural related complications were reported.

Conclusion: Dural sinus angioplasty and stenting is relatively safe, feasible, and clinically efficacious for patients with symptomatic sinus stenosis who have failed standard therapy. The long-term durability of patency and clinical improvement remains unknown.
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September 2015

Stenting and angioplasty of small cerebral arteries in symptomatic intracranial atherosclerotic disease.

Interv Neurol 2014 May;2(3):123-131

Department of Neurology, Medical College of Wisconsin and Froedtert Hospital, Milwaukee, Wisconsin ; Department of Neurosurgery, Medical College of Wisconsin and Froedtert Hospital, Milwaukee, Wisconsin ; Department of Radiology, Medical College of Wisconsin and Froedtert Hospital, Milwaukee, Wisconsin.

Background: Intracranial atherosclerotic disease (ICAD) is a common cause of stroke with a poor natural history despite medical therapy. Few studies have investigated endovascular therapies for the treatment of symptomatic ICAD in distal intracranial arteries. Here, we present the feasibility and safety of balloon angioplasty with and without stenting in patients with medically refractory small artery symptomatic ICAD.

Method: Personal logs were reviewed to identify patients who were treated for small artery ICAD (stenosis > 50%) using angioplasty ± stenting. Small cerebral arteries were defined by a diameter ≤ 2 mm or any branch distal to a large intracranial vessel (i.e. distal to ICA, M1, A1, Vertebrobasilar trunk). Patient characteristics, clinical manifestations, treatment, hospital course, and follow up data was collected and analyzed.

Results: Ten patients (12 arteries) were treated with either primary balloon angioplasty (58.3%) or angioplasty with stenting (41.6 %) with 100% technical success rate. Mean pre-treatment stenosis was 79.9% while mean post-treatment stenosis was 19.0%. There were no major peri-procedural complications including symptomatic intracranial hemorrhage or mortality; three cases were complicated by groin hematoma. Patients were followed for a mean total of 18.6 months with only one symptomatic restenosis which was re-treated successfully. All patients had good functional outcome with a mRS of either 0 (80%) or 1 (20%) on follow up.

Conclusion: In our case series, treatment of symptomatic small artery ICAD with angioplasty ± stenting was safe and effective. These interventions should be considered as an alternative treatment for ICAD patients refractory to medical therapy.
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May 2014

Endovascular reconstruction for progressively worsening carotid artery dissection.

J Neurointerv Surg 2015 Jan 3;7(1):32-9. Epub 2014 Jan 3.

Departments of Neurology, The Medical College of Wisconsin and Froedtert Hospital, Milwaukee, Wisconsin, USA Department of Neurosurgery, The Medical College of Wisconsin and Froedtert Hospital, Milwaukee, Wisconsin, USA Department of Radiology, The Medical College of Wisconsin and Froedtert Hospital, Milwaukee, Wisconsin, USA.

Background: Carotid artery dissection is an important cause of stroke in young patients. Selection criteria for endovascular repair have not been well defined and limited data exist on long-term outcomes of stent reconstruction.

Objective: To report the immediate and long-term clinical and radiographic outcomes of patients treated with stent placement for progressively worsening symptomatic carotid arterial dissection despite antithrombotic therapy.

Methods: A single institution neuro-endovascular database was accessed to identify consecutive cases in which carotid artery dissection was treated with endovascular repair between 2006 and 2012. Clinical, demographic, radiographic, and procedural data were obtained through chart review.

Results: A total of 22 patients were identified and included 27 carotid artery dissection repairs with stent implantation. The mean age was 43 years (±8.7) with 13 patients being women. Traumatic dissections were seen in 9 (40.9%) patients and spontaneous dissections in 13 (59.1%) patients. All patients were symptomatic and were started on antithrombotic therapy on diagnosis. Most common indications for treatment included recurrent ischemia despite antithrombotic therapy in 15 (55.5%) arteries and enlarging dissecting aneurysm in 4 (14.8%) arteries. Mean degree of stenosis was 79.1%. Mean number of stents used was 1.88 (range 1-4). There was 1 (4.5%) asymptomatic peri-procedural thromboembolic event. Median clinical follow-up was 14 months (range 3-40) and median imaging follow-up was 14 months (range 3-38). There was 1 (4.5%) case of recurrent transient ischemic attack. There was no death, significant restenosis or stroke in the territory of the treated vessel during the duration of the follow-up.

Conclusions: Endovascular stent reconstruction for the treatment of selected patients with progressively worsening carotid dissection despite medical management is feasible with acceptable immediate and long-term clinical and radiographic outcomes. To be able to draw more robust conclusions, further evaluation with larger number of patients and longer follow-up is needed.
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January 2015

Safety and predictors of aneurysm retreatment for remnant intracranial aneurysm after initial endovascular embolization.

J Neurointerv Surg 2014 Sep 16;6(7):490-4. Epub 2013 Aug 16.

Department of Neurology, Medical College of Wisconsin and Froedtert Hospital, Milwaukee, Wisconsin, USA Department of Neurosurgery, Medical College of Wisconsin and Froedtert Hospital, Milwaukee, Wisconsin, USA Department of Radiology, Medical College of Wisconsin and Froedtert Hospital, Milwaukee, Wisconsin, USA.

Introduction: Aneurysmal subarachnoid hemorrhage (SAH) is a rare but devastating form of stroke. Endovascular therapy has been criticized for its higher rate of recanalization and retreatment. The safety and predictors of retreatment are unknown. We report the clinical outcomes, imaging outcomes and predictors for aneurysm retreatment after initial endovascular embolization.

Method: We identified patients who underwent endovascular retreatment from July 2005 through November 2011. Aneurysm and patient data were collected. Periprocedural complications were reported as intraoperative perforation (IOP) or thromboembolic event (TEE). Aneurysm and patient characteristics were compared between aneurysms requiring retreatment and those not requiring retreatment to evaluate aneurysm retreatment predictors.

Results: A total of 111/871 (13%) aneurysms underwent retreatment. Two (0.2%) were retreated for recurrent acute SAH, 82 (74%) aneurysms were located in the anterior circulation, 47 (42%) required stent and 5 (5%) required balloon assist during retreatment. There were a total of 5 (5%) IOP and 6 (5%) TEE from which 2 (2%) and 1 (1%) were symptomatic, respectively. Overall symptomatic events rate were 2.7%. Patients were followed up for an average of 15±14 months. Seven (0.8%) aneurysms required a second retreatment without any recurrent SAH. Multivariable analysis revealed an OR for aneurysms requiring retreatment of 2.965 for aneurysms presenting as aneurysmal SAH, 1.791 for aneurysms in the posterior circulation and 1.053 for aneurysms with large dome size.

Conclusions: Aneurysm retreatment is a safe option without a significant increase in morbidity or mortality. SAH, posterior circulation aneurysms and larger aneurysm dome size are predictors of aneurysms requiring retreatment.
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September 2014

Design of the Vitesse Intracranial Stent Study for Ischemic Therapy (VISSIT) trial in symptomatic intracranial stenosis.

J Stroke Cerebrovasc Dis 2013 Oct 21;22(7):1131-9. Epub 2012 Dec 21.

Department of Neurology, Medical College of Wisconsin/Froedtert Hospital, Milwaukee, Wisconsin; Department of Neurosurgery, Medical College of Wisconsin/Froedtert Hospital, Milwaukee, Wisconsin; Department of Radiology, Medical College of Wisconsin/Froedtert Hospital, Milwaukee, Wisconsin. Electronic address:

Background: Patients with high-grade symptomatic intracranial stenosis (≥ 70%) have an increased risk of recurrent stroke despite medical treatment with antiplatelet or anticoagulant therapy. Intracranial stenting has been proposed as a viable treatment option for this high-risk patient population; however, evaluation of this therapy in randomized multicenter trials is needed. In this article, we present the design and methods of the Vitesse Intracranial Stent Study for Ischemic Therapy (VISSIT) trial for symptomatic intracranial stenosis.

Methods: The VISSIT trial is a randomized control study designed to evaluate the safety, probable benefit, and effectiveness of the PHAROS Vitesse neurovascular balloon-expandable stent system plus medical therapy versus medical therapy alone in patients with cerebral or retinal ischemia due to neurovascular stenosis (≥ 70%) for preventing the primary composite end point: stroke in the same territory (distal to the target lesion) as the presenting event within 12 months of randomization or hard transient ischemic attack in the same territory (distal to the target lesion) as the presenting event from day 2 through month 12 postrandomization.

Results: Enrollment began in February 2009 and was halted in January 2012 with 112 subjects enrolled into the study. Clinical follow-up will continue for the planned period of 12 months postrandomization.

Conclusions: The VISSIT trial may provide valuable insight into the use of balloon-expandable intracranial stent as a treatment option for high-risk patients. Lessons learned from this trial may better guide future clinical trial design on best patient selection, stenting techniques, and periprocedural management.
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October 2013

Complications of endovascular therapy for acute ischemic stroke and proposed management approach.

Neurology 2012 Sep;79(13 Suppl 1):S192-8

Department of Neurology, Medical College of Wisconsin, Milwaukee, WI, USA.

Over the past decade, endovascular therapy has emerged as a promising therapeutic approach for select patients with acute ischemic stroke. However, the morbidity, mortality, and complication rates in intra-arterial recanalization trials are higher than in the National Institute of Neurological Disorders and Stroke trial of IV tissue plasminogen activator. This review discusses common complications associated with endovascular therapy for acute ischemic stroke, avoidance of complications, and management of some of the common complications.
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September 2012

The Penumbra system for mechanical thrombectomy in endovascular acute ischemic stroke therapy.

Neurology 2012 Sep;79(13 Suppl 1):S135-41

Department of Neurology, Michigan State University, East Lansing, MI, USA.

Background: Efficacy of IV systemic thrombolysis is limited in patients with severe acute ischemic stroke and large-vessel occlusion. Mechanical thrombectomy has been the mainstay therapy in large-vessel occlusion. This review focuses on the Penumbra aspiration device.

Method: Literature review.

Results: The Penumbra prospective studies were reviewed and results are presented. The pivotal single-arm prospective trial that led to its approval by the US Food and Drug Administration enrolled 125 patients within 8 hours of symptom onset and demonstrated an 82% recanalization rate, to Thrombolysis in Myocardial Ischemia (TIMI) scores of 2 and 3. The risk of symptomatic intracranial hemorrhage was 10%, and modified Rankin Scale (mRS) score of ≤ 2 was 25%. In the postmarketing registry, 157 vessels were treated, with 87% achieving TIMI 2 and 3 recanalization and 41% having an mRS score of ≤ 2.

Conclusion: The Penumbra aspiration system is an effective tool to safely revascularize large-vessel occlusions in patients within 8 hours of onset of acute ischemic stroke who are either refractory to or excluded from IV thrombolytic therapy. Further prospective, randomized controlled trials will be needed to address whether this ability translates into neurologic improvement and better functional outcomes for our patients.
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September 2012

Venous sinus pulsatility and the potential role of dural incompetence in idiopathic intracranial hypertension.

Neurosurgery 2012 Oct;71(4):877-83

Department of Neurology, Medical College of Wisconsin and Froedtert Hospital, Milwaukee, Wisconsin 53226, USA.

Background: Idiopathic intracranial hypertension (IIH) remains a poorly understood and therapeutically challenging disease. Enthusiasm has emerged for endovascular therapy with stent reconstruction of dural sinus narrowing; however, a complete understanding of the hydrodynamic dysequilibrium is lacking.

Objective: To review and characterize catheter manometry findings including pulsatility changes within the venous sinuses in IIH.

Methods: Cases of venous sinus stent implantation for IIH were retrospectively reviewed.

Results: Three cases of venous sinus stent implantation for treatment of IIH are reported. All cases demonstrated severe narrowing (>70%) within the transverse sinus and a high pressure gradient across the lesion (>30 mm Hg). Stent implantation resulted in pulsatility attenuation, correction of pressure gradient, and improvement of flow.

Conclusion: We report the finding of high venous sinus pulsatility attenuation after stent implantation for dural sinus narrowing and propose the hypothesis that this finding is a marker of advanced dural sinus incompetence. This characteristic may be useful in identifying patients who would benefit from endovascular stent remodeling.
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October 2012

Surveillance imaging after intracranial stent implantation: non-invasive imaging compared with digital subtraction angiography.

J Neurointerv Surg 2013 Jul 28;5(4):361-5. Epub 2012 May 28.

Medical College of Wisconsin, Milwaukee, Wisconsin, USA.

Background: Digital subtraction angiography (DSA) is the gold standard imaging for detection of in-stent restenosis (ISR) but there is limited literature on optimal non-invasive surveillance imaging. In this study, the ability of CT angiography (CTA) and MR angiography (MRA) compared with DSA in recognizing ISR was assessed.

Methods: A single center database of patients treated with stent implantation for ICAD was accessed. All patients who underwent follow-up imaging with DSA paired with either MRA or CTA within 30 days were included. Two angiography readers and two non-invasive imaging readers measured restenosis with a submillimeter digital caliper. ISR was categorized as: none/minimal, mild (<50%), moderate (≥50-70%) or severe (≥70%). Analysis was performed with weighted κ statistics.

Results: 17 cases of individual stents that underwent surveillance imaging with paired DSA and CTA and five stents with paired DSA and MRA were identified. Of those undergoing DSA and CTA, inter-reader agreement produced κ=0.68 (95% CI 0.40 to 0.95) for DSA and κ=0.75 (95% CI 0.55 to 0.95) for CTA. Agreement across CTA and DSA was κ=0.36 (95% CI 0.26 to 0.52). Of those undergoing DSA and MRA, inter-reader agreement produced κ=0.71 (95% CI 0.27 to 1.00) for DSA and κ=1.00 (95% CI 1.00 to 1.00) for MRA. Agreement across MRA and DSA was κ=0.34 (95% CI 0.18 to 0.51).

Conclusions: Good inter-reader agreement exists within DSA, CTA and MRA. However, when comparing non-invasive imaging (CTA and MRA) with DSA, only fair agreement exists. These data suggest that CTA and MRA are not comparable to DSA for evaluation of ISR.
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July 2013

Multimodal endovascular therapy of traumatic and spontaneous carotid cavernous fistula using coils, n-BCA, Onyx and stent graft.

J Neurointerv Surg 2011 Sep 10;3(3):255-62. Epub 2011 Jan 10.

Department of Neurology, Medical College of Wisconsin and Froedtert Hospital, Milwaukee, Wisconsin 53226, USA.

Background And Purpose: Carotid cavernous fistula (CCF) can be classified as either direct or indirect according to the arterial feeder source. The current standard treatment for CCF is endovascular embolization. In this case series, 21 CCF (direct and indirect) embolization procedures were treated with multimodal endovascular therapy to explore safety, technique and clinical efficacy.

Method And Patients: The neurointerventional database was reviewed for all cases of CCF. Demographic information, indications for the procedure, presenting symptoms, endovascular therapy types, complications and procedure angiographic and clinical efficacy were collected.

Results: 21 CCF embolization procedures were performed using multimodal therapy on 15 patients (eight females and seven males) with a mean age of 56.4±22.4 years (15-90 years), with 60% traumatic CCF and 40% spontaneous CCF presenting mainly with typical visual symptoms. 10 patients were treated in one session, four patients underwent two sessions and one required three sessions of endovascular therapy. Complete fistula occlusion was achieved in 10/15 patients (73.3%) in one session and in 14/15 (93.3%) patients after two or more sessions. One patient's symptoms (case No 15) improved dramatically after the second session despite incomplete obliteration of the CCF. No periprocedural complications were reported. Long term follow-up showed one recurrence of the CCF with a mean follow-up time of 201±17.2 months (range 1-56 months). Patient No 6 was lost to follow-up.

Conclusion: Multimodal endovascular embolization of CCF appears to be safe with a high success rate of complete obliteration. This case series demonstrates complete occlusion in 73.3% of the patients after one session and in 93.3% after the second session.
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September 2011

Initial experience with the coaxial dual-lumen ascent balloon catheter for wide-neck aneurysm coil embolization.

Front Neurol 2011 19;2:52. Epub 2011 Aug 19.

Department of Neurology, Froedtert Hospital and Medical College of Wisconsin Milwaukee, WI, USA.

Introduction: Techniques for coil embolization of wide-neck cerebral aneurysms include the use of stents and temporary occlusion with compliant non-detachable balloons to safely allow dense packing of the aneurysm lumen with detachable coils. We describe the use of a new balloon device for assisting in wide-neck aneurysm coil treatment.

Methods: A single institution neuroendovascular database was accessed to identify cases in which the Ascent balloon (Codman Neurovascular, Raynham, MA, USA) was used for aneurysm coil embolization. Clinical, demographic, and angiographic data were obtained through chart review.

Results: Eleven cerebral aneurysm cases were treated using the Ascent balloon during the first 12-month period that the new device was available at our institution. Three of the patients presented with ruptured aneurysms. All aneurysms were large (maximum diameter 6 mm or greater), with an average maximum diameter of 9.4 mm, and an average neck diameter of 5.5 mm. Complete occlusion with coil embolization (Raymond class I) was achieved in all cases. The Ascent balloon was successfully positioned across the neck of the aneurysm in nine patients.

Conclusion: This initial experience demonstrates the feasibility and immediate outcomes of the coaxial dual-lumen design Ascent balloon catheter used as an assistive device in coil embolization of wide-neck cerebral aneurysms. This device contributes to the growing number of assistive devices for the treatment of complex cerebral aneurysms.
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November 2011

Cavernous carotid pseudoaneurysm after endoscopic sphenoid mucocele marsupialization.

Arch Otolaryngol Head Neck Surg 2010 Apr;136(4):407-10

Department of Otolaryngology, Medical College of Wisconsin, Milwaukee, WI, USA.

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April 2010

Stent-assisted parent artery occlusion of giant cerebrovascular aneurysms to avoid mass effect.

J Neuroimaging 2009 Oct 18;19(4):370-4. Epub 2009 May 18.

Neurointerventional Section, Department of Neurology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.

Background: Endovascular treatment of giant cerebrovascular aneurysms (GCA) may be challenging due to risk of worsening mass effect, thromboembolism, rupture, and recurrence. The purpose of this study was to provide a preliminary evaluation of GCA therapy using stent-assisted coil parent artery occlusion (PAO) to reduce the likelihood of mass effect, aneurysm recurrence, and vessel recanalization.

Materials And Methods: Five patients with GCAs were treated by PAO by deploying detachable coils within a Neuroform-3 stent across the aneurysm neck. Patients were monitored clinically to note any changes after treatment. Magnetic resonance angiography was performed 3 to 12 months after stent placement, and incomplete PAO and aneurysm recurrence were noted.

Results: Stent-assisted PAO was technically successful in all GCAs with no residual aneurysm filling and without any coil herniation into the aneurysm sac. None of the patients had recanalization of the vessel or GCA or clinical worsening over a follow-up period of 3-17 months. Symptomatic mass effect improved in 2 and resolved in 2 patients.

Conclusion: Based on our preliminary experience, stent-assisted PAO in GCAs is technically feasible and may be a valid option in patients who tolerate balloon test occlusion to minimize the likelihood of increased mass effect from coil embolization.
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October 2009

Pediatric cerebral angiography: analysis of utilization and findings.

Pediatr Neurol 2009 Feb;40(2):98-101

Department of Neurology, Medical College of Wisconsin and Froedtert Hospital, Milwaukee, Wisconsin 53226, USA.

Pediatric neuroendovascular procedures are being performed with increasing frequency, for various indications. Reported here is the experience of interventionally trained neurologists performing pediatric cerebral diagnostic angiography between August 1, 2005, and April 30, 2008, at a single tertiary institution. Data regarding patient demographics, diagnostic indication and angiographic diagnosis, procedural complications, and procedural specifications were recorded to assess practice patterns and to track procedural morbidity. In all, 42 patients had 46 procedures during the study period. Mean age was 9.97 years (standard deviation S.D. = 5.39; range, 0.3-18 years); 22/42 were male (52%). Known or suspected vascular malformation was the diagnostic indication for 20 patients; of these, 12 had an arteriovenous malformation, 5 had venous abnormalities, and 3 exhibited no angiographic vascular malformations. In 13 total procedures there was no angiographic pathology. General anesthesia was used in 29/46 procedures (63%). A total of 190 cerebral arteries were individually selected, with a mean number of vessels catheterized of 4.1 (S.D. = 1.7) per procedure. No procedural thromboembolic complications, iatrogenic arterial dissection, or neurologic or vascular access site complications occurred. In conclusion, pediatric cerebral angiography seems to be generally safe, although there should be a strong diagnostic indication, given the inherent procedural risk.
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February 2009

Interventional acute ischemic stroke therapy with intracranial self-expanding stent.

Stroke 2008 Aug 12;39(8):2392-5. Epub 2008 Jun 12.

Background And Purpose: Rapid and safe recanalization of occluded intracranial arteries in acute ischemic stroke (AIS) is challenging. Newly available self-expanding intracranial atherosclerotic stents (SEIS), which can be deployed rapidly and safely, make acute stenting an option for treating AIS. We present the feasibility of this technique.

Methods: A retrospective analysis evaluated procedural protocols and clinical response to treatment in patients with AIS treated with SEIS. Descriptive statistics are presented with initial and follow-up National Institutes of Health Stroke Scale and modified Rankin Score.

Results: Nine patients with AIS underwent acute SEIS placement. There was successful deployment of the Neuroform (n=4) and Wingspan (n=4/5) stents in the M1/M2 (n=5) and M3 (n=1) middle cerebral artery segments, intracranial internal carotid artery (one of 2), and intracranial vertebrobasilar junction (one). Mean time of SEIS deployment from AIS onset was 5.1 hours. Complete (Thrombolysis in Cerebral Ischemia/Thrombolysis in Myocardial Ischemia 3) and partial/complete (Thrombolysis in Cerebral Ischemia/Thrombolysis in Myocardial Ischemia 2 or 3) recanalization occurred in 67% and 89%, respectively. One intracranial hemorrhage (11%) and one acute in-stent thrombosis (successfully treated with abciximab and balloon angioplasty) occurred. Stroke-related mortality occurred in 3 of 9 (33%) patients and survivors had modified Rankin Score < or = 2. Follow-up angiography (mean, 8 months; range, 2 to 14 months) in 4 of 9 patients showed no stent restenosis.

Conclusions: This preliminary experience with SEIS in refractory AIS demonstrated the technical feasibility and high rate of recanalization with acute stenting. Long-term safety and strategies to limit in-stent thrombosis and optimize periprocedural management are crucial before initiating future randomized efficacy studies with SEIS in AIS refractory to standard therapy.
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August 2008

Takotsubo cardiomyopathy associated with seizures.

Neurocrit Care 2008 ;9(1):112-7

Department of Neurology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.

Background: Takotsubo syndrome is a reversible neuromyocardial failure that has been thought to be related to an acute catecholamine toxicity of the myocardium brought upon by a stressful event. The neurocritical care unit population is particularly vulnerable for this condition given the acute presentation of neurological emergencies, which most often can be catastrophic. We present a case series of this syndrome and a review of the literature.

Method: Our recent experience with three cases that were prospectively identified with the diagnosis of Takotsubo syndrome is reported with clinical presentation, evaluation, and management approach. Review of the literature is presented in the discussion.

Results: We present three episodes of Takotsubo neuromyocardial syndrome in two patients that were admitted to our neurointensive care unit that presented with seizures and had typical clinical presentation, echocardiographic and cardiac catheterization findings. All the episodes were treated with vasoactive medications, ventilatory support, afterload and preload reduction, and treatment of the underlying condition. There was complete reversal of their symptoms and findings in each episode.

Conclusions: Patients with critical neurological illnesses such as large ischemic or hemorrhagic stroke, status epilepticus, recurrent seizure activities as in our study may be at a higher risk for Takotsubo neuromyocardial syndrome.
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October 2008

Cerebral infarction associated with acute subarachnoid hemorrhage.

Neurocrit Care 2007 ;7(1):10-7

Neurological Intensive Care Unit, Division of Stroke and Critical Care, Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.

Background: Cerebral infarction is a common complication of aneurysmal subarachnoid hemorrhage (SAH), but usually occurs several days after onset as a complication of vasospasm or aneurysm repair. The frequency, causes, and clinical impact of acute infarction associated with the primary hemorrhage are poorly understood.

Methods: We evaluated the presence of cerebral infarction on admission CT in 487 patients admitted within 3 days of SAH onset to our center between July 1996 and September 2002. Infarctions due to angiography or treatment complications were rigorously excluded. Outcome at 3 months was assessed with the modified Rankin Scale.

Results: A total of 17 patients (3%) had acute infarction on admission CT; eight had solitary and nine had multiple infarcts. Solitary infarcts usually appeared in the vascular territory distal to the ruptured aneurysm, whereas multiple infarcts tended to be territorial and symmetric. Global cerebral edema (P < 0.001), coma on presentation (P = 0.001), intraventricular hemorrhage (P = 0.002), elevated APACHE-II physiological subscores (P = 0.026) and loss of consciousness at onset (P = 0.029) were associated with early cerebral infarction. Mortality (P = 0.003) and death or moderate-to-severe disability (mRS 4-6, P = 0.01) occurred more frequently in the early cerebral infarction group.

Conclusions: Early cerebral infarction on CT is a rare but devastating complication of acute SAH. The observed associations with coma, global cerebral edema, intraventricular hemorrhage, and loss of consciousness at onset suggest that intracranial circulatory arrest may play a role in the pathogenesis of this disorder.
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December 2007

A phase 2 study of tramiprosate for cerebral amyloid angiopathy.

Alzheimer Dis Assoc Disord 2006 Oct-Dec;20(4):269-74

Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

Background And Purpose: No treatments have been identified to lower the risk of intracerebral hemorrhage due to cerebral amyloid angiopathy (CAA). A potential approach to prevention is the use of agents that interfere with the pathogenic cascade initiated by the beta-amyloid peptide (Abeta). Tramiprosate (3-amino-1-propanesulfonic acid) is a candidate molecule shown in preclinical studies to reduce CAA in a transgenic mouse model.

Methods: We performed a 5-center phase 2 double-blinded trial to evaluate the safety, tolerability, and pharmacokinetics of tramiprosate in subjects with lobar intracerebral hemorrhage. Twenty-four subjects age > or =55 years with possible or probable CAA were randomized to receive 12 weeks of tramiprosate at 1 of 3 oral doses (50, 100, or 150 mg twice daily). Subjects were followed for clinical adverse effects, laboratory, vital sign, electrocardiogram, cognitive, or functional changes, appearance of new symptomatic or asymptomatic hemorrhages, and pharmacokinetic parameters.

Results: Enrolled subjects were younger (mean age 70.8+/-5.4, range 61 to 78) and had more advanced baseline disease (measured by number of previous hemorrhages) than consecutive subjects in a CAA natural history cohort. No concerning safety issues were encountered with treatment. Nausea and vomiting were the most common adverse events and were more frequent at high doses. Nine subjects had new symptomatic or asymptomatic hemorrhages during treatment; all occurred in subjects with advanced baseline disease, with no apparent effect of drug dosing assignment.

Conclusions: These data suggest that tramiprosate can be given safely to subjects with suspected CAA and support future efficacy trials.
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February 2007

Recent steps toward a reconstructive endovascular solution for the orphaned, complex-neck aneurysm.

Neurosurgery 2006 Nov;59(5 Suppl 3):S77-92; discussion S3-13

Department of Radiology, New York University Medical Center, New York 10016, USA.

Objective: The purposes of this article are to summarize recent developments and concerns in endovascular aneurysm therapy leading to the adjunctive use of endoluminal devices, to review the published literature on stent-supported coil embolization of cerebral aneurysms, and to describe our experience with this technique in a limited subgroup of problematic complex aneurysms over a medium-term follow-up period.

Methods: Between January 2003 and June 2004, 28 individuals among 157 patients with cerebral aneurysms we evaluated were identified as harboring aneurysms with exceptionally broad necks. Out of these 28 patients, 16 were treated with a combination of stents and detachable coils, preserving the parent artery. Recorded data included patient demographics, the clinical presentation, aneurysm location and characteristics, procedural details, and clinical and angiographic outcome.

Results: Over an 18-month period, 16 patients with large cerebral aneurysms additionally characterized by neck sizes between 7 and 14 mm were treated, using combined coil embolization of the aneurysm with stent reconstruction of the aneurysm neck. Thirteen out of the 16 aneurysms were occluded at angiographic reevaluation between 11 and 24 months (mean angiographic follow-up, 17.5 mo). There were no treatment-related deaths or clinically evident neurological complications. Thirteen patients experienced excellent clinical outcomes, with good outcomes in two patients and a poor visual outcome in one patient (mean clinical follow-up, 29 mo). A single technical complication occurred, involving transient nonocclusive stent-associated thrombus, which was treated uneventfully with abciximab.

Conclusion: Stent-supported coil embolization of large, complex-neck cerebral aneurysms seems to provide superior medium-term anatomic reconstruction of the parent artery compared with historic series of aneurysms treated exclusively with endosaccular coils. In the near future, increasingly sophisticated endoluminal devices offering higher coverage of the neck defect will likely enable more definitive endovascular treatment of complex cerebral aneurysms and further expand our ability to manipulate the vascular biology of the parent artery.
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November 2006

Cardiac troponin elevation, cardiovascular morbidity, and outcome after subarachnoid hemorrhage.

Circulation 2005 Nov;112(18):2851-6

Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY, USA.

Background: Cardiac troponin I (cTI) release occurs frequently after subarachnoid hemorrhage (SAH) and has been associated with a neurogenic form of myocardial injury. The prognostic significance and clinical impact of these elevations remain poorly defined.

Methods And Results: We studied 253 SAH patients who underwent serial cTI measurements for clinical or ECG signs of potential cardiac injury. These patients were drawn from an inception cohort of 441 subjects enrolled in the Columbia University SAH Outcomes Project between November 1998 and August 2002. Peak cTI levels were divided into quartiles or classified as undetectable. Adverse in-hospital events were prospectively recorded, and outcome at 3 months was assessed with the modified Rankin Scale. Admission predictors of cTI elevation included poor clinical grade, intraventricular hemorrhage, loss of consciousness at ictus, global cerebral edema, and a composite score of physiological derangement (all P< or =0.01). Peak cTI level was associated with an increased risk of echocardiographic left ventricular dysfunction (odds ratio [OR], 1.3 per quintile; 95% CI, 1.0 to 1.7; P=0.03), pulmonary edema (OR, 2.1 per quintile; 95% CI, 1.6 to 2.7; P<0.001), hypotension requiring pressors (OR, 1.9 per quintile; 95% CI, 1.5 to 2.3; P<0.001), and delayed cerebral ischemia from vasospasm (OR, 1.3 per quintile; 95% CI, 1.07 to 1.7; P=0.01). Peak cTI levels were predictive of death or severe disability at discharge after controlling for age, clinical grade, and aneurysm size (adjusted OR, 1.4 per quintile; 95% CI, 1.1 to 1.9; P=0.02), but this association was no longer significant at 3 months.

Conclusions: cTI elevation after SAH is associated with an increased risk of cardiopulmonary complications, delayed cerebral ischemia, and death or poor functional outcome at discharge.
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November 2005

Herniation secondary to critical postcraniotomy cerebrospinal fluid hypovolemia.

Neurosurgery 2005 Aug;57(2):286-92; discussion 286-92

Department of Neurosurgery, Columbia University, New York, New York 10032, USA.

Objective: Cerebrospinal fluid hypovolemia resulting in postural headaches is a well-known clinical entity, but severe forms of cerebrospinal fluid hypovolemia with altered mental status and signs of transtentorial herniation ("brain sag") have rarely been reported. This article describes the clinical features of brain sag after craniotomy in an attempt to increase recognition of this syndrome.

Methods: Between April 2001 and January 2003, 220 consecutive patients with subarachnoid hemorrhage were prospectively enrolled in the Columbia Subarachnoid Hemorrhage Outcomes Project; 137 underwent craniotomy for aneurysm clipping. Among these patients, the diagnosis of brain sag was made when all three of the following criteria were present: clinical signs of transtentorial herniation, head computed tomographic scans revealing effacement of the basal cisterns with an oblong brainstem, and improvement of symptoms after placement of the patient in the Trendelenburg position (-15 to -30 degrees). For each patient, the symptoms, clinical course, and subsequent response to treatment were characterized. In addition, brainstem dimensions were measured on computed tomographic scans taken before, during, and after resolution of brain sag. A "sag ratio" was generated for these time points by dividing the maximum anteroposterior distance by the maximum bipeduncular distance.

Results: Eleven (8.0%) of 137 aneurysmal subarachnoid hemorrhage patients treated by craniotomy and an intraoperative spinal drain met the criteria for brain sag. Signs of transtentorial herniation developed most commonly between 2 and 4 days postoperatively. Pupillary asymmetry was noted in 10 (91.0%) of 11 patients, whereas the other patient demonstrated extensor posturing. The Trendelenburg position reversed the symptoms in all patients. The mean sag ratios before, during, and after resolution of brain sag were 0.91 +/- 0.03 (mean +/- standard error), 1.18 +/- 0.03, and 0.91 +/- 0.03, respectively. This represented a 30.9% elongation of the brainstem during sag (P < 0.001) and a 23.6% change back to baseline after resolution of the syndrome (P < 0.002). There was no significant difference between the presag and postsag ratios.

Conclusion: Severe cerebrospinal fluid hypovolemia after craniotomy may produce a dramatic herniation syndrome that is completely reversed by the Trendelenburg position. Brain sag should be included in the differential diagnosis for acute postoperative clinical deterioration in this patient population.
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August 2005

Chemical meningitis after cerebral aneurysm treatment using two second-generation aneurysm coils: report of two cases.

Neurosurgery 2004 Nov;55(5):1222

Departments of Radiology and Neurological Surgery, Neurological Institute, Columbia and Cornell University Medical Centers, 710 West 168th Street, New York, NY 10032, USA.

Objective And Importance: In the quest for effective and durable endovascular aneurysm treatment, second-generation aneurysm coils endeavor to increase the biological healing response to the implanted material. We report two cases of large cerebral aneurysms treated concurrently with both available second-generation aneurysm coils and the subsequent development of symptomatic nonbacterial meningitis.

Clinical Presentation: Two previously healthy patients underwent endovascular treatment for large (>=2 cm) cerebral aneurysms. Both aneurysms were treated using multiple Hydrogel coils (MicroVention, Inc., Aliso Viejo, CA) and Matrix coils (Boston Scientific/Target, Fremont, CA). Careful aseptic technique was observed throughout each procedure, and prophylactic intravenous antibiotics were administered during the perioperative period to both patients. Treatment proceeded uneventfully in both cases with excellent aneurysm occlusion and no immediate postoperative neurological deficits.

Intervention: In both cases, the patients were discharged from hospital but quickly were readmitted with stigmata of meningitis. Imaging demonstrated durable occlusion of the aneurysms in both patients and also abnormalities indicative of perianeurysmal and diffuse intracranial inflammatory response. Complete septic workup failed to identify an organism in either patient. Both patients responded to treatment with corticosteroid medication used to modulate the inflammatory response induced by the coil implants.

Conclusion: Second-generation aneurysm coils were developed to promote more durable occlusion of cerebral aneurysms by promoting more complete volumetric aneurysm occlusion or by eliciting a more prolific inflammatory response. The concurrent use of Hydrogel and Matrix coil systems in large aneurysms may cause an exuberant inflammatory response with both local and systemic manifestations. Although vigilant evaluation and treatment for presumptive bacterial meningitis is required in all such cases, patients respond to immunomodulatory therapy with corticosteroids. More information to understand better the interaction of Hydrogel and Matrix coils is needed.
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November 2004

Predictors and impact of aneurysm rebleeding after subarachnoid hemorrhage.

Arch Neurol 2005 Mar;62(3):410-6

Department of Neurology, College of Physicians and Surgeons of Columbia University, New York, NY, USA.

Background: Aneurysm rebleeding has historically been an important cause of mortality after subarachnoid hemorrhage (SAH).

Objective: To describe the frequency and impact of rebleeding in the modern era of aneurysm care, which emphasizes early surgical or endovascular treatment.

Design: Inception cohort.

Setting: Tertiary care medical center.

Patients: A total of 574 patients enrolled in the Columbia University SAH Outcomes Project between August 1996 and June 2002. Early aneurysm repair was performed whenever feasible.

Main Outcome Measures: Rebleeding was defined by prespecified clinical and radiographic criteria, excluding prehospital, intraprocedural, and postrepair events. Functional outcome was assessed at 3 months with the modified Rankin Scale. Multiple logistic regression was used to identify predictors of rebleeding, poor functional outcome, and mortality.

Results: Rebleeding occurred in 40 (6.9%) of the 574 patients; most cases (73%) occurred within 3 days of ictus. Hunt-Hess grade on admission (odds ratio [OR], 1.92 per grade; 95% confidence interval [CI], 1.33-2.75; P<.001) and maximal aneurysm diameter (OR, 1.07/mm; 95% CI, 1.01-1.13; P = .005) were independent predictors of rebleeding. After controlling for Hunt-Hess grade and aneurysm size, rebleeding was associated with a markedly reduced chance of survival with functional independence (modified Rankin Scale score,
Conclusions: Despite an aggressive management strategy, rebleeding still occurred in 6.9% of patients and was associated with a dismal outcome. Poor Hunt-Hess grade and larger aneurysm size are related to rebleeding. Pharmacologic therapy to reduce the risk of rebleeding before aneurysm repair, particularly in patients with poor grade neurologic status and large aneurysms, deserves renewed attention.
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March 2005

Effect of prior statin use on functional outcome and delayed vasospasm after acute aneurysmal subarachnoid hemorrhage: a matched controlled cohort study.

Neurosurgery 2005 Mar;56(3):476-84; discussion 476-84

Department of Neurology, Division of Stroke and Critical Care Neurology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.

Objective: Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins), which exhibit beneficial cerebrovascular effects by modulating inflammation and nitric oxide production, have not been evaluated in acute aneurysmal subarachnoid hemorrhage (SAH) patients. The effect of prior statin use on 14-day functional outcome and on prevention of vasospasm-induced delayed cerebral ischemia (DCI) or stroke during hospitalization was analyzed.

Methods: We conducted a 1:2 matched (age, admission Hunt and Hess grade, vascular disease/risk history) cohort study of 20 SAH patients on statins and 40 SAH controls. The primary outcome was functional outcome at 14 days (Modified Lawton Physical Self-Maintenance Scale and Barthel Index scale scores). Secondary outcomes were 14-day mortality, Modified Rankin Scale score, DCI, DCI supported by angiography/transcranial Doppler [TCD], cerebral infarctions of any type, and TCD highest mean velocity elevation.

Results: Statin users demonstrated a significant protective effect on 14-day Barthel Index scale and Modified Lawton Physical Self-Maintenance Scale scores (77 +/- 10 versus 39 +/- 8, P = 0.003; 12 +/- 7 versus 19 +/- 9, P = 0.03, respectively). Moreover, statin users demonstrated a significantly lower incidence of DCI and DCI supported by angiography/TCD (10% versus 43%, P = 0.02; 5% versus 35%, P = 0.01, respectively), cerebral infarctions of any type (25% versus 63%, P = 0.01), and baseline-to-final TCD highest mean velocity change of 50 cm/s or greater (18% versus 51%, P = 0.03).

Conclusion: SAH statin users demonstrated significant improvement in 14-day functional outcome, a significantly lower incidence of DCI and cerebral infarctions of any type, as well as prevention of TCD highest mean velocity elevation. However, we did not find a significant statin impact on mortality or global outcome (Modified Rankin Scale) in this small sample. This study provides clinical evidence for the potential therapeutic benefit of statins after acute SAH.
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March 2005

Phenytoin exposure is associated with functional and cognitive disability after subarachnoid hemorrhage.

Stroke 2005 Mar 20;36(3):583-7. Epub 2005 Jan 20.

Department of Neurology, Northwestern University, Chicago, Ill, USA.

Background And Purpose: Phenytoin (PHT) is routinely used for seizure prophylaxis after subarachnoid hemorrhage (SAH), but may adversely affect neurologic and cognitive recovery.

Methods: We studied 527 SAH patients and calculated a "PHT burden" for each by multiplying the average serum level of PHT by the time in days between the first and last measurements, up to a maximum of 14 days from ictus. Functional outcome at 14 days and 3 months was measured with the modified Rankin scale, with poor functional outcome defined as dependence or worse (modified Rankin Scale > or =4). We assessed cognitive outcomes at 14 days and 3 months with the telephone interview for cognitive status.

Results: PHT burden was associated with poor functional outcome at 14 days (OR, 1.5 per quartile; 95% CI, 1.3 to 1.8; P<0.001), although not at 3 months (P=0.09); the effect remained (OR, 1.6 per quartile; 95% CI, 1.2 to 2.1; P<0.001) after correction for admission Glasgow Coma Scale, fever, stroke, age, National Institutes of Health Stroke Scale > or =10, hydrocephalus, clinical vasospasm, and aneurysm rebleeding. Seizure in hospital (OR, 4.1; 95% CI, 1.5 to 11.1; P=0.002) was associated with functional disability in a univariate model only. Higher quartiles of PHT burden were associated with worse telephone interview for cognitive status scores at hospital discharge (P<0.001) and at 3 months (P=0.003).

Conclusions: Among patients treated with PHT, burden of exposure to PHT predicts poor neurologic and cognitive outcome after SAH.
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March 2005