Publications by authors named "Aman B Patel"

85 Publications

Sex-specific differences in presentations and determinants of outcomes after endovascular thrombectomy for large vessel occlusion stroke.

J Neurol 2021 May 29. Epub 2021 May 29.

Neurology, Massachusetts General Hospital, 55 Fruit St, WAC-7-721, Boston, MA, USA.

Introduction: Sex-specific differences in ischemic stroke outcomes are prevalent. We sought to investigate sex differences in the determinants of reperfusion and functional outcomes after endovascular thrombectomy (EVT) for emergent large vessel occlusion ischemic stroke (ELVO).

Methods: Patients presenting to a single referral center with an anterior circulation ELVO that underwent EVT from 2011 to 2019 were included in this retrospective analysis. Sex differences in history, presentation, adequate reperfusion (TICI 2b-3), and 90-day good outcome [delta modified Rankin Scale (mRS) ≤ 2 from pre-stroke] were examined. Multivariable logistic regression analyses were performed to assess sex-specific associations with outcomes.

Results: Three hundred and eighty-one consecutive ELVO patients were identified. Women (N = 193) were older (75 vs 64 years, p < 0.0001), had more pre-stroke disability (17% vs 9%, p = 0.032), more atrial fibrillation (41% vs 30%, p = 0.033), but less carotid atherosclerosis (8% vs 16%, p = 0.027). Rates of TICI 2b-3 and good outcome were similar between sexes. Carotid atherosclerosis (OR 0.315, 95% CI 0.130, 0.762) and dissection (OR 0.124, 95% CI 0.027, 0.569) independently decreased the odds of TICI 2b-3 among men but not women. Older age, more severe stroke, and not achieving TICI 2b-3 independently decreased the odds of good outcome among both sexes, while prior stroke (OR 0.258, 95% CI 0.083, 0.797) and hemorrhagic transformation (OR 0.111, 0.021, 0.592) were determinants exclusive to men.

Conclusion: In a real-world analysis of ELVO stroke patients treated with EVT, we found that despite advanced age and more pre-stroke disability, women have comparable reperfusion rates and functional outcomes compared to men. Sex-specific determinants of reperfusion and functional outcome were identified that require further study.
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http://dx.doi.org/10.1007/s00415-021-10628-0DOI Listing
May 2021

The Woven EndoBridge device for ruptured intracranial aneurysms: international multicenter experience and updated meta-analysis.

Neuroradiology 2021 May 25. Epub 2021 May 25.

Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Neuroendovascular Program, 55 Fruit St, WAC 745, Boston, MA, USA.

Purpose: The Woven EndoBridge (WEB) can be used to treat wide-necked aneurysms without antiplatelet medications, suggesting it may have advantages in the setting of aneurysmal subarachnoid hemorrhage (aSAH). The goal was assessment of safety and efficacy of WEB in aSAH given the delayed nature of aneurysmal thrombosis.

Methods: An international retrospective analysis of patients with aSAH treated with WEB was conducted at 7 tertiary centers from 2016 to 2020. Outcomes included rates of rebleeding, retreatment, complications, and complete occlusion. Furthermore, a systematic review and meta-analysis was conducted from 2011 to 2020 assessing the same outcomes. All pooled event rates were calculated using a random effect model.

Results: Consecutive patients with aSAH harbored 25 aneurysms that were treated with 29 WEB devices. The mean age was 53 years, and 65% were female. Zero experienced rebleeding, 2 were retreated, 2 experienced complications, 16 were completely occluded at 3 months, and 21 were completed occluded at 9-12 months. Meta-analysis of 309 WEB treatments for aSAH from 7 case series revealed 2.5% (95% CI 1-5%) had rebleeding, 9% (95% CI 4-17%) were retreated, 17% (95% CI 10-30%) had complications, and 61% (95% CI 51-71%) were completely occluded at 3-6 months.

Conclusion: WEB embolization in the setting of aSAH provides similar protection against rebleeding with comparable retreatment rates to traditional approaches. However, there is a higher rate of incomplete radiographic occlusion and operative complications compared to WEB embolization of unruptured aneurysms. Long-term prospective studies are needed to fully delineate the role of WEB embolization in aSAH.
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http://dx.doi.org/10.1007/s00234-021-02727-6DOI Listing
May 2021

Evolutionary design of magnetic soft continuum robots.

Proc Natl Acad Sci U S A 2021 May;118(21)

Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;

Worldwide cardiovascular diseases such as stroke and heart disease are the leading cause of mortality. While guidewire/catheter-based minimally invasive surgery is used to treat a variety of cardiovascular disorders, existing passive guidewires and catheters suffer from several limitations such as low steerability and vessel access through complex geometry of vasculatures and imaging-related accumulation of radiation to both patients and operating surgeons. To address these limitations, magnetic soft continuum robots (MSCRs) in the form of magnetic field-controllable elastomeric fibers have recently demonstrated enhanced steerability under remotely applied magnetic fields. While the steerability of an MSCR largely relies on its workspace-the set of attainable points by its end effector-existing MSCRs based on embedding permanent magnets or uniformly dispersing magnetic particles in polymer matrices still cannot give optimal workspaces. The design and optimization of MSCRs have been challenging because of the lack of efficient tools. Here, we report a systematic set of model-based evolutionary design, fabrication, and experimental validation of an MSCR with a counterintuitive nonuniform distribution of magnetic particles to achieve an unprecedented workspace. The proposed MSCR design is enabled by integrating a theoretical model and the genetic algorithm. The current work not only achieves the optimal workspace for MSCRs but also provides a powerful tool for the efficient design and optimization of future magnetic soft robots and actuators.
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http://dx.doi.org/10.1073/pnas.2021922118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166154PMC
May 2021

Direct vs Indirect Revascularization in a North American Cohort of Moyamoya Disease.

Neurosurgery 2021 May 6. Epub 2021 May 6.

Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Background: In adults with ischemic moyamoya disease (MMD), the efficacy of direct vs indirect revascularization procedures remains a matter of debate.

Objective: To investigate the outcomes of ischemic MMD in a North American cohort treated by direct and indirect revascularizations.

Methods: We retrospectively reviewed medical records of adult patients with MMD with ischemic presentation from 1984 to 2018 at the Brigham and Women's Hospital and Massachusetts General Hospital who underwent either direct or indirect bypasses. Early postoperative events and outcome at more than 6 mo postoperatively were evaluated using multivariable logistic regression analyses. Multivariable Cox proportional hazards regression analyses were used to evaluate delayed ischemic and hemorrhagic events. Analyses were performed per hemisphere.

Results: A total of 95 patients with MMD and 127 hemispheres were included in this study. A total of 3.5% and 8.6% of patients had early surgical complications in the direct and indirect bypass cohorts, respectively (P = .24). Hemispheres with direct bypasses had fewer long-term ischemic and hemorrhagic events at latest follow-up (adjusted hazard ratio [HR] 0.19, 95% confidence interval [CI] 0.058-0.63, P = .007; median follow-up 4.5 [interquartile range, IQR 1-8] yr). There was no difference between the direct and indirect bypass groups when the endpoint was limited to infarction and hemorrhage only (P = .12). There was no difference in outcome (modified Rankin Scale [mRS] ≥ 3) between the 2 cohorts (P = .92).

Conclusion: There was no difference in early postoperative events, long-term infarction or hemorrhage, or clinical outcome between direct and indirect revascularization. However, there was a significant decrease in all ischemic and hemorrhagic events combined in direct revascularizations compared to indirect revascularizations.
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http://dx.doi.org/10.1093/neuros/nyab156DOI Listing
May 2021

#RadialFirst and #RadialForNeuro: A descriptive analysis of Twitter conversations regarding transradial access.

Neuroradiol J 2021 Apr 30:19714009211012363. Epub 2021 Apr 30.

Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, USA.

Background: Transradial access for neurointerventional procedures was adopted and modified from cardiovascular intervention and is increasingly established as a safe and effective alternative to transfemoral catheterization. As social media influences public opinion on medical treatment, this study analyzes Twitter conversations to elucidate social media's depiction of transradial access as a neurointerventional tool.

Materials And Methods: Twitter hashtags #RadialFirst and #RadialForNeuro were evaluated using a mixed-method analysis of quantitative social media metrics and qualitative thematic analysis.

Results: Between January 2015 and April 2020, 104,146 tweets from 141 countries employed the hashtag #RadialFirst (2015 (1); 2016 (0); 2017 (22,804); 2018 (33,074); 2019 (38,352); 2020 (9,915 January-April)). These generated 226,909,374 impressions and were retweeted 80,120 times by 13,707 users. Media was present in 62.5% of tweets (e.g. wrist image, angiographic runs) but only 14.5% had a reference article. Physicians authored 70.8% of tweets; interventional cardiologists accounted for 83% of top 100 influencers. #RadialForNeuro is more nascent (6 posts in 2019; 323 posts January-April 2020), with 392,662 impressions, and 254 retweets by 177 users; physicians authored 35.6%. Compared to #RadialFirst, #RadialforNeuro tweets were more likely to include media (76%), less likely to include citations (9.7%), and more likely to discuss complications and troubleshooting techniques.

Conclusion: Twitter activity regarding transradial access permits information dissemination and discussion on approach benefits and challenges. However, many posts arise from non-physician sources and lack links to peer-reviewed publication. The public should be mindful that tweets may reflect opinions, rather than experience or scientific evidence.
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http://dx.doi.org/10.1177/19714009211012363DOI Listing
April 2021

Electroencephalography, Hospital Complications, and Longitudinal Outcomes After Subarachnoid Hemorrhage.

Neurocrit Care 2021 Jan 22. Epub 2021 Jan 22.

Department of Neurology, Massachusetts General Hospital, 55 Fruit Street, Lunder 644, Boston, MA, 02114, USA.

Background: Following non-traumatic subarachnoid hemorrhage (SAH), in-hospital delayed cerebral ischemia is predicted by two chief events on continuous EEG (cEEG): new or worsening epileptiform abnormalities (EAs) and deterioration of cEEG background frequencies. We evaluated the association between longitudinal outcomes and these cEEG biomarkers. We additionally evaluated the association between longitudinal outcomes and other in-hospital complications.

Methods: Patients with nontraumatic SAH undergoing ≥ 3 days of cEEG monitoring were enrolled in a prospective study evaluating longitudinal outcomes. Modified Rankin Scale (mRS) was assessed at discharge, and at 3- and 6-month follow-up time points. Adjusting for baseline severity in a cumulative proportional odds model, we modeled the mRS ordinally and measured the association between mRS and two forms of in-hospital cEEG deterioration: (1) cEEG evidence of new or worsening epileptiform abnormalities and (2) cEEG evidence of new background deterioration. We compared the magnitude of these associations at each time point with the association between mRS and other in-hospital complications: (1) delayed cerebral ischemia (DCI), (2) hospital-acquired infections (HAI), and (3) hydrocephalus. In a secondary analysis, we employed a linear mixed effects model to examine the association of mRS over time (dichotomized as 0-3 vs. 4-6) with both biomarkers of cEEG deterioration and with other in-hospital complications.

Results: In total, 175 mRS assessments were performed in 59 patients. New or worsening EAs developed in 23 (39%) patients, and new background deterioration developed in 24 (41%). Among cEEG biomarkers, new or worsening EAs were independently associated with mRS at discharge, 3, and 6 months, respectively (adjusted cumulative proportional odds 4.99, 95% CI 1.60-15.6; 3.28, 95% CI 1.14-9.5; and 2.71, 95% CI 0.95-7.76), but cEEG background deterioration lacked an association. Among hospital complications, DCI was associated with discharge, 3-, and 6-month outcomes (adjusted cumulative proportional odds 4.75, 95% CI 1.64-13.8; 3.4; 95% CI 1.24-9.01; and 2.45, 95% CI 0.94-6.6), but HAI and hydrocephalus lacked an association. The mixed effects model demonstrated that these associations were sustained over longitudinal assessments without an interaction with time.

Conclusion: Although new or worsening EAs and cEEG background deterioration have both been shown to predict DCI, only new or worsening EAs are associated with a sustained impairment in functional outcome. This novel finding raises the potential for identifying therapeutic targets that may also influence outcomes.
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http://dx.doi.org/10.1007/s12028-020-01177-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822587PMC
January 2021

White Matter Acute Infarct Volume After Thrombectomy for Anterior Circulation Large Vessel Occlusion Stroke is Associated with Long Term Outcomes.

J Stroke Cerebrovasc Dis 2021 Mar 29;30(3):105567. Epub 2020 Dec 29.

Department of Neurology, Massachusetts General Hospital, Harvard Medical School, USA.

Objectives: Despite the proven efficacy of endovascular thrombectomy (EVT) for large vessel occlusion stroke, over half treated remain functionally disabled or die. Infarct topography may have implications for prognostication, patient selection, and the development of tissue-specific neuroprotective agents. We sought to quantify white matter injury in anterior circulation acute infarcts post-EVT to understand its significance and identify its determinants.

Materials And Methods: Demographics, history, presentations, and outcomes for consecutive patients treated with EVT were recorded in a prospectively maintained database at a single center. Acute infarct masks were coregistered to standard space. Standard atlases of white matter, cortex, and basal ganglia were used to determine region-specific infarct volumes.

Results: 167 individuals were identified with median age 69 years and 53% women. 85% achieved adequate reperfusion (TICI 2b-3) after EVT; 43% achieved 90-day functional independence (mRS 0-2). Median infarct volumes were 45cc (IQR 18-122) for total, 17cc (6-49) for white matter, 21cc (4-53) for cortex, and 5cc (1-8) for basal ganglia. The odds of 90-day mRS 0-2 were reduced in patients with larger white matter infarct volume (cc, OR=0.89, 95%CI=0.81-0.96), independent of cortex infarct volume, basal ganglia infarct volume, age, NIHSS, and TICI 2b-3 reperfusion. Reperfusion-to-MRI time was associated with white matter infarct volume (hr, β=0.119, p=0.017), but not cortical or basal ganglia infarct volume.

Conclusions: These data quantitatively describe region-specific infarct volumes after EVT and suggest the clinical relevance of white matter infarct volume as a predictor of long-term outcomes. Further study is warranted to examine delayed white matter infarction and the significance of specific white matter tracts.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880897PMC
March 2021

Treatment Approaches and Outcomes for Acute Anterior Circulation Stroke Patients with Tandem Lesions.

J Stroke Cerebrovasc Dis 2021 Feb 26;30(2):105478. Epub 2020 Nov 26.

Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, 55 Fruit St, Boston, MA 02114, USA.

Objectives: Endovascular thrombectomy (EVT) has revolutionized stroke care for large vessel occlusions (LVOs). However, over half treated remain functionally disabled or die. Patients with tandem lesions, or severe stenosis/occlusion of the cervical internal carotid artery (ICA) with intracranial LVO, may have technical EVT challenges and worse outcomes. We sought to compare treatments and outcomes for patients with anterior circulation tandem lesions versus isolated LVOs.

Materials And Methods: Consecutive tandem lesion and isolated intracranial LVO patients were identified at a single center. Demographics, medical history, presentations, treatments, and outcomes were collected and analyzed.

Results: From 381 EVT patients, 62 had tandem lesions related to atherosclerosis (74%) or dissection (26%). Compared to isolated intracranial LVOs, they were younger (63 vs 70, p = 0.003), had less atrial fibrillation (13% vs 40%, p < 0.0001), less adequate reperfusion (TICI 2b-3, 58% vs 82%, p < 0.0001), more intracranial hemorrhage (ICH, 13% vs 5%, p = 0.037), but similar 90-day functional independence (mRS 0-2, 34% vs 43%, p = 0.181). The cervical ICA was treated before intracranial EVT (57%), after (13%), not acutely (22%), or was inaccessible (8%). Acute cervical ICA treatments were stenting (57%) or angioplasty alone (13%). Neither acute stenting nor order of treatment was associated with outcomes (TICI 2b-3, ICH, or 90-day mRS 0-2). Among acutely stented, neither alteplase nor antiplatelets were associated with outcomes or stent patency.

Conclusions: Tandem lesions were associated with less reperfusion, more ICH, but similar 90-day functional independence. No treatment approach was associated with outcomes. These data illustrate the technical challenges of tandem lesion treatment and underscore the importance of developing new approaches.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855424PMC
February 2021

Toward a more inclusive paradigm: thrombectomy for stroke patients with pre-existing disabilities.

J Neurointerv Surg 2020 Oct 30. Epub 2020 Oct 30.

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

Background: Persons with pre-existing disabilities represent over one-third of acute stroke presentations, but account for a far smaller proportion of those receiving endovascular thrombectomy (EVT) and thrombolysis. This is despite existing ethical, economic, legal, and social directives to maximize equity for this vulnerable population. We sought to determine associations between baseline modified Rankin Scale (mRS) and outcomes after EVT.

Methods: Individuals who underwent EVT were identified from a prospectively maintained database. Demographics, medical history, presentations, treatments, and outcomes were recorded. Baseline disability was defined as baseline mRS≥2. Accumulated disability was defined as the delta between baseline mRS and absolute 90-day mRS.

Results: Of 381 individuals, 49 had baseline disability (five with mRS=4, 23 mRS=3, 21 mRS=2). Those with baseline disability were older (81 vs 68 years, P<0.0001), more likely female (65% vs 49%, P=0.032), had more coronary disease (39% vs 20%, P=0.006), stroke/TIA history (35% vs 15%, P=0.002), and higher NIH Stroke Scale (19 vs 16, P=0.001). Baseline mRS was associated with absolute 90-day mRS ≤2 (OR=0.509, 95%CI=0.370-0.700). However, baseline mRS bore no association with accumulated disability by delta mRS ≤0 (ie, return to baseline, OR=1.247, 95%CI=0.943-1.648), delta mRS ≤1 (OR=1.149, 95%CI=0.906-1.458), delta mRS ≤2 (OR 1.097, 95% CI 0.869-1.386), TICI 2b-3 reperfusion (OR=0.914, 95%CI=0.712-1.173), final infarct size (P=0.853, β=-0.014), or intracerebral hemorrhage (OR=0.521, 95%CI=0.244-1.112).

Conclusions: While baseline mRS was associated with absolute 90-day disability, there was no association with accumulated disability or other outcomes. Patients with baseline disability should not be routinely excluded from EVT based on baseline mRS alone.
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http://dx.doi.org/10.1136/neurintsurg-2020-016783DOI Listing
October 2020

Infarct Growth despite Endovascular Thrombectomy Recanalization in Large Vessel Occlusive Stroke.

J Neuroimaging 2021 01 29;31(1):155-164. Epub 2020 Oct 29.

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

Background And Purpose: Endovascular thrombectomy (EVT) has revolutionized large vessel occlusion stroke care. However, not all patients with good endovascular results achieve good outcomes. We sought to understand the clinical significance of magnetic resonance imaging defined infarct growth despite adequate reperfusion and identify associated clinical and radiographic variables.

Methods: History, presentation, treatments, and outcomes for consecutive EVT patients at a referral center were collected. Adequate reperfusion was defined as thrombolysis in cerebral infarction (TICI) score 2b-3. Region-specific infarct volumes in white matter, cortex, and basal ganglia were determined on diffusion-weighted imaging. Infarct growth was defined as post-EVT minus pre-EVT volume. Good outcome was defined as 90-day modified Rankin Scale ≤2.

Results: Forty-four patients with adequate reperfusion were identified with median age 72 years; 64% were women. Each region showed infarct growth: white matter (median pre-EVT 7 cubic centimeters [cc], post-EVT 16 cc), cortex (4 cc, 15 cc), basal ganglia (2 cc, 4 cc), total (20 cc, 39 cc). In multivariable regression, total infarct growth independently decreased the odds of good outcome (odds ratio = .946, 95% CI = .897, .998). Further multivariable analyses for determinants of infarct growth identified female sex was associated with less total growth (β = -.294, P = .042), TICI 3 was associated with less white matter growth (β = -.277, P = .048) and cortical growth (β = -.335, P = .017), and both female sex (β = -.332, P = .015) and coronary disease (β = -.337, P = .015) were associated with less cortical growth.

Conclusions: Infarct growth occurred despite adequate reperfusion, disproportionately in the cortex, and independently decreased the odds of good outcome. Infarct growth occurred while patients were hospitalized and may represent a therapeutic target. Potential determinants of region-specific infarct growth were identified that require confirmation in larger studies.
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http://dx.doi.org/10.1111/jon.12796DOI Listing
January 2021

Microsurgical Clipping of Intracranial Aneurysms in the Endovascular Era.

Cardiol Rev 2021 Jan/Feb;29(1):15-19

From the Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA.

The treatment of intracranial aneurysms (IA) began in the late 19th century. Some degree of controversy has always surrounded the best treatment modality for IA. Cushing and Dandy debated about cervical carotid ligation as the only surgical alternative before the introduction of microsurgical clipping. In the early 21st century, the debate has centered on surgical versus^ endovascular techniques. With the advent of newer endovascular techniques and devices, there has been a dramatic shift in treatment paradigms toward endovascular intervention that is preferred by both physicians and patients. However, there will always be a need for microsurgical cerebrovascular expertise since some aneurysms cannot or should not be embolized. This creates a difficult conundrum as only the most complex of aneurysms will require open surgery, but the lack of volume and training will be a challenge in teaching and maintaining the surgical expertise required to safely treat them. The purpose of this review is to discuss the history of IA treatment and critically evaluate the current state of the art of IA treatment, with a specific focus on the necessary role microsurgical clipping continues to play in the current treatment landscape.
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http://dx.doi.org/10.1097/CRD.0000000000000343DOI Listing
September 2020

Long-term follow-up results of the SMART coil in the endovascular treatment of intracranial aneurysms.

Interv Neuroradiol 2021 Apr 15;27(2):200-206. Epub 2020 Sep 15.

Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA.

Background: The Penumbra SMART coil is a novel device that becomes progressively softer from its distal to proximal end to maximize coil packing and prevent microcatheter prolapse or coil migration. Here, we report a large series of patients detailing the long-term experience of a single institution using the SMART coil among patients with intracranial aneurysms (IAs).

Methods: Prospective data of 105 consecutive patients with 106 IAs treated using SMART coils was collected between March 2015 and July 2018. Clinical and angiographic data were analyzed.

Results: Forty-nine patients (46.7%) presented with subarachnoid hemorrhage and 16 (14.2%) had recurrent aneurysms. Two patients had minor intraprocedural ruptures and remained neurologically stable. One patient had a thromboembolic complication with progressive neurologic decline. There was only one case microcatheter prolapse related to placement of a stent before coiling. An initial post-treatment modified Raymond-Roy Occlusion Classification (mRROC) I or II closure was achieved in 56 (52.8%) aneurysms. The average time to last follow-up was 8.4 months at which 70 (81.4%) aneurysms had mRROC I or II occlusion and a major recurrence was seen in 5 (5.8%) patients. Thirteen (12.3%) aneurysms required re-treatment of which one aneurysm was clipped.

Conclusions: The Penumbra SMART coil is safe and effective for the endovascular treatment of appropriately selected IAs. Additional studies at multiple centers comparing safety and efficacy profile over long-term periods to other mainstream coils are necessary.
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http://dx.doi.org/10.1177/1591019920956890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050520PMC
April 2021

Sex and Genetic Background Effects on the Outcome of Experimental Intracranial Aneurysms.

Stroke 2020 10 11;51(10):3083-3094. Epub 2020 Sep 11.

Neurovascular Research Laboratory, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown (T.Y., T.S., T.T., D.Y.C., T.Q., A.M., C.A.).

Background And Purpose: Intracranial aneurysm formation and rupture risk are, in part, determined by genetic factors and sex. To examine their role, we compared 3 mouse strains commonly used in cerebrovascular studies in a model of intracranial aneurysm formation and rupture.

Methods: Intracranial aneurysms were induced in male CD1 (Crl:CD1[ICR]), male and female C57 (C57BL/6NCrl), and male 129Sv (129S2/SvPasCrl or 129S1/SvImJ) mice by stereotaxic injection of elastase at the skull base, combined with systemic deoxycorticosterone acetate-salt hypertension. Neurological deficits and mortality were recorded. Aneurysms and subarachnoid hemorrhage grades were quantified postmortem, either after spontaneous mortality or at 7 to 21 days if the animals survived. In separate cohorts, we examined proinflammatory mediators by quantitative reverse transcriptase-polymerase chain reaction, arterial blood pressure via the femoral artery, and the circle of Willis by intravascular latex casting.

Results: We found striking differences in aneurysm formation, rupture, and postrupture survival rates among the groups. 129Sv mice showed the highest rates of aneurysm rupture (80%), followed by C57 female (36%), C57 male (27%), and CD1 (21%). The risk of aneurysm rupture and the presence of unruptured aneurysms significantly differed among all 3 strains, as well as between male and female C57. The same hierarchy was observed upon Kaplan-Meier analysis of both overall survival and deficit-free survival. Subarachnoid hemorrhage grades were also more severe in 129Sv. CD1 mice showed the highest resistance to aneurysm rupture and the mildest outcomes. Higher mean blood pressures and the major phenotypic difference in the circle of Willis anatomy in 129Sv provided an explanation for the higher incidence of and more severe aneurysm ruptures. TNFα (tumor necrosis factor-alpha), IL-1β (interleukin-1-beta), and CCL2 (chemokine C-C motif ligand 2) expressions did not differ among the groups.

Conclusions: The outcome of elastase-induced intracranial aneurysm formation and rupture in mice depends on genetic background and shows sexual dimorphism.
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http://dx.doi.org/10.1161/STROKEAHA.120.029651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530050PMC
October 2020

Experience With the Pipeline Embolization Device for Posterior Circulations Aneurysms: A Multicenter Cohort Study.

Neurosurgery 2020 Jul 6. Epub 2020 Jul 6.

Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China.

Background: The Pipeline Embolization Device (PED; Medtronic) has been used off-label for the treatment of challenging posterior circulation aneurysms. Data on this modality are primarily limited to small retrospective single-center series.

Objective: To assess safety and efficacy of this treatment by establishing an international, multicenter collaboration.

Methods: Consecutive posterior circulation aneurysms treated with the PED from 2012 to 2019 across 11 neurovascular centers were retrospectively reviewed. Baseline demographics, aneurysm and treatment characteristics, complications, occlusion status, and functional outcome were assessed.

Results: There were 149 posterior circulation aneurysms treated with PED in 146 patients. A total of 24 (16.4%) patients presented with subarachnoid hemorrhage. Most aneurysms were dissecting/blister (36.2%) in morphology, followed by saccular (35.6%) and fusiform (28.2%). The most common locations were the vertebral (51.7%) and basilar arteries (22.8%). Complete or near-complete occlusion (>90%) was achieved in 90.9% of aneurysms at a median follow-up of 12 mo. Dissecting/blister aneurysms were most likely to occlude (P = .06). Symptomatic neurologic complications occurred in 9.4% of aneurysms, associated with larger size, ruptured presentation, presentations with brain stem compression, cranial nerve palsy, or stroke. Favorable functional outcome (modified Rankin Score 0-2) was achieved in 86.2% of patients. There were 6 fatalities of which 4 occurred in aneurysmal subarachnoid hemorrhage patients.

Conclusion: This multicenter study shows that PED for the treatment of posterior circulation is preferentially used for the treatment of fusiform and dissecting/blister aneurysm morphologies. Despite the challenges presented by these less-common morphologies, flow diversion may be performed with a neurologic complication rate of about 10% and favorable long-term aneurysm occlusion rates.
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http://dx.doi.org/10.1093/neuros/nyaa277DOI Listing
July 2020

Comparison of PED and FRED flow diverters for posterior circulation aneurysms: a propensity score matched cohort study.

J Neurointerv Surg 2021 Feb 1;13(2):153-158. Epub 2020 Jul 1.

Department of Neuroradiology, Friedrich Alexander University Erlangen Nuremberg Faculty of Medicine, Erlangen, Bayern, Germany.

Background: Flow diversion is a common endovascular treatment for cerebral aneurysms, but studies comparing different types of flow diverters are scarce.

Objective: To perform a propensity score matched cohort study comparing the Pipeline Embolization Device (PED) and Flow Redirection Intraluminal Device (FRED) for posterior circulation aneurysms.

Methods: Consecutive aneurysms of the posterior circulation treated at 25 neurovascular centers with either PED or FRED were collected. Propensity score matching was used to control for age, duration of follow-up imaging, adjunctive coiling, and aneurysm location, size, and morphology; previously ruptured aneurysms were excluded. The two devices were compared for the following outcomes: procedural complications, aneurysm occlusion, and functional outcome.

Results: A total of 375 aneurysms of the posterior circulation were treated in 369 patients. The PED was used in 285 (77.2%) and FRED in 84 (22.8%) procedures. Aneurysms treated with the PED were more commonly fusiform and larger than those treated with FRED. To account for these important differences, propensity score matching was performed resulting in 33 PED and FRED unruptured aneurysm pairs. No differences were found in occlusion status and neurologic thromboembolic or hemorrhagic complications between the two devices. The proportion of patients with favorable functional outcome was higher with FRED (100% vs 87.9%, p=0.04).

Conclusion: Comparative analysis of PED and FRED for the treatment of unruptured posterior circulation aneurysms did not identify significant differences in aneurysm occlusion or neurologic complications. Variations in functional outcomes warrant additional investigations.
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http://dx.doi.org/10.1136/neurintsurg-2020-016055DOI Listing
February 2021

Reply to author: Further expansion on the horizon? Thrombectomy for stroke after cardiothoracic surgery.

J Thorac Cardiovasc Surg 2020 08 17;160(2):e49-e50. Epub 2020 Apr 17.

Department of Neurosurgery, Massachusetts General Hospital, Boston, Mass; Department of Neurology, Massachusetts General Hospital, Boston, Mass.

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http://dx.doi.org/10.1016/j.jtcvs.2020.02.104DOI Listing
August 2020

Evaluation of andexanet alfa and four-factor prothrombin complex concentrate (4F-PCC) for reversal of rivaroxaban- and apixaban-associated intracranial hemorrhages.

J Thromb Haemost 2020 07 12;18(7):1637-1647. Epub 2020 May 12.

Department of Pharmacy, Massachusetts General Hospital, Boston, MA, USA.

Background/objective: Before approval of andexanet alfa, off-label treatment with 4-factor prothrombin complex concentrate (4F-PCC) was often utilized for the management of life-threatening hemorrhages associated with oral factor Xa inhibitors. We evaluated the operational processes and outcomes of patients with oral factor Xa inhibitor-associated intracranial hemorrhages (ICH) treated with andexanet alfa or 4F-PCC.

Methods: We performed a retrospective, single-center case series of rivaroxaban or apixaban-associated ICH between 2016-2019 treated with andexanet alfa or 4F-PCC. Good or excellent hemostatic effectiveness, good functional outcome (Glasgow Outcome Score [GOS]> 3) at hospital discharge, and incidence of thrombosis within 30 days were reported.

Results: Eighteen patients were included in the andexanet alfa cohort and 11 in the 4F-PCC cohort. Excellent or good hemostasis occurred in 88.9% of andexanet alfa-treated patients and 60% of 4F-PCC-treated patients. Good functional outcome on discharge occurred in 55.6% of andexanet alfa-treated patients and 9.1% of 4F-PCC-treated patients. Thrombotic complications occurred in 16.7% of andexanet alfa-treated patients and 9.1% of 4F-PCC-treated patients. Median order-to-administration time was 1.1 hours [0.8-1.4] versus 0.5 hours [0.1-0.8] in the andexanet alfa and 4F-PCC group, respectively. The median cost of therapy was $29970/patient versus $6925/patient in the andexanet alfa and 4F-PCC group, respectively.

Conclusions: We observed higher rates of occurrence of good or excellent hemostasis and GOS > 3 on hospital discharge and increased incidence of thrombosis in patients who received andexanet alfa compared to 4F-PCC for oral factor Xa inhibitor reversal. However, patients receiving 4F-PCC had lower pre-reversal Glasgow Coma Scale (GCS)score and larger pre-reversal ICH volume.
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http://dx.doi.org/10.1111/jth.14838DOI Listing
July 2020

Soluble ST2 Is Associated With New Epileptiform Abnormalities Following Nontraumatic Subarachnoid Hemorrhage.

Stroke 2020 04 11;51(4):1128-1134. Epub 2020 Mar 11.

From the Department of Neurology (I.A.L., S.F.Z., M.B.W., R.L.S., T.L.-M., W.T.K., E.S.R.), Massachusetts General Hospital, Boston.

Background and Purpose- We evaluated the association between 2 types of predictors of delayed cerebral ischemia after nontraumatic subarachnoid hemorrhage, including biomarkers of the innate immune response and neurophysiologic changes on continuous electroencephalography. Methods- We studied subarachnoid hemorrhage patients that had at least 72 hours of continuous electroencephalography and blood samples collected within the first 5 days of symptom onset. We measured inflammatory biomarkers previously associated with delayed cerebral ischemia and functional outcome, including soluble ST2 (sST2), IL-6 (interleukin-6), and CRP (C-reactive protein). Serial plasma samples and cerebrospinal fluid sST2 levels were available in a subgroup of patients. Neurophysiologic changes were categorized into new or worsening epileptiform abnormalities (EAs) or new background deterioration. The association of biomarkers with neurophysiologic changes were evaluated using the Wilcoxon rank-sum test. Plasma and cerebrospinal fluid sST2 were further examined longitudinally using repeated measures mixed-effects models. Results- Forty-six patients met inclusion criteria. Seventeen (37%) patients developed new or worsening EAs, 21 (46%) developed new background deterioration, and 8 (17%) developed neither. Early (day, 0-5) plasma sST2 levels were higher among patients with new or worsening EAs (median 115 ng/mL [interquartile range, 73.8-197]) versus those without (74.7 ng/mL [interquartile range, 44.8-102]; =0.024). Plasma sST2 levels were similar between patients with or without new background deterioration. Repeated measures mixed-effects modeling that adjusted for admission risk factors showed that the association with new or worsening EAs remained independent for both plasma sST2 (β=0.41 [95% CI, 0.09-0.73]; =0.01) and cerebrospinal fluid sST2 (β=0.97 [95% CI, 0.14-1.8]; =0.021). IL-6 and CRP were not associated with new background deterioration or with new or worsening EAs. Conclusions- In patients admitted with subarachnoid hemorrhage, sST2 level was associated with new or worsening EAs but not new background deterioration. This association may identify a link between a specific innate immune response pathway and continuous electroencephalography abnormalities in the pathogenesis of secondary brain injury after subarachnoid hemorrhage.
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http://dx.doi.org/10.1161/STROKEAHA.119.028515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123848PMC
April 2020

Erratum: Prolonged monitoring of cerebral blood flow and autoregulation with diffuse correlation spectroscopy in neurocritical care patients.

Neurophotonics 2020 01 20;7(1):019801. Epub 2020 Feb 20.

Massachusetts General Hospital, Department of Neurology, Boston, Massachusetts, United States.

[This corrects the article DOI: 10.1117/1.NPh.5.4.045005.].
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http://dx.doi.org/10.1117/1.NPh.7.1.019801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7032410PMC
January 2020

Initial experience with React 68 aspiration catheter.

Interv Neuroradiol 2020 Jun 22;26(3):358-363. Epub 2020 Jan 22.

Department of Neurosurgery, the Massachusetts General Hospital, Boston, MA, USA.

Introduction: We describe our initial experience with the React 68 catheter (Medtronic, Dublin, Ireland), an FDA-approved catheter designed for aspiration in cases of emergent large vessel occlusion, as compared with the ACE 68 catheter (Penumbra, Alameda, CA).

Methods: This observational study followed consecutive patients treated with the React catheter over a seven-month period at a comprehensive stroke center. Use of the device was per discretion of the operator. Patient demographics, thrombectomy technique, reperfusion scoring, and disposition were assessed. Performance was compared with patients treated with the ACE 68 catheter over a comparable period.

Results: We treated 47 patients using the React 68 catheter using either aspiration alone or a combination of aspiration and stent retriever technique. The catheter was used in a variety of circumstances including proximal and distal occlusions involving the anterior and posterior circulation. Modified TICI 2b-3 was achieved in 45 of the 47 patients. The React 68 was comparable to the ACE 68 by all performance measures.

Conclusion: The React 68 catheter is a large-bore reperfusion catheter with trackability suitable for use in direct aspiration for recanalization of emergent large vessel occlusion.
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http://dx.doi.org/10.1177/1591019919898923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7254626PMC
June 2020

High-throughput metabolite profiling: identification of plasma taurine as a potential biomarker of functional outcome after aneurysmal subarachnoid hemorrhage.

J Neurosurg 2019 Nov 22:1-8. Epub 2019 Nov 22.

3Division of Neurocritical Care and Center for Genomic Medicine, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts; and.

Objective: Metabolite profiling (or metabolomics) can identify candidate biomarkers for disease and potentially uncover new pathways for intervention. The goal of this study was to identify potential biomarkers of functional outcome after subarachnoid hemorrhage (SAH).

Methods: The authors performed high-throughput metabolite profiling across a broad spectrum of chemical classes (163 metabolites) on plasma samples taken from 191 patients with SAH who presented to Massachusetts General Hospital between May 2011 and October 2016. Samples were drawn at 3 time points following ictus: 0-5, 6-10, and 11-14 days. Elastic net (EN) and LASSO (least absolute shrinkage and selection operator) machine learning analyses were performed to identify metabolites associated with 90-day functional outcomes as assessed by the modified Rankin Scale (mRS). Additional univariate and multivariate analyses were then conducted to further examine the relationship between metabolites and clinical variables and 90-day functional outcomes.

Results: One hundred thirty-seven (71.7%) patients with aneurysmal SAH met the criteria for inclusion. A good functional outcome (mRS score 0-2) at 90 days was found in 79 (57.7%) patients. Patients with good outcomes were younger (p = 0.002), had lower admission Hunt and Hess grades (p < 0.0001) and modified Fisher grades (p < 0.0001), and did not develop hydrocephalus (p < 0.0001) or delayed cerebral ischemia (DCI) (p = 0.049). EN and LASSO machine learning methods identified taurine as the leading metabolite associated with 90-day functional outcome (p < 0.0001). Plasma concentrations of the amino acid taurine from samples collected between days 0 and 5 after aneurysmal SAH were 21.9% (p = 0.002) higher in patients with good versus poor outcomes. Logistic regression demonstrated that taurine remained a significant predictor of functional outcome (p = 0.013; OR 3.41, 95% CI 1.28-11.4), after adjusting for age, Hunt and Hess grade, modified Fisher grade, hydrocephalus, and DCI.

Conclusions: Elevated plasma taurine levels following aneurysmal SAH predict a good 90-day functional outcome. While experimental evidence in animals suggests that this effect may be mediated through downregulation of pro-inflammatory cytokines, additional studies are required to validate this hypothesis in humans.
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http://dx.doi.org/10.3171/2019.9.JNS191346DOI Listing
November 2019

Multimodal cerebral arteriovenous malformation treatment: a 12-year experience and comparison of key outcomes to ARUBA.

J Neurosurg 2019 Nov 1:1-10. Epub 2019 Nov 1.

1Department of Radiology, Massachusetts General Hospital, Harvard Medical School.

Objective: Curative treatment of unruptured brain arteriovenous malformations (AVMs) remains controversial after the only randomized controlled trial, A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA), was halted prematurely because interim analysis revealed superiority of the medical management group. In contrast, meta-analyses of retrospective cohorts suggest that intervention is much safer than was found in ARUBA.

Methods: The authors retrospectively analyzed 318 consecutive adult patients with brain AVMs treated at their institution with embolization, surgery, and/or proton beam radiosurgery. Analysis was performed in 142 ARUBA-eligible patients (baseline modified Rankin Scale [mRS] score 0-1, no history of hemorrhage), and results were compared to primary and secondary outcomes from ARUBA, as well as to natural history cohorts.

Results: The annualized stroke rate (hemorrhagic or ischemic) in this cohort was 1.8%, 4.9% in the first 12 months and 0.8% after the first 12 months, which was lower than in natural history studies and the ARUBA medical management arm (p = 0.001). The primary ARUBA endpoint of symptomatic stroke was reached in 13 patients (9.2%), which compares favorably to the ARUBA intervention arm (39.6%, p = 0.0001) and is similar to the ARUBA medical management arm (9.2%, p = 1.0). The secondary ARUBA endpoint (mRS score ≥ 2 at 5 years of follow-up) was reached in 14.3% of patients, compared to 40.5% in the ARUBA intervention arm (p = 0.002) and 16.7% in the ARUBA medical management arm (p = 0.6).

Conclusions: This multimodal approach to the selection and treatment of patients with brain AVMs yields good clinical outcomes with key safety endpoints (stroke, death, and mRS score 0-1) better than the ARUBA intervention arm and similar to the ARUBA medical arm at 5 years of follow-up. Results compare favorably to natural history cohorts at longer follow-up times. This suggests that tertiary care centers with integrated programs, expertise in patient selection, and individualized treatment approaches may allow for better clinical outcomes than reported in ARUBA. It supports current registry studies and merits consideration of future randomized controlled trials in patients with brain AVMs.
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http://dx.doi.org/10.3171/2019.8.JNS19998DOI Listing
November 2019

Soluble ST2 links inflammation to outcome after subarachnoid hemorrhage.

Ann Neurol 2019 09 30;86(3):384-394. Epub 2019 Jul 30.

Division of Neurocritical Care, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA.

Objective: To investigate whether soluble growth stimulation expressed gene 2 (sST2), a prognostic marker in cardiovascular and inflammatory disorders, is associated with neurological injury after aneurysmal subarachnoid hemorrhage (SAH).

Methods: We studied SAH patients from 2 independent cohorts. Outcome assessments included functional status at 90 days using the modified Rankin Scale (mRS), mortality, and delayed cerebral ischemia (DCI). The relationships between sST2 plasma level and outcome measures were assessed in both cross-sectional and longitudinal analysis. Primary blood mononuclear cells from SAH patients and elective aneurysm controls were analyzed by multiparameter flow cytometry.

Results: In the discovery cohort, sST2 predicted 90-day mRS 3-6 (C index = 0.724, p < 0.001) and mortality in Kaplan-Meier analysis (p < 0.001). The association with functional status was independent of age, sex, World Federation of Neurosurgical Societies score, modified Fisher score, treatment modality, and cardiac comorbidities (adjusted odds ratio = 2.28, 95% confidence interval = 1.04-5.00, p = 0.039). Higher sST2 concentration was observed in those patients with DCI (90.8 vs 53.7ng/ml, p = 0.003). These associations were confirmed in a replication cohort. In patients with high sST2, flow cytometry identified decreased expression of CD14 (4.27 × 10 ± 2,950 arbitrary unit (AU) vs 5.64 × 10 ± 1,290 AU, p < 0.001), and increased expression of CD16 (39,960 ± 272 AU vs 34,869 ± 183 AU, p < 0.001).

Interpretation: Plasma sST2 predicts DCI, functional outcome, and mortality after SAH, independent of clinical and radiographic markers. Elevated sST2 is also associated with changes in CD14 CD16 monocytes. ANN NEUROL 2019;86:384-394.
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http://dx.doi.org/10.1002/ana.25545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6727654PMC
September 2019

Comparison of predictive grading systems for procedural risk in endovascular treatment of brain arteriovenous malformations: analysis of 104 consecutive patients.

J Neurosurg 2019 Jun 14:1-9. Epub 2019 Jun 14.

2Neurosurgery, and.

Objective: Several grading systems for procedural risk in the endovascular treatment of brain arteriovenous malformations (AVMs) have been proposed, including the Buffalo, Puerto Rico, and AVM embocure scoring systems. The authors sought to validate these systems in an independent patient cohort and compare each system to the established Spetzler-Martin (SM) scale.

Methods: One hundred four consecutive patients underwent adjunctive endovascular embolization of brain AVMs between 2002 and 2016 with the goal of reducing the surgical or hemorrhagic risk before definitive radiosurgical treatment. Baseline clinical and AVM characteristics, complications, and degree of AVM nidus reduction were obtained retrospectively. Univariate and multivariate comparisons and receiver operating characteristic (ROC) curve analyses were performed.

Results: Ten major (9.6%) and 16 minor (15.4%) complications were encountered in 24 patients (23.1%). An arterial pedicle size < 1 mm (p = 0.001) and a greater number of pedicles (p = 0.039) were predictors of complication occurrence. Only the Buffalo score predicted the complication rate on univariate (p = 0.039) and multivariate (p = 0.001) analyses. ROC curve analysis revealed a greater area under the curve (AUC) of the Buffalo score (0.703) compared to the Puerto Rico score (p = 0.028), AVM embocure score (AVMES; p = 0.010), and SM grade (SMG; p = 0.030). The Buffalo score, Puerto Rico score, and AVMES but not the SMG predicted > 85% nidus reduction. The AUCs for the different scoring systems were not significantly different.

Conclusions: The major complication rate of 9.6% is within the range of rates reported in the literature and emphasizes that brain AVM embolization is not a low-risk procedure. The Buffalo score but not the Puerto Rico score, AVMES, or SMG predicted the endovascular procedural risk. All three endovascular scores but not the SMG predicted a > 85% nidus reduction rate in this cohort embolized as part of a multimodal AVM treatment.
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http://dx.doi.org/10.3171/2019.4.JNS19266DOI Listing
June 2019

Intermittent CSF drainage and rapid EVD weaning approach after subarachnoid hemorrhage: association with fewer VP shunts and shorter length of stay.

J Neurosurg 2019 Apr 26;132(5):1583-1588. Epub 2019 Apr 26.

1Division of Neurocritical Care and Emergency Neurology, Department of Neurology.

Objective: There is variability and uncertainty about the optimal approach to the management and discontinuation of an external ventricular drain (EVD) after subarachnoid hemorrhage (SAH). Evidence from single-center randomized trials suggests that intermittent CSF drainage and rapid EVD weans are safe and associated with shorter ICU length of stay (LOS) and fewer EVD complications. However, a recent survey revealed that most neurocritical care units across the United States employ continuous CSF drainage with a gradual wean strategy. Therefore, the authors sought to determine the optimal EVD management approach at their institution.

Methods: The authors reviewed records of 200 patients admitted to their institution from 2010 to 2016 with aneurysmal SAH requiring an EVD. In 2014, the neurocritical care unit of the authors' institution revised the internal EVD management guidelines from a continuous CSF drainage with gradual wean approach (continuous/gradual) to an intermittent CSF drainage with rapid EVD wean approach (intermittent/rapid). The authors performed a retrospective multivariable analysis to compare outcomes before and after the guideline change.

Results: The authors observed a significant reduction in ventriculoperitoneal (VP) shunt rates after changing to an intermittent CSF drainage with rapid EVD wean approach (13% intermittent/rapid vs 35% continuous/gradual, OR 0.21, p = 0.001). There was no increase in delayed VP shunt placement at 3 months (9.3% vs 8.6%, univariate p = 0.41). The intermittent/rapid EVD approach was also associated with a shorter mean EVD duration (10.2 vs 15.6 days, p < 0.001), shorter ICU LOS (14.2 vs 16.9 days, p = 0.001), shorter hospital LOS (18.2 vs 23.7 days, p < 0.0001), and lower incidence of a nonfunctioning EVD (15% vs 30%, OR 0.29, p = 0.006). The authors found no significant differences in the rates of symptomatic vasospasm (24.6% vs 20.2%, p = 0.52) or ventriculostomy-associated infections (1.3% vs 8.8%, OR 0.30, p = 0.315) between the 2 groups.

Conclusions: An intermittent CSF drainage with rapid EVD wean approach is associated with fewer VP shunt placements, fewer complications, and shorter LOS compared to a continuous CSF drainage with gradual EVD wean approach. There is a critical need for prospective multicenter studies to determine if the authors' experience is generalizable to other centers.
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http://dx.doi.org/10.3171/2019.1.JNS182702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402493PMC
April 2019

Noninvasive Vagus Nerve Stimulation Prevents Ruptures and Improves Outcomes in a Model of Intracranial Aneurysm in Mice.

Stroke 2019 05;50(5):1216-1223

From the Neurovascular Research Laboratory, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown (T.S., T.T., T.Q., C.A.).

Background and Purpose- Inflammation is a critical determinant of aneurysmal wall destabilization, growth, and rupture risk. Targeting inflammation may suppress aneurysm rupture. Vagus nerve stimulation (VNS) has been shown to suppress inflammation both systemically and in the central nervous system. Therefore, we tested the effect of a novel noninvasive transcutaneous VNS approach on aneurysm rupture and outcome in a mouse model of intracranial aneurysm formation with wall inflammation. Methods- Aneurysms were induced by a single stereotaxic injection of elastase into the cerebrospinal fluid at the skull base, combined with systemic deoxycorticosterone-salt hypertension, without or with high-salt diet, for mild or severe outcomes, respectively. Cervical VNS (two 2-minute stimulations 5 minutes apart) was delivered once a day starting from the day after elastase injection for the duration of follow-up. Transcutaneous stimulation of the femoral nerve (FNS) served as control. Multiple aneurysms developed in the circle of Willis and its major branches, resulting in spontaneous ruptures and subarachnoid hemorrhage, neurological deficits, and mortality. Results- In the milder model, VNS significantly reduced aneurysm rupture rate compared with FNS (29% versus 80%, respectively). Subarachnoid hemorrhage grades were also lower in the VNS group. In the more severe model, both VNS and FNS arms developed very high rupture rates (77% and 85%, respectively). However, VNS significantly improved the survival rate compared with FNS after rupture (median survival 13 versus 6 days, respectively), without diminishing the subarachnoid hemorrhage grades. Chronic daily VNS reduced MMP-9 (matrix metalloproteinase-9) expression compared with FNS, providing a potential mechanism of action. As an important control, chronic daily VNS did not alter systemic arterial blood pressure compared with FNS. Conclusions- VNS can reduce aneurysm rupture rates and improve the outcome from ruptured aneurysms.
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http://dx.doi.org/10.1161/STROKEAHA.118.023928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476688PMC
May 2019

Decreased wall shear stress at high-pressure areas predicts the rupture point in ruptured intracranial aneurysms.

J Neurosurg 2019 Mar 15;132(4):1116-1122. Epub 2019 Mar 15.

1Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.

Objective: Degenerative cerebral aneurysm walls are associated with aneurysm rupture and subarachnoid hemorrhage. Thin-walled regions (TWRs) represent fragile areas that may eventually lead to aneurysm rupture. Previous computational fluid dynamics (CFD) studies reported the correlation of maximum pressure (Pmax) areas and TWRs; however, the correlation with aneurysm rupture has not been established. This study aims to investigate this hemodynamic correlation.

Methods: The aneurysmal wall surface at the Pmax areas was intraoperatively evaluated using a fluid flow formula under pulsatile blood flow conditions in 23 patients with 23 saccular middle cerebral artery (MCA) bifurcation aneurysms (16 unruptured and 7 ruptured). The pressure difference (Pd) at the Pmax areas was calculated by subtracting the average pressure (Pave) from the Pmax and normalized by dividing this by the dynamic pressure at the aneurysm inlet side. The wall shear stress (WSS) was also calculated at the Pmax areas, aneurysm dome, and parent artery. These hemodynamic parameters were used to validate the correlation with TWRs in unruptured MCA aneurysms. The characteristic hemodynamic parameters at the rupture points in ruptured MCA aneurysms were then determined.

Results: In 13 of 16 unruptured aneurysms (81.2%), Pmax areas were identified that corresponded to TWRs. In 5 of the 7 ruptured cerebral aneurysms, the Pmax areas coincided with the rupture point. At these areas, the Pd values were not higher than those of the TWRs in unruptured cerebral aneurysms; however, minimum WSS, time-averaged WSS, and normalized WSS at the rupture point were significantly lower than those of the TWRs in unruptured aneurysms (p < 0.01).

Conclusions: At the Pmax area of TWRs, decreased WSS appears to be the crucial hemodynamic parameter that indicates the risk of aneurysm rupture.
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http://dx.doi.org/10.3171/2018.12.JNS182897DOI Listing
March 2019

DEFUSE 3 Non-DAWN Patients.

Stroke 2019 03;50(3):618-625

Stanford Stroke Center, Stanford University Medical Center, Palo Alto, CA (S.H., M. Mlynash, M.G.L., M. Marks, G.W.A.).

Background and Purpose- DAWN (Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention With Trevo) and DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) established thrombectomy for patients with emergent large vessel occlusions presenting 6 to 24 hours after symptom onset. Given the greater inclusivity of DEFUSE 3, we evaluated the effect of thrombectomy in DEFUSE 3 patients who would have been excluded from DAWN. Methods- Eligibility criteria of the DAWN trial were applied to DEFUSE 3 patient data to identify DEFUSE 3 patients not meeting DAWN criteria (DEFUSE 3 non-DAWN). Reasons for DAWN exclusion in DEFUSE 3 were infarct core too large, National Institutes of Health Stroke Scale (NIHSS) score 6 to 9, and modified Rankin Scale score of 2. Subgroups were compared with the DEFUSE 3 non-DAWN and entire DEFUSE 3 cohorts. Results- There were 71 DEFUSE 3 non-DAWN patients; 31 patients with NIHSS 6 to 9, 33 with core too large, and 13 with premorbid modified Rankin Scale score of 2 (some patients met multiple criteria). For core-too-large patients, median 24-hour infarct volume was 119 mL (interquartile range, 74.6-180) versus 31.5 mL (interquartile range, 17.6-64.3) for core-not-too-large patients ( P<0.001). Complications and functional outcomes were similar between the groups. Thrombectomy in core-too-large patients compared with the remaining DEFUSE 3 non-DAWN patients conveyed benefit for functional outcome (odds ratio, 20.9; CI, 1.3-337.8). Comparing the NIHSS 6 to 9 group with the NIHSS ≥10 patients, modified Rankin Scale score 0 to 2 outcomes were achieved in 74% versus 22% ( P<0.001), with mortality in 6% versus 23% ( P=0.024), respectively. For patients with NIHSS 6 to 9 compared with the remaining DEFUSE 3 non-DAWN patients, thrombectomy trended toward a better chance of functional outcome (odds ratio, 1.86; CI, 0.36-9.529). Conclusions- Patients with pretreatment core infarct volumes <70 mL but too large for inclusion by DAWN criteria demonstrate benefit from endovascular therapy. More permissive pretreatment core thresholds in core-clinical mismatch selection paradigms may be appropriate. In contrast to data supporting a beneficial treatment effect across the full range of NIHSS scores in the entire DEFUSE 3 population, only a trend toward benefit of thrombectomy in patients with NIHSS 6 to 9 was found in this small subgroup.
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http://dx.doi.org/10.1161/STROKEAHA.118.023310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768068PMC
March 2019

Protocols for Endovascular Stroke Treatment Diminish the Weekend Effect Through Improvements in Off-Hours Care.

Front Neurol 2018 18;9:1106. Epub 2018 Dec 18.

Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, United States.

The weekend effect is a well-recognized phenomenon in which patient outcomes worsen for acute strokes presenting outside routine business hours. This is attributed to non-uniform availability of services throughout the week and evenings and, though described for intravenous thrombolysis candidates, is poorly understood for endovascular stroke care. We evaluated the impact of institutional protocols on the weekend effect, and the speed and outcome of endovascular therapy as a function of time of presentation. This study assesses a prospective observational cohort of 129 consecutive patients. Patients were grouped based on the time of presentation during regular work hours (Monday through Friday, 07:00-19:00 h) vs. off-hours (overnight 19:00-07:00 h and weekends) and assessed for treatment latency and outcome. Treatment latencies did not depend on the time of presentation. The door to imaging interval was comparable during regular and off-hours (median time 21 vs. 19 min, respectively, < 0.50). Imaging to groin puncture was comparable (71 vs. 71 min, < 1.0), as were angiographic and functional outcomes. Additionally, treatment intervals decreased with increased protocol experience; door-to-puncture interval significantly decreased from the first to the fourth quarters of the study period (115 vs. 94 min, respectively, < 0.006), with the effect primarily seen during off-hours with a 28% reduction in median door-to-puncture times. Institutional protocols help diminish the weekend effect in endovascular stroke treatment. This is driven largely by improvement in off-hours performance, with protocol adherence leading to further decreases in treatment intervals over time.
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http://dx.doi.org/10.3389/fneur.2018.01106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305592PMC
December 2018

The Role of Collateral Circulation in Branch Vessel Occlusion After Flow Diversion.

World Neurosurg 2018 Dec 26. Epub 2018 Dec 26.

Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts, USA.

Background: Flow diversion for treatment of intracranial aneurysms frequently necessitates covering adjacent branch vessels. Although branch vessel occlusion is common, associated clinical deficits are rare. It has been hypothesized that clinically silent branch vessel occlusion is due to underlying collateral circulation. To study the role of collateral circulation in covered branch vessel occlusion, we assessed collateral vessels and altered branch vessel flow on transfemoral catheter angiography in patients undergoing flow diversion of intracranial aneurysms.

Methods: Angiograms obtained before treatment, immediately after treatment, and during follow-up were evaluated for branch vessel flow patterns and associated collateral circulation in a consecutive retrospective cohort of 84 patients from 2011 to 2017 with branch vessel coverage related to aneurysm flow diversion using the Pipeline embolization device.

Results: We identified 142 branch vessels covered by the Pipeline device construct for treatment of 89 aneurysms, predominately in the anterior circulation (>90%). Collateral circulation was observed in approximately one third of these vessels and was associated with diminished (P < 0.001) or absent (P < 0.001) flow on follow-up angiography. Only 2 of 80 terminal branch vessels (no collaterals) were occluded, and these occurred in a patient with Pipeline device construct thrombosis. Altered branch vessel flow was not associated with vascular risk factors, treatment technique, or outcome measures, including new or worsening neurologic deficit.

Conclusions: Altered flow in branch vessels covered during flow diversion reflects underlying collateral circulation and is not associated with downstream ischemic deficits.
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http://dx.doi.org/10.1016/j.wneu.2018.12.064DOI Listing
December 2018