A steroid receptor coactivator small molecule "stimulator" attenuates post-stroke ischemic brain injury.

Introduction: Pathologic remodeling of the brain following ischemic stroke results in neuronal loss, increased inflammation, oxidative stress, astrogliosis, and a progressive decrease in brain function. We recently demonstrated that stimulation of steroid receptor coactivator 3 with the small-molecule stimulator MCB-613 improves cardiac function in a mouse model of myocardial ischemia. Since steroid receptor coactivators are ubiquitously expressed in the brain, we reasoned that an MCB-613 derivative (MCB-10-1), could protect the brain following ischemic injury. To test this, we administered MCB-10-1 to rats following middle cerebral artery occlusion and reperfusion. Methods: Neurologic impairment and tissue damage responses were evaluated on day 1 and day 4 following injury in rats treated with control or 10-1. Results: We show that 10-1 attenuates injury post-stroke. 10-1 decreases infarct size and mitigates neurologic impairment. When given within 30 min post middle cerebral artery occlusion and reperfusion, 10-1 induces lasting protection from tissue damage in the ischemic penumbra concomitant with: (1) promotion of reparative microglia; (2) an increase in astrocyte NRF2 and GLT-1 expression; (3) early microglia activation; and (4) attenuation of astrogliosis. Discussion: Steroid receptor coactivator stimulation with MCB-10-1 is a potential therapeutic strategy for reducing inflammation and oxidative damage that cause neurologic impairment following an acute ischemic stroke.

Impact of histological clot composition on preprocedure imaging and mechanical thrombectomy.

INTRODUCTION: We studied the relationship of acute ischemic stroke (AIS) large-vessel occlusion clot composition with vessel recanalization and preprocedure imaging. SUBJECTS AND METHODS: Individual clots from AIS patients who underwent mechanical thrombectomy (MT) between September 2016 and September 2018 were examined. Clot composition was analyzed histologically through a trichrome staining and image segmentation, and the area occupied by red blood cells (RBCs), fibrin, or mixed composition was quantified. RESULTS: Forty-three patients (65.4 ± 12.7 years, 39% of females) who underwent 92 retrieval passes (mean 2.14, range 1-6) were included in this study. Fibrin (44%) occupied the greatest area, followed by mixed composition (34%) and RBCs (22%). A stent retriever was deployed in 81% of cases, 20 patients (47%) achieved first-pass efficacy (FPE) (thrombolysis in cerebral infarction [TICI] 2b-3 after first pass), 41 (95%) achieved successful revascularization (TICI 2b-3), and 21 (49%) had good outcome (modified Rankin Scale [mRS] ≤2) at 90 days. Hyperdense artery sign (HAS) on initial computed tomography was correlated with mixed clot composition (P = 0.01) and lack of fibrin content (P = 0.03). In the univariate analysis, FPE was associated with RBC clot area, atrial fibrillation, and occlusion location but not with fibrin clot area, mixed clot area, stroke etiology, thrombectomy technique, distal emboli, or 90-day mRS. In the multivariate analysis, FPE was significantly correlated with low RBC clot area (odd ratio = 0.96, confidence interval [0.92.99], P = 0.034) but not with atrial fibrillation or location. CONCLUSION: Our results suggest that HAS is correlated with mixed clot composition and lower fibrin content and that lower RBC clot composition is associated with FPE in patients undergoing MT.

A retrospective anatomical study of the cerebral dural venous sinus outflow pathways utilizing three-dimensional rotational venography.

OBJECTIVE: Proper blood flow is essential for the maintenance of homeostasis for the human cerebrum. The dural venous sinuses comprise the dominant cerebral venous outflow path. Understanding the spatial configuration of the dural venous sinuses can provide valuable insight into several pathological conditions. Previously, only two-dimensional or cadaveric data have been used to understand cerebral outflow. For the first time, we applied three-dimensional rotational venography (3D-RV) to study and provide detailed quantitative morphological measurements of the terminal cerebral venous sinus system in several pathological states. SUBJECTS AND METHODS: Patients who underwent a 3D-RV procedure were identified by reviewing our local institution's endovascular database. Patients with high-quality angiographic images were selected. Eighteen patients were included (37.1 ± 3.8 years). Sinuses were divided into four segments, starting at the torcula and ending at the internal jugular vein. Segment length, 3D displacement, and cross-sectional area were measured. RESULTS: The transverse sinus (60.2 mm) was the longest segment, followed by the sigmoid sinus (55.1 mm). Cross-sectional areas were smallest at the middle of the transverse sinus (21.3 mm2) but increased at the sigmoid sinus (33.5 mm2) and at the jugular bulb (49.7 mm2). The only variation in displacements of venous flow was at the sigmoid-jugular junction, where 55% of cases had lateral displacements versus 45% medial, and 78% superior versus 22% inferior. CONCLUSIONS: We describe the terminal venous sinus system of patients with a variety of diagnoses, detailing segment length, cross-sectional area, and 3D path.

Middle meningeal artery embolization for chronic subdural hematoma in cancer patients with refractory thrombocytopenia.

OBJECTIVE: Surgical evacuation of chronic subdural hematoma (SDH) in cancer patients is often contraindicated owing to refractory thrombocytopenia. Middle meningeal artery embolization (MMAE) recently emerged as a potential alternative to surgical evacuation for patients with chronic SDH. The goal of this study was to evaluate the safety and efficacy of MMAE for chronic SDH in cancer patients with refractory thrombocytopenia. METHODS: A multiinstitutional registry was reviewed for clinical and radiographic outcomes of cancer patients with transfusion-refractory thrombocytopenia and baseline platelet count < 75 K/µl, who underwent MMAE for chronic SDH. RESULTS: MMAE was performed on a total of 31 SDHs in 22 patients, with a mean ± SD (range) platelet count of 42.1 ± 18.3 (9-74) K/µl. At the longest follow-up, 24 SDHs (77%) had reduced in size, with 15 (48%) showing > 50% reduction. Two patients required surgical evacuation after MMAE. There was only 1 procedural complication; however, 16 patients (73%) ultimately died of cancer-related complications. Median survival was significantly longer in the 16 patients with improved SDH than the 6 patients with worsened SDH after MMAE (185 vs 24 days, p = 0.029). Length of procedure, technical success rate, SDH size reduction, and complication rate were not significantly differ between patients who underwent transfemoral and transradial approaches. CONCLUSIONS: Transfemoral or transradial MMAE is a potential therapeutic option for thrombocytopenic cancer patients with SDH. However, treatment benefit may be marginal for patients with high disease burden and limited life expectancy. A prospective trial is warranted to address these questions.

Double-barrel STA-MCA bypass for cerebral revascularization: lessons learned from a 10-year experience.

OBJECTIVE: In select patients, extracranial-intracranial (EC-IC) bypass remains an important tool for cerebral revascularization. Traditionally, superficial temporal artery-middle cerebral artery (STA-MCA) bypass was performed using one limb of the STA only. In an attempt to augment flow and to direct flow to different ischemic areas of the brain, the authors adopted a "double-barrel" technique in which both branches of the STA are used to revascularize distinct MCA territories. METHODS: A series of consecutive double-barrel STA-MCA bypasses performed between 2010 and 2020 were reviewed. Each anastomosis was directed to augment flow to a territory most at risk based on preoperative perfusion studies, cerebral angiography, and intraoperative indocyanine green data. CT perfusion and CTA were routinely used to evaluate postoperative augmentation and graft patency. Patient perioperative outcomes, surgical complications, and modified Rankin Scale (mRS) scores at the last follow-up were reported. RESULTS: Forty-four patients (16 males, 28 females) successfully underwent double-barrel STA-MCA bypass on 54 cerebral hemispheres: 28 operations were for moyamoya disease, 23 for atherosclerotic disease refractory to medical therapy, 2 for complex cerebral aneurysms, and 1 for carotid occlusion as a sequela of cavernous meningioma growth. Ten patients underwent multiple operations, 9 of whom had moyamoya disease/syndrome, with the subsequent operation on the contralateral hemisphere. The average patient age at surgery was 45.1 years (range 14-73 years), with a mean follow-up time of 22.1 months. Intraoperative graft patency was confirmed in 100% of cases, and 101 (98.1%) of the 103 anastomoses with imaging follow-up were patent. Perfusion to the revascularized hemisphere was improved in 88.2% of cases. Perioperative ischemic and hemorrhagic complications occurred in 8 procedures (2 were asymptomatic), whereas remote ischemic and hemorrhagic events occurred in 7 cases. There was no mortality in the series, and the mean patient mRS scores were 1.72 at presentation and 1.15 at the last follow-up. CONCLUSIONS: The high rates of intraoperative and postoperative patency support the feasibility of dual-anastomosis STA-MCA bypass for revascularization. The perioperative complication rate is not significantly different from that of single-anastomosis bypass. The functional outcomes at follow-up and perfusion improvement postoperatively support the efficacy and safety of this method as a treatment strategy.

Middle Meningeal Artery Embolization for Chronic Subdural Hematoma: A Multi-Center Experience of 154 Consecutive Embolizations.

BACKGROUND: Middle meningeal artery (MMA) embolization has emerged as a promising treatment for chronic subdural hematoma (cSDH). OBJECTIVE: To determine the safety and efficacy of MMA embolization. METHODS: Consecutive patients who underwent MMA embolization for cSDH (primary treatment or recurrence after conventional surgery) at 15 centers were included. Clinical details and follow-up were collected prospectively. Primary clinical and radiographic outcomes were the proportion of patients requiring additional surgical treatment within 90 d after index treatment and proportion with > 50% cSDH thickness reduction on follow-up computed tomography imaging within 90 d. National Institute of Health Stroke Scale and modified Rankin Scale were also clinical outcomes. RESULTS: A total of 138 patients were included (mean age: 69.8, 29% female). A total of 15 patients underwent bilateral interventions for 154 total embolizations (66.7% primary treatment). At presentation, 30.4% and 23.9% of patients were on antiplatelet and anticoagulation therapy, respectively. Median admission cSDH thickness was 14 mm. A total of 46.1% of embolizations were performed under general anesthesia, and 97.4% of procedures were successfully completed. A total of 70.2% of embolizations used particles, and 25.3% used liquid embolics with no significant outcome difference between embolization materials (P > .05). On last follow-up (mean 94.9 d), median cSDH thickness was 4 mm (71% median thickness reduction). A total of 70.8% of patients had >50% improvement on imaging (31.9% improved clinically), and 9 patients (6.5%) required further cSDH treatment. There were 16 complications with 9 (6.5%) because of continued hematoma expansion. Mortality rate was 4.4%, mostly unrelated to the index procedure but because of underlying comorbidities. CONCLUSION: MMA embolization may provide a safe and efficacious minimally invasive alternative to conventional surgical techniques.

Cognitive outcomes after unruptured intracranial aneurysm treatment with endovascular coiling.

BACKGROUND: We aimed to determine the effects of endovascular coiling of unruptured intracranial aneurysms (UIAs) on cognition to inform treatment decisions. We present the first study using the Montreal Cognitive Assessment (MoCA) to determine neurocognitive changes after endovascular coiling. METHODS: We prospectively collected data on all patients with UIAs undergoing endovascular coiling, primary or assisted. Patients completed the MoCA prior to intervention and 1 month and 6 months' post-procedure. A repeated measures linear mixed effects model was used to compare pre-procedure and post-procedure cognition. RESULTS: Thirty-three patients with 33 aneurysms who underwent coiling from April 2017 to May 2020 were included (mean age 55.5, 81.8% female). All procedures used general anesthesia. There was no difference between baseline and post-procedure MoCA scores at any time interval (P>0.05). Mean MoCA scores at baseline, 1 month post-procedure, and 6 months' post-procedure were 25.4, 26.8, and 26.3 respectively. There was also no difference between pre- and post-procedure scores on any individual MoCA domain (visuospatial, naming, memory, attention, language, abstraction, delayed recall, and orientation) at any time interval (P>0.05). Seventeen patients had follow-up MRI or CT imaging, of which 11.8% showed radiographic changes or ischemia. 77.8% of patients with 6-month angiographic follow-up achieved class I, and 22.2% achieved class II Raymond-Roy Occlusion. Thirty-two out of 33 patients had follow-up mRS ≤2. CONCLUSION: Our study suggests that endovascular coiling does not diminish neurocognitive function. Patients with UIAs in our cohort also had baseline MoCA scores below the cut-off for mild cognitive impairment despite pre-procedure mRS and NIHSS of 0.

Comparison of First-Pass Efficacy Among Four Mechanical Thrombectomy Techniques: A Single-Center Experience.

BACKGROUND: First-pass efficacy (FPE) is an established marker of technical and clinical efficacy among mechanical thrombectomy (MT) techniques. It is unclear what the optimal approach is in achieving FPE. We present a single-center experience comparing rates of FPE among 2 MT techniques and evaluate the potential predictors of FPE among other outcomes. METHODS: A single-center retrospective analysis was carried out of patients with consecutive large-vessel occlusion strokes (LVOS) of anterior circulation from September 2015 to April 2019 who underwent MT and for whom data were available on the status of FPE. Four MT techniques were identified: ADAPT (a direct first-pass aspiration), SrADAPT (stent retriever with aspiration), SRBG (stent retriever with balloon guide catheter), and STRAP (stent retriever-aspiration and proximal flow arrest). The primary outcome was FPE and secondary outcomes included the rate of successful reperfusion. RESULTS: Among 226 patients with LVOS of the anterior circulation who underwent MT, data were available for 164 on FPE for the 4 MT techniques. SRBG was the most prevalent technique. No significant difference was found in rates of FPE among the 4 MT techniques (P = 0.332). No independent predictors of FPE were identified on multivariable analysis. STRAP had the highest rate of successful reperfusion compared with the other techniques (P = 0.049) and was the only independent predictor of that outcome (P = 0.027). CONCLUSIONS: Among patients with LVOS of the anterior circulation, the rate of FPE did not differ among the 4 MT techniques. There were no predictors of FPE among the studied variables. STRAP was the only predictor of successful reperfusion.

Intra-Arterial Glycoprotein IIb/IIIa Inhibitor Treatment for Symptomatic Intracranial Atherosclerotic Stenosis Presenting as Large Vessel Occlusions.

Introduction There is no consensus on the optimal treatment for acute ischemic stroke (AIS) large vessel occlusions (LVOs) or near-occlusions with underlying intracranial atherosclerotic stenosis (ICAS). We report the first American series using intra-arterial (IA) glycoprotein IIb/IIIa inhibitors (GPIs) as a stand-alone revascularization technique for ICAS presenting with large vessel ischemic syndromes. Methods Records at two centers of 140 patients presenting with AIS undergoing stroke intervention from January 2017 to June 2019 were retrospectively reviewed. Patients treated with IA GPIs were identified, and baseline factors, imaging, procedural characteristics, hospital course, and outcomes were collected. Six patients with ICAS underlying their acute symptomatic near occlusion or LVO were treated with IA GPI. Four near-occlusions were treated with IA GPI as the first-line therapy, while two LVOs were treated with IA GPI as an adjunct therapy to thrombectomy. Results The mean age was 61.3 years (range 36-79), presentation National Institute of Health Stroke Scale (NIHSS) was 10 (4-18), time from last seen well to treatment was 434.5 minutes (164-1290), and time from groin puncture to revascularization was 67.3 minutes (26-94). Three patients received intravenous (IV) tissue plasminogen activator (tPA), and all patients received an IA weight-based GPI infusion. Five patients had thrombolysis in cerebral ischemia (TICI) 3, and one patient had TICI 2b. The mean discharge NIHSS was 2.5 (0-8). The mean modified Rankin scale was 1.3 (range 0-4) at discharge and .8 at three months. No patients had a postprocedural symptomatic hemorrhage. Conclusion Our results highlight the utility of IA GPI administration as the first-line therapy for symptomatic ICAS near occlusions or as a rescue technique after failed thrombectomy for LVO patients suspected of underlying ICAS.

Expanding Indications for Flow Diverters: Ruptured Aneurysms, Blister Aneurysms, and Dissecting Aneurysms.

BACKGROUND: The safety and efficacy of flow diversion (FD) in the treatment of cerebral aneurysms have been reported by many studies. FD has enabled the treatment of complex aneurysms and aneurysms that were previously untreatable by conventional means. It has achieved high rates of obliteration with essentially no recanalization, and its indications have continued to expand, now including ruptured aneurysms, blister aneurysms, and dissecting aneurysms. OBJECTIVE: To provide a review on the outcomes of studies covering the use of FD in the settings of ruptured, blister, and dissecting aneurysms. In addition, to discuss dual antiplatelet therapy (DAPT) used in preparation for FD deployment in these scenarios, including associated complications with DAPT use in the acute rupture setting. METHODS: References for this topical review were identified by PubMed searches between January 2000 and January 2019. The search terms "aneurysm", "flow diverter", "stent", "pipeline", "ruptured", "blister", and "dissecting aneurysms" were used. RESULTS: FD carries a higher complication rate in the acute rupture setting than for unruptured aneurysms. Patient selection is of paramount importance for achieving good functional and angiographic outcomes. DAPT still remains challenging, especially in ruptured aneurysms. Advancements in surface modification of flow diverters can reduce the risk of thromboembolism and perhaps lead to a safer antiplatelet regimen. CONCLUSION: In summary, FD shows promise to be an effective treatment for ruptured, blister, and dissecting aneurysms.

Gastrointestinal stromal tumor with intracranial metastasis: case presentation and systematic review of literature.

BACKGROUND: Intracranial metastasis of Gastrointestinal Stromal Tumors (GISTs) is rare but presents unique treatment challenges. We present a case of intracranial metastasis of GIST with a systematic review of the literature. A literature search using key terms "'gastrointestinal stromal tumor' AND brain AND metastasis"" was conducted through May 2019 via Embase and Pubmed according to PRISMA guidelines. Only cases describing intradural metastases rather than calvarial or intraorbital metastases were included. CASE PRESENTATION: A 57-year-old woman with history of GIST metastatic to the liver presented with a six-week history of left facial weakness, left hearing loss, and left facial numbness, and a one-week history of headaches, gait disturbance, and dizziness. MRI revealed a contrast-enhancing dural-based left middle cranial fossa mass measuring 2.9 cm × 3.1 cm × 3.4 cm with extension into the internal auditory canal and cerebral edema. A left temporal craniotomy was performed to excise the lesion, and the patient was discharged to a rehabilitation facility at her preoperative baseline. Intraoperative pathology revealed a spindle cell neoplasm, postoperative MRI demonstrated gross total resection of the lesion, and microscopic analysis demonstrated sheets of spindled tumor cells with short ovoid, irregular, hyperchromatic nuclei and scattered large atypical nuclei without extensive necrosis. Immunohistochemical staining was positive for KIT proto-oncogene (CD117, c-KIT), and the patient was put on imatinib (400 mg/day). CONCLUSIONS: Of the 18 cases analyzed and our present case, metastasis typically involved the cerebrum with only one in infratentorial elements. The tumors in seven of the cases involved the dura, and one case metastasized to the pituitary. Eight patients died following treatment. Surgery remains the mainstay of intracranial metastatic GIST, however there are many reports of good responses to radiation or chemotherapy alone. More investigation is required to determine the best treatment course for these patients.

Cognitive outcomes after unruptured intracranial aneurysm treatment with flow diversion.

OBJECTIVE: Flow diversion is increasingly used to treat a variety of intracranial aneurysms with good safety and efficacy; however, there is some evidence that this treatment is associated with a larger postoperative ischemic burden on imaging than that with other traditional endovascular modalities. These findings typically do not manifest as neurological deficits, but any subtle effects on cognition remain unknown. In this study, the authors describe the neurocognitive performance of a cohort of patients with unruptured intracranial aneurysms (UIAs) before and after treatment with flow diversion. This is the first report of cognitive outcomes following aneurysm treatment with flow diversion. METHODS: The authors prospectively collected data on cognitive function using the Montreal Cognitive Assessment (MoCA) tool in patients with UIAs who were undergoing endovascular aneurysm treatment with flow diversion between June 2017 and July 2019. Patients completed the MoCA prior to intervention, at the 1-month follow-up after treatment, and again at 6 months after the procedure. All patients with UIAs treated with flow diversion were included regardless of age, aneurysm location, or morphology, unless their functional status precluded completion of the MoCA instrument. A repeated-measures linear mixed-effects model was used to compare preintervention and postintervention cognitive status at the time intervals outlined. RESULTS: Fifty-one patients with 61 aneurysms underwent endovascular aneurysm treatment with flow diversion (mean age 52.5 years, 90.2% females). There was no difference between baseline and postprocedure MoCA scores at any time interval (p > 0.05). The MoCA scores at baseline, 1 month postprocedure, and 6 months postprocedure were 26.1, 26.2, and 26.6, respectively. There was also no difference between pre- and postprocedure scores on any individual domain of the instrument (visuospatial, naming, attention, language, abstraction, delayed recall, and orientation) at any time interval (p > 0.05). Thirty-four patients had follow-up MRI or CT imaging, 5 of whom showed radiographic changes or ischemia. All patients with follow-up clinical evaluation had a 6-month modified Rankin Scale score ≤ 2. CONCLUSIONS: Flow diversion is increasingly used in the treatment of intracranial aneurysms. This study suggests that this treatment may not alter neurocognitive function. Larger patient samples and longer follow-ups with other tests of cognitive functions are needed to confirm these findings.

Early postmarket results with PulseRider for treatment of wide-necked intracranial aneurysms: a multicenter experience.

OBJECTIVE: Traditionally, stent-assisted coiling and balloon remodeling have been the primary endovascular treatments for wide-necked intracranial aneurysms with complex morphologies. PulseRider is an aneurysm neck reconstruction device that provides parent vessel protection for aneurysm coiling. The objective of this study was to report early postmarket results with the PulseRider device. METHODS: This study was a prospective registry of patients treated with PulseRider at 13 American neurointerventional centers following FDA approval of this device. Data collected included clinical presentation, aneurysm characteristics, treatment details, and perioperative events. Follow-up data included degree of aneurysm occlusion and delayed (> 30 days after the procedure) complications. RESULTS: A total of 54 aneurysms were treated, with the same number of PulseRider devices, across 13 centers. Fourteen cases were in off-label locations (7 anterior communicating artery, 6 middle cerebral artery, and 1 A1 segment anterior cerebral artery aneurysms). The average dome/neck ratio was 1.2. Technical success was achieved in 52 cases (96.2%). Major complications included the following: 3 procedure-related posterior cerebral artery strokes, a device-related intraoperative aneurysm rupture, and a delayed device thrombosis. Immediately postoperative Raymond-Roy occlusion classification (RROC) class 1 was achieved in 21 cases (40.3%), class 2 in 15 (28.8%), and class 3 in 16 cases (30.7%). Additional devices were used in 3 aneurysms. For those patients with 3- or 6-month angiographic follow-up (28 patients), 18 aneurysms (64.2%) were RROC class 1 and 8 (28.5%) were RROC class 2. CONCLUSIONS: PulseRider is being used in both on- and off-label cases following FDA approval. The clinical and radiographic outcomes are comparable in real-world experience to the outcomes observed in earlier studies. Further experience is needed with the device to determine its role in the neurointerventionalist's armamentarium, especially with regard to its off-label use.