Citations

Pituitary tumor transforming gene (PTTG) was initially found to be overexpressed in GH4 rat pituitary adenomas (PA). PTTG overexpression has been correlated with patient survival, tumor grade, and/or invasiveness in several tumors including those of thyroid, breast, lung, and colon. Studies of PTTG as a prognostic indicator in PAs are limited and show conflicting results. We investigated PTTG immunostaining in 79 PAs of different subtypes (growth hormone (GH), 12; prolactin (PRL), 6, adrenocorticotropic hormone (ACTH), 11, gonadotroph, 21; null cell, 29) in relation to clinico‐pathological variables including patient age and sex, as well as tumor size, and invasiveness. The streptavidin‐biotin‐peroxidase method was used, with a monoclonal PTTG antibody (Abcam, Cambridge, UK). PTTG expression was found to be cytoplasmic in all PAs, with highest levels being present in GH adenomas and lowest in the PRL ones. No correlation was found with patient age, sex, tumor size or invasiveness. Thus, it appears that PTTG cannot serve as a prognostic marker in patients with PAs. PTTG has been implicated in several tumorigenic processes including angiogenesis, DNA damage repair and invasiveness. PTTG overexpression in PA warrants further research into its role in PA initiation and progression.

Angiotensin II produces oxidative stress and endothelial dysfunction. ACE2 converts angiotensin II to angiotensin 1–7 and may protect against effects of angiotensin II. We tested the hypothesis that ACE2 deficiency increases oxidative stress and vasomotor dysfunction in cerebral arteries, and examined the role of ACE2 in vascular aging. ACE2 was present at relatively low levels in cerebral arteries. Systolic arterial pressure was similar in adult and old ACE2 knockout (KO) and wild‐type (WT) mice. Maximal dilatation to acetylcholine (ACh) was impaired in the basilar artery from adult ACE2 KO mice compared to adult WT. In old mice, maximal dilatation to ACh was impaired in WT mice but severely impaired in ACE2 KO mice (P<0.05). The antioxidant tempol (1 mM) improved responses to ACh in adult and old ACE2 KO and WT mice. Nitrotyrosine staining in the basilar artery was increased in adult ACE2 KO mice and in old ACE2 KO and WT mice. Expression of NAD(P)H oxidase subunits Nox2 and p47phox, and of pro‐inflammatory molecules Rcan1 and TNFα, was increased in cerebral arteries from old ACE2 KO and WT animals. In summary, ACE2 deficiency impaired vasomotor function in cerebral arteries from adult mice and augments endothelial dysfunction during aging. Oxidative stress plays a critical role in cerebrovascular dysfunction induced by ACE2 deficiency and aging. NIH grants NS‐24621, HL‐38091, HL‐62984; AHA 0815525G, 10PRE3780044.

Abstract Basilar artery occlusions (BAOs) are devastating ischemic strokes that account for 1% of all strokes with high morbidity and mortality; however, neuroendovascular techniques such as ADAPT have recently revolutionized the clinical outcomes of these patients. 1-3 Common underlying pathology in patients with BAO include intracranial atherosclerotic disease (ICAD) as well as thromboembolic origin. 4 Basilar artery ICAD in a setting of acute stroke portends a poor prognosis and post-thrombectomy residual critical flow limiting stenosis treatment options, including balloon angioplasty with or without stent placement. 5-7 We present a video illustration of neuroendovascular technique and challenges encountered when managing this pathology. Image at 5:42 reprinted with permission from Alawieh et al, Lessons learned over more than 500 stroke thrombectomies using ADAPT with increasing aspiration catheter size, Neurosurgery , 86(1), 2020, pp. 61-70, with permission from the Congress of Neurological Surgeons. 1

OBJECTIVE The authors’ goal was to use a multicenter, observational cohort study to determine whether supramarginal resection (SMR) of FLAIR-hyperintense tumor beyond the contrast-enhanced (CE) area influences the overall survival (OS) of patients with isocitrate dehydrogenase–wild-type (IDH-wt) glioblastoma after gross-total resection (GTR). METHODS The medical records of 888 patients aged ≥ 18 years who underwent resection of GBM between January 2011 and December 2017 were reviewed. Volumetric measurements of the CE tumor and surrounding FLAIR-hyperintense tumor were performed, clinical variables were obtained, and associations with OS were analyzed. RESULTS In total, 101 patients with newly diagnosed IDH-wt GBM who underwent GTR of the CE tumor met the inclusion criteria. In multivariate analysis, age ≥ 65 years (HR 1.97; 95% CI 1.01–2.56; p < 0.001) and contact with the lateral ventricles (HR 1.59; 95% CI 1.13–1.78; p = 0.025) were associated with shorter OS, but preoperative Karnofsky Performance Status ≥ 70 (HR 0.47; 95% CI 0.27–0.89; p = 0.006), MGMT promotor methylation (HR 0.63; 95% CI 0.52–0.99; p = 0.044), and increased percentage of SMR (HR 0.99; 95% CI 0.98–0.99; p = 0.02) were associated with longer OS. Finally, 20% SMR was the minimum percentage associated with beneficial OS (HR 0.56; 95% CI 0.35–0.89; p = 0.01), but > 60% SMR had no significant influence (HR 0.74; 95% CI 0.45–1.21; p = 0.234). CONCLUSIONS SMR is associated with improved OS in patients with IDH-wt GBM who undergo GTR of CE tumor. At least 20% SMR of the CE tumor was associated with beneficial OS, but greater than 60% SMR had no significant influence on OS.

Abstract In-stent stenosis has a reported prevalence of 14% to 19% at 1-yr follow-up after carotid stenting and is associated with an increased risk of acute ischemic stroke. 1,2 Risk factors include female sex, diabetes, and dyslipidemia. Cutting balloon angioplasty is a safe and effective treatment modality for the treatment of carotid in-stent stenosis, and alternative treatment options include observation with medical management and placement of another stent. 3,4 The authors present the case of a 61-yr-old man with carotid in-stent restenosis and progressive worsening on serial imaging with ultrasound. The patient had a history of carotid stenting for symptomatic stenosis 6 mo prior and was maintained on aspirin and clopidogrel. In light of the progressive worsening, the in-stent stenosis was confirmed on computed tomography (CT) angiogram. The options were discussed with the patient and he consented for treatment with cutting balloon angioplasty. Final angiogram showed improvement of the luminal diameter with a residual stenosis of 15%. The patient tolerated the procedure well and was discharged home on postoperative day 1. Follow-up ultrasound demonstrated moderate improvement in peak systolic velocities, and the plan is to continue observation with a clinical follow-up and repeat carotid Dopplers at 3 mo.

Abstract Embolic protection devices (EPDs) have become a standard of care during internal carotid artery revascularization. 1,2 This video is about a 57-yr-old-male who presented with a wake-up stroke with a left hemispheric syndrome. Head computed tomography angiography (CTA) revealed tandem occlusions of the proximal left internal carotid artery (ICA) and of the distal left middle cerebral artery (MCA) with an ASPECT (Alberta Stroke Program Early CT Score) score of 6. The patient underwent a cerebral angiogram and was treated with balloon angioplasty with a distal EPD and mechanical thrombectomy. The EPD became occluded with thrombus from the ICA and was retrieved through a 6-Fr Sofia (MicroVention) under continuous aspiration. Successful revascularization of the proximal ICA and distal MCA was achieved. No procedure-related complications occurred, and the patient's neurological exam improved. Tandem occlusions can occur in up to 15% of strokes. The optimal treatment can be controversial, but mechanical thrombectomy and ICA revascularization with a distal EPD appear to be safe and effective in selected patients. 3 Consent was obtained for the procedure and for the video production.

This study compared the effects of self-selected exercise intensity (SEI) versus predetermined exercise intensity (PEI) on blood pressure (BP) and arterial stiffness in adolescents with obesity. A total of 37 adolescents, 14.7 (1.6) years old, body mass index ≥95th percentile were randomly allocated into SEI (n = 18; 12 boys) or PEI (n = 19; 13 boys). Both groups exercised for 35 minutes on a treadmill, 3 times per week, for 12 weeks. The SEI could set the speed at the beginning of the sessions and make changes every 5 minutes. The PEI adolescents were trained at an intensity set at 60% to 70% of heart rate reserve. Brachial and central BP, pulse pressure, augmentation index, and carotid–femoral pulse wave were determined at baseline and after 12 weeks. Both groups reduced brachial systolic BP (SEI, Δ = −9 mm Hg; PEI, Δ = −4 mm Hg; P < .01), central systolic BP (SEI, Δ = −4 mm Hg; PEI, Δ = −4 mm Hg; P = .01), and central pulse pressure (SEI, Δ = −4 mm Hg; PEI, Δ = −3 mm Hg; P = .02) without differences between groups. No changes in the augmentation index and carotid–femoral pulse wave were observed in either group. The SEI induced similar changes in various cardiovascular outcomes compared with PEI in adolescents with obesity.

Background Several animal studies have demonstrated that mechanical thrombectomy (MT) for acute ischemic stroke (AIS) may cause vessel wall injury (VWI). However, the histological changes in human cerebral arteries following MT are difficult to determine. Objective To investigate the occurrence of VWI during MT by histological and immunohistochemical evaluation of AIS clots. Methods As part of the multicenter STRIP registry, 277 clots from 237 patients were analyzed using Martius Scarlett Blue stain and immunohistochemistry for CD34 (endothelial cells) and smooth muscle actin (smooth muscle cells). Results MT devices used were aspiration catheters (100 cases), stentriever (101 cases), and both (36 cases). VWI was found in 33/277 clots (12%). There was no significant correlation between VWI and MT device. The degree of damage varied from grade I (mild intimal damage, 24 clots), to grade II (relevant intimal and subintimal damage, 3 clots), and III (severe injury, 6 clots). VWI clots contained significantly more erythrocytes (p=0.006*) and less platelets/other (p=0.005*) than non-VWI clots suggesting soft thrombus material. Thrombolysis correlated with a lower rate of VWI (p=0.04*). VWI cases showed a significantly higher number of passes (2 [1–4] vs 1 [1–3], p=0.028*) and poorer recanalization outcome (p=0.01*) than cases without VWI. Conclusions Histological markers of VWI were present in 12% of AIS thrombi, suggesting that VWI might be related to MT. VWI was associated with soft thrombus consistency, higher number of passes and poorer revascularization outcome. There was no significant correlation between VWI and MT device.

Abstract Intracranial atherosclerotic disease (ICAD) is a common cause of stroke. Antiplatelet therapy is the mainstay for symptomatic ICAD treatment. Endovascular management with submaximal angioplasty and/or intracranial stenting is reserved for patients with repeated ischemic events despite optimal medical therapy. We demonstrate intracranial angioplasty and stenting technique, technique indications, and sizing of stent and target vessel diameter. Stenting and angioplasty have been described in the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis and Wingspan Stent System Post Market Surveillance trials. 1,2 Submaximal angioplasty has also been described. 3 This patient, who had been on dual antiplatelet therapy for several months, initially presented with occlusion of the left middle cerebral artery M2 inferior division and underwent mechanical thrombectomy with successful reperfusion. Postoperatively, the patient's symptoms did not improve. Medical management was optimized with heparin infusion. However, repeat stroke study demonstrated M2 inferior division reocclusion. A decision was made to proceed with intracranial angioplasty and stenting. P2Y12 levels were therapeutic. Under moderate conscious sedation, submaximal angioplasty of up to 80% of the normal M2 caliber was attempted. However, we observed persistent high-grade stenosis of the M2 inferior division. The major risk of crossing the lesion for angioplasty is vessel perforation. To safely perform this maneuver, we used a J-configured Synchro-2 microwire (Stryker). Because of the patient's recent thrombectomy, we also had prior tactile feedback about how much resistance was encountered while crossing the occlusion. We then deployed a balloon-mounted intracranial stent for optimal radial force across the stenotic area to restore perfusion. Postoperative computed tomography perfusion showed resolution of the previously noticed perfusion deficit. The patient gave informed consent for the procedures and video recording. Institutional review board approval was deemed unnecessary. Video. ©University at Buffalo Neurosurgery, September 2020. With permission.