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Introduction: Hypertensive cerebral small vessel disease (HTN-cSVD) is the predominant microangiopathy in patients with a combination of lobar and deep cerebral microbleeds (CMBs) and intracerebral hemorrhage (mixed ICH/CMB). We tested the hypothesis that cerebral amyloid angiopathy (CAA) is also a contributing microangiopathy in mixed ICH/CMB patients with cortical superficial siderosis (cSS), a marker that is strongly associated with CAA. Methods: Brain MRIs from a prospective database of consecutive non-traumatic ICH patients admitted to a single referral center (2003 to 2019) were reviewed for the presence of CMBs, cSS, and non-hemorrhagic CAA markers (lobar lacunes, centrum semiovale enlarged perivascular spaces (CSO-EPVS), and multispot pattern of leukoaraiosis). The frequency of CAA markers and left ventricular hypertrophy (LVH), a marker for hypertensive end-organ damage, were compared between mixed ICH/CMB patients with cSS (mixed +cSS ) and without cSS (mixed -cSS ) in univariate and multivariate models. Results: Of the 1824 ICH patients, 40 had mixed +cSS and 256 had mixed -cSS . LVH was less common in patients with mixed +cSS compared to those with mixed -cSS (34% vs. 59%, p = 0.01). The frequency of multispot pattern (18% vs. 4%, p < 0.01) and severe CSO-EPVS (33% vs. 11%, p < 0.01) were higher in patients with mixed +cSS compared to mixed -cSS , whereas lobar lacune frequency was similar (23% vs. 20%, p = 0.67). In a logistic regression model, older age (aOR 1.04 per year, 95% CI [1.01-1.08], p = 0.01), presence of multispot pattern (aOR 5.82, 95% CI [1.82-18.60], p < 0.03), severe CSO-EPVS (aOR 4.08, 95% CI [1.73-9.61], p < 0.01), and LVH (aOR 0.43, 95% CI [0.20-0.94], p = 0.03) were independently associated with mixed +cSS after further adjustment for sex and hypertension (Table). Conclusions: CAA and HTN-cSVD appear to confer injury in patients with mixed ICH/CMB and cSS, a finding that warrants confirmation in studies incorporating advanced imaging/pathology.

Introduction: About ~10% of acute ischemic stroke (AIS) patients experience multiple acute lesions (MAL). However, the spatial distribution and clinical implications of such MAL are incompletely understood. Here, we scrutinized MAL in a large, radiologically deep-phenotyped cohort of AIS patients. Methods: We analyzed imaging and clinical data of 2.485 AIS patients [age: 63.3±14.8, 39%women] of the multi-site MRI-GENIE study. We computed occurrences of (i) MAL within one and, (ii) MAL in several vascular supply territories (with single or multiple lesions within single territories). We furthermore evaluated associations between the presence of MAL in multiple territories and stroke severity, white matter hyperintensity (WMH) and stroke lesion volumes, etiology, age and sex. Results: Half of all patients, i.e., 49.7%, presented with a single lesion. Another 37.3% experienced MAL in a single vascular territory, while 13% featured lesions in multiple vascular territories. For most vascular territories (anterior, middle and posterior cerebral artery, cerebellum) the ratio between single to multiple lesions in that territory equaled ~52%, only the brainstem region comprised fewer multiple compared to single lesions (19%). Combinations of anterior and posterior circulation lesions occurred in 5.6% of all patients, bilateral stroke in the anterior circulation in 3.4%. When comparing patients with lesions in only one compared to in more than one territory, there were no significant differences in WMH or lesion volume, stroke severity, age or sex ( p FDR-corrected >0.05). Patients with lesions in multiple territories had a significantly lower frequency of small vessel occlusions, but a significantly higher frequency of stroke of undetermined etiology. Differences in cardioembolic stroke frequency were only significant before correction for multiple comparisons ( p uncorrected =0.025). Frequencies of large vessel occlusions did not differ between the groups. Conclusions: Multiple lesions, especially those within one vascular territory, occurred frequently. Overall, there were no significant associations between MAL and stroke severity or cardioembolic stroke. Future studies are warranted to explore these findings in greater detail.

Purpose Large aneurysms often present a challenge for endovascular navigation, as they may require utilization of “around-the-world” technique for distal access. In this study, we describe the use of a pipeline stent to stabilize the microcatheter allowing gradual unsheathing and straightening of the microcatheter within the aneurysm enabling stent deployment. Methods A pipeline stent is partially deployed distal to the aneurysm, after using intra-aneurysmal loop (“around-the-world”) to cross the aneurysm. Partially unsheathed, using its radial force and vessel wall friction to establish an anchoring point, the microcatheter is stabilized and pulled with the stent locked to gradually to allow loop reduction and microsystem straightening, allowing unsheathing as the microsystem is aligned with the inflow and outflow vessel. Results Two patients harboring cavernous segment aneurysms (measuring 18 × 12 mm and 21 × 24 mm) were treated by 3.75 × 25 mm and 4.25 × 25 mm pipeline devices, respectively, using this technique, deployed through a Phenom 0.027” microcatheter. Patients did well clinically with no thromboembolic complications, as follow-up imaging demonstrated good wall apposition and appreciable contrast stagnation. Conclusion Anchoring for loop reduction was previously described using a non-flow diverter stents or balloon requiring additional devices and exchange maneuvers to deploy a pipeline. The “pipe anchor” technique describes the use of a partially deployed flow diverter system as an anchor. This report suggests that pipeline radial force, albeit low, is sufficient. We believe that this method is worthy of consideration in select cases as a first choice and can be valuable tool in the armamentarium of the endovascular neurosurgeon.

Importance Hyperglycemia during acute ischemic stroke is common and is associated with worse outcomes. The efficacy of intensive treatment of hyperglycemia in this setting remains unknown. Objectives To determine the efficacy of intensive treatment of hyperglycemia during acute ischemic stroke. Design, Setting, and Participants The Stroke Hyperglycemia Insulin Network Effort (SHINE) randomized clinical trial included adult patients with hyperglycemia (glucose concentration of >110 mg/dL if had diabetes or ≥150 mg/dL if did not have diabetes) and acute ischemic stroke who were enrolled within 12 hours from stroke onset at 63 US sites between April 2012 and August 2018; follow-up ended in November 2018. The trial included 1151 patients who met eligibility criteria. Interventions Patients were randomized to receive continuous intravenous insulin using a computerized decision support tool (target blood glucose concentration of 80-130 mg/dL [4.4-7.2 mmol/L]; intensive treatment group: n = 581) or insulin on a sliding scale that was administered subcutaneously (target blood glucose concentration of 80-179 mg/dL [4.4-9.9 mmol/L]; standard treatment group: n = 570) for up to 72 hours. Main Outcomes and Measures The primary efficacy outcome was the proportion of patients with a favorable outcome based on the 90-day modified Rankin Scale score (a global stroke disability scale ranging from 0 [no symptoms or completely recovered] to 6 [death]) that was adjusted for baseline stroke severity. Results Among 1151 patients who were randomized (mean age, 66 years [SD, 13.1 years]; 524 [46%] women, 923 [80%] with diabetes), 1118 (97%) completed the trial. Enrollment was stopped for futility based on prespecified interim analysis criteria. During treatment, the mean blood glucose level was 118 mg/dL (6.6 mmol/L) in the intensive treatment group and 179 mg/dL (9.9 mmol/L) in the standard treatment group. A favorable outcome occurred in 119 of 581 patients (20.5%) in the intensive treatment group and in 123 of 570 patients (21.6%) in the standard treatment group (adjusted relative risk, 0.97 [95% CI, 0.87 to 1.08],P = .55; unadjusted risk difference, −0.83% [95% CI, −5.72% to 4.06%]). Treatment was stopped early for hypoglycemia or other adverse events in 65 of 581 patients (11.2%) in the intensive treatment group and in 18 of 570 patients (3.2%) in the standard treatment group. Severe hypoglycemia occurred only among patients in the intensive treatment group (15/581 [2.6%]; risk difference, 2.58% [95% CI, 1.29% to 3.87%]). Conclusions and Relevance Among patients with acute ischemic stroke and hyperglycemia, treatment with intensive vs standard glucose control for up to 72 hours did not result in a significant difference in favorable functional outcome at 90 days. These findings do not support using intensive glucose control in this setting. Trial Registration ClinicalTrials.gov Identifier:NCT01369069

Background: Toward discovering novel stroke therapies, recent research has shown that activation of the newly-discovered angiotensin converting enzyme 2/angiotensin-(1-7)/mas (ACE2/Ang-(1-7)/Mas) pathway, a counter-regulatory axis of the brain renin-angiotensin system, is neuroprotective in ischemic stroke in rats. Specifically, intraventricular administration of the novel ACE2 activator diminazine aceturate (DIZE) before and during an ischemic stroke decreases cerebral infarct and neurologic deficits. Efficacy must now be demonstrated using minimally-invasive methods if this therapy is to be translated to the care of human patients. In this study, we assessed the hypothesis that systemic administration of DIZE post ischemic stroke would be neuroprotective. Methods: Adult male Sprague-Dawley rats underwent ischemic stroke by endothelin-1 induced middle cerebral artery occlusion and were randomly divided into 2 groups (n=9-10/set): 1) intraperitoneal (IP) administrations of DIZE (7.5 mg/kg) at 4, 24, and 48 h after stroke; 2) IP administrations of 0.9% saline vehicle at the same time points. At 24 and 72 h after stroke, rats underwent blinded neurologic assessments. Immediately following the 72 h tests, animals were sacrificed, cerebral infarct volumes assessed by TTC staining, and IL-1β expression in the stroke region analyzed by rt-PCR. Data are expressed as mean ± SEM with significance inferred at p Results: Mean infarct volume was significantly decreased by IP injections of DIZE (9.4% ± 4.35) as compared to control (22.8%±3.6, p=0.039). At 24 h post stroke, neurologic deficits (Garcia Scale) were significantly improved in the DIZE treated group (16.7±0.40) versus the saline group (15.22±0.57, p=0.037). Although DIZE tended to improve neurologic deficits 72 h post stroke, this trend was not significant. Finally, DIZE treatment significantly reduced mRNA expression of IL-1β (0.43 ± 0.14) in the cerebral cortical stroke region as compared to saline treatment (1.47±0.08, p=0.001). Conclusions: Our findings suggest that targeting the ACE2/Ang-(1-7)/Mas axis post stroke can improve function, decrease inflammation, and reduce infarct volume - a significant translational step in brain renin-angiotensin system research.