Enlighten-Research publications by members of the University of Glasgow http://eprints.gla.ac.uk Minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation (MISTIE III): a randomised, controlled, open-label phase 3 trial with blinded endpoint

Our results demonstrated that MT+IVT patients had better functional outcomes, lower mortality, higher rate of successful recanalization, requiring lower number of device passes, and equal odds of symptomatic intracerebral hemorrhage compared with MT-IVT patients. The results support the current guidelines of offering intravenous thrombolysis to eligible patients even if they are being considered for mechanical thrombectomy. Because the data are compiled from studies where the 2 groups differed based on eligibility for intravenous thrombolysis, randomized trials are necessary to accurately evaluate the added value of intravenous thrombolysis in patients treated with mechanical thrombectomy.

BackgroundThe COVID-19 pandemic has disrupted established care paths worldwide. Patient awareness of the pandemic and executive limitations imposed on public life have changed the perception of when to seek care for acute conditions in some cases. We sought to study whether there is a delay in presentation for acute ischemic stroke patients in the first month of the pandemic in the US.MethodsThe interval between last-known-well (LKW) time and presentation of 710 consecutive patients presenting with acute ischemic strokes to 12 stroke centers across the US were extracted from a prospectively maintained quality database. We analyzed the timing and severity of the presentation in the baseline period from February to March 2019 and compared results with the timeframe of February and March 2020.ResultsThere were 320 patients in the 2-month baseline period in 2019, there was a marked decrease in patients from February to March of 2020 (227 patients in February, and 163 patients in March). There was no difference in the severity of the presentation between groups and no difference in age between the baseline and the COVID period. The mean interval from LKW to the presentation was significantly longer in the COVID period (603±1035 min) compared with the baseline period (442±435 min, P<0.02).ConclusionWe present data supporting an association between public awareness and limitations imposed on public life during the COVID-19 pandemic in the US and a delay in presentation for acute ischemic stroke patients to a stroke center.

BackgroundCurrent guidelines suggest treating blood pressure above 180/105 mm Hg during the first 24 hours in patients with acute ischemic stroke undergoing any form of recanalization therapy. Currently, no studies exist to guide blood pressure management in patients with stroke treated specifically with mechanical thrombectomy. We aimed to determine the association between blood pressure parameters within the first 24 hours after mechanical thrombectomy and patient outcomes.Methods and ResultsWe retrospectively studied a consecutive sample of adult patients who underwent mechanical thrombectomy for acute ischemic stroke of the anterior cerebral circulation at 3 institutions from March 2015 to October 2016. We collected the values of maximum, minimum, and average values of systolic blood pressure, diastolic blood pressure, and mean arterial pressures in the first 24 hours after mechanical thrombectomy. Primary and secondary outcomes were patients’ functional status at 90 days measured on the modified Rankin scale and the incidence and severity of intracranial hemorrhages within 48 hours. Associations were explored using an ordered multivariable logistic regression analyses. A total of 228 patients were included (mean age 65.8±14.3; 104 males, 45.6%). Maximum systolic blood pressure independently correlated with a worse 90‐day modified Rankin scale and hemorrhagic complications within 48 hours (adjusted odds ratio=1.02 [1.01–1.03], P=0.004; 1.02 [1.01–1.04], P=0.002; respectively) in multivariable analyses, after adjusting for several possible confounders.ConclusionsHigher peak values of systolic blood pressure independently correlated with worse 90‐day modified Rankin scale and a higher rate of hemorrhagic complications. Further prospective studies are warranted to identify whether systolic blood pressure is a therapeutic target to improve outcomes.

SUMMARY Retinitis pigmentosa (RP) initiates with diminished rod photoreceptor function, causing peripheral and nighttime vision loss. However, subsequent loss of cone function and high-resolution daylight and color vision is most debilitating. Visual pigment-rich photoreceptor outer segments (OS) undergo phagocytosis by the retinal pigment epithelium (RPE), and the RPE also acts as a blood-outer retinal barrier transporting nutrients, including glucose, to photoreceptors. We provide evidence that contact between externalized phosphatidylserine (PS) on OS tips and apical RPE receptors activates Akt, linking phagocytosis with glucose transport to photoreceptors for new OS synthesis. As abundant mutant rod OS tips shorten in RP, Akt activation is lost, and onset of glucose metabolism in the RPE and diminished glucose transport combine to cause photoreceptor starvation and accompanying retinal metabolome changes. Subretinal injection of OS tip mimetics displaying PS restores Akt activation, glucose transport, and cone function in end-stage RP after rods are lost.

Object Aneurysmal subarachnoid hemorrhage (aSAH) predisposes to delayed neurological deficits, including stroke and cognitive and neuropsychological abnormalities. Heparin is a pleiotropic drug that antagonizes many of the pathophysiological mechanisms implicated in secondary brain injury after aSAH. Methods The authors performed a retrospective analysis in 86 consecutive patients with Fisher Grade 3 aSAH due to rupture of a supratentorial aneurysm who presented within 36 hours and were treated by surgical clipping within 48 hours of their ictus. Forty-three patients were managed postoperatively with a low-dose intravenous heparin infusion (Maryland low-dose intravenous heparin infusion protocol: 8 U/kg/hr progressing over 36 hours to 10 U/kg/hr) beginning 12 hours after surgery and continuing until Day 14 after the ictus. Forty-three control patients received conventional subcutaneous heparin twice daily as deep vein thrombosis prophylaxis. Results Patients in the 2 groups were balanced in terms of baseline characteristics. In the heparin group, activated partial thromboplastin times were normal to mildly elevated; no clinically significant hemorrhages or instances of heparin-induced thrombocytopenia or deep vein thrombosis were encountered. In the control group, the incidence of clinical vasospasm requiring rescue therapy (induced hypertension, selective intraarterial verapamil, and angioplasty) was 20 (47%) of 43 patients, and 9 (21%) of 43 patients experienced a delayed infarct on CT scanning. In the heparin group, the incidence of clinical vasospasm requiring rescue therapy was 9% (4 of 43, p = 0.0002), and no patient suffered a delayed infarct (p = 0.003). Conclusions In patients with Fisher Grade 3 aSAH whose aneurysm is secured, postprocedure use of a low-dose intravenous heparin infusion may be safe and beneficial.

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BACKGROUND:Minimally invasive surgery procedures, including stereotactic catheter aspiration and clearance of intracerebral hemorrhage (ICH) with recombinant tissue plasminogen activator hold a promise to improve outcome of supratentorial brain hemorrhage, a morbid and disabling type of stroke. A recently completed Phase III randomized trial showed improved mortality but was neutral on the primary outcome (modified Rankin scale score 0 to 3 at 1 yr). OBJECTIVE: To assess surgical performance and its impact on the extent of ICH evacuation and functional outcomes. METHODS: Univariate and multivariate models were used to assess the extent of hematoma evacuation efficacy in relation to mRS 0 to 3 outcome and postulated factors related to patient, disease, and protocol adherence in the surgical arm (n = 242) of the MISTIE trial. RESULTS: Greater ICH reduction has a higher likelihood of achieving mRS of 0 to 3 with a minimum evacuation threshold of ≤15 mL end of treatment ICH volume or ≥70% volume reduction when controlling for disease severity factors. Mortality benefit was achieved at ≤30 mL end of treatment ICH volume, or >53% volume reduction. Initial hematoma volume, history of hypertension, irregular-shaped hematoma, number of alteplase doses given, surgical protocol deviations, and catheter manipulation problems were significant factors in failing to achieve ≤15 mL goal evacuation. Greater surgeon/site experiences were associated with avoiding poor hematoma evacuation. CONCLUSION: This is the first surgical trial reporting thresholds for reduction of ICH volume correlating with improved mortality and functional outcomes. To realize the benefit of surgery, protocol objectives, surgeon education, technical enhancements, and case selection should be focused on this goal.