Freeman, William D.

Introduction Poor‐grade aneurysmal subarachnoid hemorrhage (aSAH) is associated with high mortality. Overall, 20–30% of aSAH are described as poor grade. Despite recent advances in management strategies, prognosis of poor‐grade aSAH remains dismal. As such, we review the most current literature regarding management strategies that can be used to decrease the risk of the four most common causes of secondary brain injury: 1) aneurysm re‐rupture, 2) hydrocephalus, 3) cerebral salt wasting, and 4) delayed cerebral ischemia/vasospasm. Methods We present a 46‐year‐old female patient with poor‐grade aSAH after a loss of consciousness following thunderclap headache. Examination showed a dilated left pupil and Glasgow Coma Scale (GCS) of 4. Imaging revealed a ruptured anterior communicating artery aneurysm, and she was subsequently taken to the neuro‐interventional radiology suite for EVD placement. On POD 7 Transcranial Doppler (TCD) suggested moderate vasospam of left MCA. Two successful balloon angioplasties of the basilar, ACA‐A1, and MCA‐M1 were successfully performed on separate consecutive days. By POD 10, intermittent severe ICP spikes required targeted temperature management (TTM) with hypothermia. On POD 24, her ICP normalized, she was no longer comatose, and her EVD was clamped and removed. She was rapidly weaned off ventilator and transitioned to rehabilitation. 3‐months postoperatively, Modified Rankin Scale score was 0. Results Based upon the result of our literature review, we propose maintaining blood pressure below 160 mmHg prior to intervention, after which it can be increased to 160–240 mmHg to prevent vasospasm. Transcranial Doppler is essential to detect vasospasm as the aSAH symptoms subtle; once identified, vasospasm can be successfully treated with balloon angioplasty. Finally, targeted temperature management, mannitol, hypertonic saline, and neuromuscular paralysis are essential for postoperative management of ICP levels. Conclusions The multimodal approach should be considered when managing poor grade aSAH. Further research in aSAH management would benefit the patients who present with poor prognosis, thereby improving patient care and leading to a standard, effective approach for aSAH management.

Objective: To report the preliminary safety, tolerability, and cerebral spinal fluid (CSF) sampling utility of serial injections of concentrated intraventricular nicardipine (IVN) in the treatment of aneurysmal subarachnoid hemorrhage (aSAH). Methods: We report the clinical, radiographic, and laboratory safety and tolerability data of a retrospective case series from a single academic medical center. All patients with aSAH developed vasospasm despite enteral nimodipine and received serial injections of concentrated IVN (2.5 mg/mL). CSF injection safety, tolerability, and utility are defined and reported. Results: A total of 59 doses of concentrated IVN were administered to three patients with poor-grade SAH. In Case 1, a 33-year-old man with modified Fisher scale (mFS) grade 4 and Hunt-Hess scale (HH) score 4 received 26 doses; in Case 2, a 36-year-old woman with mFS grade 4 and HH score 5 received 13 doses; and in Case 3, a 70-year-old woman with mFS grade 3 and HH score 4 received 20 doses. No major safety or tolerability events occurred. Two patients were discharged to a rehabilitation facility, and one died after discharge from the hospital. Conclusions: A concentrated 4 mg IVN dose (2.5 mg/mL) in a 1.6 mL injection appears relatively safe and tolerable and potentially offers a second-line strategy for treating refractory vasospasm in poor-grade SAH without compromising intracranial pressure or cerebral perfusion pressure.

Abstract We present the case of a 61-year-old woman with a history of orthotopic heart transplant who was hospitalized with new-onset headache. Magnetic resonance imaging (MRI) of the brain revealed T2 hyperintense signal involving the left occipital lobe with leptomeningeal enhancement and mild vasogenic edema. Initial neurologic examination was normal; however, after 7 days she developed imbalance, visual disturbances, night sweats, bradyphrenia, alexia without agraphia, and right hemianopsia. Brain MRI showed enlargement of the left occipital mass and worsening edema. Stereotactic needle biopsy showed nondiagnostic necrosis. The patient continued to deteriorate despite dexamethasone. Cerebrospinal fluid (CSF) suggested infection, and cytomegalovirus CSF polymerase chain reaction (PCR) was positive. The patient received vancomycin, imipenem, and ganciclovir. After obtaining a positive serum beta-D-glucan (Fungitell), amphotericin was added. Despite best medical efforts, the patient died. Postmortem broad-range PCR sequencing of the brain tissue was positive for rare amoeba Balamuthia mandrillaris.

Importance In patients with severe aortic valve stenosis at intermediate surgical risk, transcatheter aortic valve replacement (TAVR) with a self-expanding supra-annular valve was noninferior to surgery for all-cause mortality or disabling stroke at 2 years. Comparisons of longer-term clinical and hemodynamic outcomes in these patients are limited. Objective To report prespecified secondary 5-year outcomes from the Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement (SURTAVI) randomized clinical trial. Design, Setting, and Participants SURTAVI is a prospective randomized, unblinded clinical trial. Randomization was stratified by investigational site and need for revascularization determined by the local heart teams. Patients with severe aortic valve stenosis deemed to be at intermediate risk of 30-day surgical mortality were enrolled at 87 centers from June 19, 2012, to June 30, 2016, in Europe and North America. Analysis took place between August and October 2021. Intervention Patients were randomized to TAVR with a self-expanding, supra-annular transcatheter or a surgical bioprosthesis. Main Outcomes and Measures The prespecified secondary end points of death or disabling stroke and other adverse events and hemodynamic findings at 5 years. An independent clinical event committee adjudicated all serious adverse events and an independent echocardiographic core laboratory evaluated all echocardiograms at 5 years. Results A total of 1660 individuals underwent an attempted TAVR (n = 864) or surgical (n = 796) procedure. The mean (SD) age was 79.8 (6.2) years, 724 (43.6%) were female, and the mean (SD) Society of Thoracic Surgery Predicted Risk of Mortality score was 4.5% (1.6%). At 5 years, the rates of death or disabling stroke were similar (TAVR, 31.3% vs surgery, 30.8%; hazard ratio, 1.02 [95% CI, 0.85-1.22]; P = .85). Transprosthetic gradients remained lower (mean [SD], 8.6 [5.5] mm Hg vs 11.2 [6.0] mm Hg; P < .001) and aortic valve areas were higher (mean [SD], 2.2 [0.7] cm 2 vs 1.8 [0.6] cm 2 ; P < .001) with TAVR vs surgery. More patients had moderate/severe paravalvular leak with TAVR than surgery (11 [3.0%] vs 2 [0.7%]; risk difference, 2.37% [95% CI, 0.17%- 4.85%]; P = .05). New pacemaker implantation rates were higher for TAVR than surgery at 5 years (289 [39.1%] vs 94 [15.1%]; hazard ratio, 3.30 [95% CI, 2.61-4.17]; log-rank P < .001), as were valve reintervention rates (27 [3.5%] vs 11 [1.9%]; hazard ratio, 2.21 [95% CI, 1.10-4.45]; log-rank P = .02), although between 2 and 5 years only 6 patients who underwent TAVR and 7 who underwent surgery required a reintervention. Conclusions and Relevance Among intermediate-risk patients with symptomatic severe aortic stenosis, major clinical outcomes at 5 years were similar for TAVR and surgery. TAVR was associated with superior hemodynamic valve performance but also with more paravalvular leak and valve reinterventions.

BACKGROUND: Loeys–Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder characterized by a classic triad of hypertelorism, bifid uvula and/or cleft palate, and generalized arterial tortuosity. There are limited data on the prevalence and rupture risk of intracranial aneurysms (IAs) in the setting of LDS, with no established guidelines. OBJECTIVE: To analyze the prevalence and rupture risk of IA in LDS. METHODS: Electronic medical records of patients with a confirmed diagnosis of LDS and available cerebrovascular imaging were reviewed. Patients were divided into 2 groups based on the presence of IA. Unmatched and propensity-matched analyses were used to identify potential risk factors for aneurysm formation. RESULTS: Records of 1111 patients were screened yielding a total of 60 patients with a diagnosis of LDS. Eighteen (30%) patients had IA, 4 (22.2%) of whom had multiple aneurysms for a total of 24 IAs. Twenty-three (95.8%) aneurysms were located in the anterior circulation; none of them were ruptured. On unmatched analysis, age ( P = .015), smoking history ( P = .034), hypertension ( P = .035), and number of extracranial aneurysms ( P < .001) were significantly higher in patients with IA. After matching for age, sex, race, stroke history, family history, and extracranial aneurysms, smoking history ( P = .009) remained significant. CONCLUSION: Patients with LDS have an increased risk of IAs, especially with a history of smoking. The prevalence rate of IAs in our series was 30%. Screening imaging should be considered at diagnosis, and patients should be encouraged to abstain from smoking. Further studies are needed to elucidate the risk of IA rupture and treatment considerations in this unique population.

Background: Elevated intracranial pressure (ICP) is one proposed mechanism leading to poor outcomes in patients with spontaneous intraventricular hemorrhage (IVH). We characterized occurrence and significance of intracranial hypertension in severe IVH requiring extraventricular drainage (EVD). Methods: Prospective analysis of ICP in the first 400 patients enrolled in the CLEAR III trial, a multicenter, double-blind, randomized study comparing EVD plus intraventricular recombinant tissue plasminogen activator (rtPA) vs. EVD plus placebo for treatment of IVH in patients with obstructive IVH and intracerebral hemorrhage (ICH) volume <30cc. Maximum and minimum ICP was recorded every 4 hours in all patients until 7 days post randomization. ICP readings were analyzed at pre-defined thresholds and proportion of high ICP events compared by clinical/radiological variables. Impact on 30 day mortality was assessed. Results: of 17,593 ICP readings, maximum ICP ranged from -4 to 115 mm Hg (median, interquartile range; 11,8); 90.2% (15,861) were ≤ 20 mm Hg, 2.0% were >30, 0.5% were >40, and 0.2% were > 50 mm Hg. Proportion of threshold events > 20 and > 30 mm Hg were more frequent in patients with persistent closure of the lower ventricular system after day 3 (p=0.047 and p=0.04, respectively), but were not correlated with initial or end of treatment (72 hours after last dose of study agent) ICH or IVH volumes. ICP elevation > 20 mm Hg occurred during a required 1 hr EVD closure time after study agent injection in 507/3364 (15.1%) injections although early re-opening of EVDs occurred in only 3.9%. Shunting for hydrocephalus was required in 18% of patients over 1 yr follow-up and was not associated with high ICP events. Percentage of ICP readings per patient > 30 mmHg and ICH/IVH volumes were independent predictors of 30 day mortality after adjustment for other outcome predictors (p=0.01; p=0.04; p<0.001, respectively). Conclusions: ICP is not frequently elevated during monitoring and drainage with an EVD in patients with severe IVH. ICP > 30 mm Hg predicts higher short-term mortality. Early opening of the lower ventricular system may reduce frequency of high ICP events. Injection of thrombolytics can be performed without additional ICP management in the majority of patients.

Objective: This study seeks to investigate the impact of antithrombotics, including Aspirin, Clopidogrel, and Warfarin, on the severity of bleeding and outcomes in patients with subarachnoid hemorrhage (SAH). We hypothesize that patients with a history of antithrombotic use have a more severe injury from SAH. Methods: Two hundred twenty-eight patients admitted to the Mayo Clinic Florida consecutively between July 2008 and July 2011 were studied retrospectively. Of this group, 77 patients had a known history of antithrombotic use while 151 did not. Both aneurysmal and non-aneurysmal cases were included in the study. Each patient’s Hunt and Hess Score, Fisher Grade, modified Rankin Scale (mRS) and Glasgow Coma Scale (GCS) were evaluated. Associations between history of antithrombotic use and severity of SAH were assessed using Spearman’s test of correlation and Mann-Whitney tests. Results: There was strong evidence of higher mRS grades in patients with a history of antithrombotic use compared to other patients (Median: 3 vs. 2, P=0.001). There was no significant difference between patients with and without a history of antithrombotic use regarding SAH Fisher grade (Median: 3 vs. 3, P=0.31) and Hunt and Hess score (Median: 2 vs. 2, P=0.93). The difference in GCS score was not statistically significant (Median: 14 vs. 15, P=0.20). Conclusion: This analysis found a significant effect of previous use of antithrombotics on overall outcome following SAH. Further analysis is needed to correlate the outcomes with specific medications and investigate the role of aggressive reversal of coagulopathy on overall outcomes.