Continuous Monitoring of Cerebral Autoregulation in Adults Supported by Extracorporeal Membrane Oxygenation.

BACKGROUND: Impaired cerebral autoregulation (CA) is one of several proposed mechanisms of acute brain injury in patients supported by extracorporeal membrane oxygenation (ECMO). The primary aim of this study was to determine the feasibility of continuous CA monitoring in adult ECMO patients. Our secondary aims were to describe changes in cerebral oximetry index (COx) and other metrics of CA over time and in relation to functional neurologic outcomes. METHODS: This is a single-center prospective observational study. We measured COx, a surrogate measurement of cerebral blood flow measured by near-infrared spectroscopy, which is an index of CA derived from the moving correlation between mean arterial pressure (MAP) and slow waves of regional cerebral oxygen saturation. A COx value that approaches 1 indicates impaired CA. Using COx, we determined the optimal MAP (MAPOPT) and lower and upper limits of autoregulation for individual patients. These measurements were examined in relation to modified Rankin Scale (mRS) scores. RESULTS: Fifteen patients (median age 57 years [interquartile range 47-69]) with 150 autoregulation measurements were included for analysis. Eleven were on veno-arterial ECMO (VA-ECMO), and four were on veno-venous ECMO (VV-ECMO). Mean COx was higher on postcannulation day 1 than on day 2 (0.2 vs. 0.09, p < 0.01), indicating improved CA over time. COx was higher in VA-ECMO patients than in VV-ECMO patients (0.12 vs. 0.06, p = 0.04). Median MAPOPT for the entire cohort was highly variable, ranging from 55 to 110 mm Hg. Patients with mRS scores 0-3 (good outcome) at 3 and 6 months spent less time outside MAPOPT compared with patients with mRS scores 4-6 (poor outcome) (74% vs. 82%, p = 0.01). The percentage of time when observed MAP was outside the limits of autoregulation was higher on postcannulation day 1 than on day 2 (18.2% vs. 3.3%, p < 0.01). CONCLUSIONS: In ECMO patients, it is feasible to monitor CA continuously at the bedside. CA improved over time, most significantly between postcannulation days 1 and 2. CA was more impaired in VA-ECMO patients than in VV-ECMO patients. Spending less time outside MAPOPT may be associated with achieving a good neurologic outcome.

Continuous Monitoring of Cerebral Autoregulation in Adults Supported by Extracorporeal Membrane Oxygenation.

Background: Impaired cerebral autoregulation (CA) is one of several proposed mechanisms of acute brain injury in patients supported by extracorporeal membrane oxygenation (ECMO). The primary aim of this study was to determine the feasibility of continuous CA monitoring in adult ECMO patients. Our secondary aims were to describe changes in cerebral oximetry index (COx) and other metrics of CA over time and in relation to functional neurologic outcomes. Methods: This is a single-center prospective observational study. We measured Cox, a surrogate measurement of cerebral blood flow, measured by near-infrared spectroscopy, which is an index of CA derived from the moving correlation between mean arterial pressure and slow waves of regional cerebral oxygen saturation. A COx value that approaches 1 indicates impaired CA. Using COx, we determined the optimal MAP (MAPOPT), lower and upper limits of autoregulation for individual patients. These measurements were examined in relation to modified Rankin Scale (mRS) scores. Results: Fifteen patients (median age=57 years [IQR=47-69]) with 150 autoregulation measurements were included for analysis. Eleven were on veno-arterial ECMO and 4 on veno-venous. Mean COx was higher on post-cannulation day 1 than on day 2 (0.2 vs 0.09, p<0.01), indicating improved CA over time. COx was higher in VA-ECMO patients than in VV-ECMO (0.12 vs 0.06, p=0.04). Median MAPOPT for entire cohort was highly variable, ranging 55-110 mmHg. Patients with mRS 0-3 (good outcome) at 3 and 6 months spent less time outside of MAPOPT compared to patients with mRS 4-6 (poor outcome) (74% vs 82%, p=0.01). The percentage of time when observed MAP was outside the limits of autoregulation was higher on post-cannulation day 1 than on day 2 (18.2% vs 3.3%, p<0.01). Conclusions: In ECMO patients, it is feasible to monitor CA continuously at the bedside. CA improved over time, most significantly between post-cannulation days 1 and 2. CA was more impaired in VA-ECMO than VV-ECMO. Spending less time outside of MAPOPT may be associated with achieving a good neurologic outcome.

Characterization of Cerebral Hemodynamics with TCD in Patients Undergoing VA-ECMO and VV-ECMO: a Prospective Observational Study.

BACKGROUND: Extracorporeal membrane oxygenation has a high risk of acute brain injury and resultant mortality. Transcranial Doppler characterizes cerebral hemodynamics in real time, but limited data exist on its interpretation in ECMO. Here, we report TCD mean flow velocity and pulsatility index in a large ECMO population. METHODS: This was a prospective cohort study at a tertiary care center. The patients were adults on venoarterial ECMO or venovenous ECMO undergoing TCD studies. RESULTS: A total of 135 patients underwent a total of 237 TCD studies while on VA-ECMO (n = 95, 70.3%) or VV-ECMO (n = 40, 29.6%). MFVs were captured reliably (approximately 90%) and were similar to a published healthy cohort in all vessels except the internal carotid artery. Presence of a recordable PI was strongly associated with ECMO mode (57% in VA vs. 95% in VV, p < 0.001). Absence of TCD pulsatility was associated with intraparenchymal hemorrhage (14.7 vs. 1.6%, p = 0.03) in VA-ECMO patients. CONCLUSIONS: Transcranial Doppler analysis in a single-center cohort of VA-ECMO and VV-ECMO patients demonstrates similar MFVs and PIs. Absence of PIs was associated with a higher frequency of intraparenchymal hemorrhage and a composite bleeding event. However, cautious interpretation and external validation is necessary for these findings with a multicenter study with a larger sample size.

Early Low Pulse Pressure in VA-ECMO Is Associated with Acute Brain Injury.

BACKGROUND: Pulse pressure is a dynamic marker of cardiovascular function and is often impaired in patients on venoarterial extracorporeal membrane oxygenation (VA-ECMO). Pulsatile blood flow also serves as a regulator of vascular endothelium, and continuous-flow mechanical circulatory support can lead to endothelial dysfunction. We explored the impact of early low pulse pressure on occurrence of acute brain injury (ABI) in VA-ECMO. METHODS: We conducted a retrospective analysis of adults with VA-ECMO at a tertiary care center between July 2016 and January 2021. Patients underwent standardized multimodal neuromonitoring throughout ECMO support. ABI included intracranial hemorrhage, ischemic stroke, hypoxic ischemic brain injury, cerebral edema, seizure, and brain death. Blood pressures were recorded every 15 min. Low pulse pressure was defined as a median pulse pressure < 20 mm Hg in the first 12 h of ECMO. Multivariable logistic regression was performed to investigate the association between pulse pressure and ABI. RESULTS: We analyzed 5138 blood pressure measurements from 123 (median age 63; 63% male) VA-ECMO patients (54% peripheral; 46% central cannulation), of whom 41 (33%) experienced ABI. Individual ABIs were as follows: ischemic stroke (n = 18, 15%), hypoxic ischemic brain injury (n = 14, 11%), seizure (n = 8, 7%), intracranial hemorrhage (n = 7, 6%), cerebral edema (n = 7, 6%), and brain death (n = 2, 2%). Fifty-eight (47%) patients had low pulse pressure. In a multivariable model adjusting for preselected covariates, including cannulation strategy (central vs. peripheral), lactate on ECMO day 1, and left ventricle venting strategy, low pulse pressure was independently associated with ABI (adjusted odds ratio 2.57, 95% confidence interval 1.05-6.24). In a model with the same covariates, every 10-mm Hg decrease in pulse pressure was associated with 31% increased odds of ABI (95% confidence interval 1.01-1.68). In a sensitivity analysis model adjusting for systolic pressure, pulse pressure remained significantly associated with ABI. CONCLUSIONS: Early low pulse pressure (< 20 mm Hg) was associated with ABI in VA-ECMO patients. Low pulse pressure may serve as a marker of ABI risk, which necessitates close neuromonitoring for early detection.

Virtual Rounding in Stroke Care and Neurology Education During the COVID-19 Pandemic - A Residency Program Survey.

BACKGROUND AND PURPOSE: During the coronavirus disease 2019 (COVID-19) pandemic, we instituted virtual inpatient stroke rounds and acute stroke evaluations via telemedicine in the emergency department. We sought to explore trainees' and experienced providers' views on stroke care and education. METHODS: The implementation and the survey took place at a single academic comprehensive stroke center in northeast Ohio in the United States. "Virtual rounding" consisted of patient presentation and discussion in the morning in on-line virtual team format followed by in-person patient rounds in small groups. Acute stroke evaluations in the emergency department included direct in-person evaluation by neurology residents with supervision over telemedicine.The neurology residents, stroke fellows, stroke nurse practitioners, and stroke staff physicians were surveyed 2 months after implementation. Quantitative data was analyzed using descriptive statistical analysis, written responses in comment sections were analyzed using content analysis. RESULTS: Thirty-two of 42 (73%) surveys were completed. Nine (45%) residents and 5 (42%) experienced providers responded that virtual rounds did not compromise learning and education on stroke service. Fifteen (75%) residents and all experienced providers agreed that virtual rounds protected caregivers from exposure to the virus. While more than a third of residents (37%) did not feel comfortable utilizing telemedicine in ED, the majority of experienced providers (89%) were at ease with it. A total of 58% of residents and 67% of experienced providers felt that they were spending less time at the bedside, and 42% of residents and 58% of experienced providers felt less connected to patients during the pandemic. CONCLUSION: Majority of neurology residents' experience was not positive utilising telemedicine as compared to other staff providers. This is likely attributed to lack of prior exposure and unpreparedness. Incorporation of telemedicine curricula in medical school and residency training could prepare the next generation physicians to effectively use these technologies and meet the growing need for telehealth services for current and future pandemics.

Clinical course of infectious intracranial aneurysm undergoing antibiotic treatment.

INTRODUCTION: Infectious intracranial aneurysm (IIA, or mycotic aneurysm) is a cerebrovascular complication of infective endocarditis. We aimed to describe the clinical course of IIAs during antibiotic treatment. METHODS: We reviewed medical records of persons with infective endocarditis who underwent cerebral angiography at a single tertiary referral center from 2011 to 2016. Aneurysms were followed with subsequent angiography for unfavorable outcome (growth, rupture, no change, or new IIA formation) or favorable outcome (regression or resolution) until endovascular therapy, aneurysm resolution, or end of observation. RESULTS: Of 618 patients included, 40 (6.5%) had 43 IIAs. Eighteen (42%) aneurysms underwent initial endovascular treatment. Twenty-five unruptured aneurysms were followed for a median 18 antibiotic days after IIA discovery (interquartile range [IQR] 4-32). Eleven (44%) aneurysms had unfavorable outcome (1 rupture, 2 new IIA formation, 6 enlargement, and 2 no change) at median 21 days (IQR 5-32). Favorable angiographic outcome was seen in 7 (28%) patients (6 resolution, 1 regression) at median 36 days (IQR 24-41). Seven aneurysms had no angiographic reevaluations but showed no evidence of rupture during clinical follow-up for median 4 days (IQR 3-12) until hospital discharge. Saccular morphology was associated with unfavorable aneurysmal outcome (p = 0.013). Longer duration of antibiotic exposure prior to IIA discovery was associated with favorable aneurysmal outcome (p = 0.046). CONCLUSION: IIAs represent a dynamic disease. Only a quarter of IIAs resolve with antibiotics alone. Saccular aneurysmal morphology might predict unfavorable aneurysmal outcome. IIA found after longer antibiotic therapy has higher likelihood of resolution or regression on antibiotic treatment.

MRI Presentation of Infectious Intracranial Aneurysms in Infective Endocarditis.

BACKGROUND: The radiographic appearance of infectious intracranial aneurysms (IIAs) of infective endocarditis (IE) on magnetic resonance imaging (MRI) of brain is varied. We aimed to describe the IIA-specific MRI features in a series of patients with IIAs. METHODS: Records of patients with active IE who had digital subtraction angiography (DSA) at a tertiary medical center from January 2011 to December 2016 were reviewed. MRIs performed prior to IIA treatment were reviewed for findings on susceptibility-weighted imaging (SWI), diffusion-weighted imaging, and T1 with and without contrast. RESULTS: Of the 732 patients with IE, 53 (7%) had IIAs. Of these, 28 patients had an evaluable pre-treatment MRI, in whom 33 IIAs were imaged. MRI to DSA median time was 1 day (interquartile range = 1-5). On MRI, 12 (36%) IIAs had SWI lesion with contrast enhancement, 7 (21%) had cerebral microbleeds, 3 (11%) had sulcal SWI lesion, 2 (6%) IIAs had abscesses, 3 (9%) had intraparenchymal hemorrhage, 3 (9%) had subarachnoid hemorrhage, and 6 (18%) had ischemic stroke at the anatomical locations of IIAs. Four IIAs (12%) had no correlating MRI findings, though those patients had MRI without contrast. CONCLUSION: The MRI features such as SWI lesion and contrast enhancement were the commonest MRI presentations associated with the presence of IIA.

The Management of Acute Ischemic Strokes and the Prevalence of Large Vessel Occlusion in Left Ventricular Assist Device.

BACKGROUND: Ischemic and hemorrhagic strokes are frequent complications among those with left ventricular assist device (LVAD). Scarce data exist regarding the prevalence of acute large vessel occlusion (LVO) and treatment of acute ischemic stroke (AIS) in this setting. METHODS: We reviewed prospectively collected data of LVAD patient registry from a single, tertiary center from October 2004 to November 2016. Among those with AIS complications, patients were divided into early stroke (during implantation hospitalization) and late stroke (post-discharge) groups, and neuroimaging was reviewed and data on acute stroke therapy were collected. RESULTS: Of 477 persons with LVAD, 49 (10.3%) AIS occurred. The majority (29/49, 59%) of AIS occurred in-hospital. Thirty-two (65%) persons had international normalized ratios less than 1.7 at the time of AIS, but none qualified to receive acute intravenous thrombolysis. Of 25 (51%) persons who underwent CT angiography (CTA), 33% (16/49) had acute LVOs. Thirty-one percent (5/16) of persons with acute LVOs underwent intra-arterial endovascular therapy. All of 5 cases presented with middle cerebral artery syndrome with a median pre-procedural National Institutes of Health Stroke Scale of 13 (interquartile range 10-18). Successful recanalization was achieved in all 5 cases. CONCLUSIONS: In-hospital strokes and acute LVOs are common in LVAD-associated AIS. Prompt evaluation with CTA and endovascular therapy should be pursued for these critically ill patients.

Challenging Diagnosis and Inpatient Rehabilitation of Acute Bilateral Neuralgic Amyotrophy Possibly Attributed to Lyme Disease: A Case Report.

Neuralgic amyotrophy (NA) is a neurologic syndrome of unknown etiology primarily affecting the brachial plexus. We are reporting an unusual case of acute bilateral NA that was possibly secondary to Lyme disease. The patient demonstrated significant functional gains and was discharged home after 2 weeks of inpatient rehabilitation, supporting the role of inpatient rehabilitation in acute NA. In this report, we discuss the diagnosis, electrodiagnostic progression, pain management, goals for inpatient rehabilitation, and overall prognosis of NA. LEVEL OF EVIDENCE: V.

Magnetic Resonance Imaging Susceptibility-Weighted Imaging Lesion and Contrast Enhancement May Represent Infectious Intracranial Aneurysm in Infective Endocarditis.

BACKGROUND: Infectious intracranial aneurysm (IIA) can complicate infective endocarditis (IE). We aimed to describe the magnetic resonance imaging (MRI) characteristics of IIA. METHODS: We reviewed IIAs among 116 consecutive patients with active IE by conducting a neurological evaluation at a single tertiary referral center from January 2015 to July 2016. MRIs and digital cerebral angiograms (DSA) were reviewed to identify MRI characteristics of IIAs. MRI susceptibility weighted imaging (SWI) was performed to collect data on cerebral microbleeds (CMBs) and sulcal SWI lesions. RESULTS: Out of 116 persons, 74 (63.8%) underwent DSA. IIAs were identified in 13 (17.6% of DSA, 11.2% of entire cohort) and 10 patients with aneurysms underwent MRI with SWI sequence. Nine (90%) out of 10 persons with IIAs had CMB >5 mm or sulcal lesions in SWI (9 in sulci, 6 in parenchyma, and 5 in both). Five out of 8 persons who underwent MRI brain with contrast had enhancement within the SWI lesions. In a multivariate logistic regression analysis, both sulcal SWI lesions (p < 0.001, OR 69, 95% CI 7.8-610) and contrast enhancement (p = 0.007, OR 16.5, 95% CI 2.3-121) were found to be significant predictors of the presence of IIAs. CONCLUSIONS: In the individuals with IE who underwent DSA and MRI, we found that neuroimaging characteristics, such as sulcal SWI lesion with or without contrast enhancement, are associated with the presence of IIA.

Therapeutic efficacy of FTY720 in a rat model of NK-cell leukemia.

NK-cell leukemia is a clonal expansion of NK cells. The illness can occur in an aggressive or chronic form. We studied cell lines from human and rat NK-cell leukemias (aggressive NK-cell leukemia) as well as samples from patients with chronic NK-cell leukemia to investigate pathogenic mechanisms. Here we report that Mcl-1 was overexpressed in leukemic NK cells and that knockdown of Mcl-1 induced apoptosis in these leukemic cells. In vitro treatment of human and rat NK leukemia cells with FTY720 led to caspase-dependent apoptosis and decreased Mcl-1 expression in a time- and-dose-dependent manner. These biologic effects could be inhibited by blockade of reactive oxygen species generation and the lysosomal degradation pathway. Lipidomic analyses after FTY720 treatment demonstrated elevated levels of sphingosine, which mediated apoptosis of leukemic NK cells in vitro. Importantly, systemic administration of FTY720 induced complete remission in the syngeneic Fischer rat model of NK-cell leukemia. Therapeutic efficacy was associated with decreased expression of Mcl-1 in vivo. These data demonstrate that therapeutic benefit of FTY720 may result from both altered sphingolipid metabolism as well as enhanced degradation of a key component of survival signaling.

Progression of transthyretin amyloid neuropathy after liver transplantation.

OBJECTIVE: To biochemically characterize peripheral nerve amyloid in subjects with transthyretin (TTR) amyloidosis and assess effect of orthotopic liver transplantation (OLT) on progression of neuropathy. METHODS: Amyloid fibrils were isolated from peripheral nerve tissues of 6 patients with TTR amyloidosis who were heterozygous for an amyloid-associated TTR mutation. Ratio of variant to wild-type TTR in the fibrils was determined by amino acid sequencing of tryptic peptides containing either the variant amino acid residue or the corresponding normal amino acid. RESULTS: Amyloid fibrils from 3 subjects who died without having received a liver transplant were composed of 60%-65% variant TTR and 35%-40% wild-type. Amyloid fibrils from a subject who died 5 years after liver transplantation contained 25% variant and 75% wild-type TTR. CONCLUSION: Ratios of variant to wild-type TTR in amyloid patients heterozygous for an amyloid-associated TTR mutation are similar to published ratios for amyloid fibrils in cardiac tissue. Survival after liver transplantation for TTR amyloidosis may be associated with progression of neuropathy due to continued deposition of amyloid derived from wild-type TTR.