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Objective: Aneurysmal subarachnoid hemorrhage (aSAH) has a high mortality rate, and hemorrhage amounts and perioperative rebleeding importantly determines prognosis. However, despite adequate treatment, prognosis is poor in many ruptured aneurysm cases. In this study, we identified and evaluated factors related to perioperative rebleeding in patients with aSAH.Methods: The medical and surgical records of 166 patients that underwent endovascular embolization for a ruptured cerebral aneurysm at a single institution from 2014 to 2016 were retrospectively analyzed to identify risk factors of rebleeding. All patients were examined for risk factors and evaluated for increased hemorrhage by brain computed tomography at 3 days after surgery.Results: This series included 54 men (32.5%) and 112 women (67.5%) of mean age 58.3±14.3 years. After procedures, 26 patients (15.7%) experienced rebleeding, and 1 of these (0.6%) experienced an intraoperative aneurysmal rupture. External ventricular drainage (EVD) (odds ratio [OR] 5.389, [95% confidence interval (CI) 1.171- 24.801]) and modified Fisher grade (OR 2.037, [95% CI 1.077-3.853]) were found to be independent risk factors of rebleeding, and perioperative rebleeding was strongly associated with patient outcomes (p＜0.001).Conclusions: We concluded the rebleeding risk after aSAH is greater in patients with large hemorrhage amounts and a high pre-operative modified Fisher grade, and thus, we caution neurosurgeons should take care in such cases.

Objectives Acute respiratory distress syndrome (ARDS) in patients with traumatic brain injury (TBI) is associated with increased mortality. Information on the prevalence of ARDS and its neurological outcome after TBI is sparse. We aimed to systematically review the prevalence, risk factors, and outcome of ARDS in TBI population. Data Sources PubMed and four other databases (Embase, Cochrane Library, Web of Science Core Collection, and Scopus) from inception to July 6, 2020. Study Selection Randomized controlled trials (RCTs) and observational studies in patients older than 18 years old. Data Extraction Two independent reviewers extracted the data. Study quality was assessed by the Cochrane Risk of Bias tool for RCTs, the Newcastle–Ottawa Scale for cohort and case–control studies. Good neurological outcome was defined as Glasgow Outcome Scale ≥ 4. Random-effects meta-analyses were conducted to estimate pooled outcome prevalence and their 95% confidence intervals (CI). Data Synthesis We included 20 studies (n = 2830) with median age of 44 years (interquartile range [IQR] = 35–47, 64% male) and 79% (n = 2237) suffered severe TBI. In meta-analysis, 19% patients (95% CI = 0.13–0.27, I2 = 93%) had ARDS after TBI. The median time from TBI to ARDS was 3 days (IQR = 2–5). Overall survival at discharge for the TBI cohort was 70% (95% CI = 0.64–0.75; I2 = 85%) and good neurological outcome at any time was achieved in 31% of TBI patients (95% CI = 0.23–0.40; I2 = 88%). TBI cohort without ARDS had higher survival (67% vs. 57%, p = 0.01) and good neurological outcomes (34% vs. 23%, p = 0.02) compared to those with ARDS. We did not find any specific risk factors for developing ARDS. Conclusion In this meta-analysis, approximately one in five patients had ARDS shortly after TBI with the median time of 3 days. The presence of ARDS was associated with worse neurological outcome and mortality in TBI. Further research on prevention and intervention strategy of TBI-associated ARDS is warranted. Supplementary Information The online version contains supplementary material available at 10.1007/s00408-021-00491-1.

The authors sought to examine the long-term cognitive outcome of patients with continuous flow left ventricular assist device (CF-LVAD).Data on long-term neurocognitive outcome in LVAD are limited. We examined the neurocognitive outcome of patients who received a CF-LVAD as destination therapy.Patients with HeartWare (HVAD) and HeartMate II who were enrolled in the ENDURANCE and ENDURANCE Supplemental trials were eligible. Cognition was evaluated with neuropsychological testing preoperatively and at 6, 12, and 24 months after implantation. General linear models identified demographic, disease, and treatment factors that predicted decline on each neurocognitive measure.Of 668 patients who completed baseline testing and at least 1 follow-up evaluation, 552 were impaired at baseline on at least 1 cognitive measure. At each follow-up, approximately 23% of tested patients declined and 20% improved relative to baseline on at least 1 cognitive measure. Of those who were intact at baseline, only 10%-12% declined in delayed memory and 11%-16% declined in executive function at all 3 follow-ups. For patients impaired at baseline, delayed memory decline was associated with the HVAD device and male sex, whereas executive function decline was associated with the HVAD device and stroke during CF-LVAD support. For patients intact at baseline, male sex and history of hypertension were associated with decline in immediate memory and executive function, respectively.Neurocognitive function remained stable or improved for most patients (∼80%) with CF-LVAD at 6, 12, and 24 months after implantation. Male sex, hypertension, HVAD, and stroke were associated with cognitive decline.

The subaxial screw fixation technique is commonly used for fixation in a wide range of cervical diseases, including traumatic, degenerative, and neoplastic diseases, rheumatoid arthritis (RA), and spondyloarthropathy. Although it is regarded as a relatively safe procedure, several complications may be encountered during surgery, such as vertebral artery (VA) and nerve root injuries, facet violation, and mass fracture. We report a case of endovascular embolization after VA injury during a high cervical spinal surgery. A 48-year-old woman was scheduled for C-1-2-3 posterior fixation. Plain radiography of the cervical spine revealed a severely unstable state. During dissection around the C1 lateral mass on the right side, sudden brisk arterial bleeding was observed. On vertebral angiography, flow voiding was noted above the right V3 portion. After checking patent collateral flow from the contralateral VA, routine coil embolization was performed to pack the V3 segment. Iatrogenic vascular injuries due to spinal surgery are rare but serious complications. For patients with RA, we recommend careful preoperative evaluation before a high cervical surgical procedure to avoid iatrogenic VA injury and endovascular interventions that are safe and effective in the diagnosis and treatment of such vascular injuries.

Acute respiratory distress syndrome (ARDS) has been associated with secondary acute brain injury (ABI). However, there is sparse literature on the mechanism of lung-mediated brain injury and prevalence of ARDS-associated secondary ABI. We aimed to review and elucidate potential mechanisms of ARDS-mediated ABI from preclinical models and assess the prevalence of ABI and neurological outcome in ARDS with clinical studies. We conducted a systematic search of PubMed and five other databases reporting ABI and ARDS through July 6, 2020 and included studies with ABI and neurological outcome occurring after ARDS. We found 38 studies (10 preclinical studies with 143 animals; 28 clinical studies with 1175 patients) encompassing 9 animal studies (n = 143), 1 in vitro study, 12 studies on neurocognitive outcomes (n = 797), 2 clinical observational studies (n = 126), 1 neuroimaging study (n = 15), and 13 clinical case series/reports (n = 15). Six ARDS animal studies demonstrated evidence of neuroinflammation and neuronal damage within the hippocampus. Five animal studies demonstrated altered cerebral blood flow and increased intracranial pressure with the use of lung-protective mechanical ventilation. High frequency of ARDS-associated secondary ABI or poor neurological outcome was observed ranging 82-86% in clinical observational studies. Of the clinically reported ABIs (median age 49 years, 46% men), the most common injury was hemorrhagic stroke (25%), followed by hypoxic ischemic brain injury (22%), diffuse cerebral edema (11%), and ischemic stroke (8%). Cognitive impairment in patients with ARDS (n = 797) was observed in 87% (range 73-100%) at discharge, 36% (range 32-37%) at 6 months, and 30% (range 25-45%) at 1 year. Mechanisms of ARDS-associated secondary ABI include primary hypoxic ischemic injury from hypoxic respiratory failure, secondary injury, such as lung injury induced neuroinflammation, and increased intracranial pressure from ARDS lung-protective mechanical ventilation strategy. In summary, paucity of clinical data exists on the prevalence of ABI in patients with ARDS. Hemorrhagic stroke and hypoxic ischemic brain injury were commonly observed. Persistent cognitive impairment was highly prevalent in patients with ARDS.

Background and Purpose: Stroke may complicate coronavirus disease 2019 (COVID-19) infection based on clinical hypercoagulability. We investigated whether transcranial Doppler ultrasound has utility for identifying microemboli and clinically relevant cerebral blood flow velocities (CBFVs) in COVID-19. Methods: We performed transcranial Doppler for a consecutive series of patients with confirmed or suspected COVID-19 infection admitted to 2 intensive care units at a large academic center including evaluation for microembolic signals. Variables specific to hypercoagulability and blood flow including transthoracic echocardiography were analyzed as a part of routine care. Results: Twenty-six patients were included in this analysis, 16 with confirmed COVID-19 infection. Of those, 2 had acute ischemic stroke secondary to large vessel occlusion. Ten non-COVID stroke patients were included for comparison. Two COVID-negative patients had severe acute respiratory distress syndrome and stroke due to large vessel occlusion. In patients with COVID-19, relatively low CBFVs were observed diffusely at median hospital day 4 (interquartile range, 3–9) despite low hematocrit (29.5% [25.7%–31.6%]); CBFVs in comparable COVID-negative stroke patients were significantly higher compared with COVID-positive stroke patients. Microembolic signals were not detected in any patient. Median left ventricular ejection fraction was 60% (interquartile range, 60%–65%). CBFVs were correlated with arterial oxygen content, and C-reactive protein (Spearman ρ=0.28 [ P =0.04]; 0.58 [ P P =0.42). Conclusions: In this cohort of critically ill patients with COVID-19 infection, we observed lower than expected CBFVs in setting of low arterial oxygen content and low hematocrit but not associated with suppression of cardiac output.

Despite the common occurrence of brain injury in patients with left ventricular assist device (LVAD), optimal neuromonitoring methods are unknown. A systematic review of PubMed and six electronic databases from inception was conducted until June 5, 2019. Studies reporting methods of neuromonitoring while on LVAD were extracted. Of 5,190 records screened, 37 studies met the inclusion criteria. The neuromonitoring methods include Transcranial Doppler ultrasound for emboli monitoring (TCD-e) (n = 13) and cerebral autoregulation (n = 3), computed tomography and magnetic resonance imaging (n = 9), serum biomarkers (n = 7), carotid ultrasound (n = 3), and near-infrared spectroscopy (n = 2). Of 421 patients with TCD-e, thromboembolic events (TEs) were reported in 79 patients (20%) and microembolic signals (MES) were detected in 105 patients (27%). Ischemic stroke was more prevalent in patients with MES compared to patients without MES (43% vs.13%, p < 0.001). Carotid ultrasound for assessing carotid stenosis was unreliable after LVAD implantation. Elevated lactate dehydrogenase (LDH) levels were associated with TEs. Significant heterogeneity exists in timing, frequency, and types of neuromonitoring tools. TCD-e and serial LDH levels appeared to have potential for assessing the risk of ischemic stroke. Future prospective research incorporating protocolized TCD-e and LDH may assist in monitoring adverse events in patients with LVAD.

OBJECTIVES:Stroke is commonly reported in patients receiving venovenous extracorporeal membrane oxygenation, but risk factors are not well described. We sought to determine preextracorporeal membrane oxygenation and on-extracorporeal membrane oxygenation risk factors for both ischemic and hemorrhagic strokes in patients with venovenous extracorporeal membrane oxygenation support.DESIGN:Retrospective analysis.SETTING:Data reported to the Extracorporeal Life Support Organization by 366 extracorporeal membrane oxygenation centers from 2013 to 2019.PATIENTS:Patients older than 18 years supported with a single run of venovenous extracorporeal membrane oxygenation.INTERVENTIONS:None.MEASUREMENTS AND MAIN RESULTS:Of 15,872 venovenous extracorporeal membrane oxygenation patients, 812 (5.1%) had at least one type of acute brain injury, defined as ischemic stroke, hemorrhagic stroke, or brain death. Overall, 215 (1.4%) experienced ischemic stroke and 484 (3.1%) experienced hemorrhagic stroke. Overall inhospital mortality was 36%, but rates were higher in those with ischemic or hemorrhagic stroke (68% and 73%, respectively). In multivariable analysis, preextracorporeal membrane oxygenation pH (adjusted odds ratio = 0.10; 95% CI, 0.03-0.35; p < 0.001), hemolysis (adjusted odds ratio = 2.27; 95% CI, 1.22-4.24; p = 0.010), gastrointestinal hemorrhage (adjusted odds ratio = 2.01; 95% CI 1.12-3.59; p = 0.019), and disseminated intravascular coagulation (adjusted odds ratio = 3.61; 95% CI, 1.51-8.66; p = 0.004) were independently associated with ischemic stroke. Pre-extracorporeal membrane oxygenation pH (adjusted odds ratio = 0.28; 95% CI, 0.12-0.65; p = 0.003), preextracorporeal membrane oxygenation Po-2 (adjusted odds ratio = 0.96; 95% CI, 0.93-0.99; p = 0.021), gastrointestinal hemorrhage (adjusted odds ratio = 1.70; 95% CI, 1.15-2.51; p = 0.008), and renal replacement therapy (adjusted odds ratio=1.57; 95% CI, 1.22-2.02; p < 0.001) were independently associated with hemorrhagic stroke.CONCLUSIONS:Among venovenous extracorporeal membrane oxygenation patients in the Extracorporeal Life Support Organization registry, approximately 5% had acute brain injury. Mortality rates increased two-fold when ischemic or hemorrhagic strokes occurred. Risk factors such as lower pH and hypoxemia during the pericannulation period and markers of coagulation disturbances were associated with acute brain injury. Further research on understanding preextracorporeal membrane oxygenation and on-extracorporeal membrane oxygenation risk factors and the timing of acute brain injury is necessary to develop appropriate prevention and management strategies.

Despite the common occurrence of neurologic complications in patients with extracorporeal membrane oxygenation (ECMO), data on magnetic resonance imaging (MRI) findings in adult ECMO are limited. We aimed to describe the MRI findings of patients after ECMO cannulation. Records of patients who underwent ECMO from September 2017 to June 2019 were reviewed. MRI studies were performed using multiplanar sequences consisting of T1-, T2-weighted, fluid attenuated inversion recovery (FLAIR), diffusion-weighted imaging (DWI), and susceptibility weighted images (SWI). Of the 78 adult patients who underwent ECMO, 26 (33%) survived. Of 26, eight patients (31%) had MRI studies, with a median age of 47 years (interquartile range [IQR]: 25–57). The median ECMO support time was 8 days (IQR: 4–25) and the median time from decannulation to MRI was 12 days (IQR: 1–34). Five (63%) of eight patients had ischemic infarcts; 4 (50%) had cerebral microhemorrhage; 2 (25%) had intracranial hemorrhage; and 1 (13%) had thoracic cord ischemic infarct. There were no patients with normal MRI. All patients underwent transcranial Doppler (TCD). Four of 8 (50%) showed presence of microemboli with TCD; 3 of 4 (75%) had ischemic infarcts; and 1 of 4 (25%) had presence of multiple cerebral microhemorrhages on MRI. All ischemic infarcts had diffuse pattern of punctate to small lesions for ECMO survivors. The location of cerebral microhemorrhages included lobar ( n = 4, 100%), deep ( n = 2, 50%), and both ( n = 2, 50%). Of the MRI studies, cerebrovascular related lesions were the most frequent, with punctate ischemic infarct being the most common type that may be associated with TCD microemboli. The results of the study suggest that subclinical cerebral lesions are commonly found in patients with ECMO support. Further research is needed to understand long-term effect of these cerebral lesions.

Here, we report the case of a 55 year old male patient without significant preexisting cardiovascular disease who received a deceased donor liver transplant. Intraoperatively, the patient developed cardiogenic shock secondary to stress-induced cardiomyopathy or Takotsubo syndrome (TTS), which was refractory to high-dose vasoactive, inotropic medical therapy. The patient was successfully managed with venoarterial extracorporeal membrane oxygenation (VA-ECMO) for 7 days, with complete recovery of cardiac function and maintenance of the hepatic graft. Given the anticipated need for only a short period of support and the expectation of full myocardial recovery, such patients may represent excellent candidates for the use of VA-ECMO.

Acute brain injury (ABI) increases morbidity and mortality in patients with veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Optimal neurologic monitoring methods have not been well-explicated. We studied the use of Near-infrared Spectroscopy (NIRS) to monitor cerebral regional oxygenation tissue saturation (rSO2) and its relation to ABI in VA-ECMO. In this prospective, observational cohort study of 39 consecutive patients, we analyzed the ability of rSO2 values from continuous bedside NIRS monitoring to predict ABI during VA-ECMO support. ABI occurred in 24 (61.5%) patients. Those with ABI had a lower pre-ECMO Glasgow Coma Scale, more blood product transfusions of pRBCs and FFP, and higher APACHEII score. Baseline rSO2 values were not significantly different between cohorts (54.25 vs 58.50, p = 0.260), while the minimum rSO2 value was lower for patients who experienced an ABI than those who did not (39.75 vs 44.50, p = 0.039). In patients with ABI, 21 (87.5%) had a drop in rSO2 of 25% from baseline, compared to only 7 (46.7%) patients without ABI (p = 0.017). By ROC analysis, we found that desaturations with >25% drop from the baseline rSO2 on VA-ECMO exhibited 86% sensitivity and 55% specificity to predict ABI, with an area under the curve of 0.68. Patients with ABI were more likely to have withdrawal of life sustaining therapy (17 vs 5, p = 0.049), while neurologic outcome and mortality were not statistically different between patients with or without ABI. Our results support that cerebral NIRS is a useful, real-time bedside neuromonitoring tool to detect ABI in VA-ECMO patients. A >25% drop from the baseline was sensitive in predicting ABI occurrence. Further research is needed to assess how to implement this knowledge to utilize NIRS in developing appropriate intervention strategy in VA-ECMO patients.

Stroke is a devastating morbidity associated with left ventricular assist device (LVAD) support. We report a comprehensive analysis of stroke subtypes in the ENDURANCE destination therapy (DT) and ENDURANCE Supplemental (DT2) trials.Patients in the combined HeartWare LVAD (HVAD) cohorts of the DT and DT2 trials were included. Neurologic events included ischemic stroke (ischemic cerebrovascular accident [ICVA]), hemorrhagic stroke (hemorrhagic cerebrovascular accident [HCVA]), and transient ischemic attack (TIA). Peri-operative strokes were defined as occurring within 2 weeks of the implant.A total of 604 patients received an HVAD in the DT (n = 296) and DT2 (n = 308) trials. Over 2 years, 178 (29.5%) had at least 1 cerebrovascular accident (CVA). Forty-four (7.3%) had HCVAs, 116 (19.2%) had ICVAs, and 44 (7.3%) had TIAs. Thirty (5.0%) had peri-operative stroke. In multivariable analysis, sub-therapeutic international normalized ratio (INR) values were independently associated with peri-operative stroke. Supra- and/or sub-therapeutic INR values, peripheral vascular disease, and presence of left ventricular thrombus were independently associated with ICVA. No aspirin and supra- and/or sub-therapeutic INR values were independently associated with TIA. No aspirin, supra- and/or sub-therapeutic INR values, and prior stroke and/or TIA were associated with HCVA. In further analysis, mean arterial pressure (MAP) was higher in the ICVA (86.8mm Hg, p = 0.002 4) and TIA (88.8mm Hg, p0.0001) groups, but not in HCVA, than in the No-CVA group (81.4mm Hg). Time in therapeutic range for INR was 65.3% for the No-CVA group, 62.9% (p = 0.59) for HCVA, 65.1% (p = 0.97) for ICVA, and 63.2% (p = 0.62) for TIA.Supra- and sub-therapeutic INR values at the time of CVA were associated with all stroke subtypes14 days post-implant. MAP was higher among those with ICVA and TIA but not with HCVA compared to without CVA. Our study demonstrates the challenges of anti-thrombotic therapy and blood pressure management in LVAD population.

Objective Chronic subdural hematoma (CSDH) is one of the most common intracranial hemorrhages. It can be managed with a simple surgical treatment such as burr-hole trephination and drainage. However, it has a relatively high recurrence rate. The mechanisms and risk factors for the recurrence have not yet been clearly identified and studies have reported varying results. Methods We analyzed 230 patients with CSDH who were treated with burr-hole trephination and drainage at our institution from March 2011 to March 2016. The patients were divided into recurrence and non-recurrence groups and the medical records of each group were used to analyze the risk factors associated with CSDH recurrence. Results After burr-hole trephination and drainage, CSDH recurrence was observed in 49 (21.3%) of the 230 patients. In univariate analysis, none of the factors showed statistical significance with respect to CSDH recurrence. In multivariate analysis, preoperative antithrombotic medication was the only independent risk factor for CSDH recurrence (odds ratio, 2.407; 95% confidence interval, 1.047-5.531). Conclusion The present study found that preoperative antithrombotic medication was independently associated with CSDH recurrence.

Objectives To review the neurocritical care aspects of patients supported by extracorporeal membrane oxygenation, including cerebral physiology, neurologic monitoring, use of sedatives and anti-seizure medications, and prevalence and management of extracorporeal membrane oxygenation associated brain injury. Data sources PubMed database search using relevant search terms related to neurologic complications, neurocritical care management, and brain injury management in patients with extracorporeal membrane oxygenation. Study selection Articles included original investigations, review articles, consensus statements and guidelines. Data extraction A detailed review of publications performed and relevant publications were summarized. Data synthesis We found no practice guidelines or management strategies for the neurocritical care of extracorporeal membrane oxygenation patients. Such patients are at high risk for hypoxic-ischemic brain injury, intracranial hemorrhage, cerebral edema, and brain death. Improving clinical outcomes will depend on better defining the neurologic complications and underlying pathophysiology that are specific to extracorporeal membrane oxygenation. Currently, insufficient understanding of the pathophysiology of neurologic complications prevents us from addressing their etiologies with specific, targeted monitoring techniques and interventions. Conclusions A large knowledge gap exists in our understanding and treatment of extracorporeal membrane oxygenation-related neurologic complications. A systematic and multidisciplinary approach is needed to reduce the prevalence of these complications and to better manage the neurologic sequelae of extracorporeal membrane oxygenation in a way that will improve patient outcomes.

In recent years, reports of diabetes mellitus (DM) cases that do not fit the traditional classification system have increased in prevalence. While insulin deficiency appears as type 1 DM (T1DM), the new type also has the clinical features of type 2 DM (T2DM); as such, this new type of DM is called ketosis-prone diabetes (KPD) and is correlated with findings of severe hyperglycemia and ketoacidosis. To provide a clear, clinical classification of DM, new classification systems are being studied. Among these, the Aβ system demonstrates the highest sensitivity and specificity in predicting clinical features and prognosis. We report 2 cases of KPD in Korean pediatric patients. The first patient was referred while in a state of diabetic ketoacidosis (DKA) and was considered to have T1DM. However, their blood glucose was well-controlled even with small doses of insulin, and the treatment was able to be changed to metformin therapy. The second patient seemed to be a typical case of T2DM because of his obesity and strong family history. However, blood glucose was not well-controlled with a regular diet, and ketosis occurred. After performing a glucagon stimulation test, both patients showed different clinical features that were finally diagnosed as type A-β+ KPD. The rapid and accurate diagnosis of KPD can reduce the duration of inappropriate insulin use and improve patients' quality of life. Further, the treatment of KPD children should be individualized according to each patient’s lifestyle to preventing recurrent DKA.

Acute ischemic stroke (AIS) is a major complication in left ventricular assist device (LVAD) population. A better understanding of clinical risk factors associated with AIS may help mitigate risk of stroke. We reviewed prospectively collected data of 477 LVAD patients from a tertiary center from October 1, 2004 to December 31, 2016. Supplemental data abstraction was performed on patients with AIS. Fifty-seven (12%) developed 61 AIS. Of 61, 17 (28%) AIS occurred perioperatively. The median time from implant to perioperative AIS was 5 days (interquartile range: 3-9). Pump thrombosis accounted for 19 (31%) of 61 AIS, and 7 (37%) presented initially with AIS before the pump thrombosis. The median lactate dehydrogenase (LDH) at the time of AIS in the pump thrombosis group (806) was higher than LDH at 1 month (437, P = 0.27) at 3 months (334, P = 0.01), and 6 months (286, P = 0.001) before AIS. Thirty-three (54%) AIS occurred while receiving inadequate antithrombotic therapy. Acute infections were common (31, 51%) in AIS and 12 (20%) were associated with acute bloodstream infection. All AIS were explained by a combination of four clinical risk factors. All LVAD-associated AIS occurred perioperatively or in conjunction with pump thrombosis, subtherapeutic anticoagulation, and bloodstream infection. The common underlying thread is occurrence of a prothrombotic state. The results of this study underscore the potential consequences of disruption of delicate hemostatic balance in patients with LVAD.

COVID-19 is an ongoing pandemic with a devastating impact on public health. Acute neurological symptoms have been reported after a COVID-19 diagnosis, however, the long-term neurological symptoms including pain is not well established. Using a prospective registry of hospitalized COVID-19 patients, we assessed pain and neurological function (including functional, cognitive and psychiatric assessments) of several hospitalized patients at 3 months. Our main finding is that 60% of the patients report pain symptoms. 71% of the patients still experienced neurological symptoms at 3 months and the most common symptoms being fatigue (42%) and PTSD (25%). Cognitive symptoms were found in 12%. Our preliminary findings suggests the importance of investigating long-term outcomes and rationalizes the need for further studies investigating the neurologic outcomes and symptoms of pain after COVID-19.

Objective Although COVID-19 is a respiratory disease, all organs can be affected including the brain. To date, specific investigations of brain injury markers (BIM) and endothelial injury markers (EIM) have been limited. Additionally, a male bias in disease severity and mortality after COVID-19 is evident globally. Sex differences in the immune response to COVID-19 may mediate this disparity. We investigated BIM, EIM and inflammatory cytokine/chemokine (CC) levels after COVID-19 and in across sexes. Methods Plasma samples from 57 subjects at Results Three BIMs: MAP2, NSE and S100B, two EIMs: sICAM1 and sVCAM1 and seven CCs: GRO IL10, sCD40L, IP10, IL1Ra, MCP1 and TNFα were significantly (p p Conclusion The acute elevation of BIMs, CCs, and EIMs and the robust associations among them at COVID-19 hospitalization are suggestive of brain and endothelial injury. Higher BIM and inflammatory markers in men additionally suggest that men are more susceptible to the risk compared to women.

Background Patients with Coronavirus disease 2019 (COVID-19)-related acute respiratory disease (ARDS) increasingly receive extracorporeal membrane oxygenation (ECMO) support. While ECMO has been shown to increase risk of stroke, few studies have examined this association in COVID-19 patients. Objective We conducted a systematic review to characterise neurological events during ECMO support in COVID-19 patients. Design Systematic review of cohort and large case series of COVID-19 patients who received ECMO support. Data Sources Studies retrieved from PubMed, EMBASE, Cochrane, Cochrane COVID-19 Study Register, Web of Science, Scopus, Clinicaltrials.gov, and mdRxiv from inception to November 11, 2020. Eligibility Criteria Inclusion criteria were a) Adult population (>18 year old); b) Positive PCR test for SARS-CoV-2 with active COVID-19 disease; c) ECMO therapy due to COVID-19 ARDS; and d) Neurological events and outcome described while on ECMO support. We excluded articles when no details of neurologic events were available. Results 1,322 patients from 12 case series and retrospective cohort studies were included in our study. The median age was 49.2, and 75% (n=985) of the patients were male. Diabetes mellitus and dyslipidaemia were the most common comorbidities (24% and 20%, respectively). Most (95%, n=1,241) patients were on venovenous ECMO with a median P:F ratio at the time of ECMO cannulation of 69.1. The prevalence of intracranial haemorrhage (ICH), ischaemic stroke, and hypoxic ischaemic brain injury (HIBI) was 5.9% (n=78), 1.1% (n=15), and 0.3% (n=4), respectively. The overall mortality of the 1,296 ECMO patients in the 10 studies that reported death was 36% (n=477), and the mortality of the subset of patients who had a neurological event was 92%. Conclusions Neurological injury is a concern for COVID-19 patients who receive ECMO. Further research is required to explore how neuromonitoring protocols can inform tailored anticoagulation management and improve survival in COVID-19 patients with ECMO support.

Background: Ischemic and hemorrhagic cerebrovascular accidents remain common among patients with centrifugal-flow left ventricular assist devices, despite improvements in survival and device longevity. We compared the incidence of neurologic adverse events (NAEs) associated with 2 contemporary centrifugal-flow left ventricular assist devices: the Abbott HeartMate3 (HM3) and the Medtronic HeartWare HVAD (HVAD). Methods: Using the Society of Thoracic Surgeons Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs), we collected data on adult patients who received a centrifugal-flow left ventricular assist device as a primary isolated implant between January 1, 2017, and September 30, 2019. Major NAEs were defined as transient ischemic attack, ischemic cerebrovascular accident, or hemorrhagic cerebrovascular accident. The association of HVAD with risk of NAE in the first year after implant was evaluated using propensity score matching to balance for preimplant risk factors. After matching, freedom from first major NAE in the HM3 and HVAD cohorts was compared with Kaplan-Meier curves. A secondary analysis using multivariable multiphase hazard models was used to identify predictors of NAE, which uses a data-driven parametric fit of the early declining and constant phase hazards and the associations of risk factor with either phase. Results: Of 6205 included patients, 3129 (50.4%) received the HM3 and 3076 (49.6%) received the HVAD. Median follow-up was 9 and 12 months (HM3 and HVAD, respectively). Patients receiving HVAD had more major NAEs (16.4% versus 6.4%, P P P P P Conclusions: HM3 is associated with lower hazard of major NAEs than is HVAD beyond the early postimplantation period and during the constant hazard phase. Defining the explanation for this observation will inform device selection for individual patients.

Background: There is growing evidence that SARS-Cov-2 infection is associated with severe neurological complications. Understanding the nature and prevalence of these neurologic manifestations is essential for identifying higher-risk patients and projecting demand for ongoing resource utilisation. This review and meta-analysis report the neurologic manifestations identified in hospitalised COVID-19 patients and provide a preliminary estimate of disease prevalence. Methods: MEDLINE, Embase and Scopus were searched for studies reporting the occurrence of neurological complications in hospitalised COVID-19 patients. Results: A total of 2,207 unique entries were identified and screened, among which 14 cohort studies and 53 case reports were included, reporting on a total of 8,577 patients. Central nervous system manifestations included ischemic stroke (n = 226), delirium (n = 79), intracranial haemorrhage (ICH, n = 57), meningoencephalitis (n = 13), seizures (n = 3), and acute demyelinating encephalitis (n = 2). Peripheral nervous system manifestations included Guillain-Barrè Syndrome (n = 21) and other peripheral neuropathies (n = 3). The pooled period prevalence of ischemic stroke from identified studies was 1.3% [95%CI: 0.9–1.8%, 102/7,715] in all hospitalised COVID-19 patients, and 2.8% [95%CI: 1.0–4.6%, 9/318] among COVID-19 patients admitted to ICU. The pooled prevalence of ICH was estimated at 0.4% [95%CI: 0–0.8%, 6/1,006]. Conclusions: The COVID-19 pandemic exerts a substantial neurologic burden which may have residual effects on patients and healthcare systems for years. Low quality evidence impedes the ability to accurately predict the magnitude of this burden. Robust studies with standardised screening and case definitions are required to improve understanding of this disease and optimise treatment of individuals at higher risk for neurologic sequelae., SCOPUS: re.j, info:eu-repo/semantics/published

Background There is growing evidence that SARS-Cov-2 infection is associated with severe neurological complications. Understanding the nature and prevalence of these neurologic manifestations is essential for identifying higher-risk patients and projecting demand for ongoing resource utilisation. This review and meta-analysis report the neurologic manifestations identified in hospitalised COVID-19 patients and provide a preliminary estimate of disease prevalence. Methods MEDLINE, Embase and Scopus were searched for studies reporting the occurrence of neurological complications in hospitalised COVID-19 patients. Results A total of 2207 unique entries were identified and screened, among which 14 cohort studies and 53 case reports were included, reporting on a total of 8,577 patients. Central nervous system manifestations included ischemic stroke (n=226), delirium (n=79), intracranial haemorrhage (ICH, n=57), meningoencephalitis (n=13), seizures (n=3), and acute demyelinating encephalitis (n=2). Peripheral nervous system manifestations included Guillain-Barre Syndrome (n=21) and other peripheral neuropathies (n=3). The pooled period prevalence of ischemic stroke from identified studies was 1.3% [95%CI: 0.9% – 1.8%, 102/7715] in all hospitalised COVID-19 patients, and 2.8% [95%CI: 1.0% - 4.6%, 9/318] among COVID-19 patients admitted to ICU. The pooled prevalence of ICH was estimated at 0.4% [95%CI: 0%-0.8%, 6/1006]. Conclusions The COVID-19 pandemic exerts a substantial neurologic burden which may have residual effects on patients and healthcare systems for years. Low quality evidence impedes the ability to accurately predict the magnitude of this burden. Robust studies with standardised screening and case definitions are required to improve understanding of this disease and optimise treatment of individuals at higher risk for neurologic sequelae.

Supplemental Digital Content is available in the text., OBJECTIVES: Stroke has been reported in observational series as a frequent complication of coronavirus disease 2019, but more information is needed regarding stroke prevalence and outcomes. We explored the prevalence and outcomes of acute stroke in an international cohort of patients with coronavirus disease 2019 who required ICU admission. DESIGN: Retrospective analysis of prospectively collected database. SETTING: A registry of coronavirus disease 2019 patients admitted to ICUs at over 370 international sites was reviewed for patients diagnosed with acute stroke during their stay. PATIENTS: Patients older than 18 years old with acute coronavirus disease 2019 infection in ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 2,699 patients identified (median age 59 yr; male 65%), 59 (2.2%) experienced acute stroke: 0.7% ischemic, 1.0% hemorrhagic, and 0.5% unspecified type. Systemic anticoagulant use was not associated with any stroke type. The frequency of diabetes, hypertension, and smoking was higher in patients with ischemic stroke than in stroke-free and hemorrhagic stroke patients. Extracorporeal membrane oxygenation support was more common among patients with hemorrhagic (56%) and ischemic stroke (16%) than in those without stroke (10%). Extracorporeal membrane oxygenation patients had higher cumulative 90-day probabilities of hemorrhagic (relative risk = 10.5) and ischemic stroke (relative risk = 1.7) versus nonextracorporeal membrane oxygenation patients. Hemorrhagic stroke increased the hazard of death (hazard ratio = 2.74), but ischemic stroke did not—similar to the effects of these stroke types seen in noncoronavirus disease 2019 ICU patients. CONCLUSIONS: In an international registry of ICU patients with coronavirus disease 2019, stroke was infrequent. Hemorrhagic stroke, but not ischemic stroke, was associated with increased mortality. Further, both hemorrhagic stroke and ischemic stroke were associated with traditional vascular risk factors. Extracorporeal membrane oxygenation use was strongly associated with both stroke and death.

Background: In a disease that has only existed for 18 months, it is difficult to be fully informed of the long-term sequelae of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Evidence is growing that most organ systems can be affected by the virus, causing severe disabilities in survivors. The extent of the aftermath will declare itself over the next 5–10 years, but it is likely to be substantial with profound socio-economic impact on society.Methods: This is an international multi-center, prospective long-term follow-up study of patients who developed severe coronavirus disease-2019 (COVID-19) and were admitted to Intensive Care Units (ICUs). The study will be conducted at international tertiary hospitals. Patients will be monitored from time of ICU discharge up to 24 months. Information will be collected on demographics, co-existing illnesses before ICU admission, severity of illness during ICU admission and post-ICU quality of life as well as organ dysfunction and recovery. Statistical analysis will consist of patient trajectories over time for the key variables of quality of life and organ function. Using latent class analysis, we will determine if there are distinct patterns of patients in terms of recovery. Multivariable regression analyses will be used to examine associations between baseline characteristics and severity variables upon admission and discharge in the ICU, and how these impact outcomes at all follow-up time points up to 2 years.Ethics and Dissemination: The core study team and local principal investigators will ensure that the study adheres to all relevant national and local regulations, and that the necessary approvals are in place before a site may enroll patients.Clinical Trial Registration:anzctr.org.au: ACTRN12620000799954.

Purpose: Targeted temperature management (TTM) is a standard of care in patients after cardiac arrest for neuroprotection. Currently, the effectiveness and efficacy of TTM after extracorporeal cardiopulmonary resuscitation (ECPR) is unknown. We aimed to compare neurological and survival outcomes between TTM vs non-TTM in patients undergoing ECPR for refractory cardiac arrest. Methods: We searched PubMed and 5 other databases for randomized controlled trials and observational studies reporting neurological outcomes or survival in adult patients undergoing ECPR with or without TTM. Good neurological outcome was defined as cerebral performance category Results: We included 35 studies (n = 2,643) with the median age of 56 years (interquartile range [IQR]: 52-59). The median time from collapse to ECMO cannulation was 58 minutes (IQR: 49-82) and the median ECMO duration was 3 days (IQR: 2.0-4.1). Of 2,643, 1,329 (50.3%) patients received TTM and 1,314 (49.7%) did not. There was no difference in the frequency of good neurological outcome at any time between TTM (29%, 95% confidence interval [CI]: 23%-36%) vs. without TTM (19%, 95% CI: 9%-31%) in patients with ECPR ( P = 0.09). Similarly, there was no difference in overall survival between patients with TTM (30%, 95% CI: 22%-39%) vs. without TTM (24%, 95% CI: 14%-34%) ( P = 0.31). A cumulative meta-analysis by publication year showed improved neurological and survival outcomes over time. Conclusions: Among ECPR patients, survival and neurological outcome were not different between those with TTM vs. without TTM. Our study suggests that neurological and survival outcome are improving over time as ECPR therapy is more widely used. Our results were limited by the heterogeneity of included studies and further research with granular temperature data is necessary to assess the benefit and risk of TTM in ECPR population.

ObjectiveTo investigate brain injury markers (BIM), endothelial injury markers (EIM) and cytokine/chemokine (CC) markers of systemic inflammation in coronavirus disease 2019 (COVID-19) and across sex.MethodsPlasma samples from 57 subjects at ResultsThree BIMs: MAP2, NSE and S100B, two EIMs: sICAM1 and sVCAM1 and seven CCs: GRO IL10, sCD40L, IP10, IL1Ra, MCP1 and TNFα were significantly (pConclusionThe acute elevation of BIMs, CCs, and EIMs and the robust associations among them at COVID-19 hospitalization suggest that brain injury is mediated by endotheliopathy and inflammation. Higher BIM and inflammatory markers in men additionally suggest that men are more susceptible to the risk compared to women.

AIMS Cannabis use has been reported as a risk factor for stroke. We systematically review the prevalence and outcomes of stroke in people with cannabis use. METHODS We searched MEDLINE and 6 other databases from inception to January 2020 for studies on the relationship between cannabis use and stroke. We followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) recommendations. Two independent reviewers extracted the data. Study quality was assessed by the Newcastle-Ottawa Scale for cohort and case-control studies. RESULTS Seventeen studies involving 3,185,560 people with cannabis use were included. Descriptive statistics demonstrated 18,676 (median 1.1%, interquartile range [IQR] 0.3%-1.3%) experienced stroke compared with 0.8% of those without use (Odds Ratio 1.17, 95% CI 1.10-1.25). Among people with cannabis use, median age was 26.2 years (IQR 25.2-34.3 years) and mostly male (median 57.8%). Of stroke subtypes, ischemic stroke was most prevalent (median 1.2%, IQR 0.4%-1.9%), followed by undefined stroke subtype (median 1.2%, IQR 1.1%-1.2%) and hemorrhagic stroke (median 0.3%, IQR 0.1%-0.6%). The majority of people with cannabis use who experienced stroke survived (median: 85.1%, IQR 83%-87.5%) and 64.0% of people experienced a good neurologic outcome, defined as modified Rankin Scale of 0 to 3. Few studies included outcomes of vasospasm or seizure. CONCLUSIONS In people with cannabis use, the prevalence of ischemic stroke and hemorrhagic stroke was 1.2% and 0.3%, respectively, higher than the prevalence of people without use (0.8% and 0.2%). There is insufficient information on timing, exposure, duration, and dose-responsive relationship.

Objective To describe apnoea test (AT) and ancillary study performance for brain death (BD) determination among patients undergoing short-term mechanical circulatory support (MCS) devices, including extracorporeal membrane oxygenation (ECMO) and intra-aortic balloon pump (IABP). Methods We retrospectively analysed data regarding use of AT and ancillary study in consecutive adult patients who were diagnosed with BD while on MCS devices (including ECMO and IABP) over a 10-year period. Results Out of 140 patients, eight were on MCS devices at the time of BD (four ECMO, two ECMO and IABP, two IABP). The most common aetiology of BD was hypoxic ischaemic brain injury (6/8, 75%). In four patients (50%), the AT was not attempted because of haemodynamic instability and ECMO; in the remaining four (50%), both AT and ancillary studies were used. In three patients on ECMO, AT was performed by reducing the ECMO sweep flow rate to a range 0.5–2.7 L/min in order to achieve hypercarbia. One patient underwent AT while on IABP which was complicated by hypotension. All patients underwent ancillary tests, most commonly transcranial Doppler ultrasonography (TCD) (7/8, 88%); among those, cerebral circulatory arrest was confirmed in six of seven patients (86%), all of whom had left ventricular ejection fracture (LVEF) ≥20% and/or were supported with IABP. Conclusions There are multiple uncertainties regarding BD diagnosis while on MCS, prompting the need for ancillary studies in most patients. Our study shows that TCD can be used to support BD diagnosis in patients on ECMO who have sufficient cardiac contractility and/or IABP to produce pulsatile flow. TCD use in ECMO patients low LVEF needs further study.

Strokes are common among patients with left ventricular devices (LVAD). We hypothesize that there is ongoing cerebral microvascular injury with LVAD support and aim to describe this among LVAD-implanted patients through post-mortem neuropathologic evaluation. We identified and reviewed medical records of LVAD patients who underwent brain autopsy between January 2006 and December 2019 at a tertiary center. Cerebral injury was defined as both gross and microscopic injuries within the intracranial space including cerebral infarct (CI), hypoxic-ischemic brain injury (HIBI), intracranial hemorrhage (ICH), and cerebral microvascular injury. Cerebral microvascular injury was defined as microscopic brain intraparenchymal or perivascular hemorrhage, perivascular hemosiderin deposition, and perivascular inflammation. Twenty-one patients (median age = 57 years, 67% male) had autopsy after LVAD support (median LVAD support = 51 days). The median time from death to autopsy was 19 h. All 21 patients had cerebral injuries and 19 (90%) patients had cerebral microvascular injuries. Fourteen patients (78%) harbored more than one type of cerebral injury. On gross examination, 8 patients (38%) had CI, and 6 patients (29%) had ICH. On microscopic exam, 12 patients (57%) had microscopic intraparenchymal hemorrhage, 3 patients (14%) had perivascular hemorrhage, 11 patients (43%) had perivascular hemosiderin deposition, 5 patients (24%) had meningeal hemorrhage, 13 patients had chronic perivascular inflammation (62%), and 2 patients had diffuse HIBI (10%). Among patients with LVAD, there is a high prevalence of subclinical microvascular injuries and cerebral microbleeds (CMBs), which may provide some insights to the cause of frequent cerebral injury in LVAD population.

Objectives: To evaluate the safety of acute ischemic stroke (AIS) therapy in patients with infective endocarditis (IE) with intravenous thrombolysis (IVT) or endovascular therapy (EVT) such as mechanical thrombectomy. Methods: We conducted a retrospective study of patients who underwent AIS therapy with IVT or EVT at a tertiary referral center from 2013 to 2017, that were later diagnosed with acute IE as the causative mechanism. We then performed a systematic review of reports of acute ischemic reperfusion therapy in IE since 1995 for their success rates in terms of neurological outcome, and mortality, and their risk of hemorrhagic complication. Results: In the retrospective portion, 8 participants met criteria, of whom 4 received IVT and 4 received EVT. Through systematic review, 24 publications of 32 participants met criteria. Combined, a total of 40 participants were analyzed: 18 received IVT alone, 1 received combined IVT plus EVT, and 21 received EVT alone. IVT compared to EVT were similar in rates of good neurologic outcomes (58% versus 76%, P= .22) and mortality (21% versus 19%, P= .87), but had higher post-therapy intracranial hemorrhage (63% versus 18% [P= .006]). Conclusion: IV thrombolysis has a higher rate of post-therapy intracranial hemorrhage compared to EVT. EVT should be considered as first-line AIS therapy for patients with known, or suspected, IE who present with a large vessel occlusion.

Despite the common occurrence left ventricular assist device (LVAD)-associated intracranial hemorrhage, the etiology of intracranial hemorrhage is uncertain. We aim to explore the impact of infection and international normalized ratio (INR) on intracranial hemorrhage in a case-crossover study. We reviewed consecutive patients with intracranial hemorrhage in a prospectively collected data of LVAD patients from a single, tertiary center from October 2004 to December 2016. Information on infection and INR values were collected at the time and 1 month before the intracranial hemorrhage as controls. Of 477 persons with LVAD, 47 (10%) developed intracranial hemorrhage (27 intracerebral, 14 subarachnoid, and 6 subdural hemorrhages). Of 47 (median age 58; 39 males), 27 (54%) persons had active infection at the time of intracranial hemorrhage; seven (21%) of 44 LVADs had infection at 1 month before intracranial hemorrhage. The relative risk of intracranial hemorrhage because of active infection compared with the infections at 1 month was 2.3 (95% CI: 1.5-3.4; p0.0001). The mean INRs at the time of intracranial hemorrhage were also significantly higher at the time of hemorrhage compared with those at 1 month (2.6 ± 1.9 vs. 1.8 ± 0.8; p = 0.01). Of 13 persons with cerebral angiogram (seven subarachnoid and six intracerebral hemorrhages), four (57%) infectious intracranial aneurysms were identified only in patients with subarachnoid hemorrhage (SAH) who also had bloodstream infections. Active infection and elevated INR were associated with LVAD-associated intracranial hemorrhage. The occurrence of both bloodstream infection and subarachnoid hemorrhage may indicate the presence of infectious intracranial aneurysm in LVAD.

Bloodstream infection is the leading cause of mortality in left ventricular assist device. Bloodstream infection is a risk factor for intracranial hemorrhage. We report three left ventricular assist device recipients who presented with bloodstream infection and developed subarachnoid hemorrhage. Case 1, a 37-year-old male with non-ischemic cardiomyopathy with HeartMate II, presented with confusion and found to have serratia bloodstream infection and left frontal lobe subarachnoid hemorrhage. Cerebral angiogram showed a right M3/M4 branch infectious intracranial aneurysm. He was treated with coil embolization and underwent device exchange. Case 2, a 41-year-old male with non-ischemic cardiomyopathy with HeartMate II presented with confusion and found to have methicillin-resistant staphylococcus aureus bloodstream infection and bilateral frontal convexity subarachnoid hemorrhage. Cerebral angiogram showed left M3 and left A3 infectious intracranial aneurysms, which were treated with antibiotics alone. Case 3, a 58-year-old female with ischemic cardiomyopathy with HeartMate II presented with fever, found to have candida albicans bloodstream infection and a parieto-occipital enhancing lesion concerning for cerebral abscess. Repeat computed tomography brain a week later showed a new right frontal subarachnoid hemorrhage. Cerebral angiogram showed a M4/M5 junction infectious intracranial aneurysm; patient was not a surgical candidate and was transitioned to hospice. This case series emphasizes that left ventricular assist device–associated subarachnoid hemorrhage may be caused by infectious intracranial aneurysms when acute bloodstream infections are present.

Background Little data exist regarding reversal and resumption of antithrombotics after left ventricular assist device (LVAD)–associated intracranial hemorrhage. Methods Prospectively collected data of LVAD patients with intracranial hemorrhage were reviewed. Coagulopathy reversal agents, antithrombotic regimens, and thrombotic (venous thromboembolism, ischemic stroke, myocardial infarction) and hemorrhagic (recurrent intracranial hemorrhage, gastrointestinal bleed, anemia requiring transfusion) complications were recorded. Results Of 405 patients, intracranial hemorrhage occurred in 39 (10%): 23 intracerebral hemorrhages, 10 subarachnoid hemorrhages, and 6 subdural hematomas. Of 27 patients who received antithrombotic reversal, 8 (30%) had inadequate coagulopathy reversal, and 3 of these patients had hemorrhage expansion or died before repeat imaging. One (4%) patient had a thrombotic complication (deep vein thrombosis). Antithrombotic therapy was resumed in 17 (100%) survivors in a median time 8 days for antiplatelet agents and 14 days for warfarin. Recurrent intracranial hemorrhage occurred within a median of 7 days of antithrombotic resumption, while ischemic stroke occurred in a median of 428 days. Patients who resumed antiplatelets alone (n = 4) had a trend toward more thrombotic events (1.37 versus 0.14 events/patient-year [EPPY]; p = 0.08), including more fatal thrombotic events (0.34 EPPY versus 0.08 EPPY; p = 0.89) compared with those resuming warfarin ± antiplatelet (n = 14). Nonfatal hemorrhage event rates were 0.34 EPPY in the warfarin ± antiplatelet versus 0 EPPY in the antiplatelet-alone group (p = 0.16). No fatal hemorrhagic events occurred. Conclusions Reversal of anticoagulation appears safe after LVAD-associated intracranial hemorrhage, though inadequate reversal was common. Resumption of warfarin ± antiplatelet was associated with fewer fatal and nonfatal thrombotic events compared with antiplatelets alone, though more nonfatal hemorrhage events occurred.

Objective Carotid artery stenting is helpful in patients with carotid artery stenosis and is a common method of treatment. However, data on the neurological consequences that might arise from, especially Asian patients after CAS is not enough. The purpose of this study was to investigate the outcome and prognostic factors affecting CAS patients. Methods From January 2013 to June 2018 it was enrolled 97 patients who underwent CAS with severe carotid artery stenosis in a single institution. We retrospectively reviewed neurologic complications such as restenosis, ipsilateral or contralateral stroke, and hyperperfusion during the 6-month follow-up period. Results There were no complication occured during the procedure in all 97 patients. Neurologic complications occurred in 30 patients (30.9%) after the procedure, and ipsilateral stroke 6 (6.2%), contralateral stroke 9 (9.4%), restenosis 2 (2.1%) and hyperperfusion 13 respectively. One of them had died (1.0%), of which the rest were discharged after symptoms improve. On univariate analysis, DM and pre-op NIHSS score was associated with the risk of CAS complication, exclusively. On the binary logistic regression for risk factors, DM (OR 0.144, 95% CI [0.029-0.718]), history of radiotheraphy (OR 36.103, 95% CI [1.009-1291.789]) and preoperative NIHSS (OR 1.266, 95% CI [1.059-1.513]) showed independent risk factors associated with post procedural neurological complications, statistically. Conclusion Carotid artery stenting is a relatively safe and reliable long-term outcome for patients with carotid artery stenosis. However, careful observation should be taken after procedure immediately for any possible complications.

Objective The new direct gradual cranial expansion surgical technique has been used to treat children with postshunt microcephaly and slit ventricle syndrome. To evaluate the feasibility of this new surgical treatment, we studied intracranial pressure (ICP) in microcephalic children with developmental delay. Methods Mean ICP, age, sex, head size, and developmental assessments were compared in 24 microcephalic children with developmental delay who had had continuous ICP monitoring. Results Children studied included 9 boys and 15 girls with a mean age of 4.9 ± 2.0 years. Mean ICP was 18.7 ± 8.6 mm Hg. Children with high ICP had significantly lower age and higher B wave ratios than children with low ICP. There were no statistically significant differences in developmental scores and head sizes between children with high ICP and children with low ICP. In multiple linear regression analysis, we observed significantly increased risk of mean ICP elevation by B wave ratio and developmental score and decreased risk of mean ICP elevation by age, but not significantly increased risk of mean ICP elevation by head circumferences (z score). Conclusions Our findings suggest that a portion of microcephalic children with developmental delay have high ICP that cannot be expected from head sizes, and high ICP has decreasing tendency with age.

Infection has been associated with stroke in patients with left ventricular assist devices (LVAD); however, little data exist on the timing, type and mortality impact of infection-related stroke. Prospectively collected data of HeartMate II (N = 332) and HeartWare (N = 70) LVAD patients from a single center were reviewed. Only strokes (ischemic or hemorrhagic) that occurred within 6 weeks following a LVAD infection were considered in analyses. The association between LVAD infections (wound, pump pocket, driveline and/or bloodstream infection [BSI]), specific pathogens and ischemic and hemorrhagic strokes was evaluated using multivariable logistic regression analysis. The impact of infection-related stroke on cumulative survival was assessed using Kaplan–Meier analysis. Of 402 patients, LVAD infection occurred in 158 (39%) including BSI in 107 (27%), driveline infection in 67 (17%), wound infection in 31 (8%) and pump pocket infection in 24 (6%). LVAD infection-related stroke occurred in 20/158 (13%) patients in a median of 4 days (0–36 days) from documented infection. In multivariable analysis, ischemic stroke was associated with wound infection (aOR 9.0, 95% CI 2.4–34.0, P = 0.001) and BSI (aOR 7.7, 95% CI 0.9–66.0, P = 0.064), and hemorrhagic stroke was associated with BSI in 100% of cases (P = 0.01). There was no association with driveline or pump pocket infection. The cumulative survival rate among patients with infection-related stroke was significantly lower compared to those with LVAD infection but no stroke (log-rank P

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. 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. 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. The MRI features such as SWI lesion and contrast enhancement were the commonest MRI presentations associated with the presence of IIA.

OBJECTIVES: Brain death determination often requires ancillary studies when clinical determination cannot be fully or safely completed. We aimed to analyze the results of ancillary studies, the factors associated with ancillary study performance, and the changes over time in number of studies performed at an academic health system. DESIGN: Retrospective cohort. SETTING: Multihospital academic health system. PATIENTS: Consecutive adult patients declared brain dead between 2010 and 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 140 brain death patients, ancillary studies were performed in 84 (60%). The false negative rate of all ancillary studies was 4% (5% of transcranial Doppler ultrasounds, 4% of nuclear studies, 0% of electroencephalograms, and 17% of CT angiography). In univariate analysis, ancillary study use was associated with female sex (odds ratio, 2.4; 95% CI, 1.21-5.01; p = 0.013) and the etiology of brain death being hypoxic-ischemic brain injury (odds ratio, 2.9; 95% CI, 1.43-5.88; p = 0.003), nontraumatic intracranial hemorrhage (odds ratio, 0.45; 95% CI, 0.21-0.96; p = 0.039), or traumatic brain injury (odds ratio, 0.22; 95% CI, 0.04-0.8; p = 0.031). In multivariable analysis, female sex (odds ratio, 5.7; 95% CI, 2.56-15.86; p = 0.004), the etiology of brain death being hypoxic-ischemic brain injury (odds ratio, 3.2; 95% CI, 1.3-8.8; p = 0.015), and the neurologists performing brain death declaration (odds ratio, 0.08; 95% CI, 0.004-0.64; p = 0.034) were factors independently associated with use of ancillary studies. Over the study period, the total number of ancillary studies performed each year did not significantly change; however, the number of electroencephalograms significantly decreased with time (odds ratio per 1-yr increase, 0.67; 95% CI, 0.49-0.90; p = 0.014). CONCLUSIONS: A large number of ancillary studies were performed despite a clinical determination of brain death; patients with hypoxic-ischemic brain injury are more likely to undergo ancillary studies for brain death determination, and neurologists were less likely to use ancillary studies for brain death. Recently, the use of electroencephalograms for brain death determination has decreased, likely reflecting significant concerns regarding its validity and reliability.

The use of left ventricular assist devices (LVADs) has been increasing in the last decade, along with the number of patients with advanced heart failure refractory to medical therapy. Ischemic stroke and intracranial hemorrhage remain the leading causes of morbidity and mortality in LVAD patients. Despite the common occurrence and the significant outcome impact, underlying mechanisms and management strategies of stroke in LVAD patients are controversial. In this article, we review our current knowledge on pathophysiology and risk factors of LVAD-associated stroke, outline the diagnostic approach, and discuss treatment strategies.

Background: Intracranial hemorrhage (ICH) is a devastating complication in patients with an implanted left ventricular assist device (LVAD) for advanced heart failure. Blood stream infection is associated with LVAD-associated ICH. We compared infectious and non-infectious ICH among LVAD recipients. Methods: Records of patients who had LVAD implantation at a tertiary care center were retrospectively reviewed. All LVAD-associated ICH were analyzed, including intraparenchymal hemorrhage (IPH), subarachnoid hemorrhage (SAH), and subdural hemorrhage (SDH). Hemorrhages were categorized into infectious and non-infectious by presence or absence of concurrent bacteremia or driveline infection. Results: Of 683 patients with an LVAD, 74 ICHs occurred in 73 patients (10.7%). IPH was most prevalent (72%), followed by SAH (27%), and SDH (23%). Multiple concurrent subtypes of hemorrhage were present in 22% of events. ICH occurred at median 188 days after implant, and was associated with a 54% in-hospital mortality. Twenty-three ICHs occurred in the setting of infection. While 20% of overall ICH occurred within 30 days of LVAD implantation, only 1 infectious ICH occurred within 30 days of implantation (4.5%). IPH without associated infection was larger (median 41 ml, interquartile range [IQR] 11-70) than without infection (median 9 ml, IQR 2-65, p= 0.04), but in hospital mortality did not differ between infectious and non-infectious ICH (52% vs 59%) or IPH (58% vs 68%). Conclusion: While timing and volume of infectious and non-infectious ICH differ, in-hospital mortality is similarly high in both groups. Further research is necessary to better understand hemorrhagic complications in LVAD patients.

Introduction: Extracorporeal cardio-pulmonary resuscitation (ECPR) is being used more frequently for refractory cardiac arrest (rCA). Stroke remains a key determinant of outcomes in patients receiving ECPR. No studies have yet analyzed sex differences in the frequency of stroke in patients with rCA treated with ECPR. Methods: Retrospective analysis of ECPR cases for rCA identified in the Extracorporeal Life Support Organization (ELSO) International Registry. Age, sex, race/ethnicity and vascular risk factors were included. Stroke was defined as “Ischemic Stroke” and “Intracranial Hemorrhage” as detected by neuroimaging. Statistical analysis: level of significance was set to p≤0.05. To assess sex differences comparative tests were used as appropriate. Results: From 1992 to 2020 a total of 7,460 adult cases of ECPR for rCA were identified; 2,276 (30%) women vs. 5,184 (69%) men; Mean age 50.3 years (±SD 17) in women vs. 54.7 years (±SD 14) in men, (p Conclusions: This is the first study evaluating sex-related differences in the frequency of stroke in patients with ECPR from the largest contemporary ELSO registry. Women were younger than men at the time of rCI and had more intracranial hemorrhages. Men were older and had more ischemic strokes. Morality was high when stroke was present. Our study has implications for future development of sex-targeted treatment strategies when implementing ECPR to reduce neurological complications and to improve outcome.

Mechanical circulatory support (MCS) devices have demonstrated improved survival outcomes in otherwise refractory cardiopulmonary failure but are associated with significant neurologic morbidity and mortality. This review aims to characterize MCS-associated brain injury and discuss the neurocritical care of this population. We found no practice guidelines or specific management strategies for the neurocritical care of patients with MCS devices. Acute brain injury was commonly observed in short-term and durable MCS devices. There is emerging evidence that a standardized neurological monitoring and management algorithm for MCS device–associated brain injury is feasible and potentially improves neurological outcomes. While MCS devices are associated with significant neurologic morbidity and mortality, there is scant evidence regarding optimal neuromonitoring and neurocritical care. With the increase in use of MCS devices for both short-term and durable applications, improved outcomes will depend on early identification and intervention of neurologic complications and further research into their pathophysiology.