Myelinosome formation represents an early stage of oligodendrocyte damage in multiple sclerosis and its animal model

Oligodendrocyte damage is a central event in the pathogenesis of the common neuro-inflammatory condition, multiple sclerosis (MS). Where and how oligodendrocyte damage is initiated in MS is not completely understood. Here, we use a combination of light and electron microscopy techniques to provide a dynamic and highly resolved view of oligodendrocyte damage in neuroinflammatory lesions. We show that both in MS and in its animal model structural damage is initiated at the myelin sheaths and only later spreads to the oligodendrocyte cell body. Early myelin damage itself is characterized by the formation of local myelin out-foldings-'myelinosomes'-, which are surrounded by phagocyte processes and promoted in their formation by anti-myelin antibodies and complement. The presence of myelinosomes in actively demyelinating MS lesions suggests that oligodendrocyte damage follows a similar pattern in the human disease, where targeting demyelination by therapeutic interventions remains a major open challenge

Abstract 147: Utilization and Application of Transcranial Doppler Emboli Monitoring for Infective Endocarditis

Introduction The rapid growth of the elderly population, an increase in cardiac disease, and notable use of intracardiac prosthetic devices has led to an increased prevalence of infective endocarditis (IE). Among the sequelae observed with an IE diagnosis, acute ischemic stroke (AIS), subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH), vasculitis, septic emboli, cerebral abscess, and infectious intracranial aneurysms (IIA) continue to complicate overall management of this disease. Current literature on neurological complications of IE includes limited data on the defined role of neuroimaging in dictating inpatient management. Transcranial doppler (TCD) emboli monitoring with high intensity signals (HITS) offers a real time, radiation‐free, relatively low cost, non‐invasive imaging option to potentially risk stratify and identify candidates for earlier intervention to prevent further cerebrovascular (CV) complications. Methods We conducted an observational study of infective endocarditis cases admitted to our institution from April 2022 to May 2023 who had TCD with HITS completed. Baseline clinical characteristics (age, sex, date and timing of TCD with HITS study, date of last positive blood culture, organism of infection, other neuroimaging utilized) were recorded. Observations recorded included the results of the TCD with HITS studies, the overall incidence and timing of neurological complications (AIS, SAH, ICH, IIA, septic emboli, cerebral abscess), timing of valve surgery, and inpatient mortality rates. A positive HITS was defined as detection of cerebral microembolism during ultrasound monitoring of bilateral middle cerebral arteries (MCA) for 30 minutes using a TCD machine (VIASONIX Dolphin IQ). Results Between April 2022 to July 2023, we identified 22 patients with confirmed left‐sided infective endocarditis who underwent TCD with HITS. Mean age was 66 years (SD, 10), and 82% were men. Leading pathogen types were Enterococcus Faecalis (27%) and Staphylococcus Epidermidis (18%). CV complications were noted in 19/22 patients (86%), the most common being AIS (82%) and IPH (18%). Two patients (9%) were found to have a positive HITS study, both of which developed septic emboli that caused ischemic stroke in one case, and hemorrhagic stroke in the other case. Average days from admission to timing of TCD with HITS study was 8.5 days. 14/22 patients underwent valve surgery (64%) during the admission on average 9.2 days after TCD with HITS study in the negative HITS group versus 5 days in the positive HITS group. Of the positive HITS cases, one of them died inpatient. Conclusion The association between neurological complications in patients with IE and cerebral microemboli detected with TCD monitoring has yet to be elucidated. While our observational study was limited by our sample size, both of our IE patients who had positive TCD with HITS studies developed more severe CV complications, and aggressive care was sought out more urgently to further minimize complications. Future directions include pursuing a prospective study incorporating TCD with HITS monitoring for patients with IE in order to risk‐stratify neurological complications and safety of valve surgery

Ischemic Optic Neuropathy Secondary to Intravascular Lymphoma

Background: To describe a case of optic neuropathy associated with intravascular lymphoma (IVL). Methods: Case report and review of the literature. Results: A case of asymmetric binocular vision loss is described, preceded by transient vision loss. Associated optic perineural enhancement and enhancing and diffusion-positive cortical lesions were observed on magnetic resonance imaging. Biopsy of the cerebellum revealed exclusively intraluminal neoplastic B-cells consistent with IVL.Conclusions: Patients with IVL may rarely present with optic nerve involvement, presumably due to small vessel occlusion. The presentation may mimic features of anterior ischemic optic neuropathy including an acute onset and disc edema. Although optic nerve enhancement and associated white matter lesions may suggest optic neuritis, enhancement of the optic nerve sheath, as in this case, has a wide differential diagnosis, which includes giant cell arteritis. IVL should be considered in atypical cases of optic neuropathy accompanied by enhancing, diffusion-positive brain lesions that are not within a specific vascular territory

Abstract 1122‐000053: Trends in Intervention Modality for Patients with Mycotic Aneurysms: A Nationwide Analysis

Introduction: Mycotic aneurysms, also known as infectious intracranial aneurysms, are sometimes responsible for intracranial hemorrhage in patients with infective endocarditis. Data regarding when and how to treat mycotic aneurysms most effectively are sparse. Given the widespread adoption of endovascular treatments for non‐infectious intracranial aneurysms and acute stroke, we hypothesized that endovascular treatment is increasingly utilized for patients with mycotic aneurysms. We examined trends in endovascular versus open neurosurgical treatment of mycotic aneurysms in patients with infective endocarditis. Methods: We performed a trends analysis using data from 2000–2015 from the National Inpatient Sample. The National Inpatient Sample is an all‐payer database that includes data for a representative sample of hospitalizations to non‐federal hospitals in the United States. We included all hospitalizations for patients with ruptured (on the basis of subarachnoid hemorrhage) or unruptured cerebral aneurysms alongside a diagnosis of infective endocarditis; diagnoses were ascertained using ICD‐9‐CM codes. Treatment modalities were categorized as endovascular versus open neurosurgical repair based on ICD‐9‐CM procedure codes. National Inpatient Sample survey weights were used to calculate nationally representative estimates. Logistic regression was used to evaluate the association between calendar year and intervention rate, presented as an odds ratio for each additional year. Results: We identified 1,015 hospitalizations for patients with a ruptured or unruptured cerebral aneurysm in the setting of infective endocarditis. Their mean age was 54.6 years (SD, 16.6), and 60.1% were male. The overall rate of intervention was 11.9% (95% CI, 9.6‐14.2%), and this rate did not change appreciably over time (p = 0.772). In comparing intervention modalities over time, there was a decrease in open neurosurgical repair (OR, 0.89; 95% CI, 0.84‐0.95; p = 0.001), offset by an increase in endovascular repair (OR, 1.07; 95% CI, 1.01‐1.14; p = 0.023) (Figure). Conclusions: Rates of mycotic aneurysm intervention during hospitalizations for infective endocarditis have not changed. However, the use of endovascular treatment has become more commonplace while the use of open neurosurgical treatments has decreased. Further directions include understanding whether this shift has improved patients’ outcomes and ultimately enumerating best practices for patients with mycotic aneurysms

Abstract 033: Trends in Cerebral Angiogram Utilization for Patients with Infective Endocarditis: A Nationwide Analysis

Introduction Infectious intracranial aneurysms (IIA) represent one of several cerebrovascular pathologies associated with infective endocarditis (IE). Neuroimaging in patients with IE, especially in those undergoing cardiac procedures, have scarcely been examined in the literature. Digital subtraction angiography (DSA), or cerebral angiogram, remains the gold standard for the detection of IIA, yet the utility of this invasive imaging modality is uncertain. Herein, we aim to better understand current national trends in the use of neuroimaging in this group of patients, and its impact on patient outcomes. Methods Hospitalizations for IE with concurrent procedures for left‐sided cardiac valve surgery (VS) were identified in the National Inpatient Sample (NIS) registry during the period of 2015‐2020 using weighted approximations and validated International Classification of Diseases, Tenth Revision, Clinical Modification (ICD‐10‐CM) diagnosis and procedural coding. The primary exposure was DSA and the trend of its use was evaluated during the study period. Multivariable logistic regression analysis was performed to evaluate the adjusted association of angiography with in‐hospital mortality, the primary study endpoint, while accounting for age and illness severity [quantified by All Patient Refined Diagnostic Related Groups (APR‐DRG) illness severity subclass]. Effect size was reported as adjusted odds ratio (aOR) with 95% confidence interval (CI) and a stringent statistical significance threshold of p < 0.001. Results This analysis identified 31,550 hospitalizations for IE treated with VS, of which 1,160 (3.7%) underwent DSA. Utilization of angiography significantly increased during the study period (trend p < 0.001; Kendall’s tau‐b = 0.002), with the rate of the final year of the study nearly doubling that of the first (2020 4.9% vs. 2015 2.5%, p < 0.001). IE VS patients undergoing angiography experienced significantly decreased mortality rates in comparison to those not receiving an angiogram (4.3% vs. 7.5%; p < 0.001). Following multivariable logistic regression analysis, angiography was significantly associated with decreased mortality, independent of age and illness severity (aOR 0.49, 95% CI 0.37, 0.66; p < 0.001). Conclusion The current literature on neurological complications of IE includes limited data on the defined role of neuroimaging in dictating management. The theoretical risk in IE patients undergoing cardiac procedures involving heparinization includes the risk of intracerebral hemorrhage, especially in those with IIA. While less invasive neuroimaging is thought to suffice in detecting bleeds, DSAs remain more sensitive for IIA detection. In our study, not only did the number of IE patients undergoing DSA increase over time, but they had better mortality rates. Future directions should focus on understanding the appropriate timing of imaging in relation to the patient’s disease course to optimize inpatient care

Cerebrovascular complications of COVID-19 and COVID-19 vaccination

The risk of stroke and cerebrovascular disease complicating infection with SARS-CoV-2 has been extensively reported since the onset of the pandemic. The striking efforts of many scientists in cooperation with regulators and governments worldwide have rapidly brought the development of a large landscape of vaccines against SARS-CoV-2. The novel DNA and mRNA vaccines have offered great flexibility in terms of antigen production and led to an unprecedented rapidity in effective and safe vaccine production. However, as mass vaccination has progressed, rare but catastrophic cases of thrombosis have occurred in association with thrombocytopenia and antibodies against PF4 (platelet factor 4). This catastrophic syndrome has been named vaccine-induced immune thrombotic thrombocytopenia. Rarely, ischemic stroke can be the symptom onset of vaccine-induced immune thrombotic thrombocytopenia or can complicate the course of the disease. In this review, we provide an overview of stroke and cerebrovascular disease as a complication of the SARS-CoV-2 infection and outline the main clinical and radiological characteristics of cerebrovascular complications of vaccinations, with a focus on vaccine-induced immune thrombotic thrombocytopenia. Based on the available data from the literature and from our experience, we propose a therapeutic protocol to manage this challenging condition. Finally, we highlight the overlapping pathophysiologic mechanisms of SARS-CoV-2 infection and vaccination leading to thrombosis

Abstract 161: Racial And Ethnic Differences In The Risk Of Ischemic Stroke After Intracerebral Hemorrhage

Byline: Marialaura Simonetto, Weill Cornell Medicine, New York, NY; Alexander E Merkler, Weill Cornell Medicine, New York, NY; Neal S Parikh, Weill Cornell Medicine, New York, NY; Kevin N Sheth, Yale Univ, New Haven, CT; Ralph L Sacco, Univ of Miami, Miami, FL; Wendy C Ziai, Johns Hopkins Univ, Baltimore, MD; Matthew E Fink, Weill Cornell Medicine, New York, NY; Hooman Kamel, Weill Cornell Medicine, New York, NY; Cenai Zhang, Weill Cornell Medicine, New York, NY; Santosh Murthy, Weill Cornell Medicine, New York, NY Background: Intracerebral hemorrhage (ICH) is associated with an increased risk of ischemic stroke. Whether there are racial and ethnic disparities in the risk of ischemic stroke after ICH is poorly understood. Hypothesis: Non-Hispanic Black and Hispanic ICH patients have a higher risk of ischemic stroke compared to White ICH patients. Methods: We retrospectively analyzed data from the Healthcare Cost and Utilization Project on all hospitalizations at all nonfederal hospitals in Florida from 2005 to 2018 and New York from 2006 to 2016. We included patients with an ICH, and without a prior or concomitant diagnosis of ischemic stroke. ICH and ischemic stroke were ascertained using validated ICD-9-CM and ICD-10-CM codes. Using Cox proportional hazard models, we studied the relationship between race and risk of ischemic stroke, after adjustment of demographics and comorbidities. Results: We included 55,582 patients with ICH- 66% Non-Hispanic White, 19% Non-Hispanic Black, and 13% Hispanic. Black and Hispanic patients were younger and had a higher prevalence of cardiovascular comorbidities; however, atrial fibrillation was more prevalent among White patients. During a median follow up period of 3.6 years (IQR 0.7-7.2), an incident ischemic stroke occurred in 3,361 (9%) Non-Hispanic White, 1,308 (12%) Non-Hispanic Black, and 858 (12%) Hispanic patients (p<.001). In adjusted Cox models, the risk of an ischemic stroke was significantly higher among Non-Hispanic Black patients (HR 1.6; 95% CI,1.4-1.7) and Hispanic patients (HR 1.4; 95% CI,1.2-1.5]), compared to non-Hispanic White patients. Conclusions: Among patients with ICH, Non-Hispanic Black and Hispanic patients had a significantly higher risk of ischemic stroke compared to Non-Hispanic White patients.Academi

Rates and Trends of Endotracheal Intubation in Patients With Status Epilepticus

Objective: Among patients with status epilepticus, we sought to determine the rate of endotracheal intubation, identify the physician specialties responsible for endotracheal intubation, and characterize the trend in use of endotracheal intubation over the last 20 years. Methods: We performed a cross-sectional study using data from 2 sources. First, we used inpatient claims between 2009 and 2015 from a nationally representative 5% sample of Medicare beneficiaries. Patients with status epilepticus were identified using International Classification of Diseases, 9th Revision, Clinical Modification ( ICD-9-CM) codes, and those who underwent endotracheal intubation were identified based on Current Procedural Terminology codes. Medical specialties of providers performing intubation were identified based on Healthcare Provider Taxonomy Codes. Second, we used claims data from the National Inpatient Sample (NIS) to estimate the annual rates and trends of endotracheal intubation and tracheostomy among patients with status epilepticus from 1995 to 2014. Results: Among 1971 Medicare beneficiaries with status epilepticus, 566 (29%) patients underwent endotracheal intubation. 375 (66%) patients were intubated on admission. The most common medical providers performing intubation in patients with status epilepticus were emergency medicine physicians (50.4%), anesthesiologists (16.4%), and pulmonary medicine physicians (10.1%). Neurologists accounted for 1.7% of all intubations. Among individuals with status epilepticus identified in the NIS, 248 681 (41.7%) were intubated. The proportion of patients intubated increased from 29.5% (95% confidence interval [CI]: 27.8%-31.3%, P = .018) in 1995 to 50.8% (95% CI: 49.6%-52%, P = .012) in 2014. The proportion of patients with status epilepticus who underwent tracheostomy increased from 2.2% (95% CI: 1.7%-2.7%, P = .005) in 1995 to 3.4% (95% CI: 3%-3.9%, P = .004) in 2014. Significance: Approximately 1 in 3 patients with status epilepticus undergo endotracheal intubation. Over the last 20 years, the proportion of patients with status epilepticus undergoing endotracheal intubation has almost doubled. Neurologists perform a small percentage of these intubations