Neurological Complications In Patients Research Articles

Vascular neurological complications in patients with COVID-19

Vascular neurological complications in patients with COVID-19

Paraneoplastic Neurological Syndromes and Beyond Emerging With the Introduction of Immune Checkpoint Inhibitor Cancer Immunotherapy.

Paraneoplastic neurological syndromes are more commonly seen with malignancies such as small cell lung cancer, thymoma, gynecological malignancies, and breast cancer as well as seminoma. With the introduction of immune checkpoint inhibitor (ICI) cancer immunotherapy we see an increase of autoimmune neurological complications in patients with malignancies not traditionally associated with paraneoplastic neurological syndromes, such as melanoma and renal cell carcinoma. Immune checkpoint inhibitors enhance antitumor immune responses resulting often in immune-related adverse effects that can affect any organ, including the central and peripheral nervous system, neuromuscular junction and muscle. Neurological complications are rare; neuromuscular complications are more common than central nervous system ones but multifocal neurological presentations are often encountered. The vast majority of neurological complications appear within 3 months of ICI initiation, but have been described even after ICI cessation. Neural autoantibody testing reveals autoantibodies in approximately half of the patients with CNS complications. Early suspicion and diagnosis is critical to avoid worsening and improve outcomes. Therapeutic strategies depend on the severity of the symptoms and initially typically involve discontinuation of ICI and high dose steroids. Further immunosuppression might be necessary. Outcomes are dependent on patient's characteristics and clinical presentations.

Neurology and COVID-19: Case Series of Neurological Complications in 96 patients Admitted at a University Hospital

There are multisystemic consequences secondary to SARS- CoV-2 infection. To characterize neurological complications in patients admitted due to SARS-CoV-2 infection. Review of medical records of patients aged over 15 years with COVID-19 evaluated by the neurology team between April and August 2020 at a university hospital. Severity of the infection, referral reasons, neurological diagnoses and laboratory results were registered. The diagnoses were defined by consensus among the members of the hospital neurology group. Cerebrovascular and inflammatory diseases of the central and peripheral nervous system were defined as "probably associated" or "possibly associated" to COVID-19. Ninety-six patients had at least 1 new neu- rological complication. 74% were admitted due to pneumonia and 20% due to a neurological disease. The most common reasons for neurological referral were impaired consciousness (39%), focal neurological deficit (24%), headache (9%) and seizures (5%). The most relevant neurological diagnoses were delirium in 48 patients, stroke in 24, critical illness polyneuropathy and myopathy in 17, seizures in 14, brachial plexopathy in 3, compressive neuropathies in 5, encephalitis in 1, possible vasculitis in 1 and Guillain-Barré syndrome in 1. Stroke and epilepsy were associated with increased length of hospital stay, but without differences in mortality. The spectrum of neurological complications of COVID-19 is wide. There are clinical entities typical of critically ill patients and also diseases associated directly and indirectly with the SARS-CoV2 infection.

Neurological Complications in Patients Requiring Durable VAD Systems after ECLS Support. On Behalf of ECLS- Durable MCS Study Group

Purpose Neurological complications are considered as most frequent complications following left ventricular device device (VAD) implantation. The aim of this multicenter study is to investigate neurological complications in patients requiring durable VADs following extra-corporeal life support (ECLS) implantation. Methods Data of eleven high volume ECLS/VAD centers are collected and evaluated to identify patients who underwent durable mechanical circulatory support system implantation after ECLS systems between January 2010 and July 2018. Preoperative parameters and postoperative outcome are analysed. Data of patients who developed postoperative neurological complication will be analysed and compared. A total of 531 patients meets the inclusion criteria. Patients who were supported with pulsatile pumps, CardioWest TAH and DeBakey VADs will be excluded. The outcome of the remaining 501 patients (mean age 53 ±2 yo, 82% male, average ECLS support duration of 7 ± 7 days and average MELD score of 19 ± 8), who were supported with either HeartWare HVAD, HeartMate II or HeartMate III pumps will be analysed. Endpoints The primary endpoint will be freedom from stroke at 30, 180, and 360 days post implant. Association of stroke events with operative strategies (using heart lung machine vs. ECLS for VAD implantation) will be evaluated. Further, factors predicting stroke events in this patient population are analyzed. We hypothesize that postoperative (after VAD Implantation) stroke complications may be higher in this sick patient population on ECLS compared to traditional VAD candidates.

The Neuroprotective Effect of Thiopental on the Postoperative Neurological Complications in Patients Undergoing Surgical Clipping of Unruptured Intracranial Aneurysm: A Retrospective Analysis.

Although thiopental improved neurological outcomes in several animal studies, there are still insufficient clinical data examining the efficacy of thiopental for patients undergoing surgical clipping of unruptured intracranial aneurysm (UIA). This study validated the effect of thiopental and investigated risk factors associated with postoperative neurological complications in patients undergoing surgical clipping of UIA. In total, 491 patients who underwent aneurysm clipping were included in this retrospective cohort study. Data regarding demographics, aneurysm characteristics, and use of thiopental were collected from electronic medical records. Propensity score matching and logistic regression analysis were used. After propensity score matching, the thiopental group showed a lower incidence of the postoperative neurological complications than non-thiopental group (5.5% vs. 17.1%, p = 0.001). In multivariate analysis, thiopental reduced the risk of postoperative neurological complications (odds ratio (OR) 0.26, 95% confidence interval (CI) 0.13 to 0.51, p < 0.001) while aneurysm size ≥ 10 mm (OR 4.48, 95% CI 1.69 to 11.87, p = 0.003), and hyperlipidemia (OR 2.24, 95% CI 1.16 to 4.32, p = 0.02) increased the risk of postoperative neurological complications. This study showed that thiopental was associated with the lower risk of neurological complications after clipping of UIA.

Clinical outcomes of renal and liver transplant patients undergoing transcatheter aortic valve replacement: analysis of national inpatient sample database

ABSTRACT Background: The transcatheter aortic valve replacement (TAVR) has recently gained traction as a viable alternative to surgical aortic valve replacement (SAVR), but data on its safety and clinical outcomes in transplant patients are limited. Methods: We retrieved relevant demographic and clinical outcome data from the U.S. National Inpatient Sample (NIS) for the year 2012–2015. The clinical outcomes of TAVR in renal transplant (RT) and liver transplant (LT) were ascertained using an adjusted odds ratio (aOR) with a 95% confidence interval (CI) on Mantzel–Hensel test. Results: A total of 62,399 TAVR patients were identified; 62,180 (99.6%) with no history of transplant, 219 (0.4%) with RT and 85 (0.1%) with LT. There was no significant difference in odds of in-hospital mortality (OR 0.61, 95% CI 0.25–1.5, p = 0.37), major cardiovascular, respiratory or neurological complications in patients with and without RT. Similarly, the odds of cardiac complications, renal and neurological complications between patients with and without LT were identical. Conclusion: Compared to non-transplant patients, TAVR appears to be associated with similar odds of major systemic complications or mortality in patients with a history of kidney or liver transplant.

CBCT Radiological Features as Predictors of Nerve Injuries in Third Molar Extractions: Multicenter Prospective Study on a Northeastern Italian Population.

Background: Neurological alterations are one of the main complications occurring after the third molar extractions. The aim of this prospective multicenter cohort study was to find out Cone Beam Computed Tomography (CBCT) features and distribution of neurological complications in patients undergoing lower third molar surgery and to determine the radiological and patient-related factors that could be correlated to the occurrence of inferior alveolar and lingual nerves injury. Material and Methods: 378 patients who underwent lower third molar extraction from March 2018 to March 2019 were included. Clinical and radiological data were collected. CBCT features were recorded following Maglione et al. classification. Symptoms and characteristics of patients who experienced neurological alterations were evaluated. Results: 193 patients needed a second-level radiological exam (CBCT). In these patients, the most common feature was Maglione class 3: a higher frequency of apical or buccal mandibular canals in direct contact with the tooth was observed. 3.17% of the patients developed a neurological complication. Maglione class 4, increased age, and operative time were all positively correlated with neurological alterations. Conclusions: while the buccal or apical position of the mandibular canal was the more common findings, the lingual position was found to have a higher correlation with a negative outcome. Age and operative time were also found to be risk factors for developing nerve injury in the considered population.

The European Academy of Neurology COVID-19 registry (ENERGY): an international instrument for surveillance of neurological complications in patients with COVID-19.

The COVID‐19 pandemic is a global public health issue. Neurological complications have been reported in up to one‐third of affected cases, but their distribution varies significantly in terms of prevalence, incidence and phenotypical characteristics. Variability can be mostly explained by the differing sources of cases (hospital vs. community‐based), the accuracy of the diagnostic approach and the interpretation of the patients’ complaints. Moreover, after recovering, patients can still experience neurological symptoms. To obtain a more precise picture of the neurological manifestations and outcome of the COVID‐19 infection, an international registry (ENERGY) has been created by the European Academy of Neurology in collaboration with European national neurological societies and the Neurocritical Care Society and Research Network. ENERGY can be implemented as a stand‐alone instrument for patients with suspected or confirmed COVID‐19 and neurological findings or as an addendum to an existing registry not targeting neurological symptoms. Data are also collected to study the impact of neurological symptoms and neurological complications on outcomes. The variables included in the registry have been selected in the interests of most countries, to favour pooling with data from other sources and to facilitate data collection even in resource‐poor countries. Included are adults with suspected or confirmed COVID‐19 infection, ascertained through neurological consultation, and providing informed consent. Key demographic and clinical findings are collected at registration. Patients are followed up to 12 months in search of incident neurological manifestations. As of 19 August, 254 centres from 69 countries and four continents have made requests to join the study.

Neurological complications in patient with COVID-19

The article presents an analysis of the literature, as well as our own research on neurological complications in patients with COVID-19. SARS-CoV-2 virus (further – COVID-19) damages the respiratory tract and lungs, leads to the development of not only acute heart, kidney, multiple organ failure, but also accompanied by symptoms of nervous system damage. The most common and severe among the neurological complications of COVID-19 are cerebrovascular diseases, acute necrotic encephalopathy, encephalitis, encephalomyelitis, hypoxic encephalopathy, Hyena-Barre syndrome. Studies have shown that patients with COVID-19 have an average risk of stroke of 5-8%. All subtypes of stroke can occur as a result of infection. Recommendations for the management of stroke patients with COVID-19 are presented. Lesions of the peripheral nervous system are manifested in the form of hyposmia, anosmia, Hyena-Barre syndrome. An association between the severity of the viral infection and the frequency and severity of neurological disorders has been established. The results of own researches of 42 patients in the postcovid period are presented. It was shown that 95.2% of patients had neurocognitive disorders of varying severity, asthenic syndrome (increased fatigue on the MF1-20 scale 13.0 points), sleep disorders, dizziness, vestibular disorders, cephalic syndrome, hyposmia in 19% of patients. The subjects also had anxiety and depressive disorders according to the HADS scale. Ischemic stroke and transient ischemic attacks (TIA) have been reported in some patients. Pathogenetically justified the feasibility of drugs that affect endothelial function.

COVID-19 pneumonia with stroke: Is it a vascular phenomenon or thrombotic event?

COVID-19 disease is known to cause pulmonary and extrapulmonary complications including effects on cardiovascular, gastrointestinal, renal, and neurovascular system. Ischemic stroke seems to be one of the most serious neurologic complications in patients with COVID-19 infection. In this case report, we have documented, 70-year-old male presented with acute respiratory syndrome with hypoxemia and neurological involvement as right hemiparesis with altered level of consciousness, COVID-19 real-time polymerase chain reaction positive, with abnormal laboratory parameters such as ferritin, lactate dehydrogenase, and D-dimer. Further investigations such as echocardiography documented cardiomyopathy and left heart dysfunction, high-resolution computed tomography thorax documented COVID pneumonia, and magnetic resonance imaging brain documented left frontoparietal and parieto-occipital lobe infarct. We have observed excellent clinical and radiological response to anticoagulation, antiplatelets, and steroids with other supportive care in critical care unit.

Evaluation of immediate complications and 10-years neurological outcomes in patients after reconstructive interventions on the ascending aorta and the aortic arch

OBJECTIVE To estimate the frequency of early postoperative neurological complications in patients undergoing planned surgery on the ascending aortic and arch of the aorta, and their long-term outcomes. MATERIAL AND METHODS The prospective study included 100 patients who were operated on at the FSBSI Petrovsky Russian Research Center of Surgery. In group I (n=50), operations were performed on the aortic arch with hypothermic circulatory arrest (26 °C) and antegrade cerebral perfusion. Patients in group II underwent prosthetics of the ascending aorta with extracorporeal circulation and moderate hypothermia (32 °C). All patients underwent monitoring of cerebral and tissue oxygenation, transcranial Doppler and testing of cognitive functions before and after surgery, and after 5 and 10 years of follow-up. RESULTS Postoperative stroke in group I was observed in 1 (2%) patient, no cases were observed in group II. Delirium was detected in 14% of patients in group I and 6% of patients in group II, its subsyndromal form was found in 6 and 4%, respectively. Moderate cognitive impairment in the immediate postoperative period was found in 42 and 26%; severe in 8% of group I. After 5 years of follow-up, the number of patients with moderate and severe cognitive impairment was 23.1 and 12.8%, respectively. After 10 years, severe disorders were identified in 37.5 and 21.9% of patients. CONCLUSION In cardiac surgery patients, intraoperative multimodal monitoring allows dynamic regulation of antegrade cerebral perfusion. Dynamic testing of cognitive functions and early detection of delirium in the immediate postoperative period improve long-term neurological treatment outcomes.

Neurologic Findings Among Inpatients With COVID-19 at a Safety-net US Hospital.

To characterize the breadth of neurologic findings associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a diverse group of inpatients at an urban, safety-net US medical center. Patients were identified through an electronic medical record review from April 15, 2020, until July 1, 2020, at a large safety-net hospital in Boston, MA, caring primarily for underserved, low-income, and elderly patients. All hospitalized adult patients with positive nasopharyngeal swab or respiratory PCR testing for SARS-CoV-2 during their hospitalization or in the 30 days before admission who received an inpatient neurologic or neurocritical care consultation or admission during the study period were enrolled. Seventy-four patients were identified (42/57% male, median age 64 years). The majority of patients self-identified as Black or African American (38, 51%). The most common neurologic symptoms at presentation to the hospital included altered mental status (39, 53%), fatigue (18, 24%), and headache (18, 18%). Fifteen patients had ischemic strokes (20%). There were 10 in-hospital mortalities, with moderately severe disability among survivors at discharge (14%, median modified Rankin Scale score of 4). Neurologic findings spanned inflammatory, vascular pathologies, sequelae of critical illness and metabolic derangements, possible direct involvement of the nervous system by SARS-CoV-2, and exacerbation of underlying neurologic conditions, highlighting a broad range of possible etiologies of neurologic complications in patients with coronavirus disease 2019 (COVID-19). Further studies are needed to characterize the infectious and postinfectious neurologic complications of COVID-19 in diverse patient populations.

Multiscale modeling of blood flow to assess neurological complications in patients supported by venoarterial extracorporeal membrane oxygenation

Computational blood flow models in large arteries elucidate valuable relationships between cardiovascular diseases and hemodynamics, leading to improvements in treatment planning and clinical decision making. One such application with potential to benefit from simulation is venoarterial extracorporeal membrane oxygenation (VA-ECMO), a support system for patients with cardiopulmonary failure. VA-ECMO patients develop high rates of neurological complications, partially due to abnormal blood flow throughout the vasculature from the VA-ECMO system. To better understand these hemodynamic changes, it is important to resolve complex local flow parameters derived from three-dimensional (3D) fluid dynamics while also capturing the impact of VA-ECMO support throughout the systemic arterial system. As high-resolution 3D simulations of the arterial network remain computationally expensive and intractable for large studies, a validated, multiscale model is needed to compute both global effects and high-fidelity local hemodynamics. In this work, we developed and demonstrated a framework to model hemodynamics in VA-ECMO patients using coupled 3D and one-dimensional (1D) models (1D→3D). We demonstrated the ability of these multiscale models to simulate complex flow patterns in specific regions of interest while capturing bulk flow throughout the systemic arterial system. We compared 1D, 3D, and 1D→3D coupled models and found that multiscale models were able to sufficiently capture both global and local hemodynamics in the cerebral arteries and aorta in VA-ECMO patients. This study is the first to develop and compare 1D, 3D, and 1D→ 3D coupled models on the larger arterial system scale in VA-ECMO patients, with potential use for other large scale applications.

Neurologic Complications in Patients With Cancer.

Neurologic complications in patients with cancer can significantly impact morbidity and mortality. Although these complications can be seen in patients without cancer as well, the purpose of this review is to highlight how the presentation, etiology, and management of delirium, seizures, cerebrovascular disease, and central nervous system infections may be different in patients with cancer. Some of the newer anticancer therapies are associated with neurologic complications. Delirium and seizures have been described in patients receiving chimeric antigen receptor (CAR) T-cell therapy and other immune effector cell therapies. Angiogenesis inhibitors can increase the risk of bleeding and clotting, including intracranial hemorrhage and stroke. The risk of opportunistic fungal infections, including aspergillosis, is elevated with the Bruton tyrosine kinase inhibitor ibrutinib. Providers should familiarize themselves with neurologic complications in patients with cancer because early diagnosis and intervention can improve outcomes. The differential diagnosis should be broad, including conventional causes as seen in patients who do not have cancer, with special consideration of etiologies specific to patients with cancer.

&lt;p&gt;Atypical Sleep and Postoperative Delirium in the Cardiothoracic Surgical Intensive Care Unit: A Pilot Prospective Study&lt;/p&gt;

PurposePostoperative delirium (POD) is a very common and serious neurological complication in patients admitted to the cardiothoracic surgical intensive care unit (CSICU). We aimed to identify a novel potential sleep-based marker for POD and investigate the relevance between atypical sleep and POD.Patients and MethodsThis was a prospective, observational study of patients admitted to the CSICU between December 2019 and February 2020 at our center. Sleep characteristics from 21:00 on postoperative day 1 to 07:00 on postoperative day 2 were assessed using polysomnography (PSG). POD from the end of PSG monitoring until postoperative day 5 was evaluated using the Confusion Assessment Method for the Intensive Care Unit.ResultsThis analysis included 20 patients admitted to the CSICU. The incidence of atypical sleep was 45.0%. Compared to patients without delirium, those with delirium had less delta power, less percentage REM sleep, and a higher proportion of atypical sleep and REM sleep loss (P < 0.05).ConclusionThe presence of atypical sleep and the absence of REM sleep were associated with POD in patients admitted to the CSICU.

Strategies to improve outcomes for acute type A aortic dissection with cerebral malperfusion.

We aimed to identify predictors of postoperative permanent neurological deficits (PNDs) and evaluate the early management of cerebral perfusion in patients undergoing surgical repair of acute type A aortic dissection with cerebral malperfusion. Between October 2009 and September 2018, a total of 197 patients with acute type A aortic dissection underwent aortic replacement. Of these, 42 (21.3%) patients had an imaging cerebral malperfusion (ICM). ICM was assessed preoperatively, which also revealed whether dissected supra-aortic branch vessels were occluded or narrowed by a thrombosed false lumen. After September 2017, early reperfusion and extra-anatomic revascularization were performed in cases with ICM. Hospital mortality rates for cases with ICM were 4.8% (2/42). Before September 2017, PND were observed in 6 patients (54.5%) with preoperative neurological symptoms (n = 11), and 7 patients (33.3%) without neurological symptoms (n = 21) in patients with ICM. Occlusion or severe stenosis of supra-aortic branch vessels (odds ratio, 7.66; P < 0.001), regardless of preoperative clinical neurological symptoms, was a risk factor for PND. After September 2017, 7 of 10 patients with ICM underwent early reperfusion and extra-anatomic revascularization. PND did not occur in any of these 7 patients. Occlusion or severe stenosis of supra-aortic branch vessels is a predictor of PND risk in patients undergoing surgery for acute type A aortic dissection. Early reperfusion and extra-anatomic revascularization may reduce the risk of neurological complications in patients with ICM, with or without neurological symptoms.

Enhanced Meningeal Lymphatic Drainage Ameliorates Neuroinflammation and Hepatic Encephalopathy in Cirrhotic Rats

Hepatic encephalopathy (HE) is a serious neurologic complication in patients with liver cirrhosis. Very little is known about the role of the meningeal lymphatic system in HE. We tested our hypothesis that enhancement of meningeal lymphatic drainage could decrease neuroinflammation and ameliorate HE. A 4-week bile duct ligation model was used to develop cirrhosis with HE in rats. Brain inflammation in patients with HE was evaluated by using archived GSE41919. The motor function of rats was assessed by the rotarod test. Adeno-associated virus 8-vascular endothelial growth factor C (AAV8-VEGF-C) was injected into the cisterna magna of HE rats 1 day after surgery to induce meningeal lymphangiogenesis. Cirrhotic rats with HE showed significantly increased microglia activation in the middle region of the cortex (P < .001) as well as increased neuroinflammation, as indicated by significant increases in interleukin 1β, interferon γ, tumor necrosis factor α, and ionized calcium binding adaptor molecule 1 (Iba1) expression levels in at least 1 of the 3 regions of the cortex. Motor function was also impaired in rats with HE (P < .05). Human brains of patients with cirrhosis with HE also exhibited up-regulation of proinflammatory genes (NFKB1, IbA1, TNF-α, and IL1β) (n= 6). AAV8-VEGF-C injection significantly increased meningeal lymphangiogenesis (P= .035) and tracer dye uptake in the anterior and middle regions of the cortex (P= .006 and .003, respectively), their corresponding meninges (P= .086 and .006, respectively), and the draining lymph nodes (P= .02). Furthermore, AAV8-VEGF-C decreased microglia activation (P < .001) and neuroinflammation and ameliorated motor dysfunction (P= .024). Promoting meningeal lymphatic drainage and enhancing waste clearance improves HE. Manipulation of meningeal lymphangiogenesis could be a new therapeutic strategy for the treatment of HE.

Brain magnetic resonance imaging in adult survivors of extracorporeal membrane oxygenation.

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.

High-Dose Methotrexate Based Therapy for the Treatment of Bing Neel Syndrome

BACKGROUND Bing-Neel Syndrome (BNS), characterised by the direct infiltration of central nervous system (CNS) with clonal lymphoplasmacytic lymphoma cells, is a rare cause of neurological complications in patients with Waldenström Macroglobulinaemia (WM). The pathophysiology/neurotropism of BNS is not well understood. Various treatments that appear to cross the blood-brain barrier are used, including chemoimmunotherapy combinations and Ibrutinib. High-dose methotrexate (HDM)-based regimens, including MATRix (methotrexate [MTX], cytarabine, thiotepa, rituximab)1and R-IDARAM (rituximab, MTX [intrathecal and intravenous], cytarabine, dexamethasone) are also used, based on the experience in high-grade CNS lymphoma; however, there are concerns regarding the appropriateness of these regimens in the indolent setting, largely due to their toxicity. This study aimed to determine the efficacy and tolerability of HDM-based, frontline treatment in a large cohort of BNS patients. METHODS A single-centre retrospective review of consecutive patients with BNS treated with HDM based regimens was undertaken. Comprehensive laboratory and CNS imaging results were collated (including whole-brain/spine MRI, bone marrow biopsy, and CSF biochemistry, cytology and MYD88 L265P mutation). Best responses achieved, according to IWWM response assessment criteria, were determined. RESULTS Between 2011 and 2020, 27 patients were treated with HDM-based chemoimmunotherapy: 14 (51.9%) with MATRix, 5 (18.5%) with MTX/cytarabine/rituximab (MAR), 2 (7.4%) with HDM only, and 6 (22.2%) with R-IDARAM. Median time from WM diagnosis to BNS diagnosis was 60 months (0-572 months), including 10 patients (37.0%) who were diagnosed with WM at the time of BNS presentation/diagnosis. Median age at diagnosis with BNS was 66 years (43-75 years), and 15/27 (55.6%) were male. CR was achieved in 6 patients (22.2%), PR in 7 (25.9%), and non-response in 8 (29.6%); PD on therapy occurred in 4 cases (14.8%) and 2 patients died before response could be assessed. Of the 14 patients who received MATRix, 5 (31.2%) achieved PR, 6 (42.9%) had stable disease and 3 (21.4%) progressed while on treatment (Figure 1A). Of the 7 who received MAR or HDM only, 4 (57.1%) achieved CR, with 1 PR and 1 SD; 1 patient died before response could be assessed. Response was not affected by prior chemotherapy (for WM), and no biological or radiological feature predicted response in this highly heterogenous population. Predicted overall survival plateaued at 71.5% 1 year after start of treatment (Figure 1B). At a median follow up of 19.4 months, 7 patients (25.9%) had died: 3 (11.1%) from progressive BNS (1 patient had received each of MATRix, R-IDARAM and HDM only), and 4 (14.8%) from treatment-related toxicity (including infection). Of the latter 4 patients (all male), 2 had received MATRix and 1 had received each of MAR and R-IDARAM. No objective response was seen in 6 of the 7 deceased patients; the remaining 1 patient achieved PR following full-dose MATRix, but subsequently relapsed and died of BNS 7 months later. Regarding dose intensity, 5/15 MATRix recipients (33.3%) received full-dose regimens (i.e. 3.5mg/m2 of MTX per cycle for 3-4 cycles); a further 5 patients received a dose reduction of MTX (to 50-75%) and 9 patients (60%) received &amp;lt;3 cycles. Treatment was discontinued early in 6 of these patients primarily due to inadequate response (SD or PD), in 2 patients due to toxicity, and in 1 patient after desirable response had been achieved. CONCLUSION In the setting of indolent CNS lymphoma, the rationale for chemoimmunotherapy is unclear. Although HDM-based therapy is used in BNS, its administration is limited by toxicity, and dose reductions may undermine dose intensity in the CSF. We observed higher rates of treatment-related mortality and only modest response rates with MATRix vs other HDM-based regimens; this primarily related to treatment related toxicity necessitating dose reduction requirements. These data suggest MATRix offers no response benefit over MAR or HDM only; indeed, the omission of thiotepa appears to allow dose optimisation of MTX and cytarabine, and does not negatively impact on outcome. If patients survive the first year of their disease/treatment, survival outcome is excellent. 1. Ferreri, A.J.M., et al.The Lancet Haematology3, e217-e227 (2016). Figure 1 Disclosures Carr: Lupin: Honoraria; Grifols: Other: Travel support; CSL: Honoraria. Wechalekar:Janssen, Takeda, Caelum, Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. D'Sa:Janssen: Honoraria, Research Funding; BeiGene: Honoraria, Research Funding; Sanofi: Honoraria.

Neurologic complications of infective endocarditis: A four's year experience of Casablanca university hospital

Clinical manifestations of infective endocarditis(IE) include systemic, cardiac, and extracardiac multiorgan symptoms and signs. Hence, neurological complications have been linked to poor outcome and remains the most frequent extracardiac signs of IE with 25% of patients experience at least one neurological event. To assess the incidence of neurological complications in patients with infective endocarditis, the risk factors for their development and their influence on the clinical outcome. Retrospective study included patients with possible or definite infective endocarditis according to the European society of cardiology modified Duke Criteria, admitted between 2016 and 2019 in the Cardiology department of Casablanca university. Seventy-one patients were male and 47 were female with a mean (SD) age = 40.3 (15.2) years. 85 episodes were designed as definite IE. Neurologic complications were identified in 24,5% patients with 22 events associated with definite IE. Nineteen complications were thought to be caused by major cerebral embolism including ischemic brain infarction and transient ischemic stroke. On the other hand, cerebral hemorrhage was found in 6 patients and no significant association between anticoagulation therapy and cerebral hemorrhage was found in our study. Neurologic complications were significantly associated with Staphylococcus aureus infection ( P = 0.017) and with IE affecting both the aortic and the mitral valves ( P = 0.03). Death during the acute phase of IE occurred in 8 episodes (30%) with neurologic complications and in 9 episodes (10%) without neurologic complications. Mortality was highly associated with neurologic complications with a P = 0.017. Our results reinforce that neurologic complications has negative impact on the outcome of patients with IE. Furthermore, appropriate antimicrobial therapy should be instituted rapidly to prevent neurologic events and reduce mortality rate.