Multicenter Comparison of the Safety and Efficacy of Clopidogrel Versus Ticagrelor for Neuroendovascular Stents.

BACKGROUND: Dual antiplatelet therapy (DAPT) is commonly employed for neuroendovascular stenting due to the significant risk of thromboembolism. Clopidogrel and aspirin are most often selected as initial DAPTs; however, there is limited literature available to support guidance of DAPT in this setting. The objective of this study was to evaluate safety and efficacy in patients whose final regimen included either DAPT with aspirin and clopidogrel (DAPT-C) or DAPT with aspirin and ticagrelor (DAPT-T). METHODS: This was a multicenter, retrospective cohort of patients who underwent neuroendovascular stenting and received DAPT between July 1, 2017, and October 31, 2020. Study participants were allocated into groups based on discharge DAPT regimen. The primary outcome was incidence of stent thrombosis at 3-6 months on DAPT-C versus DAPT-T, as defined by the presence of thrombus on imaging or new onset stroke. Secondary outcomes included major and minor bleeding and death within 3-6 months after the procedure. RESULTS: Five hundred and seventy patients were screened across 12 sites. Of those, 486 were included (DAPT-C n = 360, DAPT-T n = 126). There was no difference in the primary outcome of stent thrombosis between the DAPT-C and DAPT-T groups (8% vs. 8%, p = 0.97) and no difference in any of the secondary safety outcomes. CONCLUSIONS: Using DAPT-C or DAPT-T regimens in a broad population of neuroendovascular stenting procedures appears to have similar safety and efficacy profiles. Further prospective evaluation is warranted to streamline the practice of DAPT selection and monitoring to determine the impact on clinical outcomes.

A Triage Model for Interhospital Transfers of Low Risk Intracerebral Hemorrhage Patients.

OBJECTIVES: Intracerebral hemorrhage comprises a large proportion of inter-hospital transfers to comprehensive stroke centers from centers without comprehensive stroke center resources despite lack of mortality benefit and low comprehensive stroke center resource utilization. The subset of patients who derive the most benefit from inter-hospital transfers is unclear. Here, we create a triage model to identify patients who can safely avoid transfer to a comprehensive stroke center. MATERIALS AND METHODS: A retrospective cohort of spontaneous intracerebral hemorrhage patients transferred to our comprehensive stroke center from surrounding centers was used. Patients with early discharge from the Neuroscience Intensive Care Unit without use of comprehensive stroke center resources were identified as low risk, non-utilizers. Variables associated with this designation were used to develop and validate a triage model. RESULTS: The development and replication cohorts comprised 358 and 99 patients respectively, of whom 78 (22%) and 26 (26%) were low risk, non-utilizers. Initial Glasgow Coma Scale and baseline hemorrhage volume were associated with low risk, non-utilizers in multivariate analysis. Initial Glasgow Coma Scale >13, intracerebral hemorrhage volume <15ml, absence of intraventricular hemorrhage, and supratentorial location had an area under curve, specificity, and sensitivity of 0.72, 91.4%, 52.6%, respectively, for identifying low risk, non-utilizers, and 0.75, 84.9%, 65.4%, respectively, in the replication cohort. CONCLUSIONS: Spontaneous intracerebral hemorrhage patients with Glasgow Coma Scale >13, intracerebral hemorrhage volume <15 ml, absence of intraventricular hemorrhage, and supratentorial location might safely avoid inter-hospital transfer to a comprehensive stroke center. Validation in a prospective, multicenter cohort is warranted.

Stroke in Patients With Peripheral Artery Disease.

Background and Purpose- Predictors of stroke and transient ischemic attack (TIA) in patients with peripheral artery disease (PAD) are poorly understood. The primary aims of this analysis were to (1) determine the incidence of ischemic/hemorrhagic stroke and TIA in patients with symptomatic PAD, (2) identify predictors of stroke in patients with PAD, and (3) compare the rate of stroke in ticagrelor- and clopidogrel-treated patients. Methods- EUCLID (Examining Use of Ticagrelor in Peripheral Artery Disease) randomized 13 885 patients with symptomatic PAD to receive monotherapy with ticagrelor or clopidogrel for the prevention of major adverse cardiovascular events (cardiovascular death, myocardial infarction, or ischemic stroke). Ischemic/hemorrhagic stroke and TIA were adjudicated and measured as incidence rates postrandomization and cumulative incidence (per patient-years). Post hoc multivariable competing risk hazards analyses were performed using baseline characteristics to determine factors associated with all-cause stroke in patients with PAD. Results- A total of 458 cerebrovascular events in 424 patients (317 ischemic strokes, 39 hemorrhagic strokes, and 102 TIAs) occurred over a median follow-up of 30 months, for a cumulative incidence of 0.87, 0.11, and 0.27 per 100 patient-years, respectively. Age, prior stroke, prior atrial fibrillation/flutter, diabetes mellitus, geographic region, ankle-brachial index <0.60, prior amputation, and systolic blood pressure were independent baseline factors associated with the occurrence of all-cause stroke. After adjustment for baseline factors, the rates of ischemic stroke and all-cause stroke remained lower in patients treated with ticagrelor as compared with those receiving clopidogrel. There was no significant difference in the incidence of hemorrhagic stroke or TIA between the 2 treatment groups. Conclusions- In patients with symptomatic PAD, ischemic stroke and TIA occur frequently over time. Comorbidities such as age, prior stroke, prior atrial fibrillation/flutter, diabetes mellitus, higher blood pressure, prior amputation, lower ankle-brachial index, and geographic region were each independently associated with the occurrence of all-cause stroke. Use of ticagrelor, as compared with clopidogrel, was associated with a lower adjusted rate of ischemic and all-cause stroke. Further study is needed to optimize medical management and risk reduction of all-cause stroke in patients with PAD. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT01732822.

Randomized trial of lacosamide versus fosphenytoin for nonconvulsive seizures.

OBJECTIVE: The optimal treatment of nonconvulsive seizures in critically ill patients is uncertain. We evaluated the comparative effectiveness of the antiseizure drugs lacosamide (LCM) and fosphenytoin (fPHT) in this population. METHODS: The TRENdS (Treatment of Recurrent Electrographic Nonconvulsive Seizures) study was a noninferiority, prospective, multicenter, randomized treatment trial of patients diagnosed with nonconvulsive seizures (NCSs) by continuous electroencephalography (cEEG). Treatment was randomized to intravenous (IV) LCM 400mg or IV fPHT 20mg phenytoin equivalents/kg. The primary endpoint was absence of electrographic seizures for 24 hours as determined by 1 blinded EEG reviewer. The frequency with which NCS control was achieved in each arm was compared, and the 90% confidence interval (CI) was determined. Noninferiority of LCM to fPHT was to be concluded if the lower bound of the CI for relative risk was >0.8. RESULTS: Seventy-four subjects were enrolled (37 LCM, 37 fPHT) between August 21, 2012 and December 20, 2013. The mean age was 63.6 years; 38 were women. Seizures were controlled in 19 of 30 (63.3%) subjects in the LCM arm and 16 of 32 (50%) subjects in the fPHT arm. LCM was noninferior to fPHT (p = 0.02), with a risk ratio of 1.27 (90% CI = 0.88-1.83). Treatment emergent adverse events (TEAEs) were similar in both arms, occurring in 9 of 35 (25.7%) LCM and 9 of 37 (24.3%) fPHT subjects (p = 1.0). INTERPRETATION: LCM was noninferior to fPHT in controlling NCS, and TEAEs were comparable. LCM can be considered an alternative to fPHT in the treatment of NCSs detected on cEEG. Ann Neurol 2018;83:1174-1185.

Implementation of Continuous Video-Electroencephalography at a Community Hospital Enhances Care and Reduces Costs.

BACKGROUND: Despite data indicating the importance of continuous video-electroencephalography (cvEEG) monitoring, adoption has been slow outside major academic centers. Barriers to adoption include the need for technologists, equipment, and cvEEG readers. Advancements in lower-cost lead placement templates and commercial systems with remote review may reduce barriers to allow community centers to implement cvEEG. Here, we report our experience, lessons learned, and financial impact of implementing a community hospital cvEEG-monitoring program. METHODS: We implemented an adult cvEEG service at Duke Regional Hospital (DRH), a community hospital affiliate, in June of 2012. Lead placement templates were used in the implementation to reduce the impact on technologists by using other bedside providers for EEG initiation. Utilization of the service, study quality, and patient outcomes were tracked over a 3-year period following initiation of service. RESULTS: Service was implemented at essentially no cost. Utilization varied from a number of factors: intensive care unit (ICU) attending awareness, limited willingness of bedside providers to perform lead placement, and variation in practice of the consulting neurologists. A total of 92 studies were performed on 88 patients in the first 3 years of the program, 24 in year one, 27 in year two, and 38 in year three, showing progressive adoption. Seizures were seen in 25 patients (27%), 19 were in status, of which 18 were successfully treated. Transfers to the main hospital, Duke University Medical Center, were prevented for 53 patients, producing an estimated cost savings of $145,750. The retained patients produced a direct contribution margin of about $75,000, and the margin was just over $100,000 for the entire monitored cohort. CONCLUSION: ICU cvEEG service is feasible and practical to implement at the community hospital level. Service was initiated at little to no cost and clearly enhanced care, increased breadth of care, increased ICU census, and reduced transfers. The system allowed for successful management of ICU patients with underlying seizures and eliminated interfacility transfers, producing a savings of $145,750. The savings combined with the retained patient revenue produced a total revenue of over $250,000 with additional revenue in professional services as well. These results suggest expansion of cvEEG monitoring to community ICUs is practical, financially sustainable, improves the level and quality of care, and reduces costs.

Association between sympathetic response, neurogenic cardiomyopathy, and venous thromboembolization in patients with primary subarachnoid hemorrhage.

INTRODUCTION: Sympathetic activation promotes hemostasis, and subarachnoid hemorrhage (SAH) is associated with pronounced sympathetic activation. This investigation will assess whether catecholaminergic activity relates to venous thrombotic events in patients with acute SAH. METHODS: Observational study of consecutive SAH grade 3-5 patients requiring ventriculostomy insertion who did not undergo open surgical treatment of cerebral aneurysm. Cerebrospinal fluid (CSF) samples were obtained within 48 h of hemorrhage for assay of catecholamines, which were related to occurrence of deep venous thrombosis (DVT) and pulmonary embolization (PE). RESULTS: Of the 92 subjects, mean age was 57 years, 76% were female, and 57% Caucasian; 11% experienced lower extremity (LE) DVT, 12% developed upper extremity (UE) or LE DVT, and 23% developed any DVT/PE. Mean time to occurrence of UE/LE DVT was 7.8 days (+/-5.9 days), and mean time to development of PE was 8.8 days (+/-5.4 days). In hazards analysis models, independent predictors of LE DVT included neurogenic cardiomyopathy (NC) [HR 4.97 (95%CI 1.32-18.7)], norepinephrine/3,4-dihydroxyphenylglycol ratio (NE/DHPG) [3.81 (2.04-7.14)], NE [5.91 (2.14-16.3)], and dopamine (DA) [2.27 (1.38-3.72)]. Predictors of UE/LE DVT included NC [5.78 (1.70-19.7)], cerebral infarction [4.01 (1.18-13.7)], NE [3.58 (1.40-9.19)], NE/DHPG [3.38 (1.80-6.33)] and DA [2.01 (1.20-3.35)]. Predictors of DVT/PE included Hunt-Hess grade (H/H) [3.02 (1.19-7.66)], NE [2.56 (1.23-5.37)] and 3,4-dihydroxyphenylalanine (DOPA) [3.49 (1.01-12.0)]. CONCLUSIONS: In severe SAH, central sympathetic activity and clinical manifestations of (nor)adrenergic activity relate to the development of venous thromboemboli. Catecholamine activation may promote hemostasis, or may represent a biomarker for venous thromboses.

Intermittent fasting with ketogenic diet: A combination approach for management of chronic diseases.

Intermittent Fasting (IF) is the consumption of food and drinks within a defined time, while the ketogenic diet (KD) switches the metabolism from glucose to fats. Continuation of intermittent fasting leads to the generation of ketones, the exact mechanism for a ketogenic diet. This article discusses the types of IF and KD, the monitoring required, and the mechanisms underlying IF and KD, followed by disorders in which the combination strategy could be applied. The strategies for successfully applying combination therapy are included, along with recommendations for the primary care physicians (PCP) which could serve as a handy guide for patient management. This opinion article could serve as the baseline for future clinical studies since there is an utmost need for developing new wholesome strategies for managing chronic disorders.

Multicenter comparison of antiplatelet treatment strategies for urgent/emergent neuroendovascular stenting.

BACKGROUND: Emergent neuroendovascular stenting presents challenges for the utilization of antiplatelet agents. METHODS: This was a multicenter, retrospective cohort of patients who underwent emergent neuroendovascular stenting. The primary endpoints were thrombotic and bleeding events in relation to the timing of antiplatelet administration, route of administration, and choice of intravenous (IV) agent and the study investigated practice variability in antiplatelet utilization. RESULTS: Five-hundred and seventy patients were screened across 12 sites. Of those, 167 were included for data analysis. For patients who presented with ischemic stroke, artery dissection and emergent internal carotid artery (ICA) stenting who received an antiplatelet agent prior to or during the procedure, 57% were given an IV antiplatelet agent; for patients who were given an antiplatelet agent after the procedure, 96% were given an oral agent. For patients who presented for aneurysm repair and received an antiplatelet agent prior to or during the procedure, 74% were given an IV agent; patients who were given an antiplatelet agent after the completion of the procedure were given an oral antiplatelet agent 90% of the time. In patients who presented with ischemic stroke, artery dissection and emergent ICA stenting who received oral antiplatelet agents post-procedure were more likely to have thrombotic events compared to those who received oral antiplatelet agents prior to or during the procedure (29% vs 9%; p = 0.04). There were no differences in the primary outcomes observed when comparing other antiplatelet treatment strategies. CONCLUSION: The optimal timing of antiplatelet administration in relation to stent placement and route of administration of antiplatelet agents is unclear. Timing and route of administration of antiplatelet agents may have an effect on thrombosis in emergent neuroendovascular stenting. Significant practice variation exists in antiplatelet agent utilization in emergent neuroendovascular stenting.

Cerebrospinal fluid catecholamine levels as predictors of outcome in subarachnoid hemorrhage.

OBJECTIVE: Subarachnoid hemorrhage (SAH) is associated with marked sympathetic activation at the time of ictus. The purpose of this study is to determine whether early central catecholamine levels measured from cerebrospinal fluid (CSF) relate to outcome in patients with SAH. METHODS: Observational study of consecutive SAH grade 3-5 patients who underwent ventriculostomy placement, but did not undergo open craniotomy for aneurysm obliteration. CSF samples were obtained during the first 48 h following symptom onset and assayed for catecholamine levels. Statistical analyses were performed to determine whether the levels predicted mortality by day 15 or mortality/disability by day 30. RESULTS: For the 102 patients included, mean age was 58, and 73% were female - 21% experienced day-15 mortality, and 32% experienced mortality/disability by day 30. Early mortality was related to Hunt-Hess (H/H) grade (p < 0.001), neurogenic cardiomyopathy (NC) (p = 0.003), cerebral infarction (p = 0.001), elevated intracranial pressure (ICP) (p = 0.029), epinephrine (EPI) level (p = 0.002) and norepinephrine/3,4-dihydroxyphenylglycol (NE/DHPG) ratio (p = 0.003). Mortality/disability was related to H/H grade (p < 0.001), NC (p = 0.018), infarction (p < 0.001), elevated ICP (p = 0.002), EPI (p = 0.004) and NE/DHPG (p = 0.014). Logistic regression identified age [OR 1.09 (95% CI 1.01-1.17)], H/H grade [9.52 (1.19-77)], infarction [10.87 (1.22-100)], ICP elevation [32.26 (2-500)], EPI [1.06 (1.01-1.10)], and (inversely) DHPG [0.99 (0.99-1.00)] as independent predictors of early mortality. For mortality/disability, H/H grade [OR 21.74 (95% CI 5.62-83)], ICP elevation [18.52 (1.93-166)], and EPI [1.05 (1.02-1.09)] emerged as independent predictors. Proportional-hazards analysis revealed age [HR 1.041 (95% CI 1.003-1.08)], H/H grade [6.9 (1.54-31.25)], NC [4.31 (1.5-12.35)], and EPI [1.032 (1.009-1.054)] independently predicted early mortality. CONCLUSIONS: CSF catecholamine levels are elevated in SAH patients who experience early mortality or disability. EPI may potentially serve as useful index of outcome in this population of patients with SAH.

Determinants of central sympathetic activation in spontaneous primary subarachnoid hemorrhage.

BACKGROUND: Subarachnoid hemorrhage (SAH) has been associated with pronounced acute sympathetic activation. The purpose of this investigation is to identify demographic, clinical, radiological, and anatomical features of SAH that relate to sympathetic activation. METHODS: Observational study of consecutive Grades 3-5 SAH patients requiring ventriculostomy and undergoing endovascular aneurysmal obliteration. All patients underwent cerebrospinal fluid (CSF) sampling within 48 h of SAH onset, and samples were assayed for various catecholamine compounds and metabolites. Univariate analyses were performed to identify variables associated with catecholamine levels, and to correlate linearity among catecholamine compounds and metabolites. Variables demonstrating a possible association and variables of interest were entered into linear regression models to determine predictors of catecholamine elevations. RESULTS: Of the 102 patients, mean age was 58 years and 74% were female; 42% were Hunt-Hess (H/H) grade 4/5, 61% had a computed tomography (CT) score of 3/4, 57% had anterior cerebral or communicating artery (ACA/ACom) aneursysms, and 23% had aneurysms in the posterior circulation. In the univariate analysis, age, gender, H/H grade, CT score, and aneurysm location demonstrated various associations with catecholamine levels, and substantial positive correlations existed between the various catecholamine compounds and metabolites. Linear regression analyses revealed H/H grade to be an independent predictor of elevated CSF epinephrine (EPI), 3,4-dihydroxyphenylalanine (DOPA) and 3,4-dihydroxyphenyl acetic acid (DOPAC) levels, and of the norepinephrine/3,4-dihydroxyphenylglycol (NE/DHPG) ratio (p < 0.05 for all analyses). Female gender independently predicted increased dopamine (DA) and DOPAC levels (p < 0.05 for two analyses), as well as possibly DOPA levels (p < 0.1). Age, CT score and aneurysm location demonstrated only inconsistent associations and trends. CONCLUSIONS: Central sympathetic activation relates to clinical severity and female gender. No definitive associations were found for age, hemorrhage amount, or aneurysm location.

Post-Transplant Lymphoproliferative Disorder: A Rare Case of CNS Involvement following Renal Transplant.

BACKGROUND: Post-transplant lymphoproliferative disorders (PTLD) are rare immunosuppression complications affecting 5% of transplant patients. Isolated central nervous system (CNS)-PTLD without nodal or extra-nodal organ involvement is rarely reported and is difficult to diagnose due to the non-specific clinical manifestations and imaging features overlapping with other common CNS lesions. CASE PRESENTATION: We present a case of a 72-year-old female subjected to a renal transplant 11 years ago with progressively worsening headaches and confusion. Imaging revealed vasogenic edema in the left frontal and bilateral temporal lobes. She was subjected to a craniotomy and excisional biopsy to obtain tissue for diagnostic and therapeutic interventions. Pathology examination showed atypical EBV-positive lymphoplasmacytic infiltrate, consistent with Polymorphic type PTLD. CONCLUSIONS: Patients diagnosed with PTLD need to have close monitoring of immunosuppressive medications while in the hospital. Early diagnosis is essential for patient survival with PTLD, as their health can deteriorate fast.

Diet-microbiome-gut-brain nexus in acute and chronic brain injury.

In recent years, appreciation for the gut microbiome and its relationship to human health has emerged as a facilitator of maintaining healthy physiology and a contributor to numerous human diseases. The contribution of the microbiome in modulating the gut-brain axis has gained significant attention in recent years, extensively studied in chronic brain injuries such as Epilepsy and Alzheimer's Disease. Furthermore, there is growing evidence that gut microbiome also contributes to acute brain injuries like stroke(s) and traumatic brain injury. Microbiome-gut-brain communications are bidirectional and involve metabolite production and modulation of immune and neuronal functions. The microbiome plays two distinct roles: it beneficially modulates immune system and neuronal functions; however, abnormalities in the host's microbiome also exacerbates neuronal damage or delays the recovery from acute injuries. After brain injury, several inflammatory changes, such as the necrosis and apoptosis of neuronal tissue, propagates downward inflammatory signals to disrupt the microbiome homeostasis; however, microbiome dysbiosis impacts the upward signaling to the brain and interferes with recovery in neuronal functions and brain health. Diet is a superlative modulator of microbiome and is known to impact the gut-brain axis, including its influence on acute and neuronal injuries. In this review, we discussed the differential microbiome changes in both acute and chronic brain injuries, as well as the therapeutic importance of modulation by diets and probiotics. We emphasize the mechanistic studies based on animal models and their translational or clinical relationship by reviewing human studies.

Apixaban or Warfarin and Aspirin or Placebo After Acute Coronary Syndrome or Percutaneous Coronary Intervention in Patients With Atrial Fibrillation and Prior Stroke: A Post Hoc Analysis From the AUGUSTUS Trial.

Importance: Data are limited regarding the risk of cerebrovascular ischemic events and major bleeding in patients with atrial fibrillation (AF) and recent acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI). Objective: Determine the efficacy and safety of apixaban or vitamin K antagonists (VKA) and aspirin or placebo according to prior stroke, transient ischemic attack (TIA), or thromboembolism (TE). Design, Setting, and Participants: In this prospective, multicenter, 2-by-2 factorial, randomized clinical trial, post hoc parallel analyses were performed to compare randomized treatment regimens according to presence or absence of prior stroke/TIA/TE using Cox proportional hazards models. Patients with AF, recent ACS or PCI, and planned use of P2Y12 inhibitors for 6 months or longer were included; 33 patients with missing data about prior stroke/TIA/TE were excluded. Interventions: Apixaban (5 mg or 2.5 mg twice daily) or VKA and aspirin or placebo. Main Outcomes and Measures: Major or clinically relevant nonmajor (CRNM) bleeding. Results: Of 4581 patients included, 633 (13.8%) had prior stroke/TIA/TE. Patients with vs without prior stroke/TIA/TE were older; had higher CHA2DS2-VASC and HAS-BLED scores; and more frequently had prior bleeding, heart failure, diabetes, and prior oral anticoagulant use. Apixaban was associated with lower rates of major or CRNM bleeding and death or hospitalization than VKA in patients with (hazard ratio [HR], 0.69; 95% CI, 0.46-1.03) and without (HR, 0.68; 95% CI, 0.57-0.82) prior stroke/TIA/TE. Patients without prior stroke/TIA/TE receiving aspirin vs placebo had higher rates of bleeding; this difference appeared less substantial among patients with prior stroke/TIA/TE (P = .01 for interaction). Aspirin was associated with numerically lower rates of death or ischemic events than placebo in patients with (HR, 0.71; 95% CI, 0.42-1.20) and without (HR, 0.93; 95% CI, 0.72-1.21) prior stroke/TIA/TE (not statistically significant). Conclusions and Relevance: The safety and efficacy of apixaban compared with VKA was consistent with the AUGUSTUS findings, irrespective of prior stroke/TIA/TE. Aspirin increased major or CRNM bleeding, particularly in patients without prior stroke/TIA/TE. Although aspirin may have some benefit in patients with prior stroke, our findings support the use of apixaban and a P2Y12 inhibitor without aspirin for the majority of patients with AF and ACS and/or PCI, regardless of prior stroke/TIA/TE status. Trial Registration: ClinicalTrials.gov Identifier: NCT02415400.

CSF catecholamine profile in subarachnoid hemorrhage patients with neurogenic cardiomyopathy.

BACKGROUND: Patients experiencing apoplectic intracranial processes may develop neurogenic cardiomyopathy (NC). The purpose of this research is to determine whether cerebrospinal fluid (CSF) catecholamine levels are elevated in subarachnoid hemorrhage (SAH) patients with NC when compared to those without NC. METHODS: Observational study of consecutive grades 3-5 SAH patients requiring ventriculostomy. All patients underwent CSF sampling for catecholamine levels, and transthoracic echocardiography (TTE) to assess for NC, within 48 h of SAH onset. Univariate analyses were performed to identify clinical and laboratory variables associated with NC. Clinical variables associated with NC in the univariate analysis were entered into logistic regression models along with the candidate catecholamine variables to identify predictors of NC. RESULTS: The study group contained 100 patients--mean age of study subjects was 58 years, 73% were female, and 15% developed NC. NC patients were more likely to have a worse clinical grade than patients without NC (80 vs. 34%, P = 0.001). NC patients possessed greater DOPA levels (5.83 vs. 4.60 nmol/l, P = 0.044), and a trend toward greater noradrenergic activity as determined by NE/DHPG ratio (0.3799 vs. 0.2519, P = 0.073). Multivariate analysis identified worse clinical grade (OR 7.09, P = 0.005) and possibly NE levels (OR 1.005, P = 0.057) as independent predictors of NC. Bivariate analysis reinforced the findings for NE (OR 1.006, P = 0.022), and also identified DOPA levels (OR 1.001, P = 0.034) and NE/DHPG (OR 22.18, P = 0.019) as predictors of NC. CONCLUSIONS: SAH patients with NC tend to have greater CSF catecholamine levels than those without NC. However, the development of NC may also be related to factors not evaluated by our study.

Life-saving hemicraniectomy for fulminant acute disseminated encephalomyelitis.

Fulminant acute disseminated encephalomyelitis (ADEM) is a rare demyelinating disorder, which most often occurs after an infection or vaccination. It frequently presents with focal neurologic signs and an altered sensorium. Patients often require critical care for airway management but are typically treated with medical therapy alone, including intravenous steroids and other immunotherapies. We present a case of dominant hemisphere fulminant ADEM in a patient who required neurosurgical intervention and a life-saving hemicraniectomy despite maximum medical therapy.

Acute inflammatory demyelinating polyneuropathy or Guillain-Barré syndrome associated with COVID-19: a case report.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global pandemic. The disease, typically characterized by bilateral pulmonary infiltrates and profound elevation of inflammatory markers, can range in severity from mild or asymptomatic illness to a lethal cytokine storm and respiratory failure. A number of recognized complications of COVID-19 infection are described in the literature. Common neurological complications include headache and anosmia. Guillain-Barré syndrome (GBS) is an uncommon complication described in isolated case reports. However, a causal relationship has yet to be established. This case report adds to the growing body of evidence that GBS is a potential COVID-19 complication. CASE PRESENTATION: A 70-year-old Caucasian woman with recently diagnosed COVID-19 infection presented to the emergency department with 4 days of gradually worsening ascending lower extremity weakness. Exam revealed bilateral lower extremity weakness, mute reflexes, and sensory loss. Soon after starting intravenous administration of immunoglobulin (IVIG), the patient developed respiratory distress, eventually requiring intubation. She remained intubated for the duration of her IVIG treatment. After five rounds of treatment, the patient was successfully extubated and transferred to acute rehab. Following 4 weeks of intense physical therapy, she was able to walk with assistance on room air. CONCLUSION: At the present time, this is one of the few reports of acute inflammatory demyelinating polyneuropathy (AIDP) or GBS associated with COVID-19 in the United States. It is unclear whether a causal relationship exists given the nature of the syndrome. However, in light of the growing number of reported cases, physicians should be aware of this possible complication when evaluating COVID-19 patients.

Nonaneurysmal Subarachnoid Hemorrhage in Scuba Diving.

BACKGROUND: Decompression illness often presents with a wide variety of vague neurologic symptoms. Animal models have suggested that intracranial hemorrhages may result from nitrogen bubble ischemic insults. However, there is a paucity of cases and no known case reported to date of non-aneurysmal subarachnoid hemorrhage after rapid ascension from diving. CASE DESCRIPTION: A 60-year-old man presented with headache, nausea, emesis, and confusion 2 days after ascending rapidly from scuba diving. Given the severity and his symptoms unremitting despite oxygen at home, a computed tomography scan of the head was obtained revealing a prepontine and right sylvian fissure subarachnoid hemorrhage with ventriculomegaly. No underlying vascular abnormality was discovered. The patient was discharged from the hospital posthemorrhage day 7, neurologically intact. CONCLUSIONS: In patients presenting with persistent headache, nausea, emesis and/or other neurologic symptoms after diving, health care providers should consider intracranial hemorrhage in their work up.

Acute Respiratory Distress Syndrome Associated With Clopidogrel in a Young Male Patient.

Background: Clopidogrel is a commonly prescribed antiplatelet drug in patients with stents and histories of arterial vascular disease. It generally has a favorable side effect profile with increasing bleeding risk as the main concern as an adverse event. Case Presentation: A 19-year-old previously healthy male presented to the neurological intensive care unit with a subarachnoid hemorrhage requiring a flow diverting stent to secure the aneurysm. The patient was stable for 2 weeks and had no changes to management or medication within 48 h of antiplatelet therapy. Within hours of first-time dosing of clopidogrel, the patient experienced a syncopal episode and dyspnea. He was difficult to arouse and using accessory muscles to breath with an otherwise benign exam. He was hypoxic with bibasilar crackles requiring bilevel positive airway pressure (BiPap). Imaging showed bilateral pulmonary edema and he was diagnosed with moderate acute respiratory distress syndrome (ARDS). Infectious, cardiogenic, and contrast-induced ARDS were ruled out. Upon cessation of clopidogrel, his pulmonary function and mental status improved. Conclusions: This is the first reported case of a young and immunocompetent patient's severe pulmonary edema leading to acute respiratory distress syndrome in association with first- time dosing of clopidogrel.

Andexanet alfa for the reversal of Factor Xa inhibitor related anticoagulation.

Andexanet alfa is a specific reversal agent for Factor Xa inhibitors. The molecule is a recombinant protein analog of factor Xa that binds to Factor Xa inhibitors and antithrombin:LMWH complex but does not trigger prothrombotic activity. In ex vivo, animal, and volunteer human studies, andexanet alfa (AnXa) was able to dose-dependently reverse Factor Xa inhibition and restore thrombin generation for the duration of drug administration. Further trials are underway to examine its safety and efficacy in the population of patients experiencing FXa inhibitor-related bleeding.