Single-Center Description of Therapeutic Anticoagulation Practices and Outcomes in Large Hemispheric Infarctions.

Background and Objectives: Large hemispheric infarctions (LHIs) are associated with significant morbidity and mortality, with limited data on therapeutic anticoagulation (AC) management. We provide a descriptive analysis of the type of therapeutic AC used, the timing of introduction, rate of of radiographic vs symptomatic hemorrhagic transformation (HT), and patient outcomes. Methods: This was a retrospective review of patients with acute ischemic stroke admitted to the Neurosciences intensive care unit at a tertiary care center from January 2012 to December 2018. Inclusion criteria included admission imaging with stroke size ≥ two-thirds of the middle cerebral artery territory, ± other vascular territory, and need for therapeutic AC. HT categories included hemorrhagic infarction types 1 and 2 and parenchymal hematoma types 1 and 2. The primary outcome included HT with and without an associated clinical change. Secondary outcomes included disposition at discharge and modified Rankin Scale (mRS) score at discharge and at follow-up when available. Results: A total of 2,317 patients were screened, 380 met the inclusion criteria for LHI, and 105 received AC. The mean age was 64 years (SD 16.8), and 50% (n = 53) were female. The mean admission NIH Stroke Scale score was 20 (SD 5.9). The mean poststroke timing to initiation of AC was 17 days (SD 10.1) (median 14 [interquartile range 10-19 days]). Indications for AC included atrial fibrillation (51%), cardiac thrombus (19%), venous thromboembolism (19%), and other (10%). Heparin was most commonly used in the very early (≤7 days) group (n = 11, 79%), whereas vitamin K antagonists without a bridge were the most commonly used among the entire cohort (n = 54, 51%). Radiographic HT was seen in 68 patients (65%) before AC initiation. After initiation of AC, 70 patients had repeat imaging, with 6 cases (6%) of worsening radiographic HT and 4 cases (4%) of symptomatic deterioration, of which 3 required reversal of AC. At discharge, 7 patients (7%) had a good outcome (mRS score 0-2). Discussion: Although radiographic HT is common among patients with LHI, it does not always portend symptomatic clinical deterioration. Further research regarding AC timing and safety is necessary.

Leptomeningeal Carcinomatosis Mimicking Reversible Cerebral Vasoconstriction Syndrome.

Leptomeningeal carcinomatosis is the result of metastatic infiltration of the leptomeninges by malignant cells originating from an extra-meningeal primary tumor site. We describe a patient with active breast cancer who presented with thunderclap headaches (THs) and imaging showing multi-segment irregular arterial narrowing of intracranial vasculature. A 58-year-old Caucasian woman with active stage IV estrogen receptor-positive breast adenocarcinoma and migraine presented with THs. Computed tomography and brain magnetic resonance imaging (MRI) without contrast were unremarkable. Over a period of one week, she had recurrent THs. Interval vessel imaging showed multi-segment irregular arterial narrowing. Treatment with verapamil was initiated for suspected reversible cerebral vasoconstriction syndrome (RCVS). She subsequently had two discrete episodes of confusion with aphasia and left upper extremity numbness. Repeat gadolinium-enhanced MRI showed nodular leptomeningeal enhancement. Lumbar puncture revealed malignant cells in the cerebrospinal fluid consistent with leptomeningeal carcinomatosis. She subsequently underwent whole brain radiation treatment and intrathecal chemotherapy and had no further episodes of TH. Our case emphasizes the importance of considering leptomeningeal carcinomatosis in the differential diagnosis of THs and reversible cerebral vasculopathy, especially in patients with known underlying active cancer. The illustration also proves the importance of a complete work-up in patients with known malignancy in the setting of suspected RCVS.

Delirium in Cardiac and Cardiovascular Surgical Intensive Care Units.

Delirium is a common occurrence in cardiac and cardiovascular surgical intensive care units. Due to multiple confounding factors, this diagnosis remains challenging for medical professionals. Multiple theories exist regarding the pathophysiology of delirium, which include disruption of neurotransmitters as well as inflammation. Delirium has been associated with prolonged hospitalizations and an increase in mortality. Although there are widely used screening tools for delirium, none have been validated in this particular patient population. Limited treatments exist for delirium, so: both pharmacologic and nonpharmacologic preventative measures should be employed in this patient population.

Nutrition in the Neurocritical Care Unit: a New Frontier.

PURPOSE OF REVIEW: This review presents the most current recommendations for providing nutrition to the neurocritical care population. This includes updates on initiation of feeding, immunonutrition, and metabolic substrates including ketogenic diet, cerebral microdialysis (CMD) monitoring, and the microbiome. RECENT FINDINGS: Little evidence exists to support differences in feeding practices among the neurocritical care population. New areas of interest with limited data include use of immunonutrition, pre/probiotics for microbiome manipulation, ketogenic diet, and use of CMD catheters for substrate utilization monitoring. SUMMARY: Acute neurologic injury incites a cascade of adrenergic and neuroendocrine events resulting in a pro-inflammatory and hypercatabolic state, which is associated with an increase in morbidity and mortality. Nutritional support provides substrates to mitigate the damaging effects of hypermetabolism. Despite this practice, studies on feeding delivery outcomes remain inconsistent. Guidelines suggest use of early enteral nutrition using standard polymeric formulas. Population heterogeneity, variability in interventions, complexities of the metabolic and inflammatory responses, and paucity of nutrition research in patients requiring neurocritical care have led to controversies in the field. It is imperative that more pragmatic and reproducible research be conducted to better understand underlying pathophysiology and develop interventions that may improve outcomes.

Description of an Association Between Leukocytosis and Clinical Outcomes in Large Hemispheric Infarctions.

BACKGROUND: Large hemispheric infarctions (LHI) are associated with significant morbidity and mortality. Leukocytosis has been observed to directly correlate with stroke severity but has not been specifically described in the LHI population. We hypothesized that patients with LHI and leukocytosis on admission have worse clinical outcomes. METHODS: Retrospective study of patients admitted to the neurosciences intensive care unit at a tertiary care center with the diagnosis of acute ischemic stroke from Jan 2012 to Dec 2018. Inclusion criteria included admission imaging with stroke size greater than two-thirds of the middle cerebral artery territory, with or without other vascular territory involvement. Patients were excluded if antibiotics were started on admission for presumed infection. White blood cell count was recorded at admission, along with Modified Rankin Scale on admission and discharge, need for mechanical ventilation, tracheostomy, and discharge disposition. Logistic regression was used for association measures. RESULTS: Of the 2,318 patients that were screened, 360 met inclusion criteria. Mean age was 64, median was 63; 51.7% were female. Mean and median NIHSS were 21. Leukocytosis on admission was seen in 139 patients (38.6%), and it was associated with need for mechanical ventilation (p<0.0001, OR 2.54, [1.64-3.95]) and mortality during hospitalization (p<0.0003, OR 2.66, [1.56-4.55]). Results persisted after correction for age and sex in a logistic regression model. CONCLUSIONS: Leukocytosis on admission in patients with LHI significantly correlated with mortality and need for mechanical ventilation. There was a trend towards association with poor outcome at discharge, although not statistically significant. Further research may identify how leukocytosis and other SIRS markers may be used to prognosticate outcomes in this challenging patient population.

Radiographic and clinical neurologic manifestations of COVID-19 related hypoxemia.

The novel coronavirus SARS-CoV-2 is known to cause hypoxemia and acute respiratory distress syndrome (ARDS) in a significant portion of those with severe disease. Survivors of critical illness and ARDS often experience neurocognitive impairment but, to date, there is scant literature correlating radiographic hypoxic brain injury to hypoxemia related to ARDS. In this case series, we describe three cases of hypoxic brain injury seen on magnetic resonance imaging (MRI) in patients with hypoxemia secondary to COVID-19-related ARDS. The lack of severe observed hypoxemia in two of the cases suggests that unrecognized or asymptomatic hypoxemia may play a role in hypoxic brain injury related to COVID-19.

Intracerebral Hemorrhage Outcomes in the Very Elderly.

BACKGROUND: There is a paucity of outcomes data in patients over 80 years presenting with intracerebral hemorrhage (ICH). The primary aim of our study is to describe outcomes in this patient population. METHOD: Retrospective study of patients admitted with primary ICH from January 2012 to July 2018. Data were obtained from the Rush University Get With The Guidelines database; only patients 80 or above were included. RESULTS: A total of 1713 patients were screened and 220 patients met inclusion criteria. About 68.2% were female and mean age was 85.6 years old. Median ICH score on admission was 2 (IQR 1-3). Location of ICH included: deep (48.2%), lobar (40%), and cerebellum (9.5%). ICH etiologies included hypertensive (51.8%), cerebral amyloid angiopathy (26.8%), coagulopathy (5.9%), and the remaining were undetermined. CT angiograms were performed in 34.5% (n = 76) of patients; of these patients one arteriovenous malformation was identified. Patients underwent the following procedures: external ventricular drains (8.6%), decompression (3.6%), and ventriculoperitoneal shunts (1.8%). Tracheostomy and percutaneous gastrostomy placement were performed in 8.2%. About 4.5% had seizures and 1.5% were treated for status epilepticus. Disposition at hospital discharge included: subacute nursing facility ([SNF] 24.1%), acute rehabilitation (23.2%), hospice (18.2%), death (18.2%), home (11.8%), long-term acute care facility ([LTAC] 3.6%), and unknown (1%). Patients with an ICH score ≥2 on admission had a roughly 6 times higher chance of experiencing an unfavorable outcome (LTAC, SNF, or death), when compared to patients with lower ICH score. CONCLUSIONS: This study shows that a significant proportion (35%) of ICH patients ≥80 years old have a good outcome, with discharge to home or to rehabilitation. Our data suggest that older patients with ICH presenting with supratentorial hemorrhages (volume < 30 cc) without intraventricular extension can have good outcomes despite their age.

Continuous Electroencephalographic Monitoring in the Intensive Care Unit: A Cross-Sectional Study.

OBJECTIVE: Research on continuous electro-encephalographic monitoring (cEEG) in the intensive care unit (ICU) has previously focused on neuroscience ICUs. This study determines cEEG utilization within a sample of specialty ICUs world-wide. METHODS: A cross-sectional electronic survey of attending level physicians across various intensive care settings. Twenty-five questions developed from consensus statements on the use of cEEG in the critically ill sent as an electronic survey. RESULTS: Of all, 9344 were queried and 417 (4.5%) responses were analyzed with 309 (74%) from the United States and 74 (18%) internationally. Intensive care units were: medical (10%), surgical (6%), neurologic/neurosurgical (12%), cardiac (4%), trauma (3%), pediatrics (29%), burn (<1%), multidisciplinary (30%), and other (5%). Intensive care units were: academic (65%), community (18%), public (3%), military (1%), and other (13%). Specialized cEEG teams were available in 71% of ICUs. Rapid 24/7 access and cEEG interpretation was available in 32% of ICUs. Interpretation changed clinical management frequently (28%) and sometimes (45%). CONCLUSIONS: Despite guideline recommendations for cEEG use, there is a discordance between availability, night coverage, and immediate interpretation. Only 27% have institutional protocols for indications and duration of cEEG monitoring. Furthermore, cEEG may be underutilized in nonneurologic ICUs as well as ICUs in smaller nonacademic affiliated hospitals and those outside of the United States.

Ketamine infusion for refractory status epilepticus: A case report of cardiac arrest.

BACKGROUND: Refractory status epilepticus (RSE) has a high mortality rate and is often difficult to treat. When traditional therapies fail ketamine may be considered. There are limited reports of adverse cardiac events with the use of ketamine for RSE and no reports of cardiac arrest in this context. OBJECTIVE: Evaluate the occurrence of cardiac arrhythmias associated with the use of ketamine for RSE. METHODS: Retrospective chart review of nine patients who underwent ketamine infusion for RSE. RESULTS: Etiology of refractory status epilepticus included autoimmune/infectious process (Zeiler et al., 2014), ischemic stroke (Bleck, 2005) and subarachnoid hemorrhage (Bleck, 2005). Of the nine patients who received ketamine, two had documented cardiac events; one remained clinically stable and the other developed multiple arrhythmias, including recurrent episodes of asystole. Once ketamine was discontinued the latter patient stabilized with the addition of anti arrhythmic therapy. CONCLUSION: Ketamine is utilized to treat refractory status epilepticus, but should be used with caution in patients with subarachnoid hemorrhage, as there may be an increased risk of life threatening arrhythmias and cardiac arrest.

Malignant cerebral edema related to Systemic Lupus Erythematosus.

BACKGROUND: The neurological manifestations of Systemic Lupus Erythematosus (SLE) are varied and incompletely described. A few case series report a benign idiopathic intracranial hypertension (IIH) related to SLE, which is responsive to immunotherapy. There are limited reports of patients with malignant cerebral edema, and diffuse white matter changes in the absence of central nervous system (CNS) vasculitis. METHODS: Case series from our tertiary care center and review of the relevant literature. RESULTS: Case one was a 32year-old woman admitted with nausea, vomiting and cranial nerve palsies. Serology was significant for a diagnosis of probable SLE. MRI was performed and showed bilateral symmetric diffuse T2/FLAIR hyperintensities throughout the white matter and cerebral angiography was unremarkable. The patient developed recalcitrant cerebral edema with intracranial hypertension despite immunosuppressive therapies and subsequently expired. Post mortem evaluation showed a white matter inflammatory process, but no vascular changes consistent with CNS vasculitis. Case two was a 29year-old woman with known SLE that presented with a loss of consciousness. Imaging included a CT that showed diffuse cerebral edema with white matter involvement and a normal cerebral angiogram. Again, despite maximal medical management the patient herniated resulting in death by neurologic criteria. CONCLUSIONS: These two cases represent a syndrome of white matter changes and diffuse cerebral edema associated with SLE that have yet to be reported in the literature. It is unclear if this process has a similar pathology to SLE related IIH. Because this syndrome causes a fulminant cerebral edema, further research is needed to better understand the underlying pathology and identify potential treatment options.

Brain iron metabolism and brain injury following subarachnoid hemorrhage: iCeFISH-pilot (CSF iron in SAH).

INTRODUCTION: Iron-mediated oxidative damage has been implicated in the genesis of cerebral vasospasm in animal models of SAH. We sought to explore the relationship between levels of non-protein bound iron in cerebrospinal fluid and the development of brain injury in patients with aneurysmal SAH. METHODS: Patients admitted with aneurysmal subarachnoid hemorrhage to a Neurointensive care unit of an academic, tertiary medical center, with Hunt and Hess grades 2-4 requiring ventriculostomy insertion as part of their clinical management were included in this pilot study. Samples of cerebrospinal fluid (CSF) were obtained on days 1, 3, and 5. A fluorometric assay that relies on an oxidation sensitive probe was used to measure unbound iron, and levels of iron-handling proteins were measured by means of enzyme-linked immunosorbent assays. We prospectively collected and recorded demographic, clinical, and radiological data. RESULTS: A total of 12 patients were included in this analysis. Median Hunt and Hess score on admission was 3.5 (IQR: 1) and median modified Fisher scale score was 4 (IQR: 1). Seven of 12 patients (58 %) developed delayed cerebral ischemia (DCI). Day 5 non-transferrin bound iron (NTBI) (7.88 ± 1 vs. 3.58 ± 0.8, p = 0.02) and mean NTBI (7.39 ± 0.4 vs. 3.34 + 0.4 p = 0.03) were significantly higher in patients who developed DCI. Mean redox-active iron, as well as day 3 levels of redox-active iron correlated with development of angiographic vasospasm in logistic regression analysis (p = 0.02); while mean redox-active iron and lower levels of ceruloplasmin on days 3, 5, and peak concentration were correlated with development of deep cerebral infarcts. CONCLUSIONS: Our preliminary data indicate a causal relationship between unbound iron and brain injury following SAH and suggest a possible protective role for ceruloplasmin in this setting, particularly in the prevention of cerebral ischemia. Further studies are needed to validate these findings and to probe their clinical significance.

Intra-arterial vasodilator therapy for parainfectious cerebral vasospasm.

Cerebrovascular complications of bacterial meningitis may include vasculitis, vasospasm or vasoconstriction, delayed cerebral infarction, venous and arterial thrombosis, intracranial aneurysm formation. The role of invasive endovascular therapies has not been well studied for infectious vasospasm, which can lead to dire neurologic consequences. We present 2 patients who were diagnosed with bacterial meningitis. Brain MRI showed areas of acute ischemia. Neurologic worsening was seen in both patients despite aggressive medical management. Follow-up imaging demonstrated significant narrowing of the intracranial vessels with associated new scattered infarcts. Both patients underwent targeted intra-arterial vasodilator infusion with angiographically improved vessel caliber and distal flow. The neurological exam subsequently stabilized in both cases. Follow-up radiographic images demonstrated no further ischemia in one of the 2 patients. Vasculopathy and vasospasm causing delayed ischemic neurologic deficit is a rare, but severe complication of acute meningitis. It can be a significant predictor of poor prognosis, and the disease may progress despite aggressive medical therapy. Although frequently used in subarachnoid hemorrhage-related vasospasm, to our knowledge, this is the first report of endovascular vasodilator treatment as adjunctive intervention in patients with meningitis associated vasculopathy.