Alcohol-related posterior reversible encephalopathy syndrome: a case report of a patient managed with a benzodiazepine-sparing regimen for alcohol withdrawal.

We report a case of posterior reversible encephalopathy syndrome (PRES) during treatment for alcohol withdrawal syndrome with gabapentin and clonidine. The patient developed severe hypertension, confusion and tremor, culminating in bilateral vision loss and a seizure. Imaging revealed posterior cerebral edema. Treatment with benzodiazepines, antihypertensives, and anti-seizure medications led to resolution. One year later, imaging showed resolution of the findings. We review the associated literature and propose the recognition of a PRES sub-entity, Alcohol-Related PRES (ARPRES), which can appear in the setting of alcohol withdrawal syndrome, chronic alcohol use, and acute alcohol intoxication, with or without hypertension.

The spectrum of Epstein-Barr virus infections of the central nervous system after organ transplantation.

BACKGROUND: Epstein-Barr virus (EBV)-related neurologic complications have a diverse presentation in transplant recipients, creating diagnostic and therapeutic challenges for clinicians. In this case series, we report unique manifestations of EBV related neurologic complications following solid organ transplant and highlight pitfalls in management. CASE PRESENTATIONS: A retrospective search of the electronic medical record of all patients from January 2015 to December 2020 who underwent solid organ transplantation and had central nervous system complications as determined by ICD-10 codes were included. Three patients with unique manifestation of EBV-related neurologic complications after liver transplantation were identified. The first was a 52-year-old man with a live-donor liver transplant 11 years prior for Budd-Chiari syndrome presented with several weeks of headache and several lesions on brain MRI; he was diagnosed with primary central nervous system post-transplant lymphoproliferative disorder. The second patient was a 63-year-old man with a deceased-donor liver transplant 16 years prior for alpha-1-antitrypsin deficiency and was found to have a stroke; he was diagnosed with EBV encephalitis. The final patient was a 75-year-old woman with a deceased-donor liver transplant six years prior for primary biliary cirrhosis who presented with four months of gait instability; she was diagnosed with EBV myelitis. A review of the literature was performed to supplement description of the different diseases. CONCLUSIONS: EBV-related central nervous infection in post-transplant patients can manifest in a variety of neurologic syndromes, which can be challenging to diagnose. Careful correlation of clinical, pathologic, and radiologic findings and a high index of suspicion are crucial in identification and appropriate management.

Feasibility of a Collaborative, Prospective Interdisciplinary Review and Pharmacy-Based Dispensing Process for Prothrombin Complex Concentrate.

BACKGROUND: Therapeutic options for rapid reversal of vitamin K antagonist therapy include 4-factor prothrombin complex concentrate (PCC4) and fresh frozen plasma (FFP). These agents have unique requirements for preparation, potential adverse effects, and cost-effectiveness considerations. OBJECTIVE: To retrospectively assess whether our process for collaborative prospective review and pharmacy preparation facilitates timely and safe warfarin reversal with PCC4 as compared with FFP and to compare effectiveness and safety of the agents in practice. METHODS: We performed a retrospective, single-center, before and after cohort study of patients requiring warfarin reversal for life-threatening bleeding or urgent invasive procedures over an 18-month period. The primary end point was time from ordering of reversal agent to administration. Secondary end points measured time to therapeutic effect and rates of adverse events. RESULTS: Of 98 patients studied, 72 received FFP, and 26 received PCC4. The median times from ordering to administration of FFP and PCC4 were 69 and 44 minutes, respectively ( P = 0.015). Median time from ordering to end of infusion was significantly shorter for PCC4 compared with FFP (54 vs 151 minutes, respectively; P < 0.0001). In all, 72% of PCC4 patients and 28% of FFP patients achieved the goal international normalized ratio (INR) of ≤1.4 at the first INR check ( P < 0.0001). Adverse reactions occurred in 4% of patients in each group. CONCLUSION: In routine clinical practice incorporating collaborative prospective review and dispensing from the institution's pharmacy, PCC4 was associated with faster administration, a higher rate of INR correction, and similar rates of adverse events compared with FFP.

Phantom-based standardization of CT angiography images for spot sign detection.

PURPOSE: The CT angiography (CTA) spot sign is a strong predictor of hematoma expansion in intracerebral hemorrhage (ICH). However, CTA parameters vary widely across centers and may negatively impact spot sign accuracy in predicting ICH expansion. We developed a CT iodine calibration phantom that was scanned at different institutions in a large multicenter ICH clinical trial to determine the effect of image standardization on spot sign detection and performance. METHODS: A custom phantom containing known concentrations of iodine was designed and scanned using the stroke CT protocol at each institution. Custom software was developed to read the CT volume datasets and calculate the Hounsfield unit as a function of iodine concentration for each phantom scan. CTA images obtained within 8 h from symptom onset were analyzed by two trained readers comparing the calibrated vs. uncalibrated density cutoffs for spot sign identification. ICH expansion was defined as hematoma volume growth >33%. RESULTS: A total of 90 subjects qualified for the study, of whom 17/83 (20.5%) experienced ICH expansion. The number of spot sign positive scans was higher in the calibrated analysis (67.8 vs 38.9% p < 0.001). All spot signs identified in the non-calibrated analysis remained positive after calibration. Calibrated CTA images had higher sensitivity for ICH expansion (76 vs 52%) but inferior specificity (35 vs 63%) compared with uncalibrated images. CONCLUSION: Normalization of CTA images using phantom data is a feasible strategy to obtain consistent image quantification for spot sign analysis across different sites and may improve sensitivity for identification of ICH expansion.

Delay in Diagnosis of Basilar Artery Stroke.

BACKGROUND: Basilar artery stroke causes substantial morbidity and mortality. Although its unusual clinical presentation potentially contributes to a delay in diagnosis, this problem has not been systematically studied. We compared intervals between symptom onset, initial presentation, and diagnosis in stroke due to basilar artery (BA) versus left middle cerebral artery (LMCA) occlusion to determine the presence of and potential reasons for diagnostic delay in BA stroke. METHODS: We retrospectively identified 21 consecutive adult patients diagnosed with BA stroke between 2009 and 2011 from our hospital's prospective stroke registry. Patients were age-, sex-, and race-matched with 21 LMCA stroke patients from the same period. All subjects had confirmed clinical and radiographic diagnosis of stroke due to occlusion or stenosis of the BA, LMCA, or left internal carotid artery. Time to diagnosis was determined independently by two investigators through medical record review. The pre-specified primary outcome was latency from emergency department (ED) arrival to stroke diagnosis. RESULTS: Median time from ED arrival to diagnosis was 8 h 24 min (IQR: 2:43-26:32) for BA and 1 h 23 min (IQR: 0:41-1:45; p < 0.001) for LMCA. Median time from symptom onset to ED arrival was 7 h 44 min (IQR 1:23-21:30) for BA and 1 h 2 min (IQR 0:36-9:41; p = 0.06) for LMCA. Four of 21 (19 %) BA patients were diagnosed within a 4-h time frame to make intravenous thrombolysis possible compared to 13 of 21 (62 %) LMCA patients (p = 0.01). CONCLUSIONS: Our results suggest that both pre-hospital and in-hospital processes cause substantial, clinically significant delays in the diagnosis of BA stroke.

ICU management of aneurysmal subarachnoid hemorrhage.

INTRODUCTION: Aneurysmal subarachnoid hemorrhage (SAH) has very high morbidity and mortality rates. Optimal intensive care unit (ICU) management requires knowledge of the potential complications that occur in this patient population. METHODS: Review of the ICU management of SAH. Level of evidence for specific recommendations is provided. RESULTS: Grading scales utilizing clinical factors and brain imaging studies can help in determining prognosis and are reviewed. Misdiagnosis of SAH is fairly common so the clinical symptoms and signs of SAH are summarized. The ICU management of SAH is discussed beginning with a focus on avoiding aneurysm re-rupture and securing the aneurysm, followed by a review of the neurologic and medical complications that may occur after the aneurysm is secured. Detailed treatment strategies and areas of current and future research are reviewed. CONCLUSIONS: The ICU management of the patient with SAH can be particularly challenging and requires an awareness of all potential neurologic and medical complications and their urgent treatments.

The effect of a neurocritical care service without a dedicated neuro-ICU on quality of care in intracerebral hemorrhage.

BACKGROUND: Introduction of neurocritical care services to dedicated neuro-ICUs is associated with improved quality of care. The impact of a neurocritical care service without a dedicated neuro-ICU has not been studied. METHODS: We retrospectively identified all patients admitted to our institution with intracerebral hemorrhage (ICH) in two 12-month periods: immediately before the arrival of the first neurointensivist ("before") and after the neurocritical care service was established ("after"). There was no nursing team, ICU housestaff/physician extender team, or physical unit dedicated to the care of patients with critical neurologic illness during either period. Using an uncontrolled before-after design, we compared clinical outcomes and performance on quality metrics between groups. RESULTS: We included 74 patients with primary supratentorial ICH. Mortality, length of stay (LOS), proportion of patients with modified Rankin Score 0-3, and destination on discharge did not differ between groups when adjusted for confounders. Time to first two consecutive systolic blood pressure (SBP) measurements <180 mmHg was shorter in the "after" cohort (mean 4.5 vs. 3.2 h, p = 0.001). Area under the curve measurement for change in SBP from baseline over the first 24 h after ED arrival demonstrated greater, sustained SBP reduction in the "after" cohort (mean -187.9 vs. -720.9, p = 0.04). A higher proportion of patients were fed without passing a dysphagia screen in the "before" group (45 vs. 0%, p < 0.001). CONCLUSIONS: Introduction of a neurocritical service without a neuro-ICU at our institution was associated with a trend toward longer ICU LOS and improvement in some key metrics of quality of care for patients with ICH.

Paroxysmal atrial fibrillation in cryptogenic stroke: a case-control study.

BACKGROUND: It is unclear if brief episodes of paroxysmal atrial fibrillation (PAF) detected by prolonged cardiac monitoring are an occult of cause of cryptogenic strokes (CS). We compared the incidence of PAF in patients with CS and patients with stroke of known cause (SKC) using prolonged ambulatory cardiac monitoring. METHODS: We prospectively enrolled patients within 3 months of ischemic stroke to undergo noninvasive cardiac monitoring for 3 weeks. Primary end point was PAF detection independently confirmed by 2 blinded cardiologists. RESULTS: The study consisted of 132 patients, 66 had CS and 66 had SKC. Episodes of PAF were detected in 16 of 64 (25%) patients with CS and 9 of 64 (14%) patients with SKC (P=.12). Duration and number of PAF episodes, PAF burden, and time of first PAF detection did not differ significantly between the 2 groups (P>.05 for all). In patients younger than 65 years, PAF was more common in the CS group (22% versus 3%; P=.07), whereas in patients 65 years or older, the rates of detection were similar (27% in CS versus 25% in SKC; P=.9). Among patients younger than 65 years with embolic imaging pattern, PAF was only observed in the CS group (21% versus 0%; P=.03). CONCLUSIONS: Very short episodes of PAF are common in patients with CS and with SKC, but their pathogenic significance is unclear. Predominance of PAF in younger patients with CS and embolic infarct pattern suggests a causative role in these cases. More research is needed before prolonged cardiac rhythm monitoring can be recommended to guide anticoagulation in CS patients.

Gummatous Neurosyphilis With Transient Worsening of Neurological Symptoms After Treatment Initiation.

Cerebral syphilitic gumma is an atypical presentation of neurosyphilis, the clinical manifestations of which depend on the size and location of the lesions. It radiologically presents as enhancing nodular lesion(s) in brain parenchyma. We present a case of a patient with cerebral syphilitic gummas who had worsening neurological symptoms a few hours after initiation of anti-syphilitic antibiotic treatment. We aim to illustrate the clinical and radiological characteristics that might be helpful to clinicians when approaching the challenges they might encounter while treating neurosyphilis.

Single institution experience with death by neurological criteria/brain death guideline adherence.

OBJECTIVE: To determine the effect on adherence to an institutional death by neurological criteria/brain death (DNC/BD) policy of implementation of a standardized DNC/BD checklist in the electronic medical record (EMR). METHODS: The retrospective study cohort included all patients admitted to our institution who were declared dead by neurologic criteria determined by ICD code (G93.82) between June 2015 and October 2019. Two investigators independently reviewed each case for adherence with institutional policy, and agreement was assessed using unweighted kappa statistics. Patient data and adherence to institutional policy before and after implementation of a standardized DNC/BD checklist were compared. RESULTS: There were 66 patients identified by the initial search and 38 were included in the final analysis, with 19 cases in both the pre- and post- checklist periods. There were no significant differences in age, cause of DNC/BD, time to DNC/BD determination, potential toxic, metabolic, physiologic confounders, or use of ancillary testing. The pre-checklist period adherence was 47.4% (n = 9/19) versus 94.6% (n = 18/19; p = 0.001) in the post-checklist EMR DNC/BD period. CONCLUSION: Implementation of a standardized EMR checklist substantially improved DNC/BD policy adherence in our institution. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence on the use of standardized EMR checklist to improve death by neurologic criteria/brain death policy adherence.

Postpartum trifecta: simultaneous eclamptic intracerebral hemorrhage, PRES, and herniation due to intracranial hypotension.

BACKGROUND: In the postpartum patient, sudden depression of consciousness may be caused by a number of etiologies and can result in serious consequences. Rapid, accurate diagnosis allows for specific treatments that optimize outcome, but diagnosis can be challenging in this population. We present a case of postpartum herniation due to intracranial hypotension in a patient with eclampsia, posterior reversible encephalopathy syndrome (PRES), and intracerebral hemorrhage (ICH). METHODS: Case report. RESULTS: A 26-year-old woman developed headache on postpartum day (PD) 1 after cesarean section with epidural anesthesia. Over the next 3 days, she developed progressively worsening headache and hypertension. On PD 5, she had a generalized seizure, leading to endotracheal intubation, propofol infusion, and transfer to our institution. By PD 6, she opened her eyes to voice, followed commands, moved all extremities, and had briskly reactive 4 mm pupils. MRI showed L parasagittal ICH with minimal mass effect, edema consistent with PRES, and brain descent with obliteration of the basal cisterns and tonsillar herniation. Later on PD 6, after diuresis for pulmonary edema, she became unresponsive with a dilated and nonreactive left pupil. She was laid flat for transport to CT, with improvement in arousal and pupil reactivity within 5 min. Intravascular volume was repleted with normal saline and albumin, and she was placed in the Trendelenburg position. Over the subsequent 8 h, she developed a dilated and nonreactive left pupil whenever her head was raised to horizontal. Her head position was gradually successfully raised over 48 h without need for a lumbar epidural blood patch. She was discharged home on PD 13 with only mild left arm dysmetria. CONCLUSIONS: Intracranial hypotension may coexist with other potential causes of cerebral herniation in the postpartum period. Establishing this diagnosis is crucial because its treatment is opposite that of other causes of herniation.

Association of Donor Brain Death Due to Stroke With Prognosis After Heart Transplantation.

BACKGROUND: The proximate cause of donor brain death is not considered a conventional risk factor in modern heart transplantation. OBJECTIVES: This study aimed to investigate the effect of the cause of donor brain death on recipients. METHODS: Using the United Network for Organ Sharing registry, long-term mortality and allograft failure were compared in recipients who underwent heart transplantation in the United States from 2005 through 2018 between allograft recipients from donors with stroke as the cause of brain death (n = 3,761) vs nonstroke causes (n = 14,677). Inverse probability weighting was used for risk adjustment. Interactions were investigated between the cause of brain death and other conventional donor risk factors for recipient mortality. RESULTS: There was an interaction between the cause of brain death and donor age (Pinteraction = 0.008). When allografts were procured from donors aged 40 years or younger, stroke as the cause of brain death was associated with an increased risk of mortality (23% vs 19% at 5 years; HR: 1.17; 95% CI: 1.02-1.35) and allograft failure (HR: 1.30; 95% CI: 1.04-1.63). When donors were older than 40 years, the cause of brain death was not associated with outcomes. CONCLUSIONS: As the cause of donor brain death, stroke had a substantially different effect on recipient and allograft survival depending on donor age. In the case of younger donor ages, stroke was associated with higher recipient mortality and allograft failure than other causes of brain death. The strength of this association decreased with increasing donor age such that the increased hazard was no longer present in donors older than approximately 40 years.

Neurologic Manifestations of Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Hospitalized Patients During the First Year of the COVID-19 Pandemic.

To describe the prevalence, associated risk factors, and outcomes of serious neurologic manifestations (encephalopathy, stroke, seizure, and meningitis/encephalitis) among patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. DESIGN: Prospective observational study. SETTING: One hundred seventy-nine hospitals in 24 countries within the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study COVID-19 Registry. PATIENTS: Hospitalized adults with laboratory-confirmed SARS-CoV-2 infection. INTERVENTIONS: None. RESULTS: Of 16,225 patients enrolled in the registry with hospital discharge status available, 2,092 (12.9%) developed serious neurologic manifestations including 1,656 (10.2%) with encephalopathy at admission, 331 (2.0%) with stroke, 243 (1.5%) with seizure, and 73 (0.5%) with meningitis/encephalitis at admission or during hospitalization. Patients with serious neurologic manifestations of COVID-19 were older with median (interquartile range) age 72 years (61.0-81.0 yr) versus 61 years (48.0-72.0 yr) and had higher prevalence of chronic medical conditions, including vascular risk factors. Adjusting for age, sex, and time since the onset of the pandemic, serious neurologic manifestations were associated with more severe disease (odds ratio [OR], 1.49; p < 0.001) as defined by the World Health Organization ordinal disease severity scale for COVID-19 infection. Patients with neurologic manifestations were more likely to be admitted to the ICU (OR, 1.45; p < 0.001) and require critical care interventions (extracorporeal membrane oxygenation: OR, 1.78; p = 0.009 and renal replacement therapy: OR, 1.99; p < 0.001). Hospital, ICU, and 28-day mortality for patients with neurologic manifestations was higher (OR, 1.51, 1.37, and 1.58; p < 0.001), and patients had fewer ICU-free, hospital-free, and ventilator-free days (estimated difference in days, -0.84, -1.34, and -0.84; p < 0.001). CONCLUSIONS: Encephalopathy at admission is common in hospitalized patients with SARS-CoV-2 infection and is associated with worse outcomes. While serious neurologic manifestations including stroke, seizure, and meningitis/encephalitis were less common, all were associated with increased ICU support utilization, more severe disease, and worse outcomes.

Incidence and predictors of myocardial infarction after transient ischemic attack: a population-based study.

BACKGROUND AND PURPOSE: Coronary artery disease is the leading cause of death after TIA. Reliable estimates of the risk of MI after TIA, however, are lacking. METHODS: Our purpose was to determine the incidence of and risk factors for MI after TIA. We cross-referenced preexisting incidence cohorts from the Rochester Epidemiology Project for TIA (1985-1994) and MI (1979-2006) to identify all community residents with incident MI after incident TIA. Incidence of MI after TIA was determined using Kaplan-Meier life-table methods. This was compared to the age-, sex-, and period-specific MI incidences in the general population. Proportional hazards regression analysis was used to examine associations between clinical variables and the occurrence of MI after TIA. RESULTS: Average annual incidence of MI after TIA was 0.95%. Relative risk for incident MI in the TIA cohort compared to the general population was 2.09 (95% CI, 1.52-2.81). This was highest in patients younger than 60 years old (relative risk, 15.1; 95% CI, 4.11-38.6). Increasing age (hazard ratio, 1.51 per 10 years; 95% CI, 1.14-2.01), male sex (hazard ratio, 2.19; 95% CI, 1.18-4.06), and the use of lipid-lowering therapy at the time of TIA (hazard ratio, 3.10; 95% CI, 1.20-8.00) were independent risk factors for MI after TIA. CONCLUSIONS: Average annual incidence of MI after TIA is ≈1%, approximately double that of the general population. The relative risk increase is especially high in patients younger than 60 years old. These data are useful for identifying subgroups of patients with TIA at highest risk for subsequent MI.

Decompressive laparotomy for refractory intracranial hypertension after traumatic brain injury.

BACKGROUND: Intracranial hypertension is a crucial modifiable risk factor for poor outcome after traumatic brain injury (TBI). Limited evidence suggests that decompressive laparotomy may be an effective treatment for refractory ICH in patients who have elevated intra-abdominal pressure. METHODS: Case report. RESULTS: We present a multi-trauma patient who sustained severe TBI in a motor vehicle collision. Intracranial pressure (ICP) was initially medically managed but became refractory to standard therapies. Emergent decompressive laparotomy performed in the surgical intensive care unit for abdominal compartment syndrome concomitantly improved the patient's ICP. CONCLUSIONS: Elevated intra-abdominal pressure can exacerbate intracranial hypertension in patients with TBI. Recognition of this condition and treatment with decompressive laparotomy may be useful in patients with intracranial hypertension refractory to optimal medical therapy.

Asymmetric posterior reversible encephalopathy syndrome complicating hemodynamic augmentation for subarachnoid hemorrhage-associated cerebral vasospasm.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a rare complication of hemodynamic augmentation for subarachnoid hemorrhage (SAH)-associated vasospasm. The roles of hyperperfusion and hypoperfusion in the genesis of PRES remain uncertain. METHODS: Case report. RESULTS: We admitted a 35-year-old woman with Hunt & Hess grade II SAH secondary to rupture of a right middle cerebral artery (MCA) aneurysm. This was surgically clipped. Beginning on hospital day 3, she developed recurrent symptomatic vasospasm of the right MCA despite hemodynamic augmentation to a MAP as high as 130 mmHg and endovascular therapy. On hospital day 7, after 36 h of sustained MAP 120-130 mmHg, her level of arousal progressively declined, culminating in stupor and two generalized tonic-clonic seizures. MRI showed widespread, yet markedly asymmetric changes consistent with PRES largely sparing the right MCA territory. After the MAP was decreased to 85-100 mmHg, she had no further seizures. 2 days later she was fully alert with mild left hemiparesis. CONCLUSIONS: PRES is a rare complication of hemodynamic augmentation that should be considered in the differential diagnosis of delayed neurological decline in patients with aneurysmal SAH-associated cerebral vasospasm. The markedly asymmetric distribution of PRES lesions with sparing of the territory affected by vasospasm supports the hypothesis that hyperperfusion underlies the pathophysiology of this disorder.

Reversible Encephalopathy Due to Venous Hypertension From Arteriovenous Hemodialysis Graft.

Venous congestive encephalopathy is a rare complication in patients with arteriovenous hemodialysis grafts. It commonly manifests as encephalopathy of fluctuating severity, often with seizures. Because these patients typically have multiple significant chronic health problems, venous hypertension's contribution to the patient's cognitive decline can easily be overlooked. This nonspecific presentation can make diagnosis challenging, therefore delaying treatment. We describe a case of progressive, fluctuating encephalopathy with seizures due to cerebral venous congestion caused by arterial shunting from an upper limb arteriovenous (AV) fistula to the proximal venous system, that was initially unrecognized, yet ultimately reversed by elimination of the source of venous hypertension.

Movement Disorder Emergencies.

Acute presentation of new movement disorders and acute decompensation of chronic movement disorders are uncommon but potentially life-threatening. Inadvertent or purposeful overdose of many psychiatric medications can result in acute life-threatening movement disorders including serotonin syndrome, neuroleptic malignant syndrome, and malignant catatonia. Early withdrawal of potentiating medications, treatment with benzodiazepines and other diagnosis-specific drugs, and providing appropriate supportive care including airway and breathing management, hemodynamic stabilization, fluid resuscitation, and renal support including possible hemodialysis are the mainstays of acute management. Many of these conditions require admission to the neurologic intensive care unit.