Pathophysiology and Management of Neurogenic Pulmonary Edema in Patients with Acute Severe Brain Injury.

Acute brain injury (ABI) consists of any acquired insult to the brain and is a significant cause of morbidity and mortality worldwide. Approximately 20% to 30% of patients with ABI develop a lung injury called neurogenic pulmonary edema (NPE), and its development often results in poor outcomes. This article provides a narrative review of the evidence regarding proposed mechanisms of injury, diagnosis, and treatment of NPE in the critical care setting. PubMed and Ovid databases were searched for observational or prospective studies relevant to the diagnosis and treatment of NPE. Overall, studies showed that although the specific mechanisms responsible for NPE remain uncertain, putative mechanisms include vaso- and venoconstriction, catecholamine release with resultant pulmonary vasoconstriction called the "blast injury theory," increased vagal tone, and increased capillary permeability. Diagnosis involves identifying signs of pulmonary edema in patients who experienced a neurologic insult. Management strategies aim to address both brain and lung injury, and treatment modalities appear to work best when balanced toward maintaining a normal physiologic state. In summary, NPE is an often underdiagnosed but important sequela of ABI, which may result in additional long-term morbidity. It is therefore an important entity for providers to recognize and tailor their clinical approach toward.

Reversible cerebral vasoconstriction syndrome (RCVS) caused by over-the-counter calcium supplement ingestion.

A 59-year-old woman was found unresponsive at home. Initial neurologic examination revealed aphasia and right-sided weakness. Laboratory results demonstrated a serum calcium level of 17.3 mg/dL (corrected serum calcium for albumin concentration was 16.8 mg/dL). Extensive workup for intrinsic aetiology of hypercalcemia was unrevealing. Further discussion with family members and investigation of the patient's home for over-the-counter medications and herbal supplements revealed chronic ingestion of calcium carbonate tablets. CT angiogram of the brain revealed multifocal intracranial vascular segmental narrowing, which resolved on a follow-up cerebral angiogram done 2 days later. These findings were consistent with reversible cerebral vasoconstriction syndrome.Appropriate blood pressure control with parenteral agents, calcium channel blockade with nimodipine and supportive care therapies resulted in significant improvement in neurologic status. By discharge, patient had near-complete resolution of neurologic symptoms.

Predictors of Ventricular Dysrhythmias in Neurology Intensive Care Unit Patients with Prolonged QTc.

INTRODUCTION: Acute neurological injury and several medications commonly administered in the Neuro ICU pose a risk of fatal cardiac dysrhythmias. The objective of this study is to identify the predictors of ventricular dysrhythmias in the Neuro ICU patients with prolonged QTc, thereby helping the clinicians make important treatment decisions. METHODS: We performed a retrospective review of all consecutive adults admitted to the Neuro ICU from January 2015 to September 2015 with a QTc interval ≥ 450 ms on electrocardiogram. RESULTS: A total of 170 patients with a mean age of 66 years (SD ± 16) were included in the final analysis. Eighty-seven patients (51%) were women. Median duration of hospitalization was 9 days (IQR 4-16). Most common primary diagnosis was ischemic stroke (38%) followed by cerebral hemorrhage (19%) and subarachnoid hemorrhage (8%). Mean QTc was 487 ms (SD ± 35, range 450-659 ms). There were 27 episodes (16%) of monomorphic non-sustained ventricular tachycardia and one episode of Torsades (1%). Three cardiac arrests (2%) were recorded, none resulting from ventricular dysrhythmias. In multivariate analysis, prolonged QTc ≥ 492 ms (p = 0.0008), supratentorial acute ischemic stroke (p = 0.005), prolonged hospitalization (p = 0.03), and premature ventricular complexes on ECG (p = 0.047) were all independently associated with increased risk of ventricular dysrhythmias. CONCLUSIONS: In this group of patients with prolonged QTc in the Neuro ICU, we observed several episodes of non-sustained ventricular tachycardia and identified important risk factors associated with their occurrence. This knowledge is essential to inform clinical decisions.

Utility of cerebrospinal fluid lactate in aneurysmal subarachnoid hemorrhage.

BACKGROUND: An external ventricular drain (EVD) treats hydrocephalus in patients with aneurysmal subarachnoid hemorrhage (aSAH). This study examines the utility of cerebrospinal fluid (CSF) lactate collected from an EVD as a proposed biomarker to predict patient outcome and vasospasm/delayed cerebral ischemia. METHODS: Consecutive adults admitted to Wake Forest Baptist Medical Center from 2010 to 2015 with aSAH were identified through the electronic medical record, and clinical variables were collected and analyzed for correlation with incidence of vasospasm and discharge outcome. RESULTS: In all, 51 patients with aSAH and an EVD had CSF lactate measured which ranged from 1.9 to 6.2 mmol/L, with a median value of 3.2 mmol/L. Vasospasm based on transcranial Doppler assessment occurred in 29 patients (57%), of which 20 (45%) were clinically symptomatic. Good outcome (discharge to home/acute rehab) occurred in 35 patients (69%). Sixteen patients (31%) had an unfavorable outcome (died/discharged to nursing homes/long-term acute care facility). In multivariate regression analysis, unfavorable outcome at discharge (P = 0.02), elevated CSF protein (P = 0.04), and admission Hunt and Hess score 3-5 (P = 0.05) were significantly associated with higher CSF lactate. The risk of symptomatic vasospasm increased with lactate in univariate analysis, but did not reach statistical significance (P = 0.077). CONCLUSION: The measurement of the CSF biochemical markers using an EVD is feasible and safe. We found that elevated CSF lactate correlates with patient outcome. Larger prospective studies are needed to test the validity of this finding and for understanding the underlying pathophysiologic mechanisms.

New Developments in Refractory Status Epilepticus.

Status epilepticus (SE) is a medical emergency and presents with either a continuous prolonged seizure or multiple seizures without full recovery of consciousness in between them. The goals of treatment are prompt recognition, early seizure termination, and simultaneous evaluation for any potentially treatable cause. Improved understanding of the pathophysiology has led to a more practical definition. New data have emerged regarding the safety and efficacy of alternative agents, which are increasingly used in the management of these patients. Continuous electroencephalogram monitoring is more widely used and has revealed a higher incidence of subclinical seizures than was previously thought.

Factors Associated with the Outcome of Very Elderly Patients with Large Hemispheric Infarction Treated with Medical Management Only.

BACKGROUND: Large ischemic stroke in the very elderly population is presumed to invariably carry a poor prognosis and clinicians may refrain from continuing intensive care. Many elderly patients are not surgical candidates, and there is a paucity of data outlining the real-world outcomes of continued medical management. Our objective is to identify the factors associated with the outcome of very elderly patients with large hemispheric infarction (LHI) treated with medical management alone. METHODS: We performed a retrospective review of all consecutive adults ≥ 70 years of age with LHI identified from a single center stroke registry between 2012 and 2016. Mean volume of infarction was calculated using the ABC/2 method. RESULTS: Of a total of 2335 patients, 71 (mean age 81 ± 7 years,) met inclusion criteria. Forty-one were women (58%). Mean admission National Institute of Health Stroke Score (NIHSS) was 21 ± 6. Intravenous tPA was administered in 30 (42%) and 9 (13%) patients underwent thrombectomy. Mean infarct volume was 175 ± 75 cc. Twenty-seven patients (38%) survived to hospital discharge; 6 (9%) eventually went home (albeit with mRS 4) and one (1%) went to assisted living. Multivariate logistic regression analysis found that admission NIHSS ≥ 20 (p = 0.0007) and mechanical ventilation within 48 h of admission (p = 0.0396) were independently associated with poor outcome. CONCLUSION: Ten percent of medically managed patients (≥ 70 years of age) with LHI can go home or to assisted living, but with a mRS of 4. Whether this is an acceptable outcome must be individualized on a case-by-case basis; however, poor prognosis should not be automatically presumed solely based on the combination of older age and a large stroke.

Safety of Phenylephrine Infusion Through Peripheral Intravenous Catheter in the Neurological Intensive Care Unit.

OBJECTIVE: The traditional approach for infusing vasopressors is to insert central venous catheters, which is associated with several complications. Phenylephrine is a commonly used vasopressor in the neurologic intensive care unit (neuro ICU), and due to its modest potency, the risk of local tissue injury from extravasation may be overestimated. The purpose of this study was to evaluate the safety of phenylephrine infusion through peripheral intravenous catheter (PIV) in the neuro ICU. PATIENTS AND METHODS: Retrospective review of all consecutive adults admitted to the neuro ICU receiving phenylephrine infusion via PIV at a tertiary academic medical center from September 2012 to November 2015. RESULTS: Two hundred seventy-seven patients with a mean age of 65 years (standard deviation [SD]: ±15) were included in the final analysis. The most common indications for phenylephrine use were hemodynamic augmentation (40%) and postoperative hypotension (32%). The most common location of PIV-infusing phenylephrine was proximal upper extremity (50%). The most common PIV gauge was 20 (41%). The mean maximum dose of phenylephrine was 79 µg/min (SD: ±53, range: 5-200) or 1.04 µg/kg/min (SD: ±0.74, range: 0.07-3.49) and was continued for a mean duration of 19 hours (SD: ±18, range: 1-129). Nine (3%) total episodes of PIV infiltration were noted, none requiring intervention for significant tissue injury or limb ischemia. CONCLUSION: Infusion of phenylephrine through PIV is safe when used in moderate doses for a short time and can be considered in lieu of placing a central line solely for this purpose.

New Developments in Refractory Status Epilepticus.

Status epilepticus (SE) is a medical emergency and presents with either a continuous prolonged seizure or multiple seizures without full recovery of consciousness in between them. The goals of treatment are prompt recognition, early seizure termination, and simultaneous evaluation for any potentially treatable cause. Improved understanding of the pathophysiology has led to a more practical definition. New data have emerged regarding the safety and efficacy of alternative agents, which are increasingly used in the management of these patients. Continuous electroencephalogram monitoring is more widely used and has revealed a higher incidence of subclinical seizures than was previously thought.

Postinterventional critical care management of aneurysmal subarachnoid hemorrhage.

PURPOSE OF REVIEW: Subarachnoid hemorrhage from a ruptured aneurysm (aSAH) is a complex disorder with the potential to have devastating effects on the brain as well as other organ systems. After more than 3 decades of research, the underlying pathophysiologic mechanisms remain incompletely understood and important questions remain regarding the evaluation and management of these patients. The purpose of this review is to analyze the recent literature and improve our understanding of certain key clinical aspects. RECENT FINDINGS: Growing body of evidence highlights the usefulness of CT perfusion scans in the diagnosis of vasospasm and delayed cerebral ischemia (DCI). Hypervolemia leads to worse cardiopulmonary outcomes and does not improve DCI. The traditional triple H therapy is falling out of favor with hemodynamic augmentation alone now considered the mainstay of medical management. Randomized controlled trials have shown that simvastatin and intravenous magnesium do not prevent DCI or improve functional outcomes after aneurysmal subarachnoid hemorrhage (aSAH). Emerging data using multimodality monitoring has further advanced our understanding of the pathophysiology of DCI in poor grade aSAH. SUMMARY: The brief review will focus on the postinterventional care of aSAH patients outlining the recent advances over the past few years.

Albuminocytologic Dissociation in Posterior Reversible Encephalopathy Syndrome.

OBJECTIVES: To describe cerebrospinal fluid (CSF) findings in patients with posterior reversible encephalopathy syndrome (PRES) and to study its association with vasogenic edema. PATIENTS AND METHODS: Retrospective review of 73 consecutive prospectively collected adults diagnosed with PRES from January 1, 2000, through December 31, 2014, who underwent lumbar puncture. RESULTS: Seventy-three patients (mean age, 51±17 years), were included in the analysis; of these, 50 (69%) were women. The most common causes for PRES were hypertension (n=61 [84%]) and immunosuppression (n=22 [30%]). Renal failure was present in 42 (58%) patients. The median interval between clinical onset of PRES and CSF analysis was 1 day (interquartile range [IQR], 0-2 days). The median opening pressure was 23 cm H2O or 17 mm Hg (IQR, 18-28 cm H2O or 13-21 mm Hg), although it was available in only 27 patients. The median CSF protein level was 58 mg/dL (IQR, 44-81 mg/dL; normal value, <35 mg/dL). The median CSF protein level was higher in patients with more extensive vasogenic edema. The median white blood cell count was 1 cell/µL (IQR, 1-2 cells/µL). CONCLUSION: Elevated CSF protein level without CSF pleocytosis commonly occurs in patients with PRES and is directly associated with the extent and topographical distribution of cerebral edema. Although mild CSF pleocytosis can also occur, it is an uncommon finding and may prompt consideration for further diagnostic testing.

An Unusually Benign Course of Extensive Posterior Circulation Occlusion.

BACKGROUND: Acute basilar artery occlusion is associated with poor outcome. In a few cases, occlusion occurs over a period allowing adequate collateral circulation to the posterior fossa. We describe a rare presentation with transient loss of consciousness (LOC) in a patient with extensive occlusion of the posterior circulation. METHODS: Case report. RESULTS: We describe a 70-year-old right-handed man with a history significant for atrial fibrillation and dolichoectasia of the basilar artery. Fourteen years ago, he had a small infarction in the pons resulting in right hemiparesis. Magnetic resonance angiogram at that time showed mild intracranial atherosclerosis. He was treated with warfarin for secondary stroke prevention. He presented to our emergency department after a witnessed spell of LOC after a large meal. On regaining consciousness, he had 2 episodes of emesis. Examination revealed only a spastic right hemiparesis from the old stroke in the pons. Cerebral angiogram showed absent flow in the mid and distal basilar arteries, both posterior cerebral arteries, and both posterior communicating arteries with bilateral stenoses of internal carotid arteries. His international normalized ratio in the emergency department was 1.1. He was treated with intravenous heparin and did well. Three months later, he underwent stent treatment of the worsening stenosis (90%) of the right internal carotid artery. CONCLUSIONS: Occasionally, collateral circulation has the potential to maintain adequate perfusion to the posterior fossa in severe cases of posterior circulation occlusion and diffuse intracranial atherosclerotic disease. Careful patient selection is essential before planning any endovascular intervention.

Long-term risk of seizures and epilepsy in patients with posterior reversible encephalopathy syndrome.

OBJECTIVE: Seizures are common in patients with posterior reversible encephalopathy syndrome (PRES), which is reported in up to 70% of cases, and antiepileptic drugs (AEDs) are commonly prescribed. There is a paucity of data regarding the risk of subsequent seizures following resolution of PRES, and therefore the optimal duration of treatment with AEDs is currently unknown. The objective of this study was to identify the frequency of recurrent seizures and epilepsy following recovery from PRES. METHODS: We performed a retrospective review of consecutive adults diagnosed with PRES between 2000 and 2010. RESULTS: One hundred twenty-seven patients, median age 53 years (interquartile range [IQR] 37-64), were included in the analysis. The most common causes of PRES were hypertension (72%) and immunosuppression (20%). Renal failure was present in 47%. Eighty-four patients (66%) had seizures at presentation (39 focal, 45 generalized), and 13 (15%) of them presented with status epilepticus. Median duration of follow-up was 3.2 years (IQR 4 months to 6.9 years). Patients with seizures were treated with AEDs for a median of 3 months (IQR 2-7). Fifteen patients (12%) had provoked seizures during the follow-up period; in eight (53%) patients seizures were caused by recurrent PRES. Only three patients had subsequent unprovoked seizures, one of whom was considered to have developed epilepsy. SIGNIFICANCE: We conclude that unprovoked seizures and epilepsy are uncommon in patients who have recovered from PRES. Discontinuation of AEDs following resolution of PRES should be considered, provided there is adequate control of risk factors, and absence of factors that could substantially lower the seizure threshold.

Cerebellar infarction.

Cerebellar infarction presents with symptoms of nausea, vomiting, and dizziness and thus mimics benign conditions such as viral gastroenteritis or labyrinthitis, which constitutes a good proportion of patients seen in the emergency department. A physician is often faced with the task of identifying the few cases in which cerebellar stroke is the underlying cause instead. In-depth knowledge of the signs and symptoms of cerebellar infarction is therefore essential. Large infarctions or the ones with hemorrhagic conversion can lead to tissue swelling and complications such as obstructive hydrocephalus and brainstem compression. This article summarizes the current multidisciplinary approach to cerebellar stroke.

Cerebellar hemorrhage.

The clinical presentation of cerebellar hemorrhage can range from symptoms mimicking ischemic stroke to catastrophic neurologic decline. Symptomatology largely depends on the size of the hemorrhage and the degree of perilesional edema. The posterior fossa is a tight compartment with virtually no additional space to accommodate the mass effect. Thus, the hematoma and its associated swelling can cause obstructive hydrocephalus and brainstem compression, in severe cases contributing to early mortality, but outcome can be good if surgical intervention is appropriately timed. This article summarizes the current multidisciplinary approach to cerebellar hemorrhage, and addresses the controversies regarding its optimal management.

Completing the apnea test: decline in complications.

INTRODUCTION: The apnea test is a crucial component of the clinical diagnosis of brain death. Apprehension about hypoxemia, hypotension, and/or cardiac arrhythmias may sometimes lead clinicians to avoid performing or prematurely terminate the apnea test. The purpose of this study was to perform a contemporary re-evaluation of the safety of the apnea test. METHODS: We performed a detailed chart review of consecutive brain dead patients who underwent an apnea test from 2008 to 2012. RESULTS: Out of 63 patients, 33 were men (52.4 %). Mean age was 46.4 years. In all but four patients (93.7 %), the apnea test was performed by a neurointensivist. Infiltrates on chest radiographs were present in 34 (54 %). Seven patients (11.1 %) had chest tubes, six of which were associated with polytrauma. Echocardiograms were obtained in 47 patients (74.6 %), and 18 patients (38.3 %) had regional wall motion abnormalities (IQR 41-65 %). Fifty patients (79.4 %) were on vasopressors prior to apnea test. Median FiO2 was 0.5 (IQR 0.4-0.6), and PEEP was 5 cm H2O (IQR 5-10). After apnea test, median pO2 was 306 mmHg (IQR 121-389). Apnea test was aborted in only one patient; this patient had required FiO2 0.9-1.0 prior to the test and desaturated during the test. Mild hypoxemia occurred in three others without any consequences. Mild hypotension occurred in 11 patients (17.4 %) and was easily managed by an increase in the vasopressor infusion. There were no instances of major cardiac arrhythmias. CONCLUSION: Apnea determined using the oxygenation diffusion method during brain death testing is very safe, provided appropriate prerequisites are met. We found a major decrease in the number of aborted or not attempted apnea tests compared to previous studies.

Sphenoid and subdural hemorrhage as a presenting sign of ruptured clinoid aneurysm.

BACKGROUND: Aneurysm rupture presenting as an isolated or pure subdural hematoma (SDH) without subarachnoid hemorrhage is an extremely rare radiographic presentation. We present a case of a ruptured internal carotid artery aneurysm with a pure SDH and concurrent sphenoid sinus hemorrhage. METHODS: Case report and review of the literature. RESULTS: We describe a case of a 48-year-old right-handed woman found comatose brought by emergency medical services to an outside hospital. A non-contrast head CT scan demonstrated bilateral acute SDHs without evidence of intraparenchymal or subarachnoid hemorrhage. A CT angiogram of the head showed a focal hyperdensity in the distal left internal carotid artery (ICA) and was confirmed by conventional cerebral angiography to be a 7-mm left supraclinoid ICA aneurysm. On repeat CT scan a new hemorrhage was seen in the sphenoid sinus indicating a re-bleeding. The aneurysm was treated with coil embolization and complete occlusion was confirmed with subsequent angiograms. The patient had an eventful hospital course complicated by a Takotsubo cardiomyopathy and pulmonary edema. She was medically treated with successful recovery of her cardiopulmonary function. She remained markedly disabled and was transferred to an inpatient rehabilitation center for continued convalescence. CONCLUSIONS: Acute subdural hematoma may be due to a ruptured clinoid carotid aneurysm. Acute hemorrhage into the sphenoid sinus can be an important clue.

Neurologic manifestations of acute liver failure.

Fulminant hepatic failure presents with a hepatic encephalopathy and may progress to coma and often brain death from cerebral edema. This natural progression in severe cases contributes to early mortality, but outcome can be good if liver transplantation is appropriately timed and increased intracranial pressure (ICP) is managed. Neurologists and neurosurgeons have become more involved in these very challenging patients and are often asked to rapidly identify patients who are at risk of cerebral edema, to carefully select the patient population who will benefit from invasive ICP monitoring, to judge the correct time to start monitoring, to participate in treatment of cerebral edema, and to manage complications such as intracranial hemorrhage or seizures. This chapter summarizes the current multidisciplinary approach to fulminant hepatic failure and how to best bridge patients to emergency liver transplantation.