Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage: The Role of the Complement and Innate Immune System.

Specific inflammatory pathways are important in the development of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Understanding the specific pathways of inflammation may be critical for finding new treatments. Evidence is accumulating that innate inflammatory cells and proteins play a more important role than cells of the adaptive inflammatory system. In this work, we review the evidence from clinical and preclinical data regarding which cells of the immune system play a role in DCI with particular emphasis on the bone-marrow-derived cells monocytes and neutrophils and the brain parenchymal microglia. In addition, we will review the evidence that complement proteins, a non-cellular part of the innate immune system, play a role in the development of DCI.

A potential therapeutic target: The role of neutrophils in the central nervous system.

Neutrophils play a critical role in immune defense as the first recruited and most abundant leukocytes in the innate immune system. As such, regulation of neutrophil effector functions have strong implications on immunity. These cells display a wide heterogeneity of function, including both inflammatory and immunomodulatory roles. Neutrophils commonly infiltrate the central nervous system (CNS) in response to varied pathological conditions. There is still little understanding of the role these cells play in the CNS in such conditions. In the present review, we will summarize what is known of neutrophil's role in cancer and Alzheimer's disease (AD), with a focus on highlighting the gaps in our understanding.

State-of-the-Art Evaluation of Acute Adult Disorders of Consciousness for the General Intensivist.

OBJECTIVES: To provide a concise review of knowledge and practice pertaining to the diagnosis and initial management of unanticipated adult patient disorders of consciousness (DoC) by the general intensivist. DATA SOURCES: Detailed search strategy using PubMed and OVID Medline for English language articles describing adult patient acute DoC diagnostic evaluation and initial management strategies including indications for transfer. STUDY SELECTION: Descriptive and interventional studies that address acute adult DoC, their evaluation and initial management, indications for transfer, as well as outcome prognostication. DATA EXTRACTION: Relevant descriptions or studies were reviewed, and the following aspects of each manuscript were identified, abstracted, and analyzed: setting, study population, aims, methods, results, and relevant implications for adult critical care practice. DATA SYNTHESIS: Acute adult DoC may be categorized by etiology including structural, functional, infectious, inflammatory, and pharmacologic, the understanding of which drives diagnostic investigation, monitoring, acute therapy, and subsequent specialist care decisions including team-based local care as well as intra- and inter-facility transfer. CONCLUSIONS: Acute adult DoC may be initially comprehensively addressed by the general intensivist using an etiology-driven and team-based approach. Certain clinical conditions, procedural expertise needs, or resource limitations inform transfer decision-making within a complex care facility or to one with greater complexity. Emerging collaborative science helps improve our current knowledge of acute DoC to better align therapies with underpinning etiologies.

Neurocritical Care Research: Collaborations for Curing Coma.

One of the most common questions asked by family members of patients with brain injuries who are in a coma is "will my loved one wake up?". Despite substantial improvements in the care of patients with neurological diseases, the medical and scientific community struggles to answer this simple question. More importantly, the technology and treatment strategies to improve the trajectory of patients with impaired consciousness in the acute setting are limited. The Curing Coma Campaign was developed by the Neurocritical Care Society as a multispecialty, multi-interest community of researchers and caretakers who are focused on patients with disorders of consciousness (DoC) in the acute phase of care. Over the first few years of the group, several publications have focused on identifying the gaps in our knowledge to encourage research in the area. In this review, the current understanding of DoC is reviewed. The work of the Curing Coma Campaign to identify gaps in our knowledge is highlighted.

The Future of Critical Care: Optimizing Technologies and a Learning Healthcare System to Potentiate a More Humanistic Approach to Critical Care.

While technological innovations are the invariable crux of speculation about the future of critical care, they cannot replace the clinician at the bedside. This article summarizes the work of the Society of Critical Care Medicine-appointed multiprofessional task for the Future of Critical Care. The Task Force notes that critical care practice will be transformed by novel technologies, integration of artificial intelligence decision support algorithms, and advances in seamless data operationalization across diverse healthcare systems and geographic regions and within federated datasets. Yet, new technologies will be relevant and meaningful only if they improve the very human endeavor of caring for someone who is critically ill.

A Case Report of Peripheral Nerve Stimulation for Acute Neuropathic Pain in Guillain-Barre Syndrome.

Guillain-Barre syndrome (GBS) is a peripheral demyelinating neuromuscular disorder occasionally associated with pharmacologically refractory neuropathic pain. We present a case of acute neuropathic pain in a 22-year-old man with GBS managed with percutaneous peripheral nerve stimulation (PNS). Following implantation of leads in the bilateral sciatic, femoral, and brachial plexus nerve distribution, the patient experienced significant pain reduction in both the upper and lower extremities. Analgesic and anxiolytic medications were reduced by 33% on the first day and by 78% on day 21. PNS is a minimally invasive, nonpharmacologic modality for treating acute neuropathic pain in GBS patients.

Hematologic counts as predictors of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

PURPOSE: Aneurysmal subarachnoid hemorrhage (SAH) is associated with high morbidity and mortality, but currently no single clinical method or ancillary test can reliably predict which subset of patients will develop delayed cerebral ischemia (DCI). The aim of this study was to find hematologic derangements and clinical factors present during the first 7 days after bleeding that could help identify patients at risk for development of DCI. MATERIALS AND METHODS: Databank analysis of patients with SAH admitted between 2010 and 2012 in a single center. Data from demographics, imaging, laboratory, and clinical factors were collected. Statistical testing was conducted to test for association to the outcome, and multivariate logistic regression was used to design a predictive model. RESULTS: Of 55 patients, 14 developed DCI (25%). Anemia and leukocytosis on the third day after bleeding were significantly correlated with the outcome (for anemia: P<.032; confidence interval, 1.12-15.16; odds ratio, 4.12; for leukocytosis: P<.046; confidence interval, 1.03-26.13; odds ratio, 5.18). Anemia and leukocytosis were still statistically significant after adjustment for age, sex, modified Fisher scale, and Hunt-Hess scale. CONCLUSION: The presence of leukocytosis and anemia during the third day after SAH was statistically correlated with the occurrence of DCI.

Effect of Age on Transcranial Doppler Velocities in Patients with Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: It is not well understood whether age impacts transcranial Doppler (TCD) mean flow velocities (MFVs) in patients with aneurysmal subarachnoid hemorrhage (SAH) with or without delayed cerebral ischemia (DCI). The aim of our study was to analyze the behavior of TCD MFV during the first 7 days after SAH in patients of different ages and correlate them with the occurrence of DCI. METHODS: This study is a databank analysis of patients with SAH admitted between 2010 and 2012 in a single center. We analyzed mean MFV of bilateral middle cerebral arteries (MCAs) in all patients enrolled in the study on days 1, 3 and 7. The correlation between age and TCD MFV was analyzed using a univariate linear regression model. RESULTS: Fifty-five patients were studied. Starting on the third day after the bleeding, increasing age was associated with slower MFVs. This trend was not affected by the interrogation of the right or left MCA. After correction to include only patients who developed DCI, the same findings persisted on days 3 and 7. CONCLUSION: Older age was correlated with a significant decrease on TCD velocities in patients with SAH, even after correction for patients who developed DCI.

Neutrophil depletion after subarachnoid hemorrhage improves memory via NMDA receptors.

Cognitive deficits after aneurysmal subarachnoid hemorrhage (SAH) are common and disabling. Patients who experience delayed deterioration associated with vasospasm are likely to have cognitive deficits, particularly problems with executive function, verbal and spatial memory. Here, we report neurophysiological and pathological mechanisms underlying behavioral deficits in a murine model of SAH. On tests of spatial memory, animals with SAH performed worse than sham animals in the first week and one month after SAH suggesting a prolonged injury. Between three and six days after experimental hemorrhage, mice demonstrated loss of late long-term potentiation (L-LTP) due to dysfunction of the NMDA receptor. Suppression of innate immune cell activation prevents delayed vasospasm after murine SAH. We therefore explored the role of neutrophil-mediated innate inflammation on memory deficits after SAH. Depletion of neutrophils three days after SAH mitigates tissue inflammation, reverses cerebral vasoconstriction in the middle cerebral artery, and rescues L-LTP dysfunction at day 6. Spatial memory deficits in both the short and long-term are improved and associated with a shift of NMDA receptor subunit composition toward a memory sparing phenotype. This work supports further investigating suppression of innate immunity after SAH as a target for preventative therapies in SAH.

Intracerebral hemorrhage: new challenges and steps forward.

Intracerebral hemorrhage (ICH) is a significant cause of morbidity and mortality. With the aging population, increased use of anticoagulants, and changing racial and ethnic landscape of the United States, the incidence of ICH will increase over the next decade. Improvements in preventative strategies to treat hypertension and atrial fibrillation are necessary to change the trajectory of this increase. Advances in the understanding of ICH at the vascular and molecular level may pave the way to new treatment options. This article discusses the epidemiology, pathophysiology, and current treatment options for patients with ICH. Differences in outcome and treatment between patients taking and not taking anticoagulant therapies are considered.