Near Infrared Spectroscopy for Poor Grade Aneurysmal Subarachnoid Hemorrhage-A Concise Review.

Delayed cerebral ischemia (DCI) disproportionately affects poor grade aneurysmal subarachnoid hemorrhage (aSAH) patients. An unreliable neurological exam and the lack of appropriate monitoring leads to unrecognized DCI, which in turn is associated with severe long-term deficits and higher mortality. Near Infrared Spectroscopy (NIRS) offers simple, continuous, real time, non-invasive cerebral monitoring. It provides regional cerebral oxygen saturation (c-rSO2), which reflects the balance between cerebral oxygen consumption and supply. Reports have demonstrated a good correlation with other cerebral oxygen and blood flow monitoring, and credible cerebrovascular reactivity indices were also derived from NIRS signals. Multiple critical c-rSO2 values have been reported in aSAH patients, based on various thresholds, duration, variation from baseline or cerebrovascular reactivity indices. Some were associated with vasospasm, some with DCI and others with clinical outcomes. However, the poor grade aSAH population has not been specifically studied and no randomized clinical trial has been published. The available literature does not support a specific NIRS-based intervention threshold to guide diagnostic or treatment in aSAH patients. We review herein the fundamental basic concepts behind NIRS technology, relationship of c-rSO2 to other brain monitoring values and their potential clinical interpretation. We follow with a critical evaluation of the use of NIRS in the aSAH population, more specifically its ability to diagnose vasospasm, to predict DCI and its association to outcome. In summary, NIRS might offer significant potential for poor grade aSAH in the future. However, current evidence does not support its use in clinical decision-making, and proper technology evaluation is required.

Acute Blood Pressure and Outcome After Intracerebral Hemorrhage: The VISTA-ICH Cohort.

BACKGROUND: Recent clinical trials suggest that it is safe to acutely lower systolic blood pressure (BP) to 140 mm Hg after ICH, but uncertainty remains regarding optimal management. We sought to better define the link between BP and outcome in ICH patients using data from the Virtual International Stroke Trials Archive (VISTA). METHODS: We performed a retrospective analysis of patients of the VISTA-ICH trials. We measured the strength of association between systolic and diastolic BP various components at different timepoints with unfavorable 3 month-outcome, defined as death or moderate-to-severe disability at 3 months (mRS of 4-6), after adjustment for known confounders. We also dichotomized BP values obtained at 24 h at different thresholds to better define an optimal treatment target. The association of BP with hematoma expansion (HE) was also analyzed. RESULTS: A total of 384 patients were included. Higher BP at 24 hours was associated with unfavorable outcome for systolic BP (OR 1.16, 95% C.I. 1.07-1.25), pulse pressure (OR 1.13, 95% C.I. 1.03-1.24), and diastolic BP (OR 1.11, 95% C.I. 1.01-1.23) per 10 mm Hg increment. The association between higher BP at 24 h and unfavorable outcome remained significant down to >140 mm Hg. Elevated systolic BP at 24 h was also associated with HE (OR 1.11, 95% C.I. 1.02-1.21 per 10 mm Hg increment). CONCLUSION: Elevated BP after ICH at 24 h is associated with poor outcome. Our results support the practice of targeting a systolic BP of 140 mm Hg.

Neuromonitoring with near-infrared spectroscopy (NIRS) in aneurysmal subarachnoid haemorrhage: a systematic review protocol.

INTRODUCTION: Aneurysmal subarachnoid haemorrhage (aSAH) is a devastating disease associated with high mortality and morbidity. The main threat to patients is delayed cerebral ischaemia (DCI). Near-infrared spectroscopy (NIRS) is a recent technology allowing continuous, non-invasive cerebral oximetry that could permit timely detection of impending DCI and appropriate intervention to improve outcomes. However, the ability of regional oxygen saturation to detect DCI, its association to the outcome, or benefits of any interventions based on NIRS data, are lacking. Our aims are to evaluate NIRS technology both as a therapeutic tool to improve outcomes in aSAH patients and as a diagnostic tool for DCI. METHODS AND ANALYSIS: MEDLINE, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews will be searched from their inception and without language restriction. Our search strategy will cover the themes of subarachnoid haemorrhage and cerebral oximetry, without limitations regarding studied outcomes. We will identify all observational and interventional human studies of adult patients hospitalised after aSAH that were monitored using NIRS. Functional outcome measures, including the modified Rankin Scale, the Glasgow Outcome Scale and the Barthel Index, will constitute the primary outcome. The Cochrane Risk of Bias tool will be used for randomised controlled trials, the ROBINS-I tool to assess non-randomised studies of interventions and the Newcastle-Ottawa Scale for cohort or case-control studies. The Quality Assessment of Diagnostic Accuracy Studies-2 will be applied to studies evaluating NIRS diagnostic accuracy for DCI. We will evaluate the quality of the evidence of the effect based on the Grading of Recommendations Assessment, Development and Evaluation methodology. ETHICS AND DISSEMINATION: Dissemination will proceed through submission for journal publication, trial registry completion and abstract presentation. Ethics approval is not required. PROSPERO REGISTRATION NUMBER: CRD42020077522.

Non-invasive cerebral perfusion monitoring in cardiac arrest patients: a prospective cohort study.

OBJECTIVES: To determine if non-invasive cerebral perfusion estimation provided by a new acousto-optic technology can be used as a reliable predictor of neurological outcome. PATIENTS AND METHODS: We performed a prospective, observational cohort study of consecutive comatose patients successfully resuscitated from out-of-hospital cardiac arrest. Patients were monitored using c-FLOW (Ornim Medical) from critical care unit admission up to 72 h, full awakening, or death. Primary outcome was favourable neurological outcome at hospital discharge, defined as a Cerebral Performance Category score of 1 or 2. RESULTS: A total of 21 patients were enrolled, without any loss to follow-up. Mean perfusion index over the monitoring period was not associated with functional outcome at hospital discharge (OR 1.03 [0.93, 1.17]). Adjustment for initial rhythm, time to return of spontaneous circulation and Glasgow coma scale motor score did not significantly alter the results (OR 1.06 [0.99, 1.12]). Mean perfusion index showed a poor discriminative value with an area under the curve of 0.60 for functional outcome (0.64 for survival). Correlation between the probes was weak (Pearson coefficient 0.35). CONCLUSION: Cerebral perfusion monitoring using a c-FLOW device in survivors of cardiac arrest is feasible, but reliability of the information provided has yet to be demonstrated. In our cohort, we were unable to identify any association between the perfusion index and clinical outcomes at discharge. As such, clinical management of cardiac arrest patients based on non-invasive perfusion index is not supported and should be limited to research protocols. The trial was registered with ClinicalTrials.gov, number NCT02575196.

Innate immunity activation in the early brain injury period following subarachnoid hemorrhage.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (SAH) is a catastrophic disease with devastating consequences, including a high mortality rate and severe disabilities among survivors. Inflammation is induced following SAH, but the exact role and phenotype of innate immune cells remain poorly characterized. We investigated the inflammatory components of the early brain injury in an animal model and in SAH patients. METHOD: SAH was induced through injection of blood in the subarachnoid space of C57Bl/6 J wild-type mice. Prospective blood collections were obtained at 12 h, days 1, 2, and 7 to evaluate the systemic inflammatory consequences of SAH by flow cytometry and enzyme-linked immunosorbent-assay (ELISA). Brains were collected, enzymatically digested, or fixed to characterize infiltrating inflammatory cells and neuronal death using flow cytometry and immunofluorescence. Phenotypic evaluation was performed at day 7 using the holding time and footprint tests. We then compared the identified inflammatory proteins to the profiles obtained from the plasma of 13 human SAH patients. RESULTS: Following SAH, systemic IL-6 levels increased rapidly, whereas IL-10 levels were reduced. Neutrophils were increased both in the brain and in the blood reflecting local and peripheral inflammation following SAH. More intracerebral pro-inflammatory monocytes were found at early time points. Astrocyte and microglia activation were also increased, and mice had severe motor deficits, which were associated with an increase in the percentage of caspase-3-positive apoptotic neurons. Similarly, we found that IL-6 levels in patients were rapidly increased following SAH. ICAM-1, bFGF, IL-7, IL-12p40, and MCP-4 variations over time were different between SAH patients with good versus bad outcomes. Moreover, high levels of Flt-1 and VEGF at admission were associated with worse outcomes. CONCLUSION: SAH induces an early intracerebral infiltration and peripheral activation of innate immune cells. Furthermore, microglia and astrocytic activation are present at later time points. Our human and mouse data illustrate that SAH is a systemic inflammatory disease and that immune cells represent potential therapeutic targets to help this population of patients in need of new treatments.

The EMCOOLs surface cooling system for fever control in neurocritical care patients: A pilot study.

OBJECTIVES: Fever occurs in up to 50% of critically-ill patients with acute neurological injury. Small temperature elevations have been correlated with increased morbidity and mortality in this patient population. We sought to evaluate a novel single-use surface cooling system for the treatment of fever in patients with acute brain injury. PATIENTS AND METHODS: We conducted a retrospective analysis of a prospective product evaluation using the EMCOOLS Flex.Pad™ system for acute fever (≥38.3 °C) in our 16-bed neuro-ICU. Four refrigerated pads (-18 °C) were applied to the chest, back, and anterior thighs. Core temperature (bladder) was continuously recorded over 4 h, and the highest Bedside Shivering Assessment Scale (BSAS) score was recorded hourly. RESULTS: Twelve subjects were included in the analysis. Mean age was 55 ±â€¯9 years, 9 patients were men, and mean weight was 85 ±â€¯12 kg. The most common primary diagnoses were subarachnoid (N = 5) and intracerebral (N = 4) hemorrhage. Application of the EMCOOLS system resulted in a linear 1.3 ±â€¯0.6 °C drop (T0avg = 38.9 °C, T90avg = 37.6 °C, P = 0.0032) in mean temperature over 90 min, followed by a plateau with only one subject rebounding to >38 °C within 4 h. Normothermia (<38.0 °C) was achieved in all but one patient (92%) in an average of 65 min. Comatose patients displayed a non-significantly higher degree of cooling at 90 min than did awake subjects (ΔTcoma = 1.74 °C vs ΔTawake = 0.74 °C hr-1, P = 0.067). There was no observed skin irritation upon removal of the device for any patients. CONCLUSION: The EMCOOLs system is a well-tolerated, safe and effective short-term intervention for control of fever in neurological patients. Future studies are needed to compare efficacy of the EMCOOLs to other devices and interventions.

Jamestown Canyon encephalitis with NORSE and electrographic response to ribavirin: a case report.

New-onset refractory status epilepticus (NORSE) is a rare condition where refractory seizures occur with no obvious cause in an otherwise healthy individual. We report here the first case of a patient with NORSE caused by Jamestown Canyon virus, an emerging virus throughout North America. This is the first patient with Jamestown Canyon virus encephalitis treated by a specific antiviral agent, in this case intravenous ribavirin, with electroencephalography (EEG) evidence of improvement. This is finally the first reported death caused by this virus, here secondary to intensive care unit complications. Therefore, Jamestown Canyon virus should be considered as a NORSE etiology, and ribavirin may be an effective treatment of that condition, especially if used early.

Desmopressin administration and rebleeding in subarachnoid hemorrhage: analysis of an observational prospective database.

OBJECTIVERebleeding remains a frequent and catastrophic event leading to poor outcome after subarachnoid hemorrhage (SAH). Reduced platelet function after the initial bleed is associated with higher risk of early rebleeding. Desmopressin (DDAVP) is a well-known hemostatic agent, and recent guidelines already suggest its use in individuals exposed to antiplatelet drugs. The authors hypothesized that DDAVP administration in patients with SAH at admission would be associated with lower risks of rebleeding.METHODSThe authors performed an observational cohort study of patients enrolled in the Columbia University SAH Outcome Project between August 1996 and July 2015. The authors compared the rate of rebleeding between patients who were and those who were not treated with DDAVP. After adjustment for known predictors, logistic regression was used to measure the association between treatment with DDAVP and risks of rebleeding.RESULTSAmong 1639 patients with SAH, 12% were treated with DDAVP. The main indication for treatment was suspected exposure to an antiplatelet agent. The overall incidence of rebleeding was 9% (1% among patients treated with DDAVP compared with 8% among those not treated). After adjustment for antiplatelet use and known predictors, treatment with DDAVP was associated with a 45% reduction in the risks of rebleeding (adjusted OR 0.55, 95% CI 0.27-0.97). DDAVP was associated with a higher incidence of hyponatremia but not with thrombotic events or delayed cerebral ischemia.CONCLUSIONSTreatment with DDAVP was associated with a lower risk of rebleeding among patients with SAH. These findings support further study of DDAVP as first-line therapy for medical hemostasis in patients with SAH.

Multimodality Monitoring: Illuminating the Comatose Human Brain.

The field of neurocritical care has evolved tremendously in recent years, a development explained vastly by the advent of neurophysiological monitoring. From basic intracranial pressure measurements to brain tissue oxygenation, microdialysis, cerebral blood flow (CBF), and surface and intracortical electroencephalography (EEG), our ability to detect and control physiologic endpoints of brain function in comatose patients has grown substantially. The integration of these data gave birth to the concept of multimodality monitoring (MMM). Real-time data acquisition and analysis systems are crucial for fully understanding the relationship between physiologic drivers such as blood pressure, temperature and end-tidal CO2, and end-point measures of brain metabolism such as brain tissue oxygen tension, CBF, lactate/pyruvate ratio, and EEG. Multimodality monitoring provides an early warning system for detecting physiological derangements that can be corrected before secondary brain injury occurs. Multimodality monitoring also allows for the creation of an optimized physiological environment for the injured brain, with the goal of preventing secondary injury events. The authors review the basic ideas and technical aspects of MMM, and therefore provide a unique window of illumination into the comatose human brain.

Management of delayed cerebral ischemia after subarachnoid hemorrhage.

For patients who survive the initial bleeding event of a ruptured brain aneurysm, delayed cerebral ischemia (DCI) is one of the most important causes of mortality and poor neurological outcome. New insights in the last decade have led to an important paradigm shift in the understanding of DCI pathogenesis. Large-vessel cerebral vasospasm has been challenged as the sole causal mechanism; new hypotheses now focus on the early brain injury, microcirculatory dysfunction, impaired autoregulation, and spreading depolarization. Prevention of DCI primarily relies on nimodipine administration and optimization of blood volume and cardiac performance. Neurological monitoring is essential for early DCI detection and intervention. Serial clinical examination combined with intermittent transcranial Doppler ultrasonography and CT angiography (with or without perfusion) is the most commonly used monitoring paradigm, and usually suffices in good grade patients. By contrast, poor grade patients (WFNS grades 4 and 5) require more advanced monitoring because stupor and coma reduce sensitivity to the effects of ischemia. Greater reliance on CT perfusion imaging, continuous electroencephalography, and invasive brain multimodality monitoring are potential strategies to improve situational awareness as it relates to detecting DCI. Pharmacologically-induced hypertension combined with volume is the established first-line therapy for DCI; a good clinical response with reversal of the presenting deficit occurs in 70 % of patients. Medically refractory DCI, defined as failure to respond adequately to these measures, should trigger step-wise escalation of rescue therapy. Level 1 rescue therapy consists of cardiac output optimization, hemoglobin optimization, and endovascular intervention, including angioplasty and intra-arterial vasodilator infusion. In highly refractory cases, level 2 rescue therapies are also considered, none of which have been validated. This review provides an overview of current state-of-the-art care for DCI management.