Blood Pressure Variability: A New Predicting Factor for Clinical Outcomes of Intracerebral Hemorrhage.

Spontaneous primary intracerebral hemorrhage (ICH) is a stroke subtype associated with the highest mortality rate. High blood pressure (BP) is the most common cause of non-lobar ICH. Recent clinical trials have been inconclusive regarding the efficacy of aggressive BP lowering to improve ICH outcome. The association between high BP and ICH prognosis is rather complex and parameters other than absolute BP levels may be involved. In this regard, there is accruing evidence that BP variability (BPV) plays a major role in ICH outcome. Different BPV indices have been used to predict hematoma growth, neurological deterioration, and functional recovery. This review highlights the available evidence about the relationship between BPV and clinical outcomes among patients. We identified standard deviation (SD), residual SD, coefficient of variation, mean absolute change, average real variability, successive variation, spectral analysis using Fourier analysis, and functional successive variation (FSV) as indices to assess BPV. Most studies have demonstrated the association of BPV with ICH outcome, suggesting a need to monitor and control BP fluctuations in the routine clinical care of ICH patients. When large inter-subject variability exists, FSV is a viable alternative quantification of BPV as its computation is less sensitive to differences in the patient-specific observation schedules for BP than that of traditional indices.

CSF Volumetric Analysis for Quantification of Cerebral Edema After Hemispheric Infarction.

BACKGROUND: Malignant cerebral edema (CED) complicates at least 20 % of large hemispheric infarcts (LHI) and may result in neurological deterioration or death. Midline shift (MLS) is a standard but crude measure of edema severity. We propose that volumetric analysis of shifts in cerebrospinal fluid (CSF) over time provides a reliable means of quantifying the spectrum of edema severity after LHI. METHODS: We identified 38 patients from 2008 to 2014 with NIHSS ≥8, baseline CT <6 h after stroke onset, at least 1 follow-up (FU) CT, and no parenchymal hematoma. The volumes of CSF (sulci, ventricles, and cisterns) ipsilateral (IL) and contralateral (CL) to infarct on baseline and FU CTs were quantified by manually assisted outlining with MIPAV image analysis software, as was infarct volume and MLS on FU CTs. Percentage change in CSF volumes (∆CSF) from baseline to FU scans was correlated with MLS and compared in those with vs. without malignant edema (defined as hemicraniectomy, osmotic therapy, or death/neurological deterioration with MLS ≥5 mm). RESULTS: 11 of 38 subjects (29 %) developed malignant edema. Neither baseline NIHSS nor CSF volume differed between those with and without edema (median NIHSS 18 vs. 13, p = 0.12, CSF volume 102 vs. 124 ml, p = 0.16). Inter-rater reliability for CSF measurements was excellent (intraclass correlation coefficient 0.97). ∆CSF correlated strongly with MLS at peak edema (r = -0.75), even adjusting for infarct volume (p = 0.009). ∆CSF was also greater in those with malignant edema [-55 % (IQR -49 to -62) vs. -36 % (-27 to -45), p = 0.004]. ∆CSF was the greatest within IL sulci [-97 % (-86 to -99) vs. -71 % (-41 to -79), p = 0.002] but also significantly greater within CL sulci in those with malignant edema [-50 % (-29 to -65) vs. -25 % (0 to -31), p = 0.014]. More than half this CSF volume reduction occurred by the time of first FU CT around 24 h after stroke, while MLS rose later. CONCLUSIONS: Volumetric CSF analysis reliably quantifies CED and distinguishes those with malignant edema and MLS from those with a more benign course after LHI. ∆CSF may provide an earlier and more sensitive indicator of edema severity across a broader dynamic range than MLS.

A Large Lambl's Excrescence Causing Embolic Stroke in a Young Patient: A Case Report and Review of Literature.

Lambl's excrescences (LEs) are thin, filiform and hypermobile strands that develop at the valvular coaptation sites of the heart. Since first described in 1856 by Vilém Dusan Lambl, there has been an increasing number of reports of central and peripheral emboli arising from cardiac LEs. LEs have been linked to ischemic strokes irrespective of age and comorbidities. We report one of the youngest reported cases in literature of an embolic stroke in a 25-year-old woman caused by a LE. A comprehensive workup was performed that revealed a large aortic valve LE. The patient was discharged on dual anti-platelet therapy with outpatient cardiology follow-up for surveillance echocardiograms. We then surveyed the literature and reviewed case reports and observational studies of LEs linked to systemic emboli. We found that most LEs are present on left-sided high-pressure valves especially the ventricular aspect of the aortic valves and that most reported cases of cerebral embolism had aortic valve LEs. The management of cardioembolic stroke secondary to LEs remains unclear. LEs have not been identified as a definite etiology of cardioembolic strokes warranting the need for large-scale studies to help guide the management of cardiac LEs in the setting of ischemic stroke.

Sleep Spindles and K-Complexes Are Favorable Prognostic Biomarkers in Critically Ill Patients.

SUMMARY: In this narrative review, we summarize recent research on the prognostic significance of biomarkers of sleep in continuous EEG and polysomnographic recordings in intensive care unit patients. Recent studies show the EEG biosignatures of non-rapid eye movement 2 sleep (sleep spindles and K-complexes) on continuous EEG in critically ill patients better predict functional outcomes and mortality than the ictal-interictal continuum patterns. Emergence of more complex and better organized sleep architecture has been shown to parallel neurocognitive recovery and correlate with functional outcomes in traumatic brain injury and strokes. Particularly interesting are studies which suggest intravenous dexmedetomidine may induce a more biomimetic non-rapid eye movement sleep state than intravenous propofol, potentially providing more restorative sleep and lessening delirium. Protocols to improve intensive care unit sleep and neurophysiological studies evaluating the effect of these on sleep and sleep architecture are here reviewed.

The relationship between oxygen and adenosine in astrocytic cultures.

Brain tissue oxygenation affects cerebral function and blood flow (CBF). Adenosine (Ado), a purine nucleoside, moderates neuronal activity, and arterial diameter. The cellular source of Ado in brain remains elusive; however, astrocytes are a logical site of production. Using astrocytic cultures, we tested the hypothesis that astrocytic derived Ado reflects cerebral oxygenation. We found that during alterations in pO(2), extracellular levels of Ado [Ado](e) changed rapidly. Graded reductions of oxygen tension revealed that[Ado](e) reached 10(-7) M to 10(-6) M with a pO(2) of 30-10mmHg, comparable with [Ado](e) and oxygen levels found in brain tissue during normoxemia. Higher O(2) levels were associated with a depression of [Ado](e). Under conditions of low pO(2) (pO(2)

The role of adenosine in hypercarbic hyperemia: in vivo and in vitro studies in adenosine 2(A) receptor knockout and wild-type mice.

OBJECT: The authors tested the hypothesis that adenosine, acting through the A(2A) receptor, is not involved in hypercarbic hyperemia by assessing the effects of increased PaCO(2) on cerebral blood flow (CBF) in vivo in wild-type and A(2A) receptor knockout mice. In addition, they evaluated the effect of abluminal pH changes in vitro on the diameter of isolated perfused penetrating arterioles harvested from wild-type and A(2A) receptor knockout mice. METHODS: The authors evaluated in a blinded fashion the CBF response during transient (60-second) hypercapnic (7% CO(2)) hypercarbia in anesthetized, ventilated C57Bl/6 wild-type and adenosine A(2A) receptor knockout mice. They also evaluated the hypercarbic response in the absence and presence of the nonselective and selective adenosine antagonists. RESULTS: Cerebral blood flow was measured using laser Doppler flowmetry. There were no differences between the CBF responses to hypercarbia in the wild-type and the knockout mice. Moreover, the hypercarbic hyperemia response was not affected by the adenosine receptor antagonists. The authors also tested the response to alteration in abluminal pH in isolated perfused, pressurized, penetrating arterioles (average diameter 63.3 +/- 3.6 microm) harvested from wild-type (6 mice) and knockout (5 mice) animals. Arteriolar dilation in response to a decrease in abluminal pH, simulating the change in vivo during hypercarbia, was similar in wild-type (15.9 +/- 2.6%) and A(2A) receptor knockout (17.7 +/- 1.3%) mice. With abluminal application of CGS 21680 (10(-6) M), an A(2A) receptor agonist, wild-type arterioles dilated in an expected manner (9.8 +/- 0.7%), whereas A(2A) receptor knockout vessels had minimal response. CONCLUSIONS: The results of the in vivo and in vitro studies in wild-type and A(2A) receptor knockout mice support the authors' hypothesis that hypercarbic vasodilation does not involve an adenosine A(2A) receptor-related mechanism.

Posterior Reversible Encephalopathy Syndrome as a Complication of Induced Hypertension in Subarachnoid Hemorrhage: A Case-Control Study.

BACKGROUND: Induced hypertension (IH) remains the mainstay of medical management for delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH). However, raising blood pressure above normal levels may be associated with systemic and neurological complications, of which posterior reversible encephalopathy syndrome (PRES) has been increasingly recognized. OBJECTIVE: To ascertain the frequency and predisposing factors for PRES during IH therapy. METHODS: We identified 68 patients treated with IH from 345 SAH patients over a 3-yr period. PRES was diagnosed based on clinical suspicion, confirmed by imaging. We extracted additional data on IH, including baseline and highest target mean arterial pressure (MAP), comparing PRES to IH-treated controls. RESULTS: Five patients were diagnosed with PRES at median 6.6 d (range 1-8 d) from vasopressor initiation. All presented with lethargy, 3 had new focal deficits, and 1 had a seizure. Although baseline MAP (prior to DCI) did not differ between cases and controls, both MAP immediately prior to IH (112 vs 90) and highest MAP targeted were greater (140 vs 120 mm Hg, both P < .01). Magnitude of MAP elevation was greater (54 vs 34 above baseline, P = .004) while degree of IH was not (37 vs 38 above pre-IH MAP). All 4 surviving PRES patients had complete resolution with IH discontinuation. CONCLUSION: PRES was diagnosed in 7% of SAH patients undergoing IH therapy, most often when MAP was raised well above baseline to levels that exceed traditional autoregulatory thresholds. High suspicion for this reversible disorder appears warranted in the face of unexplained neurological deterioration during aggressive IH.

Regulation of cerebral vasculature in normal and ischemic brain.

We outline the mechanisms currently thought to be responsible for controlling cerebral blood flow (CBF) in the physiologic state and during ischemia, focusing on the arterial pial and penetrating microcirculation. Initially, we categorize the cerebral circulation and then review the vascular anatomy. We draw attention to a number of unique features of the cerebral vasculature, which are relevant to the microcirculatory response during ischemia: arterial histology, species differences, collateral flow, the venous drainage, the blood-brain barrier, astrocytes and vascular nerves. The physiology of the arterial microcirculation is then assessed. Lastly, we review the changes during ischemia which impact on the microcirculation. Further understanding of the normal cerebrovascular anatomy and physiology as well as the pathophysiology of ischemia will allow the rational development of a pharmacologic therapy for human stroke and brain injury.

Comparing External Ventricular Drains-Related Ventriculitis Surveillance Definitions.

OBJECTIVE To evaluate the agreement between the current National Healthcare Safety Network (NHSN) definition for ventriculitis and others found in the literature among patients with an external ventricular drain (EVD) DESIGN Retrospective cohort study from January 2009 to December 2014 SETTING Neurology and neurosurgery intensive care unit of a large tertiary-care center PATIENTS Patients with an EVD were included. Patients with an infection prior to EVD placement or a permanent ventricular shunt were excluded. METHODS We reviewed the charts of patients with positive cerebrospinal fluid (CSF) cultures and/or abnormal CSF results while they had an EVD in place and applied various ventriculitis definitions. RESULTS We identified 48 patients with a total of 52 cases of ventriculitis (41 CSF culture-positive cases and 11 cases based on abnormal CSF test results) using the NHSN definition. The most common organisms causing ventriculitis were gram-positive commensals (79.2%); however, 45% showed growth of only 1 colony on 1 piece of media. Approximately 60% of the ventriculitis cases by the NHSN definition met the Honda criteria, approximately 56% met the Gozal criteria, and 23% met Citerio's definition. Cases defined using Honda versus Gozal definitions had a moderate agreement (κ=0.528; P<.05) whereas comparisons of Honda versus Citerio definitions (κ=0.338; P<.05) and Citerio versus Gozal definitions (κ=0.384; P<.05) had only fair agreements. CONCLUSIONS The agreement between published ventriculostomy-associated infection (VAI) definitions in this cohort was moderate to fair. A VAI surveillance definition that better defines contaminants is needed for more homogenous application of surveillance definitions between institutions and better comparison of rates. Infect Control Hosp Epidemiol 2017;38:574-579.

Role of adenosine A2 receptors in regulation of cerebral blood flow during induced hypotension.

The mechanisms responsible for vascular autoregulation in the brain during changes in mean arterial blood pressure are ambiguous. Potentially, adenosine, a purine nucleoside and potent vasodilator, may be involved as earlier studies have documented an increase in brain adenosine concentrations with cerebral ischemia and hypotension. Consequently, we tested the hypothesis that adenosine is involved in vasodilatation during hypotension within the autoregulatory range (>50 mm Hg) by exposing adenosine 2a receptor (A2aR) knockout and wild type (WT) mice to short (2 to 5 mins) periods of hypotension. We found that autoregulation was significantly (P<0.05) impaired by 29% in A2a knockout mice as compared with WT animals. Furthermore, the A2R antagonist (A2a>A2b:10-85>1), ZM-241385, in a dose (1, 5, 10 mg/kg, intraperitoneally)-related manner, attenuated autoregulation in WT mice. In knockout mice treated with ZM-2413585 (5 and 10 mg/kg), autoregulation was further impaired indicating that A2b receptors also participated in cerebral vasodilatation. Treatment with dipyridamole (1.0 mg/kg) that increases extracellular concentrations of adenosine improved autoregulation in the A2aR knockout mice. We would conclude that adenosine through both A2a and A2b receptors is involved in physiologic vascular regulation during hypotension even within the autoregulatory range.

Cerebral blood flow response in adenosine 2a receptor knockout mice during transient hypoxic hypoxia.

We evaluated cerebral blood flow by laser Doppler during 30 secs of hypoxia (0.10 FiO(2)) in anesthetized, ventilated adenosine 2a receptor knockout (A2aR KO) and wild-type (WT) mice to test the hypothesis that cerebral hypoxic hyperemia in KO mice would be attenuated. We also studied the effects of selective and nonselective A2aR antagonists. During 30 secs of hypoxia, P(a)O(2) decreased significantly (P<0.05) and to a similar degree in both types of mice, whereas P(a)CO(2) remained relatively stable. However, mean arterial blood pressure (MABP) decreased to a greater extent (P<0.05) during hypoxia in KO mice (58.6+/-1.5 mm Hg) than in WT animals (76.1+/-3.2 mm Hg). Consequently, in a separate group of mice, we stabilized and matched MABP during hypoxia. Hypoxic hyperemia was attenuated by 38% (P<0.05) in KO animals whose MABP was uncontrolled, and by 81% (P<0.05) in KO animals whose MABP changes were matched to the MABP in the hypoxic WT mice. In animals treated with adenosine antagonists, hypoxic hyperemia was decreased by 44% to 48% (P<0.05) in WT mice, but was without effect in KO mice. We conclude that adenosine via A2aR is responsible for a significant proportion of the hyperemia during hypoxia.