Failure Of Autoregulation Research Articles

Predicting outcome after aneurysmal subarachnoid hemorrhage by exploitation of signal complexity: a prospective two-center cohort study

BackgroundSignal complexity (i.e. entropy) describes the level of order within a system. Low physiological signal complexity predicts unfavorable outcome in a variety of diseases and is assumed to reflect increased rigidity of the cardio/cerebrovascular system leading to (or reflecting) autoregulation failure. Aneurysmal subarachnoid hemorrhage (aSAH) is followed by a cascade of complex systemic and cerebral sequelae. In aSAH, the value of entropy has not been established yet.MethodsaSAH patients from 2 prospective cohorts (Zurich—derivation cohort, Aachen—validation cohort) were included. Multiscale Entropy (MSE) was estimated for arterial blood pressure, intracranial pressure, heart rate, and their derivatives, and compared to dichotomized (1–4 vs. 5–8) or ordinal outcome (GOSE—extended Glasgow Outcome Scale) at 12 months using uni- and multivariable (adjusted for age, World Federation of Neurological Surgeons grade, modified Fisher (mFisher) grade, delayed cerebral infarction), and ordinal methods (proportional odds logistic regression/sliding dichotomy). The multivariable logistic regression models were validated internally using bootstrapping and externally by assessing the calibration and discrimination.ResultsA total of 330 (derivation: 241, validation: 89) aSAH patients were analyzed. Decreasing MSE was associated with a higher likelihood of unfavorable outcome independent of covariates and analysis method. The multivariable adjusted logistic regression models were well calibrated and only showed a slight decrease in discrimination when assessed in the validation cohort. The ordinal analysis revealed its effect to be linear. MSE remained valid when adjusting the outcome definition against the initial severity.ConclusionsMSE metrics and thereby complexity of physiological signals are independent, internally and externally valid predictors of 12-month outcome. Incorporating high-frequency physiological data as part of clinical outcome prediction may enable precise, individualized outcome prediction. The results of this study warrant further investigation into the cause of the resulting complexity as well as its association to important and potentially preventable complications including vasospasm and delayed cerebral ischemia.

Abstract 135: Identifying Optimal Mean Arterial Pressure in Cardiac Arrest Patients: Are Precision Medicine Approaches Feasible?

Introduction: Loss of cerebral autoregulation after cardiac arrest (CA) is associated with worse outcomes. A population-based mean arterial pressure (MAP) threshold, such as a post-resuscitation goal of ≥ 65 mmHg, may be insufficient to account for patient-specific factors, like autoregulatory failure. We investigated the feasibility of determining optimal MAP (MAP OPT ) using regional cerebral tissue oxygen monitoring with near-infrared spectroscopy (NIRS). Hypothesis: Autoregulatory failure and MAP OPT can be identified in individual patients after CA. Methods: We prospectively enrolled adult comatose CA survivors undergoing invasive MAP and regional cerebral oxygen monitoring with NIRS in an ICU between April 2022 and May 2023. Tissue oxygenation autoregulatory index (TOx) was derived using a moving Pearson correlation coefficient of 30 consecutive, 10-second averaged values of MAP and tissue oxygen index signals. TOx ≥ 0.3 defined impaired autoregulation. MAP values were divided into bins of 5 mmHg for which each corresponding TOx was averaged. Parabolic curve fitting determined the MAP value with the lowest associated TOx value (MAP OPT ). Results: Of 35 patients enrolled, 74.3% experienced out-of-hospital cardiac arrest with a mean (SD) age of 55.0 (13.9) years. Six (17.1%) patients survived to hospital discharge and 4 (11.4%) progressed to brain death. Monitoring was initiated at a median [IQR] of 14.9 [10.9 - 20.6] hours from CA for a duration of 47.5 [27.1 - 75.1] hours. The time spent with impaired autoregulation was 22.6 [18.4 - 31.6] % of the recording duration, corresponding to 10.1 [6.9 - 15.9] hours. MAP OPT could be identified in 33 (94.3%) patients and 47.7 [32.1 - 59.6] % of the recording duration. The average MAP OPT was <75 mmHg in 2 (6.1%), 75 - 85 mmHg in 14 (42.4%), and >85 mmHg in 17 (51.5%) patients. MAP OPT did not differ between survivors and non-survivors (mean (SD) 87.2 (9.6) vs. 88.2 (12.1) mmHg respectively, p=0.86). Conclusion: MAP OPT could be identified in all but two patients and calculated for half of the recording duration. Average MAP OPT was ≥ 75 mmHg in 94% of our cohort. Future studies are needed to evaluate whether targeting personalized physiologic thresholds influences outcomes.

Sequential carotid Doppler study in acute stroke and its clinical correlation: A prospective study.

Resistive index (RI) and pulsatility index (PI) assessed on carotid Doppler assess the hemodynamic status of cranial vasculature. They are related to the severity of stroke and help determine the overall outcome. This study was done to compare the hospital stay and stroke severity with RI and PI of both internal carotid arteries. Patients >18 years of age presenting within 48 h of anterior circulation stroke (either ischemic or hemorrhagic) were included. They were divided into two groups based on their length of stay (LOS). They were assessed clinically on days 1, 3, and 5, and underwent a carotid Doppler study on the same days. The Doppler parameters were correlated with the LOS and stroke severity for possible associations. One hundred and one patients were included. Forty-seven patients had a favorable outcome based on LOS. In this group, significant decrease in RI and PI scores was seen from days 1 to 3. In patients with unfavorable outcome, there was a significant increase in PI on days 1-3 and days 1-5. The National Institutes of Health Stroke Scale decreased significantly from days 1 to 5 in favorable group. For those with an unfavorable outcome and prolonged LOS, PI continues to increase suggesting a failure of autoregulation. Carotid Doppler can be a simple bedside tool to predict outcome in patients with acute stroke.

#3462 A STUDY OF ETIOLOGY OF ACUTE KIDNEY INJURY AND ACUTE ON CHRONIC KIDNEY DISEASE AMONGST IN-HOSPITAL PATIENTS IN A TERTIARY CARE CENTRE IN INDIA

Abstract Background and Aims Acute kidney injury (AKI) is the leading cause of nephrology consultation and is associated with high mortality rates. The primary causes of AKI include sepsis, ischemia, hypoxia or nephrotoxicity. An underlying feature is a rapid decline in GFR usually associated with a decrease in renal blood flow. Inflammation represents an important additional component of AKI leading to the extension phase of injury, which may be associated with insensitivity to vasodilator therapy. Recent data suggest that AKI represents a potential link to chronic kidney disease (CKD) in surviving patients. Patients with CKD may be at risk for the development of a transient decrease in renal function consistent with AKI. Such rapidly declining renal function causing an acute deterioration of CKD is termed acute-on-chronic kidney disease (ACKD). The mechanisms by which these occur include failure of auto-regulation, abnormal vasodilatation, susceptibility to antihypertensive agents & side effects of medication. The successful recovery from AKI depends on the degree to which these repair processes ensue & these may be compromised in elderly or CKD patients. Aim To determine the burden of AKI among the in-hospital patients & their progression to CKD if at all along with the number & cause of the cases of CKD who develop ACKD due to an acute insult. Method The first 100 consecutive patients admitted with Acute Kidney Injury and Acute on Chronic Kidney Disease in the Department of General Medicine, Nephrology, Intensive care unit in KPC Medical College & Hospital, Kolkata, were selected for the study. Inclusion criteria: • Patients admitted with AKI, ACKD or developing them during the course of stay. • CKD stages I to V with acute exacerbation (reduced GFR, reduced urine output). Exclusion criteria: • Patients <14 years • ESRD patients already on hemodialysis. • Patients with acute Glomerulonephritis (due to the unavailability of biopsy in our institution) • Patients not giving consent to participate in the study. For statistical analysis, data were entered into a Microsoft excel spreadsheet and then analyzed by SPSS and GraphPad Prism version 5. Data had been summarized as mean and standard deviation for numerical variables and count and percentages for categorical variables. Unpaired proportions were compared by Chi-square test or Fischer's exact test, as appropriate. p-value ≤ 0.05 was considered statistically significant. Results ● Out of the first 100 consecutive patients fulfilling the study criteria, 33 patients had AKI & 15 patients had ACKD. ● The male population was higher than the female population. ● T2DM and HTN were more common in ACKD patients than the AKI patients. ● Patients with AKI were clinically dehydrated compared to patients with ACKD. ● Metabolic acidosis was less in AKI patients. ● Most of the ACKD patients had sepsis than the AKI patients. Conclusion The most common etiology of AKI amongst in-hospital patients is dehydration whereas that of ACKD is sepsis associated with more incidence of metabolic acidosis & comorbidities. Earlier diagnosis of AKI represents an important area in treating patients with AKI that has spawned increased awareness of the potential that biomarkers of AKI may play in the future.

Transient Bilateral Central Scotoma on Awakening: A Distinct Phenomenon.

Transient vision loss can be an alarming symptom owing to potentially serious etiologies such as thromboembolism or giant cell arteritis. Transient monocular vision loss (TVML) on awakening has been recently described as a benign phenomenon (Bouffard et al, 2017). Our objective was to describe the unique phenomenon of transient binocular vision loss (TBVL) on awakening. Retrospective observational case series of 5 patients who experienced TBVL on awakening seen in the neuro-ophthalmology clinic at the Mayo Clinic between 2016 and 2020. Patients who described generalized blurred vision and those with monocular transient vision loss were excluded. The median age was 81.4 years (range, 68-92 years), and all were male. Every patient described a stereotyped transient bilateral central scotoma on awakening with slightly irregular borders and mild asymmetry between the 2 eyes lasting between 15 and 90 minutes. Frequency ranged from 3 to 7 times per week, and there was a median of 319 episodes (range, 126-728 episodes) before evaluation in the neuro-ophthalmology clinic. All patients had normal optic nerves, and no plaques were noted in the retinal vessels. All 5 had macular drusen, which were predominantly extrafoveal and mild. Two patients underwent electrophysiology testing, which were both normal on full-field electroretinogram (ERG), but there was blunted central wave forms on multifocal ERG. Two patients underwent dark adaptation testing, which showed both prolong and diminished dark adaptation. Neuroimaging and thromboembolic workup were unrevealing. TBVL is a distinct phenomenon from TMVL on awakening, which has a different demographic and symptomology. The etiology is unclear but seems to be a focal macular process in conjunction with an autoregulatory failure resulting in a supply-demand mismatch during low-light conditions.

Cerebral hyperperfusion syndrome after endovascular stent graft reconstruction for postirradiated carotid blowout syndrome: a case report

Background: Cerebral hyperperfusion syndrome (CHS) is a failure of autoregulation after a revascularization procedure. It has rarely been reported in patients with no pre-existing cerebral hypoperfusion. Case Report: We present a rare case of a patient who underwent stent graft implantation to treat postirradiated carotid blowout syndrome. The patient developed hypertension, focal neurological deficit, and seizures after the procedure; neuroimages revealed ipsilateral cerebral edema, swelling, and increased cerebral perfusion. CHS was diagnosed based on clinical and radiological findings. The patient recovered gradually after receiving supportive care. Conclusion: Owing to the risk of CHS, monitoring for cerebral perfusion and prevention of hypertension is suggested for patients who undergo stent graft placement for postirradiated carotid blowout syndrome.

Maladaptation of renal hemodynamics contributes to kidney dysfunction resulting from thoracic spinal cord injury in mice.

Renal dysfunction is a hallmark of spinal cord injury (SCI). Several SCI sequalae are implicated; however, the exact pathogenic mechanism of renal dysfunction is unclear. Herein, we found that T3 (T3Tx) or T10 (T10Tx) complete thoracic spinal cord transection induced hypotension, bradycardia, and hypothermia immediately after injury. T3Tx-induced hypotension but not bradycardia or hypothermia slowly recovered to levels in T10Tx SCI and uninjured mice ∼16 h after injury as determined by continuous radiotelemetry monitoring. Both types of thoracic SCI led to a marked decrease in albuminuria and proteinuria in all phases of SCI, whereas the kidney injury marker neutrophil gelatinase-associated lipocalin rapidly increased in the acute phase, remaining elevated in the chronic phase of T3Tx SCI. Renal interstitial and vascular elastin fragmentation after SCI were worsened during chronic T3Tx SCI. In the chronic phase, renal vascular resistance response to a step increase in renal perfusion pressure or a bolus injection of angiotensin II or norepinephrine was almost completely abolished after T3Tx SCI. Bulk RNA-sequencing analysis showed enrichment of genes involved in extracellular matrix remodeling and chemokine signaling in the kidney from T3Tx SCI mice. The serum level of interleukin-6 was elevated in the acute but not chronic phase of T3Tx and T10Tx SCI, whereas the serum amyloid A1 level was elevated in both acute and chronic phases. We conclude that tissue fibrosis and hemodynamic impairment are involved in renal dysfunction resulting from thoracic SCI; these pathological alterations, exacerbated by high thoracic-level injury, is mediated at least partly by renal microvascular extracellular matrix remodeling.NEW & NOTEWORTHY Urinary complications resulting from thoracic spinal cord injury (SCI) greatly affects quality of life and contributes to morbidity and mortality in patients with SCI. Herein, we showed that thoracic SCI initiates changes in the structure and function of the renal microvasculature that leads to autoregulation failure in the chronic phase of high thoracic-level injury. Our study identified extracellular matrix regulators and cytokine/chemokine signaling as potential targets for developing novel therapeutics for restoring renal function following SCI.

Cerebral perfusion in posterior reversible encephalopathy syndrome measured with arterial spin labeling MRI

Background and purposeThe pathophysiologic basis of posterior reversible encephalopathy syndrome (PRES) remains controversial. Hypertension (HTN)-induced autoregulatory failure with subsequent hyperperfusion is the leading hypothesis, whereas alternative theories suggest vasoconstriction-induced hypoperfusion as the underlying mechanism. Studies using contrast-based CT and MR perfusion imaging have yielded contradictory results supporting both ideas. This work represents one of the first applications of arterial spin labeling (ASL) to evaluate cerebral blood flow (CBF) changes in PRES. Materials and methodsAfter obtaining Institutional Review Board approval, MRI reports at our institution from 07/2015 to 09/2020 were retrospectively searched and reviewed for mention of “PRES” and “posterior reversible encephalopathy syndrome.” Of the resulting 103 MRIs (performed on GE 1.5 Tesla or 3 Tesla scanners), 20 MRIs in 18 patients who met the inclusion criteria of clinical and imaging diagnosis of PRES and had diagnostic-quality pseudocontinuous ASL scans were included. Patients with a more likely alternative diagnosis, technically non-diagnostic ASL, or other intracranial abnormalities limiting assessment of underlying PRES features were excluded. Perfusion in FLAIR-affected brain regions was qualitatively assessed using ASL and characterized as hyperperfusion, normal, or hypoperfusion. Additional quantitative analysis was performed by measuring average gray matter CBF in abnormal versus normal brain regions. ResultsHTN was the most common PRES etiology (65%). ASL showed hyperperfusion in 13 cases and normal perfusion in 7 cases. A hypoperfusion pattern was not identified. Quantitative analysis of gray matter CBF among patients with visually apparent hyperperfusion showed statistically higher perfusion in affected versus normal appearing brain regions (median CBF 100.4 ml/100 g-min vs. 61.0 ml/ 100 g-min, p < 0.001). ConclusionElevated ASL CBF was seen in the majority (65%) of patients with PRES, favoring the autoregulatory failure hypothesis as a predominant mechanism. Our data support ASL as a practical way to assess and noninvasively monitor cerebral perfusion in PRES that could potentially alter management strategies.

STATE OF AUTONOMIC REGULATION AND CEREBROVASCULAR REACTIVITY IN PATIENTS WITH HEADACHE WITH ARTERIAL HYPERTENSION.

The aim: A comprehensive assessment of the state of the autonomic nervous system and cerebrovascular reactivity of the cerebral blood flow in the patients with the headache accompanied by arterial hypertension (AH) and somatoform autonomic dysfunction (SAD). Materials and methods: We conducted the clinical, autonomic regulation and Doppler sonography examination of 124 young patients (18-45 years old), including 51 men and 73 women in the conditions of the clinical base of the Kharkiv Medical Academy of Postgraduate Education in 2018-2021. All patients with cephalgias were divided into three groups: with AH stage II (Group I - 41 patients), AH stage I (Group II - 40 patients), SAD (Group III - 43 patients). The control group consisted of 50 patients of the corresponding gender and age. Results: The intensity of cephalalgia in patients with SAD was maximum. The autonomic tone (AT) was changed in 68.5%examined patients. It had a pronounced shift towards sympathicotonia. According to the visual analogue scale the maximum intensity of cephalgias was against the sympathicotonia. In the groups with organic lesions of the cerebral vessels the latent period delay was registered with the progression of the organic pathology. The regularity was revealed - the shortening of the evoked skin sympathetic potentials latency with the severity of cephalalgia, which can be interpreted as an increase in ergotropic effects with the realisation of the pain syndrome. The obtained data on the state of the AT indicate the depletion of the ergotropic processes with the progression of cerebral ischemia with a known increase in parasympathicotonia. In the patients of SAD group the CrCO2 and KrFNTvalues were significantly increased, in AH stage I group they slightly exceeded the standard values , in AH stage II group they were reduced. The reactivity to the orthostatic loads and functional metabolic test in all groups exceeded the control values. Conclusions: 1. The cephalgic syndrome is one of the main symptoms of the autonomic dysfunction and arterial hypertension; the frequency and intensity of the headache increases with the hyperreactivity of the sympathetic system. 2. The SSP data indicate that the sympathetic activity triggers and maintains the pain syndrome, and can also be realized in the form of arterial hypertension. 3. The dysfunction of the central link of the GSR indicates the instability of the autonomous regulation, the work of the limbic-reticular complex, which is clinically manifested by the changes in the cerebral vascular tone. 4. The cerebrovascular hyperreactivity as a sign of the search for the optimal sanogenetic variant of the cerebral hemodynamics in patients with SAD and AH stage I occurs predominantly due to the vasodilatory component. 5. In the patients with AH stage II the vasoconstrictor reactions are observed with the depletion of the vasodilation reserves, which is a marker of the autoregulation failure.

Transient Hypoperfusion to Ischemic/Anoxic Spreading Depolarization is Related to Autoregulatory Failure in the Rat Cerebral Cortex

BackgroundIn ischemic stroke, cerebral autoregulation and neurovascular coupling may become impaired. The cerebral blood flow (CBF) response to spreading depolarization (SD) is governed by neurovascular coupling. SDs recur in the ischemic penumbra and reduce neuronal viability by the insufficiency of the CBF response. Autoregulatory failure and SD may coexist in acute brain injury. Here, we set out to explore the interplay between the impairment of cerebrovascular autoregulation, SD occurrence, and the evolution of the SD-coupled CBF response.MethodsIncomplete global forebrain ischemia was created by bilateral common carotid artery occlusion in isoflurane-anesthetized rats, which induced ischemic SD (iSD). A subsequent SD was initiated 20–40 min later by transient anoxia SD (aSD), achieved by the withdrawal of oxygen from the anesthetic gas mixture for 4–5 min. SD occurrence was confirmed by the recording of direct current potential together with extracellular K+ concentration by intracortical microelectrodes. Changes in local CBF were acquired with laser Doppler flowmetry. Mean arterial blood pressure (MABP) was continuously measured via a catheter inserted into the left femoral artery. CBF and MABP were used to calculate an index of cerebrovascular autoregulation (rCBFx). In a representative imaging experiment, variation in transmembrane potential was visualized with a voltage-sensitive dye in the exposed parietal cortex, and CBF maps were generated with laser speckle contrast analysis.ResultsIschemia induction and anoxia onset gave rise to iSD and aSD, respectively, albeit aSD occurred at a longer latency, and was superimposed on a gradual elevation of K+ concentration. iSD and aSD were accompanied by a transient drop of CBF (down to 11.9 ± 2.9 and 7.4 ± 3.6%, iSD and aSD), but distinctive features set the hypoperfusion transients apart. During iSD, rCBFx indicated intact autoregulation (rCBFx < 0.3). In contrast, aSD was superimposed on autoregulatory failure (rCBFx > 0.3) because CBF followed the decreasing MABP. CBF dropped 15–20 s after iSD, but the onset of hypoperfusion preceded aSD by almost 3 min. Taken together, the CBF response to iSD displayed typical features of spreading ischemia, whereas the transient CBF reduction with aSD appeared to be a passive decrease of CBF following the anoxia-related hypotension, leading to aSD.ConclusionsWe propose that the dysfunction of cerebrovascular autoregulation that occurs simultaneously with hypotension transients poses a substantial risk of SD occurrence and is not a consequence of SD. Under such circumstances, the evolving SD is not accompanied by any recognizable CBF response, which indicates a severely damaged neurovascular coupling.

Cerebral Autoregulation during Postural Change in Patients with Cervical Spinal Cord Injury-A Carotid Duplex Ultrasonography Study.

Patients with a spinal cord injury (SCI) frequently experience sudden falls in blood pressure during postural change. Few studies have investigated whether the measurement of blood flow velocity within vessels can reflect brain perfusion during postural change. By performing carotid duplex ultrasonography (CDU), we investigated changes in cerebral blood flow (CBF) during postural changes in patients with a cervical SCI, determined the correlation of CBF change with presyncopal symptoms, and investigated factors affecting cerebral autoregulation. We reviewed the medical records of 100 patients with a cervical SCI who underwent CDU. The differences between the systolic blood pressure, diastolic blood pressure, and CBF volume in the supine posture and after 5 min at 50° tilt were evaluated. Presyncopal symptoms occurred when the blood flow volume of the internal carotid artery decreased by ≥21% after tilt. In the group that had orthostatic hypotension and severe CBF decrease during tilt, the body mass index and physical and functional scores were lower than in other groups, and the proportion of patients with a severe SCI was high. The higher the SCI severity and the lower the functional score, the higher the possibility of cerebral autoregulation failure. CBF should be assessed by conducting CDU in patients with a high-level SCI.

Cyclophosphamide Induced Posterior Reversible Encephalopathy Syndrome (PRES) in a Patient with Lupus Nephritis

Immunosuppressant agent cyclophosphamide is a therapeutic option for treatment of systemic lupus erythematosus (SLE). Cyclophosphamide use is a predisposing factor to development of posterior reversible encephalopathy syndrome (PRES). PRES is a clinical syndrome of headache, altered mental status, changes in vision and seizures. Precipitating factors for PRES are multifactorial and include cytotoxic medications, changes in blood pressure, metabolic derangements and autoregulatory failure. We report a rare case of cyclophosphamide induced PRES in a patient with SLE. This case highlights the importance of early recognition of this serious adverse effect of cyclophosphamide.

Physiological Responses to In-Bed Cycle Ergometry Treatment in Intensive Care Unit Patients with External Ventricular Drainage.

PurposeEvidence suggests that early physical activity can be accomplished safely in the neurocritical care unit (NCCU); however, many NCCU patients are often maintained in a state of inactivity due to impaired consciousness, sensorimotor deficits, and concerns for intracranial pressure elevation or cerebral hypoperfusion in the setting of autoregulatory failure. Structured in-bed mobility interventions have been proposed to prevent sequelae of complete immobility in such patients, yet the feasibility and safety of these interventions is unknown. We studied neurological and hemodynamic changes before and after cycle ergometry (CE) in a subset of NCCU patients with external ventricular drains (EVDs).MethodsPatients admitted to the NCCU who had an EVD placed for cerebrospinal fluid drainage and intracranial pressure (ICP) monitoring underwent supine CE therapy with passive and active cycling settings. Neurologic status, ICP and hemodynamic parameters were monitored before and after each CE session.ResultsTwenty-seven patients successfully underwent in-bed CE in the NCCU. No clinically significant changes were recorded in neurologic or in physiological parameters before or after CE. There were no device dislodgements or other adverse effects requiring cessation of a CE session.ConclusionThese data suggest that supine CE in a heterogeneous cohort of neurocritical care patients with EVDs is safe and tolerable. Larger prospective studies are needed to determine the efficacy and optimal dose and timing of supine CE in neurocritical care patients.

Amyloid Beta Peptides and Th1 Cytokines Modulate Human Brain Vascular Smooth Muscle Tonic Contractile Capacity In Vitro: Relevance to Alzheimer's Disease?

Alzheimer’s Disease (AD) is a neurodegenerative condition characterized both by the presence of tau protein neurofibrillary tangles and amyloid beta (Aβ) containing extracellular “plaques”. The cleavage of amyloid precursor protein (APP) yields several Aβ peptides. Although Aβ toxicity to neurons has been described extensively, its effects on other components of the neurovasculature such as vascular smooth muscle cells have been less well characterized. AD is now also recognized as a neurovascular disease characterized by cerebral microbleeds and disturbances in autoregulation. AD is also a neuroinflammatory condition in which several proinflammatory cytokines are elevated and may contribute to the intensification of AD severity. Cerebral autoregulation (the mechanism by which brain blood flow is maintained despite changes in perfusion pressure) is extremely tightly controlled in the brain and shows disturbances in AD. The failure of autoregulation in AD may make the brain susceptible to cerebral microbleeds through a reduced capacity to limit blood flow when pressure is increased. Conversely, reduced vasodilation during low flow might could also exacerbate tissue hypoxia. Currently, whether and how Aβ peptides and inflammatory cytokines depress brain smooth muscle cell tonic contraction is not known, but could reveal important targets in the preservation of autoregulation which is disturbed in AD. We used a collagen gel contractility assay to evaluate the influence of Aβ25-35, Aβ1-40 and Aβ1-42 peptides and inflammatory cytokines on the tonic contractility of human brain vascular smooth muscle cells (HBVSMC) as an in vitro model of cerebral autoregulation. We found that 5 and 10 μM Aβ1-42 significantly depressed HBVSM contractility, while Aβ1-40 5–20 μM had no effect on contractility. Conversely, Aβ25-35 (1–50 μM) increased contractility. Interestingly, the inflammatory cytokines TNF-α (20 ng/mL), IL-1β (20 ng/mL) and IFN-γ (1000 U/mL) also depressed HBVSM tonic contractility alone and in combination. These data suggest that both the inflammatory milieu in AD as well as the abundance of Aβ peptides may promote autoregulatory failure and increase brain susceptibility to dysregulated perfusion and microbleeds which are an important and devastating characteristic of AD.

CYTOTOXIC EDEMA IN CHEMOTHERAPY-ASSOCIATED POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME

SESSION TITLE: Medical Student/Resident Critical Care Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Posterior reversible encephalopathy syndrome (PRES) is a clinical radiographic syndrome characterized by seizures, visual disturbances and altered mental status. MRI of the brain exhibits vasogenic edema. Failure of autoregulation of cerebral arteries and disruption of the endothelium of the blood-brain-barrier are the two mechanisms underlying vasogenic edema. PRES has many triggers, including the use of chemotherapeutic agents. We present the case of a patient on treatment with paclitaxel/carboplatin, diagnosed with PRES, with radiographic evidence of both vasogenic and cytotoxic edema. CASE PRESENTATION: A 61-year-old male diagnosed with squamous cell carcinoma of the lung, recently started on Carboplatin and Paclitaxel, presented to the hospital with altered mental status. He was afebrile, blood pressure 117/77 mmHg, pulse 105 and respiratory rate 24. Physical exam revealed an unresponsive male in respiratory distress. Initial CT brain and blood investigations were unremarkable. He was admitted to the ICU and intubated for failure to protect his airway. MRI brain, revealed hyperintensities on T2-weighted and FLAIR imaging with patchy restricted diffusion involving bilateral fronto-parieto-occipital cortex typical of vasogenic edema and PRES. During further workup, he was found to have a left atrial thrombus from tumor invasion. He was started on anticoagulation and loaded with levetiracetam. He was noted to have dense hemiparesis two days later and underwent CT angiography of the brain which confirmed vasogenic with cytotoxic edema and diffusely increased vascularity as a consequence of decreased cerebral autoregulation. He regained consciousness and tolerated extubation, with complete resolution of hemiparesis. Following extubation, he was found to have visual disturbances which resolved and he was discharged with no neurological deficits. DISCUSSION: PRES with both vasogenic and cytotoxic edema is rare. Our patient had a recent MRI brain and PET/CT for tumor staging, which was negative for brain metastasis. There was a lack of evidence supporting an alternative cause for development of cytotoxic edema making PRES the most likely cause. Several studies have reported cytotoxic edema in PRES. In them, endothelial dysfunction seems to cause both vasogenic and cytotoxic edema occurs in PRES, with areas surrounding marked vasogenic edema usually progressing to cytotoxic edema. CONCLUSIONS: There is increasing evidence for development of PRES with several chemotherapy agents like carboplatin/paclitaxel. It may be characterized by vasogenic as well as cytotoxic edema. Cytotoxic edema is probably related to local decreased perfusion and arteriolopathy. Further research is warranted to understand the pathophysiologic mechanisms involved. It is important to recognize symptoms early and have a high clinical suspicion in spite of radiological evidence of cytotoxic edema, as PRES generally has an excellent prognosis with complete resolution. Reference #1: Janjua, T. K., Hassan, M., Afridi, H. K., & Zahid, N. A. (2017). Oxaliplatin-induced posterior reversible encephalopathy syndrome (PRES). BMJ case reports, 2017, bcr2017221571. https://doi.org/10.1136/bcr-2017-221571 Reference #2: Roth, C., & Ferbert, A. (2011). The posterior reversible encephalopathy syndrome: what's certain, what's new?. Practical neurology, 11(3), 136 -144. https://doi.org/10.1136/practneurol-2011-000010 Reference #3: Gao, B., Yu, B. X., Li, R. S., Zhang, G., Xie, H. Z., Liu, F. L., & Lv, C. (2015). Cytotoxic Edema in Posterior Reversible Encephalopathy Syndrome: Correlation of MRI Features with Serum Albumin Levels. AJNR. American journal of neuroradiology, 36(10), 1884 -1889. https://doi.org/10.3174/ajnr.A4379 DISCLOSURES: No relevant relationships by Bilal Bangash, source=Web Response No relevant relationships by Michael Buscher, source=Web Response No relevant relationships by Jay Parekh, source=Web Response No relevant relationships by Prachi Pednekar, source=Web Response No relevant relationships by Pranav Sharma, source=Web Response

Posterior Reversible Encephalopathy Syndrome in COVID-19 Disease: a Case-Report.

Posterior reversible encephalopathy syndrome (PRES) is a clinical syndrome that can include headache, altered consciousness, visual disturbances, and seizures, usually related to autoregulatory cerebral failure and hypertension. The neuroimaging is essential to diagnosis, showing white matter vasogenic edema in posterior areas. We present a case of a 66-year-old woman with severe pneumonia by SARS-CoV-2 who developed a posterior reversible encephalopathy syndrome with a typical clinical and radiological presentation, after being treated with anti-interleukin treatment (anakinra and tocilizumab) following local guidelines. We report a case of posterior reversible encephalopathy syndrome in a patient with COVID-19 disease, possibly related to anti-IL-1 or anti-IL-6, suggesting that anti-interleukin treatments may cause this syndrome, at least in patients with predisposing conditions such as infections and hydroelectrolytic disorders.

The Dynamic Progression of Hyperintensity Ratio as a Marker of Cerebral Autoregulatory Failure in Large Vessel Occlusion Stroke (4728)

The Dynamic Progression of Hyperintensity Ratio as a Marker of Cerebral Autoregulatory Failure in Large Vessel Occlusion Stroke (4728)

Relationship between Measures of Cerebrovascular Reactivity and Intracranial Lesion Progression in Acute Traumatic Brain Injury Patients: A CENTER-TBI Study.

Failure of cerebral autoregulation has been linked to unfavorable outcome after traumatic brain injury (TBI). Preliminary evidence from a small, retrospective, single-center analysis suggests that autoregulatory dysfunction may be associated with traumatic lesion expansion, particularly for pericontusional edema. The goal of this study was to further explore these associations using prospective, multi-center data from the Collaborative European Neurotrauma Effectiveness Research in TBI (CENTER-TBI) and to further explore the relationship between autoregulatory failure, lesion progression, and patient outcome. A total of 88 subjects from the CENTER-TBI High Resolution ICU Sub-Study cohort were included. All patients had an admission computed tomography (CT) scan and early repeat scan available, as well as high-frequency neurophysiological recordings covering the between-scan interval. Using a novel, semiautomated approach at lesion segmentation, we calculated absolute changes in volume of contusion core, pericontusional edema, and extra-axial hemorrhage between the imaging studies. We then evaluated associations between cerebrovascular reactivity metrics and radiological lesion progression using mixed-model regression. Analyses were adjusted for baseline covariates and non-neurophysiological factors associated with lesion growth using multi-variate methods. Impairment in cerebrovascular reactivity was significantly associated with progression of pericontusional edema and, to a lesser degree, intraparenchymal hemorrhage. In contrast, there were no significant associations with extra-axial hemorrhage. The strongest relationships were observed between RAC-based metrics and edema formation. Pulse amplitude index showed weaker, but consistent, associations with contusion growth. Cerebrovascular reactivity metrics remained strongly associated with lesion progression after taking into account contributions from non-neurophysiological factors and mean cerebral perfusion pressure. Total hemorrhagic core and edema volumes on repeat CT were significantly larger in patients who were deceased at 6 months, and the amount of edema was greater in patients with an unfavourable outcome (Glasgow Outcome Scale-Extended 1-4). Our study suggests associations between autoregulatory failure, traumatic edema progression, and poor outcome. This is in keeping with findings from a single-center retrospective analysis, providing multi-center prospective data to support those results.

Relationship Between Measures of Cerebrovascular Reactivity and Intracranial Lesion Progression in Acute TBI Patients: an Exploratory Analysis

BackgroundFailure of cerebral autoregulation and progression of intracranial lesion have both been shown to contribute to poor outcome in patients with acute traumatic brain injury (TBI), but the interplay between the two phenomena has not been investigated. Preliminary evidence leads us to hypothesize that brain tissue adjacent to primary injury foci may be more vulnerable to large fluctuations in blood flow in the absence of intact autoregulatory mechanisms. The goal of this study was therefore to assess the influence of cerebrovascular reactivity measures on radiological lesion expansion in a cohort of patients with acute TBI.MethodsWe conducted a retrospective cohort analysis on 50 TBI patients who had undergone high-frequency multimodal intracranial monitoring and for which at least two brain computed tomography (CT) scans had been performed in the acute phase of injury. We first performed univariate analyses on the full cohort to identify non-neurophysiological factors (i.e., initial lesion volume, timing of scan, coagulopathy) associated with traumatic lesion growth in this population. In a subset analysis of 23 patients who had intracranial recording data covering the period between the initial and repeat CT scan, we then correlated changes in serial volumetric lesion measurements with cerebrovascular reactivity metrics derived from the pressure reactivity index (PRx), pulse amplitude index (PAx), and RAC (correlation coefficient between the pulse amplitude of intracranial pressure and cerebral perfusion pressure). Using multivariate methods, these results were subsequently adjusted for the non-neurophysiological confounders identified in the univariate analyses.ResultsWe observed significant positive linear associations between the degree of cerebrovascular reactivity impairment and progression of pericontusional edema. The strongest correlations were observed between edema progression and the following indices of cerebrovascular reactivity between sequential scans: % time PRx > 0.25 (r = 0.69, p = 0.002) and % time PAx > 0.25 (r = 0.64, p = 0.006). These associations remained significant after adjusting for initial lesion volume and mean cerebral perfusion pressure. In contrast, progression of the hemorrhagic core and extra-axial hemorrhage volume did not appear to be strongly influenced by autoregulatory status.ConclusionsOur preliminary findings suggest a possible link between autoregulatory failure and traumatic edema progression, which warrants re-evaluation in larger-scale prospective studies.

Abstract 12: Cerebrovascular Pressure Reactivity Predicts Outcome in Diffuse Hypoxic-Ischemic Brain Injury

Introduction: Outcome prediction after diffuse hypoxic-ischemic brain injury (HIBI), which most commonly occurs after sudden cardiac arrest, remains fraught with uncertainty. Cerebral autoregulation (CA) normally limits fluctuations in cerebral blood flow through pressure induced changes in cerebral arteriolar diameter. CA is disrupted after brain injury, and the degree of autoregulatory failure correlates with the severity of brain injury. CA measurements may thus enable more accurate outcome prediction after HIBI. Hypothesis: We hypothesized that the degree of impairment in cerebrovascular pressure reactivity, one of the principle mechanisms of CA, correlates with the extent of HIBI and can predict outcome. Methods: Intracranial pressure (ICP) and mean arterial pressure (MAP) were continuously recorded for all subjects. The Pressure Reactivity Index (PRx) was calculated as a moving linear correlation coefficient between ICP and MAP for each 30 sec data epoch. PRx is positive when ICP increases in concert with MAP and implies impaired pressure reactivity. For each subject, both the mean PRx for the entire recording session as well as the proportion of PRx values &gt; 0.2 (previously found to predict poor outcome in TBI) were calculated. Results: We included 22 consecutive patients with HIBI who underwent invasive ICP monitoring in this single center observational study between 02/2016-02/2018. Median age was 41 (range 20-77), 36% (8/22) survived to hospital discharge, and 18% (4/22) had return of consciousness. The median time of ICP monitoring was 101 hr (range 8-381 hr). HIBI was due to cardiac arrest in 19/22 patients and prolonged hypoxia in 3/22. Mean PRx was significantly higher in patients without return of consciousness (0.49 ± 0.05 vs. 0.036 ± 0.032, p = 0.001), as was the proportion of PRx values &gt; 0.2 (0.73 ± 0.037 vs 0.34 ± 0.058, p &lt; 0.001). All patients with return of consciousness had mean PRx &lt; 0.2. Using this cutoff value, PRx had a 94% sensitivity and 100% specificity for predicting death or vegetative state. Conclusions: Continuous pressure reactivity measurements correlate with outcome after HIBI, and may be a useful adjunct for neuroprognostication. Future studies are needed to validate these findings in larger cohorts.