Cerebral Autoregulation-Based Blood Pressure Management In The Neuroscience Intensive Care Unit: Towards Individualizing Care In Ischemic Stroke And Subarachnoid Hemorrhage

The purpose of this thesis is to review the concept of cerebral autoregulation, to establish the feasibility of continuous bedside monitoring of autoregulation, and to examine the impact of impaired autoregulation on functional and clinical outcomes following subarachnoid hemorrhage and ischemic stroke. Autoregulation plays a key role in the regulation of brain blood flow and has been shown to fail in acute brain injury. Disturbed autoregulation may lead to secondary brain injury as well as worse outcomes. Furthermore, there exist several methodologies, both invasive and non-invasive, for the continuous assessment of autoregulation in individual patients. Resultant autoregulatory parameters of brain blood flow can be harnessed to derive optimal cerebral perfusion pressures, which may be targeted to achieve better outcomes. Multiple studies in adults and several in children have highlighted the feasibility of individualizing mean arterial pressure in this fashion. The thesis herein argues for the high degree of translatability of this personalized approach within the neuroscience intensive care unit, while underscoring the clinical import of autoregulation monitoring in critical care patients. In particular, this document recapitulates findings from two separate, prospectively enrolled patient groups with subarachnoid hemorrhage and ischemic stroke, elucidating how deviation from dynamic and personalized blood pressure targets associates with worse outcome in each cohort. While definitive clinical benefits remain elusive (pending randomized controlled trials), autoregulation-guided blood pressure parameters wield great potential for constructing an ideal physiologic environment for the injured brain. The first portion of this thesis discusses basic autoregulatory physiology as well as various tools to interrogate the brain’s pressure reactivity at the bedside. It then reviews the development of the optimal cerebral perfusion pressure as a biological hemodynamic construct. The second chapter pertains to the clinical applications of bedside neuromonitoring in patients with aneurysmal subarachnoid hemorrhage. In this section, the personalized approach to blood pressure monitoring is discussed in greater detail. Finally, in the third chapter, a similar autoregulation-oriented blood pressure algorithm is applied to a larger cohort of patients with ischemic stroke. This section contends that our novel, individualized strategy to hemodynamic management in stroke patients represents a better alternative to the currently endorsed practice of maintaining systolic blood pressures below fixed and static thresholds

The Role of Estrogen (Estradiol and Estrone) on the Development of Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage

Delayed cerebral ischemia (DCI) is a significant complication following aneurysmal subarachnoid hemorrhage (aSAH). Recent evidence has suggested that biochemical mediators alter cerebral perfusion resulting in neurological decline. Estrogens (estrone–E1 and estradiol–E2) are mediators with demonstrated neuroprotective properties that could be implicated in DCI. The impact of E1 or E2 on outcomes in humans following aSAH has been understudied. The purpose of this study was to examine the association between E1 and E2 levels and DCI following aSAH. Plasma and cerebral spinal fluid (CSF) samples collected after hemorrhage on 99 acute, adult aSAH patients admitted to the Neurovascular ICU enrolled in a NIH funded study-RO1NR004339. Three plasma and up to 5 CSF samples were selected for E1 and E2 analysis from each patient representing early(1–4), middle(4-6) and late(7-10) days after hemorrhage and were assayed using liquid chromatography-tandem mass spectrometry. DCI was operationalized as radiographic/ultrasonic evidence of impaired cerebral blood flow accompanied by neurological deterioration. Statistical analysis included detailed descriptive, group based trajectory and multiple logistic regression using SAS v9.2. Group based trajectory identified 2 groups over time for both plasma E1 (61.4% E1-high and 38.6% E1-low) and E2 (48% E2-high and 52% E2-low) values using censored normal model. Weighted Chi Square analysis identified differences between trajectory groups by gender(p=.02), menopause(.05), age(p<.001) and fisher grade(p=.008) with patients in the high E1 group having higher severity of injury than those in the low E1 group. Likewise, patients with higher HH (E1 p=.01, E2 p=.02) and Fisher (E1 p=.008, E2 p=.08) were more likely to have higher plasma estrogen levels. The presence of DCI was also significantly associated with higher levels of plasma E1(p=.002) and E2(p=.03) and the high E1 trajectory group(p=.09). CSF was evaluated in 36 aSAH patients. Similar correlations between higher E1 and E2 CSF concentrations and severity of injury and DCI were noted. These results provide the first clinical evidence that E1 and E2 concentrations in plasma and CSF are associated with severity of injury and DCI and provide incentive for future studies to clarify the potential role of estrogen in ischemic complications after aSAH

Stent-assisted reconstructive endovascular repair of intracranial aneurysms: long-term clinical and angiographic follow-up

Abstract Background and Purpose: The development of self-expanding stents dedicated to intracranial use has significantly widened the applicability of endovascular therapy to many intracranial aneurysms. The purpose of this study was to report the angiographic and clinical outcomes of wide-necked intracranial aneurysms treated with stent. Methods: Between January 2007 and October 2011 we deployed 22 stents in 20 patients with wide-necked cerebral aneurysms. Inclusion criteria restricted the group to adult patients with wide-necked intracranial aneurysms (ruptured and unruptured lesions). Immediate post-procedural angiographic studies were performed to evaluate successful occlusion of the aneurysm as well as patency of the parent vessel. We assessed long term angiography follow-up to detect in-stent stenosis, progressive thrombosis, recurrence and need for retreatment. Clinical outcome was assessed with the modifing Ranking Scale (mRS). Results: Technical success was obtained in all 22 (100%) cases. Angiography immediately after treatment procedure showed complete occlusion in 7 aneurysms (35%), neck remnant in 11 (55%), incomplete occlusion in 1 (5%) and partial occlusion in 1 (5%). During the endovascular embolization procedure no rupture of the sac or bleeding complication occurred; none of the patients needed undergoing surgical crossover. Procedure-related adverse events occurred in one (5%) patient: a brachial artery pseudoaneurysm. Three (15%) patients had neurological complications after procedure, whose 1 (5%) transitory complication spontaneusly resolved. Two patients (10%), had acute complete in-stent thrombosis which resolved after intraarterial administration of abciximab and placement of a new stent in-stent. Of the 20 patients treated with stent deployment, a follow-up imaging study was available in all 19 surviving patients (95%) at an average of 16.2 months (range, 6 to 50 months). The first follow-up DSA, compared with initial angiography, showed no changes in 14 aneurysms (73.7%), progressive thrombosis in 3 (15.7%), and major recurrence in 2 (10.5%). The overall rate of succesful procedure to 6 months is 89.5%; there was 1 case of asintomatic moderate endothelial hyperplasia. The further follow-up imaging study, showed no changes in 17 (89.5%) of the 19 surviving patients, 1 progressive thrombosis and 1 minor recurrence. One month- and long term (average of 16.2 months; range, 6 to 50 months) clinical follow-up showed no worsening in the mRS in 18 (90%) of 20 patients, 1 (5%) mRS 2 and 1 (5%) mRS 6. All the survived patients are alive and we did not observe periprocedural or long-term intracranial bleeding events or symptomatic stent related stenosis/occlusion complication. Conclusions: Our findings suggest that the endovascular treatment of intracranial aneurysms by stenting is feasible, effective and safe; follow-up results proved intact parent arteries and stable occlusion rates in the majority of treated aneurysms. Nevertheless, long-term data on safety and efficacy and larger patient groups are necessary

Evidence that a Panel of Neurodegeneration Biomarkers Predicts Vasospasm, Infarction, and Outcome in Aneurysmal Subarachnoid Hemorrhage

Biomarkers for neurodegeneration could be early prognostic measures of brain damage and dysfunction in aneurysmal subarachnoid hemorrhage (aSAH) with clinical and medical applications. Recently, we developed a new panel of neurodegeneration biomarkers, and report here on their relationships with pathophysiological complications and outcomes following severe aSAH. Fourteen patients provided serial cerebrospinal fluid samples for up to 10 days and were evaluated by ultrasonography, angiography, magnetic resonance imaging, and clinical examination. Functional outcomes were assessed at hospital discharge and 6–9 months thereafter. Eight biomarkers for acute brain damage were quantified: calpain-derived α-spectrin N- and C-terminal fragments (CCSntf and CCSctf), hypophosphorylated neurofilament H

Aneurysmal Subarachnoid Hemorrhage

Aneurysmal subarachnoid hemorrhage (SAH) is a devastating neurological syndrome, which occurs at a rate of 3–25 per 100,000 population. Smoking and hypertension are the most important risk factors of subarachnoid hemorrhage. Rupture of cerebral aneurysm leads to rapid spread of blood into cerebrospinal fluid and subsequently leads to sudden increase of intracranial pressure and severe headache. Subarachnoid hemorrhage is associated with neurological (such as re‐bleeding and vasospasm) and systemic (such as myocardial injury and hyponatremia) complications that are causes of high mortality and morbidity. Although patients with poor‐grade subarachnoid hemorrhage are at higher risk of neurological and systemic complications, the early and aggressive management of this group of patient has decreased overall mortality by 17% in last 40 years. Early aneurysm repair, close monitoring in dedicated neurological intensive care unit, prevention, and aggressive management of medical and neurological complications are the most important strategies to improve outcome

Imaging Predictors of Outcome in Acute Spontaneous Subarachnoid Hemorrhage: a Review of the Literature

Spontaneous subarachnoid hemorrhage (SAH) accounts for about 5% of strokes, but has a very high morbidity and mortality. Many survivors are left with important cognitive impairment and are severely incapacitated. Prediction of complications such as vasospasm and delayed cerebral ischemia, and of clinical outcome after SAH, is challenging. Imaging studies are essential in the initial evaluation of SAH patients and are increasingly relevant in assessing for complications and prognosis. In this article, we reviewed the role of imaging studies in evaluating early brain injury and predicting complications as well as clinical and neuropsychological prognosis after acute SAH.info:eu-repo/semantics/publishedVersio