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Background: Optimal pharmacologic thromboprophylaxis dosing is not well described in patients with subarachnoid hemorrhage (SAH) with an external ventricular drain (EVD). Our patients with SAH with an EVD who receive prophylactic enoxaparin are routinely monitored using timed anti-Xa levels. Our primary study goal was to determine the frequency of venous thromboembolism (VTE) and secondary intracranial hemorrhage (ICH) for this population of patients who received pharmacologic prophylaxis with enoxaparin or unfractionated heparin (UFH)., Methods: A retrospective chart review was performed for all patients with SAH admitted to the neurocritical care unit at Emory University Hospital between 2012 and 2017. All patients with SAH who required an EVD were included., Results: Of 1,351 patients screened, 868 required an EVD. Of these 868 patients, 627 received enoxaparin, 114 received UFH, and 127 did not receive pharmacologic prophylaxis. VTE occurred in 7.5% of patients in the enoxaparin group, 4.4% in the UFH group (p = 0.32), and 3.2% in the no VTE prophylaxis group (p = 0.08). Secondary ICH occurred in 3.83% of patients in the enoxaparin group, 3.51% in the UFH group (p = 1), and 3.94% in the no VTE prophylaxis group (p = 0.53). As steady-state anti-Xa levels increased from 0.1 units/mL to > 0.3 units/mL, there was a trend toward a lower incidence of VTE. However, no correlation was noted between rising anti-Xa levels and an increased incidence of secondary ICH. When compared, neither enoxaparin nor UFH use was associated with a significantly reduced incidence of VTE or an increased incidence of ICH., Conclusions: In this retrospective study of patients with nontraumatic SAH with an EVD who received enoxaparin or UFH VTE prophylaxis or no VTE prophylaxis, there was no statistically significant difference in the incidence of VTE or secondary ICH. For patients receiving prophylactic enoxaparin, achieving higher steady-state target anti-Xa levels may be associated with a lower incidence of VTE without increasing the risk of secondary ICH., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background: Infectious intracranial aneurysms (IIAs) are rare complications of infective endocarditis (IE). Data on management and long-term outcomes remain limited., Objective: To retrospectively study long-term outcomes of IIAs in patients treated medically or surgically., Methods: Adult cases of IE and/or IIAs admitted to Emory or Grady Healthcare Systems between May 2015 and May 2020 were reviewed for demographic, clinical, and radiographic variables for up to 2 years. Primary outcome measure was 2-year survival., Results: Among 1714 cases of IE, intracerebral hemorrhage occurred in 322 patients and IIAs in 17 patients. The presence of IIAs in IE was associated with higher odds of disposition to hospice/death (odds ratio = 6.9). Including non-IE patients, 24 patients had 38 IIAs mainly involving the distal middle cerebral artery and 16 were ruptured on admission. IIAs were predominantly treated with antibiotics as the primary approach. Open microsurgery was the primary approach for 5 aneurysms and was used as salvage in 7 IIAs. Endovascular management was the primary approach for 2 IIAs and used as salvage for 5 IIAs with antibiotic failure. Medical management had high rate of treatment failure (15/31) which predominantly occurred within 2 weeks of onset. The 2-year survival in this cohort was 70% (17/24)., Conclusion: IIAs are rare complications of IE with a poor prognosis. Patients treated with antibiotics have higher risk of treatment failure requiring salvage surgical or endovascular intervention. Medical treatment failure occurred mostly within 2 weeks of onset and had a negative prognostic value emphasizing the need for close follow-up and early surgical or endovascular management., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Objective: Cerebral vasospasm and delayed cerebral ischemia (DCI) contribute to poor outcome following subarachnoid hemorrhage (SAH). With the paucity of effective treatments, the authors describe their experience with intrathecal (IT) nicardipine for this indication., Methods: Patients admitted to the Emory University Hospital neuroscience ICU between 2012 and 2017 with nontraumatic SAH, either aneurysmal or idiopathic, were included in the analysis. Using a propensity-score model, this patient cohort was compared to patients in the Subarachnoid Hemorrhage International Trialists (SAHIT) repository who did not receive IT nicardipine. The primary outcome was DCI. Secondary outcomes were long-term functional outcome and adverse events., Results: The analysis included 1351 patients, 422 of whom were diagnosed with cerebral vasospasm and treated with IT nicardipine. When compared with patients with no vasospasm (n = 859), the treated group was significantly younger (mean age 51.1 ± 12.4 years vs 56.7 ± 14.1 years, p < 0.001), had a higher World Federation of Neurosurgical Societies score and modified Fisher grade, and were more likely to undergo clipping of the ruptured aneurysm as compared to endovascular treatment (30.3% vs 11.3%, p < 0.001). Treatment with IT nicardipine decreased the daily mean transcranial Doppler velocities in 77.3% of the treated patients. When compared to patients not receiving IT nicardipine, treatment was not associated with an increased rate of bacterial ventriculitis (3.1% vs 2.7%, p > 0.1), yet higher rates of ventriculoperitoneal shunting were noted (19.9% vs 8.8%, p < 0.01). In a propensity score comparison to the SAHIT database, the odds ratio (OR) to develop DCI with IT nicardipine treatment was 0.61 (95% confidence interval [CI] 0.44-0.84), and the OR to have a favorable functional outcome (modified Rankin Scale score ≤ 2) was 2.17 (95% CI 1.61-2.91)., Conclusions: IT nicardipine was associated with improved outcome and reduced DCI compared with propensity-matched controls. There was an increased need for permanent CSF diversion but no other safety issues. These data should be considered when selecting medications and treatments to study in future randomized controlled clinical trials for SAH.

Background: Patients who present to the hospital for infectious complications of intravenous opioid use are at high risk for against-medical-advice discharge and readmissions. The role of medication-assisted treatment for inpatients is not clear. We aimed to assess outcomes prior to and after rollout of an inpatient buprenorphine-based opioid use disorder protocol, as well as to assess outcomes in general for medication-assisted therapy., Methods: This was a retrospective observational cohort study at our community hospital in New Hampshire. The medical record was searched for inpatients with a complication of intravenous opioid use. We searched for admissions 11 months prior to and after the November 2018 buprenorphine protocol rollout., Results: Rates of medication-assisted therapy usage and buprenorphine linkage increased significantly after protocol rollout. Rates of against-medical-advice discharge did not decrease after protocol rollout, nor did readmissions. However, when evaluating the entire group of patients regardless of date of presentation or protocol use, against-medical-advice discharge rates were substantially lower for patients receiving medication-assisted therapy compared with those receiving supportive care only (30.0% vs 59.6%). Readmissions rates were lower for patients who were discharged with any form of ongoing medication-assisted therapy compared with those who were not (30-day all-cause readmissions 18.8% vs 35.1%; 30-day opioid-related readmissions 10.1% vs 29.9%; 90-day all-cause readmissions 27.3% vs 42.7%; 90-day opioid-related readmissions 15.1% vs 33.3%)., Conclusions: There is a strong association between medication-assisted therapy and reduced against-medical-advice discharge rates. Additionally, maintenance medication-assisted therapy at time of discharge is strongly associated with reduced readmissions rates., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Critically ill aneurysmal subarachnoid hemorrhage (aSAH) patients suffer from systemic complications at a high rate. Hyperglycemia is a common intensive care unit (ICU) complication and has become a focus after aggressive glucose management was associated with improved ICU outcomes. Subsequent research has suggested that glucose variability, not a specific blood glucose range, may be a more appropriate clinical target. Glucose variability is highly correlated to poor outcomes in a wide spectrum of critically ill patients. Here, we investigate the changes between subsequent glucose values termed "inter-measurement difference," as an indicator of glucose variability and its association with outcomes in patients with aSAH., Methods: All SAH admissions to a single, tertiary referral center between 2002 and 2016 were screened. All aneurysmal cases who had more than 2 glucose measurements were included (n = 2451). We calculated several measures of variability, including simple variance, the average consecutive absolute change, average absolute change by time difference, within subject variance, median absolute deviation, and average or median consecutive absolute percentage change. Predictor variables also included admission Hunt and Hess grade, age, gender, cardiovascular risk factors, and surgical treatment. In-patient mortality was the main outcome measure., Results: In a multiple regression analysis, nearly all forms of glucose variability calculations were found to be correlated with in-patient mortality. The consecutive absolute percentage change, however, was most predictive: OR 5.2 [1.4-19.8, CI 95%] for percentage change and 8.8 [1.8-43.6] for median change, when controlling for the defined predictors. Survival to ICU discharge was associated with lower glucose variability (consecutive absolute percentage change 17% ± 9%) compared with the group that did not survive to discharge (20% ± 15%, p < 0.01). Interestingly, this finding was not significant in patients with pre-admission poorly controlled diabetes as indicated by HbA1c (OR 0.45 [0.04-7.18], by percentage change). The effect is driven mostly by non-diabetic patients or those with well-controlled diabetes., Conclusions: Reduced glucose variability is highly correlated with in-patient survival and long-term mortality in aSAH patients. This finding was observed in the non-diabetic and well-controlled diabetic patients, suggesting a possible benefit for personalized glucose targets based on baseline HbA1c and minimizing variability. The inter-measure percentage change as an indicator of glucose variability is not only predictive of outcome, but is an easy-to-use tool that could be implemented in future clinical trials.

In response to comments raised, we acknowledge the shortcomings of our study. It is a small study. However, it is a pilot study, which is not meant to create generalizable data, rather to explore new potential directions. To this end, our conclusions were clearly supported by the results. We demonstrated that administration of 16.4% NaCl/Na-acetate solution was feasible, safe, and was associated with lower rates of AKI. We share the call that large RCTs are required to follow this pilot study and hope that our data will stimulate the ongoing discussion regarding the role of chloride in AKI mechanism., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Background: Recent reports have demonstrated that among patients with subarachnoid hemorrhage (SAH) treated with hypertonic NaCl, resultant hyperchloremia has been associated with the development of acute kidney injury (AKI). We report a trial comparing the effect of two hypertonic solutions with different chloride contents on the resultant serum chloride concentrations in SAH patients, with a primary outcome aimed at limiting chloride elevation., Methods: A low ChloridE hyperTonic solution for brain Edema (ACETatE) trial is a single-center, double-blinded, double-dummy, randomized pilot trial comparing bolus infusions of 23.4% NaCl and 16.4% NaCl/Na-acetate for the treatment of cerebral edema in patients with SAH. Randomization occurred when patients developed hyperchloremia (serum Cl - ≥ 109 mmol/L) and required hyperosmolar treatment., Results: We enrolled 59 patients, of which 32 developed hyperchloremia and required hyperosmolar treatment. 15 patients were randomized to the 23.4% NaCl group, and 17 patients were randomized to the 16.4% NaCl/Na-acetate group. Although serum chloride levels increased similarly in both groups, the NaCl/Acetate group showed a significantly lower Cl - load at the end of the study period (978mEq vs. 2,464mEq, p < 0.01). Secondary outcome analysis revealed a reduced rate of AKI in the Na-acetate group (53.3% in the NaCl group vs. 11.8% in the Na-acetate group, p = 0.01). Both solutions had similar effects on ICP reduction, but NaCl/Acetate treatment had a more prominent effect on immediate post-infusion Na + concentrations (increase of 2.2 ± 2.8 vs. 1.4 ± 2.6, ( p < 0.01)). Proximal tubule renal biomarkers differed in concentration between the two groups., Conclusions: Our pilot trial showed the feasibility and safety of replacing 23.4% NaCl infusions with 16.4% NaCl/Na-acetate infusions to treat cerebral edema in patients with SAH. The degree of hyperchloremia was similar in the two groups. 16.4% NaCl/Na-acetate infusions led to lower Cl - load and AKI rates than 23.4% NaCl infusions. Further multi-center studies are needed to corroborate these results., Trial Registration: clinicaltrials.gov # NCT03204955, registered on 6/28/2017., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Background: Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening condition that results from a ruptured cerebral vessel. Cerebral edema and vasospasm are common complications and frequently require treatment with hypertonic solutions, in particular hypertonic sodium chloride (NaCl). We have previously shown that hyperchloremia in patients with aSAH given hypertonic NaCl is associated with the development of acute kidney injury (AKI), which leads to higher morbidity and mortality. Our current trial aims to study the effect of two hypertonic solutions with different chloride content on serum chloride concentrations in patients with aSAH who are at risk for AKI., Methods: A low ChloridE hyperTonic solution for brain Edema (ACETatE) is a single center, double-blinded, double-dummy pilot trial comparing bolus doses of 23.4% NaCl and 16.4% NaCl/Na-Acetate for the treatment of cerebral edema in patients with aSAH. All patients will be enrolled within 36 h following admission. Randomization will occur once patients who receive hypertonic treatment for cerebral edema develop hyperchloremia (serum Cl - concentration ≥ 109 mmol/L). Subsequent treatment will consist of either NaCl 23.4% or NaCl/Na-Acetate 16.4%. The primary outcome of this study will be the change in serum Cl - concentrations during treatment. Secondary outcomes will include incidence of AKI, mortality, changes in intracranial pressure, and extent of hypernatremia., Discussion: In patients with aSAH, hyperchloremia is a known risk factor for subsequent development of AKI. The primary goal of this pilot study is to determine the effect of two hypertonic solutions with different Cl - content on serum Cl - concentrations in patients with aSAH who have already developed hyperchloremia. Data will be collected prospectively to determine the extent to which the choice of hypertonic saline solution affects subsequent serum Cl - concentrations and the occurrence of AKI. This approach will allow us to obtain preliminary data to design a large randomized trial assessing the effects of chloride-sparing hypertonic solutions on development of AKI in patients with SAH. This pilot study is the first to prospectively evaluate the relationship between hypertonic solution chloride content and its effect on serum electrolytes and renal function in aSAH patients at risk of AKI due to hyperchloremia., Trial Registration: Clinicaltrials.gov, NCT03204955 . Registered on 28 June 2017.

Subarachnoid hemorrhage (SAH) is a neurological emergency because it may lead to sudden neurological decline and death and, depending on the cause, has treatment options that can return a patient to normal. Because there are interventions that can be life-saving in the first few hours after onset, SAH was chosen as an Emergency Neurological Life Support (ENLS) protocol.

Subarachnoid hemorrhage (SAH) is a neurological emergency because it may lead to sudden neurological decline and death and, depending on the cause, has treatment options that can return a patient to normal. Because there are interventions that can be life-saving in the first hour of onset, SAH was chosen as an Emergency Neurological Life Support protocol.

Objective: This comparative study of two adult neuro critical care units examined the impact of patient- and family-centered design on nurse-family interactions in a unit designed to increase family involvement., Background: A growing evidence base suggests that the built environment can facilitate the delivery of patient- and family-centered care (PFCC). However, few studies examine how the PFCC model impacts the delivery of care, specifically the role of design in nurse-family interactions in the adult intensive care unit (ICU) from the perspective of the bedside nurse., Methods: Two neuro ICUs with the same patient population and staff, but with different layouts, were compared. Structured observations were conducted to assess changes in the frequency, location, and content of interactions between the two units. Discussions with staff provided additional insights into nurse attitudes, perceptions, and experiences caring for families., Results: Nurses reported challenges balancing the needs of many stakeholders in a complex clinical environment, regardless of unit layout. However, differences in communication patterns between the clinician- and family-centered units were observed. More interactions were observed in nurse workstations in the PFCC unit, with most initiated by family. While the new unit was seen as more conducive to the delivery of PFCC, some nurses reported a loss of workspace control., Conclusions: Patient- and family-centered design created new spatial and temporal opportunities for nurse-family interactions in the adult ICU, thus supporting PFCC goals. However, greater exposure to unplanned family encounters may increase nurse stress without adequate spatial and organizational support., (© The Author(s) 2015.)

Background: Severe subarachnoid hemorrhage may be associated with regional wall motion abnormalities (RWMA) in the absence of epicardial coronary occlusion. The RWMA extends beyond the distribution of a single coronary artery and may present in a typical tako-tsubo cardiomyopathy pattern. Other variants have also been recognized, including an inverted tako-tsubo pattern of severe basal hypokinesis that spares the apex. The mechanism of this cardiomyopathy is not well understood but likely involves catecholamine excess. While classic tako-tsubo cardiomyopathy from emotional stress carries a favorable prognosis, cardiac dysfunction from subarachnoid hemorrhage is a marker of overall poor prognosis., Methods: We collected cases over a period of 4 years at a large teaching hospital. The cases represent cardiac dysfunction in the setting of subarachnoid hemorrhage in the unusual distribution of basal hypokinesis with relative sparing of the apex (inverted tako-tsubo pattern)., Results: A total of four cases were identified. All cases were female between the ages 43-67 years and had echocardiographic evidence of basal hypokinesis after suffering from an intracranial hemorrhage., Conclusions: The typical and inverted patterns may represent a spectrum within the same disease process or distinct clinical entities with dramatically different prognostic implications. Larger studies comparing the two presentations will help elucidate this further.

Subarachnoid hemorrhage (SAH) is a neurological emergency because it may lead to sudden neurological decline and death and, depending on the cause, has treatment options that can return a patient to normal. Because there are interventions that can be life-saving in the first hour of onset, SAH was chosen as an Emergency Neurological Life Support protocol.

The Uniform Determination of Death Act indicates that "an individual who has sustained either (1) irreversible cessation of circulatory and respiratory functions, or (2) irreversible cessation of all functions of the entire brain, including the brain stem, is dead," with brain death being determined based on "accepted medical standards." The AAN has published practice guidelines providing medical standards for the determination of brain death. The most recent AAN guideline update notes that "because of the deficiencies in the evidence base, clinicians must exercise considerable judgment when applying the criteria in specific circumstances" and that "ancillary tests can be used when uncertainty exists about the reliability of parts of the neurologic examination or when the apnea test cannot be performed. This article presents two cases commonly encountered in clinical practice in which the findings of the guideline-specified clinical neurologic assessment may be difficult to interpret, hampering the clinical determination of brain death. In these circumstances, ancillary testing specifically assessing for cerebral circulatory arrest may be helpful.

Intensive care units (ICUs) have important but challenging sound environments. Alarms and equipment generate high levels of noise and ICUs are typically designed with hard surfaces. A poor sound environment can add to stress and make auditory tasks more difficult for clinicians. However few studies have linked more detailed analyses of the sound environment to nurse wellbeing and performance. This study is aimed at understanding the relationships between objective acoustic measures and self-reported nurse outcomes. Two 20-bed ICUs with similar patient acuity and treatment models were tested: A recently built neurological ICU and a 1980s-era medical-surgical ICU. The medical-surgical ICU was perceived as louder, more annoying, and having a greater negative impact of noise on work performance, health outcomes, and anxiety as compared to the neurological ICU. Surprisingly, there were little differences between two ICU sound environments based on traditional overall noise measures. The objective differences between the occupied sound environments in the two units only emerged through a more comprehensive analysis of the "occurrence rate" of peak and maximum levels, frequency content, and the speech interference level. Furthermore, mid-level transient sound occurrence rates were significantly and positively correlated to perceived annoyance and loudness levels., (© 2011 Acoustical Society of America)

The management of the acute ischemic stroke patient spans the time course from the emergency evaluation and treatment period through to the eventual discharge planning phase of stroke care. In this article we evaluate the literature and describe what have become standard treatments in the care of the stroke patient. We will review the literature that supports the use of a dedicated stroke unit for routine stroke care which has demonstrated reduced rates of morbidity and mortality. Also reviewed is the use of glycemic control in the initial setting along with data supporting the use of prophylactic treatments options in order to aide in the prevention of life threatening medical complications. In addition, lifesaving treatments will be discussed in light of new literature demonstrating reduced mortality in large hemispheric stroke patients undergoing surgical decompressive surgery. Both medical and surgical treatment options are discussed and compared.

Background: Intensivist staffing of intensive care units (ICUs) has been associated with a reduction in in-hospital mortality. These improvements in patient outcomes have been extended to neurointensivist staffing of neuroscience ICUs for patients with intracranial hemorrhage and traumatic brain injury., Objective: The primary objective of this study is to determine if hospital outcomes (measured by discharge status) for patients admitted with aneurysmal subarachnoid hemorrhage changed after the introduction of a neurointensivist-led multidisciplinary neurocritical care team., Methods: The authors retrospectively identified 703 patients admitted to the neuroscience ICU with a diagnosis of aneurysmal subarachnoid hemorrhage at a single academic tertiary care hospital between January 1, 1995 and December 31, 2002. It was compared with discharge outcomes for those patients treated prior to and following the development of a multidisciplinary neurocritical care team., Results: Patients treated after the introduction of a neurocritical care team were significantly more likely to be discharged to home (25.2% vs. 36.5%) and less likely to be discharged to a rehab facility (25.2% vs. 36.5%). Patients treated after introduction of a neurocritical care team were also more likely to receive definitive aneurysm treatment (10.9% vs. 18%)., Conclusion: The implementation of a neurointensivist-led neurocritical care team is associated with improved hospital discharge disposition for patients with aneurysmal subarachnoid hemorrhage.

Background: Cerebral arterial vasospasm and delayed ischemic neurological deficits are significant contributors to morbidity and mortality following aneurysmal subarachnoid hemorrhage. Additional treatment modalities are needed. Intraventricular nicardipine has been suggested as a potential therapy for the treatment of cerebral vasospasm. It is an appealing option for multiple reasons: many of these patients already have ventricular drains in place, it can be safely administered at the bedside, and can be used in patients for whom conventional therapies are either not effective or not tolerated., Methods: Retrospective case series of all patients who received intraventricular nicardipine for the treatment of cerebral vasospasm from January 2006 to June 2007 at a university tertiary care hospital., Results: Sixty-four patients received intraventricular nicardipine during the study period. Forty-two patients met inclusion criteria. Intraventricular nicardipine administration was associated with a reduction of the mean cerebral blood flow velocity of 26.3 cm/s in the middle cerebral artery and 7.4 cm/s in the anterior cerebral artery. This reduction was maintained over 24 h with continued administration., Conclusions: Intraventricular nicardipine was associated with a significant and sustained reduction in mean cerebral blood flow velocity as measured by transcranial Doppler when used in the treatment of suspected cerebral vasospasm following aneurysmal subarachnoid hemorrhage. We do not find significant safety concerns related to elevations of intracranial pressure or ventricular catheter related infections. Further prospective studies are warranted to better determine the efficacy and safety of this therapy.

Emory University Hospital recently converted its neurocritical care unit into an environment that enhances involvement of the patient's family. Each patient room now has an adjacent family area with comfortable accommodations for daytime and nighttime use. The new unit design, which drew from evidence on the impact of the physical environment on patient outcomes, facilitates better interactions between families and the medical team, and early studies show that patient satisfaction and staff satisfaction have increased. This article describes the impetus for and process of the unit redesign, as well as initial results and lessons learned.

We describe four cases in which abciximab was used as a thrombolytic rescue agent in the setting of thrombotic events complicating interventional neuroradiologic procedures. After IV administration of abciximab, the thrombus resolved within 30 min in three cases, whereas no thrombolysis occurred in the fourth case despite the addition of intraarterial tissue plasminogen activator. Further evaluation of glycoprotein IIb-IIIa inhibitors in patients with cerebral thromboembolic events is necessary to prove clinical efficacy.

Occlusion of an internal carotid artery stent was identified immediately post placement in a patient who had restenosis after prior angioplasty. An IV dose of abciximab was administered, and serial angiograms were performed. This resulted in partial resolution of the thrombus at 10 minutes and complete resolution at 20 minutes.

Background and Purpose: Atherosclerosis of the major intracranial arteries is an important cause of ischemic stroke. We established measurement criteria to assess percent stenosis of a major intracranial artery (carotid, middle cerebral, vertebral, basilar) and determined the interobserver/intraobserver agreements and interclass/intraclass correlations of these measurements., Methods: We defined percent stenosis of an intracranial artery as follows: percent stenosis = [(1 - (D(stenosis)/D(normal)))] x 100, where D(stenosis) = the diameter of the artery at the site of the most severe stenosis and D(normal) = the diameter of the proximal normal artery. If the proximal segment was diseased, contingency sites were chosen to measure D(normal): distal artery (second choice), feeding artery (third choice). Using a hand-held digital caliper, three neuroradiologists independently measured D(stenosis) and D(normal) of 24 stenotic intracranial arteries. Each observer repeated the readings 4 weeks later. We determined how frequently two observers' measurements of percent stenosis of each of the 24 diseased arteries differed by 10% or less., Results: Among the three pairs of observers, interobserver agreements were 88% (observer 1 versus observer 2), 79% (observer 1 versus observer 3), 75% (observer 2 versus observer 3) for the first reading and were 75% (observer 1 versus observer 2), 100% (observer 1 versus observer 3), and 71% (observer 2 versus observer 3) for the second reading. Intraobserver agreement for each of the observers was 88%, 83%, and 100%. Interclass correlation was 85% (first reading) and 87% (second reading). Intraclass correlation was 92% (first and second readings combined)., Conclusion: This method shows good interobserver and intraobserver agreements for the measurement of intracranial stenosis of a major artery. If validated in subsequent studies, this method may serve as a standard for the measurement of percent stenosis of an intracranial artery.

The present experiments examined the role of the serotonergic system in the learned helplessness phenomenon. In Experiment 1, a 200 mg/kg dose of 1-tryptophan injected 30 min prior to testing disrupted acquisition of Fixed Ratio 2 shuttle escape behavior. In Experiment 2, a 100 mg/kg dose of 5-HTP produced interference with the acquisition of the escape response. Furthermore, this interference was prevented by treatment with the serotonergic antagonist methysergide. In Experiment 3, animals were pretreated with a subeffective dose of 1-tryptophan in combination with subeffective exposure to inescapable shock. These animals showed a deficit in the acquisition of FR-2 shuttle escape. In Experiment 4, combined exposure to a subeffective dose of 5-HTP and inescapable shock (40 trials) resulted in an acquisition deficit. This deficit was reversed by methysergide. Experiment 5 showed that the detrimental effects of exposure to prolonged (80 trials) of inescapable shock can be prevented by treatment with methysergide. These studies implicate the serotonergic system as a possible mediator of the learned helplessness phenomenon.