Hypnosis-Assisted Awake Craniotomy for Eloquent Brain Tumors: Advantages and Pitfalls.

BACKGROUND: Awake craniotomy (AC) is recommended for the resection of tumors in eloquent areas. It is traditionally performed under monitored anesthesia care (MAC), which relies on hypnotics and opioids. Hypnosis-assisted AC (HAAC) is an emerging technique that aims to provide psychological support while reducing the need for pharmacological sedation and analgesia. We aimed to compare the characteristics and outcomes of patients who underwent AC under HAAC or MAC. METHODS: We retrospectively analyzed the clinical, anesthetic, surgical, and neuropsychological data of patients who underwent awake surgical resection of eloquent brain tumors under HAAC or MAC. We used Mann-Whitney U tests, Wilcoxon signed-rank tests, and repeated-measures analyses of variance to identify statistically significant differences at the 0.05 level. RESULTS: A total of 22 patients were analyzed, 14 in the HAAC group and 8 in the MAC group. Demographic, radiological, and surgical characteristics as well as postoperative outcomes were similar. Patients in the HAAC group received less remifentanil (p = 0.047) and propofol (p = 0.002), but more dexmedetomidine (p = 0.025). None of them received ketamine as a rescue analgesic. Although patients in the HAAC group experienced higher levels of perioperative pain (p < 0.05), they reported decreasing stress levels (p = 0.04) and greater levels of satisfaction (p = 0.02). CONCLUSION: HAAC is a safe alternative to MAC as it reduces perioperative stress and increases overall satisfaction. Further research is necessary to assess whether hypnosis is clinically beneficial.

The Enhanced Recovery After Surgery protocol for the perioperative management of pituitary neuroendocrine tumors/pituitary adenomas.

OBJECTIVE: Enhanced Recovery After Surgery (ERAS) is a multimodal perioperative care pathway that has radically modified the management of patients in multiple surgical specialties. Until now, no ERAS Society guidelines have been formulated for the management of cranial pathologies. During the process of ERAS certification for their neurosurgical department, the authors formulated an ERAS protocol for the perioperative care of patients with pituitary neuroendocrine tumors (PitNET), along with a compliance checklist to monitor the adherence to it and its feasibility. The authors describe the protocol and checklist and report the results, including a cost-minimization analysis, with the application of the ERAS philosophy. METHODS: The steps that led to the development of this ERAS protocol, including items concerning the preoperative, intraoperative, and postoperative period, are detailed. The authors report their preliminary results through the comparison of the care practice of a historical cohort with a consecutive surgical cohort of patients with PitNET who underwent operation after the implementation of this ERAS protocol. A compliance checklist with key performance indicators was useful to monitor the adherence to the protocol and the changes in the perioperative management. RESULTS: Following the introduction of this ERAS protocol, the authors significantly shortened the duration of the antibiotic therapy (p < 0.00001) and increased the use of mechanical (p < 0.00001) and pharmacological measures to prevent deep venous thrombosis (p = 0.002). The median length of hospital stay was significantly shorter for the ERAS group (p = 0.00014), and there was no increase in readmission rate or postoperative complications. The documentation and data tracking strongly improved in the ERAS cohort and the authors were more attentive in pain evaluation (p = 0.001), postoperative hormonal supplementation (p = 0.001) and early feeding and mobilization (p = 0.0008 and p < 0.00001, respectively). More patients were discharged on day 3 after surgery in the ERAS group (p < 0.00001). The compliance to the whole process increased from 64.2% to 89.5% (p = 0.016), and the compliance per patient was also found to have significantly increased (p < 0.00001). CONCLUSIONS: The introduction of a standardized ERAS protocol for the perioperative management of patients with PitNET allowed the authors to improve the multidisciplinary management of these patients. With the application of simple cost-effective interventions and with the avoidance of unnecessary measures, gains were made in terms of early mobilization and feeding, thereby resulting in a shorter in-hospital stay.

Implementation of the Enhanced Recovery After Surgery (ERAS®) program in neurosurgery.

BACKGROUND: Over the past decade, Enhanced Recovery After Surgery (ERAS®) guidelines have been proven to simplify postoperative care and improve recovery in several surgical disciplines. The authors set out to create and launch an ERAS® program for cranial neurosurgery that meets official ERAS® Society standards. The authors summarize the successive steps taken to achieve this goal in two specific neurosurgical conditions and describe the challenges they faced. METHODS: Pituitary neuroendocrine tumors (Pit-NET) resected by a transsphenoidal approach and craniosynostosis (Cs) repair were selected as appropriate targets for the implementation of ERAS® program in the Department of Neurosurgery. A multidisciplinary team with experience in managing these pathologies was created. A specialized ERAS® nurse coordinator was hired. An ERAS® certification process was performed involving 4 seminars separated by 3 active phases under the supervision of an ERAS® coach. RESULTS: The ERAS® Pit-NET team included 8 active members. The ERAS® Cs team included 12 active members. Through the ERAS® certification process, areas for improvement were identified, local protocols were written, and the ERAS® program was implemented. Patient-centered strategies were developed to increase compliance with the ERAS® protocols. A prospective database was designed for ongoing program evaluation. Certification was achieved in 18 months. Direct costs and time requirements are reported. CONCLUSION: Successful ERAS® certification requires a committed multidisciplinary team, an ERAS® coach, and a dedicated nurse coordinator.

Prolonged Opioid Use and Pain Outcome and Associated Factors after Surgery under General Anesthesia: A Prospective Cohort Association Multicenter Study.

BACKGROUND: There is insufficient prospective evidence regarding the relationship between surgical experience and prolonged opioid use and pain. The authors investigated the association of patient characteristics, surgical procedure, and perioperative anesthetic course with postoperative opioid consumption and pain 3 months postsurgery. The authors hypothesized that patient characteristics and intraoperative factors predict opioid consumption and pain 3 months postsurgery. METHODS: Eleven U.S. and one European institution enrolled patients scheduled for spine, open thoracic, knee, hip, or abdominal surgery, or mastectomy, in this multicenter, prospective observational study. Preoperative and postoperative data were collected using patient surveys and electronic medical records. Intraoperative data were collected from the Multicenter Perioperative Outcomes Group database. The association between postoperative opioid consumption and surgical site pain at 3 months, elicited from a telephone survey conducted at 3 months postoperatively, and demographics, psychosocial scores, pain scores, pain management, and case characteristics, was analyzed. RESULTS: Between September and October 2017, 3,505 surgical procedures met inclusion criteria. A total of 1,093 cases were included; 413 patients were lost to follow-up, leaving 680 (64%) for outcome analysis. Preoperatively, 135 (20%) patients were taking opioids. Three months postsurgery, 96 (14%) patients were taking opioids, including 23 patients (4%) who had not taken opioids preoperatively. A total of 177 patients (27%) reported surgical site pain, including 45 (13%) patients who had not reported pain preoperatively. The adjusted odds ratio for 3-month opioid use was 18.6 (credible interval, 10.3 to 34.5) for patients who had taken opioids preoperatively. The adjusted odds ratio for 3-month surgical site pain was 2.58 (1.45 to 4.4), 4.1 (1.73 to 8.9), and 2.75 (1.39 to 5.0) for patients who had site pain preoperatively, knee replacement, or spine surgery, respectively. CONCLUSIONS: Preoperative opioid use was the strongest predictor of opioid use 3 months postsurgery. None of the other variables showed clinically significant association with opioid use at 3 months after surgery.

Three-Minute Diagnostic Assessment for Delirium using the Confusion Assessment Method (3D-CAM): French translation and cultural adaptation.

PURPOSE: The routine use of validated diagnostic instruments is key to identifying delirious patients early and expediting care. The 3-Minute Diagnostic Assessment for Delirium using the Confusion Assessment Method (3D-CAM) instrument is a brief, easy to use, sensitive, and specific delirium assessment tool for hospitalized patients. We aimed to translate the original English version into French, and then adapt it to older high-risk patients. METHODS: Translation and adaptation of the questionnaire were guided by an expert committee and the 3D-CAM instrument developer. During the translation phase, we achieved semantic and conceptual equivalence of the instrument by conducting forward and backward translations. During the adaptation phase, we assessed the face validity, clarity of wording, and ease of use of the translated questionnaire by administering it to 30 patients and their caregivers in peri-interventional and medical intermediate care units. During both phases, we used qualitative (goal and adequacy of the questionnaire) and quantitative (Sperber score, clarity score) criteria. RESULTS: Translation: four items were judged inadequate and were revised until all reached a Sperber score of < 3/7. Face validity: 91% of patients thought the questionnaire was designed to assess memory, thoughts, or reasoning. Clarity: eight items required adjustments until all scored ≥ 9/10 for clarity. Ease of use: all bedside caregivers reported that the questionnaire was easy to complete after receiving brief instructions. CONCLUSIONS: We produced a culturally adapted French version of the 3D-CAM instrument that is well understood and well-received by older high-risk patients and their caregivers.

RéSUMé: OBJECTIF: L'administration systématique d'instruments diagnostiques validés est essentielle pour identifier précocement les patients confus. Le questionnaire 3D-CAM (3 Minute Diagnostic Confusion Assessment Method) est un outil d'évaluation bref, facile à administrer en milieu hospitalier, sensible et spécifique pour l'état confusionnel. Notre objectif était de le traduire en français, puis de l'adapter à une population de patients âgés à haut risque. MéTHODE: La traduction et l'adaptation ont été guidées par un comité d'experts et le développeur de l'instrument. Nous avons atteint une équivalence sémantique et conceptuelle en menant des traductions antérogrades, puis rétrogrades. Nous avons évalué la validité de contenu, la clarté lexicale, et la facilité d'administration du questionnaire en le soumettant à 30 patients et 30 soignants dans des unités de soins intermédiaires médicaux et péri-interventionnels. Durant les phases de traduction et d'adaptation, nous avons utilisé des critères qualitatifs et quantitatifs. RéSULTATS: Traduction : quatre questions ont été jugées inadéquates et ont été révisées pour atteindre un score de Sperber < 3/7. Validité de contenu : 91% des patients pensaient que le questionnaire était conçu pour évaluer la mémoire, les pensées, ou le raisonnement. Clarté : huit questions ont dû être modifiées pour atteindre un score de clarté ≥ 9/10. Facilité d'administration : tous les soignants pensaient que le questionnaire était facile à utiliser après une brève formation. CONCLUSIONS: Nous avons produit une version française du questionnaire 3D-CAM qui est adaptée aux patients âgés à haut risque et aux soignants en milieu de soins aigus.

Safety of Nitrous Oxide Anesthesia in a Selected Group of Patients Undergoing Neurosurgery: An Exploratory Subgroup Analysis of the ENIGMA Trials.

BACKGROUND: The Evaluation of Nitrous Oxide in the Gas Mixture for Anesthesia (ENIGMA)-I and ENIGMA-II were randomized clinical trials that assessed the safety of nitrous oxide anesthesia in patients undergoing noncardiac surgery. In this study, we performed an exploratory pooled analysis of both ENIGMA trials to assess the safety of nitrous oxide in a selected group of patients undergoing neurosurgery. METHODS: Data from each ENIGMA trial were collated into a single database. Information regarding patient demographics, comorbidities, medication use, anesthesia, surgical procedure, and postoperative complications was extracted. Multivariate logistic regression was conducted for postoperative complications to assess the risk associated with nitrous oxide. RESULTS: A total of 830 patients were included in our analysis: 417 received nitrous oxide anesthesia, and 413 received nitrous oxide-free anesthesia. Baseline patient and perioperative characteristics were comparable. Procedural data were available for 535 patients (64%); of these, 507 (95%) underwent spinal neurosurgery and 28 (5%) underwent cranial neurosurgery. Patients in the nitrous oxide group had lower inspired oxygen concentration (30% vs. 38%; P<0.001) and end-tidal volatile agent concentration (0.56 vs. 0.89 minimal alveolar concentration equivalents; P<0.001) compared with the nitrous oxide-free group. Use of nitrous oxide was not associated with increased risk of postoperative complications (myocardial infarction, cardiac arrest, stroke, infection, severe vomiting, fever, pneumonia, pneumothorax, blood transfusion, venous thromboembolism, or death) (odds ratio: 1.22; 95% confidence interval: 0.89-1.65; P=0.22) or prolonged length of hospital stay (median 5.0 vs. 4.2 d for nitrous oxide and nitrous oxide-free groups; P=0.28). CONCLUSION: Nitrous oxide did not increase the risk of postoperative complications or prolonged length of hospital stay in the neurosurgical cohort enrolled in the ENIGMA-I and ENIGMA-II trials.

Association Between High Deductible Health Plans and Cost-Related Non-adherence to Medications Among Americans with Diabetes: an Observational Study.

BACKGROUND: For people with diabetes, adherence to prescribed medications is essential. However, the rising prevalence of high-deductible health plans (HDHPs), and prices of diabetes medications such as insulin, could deter adherence. OBJECTIVE: To assess the impact of HDHP on cost-related medication non-adherence (CRN) among non-elderly adults with diabetes in the US. DESIGN: Repeated cross-sectional survey. SETTING: National Health Interview Survey, 2011-2018. PARTICIPANTS: A total of 7469 privately insured adults ages 18-64 with diabetes who were prescribed medications and enrolled in a HDHP or a traditional commercial health plan (TCP). MAIN MEASURES: Self-reported measures of CRN were compared between enrollees in HDHPs and TCPs overall and among the subset using insulin. Analyses were adjusted for demographic and clinical characteristics using multivariable linear regression models. KEY RESULTS: HDHP enrollees were more likely than TCP enrollees to not fill a prescription (13.4% vs 9.9%; adjusted percentage point difference (AD) 3.4 [95% CI 1.5 to 5.4]); skip medication doses (11.4% vs 8.5%; AD 2.8 [CI 1.0 to 4.7]); take less medication (11.1% vs 8.8%; AD 2.3 [CI 0.5 to 4.0]); delay filling a prescription to save money (14.4% vs 10.8%; AD 3.0 [CI 1.1 to 4.9]); and to have any form of CRN (20.4% vs 15.5%; AD 4.4 [CI 2.2 to 6.7]). Among those taking insulin, HDHP enrollees were more likely to have any CRN (25.1% vs 18.9%; AD 5.9 [CI 1.1 to 10.8]). CONCLUSION: HDHPs are associated with greater CRN among people with diabetes, particularly those prescribed insulin. For people with diabetes, enrollment in non-HDHPs might reduce CRN to prescribed medications.

Mobile Smartphone Technology Is Associated With Out-of-hospital Cardiac Arrest Survival Improvement: The First Year "Greater Paris Fire Brigade" Experience.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) remains associated with very high mortality. Accelerating the initiation of efficient cardiopulmonary resuscitation (CPR) is widely perceived as key to improving outcomes. The main goal was to determine whether identification and activation of nearby first responders through a smartphone application named Staying Alive (SA) can improve survival following OHCA in a large urban area (Paris). METHODS: We conducted a nonrandomized cohort study of all adults with OHCA managed by the Greater Paris Fire Brigade during 2018, irrespective of mobile application usage. We compared survival data in cases where SA did or did not lead to the activation of nearby first responders. During dispatch, calls for OHCA were managed with or without SA. The intervention group included all cases where nearby first responders were successfully identified by SA and actively contributed to CPR. The control group included all other cases. We compared survival at hospital discharge between the intervention and control groups. We analyzed patient data, CPR metrics, and first responders' characteristics. RESULTS: Approximately 4,107 OHCA cases were recorded in 2018. Among those, 320 patients were in the control group, whereas 46 patients, in the intervention group, received first responder-initiated CPR. After adjustment for confounders, survival at hospital discharge was significantly improved for patients in the intervention group (35% vs. 16%, adjusted odds ratio = 5.9, 95% confidence interval = 2.1 to 16.5, p < 0.001). All CPR metrics were improved in the intervention group. CONCLUSIONS: We report that mobile smartphone technology was associated with OHCA survival through accelerated initiation of efficient CPR by first responders in a large urban area.

Comparison of two simple models for prediction of short term mortality in patients after severe traumatic brain injury.

INTRODUCTION: The subscale motor score of Glasgow Coma Scale (msGCS) and the Abbreviated Injury Score of head region (HAIS) are validated prognostic factors in traumatic brain injury (TBI). The aim was to compare the prognostic performance of a HAIS-based prediction model including HAIS, pupil reactivity and age, and the reference prediction model including msGCS in emergency department (ED), pupil reactivity and age. METHODS: Secondary analysis of a prospective epidemiological study including patients after severe TBI (HAIS > 3) with follow-up from the time of accident until 14 days or earlier death was performed in Switzerland. Performance of prediction, based on accuracy of discrimination [area under the receiver-operating curve (AUROC)], calibration (Hosmer-Lemeshow test) and validity (bootstrapping with 2000 repetitions to correct) for optimism of the two prediction models were investigated. A non-inferiority approach was performed and an a priori threshold for important differences was established. RESULTS: The cohort included 808 patients [median age 56 {inter-quartile range (IQR) 33-71}, median motor part of GCS in ED 1 (1-6), abnormal pupil reactivity 29.0%] with a death rate of 29.7% at 14 days. The accuracy of discrimination was similar (AUROC HAIS-based prediction model: 0.839; AUROC msGCS-based prediction model: 0.826, difference of the 2 AUROC 0.013 (-0.007 to 0.037). A similar calibration was observed (Hosmer-Lemeshow X2 11.64, p = 0.168 vs. Hosmer-Lemeshow X2 8.66, p = 0.372). Internal validity of HAIS-based prediction model was high (optimism corrected AUROC: 0.837). CONCLUSIONS: Performance of prediction for short-term mortality after severe TBI with HAIS-based prediction model was non-inferior to reference prediction model using msGCS as predictor.

Impact of Cognitive Dysfunction on Survival in Patients With and Without Statin Use Following Carotid Endarterectomy.

BACKGROUND: Early cognitive dysfunction (eCD) is a subtle form of neurological injury observed in ∼25% of carotid endarterectomy (CEA) patients. Statin use is associated with a lower incidence of eCD in asymptomatic patients having CEA. OBJECTIVE: To determine whether eCD status is associated with worse long-term survival in patients taking and not taking statins. METHODS: This is a post hoc analysis of a prospective observational study of 585 CEA patients. Patients were evaluated with a battery of neuropsychometric tests before and after surgery. Survival was compared for patients with and without eCD stratifying by statin use. At enrollment, 366 patients were on statins and 219 were not. Survival was assessed by using Kaplan-Meier methods and multivariable Cox proportional hazards models. RESULTS: Age ≥75 years (P = .003), diabetes mellitus (P < .001), cardiac disease (P = .02), and statin use (P = .014) are significantly associated with survival univariately (P < .05) by use of the log-rank test. By Cox proportional hazards model, eCD status and survival adjusting for univariate factors within statin and nonstatin use groups suggested a significant effect by association of eCD on survival within patients not taking statin (hazard ratio, 1.61; 95% confidence interval, 1.09-2.40; P = .018), and no significant effect of eCD on survival within patients taking statin (hazard ratio, 0.98; 95% confidence interval, 0.59-1.66; P = .95). CONCLUSION: eCD is associated with shorter survival in patients not taking statins. This finding validates eCD as an important neurological outcome and suggests that eCD is a surrogate measure for overall health, comorbidity, and vulnerability to neurological insult. ABBREVIATIONS: aHR, adjusted hazards ratiosCEA, carotid endarterectomyCI, confidence intervalDM, diabetes mellituseCD, early cognitive dysfunctionNDI, National Death IndexNLR, neutrophil/lymphocyte ratioSD, standard deviationSEM, standard error of the mean.

Factors that correlate with the decision to delay extubation after multilevel prone spine surgery.

BACKGROUND: Multilevel spinal decompressions and fusions often require long anesthetic and operative times, which may result in airway edema and prolonged postoperative intubation. Delayed extubation can lead to bronchopulmonary infections and other complications. This study analyzed which factors correlated with the decision to delay extubation after multilevel spine surgery. METHODS: We reviewed the records of 289 patients who underwent multilevel spine surgery lasting ≥8 hours in the prone position from 2006 to 2012. Variables hypothesized to affect the decision of the anesthesiologist to delay extubation at the end of the surgery were collected. These included preoperative factors (age, sex, ASA class, history of obstructive sleep apnea, BMI, previous spine surgery, current cervical surgery, anterior in addition to posterior spine surgery, emergency surgery) and intraoperative factors (difficult intubation, number of surgical levels, case time, estimated blood loss, fluid and blood administration, attending handoff and resident handoff, and case end time). We also compared the incidence of pulmonary postoperative complications between patients extubated at the end of the case to patients who had a delayed extubation. RESULTS: A total of 126 patients (44%) were kept intubated after multilevel spine surgery. Multiple linear regression analysis showed factors that correlated with prolonged intubation which included age, ASA class, procedure duration, extent of surgery, total crystalloid volume administered, total blood volume administered, and the case end time. Patients who had a delayed extubation had a 3-fold higher rate of postoperative pneumonia. CONCLUSIONS: Our study found that age, ASA class, procedure duration, extent of surgery, and total crystalloid and blood volume administered correlate with the decision to delay extubation in multilevel prone spine surgery. It also finds that the time the case ends is an independent variable that correlates with the decision not to extubate at the end of a long multilevel spinal surgery. The incidence of postoperative pneumonia is higher in patients who had a delayed extubation after surgery.

Electrophysiological recording in the brain of intact adult zebrafish.

Previously, electrophysiological studies in adult zebrafish have been limited to slice preparations or to eye cup preparations and electrorentinogram recordings. This paper describes how an adult zebrafish can be immobilized, intubated, and used for in vivo electrophysiological experiments, allowing recording of neural activity. Immobilization of the adult requires a mechanism to deliver dissolved oxygen to the gills in lieu of buccal and opercular movement. With our technique, animals are immobilized and perfused with habitat water to fulfill this requirement. A craniotomy is performed under tricaine methanesulfonate (MS-222; tricaine) anesthesia to provide access to the brain. The primary electrode is then positioned within the craniotomy window to record extracellular brain activity. Through the use of a multitube perfusion system, a variety of pharmacological compounds can be administered to the adult fish and any alterations in the neural activity can be observed. The methodology not only allows for observations to be made regarding changes in neurological activity, but it also allows for comparisons to be made between larval and adult zebrafish. This gives researchers the ability to identify the alterations in neurological activity due to the introduction of various compounds at different life stages.

The effect of antihypertensive class on intraoperative pressor requirements during carotid endarterectomy.

BACKGROUND: Certain classes of antihypertensive drugs have been associated with intraoperative hypotension, and frequently, patients are receiving multiple classes of antihypertensive medications. We sought to determine whether one class of antihypertensive medication either alone, or in combination with other classes of antihypertensive medications, increased the probability of intraoperative hypotension, determined by the amount of vasopressor required during carotid endarterectomy (CEA) performed under general anesthesia with specific arterial blood pressure management. METHODS: This is a post hoc analysis of 252 patients scheduled for elective CEA under general anesthesia, all of whom participated in a prospective evaluation of cognitive dysfunction. Patients were characterized by class and number of preoperative antihypertensive medications taken. A predetermined anesthetic regimen was administered to all patients, with a phenylephrine infusion titrated to maintain mean arterial blood pressure at baseline before clamping the carotid artery, and approximately 20% above baseline during clamping. Computerized anesthesia records were used to record hemodynamics and to quantify medication administered intraoperatively. RESULTS: Patients taking diuretics as part of their antihypertensive regimen required significantly more (1.6 times) total intraoperative phenylephrine than those not taking diuretics, independently of the number of other antihypertensive medications. This difference in the phenylephrine requirement occurs only during the preclamp period, i.e., from induction to application of carotid artery clamping for the maintenance of preoperative blood pressure. However, in contrast to this result, there is no difference in pressor requirement comparing classes of antihypertensive medications to increase the mean arterial blood pressure 20% above baseline during the period when the carotid artery is clamped. CONCLUSION: Diuretics are associated with increased vasopressor requirements in patients having a CEA under general anesthesia in the preclamp period, which is likely true for any patient having a general anesthetic.

MMP-9 levels in elderly patients with cognitive dysfunction after carotid surgery.

Approximately 25% of elderly patients scheduled for carotid endarterectomy (CEA) develop post-operative cognitive dysfunction (CD). We tested the hypothesis that the plasma levels of matrix metalloproteinase 9 (MMP-9) are predictive of moderate to severe CD after CEA. A total of 73 patients were prospectively enrolled in this Institutional Review Board-approved study. Plasma samples were obtained at baseline and day 1 post-surgery. We measured the plasma concentrations of both MMP-9 and its inhibitor, tissue inhibitor of metalloproteinases 1 (TIMP-1). We estimated the MMP-9 activity by calculating the MMP-9:TIMP-1 ratio. The cognitive performance day 1 post-surgery was quantified with z-scores, using a control group who were undergoing spinal surgery. The criteria used to define CD was performance of >or=1.5 standard deviations worse than the control group; approximately 19% of eligible patients developed CD. Compared to patients without CD, this group had both higher total (81.66+/-12.25 ng/mL versus [vs.] 43.18+/-4.44 ng/mL, p=0.005) and activity (0.88+/-0.24 ng/mL vs. 0.54+/-0.06 ng/mL, p=0.003) MMP-9 levels at baseline. All of the results were adjusted for age, diabetes and neurovascular symptoms.

Incidence of moderate to severe cognitive dysfunction in patients treated with carotid artery stenting.

OBJECTIVE: Approximately 25% of patients with carotid artery stenosis treated with carotid endarterectomy develop cognitive dysfunction (CD) between 1 day and 1 month after surgery compared with a control group. We hypothesized that patients with carotid artery stenosis treated with carotid artery stenting (CAS) performed under cerebral embolic protection also develop CD at similar time points compared with a control group. METHODS: Twenty-four patients scheduled for elective CAS were enrolled in a prospective institutional review board-approved study to evaluate cognitive function with a battery of 6 neuropsychometric tests before, and 1 day and 1 month after, CAS. Test performance was compared with 23 patients undergoing coronary artery procedures (control group). The mean and standard deviation of the difference scores in the control group were used to generate Z scores. We used a previously described point system to transform negative Z scores into injury points for each neuropsychometric test. Global performance is presented as average deficit score (sum of injury points divided by the number of completed tests). All patients underwent the procedures with mild sedation. Results were analyzed in 2 ways: group-rate and event-rate analysis. Outcome was dichotomized by defining moderate to severe CD as average deficit score at least 1.5 standard deviations worse than the control group. Fisher tests and multivariate logistic regression models were used to analyze group performance. RESULTS: Control patients tended to be younger and had a lower incidence of stroke or previous transient ischemic attack. One day after surgery, 41% of patients (10 of 24) treated with CAS developed moderate to severe CD (P = 0.0422). Average deficit score was also significantly higher in the CAS group at 1 day (P = 0.0265). These differences were independent of age and history of stroke/transient ischemic attack. Interestingly, we found that the absence of oral statin medication may increase the probability of CD. By 1 month, 9% of patients (1 of 11) treated with CAS presented with CD. Other patients were lost to follow-up. CONCLUSION: CAS is associated with a decline in cognitive performance that is at least moderate 1 day after surgery.

Inducible nitric oxide synthase promoter polymorphism affords protection against cognitive dysfunction after carotid endarterectomy.

BACKGROUND AND PURPOSE: Cognitive dysfunction occurs in 9% to 23% of patients during the first month after carotid endarterectomy (CEA). A 4-basepair (AAAT) tandem repeat polymorphism (either 3 or 4 repeats) has been described in the promoter region of inducible nitric oxide synthase (iNOS), a gene with complex roles in ischemic injury and preconditioning against ischemic injury. We investigated whether the 4-repeat variant (iNOS(+)) affects the incidence of cognitive dysfunction after CEA. METHODS: One-hundred eighty-five CEA and 60 spine surgery (control) subjects were included in this nested cohort analysis. Subjects underwent a battery of 7 neuropsychometric tests before and 1 day and 1 month after surgery. Multivariate logistic regression analyses were performed to determine if the iNOS promoter variant was independently associated with the incidence of cognitive dysfunction at 1 day and 1 month. Further, all right-hand-dominant CEA subjects were grouped by operative side and performance on each test was compared between iNOS(+) and iNOS(-) groups. RESULTS: Forty-four of 185 CEA subjects had at least 1 iNOS promoter allele containing 4 copies of the tandem repeat (iNOS(+)). iNOS(+) status was significantly protective against moderate/severe cognitive dysfunction 1 month after CEA. Right-hand-dominant iNOS(+) CEA subjects undergoing left-side CEA performed significantly better than iNOS(-) subjects on a verbal learning test and those undergoing right-side CEA performed significantly better on a test of visuospatial function. CONCLUSIONS: We demonstrate an iNOS promoter polymorphism variant provides protection against moderate/severe cognitive dysfunction 1 month after CEA. Further, this protection appears to involve cognitive domains localized ipsilateral to the operative carotid artery.

Neurocognitive performance in hypertensive patients after spine surgery.

BACKGROUND: Cognitive dysfunction is fairly common after noncardiac surgery and may be related to intraoperative blood pressure management. The authors present an analysis of risk factors for cognitive deterioration after spine surgery in older patients, with particular emphasis on intraoperative blood pressure in normotensive and hypertensive patients. METHODS: This is a post hoc cohort analysis of 45 patients enrolled before undergoing lumbar laminectomy or microdiscectomy. The patients underwent a battery of 5 neuropsychometric tests preoperatively, and 1 day and 1 month postoperatively. Computerized anesthesia records were used to obtain intraoperative mean arterial pressure (MAP) data. Simple linear regressions between intraoperative MAP and postoperative cognitive performance were performed, and multivariate linear regression models of postoperative cognitive performance were constructed to analyze potential risk factors for cognitive decline after surgery. RESULTS: Twenty-one normotensive patients (mean age, 62.4 yr) and 24 hypertensive patients (mean age, 67.9 yr) were included in this analysis. There was a significant positive relationship between minimum intraoperative MAP values and 1-day cognitive performance by simple linear regression in hypertensive (P = 0.003), but not normotensive, patients. In multivariate linear regression analysis of cognitive performance, there was a significant interaction between hypertension and minimum intraoperative MAP at 1 day and 1 month. CONCLUSIONS: In hypertensive patients, there was a significant relationship between minimum intraoperative MAP and decline in cognitive function 1 day and 1 month after surgery. A prospective controlled trial of intraoperative blood pressure control, especially during induction of anesthesia when MAP values typically drop, is needed to confirm these findings.

Intravascular ultrasound of symptomatic intracranial stenosis demonstrates atherosclerotic plaque with intraplaque hemorrhage: a case report.

BACKGROUND: Intracranial artery stenosis is assumed to represent atherosclerotic plaque. Catheter cerebral arteriography shows that intracranial stenosis may progress, regress, or remain unchanged. It is counterintuitive that atherosclerotic plaque should spontaneously regress, raising questions about the composition of intracranial stenoses. Little is known about this disease entity in vivo. We provide the first demonstration of in vivo atherosclerotic plaque with intraplaque hemorrhage using intravascular ultrasound (IVUS). CASE DESCRIPTION: A 35-year-old man with multiple vascular risk factors presented with recurrent stroke failing medical therapy. Imaging demonstrated left internal carotid artery occlusion, severe intracranial right internal carotid artery stenosis, and cerebral perfusion failure. Cerebral arteriography with IVUS confirmed 85% stenosis of the petrous right carotid artery due to atherosclerotic plaque with intraplaque hemorrhage. Intracranial stent-supported angioplasty was performed with IRB approval. The patient recovered without complication. CONCLUSIONS: This case supports the premise that symptomatic intracranial stenosis can be caused by atherosclerotic plaque complicated by intraplaque hemorrhage similar to coronary artery plaque. IVUS provides additional characteristics that define intracranial atherosclerosis and high-risk features. To our knowledge, this is the first report of stroke due to unstable atherosclerotic plaque with intraplaque hemorrhage in vivo.

Inducing chaos by resonant perturbations: theory and experiment.

We propose a scheme to induce chaos in nonlinear oscillators that either are by themselves incapable of exhibiting chaos or are far away from parameter regions of chaotic behaviors. Our idea is to make use of small, judiciously chosen perturbations in the form of weak periodic signals with time-varying frequency and phase, and to drive the system into a hierarchy of nonlinear resonant states and eventually into chaos. We demonstrate this method by using numerical examples and a laboratory experiment with a Duffing type of electronic circuit driven by a phase-locked loop. The phase-locked loop can track the instantaneous frequency and phase of the Duffing circuit and deliver resonant perturbations to generate robust chaos.