Influence of angiotensin II receptor subtypes of the paraventricular nucleus on the physiological responses induced by angiotensin II injection into the medial septal area

Objective - We determined the effects of losartan and PD 123319 (antagonists of the AT1 and AT2 angiotensin receptors, respectively), and [Sar1, Ala8] ANG II (a relatively peptide antagonist of angiotensin receptors) injected into the paraventricular nucleus (PVN) on water and 3% NaCl intake, and the diuretic, natriuretic, and pressor effects induced by administration of angiotensin II (ANG II) into the medial septal area (MSA) of conscious rats. Methods - Holtzman rats were used. Animals were anesthetized with tribromoethanol (20 mg) per 100 grams of body weight, ip. A stainless steel guide cannula was implanted into the MSA and PVN. All drugs were injected in 0.5-μl volumes for 10-15 seconds. Seven days after brain surgery, water and 3% NaCl intake, urine and sodium excretion, and arterial blood pressure were measured. Results - Losartan (40 nmol) and [Sar1, Ala8] ANG II (40 nmol) completely eliminated whereas PD 123319 (40 nmol) partially blocked the increase in water and sodium intake and the increase in arterial blood pressure induced by ANG II (10 nmol) injected into the MSA. The PVN administration of PD 123319 and [Sar1, Ala8] ANG II blocked whereas losartan attenuated the diuresis and natriuresis induced by MSA administration of ANG II. Conclusion - MSA involvement with PVN on water and sodium homeostasis and arterial pressure modulation utilizing ANGII receptors is suggested.

Whole-body computerized tomography and concomitant spine and head injuries A study of 355 cases

The authors present a prospective study on the coexistence of spinal injury (SI) and severe traumatic brain injury (TBI) in patients who were involved in traffic accidents and arrived at the Emergency Department of Hospital das Clinicas of the University of Sao Paulo between September 1, 2003 and December 31, 2009. A whole-body computed tomography was the diagnostic method employed in all cases. Both lesions were observed simultaneously in 69 cases (19.4%), predominantly in males (57 individuals, 82.6%). Cranial injuries included epidural hematoma, acute subdural hematoma, brain contusion, ventricular hemorrhage and traumatic subarachnoid hemorrhage. The transverse processes were the most fragile portion of the vertebrae and were more susceptible to fractures. The seventh cervical vertebra was the most commonly affected segment, with 24 cases (34.78%). The distribution of fractures was similar among the other cervical vertebrae, the first four thoracic vertebrae and the lumbar spine. Neurological deficit secondary to SI was detected in eight individuals (11.59%) and two individuals (2.89%) died. Traumatic subarachnoid hemorrhage was the most common intracranial finding (82.6%). Spinal surgery was necessary in 24 patients (34.78%) and brain surgery in 18 (26%). Four patients (5.79%) underwent cranial and spinal surgeries. The authors conclude that it is necessary a judicious assessment of the entire spine of individuals who presented in coma after suffering a brain injury associated to multisystemic trauma and whole-body CT scan may play a major role in this scenario.

An anatomical analysis of the mini-modified orbitozygomatic and supra-orbital approaches

Seven sides of cadaver heads were used to compare the surgical exposures provided by the mini-modified orbitozygomatic (MOz) and supra-orbital (SO) approaches. The Optotrak 3020 computerized tracking system (Northern Digital, Waterloo, ON, Canada) was utilized to evaluate the area of anatomical exposure defined by six points: (1) ipsilateral sphenoid ridge; (2) most distal point of the ipsilateral middle cerebral artery (MCA); (3) most distal point of the ipsilateral posterior cerebral artery (PCA); (4) most distal point of the contralateral PCA; (5) most distal point of the contralateral MCA; and (6) contralateral sphenoid ridge. Additionally, angles of approach for the ipsilateral MCA bifurcation, ipsilateral ICA bifurcation, basilar artery tip, contralateral MCA and ICA bifurcation and anterior communicating artery (AcomA) were evaluated, first for SO and then for MOz. An image guidance system was used to evaluate the limits of surgical exposure. No differences in the area of surgical exposure were noted (p > 0.05). Vertical angles were significantly wider for the ipsilateral and contralateral ICA bifurcation, AcomA, contralateral MCA and basilar tip (p < 0.05) for MOz. No differences in horizontal angles were observed between the approaches for the six targets (p > 0.05). There were no differences in the limits of exposure. MOz affords no additional surgical working space. However, our results demonstrate systematically that vertical exposure is improved. The MOz should be performed while planning an approach to these regions and a wider exposure in the vertical axis is needed. (C) 2012 Elsevier Ltd. All rights reserved.

Addresses and other papers,

The early history of practical anatomy.--The history of the Philadelphia school of anatomy and its relation to medical teaching.--Our recent debts to vivisection.--Recent progress in surgery.--The new era in medicine and its demands upon the profession and the college.--The real rewards of medicine.--Medicine as a career for educated men.--Vivisection and brain surgery.--Medical education.--The advantages of an academic training for a medical career.--Literary methods in medicine.--Address at the unveiling of the statue of the late Prof. Samuel D. Gross, M.D.--Semicentennial address in surgery before the American medical association.--The debt of the public to the medical profession.--The endowment of medical colleges.--The ideal physician.--Address at the Royal college of surgeons of England at the conferring of honorary degrees at the centenary celebration of the granting of its present charter.--The progress of surgery in the nineteenth century.--The mission of a medical college.--The duties and responsibilities of trustees of public medical institutions.--The qualities essential to success in medicine.--The cheerfulness of death.--The need for increased endowments for medical instruction.--Age and youth in medicine.--Surgical reminiscences of the civil war.

Physiological Responses to Brain Stimulation During Limbic Surgery: Further Evidence of Anterior Cingulate Modulation of Autonomic Arousal

Background: In view of conflicting neuroimaging results regarding autonomic-specific activity within the anterior cingulate cortex (ACC), we investigated autonomic responses to direct brain stimulation during sterecitactic limbic surgery. Methods: Skin conductance activity and accelerative heart rate responses to multi-voltage stimulation of the ACC (n = 7) and paralimbic subcauclate (n = 5) regions were recorded during bilateral anterior cingulotomy and bilateral subcauclate tractotomy (in patients that had previously received an adequate lesion in the ACC), respectively. Results: Stimulations in both groups were accompanied by increased autonomic arousal. Skin conductance activity was significantly increased during ACC stimulations compared with paralimbic targets at 2 V (2.34 +/- .68 [score in microSiemens +/- SE] vs. .34 +/- .09, p = .013) and 3 V (3.52 +/- .86 vs. 1.12 +/- .37, p = .036), exhibiting a strong ""voltage-response"" relationship between stimulus magnitude and response amplitude (difference from 1 to 3 V = 1.15 +/- .90 vs. 3.52 +/- .86, p = .041). Heart rate response was less indicative of between-group differences. Conclusions: This is the first study of its kind aiming at seeking novel insights into the mechanisms responsible for central autonomic modulation. It supports a concept that interregional interactions account for the coordination of autonomic arousal.

Role of surgery in the management of brain arteriovenous malformations: prospective cohort study.

BACKGROUND AND PURPOSE: Management of brain arteriovenous malformation (bAVM) is controversial. We have analyzed the largest surgical bAVM cohort for outcome. METHODS: Both operated and nonoperated cases were included for analysis. A total of 779 patients with bAVMs were consecutively enrolled between 1989 and 2014. Initial management recommendations were recorded before commencement of treatment. Surgical outcome was prospectively recorded and outcomes assigned at the last follow-up visit using modified Rankin Scale. First, a sensitivity analyses was performed to select a subset of the entire cohort for which the results of surgery could be generalized. Second, from this subset, variables were analyzed for risk of deficit or near miss (intraoperative hemorrhage requiring blood transfusion of ≥2.5 L, hemorrhage in resection bed requiring reoperation, and hemorrhage associated with either digital subtraction angiography or embolization). RESULTS: A total of 7.7% of patients with Spetzler-Ponce classes A and B bAVM had an adverse outcome from surgery leading to a modified Rankin Scale >1. Sensitivity analyses that demonstrated outcome results were not subject to selection bias for Spetzler-Ponce classes A and B bAVMs. Risk factors for adverse outcomes from surgery for these bAVMs include size, presence of deep venous drainage, and eloquent location. Preoperative embolization did not affect the risk of perioperative hemorrhage. CONCLUSIONS: Most of the ruptured and unruptured low and middle-grade bAVMs (Spetzler-Ponce A and B) can be surgically treated with a low risk of permanent morbidity and a high likelihood of preventing future hemorrhage. Our results do not apply to Spetzler-Ponce C bAVMs.

The effect of the N-methyl-D-aspartate receptor antagonist dextromethorphan on perioperative brain injury in children undergoing cardiac surgery with cardiopulmonary bypass: results of a pilot study.

Experimental evidence indicates a role of the N-methyl-D-aspartate receptor in the pathogenesis of brain injury occurring during cardiac surgery with cardiopulmonary bypass (CPB). Dextromethorphan is a noncompetitive antagonist of this receptor with a favorable safety profile. Thirteen children age 3-36 months undergoing cardiac surgery with expected CPB of 60 minutes or more were randomly assigned to treatment with dextromethorphan (36-38 mg/kg/day) or placebo administered by naso-gastric tube. Dextromethorphan was absorbed well and reached putative therapeutic levels in blood and cerebrospinal fluid. Adverse effects were not observed. Mild hemiparesis developed after operation in one child of each group, and severe encephalopathy in one of the placebo group. Sharp waves were recorded in postoperative continuous electroencephalography in all placebo (n = 7) but only in 2/6 dextromethorphan treated children (p = 0.02). Pre- and postoperative cranial magnetic resonance imaging (MRI) revealed less pronounced ventricular enlargement in the dextromethorphan group (not significant). An increase of periventricular white matter lesions was visible in two placebo-treated children only. No elevations of cerebrospinal fluid enzymes were observed in either group. Although children with dextromethorphan showed less abnormalities in electroencephalography and MRI, dissimilarities of the treatment groups by chance diminished conclusions to possible protective effects of dextromethorphan at this time.

Serum and CSF levels of neuron-specific enolase (NSE) in cardiac surgery with cardiopulmonary bypass: a marker of brain injury?

We investigated whether neuron-specific enolase (NSE) in serum or cerebrospinal fluid (CSF) reflects subtle or manifest brain injury in children undergoing cardiac surgery using cardiopulmonary bypass (CPB). NSE was measured in serum (s-NSE) before, and up to, 102 h after surgery in 27 children undergoing cardiac surgery with CPB. In 11 children, CSF-NSE was also measured 48 or 66 h post-surgery. As erythrocytes contain NSE, hemoglobin concentration in the samples was determined spectrophotometrically at 550 nm (cut-off limit: absorbance 0.4 = 560 mg/l) in 14 children and in a further 13 children by spectroscopic multicomponent analysis (cut-off limit 5 micromol/l = 80 mg/l). One hundred and one of 214 post-operative serum samples (47%) had to be discarded because of hemolysis (18% spectrophotometrically at 550 nm and 88% with spectroscopic multicomponent analysis). On the first and second post-operative day, the median s-NSE values were significantly higher when compared with samples taken after 54 h or longer (P = 0.008 and P = 0.002). All CSF-NSE levels were within the normal range and below the s-NSE measured in the same patient. Although in our study elevated s-NSE seems to indicate brain injury in CPB-surgery, the low concentration of NSE in the post-operative CSF of 11 children puts the neuronal origin of s-NSE in question. NSE from other non-neuronal tissues probably contributes to the elevated s-NSE. Additionally, normal post-operative CSF-NSE values in two children with post-operative neurological sequelae might question the predictive value of CSF-NSE with regard to brain injury.

Role of surgery in the management of brain arteriovenous malformations: prospective cohort study.

BACKGROUND AND PURPOSE: Management of brain arteriovenous malformation (bAVM) is controversial. We have analyzed the largest surgical bAVM cohort for outcome. METHODS: Both operated and nonoperated cases were included for analysis. A total of 779 patients with bAVMs were consecutively enrolled between 1989 and 2014. Initial management recommendations were recorded before commencement of treatment. Surgical outcome was prospectively recorded and outcomes assigned at the last follow-up visit using modified Rankin Scale. First, a sensitivity analyses was performed to select a subset of the entire cohort for which the results of surgery could be generalized. Second, from this subset, variables were analyzed for risk of deficit or near miss (intraoperative hemorrhage requiring blood transfusion of ≥2.5 L, hemorrhage in resection bed requiring reoperation, and hemorrhage associated with either digital subtraction angiography or embolization). RESULTS: A total of 7.7% of patients with Spetzler-Ponce classes A and B bAVM had an adverse outcome from surgery leading to a modified Rankin Scale >1. Sensitivity analyses that demonstrated outcome results were not subject to selection bias for Spetzler-Ponce classes A and B bAVMs. Risk factors for adverse outcomes from surgery for these bAVMs include size, presence of deep venous drainage, and eloquent location. Preoperative embolization did not affect the risk of perioperative hemorrhage. CONCLUSIONS: Most of the ruptured and unruptured low and middle-grade bAVMs (Spetzler-Ponce A and B) can be surgically treated with a low risk of permanent morbidity and a high likelihood of preventing future hemorrhage. Our results do not apply to Spetzler-Ponce C bAVMs.

Manual reaction times and brain dynamics after 'awake surgery' of slow-growing tumors invading the parietal area. A case report

Primary objectives: Awake surgeries of slow-growing tumours invading the brain and guided by direct electrical stimulation induce major brain reorganizations accompanied with slight impairments post-operatively. In most cases, these deficits are so slight after a few days that they are often not detectable on classical neuropsychological evaluations. Consequently, this study investigated whether simple visuo-manual reaction time paradigms would sign some level of functional asymmetries between both hemispheres. Importantly, the visual stimulus was located in the saggital plane in order to limit attentional biases and to focus mainly on the inter-hemispheric asymmetry. Methods and procedures: Three patients (aged 41, 59 and 59 years) after resections in parietal regions and a control group (age¼44, SD¼6.9) were compared during simple uni- and bimanual reaction times (RTs). Main outcomes and results: Longer RTs were observed for the contralesional compared to the ipsilesional hand in the unimanual condition. This asymmetry was reversed for the bimanual condition despite longer RTs. Conclusion and clinical implications: Reaction time paradigms are useful in these patients to monitor more precisely their functional deficits, especially their level of functional asymmetry, and to understand brain (re)organization following slowgrowing lesions.

Surgery for unruptured arteriovenous malformations of the brain is better than conservative management for selected cases : a prospective cohort study

Object. The aim of this study was to identify patients who are likely to benefit from surgery for unruptured brain arterriovenous malformations (ubAVMs). Methods. The authors' database was interrogated for the risk and outcome of hemorrhage after referral and the out- come from surgery. Furthermore, the outcome from surgery incorporated those cases excluded from surgery because of perceived greater risk (sensitivity analysis). Finally, a comparison was made for the authors' patients between the natural history and surgery. Data were collected for 427 consecutively enrolled patients with ubAVMs in a database that in- cluded patients who were conservatively managed. Kaplan-Meier analysis was performed on patients observed for more than 1 day to determine the risk of hemorrhage. Variables that may influence the risk of first hemorrhage were assessed using Cox proportional hazard regression models and Kaplan-Meier life table analyses from referral until the first occur- rence of the following: hemorrhage, treatment, or last review. The outcome from surgery (leading to a new permanent neurological deficit with last review modified Rankin Scale [mRS] score > 1) was determined. Further sensitivity analy- sis was made to predict risk from surgery for the total ubAVM cohort by incorporating outcomes of surgical cases as well as cases excluded from surgery because of perceived risk, and assuming an adverse outcome for these excluded cases. Results. A total of 377 patients with a ubAVM were included in the analysis of the risk of hemorrhage. The 5-year risk of hemorrhage for ubAVM was 11.5%. Hemorrhage resulted in an mRS score > 1 in 14 cases (88% [95% CI 63%-98%]). Patients with Spetzler-Ponce Class A ubAVMs treated by surgery (n = 190) had a risk from surgery of 1.6% (95% CI 0.3%-4.8%) for a permanent neurological deficit leading to an mRS score > 1 and 0.5% (95% CI< 0.1%-3.2%) for a permanent neurological deficit leading to an mRS score > 2. Patients with Spetzler-Ponce Class B ubAVMs treated by surgery (n = 107) had a risk from surgery of 14.0% (95% CI 8.6%-22.0%) for a permanent neurological deficit leading to an mRS score > 1. Sensitivity analysis of Spetzler-Ponce Class B ubAVMs, including those in patients excluded from surgery, showed that the true risk for surgically eligible patients may have been as high as 15.6% (95% CI 9.9%-23.7%) for mRS score > 1, had all patients who were perceived to have a greater risk experienced an adverse outcome. Patients with Spetzler-Ponce Class C ubAVMs treated by surgery (n = 44) had a risk from surgery of 38.6% (95% CI 25.7%-53.4%) for a permanent neurological deficit leading to an mRS score >1. Sensitivity analysis of Class C ubAVMs, including those harbored by patients excluded from surgery, showed that the true risk for surgically eligible patients may have been as high as 60.9% (95% CI 49.2%-71.5%) for mRS score > 1, had all patients who were perceived to have a greater risk experienced an adverse outcome. Conclusion. Surgical outcomes for Spetzler-Ponce Class ubAVMs are better than those for conservative management.

Gamma Knife Surgery versus Linac for Brain Metastasis: Which Technique for Which Patient? Analysis of an Historical Cohort of 63 Consecutive Patients Harboring 130 Lesions

Objectives: We present the retrospective analysis of a single-institution experience for radiosurgery (RS) in brain metastasis (BM) with Gamma Knife (GK) and Linac. Methods: From July 2010 to July 2012, 28 patients (with 83 lesions) had RS with GK and 35 patients (with 47 lesions) with Linac. The primary outcome was the local progression-free survival (LPFS). The secondary outcome was the overall survival (OS). Apart a standard statistical analysis, we included a Cox regression model with shared frailty, to modulate the within-patient correlation (preliminary evaluation showed a significant frailty effect, meaning that the correlation within patient could be ignored). Results: The mean follow-up period was 11.7 months (median 7.9, 1.7-22.7) for GK and 18.1 (median 17, 7.5-28.7) for Linac. The median number of lesions per patient was 2.5 (1-9) in GK compared with 1 (1-3) in Linac. There were more radioresistant lesions (melanoma) and more lesions located in functional areas for the GK group. The median dose was 24 Gy (GK) compared with 20 Gy (Linac). The LPFS actuarial rate was as follows: for GK at 3, 6, 9, 12, and 17 months: 96.96, 96.96, 96.96, 88.1, and 81.5%, and remained stable till 32 months; for Linac at 3, 6, 12, 17, 24, and 33 months, it was 91.5, 91.5, 91.5, 79.9, 55.5, and 17.1%, respectively (p = 0.03, chi-square test). After the Cox regression analysis with shared frailty, the p-value was not statistically significant between groups. The median overall survival was 9.7 months for GK and 23.6 months for Linac group. Uni- and multivariate analysis showed a lower GPA score and noncontrolled systemic status were associated with lower OS. Cox regression analysis adjusting for these two parameters showed comparable OS rate. Conclusions: In this comparative report between GK and Linac, preliminary analysis showed that more difficult cases are treated by GK, with patients harboring more lesions, radioresistant tumors, and highly functional located. The groups look, in this sense, very heterogeneous at baseline. After a Cox frailty model, the LPFS rates seemed very similar (p < 0.05). The OS was similar, after adjusting for systemic status and GPA score (p < 0.05). The technical reasons for choosing GK instead of Linac were the anatomical location related to highly functional areas, histology, technical limitations of Linac movements, especially lower posterior fossa locations, or closeness of multiple lesions to highly functional areas optimal dosimetry with Linac