Ultrasound-tagged near-infrared spectroscopy does not disclose absent cerebral circulation in brain-dead adults.

BACKGROUND: Near-infrared spectroscopy, a non-invasive technique for monitoring cerebral oxygenation, is widely used, but its accuracy is questioned because of the possibility of extra-cranial contamination. Ultrasound-tagged near-infrared spectroscopy (UT-NIRS) has been proposed as an improvement over previous methods. We investigated UT-NIRS in healthy volunteers and in brain-dead patients. METHODS: We studied 20 healthy volunteers and 20 brain-dead patients with two UT-NIRS devices, CerOx™ and c-FLOW™ (Ornim Medical, Kfar Saba, Israel), which measure cerebral flow index (CFI), a parameter related to changes in cerebral blood flow (CBF). Monitoring started after the patients had been declared brain dead for a median of 34 (range: 11-300) min. In 11 cases, we obtained further demonstration of absent CBF. RESULTS: In healthy volunteers, CFI was markedly different in the two hemispheres in the same subject, with wide variability amongst subjects. In brain-dead patients (median age: 64 yr old, 45% female; 20% traumatic brain injury, 40% subarachnoid haemorrhage, and 40% intracranial haemorrhage), the median (inter-quartile range) CFI was 41 (36-47), significantly higher than in volunteers (33; 27-36). CONCLUSIONS: In brain-dead patients, where CBF is absent, the UT-NIRS findings can indicate an apparently perfused brain. This might reflect an insufficient separation of signals from extra-cranial structures from a genuine appraisal of cerebral perfusion. For non-invasive assessment of CBF-related parameters, the near-infrared spectroscopy still needs substantial improvement.

A Novel Cooling Device for Targeted Brain Temperature Control and Therapeutic Hypothermia: Feasibility Study in an Animal Model.

BACKGROUND: Therapeutic hypothermia (i.e., temperature management) is an effective option for improving survival and neurological outcome after cardiac arrest and is potentially useful for the care of the critically ill neurological patient. We analyzed the feasibility of a device to control the temperature of the brain by controlling the temperature of the blood flowing through the neck. METHODS: A lumped parameter dynamic model, with one-dimensional heat transfer, was used to predict cooling effects and to test experimental hypotheses. The cooling system consisted of a flexible collar and was tested on 4 adult sheep, in which brain and body temperatures were invasively monitored for the duration of the experiment. RESULTS: Model-based simulations predicted a lowering of the temperature of the brain and the body following the onset of cooling, with a rate of 0.4 °C/h for the brain and 0.2 °C/h for the body. The experimental findings showed comparable cooling rates in the two body compartments, with temperature reductions of 0.6 (0.2) °C/h for the brain and 0.6 (0.2) °C/h for the body. For a 70 kg adult human subject, we predict a temperature reduction of 0.64 °C/h for the brain and 0.43 °C/h for the body. CONCLUSIONS: This work demonstrates the feasibility of using a non-invasive method to induce brain hypothermia using a portable collar. This device demonstrated an optimal safety profile and represents a potentially useful method for the administration of mild hypothermia and temperature control (i.e., treatment of hyperpyrexia) in cardiac arrest and critically ill neurologic patients.

My paper 20 years later: cerebral venous oxygen saturation studied with bilateral samples in the internal jugular veins.

INTRODUCTION: Jugular oxygen saturation monitoring was introduced in neurointensive care after severe traumatic brain injury (TBI) to explore the adequacy of brain perfusion and guide therapeutic interventions. The brain was considered homogeneous, and oxygen saturation was taken as representative of the whole organ. We investigated whether venous outflow from the brain was homogeneous by measuring oxygen saturation simultaneously from the two jugular veins. METHODS: In 32 comatose TBI patients both internal jugular veins (IJs) were simultaneously explored using intermittent samples; hemoglobin saturation was also recorded continuously by fiber-optic catheters in five patients. In five cases long catheters were inserted bilaterally upstream, up to the sigmoid sinuses. MAIN FINDINGS: On average, measurements from the two sides were in agreement (mean and standard deviation of the differences between the saturation of the two IJs were respectively 5.32 and 5.15). However, 15 patients showed differences of more than 15 % in hemoglobin saturation at some point; three others showed differences larger than 10 %. No relationship was found between the computed tomographic scan data and the hemoglobin saturation pattern. DISCUSSION/CONCLUSION: Several groups have confirmed differences between oxygen saturation in the two jugular veins. After years of enthusiasm, interest for jugular saturation has decreased and more modern methods, such as tissue oxygenation monitoring, are now available. Jugular saturation monitoring has low sensitivity, with the risk of missing low saturation, but high specificity; moreover it is cheap, when used with intermittent sampling. Monitoring the adequacy of brain perfusion after severe TBI is essential. However the choice of a specific monitor depends on local resources and expertise.

Risk of perioperative seizures in patients undergoing craniotomy with intraoperative brain mapping.

BACKGROUND: The identification of risk factors associated with perioperative seizures would be of great benefit to the anesthesiologist in managing brain tumor patients undergoing craniotomy with intraoperative brain mapping. METHODS: A series of 316 supratentorial craniotomies for tumor resection, in which intraoperative brain mapping was used, were analyzed. From January 2005 to December 2010 the occurrence of intraoperative and immediate postoperative clinical seizures was prospectively recorded into a database. Demographic data, tumor characteristics, preoperative seizure control, intraoperative events and anesthetic management were evaluated as risk factors for intraoperative clinical seizures. Additionally, the association between intraoperative clinical seizures and immediate postoperative seizures was evaluated. In order to determine the best predictors of intraoperative and immediate postoperative clinical seizures, a multivariable analysis by logistic regression was performed. RESULTS: Younger age, location of the tumor in the frontal and parietal lobe, brain mapping conducted under general anesthesia and non physiologic values of arterial carbon dioxide (PaCO2) during brain mapping were independent positive risk factors for the development of intraoperative clinical seizures. Location of tumor in the frontal lobe, antiepileptic polytherapy, intraoperative seizures requiring pharmacologic treatment during brain mapping, and blood on postoperative CT scan were independent positive risk factors for the development of immediate postoperative seizures. CONCLUSION: Clinical seizures are common intraoperative and postoperative complications of supratentorial craniotomies with intraoperative brain mapping. The identification of those patients at higher risk of seizures may guide intraoperative and postoperative medical management.

Hypothermia for brain protection in the non-cardiac arrest patient.

This review focuses on the potential application of hypothermia in adults suffering traumatic brain injury (TBI). Hypothermia is neuroprotective, reducing the damaging effects of trauma to the brain in a variety of experimental situations, such as brain ischemia and brain injury, but it has failed to demonstrate outcome improvement in a major controlled, randomized trial. The evidence for the use of hypothermia as a protective procedure is scarce and contradictory. However, evidence does suggest that hypothermia is effective in reducing intracranial hypertension after head injury. Since hypothermia has important side effects, further work is necessary before introducing this procedure into clinical practice for TBI.

Neuroprotective effect of adenoviral-mediated gene transfer of TIMP-1 and -2 in ischemic brain injury.

Gene therapy may be a promising approach for treatment of brain ischemia. We and others previously demonstrated that increased activity of matrix metalloproteinases (MMPs) contributes to the tissue damage that results from ischemic injury. The proteolysis of MMPs is tightly controlled by tissue inhibitors of MMPs (TIMPs). In this study, we examined whether adenoviral-mediated gene transfer of TIMP-1 and TIMP-2 could protect against neuronal damage induced by global cerebral ischemia in mice. An adenovirus expressing TIMP-1 or TIMP-2 (AdTIMP-1 or AdTIMP-2) or a control adenovirus (RAd60) or vehicle was injected into the striatum 3 days before transient global cerebral ischemia. The extent of neuronal damage was quantified 3 days post-ischemia. There was no significant difference in the extent of neuronal damage in vehicle as compared to RAd60-treated mice. In contrast, neuronal damage was reduced, by approximately 50%, after gene transfer of AdTIMP-1 (P<0.001) and AdTIMP-2 (P< 0.01) as compared to controls. This study provides the first in vivo evidence of the protective effects of TIMP-1 and TIMP-2 via gene transfer in global ischemia.

Impact of pyrexia on neurochemistry and cerebral oxygenation after acute brain injury.

BACKGROUND: Postischaemic pyrexia exacerbates neuronal damage. Hyperthermia related cerebral changes have still not been well investigated in humans. OBJECTIVE: To study how pyrexia affects neurochemistry and cerebral oxygenation after acute brain injury. METHODS: 18 acutely brain injured patients were studied at the onset and resolution of febrile episodes (brain temperature > or = 38.7 degrees C). Intracranial pressure (ICP), brain tissue oxygen tension (PbrO2), and brain tissue temperature (Tbr) were recorded continuously; jugular venous blood was sampled intermittently. Microdialysis probes were inserted in the cerebral cortex and in subcutaneous tissue. Glucose, lactate, pyruvate, and glutamate were measured hourly. The lactate to pyruvate ratio was calculated. RESULTS: Mean (SD) Tbr rose from 38 (0.5) to 39.3 (0.3) degrees C. Arteriojugular oxygen content difference (AJD(O2)) fell from 4.2 (0.7) to 3.8 (0.5) vol% (p < 0.05) and PbrO2 rose from 32 (21) to 37 (22) mm Hg (p < 0.05). ICP increased slightly and no significant neurochemical alterations occurred. Opposite changes were recorded when brain temperature returned towards baseline. CONCLUSIONS: As long as substrate and oxygen delivery remain adequate, hyperthermia on its own does not seem to induce any further significant neurochemical alterations. Changes in cerebral blood volume may, however, affect intracranial pressure.

[Cerebral oxygen consumption and ischemia in traumatic brain injury]. / Consumo cerebrale di ossigeno e ischemia nel danno cerebrale traumatico.

AIM: Clinical and experimental studies have shown a reduction of cerebral blood flow (CBF) and metabolic alterations following traumatic brain injury (TBI). The incidence of ischemia and the meaning of post-traumatic metabolic alterations are still unclear. METHODS: Revision of CBF and metabolic changes following TBI based on the literature and on our clinical experience. RESULTS: Cerebral ischemia and metabolic alterations are part of the secondary insults/damage leading to an increased damage following TBI. Global ischemia occurs early following TBI as shown by CBF measurements and by greater values of arterio-jugular difference of oxygen (AJDO(2)) during the 1(st) 24 hours postinjury. Post-traumatic ischemia should be defined based on the relationships between CBF and on the metabolic requirements of the brain. Regional ischemia occurs more frequently than global ischemia as shown by regional monitoring of cerebral oxygenation. Following TBI there is a transient phase of increased glycolitic activity followed by a more prolonged phase of reduced metabolic rate of glucose (CMRglc) and oxygen (CMRO(2)). The extent of CMRO(2) reduction is a marker of injury severity and it is associated with unfavorable outcome. CONCLUSION: Cerebral ischemia occurs following TBI and should be defined based on CBF value and the metabolic needs of the brain. Global monitoring of cerebral oxygenation adequacy should be combined with regional monitoring. The meaning of high AJDO(2) values should be reconsidered: if they can highlights potential ischemia they are also showing a still living brain with a partially preserved oxygen extraction capability.

Head injury, subarachnoid hemorrhage and intracranial pressure monitoring in Italy.

BACKGROUND: Intracranial pressure monitoring is recommended for the management of severe head injury and is increasingly used during intensive care for other pathologies, such as subarachnoid hemorrhage. However, it is still not uniformly applied in different centers. The objectives of this paper are to summarize the frequency and the modalities of intracranial pressure (ICP) monitoring in different centers in Italy; to describe its use in traumatic brain injury (TBI) and in subarachnoid hemorrhage (SAH); and to identify areas for improvement. METHODS: The medical directors of either the neurosurgical department or the intensive care unit, or both, of every Italian neurosurgical center were personally interviewed. They answered specific questions about TBI and SAH patients admitted, and ICP monitoring used, in their units. Data were cleared of any obvious inconsistencies and entered in a database for analysis. All analyses were based simply on the data declared. FINDINGS: The clinical information was obtained from 9137 TBI cases, of whom 4240 severe, and 3151 SAH patients. Among the 106 participating centers, 15 did not use ICP monitoring at all. The remaining 91 had used 3293 ICP devices during the year 2001; 146 were used in tumor cases, 2009 in TBI, and 1138 in SAH. Twenty-two percent of TBI cases admitted to centers with ICP equipment were monitored. Restricting this analysis to severe cases, 47% of TBI with a GCS <8 had ICP. On average, 36% of SAH underwent ICP monitoring. The proportions of head injury and SAH cases who underwent ICP monitoring varied widely in the different centers. Dividing the country into three main areas (north, center and south), there were considerable differences both in the rate of admissions per million inhabitants and in the frequency of ICP monitoring. INTERPRETATION: ICP monitoring in Italy is used in most, but not all, centers. ICP is measured fairly extensively in head injury cases, but a significant proportion of SAH patients is monitored as well. There are substantial differences in the frequency of ICP monitoring in different parts of the country. The use of ICP for both these indications, and the rates of admission to specialized centers, could be improved.

[How to quantify the severity of brain injury during intensive care after adult head trauma]. / Valutazione della gravità del danno cerebrale nel corso di terapia intensiva dopo trauma cranico nell'adulto.

Adequate early assessment of brain damage is essential. Location, extension and severity of structural damage affect brain function and ultimately determine the outcome. The extent of functional impairment, and the morphology of intracranial lesions, require specific treatment, often a combination of medical and surgical interventions. Brain damage usually evolves over time, and repeated assessments are necessary. Clinical evaluation is often biased by concomitant sedation and/or anesthesia, but remains necessary. A revision of the literature is presented. Brain damage is assessed combining clinical and instrumental data. Clinical examination is performed assessing the 3 components of the Glasgow Coma Scale. Spontaneous or stimulated (pain stimulus) eye opening, verbal and motor responses are observed after hemodynamic and respiratory stabilisation. Unfortunately a significant proportion of patients can not be properly examined for several reasons: eye opening can be altered by palpebral and facial injuries, verbal response can be impaired by maxillo-facial injuries or by endotracheal intubation, and motor response remains the most consistent parameter. Sedation, analgesia and myorelaxants, however, can profoundly diminish or abolish the motor response to maximal stimulation, so that examination should be performed after clearance of drugs. Often alcohol or other substances can further impair the neurological performances. Pupils diameter and reactivity to light should be observed, excluding pharmacologic effects (as dilation due to catecholamines) and direct ocular or orbital damage. The CT scan is necessary for disclosing surgical masses and for identifying the extent of diffuse damage and the location of focal lesions. These data should be combined with additional functional exploration, as provided by cerebral extraction of oxygen and electrophysiologic data. Early estimation of cerebral damage is complex and prone to mistakes. Accurate, repeated evaluations, based on the combination of clinical observation and imaging, are necessary.

Cerebral veno-arterial pCO2 difference as an estimator of uncompensated cerebral hypoperfusion.

The aim of the present study was to assess the veno-arterial difference in pCO2 (delta pCO2) as an indicator of ischemia compared to the arteriovenous O2 difference (AVDO2). Staircase cerebral blood flow (CBF) reductions were obtained in seven domestic pigs by inducing intracranial hypertension: CBF 100%, 50-60% of baseline, 20-30% of baseline. ICP, MAP, CPP and CBF (Laser-Doppler method) were continuously recorded. The superior sagittal sinus was punctured to determine AVDO2 and delta pCO2. AVDO2 was 5.9 (+/- 1.78, range 3.3-7.4), 7.01 (+/- 1.31, range 5-8.9) and 8.17 (+/- 1.51, range 6.0-11.3) ml/100 ml in the three CBF steps (p = 0.001). CBF impairment was accompanied by the following increases in delta pCO2: from 10 (+/- 4, range 4-15) mmHg to 14.5 (+/- 4.11, range 10-27) mmHg, and to 31.2 (+/- 9.0, range 17-39) mmHg (p < 0.001). When CBF declines AVDO2 increases, indicating greater extraction of O2 to satisfy the aerobic metabolism. However, this mechanism can no longer compensate once a critical CBF threshold is reached. delta pCO2 rises slowly during moderate CBF reduction because of defective washout; the rise is impressive during marked CBF impairment when anaerobic metabolism takes place with proton buffering in CO2 and H2O. Therefore, when the brain's ability to compensate for low blood flow is exceeded, CO2 production outweighs O2 extraction.

[Cerebral tissue oxygen monitoring: a useful thing?]. / Monitoraggio dell'ossigenazione tissutale cerebrale: a cosa serve?

Monitoring cerebral oxygenation has been one of the main fields of interest in neurointensive care during the past few years. In fact it is strongly believed that restoring adequate cerebral oxygenation is the premise to maintaining the viability and restoring the function of the damaged CNS. Global monitoring provides an indirect estimation of adequacy of substrates supply to the brain. Local measurement of brain oxygen tension (ptiO2) is possible through a Clark electrode implanted into the cerebral parenchyma. The paper describes the physical basis of the monitoring, the pathophysiology of ptiO2 and its clinical use.

[Cranial trauma and multiple trauma: from the street to the operating room]. / Trauma cranico e politrauma: dalla strada alla sala operatoria.

Brain injury occurs with a range of severity: even less severe cases should be carefully observed since they may deteriorate. By definition severe head injury has a Glasgow Coma Scale score of 8 or less; comatose patients are defined as cases who do not obey commands, do not open their eyes and do not speak. Very often (50% of case in our series) brain injury is associated with relevant extracranial injuries that may add to the severity of cases and may worsen outcome. The conceptual framework for treating head injury is based on the evidence that after the impact, the initial damage may be exacerbated by insults capable of further disturbing cerebral metabolism, leading to a final damage defined as secondary damage. Secondary damage represents the final end of many pathways that can be studied at the biochemical level and are centered in a calcium influx into the neuronal cell. Most probably there is a genetic susceptibility to secondary damage leading to a range of cellular dysfunctions for any given level of insult. The management of traumatic brain injury is aimed at interrupting the chain of events leading to secondary brain damage and from this perspective the fact that damage may develop over time can be seen as a window of opportunity for timely treatment. The milestone of treatment is the removal of surgical masses. This surgical treatment can be performed only in a brain that is properly perfused and once coagulation is preserved. Therefore the organization of treatment from rescue to neuro-traumatological centers should provide appropriate restoration of the volume and a normal oxygen delivery to the brain and to the overall organism.

[Diagnosis of non-palpable lesions of the breast with stereotactic excisional biopsy with cannula. Advanced Breast Biopsy Instrumentation (ABBI) with fine diameter of 20 mm]. / Diagnosi delle lesioni non palpabili della mammella mediante la biopsia escissionale stereotassica con cannula. Advanced Breast Biopsy Instrumentation (ABBI) con diametro fino a 20 mm.

PURPOSE: To evaluate the advisability of use by interventional radiologists of the ABBI system for stereotactic biopsy in the diagnosis of mammographically detected nonpalpable breast lesions considered suspicious for cancer. MATERIAL AND METHODS: Breast biopsy with the ABBI cannula, available in various diameters, was offered to 61 patients who gave their informed consent and was performed in 36. Reasons for exclusion were insufficient thickness of the compressed breast (37.5%), the lesion site (50%) and the failure to detect the lesion with stereotactic mammography (12.5%). The procedure was carried out under local anesthesia in an outpatient setting. Fifteen nodules, 15 groups of microcalcifications and 6 nodules with calcifications were excised. The diameter of the ABBI cannula used was 20 mm in 32 cases and 15 mm in four cases. RESULTS: A definitive histological diagnosis was obtained in all cases, with the identification of 20 neoplasms (56%) and 16 benign lesions (44%). The lesions margins were involved in 14 cases of malignancy. All the patients with a diagnosis of malignancy underwent surgery. No residual tumor was found in five cases. The mean diameter of the lesions removed was 11-12 mm. The only complications were two late hematomas which were drained by simple percutaneous aspiration. The procedure was well tolerated by all patients except one who experienced a vagal attack due to emotional stress. CONCLUSIONS: Stereotactic breast biopsy with an ABBI surgical cannula can be carried out autonomously by interventional radiologists, safely and with diagnostic accuracy.

Stereotactic excisional breast biopsy performed by interventional radiologists using the advanced breast biopsy instrumentation system.

The Advanced Breast Biopsy Instrumentation (ABBI) system, which uses surgical cannulas up to 20 mm in diameter, is an alternative to conventional surgical biopsy for the diagnosis of non-palpable breast lesions. Since the need for radiological skill outweighs the surgical content of the technique, we evaluated the feasibility of complete management of the procedure by interventional radiologists. 35 of the 111 patients originally scheduled for the procedure were excluded, three because the lesion could not be visualized and 32 because of insufficient thickness of the compressed breast. The procedure had to be abandoned in one case due to a technical failure. 77 stereotactic excisional breast biopsy procedures were performed using the ABBI system in 75 patients with suspicious non-palpable mammographic lesions. The procedure was carried out under local anaesthesia in the radiology department, using a dedicated Lorad (R) radiographic system. 31 (40%) masses without calcifications, 11 (14%) masses with calcifications and 35 (46%) clusters of microcalcifications without tumour mass were sampled. 43 (56%) benign lesions and 34 (44%) malignant lesions were diagnosed. The overall mean diameter of the lesions was 8.7 mm (range 3-22 mm). All 34 patients with malignancies and lobular carcinoma in situ subsequently underwent surgery, the results of which are reported. Three (4%) haematomas were detected and aspirated percutaneously. Two technical problems occurred: an ABBI cannula malfunction, and a computer failure of the digital imaging system during the procedure. The average procedure time was 80 min and the cost of each procedure was 2,800,000 Italian lire (1555 US$). It is concluded that tissue sampling with the ABBI system can be performed entirely by radiologists without significant problems. The procedure was well tolerated by all patients. The quality of the biopsy specimen was identical to that of a surgical specimen but with the advantages of stereotactic precision for localization of the lesion.

Study on radon emission in a fault located in the Bergamask Pre-Alps

At Bedulita in the Orobic Prealps the Institute of Applied Physics has placed a radon continuos monitoring station. The experimental apparatus is located in a dry well, 4 metres deep, on an active fault. Radon is measured by means of a NaI detector that reveals the y quanta of Radon decay products. The hourly are recorded on magnetic diskette every hour. The station has worked since 1989 until 1992. The seasonal variation with winter minima and summer maxima present in all the four years of measurements appears very interesting. We have also noticed a diurnal modulation and some sudden peaks during the months of lower emission. Twice a week, during June and July 1992 helium has been measured. The air samples collected in the dry well has been analysed in the laboratoey of the Institute by a mass spectrometer. The correlation between He and Rn is evident.(AU)

Radon levels in a deep geothermal well in the Po plain

The continuous study of radon concentrations in deep aquifers provides important information on the geophysics structure of aquifers and of the earth crust in general. Several studies, in particular, evidence the connection between radon concentration and earthquake. To be able to investigate these phenomena, the Institute for Applied General Physics has installed a station for the continuous radon monitoringin a geothermal 4000m deep well. This station is located at Rodigo in the Po plain close to Mantova. The radon level is measured with a 3"x3" Nal detector connected with a single channel analyser which detects y quanta over 900 Kev. The water from the head of the well flows at 100 litres per hour, in an almost cylindrically shaped container with a capacity of 200 litres, inside which there id the detector placed in a suitable housing. In this work, a correlation between radon levels and crust tides is discussed. Also owing to the exiguity of radon oscillation, at this stage of the studies it is not possible, however, to give a satisfactory explanation of the phenomena.(AU)