Impact of rapid genetic counselling and testing on the decision to undergo immediate or delayed prophylactic mastectomy in newly diagnosed breast cancer patients: findings from a randomised controlled trial.

BACKGROUND: Female breast cancer patients with a BRCA1/2 mutation have an increased risk of contralateral breast cancer. We investigated the effect of rapid genetic counselling and testing (RGCT) on choice of surgery. METHODS: Newly diagnosed breast cancer patients with at least a 10% risk of a BRCA1/2 mutation were randomised to an intervention group (offer of RGCT) or a control group (usual care; ratio 2 : 1). Primary study outcomes were uptake of direct bilateral mastectomy (BLM) and delayed contralateral prophylactic mastectomy (CPM). RESULTS: Between 2008 and 2010, we recruited 265 women. On the basis of intention-to-treat analyses, no significant group differences were observed in percentage of patients opting for a direct BLM (14.6% for the RGCT group vs 9.2% for the control group; odds ratio (OR) 2.31; confidence interval (CI) 0.92-5.81; P=0.08) or for a delayed CPM (4.5% for the RGCT group vs 5.7% for the control group; OR 0.89; CI 0.27-2.90; P=0.84). Per-protocol analysis indicated that patients who received DNA test results before surgery (59 out of 178 women in the RGCT group) opted for direct BLM significantly more often than patients who received usual care (22% vs 9.2%; OR 3.09, CI 1.15-8.31, P=0.03). INTERPRETATION: Although the large majority of patients in the intervention group underwent rapid genetic counselling, only a minority received DNA test results before surgery. This may explain why offering RGCT yielded only marginally significant differences in uptake of BLM. As patients who received DNA test results before surgery were more likely to undergo BLM, we hypothesise that when DNA test results are made routinely available pre-surgery, they will have a more significant role in surgical treatment decisions.

Comparison of transcranial Doppler ultrasonography and positron emission tomography using a three-dimensional template of the middle cerebral artery.

OBJECTIVE: Transcranial Doppler (TCD) measures blood flow velocities (BFV) and is an indirect method of assessing cerebral blood flow (CBF). Positron emission tomography (PET) is a direct method to measure CBF. This study evaluates the correlations between TCD and PET findings Methods: Nine patients with a symptomatic carotid artery stenosis, who underwent CEA, were studied pre- and post-operatively on the ipsi- and contralateral sides. Measurements of the BFV, CO(2) reactivity, CBF, cerebral blood volume (CBV) and mean vascular transit time (MVTT) were performed using a three-dimensional volume of interest (VOI) for the middle cerebral artery (MCA). RESULTS: CBF in the MCA region, as measured with PET, shows a good correlation with BFV, as measured with TCD, with similar pattern for total, gray and white matter MCA territory (Pearson's correlation coefficients: 0.751, 0.748 and 0.748, respectively). This correlation was found in the pre-operative as well as the post-operative state. No association could be demonstrated between CO(2) reactivity and CBV or (Pearson's correlation coefficients: 0.051 and 0.166, respectively). CONCLUSION: With PET, it is possible to create three-dimensional VOI of arterial territories. CBF measured in these VOI seems to correlate with BFV before and after CEA on ipsi- and contralateral sides, while CBV shows no association with pre-operative CO(2) reactivity.

Aberrant resting-state oscillatory brain activity in Parkinson's disease patients with visual hallucinations: An MEG source-space study.

To gain insight into possible underlying mechanism(s) of visual hallucinations (VH) in Parkinson's disease (PD), we explored changes in local oscillatory activity in different frequency bands with source-space magnetoencephalography (MEG). Eyes-closed resting-state MEG recordings were obtained from 20 PD patients with hallucinations (Hall+) and 20 PD patients without hallucinations (Hall-), matched for age, gender and disease severity. The Hall+ group was subdivided into 10 patients with VH only (unimodal Hall+) and 10 patients with multimodal hallucinations (multimodal Hall+). Subsequently, neuronal activity at source-level was reconstructed using an atlas-based beamforming approach resulting in source-space time series for 78 cortical and 12 subcortical regions of interest in the automated anatomical labeling (AAL) atlas. Peak frequency (PF) and relative power in six frequency bands (delta, theta, alpha1, alpha2, beta and gamma) were compared between Hall+ and Hall-, unimodal Hall+ and Hall-, multimodal Hall+ and Hall-, and unimodal Hall+ and multimodal Hall+ patients. PF and relative power per frequency band did not differ between Hall+ and Hall-, and multimodal Hall+ and Hall- patients. Compared to the Hall- group, unimodal Hall+ patients showed significantly higher relative power in the theta band (p = 0.005), and significantly lower relative power in the beta (p = 0.029) and gamma (p = 0.007) band, and lower PF (p = 0.011). Compared to the unimodal Hall+, multimodal Hall+ showed significantly higher PF (p = 0.007). In conclusion, a subset of PD patients with only VH showed slowing of MEG-based resting-state brain activity with an increase in theta activity, and a concomitant decrease in beta and gamma activity, which could indicate central cholinergic dysfunction as underlying mechanism of VH in PD. This signature was absent in PD patients with multimodal hallucinations.

Peroperative neuromonitoring during carotid endarterectomy in relation to preoperative positron emission tomography findings.

OBJECTIVES: To compare stump pressure (SP), transcranial Doppler (TCD), electroencephalography (EEG) and selective shunting during carotid endarterectomy (CEA) with preoperative positron emission tomography (PET) parameters. MATERIALS AND METHODS: Preoperative PET measurements and peroperative neuromonitoring were performed in ten patients undergoing CEA for symptomatic carotid artery disease. PET parameters measured were cerebral blood flow (CBF), oxygen extraction fraction (OEF), cerebral oxygen metabolism (CMRO(2)), cerebral blood volume (CBV), mean vascular transit time (MVTT) and cerebral perfusion pressure (CPP). Results of these measurements in ipsilateral medial cerebral artery (MCA), ipsilateral hemisphere and total cerebrum were compared with absolute mean SP, mean SP<40mmHg, TCD, EEG changes and selective shunting. RESULTS: None of the PET parameters showed any significant correlations with peroperative neuromonitoring findings. There were only trends for correlations of CBF and MVTT with TCD changes and of CPP and CMRO(2) with selective shunting. CONCLUSIONS: Preoperative PET examinations are not useful for predicting the need for shunting during CEA.

Increase in alpha rhythm frequency after carotid endarterectomy.

OBJECTIVES: Besides preventing stroke, carotid endarterectomy (CEA) is reported to improve cerebral circulation and brain function. We tested whether this improvement is reflected by changes in the qEEG. METHODS: qEEG changes in 166 patients with a >70% stenosis of the internal carotid artery (ICA) were assessed after subtraction of the preoperative and postoperative spectra (eyes closed condition) before and 3 months after CEA. The mean frequency of the alpha band (MFA), the peak frequency of the alpha band (F alpha), and bands with limits relative to each patient's F alpha were studied in relation to neurological symptoms, patency or occlusion of the contralateral ICA, shunt requirement, and side of surgery. RESULTS: MFA and F alpha significantly increased over both hemispheres. After alignment on F alpha, a decrease of spectral band power was seen below F alpha, and a band power increase above F alpha. The group of patients with a contralateral ICA occlusion showed significantly more improvement than the group without. The group of patients with neurological deficits showed a tendency for improvement. No differences were found concerning shunt requirement or the side of surgery. CONCLUSIONS: After CEA the alpha rhythm frequency increases. In general, patients with a contralateral ICA occlusion improve more than other patients, in agreement with data from the literature on cerebral circulation and brain function.

Transcranial pulsed Doppler measurements of blood flow velocity in the middle cerebral artery: reference values at rest and during hyperventilation in healthy children and adolescents in relation to age and sex.

Transcranial pulsed Doppler (TCD) measurement of blood flow velocity in the middle cerebral artery was performed in 76 healthy children and adolescents (age 2-19 years), to obtain normative reference data, both at rest and during hyperventilation (from 10 years on). The Mean Flow Velocity (MFV) decreased with increasing age. Girls of 10 years or older showed a tendency for higher MFV values than boys of the same age. In combination with a previous study, this suggests that females in their reproductive years have higher maximal MFV values than males. The MFV values, during hyperventilation, were higher in girls than in boys. This gender difference, as in adults, disappeared gradually at lower levels of pCO2. At the lowest pCO2 levels, systolic minus diastolic blood flow velocity was more sensitive to vascular changes than MFV. With TCD measurements, age, sex, and pCO2 have to be taken into account, for a correct interpretation of the data obtained.

Transcranial pulsed Doppler measurements of blood velocity in the middle cerebral artery: reference values at rest and during hyperventilation in healthy volunteers in relation to age and sex.

Transcranial pulsed Doppler analysis of blood velocity in the middle cerebral artery was performed in 120 healthy volunteers (age 20-70 y, 12 male and 12 female subjects per decade), meeting strict selection criteria. The intention was to create normative reference data, both at rest and during hyperventilation, for the assessment of abnormality in patients with cerebral vascular disorders. The measured blood velocity at rest decreased significantly with increasing age. Females up to 50 years of age had significantly higher blood velocity values than males. Blood velocity diminution was induced by means of voluntary hyperventilation, under capnographic control. An age related decline of blood velocity as present at rest was not found during hyperventilation, thus the relative value of hyperventilation induced changes diminished with increasing age. The pCO2 related change in the blood velocity index appeared not to be a constant value, as suggested by previous authors. The blood velocity index was largest in the change from resting condition to 4 kPa pCO2, and smallest in the change 3 kPa pCO2 to 2 kPa pCO2. When examining the blood velocity in the MCA, the age, sex and end-tidal pCO2 pressure have to be taken into account for a correct interpretation of the data obtained.

[Neuromonitoring of patients following severe brain trauma]. / Neuromonitoring bij patiënten na ernstig traumatisch hersenletsel.

To a considerable extent, the neurological outcome of patients with severe brain trauma is determined by the primary injury caused by the accident. Substantial progress has been made in our understanding of the pathophysiological processes resulting in secondary brain damage after brain trauma, partly as a result of the introduction of advanced techniques of neuromonitoring. Early recognition and treatment of the symptoms leading to this type of brain damage seems crucial to the effort to improve the neurological outcome in these patients. Useful modern neuromonitoring techniques include: measurement of the intracranial and cerebral perfusion pressure and continuous electroencephalography. Methods that are also reliable and readily applicable, but less relevant clinically, include cerebral microdialysis of fluid from the extracellular space, determination of the parenchymal oxygen tension, and determination of the venous oxygen saturation. Other techniques that are not clinically applicable include: determination of the cerebral blood flow, the cortical tissue perfusion or the regional cerebral oxygenation.

Asymptomatic carotid artery stenosis: past, present and future. How to improve patient selection?

BACKGROUND: The role of carotid endarterectomy (CEA) for asymptomatic carotid artery stenosis (aCAS) remains a matter of debate. It seems that not only the degree of stenosis, but also other factors have to be taken in account to improve patient selection and increase the benefit of CEA for aCAS. METHODS AND RESULTS: The literature pertaining aCAS was reviewed in order to describe the natural history, risk of stroke and benefit of CEA for patients with aCAS in regard to several factors. CONCLUSION: The benefit of CEA for aCAS is low. Current factors influencing the indication for CEA are severity of stenosis, age, contralateral disease, stenosis progression to >80%, gender, concomitant operations and life expectancy. To improve patient selection investigations will concentrate on plaque characteristics and instability and cerebral hemodynamics and metabolism.

Seizure detection in adult ICU patients based on changes in EEG synchronization likelihood.

INTRODUCTION: Seizures are common in Intensive Care Unit (ICU) patients, and may increase neuronal injury. PURPOSE: To explore the possible value of synchronization likelihood (SL) for the automatic detection of seizures in adult ICU patients. METHODS: We included EEGs from ICU patients with a variety of diagnoses. The gold standard for further analyses was the consensus judgment of three clinical neurophysiologists who classified 150 scalp EEG epochs as "definitely epileptiform," "definitely non epileptiform," or "uncertain." SL estimates the statistical interdependencies between two time series, such as two EEG channels. We computed the average synchronization by calculating the SL between one channel and every other channel, and taking the mean of these values. RESULTS: The mean SL in the 38 "definitely epileptiform" epochs ranged from 0.095 to 0.386 (mean 0.189; SD 0.066). In the 34 "definitely nonepileptiform" epochs the mean SL ranged from 0.087 to 0.158 (mean 0.115; SD 0.016; p < 0.0005). The area under the ROC curve was 0.812 (95% Confidence Interval 0.725 to 0.898). CONCLUSION: The mean SL may distinguish between seizure and nonseizure epochs, and may prove helpful to monitor epileptic activity in ICU patients.

Flow redistribution in the major cerebral arteries after carotid endarterectomy: a study with transcranial Doppler scan.

PURPOSE: This open single-center prospective study aimed to determine the redistribution of blood flow within the circle of Willis and through collateral pathways after carotid endarterectomy. Blood flow velocity and flow direction in the major cerebral arteries were determined, both at rest and during CO(2) inhalation. METHODS: Carotid endarterectomy was performed in 148 patients with a 70% or greater diameter stenosis of the internal carotid artery while patients were under general anesthesia. Arteriotomy closure was done with a venous patch. Selective shunting was performed with an electroencephalogram. Baseline blood flow velocity of the basal cerebral arteries was measured by means of transcranial Doppler sonography preoperatively (within 1 week before surgery) and 3 months postoperatively. At the same times, cerebrovascular reactivity was calculated during CO(2) inhalation insonating both middle cerebral arteries. RESULTS: Baseline blood flow velocity in the ipsilateral middle cerebral artery hardly changed 3 months postoperatively, but there was a considerable redistribution of flow in the circle of Willis. This was characterized by a decrease in contribution from the contralateral hemisphere through the anterior communicating artery, reduced cerebropetal flow rates in the ophthalmic artery, and smaller contribution of the posterior collateral sources. The CO(2) reactivity on the side of surgery increased in all patients. In patients with a contralateral occlusion, CO(2) reactivity increased on both sides. The redistribution of flow was most pronounced in patients who needed intraoperative shunting and in patients with a contralateral internal carotid artery occlusion. CONCLUSION: After carotid endarterectomy, flow redistribution, as expressed by changes in blood flow velocity values, occurs in the circle of Willis. The contribution of collateral sources is diminished, and the CO(2) reactivity increases, both of which reflect improvement of the hemodynamic condition. The most improvement occurs in patients with contralateral occlusion.

A comparison of cerebral hemodynamic parameters between transient monocular blindness patients, transient ischemic attack patients and control subjects.

PURPOSE: To assess whether patients with transient monocular blindness (TMB) and patients with hemispheric transient ischemic attacks (hTIA) differ from each other with respect to cerebral hemodynamic parameters. METHODS: Seventeen TMB patients and 23 hTIA patients with a moderate to severe stenosis or an occlusion of the internal carotid artery (ICA) underwent magnetic resonance (MR) angiography, (1)H MR spectroscopy and transcranial Doppler sonography. Thirty-one control subjects were investigated to obtain reference values for the MR investigations. Quantitative flow was measured in the ICAs, the basilar artery and the middle cerebral arteries (MCA). Metabolic changes in the MCA territory were studied by assessing N-acetyl-aspartate (NAA)/choline ratios and prevalences of lactate. The prevalence of collateral flow was assessed in the circle of Willis and the ophthalmic arteries. The vasomotor reactivity was studied by measuring the CO(2) reactivity of the MCA territories. RESULTS: Quantitative flow in the cerebropetal arteries and the MCAs did not differ between TMB patients and hTIA patients. Also patterns of collateral flow, prevalence of lactate and CO(2) reactivity were similar. The mean ipsilateral NAA/choline ratio was lower in hTIA patients compared with TMB patients (p < 0.01), and was predominantly correlated with symptomatology (p < 0.01), i.e. whether patients had TMB or hTIA, and not with ipsilateral MCA flow (p = 0.2) or ipsilateral CO(2) reactivity (p = 0.7). CONCLUSION: The results of this study indicate that there are no cerebral hemodynamic differences between TMB patients and hTIA patients. It is therefore unlikely that hemodynamic factors account for differences in clinical characteristics between the two patient groups.

Carotid endarterectomy with transcranial Doppler and electroencephalographic monitoring. A prospective study in 130 operations.

BACKGROUND AND PURPOSE: We report the results of combined recording of hemodynamic and thromboembolic phenomena during carotid endarterectomy by means of computerized electroencephalography as well as transcranial Doppler ultrasonography. The study focuses on the additional value of transcranial Doppler to detect ischemia during surgery. METHODS: Combined monitoring was performed in 130 consecutive operations, using standard anesthesiological, surgical, and neurophysiological procedures. RESULTS: A reduction of > or = 70% of blood flow velocities in the middle cerebral artery during cross-clamping was measured in 16 patients. In seven of these cases there were no severe electroencephalographic changes and a shunt was not used, but one of the patients developed a subcortical infarct with slight disability. In 55 patients, 75 episodes of embolization were detected by transcranial Doppler. In one of these, with massive embolization after release of the clamp, an intraoperative stroke occurred without changes on cranial computerized tomography or neurological disability on follow-up. In the other 54 patients, intraoperative embolization did not cause clinical or neuroradiological symptoms. Electroencephalographic changes occurred in only two of the 75 episodes. In addition to the two nondisabling strokes during surgery (1.5%), six strokes occurred within 5 days of operation, including one hemorrhage. There was no significant relation between contralateral carotid occlusion and stroke (p = 0.6). CONCLUSIONS: During carotid endarterectomy, transcranial Doppler immediately provides information about thromboembolism and hemodynamic changes that are not detected by electroencephalography alone. Acoustic feedback from the transcranial Doppler monitoring unit has a direct influence on the surgical technique. Transcranial Doppler ultrasound may be a useful tool in the study and prevention of intraoperative stroke.

New ways of performing in vivo flow velocity measurements in the basilar artery.

The basilar artery is the only large artery in which two flows merge, and this is reflected in the flow downstream. We report quantitative flow-velocity measurements with a phase-based MR technique, i.e. the Fourier velocity encoding method, in the basilar artery of a volunteer. To our knowledge, this has not previously been performed successfully. A comparison is made with the results of flow velocity measurements in the basilar artery with transcranial Doppler ultrasonography; the techniques agreed very well. Although Doppler ultrasonography is still most widely used, no information on the flow rate and the flow velocity distribution in the basilar artery can be provided. MR flow measurement techniques appear promising when detailed information on the flow velocity distribution and flow rate is needed.

Changes in health-related quality of life after carotid endarterectomy.

OBJECTIVES: Carotid endarterectomy (CEA) is intended to prevent stroke and therefore to extend lifespan. Whether CEA also influences health-related quality of life (HRQOL) is largely unknown. This study aimed to assess HRQOL-changes after CEA. DESIGN: Prospective study, data assessment within 1 week before and 3 months after CEA. MATERIALS: Patient classification (n = 70) was based on presenting neurological symptoms (none (24), transient (26), or permanent (20)), patency or occlusion (27%) of the contralateral internal carotid artery and intraoperative shunt requirement (28%). METHODS: HRQOL was investigated with the Sickness Impact Profile (SIP). Analysis of variance was used to adjust for the influence of preoperative differences in functional impairment and comorbidity on the changes found. RESULTS: Preoperative findings showed that the SIP scores of stroke patients and shunted patients were significantly higher (indicating poorer HRQOL) than those of the other patients. No adverse effect of CEA was observed. Analysis of variance revealed that neurological classification was not reflected to HRQOL changes. However, patients with contralateral occlusion showed a significant postoperative improvement (f = 4.99, p < 0.05). CONCLUSIONS: HRQOL improvement after CEA is restricted to patients with occlusion of the contralateral carotid artery. Assessment of outcome of CEA should be related not only to neurological classification, but also to haemodynamic factors such as contralateral occlusion.

The impact of repeated short episodes of circulatory arrest on cerebral function. Reassuring electroencephalographic (EEG) findings during defibrillation threshold testing at defibrillator implantation.

The impact of circulatory arrest on EEG features during defibrillation threshold testing for implantation of a cardioverter defibrillator has been disputed. Cumulation of cerebral ischemic effects during threshold testing has been observed, and consequently the advice was given to avoid short intervals between tests and to limit the test number. This study investigated the duration of EEG signs of cerebral ischemia as well as the occurrence of cumulation. EEGs were recorded during standardized general anesthesia. Subsequent tests were performed after recovery of EEG, electrocardiogram, systemic arterial blood pressure, and heart rate. In 36 consecutive survivors of out-of-hospital cardiac arrest 286 episodes of induced circulatory arrest were analyzed. Ischemic EEG changes were present in all episodes of circulatory arrest, consisting of slowing, progressing to absence of activity. The relation between the onset time or recovery time and the test number and test interval was studied. A highly significant correlation between circulatory arrest and recovery time was found (P < 0.001). A significant negative correlation existed between test number and recovery time (P < 0.05). Test interval was not related with either onset or recovery time. We conclude that repeated threshold tests which are monitored by assessment of EEG and hemodynamics are not associated with cumulative EEG changes as a result of ischemia. Our results do not support the advice that the number of tests should be limited.