Doppler and Duplex Sonography for the Diagnosis of the Irreversible Cessation of Brain Function ("Brain Death"): Current Guidelines in Germany and Neighboring Countries.

Extra- and transcranial sonography of brain-supplying arteries is accepted worldwide in brain death protocols as a valid "ancillary" method of proving brain circulatory arrest. Color-coded duplex sonography and CT angiography have been newly incorporated in the fourth update of the German Medical Association's guidelines for the determination of the irreversible cessation of brain function ("brain death"), effective July 2015. The updated guidelines address in more detail the diagnostic procedures and the required qualifications of the examiners. The present article summarizes the guidelines and the recommendations regarding the application and documentation of ultrasound findings for the diagnosis of brain circulatory arrest in children and adults, as valid in Germany. The method, limitations, and procedure in the case of inconclusive findings are described. Age-related minimum values of mean arterial pressure for the diagnosis of cerebral circulatory arrest in children are presented. A concise overview of the respective regulations for the use of sonography for diagnosing brain death in other countries, especially in the countries neighboring Germany, is given.

Superspreading and the effect of individual variation on disease emergence.

Population-level analyses often use average quantities to describe heterogeneous systems, particularly when variation does not arise from identifiable groups. A prominent example, central to our current understanding of epidemic spread, is the basic reproductive number, R(0), which is defined as the mean number of infections caused by an infected individual in a susceptible population. Population estimates of R(0) can obscure considerable individual variation in infectiousness, as highlighted during the global emergence of severe acute respiratory syndrome (SARS) by numerous 'superspreading events' in which certain individuals infected unusually large numbers of secondary cases. For diseases transmitted by non-sexual direct contacts, such as SARS or smallpox, individual variation is difficult to measure empirically, and thus its importance for outbreak dynamics has been unclear. Here we present an integrated theoretical and statistical analysis of the influence of individual variation in infectiousness on disease emergence. Using contact tracing data from eight directly transmitted diseases, we show that the distribution of individual infectiousness around R(0) is often highly skewed. Model predictions accounting for this variation differ sharply from average-based approaches, with disease extinction more likely and outbreaks rarer but more explosive. Using these models, we explore implications for outbreak control, showing that individual-specific control measures outperform population-wide measures. Moreover, the dramatic improvements achieved through targeted control policies emphasize the need to identify predictive correlates of higher infectiousness. Our findings indicate that superspreading is a normal feature of disease spread, and to frame ongoing discussion we propose a rigorous definition for superspreading events and a method to predict their frequency.

Complete basilar artery assessment by transcranial color-coded duplex sonography using the combined transforaminal and transtemporal approach.

PURPOSE: Visualization of the basilar artery (BA) by transcranial color-coded duplex sonography (TCCD) can be challenging. The detection of stenosis or occlusion of the BA often has to rely on indirect signs like a highly pulsatile flow in the vertebral arteries. In case of a distal BA occlusion, however, the flow of the VAs can even be normal. The aim of our TCCD study was to visualize a maximum length of the BA combining the customarily used transforaminal appraoch for the proximal part and the less well known transtemporal coronal approach for the distal BA segment. MATERIALS AND METHODS: TCCD was performed in 60 subjects with a good temporal bone window. Detectable extracranial or intracranial pathology was previously excluded. The BA was insonated using the transforaminal and transtemporal insonation plane and the visible length was measured. In one subject MRA was performed to substantiate our findings. RESULTS: The BA was visualized in all subjects via both approaches. The maximal detectable BA length via the transforaminal and transtemporal approach was 26 ± 8 mm and 18 ± 5 mm, respectively. Assuming a previously reported average anatomical total BA length of 33 ± 6 mm, we supposed complete vessel visualization in 44 subjects (73 %). CONCLUSION: The combined transforaminal and transtemporal insonation approach may permit total BA insonation, thus facilitating the evaluation of BA pathology.

Superior cerebellar artery - a potential pitfall in transcranial posterior cerebral artery insonation.

PURPOSE: Transcranial color-coded duplexsonography (TCCD) of the posterior cerebral artery (PCA) is commonly performed in an axial midbrain insonation plane. The proximal PCA is easily identified as a vessel, originating from the top of the basilar artery (BA). However, the initial segment of the superior cerebellar artery (SCA) also originates from the top segment of the BA and runs in parallel. Therefore, it is possible to confuse the two vessels. The aim of our study is to anatomically differentiate the proximal PCA and SCA by means of TCCD in the coronal plane using a transtemporal approach and to analyze and compare their flow responses during a visual stimulus paradigm. MATERIALS AND METHODS: 60 subjects without a relevant vascular pathology and with a good temporal bone window were examined. The distal BA, the proximal PCA and the SCA were insonated using a coronal insonation plane and identified by their anatomical relationship. The visible length was measured and the blood flow velocities were recorded at rest and during visual stimulation. RESULTS: The identification and differentiation of both vessels was successful in 101 of 120 hemispheres (84.2 %). The PCA systolic flow velocities at rest and during visual stimulation were 58.4 +/- 11 and 71.8 +/- 13 cm/sec (23.6 % increase), while the SCA velocities were 50.7 +/- 12 and 53.5 +/- 13 cm/sec, respectively (5.8 % increase). The difference was significant (p < 0.001). CONCLUSION: Using the coronal transtemporal insonation approach, TCCD makes it possible to identify and distinguish the proximal PCA and SCA. Our study is the first to provide a systematic ultrasound assessment of the SCA and includes data on normal flow velocities and reactivity to a visual stimulus.

Does routine transcranial duplex ultrasound heat up the patient brain?

PURPOSE: The effect of transcranial duplex ultrasound (US) on the intraventricular temperature in patients was analyzed. Temperature increases during examination have been identified as a potential risk factor but only data from model studies is currently available. MATERIALS AND METHODS: Patients who had an intracranial pressure/temperature transducer implanted and underwent US assessment were included. In an examination series (B-mode, combined B- and color mode, combined B- and color mode plus Doppler, 3 min for each mode), the intracranial thermodilution thermistor was focused while intraventricular temperature and body temperature (bladder catheter or rectal probe) were recorded continuously and temperature changes were analyzed. RESULTS: Thirty-one US examinations were performed in 14 patients. Twenty-six examinations in 9 patients in which the intracranial temperature probe was depicted were included. Initial patient temperatures ranged from 35.1dgC to 38.7dgC. No significant increase or decrease in intracranial temperature was seen after the first (B-mode), second (B- and color mode) and third (B- and color mode plus Doppler) duplex US examination. T-test for paired samples showed a constant temperature throughout US examination (two-sided significance: 1.000, 1.000, 0.731). CONCLUSION: Routine transcranial duplex ultrasound does not increase the intracranial temperature in patients.

Ultrasound perfusion imaging of small stroke involving the thalamus.

PURPOSE: Ultrasound (US) perfusion imaging of ischemic stroke has mainly been applied to large middle cerebral artery infarction. We investigated whether small stroke involving the thalamus can also be detected. MATERIALS AND METHODS: Phase inversion harmonic imaging (PIHI) was applied to patients with small infarctions involving the thalamus (maximal longitudinal infarct diameter less than 3 cm). PIHI was performed from both the left and right side in axial diencephalic planes. Infarct size and location as well as perfusion properties (MTT maps) were known from MRI. US perfusion parameters were derived from the signal enhancement time course (bolus kinetics, SonoVue for peak-signal increase and time-to-peak. RESULTS: Seventeen patients (52 +/- 11 years, 24% female) with 18 strokes (16 unilateral, 1 bilateral) were included. Six US examinations (18%) were inadequate for analysis due to an insufficient transtemporal bone window. US perfusion depicted 90 % of infarcts with a longitudinal diameter of more than 2 cm. Infarcts with a longitudinal diameter of less than 2 cm were hardly identified. CONCLUSION: PIHI allows identification of a small infarction involving the thalamus subject to infarct size.

Social information drives ecological outcomes among competing species.

Through its behavior, an organism intentionally or unintentionally produces information. Use of this "social information" by surrounding conspecifics or heterospecifics is a ubiquitous phenomenon that can drive strong correlations in fitness-associated behaviors, such as predator avoidance, enhancing survival within and among competing species. By eliciting indirect positive interactions between competing individuals or species, social information might alter overall competitive outcomes. To test this potential, we present new theory that quantifies the effect of social information, modeled as predator avoidance signals/cues, on the outcomes from intraspecific and interspecific competition. Our analytical and numerical results reveal that social information can rescue populations from extinction and can shift the long-term outcome of competitive interactions from mutual exclusion to coexistence, or vice versa, depending on the relative strengths of intraspecific and interspecific social information and competition. Our findings highlight the importance of social information in determining ecological outcomes.

Incompetence of internal jugular valve in patients with primary exertional headache: a risk factor?

The pathophysiology of primary exertional headache (EH) is unknown. Physical exertion is associated with Valsalva-like manoeuvres (VM). VM leads to increased intrathoracic pressure and reduces cerebral venous drainage. Internal jugular vein valve incompetence (IJVVI) leads to retrograde venous flow during VM with transient increase of intracranial pressure. We analysed the prevalence of IJVVI in EH patients using duplex ultrasound. Bilateral measurements were performed at rest and during VM in 20 patients and 40 controls. Incompetence was concluded if retrograde venous flow could be seen in the jugular Doppler spectrum during repeated VM. Seventy percent of EH patients and 20% of controls demonstrated IJVVI, yielding a significant difference (P = 0.0004). IJVVI was always observed on the dominant venous drainage side. Our study suggests that intracranial venous congestion caused by retrograde jugular venous flow might play a role in the pathophysiology of EH with IJVVI as a risk factor.

The Posterior Cerebral Artery and its Main Cortical Branches Identified with Noninvasive Transcranial Color-Coded Duplex Sonography.

PURPOSE: To differentiate PCA segments and cortical branches by means of transcranial color-coded duplex sonography (TCCD) and to measure flow parameters at rest and during visual stimulation. MATERIALS AND METHODS: 60 healthy subjects with a good acoustic temporal bone window were examined. The main stem of the PCA (P1, P2 and P3) and 4 main cortical branches - the anterior temporal artery (ATA), the occipital temporal artery (OTA), the parietooccipital artery (POA) and the calcarine artery (CA) - were assessed using an axial transtemporal approach. Systolic and diastolic blood flow velocities (BFVs) were recorded at rest and during visual stimulation. RESULTS: Identification of the P1 segment of the PCA was successful in 97.5% (117/120) of cases. The P2 and P3 segments were visualized in all cases. The 4 main cortical branches could be identified to varying degrees: ATA in 88%, OTA in 96%, POA in 69% and CA in 62%. There was an evoked flow response in the P2 main stem and in all cortical branches. The most pronounced increase in diastolic/systolic BFV after visual stimulation test was seen in the CA (42%/35%), followed by P2 (30%/24%), the POA (27%/27%), the OTA (16%/13%) and the ATA (9%/8%). CONCLUSION: Insonation through the temporal bone window with TCCD confidently allows the assessment of the P1 to P3 segments of the PCA as well as the 2 proximal branches, the ATA and the OTA. An ultrasound-based classification of PCA anatomy and its cortical branches may be used as a noninvasive method for the evaluation of posterior circulation pathology.

Age-related changes of oxygen free radical production in the rat brain slice after hypoxia: on-line measurement using enhanced chemiluminescence.

Superoxide radical production in brain slices of 12-, 24- and 60-day-old rats was measured online during and after 15 min of hypoxia with lucigenin enhanced chemiluminescence. We found a typical radical burst after reoxygenation which developed with aging and is almost nonexistent in the youngest and most prominent in the oldest group. This cannot be explained by a decreasing tissue superoxide dismutase (SOD) concentration in the brain with aging, since the concentration of the enzyme, determined in the same age groups, increased with age.

Assessment of blood flow velocity and diameter of the middle cerebral artery during the acetazolamide provocation test by use of transcranial Doppler sonography and MR imaging.

BACKGROUND AND PURPOSE: Our purpose was to show changes in the diameter of the M1 segment of the middle cerebral artery (MCA) by using high-resolution MR imaging in patients with chronic internal carotid artery occlusion after IV administered acetazolamide challenge. Changes in blood flow velocity of the basal cerebral arteries are thought to correlate with changes of cerebral blood flow. Changes in the diameter of the basal cerebral arteries, however, might influence the validity of transcranial Doppler measurements. METHODS: Eight patients with internal carotid artery occlusion who were undergoing acetazolamide testing for assessment of cerebrovascular vasomotor reactivity were included in the study. Blood flow velocities of both MCAs were measured with transcranial Doppler sonography before and 25 minutes after the administration of acetazolamide. Before and 15 minutes after the administration of medication, MR imaging was performed contralateral to the occlusion side. A T2-weighted turbo-gradient spin-echo sequence was chosen to show a cross section of the M1 segment in high resolution (pixels, 0.27 x 0.29 mm). Based on interpolated data, the smallest and greatest MCA diameters were determined. RESULTS: We did not find changes in the diameter of the MCA after acetazolamide provocation testing with high-resolution MR imaging in patients with occlusive extracranial carotid artery disease. CONCLUSION: The results of our study support the hypothesis that changes in MCA flow velocity measured by transcranial Doppler sonography reflect relative changes in cerebral blood flow after acetazolamide provocation testing.

Magnetic resonance imaging in transient global amnesia: lessons learned from 198 cases.

PURPOSE: Patients with transient global amnesia (TGA) present with a characteristic clinical syndrome although other differential diagnoses have to be considered. Diffusion-weighted imaging (DWI) represents a highly specific diagnostic tool in the context of TGA; however, standard clinical DWI often fails to detect the small characteristic hippocampal lesions. The diagnostic success of DWI sequences in TGA patients was analyzed with respect to slice thickness and time interval between symptom onset. METHODS: Magnetic resonance imaging (MRI) studies of 198 patients with clinically diagnosed TGA were retrospectively analyzed. All DWI studies were grouped according to the slice thickness applied (3 mm, 5 mm and 6 mm). The three groups were assessed for group-specific detection rates of hippocampal lesions with diffusion restriction. In addition the detection rates were evaluated with respect to the time interval between TGA symptom onset and MRI examination. RESULTS: A significant increase in detection rates (about 8.4% per mm) was found when thinner slices were acquired (44.7% for 3 mm, 27.1% for 5 mm and 19.6% for 6 mm slice thickness). The detection rate was highest (up to 80%) when MRI was performed 2 days after TGA symptom onset. CONCLUSIONS: The MRI protocol in patients with TGA should include a DWI sequence with a slice thickness of 3 mm or less. The examination should be performed on day 2 after symptom onset to fully exploit the diagnostic value of DWI which represents a sensitive and specific diagnostic tool for patients with TGA.

Venous drainage in multiple sclerosis: a combined MRI and ultrasound study.

BACKGROUND: Chronic cerebrospinal venous insufficiency (CCSVI) was proposed as the causal trigger for developing multiple sclerosis (MS). However, current data are contradictory and a gold standard for venous flow assessment is missing. OBJECTIVE: To compare structural magnetic resonance venography (MRV) and dynamic extracranial color-coded duplex sonography (ECCS) in a cohort of patients with MS. METHODS: We enrolled 40 patients (44 ± 10 years). All underwent contrast-enhanced MRV for assessment of internal jugular vein (IJV) and azygos vein (AV) narrowing, graded into 3 groups: 0%-50%, 51%-80%, and >80%. ECCS analysis of blood flow direction, cross-sectional area (CSA), and blood volume flow (BVF) in both IJV and vertebral veins (VV) occurred in the supine and upright body position. RESULTS: MRV identified 1 AV narrowing. IJV analysis yielded 12 patients for group 1 (30%), 19 patients for group 2 (48%), and 9 patients for group 3 (22%). By ECCS criteria, 4 patients (10%) presented with venous drainage abnormalities. Jugular BVF was different only between groups 1 and 3 (616 ± 133 vs. 381 ± 213 mL/min, p = 0.02). No other parameters in supine position and none of the parameters in the upright body position, apart from the IJV-BVF decrease in groups 1 and 3 (479 ± 172 vs. 231 ± 144 mL/min, p = 0.01), were different. CONCLUSIONS: Our ECCS data contradict the postulated 100% prevalence of CCSVI criteria in MS. MRV seems more sensitive to detect IJV narrowing compared to ECCS. A measurable hemodynamic effect only exists in vessel narrowings >80%. Our combined data argue against a causal relationship of venous narrowing and MS, favoring the rejection of the CCSVI hypothesis.

Transcranial color-coded sonography successfully visualizes all intracranial parts of the internal carotid artery using the combined transtemporal axial and coronal approach.

BACKGROUND AND PURPOSE: Visualization of the intracranial internal carotid artery (ICA) with transcranial color-coded sonography (TCCS) by using the transtemporal coronal plane has been described previously. Because this approach is limited to the vertical running ICA segments, we investigated the feasibility of using TCCS to visualize all intracranial ICA segments by adding the transtemporal axial approach to the coronal plane. MATERIALS AND METHODS: Subjects with excellent transtemporal acoustic windows were examined by TCCS by using standardized axial and coronal planes. Identification rate, flow velocities, pulsatility and resistance indices, and length (as visible in color-coded power mode) were determined. RESULTS: A total of 120 intracranial ICAs from 60 subjects were investigated. By switching between the axial and coronal insonation planes, all intracranial segments of the ICA could be investigated in 100% of subjects-with the exception of the horizontal part of the petrosal ICA, which was identified in 96.7% of subjects. CONCLUSIONS: TCCS becomes a reliable tool in investigating all parts of the intracranial ICA by adding the transtemporal axial approach to the coronal plane.

Internal jugular vein valve incompetence and intracranial venous anatomy in transient global amnesia.

BACKGROUND: Recently a causal relation between internal jugular vein valve incompetence (IJVVI) and transient global amnesia (TGA) has been suggested. IJVVI is postulated to provoke a transient mesiotemporal ischaemia by venous congestion. This mechanism requires a patent venous pathway from the affected IJV through the transverse sinus, confluens, straight sinus (SS), vein of Galen into the basal vein of Rosenthal and the internal cerebral veins. OBJECTIVE: To study IJVVI in TGA patients in relation to the intracranial venous anatomy. METHODS: IJVVI was defined if a repeated Valsalva manoeuvre (VM) led to a retrograde jugular flow detected by extracranial duplex ultrasound. Non-contrast venous MR angiography (MRA) was performed to analyse intracranial drainage patterns of the SS in relation to the side of the IJVVI. SS drainage was differentiated into three groups: predominantly right, left, and bilateral drainage. Ultrasound studies were performed in 25 TGA patients and 85 age matched controls. Twenty patients underwent venous MRA. RESULTS: Sixty eight per cent of patients and 33% of controls showed unilateral or bilateral IJVVI (p = 0.0025). In 36% of patients a TGA preceding VM was reported. Drainage pattern of SS and side of IJVVI corresponded in five of eight patients (63%) with VM and four of 12 patients without VM (33%, p = 0.0994). CONCLUSION: Our study confirms the significantly higher prevalence of IJVVI in TGA patients. However, no specific IJVVI related intracranial venous drainage patterns could be found to further support the hypothesis of a direct causal relation between IJVVI and TGA.

Chaos and population disappearances in simple ecological models.

A class of truncated unimodal discrete-time single species models for which low or high densities result in extinction in the following generation are considered. A classification of the dynamics of these maps into five types is proven: (i) extinction in finite time for all initial densities, (ii) semistability in which all orbits tend toward the origin or a semistable fixed point, (iii) bistability for which the origin and an interval bounded away from the origin are attracting, (iv) chaotic semistability in which there is an interval of chaotic dynamics whose compliment lies in the origin's basin of attraction and (v) essential extinction in which almost every (but not every) initial population density leads to extinction in finite time. Applying these results to the Logistic, Ricker and generalized Beverton-Holt maps with constant harvesting rates, two birfurcations are shown to lead to sudden population disappearances: a saddle node bifurcation corresponding to a transition from bistability to extinction and a chaotic blue sky catastrophe corresponding to a transition from bistability to essential extinction.

Host-limited dynamics of autoparasitoids.

Autoparasitoids, an important class of intraguild predators used in classical biological control, have a unique biology. Females develop as primary endoparasitoids of scale insects and whiteflies. Males develop at the expense of conspecific or heterospecific parasitoid prepupae. To evaluate the effect of autoparasitism on host suppression, system stability, and parasitoid coexistence, stage-structured differential equation models are developed and analysed. For a host-parasitoid system, autoparasitism stabilizes host-parasitoid oscillations generated by developmental delays of the parasitoid. In host-autoparasitoid-primary parasitoid systems, a distinction between obligate (i.e. parasitoid only attacks conspecifics for the production of males) and facultative (i.e. parasitoid attacks conspecifics and heterospecifics for the production of males) autoparasitism is drawn. Coexistence between an obligate autoparasitoid and primary parasitoid occurs if and only if the autoparasitoid can invade at lower host densities than the primary parasitoid, and the primary parasitoid can suppress the host to a lower equilibrium density than the autoparasitoid. When coexistence occurs, the primary parasitoid determines the host equilibrium abundance. Interactions between facultative autoparasitoids and primary parasitoids can lead to a priority effect, and, less likely, to coexistence. When coexistence occurs, the invasion of the facultative autoparasitoid into the host-primary parasitoid system raises the equilibrium density of the host. In either coexistence scenario, the invasion of an autoparasitoid can stabilize an unstable host-primary parasitoid system. The analysis concludes by showing that the introduction of an autoparasitoid to a host-primary parasitoid system can improve host suppression in the short-term despite possible long-term disruption.

Transcranial ultrasonography of cerebral veins and sinuses.

Transcranial ultrasonography has become a valuable diagnostic tool for the bed-side evaluation of cerebral hemodynamics. While the assessment of arterial blood flow is well established, analysis of venous hemodynamics by transcranial ultrasonography is a new application of the method. The present review summarises the current state of transcranial venous ultrasound in adults by means of transcranial Doppler (TCD) and transcranial colour-coded duplex sonography (TCCS). It gives a critical overview regarding current and possible future clinical applications of the techniques.

Effects of prolonged head-down tilt on internal jugular vein cross-sectional area.

BACKGROUND: Head-down tilt is often used to assist cannulation of the internal jugular vein (IJV). However, the optimal duration of tilt before cannulation is not well defined. METHODS: Fifteen healthy volunteers were studied by B-mode duplex sonography to assess changes in cross-sectional area (CSA) of the right IJV during 10 degrees head-down tilt. RESULTS: Median CSA in the supine position was 102 mm(2) [range 16-266, mean (SD) 113 (69)]. CSA increased to 139 mm(2) [23-388, 158 (93)] immediately after tilting (P<0.0001, repeated measures ANOVA). No significant further change was noted in the next 20 min. CSA returned to baseline level after return to the supine position. CONCLUSION: The 10 degrees head-down tilt manoeuvre in healthy volunteers causes an immediate, significant increase in CSA in the right IJV. A longer tilt did not cause further increase in jugular CSA.