Tutorials. Abstracts. TCD protocol. Supraortic vessels

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1 Abstracts Cerebrovasc Dis 04;7(suppl):-6 Tutorials T Supraortic vessels E. Bartels Center for Neurological Vascular Diagnostics Neurological office, München, Germany In this lecture the scanning protocol for the examination of extracranial brain supplying arteries using color-coded duplex ultrasonography, the normal results and some typical vascular pathological findings will be presented. A linear-array transducer with an operating frequency of 5-0 MHz is used for imaging cervical vessels. ree different approaches are convenient to insonate the extracranial carotid arteries: transverse, anterolateral longitudinal and posterolateral longitudinal projection. e internal carotid artery (ICA) differs from the external carotid artery (ECA) in that its lumen is usually wider at the origin (carotid sinus or carotid bulb). In the carotid sinus, in addition to the red laminar flow a blue coded area so called flow separation zone - can be observed. e branches of the ECA (superior thyroid artery and lingual artery) can o en be well imaged. It is possible to differentiate between the cervical arteries by recording the corresponding spectral waveforms from the representative segments of the vessel. e spectral waveform of the ICA is characterized by a high diastolic component. e audio signal of the ICA is so and slightly hissing, that of the ECA is sharper and lashing. To obtain a more exact measurement of flow velocity, angle correction is carried out by manually positioning the cursor of the sample volume as parallel as possible to the vessel wall. In examination of the vertebral arteries (VA), for an initial orientation the transducer is positioned in the midcervical region paramedian perpendicularly in the anteroposterior plane, so that the distal V and the proximal V segments are visible. Due to the acoustic shadow caused by the transverse processes of the 6 th to the rd vertebrae, this section is the easiest to identify in a B-mode image. Between the transverse processes of the cervical spine the vertebral artery and usually the corresponding vertebral vein appear to follow a straight course. e imaging of the cervical course, the atlas loop region (V segment) and the origin of the VA - with the typical hemodynamic characteristics - will be presented in detail. Conclusion: Color-coded duplex ultrasonography is a valuable method in neurovascular diagnostics. In the hands of an experienced examiner, it is a reliable tool in the evaluation of cerebrovascular diseases. T TCD protocol Z. Garami Methodist Hospital, Houston, Texas, USA e goals of a non-image-guided single gate spectral TCD examination are:. to follow the course of each major branch of the circle of Willis with spectral display;. identify, optimize and store the highest velocity signals;. TCD spectra should be obtained at least two key-points per artery and 4. identify, optimize and store any abnormal or unusual waveforms. Transorbital insonation steps : (I am starting with transorbital so after that I can increased the power for the rest of the exam): Step : Decrease power to minimum (7 mw) or 0%. Set the depth at 50 mm, place the transducer over eyelid and angle it slightly medially. Determine flow pulsatility and direction in the distal ophthalmic artery. Step : Increase the depth to mm and find the ICA siphon flow signals. e siphon signals are usually located medially in the orbital window. Store bidirectional signals at 6 mm (C or the siphon genu). Transtemporal insonation steps: Step : Set the depth at mm (mid point of the M MCA segment was established at approximately 50 mm depth. Place the probe above zygomatic arch and aim it slightly upwards and anterior to the contralateral ear/window. Find any flow signal (window), and avoid too anterior and too posterior angulation. Find a flow signal directed towards the probe which resembles MCA flow. A normal MCA flow is a low resistance waveform similar to the ICA flow pattern. By decreasing the depth, follow the signal to the distal M key-point of insonation without losing the signal. O en, a slight adjustment of the probe angulation is needed. Store distal M MCA signal at 45 mm. If bi-directional signals are found, store the highest velocity signal in each direction (distal M proximal M branches). Step : Follow the signals until they disappear at shallow 0-45 mm depths. Store any abnormal signal. Return to the distal M MCA signal. Step : Follow the M MCA stem to its origin at mm depths dependently on the size of adult patient skull. Pay attention to the sound and velocity changes since insonation of the terminal ICA is also possible at these depths. Find the ICA bifurcation at approximately 65 mm (range mm in adutls) and obtain both proximal M MCA and proximal A ACA signals. Store a bi-directional signal of the bifurcation (M/A). Step 4: Follow the A ACA signal to mm depths. Store the distal A ACA signal at 70 mm. Step 5: Follow the distal A ACA signal to the midline depth Fax karger@karger.ch 04 S. Karger AG, Basel /4/ $9.50 Accessible online

2 range (75 80 mm). e A ACA signal may disappear or a bi-directional signal may appear at the midline depth. Store any abnormal signals. Return to bifurcation at 65 mm. Step 6: Find the terminal ICA signal just inferior and sometimes slightly posterior to the bifurcation at mm. If the probe is angled inferior and anterior to the ICA bifurcation at mm depths, the distal part of the supraclinoid siphon can be found through the temporal window. Store any abnormal signal.return to the bifurcation at 65 mm. Step 7: Set the depth at 6 mm and slowly turn the transducer posteriorly by 0-0 degrees. Usually there is a flow gap between the ICA bifurcation and the PCA signals. Find PCA signals directed towards (P) and away (P) from the probe at a depth range of mm. Store the PCA signals with the highest velocity. Transforaminal insonation steps: Step : Set the system back to full power. Place the transducer at midline an inch below the edge of the skull and aim it at the bridge of the nose. Set the depth at 75 mm (presumed location of both terminal VA s and proximal BA). Identify a flow signal directed away from the probe, i.e. find the window. is signal can be arbitrarily assigned to the terminal vertebral arteries (slightly lateral probe angulation) or the proximal basilar artery (medial and slighlty upward angulation). Increasing the depth, follow the flow directed away from the probe. is depth increase presumably focuses the beam on the proximal BA in most adults. Store the proximal BA signal arbitrarilly assigned to the depth of 80 mm. Step : Follow the basilar artery to 90 mm (mid-ba segment). Bidirectional signals may be found at various depths with a low resistance flow in the cerebellar arteries directed towards the probe. Store any abnormal signals. Step : Follow the distal BA segment to the depth of 00+ mm until it disappears or is replaced by the anterior circulation signals. Store the highest velocity signal obtained at the most distal depth of the basilar artery insonation. Step 4: Follow the stem of the basilar artery backwards while decreasing the depth of insonation to 80 mm and confirm previous findings. Step 5: Place the probe about an inch laterally to the midline and aim towards the bridge of the nose or slightly towards the contralateral eye.find the vertebral artery (VA) flow signal directed away from the probe. Follow the course of the terminal VA segment intracranially from 80 mm to 40 mm. Store the VA signals at 60 mm or at the depth of the highest velocity signal. Step 6: Place the probe on the contralateral side an inch off the midline position. Repeat the VA examination steps for the contralateral vessel from 80 to 40 mm. Store the VA signals at 60 mm or at the depth of the highest velocity signal. Submandibular insonation steps (only for SAH protocol): Step : Place the probe laterally under the jaw anterior and medial to the sterno-cleido-mastoid muscle. Aim the transducer upwards and slightly medially. Set the depth at 50 mm. Find a low resistance flow directed away from the probe. Step : Increase the depth from 50 to 60 mm and decrease to 40 mm. Store the distal ICA signal at the depth that shows the highest velocity signal. At a shallow depth, perform the temporal artery tap to differentiate with the external carotid artery flow signals. T Transcranial colour-coded Duplex sonography (TCCS) J.M. Valdueza Neurological Center, Segeberger Kliniken, Bad Segeberg, Germany Insonation planes facilitate the anatomical orientation using TCCS. As in MRI and CT, the axial planes are of greatest relevance. B-mode visualization of bone, parenchyma, vessel sheaths and ventricles are helpful in identification of planes. Transtemporally, five axial (lower pons, upper pons, midbrain, thalamus, cella media) and two coronal (anterior and posterior) planes should be distinguished. TCCS starts with a transtemporal axial insonation. In the midbrain plane the M and M of the MCA, the A and A of the ACA, and P and proximal P of the PCA and the head of the basilar artery (BA) were visualized. By lowering the insonation angle by approximately 0 the upper pontine plane displayed the carotid siphon, ophthalmic artery (OA), posterior communicating artery. Tilting another 0 the lower pontine plane the C6 of the ICA is visualized. Pointing the transducer 0 upward from the midbrain plane, the thalamic plane is displayed with both hypoechogenic thalami embracing the third ventricle and the hyperechogenic pineal gland. Here the M, M, distal P and P can be seen. e cella media plane is of less importance. Transtemporal coronal planes may be the first choice to analyze craniocaudally orientated vessels. e anterior coronal plane particularly facilitates the visualization of the intracranial ICA. e posterior coronal plane is useful to analyze the BA and to distinguish the proximal PCA from the superior cerebellar artery. Transforaminally the distal vertebral artery (VA) V and V4, and the at least proximal part of the BA can be visualized. Finally, the OA is detectable via a transorbital approach. In excellent insonation conditions and with good anatomical knowledge more peripheral vessel segments, cerebellar arteries and even cortical branches may be seen. Signal quality depends mainly on power, gain, and filters. e size of the colour window and the PRF further influence the sensitivity of colour and flow signal. Angle-correction of flow velocities is only recommended if a straight vessel segment of at least to.5 cm can be visualized. T4 Carotid intima-media thickness (cimt) T. Rundek Department of Neurology and Department of Public Health Sciences, University of Miami, Miller School of Medicine, Miami, FL, USA Carotid atherosclerotic disease plays a large role in the etiology of stroke. B-mode carotid ultrasound has been widely used to detect subclinical carotid atherosclerosis by quantifying carotid intima media thickness (cimt) and carotid plaque (CP). Both cimt and CP have been accepted surrogate imaging biomarkers of subclinical atherosclerosis until recently when it became increasingly Cerebrovasc Dis 04;7(suppl):-6 9th Meeting of the European Society of Neurosonology and Cerebral Hemodynamics

3 clear that cimt and CP might be genetically and biologically distinct atherosclerotic phenotypes with evidence of heterogeneous etiology. In addition, carotid atherosclerotic plaque burden, defined as the two-dimensional total plaque area (TPA) or tree-dimensional total plaque volume is a powerful non-invasive imaging tool for vascular risk estimation and may be a stronger predictor for future ischemic stroke than cimt. cimt and CP have been associated with prevalent and incident atherosclerotic disease with variable effects. Whether cimt and CP are distinct phenotypes or represent a single trait at a different stage of atherosclerotic lesion development is still unclear and under intense research investigations. cimt may represent adaptive changes to increased shear stress with aging and therefore the pathophysiological significance of arterial wall thickening with regard to transformation into atherosclerotic plaque may be questionable. Experimental and epidemiological studies have not yet clarified this dilemma. is live demonstration will present a cimt ultrasound scanning protocol and discuss various approaches to measuring cimt and plaque in the context of adaptive changes in the arterial wall with aging and their relations to the development of atherosclerosis. T5 Cerebrovascular reactivity assessment F.A. Sorond Cerebrovascular Laboratory, Brigham and Women s Hospital, Boston, MA, USA Changes in arterial PaCO have profound effect on the healthy cerebrovascular bed. Aging and vascular disease are associated with impaired sensitivity of the cerebral vessels to changes in arterial PaCO. Transcranial Doppler ultrasound can be used to measure the responsiveness of the cerebral vessels to changes in arterial PaCO. Increased PaCO causes vasodilatation of the resistance arterioles resulting in increased cerebral blood flow velocity in the large arteries and decreased PaCO causes a reduction in cerebral blood flow velocity due to arteriolar vasoconstriction. Cerebrovascular reactivity or cerebral vasoreactivity is a measure of the relative changes in cerebral blood flow velocity to changes in PaCO. Changes in CO can be induced by breath-holding, CO -rebreathing, acetazolamide, or by ventilatory alterations (hypo or hyper) of CO. It is important to note that the traditional measures of cerebrovascular (or vasomotor) reactivity or cerebral vasoreactivity are not the same as the measures of cerebral autoregulation and therefore the terms should not be used interchangeably. Dissociation between cerebrovascular reactivity and cerebral autoregulation has been demonstrated in many medical conditions such as hypertension, sleep apnea, congestive heart failure, carotid artery stenosis and cerebral ischemia. e aim of this tutorial is to ) give an overview of the methodologies used to measure cerebral vasoreactivity and ) demonstrate one of the approaches for measurement of cerebral vasoreactivity. T6 Patent foramen ovale detection F. Sallustio Stroke Unit, Department of System Medicine, University of Rome Tor Vergata, Rome, Italy Diagnostic interest: Patent foramen ovale (PFO) has been associated with paradoxical embolism through a permanent or transient right-to-le shunt (RLS). Despite a conclusive proof of a relationship between PFO and its clinical manifestations remains elusive, PFO detection still represents an important step in the diagnostic work-up of cryptogenic stroke. For this purpose contrastenhanced transcranial Doppler (c-tcd) is a valid tool and alternative to transesophageal echocardiography (TEE) - considered the gold standard - taking into account the high concordance between them reported in the literature. Technique of examination: With the patient in supine position and a needle inserted into the cubital vein, insonation of at least one middle cerebral artery (MCA) is performed. e contrast agent (CA) is prepared by a 9 ml isotonic saline solution agitated with ml air and injected as a bolus through a three-way stopcock. In presence of RLS the contrast agent bypasses the pulmonary circulation and reaches the basal cerebral arteries where is detected by TCD as microembolic signals (MES). If any or only few MES are detected under basal conditions, the examination is repeated during a Valsalva maneuver. Diagnostic criteria: Doppler spectra are stored for offline analysis of the time of occurrence and number of MES in order to define the size of RLS based on a four-level categorization: ) 0 MES (negative results); ) -0 MES; ) >0 MES but without curtain (a shower of MES where a single signal cannot be identified); 4) curtain. Conclusion: Considering that PFO diagnosis requires both a physiologic and anatomic definition, c-tcd and TEE should be considered as complementary methods to improve the diagnostic accuracy in clinical practice. T7 Brain parenchyma imaging U. Walter Department of Neurology, University of Rostock, Rostock, Germany Transcranial B-mode sonography (TCS) is a non-invasive, lowcost, short-duration neuroimaging method that allows high-resolution imaging of deep brain structures in patients with inflammatory and degenerative brain diseases. Hyperechogenicity of the substantia nigra (SN), a TCS finding present in about 90% of patients with idiopathic Parkinson s disease (PD), is already present in presymptomatic disease stages. e results of recent longitudinal studies suggest that TCS of SN may serve as a screening tool for detecting subjects at risk of later developing PD. In a large study we could show in addition that the combination of TCS with simple olfaction and motor tests already at very early disease stages discriminates PD from other parkinsonian disorders. In turn, nor- Abstracts Tutorials Cerebrovasc Dis 04;7(suppl ):-6

4 mal SN echogenicity in combination with lenticular nucleus hyperechogenicity indicates an atypical Parkinsonian syndrome rather than PD with a specificity of more than 95%. TCS detects characteristic basal ganglia changes also in other movement disorders such as lenticular nucleus hyperechogenicity in idiopathic dystonia and caudate nucleus hyperechogenicity in Huntington's disease. Lenticular nucleus hyperechogenicity in Wilson s disease has recently been proven histochemically to be caused by copper accumulation, while the same TCS finding is caused by iron accumulation in hereditary disorders with brain iron accumulation such as PKAN and MPAN. Reduced echogenicity of midbrain raphe is frequent in depressive disorders and correlated with both, suicidal ideation and responsivity to serotonin reuptake inhibitors. An elegant application of TCS is the intra- and postoperative localization of deep brain stimulation electrodes in patients with movement disorders. Upcoming technologies such as digitized image analysis and TCS-MRI fusion imaging will promote novel diagnostic applications of TCS. T8 Transcranial imaging of the venous system E. Stolz Dept. of Neurology, Caritasklinikum, St. Theresia, Saarbruecken and Justus-Liebig-University Giessen, Germany This presentation summarizes the steps necessary to perform an ultrasound examination of the intracranial venous system. Machine settings consist of (a) a low-flow sensitive color program, (b) a low wall filter setting, (c) a reduced pulse repetition frequency, and (d) an increased color gain at the threshold of color artifacts. rough the temporal bone window the deep middle cerebral vein is found adjacent to the middle cerebral artery and the basal vein by following the posterior cerebral artery to its P segment. e venous signal emerging behind the echogenic pineal gland belongs to the great cerebral vein of Galen. e sphenoparietal and superior petrosal sinuses are found in the echogenic lesser and mayor wing of the sphenoid bone. By upwards rotation of the anterior transducer tip the examination plane is aligned with the plane of the cerebellar tentorium, where the straight sinus is depicted. By downwards tilt of the probe the transverse sinus can be examined. If acoustic penetration is good, the paramedian frontal bone window allows examination of the internal cerebral veins and the vein of Galen, while through the occipital bone window the straight sinus and the vein of Galen might be depicted. In the transnuchal plane the inferior petrosal sinus can be insonated. In every venous structure flow velocities are measured and flow direction is registered. T9 TCCS insonation with fusion MRI imaging S.J. Schreiber Dept. of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany TCCS is a well-established method for studying intracranial parenchymal and vascular structures. However, the need to insonate through the transcranial bone windows o en results in oblique imaging planes, which may impair easy allocation of structures, e.g. within the brain parenchyma and hinder a direct comparison with other imaging techniques. Ultrasound fusion imaging (UFI) is a new technique, permitting an online matching and comparison of live ultrasound images with pre-registered CT or MR images by means of a local electromagnetic field. In the tutorial, the principles and the setup of the technique for transcranial UFI is demonstrated and examples of its use in assessing established insonation planes as well as some examples of potential clinical applications are given. Consensus Meeting C Sickle cell disease (SCD) in children: Clinical features and neurologic complications L. Sainati Onco-ematologia Pediatrica, Dipartimento della donna e del bambino, Azienda Ospedaliera di Padova, Italy SCD is a monogenetic disorder caused by a mutation in the β- globin gene in which a nucleotide is changed from thymine to adenine and the glutamic acid is replaced by a valine. It is one of the most common genetic diseases worldwide. e mutation produce a hydrophobic binding in the deoxygenated HbS tetramer with consequent polymerization, precipitation and disruption of erythrocyte shape and its flexibility. is is cause of cellular dehydratation, oxidative stress and haemolysis. e disease is due to two major pathophysiological processes: vaso-occlusion with ischemiareperfusion injury and haemolytic anaemia. e most dramatic event is stroke, mostly associated with vasculopathy affecting the distal internal carotid and middle cerebral arteries, although extracranial vasculopathy can be present. Contributory factors in pathogenesis include anaemia, leucocytosis hypoxaemia, abnormal rheology causing endothelial damage, nitric oxide deficiency associated with haemolysis, and impaired regulation of blood flow causing hyperaemia. e vasculopathy starts in infancy, with higher incidence between and 5 years old; by the age of 8 % of the patients had 4 Cerebrovasc Dis 04;7(suppl):-6 9th Meeting of the European Society of Neurosonology and Cerebral Hemodynamics

5 an overt. Chronic transfusion keeping HbS lower than 0% prevent primary stroke; but this procedure is very demanding and it is associated with severe complication as iron overload or infection. It is necessary to select patients that need to be treated. TCD is able to select patients with higher risk. In a large number of patient it has been demonstrated that using an appropriate TCD protocol is possible to stratify the patients in categories depending on the blood speed of two intracranic vessels (MCA and dica). e patients with speed higher that 00 cm/sec have 0% of risk to present a stroke in the year if not treated and are protected if undergo a program of chronic transfusion. In these patients a SCT, the only curative treatment available at the moment, could be indicated. C TCD in sickle cell disease and stroke risk S. Mazzucco Stroke Prevention Research Unit, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK Sickle cell disease refers to at least 5 different genotypes of haemoglobinopathies, from the homozygous (Hb SS) form of the disease, also called sickle cell anemia (SCA) to other conditions caused by combinations of the hemoglobin S allele with other hereditary hemoglobin disorders such as Hb S/ß+ thalassemia and Hb S/ß0 thalassemia. Stroke is one of the possible protean presentation of the disease, which overall results in a reduction of 5 to 0 years of life expectancy of SCD patients compared to the general population. In high income countries, several aspects of the management of SCD patients have contributed to decrease both mortality and disability. One is primary prevention of strokes through the identification and of high risk children using transcranial Doppler (TCD), and early treatment with red blood cell transfusions. Current guidelines for TCD screening and risk stratification of children with SCD are mainly based on the Stroke Prevention Trial in Sickle Cell Anemia (STOP), which included patients with SCA aged between and 6 years. Nevertheless, across the world, many different versions of this protocol are used, according to local needs, infrastructure accessibility, training, and health care policy. Accordingly, there is some heterogeneity in the actual delivery of the screening protocol, and some issues are not universally acknowledged, like the reliability of imaging TCD in children screening, generalizability of TCD cut-off to genotypes other than SCA, the cerebral blood flow velocity on which clinical decision should be made, the physiological and pathological factors that should contribute to clinical management (fever, anemia, respiratory infections). e aim of the Consensus Conference is to acknowledge the existence of these o en overlooked issues and to find and agreement upon them in order to standardize the practice of screening children with SCD in European Countries. C Issues with the application of TCD imaging in screening children with sickle cell disease S. Padayachee Ultrasonic Angiology Department, Guy s & St Thomas NHS Foundation Trust, London, UK e STOP trial provides Level evidence of the efficacy of Transcranial Doppler Ultrasound (TCD) screening for significant reduction of primary stroke risk in children with sickle cell disease. is is achieved if lifelong transfusion is offered to children with blood velocities of >00cm/s in the middle cerebral or terminal internal carotid arteries. As a result, TCD surveillance is considered standard management for the prevention of stroke in children with SCD. However, some 5 years since the STOP trial, screening remains inadequate with under 50% of children with SCD receiving TCD screening in Europe. e major limiting factor is the lack of adequately trained TCD operators but other factors influence the success of TCD screening including; lack of standardisation with respect to TCD protocols, STOP velocity thresholds and the level of experience of personnel performing TCD screening. e urgent need for TCD screening, particularly in remote areas or where there are small numbers to screen, currently outweighs concerns regarding the accuracy of TCD screening when performed by inexperienced operators. Reports that TCD imaging can underestimate non-imaging TCD are inconsistent and may be largely protocol-related. Current recommendations are inconsistent with respect to STOP imaging velocity thresholds and may result in erroneous treatment selection. is presentation reviews factors influencing successful TCD screening and focuses on protocol issues related to imaging TCD. e impact of modular TCD training to address issues of protocol standardisation, quality assurance and to enable more widespread delivery of accurate TCD screening will be discussed. Lectures L The sound of ultrasound R. Aaslid Hemodynamics AG, Bern, Switzerland Ultrasound is by definition not audible but our clinical instruments transform the ultrasound into audible sound. is process is non-linear, and the actual sound we hear depends to a great extent on the instrument design and on the settings selected by the operator. is presentation will demonstrate and discuss how the actual audible sound is affected by hardware and so ware Abstracts Lectures Cerebrovasc Dis 04;7(suppl ):-6 5

6 in the instrument, and give an overview of how to achieve optimal settings. In patients with cerebrovascular disease, we shall expect a wide spectrum of sounds. e Doppler shi created by the moving blood is the most prominent part of the audible signal. But the sound (and the spectral display) is also influenced by other physical phenomena. It is important to be aware of the non-doppler part of the sound and some examples of this will be presented. In clinical cases, an experienced operator can make an assessment of the cerebral circulation just by listening to the sound. e presentation will demonstrate how different pathologies create different sound patterns. And last but not least: how to use the sound of ultrasound to optimize the exam and the efficacy of the procedure. L Pre-hospital thrombolysis is the ultrasound diagnosis of occlusion enough? F. Schlachetzki, M. Herzberg, K. Pflug, R. Backhaus, D. Baldaranov, M. Ertl, S. Boy Department of Neurology, University of Regensburg, Bezirksklinikum Regensburg, Germany Rapid stroke diagnosis is the pre-requisite for successful ischemic stroke therapy and IV thrombolysis to recanalize occluded brain supplying arteries to date remains the only approved medical therapy. Pre-hospital stroke therapy based on mobile ultrasound equipment is an intriguing thought as it may a) shorten stroke symptom-to-therapy times, b) introduce therapy to stroke patients in rural areas lacking dedicated stroke units and c) combine sonothrombolysis therapy under real-time diagnostic surveillance. We could recently demonstrate that an experienced neurologist equipped with a mobile color-duplex system and ultrasound contrast agents can diagnose middle cerebral artery occlusion (MCAO) with 90% sensitivity and a specificity of 98%. However, apart from these major stroke syndromes, sensitivity and specificity drops to 94% and 48%, respectively, when aiming to diagnose any stroke. ese data imply that, at the moment, prehospital thrombolysis based on neurological examination and transcranial ultrasound might only be possible in severe hemispheric stroke compatible with contralateral diagnosed MCAO when additional information such as untreated atrial fibrillation and exclusion brain hemorrhage i.e. by point-of-care glial fibrillary acidic protein detection becomes available. At the moment, pre-hospital appears a daring deed based on pathophysiology but with the addition of telecommunication to dedicated stroke centers it has the potential to become widespread option decreasing the stroke burden for society. L Sonothrombolysis: A 5 years perspective A. V. Alexandrov, on behalf of CLOTBUSTER investigators Department of Neurology, The University of Tennessee Health Science Center, Memphis, TN, USA Background: Transmission of a mechanical energy momentum to a thrombus/residual flow interface facilitates delivery of tissue plasminogen activator (tpa) to binding sites thereby facilitating enzymatic fibrinolysis with ultrasound in MHz frequency range. Methods: a er initial observations of dramatic clinical recovery during tpa infusion coupled with transcranial Doppler monitoring, our collaborative group developed a novel operator independent therapeutic device for delivery of pulsed wave ultrasound energy at doses of patient exposure in the CLOTBUST trial. We have tested the device in phase II studies and demonstrated its safety and signal of efficacy in augmentation of tpa induced recanalization of intracranial occlusions in acute stroke patients. Results: We are conducting a phase III multi-national randomized double blind trial of sonothrombolysis (CLOTBUSTER, NCT all patients with NIHSS scores >0 points receive iv tpa per national label, half exposed to MHz pulsed wave ultrasound, half to sham delivered thru the operator-independent device. Primary outcome is modified Rankin score 0- at month. Projected sample size 80 patients, enrollment commenced in spring 0 with up to 70 sites being activated in 4 countries. Conclusions: CLOTBUSTER trial is the first phase trial of sonothrombolysis in clinical medicine. It is also a controlled trial of a device in acute ischemic stroke powered to demonstrate efficacy to improve outcomes a er stroke. L4 Ultrasound diagnosis and clinical correlations of intracranial arteries stenosis C. Baracchini Department of Neuroscience, University of Padova School of Medicine, Padova, Italy Stroke is a dynamic disease, consequently static neuroimaging studies (CT, MRI) characterize this process only partially. Transcranial ultrasound provides not only static imaging, but mainly accurate information on cerebral hemodynamics thus offering invaluable information on the pathophysiology of stroke allowing for tailored treatment and representing the ideal modality for following disease progression and therapeutic effects. Direct ultrasound criteria for proximal intracranial artery occlusion include no flow signal and minimal flow signal, while blunted flow signal and dampened flow signal are criteria for distal occlusion. Direct criteria for intracranial artery stenosis include progressive focal increase of blood flow velocities in 50% stenosis or paradoxical velocity decrease with very severe stenosis, near-occlusion or diffuse intracranial disease. Indirect criteria for intracranial arterial occlusion/high grade stenosis comprise high resistance in the feed- 6 Cerebrovasc Dis 04;7(suppl):-6 9th Meeting of the European Society of Neurosonology and Cerebral Hemodynamics

7 ing vessel or in the proximal segment of the occluded vessel, flow diversion and signs of collateralization. e causative nature of intracranial artery occlusion/stenosis (embolic, atherothrombotic, dissective, arteritic), the site (anterior vs posterior circulation, main stem vs branch obstruction) and the time to occlusion (acute vs chronic) partly determine the quality of collaterals activated (adequate vs inadequate) and consequently define the clinical presentation and outcome. Neurological deterioration can be prevented by supporting collateral flow and by the ultrasound detection of cerebral hemodynamic perturbations such as hyperemia (a er systemic thrombolysis and intra-arterial reperfusion) and blood flow steals which can occur at any level of the intracranial circulation (large proximal vessels, small distal vessels). Finally, the study of vasomotor reactivity recognizes patients at higher risk of hemodynamic stroke, while microembolic signal detection identifies patients who are at higher risk of athero-embolic stroke and might benefit from a more aggressive treatment. L5 Patient selection for interventions and treatments S. Mangiafico Careggi University Hospital Interventional Neuroradiology Unit, Florence, Italy Since SAMMPRIS was published in 0, symptomatic patients with intracranial atherosclerotic stenosis all have to be treated with aggressive medical therapy before carrying out an endovascular approach due to the high 0 day-mortality rate in patients treated with stenting. Even though the SAMMPRIS long term follow-up results have been recently published and show the superiority of medical treatment in the prevention of a second ischaemic attack a er months, many single centres published their own series and proved the effectiveness and safety of stenting, and PTA, in their hands. Some scientific societies critically analysed the SAMMPRIS, too, authorising the use of Wingspan and PTA, despite medical therapy in their countries, considering the lower rate of adverse events in the clinical practice and the data reported in the Wingspan humanitarian device exception study, and Wingspan registries that showed a lower complication rate in comparison to SAMMPRIS. Surely intracranial atherosclerosis is a complex disease carrying a high risk of recurrence of ischaemic stroke and death, both in patients treated with medical therapy and stenting, or PTA: for this reason, analysing case by case all the different patients is absolutely necessary. A weak point in the planning of SAMMPRIS is that it attempts to compare two therapies (medical versus stent-assisted angioplasty) intended for different purposes; stent assisted angioplasty was, by defined indication, never intended for use in any but failed medical outcomes and can, in no way, be considered as an appropriate competitive therapy for patients with intracranial stenosis responsive to medical management. Balloon angioplasty and stenting is unsuitable for indiscriminate application and should be reserved for appropriate patients who fail optimized medical regimens. On the other hand, it should be well kept in mind that carefully performed angioplasty and stent deployment may prevent stroke and permanent disability in the most critical cases. In the future, we expect new medical protocols to reduce the evolution of the stenosis and, in the cases treated with stenting, that new drugs to reduce the restenosis come on the market. L6 Review of the ultrasound criteria for quantification of ICA stenosis J. Klingelhöfer Department of Neurology, Medical Center Chemnitz, Chemnitz, Germany e classification of internal carotid artery (ICA) stenosis is of great impact. e degree of stenosis is the main criterion for the decision between an invasive or non-invasive treatment of extracranial ICA stenoses. By now the NASCET criteria have been internationally approved for ICA grading. All ultrasound criteria do have limitations and can therefore cause pitfalls in determining the degree of stenosis using one criterion exclusively. e approach of peak systolic velocity (PSV) for many reasons and no matter what threshold-psv was chosen is of limited value if taken as the primary and only criterion. erefore a multi-parametric grading of stenoses should be favoured. e multi-parametric DEGUM ultrasound criteria have been revised and a novel differentiation between main (primary) and additional (secondary) criteria has been proposed. Recently a similar consensus was reached by the Neurosonology Research Group (NSRG) of the WFN (Stroke 0; 4: 96-). e differentiation between main and additional criteria is caused by their different reliability. Main criteria include the following: imaging of the stenosis in B-mode sonography; visualization of the stenosis by color-coded imaging of flow; measurement of PSV in the area of greatest narrowing of the lumen; measurement of PSV in the poststenotic segment; assessment of the collateral supply. Additional criteria include the following: prestenotic flow velocity deceleration in the common carotid artery; evidence of poststenotic flow disturbances; end-diastolic flow velocity in the area of greatest narrowing of the lumen; the so-called confetti-sign; the carotid ratio. e main advantage of a multi-parametric grading of ICA stenoses is the synergetic effect of the different single criterion. Combining these ultrasound criteria, neurosonography allows reliable and reproducible grading of carotid stenoses as a basis for decision making. L7 The unstable carotid artery plaque D. Russell Neurology Department, Oslo University Hospital, Rikshospitalet, Oslo, Norway Several non-invasive imaging modalities have shown their potential to identify unstable carotid artery plaques. Echolucent plaques are thought to be more unstable than echo-rich plaques Abstracts Lectures Cerebrovasc Dis 04;7(suppl ):-6 7

8 and carotid plaque surface irregularities may correlate with the presence of cerebrovascular symptoms. Symptomatic patients with microembolic signals (MES), assessed by TCD, have been shown to be at high risk for developing ipsilateral stroke. Whether MES positive asymptomatic patients also are at increased risk has not been clarified. e use of microbubble-based ultrasound contrast agents may be helpful in detecting plaque surface irregularities and plaque neovascularization. MRI characterization of carotid plaque has shown that the presence of intraplaque hemorrhage, lipid-rich necrotic core, and thinning/rupture of the fibrous cap on MRI is associated with increased risk of future stroke or transient ischemic attacks. e use of a contrast agent improves quantification of total plaque burden, and contrast between fibrous cap and lipid core. Dynamic contrast-enhanced MRI allows assessment of plaque neovascularization. Currently, there are few in vivo human studies on functional imaging of carotid plaques: these initial studies have shown the potential of USPIO-enhanced MRI and 8F-FDG PET to identify inflammation, the potential of annexin A5 scintigraphy to identify cell death, and the potential of platelet scintigraphy to depict plaque thrombosis. More research is needed to determine their value in risk stratification. Biomarkers have been shown to improve prediction independent of conventional risk factors. Matrix metalloproteinase 7 (MMP-7) and the calcium-binding proteins calgranulins (S00A) are two such candidates. It is at present undecided whether one imaging modality or a multimodality approach is the most effective. Prospective clinical trials are needed to demonstrate if imaging methods do indeed result in an improvement in defining unstable carotid artery plaques and if they can predict patient outcomes, particularly in asymptomatic subjects. L8 Carotid stenosis, impaired cerebral hemodynamics and cognitive impairment L. Buratti, M. Silvestrini Neurological Clinic, Marche Polytechnic University, Ancona, Italy Many investigations have suggested an association between carotid occlusive disease and cognitive impairment. Available data allow the hypothesis that carotid disease may promote dementia through an impairment of cerebral hemodynamics rather than via atherosclerotic processes. Patients with severe carotid stenosis and unilateral impairment of cerebral hemodynamics were reported to have poorer performances in cognitive domains related to the hemisphere ipsilateral to the stenosis. In Alzheimer Disease patients, an impaired vasomotor reactivity was also associated with an unfavorable evolution of cognitive functions and other prospective studies confirmed the importance of altered cerebral hemodynamics in Alzheimer Disease physiopathology. Subjects with severe carotid stenosis and impaired cerebral vasomotor reactivity were described to have a greater extent of cognitive decline at months compared with patients with preserved hemodynamic function or without carotid disease as well as a higher rate of conversion from MCI to AD. An improvement in cognitive function following revascularization approaches may be expected from the reduced embolism and the improved hemodynamics achieved. Given all the implications for individuals and societies of loss of cognition, its prevention should be considered, along with stroke events, as a factor in determining the balance of the risks and benefits of therapy for carotid steno-occlusive disease. erefore, it would be desirable in the design of future comparative studies of treatment strategies for carotid atherosclerotic disease to consider cognitive outcome as an endpoint. L9 Is myosonology comparable to the EMG needle? M. Siebler Neurologie, MediClin Fachklinik Rhein/Ruhr, Essen, Germany Similar to the nerve ultrasound, sonomyography (SMG) is a promising non-invasive bedside method to visualize the morphology (atrophy, destruction, tumour) of muscles from the extremities. Moreover, the technique allows measuring voluntary muscle kinetics and the detection of pathological spontaneous movements like fasciculation and fibrillations, o en not visible by inspection of the patient. SMG offers the clear advantage to identify the anatomical position of the muscle and the needle position during EMG, biopsy or Botox application. Needle EMG is the gold standard to prove denervation (recording of fasciculation, positive sharp waves, fibrillation) and could not be replaced by SMG (electrical versus morphological information). However, ultrasound could improve the sensitivity for pathological EMG results due to the possibility for fast scanning a great number of muscles and muscle segments. us, the combined use of ultrasound and EMG to detect fasciculation increase the diagnostic sensitivity of Aiwaj criteria for ALS. Muscle ultrasound is also supporting the assessment of critical illness neuro-myopathy in the early stage. Especially when invasive EMG is not possible due to current anticoagulation, SMG could help to classify axonal lesions e.g. in the diagnostic of neuropathy. In conclusion, EMG and SMG are complementary methods which improve the neurological diagnostic in peripheral neurological diseases and should be more and more part of the neurological investigation tool. L0 Botulin toxin infiltration under ultrasound guidance U. Walter Department of Neurology, University of Rostock, Rostock, Germany Botulinum neurotoxin (BoNT) injection has been increasingly used for treating muscular spasticity and dystonia. Unlike other techniques of precision targeting such as electromyography or computed tomography that have been described to minimize undesirable BoNT effects, B-mode ultrasound allows immediate and 8 Cerebrovasc Dis 04;7(suppl):-6 9th Meeting of the European Society of Neurosonology and Cerebral Hemodynamics

9 high-resolution imaging of the injection needle position within the target region. Visual identification of muscles or glands and depth control of needle placement are the key features of ultrasoundguided injection that lead to improved targeting and safety of BoNT injections. Ultrasound may be helpful to validate already established injection techniques or when learning the correct injection technique. Ultrasound-guided BoNT injection has been recommended as a standard procedure in treatment of lower leg spasticity in children with cerebral palsy. In recent years, this technique has been increasingly used also for the exact targeting of BoNT injection in single forearm muscles (e.g. the flexor digitorum superficialis or the flexor digitorum profundus muscle of single fingers) of patients with writers or musicians cramp, or with mild post-stroke spasticity. An emerging application is the ultrasoundguided BoNT injection into deep cervical and nuchal muscles in patients with cervical dystonia, such as the scalene muscles, the longissimus capitis muscle, and the obliquus capitis inferior muscle. Distinct targets for BoNT infiltration such as the omohyoid muscle, as well as the parotid, submandibular or sublingual glands can be practically only targeted with ultrasound. e upcoming MRI-ultrasound fusion imaging techniques that are available already today with advanced ultrasound systems promise the ultrasound-guided targeting also of small deep muscles such as the longus colli muscle in patients with antecollis, and the piriformis muscle in patients suffering from the piriformis syndrome. L Sonography of the eye N. Carraro, V.M. Sarra Clinica Neurologica, Azienda Ospedaliera Universitaria Ospedali Riuniti, Trieste, Italy For a neurosonologist the examination of the eye by ultrasound means widening the study of the extracranial carotid arteries in order to evaluate the ophthalmic artery s flow. is practice does not seem to be very frequent in the general practice. It could be considered useless searching for an information, low sensitive and specific as the inversion of the ophthalmic flow when an high stenosis and/or occlusion of internal carotid artery is investigated. Nevertheless, in our opinion a careful and complete evaluation of the development of the collateral circulation can significantly contribute to understand the compensation for the blood support because its presence and amount may be weighty for therapeutical decisions. e observation of the ophthalmic structures allows also to detect other vascular components as well, i.e. medial and lateral choroidal arteries, central retinal artery, central retinal vein and ophthalmic veins, the retrobulbar orbital space and the eyeball s main components and, for it s specific neurological interest, the optic nerve with meningeal sheath. is very peculiar site has aroused a keen attention for the relationship between its diameter at mm from the retinal plane and the presence of intracranial hypertension; moreover the atrophy induced by previous retrobulbar optic neuritis can also be identified. With regard to the assessment of the eyeball s components the neurosonological contribution depends on its specific clinical knowledge and one must remember that the ocular ultrasonography is only a part of the ophthalmological ultrasound evaluation labeled Standardized Echography by KC Ossoinig, which cannot be replaced by the duplex evaluation alone. Nevertheless, some aspects of ocular pathology can be identified and documented with excellent detail if the most recent equipments are used. L Translational neurosonology: From the laboratory to daily clinical practice M. Kaps Department of Neurology, Justus-Liebig-University Giessen, Giessen, Germany ere is ongoing technical development in the field of Neurosonology, which translates stepwise from preclinical research and clinical proof of concept studies to daily routine and finally to guidelines. e spectrum of available applications ranges from traditional cerebrovascular testing with well established examinations such as classification of internal carotid stenosis to exploratory research projects in the field of therapeutic ultrasound. Actually, nonvascular applications like imaging in movement disorders or peripheral nervous system are gaining rapidly interest and clinical relevance since the distance from bench to bedside is very short. e talk will provide an actualized status of the continuous process of translation in Neurosonology with especial emphasize on promising research opportunities. L Criteria for vasospasm identification, grading and follow-up G. Tsivgoulis Assistant Professor of Neurology, School of Medicine, University of Athens, Greece Cerebral vasospasm is a delayed sustained contraction of the cerebral arteries which may be induced by blood products that remain in contact with the outside of cerebral vessel a er subarachnoid hemorrhage (SAH). Arterial vasospasm is a complication of SAH which becomes symptomatic in more than 5% of patients leading to a delayed ischemic deficit. Vasospasm occurring a er SAH renders narrowing of intracranial arteries, and if there is a severe stenosis ( mm) blood flow decrease with high velocities may be detected. e most common location affected by vasospasm is the middle cerebral artery (MCA), anterior cerebral artery (ACA), basilar and terminal vertebral artery, or distal branches. TCD (Transcranial Doppler) was initially developed with a purpose to non-invasively detect and monitor vasospasm a er SAH and it is now a standard method for detection, quantification and monitoring the severity of vasospasm a er SAH and assessment of treatment. e present lecture will outline the correlation of TCD mean flow veloc- Abstracts Lectures Cerebrovasc Dis 04;7(suppl ):-6 9

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