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V./4.6.: Workup except neuroimaging
V./4.6.1.: Investigations in the acute stage
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Severity of stroke has to be established by neurologic examination using a specific scale such as the National Institutes of Health Stroke Scale (NIHSS). Apart from that, pulmonary and respiratory as well as cardiac functions are also judged, blood pressure and pulse, oxygen saturation measured; the first examination should also assign early signs of dysphagia. Blood tests have to be done: blood chemistry, glucose, coagulation and hematologic profile are examined.
Detailed history taking should contain data on cardiovascular risk factors, conditions and medications that may cause bleeding complications. Conditions that could result in „stroke-like” disease should also survey.
Urgent neuroimaging examination, brain CT and/or MRI have to be done (details are in the radiology chapter).
With the results from the history, urgent clinical findings, laboratory and neuroimaging specific, acute treatment method of stroke have to be judged. These examinations equally have to be done in TIA or stroke after the therapeutic time window. 12 lead ECG also important in all patients.
V./4.6.2.: Doppler ultrasonography of the carotids
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Listening to bruit above the carotids as well as above the heart, is part of the physical examination. In case of carotid stenosis, bruit may be heard.
Ultrasonography of the carotid vessels is to be done in all stroke or TIA patients to evaluate etiology and help to choose treatment method. In asymptomatic patients with cardiovascular risk factors, screening of the carotids should be planned.
Colour coded duplex ultrasonography is used. Using the B-mode, the examiner follows the position of the vessel, normal position, kinking (lesser then 90-degree curve) or coiling (spiral-like segment) can be found. Sometimes aneurysm or pseudo aneurysm is also visible.
From the longitudinal aspect of the common carotid artery (CCA), the inner most layers of the vessel, intimal layer and the media is visualized (better on the wall far away from the transducer). Intimal-media thickness (IMT) can be measured; normal value is 0.4-0.8 mm. Atherosclerotic plaques are elevated into the lumen after artery. The surface can be smooth, rough or exulcerated. Regarding echodensity, plaques can be echolucent (soft) with similarly dark density to blood; e.g. plaques rich in lipids, swollen or hemorrhagic plaques or fresh thrombosis. Isodens, medium density plaques are the fibrotic ones, and the chronic thrombi. Calcificated plaques are hyperdens. Soft plagues carry higher stroke risk. Homogenous atherosclerotic plaques consist of similar vessel wall changes; heterogeneous plaques contain different echodensity parts.
Then carotids are examined by the colour-doppler mode. By this method, stenosis or soft plaques become visible: colour signal is narrowed, turbulence with so called „confetti phenomenon” could be seen.
Velocity of the flow is measured in all segments using the Dopper method. In case of at least 50% carotid stenosis flow velocity is increased; velocity is proportionally increased further with the severity of the stenosis. Peak systolic and end diastolic velocity, spectral change of the Doppler curve, ICA/CCA index and residual lumen of the vessel in B- and colour modes help to establish the degree of the stenosis above 50% quite accurately.
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The severity of the stenosis by that method correlates well with the results of angiography. International standard to establish stenosis in e.g. the North American Symptomatic Carotid Endarterectomy Trial (NASCET) is as follows: diameter of the residual lumen is compared to the normal lumen of the distal segment. For example, the European Carotid Surgery Trialists’ Collaborative Group (ECST) compared the diameter of the residual lumen with the former diameter of the normal vessel in the same level. Stenosis above 70% is labelled significant. In case of ICA occlusion, flow velocity falls to zero in the origin of the vessel, or ineffective spikes could be detected in case of fresh thrombosis.
The most precise, sensitive and specific non-invasive method to diagnose severity of the stenosis is the contrast enhanced MRI angiography followed by the colour-coded carotid ultrasonography, CT-angiography and non-contrast MRI angiography. In certain cases digital substraction angiography (DSA) have to be done, when other investigation methods did not give the same result or intervention (stenting) is planned.
According to the national recommendation, the stenosis has to be established by two different non-invasive methods or gold standard DSA have to be made. The fact that, the results of the Doppler ultrasonography highly depends on the experience of the examiner has to be emphasized. It is a non-invasive technique capable of bedside repetitions, which are advantages.
Apart from atherothrombotic diseases, ultrasonography can be used for the diagnosis of dissection, if the pseudo-lumen becomes visible. If the location of the dissection is on a distal segment, so called indirect signs e.g. occlusion, changes suggestive of distal stenosis may be found. In these cases dissection can be proved with further imaging methods.
V./4.6.3.: Transcranial Doppler ultrasonography
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Transcranial Doppler ultrasonography (TCD) is capable of detection of the flow in the vessels of the Willis circle (or basal arteries). Low frequency (1.5-2 MHz) and high intensity pulse wave is used, which could enter in some well-defined parts of the skull. These anatomical accustic Doppler windows are the orbit or the superior orbital fissure through which the ophthalmic artery and siphon of the carotid artery can be examined. Through the foramen magnum transforaminal (or transnuchal), measurement of the intracranial segment of VA, BA or even PCA is possible.
Additionally an accustic window exists without real gap in the skull, but with so thin bone, that high intensity pulse wave can penetrate through it. It is the temporal accustic window of the temporal bone right in front of the external ear canal below the zygomatic arch. MCA, ACA and PCA can be examined through it. One have to mention, that in some patients, particularly elder and women lack the temporal window because with the change in the bone structure Doppler waves cannot pass through.
Transcranial colour Doppler (TCCD) show the flow in the vessel as colour coded.
In severe stenosis velocity of the flow is increased, location of the stenosis is visible by colour-mode and post-stenotic turbulence can be found. Sensitivity could be strengthening with the use of contrast material. Intracranial collaterals can be mapped in case of extracranial artery occlusion.
Microembolisation can be proved in atrial fibrillation or emboli from an exulcerated carotid plaque. In case paradox emboli are suspected, patent foramen ovale, (PFO) can be indirectly visible. Intravenous contrast material containing micro-bubbles is injected, and air-emboli detected by TCD.
In the treatment of acute stroke along with the systemic thrombolysis, high intensity radiofrequency waves are used. In some cases, effect of the thrombolytic therapy is enhanced by injection of contrast material containing microbubbles. This method enhances the effect of the thrombolytic agent locally, inside the thrombus.
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Cerebral autoregulation maintains blood flow regardless of changes in the systemic blood pressure between mean arterial pressures of 50-150 mmHg. Vasomotor reactivity (VMR) is measured to determine capacity of autoregulation. CO2-inhalation or intravenous acetazolamid injection causes the cerebral arterioles to dilate result in hyperperfusion of the capillary circulation. MCA flow velocity will consequently increase (without change of the diameter), which can be measured by TCD.
Depleted autoregulation is diagnosed if the velocity of the flow is not or slightly increases since the arterioles and capillary system are already maximally dilated to provide brain perfusion. This finding is typical in severe ICA stenosis and occlusion. The information provided by this investigation could be important to the vascular surgeon and the anaesthesiologist. If operated, VMR could normalize after a few months. Simple and easy way to examine cerebrovascular reserve capacity is the measure of the breath-holding index.
V./4.6.4.: Echocardiography
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Echocardiography of a stroke patient is utmost important in the following groups: heart disease is suspected based on history, physical examination or ECG; cardioembolism is suspected (e.g. because multiple infarcts are present in more then one arterial territories); paradox emboli or disease of the aorta can be presumed or if etiology of the stroke is not found.
Holter ECG for 24 hours is recommended to all stroke or TIA patients, if arrhythmia is suspected or no etiology identified.
V./4.6.5.: Other methods
If a stroke patient does not have atherosclerosis in the carotids and cardiogen source cannot be identified, other rare etiology have to be looked for. Prothrombotic states with possible Leiden mutation, low level of protein C or S, low activity of antithrombin III, dysfibrinogemia, and mutation of prothrombin gene, antiphospholipid syndrome and increased homocystein level should be examined in specific laboratories.
Some genetic based diseases cause stroke such as the CADASIL (cerebral autosomic dominant arteriopathy with subcortical infarcts and leukoencephalopathy) or MELAS (mitochondrial encephalopathy, lactacidosis and stroke-like syndrome). Fabry disease (X-linked lysosomal storage disease) accompanied by the young onset ischemic stroke with multiorgan involvement.
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