Recanalization of acute symptomatic occlusions of the internal carotid artery.

BACKGROUND: Little is known about the natural course of internal carotid artery (ICA) occlusion and its possible recanalization. The present study was designed to evaluate recanalization rates of extracranial ICA occlusions in acute stroke patients by means of color-coded duplex sonography (CCDS). METHODS: 305 patients with acute ischemia in the territory of the middle cerebral artery were included in this study. All patients had a neurological examination on admission and on discharge and were rated by means of the European Stroke Scale (ESS). Extracranial color-coded duplexsonography, transcranial Doppler sonography and cranial computed tomography were immediately performed after admission and within 7 days. RESULTS: 254 patients showed no sign of hemodynamic relevant stenosis greater than 70% of the ICA. 21 patients had symptomatic high grade ICA stenosis. 20 patients had an acute occlusion and 10 patients an old ICA occlusion as judged by duplex sonographic criteria. Six patients (5 male, 1 female; age range 57 to 77 years) with an acute atherothrombotic or cardioembolic occlusion showed a recanalization of the ICA in the follow-up ultrasonography. Two patients with cardiogenic embolic occlusion of the ICA had the most favorable outcome and these patients showed no residual stenosis. 4 patients who had ultrasound findings consistent with atherosclerosis on follow-up examination (2 high-grade stenosis, 2 with carotid plaques) did not show a notable improvement of their ESS-score. Patients with carotid plaques developed complete MCA infarctions; the other 4 patients had partial anterior circulation infarction on follow-up CT. CONCLUSIONS: The present study showed that recanalization of the occluded ICA in acute stroke patients is more frequent than generally presumed. CCDS should be routinely performed in the follow-up of stroke patients as spontaneous recanalization may influence clinical outcome.

Distribution of artificially-produced microembolic signals into the cerebral circulation.

According to clinical observations, cardiogenic embolism occurs more often in the anterior than in the posterior cerebral circulation. An ultrasound (US) contrast agent was used to artificially produce microembolic signals (MES) to imitate the intracranial distribution of systemic emboli. Systemic microemboli were simulated by IV administered US agent (Levovist(R) 300 mg/mL as bolus). A total of 20 patients were monitored by means of transcranial Doppler sonography (TCD), 3 min after the injection, with a 2-MHz transducer simultaneously at 50 mm (middle cerebral artery, MCA, on one side) and 90 mm (basilar artery, BA). Four 3-min recordings were done (two of the right MCA, two of the left MCA, with the BA, respectively). Three observers and an automatic detection system independently performed an off-line analysis. A total of 160 recordings were analyzed. The mean numbers of detected high-intensity transient signals (HITS) were 34.5 +/- 28.2 in the right MCA (simultaneously registered HITS in the BA: 9.4 +/- 16.8) and 39.1 +/- 34.2 in the left MCA (simultaneously registered HITS in the BA: 12.2 +/- 14.5). Only 21.4 to 23.7% of all HITS were recorded in the BA. Microembolic signals artificially produced by means of US contrast agent made it possible to mimic the physiologic distribution of small embolic particles. In future, these might help to investigate the distribution of systemic emboli in different vascular territories in various pathologic conditions of the cerebral blood flow.

Ultrasonic assessment of physiological echo-contrast agent distribution in brain parenchyma with transient response second harmonic imaging.

OBJECTIVES: The present study was designed to provide normal data of transient response second harmonic imaging (TRSHI) examinations of cerebral echo contrast enhancement using different modes of electrocardiogram (ECG) gating and echo-contrast agent doses. MATERIALS AND METHODS: Fifty-five patients were examined in an axial diencephalic plane of section using the transtemporal acoustic bone window. TRSHI examinations (ECG gating: systolic, frame-rate once every 2 cardiac cycles = "basical instrument setting") could be performed in 50 individuals with adequate insonation conditions after application of 4 g of a galactose-based microbubbles suspension in a concentration of 400 mg/ml. For comparison, diastolic ECG gating (20 patients), cardiac-cycle triggering frequency of once every 2 seconds (15 patients), or an echo contrast agent dose of 2 g Levovist (15 patients) were used. Analysis of peak intensities (PIs) and areas under the curve (AUCs) was done in posterior (region of interest [ROI]a) and anterior (ROIb) parts of the thalamus, in the lentiform nucleus (ROIc), and the white matter (ROId). RESULTS: In 41 patients with basical instrument setting, characteristic time intensity curve (TIC) could be detected in all ROIs. In ROIa (90%) and ROIb (82%), focal contrast enhancement was most difficult to visualize, and in ROIc and ROId, characteristic TICs were observable in more than 90% of the examinations. Background subtracted PIs and AUCs were significantly higher in ROIc (mean PI: 12.2 +/- 8 acoustic units [AUs]; mean AUC: 598.8 +/- 451.1 AU x Cardiac cycles), and ROId (11.8 +/- 6.9; 559.2 +/- 404) as compared to ROIa (8.3 +/- 5.2; 368.9 +/- 242.7) and ROIb (7.1 +/- 4.7; 298.2 +/- 199.1) (P < .0001). Values for corresponding examinations with a diastolic ECG gating and a cardiac cycle triggering frequency of once every 2 seconds were not different as compared to the basical instrument setting. A 4 g Levovist dose increased the portion of typical TIC in all ROIs. PI of 4 g examinations were significantly higher in ROId and ROIb as compared to the 2 g examination. CONCLUSION: Our findings indicate that TRSHI allows noninvasive assessment of focal cerebral contrast enhancement in the majority of patients with adequate insonation conditions. This study provides data about normal quantitative and qualitative TRSHI values in patients without cerebrovascular diseases. A dose of 4 g Levovist is recommended in those individuals with inaccurate echo contrast enhancement using the 2 g dose.

Contrast agent specific imaging modes for the ultrasonic assessment of parenchymal cerebral echo contrast enhancement.

Previous work has demonstrated that cerebral echo contrast enhancement can be assessed by means of transcranial ultrasound using transient response second harmonic imaging (HI). The current study was designed to explore possible advantages of two new contrast agent specific imaging modes, contrast burst imaging (CBI) and time variance imaging (TVI), that are based on the detection of destruction or splitting of microbubbles caused by ultrasound in comparison with contrast harmonic imaging (CHI), which is a broadband phase-inversion-based implementation of HI. Nine healthy individuals with adequate acoustic temporal bone windows were included in the study. Contrast harmonic imaging, CBI, and TVI examinations were performed in an axial diencephalic plane of section after an intravenous bolus injection of 4 g galactose-based microbubble suspension in a concentration of 400 mg/mL. Using time-intensity curves, peak intensities and times-to peak-intensity (TPIs) were calculated off-line in anterior and posterior parts of the thalamus, in the region of the lentiform nucleus, and in the white matter. The potential of the different techniques to visualize cerebral contrast enhancement in different brain areas was compared. All techniques produced accurate cerebral contrast enhancement in the majority of investigated brain areas. Contrast harmonic imaging visualized signal increase in 28 of 36 regions of interest (ROIs). In comparison, TVI and CBI examinations were successful in 32 and 35 investigations, respectively. In CHI examinations, contrast enhancement was most difficult to visualize in posterior parts of the thalamus (6 of 9) and the lentiform nucleus (6 of 9). In TVI examinations, anterior parts of the thalamus showed signal increase in only 6 of 9 examinations. For all investigated imaging modes, PIs and TPIs in different ROIs did not differ significantly, except that TVI demonstrated significantly higher PIs in the lentiform nucleus as compared with the thalamus and the white matter (P < 0.05). The current study demonstrates for the first time that CBI and TVI represent new ultrasonic tools that allow noninvasive assessment of focal cerebral contrast enhancement and that CBI and TVI improve diagnostic sensitivity as compared with CHI.

Ultrasonic evaluation of pathological brain perfusion in acute stroke using second harmonic imaging.

OBJECTIVE: To evaluate the use of transient response second harmonic imaging (HI) by means of ultrasound to assess abnormalities of cerebral echo contrast agent enhancement in patients with acute stroke. METHODS: The study comprised 25 patients with acute onset of hemispheric stroke (<24 h) with sufficient insonation conditions and 14 control subjects without cerebrovascular disease. All stroke patients had HI, extracranial and transcranial colour coded duplex examinations of the arteries supplying the brain, and clinical examinations (European stroke scale) performed in the acute phase, on day 2, and within 1 week. Acute CT was repeated within 1 week and facultatively accompanied by angiography. Examinations using HI were performed in an axial diencephalic plane of section using the transtemporal acoustic bone window. After bolus application of galactose based microbubbles, 61 ultrasound images with a cardiac cycling triggering frequency of once every 2 seconds were recorded and evaluated off line. Focal perfusion deficit was identified if no contrast enhancement was visualised in a circumscribed region of interest and insufficient temporal bone window was excluded. In cases of reappearance of contrast enhancement reperfusion was assessed. RESULTS: Adequate cerebral contrast enhancement could be seen in 21 subjects. In seven, a large hemispheric deficit of contrast enhancement affecting the entire middle cerebral artery (MCA) territory was detectable; the lentiform nucleus was affected in three subjects. Assessment of cerebral contrast abnormalities was possible in two patients with superficial MCA infarctions but in none of the patients with lacunar ischaemias. None of the control persons had focal deficits of cerebral echo contrast enhancement. In all patients with complete MCA infarction and striatocapsular infarction, presumed ischaemic areas in HI examinations correlated with final CT findings. Overall sensitivity and specifity of HI examinations for predicting size and localisation of the infarction were 75 and 100%, respectively. During follow up, reappearance of contrast enhancement was determined in three patients, in two patients circulatory arrest due to malignant brain oedema with missing contrast enhancement in the entire cerebral hemisphere could be seen. Extent of contrast enhancement deficits significantly correlated with the clinical status on admission and after 1 week (p<0.01). CONCLUSIONS: Second harmonic imaging is the first ultrasonic technique that enables visualisation of pathological cerebral echo contrast enhancement. Because this method identifies deficits of focal contrast enhancement in patients with acute stroke and allows estimation of the final infarct size and clinical prognosis, it may help to select and monitor patients for invasive therapies.

Second harmonic imaging In acute middle cerebral artery infarction. Preliminary results.

BACKGROUND: Second harmonic imaging (SHI) is a new ultrasound technique that is able to detect microbubbles in the tissue vascular space. The aim of this pilot study was to prove that this technique may detect focal abnormalities of cerebral echo-contrast enhancement in acute hemispheric stroke. CASE DESCRIPTIONS: Two male patients (aged 72 and 64 years) were included who presented with acute onset of severe hemiparesis and no established demarcation of the ischemic area in CT scans. After bolus application of galactose-based microbubbles, axial SHI examinations in a diencephalic plane of sections were performed using the transtemporal approach. Ultrasound investigations were recorded and evaluated offline. In both individuals demarcated focal abnormalities of cerebral contrast enhancement were detectable: in patient 1 the region of the lentiform nucleus and the adjacent parts of the temporoparietal lobe was affected, and in patient 2 a large region including the lentiform nucleus and cortical white matter was involved for at least 24 hours. Follow-up CT scans demonstrated a striatocapsular infarct in patient 1 and complete MCA infarction in patient 2, correlating with the presumed ischemic area in acute ultrasound examinations. The patient with complete MCA infarction showed missing contrast enhancement in the entire hemisphere of the affected side in follow-up SHI examinations. He died of malignant space-occupying brain edema. In the patient with the striatocapsular infarction, reappearance of echo-contrast enhancement in the ischemic area was assessable after 1 week. CONCLUSIONS: SHI may identify focal abnormalities of cerebral echo-contrast enhancement in acute hemispheric stroke. Furthermore, this technique helps to determine size, localization, and prognosis of the ischemic region and could be useful for bedside assessment of echo-contrast agent distribution related to brain tissue perfusion.

Knowing no fear.

People with brain injuries involving the amygdala are often poor at recognizing facial expressions of fear, but the extent to which this impairment compromises other signals of the emotion of fear has not been clearly established. We investigated N.M., a person with bilateral amygdala damage and a left thalamic lesion, who was impaired at recognizing fear from facial expressions. N.M. showed an equivalent deficit affecting fear recognition from body postures and emotional sounds. His deficit of fear recognition was not linked to evidence of any problem in recognizing anger (a common feature in other reports), but for his everyday experience of emotion N.M. reported reduced anger and fear compared with neurologically normal controls. These findings show a specific deficit compromising the recognition of the emotion of fear from a wide range of social signals, and suggest a possible relationship of this type of impairment with alterations of emotional experience.

Transient response harmonic imaging: an ultrasound technique related to brain perfusion.

BACKGROUND AND PURPOSE: Gray-scale harmonic imaging is the first method to visualize blood perfusion and capillary blood flow with ultrasound after intravenous contrast agent application. The purpose of the present study was to evaluate the potential of transient response second harmonic imaging (TRsHI) to assess normal echo contrast characteristics in different brain areas by transcranial ultrasound. METHODS: In 18 patients without cerebrovascular diseases, TRsHI examinations were performed bilaterally with the use of the transtemporal approach after application of 6.5 mL of a galactose-based microbubble suspension (400 mg/mL). The transmission rate was once every 4 cardiac cycles. Regional cerebral contrast was visually assessed and then quantified off-line with the use of time-intensity curves. In 4 different regions of interest (ROI) (posterior part of the thalamus [ROIa], anterior part of the thalamus [ROIb], lentiform nucleus [ROIc], and white matter [ROId]), the following parameters were evaluated: peak intensity, area under the curve (AUC), and time to peak intensity. AUC ratios for ROIc/a, d/a, c/b, and d/b were calculated. RESULTS: In all patients parenchymal contrast enhancement was visually detectable. One hundred thirty-one characteristic time-intensity curves (baseline phase, peak contrast intensity, slow washout phase) were demonstrable in 144 ROIs. In ROIc and ROId, characteristic contrast curves could be observed most frequently (68/72 examinations), whereas time-intensity curves in ROIa and ROIb could not be evaluated because of inadequate contrast enhancement in 9 of 72 examinations. Time to peak intensity varied between 20 and 52 cardiac cycles; in 1 patient it was 88 cardiac cycles. In all individuals AUCs and in 16 of 18 subjects peak intensity in ROIc and ROId showed a 2- to 10-fold increase compared with ROIa and ROIb. In no examination did AUC ratios show a >2-fold side difference irrespective of the ROI. CONCLUSIONS: The present study demonstrates for the first time that TRsHI produces accurate contrast in different brain areas and represents an ultrasonic tool related to brain perfusion. Absolute values of quantitative parameters show high variations caused by different temporal bone thicknesses and a complex relationship between echo contrast concentrations and measurements of optic intensities. Ratios between different ROIs help to compare contrast enhancement in different brain areas. Furthermore, because of the fact that attenuation of contrast enhancement in TRsHI depends strictly on the insonation depth, harmonic imaging studies of brain perfusion cannot be compared directly with other imaging techniques such as positron emission tomography.

Diagnosis and monitoring of middle cerebral artery occlusion with contrast-enhanced transcranial color-coded real-time sonography in patients with inadequate acoustic bone windows.

Transcranial color-coded real-time sonography (TCCS) is an emerging diagnostic technique that allows noninvasive imaging of intracranial vessels within parenchymal structures. However, in some patients, transcranial ultrasound is particularly hindered by insufficient ultrasound penetration through the temporal bone. The present study evaluates whether or not application of an echo-contrast agent in ultrasound-refractory patients with middle cerebral artery (MCA) trunk occlusion enhances image acquisition enough to yield accurate diagnoses. Contrast-enhanced (CE) TCCS examinations, computed tomography scans and angiographic studies were performed in 20 patients with clinical symptoms suggestive of MCA occlusion within 12 h of the onset of symptoms. For comparison, 20 control persons without history or clinical signs for cerebrovascular diseases were examined using CE-TCCS. In none of the patients or control subjects did unenhanced TCCS investigations depict any color-coded vascular signal of an intracranial vessel. After application of 9 mL of 400 mg/mL galactose-based microbubbles, CE-TCCS was performed. In subjects with MCA occlusion, CE-TCCS examinations were repeated within 24 h, 48 h and 5 days after stroke. In stroke patients (n = 20), CE-TCCS showed an occluded MCA main stem in 11 patients, and this vessel was clearly demonstrable on the unaffected side. On the affected side, the posterior cerebral artery (PCA) and anterior cerebral artery (ACA) could be visualized in 8 of 11 subjects; in 3 patients, at least 1 of these vessels was detectable. Angiographic studies confirmed the diagnosis of MCA trunk occlusion in all 11 individuals. In follow-up investigations, 3 stroke patients had angiographic and CE-TCCS examinations consistent with vessel reperfusion. Nine stroke patients had a patent MCA shown in angiographic and CE-TCCS examinations. In the control group, the MCA trunk could be visualized in all subjects by CE-TCCS. CE-TCCS is a sensitive and specific ultrasound method for the diagnosis of MCA trunk occlusion that overcomes the anatomical hindrance of inadequate acoustic bone window. This technique may help to identify patients suitable for thrombolytic therapies and monitor their response.

Comparison of transcranial power Doppler and contrast-enhanced color-coded sonography in the identification of intracranial arteries.

Power-based transcranial color-coded sonography and contrast-enhanced transcranial color-coded sonography are ultrasonographic techniques that allow improved visualization of vascular structures. The present study was designed to investigate and compare the diagnostic capacity and applicability of both methods in the assessment of intracranial vessels of the circle of Willis (33 patients) and the vertebrobasilar system (21 patients). Compared to conventional transcranial color-coded sonography, both power-based and contrast-enhanced transcranial color-coded sonography improved the diagnostic sensitivity in identifying peripheral segments and small vessels of the circle of Willis. Contrast-enhanced transcranial color-coded sonography was significantly superior to power-based transcranial color-coded ultrasonography in the depiction of the second segment of the middle cerebral artery (66 of 66 versus 60 of 66, P < 0.005), both segments of the anterior cerebral artery (66 of 66 versus 56 of 66 for the A1 segment, P < 0.005; 61 of 66 versus 44 of 66 for the A2 segment, P < 0.005), the first segment of the posterior cerebral artery (66 of 66 versus 55 of 66, P < 0.005), and the basilar artery using the transtemporal approach (21 of 21 versus 15 of 21, P < 0.05). Using the transforaminal approach contrast-enhanced transcranial color-coded real-time sonography did not increase fine resolution of the vertebrobasilar system compared to power Doppler sonography. In conclusion, contrast-enhanced transcranial color-coded real-time sonography further improves the diagnostic potential of power Doppler sonography in the identification of vascular structures of the circle of Willis. Contrast-enhanced transcranial color-coded sonography and power Doppler sonography are equally effective in visualizing the vertebrobasilar system with branches.

Intravenous immunoglobulin (IVIG) treatment for patients with primary or secondary progressive multiple sclerosis -- outline of a double-blind randomized, placebo-controlled trial.

We present the design of a double-blind, randomised placebo-controlled phase III study to evaluate safety and efficacy of IVIG in the treatment of patients suffering from primary or secondary chronic progressive multiple sclerosis. The primary endpoint is disability. Two measures of disability were chosen in order to assess the primary end point (a) sustained improvement (assessed at month 6, confirmed at month 9) and (b) progression to increasing disability of the disease (sustained for 3 months) at any time during the course of this 2 years study. The disability is measured by the Extended Disability Status Scale (EDSS). Secondary end points include the assessment of visual function, functions of the upper extremity, cognitive functions, depression and quality of life.

Insufficient and absent acoustic temporal bone window: potential and limitations of transcranial contrast-enhanced color-coded sonography and contrast-enhanced power-based sonography.

The aim of this study was to investigate the diagnostic potential of contrast-enhanced transcranial color-coded sonography (CE-TCCS) and contrast-enhanced transcranial power-based sonography (CE-TPS) in patients with insufficient or absent acoustic bone windows (IABW). Due to temporal bone thickness, the basal cerebral circulation could not be insonated in 21 of 172 patients using unenhanced transcranial color-coded real-time sonography (TCCS) and transcranial power-based sonography. Additional CE-TCCS and CE-TPS were performed after application of 400 mg/ml galactose microbubble suspension. In both modalities, the use of echo-contrast agents allowed visualisation of the first segment of the middle cerebral artery (MCA) in all patients. The A1 segment of the anterior cerebral artery (67% in CE-TCCS; 81% in CE-TPS), P1 segment of the posterior cerebral artery (71% in CE-TCCS; 76% in CE-TPS) and the basilar artery (48% in CE-TCCS; 67% in CE-TPS) were depictable in the majority of the examinations. The M3 (5% in CE-TCCS; 33% in CE-TPS; p < 0.05), P2 (24% in CE-TCCS; 71% in CE-TPS; p < 0.005), P3 segments (0% in CE-TCCS; 43% in CE-TPS; p < 0.005) and the posterior communicating artery (5% in CE-TCCS; 33% in CE-TPS; p < 0.05) were detected in a significantly greater proportion of subjects using power Doppler. In conclusion, CE-TCCS and CE-TPS appear to be sensitive ultrasonic tools that provide reliable data regarding the basal cerebral circulation in patients with IABW. Furthermore, CE-TPS offers advantages over CE-TSSC in the identification of small-caliber arteries and vessels that run at unfavorable angels to the ultrasound beam. Both methods can overcome hyperostosis of the skull that is a major hindrance in transcranial ultrasonography, and may be helpful in the diagnosis of occlusive diseases of intracranial vessels.

Power-based versus conventional transcranial color-coded duplex sonography in the assessment of the vertebrobasilar-posterior system.

BACKGROUND: Power Doppler (PD) is a new ultrasonic technique that allows improved visualization of vascular structures. The aim of our study was to compare the ability of power-based transcranial color-coded duplex sonography (p-TCCS) to conventional transcranial color-coded duplex sonography (TCCS) and contrast-enhanced transcranial color-coded duplex sonography (CE-TCCS) in the visualization of the vertebrobasilar system. METHODS: In 41 patients without cerebrovascular diseases, we evaluated and compared identification rates of major vessels of the vertebrobasilar system and branches using both ultrasound (US) techniques. In 9 patients we performed additional CE-TCCS studies. Furthermore, the possibility of visualization of the basilar artery (BA) and the vertebral arteries (VA) over the long course was investigated. RESULTS: TCCS and p-TCCS were equally effective at showing the VAs (74 of 82 v 80 of 82), proximal segments of the BA (37 of 41 v 41 of 41) and P1 segments of the posterior cerebral artery (PCA) (72 of 82 v 82 of 82). However, the diagnostic sensitivity of p-TCCS was significantly better for peripheral segments of the PCA (34 of 82 v 68 of 82 for P2 and 2 of 82 v 24 of 82 for P3 segments, P<.001), distal parts of the BA (25 of 41 v 38 of 41, P<.01), the anterior inferior cerebellar artery (AICA) (0 of 82 v 8 of 82, P<.0001) and the posterior inferior cerebellar artery (PICA) (13 of 82 v 34 of 82, P<.001). Furthermore, using transtemporal coronal sections, p-TCCS allowed visualization of the BA over the complete course in connection with one or both VAs in half of the patients. Except P2 and P3 segments, CE-TCCS did not increase resolution compared with p-TCCS. CONCLUSIONS: PD offers significant advantages over color-coded sonography in imaging the BA and small-calibre vessels like the PICA, AICA, and peripheral segments of the PCA. P-TCCS in combination with TCCS increases the diagnostic sensitivity to identify vascular structures of the vertebrobasilar system.

Visual hallucinosis: the major clinical determinant of distorted chromatic contour perception in Parkinson's disease.

Recently distorted chromatic contour perception has been demonstrated in Parkinson's disease (PD). The aim of our study is to determine the clinical factors which influence chromatic contour perception in PD. Chromatic and achromatic contour perception, colour discrimination and clinical data were evaluated in 73 patients with PD. We used a computer-aided method to determine the chromatic fusion time (CFT) which indicates the acuity of monochromatic contour perception. Chromatic CFT was generally shortened in patients as compared to controls (p < 0.01), whereas achromatic CFT was not significantly different. Variance analysis revealed the ability of colour discrimination and the risk of visual hallucinations as statistically significant (p < 0.05) variables influencing contour perception of certain stimuli. In contrast, disease stage, disease duration and disease severity have no relevant effect on chromatic contour perception in Parkinson's disease. On the basis of those properties one may suggest that distorted chromatic contour perception is due to an impairment at a central stage of visual processing in PD and an imbalance of the serotonergic system. Whether CFT is a reliable method to predict the individual risk of hallucinosis in PD has to be evaluated.