Mario Siebler - Academia.edu (original) (raw)
Papers by Mario Siebler
Stroke, 1998
Inflammatory mechanisms have been implicated in the pathogenesis of atherosclerosis. In this stud... more Inflammatory mechanisms have been implicated in the pathogenesis of atherosclerosis. In this study, we investigated whether the extent of inflammatory infiltration in high-grade stenoses of the internal carotid artery (ICA) correlates to clinical features of plaque destabilization. Endarterectomy specimens from 37 consecutive patients undergoing surgery for high-grade ICA stenosis were stained immunocytochemically for macrophages (CD68) and T cells (CD3). The staining was quantified by planimetry of immunostained areas (CD68) or counting individual cells (CD3). Clinical evidence of plaque instability was provided by the preoperative assessment of recent ischemic symptoms attributable to the stenosis and of the occurrence of cerebral microembolism in transcranial Doppler ultrasound monitoring of the ipsilateral middle cerebral artery. The percentage of macrophage-rich areas and number of T cells per mm2 section area were larger in recently symptomatic patients than in asymptomatic patients (macrophages: 18+/-10% versus 11+/-4%, P=0.005; T cells: 71.2+/-34.4 versus 40.5+/-31.4 mm2, P=0.005). The presence of microembolism was associated with an increase in macrophage-rich areas (P=0.011). Macrophage (19+/-10% versus 9+/-3%, P=0.0009) and T cell (71.5+/-39.0 versus 46.4+/-22 mm2, P=0.045) infiltration were more pronounced in predominantly atheromatous than in fibrous plaques, but did not correlate significantly to the presence of surface ulceration or luminal thrombosis. Our data suggest a role of plaque-infiltrating macrophages and T cells in the clinical destabilization of high-grade ICA stenoses. Inflammatory mechanisms may be a therapeutic target in patients with symptomatic ICA disease.
Stroke, 2011
Tirofiban is a highly selective, fast-acting nonpeptide glycoprotein IIb/IIIa platelet receptor a... more Tirofiban is a highly selective, fast-acting nonpeptide glycoprotein IIb/IIIa platelet receptor antagonist with a short half-life time. Glycoprotein IIb/IIIa antagonists are effective for the treatment of acute coronary syndromes proven in large clinical trials. Safety and efficacy in patients with ischemic stroke are uncertain. This was addressed in the Safety of Tirofiban in acute Ischemic Stroke (SaTIS) trial. Two hundred sixty patients with acute ischemic stroke were randomized in a placebo-controlled, prospective, open-label treatment, blinded outcome reading multicenter trial. Subjects with a National Institutes of Health Stroke Scale between 4 and 18 received intravenously either tirofiban or placebo within 3 to 22 hours after symptom onset for 48 hours. The primary end point was the rate of cerebral bleeding as measured in follow-up CT scans 2 to 7 days after inclusion. The secondary end point was clinical efficacy within 1 week (National Institutes of Health Stroke Scale, modified Rankin Scale) and after 5 months (Barthel Index, modified Rankin Scale). The rate of cerebral hemorrhagic transformation (I/II) and parenchymal hemorrhage (I/II) did not differ between both groups (tirofiban 36 of 120; placebo 33 of 124: OR, 1.18; 95% CI, 0.66 to 2.06). Mortality after 5 months was significantly lower in patients treated with tirofiban (3 of 130 [2.3%] versus 11 of 126 [8.7%]; OR, 4.05; 95% CI, 1.1 to 14.9). No difference in neurological/functional outcome was found after 1 week and after 5 months. We conclude that tirofiban might be safe in acute moderate ischemic stroke even when administered within a large time window after symptom onset and might save lives in the late outcome. Clinical Trial Registration- URL: www.strokecenter.org/trials/. Trial name: SaTIS. Enrollment began before July 1, 2005.
Stroke, 1995
The purpose of this study was the evaluation of intraobserver, interobserver, and intrasubject va... more The purpose of this study was the evaluation of intraobserver, interobserver, and intrasubject variability in the Doppler detection of microembolic signals in patients with mechanical prosthetic valves. Simultaneously, the feasibility of automated embolus detection by means of a neuronal network was investigated. From 25 patients with mechanical prosthetic heart valves, single transcranial Doppler monitoring sessions of 30 minutes' duration were recorded on videotape, randomized, and subsequently analyzed by eight independent trained observers from three centers. Three observers evaluated these tapes on three separate occasions, blinded to their previous results. An additional 48 patients with prosthetic heart valves were repetitively monitored with transcranial Doppler ultrasonography for 30 minutes three times within 1 year to examine the long-term variability in the occurrence of microembolic signals. Finally, in an effort to assess the short-term intrasubject variability, 20 patients were examined for 90 minutes, and the results of the three 30-minute periods were compared. The interobserver, intraobserver, and intrasubject (both short- and long-term) variability was evaluated. No significant differences in microembolic signal counts were found among the different observers, between the human observers and the neuronal network, or among the three separate evaluations of stored data by the same observer. The same was true for repeat examinations of the same patient (P > .05, Student's two-paired t test and Friedman's test). The detection of microembolic signals in patients with prosthetic cardiac valves is a reproducible technique. The reliable performance of the neuronal network argues for a broader use of this device. The intrasubject stability of the microembolic rate over 1 year supports the concept that the underlying emboligenic process is associated with intrinsic mechanical properties of the valve implant and not due to a thromboembolic process in the heart.
Stroke, 1995
Previous work has shown that cerebral microembolism detected with transcranial Doppler sonography... more Previous work has shown that cerebral microembolism detected with transcranial Doppler sonography distal to internal carotid artery stenosis occurs more frequently in recently symptomatic compared with asymptomatic patients. It has remained unclear whether cerebral microembolism also indicates a higher risk of future cerebral or retinal ischemia. Sixty-four asymptomatic patients with unilateral 70% to 90% internal carotid artery stenosis were investigated prospectively (mean follow-up, 72 weeks). Five patients developed ischemic symptoms attributable to the stenosis (transient ischemic attack, 2 patients; stroke, 3 patients). A microembolic rate of > or = 2 per hour in the ipsilateral middle cerebral artery was associated with a substantially increased risk of developing ischemia of the corresponding carotid territory (odds ratio, 31; 95% confidence interval, 3 to 302; P = .005). This prospective pilot study suggests that cerebral microembolism detected with transcranial Doppler sonography may define a high-risk subgroup among patients with asymptomatic high-grade internal carotid artery stenosis.
Stroke, 2006
Stenosis) trial proved the effectiveness of the combination of clopidogrel and aspirin compared w... more Stenosis) trial proved the effectiveness of the combination of clopidogrel and aspirin compared with aspirin alone in reducing presence and number of microembolic signals (MES) in patients with recently symptomatic carotid stenosis. The present study aimed at installing primary and secondary quality control measures in CARESS because MES evaluation relies on subjective judgment by human experts. Methods-As primary quality control, centers participating in CARESS evaluated a reference digital audio tape (DAT) before the study containing both MES and artifacts. Interobserver agreement of classifying signals as MES was expressed as proportions of specific agreement of positive ratings (psϮvalues). For all DATs included in CARESS (nϭ300), online number of MES and off-line number of MES read by the central reader were compared using correlation coefficients. As secondary control, a sample of 16 of 300 DATs was cross-validated by another independent reader (post-trial validator).
RöFo - Fortschritte auf dem Gebiet der Röntgenstrahlen und der bildgebenden Verfahren, 2007
Radiology, 2001
In four patients with acute basilar artery thrombosis, complete arterial recanalization and good ... more In four patients with acute basilar artery thrombosis, complete arterial recanalization and good neurologic outcome were achieved with a treatment combining alteplase with tirofiban. In no cases were cerebral or extracerebral hemorrhagic complications observed. Combined fibrinolytic agents and glycoprotein IIb/IIIa inhibitors may have high potential in the treatment of acute cerebrovascular thrombosis.
Neurorehabilitation and Neural Repair, 2006
Recovery from hemiparetic stroke is variable. An important goal for clinicians and clinical resea... more Recovery from hemiparetic stroke is variable. An important goal for clinicians and clinical researchers is to identify predictors of recovery. The initial phase after acute ischemic stroke is considered to be of major importance for neurological outcome. The authors sought to determine in patients with acute ischemic stroke whether early motor recovery, as measured by repetitive isometric index-thumb oppositions, is correlated with ischemic lesion volume. Thirty-six acute hemiparetic stroke patients with residual hand function were investigated. The European Stroke Scale (ESS) score was determined on admission and at discharge. Performance of repetitive index finger-thumb pinch movements was measured daily during the 1st 8 days after stroke onset. Brain ischemia volume was determined digitally in time-to-peak magnetic resonance images of per-fusion. The recovery of patients with (P = 0.002) and without (P < 0.001) thrombolysis as assessed with the ESS was paralleled by an increase in isometric grip force and movement rate (P < 0.05). Recovery was predicted by the area of moderately impaired perfusion indicated by the per-fusion mismatch volume (r = 0.578, P < 0.001). In acute stroke, recovery of hand function is predicted by the volume of salvageable ischemic tissue, as determined by the perfusion mismatch.
Neuroradiology, 2000
Although there is a rapidly growing body of data on diffusion-and perfusion-weighted MRI (DWI, PW... more Although there is a rapidly growing body of data on diffusion-and perfusion-weighted MRI (DWI, PWI) in acute stroke , relatively little information is available on findings in transient ischaemic syndromes, in particular concerning PWI. In the largest study reported to date, Kidwell et al. analysed DWI findings in patients with transient ischaemic attacks (TIAs). More than half the patients in this study had normal DWI and, in those with positive DWI studies the lesions were small and relatively subtle. This suggests that DWI alone may not be sufficient to identify the pathophysiology underlying transient ischaemic syndromes.
Neuroradiology, 2009
Introduction Thrombolysis has been shown to improve neurological recovery in acute stroke. But th... more Introduction Thrombolysis has been shown to improve neurological recovery in acute stroke. But the response to thrombolysis is variable across patients. We sought to investigate this variability by analyzing the lesion patterns following systemic thrombolysis with recombinant tissue plasminogen activator (rtPA) and tirofiban in middle cerebral artery (MCA) stroke. Methods One hundred three consecutive stroke patients (67±14 years) were grouped according to the site of MCA occlusion and successful or failed recanalization as assessed with magnetic resonance angiography. Infarct lesions were analyzed in T2-weighted magnetic resonance images after 10 days. Results Patients recovered markedly upon successful recanalization following thrombolysis (p<0.05) but remained severely impaired when there was no recanalization within 24 h. Infarct lesions were smaller after successful than after failed recanalization (p<0.005). They occurred throughout the cerebral cortex on the cerebral convexity in distal MCA occlusions with large individual heterogeneity. In contrast, there was a large lesion overlap in insular cortex, basal ganglia, internal capsule, and paraventricular white matter in proximal MCA occlusions. Conclusion Systemic thrombolysis with rtPA and tirofiban of MCA occlusions resulted in early neurological recovery and preferentially peri-insular infarcts. In failed recanalization of the MCA stem there was a large lesion overlap in the hemispheric white matter and a lack of recovery.
Neurology, 1994
Using transcranial Doppler (TCD) ultrasonography in patients with high-grade (&amp;gt; or... more Using transcranial Doppler (TCD) ultrasonography in patients with high-grade (&amp;gt; or = 70%) internal carotid artery (ICA) stenosis, we examined the relation between the rate of TCD-detected silent microembolism of the ipsilateral middle cerebral artery and a history of recent (&amp;lt; 121 days) ischemic symptoms attributable to the diseased ICA. In the so-defined neurologically symptomatic group (n = 33 patients), silent microembolic events occurred in 27 subjects (overall mean rate, 14/h +/- 29). Among 56 neurologically asymptomatic patients matched for the degree of ICA stenosis, only nine showed such events (overall mean rate, 0.35/h +/- 1.4). Across all 89 patients studied, an individual microembolic event rate &amp;gt; or = 2/h had a positive predictive value of 0.88 for a history of recent symptoms. Our data suggest that TCD monitoring can provide reliable paraclinical evidence of &amp;quot;unstable ICA disease.&amp;quot;
Neurology, 1990
We recorded cerebral blood flow velocity (CBFV) for the assessment of CO2-regulated alterations d... more We recorded cerebral blood flow velocity (CBFV) for the assessment of CO2-regulated alterations during apnea by means of transcranial Doppler ultrasound in a patient with obstructive sleep apnea syndrome. CBFV increased up to doubled peak flow values during obstructive apneic phases. The results provide evidence for a normal CO2 regulation of CBFV leading to periodic vascular stress during the night.
Neurology, 1995
We monitored breathing pattern and arterial oxygen saturation in 32 conscious patients with acute... more We monitored breathing pattern and arterial oxygen saturation in 32 conscious patients with acute ischemic stroke. Seventeen (53%) had Cheyne-Stokes respiration with concomitant drops in oxygen saturation, unrelated to infarct location. The ventilatory disturbance promptly reversed after intravenous theophylline ethylenediamine or oxygen inhalation. The therapy is a simple way of improving arterial oxygenation in a large subgroup of patients with acute ischemic stroke.
Neurology, 2004
To determine the effect of systemic thrombolysis with low-dose recombinant tissue plasminogen act... more To determine the effect of systemic thrombolysis with low-dose recombinant tissue plasminogen activator (rtPA) and the body-weight adjusted platelet GPIIb/IIIa receptor antagonist tirofiban, the authors performed lesion volumetry on magnetic resonance perfusion and diffusion images recorded before thrombolysis and on T2-weighted magnetic resonance images on day 8. Treatment with rtPA and tirofiban (n = 13) resulted in a 50% lesion reduction (p < 0.03), while lesion reduction was less in rtPA treatment (n = 16) and absent in nontreated patients (n = 18).
Neurochemical Research, 2006
Cell death after stroke involves apoptotic, autophagocytic and necrotic mechanisms which may caus... more Cell death after stroke involves apoptotic, autophagocytic and necrotic mechanisms which may cause the release of cytosolic proteins to the extracellular space. Aldolase C (AldC) is the brain specific isoform of the glycolytic enzyme fructose-1,6-bisphosphate aldolase. According to its characteristic striped expression pattern in the adult cerebellum AldC is also termed zebrin II. Here, we demonstrate release of AldC into the cerebrospinal fluid (CSF) after stroke in vivo. Studies with cell cultures confirmed that AldC is released to the extracellular space after hypoxia. Moreover, addition of purified recombinant AldC to networks of cortical neurons plated on multielectrode arrays reversibly inhibited the spontaneous generation of action potentials at AldC concentrations which can be expected to occur after lesions of the human cerebral cortex. This mechanism could be relevant in the pathogenesis of the electrophysiological changes in the penumbra region after stroke.
Journal of Vascular Surgery, 1996
Purpose: Pathoanatomic studies suggest that plaque surface disruption, particularly ulceration, p... more Purpose: Pathoanatomic studies suggest that plaque surface disruption, particularly ulceration, plays a key role in the destabilization of internal carotid artery stenosis. Until now, the validity of color-flow Doppler-assisted duplex imaging in detecting such pathoanatomically defined plaque surface abnormalities is unclear. Methods: We prospectively determined the interobserver reliability and validity of detecting plaque ulceration by means of preoperative color-flow Doppler-assisted duplex imaging in 43 consecutive patients with high-grade (_> 70%) internal carotid artery stenosis, comparing these ultrasonographic findings with pathoanatomic evaluations of the corresponding endarterectomy specimens. Results: Interobserver reliabilities for detecting carotid plaque ulceration were ,: = 0.57 for ultrasonography and x = 0.82 for the pathologic reference method. Color-flow Doppler-assisted duplex imaging (observer consensus) failed to detect pathoanatomicaUy defined ulceration (X 2 = 0.43; p = 0.51). Likewise, sensitivity, specificity, overall accuracy, and positive predictive value were poor (33%, 67%, 56%, and 46%, respectively). Conclusions: We conclude from our data that color-flow Doppler-assisted duplex imaging is not a reliable or valid means to identify plaque ulceration in high-grade carotid artery lesions. (J VASC SURG 1996;23:461-5.) Several pathohistologic investigations have provided evidence that the disruption of internal carotid artery (ICA) atherosclerotic plaques eventually leading to plaque ulceration and intraluminal thrombosis is the key event in converting asymptomatic into symptomatic ICA lesions, l-s Thus the early or even presymptomatic detection of plaque surface disruption, especially plaque ulceration, may be of prognostic and therapeutic relevance.
Journal of Vascular Surgery, 2008
We hypothesized that a subgroup of patients with frank stroke due to sudden occlusion of the inte... more We hypothesized that a subgroup of patients with frank stroke due to sudden occlusion of the internal carotid artery could safely undergo surgery to restore carotid patency and to rescue brain tissue not yet irreversibly damaged if current stroke diagnostic methods were applied. From November 1997 to March 2007, 1810 patients underwent carotid endarterectomy of the internal carotid artery for occlusive disease at our department. Within the same period, 5369 patients were examined at our stroke unit, and 502 from this cohort underwent internal carotid artery reconstruction. A subgroup of 35 patients (28 men, 7 women; mean age, 61 +/- 10 years) underwent urgent surgical revascularization due to an acute internal carotid artery occlusion &amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; or =72 hours (mean 25 +/- 17 hours) after the onset of stroke symptoms and &amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; or =36 hours (mean 16 +/- 10 hours) after admission to our stroke unit. Our diagnostic workup consisted of extracranial intracranial duplex sonography, cerebral computed tomography, digital subtraction angiography, magnetic resonance imaging, and angiography, including diffusion- and perfusion-weighted imaging, to discriminate between viable and irreversibly damaged brain tissue. The study excluded patients who presented an impaired level of consciousness, occlusion of the intracranial internal carotid artery, occlusion of the ipsilateral middle cerebral artery, or infarction more than one-third of the territory perfused by the middle cerebral artery. Imaging showed signs of recent ischemic infarction in all 35 cases. On admission, eight patients (23%) scored 0 to 2 points and 27 (77%) scored 3 to 5 points in Rankin scale. Confirmed by postoperative Doppler and duplex sonography at discharge, internal carotid artery patency could be achieved in 30 of 35 cases (86%). Intracranial hemorrhage occurred in two patients (6%) and reinfarction in another two (6%). Two patients died during their hospital stay (30-day mortality, 6%). Compared with the preoperative neurologic status, rates of clinical improvement (&amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or =1 point in Rankin scale), stability, and deterioration were 57%, 31%, and 6%, respectively. Restoration of blood flow in an acutely occluded internal carotid artery can only be achieved in the acute stage. Our pilot study demonstrated that a thorough diagnostic workup allows selection of patients who may benefit from urgent revascularization of acute internal carotid artery occlusion in the stage of an acute stroke. A prospective randomized multicenter trial comparing surgery with conservative medical treatment is needed.
Journal of Neurology, 2012
Journal of Neurology, 1998
Stroke, 1998
Inflammatory mechanisms have been implicated in the pathogenesis of atherosclerosis. In this stud... more Inflammatory mechanisms have been implicated in the pathogenesis of atherosclerosis. In this study, we investigated whether the extent of inflammatory infiltration in high-grade stenoses of the internal carotid artery (ICA) correlates to clinical features of plaque destabilization. Endarterectomy specimens from 37 consecutive patients undergoing surgery for high-grade ICA stenosis were stained immunocytochemically for macrophages (CD68) and T cells (CD3). The staining was quantified by planimetry of immunostained areas (CD68) or counting individual cells (CD3). Clinical evidence of plaque instability was provided by the preoperative assessment of recent ischemic symptoms attributable to the stenosis and of the occurrence of cerebral microembolism in transcranial Doppler ultrasound monitoring of the ipsilateral middle cerebral artery. The percentage of macrophage-rich areas and number of T cells per mm2 section area were larger in recently symptomatic patients than in asymptomatic patients (macrophages: 18+/-10% versus 11+/-4%, P=0.005; T cells: 71.2+/-34.4 versus 40.5+/-31.4 mm2, P=0.005). The presence of microembolism was associated with an increase in macrophage-rich areas (P=0.011). Macrophage (19+/-10% versus 9+/-3%, P=0.0009) and T cell (71.5+/-39.0 versus 46.4+/-22 mm2, P=0.045) infiltration were more pronounced in predominantly atheromatous than in fibrous plaques, but did not correlate significantly to the presence of surface ulceration or luminal thrombosis. Our data suggest a role of plaque-infiltrating macrophages and T cells in the clinical destabilization of high-grade ICA stenoses. Inflammatory mechanisms may be a therapeutic target in patients with symptomatic ICA disease.
Stroke, 2011
Tirofiban is a highly selective, fast-acting nonpeptide glycoprotein IIb/IIIa platelet receptor a... more Tirofiban is a highly selective, fast-acting nonpeptide glycoprotein IIb/IIIa platelet receptor antagonist with a short half-life time. Glycoprotein IIb/IIIa antagonists are effective for the treatment of acute coronary syndromes proven in large clinical trials. Safety and efficacy in patients with ischemic stroke are uncertain. This was addressed in the Safety of Tirofiban in acute Ischemic Stroke (SaTIS) trial. Two hundred sixty patients with acute ischemic stroke were randomized in a placebo-controlled, prospective, open-label treatment, blinded outcome reading multicenter trial. Subjects with a National Institutes of Health Stroke Scale between 4 and 18 received intravenously either tirofiban or placebo within 3 to 22 hours after symptom onset for 48 hours. The primary end point was the rate of cerebral bleeding as measured in follow-up CT scans 2 to 7 days after inclusion. The secondary end point was clinical efficacy within 1 week (National Institutes of Health Stroke Scale, modified Rankin Scale) and after 5 months (Barthel Index, modified Rankin Scale). The rate of cerebral hemorrhagic transformation (I/II) and parenchymal hemorrhage (I/II) did not differ between both groups (tirofiban 36 of 120; placebo 33 of 124: OR, 1.18; 95% CI, 0.66 to 2.06). Mortality after 5 months was significantly lower in patients treated with tirofiban (3 of 130 [2.3%] versus 11 of 126 [8.7%]; OR, 4.05; 95% CI, 1.1 to 14.9). No difference in neurological/functional outcome was found after 1 week and after 5 months. We conclude that tirofiban might be safe in acute moderate ischemic stroke even when administered within a large time window after symptom onset and might save lives in the late outcome. Clinical Trial Registration- URL: www.strokecenter.org/trials/. Trial name: SaTIS. Enrollment began before July 1, 2005.
Stroke, 1995
The purpose of this study was the evaluation of intraobserver, interobserver, and intrasubject va... more The purpose of this study was the evaluation of intraobserver, interobserver, and intrasubject variability in the Doppler detection of microembolic signals in patients with mechanical prosthetic valves. Simultaneously, the feasibility of automated embolus detection by means of a neuronal network was investigated. From 25 patients with mechanical prosthetic heart valves, single transcranial Doppler monitoring sessions of 30 minutes' duration were recorded on videotape, randomized, and subsequently analyzed by eight independent trained observers from three centers. Three observers evaluated these tapes on three separate occasions, blinded to their previous results. An additional 48 patients with prosthetic heart valves were repetitively monitored with transcranial Doppler ultrasonography for 30 minutes three times within 1 year to examine the long-term variability in the occurrence of microembolic signals. Finally, in an effort to assess the short-term intrasubject variability, 20 patients were examined for 90 minutes, and the results of the three 30-minute periods were compared. The interobserver, intraobserver, and intrasubject (both short- and long-term) variability was evaluated. No significant differences in microembolic signal counts were found among the different observers, between the human observers and the neuronal network, or among the three separate evaluations of stored data by the same observer. The same was true for repeat examinations of the same patient (P > .05, Student's two-paired t test and Friedman's test). The detection of microembolic signals in patients with prosthetic cardiac valves is a reproducible technique. The reliable performance of the neuronal network argues for a broader use of this device. The intrasubject stability of the microembolic rate over 1 year supports the concept that the underlying emboligenic process is associated with intrinsic mechanical properties of the valve implant and not due to a thromboembolic process in the heart.
Stroke, 1995
Previous work has shown that cerebral microembolism detected with transcranial Doppler sonography... more Previous work has shown that cerebral microembolism detected with transcranial Doppler sonography distal to internal carotid artery stenosis occurs more frequently in recently symptomatic compared with asymptomatic patients. It has remained unclear whether cerebral microembolism also indicates a higher risk of future cerebral or retinal ischemia. Sixty-four asymptomatic patients with unilateral 70% to 90% internal carotid artery stenosis were investigated prospectively (mean follow-up, 72 weeks). Five patients developed ischemic symptoms attributable to the stenosis (transient ischemic attack, 2 patients; stroke, 3 patients). A microembolic rate of &amp;gt; or = 2 per hour in the ipsilateral middle cerebral artery was associated with a substantially increased risk of developing ischemia of the corresponding carotid territory (odds ratio, 31; 95% confidence interval, 3 to 302; P = .005). This prospective pilot study suggests that cerebral microembolism detected with transcranial Doppler sonography may define a high-risk subgroup among patients with asymptomatic high-grade internal carotid artery stenosis.
Stroke, 2006
Stenosis) trial proved the effectiveness of the combination of clopidogrel and aspirin compared w... more Stenosis) trial proved the effectiveness of the combination of clopidogrel and aspirin compared with aspirin alone in reducing presence and number of microembolic signals (MES) in patients with recently symptomatic carotid stenosis. The present study aimed at installing primary and secondary quality control measures in CARESS because MES evaluation relies on subjective judgment by human experts. Methods-As primary quality control, centers participating in CARESS evaluated a reference digital audio tape (DAT) before the study containing both MES and artifacts. Interobserver agreement of classifying signals as MES was expressed as proportions of specific agreement of positive ratings (psϮvalues). For all DATs included in CARESS (nϭ300), online number of MES and off-line number of MES read by the central reader were compared using correlation coefficients. As secondary control, a sample of 16 of 300 DATs was cross-validated by another independent reader (post-trial validator).
RöFo - Fortschritte auf dem Gebiet der Röntgenstrahlen und der bildgebenden Verfahren, 2007
Radiology, 2001
In four patients with acute basilar artery thrombosis, complete arterial recanalization and good ... more In four patients with acute basilar artery thrombosis, complete arterial recanalization and good neurologic outcome were achieved with a treatment combining alteplase with tirofiban. In no cases were cerebral or extracerebral hemorrhagic complications observed. Combined fibrinolytic agents and glycoprotein IIb/IIIa inhibitors may have high potential in the treatment of acute cerebrovascular thrombosis.
Neurorehabilitation and Neural Repair, 2006
Recovery from hemiparetic stroke is variable. An important goal for clinicians and clinical resea... more Recovery from hemiparetic stroke is variable. An important goal for clinicians and clinical researchers is to identify predictors of recovery. The initial phase after acute ischemic stroke is considered to be of major importance for neurological outcome. The authors sought to determine in patients with acute ischemic stroke whether early motor recovery, as measured by repetitive isometric index-thumb oppositions, is correlated with ischemic lesion volume. Thirty-six acute hemiparetic stroke patients with residual hand function were investigated. The European Stroke Scale (ESS) score was determined on admission and at discharge. Performance of repetitive index finger-thumb pinch movements was measured daily during the 1st 8 days after stroke onset. Brain ischemia volume was determined digitally in time-to-peak magnetic resonance images of per-fusion. The recovery of patients with (P = 0.002) and without (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) thrombolysis as assessed with the ESS was paralleled by an increase in isometric grip force and movement rate (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). Recovery was predicted by the area of moderately impaired perfusion indicated by the per-fusion mismatch volume (r = 0.578, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). In acute stroke, recovery of hand function is predicted by the volume of salvageable ischemic tissue, as determined by the perfusion mismatch.
Neuroradiology, 2000
Although there is a rapidly growing body of data on diffusion-and perfusion-weighted MRI (DWI, PW... more Although there is a rapidly growing body of data on diffusion-and perfusion-weighted MRI (DWI, PWI) in acute stroke , relatively little information is available on findings in transient ischaemic syndromes, in particular concerning PWI. In the largest study reported to date, Kidwell et al. analysed DWI findings in patients with transient ischaemic attacks (TIAs). More than half the patients in this study had normal DWI and, in those with positive DWI studies the lesions were small and relatively subtle. This suggests that DWI alone may not be sufficient to identify the pathophysiology underlying transient ischaemic syndromes.
Neuroradiology, 2009
Introduction Thrombolysis has been shown to improve neurological recovery in acute stroke. But th... more Introduction Thrombolysis has been shown to improve neurological recovery in acute stroke. But the response to thrombolysis is variable across patients. We sought to investigate this variability by analyzing the lesion patterns following systemic thrombolysis with recombinant tissue plasminogen activator (rtPA) and tirofiban in middle cerebral artery (MCA) stroke. Methods One hundred three consecutive stroke patients (67±14 years) were grouped according to the site of MCA occlusion and successful or failed recanalization as assessed with magnetic resonance angiography. Infarct lesions were analyzed in T2-weighted magnetic resonance images after 10 days. Results Patients recovered markedly upon successful recanalization following thrombolysis (p<0.05) but remained severely impaired when there was no recanalization within 24 h. Infarct lesions were smaller after successful than after failed recanalization (p<0.005). They occurred throughout the cerebral cortex on the cerebral convexity in distal MCA occlusions with large individual heterogeneity. In contrast, there was a large lesion overlap in insular cortex, basal ganglia, internal capsule, and paraventricular white matter in proximal MCA occlusions. Conclusion Systemic thrombolysis with rtPA and tirofiban of MCA occlusions resulted in early neurological recovery and preferentially peri-insular infarcts. In failed recanalization of the MCA stem there was a large lesion overlap in the hemispheric white matter and a lack of recovery.
Neurology, 1994
Using transcranial Doppler (TCD) ultrasonography in patients with high-grade (&amp;gt; or... more Using transcranial Doppler (TCD) ultrasonography in patients with high-grade (&amp;gt; or = 70%) internal carotid artery (ICA) stenosis, we examined the relation between the rate of TCD-detected silent microembolism of the ipsilateral middle cerebral artery and a history of recent (&amp;lt; 121 days) ischemic symptoms attributable to the diseased ICA. In the so-defined neurologically symptomatic group (n = 33 patients), silent microembolic events occurred in 27 subjects (overall mean rate, 14/h +/- 29). Among 56 neurologically asymptomatic patients matched for the degree of ICA stenosis, only nine showed such events (overall mean rate, 0.35/h +/- 1.4). Across all 89 patients studied, an individual microembolic event rate &amp;gt; or = 2/h had a positive predictive value of 0.88 for a history of recent symptoms. Our data suggest that TCD monitoring can provide reliable paraclinical evidence of &amp;quot;unstable ICA disease.&amp;quot;
Neurology, 1990
We recorded cerebral blood flow velocity (CBFV) for the assessment of CO2-regulated alterations d... more We recorded cerebral blood flow velocity (CBFV) for the assessment of CO2-regulated alterations during apnea by means of transcranial Doppler ultrasound in a patient with obstructive sleep apnea syndrome. CBFV increased up to doubled peak flow values during obstructive apneic phases. The results provide evidence for a normal CO2 regulation of CBFV leading to periodic vascular stress during the night.
Neurology, 1995
We monitored breathing pattern and arterial oxygen saturation in 32 conscious patients with acute... more We monitored breathing pattern and arterial oxygen saturation in 32 conscious patients with acute ischemic stroke. Seventeen (53%) had Cheyne-Stokes respiration with concomitant drops in oxygen saturation, unrelated to infarct location. The ventilatory disturbance promptly reversed after intravenous theophylline ethylenediamine or oxygen inhalation. The therapy is a simple way of improving arterial oxygenation in a large subgroup of patients with acute ischemic stroke.
Neurology, 2004
To determine the effect of systemic thrombolysis with low-dose recombinant tissue plasminogen act... more To determine the effect of systemic thrombolysis with low-dose recombinant tissue plasminogen activator (rtPA) and the body-weight adjusted platelet GPIIb/IIIa receptor antagonist tirofiban, the authors performed lesion volumetry on magnetic resonance perfusion and diffusion images recorded before thrombolysis and on T2-weighted magnetic resonance images on day 8. Treatment with rtPA and tirofiban (n = 13) resulted in a 50% lesion reduction (p < 0.03), while lesion reduction was less in rtPA treatment (n = 16) and absent in nontreated patients (n = 18).
Neurochemical Research, 2006
Cell death after stroke involves apoptotic, autophagocytic and necrotic mechanisms which may caus... more Cell death after stroke involves apoptotic, autophagocytic and necrotic mechanisms which may cause the release of cytosolic proteins to the extracellular space. Aldolase C (AldC) is the brain specific isoform of the glycolytic enzyme fructose-1,6-bisphosphate aldolase. According to its characteristic striped expression pattern in the adult cerebellum AldC is also termed zebrin II. Here, we demonstrate release of AldC into the cerebrospinal fluid (CSF) after stroke in vivo. Studies with cell cultures confirmed that AldC is released to the extracellular space after hypoxia. Moreover, addition of purified recombinant AldC to networks of cortical neurons plated on multielectrode arrays reversibly inhibited the spontaneous generation of action potentials at AldC concentrations which can be expected to occur after lesions of the human cerebral cortex. This mechanism could be relevant in the pathogenesis of the electrophysiological changes in the penumbra region after stroke.
Journal of Vascular Surgery, 1996
Purpose: Pathoanatomic studies suggest that plaque surface disruption, particularly ulceration, p... more Purpose: Pathoanatomic studies suggest that plaque surface disruption, particularly ulceration, plays a key role in the destabilization of internal carotid artery stenosis. Until now, the validity of color-flow Doppler-assisted duplex imaging in detecting such pathoanatomically defined plaque surface abnormalities is unclear. Methods: We prospectively determined the interobserver reliability and validity of detecting plaque ulceration by means of preoperative color-flow Doppler-assisted duplex imaging in 43 consecutive patients with high-grade (_> 70%) internal carotid artery stenosis, comparing these ultrasonographic findings with pathoanatomic evaluations of the corresponding endarterectomy specimens. Results: Interobserver reliabilities for detecting carotid plaque ulceration were ,: = 0.57 for ultrasonography and x = 0.82 for the pathologic reference method. Color-flow Doppler-assisted duplex imaging (observer consensus) failed to detect pathoanatomicaUy defined ulceration (X 2 = 0.43; p = 0.51). Likewise, sensitivity, specificity, overall accuracy, and positive predictive value were poor (33%, 67%, 56%, and 46%, respectively). Conclusions: We conclude from our data that color-flow Doppler-assisted duplex imaging is not a reliable or valid means to identify plaque ulceration in high-grade carotid artery lesions. (J VASC SURG 1996;23:461-5.) Several pathohistologic investigations have provided evidence that the disruption of internal carotid artery (ICA) atherosclerotic plaques eventually leading to plaque ulceration and intraluminal thrombosis is the key event in converting asymptomatic into symptomatic ICA lesions, l-s Thus the early or even presymptomatic detection of plaque surface disruption, especially plaque ulceration, may be of prognostic and therapeutic relevance.
Journal of Vascular Surgery, 2008
We hypothesized that a subgroup of patients with frank stroke due to sudden occlusion of the inte... more We hypothesized that a subgroup of patients with frank stroke due to sudden occlusion of the internal carotid artery could safely undergo surgery to restore carotid patency and to rescue brain tissue not yet irreversibly damaged if current stroke diagnostic methods were applied. From November 1997 to March 2007, 1810 patients underwent carotid endarterectomy of the internal carotid artery for occlusive disease at our department. Within the same period, 5369 patients were examined at our stroke unit, and 502 from this cohort underwent internal carotid artery reconstruction. A subgroup of 35 patients (28 men, 7 women; mean age, 61 +/- 10 years) underwent urgent surgical revascularization due to an acute internal carotid artery occlusion &amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; or =72 hours (mean 25 +/- 17 hours) after the onset of stroke symptoms and &amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; or =36 hours (mean 16 +/- 10 hours) after admission to our stroke unit. Our diagnostic workup consisted of extracranial intracranial duplex sonography, cerebral computed tomography, digital subtraction angiography, magnetic resonance imaging, and angiography, including diffusion- and perfusion-weighted imaging, to discriminate between viable and irreversibly damaged brain tissue. The study excluded patients who presented an impaired level of consciousness, occlusion of the intracranial internal carotid artery, occlusion of the ipsilateral middle cerebral artery, or infarction more than one-third of the territory perfused by the middle cerebral artery. Imaging showed signs of recent ischemic infarction in all 35 cases. On admission, eight patients (23%) scored 0 to 2 points and 27 (77%) scored 3 to 5 points in Rankin scale. Confirmed by postoperative Doppler and duplex sonography at discharge, internal carotid artery patency could be achieved in 30 of 35 cases (86%). Intracranial hemorrhage occurred in two patients (6%) and reinfarction in another two (6%). Two patients died during their hospital stay (30-day mortality, 6%). Compared with the preoperative neurologic status, rates of clinical improvement (&amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or =1 point in Rankin scale), stability, and deterioration were 57%, 31%, and 6%, respectively. Restoration of blood flow in an acutely occluded internal carotid artery can only be achieved in the acute stage. Our pilot study demonstrated that a thorough diagnostic workup allows selection of patients who may benefit from urgent revascularization of acute internal carotid artery occlusion in the stage of an acute stroke. A prospective randomized multicenter trial comparing surgery with conservative medical treatment is needed.
Journal of Neurology, 2012
Journal of Neurology, 1998