Andreas Schwartz

Noninvasive monitoring of internal carotid artery dissection.

Background and Purpose Internal carotid artery dissection has increasingly been reported as a cause of transient ischemic attack or stroke. However, scarce data exist on the natural history of the arterial lesions and the temporal profile of recanalization. Methods We followed 48 patients with 50 angiographicalry confirmed internal carotid artery dissections by sequential duplex Doppler studies in 2- to 4-day intervals during the first weeks after the onset of symptoms and after 4 weeks in 1- to 2-month intervals for up to 2 years. We assessed sonographic features as well as the frequency and time course of resolution. Results Initial Doppler findings were abnormal in all patients, most of whom (68%) presented with a characteristic bidirectional high-resistance Doppler signal in the internal carotid artery. Gradual recanalization was found in 68% of the dissections after an average interval of 51 days. Changes of Doppler flow patterns in follow-up studies and features of intra-arterial angiography correlated with the development of internal carotid artery dissection and mirrored the recanalization process. Conclusions Our findings suggest that Doppler sonography provides early recognition of internal carotid artery dissection and monitoring of its resolution. Thus, ultrasound studies may guide clinical decisions according to the development of the dissection.

Cerebral blood flow and cerebrovascular reserve capacity: estimation by dynamic magnetic resonance imaging.

We have developed a new method for estimation of regional CBF (rCBF) and cerebrovascular reserve capacity on a pixel-by-pixel basis by means of dynamic magnetic resonance imaging (MRI). Thirteen healthy volunteers, 8 patients with occlusion and/or high grade stenosis of the internal carotid artery (ICA), and 2 patients with acute stroke underwent dynamic susceptibility-weighted contrast enhanced MRI. Using principles of indicator dilution theory and deconvolution analysis, maps of rCBF, regional cerebral blood volume, and of the mean transit time (MTT) were calculated. In patients with ICA occlusion/stenosis, cerebrovascular reserve capacity was assessed by the rCBF increase after acetazolamide stimulation. Mean gray and white matter rCBF values in normals were 67.1 and 23.7 mL · 100 g−1 · min−1, respectively. Before acetazolamide stimulation, six of eight patients with ICA occlusions showed decreased rCBF values; and in seven patients increased MTT values were observed in tissue ipsilateral to the occlusion. After acetazolamide stimulation, decreased cerebrovascular reserve capacity was observed in five of eight patients with ICA occlusion. In acute stroke, rCBF in the central core of ischemia was less than 8 mL · 100 g−1 · min−1. In peri-infarct tissue, rCBF and MTT were higher than in unaffected tissue but rCBF was normal. Dynamic MRI provides important clinical information on the hemodynamic state of brain tissue in patients with occlusive cerebrovascular disease or acute stroke.

Early treatment with aspirin plus extended-release dipyridamole for transient ischaemic attack or ischaemic stroke within 24 h of symptom onset (EARLY trial): a randomised, open-label, blinded-endpoint trial

BACKGROUND Little is known about the best antiplatelet treatment immediately after ischaemic stroke or transient ischaemic attack (TIA). The EARLY trial aimed to compare outcome in patients given aspirin plus extended-release dipyridamole twice daily either within 24 h of stroke or TIA or after 7 days of aspirin monotherapy. METHODS In 46 stroke units in Germany, patients aged 18 years or more who presented with symptoms of an acute ischaemic stroke that caused a measurable neurological deficit (National Institutes of Health stroke scale score < or =20) were randomly assigned to receive 25 mg aspirin plus 200 mg extended-release dipyridamole open-label twice daily or 100 mg aspirin monotherapy open-label once daily for 7 days. Patients were randomised by use of a pseudorandom number generator. All patients were then given open-label aspirin plus extended-release dipyridamole for up to 90 days. The primary endpoint was modified Rankin scale score as recorded by centralised, blinded assessment by telephone (tele-mRS) at 90 days. Vascular adverse events (non-fatal stroke, TIA, non-fatal myocardial infarction, and major bleeding complications) and mortality were assessed in a composite safety and efficacy endpoint. Patients were analysed as treated. This trial is registered, number NCT00562588. FINDINGS Between July, 2007, and February, 2009, 543 patients were treated: 283 received early aspirin plus extended-release dipyridamole and 260 received aspirin plus extended-release dipyridamole after 7 days on aspirin. At day 90, 154 (56%) patients in the aspirin plus early extended-release dipyridamole group and 133 (52%) in the aspirin plus later extended-release dipyridamole group had no or mild disability (tele-mRS 0 or 1; difference 4.1%, 95% CI -4.5 to 12.6, p=0.45). 28 patients in the early initiation group and 38 in the late initiation group reached the composite endpoint (hazard ratio 0.73, 95% CI 0.44-1.19 p=0.20). INTERPRETATION Early initiation of aspirin plus extended-release dipyridamole within 24 h of stroke onset is likely to be as safe and effective in preventing disability as is later initiation after 7 days. FUNDING Boehringer Ingelheim.

Middle Cerebral Artery Stenoses: Assessment by Magnetic Resonance Angiography and Transcranial Doppler Ultrasound

Magnetic resonance angiography (MRA) findings of uni- or bilateral middle cerebral artery (MCA) stenosis were compared with results of transcranial Doppler ultrasound (TCD) and digital subtraction ang

Changes in Coagulation and Fibrinolysis Markers in Acute Ischemic Stroke Treated With Recombinant Tissue Plasminogen Activator

BACKGROUND AND PURPOSE Shifts of the balance between coagulation and fibrinolysis play a crucial role in pathogenesis and treatment of cerebral ischemia. In this study, we characterized the kinetics of hemostatic abnormalities induced by acute ischemic stroke and its thrombolytic (recombinant tissue plasminogen activator [rtPA]) or anticoagulant (heparin) treatment. METHODS Systemic generation of molecular markers of hemostasis (fibrin monomer, D-dimer, thrombin-antithrombin complex, and fibrinopeptide 1.2) was monitored in acute ischemic stroke, and the effects of thrombolytic and anticoagulant treatments were analyzed. RESULTS Thrombolysis with rtPA induced a massive response of markers of coagulation activation and fibrin formation that peaked after 1 to 3 hours and persisted for up to 72 hours. In contrast, only minor hemostatic changes were induced by acute ischemic stroke itself. Administration of heparin did not significantly affect these hemostatic abnormalities. CONCLUSIONS This first characterization of the coagulation activation induced by rtPA treatment for acute ischemic stroke and the failure to abolish such hemostatic abnormalities by heparin may be of value for further refinement of the currently discussed thrombolytic therapy and the controversial adjunctive anticoagulant prophylaxis in stroke patients.

Assessment of Regional Cerebral Blood Volume in Acute Human Stroke by Use of Single-Slice Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging

BACKGROUND AND PURPOSE The purpose of this study was to evaluate the clinical usefulness of dynamic susceptibility contrast-enhanced MRI (DSC-MRI) in acute cerebral ischemia. METHODS During bolus injection of gadolinium-diethylenetriamine pentaacetic acid, a series of rapid T2*-weighted images was recorded from one slice. Concentration-time curves and images of regional cerebral blood volume (rCBV) were calculated from this data set. DSC-MRI, MR angiography, conventional spin-echo MRI (SE-MRI), and CT were performed in 11 patients within 6 hours after stroke onset and before thrombolytic or anticoagulant treatment was begun. A follow-up MRI examination was performed 24 to 48 hours after stroke onset. RESULTS In 7 of 11 patients (group 1) with territorial infarcts of the middle (n = 6) or posterior cerebral artery (n = 1), DSC-MRI showed reduced rCBV in the affected territory before conventional SE-MRI displayed ischemic lesions. DSC-MRI was helpful to differentiate severely ischemic tissue from peri-infarct parenchyma. Partial reperfusion (n = 3), unchanged reduction of rCBV (n = 2), and progressive reduction of rCBV (n = 2) were observed in the follow-up study. Normal DSC-MRI findings were present in 4 of 11 patients (group 2) with lacunar infarcts. CONCLUSIONS DSC-MRI accomplished the detection of the ischemic territory in the very early stage (< 6 hours) before SE-MRI delivered unequivocal results. DSC-MRI might be helpful to discriminate completely ischemic tissue from potentially salvageable ischemic parenchyma at risk and may play an important role in stroke therapy and evaluation.

Magnetic resonance angiography in vertebrobasilar ischemia.

Background and Purpose Magnetic resonance angiography is a new, noninvasive technique whose diagnostic value in vertebrobasilar artery disease has not yet been determined. Methods Forty-one patients with acute cerebellar and/or brain-stem ischemia were examined by routine magnetic resonance imaging, extracranial and transcranial Doppler ultrasound, and selective intraarterial arteriography. Results were correlated with magnetic resonance angiography. Magnetic resonance angiography was accomplished using a three-dimensional time-of-flight gradient-echo technique. Results Magnetic resonance angiography correctly identified all occlusions, stenoses, and an aneurysm within the distal vertebrobasilar system as revealed by conventional intra-arterial arteriography but missed the diagnosis of vertebral artery dissection in one case. This results in a sensitivity of magnetic resonance angiography of 97% and a specificity of 98.9%. However, the degree of stenoses was difficult to evaluate by magnetic resonance angiography. At least for severe obstructive lesions, this drawback can be eliminated by application of presaturation pulses, which allow the analysis of flow direction and collateral blood flow. Doppler ultrasound studies add useful hemodynamic information for less severe degrees of stenoses. Conclusions The combined use of magnetic resonance angiography and Doppler ultrasound findings may replace the invasive intra-arterial arteriography examination in many patients with suspected macroangiopathy of the vertebrobasilar arteries.

Are Gait Disturbances and White Matter Degeneration Early Indicators of Vascular Dementia

The objective of this study was to correlate clinical and brain imaging findings with walking inabilities in patients with possible vascular dementia. For 24 patients with suspected initial vascular dementia according to DSM-III-R, structured neurological, neuropsychological and neuroimaging (magnetic resonance tomography) examinations were evaluated alongside computerized gait analysis. All patients revealed an increased variability of gait lines of various degrees: mild (11%), moderate (32%) and severe (57%). Lateralization of gait patterns was present in 68% and bipedal instabilities of posture in 54%. These findings were significantly correlated with frontal periventricular white matter lesions (WMLs), which probably affect the thalamo-cortico-mediocapsular pathways. The association of gait abnormalities with WMLs of the frontocentral subcortical and periventricular territories in patients with possible vascular dementing illnesses may be used as an early indicator of the disease for follow-up and treatment trials. However, since the degree of gait impairment varies considerably relative to the common mild intellectual limitations, these structural lesions are unlikely to be directly related to the dementing process.

Power Doppler Imaging of Carotid Artery Stenosis Comparison With Color Doppler Flow Imaging and Angiography

BACKGROUND AND PURPOSE Power Doppler imaging (PDI) is a new sonographic technique that has recently been introduced for vascular application. Since the technical principles of PDI may provide increased sensitivity to visualize the continuity of blood flow in arterial stenoses, we investigated the diagnostic significance of PDI and the intermethod relationship for the measurement and classification of internal carotid artery (ICA) stenosis in comparison with both color Doppler flow imaging (CDFI) and angiography. METHODS One hundred patients with a total of 128 ICA stenoses (50% to 69%, n = 37; 70% to 79%, n = 27; 80% to 99%, n = 64) and 12 ICA occlusions were consecutively investigated by means of PDI, CDFI, and intra-arterial angiography (n = 48). Reduction of the intrastenotic lumen was measured on longitudinal and transverse views of PDI and CDFI for the calculation of the degree of diameter and area stenosis, respectively. Angiographic stenosis was determined with the use of the North American Symptomatic Carotid Endarterectomy Trial (NASCET), European Carotid Surgery Trial (ECST), and common carotid (CC) methods. RESULTS PDI provided significantly more excellent or good (92% versus 79%; P < .01) displays of the intrastenotic lumen than CDFI, particularly in complicated high-grade stenosis. While linear regression analysis demonstrated a high overall correlation between PDI and CDFI for diameter (r = .88; P < .001) and area stenosis (r = .79; P < .001), categorization of ICA stenosis revealed best agreement for 80% to 99% area stenoses. Since angiography frequently either underclassified (NASCET method) or overclassified (ECST, CC methods) the degree of ICA stenosis in comparison to both PDI and CDFI, the sonographic-angiographic correlation was only moderate (regression coefficients ranged from .62 to .70; P < .001). CONCLUSIONS PDI further improves the assessment of ICA stenosis by providing better visualization of the stenotic vascular lumen than CDFI. Sonographic imaging of the stenotic plaque on both PDI and CDFI provided a direct measurement of the local degree of stenosis, while the angiographic grade of stenosis essentially depended on the method used for evaluation.

Lack of Evidence of Acute Ischemic Tissue Change in Transient Global Amnesia on Single-Shot Echo-Planar Diffusion-Weighted MRI

BACKGROUND AND PURPOSE There is uncertainty concerning the etiology of transient global amnesia (TGA). Previous CT and MRI studies have indicated that permanent structural abnormality is rare in TGA. Diffusion-weighted (DW) MRI is very sensitive to early ischemic parenchymal changes and has recently demonstrated embolic infarction in the posterior cerebral artery territory in 2 TGA patients. We report the findings of DW MRI in 8 patients in acute stages of TGA. METHODS Conventional and echo-planar DW MRI was performed in 2 patients in the active phase and 6 patients in the recovery phase (1 to 8 hours after cessation of anterograde memory dysfunction) of spontaneously occurring TGA. RESULTS None of the patients showed signs of hyperintensity on DW images or hypointensity on quantitative apparent diffusion coefficient (ADC) maps to suggest regional decreases of water mobility or acute T2 changes on transverse or coronal slices. CONCLUSIONS We were unable to detect ADC or acute T2 changes with echo-planar DW MRI in patients with TGA, which suggests that mechanisms other than ischemic infarction may cause TGA. We did not identify spreading depression-associated changes of the ADC. Further refinement of MRI sequences may be necessary to detect subtle or transient signal change in brain parenchyma.