Combined thrombolysis with abciximab and rtPA in patients with middle cerebral artery occlusion.

BACKGROUND: In patients with acute middle cerebral artery (MCA) occlusion, recanalization rates with intravenous (IV) recombinant tissue plasminogen activator (rtPA) are limited. Aim- We evaluated the feasibility and safety of combined IV thrombolysis with abciximab and reduced dose rtPA in a 3- to 6-h time window. METHODS: We prospectively (March 2002 to February 2005) studied patients with symptomatic MCA occlusion on computed tomography (CT) angiography and absence of major early ischemic changes (EIC) on non-contrast CT (NCCT) within 3-6 h from symptom onset. Patients were treated with IV abciximab and half-standard dose rtPA. Outcome parameters were symptomatic intracerebral hemorrhage (sICH), early clinical improvement and functional independence at discharge (modified Rankin Scale score < or = 2). RESULTS: Of 13 patients, mean age was 62 +/- 11 years, onset-to-treatment time 4.8 +/- 0.9 h and median baseline National Institutes of Health Stroke Scale score 11 (interquartile range 6.5-13.5). sICH occurred in one patient (8%). We observed early clinical improvement in four patients (31%). Six patients (46%) were functionally independent at discharge. CONCLUSIONS: In patients with acute symptomatic MCA occlusion and absence of major EIC on NCCT, combined IV thrombolysis with abciximab and half-standard dose rtPA was feasible and seemed to be safe if applied within 3-6 h from symptom onset.

CT angiography source images predict final infarct extent in patients with basilar artery occlusion.

BACKGROUND AND PURPOSE: The posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS) is a 10-point grading system to quantify ischemic changes in the posterior circulation. We analyzed whether pc-ASPECTS on CT angiography (CTA) source images (CTASI) predicted the final infarct extent and hemorrhagic transformation (HT) rate in patients with basilar artery occlusion. MATERIALS AND METHODS: A pc-ASPECTS score of 10 indicates absence of visible ischemic changes in the posterior circulation, and pc-ASPECTS score of 0 indicates ischemic changes in the midbrain, pons, and bilateral thalami, posterior circulation territories, and cerebellar hemispheres. We retrospectively studied patients with basilar artery occlusion on CTA within 24 hours from symptom onset. We applied pc-ASPECTS to noncontrast CT (NCCT), CTASI, and follow-up images by 3-reader-consensus and assessed HT on follow-up images. We calculated Spearman correlation coefficients and performed linear regression analysis. Final infarct extent and HT rates were compared across dichotomized CTASI pc-ASPECTS groups (>/= 8 vs < 8). RESULTS: Among 43 patients, median (range) onset to CTA time was 5.0 hours (range, 0.7-24 hours). Pc-ASPECTS on CTASI (r = 0.75; P < .001) but not NCCT (r = 0.29; P = .063) correlated with pc-ASPECTS on follow-up scans. Linear regression demonstrated a significant positive relationship between pc-ASPECTS on CTASI and follow-up scans (R(2) = 0.58; P < 01). Median follow-up pc-ASPECTS was lower in patients with a CTASI pc-ASPECTS < 8 compared with patients with a CTASI pc-ASPECTS of 8 or more, respectively (P < .001). HT rates were 27.3% vs 9.5%, respectively (P = .24). None of 8 patients without thrombolysis had HT on follow-up scans. CONCLUSIONS: The extent of hypoattenuation on CTASI predicts the final infarct extent in patients with basilar artery occlusion.

[Stroke and atrial fibrillation]. / Schlaganfall und Vorhofflimmern.

Approximately 80% of all strokes are ischemic, the remaining being hemorrhagic. The major reason for cerebral ischemia is occlusion of a cerebral artery by a cardiac thrombus in a patient with atrial fibrillation. This article focuses on the therapeutic management of patients with cerebral ischemia due to atrial fibrillation and is based on the guidelines of the German Society of Neurology and the European Stroke Organization: Patients with cerebral ischemia and atrial fibrillation require oral anticoagulation with an INR of 2.0-3.0. After a TIA (transient ischemic attack) or minor ischemic stroke, anticoagulation can be initiated within the first week after the stroke. Combination therapy of aspirin and clopidogrel is less effective than oral anticoagulation.

Endovascular therapy of symptomatic intracranial stenosis in patients with impaired regional cerebral blood flow or failure of medical therapy.

BACKGROUND AND PURPOSE: Symptomatic intracranial stenoses have a high risk for a recurrent stroke if treated medically. Although angioplasty and stent placement are proposed treatment options, data on longer-term outcome are limited. MATERIALS AND METHODS: We analyzed all endovascular procedures on symptomatic intracranial stenosis at our institution from January 1998 to December 2005. We retrospectively assigned patients to group A (symptoms despite antithrombotic therapy) or group B (impaired regional cerebral blood flow [rCBF]). Primary outcome events were periprocedural major complications or recurrent ischemic strokes in the territory of the treated artery. We used the Kaplan-Meier method to calculate survival probabilities. RESULTS: The procedural technical success rate was 92% (35/38) with periprocedural major complications in 4 cases (10.5%; group A [8.3%, 2/24], group B [14.3%, 2/14]). Median (range) follow-up for the 33 patients with technically successful procedures was 21 (0-72) months. Recurrent ischemic strokes occurred in 15% (3/20) of patients in group A and 0% (0/13) of patients in group B. Overall, there were 21% (7/33) primary outcome events (group A [25%, 5/20], group B [15%, 2/13]). There was a nonsignificant trend for better longer-term survival free of a major complication or recurrent stroke in patients with impaired rCBF compared with patients who were refractory to medical therapy treatment (Kaplan-Meier estimate 0.85 [SE 0.10] vs 0.72 [SE 0.11] at 2 years, respectively). CONCLUSION: Interventional treatment of symptomatic intracranial stenosis carries significant risk for complications and recurrent stroke in high-risk patients. The observation that patients with impaired rCBF may have greater longer-term benefit than medically refractory deserves further study.

Cerebrovascular response time to a breath-holding challenge.

BACKGROUND: To evaluate the timecourse of cerebrovascular reserve response to breath-holding. PATIENTS AND METHODS: Using simultaneous bilateral transcranial Doppler (TCD) recordings from the MCA during a breath-holding challenge, we measured the time interval between baseline and peak blood flow velocity values in 25 patients with critical unilateral internal carotid artery (ICA) stenosis (> 85% lumen diameter reduction), in 9 patients with a non-critical (70-85%) ICA-stenosis and in 27 normal controls. RESULTS: Normal controls and patients with non-critical stenosis reached peak MCA velocities on both sides almost simultaneously. For the patients with critical stenosis the peak response time ipsilateral to the stenosis was delayed 2.40 +/- 3.43 sec compared to the opposite side. This delay resolved after carotid endarterectomy. CONCLUSIONS: In response to a breath-holding challenge unilateral critical ICA stenosis is associated with a significant ipsilateral prolongation of the rise time from baseline to peak MCA velocity.

Recanalization after intravenous thrombolysis: does a recanalization time window exist?

BACKGROUND: To evaluate the time course of major vessel recanalization under IV thrombolysis in relation to functional outcome in acute ischemic stroke. METHODS: A total of 99 patients with an acute anterior circulation vessel occlusion who underwent IV thrombolysis were included. All patients had a standardized admission and follow-up procedure. Color-coded duplex sonography was performed on admission, 30 minutes after thrombolysis, and at 6 and 24 hours after onset of symptoms. Recanalization was classified as complete, partial, and absent. Functional outcome was rated with the modified Rankin Scale on day 30. RESULTS: Complete recanalization occurred significantly more frequently in patients with multiple branch occlusions compared to those with mainstem occlusion (OR 5.33; 95% CI, 2.18 to 13.05; p < 0.0001) and was associated with lower NIH Stroke Scale (NIHSS) scores (p < 0.001). Not the specific time point of recanalization at 6 or 24 hours after stroke onset, but recanalization per se within 24 hours (OR 7.8; 95% CI 2.2 to 28.2; p = 0.002) was significantly associated with a favorable outcome. Multivariate analysis revealed recanalization at any time within 24 hours and NIHSS scores on days 1 and 7 together explaining 75% of the functional outcome variance 30 days after stroke. CONCLUSIONS: Complete recanalization up to 24 hours after stroke onset is significantly associated with the short-term clinical course and functional outcome 30 days after acute stroke.

Echo-enhanced transcranial color-coded duplex sonography in the diagnosis of cerebrovascular events: a validation study.

BACKGROUND AND PURPOSE: Transcranial color-coded duplex sonography (TCCD) is a diagnostic technique for evaluation of intracranial arteries in patients with acute stroke. Echo-enhancing contrast agents (EEAs) are necessary to visualize intracranial vessels in up to 30% of patients because of limited acoustic bone windows. In this study, we assessed the diagnostic efficacy of echo-enhanced TCCD (eTCCD) in correlation with the gold standard, digital subtraction angiography (DSA). METHODS: We prospectively evaluated all patients with eTCCD who subsequently underwent DSA for evaluation of cerebrovascular symptoms over a 24-month period. We administered Levovist as an EEA. Two blinded reviewers analyzed all eTCCD findings and correlated them with DSA. RESULTS: We included 132 consecutive patients (40 women, 92 men; mean age, 58 +/- 14 years) with 164 datasets: 24/164 had normal findings, 98/164 had abnormalities of extracranial carotid arteries, 32/164 had abnormalities of intracranial arteries, and 21/164 had abnormalities in vertebrobasilar circulation as determined by DSA. For eTCCD, we found a sensitivity of 82% (95% confidence interval [CI]: 75%-90%), a specificity of 98% (95% CI: 90%-100%), a positive predictive value of 99% (95% CI: 94%-100%), and a negative predictive value of 75% (95% CI: 64%-85%); 7/164 (4%) examinations were inconclusive because of insufficient bone windows. The interobserver agreement was almost perfect (kappa value, 0.92; 95% CI: 0.87-0.97). CONCLUSION: eTCCD provides high diagnostic validity for the status of the major intracranial arteries. In particular, a normal vessel status reliably assessed by an experienced sonographer could supersede further imaging procedures. In patients with acute ischemic stroke not eligible for established angiographic techniques, eTCCD may be useful as an alternative imaging technique.

[Miller Fisher syndrome: case report and review with discussion of differential diagnosis and nosology]. / Miller-Fisher-Syndrom: Diskussion der Differenzialdiagnostik und Nosologie anhand einer Kasuistik.

We report a 52-year-old patient with Miller Fisher syndrome and discuss Wernicke's encephalopathy as one important differential diagnosis. This article focuses on diagnostic criteria and possible nosological relations between Miller Fisher syndrome, Guillain-Barré syndrome with ophthalmoplegia, Bickerstaff's brainstem encephalitis, and acute ophthalmoparesis without ataxia.

Transcatheter closure of patent foramen ovale (PFO) in patients with paradoxical embolism. Periprocedural safety and mid-term follow-up results of three different device occluder systems.

AIMS: Interventional PFO closure has previously been reported to reduce the risk for recurrent thromboembolic events. The aim of the present study was to evaluate three different occluder systems in respect to (a) the safety and practicability and (b) the mid-term risk of recurrent thromboembolic events. METHODS AND RESULTS: Since 08/98 until 12/02, 307 consecutive patients (138 women, 169 men, mean age 43 years) with a symptomatic PFO underwent PFO closure using the PFO-Star ( n=177), Amplatzer PFO occluder ( n=69) and CardioSeal/Starflex ( n=61 ). Implantation was successful in all patients. Periinterventional complications occurred in 9 patients (5x ST-segment elevations, 1x arteriovenous fistula, 2x TIA, 1x device dislodgement). All of them were reversible and not associated with a specific type of device. During the median follow-up of 24 months (25/75th percentiles: 14/37 months), the annual risk of recurrence was 0.6% for TIA, 0% for stroke and 0.2% for peripheral embolism (PFO-Star: 0.8%, Amplatzer PFO occluder: 0.7% and CardioSeal/Starflex: 1.0%). CONCLUSION: Interventional PFO closure appears to be safe and a promising technique in symptomatic PFO patients with a low incidence of periinterventional complications and recurrent thromboembolic events using three different devices (PFO-Star, Amplatzer PFO occluder or the CardioSeal/Starflex).

Basilar and middle cerebral artery reserve: a comparative study using transcranial Doppler and breath-holding techniques.

BACKGROUND AND PURPOSE: A 1997 report suggests that the posterior circulation of the normal brain has diminished vasoreactivity compared with the anterior circulation. To further study this, we quantified and compared the vasodilatory capacities of the middle cerebral (MCA) and basilar artery (BA) territories in response to changes in PaCO(2), as indices of respective cerebrovascular reserve (CVR). If posterior circulation CVR is indeed physiologically lower than that of the MCA, it might indicate a greater risk of low-flow ischemia distal to basilar obstructive cerebrovascular lesions and provide a rationale for earlier treatment of such lesions with interventional techniques. We also wished to establish normal baseline CVR values for the posterior circulation. METHODS: Twelve patients with signs and/or symptoms suggestive of posterior circulation disease but without flow-limiting obstructive changes and 11 normal controls were entered into the study. With the use of transcranial Doppler techniques, alterations in blood flow velocity in response to sequential breath-holding trials of varying duration were simultaneously monitored in both MCAs and the BA. CVR was measured as the percent velocity increase (during breath-holding) from resting baseline values. RESULTS: No significant differences were found in CVR between the MCA and BA territories in or between patients and controls. CONCLUSIONS: Our study suggests that the anterior and posterior circulations have similar reserve capacities in individuals without flow-limiting cerebrovascular obstructive lesions and that the BA territory, relative to the MCA territory, is not at increased risk for low-flow stroke on the basis of limited reserve potential.

Ultrasound in acute stroke: a review.

Ultrasound is widely used for assessment of neurovascular disease, mainly during the subacute or chronic phases of cerebral ischaemia. The availability of aggressive and potentially harmful treatments for acute ischaemic stroke demands fast, and noninvasive examination of the intracranial vasculature. Current ultrasound techniques have the potential to provide essential information about the intracranial arteries in acute stroke. Application of echo-enhancing agents promises to effectively extend current techniques. The clinical significance of sonography in acute stroke needs to be evaluated prospectively and compared with other radiological techniques.

Echo-enhanced transcranial color-coded duplexsonography to study collateral blood flow in patients with symptomatic obstructions of the internal carotid artery and limited acoustic bone windows.

We prospectively evaluated 30 consecutive patients with echo-enhanced transcranial color-coded duplexsonography (TCCD) and correlative transfemoral digital subtraction angiography to assess the diagnostic efficacy of echo-enhanced TCCD for evaluation of collateral pathways through the circle of Willis in patients with limited acoustic bone windows and critical symptomatic carotid disease. Echo-enhanced TCCD detected collateral blood flow through the anterior communicating artery in 16 of 18 patients (sensitivity 89%, 95% CI 65-99%) and was false positive in one out of 12 patients without collateral flow (specificity 92%, 95% CI 59-100%). For the posterior communicating artery, sensitivity was 11/14 (79%, 95% CI 49-95%) and specificity was 15/16 (94%, 95% CI 70-100%). Echo-enhanced TCCD enables to study collateral blood flow through the communicating arteries of the circle of Willis with high sensitivity and specificity in patients with obstructions of the internal carotid artery and limited acoustic bone windows.

Contrast-enhanced transcranial color-coded duplexsonography in stroke patients with limited bone windows.

BACKGROUND AND PURPOSE: Thickening of the temporal bone in stroke-age patients may obviate sonographic evaluation of the circle of Willis in 20% to 30% of patients. We assessed the diagnostic efficacy of contrast-enhanced transcranial color-coded duplexsonography (TCCD) for noninvasive evaluation of the circle of Willis in stroke patients with limited bone windows. METHODS: Of 171 consecutive patients who presented with ischemic symptoms in the middle cerebral artery (MCA) territory, 49 patients (32 female, 17 male; age range, 70.5+/-10.6 years) had no detectable colorflow signals from the circle of Willis by TCCD because of limited acoustic windows. These 49 patients received an IV injection of a sonographic contrast-enhancing agent, Levovist (Schering; Berlin, Germany), and were re-examined. Correlative imaging studies of the circle of Willis were obtained in 42 of 49 of these patients. RESULTS: In 38 of 49 patients, contrast-enhanced TCCD enabled full visualization of the circle of Willis bilaterally; in an additional five patients, contrast-enhanced TCCD revealed only the portion of the circle of Willis ipsilateral to the probe through one temporal bone. In six of these 43 patients, contrast-enhanced TCCD showed MCA stenosis and MCA occlusion in three; three of the six cases of MCA stenosis and all three cases of the MCA occlusion were found on the symptomatic side. In six of 49 patients, no colorflow signals were obtained after contrast enhancement. All contrast-enhanced TCCD findings were confirmed by CT angiography, transfemoral digital subtraction angiography, MR angiography, or a combination of all three correlative studies. Levovist produced no serious adverse events. CONCLUSION: In stroke-age patients with limited acoustic windows, contrast-enhancement with Levovist can markedly increase the sensitivity of TCCD and increase the detection of clinically relevant intracranial arterial disease.

Noninvasive assessment of the circle of Willis in cerebral ischemia: the potential of CT angiography and contrast-enhanced transcranial color-coded duplexsonography.

Thirty-four patients with acute hemispheric ischemic strokes underwent both CT angiography and contrast-enhanced transcranial color-coded duplexsonography (TCCD) to study the effectiveness of the combined noninvasive techniques for evaluation of the circle of Willis. In 3/34 patients, CT angiography and contrast-enhanced TCCD demonstrated middle cerebral artery (MCA) occlusion, in 5 others MCA stenosis. A severe posterior cerebral artery stenosis was missed by CT angiography. In 8 patients, contrast-enhanced TCCD failed because of poor bone windows. In these patients, CT angiography was normal. CT angiography and contrast-enhanced TCCD are complementary noninvasive diagnostic tools. Disagreements between the diagnostic findings of these methods still need further evaluation by digital subtraction angiography.

Cerebrovascular reserve before and after vertebral artery angioplasty.

The selection of patients with severe vertebrobasilar artery stenosis for angioplasty is based mainly on clinical experience rather than on controlled data. We present a patient with severe vertebral artery stenosis in whom we could document the positive effect of angioplasty on posterior circulation hemodynamics by using transcranial Doppler sonography.

Dodecafluoropentane ultrasonic contrast enhancement in carotid diagnosis: preliminary results.

To assess the efficacy in carotid diagnosis of an investigational dodecafluoropentane ultrasonic contrast enhancing agent, we compared B-mode, color flow, and duplex Doppler findings in 16 patients with common carotid artery bifurcation disease after dodecafluoropentane and saline injections. Dodecafluoropentane produced enhanced backscatter in all patients for 4 to 20 min (mean, 8.4+/-4.74 min) after intravenous injection. In six patients this enhancement improved the color flow and pulsed Doppler signal detection in areas of sonographic shadowing. The enhanced color flow information changed the diagnostic impression in one case. Dodecafluoropentane produced enhanced backscatter in the carotid artery in all patients, and for a mean duration longer than that reported for other agents. It has the potential to improve the efficacy of carotid ultrasonic evaluation.