Background and Purpose-We aimed to identify and determine the clinical relevance of parameters predictive of stroke recurrence and vessel occlusion before carotid endarterectomy. Methods-One hundred forty-three consecutive patients (105 men; mean age, 66.1Ϯ8 years) with symptomatic severe carotid artery stenosis were prospectively followed up until carotid endarterectomy. Patients had suffered an ischemic vascular event in the ipsilateral anterior circulation 9.6 days (median; range, 0 to 92 days) before presentation and assessment of stenosis. Admission examination included medical history, neurological status, extracranial and transcranial Doppler/duplex sonography, CT/MRI, ECG, and routine laboratory examination. All patients were reevaluated in the same way the day before surgery (without CT/MRI) and at recurrence of an ischemic event (including CT/MRI). Results-The end point of follow-up after 19.0 days (median; range, 0 to 118) was carotid endarterectomy in 120 patients, ipsilateral recurrent ischemia in 15 patients (7 transient events and 8 disabling strokes, with carotid occlusion in 4), and (asymptomatic) carotid occlusion in 8 patients. An exhausted cerebrovascular reactivity as determined by a Doppler CO 2 test in the middle cerebral artery ipsilateral to the stenosis was the only independent predictive parameter for disabling stroke (odds ratio [OR], 9.7; 95% confidence interval [CI], 2.1 to 44.1; Pϭ0.003). Stroke rate in patients with exhausted reactivity was 27% per month compared with 5.2% in those with normal reactivity. Progression of stenosis toward occlusion was observed in 12 patients and correlated with decreased poststenotic peak systolic velocity (OR, 0.75; 95% CI, 0.62 to 0.90; Pϭ0.002), poststenotic arterial narrowing (OR, 22.7; 95% CI, 3.6 to 141.6; Pϭ0.001), and very severe stenosis (OR, 13.6; 95% CI, 2.2 to 83.7; Pϭ0.005). In patients without hemodynamic compromise, occlusion was not associated with increased stroke risk. Conclusions-Patients with recently symptomatic high-grade carotid artery stenosis and ipsilateral hemodynamic compromise are at high risk for early disabling stroke. Assessment of the hemodynamic status is recommended after diagnosis of severe carotid stenosis in symptomatic patients to further investigate and evaluate whether these patients may benefit from early endarterectomy.

Background and Purpose-We sought to evaluate the diagnostic value of echo-enhanced transcranial color-coded duplex sonography (TCCD) and the clinical relevance of vascular pathology assessed by sonography for early clinical outcome in acute ischemic stroke. Methods-We present 23 consecutive patients with an anterior circulation stroke in whom clinical examination, CT, and ultrasonography were performed within 5 hours after the onset of symptoms. Transcranial Doppler sonography (TCD) and unenhanced and contrast-enhanced TCCD (Levovist, 4 g, 300 mg/mL) were compared for their ability to detect middle cerebral artery (MCA) occlusion and flow velocity reduction suggesting hemodynamic impairment in the MCA distribution pathway. Sonographic examination times were registered. Baseline clinical characteristics and CT findings were assessed. Neurological deficit was quantified according to the National Institutes of Health Stroke Scale score, with an early clinical improvement defined as decrease of the score by 4 or more points or a complete resolution of the deficit on day 4. Results-Contrast-enhanced TCCD enabled diagnosis of intracranial vascular pathology in 20 affected hemispheres, whereas unenhanced TCCD and TCD were conclusive in 7 and 14 hemispheres, respectively (Pϭ0.0001). Contrastenhanced TCCD was superior in evaluating distal carotid (carotid-T) occlusion and differentiating major vessel occlusions from patent arteries with flow velocity diminution. Mean examination time for enhanced TCCD ranged from 5 to 7 minutes, depending on the number of investigated vessels (without or with MCA branches). Logistic regression selected a patent MCA without reduced blood flow velocity as the only independent predictor for an early clinical improvement (PϽ0.01). Conclusions-Contrast-enhanced TCCD is a promising tool for early prognosis in anterior circulation stroke. It is considered superior to unenhanced TCCD and TCD. (Stroke. 1998;29:955-962.)

The dopamine-D2-agonist pramipexole (PPX) was tested for blocking mitochondrial permeability transition (PT) in order to give a possible explanation for its neuroprotective effect seen in PPX-treated Parkinson's disease patients. Patch-clamp techniques for studying single-channel currents in the inner mitochondrial membrane and large-amplitude swelling of energized mitochondria were used to study PPX action on the permeability transition pore (PTP), a key player in the mitochondrial route of the apoptotic cascade. Identity of the PTP was proven by measuring the concentration-response relation for cyclosporin A-blockade (IC50=26 nM). PPX inhibits the PTP reversibly with an IC50 of 500 nM, which is close to the values determined earlier as plasma concentrations after PPX medication in patients. Interaction of PPX with the PTP is further supported by demonstrating that it abolished Ca2+-triggered swelling in functionally intact mitochondria. Blockade of the PTP by PPX was attenuated by increasing concentrations of inorganic phosphate and by acidification. We suggest that PPX could exert part of its neuroprotective effect by inhibition of the PTP and thus, probably, blocking of the mitochondrial pathway of the apoptosis cascade.

Background and Purpose-The present study investigated the influence of the antiplatelet agent acetylsalicylic acid (ASA) on cerebral microembolism as detected by transcranial Doppler sonography (TCD). Methods-Nine patients with recent transient ischemic attack or minor stroke of arterial origin were investigated. Eight had not received an antiplatelet or anticoagulant medication before TCD, and in 1 patient a preexisting ASA medication (100 mg/d) had not been changed since the onset of stroke symptoms. An initial 1-hour TCD monitoring was extended for an additional 2.5 hours after an intravenous bolus injection of 500 mg ASA and was repeated for 1 hour on the following day.

Cerebrovascular reserve capacity evaluated by preoperative transcranial Doppler carbon dioxide testing is a major determinant of stroke risk in patients with carotid artery stenosis/occlusion undergoing cardiac surgery with cardiopulmonary bypass. Its assessment facilitates identification of patients with an excess perioperative stroke risk.