L-arginine and S-nitrosoglutathione reduce embolization in humans.

BACKGROUND: L-Arginine reduces platelet aggregation and adhesion in ex vivo studies, but there is no evidence as yet that it has a therapeutic effect on clinical end points. Doppler ultrasound can detect cerebral emboli noninvasively. Such embolic signals are common after carotid endarterectomy, and their frequency predicts risk of stroke recurrence. We used this situation to determine the antiplatelet efficacy of L-arginine and S-nitrosoglutathione (GSNO), a physiological nitric oxide donor with possible platelet specificity. METHODS AND RESULTS: Patients undergoing carotid endarterectomy were randomized in a double-blind manner between L-arginine (n=14), GSNO (n=14), or placebo (n=14) administered intravenously for 90 minutes, starting 30 minutes after skin closure. All patients were pretreated with aspirin and given heparin during surgery. Transcranial Doppler recordings were made from the ipsilateral middle cerebral artery for 4 hours after surgery, beginning 30 minutes after skin closure, and also at 6 and 24 hours. There were highly significant reductions in the number of Doppler embolic signals in the L-arginine and GSNO groups; first 4 hours, median (range) number of embolic signals, placebo 44.7 (6 to 778), L-arginine 9.5 (0 to 225), and GSNO 0.8 (0 to 8), both P<0.001 versus control values. The reduction in the signals persisted at the 24-hour recording. CONCLUSIONS: Intravenous L-arginine and GSNO attenuate Doppler embolic signals in humans. Modulation of the NO system with these agents may have applications in the treatment of thromboembolic disease. This study demonstrates the potential application of ultrasonic embolic signal detection to examine the efficacy of new antiplatelet agents in relatively small numbers of patients.

[Cerebral deep vein thrombosis associated with rectal cancer]. / Rectumcarcinomával társult agyi mélyvénás thrombosis.

The authors report a case where the patient suffered from deep cerebral venous thrombosis, which developed beside cerebral metastases of a colorectal cancer. The pathogenesis and diagnosis of this disease are also discussed. This rare location of thrombosis is mainly due to hypercoagulable state seen in the use of oral contraceptive drugs, Behçet syndrome, nephrotic syndrome, and as paraneoplastic syndrome in malignant diseases. Literature reports less than 50 cases of deep cerebral venous thrombosis, of which less than 10 are evoked by malignant disease. The symptoms of DCVT can mimic cerebral metastases in cancer patients. The course of disease is aggressive, the prognosis is poor. Even if the patients survive considerable neurological deficits may remain. Authors emphasize the importance of current modern diagnostic imaging methods in the diagnosis. The possibility of deep cerebral venous thrombosis must be taken into account if sudden neurological symptoms develop in a cancer patient.

Evaluation of new online automated embolic signal detection algorithm, including comparison with panel of international experts.

BACKGROUND AND PURPOSE: The clinical application of Doppler detection of circulating cerebral emboli will depend on a reliable automated system of embolic signal detection; such a system is not currently available. Previous studies have shown that frequency filtering increases the ratio of embolic signal to background signal intensity and that the incorporation of such an approach into an offline automated detection system markedly improved performance. In this study, we evaluated an online version of the system. In a single-center study, we compared its performance with that of a human expert on data from 2 clinical situations, carotid stenosis and the period immediately after carotid endarterectomy. Because the human expert is currently the "gold standard" for embolic signal detection, we also compared the performance of the system with an international panel of human experts in a multicenter study. METHODS: In the single-center evaluation, the performance of the software was tested against that of a human expert on 20 hours of data from 21 patients with carotid stenosis and 18 hours of data from 9 patients that was recorded after carotid endarterectomy. For the multicenter evaluation, a separate 2-hour data set, recorded from 5 patients after carotid endarterectomy, was analyzed by 6 different human experts using the same equipment and by the software. Agreement was assessed by determining the probability of agreement. RESULTS: In the 20 hours of carotid stenosis data, there were 140 embolic signals with an intensity of > or =7 dB. With the software set at a confidence threshold of 60%, a sensitivity of 85.7% and a specificity of 88.9% for detection of embolic signals were obtained. At higher confidence thresholds, a specificity >95% could be obtained, but this was at the expense of a lower sensitivity. In the 18 hours of post-carotid endarterectomy data, there were 411 embolic signals of > or =7-dB intensity. When the same confidence threshold was used, a sensitivity of 95.4% and a specificity of 97.5% were obtained. In the multicenter evaluation, a total of 127 events were recorded as embolic signals by at least 1 center. The total number of embolic signals detected by the 6 different centers was 84, 93, 108, 92, 63, and 78. The software set at a confidence threshold of 60% detected 90 events as embolic signals. The mean probability of agreement, including all human experts and the software, was 0.83, and this was higher than that for 2 human experts and lower than that for 4 human experts. The mean values for the 6 human observers were averaged to give P=0.84, which was similar to that of the software. CONCLUSIONS: By using the frequency specificity of the intensity increase occurring with embolic signals, we have developed an automated detection system with a much improved sensitivity. Its performance was equal to that of some human experts and only slightly below the mean performance of a panel of human experts

Cerebrovascular reserve capacity in patients with hyperlipidemia.

PURPOSE: Because recent data are conflicting, it is not certain whether hyperlipidemia is an independent risk factor for cerebrovascular diseases. Decreased cerebrovascular reserve capacity refers to the decreased ability of the cerebral arterioles to adapt in critical conditions and probably predicts a higher risk of stroke. The aim of this study was to compare cerebrovascular reserve capacity in hyperlipidemic patients and healthy controls using transcranial Doppler sonography. METHODS: Thirty-four hyperlipidemic patients and 21 healthy controls were examined. With transcranial Doppler sonography, the mean blood flow velocity in the middle cerebral artery was registered at rest and at 5, 10, 15, and 20 minutes after intravenous administration of 1,000 mg acetazolamide. Cerebrovascular reactivity and reserve capacity were calculated from mean blood flow velocities. Various laboratory measurements were also made and assessed for correlation with resting cerebral blood flow velocity and cerebrovascular reserve capacity. RESULTS: No significant differences could be observed between controls and hyperlipidemic patients in cerebrovascular reactivity or cerebrovascular reserve capacity. No correlation was found between various laboratory measurements and resting cerebral blood flow velocity or cerebrovascular reserve capacity. CONCLUSIONS: We could not demonstrate any differences in cerebrovascular reserve capacity between hyperlipidemic patients and healthy controls. Thus, the vasodilatory ability of the cerebral arterioles seems to remain unchanged in this patient group and is not correlated with the severity of hyperlipidemia.

Clinical application of asymptomatic embolic signal detection in acute stroke: a prospective study.

BACKGROUND AND PURPOSE: The detection of asymptomatic embolization with the use of Doppler ultrasound has a number of potential applications in patients with acute stroke. It may provide information on the stroke pathogenesis in individual cases, identify patients with continued embolization, and allow localization of the active embolic source. METHODS: We recruited 119 patients with acute anterior circulation infarction within 72 hours of stroke onset. Transcranial Doppler recordings were possible in 100 (84.0%). Bilateral 1-hour middle cerebral artery (MCA) recordings were made and saved on digital audiotape for blinded offline analysis. When embolic signals were detected during screening of the first recording, simultaneous recording was performed from the ipsilateral MCA and common carotid artery for an additional 30 minutes. In all patients with embolic signals at screening and in matched negative controls, recordings were repeated on days 4, 7, and 14. RESULTS: Embolic signals were detected in the symptomatic MCA in 16 patients (16%). They were more common in patients with carotid stenosis (P<0.0001), occurring in 50% of this group. They were rare in patients with cardioembolic stroke (4.5%) and were not detected in patients with lacunar stroke. In the 16 patients with embolic signals, the proportion with embolic signals fell over time (P=0. 0025), but they were still present in a third at 2 weeks. In 10 patients, localization of the embolic source was possible by simultaneous recording from the MCA and the ipsilateral common carotid artery. CONCLUSIONS: Continued asymptomatic embolization is common after stroke in patients with carotid artery disease and is still present in a significant proportion at 2 weeks. The technique may identify patients at risk of further stroke for more aggressive antiplatelet therapy; this needs to be tested in large prospective studies. The technique may also allow localization of the active embolic source.

[Assessment of cerebrovascular reactivity in patients with symptomatic and asymptomatic atherosclerotic carotid artery lesions]. / A cerebrovascularis reaktivitás vizsgálata az arteria carotisok tünetmentes és tünetet okozó atheroscleroticus laesióiban szenvedö betegekben.

AIMS: Strokes caused by hemodynamically significant internal carotid artery stenoses and occlusions are believed to be embolic or hemodynamic of origin. The aim of the study was to assess cerebral hemodynamic compromises of significant carotid artery stenosis of occlusion using vasodilatory testing (acetazolamide test) in asymptomatic and symptomatic patients. PATIENTS AND METHODS: 36 patients with unilateral, hemodynamically significant carotid stenosis were investigated using transcranial Doppler acetazolamide-test. There were 12 asymptomatic and 24 symptomatic patients. The middle cerebral artery mean blood flow velocity was measured at rest and after intravenous injection of 1 g acetazolamide. The absolute mean blood flow velocities and the cerebrovascular reactivity was compared at the stenotic and non-stenotic side. In a further analysis the mean velocities and the cerebrovascular reactivity values of the stenotic side were compared. Results of acetazolamide test performed on 28 healthy volunteers were used as control values. RESULTS: There were no side-differences between the middle cerebral artery mean blood flow velocity and cerebrovascular reactivity values in the asymptomatic group. In the symptomatic group, however middle cerebral artery mean velocity and cerebrovascular reactivity after acetazolamide was significantly lower on the stenotic side, than on the non-stenotic one. Comparing the different groups non-stenotic sides did not differ to each other in their cerebral blood flow velocity and cerebrovascular reactivity. In the symptomatic patients, however, cerebral blood flow velocity and cerebrovascular reserve capacity after acetazolamide was lower, than that of the stenotic side of asymptomatic patients and controls. CONCLUSIONS: The transcranial Doppler is a suitable method for detecting altered cerebral hemodynamics in significant carotid stenosis. Impaired cerebrovascular reactivity may refer to the impairment of cerebral autoregulatory mechanisms.

Cerebrovascular reactivity measured by transcranial Doppler in migraine.

Changes in the diameter of intracranial arteries might have a major role in the pathophysiology of migraine. Though several studies have found alterations in velocity of blood flow and in cerebral vasomotor reactivity of intracranial arteries in migraineurs in headache-free periods, as well as during migraine attacks, the results are inconclusive. To determine if intracranial hemodynamic characteristics of patients with migraine differ from those of controls, we measured baseline velocity of blood flow by transcranial Doppler in the middle cerebral arteries in headache-free periods in 51 migraine patients and in 101 age-matched controls. Cerebrovascular reactivity was measured after intravenous administration of acetazolamide in 12 migrainous patients and in 19 controls. Baseline mean velocity was significantly higher in the migraine group (70 versus 65 and 72 versus 65 cm/s with P = 0.02 and P = 0.0007 on the left and right sides, respectively). The difference stayed significant during acetazolamide stimulation, but the course of response did not differ between controls and migraineurs. Despite statistical significance, absolute differences were small. Therefore, middle cerebral artery velocity measurements and the acetazolamide test are not useful for the diagnosis of migraine in the interictal period.