The Debrecen Stroke Database: demographic characteristics, risk factors, stroke severity and outcome in 8088 consecutive hospitalised patients with acute cerebrovascular disease.

BACKGROUND: High stroke mortality in central-eastern European countries might be due to higher stroke incidence, more severe strokes or less effective acute care than in countries with lower mortality rate. Hospital databases usually yield more detailed information on risk factors, stroke severity and short-term outcome than population-based registries. PATIENTS AND METHODS: The Debrecen Stroke Database, data of 8088 consecutively hospitalised patients with acute cerebrovascular disease in a single stroke centre in East Hungary between October 1994 and December 2006, is analysed. Risk factors were recorded and stroke severity on admission was scored by the Mathew stroke scale. The modified Glasgow outcome scale was used to describe patient condition at discharge. RESULTS: Mean age was 68+/-13 years, 11.4% had haemorrhagic stroke. The rate of hypertension on admission was 79% in men, and 84% in women, 40.3% of men and 19.8% of women were smokers, and 34% of all patients had a previous cerebrovascular disease in their history. Case fatality was 14.9%, and 43% had some disability at discharge. Outcome at discharge was worse with higher age, higher glucose, higher blood pressure, higher white cell count and erythrocyte sedimentation rate and more severe clinical signs on admission. In multivariate analysis admission blood pressure lost its significance in predicting outcome. CONCLUSIONS: In this large Hungarian stroke unit database hypertension on admission, smoking and previous cerebrovascular disease were more frequent than in most western databases. These findings indicate major opportunities for more efficient stroke prevention in this and probably other eastern European countries.

Transcranial Doppler monitoring in hypertensive patients during physical exercise.

PURPOSE: To evaluate the diagnostic value of a combined method, i.e. ergometer cycling with continuous bilateral transcranial Doppler monitoring (TCD) to detect cerebral hemodynamic abnormalities in recently diagnosed hypertensive patients. METHODS: 30 neurologically symptom-free, nontreated patients with essential hypertension and 30 age- and sex-matched controls were studied. Carotid ultrasound, resting ECG and blood parameters were investigated. Cycling ergometry was performed according to the WHO protocol. Blood pressure, heart rate, end-tidal CO2 (etCO2) and bilateral middle cerebral artery (MCA) blood flow velocity (MV) were monitored. RESULTS: At rest, MV in the MCA did not differ significantly between controls and hypertensive subjects. MV continuously increased in controls until the end of loading whereas a plateau was reached at 4 min in hypertensive subjects. During 6 min of cycling, the time course of absolute values of MV in the MCA and that of the changes in the ratio of mean velocity/end-tidal CO2 (DeltaMV/DeltaetCO2) differed significantly between hypertensive subjects and controls (p = 0.03 and p = 0.02, respectively). CONCLUSION: Ergometer cycling combined with TCD revealed altered vasoreactivity, therefore this may be a sensitive method for the detection of early hemodynamic impairment in nontreated hypertensive subjects.

A possible role of decreased oxidative resistance of low-density lipoproteins in the early formation of carotid atherosclerosis.

Ischaemic stroke ranks among the most important causes of death and disability in developed countries. Abnormal lipid metabolism is among the several factors that have a role in the pathogenesis of atherosclerosis. We hypothesize that the decreased resistance of low-density lipoproteins against oxidative stress is an independent risk factor for cerebral atherosclerosis and suggest testing this hypothesis by ultrasonographic evaluation of the carotid artery and correlating this finding to plasma values of compounds that play a role in lipid metabolism. By measuring the oxidative resistance of low-density of lipoprotein the risk for ischaemic stroke can be predicted.

Cerebral blood flow and glucose metabolism in mitochondrial disorders.

OBJECTIVE: To investigate cerebral metabolism by 2-[18F]fluorodeoxy-d-glucose (FDG) uptake using PET and cerebrovascular reverse capacity by transcranial Doppler sonography (TCD) in different mitochondrial diseases (mitochondrial myopathy; mitochondrial encephalopathy, lactacidosis, and stroke-like episodes [MELAS]; and chronic external ophthalmoplegia). BACKGROUND: Previous studies on individual patients with mitochondriopathies revealed abnormal accumulations of mitochondria in endothelium, smooth muscle cells, and pericytes of blood vessels in different parts of the nervous system (cerebrum, cerebellum, sural nerve) and skeletal muscle. On this basis, some investigators suggested a pathogenic role of vascular involvement in the MELAS syndrome and other encephalopathies. smhd1 DESIGN/METHODS: The authors investigated neuronal metabolism and cerebrovascular involvement with PET in 5 cases and with TCD with acetazolamide stimulation in 15 cases. The patients were divided into three groups: 1) interictal MELAS (n = 4); 2) progressive external ophthalmoplegia (n = 6); and 3) pure mitochondrial myopathy and neuropathy (n = 5). The results were compared with those from matched normal control subjects. The diagnoses were based on clinical phenotype as well as histopathologic and molecular analysis. RESULTS: Cerebral glucose uptake was impaired in all patients, both with and without CNS symptoms, particularly in the occipital and temporal lobes. The vasoreactivity of the small arterioles to acetazolamide did not differ significantly between the patients and healthy control subjects or between the different groups of mitochondrial disorders. CONCLUSIONS: MELAS does not appear to be a functional disturbance of arterioles leading to an ischemic vascular event. The clinical symptoms in MELAS are not the result of a mitochondrial angiopathy but are the consequences of a mitochondrial cytopathy affecting neurons or glia. There is no correlation between the decreased glucose metabolism and the duration of the disease.

Gender-related differences in acetazolamide-induced cerebral vasodilatory response: a transcranial Doppler study.

Cerebrovascular reactivity, cerebrovascular reserve capacity, and velocity acceleration can be easily and reliably assessed by measuring acetazolamide-induced changes using transcranial Doppler. The authors' aim was to determine whether there are gender-related differences in these parameters. Fifty-six healthy subjects (27 males, 29 females) were examined using transcranial Doppler. Velocities in the middle cerebral artery on both sides were recorded before and at 5, 10, 15, and 20 minutes after intravenous administration of 1 g acetazolamide. The baseline mean flow velocity in the middle cerebral artery was significantly higher in women than in men (p < 0.02). After acetazolamide administration, significantly higher cerebrovascular reactivity, cerebrovascular reserve capacity, and velocity acceleration were observed in females than in males (p < 0.001 in all cases). Subgroup analysis showed that women before menopause responded with higher cerebrovascular reserve capacity and velocity acceleration than age-matched men (p < 0.01 and p < 0.001, respectively), but no significant difference was found between females after menopause and men of similar age.

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.

Cations of cisternal cerebrospinal fluid in humans and the effect of different doses of nimodipine on CSF calcium after stroke.

Cisternal samples of cerebrospinal fluid (CSF) were analyzed for protein, albumin, sodium (Na), potassium (K), and calcium (Ca) content in 21 control subjects and 64 patients who had experienced acute stroke. A second cisternal CSF sample was taken in 37 of the stroke patients after 2-3 weeks treatment with the calcium antagonist nimodipine. Increased permeability of the blood-brain barrier was reflected by the significantly higher CSF/serum ratio of albumin in stroke patients than in control subjects (0.0046 vs. 0.0028,p = 0.0012). Serum and CSF concentrations of Na, K, and Ca did not differ between control subjects and stroke patients. In control subjects and in stroke patients, concentration of calcium in cisternal CSF ([Ca]) was smaller than values reported by others in lumbar samples. In stroke patients, the pH of CSF was lower than that of simultaneously taken blood (7.38 vs. 7.44, p < 0.001). No differences between stroke patients and control subjects were found for the cisternal CSF/serum ratios of Na (1.0 and 0.99), K (0.61 and 0.63), and Ca (0.25 and 0.24). When patients and controls were pooled together, CSF total [Ca] correlated weakly with serum total [Ca] (Spearman r = 0.28, p = 0.014) and with serum ionized [Ca] (Spearman r = 0.27, p = 0.016). After 2-3 weeks of nimodipine treatment, CSF [Ca] was significantly lower in the subgroup treated with 60 mg nimodipine four times daily (240 mg/d) than with 30 mg four times daily. A nimodipine dosage of 30 mg four times daily (120 mg/d) did not affect CSF [Ca]. A 240 mg daily dosage, but not a 120 mg daily dosage, of nimodipine may affect the Ca transport system in humans at the choroid plexus.

[Carotid atherosclerotic lesions in stroke patients with diabetes mellitus]. / Az arteria carotisok atheroscleroticus laesióinak vizsgálata diabetes mellitusban szenvedö cerebrovascularis betegekben.

The aim of the study was to assess the incidence of atherosclerotic lesions on carotid arteries among diabetic subjects suffering from cerebrovascular accident. A further aim was to investigate the relationship between the severity of the carotid lesion, the stroke subtype and the fatal outcome. One hundred and sixty eight patients treated because of cerebrovascular accident at the Dept. of Neurology University Medical School of Debrecen were studied. The age of the patients, the duration of diabetes and hypertension were registrated. Base on duplex scanning carotid lesions were divided in 6 groups of severity (normal, intimal sclerosis, slight, moderately severe, severe stenosis and occlusion). Based on clinical signs and CT results stroke subtypes were divided into five groups (lacunar and non-lacunar infarctions, hemorrhages, normal CT and others). The relationship between severity of carotid lesions, stroke subtype and lethal outcome was assessed using statistical tests. Carotid stenosis of different severity was detected in 60% of the cases. Severity of stenosis was independent from duration of diabetes, but it was positively related to duration of hypertension (p = 0.016). In 1/3 of the patients lacunar strokes, in another 1/3 non-lacunar strokes were observed. No significant relationship was found between severity of carotid stenosis, stroke subtype and lethal outcome of the patients (p = 0.53 and p = 0.26 respectively). Diabetic patients suffering from stroke have a higher incidence of carotid artery atherosclerotic lesions than diabetics without stroke. A special attention should be paid to the carotid duplex sonography in order to detect diabetic cerebral macroangiopathies in early, asymptomatic stage.

Power Doppler imaging and color Doppler flow imaging for the evaluation of normal and pathological vertebral arteries.

Recently, an ultrasound method for vascular applications using the amplitude of the reflected echosignal for the generation of intravascular color signals has been introduced. We compared the utility of this power Doppler imaging (PDI) with conventional color Doppler flow imaging (CDFI) for examination of vertebral arteries (VA). Forty-nine patients with signs and symptoms suggesting ischemia within the posterior circulation were evaluated. Quality of blood flow visualization by PDI and CDFI at the different VA segments was classified according to a four point scale. Furthermore, combined sonographic findings were correlated with the results of digital substraction and/or magnetic resonance angiography (DSA, MRA). Power Doppler imaging provided a significantly superior visualization of the intertransversal VA, whereas display of the intracranial V4 segment was superior significantly on CDFI. Both methods were complementary for the evaluation of the VA at the origin. With respect to the angiographic findings, combined CDFI and PDI achieved a sensitivity of 90.63% and a specificity of 97.22% for the differentiation of healthy and pathologic VAs. Power Doppler imaging is complementary to CDFI for the sonographic assessment of VA disease. Combined use of PDI and CDFI achieves a high sensitivity and specificity, thus increasing diagnostic confidence.

[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.

Impairment of cerebrovascular reactivity in long-term type 1 diabetes.

The early preclinical detection of cerebrovascular complications in individuals with diabetes is one of the goals of care described in the St. Vincent Declaration. In accordance with this goal, the aim of the present work was to investigate whether altered cerebral microvascular function in patients suffering from type 1 diabetes can be detected with a transcranial Doppler probe after the administration of acetazolamide. A total of 72 type 1 diabetic patients and 40 healthy control subjects entered the study. Patients were divided into two groups: those with long-term diabetes (disease duration of >10 years, n = 37) and those with short-term diabetes (disease duration of < or =10 years, n = 35). Mean blood-flow velocity in the middle cerebral artery (MCAV) was measured at rest and at 5, 10, 15, and 20 min after intravenous administration of 1 g acetazolamide with a transcranial Doppler probe and expressed as the percentage change from the pretest measurement. The percentage increase in MCAV (cerebrovascular reactivity) was calculated at each time point and compared between the groups. Cerebrovascular reserve capacity (CRC), expressed as the maximal percentage increase of the MCAV, was compared between the groups. Additionally, a reproducibility study of CRC was performed in 10 patients, using intraclass correlations. Cerebrovascular reactivity in the long-term diabetes group was lower (means +/- SD: 5 min, 23.4 +/- 15.4%; 10 min, 28.8 +/- 17.0%; 15 min, 30.0 +/- 15.6%; 20 min, 24.2 +/- 17.8%) than that of the control subjects (5 min, 43.5 +/- 23.9%; 10 min, 55.3 +/- 24.0%; 15 min, 56.7 +/- 23.8%; 20 min, 54.8 +/- 25.9%) and the short-term diabetic patients (5 min, 43.6 +/- 25.9%; 10 min, 52.2 +/- 27.7%; 15 min, 55.3 +/- 32.2%; 20 min, 45.8 +/- 35.8%). CRC was lower in the long-term diabetes group than in the control group or the short-term diabetes group. Impairment of cerebrovascular reactivity was associated with retino- and nephropathy and increased levels of fibrinogen. In contrast, CRC was independent from actual glucose, insulin, glycosylated hemoglobin, von Willebrand factor antigen, and alpha-2 macroglobulin levels. Transcranial Doppler measurements of the changes in MCAV after stimulation with acetazolamide can detect altered cerebral microvascular function in patients with diabetes. Cerebrovascular reactivity and reserve capacity are reduced in patients with long-term diabetes. Further prospective studies should delineate the clinical significance of our results.

Cerebrovascular reactivity in hypertensive patients: a transcranial Doppler study.

PURPOSE: We studied the usefulness of transcranial Doppler sonography for assessing changes in vasoreactivity in patients with hypertension and the hemodynamic consequences of hypertension. METHODS: The study group comprised 25 patients with chronic severe hypertension and 25 age- and sex-matched healthy subjects. Cerebrovascular reserve capacity was assessed by transcranial Doppler recording of the blood flow velocity in both middle cerebral arteries before and 5, 10, 15, and 20 minutes after intravenous injection of 1 g of acetazolamide (Diamox). Blood pressure, blood gases, and other blood parameters were also measured before and after acetazolamide injection. The sizes of the left atrium, left ventricle, and aortic root were measured by echocardiography and correlated with the vasoreactivity after acetazolamide injection. RESULTS: After acetazolamide injection, no significant changes in blood pressure were observed in either group. The mean blood flow velocity in the middle cerebral arteries of hypertensive patients (60.8 +/- 2.6 cm/sec) was not significantly different from that of controls (58.8 +/- 1.9 cm/sec) before acetazolamide injection. Ten minutes after acetazolamide injection, the percentage change in blood flow velocity was significantly lower in the hypertensive group (36.2 +/- 4.5%) than in the controls (52.6 +/- 3.7%). A significant negative correlation (p < 0.05) between decreased vasoreactivity and increased size of the left atrium and aortic root was observed. CONCLUSIONS: Vasoreactivity decreases in hypertensive patients without neurologic deficits or computed tomography abnormalities. Enlargement of the left atrium correlates well with the severity of the impairment in vasoreactivity. Transcranial Doppler sonography can be a sensitive tool in the investigation of vascular impairment caused by hypertension and in the follow-up of hypertensive patients.

Combined electroencephalography and measurements of transcranial blood flow velocity during orthostatic testing--a new approach to assess syncope of unknown origin?

Differential diagnosis of syncope and seizures frequently imposes a major problem, particularly if interictal examinations are normal. We performed orthostatic testing combined with surface electroencephalography (EEG) and non-invasive measurements of cerebral blood flow velocity. Ten healthy controls, ten patients with confirmed diagnosis of epilepsy and 25 patients with history of syncope of unknown origin were examined. The following parameters were evaluated continuously and simultaneously during orthostatic challenge: computerized EEG with synchronous video-monitoring, transcranial Doppler sonography (TCD), heart rate and blood pressure. Isolated cerebrovascular dysregulation (i.e. a drop in cerebral perfusion despite the absence of a significant drop in peripheral blood pressure) occurred in 2/10 controls, 3/10 patients with epilepsy and 11/25 patients with syncope of unknown origin. The combined EEG and TCD measurements represent a new approach to the work-up of patients with otherwise unexplained syncope, helping us to understand the interdependence of neuronal activity and peripheral/cerebrovascular autoregulation under postural stress.

[Cerebrovascular reactivity in insulin dependent diabetes mellitus studied by an acetazolamide test]. / A cerebrovascularis reaktivitás vizsgálata inzulin dependens diabetes mellitusban acetazolamid-teszttel.

The aim of this study was to investigate, whether the cerebrovascular reactivity (CR) was altered in diabetes mellitus and to evaluate the influence of diabetes's duration on cerebrovascular reactivity. Transcranial Doppler-Acetazolamide tests were performed on 20 insulin-dependent diabetics and in 19 controls. Patients were divided into two groups, each group consisted of 10 patients: diabetics with > 10 years disease duration and with < 10 years diseases duration. Middle cerebral artery mean velocities were measured at rest and after i.v. administration of Ig Acetazolamide (AZ). There were no differences in the absolute velocities between controls and diabetics. The percentual increase of the mean velocity after AZ was slower and less intensive in longterm diabetics (means +/- SE: 5 min: 19.4 +/- 2.8%, 10 min: 28 +/- 3.6%, 15 min: 25.7 +/- 3.8%, 20 min: 23.9 +/- 4.3%), than that in controls (5 min: 32.3 +/- 4.3% -p < 0.05-, 10 min: 45.1 +/- 4.9% -p < 0.05-, 15 min: 47.5 +/- 4.3% -p < 0.01-, 20 min: 46.5 +/- 4.7% -p < 0.01) as well as in diabetics with < 10 years disease duration (5 min.: 39.5 +/- 7% -p < 0.05-, 10 min.: 49.2 +/- 6.5% -p < 0.05-, 15 min.: 53.9 +/- 8.6% -p < 0.01-, 20 min: 32.9 +/- 5.9% -n.s.). The cerebrovascular reactivity is impaired in diabetics after long duration of the disease. The altered cerebrovascular reactivity might be caused by angiopathy of the cerebral arterioles.

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.

[Significance of computer analysis of dynamic brain scintigraphy in patients with cerebrovascular disorders]. / Dinamikus agyszcintigráfiás vizsgálatok számítógépes elemzésének jelentösége cerebrovascularis betegek vizsgálatában.

Dynamic cerebral scintigraphy was performed on 41 patients with cerebrovascular disease. The diagnostic value of parametric images formed by a computer was correlated to angiographic findings and clinical sings, respectively. Having the appropriate software these examinations can be performed with traditional gamma-cameras. Analysis of parametric pictures increases the reliability of the method. Analysis of cinematic display of serial images had the highest sensitivity and accuracy, while time-of-maximum pictures had the highest specificity. In departments, where digitized subtraction angiography, single photon emission computed tomography or positron emission tomography is not available, the non invasive dynamic brain scintigraphy is a useful screening method, its application is proposed by the authors.