[Interdisciplinary approach to vestibular system impairment]. / A vestibularis rendszer károsodásainak interdiszciplináris szemlélete.

In the first part of this review the definition of vertigo/dizziness was discussed. The major difference between the two signs is the existence of the direction, which is specific for vertigo. Dizziness is a frequent complaint in the clinical practice. Its frequency is increasing with advance of age, to intimate the play of declining cognitive process in the pathogenesis of its. The popular health significance of vertigo is in the rowing number of the patients. The onset of the most cases with acute vertigo appears between secundums and minutes so the patients will be provided in circumstances of emergency department. First of all three form should be take into account: neuronitis vestibularis, benign paroxysmal positional vertigo and Meniere syndrome. Without typical periferal signs of vertigo, central cause should be searched, principally stroke (lysis possibility). The differential diagnose of the different dizziness/vertigo forms according to the elapsed time of the onset or congenital and acquired nystagmus was created in tables. The recommendations of the therapy of acute and chronic dizziness/vertigo syndromes are, lack of results of evidence based trials doubtful. The more often used drugs based on clinical trials are discussed as vinpocetine, betahistine and piracetam. The in vitro and in vivo data suggest that the last molecule is eligible to use both in periferal and central type of vertigo syndromes.

Connection between genetically determined blood coagulation factors and haemorheology.

BACKGROUND: The phenotype caracteristic of blood clotting factors are well known, however few data has been documented about effects on haemorheology. The connection among genetic polymorphisms, haemorheological factors and vascular mortality is also studied poorly. PURPOSE: Our aim was: to study six genetic polymorphisms of blood clotting factors, which presents the role of platelet-plasmaprotein-endothel system in thrombotic course in controls and ischaemic stroke cohort. Second, to study the connection of genotypes and haemorheologic factors and both with five years vascular mortality in patients. PATIENTS AND METHODS: It was studied the genetic polymorhisms of GP IIb/IIIa Leu33Pro, prothrombin gene G20210A, ACE I/D, fibrinogen gene-455 G/A, Leiden mutation and MTHFR C677T alleles or genotypes in blood samples of 433 ischaemic stroke patients and 173 controls by PCR. Haematocrit values, plasma fibrinogen (FIB) concentration, whole blood viscosity (WBV) at 90 s(-1) and also the plasma viscosity (PV) were measured. Vascular mortality of patients were followed during five years and studied by curves Kaplan-Meier. RESULTS: A higher plasma FIB concentration in non smoker patients, carrying A alleles of FIB gene could be observed as compared to wild types (p<0.05). Also a moderate WBV increasing in smoker patients with A alleles was found against wild types (p=0.11), at the same time we observed a significant WBV increasing in non smoker patients (p<0.05). The highest quartile of PV showed a connection with Leiden mutation in whole group of patients (p=0.01), in subgroup of young patients (<50 years) (p=0.03) and also in non smoker groups (p<0.05) as compared to patients having wild types. No association could be detected between different genetic polymorphisms and vascular mortality, however it was observed significant mortality increasing in patients having PV above 1.51 mPa s (p=0.03). CONCLUSION: Certain genetic polymorphisms of coagulation system could result unfavorable haemorheological changes, however non of them increases the mortality. The connection between higher mortality and PV focuses the attention for the necessity of PV measuring and correction in stroke patients.

The effects of platelet receptor GPIIb/IIIa polymorphism (Leu Pro33) on the receptor expression and platelet aggregation in patients with ischaemic stroke.

Platelet hyperaggregation in ischaemic stroke patients is a proven finding, and associated with increased expression of the platelet surface GPIIb/IIIa receptor. The polymorphism occurs at nucleotide position 1565 of the GPIIIa gene resulting a 33Leu-Pro change. Data are conflicting regarding the abnormal function of the PlA1/A2 receptor in stroke. The aim of the study was to address the difference of platelet receptor function in ischemic stroke patients with the wild PlA1/A1 and heterozygous PlA1/A2 genotype. A total of 51 patients with PA1/A1 and 54 patients with PlA1/A2 genotypes were enrolled. Polymerase chain reaction was used for genotyping of platelets. Platelet aggregation was measured in whole blood and in platelet rich plasma (PRP). Flow cytometry was used for measuring surface molecule expression (CD42b, CD41a, CD61, CD62P) and fibrinogen binding capacity of cells with phosphate buffer solution (PBS) in comparison with activation by ristocetin in whole blood as well as by adenosine diphosphate (ADP) in PRP. In comparison with wild types, platelets carrying the PlA1/A2 genotypes showed hyperaggregation measured in whole blood and induced by ristocetin (p< 0.05). Using whole blood flow cytometry with ristocetin induction, the CD62P+/FIB- (P selectin) and the CD62P+/FIB+ were more expressed in heterozygous platelets as compared to wild types (p< 0.01 and p< 0.05), respectively. According to mean fluorescence intensity with ADP induction, an increased expression of CD61+, CD61+/CD41+ and CD62P+ in PlA1/A2 platelets were detected as compared to the group carrying the wild type (p< 0.0001, p= 0.006, p= 0.0001), respectively. These findings support the possibility that in ischaemic stroke patients, platelets carrying PlA1/A2 genotypes can be activated by different inductors in a way, which leads to permanent hyperfunction of platelet surface receptor GPIIIa.

Contribution of the -455G/A polymorphism at beta-fibrinogen gene and of the Leiden mutation to hemorheological parameters in ischemic stroke patients.

UNLABELLED: The concentration of plasma fibrinogen (FIB) is an important factor in the coagulation cascade and also in the determination of blood and plasma viscosity depending on both genetic and acquired factors. The -455G/A polymorphism of the beta-FIB gene is connected to the plasma concentration of FIB but the effect of Leiden mutation on hemorheological parameters is unclear. The two genetic polymorphisms were studied by polymerase chain reaction in healthy subjects and ischemic stroke cohort and the effects on the concentration of plasma FIB, whole blood and plasma viscosity of patients as well. A total of 278 ischemic stroke patients and 173 control subjects were enrolled. Marcro-rheological parameters as plasma FIB concentration, whole blood viscosity (90 sec(-1) shear rate) and plasma viscosity have been measured also in the subgroup of young (age < 50 years) and in a subgroup of non-smoker patients. RESULTS: No significant difference was found in the prevalency of H1/H2 genotype between controls and cases in pooled stroke group OR 0.95 (95% CI: 0.47-1.27), however H2/H2 genotype frequency was increased in young subgroup of patients (OR: 1.66 95% CI: 0.52-5.25). Plasma FIB concentration was increased both in the total cohort (p < 0.05) and in the non-smoker subgroup (p < 0.03) of patients carried H2/H2 as compared to H1/H1 genotype and the prevalence was increased in the group of patients having plasma FIB concentration > 4 g/l (p < 0.05). The whole blood viscosity was elevated in the H2/H2 group as compared to the group carrying wild type (p < 0.03). A tendency of increased plasma viscosity in the group of patients with H2/H2 genotype as compared to wild type was found (p = 0.07). Leiden mutation prevalence showed an increased risk OR: 1.67 (95% CI: 0.75-3.70) in the young patients group as compared to controls. In patients who have had the highest plasma viscosity, higher frequency of Leiden mutation was detected as compared to wild type, in total group (p = 0.01), in young patients (p = 0.03) and in subgroup of non-smoker patients (p = 0.05). CONCLUSIONS: Our findings support the notion that the homozigous variant of beta-FIB gene can raise both plasma FIB concentration and whole blood viscosity. Leiden mutation connected to the elevation of plasma viscosity could demonstrate a new pathway of increased thrombophylic potential in ischemic stroke patients.

Intra-arterial Thrombolysis in Second Trimester of Pregnancy. A Case Report.

Here we present a successful intra-arterial thrombolysis performed in the second trimester of pregnancy (21 weeks). The intervention resulted in complete recanalization of the occluded right middle cerebral artery and favourable clinical and gestational outcome. Together with cases described in respective medical literature our report affirms that in pregnancy acute ischemic stroke could be treated effectively applying intra-arterial thrombolysis (using rt-PA). This therapy could provide opportunity to help in such desperate situations.

Measurement of platelet aggregation during antiplatelet therapy in ischemic stroke.

Aspirin, ticlopidine and clopidogrel are used as a pharmacological means to efficiently decrease the number of reoccurrence of ischemic stroke (100-325 mg/d). This antiplatelet treatment could prevent the secondary stroke by approximately 22%. Laboratory effective platelet inhibition for the clinician, and methods for routine screening evaluation for the laboratory were studied. (1) For the standardisation of platelet aggregation technology blood samples of 150 healthy persons were studied in 5 centres. CARAT TX computerised optical aggregometer was used for measuring with collagen (2 microg/ml), epinephrine (10 microM), arachidonic acid 0.5 mM and ADP 5 microM as inductors. (2) Laboratory tests were compared in each centres performed in platelet-rich plasma of ischemic cardiovascular and stroke patients (n=823) taking 100-325 mg aspirin/d. (3) Blood samples of 555 ischemic stroke patients treated with aspirin (100-325 mg/d), 96 patients treated with ticlopidine (500 mg/d), and 67 patients treated with clopidogrel (75 mg/d) were evaluated, respectively.(1) The mean of maximal aggregation (%) - 2SD of untreated controls (n=150) were detected for collagen with 64%, epinephrine 59% and ADP 62%. (2) In 823 aspirin treated patients were found similar inhibition in different centres with same methods for standardisation. The mean inhibition level was in case of collagen 38%, epinephrine 37% and ADP 61%. (3) The distribution of ineffective platelet inhibition was detected in 17% of aspirin group (collagen and epinephrine), 4% of ticlopidine and 18% of clopidogrel group with ADP, respectively. Our findings were in the stroke cohort: effective inhibition levels: 36% in aspirin group, 73% in ticlopidine and 25% treated with clopidogrel. Platelet aggregation tests could help to find the optimal, and "custom taylored" dose of antiaggregating drugs in the secondary prevention of ischemic stroke.

Effects of blood hyperviscosity on functional integrity in the brain stem: a brain stem evoked auditory potential study.

Clinical hemorheological and brain stem auditory evoked potential (BAEP) investigations were performed in patients with ischaemic brain stem stroke. Lesions were verified by MRI. 55 healthy persons with negative rheological and BAEP findings were used as controls (group A/1). 33 stroke patients with negative rheological parameters (group A/2) and 34 patients with hyperviscosity (group A/3) were also enrolled. In group A/3 bilateral pathological BAEP patterns were found, that could be explained by microcirculatory disturbances. 36 persons with verified blood hyperviscosity, but without neurological signs were also examined (group A/4). In this group, as in group A/3, either total lack of any waveforms, or a bilateral prolongation of wave III was observed. In 31 cases of group A/4, control BAEP was performed after effective haemodilution therapy, and 6-12 months later (group B/1). Here, normalization of rheological profile had a temporary beneficial effect on BAEP in 14 of 18 cases with former wave III prolongation, but had no effect on BAEP patterns in 13 cases, where lack of waves had been verified by the first investigation. These data suggest that hyperviscosity can result in subclinical pathological symmetric BAEP patterns, both in ischaemic stroke patients and in hyperviscosity patients without neurological symptoms.

[Investigation of insertion/deletion polymorphism of the ACE gene in stroke patients]. / Stroke-betegek insertiós-deletiós ACE-gén-polimorfizmusának vizsgálata.

INTRODUCTION: This is the first Hungarian paper on the insertion/deletion polymorphism of ACE gene in stroke patients. According to literature data, the role of this polymorphism is controversial in the pathogenesis of stroke. The aim was to study the prevalence of the polymorphism in healthy persons and in stroke patients. PATIENTS AND METHODS: Blood samples from 173 unrelated healthy donors and 253 stroke patients were investigated by polymerase chain reaction (PCR). PrevIous stroke was documented by CT or MRI and CDS. A routine questionnaire was used to study previous vascular events and the risk profile of patients. RESULTS: I/I allele was found in 20%, I/D 52% and D/D 28% in the healthy group. Prevalence of the pathologic D/D allele did not differ between healthy and patients group (28% and 27%, OR: 0.88, and in subgroup age under 50 years OR: 1.00). No correlation was found between D/D and conventional risk profile but a positivE correlation was found in young patients having D/D and hyperlipidemia (p < 0.05) and hyperfibrinogenemia (p < 0.05). D/D prevalence was found higher in patients with family anamnesis of myocardial infarction (p < 0.05). Very low prevalence of D/D allele was found in cardiogen embolic group (p > 0.05). CONCLUSIONS: The ACE polymorphism does not seem to be an independent risk factor for stroke. However, in young stroke patients with D/D allele, hyperlipidemia and/or hyperfibrinogenemia present very high risk for stroke.

[Genetics of blood coagulation in young stroke patients]. / Véralvadási genetika fiatalkori stroke-ban.

BACKGROUND AND PURPOSE: The classical risk factors did not explain all the possible etiology of cerebral stroke. Genetic polymorphisms responsible for thrombophilia were implicated recently as risk factors of stroke. In this genetico-epidemiological study the author's aim was to analyse the tendency of genetic polymorphisms to cluster in a cohort of young and elderly stroke patients and in healthy subjects in Hungary. METHODS: 253 patients with stroke were compared with 173 healthy blood donors on the basis of genetic polymorphisms of platelet GP IIb/IIIa receptor (33 LeuPro), prothrombin gene G20210A, Factor V Leiden mutation, ACE I/D, methylenetetrahydrofolate reductase (MTHFR) and beta fibrinogen gene G455A. These data were acquired using PCR. Questionnaires were used to investigate the family history and to determine the risk factor profile. The subtypes of stroke were analysed in a stroke cohort grouped according to different polymorphisms. RESULTS: An increased frequency of GP IIIa heterozygosity was found as compared to a West-European stroke cohort (31% versus 19%). The prothrombin gene variant (2.9% European and 4.8% in Hungary) was also found to increase in frequency. In young stroke patients (age < 50) compared with control subjects the odds ratios were higher: in prothrombin gene (OR: 4.9), in Leiden mutation (OR: 1.67), in fibrinogen gene (OR: 1.64) and in MTHFR(+/+) (OR: 1.58). Clustering of two polymorphisms could only be detected in young patients. These clustering polymorphisms were GP IIb/IIIa with prothrombin G20210A variant (OR: 6.74, 95% CI 1.1-18.2) and prothrombin gene variant with MTHFR (OR: 5.3, CI95 1.2-8.3). CONCLUSION: Selected and clustered genetic polymorphisms of haemostatic factors could be responsible for the high stroke morbidity in Central Europe. The presence and clustering tendency of these factors have been described in young stroke victims.

[Significance of Factor V gene A506G mutation (Leiden) in the pathogenesis of ischemic stroke]. / Van-e jelentósége az V. faktor gén A506G (Leiden-féle) mutációjának ischaemiás stroke esetén?

BACKGROUND: There are conflicting data about the role of Leiden mutation in the pathogenesis of cerebral arterial thrombosis. In order to obtain relevant data, authors investigated the prevalence of factor V Leiden (A506G) both in healthy subjects and in a subgroup of ischaemic stroke patients. MATERIAL AND METHODS: Blood samples of 171 healthy persons and 254 ischaemic stroke patients were examined by PCR method for Leiden mutation. Ischaemic lesions in the stroke group were documented by CT or MRI. A routine questionnaire was used to study the family history of vascular events (hypertension, diabetes, POAD, stroke, myocardial infarction) of patients. Conventional vascular risk factors of patients were also documented. RESULTS: The prevalence of Leiden mutation was 7.2% in healthy persons and 11.9% in stroke patients. The OR for 254 patient was 1.45 (0.71-2.97). In the subgroup of young patients: age < 50 (n = 134) the OR was 1.67 (0.75-3.70) and in the elderly patients group: age > 50 (n = 120) the OR was 1.21 (0.50-2.89). In the family history of stroke patients having Leiden mutation (hetero- and homozygosity) the stroke prevalence was higher (p = 0.01). In the ischaemic stroke group, age < 50 with polymorphism a tight correlation with hyperlipidaemia (p = 0.03) was found. In the group of age < 50 with heterozygosity for Leiden, a lower plasma fibrinogen concentration (p = 0.02) was found. The polymorphism showed no correlation with the hypertension, hyperuricaemia, migraine, diabetes mellitus, smoking, alcohol consumption and CDS status of patients. CONCLUSION: When comparing stroke patients to control population there is no significant increase in the frequency of Leiden mutation. Leiden mutation together with hyperlipidaemia and stroke in the family history results in high risk for ischaemic stroke in young patients.

Factor XIII-A subunit Val34Leu polymorphism in fatal atherothrombotic ischemic stroke.

Factor XIII (FXIII) is a regulator of fibrinolysis and clot firmness. Val34Leu polymorphism of its potentially active A subunit (FXIII-A) leads to faster activation of FXIII, influences clot structure and provides a moderate protection against coronary artery disease. The effect of FXIII-A Val34Leu polymorphism on the risk of atherothrombotic ischemic stroke (AIS) has been investigated in a few studies with contradictory results. In all previous studies, only patients surviving AIS were enrolled and sex-specific effects were not explored. In this retrospective multicenter cohort, we investigated the effect of FXIII-A Val34Leu polymorphism on the risk of fatal AIS in women and men. DNA isolation and genetic determinations in the case of 316 patients who died of AIS were carried out on paraffin-embedded tissue specimens. Genetic analyses for population controls, patients with history of AIS and sex-matched controls were performed on extracted genomic DNA from peripheral blood leukocytes. The prevalence of homozygous wild-type, and heterozygous genotypes, Leu34 carriers and Leu34 allele was not different significantly between the patients with fatal AIS and their respective controls. Logistic regression analysis with age as co-variant demonstrated that in women, homozygous presentation of Leu34 allele represented a more than three-fold increased risk of AIS with fatal outcome. The results demonstrate that FXIII-A Val34Leu polymorphism does not influence the occurrence of AIS, but has an effect on the severity of its outcome. This effect is sex-specific and in homozygous women, the prothrombotic/antifibrinolytic effects of FXIII-A Val34Leu polymorphism seem to prevail.

Comparison of a new P2Y12 receptor specific platelet aggregation test with other laboratory methods in stroke patients on clopidogrel monotherapy.

BACKGROUND: Clinical studies suggest that 10-50% of patients are resistant to clopidogrel therapy. ADP induced platelet aggregation, a widely used test to monitor clopidogrel therapy, is affected by aspirin and is not specific for the P2Y12 receptor inhibited by clopidogrel. OBJECTIVES: To develop a P2Y12-specific platelet aggregation test and to compare it with other methods used for monitoring clopidogrel therapy. PATIENTS/METHODS: Study population included 111 patients with the history of ischemic stroke being on clopidogrel monotherapy and 140 controls. The effect of clopidogrel was tested by a newly developed ADP(PGE1) aggregation test in which prostaglandin E1 treated platelets are used. Results of conventional ADP induced platelet aggregation, VerifyNow P2Y12 assay and ADP(PGE1) aggregation were compared to those obtained by flow cytometric analysis of vasodilator stimulated phosphoprotein (VASP) phosphorylation. Reference intervals for all assays were determined according to the guidelines of Clinical Laboratory Standards Institute. RESULTS: The P2Y12-specificity of ADP(PGE1) test was proven by comparing it with ADP aggregation in the presence of P2Y1 antagonist, adenosine 3', 5'-diphosphate. The method was not influenced by aspirin treatment. Approximately 50% of patients were clopidogrel resistant by conventional ADP aggregation and VerifyNow tests. The ADP(PGE1) method and the VASP phosphorylation assay identified 25.9% and 11.7% of patients as non-responders, respectively. ADP(PGE1) aggregation showed good correlation with VASP phosphorylation and had high diagnostic efficiency. CONCLUSION: The new ADP(PGE1) method is a reliable test for monitoring P2Y12 receptor inhibition by platelet aggregation. As a subset of patients are non-responders, monitoring clopidogrel therapy by adequate methods is essential.

Factor XIII A subunit Val34Leu polymorphism in patients suffering atherothrombotic ischemic stroke.

INTRODUCTION: Factor XIII (FXIII) is a key regulator of fibrinolysis and clot firmness. Val34Leu polymorphism of its potentially active A subunit (FXIII-A) leads to faster activation of FXIII, influences clot structure and provides a moderate protection against coronary artery disease. The effect of FXIII A subunit (FXIII-A) Val34Leu polymorphism on the risk of ischemic stroke (IS) has been investigated in a few studies with contradictory results. In spite of their fundamental difference in pathogenesis and hemostatic pathomechanism, only four small studies investigated the effect of FXIII-A Val34Leu polymorphism on the risk of atherothrombotic IS (AIS) separately from cardioembolic IS. Gender specific effect of the polymorphism on the risk of AIS has not been explored. In the present study we investigated the effect of FXIII-A Val34Leu polymorphism on the risk of AIS on a large patient population. MATERIALS AND METHODS: A population control group of 1,146 randomly selected individuals, 496 patients surviving AIS and their age and sex-matched controls selected from the population control group were included in the study. FXIII-A Val34Leu genotype was determined on DNA samples, obtained from peripheral blood leukocytes, by fluorescence resonance energy transfer detection using melting curve analysis. RESULTS: Neither sex nor age affected the distribution of FXIII-A Val34Leu genotypes in population control group. No association was revealed between the risk of AIS and FXIII-A Leu34 carriership and homozygous or heterozygous presentation of Leu34 allele in either gender. CONCLUSION: FXIII-A Val34Leu polymorphism fails to influence the risk of AIS.

Frequencies of four ATP-binding cassette transporter G8 polymorphisms in patients with ischemic vascular diseases.

ATP-binding cassette transporter G8 (ABCG8) was found to participate in plant sterol and cholesterol (CHOL) transport; however, the potential associations of ABCG8 genetic variants and ischemic vascular diseases are largely unknown. Determinations of allele frequencies of four common ABCG8 polymorphisms (D19H, Y54C, T400K, and A632V) were carried out in 241 unrelated patients with ischemic stroke, 148 patients with coronary heart disease, and 191 blood donors (controls). Allele frequencies of the investigated polymorphisms in patient groups showed no significant differences compared with controls. There was a tendency toward reduced 54YY-genotype frequency among male patients with stroke. On stratification by age at disease onset, male patients with stroke under the age of 50 (n = 62) showed significantly reduced 54YY-frequency compared with male controls (n = 92; 24.2% vs. 41.3%; odds ratio: 0.45 [95% confidence intervals: 0.22-0.93]; p = 0.038). No such associations were found among women. In healthy controls, CHOL levels of individuals with the 54YY genotype (n = 71; median: 4.51 mM, 25th-75th percentiles: 4.19-5.43) were significantly reduced compared with 54YC and 54CC individuals combined (n = 120; median: 4.95 mM, 25th-75th percentiles: 4.42-5.88, p = 0.009). Further, we identified a new ABCG8-variant, T401S, in a control subject. In conclusion, ABCG8 54YY-genotype may be a potential protecting factor against ischemic stroke in young men and may influence plasma CHOL levels.

Decreased frequencies of ABCA1 polymorphisms R219K and V771M in Hungarian patients with cerebrovascular and cardiovascular diseases.

BACKGROUND AND PURPOSE: Genetic polymorphisms in ABC transporter A1 (ABCA1) may alter the regulation of plasma high-density lipoprotein (HDL), promoting or protecting from vascular diseases. METHODS: We investigated 244 unrelated, consecutively enrolled patients with ischemic stroke, 150 patients with coronary heart disease (CHD) and 193 blood donors for allele frequencies (AFs) of three common ABCA1 polymorphisms (R219K, V771M and I883M). RESULTS: Compared to controls (30.8 +/- 4.7 and 4.9 +/- 2.2%, respectively), decreased AFs were found in both patient groups for R219K and V771M (28.7 +/- 4.1 and 3.1 +/- 1.6% in stroke, and 25.7 +/- 5.0%; 1.3 +/- 1.3% in CHD patients, respectively). In a subset of stroke patients younger than 50, both variants occurred in significantly lower frequencies (22.4 +/- 5.5 and 1.8 +/- 1.7%, respectively). Similarly, among CHD patients younger than 60, AFs of R219K and V771M (22.6 +/- 7.5 and 0 +/- 1.6%, respectively) were decreased. V771M was almost exclusively (35/36) found in individuals carrying the R219K allele. CONCLUSIONS: Our data confirm earlier observations that ABCA1 R219K and V771M polymorphisms may be associated with a protective role against CHD and extend those to another important pathologic condition, namely stroke.

Antiplatelet therapy in ischemic stroke.

Stroke is the third leading cause of death and the leading cause of disability in the developed world. Atherothrombosis is the underlying condition that results in events leading to ischemic stroke and vascular death. Antiplatelet therapy is commonly used for both acute stroke and in secondary prevention. Numerous trials and meta-analyses have left little doubt that antiplatelet therapy effectively reduces stroke risk in patients with prior stroke or transient ischemic attack. Current antiplatelet agents include acetylsalicylic acid, clopidogrel, ticlopidine and extended release dipyridamole with low doses of acetylsalicyclic acid (aspirin). The optimum doses of antiplatelet drugs depend upon several variables, such as genetic and environmental factors, so that clinical and laboratory response for dosage varies for each patient. Recently, the correlation between the laboratory-measurable effect of antiplatelet agents and the clinical effectiveness on the mortality of ischemic stroke and cardiovascular patients has been documented. Due to the side effect of bleeding with different antithrombotic drugs, their future employment will be determined in combination with low dosages of each component. Laboratory-controlled, tailored drug therapy will be needed for long-lasting secondary prevention of ischemic stroke.