Temporal changes in regulatory T cell subsets defined by the transcription factor Helios in stroke and their potential role in stroke-associated infection: a prospective case-control study.

BACKGROUND: Regulatory T cells (Tregs) are involved in the systemic immune response after ischemic stroke. However, their role remains unclear, and the effect appears to be both neuroprotective and detrimental. Treg suppressor function may result in immunodepression and promote stroke-associated infection (SAI). Thus we assume that the bidirectional effects of Tregs may be in part attributed to the intracellular transcription factor Helios. Tregs with Helios expression (H+ Tregs) constitute 70-90% of all Treg cells and more frequently than Helios-negative Tregs (H- Tregs) express molecules recognized as markers of Tregs with suppressor abilities. METHODS AND RESULTS: We prospectively assessed the circulating Treg population with flow cytometry in 52 subjects on days 1, 3, 10 and 90 after ischemic stroke and we compared the results with those obtained in concurrent age-, sex- and vascular risk factor-matched controls. At all studied time points the percentage of H+ Tregs decreased in stroke subjects-D1: 69.1% p < 0.0001; D3: 62.5% (49.6-76.6), p < 0.0001; D10: 60.9% (56.5-72.9), p < 0.0001; D90: 79.2% (50.2-91.7), p = 0.014 vs. controls: 92.7% (81.9-97.0) and the percentage of H- Tregs increased accordingly. In patients with SAI the percentage of pro-suppressor H+ Tregs on post-stroke day 3 was higher than in those without infection (p = 0.03). After adjustment for confounders, the percentage of H+ Tregs on day 3 independently correlated with SAI [OR 1.29; CI 95%: 1.08-1.27); p = 0.02]. Although the percentage of H+ Tregs on day 3 correlated positively with NIHSS score on day 90 (rS = 0.62; p < 0.01) and the infarct volume at day 90 (rS = 0.58; p < 0.05), in regression analysis it was not an independent risk factor. CONCLUSIONS: On the first day after stroke the proportion of H+ vs. H- Tregs changes in favor of pro-inflammatory H- Tregs, and this shift continues toward normalization when assessed on day 90. A higher percentage of pro-suppressive H+ Tregs on day 3 independently correlates with SAI and is associated positively with NIHSS score, but it does not independently affect the outcome and stroke area in the convalescent phase of stroke.

Genetic testing and the phenotype of Polish patients with Unverricht-Lundborg disease (EPM1) - A cohort study.

AIM OF THE STUDY: The aim of this study was to explore genetic findings and the phenotype in Polish patients with Unverricht-Lundborg disease (ULD). MATERIALS AND METHODS: We retrospectively evaluated mutations in the cystatin B (CSTB) gene and clinical presentation in a cohort of patients with ULD. The study population consisted of 19 (14 males) patients with genetically confirmed disease. RESULTS: Sixteen patients were homozygous for the expanded dodecamer repeat mutation alleles, one subject was compound heterozygous for the dodecamer repeat expansion and other mutation, in two, the type of mutation has not yet been established. The numbers of repeats in the CSTB gene varied from 60 to 81. Clinical information was available for 16 subjects. The disease course was progressive in all patients, leading to severe disability, mainly due to myoclonus, in nine. CONCLUSIONS AND CLINICAL IMPLICATIONS: Genetic findings and the clinical picture of our patients with ULD were in accordance with available studies. The most common genetic defect underlying ULD was homozygosity for an unstable expansion of a dodecamer repeat in the CSTB gene. Patients with action or/and stimulus sensitive myoclonus or intractable myoclonus epilepsy, especially with onset in late childhood/adolescence should be screened for ULD.

Effect of acetylsalicylic acid intake on platelet derived microvesicles in healthy subjects.

Platelet-derived microvesicles (pMVs) are released from platelets in physiological and pathological conditions and exhibit a wide range of prothrombotic, antithrombotic, proatherogenic, and pro-inflammatory properties. Antiplatelet agents, such as acetylsalicylic acid (ASA), are widely used for the prevention and treatment of vascular diseases, but their impact on pMV release remains poorly understood and contradictory mainly because of discrepancies in the methodology and lack of well-standardized MV assessment protocols. The present study investigated the effects of ASA not only on total pMV release but also on their phenotypes defined using the surface expression of pro-inflammatory (CD40L, CD62P, CD31) and procoagulant (PS, PAC-1) markers in healthy subjects. Fifty healthy volunteers were enrolled in the study and received a daily dose of 150 mg ASA for 3 consecutive days. Circulating pMVs were characterized and quantified before and after the intervention period using flow cytometry. Serum levels of thromboxane B2 (TXB2) and whole blood impedance platelet aggregation under arachidonic acid (AA) stimulation were also investigated to assess ASA compliance. In general, ASA did not effect pMV numbers in healthy subjects despite its effective inhibition of platelet aggregation Moreover, in premenopausal women, we noticed an increase in the number of pMVs. Further studies are needed to assess whether dose modification of ASA or combinations or changes in antiplatelet therapy would reduce pMV formation, especially in patients with cardiovascular risk factors.

Unverricht-Lundborg disease: Clinical course and seizure management based on the experience of polish centers.

The purpose of this paper was to present our experience following the longterm treatment of 11 patients with Unverricht-Lundborg disease (ULD) confirmed by molecular testing. METHODS: We analyzed the clinical course, cognitive state, neuroimaging and neurophysiology results. RESULTS: The data were collected from 9 unrelated families (F/M: 4/7) aged 25-49. The most frequent early manifestations of ULD include generalized tonic-clonic seizures (GTCS) accompanied by myoclonus 2 years later. Myoclonus was observed in all of the patients; its severity made it impossible for 91% to move independently. In two patients- mild atrophy of brain were observed in the MRI. More than half of the patients who underwent evoked potential presented no abnormalities. The dominant EEG-change was slow background activity in all of the patients. Seven patients had generalized seizure activity. The patients received antiepileptic therapy modifications depending on the severity of symptoms and stage of the disease. Five patients received N-acetyl-cysteine. CONCLUSIONS: ULD patients require anti-epileptic polytherapy, mostly benefitting from managing GTCS and myoclonus with valproic acid and clonazepam treatment. Patients may benefit from add-on therapy with levetiracetam or topiramate. An increase in myoclonus, resulting from the progressive nature of the disease leads to significant disability in the majority of patients.

Association of platelet-derived microvesicles and their phenotypes with carotid atherosclerosis and recurrent vascular events in patients after ischemic stroke.

INTRODUCTION: Platelet-derived microvesicles (pMVs) exhibit procoagulant and proinflammatory properties and play a role in the development and progression of atherosclerosis. The study examined the association between the total number of pMVs and their phenotypes with carotid atherosclerosis and recurrent vascular events (VEs) in patients in the convalescent phase of ischemic stroke (IS). MATERIALS AND METHODS: The study group consisted of 72 patients with IS secondary to large artery atherosclerosis (LAA) (n = 40) and small arteries occlusion (SAO) (n = 32) and 69 matched cardiovascular disease risk-factor (RF) controls. Total pMV number, defined as CD61+ microvesicles (MVs), and their phenotypes, defined as the surface expression of proinflammatory (CD40L, CD62P, CD31) and procoagulant (PS, PAC-1) markers, were characterized and quantified using flow cytometry. The mean common carotid intima-media thickness (CCA mean IMT), maximal common carotid IMT (CCA max IMT) and maximal bifurcation IMT (BIF max IMT) were measured bilaterally using B-mode, color Doppler ultrasonography. All study subjects were observed for one-year to establish the occurrence of VEs. RESULTS: No differences in pMV parameters between LAA and SAO stroke subjects and between stroke subgroups and controls were found. Stroke patients with carotid atherosclerosis exhibited higher concentration of CD62P+/CD61+ and PAC-1+/CD61+ MVs compared to patients without the atherosclerosis. Positive associations between total number of pMVs, AnV+ MVs and AnV+/CD61+ MVs and atherosclerotic thickening of carotid intima-media in stroke patients were found. Elevated concentration of AnV+/CD61+, PAC-1+/CD61+, CD61P+/CD61+ and CD31+/CD61+ MVs, were revealed in stroke patients who suffered from recurrent VE in one-year follow-up period. Negative correlation of pMVs and CD62P+/CD61+ MVs concentration as well as percentage of total CD61+ in AnV+ population of MVs and time elapsed from IS in convalescent stroke subjects was revealed. CONCLUSION: Our results confirm positive correlations between total pMV number, the number of PAC-1+/CD61+ and CD62+/CD61+ MVs and carotid atherosclerosis in stroke subjects. Some pMV parameters may exhibit a predictive value for the next VE in groups with a history of stroke. pMVs and some of their phenotypes decline over time elapsed from stroke in convalescent stroke subjects.

Association of platelet-derived microvesicles with high on-treatment platelet reactivity in convalescent ischemic stroke patients treated with acetylsalicylic acid

Introduction: Elevated concentrations of platelet-derived microvesicles are found in cerebrovascular diseases. The impact of acetylsalicylic acid on these microvesicles remains inconsistent, despite its well-established effect on platelet aggregation. High residual platelet aggregation is defined as high on-treatment platelet reactivity, while "treatment failure" is the occurrence of vascular events despite antiplatelet treatment. The aim of this study was to determine whether the antiaggregatory effect of acetylsalicylic acid correlates with platelet-derived microvesicles in convalescent ischaemic stroke patients and cardiovascular risk factor controls as well as to evaluate the association between high on-treatment platelet reactivity and recurrent vascular events with the studied platelet-derived microvesicle parameters. Material and methods: The study groups consisted of 76 convalescent stroke patients and 74 controls. Total platelet-derived microvesicles, annexino-positive microvesicles number, and platelet-derived microvesicles with surface expression of proinflammatory (CD40L, CD62P, CD31) and procoagulant (PS, GPIIb/IIIa) markers were characterized and quantified using flow cytometry. Cyclooxygenase-1-specific platelet responsiveness, with whole blood impedance platelet aggregation under arachidonic acid stimulation and the serum concentration of thromboxane B2, were evaluated. Results: Neither acetylsalicylic acid intake nor modification of its daily dose caused statistically significant differences in the studied microvesicle parameters. Additionally, no statistically significant differences in the studied microvesicle parameters were revealed between high on-treatment platelet reactivity and non-high on-treatment platelet reactivity subjects in either study subgroup. However, elevated concentrations of PAC-1+/CD61+, CD62P+/CD61+ and CD31+/CD61+ microvesicles were found in stroke patients with treatment failure, defined in this study as a recurrent vascular events in a one-year follow-up period. Conclusions: This study revealed no relationship between circulating microvesicle number and platelet aggregation. The procoagulant and proinflammatory phenotype of circulating platelet-derived microvesicles might contribute to acetylsalicylic acid treatment failure.

[The level of experienced stress and personality traits in health professionals - the Polish study]. / Poziom odczuwanego stresu a cechy osobowosci u pracowników sluzby zdrowia ­ badania polskie.

Among professions of social services the highest level of stress is connected with health care and saving lives. This work demands making decisions, rapid changes, coordination of unforeseen requirements, moreover abounds in critical situations. One of the important factors affecting an ability of managing stressful situations are personality traits. AIM: The aim of this study was to verify hypothesis if there is a connection between personality traits (extraversion, neuroticism, psychoticism) and level of perceived stress among health care workers. MATERIALS AND METHODS: 180 participants of training (Certificated Partner of the Mental Health Center conducted in Poland) were selected to the analysis: psychologists, paramedics, nureses and doctors. Research was conducted using the Perceived Stress Scale (PSS-10) and Eysenck Personality Questionnaire (EPQ-R). RESULTS: Statistically significant corellation was observed in relation to subjectively experienced tension and results in scale of Psychoticism and Neuroticism (positive relationship). In case of extraversion scale corellation has negative character, but is not statistically important. CONCLUSIONS: Neuroticism as a state feature of character dominate among helath care workers. Both neuroticism and psychoticism conduce to negative effects of experienced stress.

Free thyroxine and TSH interact with secreted protein acidic and rich in cysteine-like 1 in ischemic stroke.

The role of the thyroid gland in ischemic stroke pathology is not well understood. As thyroid hormones modulate the extracellular matrix, we explored the possible link between them and secreted protein acidic and rich in cysteine like 1 (SC1) - one of the extracellular matrix molecules. In the 81 patients with acute ischemic stroke, serum SC1 levels were much higher compared with 30 control subjects: 4.47 vs 2.43ng/mL (p<0.001). Serum levels of free thyroxine (fT4) were higher in stroke subjects compared to those of controls (p=0.03). In stroke patients, TSH concentration was lower than in the control group (p=0.03). SC1 levels positively correlated with fT4 levels (p=0.02) and negatively with TSH (p=0.03) in stroke patients. Our results confirmed the association between thyroid hormones and SC1 - extracellular matrix protein.

The Association between Serum Matricellular Protein: Secreted Protein Acidic and Rich in Cysteine-Like 1 Levels and Ischemic Stroke Severity.

BACKGROUND: The role of matricellular proteins like secreted protein acidic and rich in cysteine-like 1 (SC1) has been shown in important functions in the central nervous system, including the regulation of synaptic stability with upregulation throughout axonal regeneration. The aim of this study was to determine whether SC1 is related to ischemic stroke severity. METHODS: A total of 132 consecutively recruited patients admitted for acute ischemic stroke were included in this observational prospective study. Stroke severity was evaluated in the National Institutes of Health (NIHSS) scale on hospital admission. RESULTS: There was a positive correlation between SC1 levels and NIHSS score (r = .22, P = .009). Compared with patients with NIHSS scores lower than 5 at admission, patients with moderate and severe stroke (NIHSS ≥ 6) had significantly higher SC1 levels: 4.84 (2.53-11.58) ng/mL versus 3.31 (1.67-8.95) ng/mL (P = .01). SC1 was an independent predictor of stroke severity at admission (adjusted odds ratio =1.25; 95% confidence interval, 1.03-1.97; P = .04). CONCLUSION: SC1 levels were independently associated with ischemic stroke severity evaluated by the NIHSS.

The Impact of Vascular Disease Treatment on Platelet-Derived Microvesicles.

Platelet-derived microvesicles (pMVs) are small, heterogeneous vesicles released from platelet membranes as a result of activation. These microvesicles possess a wide range of properties, including prothrombotic, proatherogenic, proinflammatory, immunomodulatory, and even anticoagulant activity. The elevated release of these microvesicles has been observed in various metabolic, inflammatory, thrombotic, and vascular diseases, including ischemic heart disease, stroke, hypertension, diabetes, and connective tissue disease. Modulation of both pMV generation and the expression of their surface molecules may have beneficial clinical implications and could become a novel therapeutic target. However, mechanisms by which pharmacological agents can modify pMV formation are elusive. The purpose of this review is to discuss the effects of drugs routinely used in primary and secondary prevention of vascular disease on the release of pMV and expression of their surface procoagulant and proinflammatory molecules.

Intracranial bleedings in patients on long-term anticoagulant treatment: Benefits from oral thrombin and factor Xa inhibitors in clinical practice.

Dabigatran, a direct thrombin inhibitor and activated factor X inhibitors, rivaroxaban and apixaban, used in the prevention of stroke or systemic embolism in patients with nonvalvular atrial fibrillation (AF), have several advantages over vitamin K antagonists (VKAs). The non-vitamin K oral anticoagulants (NOACs) have been shown to reduce the risk of intracranial bleedings by 50%. The current review summarizes the available data on the epidemiology, mechanisms and treatment of intracranial bleedings observed on oral anticoagulation with the focus on the specificity of NOACs in this context.

Neurological complications of underwater diving.

The diver's nervous system is extremely sensitive to high ambient pressure, which is the sum of atmospheric and hydrostatic pressure. Neurological complications associated with diving are a difficult diagnostic and therapeutic challenge. They occur in both commercial and recreational diving and are connected with increasing interest in the sport of diving. Hence it is very important to know the possible complications associated with this kind of sport. Complications of the nervous system may result from decompression sickness, pulmonary barotrauma associated with cerebral arterial air embolism (AGE), otic and sinus barotrauma, high pressure neurological syndrome (HPNS) and undesirable effect of gases used for breathing. The purpose of this review is to discuss the range of neurological symptoms that can occur during diving accidents and also the role of patent foramen ovale (PFO) and internal carotid artery (ICA) dissection in pathogenesis of stroke in divers.

Enhanced platelet-derived microparticle formation is associated with carotid atherosclerosis in convalescent stroke patients.

Platelets participate in the development and progression of atherosclerosis. During this process they interact with endothelial cells and leukocytes. Therefore, we investigated the associations between carotid atherosclerosis and platelet reactivity markers. The platelet surface expression of P-selectin (CD62P) and the activated GPIIb/IIIa receptor (corresponding to increased binding of PAC-1), as well as the fraction of platelet-derived microparticles (PMPs) prior to and after platelet stimulation with TRAP or ADP, were determined using flow cytometry in 94 subjects in the convalescent phase of ischaemic stroke and in 76 disease controls. The mean common carotid intima-media thickness (CCA(mean) IMT), maximal common carotid IMT (CCA(max) IMT) and maximal bifurcation IMT (BIF(max) IMT) were measured bilaterally using B mode, colour Doppler ultrasonography. In stroke subjects IMT within CCA and BIF were greater than in disease controls and the percentage of PMPs prior to and after ex vivo stimulation with agonists was significantly higher than in controls. Multiple regression analysis revealed that PMPs were positively and independently correlated with both CCA(mean) IMT (ß = 0.23; p < 0.01) and stroke (ß = 0.21; p<0.01), while PAC-1 binding to platelets activated with ADP was negatively and independently associated with CCA(mean) IMT (ß = -0.29; p<0.001) and atherosclerotic carotid plaque presence (ß = -0.28, p = 0.003). We found a positive association between enhanced PMP formation and atherosclerotic thickening of carotid intima-media or carotid plaque in patients after ischaemic stroke. We demonstrated that diminished expression of active GPIIb/IIIa in the ADP-activated platelets is associated with increased carotid IMT, independently of stroke.

[Neuropathies in the course of primary hepatotropic virus infections]. / Neuropatie w przebiegu zakazen wirusami pierwotnie hepatotropowymi.

The primary hepatotropic viruses are associated with various extrahepatic manifestations including peripheral nervous system disorders. The pathogenesis of these complications is not clear-cut. Patients with confirmed liver damage coexisting with peripheral nervous system manifestations, especially Guillain-Barré syndrome, mononeuropathy, mononeuropathy multiplex and polyneuropathy should be screened for the viral hepatitis in the differential diagnosis. There are no defined strategies of treatment for these manifestations, so the therapy should be individualized. The purpose of this review is to discuss the etiology, pathogenesis and treatment of the neuropathies in the course of primary hepatotropic viral infections such as hepatitis A, B, C and E viruses.

[Metabolic syndrome as the risk factor for ischaemic stroke]. / Zespól metaboliczny jako czynnik ryzyka niedokrwiennego udaru mózgu.

Metabolic syndrome (MetS) is a heterogeneous clinical entity represented by the occurrence of central obesity, hyperlipidaemia, hyperglycaemia and hypertension. The results of previous studies have shown that the probable common underlying pathophysiological factor for MetS is the insulin resistance phenomenon. However, the pathogenesis of the syndrome is still not well known. We present substantial information on MetS and the relationships between stroke and MetS as a compound entity, while individual components of MetS are well known risk factors for both first-in-life and recurrent ischaemic stroke. We also discuss primary and secondary stroke prevention in subjects with MetS.

Reactive leptin resistance and the profile of platelet activation in acute ischaemic stroke patients.

Leptin is an adipokine that in vitro enhances agonist-induced platelet aggregation and adipokine expression. Hyperleptinaemia represents a risk factor for cardiovascular disease. We conducted a prospective evaluation of the potential link between blood platelet activation and plasma leptin levels in post-stroke patients. Using five-colour flow cytometry, the platelet surface expression of CD40L, CD62P, the subpopulations of monocyte-platelet aggregates and platelet-derived microparticles (PMPs) as well as the plasma leptin, soluble leptin receptor (sOb-R), leptin/sOb-R ratio, the plasma adiponectin, and leptin/adiponectin ratio were assessed in 98 stroke patients on the first (V0), 10th (V1 ) and 90th (V2) day after stroke and once in 78 age-, gender- and vascular risk factor-matched disease controls. We demonstrated that at V0 leptin resistance, defined as leptin/sOb-R ratio, was higher than in the controls [1.1 (0.5-1.8 vs. 0.5 (0.2-1.1); p=0.02]. After adjustment according to the factors which influence platelet activation, we confirmed the relationship between percentage of circulating PMPs and plasma leptin level (B=0.18; p=0.02) or the leptin/sOb-R ratio (B=0.23; p=0.02) in normal-weight subjects in the acute phase of stroke. No correlation could be demonstrated between the adipokine parameters and the percentage of monocyte-platelet aggregates or expression of platelet pro-inflammatory glycoproteins. In conclusion, formation of PMPs on the first day following an ischaemic stroke shows a positive correlation with leptin levels and with resistance to leptin. Leptin level does not seem to affect the expression of platelet surface proinflammatory glycoproteins.

[Cryptogenic stroke - patent foramen ovale - migraine with aura: incidental triad or significant relationship? Part I]. / Udar kryptogenny - drozny otwór owalny - migrena z aura: przypadkowa triada czy zwiazek przyczynowo-skutkowy? Czesc I.

In the first part of the paper we discuss the association between patent foramen ovale (PFO) and cryptogenic stroke. Patent foramen ovale is a remnant of the fetal circulation, found in about quarter of the general population. According to many authors, this common anatomical anomaly is of no or limited clinical significance. However, the results of some clinical studies suggest higher prevalence of PFO among subjects with either cryptogenic stroke or migraine with aura. To date, the answer to the question whether PFO is an independent risk factor for stroke remains equivocal. The purpose of this review is to discuss the role of PFO in pathophysiology of both symptomatic and asymptomatic ischaemic lesions and to analyze the coexisting factors that increase the risk of stroke. We also discuss the effectiveness of either pharmacological treatment or PFO closure in secondary stroke prevention.

[Cryptogenic stroke - patent foramen ovale - migraine with aura: incidental triad or significant relationship? Part II]. / Udar kryptogenny - drozny otwór owalny - migrena z aura: przypadkowa triada czy zwiazek przyczynowo-skutkowy? Czesc II.

In the second part of the paper, we discuss the relationship between migraine with aura and either patent foramen ovale (PFO) or stroke. The results of the studies suggest that PFO with right-to-left shunt is more prevalent among patients suffering from migraine with aura. Moreover, migraine with aura is a risk factor for ischaemic stroke in women and the risk increases when they have additional vascular risk factors such as taking oral contraception and smoking. However, the pathophysiology of these phenomena remains hypothetical. The most frequently reported theory suggests paradoxical embolism as a mechanism of the above-mentioned pathologies. In this paper we compare the pros and cons of the general theories. We discuss the percutaneous closure of PFO in patients with migraine, regarding the benefit/risk ratio.

Upregulation of CD40 ligand and enhanced monocyte-platelet aggregate formation are associated with worse clinical outcome after ischaemic stroke.

The white blood cell count and mean platelet volume determined shortly after the symptom onset are known as independent predictors for clinical outcome after stroke. In the present study we sought to evaluate the prognostic value of platelet-derived inflammatory biomarkers measured prospectively after an ischaemic event. Using five-colour flow cytometry, the platelet surface expression of CD40L, CD62P and subpopulations of leukocyte-platelet aggregates were assessed in 93 stroke patients on the first (V(0)), 10th (V(1)) and 90th (V(2)) day after stroke, and once in 65 disease controls. The clinical outcome was evaluated using the Scandinavian Stroke Scale (SSS) and modified Rankin Scale (mRS) at the same time points as blood sampling and 24 months after the event. Patients with either CD40L surface expression or the percentage of monocyte-platelet aggregates (M-plt) in the third tertile (T3) at V0 had a significantly lower score on the SSS at V(1). Patients with the percentage M-plt at V(0) higher than the median value of M-plt in controls were at increased risk of SSS < 40 at V(1) (odds ratio: 2.6; 95% confidence interval [CI]: 1.4 - 8.7; p=0.006). Patients with the percentage of M-plt in T3 at V(0) showed progressive decline in survival (hazard ratio [HR]: 1.6; 95% CI: 1.1-1.9; p=0.02) and a significantly higher number of recurrent vascular events (HR: 2.64; 95% CI: 1.3-3.2; p=0.02) when compared to the first tertile. In conclusion, increased levels of M-plt could be a predictive marker for both early outcome and long-term prognosis while increased CD40L was correlated with worse clinical outcome.

Chronic hyper-reactivity of platelets resulting in enhanced monocyte recruitment in patients after ischaemic stroke.

Although the platelet activation profile after stroke is a well-known issue, the platelet reactivity assessed prospectively after ischaemic stroke still remains equivocal. The aim of this study was to evaluate the reactivity of platelets in response to stimulation with thrombin receptor-activating peptide (TRAP) at 1, 10 and 90 days after ischaemic stroke and to compare it with results obtained in control groups. We determined the increment in surface expression of CD62P, CD40L and monocyte- and granulocyte-platelet aggregate formation using five-colour flow cytometry in 86 subjects after an ischaemic event, in 62 disease controls, and in 38 healthy volunteers. We assessed the plasma levels of CD62P and CD40L soluble forms. In patients after stroke a significantly lower increment in CD62P surface expression (p < 0.01) and higher increments in both CD40L platelet surface expression (p < 0.01) and monocyte-platelet aggregate percentage (p < 0.01) were found at every studied time point, as compared with the control groups. Plasma levels of soluble CD62P (sCD62P) and soluble CD40L (sCD40L) were increased in stroke subjects in both the acute and the subacute phase of the stroke and they dropped to levels observed in controls at day 90 after the ischaemic incident. In all studied groups a positive correlation was noted between plasma levels of sCD62P and sCD40L. In conclusion, while at 3-month follow-up the levels of soluble forms normalize in stroke patients, the profile of platelet reactivity in response to activation with TRAP differs from that observed in the controls despite the secondary stroke prevention.