Przemysław Puz

Inflammatory markers in patients with internal carotid artery stenosis.

Introduction Available reports underline the significance of the inflammatory process in the development, progression and destabilisation of atherosclerotic plaques in the internal carotid artery (ICA). The aim of this study was to evaluate the relationship between the degree of ICA stenosis, ultrasound plaque morphology and serum concentration of selected inflammatory markers. Material and methods Sixty-five patients with ICA stenosis > 50% (39 symptomatic) and 30 healthy volunteers were enrolled in the study. Clinical, neurological examination and laboratory evaluation (leucocyte count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), fibrinogen, tumour necrosis factor-α (TNF-α), interleukins (1β, 6 and 10), anti-cytomegalovirus IgG antibody titre) were performed. Stenosis grade ≥ 70%, ulcerations on the plaque surface and a hypoechoic (or predominantly hypoechoic) structure of the plaque, obtained by colour-coded duplex examination, were accepted as the characteristics of unstable stenoses. Results Unstable ultrasound features of ICA stenosis were found significantly more often in symptomatic than in asymptomatic patients (71.79% vs. 30.71% for stenosis degree ≥ 70%, p = 0.001 and 61.23% vs. 38.46% for unstable plaque morphology, p = 0.01). Patients with ICA stenosis had significantly higher serum concentrations of interleukin-6, fibrinogen, ESR and higher CRP values than the individuals from the control group (p = 0.001, p = 0.009, p = 0.036, p = 0.009 respectively). Patients with unstable plaques structure had significantly higher concentrations of TNF-α, interleukin-6, fibrinogen, higher number of leukocytes, monocytes and higher CRP values than patients with stable plaques (p = 0.008, p = 0.049, p = 0.012, p = 0.0002, p = 0.006, p = 0.0003 respectively). No significant differences in above-mentioned parameters between the groups with stenosis < 70% and ≥ 70% were found. Conclusions There is a relationship between the activity of the selected inflammatory markers in serum and atherosclerotic unstable internal carotid artery stenosis. There is no relationship between serum concentration of inflammatory markers and degree of carotid artery stenosis.

Efficacy and safety assessment of alteplase in the treatment of stroke — gender differences

Abstract Background: Evidence for gender disparity in response to pharmacological thrombolysis for acute stroke treatment is inconclusive. Objective: To compare the effectiveness and safety of alteplase used in the treatment of male and female stroke patients. Material and methods: One thousand and seventy-seven patients who recently had their first-ever clinically apparent stroke (group I: 113 patients treated with intravenous alteplase and group II: 964 not treated with alteplase) were qualified. Groups I and II were divided into subgroups based on gender and were analysed based on: the age when they had a stroke, presence of key stroke risk factors (quantitatively: ≤ or >3), neurological state according to NIHSS in the first day of stroke, mortality rate, and the modified Rankin scale (mRS) at day 90 after the stroke. In group I, other determinants were additionally assessed: recent lesions as appeared on CT scans of the head in the first day of stroke and 24 hours after recombinant tissue plasminogen activator (rtPA), neurological state according to NIHSS in the second day of stroke, and the incidence of iatrogenic bleeding. Results: The age of the onset of stroke was older in women both in group I and group II. Apart from lipid disorders, no statistically significant differences in the distribution of other risk factors for stroke between groups I and II were found. The neurological state (according to the NIHSS scale) on the first day of the disease was significantly more severe in women both in group I and group II. In group II, the level of functioning according to the mRS scale at day 90 day after the onset of the disease was significantly more severe in women; there was no significant difference in group I. Among patients from group I, a significantly greater improvement, according to the NIHSS scale, was found in women 24 hours after rtPA administration in comparison with men. The presence of focal ischemia, responsible for the occurrence of stroke, on the CTs of the head performed 24 hours after rtPA administration, was also significantly more often found in women (in group I). No statistically significant differences in the incidence of complications after rtPA between women and men in group I were observed. In multivariate methods, we did not find any impact of factors other than gender on the outcome after stroke. Conclusions: The use of alteplase in women during the treatment of stroke is associated with a greater and faster improvement in their neurological state in comparison with men. Treating stroke with alteplase in women improves long-term prognosis regarding self-efficacy in everyday functioning. Finally, there are no gender-related differences regarding the safety of intravenous thrombolytic therapy.

Elevated factor VIII level and stroke in patients without traditional risk factors associated with cardiovascular diseases

Introduction Hemostasis is affected by interactions between physiological processes, including those connected with the coagulation system, whose essence is converting fibrinogen into fibrin. The role of factor VIII (FVIII) consists in activating factor X, which directly participates in the generation of thrombin, which is able to produce stable fibrin, which in turn forms blood clots. There are divergent opinions regarding the significance of high levels of FVIII in stroke pathogenesis. Aim The aim of our study was to evaluate FVIII activity in individuals with cryptogenic stroke in order to determine a potential relationship between it and cerebral ischemia. Material and methods Nine patients suffering with stroke were used in this study: six women and three men aged 49–63 years. In all of the patients, the presence of known and potential risk factors for stroke had been excluded during previous diagnostic procedures. These patients accounted for 1.2% of the 719 people who suffered a stroke and were hospitalized in 2011 at the Stroke Unit. FVIII activity was examined in each of the nine qualified subjects within 1–2 months of the occurrence of stroke (the first test) and repeated (the second test) in five patients with abnormal results obtained from the first examination. Results Increased activity of FVIII was found in 5 out of 9 patients. In patients with abnormal results, elevated FVIII was found in follow-up examinations in the 8th–10th month following stroke. Hemodynamic abnormalities in carotid or cerebral artery (presence of thrombus) were found in 3 of the 5 patients with increased FVIII levels. In the first 24 hours following stroke the neurological state of patients with abnormal FVIII was worse than individuals with normal FVIII activity. The patients with abnormal FVIII levels were found to be more disabled in the examination of self-dependence on the 90th day after stroke. Conclusion When searching for the causes of stroke, it is worth examining the coagulation system, including FVIII concentration, the abnormality of which may play a significant part in brain ischemia. More research is needed to determine the relationship between abnormal FVIII activity and stroke.INTRODUCTION Hemostasis is affected by interactions between physiological processes, including those connected with the coagulation system, whose essence is converting fibrinogen into fibrin. The role of factor VIII (FVIII) consists in activating factor X, which directly participates in the generation of thrombin, which is able to produce stable fibrin, which in turn forms blood clots. There are divergent opinions regarding the significance of high levels of FVIII in stroke pathogenesis. AIM The aim of our study was to evaluate FVIII activity in individuals with cryptogenic stroke in order to determine a potential relationship between it and cerebral ischemia. MATERIAL AND METHODS NINE PATIENTS SUFFERING WITH STROKE WERE USED IN THIS STUDY: six women and three men aged 49-63 years. In all of the patients, the presence of known and potential risk factors for stroke had been excluded during previous diagnostic procedures. These patients accounted for 1.2% of the 719 people who suffered a stroke and were hospitalized in 2011 at the Stroke Unit. FVIII activity was examined in each of the nine qualified subjects within 1-2 months of the occurrence of stroke (the first test) and repeated (the second test) in five patients with abnormal results obtained from the first examination. RESULTS Increased activity of FVIII was found in 5 out of 9 patients. In patients with abnormal results, elevated FVIII was found in follow-up examinations in the 8th-10th month following stroke. Hemodynamic abnormalities in carotid or cerebral artery (presence of thrombus) were found in 3 of the 5 patients with increased FVIII levels. In the first 24 hours following stroke the neurological state of patients with abnormal FVIII was worse than individuals with normal FVIII activity. The patients with abnormal FVIII levels were found to be more disabled in the examination of self-dependence on the 90th day after stroke. CONCLUSION When searching for the causes of stroke, it is worth examining the coagulation system, including FVIII concentration, the abnormality of which may play a significant part in brain ischemia. More research is needed to determine the relationship between abnormal FVIII activity and stroke.

Assessment of cerebral embolism and vascular reserve parameters in patients with carotid artery stenosis

AIM Carotid artery stenosis can result in the brain tissue injury related to the intracranial aterial flow disturbances as well as microembolic complications. The choice of the proper therapy in patients with carotid artery stenosis, especially asymptomatic, remains still a significant clinical problem. The study aim was an assessment of the cerebral embolism and brain vascular reserve parameters in patients with carotid artery stenosis regarding the occurrence of the clinical symptoms, the degree of stenosis as well as plaque morphology. METHODS The study included 60 patients, with internal carotid artery stenosis. The degree of stenosis, the atherosclerotic plaque surface and morphology were assessed by the means of Duplex Doppler ultrasound. Cerebrovascular reactivity (vasomotor reactivity reserve test and Breath Holding Index) and monitoring of the microembolic signals (MES) were assessed with transcranial Doppler ultrasound examination (TCD). RESULTS The vasoreactivity parameters were significantly lower in the group of patients with stenosis ≥70% and in patients with ulcerations on the plaque surface. Microembolic signals were recorded significantly more often in symptomatic patients; in patients with stenosis ≥70%; in patients with ulcerations on the plaque surface and those with hypoechogenic plaque structure. CONCLUSIONS Microembolic signals in patients with symptomatic carotid stenosis are one of the ultrasound features of unstable carotid stenosis. Worse reactivity parameters of the cerebral arteries are associated with the presence of a large degree of carotid artery stenosis.

Repeated measurements of serum concentrations of TNF-alpha, interleukin-6 and interleukin-10 in the evaluation of internal carotid artery stenosis progression

BACKGROUND AND AIMS The inflammatory process (with TNFα, interleukin-6 and interleukin-10 involvement) plays a key role in the development, progression and destabilization of atherosclerotic plaques. The aim of this study was to assess the importance of double-checked measurements of TNFα, interleukin-6 (IL-6) and interleukin-10 (Il-10) serum levels in patients with internal carotid artery (ICA) stenosis to determine the dynamics of changes in the stenosis degree and in the ultrasound plaque morphology. METHODS The study included 65 patients with ICA stenosis. Ultrasound of the carotid arteries was performed during qualification and every 3 months to identify any progression of stenosis degree and dynamics of changes in plaque morphology. Serum concentrations of TNF-alpha, IL-6 and IL-10 were measured during qualification and at month 6 of the study. Calculations considered cytokine concentrations and their indices determined as relative differences of cytokine levels assessed in the first and in second tests. RESULTS Patients with increasing degree of ICA stenosis had higher indices of IL-6 and IL-10 than patients without any increase in the stenosis degree. In patients with unfavorable dynamics of changes in plaque morphology, significantly higher levels of interleukin-6 were found in the second test; these patients had higher indices of IL-6 and IL-10 than patients with favorable dynamics of atherosclerotic plaque morphology on ultrasound. CONCLUSIONS Long-term trends in serum concentrations of IL-6 and IL-10 in patients with ICA stenosis allow to predict the progression of the degree of stenosis and the unfavorable change of atherosclerotic plaque morphology.

Efficacy and safety of mitoxantrone use in primary and secondary progressive multiple sclerosis - study site experience based on the therapy of 104 patients.

ABSTRACT Mitoxantrone (MX) is used in patients with primary and secondary progressive as well as relapsing–remitting type of multiple sclerosis (PPMS, SPMS, RRMS). The objective of our project was to evaluate the efficacy and safety of MX use in patients with PPMS and SPMS. Methods: The retrospective study included 104 patients (mean age 54.2 ± 9.0), with PPMS (13.46%) and SPMS (86.54%) treated with MX. During single cycle of the MX therapy a dose of 12 mg/m2 of body surface area was administered and next cycles every three months up to a total dose of 140 mg/m2 were realized. Results: The course of the therapy was completed by 95 patients (91.34%) including 73 patients who received a scheduled whole dose. The average cumulative dose per patient was 75.2 mg/m2. Thirty-two patients reported nausea after MX administration, 20 revealed increase in the incidence of infection and 19 patients hair loss. Twenty-two patients discontinued therapy (seven patients because of the progress of disability). Independent risk factors for deterioration were: age and the form of PPMS (RR 1.56 [95% CI: 1.17–2.07] and RR 2.8 [95% CI: 1.08–7.21], respectively). Five patients revealed a asymptomatic decrease in EF value <50% or 10% in relation to the previous test. Conclusions: MX therapy enables us to stabilize the disease without causing any significant side effects in most patients with progressive disease as compared to patients with primary progressive disease with a comparable safety profile. Larger benefits of MX therapy are associated with the patients with secondary progressive disease.

Rivaroxaban in secondary cardiogenic stroke prevention: two-year single-centre experience based on follow-up of 209 patients

BACKGROUND The main goal of treatment in patients with atrial fibrillation is to counteract the effects of embolisation, considering the relatively high risk of cerebral embolic events. AIM An assessment of the efficacy and safety of rivaroxaban in secondary stroke prevention in patients with non-valvular atrial fibrillation (NVAF). METHODS The study concerned 209 NVAF patients (male/female: 117/92; mean age 65.3 years [41-85]), who used rivaroxaban as secondary prevention of cardiogenic stroke. The patients were followed up for 24 months: the control visits were performed 12 and 24 months after the onset of the inclusion. The following aspects were analysed: the occurrence of recurrent stroke and/or transient ischaemic attack (TIA) during rivaroxaban treatment, bleeding episodes with their placement and severity assessment, drug tolerance, and evaluation of the patients medical records including laboratory tests (e.g. creatinine clearance) and concomitant therapy. All patients underwent physical examination as well as neurological assessment. RESULTS The mean CHA2DS2-VASc in the study group was 4.16, and the mean HAS-BLED value was 3.31. During the follow-up 13 deaths were noted (6.22%), ischaemic stroke was diagnosed in five (2.39%) subjects, and TIA in three (1.43%) patients. Bleeding complications were reported in 25 (11.96%) patients, two of which were classified as major bleedings (0.95%): an intracranial bleeding (1) and a bleeding from the genital tract (1). CONCLUSIONS For patients with NVAF and cerebrovascular events, the use of rivaroxaban in a real-world clinical setting results in a highly efficacious treatment profile and acceptable safety.

Diagnostic methods used in searching for markers of atrophy in patients with multiple sclerosis

Abstract The results of available studies on assessment of neurodegenerative lesions in multiple sclerosis (MS) patients using different approaches have not been conclusive. Currently, clinical assessment is the most commonly used (involving primarily mobility assessment), along with magnetic resonance imaging and electrophysiological testing. In this review we describe available clinical, neuroimaging, electrophysiological and laboratory tests used to assess the neurodegeneration in MS. Laboratory markers to determine the risk of disease, its conversion and prognosis in MS patients are being constantly sought. Cerebrospinal fluid (CSF) sample collection is invasive and constitutes a burden to a patient, so serum biomarkers are being investigated. Optimistic preliminary results of studies assessing neurofilament light chains (NFL) in serum of MS patients, encourage further research. The possibility to use such marker (or a group of markers) would significantly facilitate clinical decisions at the stage of diagnosis and treatment. Currently used treatments have limited efficacy and are associated with numerous adverse effects. Additional information from available clinical, imaging, electrophysiological or laboratory biomarker or a group of biomarkers, which predict the course and prognosis, will facilitate choosing optimal treatment and its escalation at the relevant stage. Conclusion: Using the diagnostic panel consisting of imaging, neurophysiology and serology testing along with clinical and neuropsychological assessment may improve the reliability of diagnostic instruments evaluating cerebral atrophy in MS patients.

Risk factor profile in patients with stroke at a young age: Stroke risk factors in young patients

Abstract Background The distribution of risk factors for stroke is related to gender and age. The main objective of study was to determine the type and frequency of stroke risk factors in patients with first-in-life stroke before the age of 50. Methods Our study included patients under the age of 50 with first-in-life stroke. The following data obtained from all participants were analyzed: a neuroimaging of the head, wide panel of blood tests, electrocardiogram, transesophageal echocardiography, ultrasound of the carotid/cerebral arteries. 24-hour ECG monitoring and angio-MRI of head were performed in most patients. Results One hundred and eighty-four patients were qualified into the study; mean age – 39 years (female 45%). The female gender was significantly more often associated with diabetes, carotid/cerebral artery stenosis, myocardial infarction, cardiomyopathy and risk factors associated with lifestyle. More than half of the patients presented at least two risk stroke factors. The most frequent categories of risk factors were related to arteries and metabolic diseases. Vascular risk factors were among the most frequent in individual age categories. Hereditary stroke-burden was significant in the patient before the age of 20.15% of the patients haven’t got known stroke risk factor. Conclusions Angiopathy is the most common risk factor for stroke at a young age. More than half of the patients with stroke at a young age have at least two independent risk factors for stroke. In the first two decades of life, the most frequent risk factors for stroke are heart diseases; arterial diseases play a dominant role in the consecutive three decades.

Safety and Efficacy of Fingolimod and Natalizumab in Multiple Sclerosis After the Failure of First-Line Therapy: Single Center Experience Based on the Treatment of Forty-Four Patients

Background In Poland, natalizumab or fingolimod treatment can be delivered as a second-line therapy to those patients with relapsing-remitting multiple sclerosis (RRMS) who demonstrated no response to interferon or glatiramer acetate treatment for a minimum of one year. The objective of this study was to evaluate the impact of second-line therapy on the frequency of relapses, the disability progression, and the occurrence of side effects. Material/Methods Analysis covered 44 RRMS patients switched from first- to second-line therapy. The annualized relapse rate, disability progression (assessed with Expanded Disability Status Scale, EDSS) and MRI results (new or enlarged T2 lesions and new Gd-positive lesions) before and after switching were compared. The occurrence of adverse events was also assessed. Results The annualized relapse rate for second-line therapy was significantly lower than for first-line therapy (0.35±0.74 vs. 2.13±0.87, p=0.00005). Median of EDSS progression with first-line therapy was significantly higher than that with natalizumab or fingolimod treatment (p=0.00002). The mean number of new or enlarged T2 and Gd+ lesions in MRI after one-year second-line treatment was significantly lower in comparison to lesions in MRI performed at the end of the first-line therapy (for T2: 0.61 vs. 4.56, p=0.0004; for Gd+: 0.13 vs. 1.98, p=0.0009). No significant differences in the clinical data, MRI results, and side effects between fingolimod and natalizumab patients have been observed. Conclusions Treatment with natalizumab or fingolimod as a second-line therapy in RRMS patients is safe and effective. Less restrictive criteria for switching should be considered.