Factor XIa inhibition with asundexian after acute non-cardioembolic ischaemic stroke (PACIFIC-Stroke): an international, randomised, double-blind, placebo-controlled, phase 2b trial.

BACKGROUND: Asundexian (Bayer AG, Leverkusen, Germany), an oral small molecule factor XIa (FXIa) inhibitor, might prevent thrombosis without increasing bleeding. Asundexian's effect for secondary prevention of recurrent stroke is unknown. METHODS: In this randomised, double-blind, placebo-controlled, phase 2b dose-finding trial (PACIFIC-Stroke), patients with acute (within 48 h) non-cardioembolic ischaemic stroke were recruited from 196 hospitals in 23 countries. Patients were eligible if they were aged 45 years or older, to be treated with antiplatelet therapy, and able to have a baseline MRI (either before or within 72 h of randomisation). Eligible participants were randomly assigned (1:1:1:1), using an interactive web-based response system and stratified according to anticipated antiplatelet therapy (single vs dual), to once daily oral asundexian (BAY 2433334) 10 mg, 20 mg, or 50 mg, or placebo in addition to usual antiplatelet therapy, and were followed up during treatment for 26-52 weeks. Brain MRIs were obtained at study entry and at 26 weeks or as soon as possible after treatment discontinuation. The primary efficacy outcome was the dose-response effect on the composite of incident MRI-detected covert brain infarcts and recurrent symptomatic ischaemic stroke at or before 26 weeks after randomisation. The primary safety outcome was major or clinically relevant non-major bleeding as defined by International Society on Thrombosis and Haemostasis criteria. The efficacy outcome was assessed in all participants assigned to treatment, and the safety outcome was assessed in all participants who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT04304508, and is now complete. FINDINGS: Between June 15, 2020, and July 22, 2021, 1880 patients were screened and 1808 participants were randomly assigned to asundexian 10 mg (n=455), 20 mg (n=450), or 50 mg (n=447), or placebo (n=456). Mean age was 67 years (SD 10) and 615 (34%) participants were women, 1193 (66%) were men, 1505 (83%) were White, and 268 (15%) were Asian. The mean time from index stroke to randomisation was 36 h (SD 10) and median baseline National Institutes of Health Stroke Scale score was 2·0 (IQR 1·0-4·0). 783 (43%) participants received dual antiplatelet treatment for a mean duration of 70·1 days (SD 113·4) after randomisation. At 26 weeks, the primary efficacy outcome was observed in 87 (19%) of 456 participants in the placebo group versus 86 (19%) of 455 in the asundexian 10 mg group (crude incidence ratio 0·99 [90% CI 0·79-1·24]), 99 (22%) of 450 in the asundexian 20 mg group (1·15 [0·93-1·43]), and 90 (20%) of 447 in the asundexian 50 mg group (1·06 [0·85-1·32]; t statistic -0·68; p=0·80). The primary safety outcome was observed in 11 (2%) of 452 participants in the placebo group versus 19 (4%) of 445 in the asundexian 10 mg group, 14 (3%) of 446 in the asundexian 20 mg group, and 19 (4%) of 443 in the asundexian 50 mg group (all asundexian doses pooled vs placebo hazard ratio 1·57 [90% CI 0·91-2·71]). INTERPRETATION: In this phase 2b trial, FXIa inhibition with asundexian did not reduce the composite of covert brain infarction or ischaemic stroke and did not increase the composite of major or clinically relevant non-major bleeding compared with placebo in patients with acute, non-cardioembolic ischaemic stroke. FUNDING: Bayer AG.

Cladribine tablets for highly active relapsing-remitting multiple sclerosis in Poland: a real-world, multi-centre, retrospective, cohort study during the COVID-19 pandemic.

INTRODUCTION: Treatment with cladribine tablets is indicated in highly active relapsing-remitting multiple sclerosis (RRMS). Cladribine tablets proved safe and effective in the pivotal CLARITY trial, but that trial included primarily treatment-naïve patients. In clinical practice however, cladribine tablets are often given to patients who have failed other treatments. Therefore, this study investigated the real-world safety and efficacy of cladribine tablets. MATERIAL AND METHODS: We gathered data from nine MS clinical centres across Poland for patients with RRMS who started treatment with cladribine tablets from December 2019 to June 2022. RESULTS: We enrolled 140 patients, with follow-up data available for 136 in year 1 and for 66 in year 2. At baseline, the mean age was 35.6 years, mean disease duration was 7.3 years, median EDSS score was 2.5, and 94% of patients were treatment- -experienced. Thirty-nine patients (27.9%) had undergone COVID-19, and 94 (67.1%) were vaccinated against COVID-19. The annualised relapse rate (ARR) decreased from 1.49 at baseline to 0.33 in year 1 (p < 0.001) and to 0.25 in year 2 (p < 0.001). The percentage of relapse-free patients increased from 11.5% at baseline to 70.2% in year 1 and 82.1% in year 2. The percentage of patients with active lesions decreased from 91.4% at baseline to 36.2% in year 1 and 18.2% in year 2. EDSS score remained stable or improved in 83.7% of patients in year 1 and 89.6% in year 2. No evidence of disease activity (NEDA-3) was achieved in 42.7% of patients in year 1 and 66.7% in year 2. Only one patient (0.72%) had grade 4 lymphopenia and 21 (15.1%) had grade 3 lymphopenia. Varicella zoster virus infections occurred in three patients. Eight patients discontinued treatment with cladribine: five due to inefficacy, one due to lymphopenia, and two due to a personal decision. CONCLUSIONS: Cladribine tablets proved safe and effective in a real-world cohort of treatment-experienced patients. However, the efficacy measures improved to a lesser extent in our cohort than in the pivotal clinical trial, which is probably due to a higher proportion of treatment-experienced patients in our cohort.

Sense of happiness in Polish patients with multiple sclerosis.

INTRODUCTION: Happiness is crucial to patient well-being and their acceptance of their disease. The aim of this study was to assess the sense of happiness in persons with multiple sclerosis (PwMS), compare it to the level of happiness in patients with other neurological conditions, and determine which factors affect the sense of happiness in PwMS. MATERIAL AND METHODS: Five hundred and eighty-nine PwMS and 145 control subjects (post-stroke patients with chronic pain syndromes and neuropathies) were included in the study. Due to the differences between the groups in terms of demographic variables, an adjusted group of PwMS (n = 145) was selected from the entire group of PwMS. All patients were assessed using the Oxford Happiness Questionnaire (OHQ), the Satisfaction with Life Scale (SLS), and the Family APGAR Questionnaire. Based on regression analysis, the study examined which variables affected the level of happiness in the groups. RESULTS: Analysis of the OHQ scores showed that PwMS had a lower sense of happiness compared to the control group in the overall score [113.21 (25-42) vs. 119.88 (25-49), respectively; p = 0.031] and the subscales (OHQ subscale 1 - 54.52 vs. 57.84, respectively; p = 0.027; subscale 2 - 35.61 vs. 37.67; respectively; p = 0.044). Based on linear regression analysis, life satisfaction (ß = 0.40; p < 0.001), positive orientation (ß = 0.32; p < 0.001), and primary education (ß = 0.08; p = 0.009) were the most significant predictors of a higher level of happiness in PwMS. Similar results were found in the control group. CONCLUSIONS: The sense of happiness in PwMS was lower than in patients with other conditions. The most important factors influencing happiness included life satisfaction and positive orientation. Influencing these predictors should be the aim of psychological interventions, especially in patients with a reduced sense of happiness.

Nocturnal non-dipping on 24-h Ambulatory Blood Pressure Monitoring in children and adolescents with obesity is associated with higher total cholesterol levels.

BACKGROUND: Few studies indicate the occurrence of abnormal nocturnal dipping of blood pressure (BP) in 35-50% of children and adolescents with obesity. The relation between that phenomenon and metabolic complications of obesity remains unclear. To evaluate the association between disorders of glucose and lipid metabolism, and nocturnal non-dipping in pediatric patients with obesity. METHODS: In 207 children (53.14% girls, mean age 14 (range 2-17), mean BMI Z-SCORE 4.38, range 2.07-10.74) standard 24-h Ambulatory Blood Pressure Monitoring was performed. Normal dipping was defined as a ≥ 10% decline in BP during the night. RESULTS: There were 106 (51.21%) cases of non-dippers. The mean 24-h nocturnal systolic BP (SBP) reduction (%) was 9.9 ± 5.5. The mean 24-h nocturnal diastolic BP (DBP) reduction (%) was 15.8 ± 8.5. There was a significant correlation between BMI Z-SCORE and mean day-time SBP (r = 0.14 P = .042). There are positive correlations between 24-h heart rate (beats/min) and BMI Z-SCORE (r = 0.15, P = .027), between fasting glucose and systolic BP Z-SCORE (r = 0.17, P = .03) and between mean diastolic BP and LDL cholesterol (r = 0.23, P = .004). Total cholesterol level was significantly higher in non-dippers (4.34 vs. 3.99 mmol/L, P = .034). There were no significant differences between non-dippers and dippers regarding fasting glucose (4.6 vs. 4.8 mmol/L), 120'post load glucose (5.7 vs. 5.9 mmol/L), insulin (19 vs. 20.2 µIU/mL), HOMA-IR (2.36 vs. 2.44), LDL cholesterol (2.64 vs. 2.51 mmol/L), HDL cholesterol (1.06 vs. 1.03 mmol/L) or triglycerides (1.36 vs. 1.34 mmol/L) levels. CONCLUSION: Nocturnal non-dipping is frequent in pediatric patients with obesity. It is associated with higher total cholesterol levels.

The Use of Armeo®Spring Device to Assess the Effect of Trunk Stabilization Exercises on the Functional Capabilities of the Upper Limb-An Observational Study of Patients after Stroke.

Almost half of stroke patients report impaired function of the upper limb and hand. Stability of the trunk is required for the proper movement of the body, including the legs and arms. The aim of the study was to analyze the effect of trunk stabilization exercises on coordinated movement of the affected upper limb in patients after stroke, using an Armoe®Spring device and the "wall" and "abacus" functional tests. Materials and methods: This is a randomized, double-blinded study. The research was carried out in the Rehabilitation Clinic on a group of 60 stroke patients who were randomly assigned to groups differing in the rehabilitation program. The study group had physiotherapy based on the NDT Bobath concept and the control group used classic exercises. The importance of the trunk for upper limb coordination was assessed on the Armeo®Spring device using three evaluation programs, "perpendicular fishing"; "horizontal fishing"; "reaction time", and two proprietary tests, "wall" and "abacus". Results: The post-treatment analysis showed significantly better results in the study group for the abacus (p < 0.001), wall (p = 0.003) tests, and a significantly higher percentage of task completion in the vertical fishing (p = 0.036) and reaction time (p = 0.009) tests. Conclusions: Physiotherapy including exercises to stabilize the trunk had a significant effect on increasing the functional efficiency of the affected upper limb and on improving the handgrip strength. The Armeo®Spring device is a good device for the functional assessment of the upper limb before and after therapy.

Onabotulinumtoxin A (ONA-BoNT/A) in the treatment of chronic migraine.

Migraine is a common primary headache disease, which reduces quality of life. About 8% of migraineurs suffer from chronic migraine (CM), which is the most severe and troublesome type. It has been proven that onabotulinumtoxinA (ONA-BoNT/A) significantly improves CM, presumably inhibiting the release of calcitonin gene-related peptide (CGRP) and other neurotransmitters from c-fibres endings, and thus decreasing activation of nociceptive pathways and transmission of pain. The aim of this position paper was to assess the place of ONA-BoNT/A for the prophylaxis of CM in adults. The authors have compared the efficacy, safety and tolerance of the toxin to those of classical oral preventive therapies as well as to recently introduced anti-CGRP-pathway monoclonal antibodies. The results of randomised controlled studies of ONA-BoNT/A have been compared to open label (real world practice) trials.

Screening diagnosis of dementia in patients following heart failure decompensation is associated with a higher relative wall thickness.

BACKGROUND: The usefulness of echocardiographic characteristics for dementia prediction in patients with heart failure decompensation (HFD) is not determined. Therefore, we sought to investigate the echocardiographic features of patients with HFD and screening diagnosis of dementia (SDD). METHODS: 139 patients aged over 65 years were hospitalized with the diagnosis of HFD. Clinical characteristics and echocardiographic characteristics were recorded during hospitalization. SDD was defined based on the result of ALFI- MMSE of <17 points. RESULTS: Patients with SDD were older (p=0.013), had thicker IVSd (p=0.021), thicker PWd (p=0.005) and had a higher RWT (0.40 vs 0.35, p=0.004) than patients without SDD, without differences in LVMI (p=0.13). There was no correlation between RWT and LVMI (r=-0.01, p=0.88). In the multivariate analysis, an older age (ß=-0.116, 95% CI -0.224 - -0.008, p=0.035, per year) and a higher RWT (ß=-0.069, 95% CI -0.137 - -0.002, p=0.045, per 0.01) influenced a lower ALFI-MMSE. For a prediction of SDD, the RWT reached the area under a ROC curve of 0.67 (95% CI 0.56-0.77, p=0.004 with sensitivity of 60% and specificity of 70% for RWT of ≥0.375). CONCLUSIONS: Apart from age, RWT reflecting left ventricular geometry changes but not hypertrophy was independently but moderately associated with SDD in patients following HFD (Tab. 4, Fig. 1, Ref. 35).

Migraine diagnosis and treatment in Poland: survey of primary care practitioners.

AIM OF THE STUDY: This study aimed to analyze the daily clinical practice of primary care practitioners (PCPs) in Poland concerning migraine patients. CLINICAL RATIONALE FOR THE STUDY: Migraine is a common chronic primary headache disease, which can be disabling if insufficiently managed. Numerous studies suggest that migraine remains underdiagnosed and undertreated. The first consultation of migraine patients is usually undertaken by a PCP. MATERIALS AND METHODS: This study was conducted in June and July 2019 in Poland using a computer-assisted web interview with 51 PCPs. The interview questions concerned knowledge of diagnostic criteria and methods of migraine treatment. RESULTS: On average, each PCP consulted 12 patients with migraine per month. More than half of PCPs (63%) listed partial diagnostic criteria for migraine without aura or mentioned aura in their responses. Only 10% of PCPs listed all diagnostic criteria for migraine without aura. Although 55% of PCPs said that they distinguished between episodic and chronic migraine, 18% provided the wrong definition. The most commonly prescribed drugs were triptans (66%), paracetamol, metamizole, or non-steroidal anti-inflammatory drugs (42%). CONCLUSIONS AND CLINICAL IMPLICATIONS: PCPs play a critical role in diagnosing, treating, and monitoring migraine; however, many of them have insufficient knowledge about its diagnosis and correct differentiation between chronic and episodic forms.

Effect of COVID-19 pandemic on stroke admissions and quality of stroke interventional treatment in Masovian Voivodeship.

AIM OF STUDY: To assess the impact of the coronavirus disease 2019 (COVID-19) pandemic on the pathway of stroke interventional services and major quality indicators of stroke reperfusion therapies in Masovian Voivodeship. MATERIALS AND METHODS: An exploratory retrospective analysis was performed at two comprehensive stroke centres to assess changes in stroke care between the early phase of the COVID-19 pandemic (weeks 10-18 of 2020) and the same period in 2019. RESULTS: Of the 419 included stroke patients, 186 (44.4%) presented during the COVID-19 period. There was an increase in in-hospital delays for reperfusion therapies, and a significant decrease in the number of acute cerebrovascular accident admissions, predominantly related to a low number of transient ischaemic attack (TIA) admissions to hospital (-20.17%). The delays were shorter in the mothership paradigm than in the drip-and-ship paradigm of acute stroke care (onset-to-groin 293 vs. 232 min, p = 0.03). No differences in stroke aetiology, large-vessel occlusion frequency, or severe stroke admissions in the COVID-19 period were observed. CONCLUSIONS AND CLINICAL IMPLICATIONS: COVID-19's emergence was correlated with a significant reduction in admissions to stroke departments, particularly for TIAs, and a prolonged delay in reperfusion stroke treatment, especially in the drip-and-ship paradigm. An educational campaign to raise public awareness of TIA and/or stroke symptoms and immediate reorganisation of stroke care during the COVID-19 era are necessary.

Clinical course and outcome of SARS-CoV-2 infection in multiple sclerosis patients treated with disease-modifying therapies - the Polish experience.

INTRODUCTION: The aim of this study was to report the course and outcome of SARS-CoV-2 infection in multiple sclerosis (MS) patients treated with disease-modifying therapies (DMTs) in Poland. A major concern for neurologists worldwide is the course and outcome of SARS-CoV-2 infection in patients with MS treated with different DMTs. Although initial studies do not suggest an unfavourable course of infection in this group of patients, the data is limited. MATERIALS AND METHODS: This study included 396 MS patients treated with DMTs and confirmed SARS-CoV-2 infection from 28 Polish MS centres. Information concerning patient demographics, comorbidities, clinical course of MS, current DMT use, as well as symptoms of SARS-CoV-2 infection, need for pharmacotherapy, oxygen therapy, and/or hospitalisation, and short-term outcomes was collected up to 30 January 2021. Additional data about COVID-19 cases in the general population in Poland was obtained from official reports of the Polish Ministry of Health. RESULTS: There were 114 males (28.8%) and 282 females (71.2%). The median age was 39 years (IQR 13). The great majority of patients with MS exhibited relapsing-remitting course (372 patients; 93.9%). The median EDSS was 2 (SD 1.38), and the mean disease duration was 8.95 (IQR 8) years. Most of the MS patients were treated with dimethyl fumarate (164; 41.41%). Other DMTs were less frequently used: interferon beta (82; 20.70%), glatiramer acetate (42; 10.60%), natalizumab (35;8.84%), teriflunomide (25; 6.31%), ocrelizumab (20; 5.05%), fingolimod (16; 4.04), cladribine (5; 1.26%), mitoxantrone (3; 0.76%), ozanimod (3; 0.76%), and alemtuzumab (1; 0.25%). The overall hospitalisation rate due to COVID-19 in the cohort was 6.81% (27 patients). Only one patient (0.3%) died due to SARS-CoV-2 infection, and three (0.76%) patients were treated with mechanical ventilation; 106 (26.8%) patients had at least one comorbid condition. There were no significant differences in the severity of SARS-CoV-2 infection regarding patient age, duration of the disease, degree of disability (EDSS), lymphocyte count, or type of DMT used. CONCLUSIONS AND CLINICAL IMPLICATIONS: Most MS patients included in this study had a favourable course of SARS-CoV-2 infection. The hospitalisation rate and the mortality rate were not higher in the MS cohort compared to the general Polish population. Continued multicentre data collection is needed to increase the understanding of SARS-CoV-2 infection impact on the course of MS in patients treated with DMTs.

Paroxysmal extreme pain disorder in family with c.3892G > T (p.Val1298Phe) in the SCN9A gene mutation - case report.

BACKGROUND: To describe the clinical phenotype of paroxysmal extreme pain disorder, an autosomal dominant condition in four members in one family with the mutation NM_002977.3:c.3892G > T (p.Val1298Phe) in the SCN9A gene. Clinical examinations and details from members of one Polish family were collected, including age at onset, features of attacks, problems between attacks, investigational results, treatments tried, and evolution over time. CASE PRESENTATION: Twenty two individuals from this family with paroxysmal extreme pain disorder were identified. Seven of them presented clinical manifestation of paroxysmal extreme pain disorder, of which and in four were identified missens mutations in the SCN9A gene (NM_002977.3:c.3892G > T). The onset of the disorder took place in the neonatal period or infancy and persists throughout life. Autonomic manifestations predominate with extreme pain, skin flushing and harlequin colour change were observed in all. Attacks of excruciating deep burning pain often appear in the rectal, or jaw areas, but also diffuse in the body. Attacks are triggered by factors such as: defecation, eating, pressure and emotion. Carbamazepine and other antiepileptic drugs were only partly effective in almost all, but the response was incomplete. CONCLUSIONS: Paroxysmal extreme pain disorder is a hereditary sodium channelopathy with pain and an autonomic nervous system dysfunction. Paroxysmal extreme pain disorder is rare, so far only 500 cases of both women and men have been described in world literature.

Treatment and management of migraine in neurological ambulatory practice in Poland by indicating therapy with monoclonal anti-CGRP antibodies.

AIM OF STUDY: To analyse Polish neurologists' familiarity with the diagnostic criteria for migraine, and how their methods of management of migraine work in daily practice. CLINICAL RATIONALE FOR STUDY: Migraine is a common primary headache disease that causes substantial disability and reduces quality of life. Many migraine patients remain undiagnosed and deprived of treatment. Migraine treatment is problematic, and many patients discontinue preventive treatment, mainly because of a lack of efficacy or adverse effects. Antibodies targeting calcitonin gene-related peptide and its receptor seem to be effective and well-tolerated agents in migraine prevention. MATERIAL AND METHODS: This study was conducted using a computer-assisted web interview conducted with 51 neurologists in Poland, who agreed to participate in the study during a phone call. The questionnaire mainly assessed methods of treatment of migraine patients and diagnostic criteria used in neurological practice. RESULTS: Only one neurologist listed all of the diagnostic criteria for migraine, and 80% of physicians in their practice used only a part of the migraine diagnostic criteria, usually the migraine without aura criteria. On average, each neurologist had 55 patients under continuous care, seeing roughly 18 patients per month. On average, neurologists estimated that 77% of all patients with migraine had episodic migraine, whereas the rest had the chronic form. Importantly, 40% of patients with chronic migraine received all available preventive treatments without a satisfactory effect. Neurologists could offer monoclonal antibodies that target the CGRP-pathway (i.e. anti-CGRP and anti-CGRP receptor monoclonal antibodies) for the prevention of chronic migraine to about one in three patients with a chronic form of the disease. CONCLUSIONS AND CLINICAL IMPLICATIONS: Migraine is underdiagnosed and undertreated in Poland. Understanding of the diagnostic criteria for migraine among neurologists is insufficient. Most neurologists in Poland see patients in whom anti-CGRP/R-targeting treatment is indicated.

Recommendations of the Polish Medical Society of Radiology and the Polish Society of Neurology for a protocol concerning routinely used magnetic resonance imaging in patients with multiple sclerosis.

Magnetic resonance imaging (MRI) is a widely used method for the diagnosis of multiple sclerosis that is essential for the detection and follow-up of the disease. OBJECTIVE: The Polish Medical Society of Radiology (PLTR) and the Polish Society of Neurology (PTN) present the second version of their recommendations for investigations routinely conducted in magnetic resonance imaging departments in patients with multiple sclerosis. This version includes new data and practical comments for electroradiology technologists and radiologists. The recommended protocol aims to improve the MRI procedure and, most importantly, to standardise the method of conducting scans in all MRI departments. This is crucial for the initial diagnostics necessary for establishing a diagnosis, as well as for MS patient monitoring, which directly translates into significant clinical decisions. INTRODUCTION: Multiple sclerosis (MS) is a chronic immune mediated inflammatory demyelinating disease of the central nervous system (CNS), the aetiology of which is still unknown. The nature of the disease lies in a CNS destruction process disseminated in time (DIT) and space (DIS). MRI detects focal lesions in the white and grey matter with high sensitivity (although with significantly lower specificity in the latter). It is also the best tool to assess brain atrophy in patients with MS in terms of grey matter volume (GMV) and white matter volume (WMV) as well as local atrophy (by measuring the volume of thalamus, corpus callosum, subcortical nuclei, and hippocampus) as parameters that correlate with disability progression and cognitive dysfunctions. Progress in MR techniques, as well as advances in postprocessing the obtained data, has driven the dynamic development of computer programs that allow for a more repeatable assessment of brain atrophy in both cross-sectional and longitudinal studies. MR imaging is unquestionably the best diagnostic tool available to follow up the course of the disease and support clinicians in choosing the most appropriate treatment strategy for their MS patient. However, to diagnose and follow up MS patients on the basis of MRI in accordance with the latest standards, the MRI study must adhere to certain quality criteria. Such criteria are the subject of this paper.

Typical variant of takotsubo cardiomyopathy in oncological patients. Two case reports and review of the literature.

Takotsubo cardiomyopathy (TCM) represents an acute systolic left ventricular dysfunction typically triggered by severe psychological or physical stress. Oncological patients due to emotional distress of the diagnosis, proinflammatory and prothrombotic nature of cancer and also physical stress often following complex anticancer therapies are at high-risk of TCM. Moreover, there are also few reports of TCM associated with oncological treatment, mostly chemotherapy. Recent data from large registries indicate a surprisingly high incidence of malignancy in TCM, significant differences in clinical characteristics and unfavorable short- and long-term clinical outcomes in this specific group of patients. Therefore, we present two case reports of TCM that occurred during active anticancer therapy. Both women were admitted with suspicion of acute coronary syndrome. The first patient underwent mastectomy two years before due to hormone receptor-positive breast cancer and on admission she was during adjuvant hormonotherapy with tamoxifen. The admission of the second patient was preceded by fifteen fractions of adjuvant external beam radiotherapy due to intermediate-risk endometrial cancer after radical hysterectomy. Based on coronary angiography type I of acute coronary syndrome was excluded. Both patients negated stressful situations in the period immediately before the symptoms onset. Within hospital course baseline apical ballooning observed in both cases fully recovered and enabled subsequent completion of oncological treatment in accordance with adopted treatment protocols without recurrence of TCM. To our knowledge, presented cases are the first reports showing direct relationship between TCM and adjuvant hormonotherapy with tamoxifen or pelvic radiotherapy.

Recommendations of the Polish Medical Society of Radiology and the Polish Society of Neurology for the routinely used magnetic resonance imaging protocol in patients with multiple sclerosis.

Magnetic resonance imaging (MRI) is a widely used method for the diagnosis of multiple sclerosis (MS) that is essential for the detection and follow-up of the disease. The Polish Medical Society of Radiology (PLTR) and the Polish Society of Neurology (PTN) present the second version of the recommendations for examinations routinely conducted in magnetic resonance imaging departments in patients with MS, which include new data and practical comments for electroradiology technicians and radiologists. The recommended protocol aims to improve the MRI procedure and, most importantly, to standardise the method of conducting scans in all MRI departments. This is crucial for the initial diagnostics that are necessary to establish a diagnosis as well as monitor patients with MS, which directly translates into significant clinical decisions. MS is a chronic idiopathic inflammatory demyelinating disease of the central nervous system (CNS), the aetiology of which is still unknown. The nature of the disease lies in the CNS destruction process disseminated in time and space. MRI detects focal lesions in the white and grey matter with high sensitivity (with significantly less specificity in the latter). It is also the best tool to assess brain atrophy in patients with MS in terms of grey matter volume and white matter volume as well as local atrophy (by measuring the volume of thalamus, corpus callosum, subcortical nuclei, hippocampus) as parameters that correlate with disability progression and cognitive dysfunctions. Progress in magnetic resonance techniques, as well as the abilities of postprocessing the obtained data, has become the basis for the dynamic development of computer programs that allow for a more repeatable assessment of brain atrophy in both cross-sectional and longitudinal studies. MRI is unquestionably the best diagnostic tool used to follow up the course of the disease and to treat patients with MS. However, to diagnose and follow up the patients with MS on the basis of MRI in accordance with the latest standards, an MRI study must meet certain quality criteria, which are the subject of this paper.

Cerebral and Extracerebral Vasoreactivity in Patients With Different Clinical Manifestations of Cerebral Small-Vessel Disease: Data From the Significance of Hemodynamic and Hemostatic Factors in the Course of Different Manifestations of Cerebral Small-Vessel Disease Study.

OBJECTIVES: Endothelial dysfunction has been implicated in the pathogenesis of cerebral small-vessel disease (SVD). Little is known about the relationship between SVD and measures of endothelium-dependent vasodilatation and cerebral vasomotor reactivity. The aim of this study was to evaluate cerebral and extracerebral endothelial dysfunction in patients with different manifestations of SVD and to assess the relationship between endothelial dysfunction and radiologic markers of SVD. METHODS: The vasomotor reactivity reserve (VMRr), breath-holding index (BHI) of the middle cerebral arteries, and brachial artery flow-mediated dilatation (FMD) were measured with ultrasound techniques in 90 patients (30 in each group) older than 60 years with extensive white matter lesions (Fazekas grade ≥ 2) with a history of lacunar stroke, vascular dementia, or parkinsonism and 30 individuals with normal magnetic resonance imaging findings (control group). All groups were matched for age, sex, hypertension, and diabetes. RESULTS: The mean age ± SD (71.8 ± 3.4 versus 71.7 ± 3.4 years), sex distribution, and prevalence of the main vascular risk factors were similar in the SVD and control groups. The VMRr (56.6% ± 18.3% versus 77.1% ± 16.9%), BHI (0.8 ± 0.3 versus 1.1 ± 0.4), and FMD (5.8% ± 4 versus 12.1% ± 5.2%) were severely impaired in the SVD groups compared to the control group (P < .01). The vascular responses to all tests was similar in the SVD groups, but they were significantly decreased in patients with severe white matter lesions, marked brain atrophy, and enlarged perivascular spaces. CONCLUSIONS: This study was the first that simultaneously evaluated cerebral and extracerebral vasodilator responses in a well-phenotyped cohort of patients with lacunar stroke, vascular dementia, or parkinsonism. The VMRr, BHI, and FMD were more severely impaired in patients with SVD, regardless of its clinical manifestation, than in control participants. All measures were significantly lower in patients with severe white-matter lesions, brain atrophy, or enlarged perivascular spaces.

Prevalence and extent of right-to-left shunt on contrast-enhanced transcranial Doppler in patients with chronic hyperventilation syndrome: results of a case-control study.

AIM: Chronic hyperventilation syndrome (CHVS) represents a frequent but poorly understood breathing pattern disorder. In a previous small pilot study, we reported a higher prevalence of right-to-left shunt (RLS) in CHVS patients than in healthy subjects. The aim of this study was to confirm those previous results from this larger and matched case-control study, and to evaluate the prevalence and grade of RLS in patients with CHVS in whom organic and psychiatric causes were excluded. CLINICAL RATIONALE FOR THE STUDY: Determining other types of CHVS triggers not related to organic or psychiatric causes which could be clinically useful. MATERIAL AND METHODS: 100 subjects (mean age 34 ± 6 years; 80% females), including 50 patients with CHVS and 50 age- and sex-matched healthy controls (CG), were prospectively recruited into this single-centre study. Vascular RLS was diagnosed using contrast-enhanced transcranial Doppler (c-TCD). RESULTS: RLS prevalence significantly increased in the CHVS group (n = 23) compared to the CG group (n = 8) (46% vs 16%; p < 0.01). Patients with CHVS and RLS tended to have more frequent permanent shunts compared to the CG (60% vs 25%; p = 0.08), but there was no difference regarding RLS grading between the groups. CONCLUSIONS AND CLINICAL IMPLICATIONS: This study confirmed our previous findings in which the prevalence of RLS in patients with CHVS was significantly higher than in an age- and sex-matched healthy control group. However, we could not confirm the results of our prior study, where RLS was larger in CHVS than in CG. The tentative association between RLS and CHVS needs to be further examined.

Effectiveness of dimethyl fumarate as first line therapy in MS patients - one center real life observation study.

Interferon ß, glatiramer acetate and dimethyl fumarate are first line of disease-modifying therapies for patients who have got relapsingremitting multiple sclerosis (RRMS). Currently, there are no precise guidelines for modifying treatment. This is the individual decision of the attending physician, which should take into account both the clinical course of the disease and the patient's preferences. Therefore, possible findings of this study may potentially improve treatment strategy and could be helpful for the clinicians to select the most appropriate therapy. AIM: The aim of this study was to evaluate and compare activity of multiple sclerosis one year before and one year after switching treatment from interferon ß or glatiramer acetate to dimethyl fumarate. The reasons for treatment modification and impact of these reasons on therapy effectiveness were studied as a secondary outcome. MATERIALS AND METHODS: This observational and retrospective study among patients with RRMS lasted for 2 years and was conducted at one medical center. Participants of the study were aged 19-61 years. All of them had been initially treated with disease-modifying drugs (DMDs) by injection: interferon or glatiramer acetate. After one-year observation patients switched therapy to dimethyl fumarate (DMF) for various reasons. RESULTS: 62 adult patients received interferon beta or glatiramer acetate in the first year. After a year all of them switched from that therapy to dimethyl fumarate. Patients in all treatment groups had similar demographic and clinical characteristics at baseline. The most common reason for change in interferon ß group were adverse effects or clinical ineffectiveness. Patients from glatiramer acetate group most often changed their therapy due to new lesions on MRI scans. Presented study shows a statistically significant decrease in radiological relapse when changing treatment from glatiramer acetate to dimethyl fumarate. At the same time, switching from interferon to dimethyl fumarate reduced the number of clinical relapses. There was no statistically significant difference in EDSS scores before and after treatment change in interferons' ß and glatiramer acetate's groups. CONCLUSIONS: The results of our study show that patients with progression of the disease should be treated with another medication. Further research is necessary to develop therapeutic position that supports therapeutic decision in an early period of MS. The observation of the presented group of patients will be continued.

Repetitive transcranial magnetic stimulation in treatment of post polio syndrome.

BACKGROUND: Post polio syndrome is a rare disease that occurs decades after polio virus infection. Repetitive transcranial magnetic stimulation (rTMS) is a treatment option with proved effectiveness in drug resistant depression. Possibly it can be helpful in therapy of other neurological diseases including post polio syndrome. OBJECTIVE: To describe a case of patient diagnosed with post polio syndrome who was treated with rTMS stimulation with a good effect. METHODS: Patient had rTMS stimulation of left prefrontal cortex twice a week for an eight weeks. Patient's health status was evaluated before treatment, after last rTMS session and after three months from the end of the treatment. RESULTS: Improvement of fatigue score, mood disturbances and motor functions was observed after treatment. CONCLUSION: rTMS can be an effective method in treatment of post polio syndrome but further studies with larger group need to be done to confirm that data.

Association between hemostatic markers, serum lipid fractions and progression of cerebral small vessel disease: A 2-year follow-up study.

INTRODUCTION: Little is known if hemostatic markers and serum lipid fractions can predict further radiological progression beyond vascular risk factors in cerebral small vessel disease (SVD). We investigated whether they are associated with SVD radiological progression and if they are related to different SVD clinical manifestations. METHODS: A single-center, prospective, cohort study with 2 years of radiological follow-up was performed in consecutive patients with different SVD manifestations. The study group consisted of 123 patients: 49 with lacunar stroke (LS), 48 with vascular dementia (VaD) and 26 with vascular parkinsonism (VaP). We assessed SVD progression by a visual SVD scale. We determined the relationship between serum or plasma concentrations of tissue factor (TF), thrombomodulin, beta-thromboglobulin (BTG), fibrinogen, D-dimer and total cholesterol, HDL-C, LDL-C, triglycerides and SVD progression by logistic regression analysis. RESULTS: 34.9% patients had SVD radiological progression: 43% had isolated WMLs progression, 23.2% had new lacunes, 34.8% had both WMLs progression and new lacunes. Fibrinogen [OR 1.02 (95% CI 1.006-1.011] was significantly associated with risk of new lacunes or WMLs progression regardless of the clinical SVD manifestation. While low HDL [OR 0.96 (0.93-1)] and TF [OR 1.07 (0.99-1.1)] were marginally associated with new lacunes, BTG [OR 1.005 (0.99-1.01)] was associated with WMLs progression. CONCLUSION: We found a relationship between fibrinogen and risk of radiological progression of SVD regardless of the clinical SVD manifestation. In addition, lower HDL and increased TF predicted development of new lacunes, and higher BTG was associated with risk of WMLs progression.