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Background. Data concerning central nervous system (CNS) alterations in ANCA-associated vasculitis with renal involvement (AAVR) are sparse. The study aimed to assess vascular and vasogenic brain alterations in patients with acute onset of AAVR and the applicability of non-contrast magnetic resonance imaging (MRI) techniques in this diagnosis. Methods. Thirty-eight patients with acute onset of AAVR were included in the study. BVAS/WG, c-ANCA, p-ANCA, renal function and perfusion, neurological assessment, and brain MRI were performed. Results. Cerebral vascular alternating narrowing and dilatation (VAND) was detected in 42.1% of patients, and the black-blood was significantly more diagnostic than the TOF technique (p < 0.001). VAND occurrence was independently associated with the concentration of p-ANCA. The vasogenic white matter lesions (VWML) were found in 94.4% of patients, and in their detection, SWAN was significantly better than the FLAIR technique (p = 0.002). The number of VWML correlated with age and cranial nerve damage. Hemosiderin deposits were found in 21.6% of patients and were associated with a gait impairment and paresthesia. Conclusions. Vascular and vasogenic alterations in the CNS are frequent in patients with acute onset of systemic ANCA-associated vasculitis with renal involvement. Non-contrast MRI is useful in the diagnosis of brain vasculitis.

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This study is designed to determine the efficacy of Cerebrolysin treatment as an add-on therapy to mechanical thrombectomy (MT) in reducing global disability in subjects with acute ischemic stroke (AIS). We have planned a single center, prospective, open-label, single-arm study with a 12-month follow-up of 50 patients with moderate to severe AIS, with a small established infarct core and with good collateral circulation who achieve significant reperfusion following MT and who receive additional Cerebrolysin within 8 h of stroke onset compared to 50 historical controls treated with MT alone, matched for age, clinical severity, occlusion location, baseline perfusion lesion volume, onset to reperfusion time, and use of iv thrombolytic therapy. The primary outcome measure will be the overall proportion of subjects receiving Cerebrolysin compared to the control group experiencing a favorable functional outcome (by modified Rankin Scale 0-2) at 90 days, following stroke onset. The secondary objectives are to determine the efficacy of Cerebrolysin as compared to the control group in reducing the risk of symptomatic secondary hemorrhagic transformation, improving neurological outcomes (NIHSS 0-2 at day 7, day 30, and 90), reducing mortality rates (over the 90-day and 12 months study period), and improving: activities of daily living (by Barthel Index), health-related quality of life (EQ-5D-5L) assessed at day 30, 90, and at 12 months. The other measures of efficacy in the Cerebrolysin group will include: assessment of final stroke volume and penumbral salvage (measured by CT/CTP at 30 days) and its change compared to baseline volume, changes over time in language function (by the 15-item Boston Naming Test), hemispatial neglect (by line bisection test), global cognitive function (by The Montreal Cognitive Assessment), and depression (by Hamilton Depression Rating Scale) between day 30 and day 90 assessments). The patients will receive 30 ml of Cerebrolysin within 8 h of AIS stroke onset and continue treatment once daily until day 21 (first cycle) and they will receive a second cycle of treatment (30 ml/d for 21 days given in the Outpatient Department or Neurorehabilitation Clinic) from day 69 to 90.

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PURPOSE: The natural clinical course of cerebral small vessel disease (CSVD) was not thoroughly described. The aim of this single center cohort study was to establish biochemical predictors of vascular events and death in CSVD patients during a 24-month follow-up. PATIENTS AND METHODS: A total of 130 functionally independent patients with marked MRI features of CSVD and recent lacunar stroke (n = 52,LS), vascular Parkinsonism (n = 28,VaP) or dementia (n = 50,VaD) were prospectively recruited. Serum markers of endothelial dysfunction, inflammation and hemostasis were determined at baseline. The primary outcome was defined as occurrence of death or any vascular events during the observation. RESULTS: The mean age was 72 ± 8.1 years, and 37.6% of the patients were women. The mean follow-up time was 22.3 ± 4.3 months, and 84.6% of patients had extensive white matter lesions on baseline MRI. The overall mortality rate was 6.9%, and vascular events or death occurred in 27% of the patients. Kaplan-Meier survival curves revealed no significant differences between CSVD groups (log rank p = 0.49). Cox regression analysis revealed that IL-1α (HR 1.4; 95%CI 1.09-1.8), IL-6 (1.4;1.1-2.2), hs-CRP (1.1;1.06-1.9), homocysteine (1.4;1.1-1.8), fibrinogen (1.4;1.05-2), and d-dimer (2.7;1.6-4.5) were significantly associated with the primary outcome. IL-1α (1.3;1.07-1.8), IL-6 (1.4;1.02-2.2), d-dimer (2.8;1.6-5) and homocysteine (1.4;1.1-1.8) remained significant after adjusting for age, sex and CSVD radiological markers. CONCLUSIONS: Our study demonstrated the important prognostic role of various circulation markers of inflammation in individuals with different clinical signs and radiological markers of CSVD. The strongest association occurred between IL-1α, IL-6 and recurrent stroke, other vascular events and death.

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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.

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BACKGROUND: Endothelial dysfunction (ED) is involved in the pathogenesis of cerebral small vessel disease (SVD), however, it is not clear if specific biomarkers related to ED are associated with radiological progression of SVD. METHODS: A single-center, prospective cohort study was conducted among consecutive, adult patients with SVD. Logistic regression was used to analyze the association of each baseline biomarker (highest vs lowest tertile) and the MRI radiological outcome after 2 years. The mean Z-score for vascular inflammation (VI) combined soluble intercellular cell adhesion molecule-1 (sICAM-1), soluble platelet selectin (sP-selectin), CD40 ligand (sCD40 L), platelet factor-4 (PF-4) and homocysteine; Z-score for systemic inflammation (SI) combined high-sensitivity C-reactive protein (hsCRP), interleukin-1α and -6 (IL-1α and IL-6, respectively) and tumor necrosis factor-α (TNF-α). RESULTS: The study group comprised 123 patients (age, mean±SD: 72.2±8 years, 49% females), with lacunar stroke (n=49), vascular dementia (n=48), and vascular parkinsonism (n=26). Moreover, 34.9% patients experienced radiological progression, 43% had progression of isolated white matter lesions (WMLs), 23.2% had new lacunes, and 34.8% had both WMLs progression and new lacunes. After adjustment for confounders (age, sex, blood pressure, MRI lesions load), the PF-4 (OR; 95% CI 5.5; 1.5-21), sCD40L (4.6; 1.1-18.6), IL-6 (7.4; 1.48-37), Z-score for VI (4.5; 1.1-18.6), and, marginally, homocysteine (4.1; 0.99-17) were associated with the risk of any radiological progression; further, homocysteine (2.4; 1.4-14), Z-score for SI (2.1; 1.2-14) and, marginally, IL-6 (6.0; 0.95 -38) were related to the development of new lacunes; PF-4 (7.9; 1.6-38) and, marginally, the Z-score for VI (4.2; 0.9-19.5) were correlated with the risk of WMLs progression. Additional adjustment for clinical SVD manifestations did not significantly alter the results. CONCLUSION: The data supports the concept that ED modulates the radiological progression of SVD and WMLs and lacunes are associated with different inflammatory markers.

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BACKGROUND: The clinical significance of aspirin resistance (AR) in patients with symptomatic cerebrovascular disease is not well known. The aim of this single-center, prospective study was to examine the prevalence, risk factors and prognostic significance of AR in patients with different clinical manifestations of cerebral small vessel disease (CSVD) over 24-month follow-up. METHODS: We studied 104 patients with MRI confirmed CSVD, including those with recent lacunar stroke (LS, n=49), vascular parkinsonism (VaP, n=16) and dementia (VaD, n=39). Platelet aggregation was evaluated with electrode platelet aggregometry (Multiplate analyzer); AR was defined as a value of ≥300 AUC*min. All patients had 24-h ABPM performed at baseline. Radiological progression was recognized based on repeated MRI examinations. RESULTS: The prevalence of AR was 26%, and it did not differ between LS, VaD, and VaP (22.4%, 28.2%, and 31.3%, respectively; p=0.7). The patients with AR had higher triglyceride levels (TG; 144.2±100 vs 109.7±48 mg/dl; p=0.09) and mean arterial blood pressure (MAP; 103.5±15.2 vs 91.7±10.5 mmHg; p<0.01) than did responders to aspirin (RTA). TG (OR 1.02; 95%CI 1-1.11; p=0.04) and MAP (OR 1.03; 95%CI 1.0-1.09; p=0.04) were independent of age, sex, statin and antihypertensive treatment risk factors for AR. The patients with AR more frequently experienced ischemic strokes than did those with RTA (OR 3.1; 98%CI 1.08-9.3; p=0.03) and had more radiological progression (OR 2.2; 95%CI 0.9-5.7; p=0.08). AR was independent of age, sex, baseline Fazekas score predictor of lacunar stroke (OR 3.79; 95%CI 1.19-12; p=0.02) and radiological progression (OR 2.9; 95%CI 1.04-8.3; p=0.04). CONCLUSIONS: The prevalence of AR was high and similar among the patients with LS, VaD, and VaP due to CSVD. Higher 24-h MAP and TG were independently related to the risk of AR. AR was associated with risk of radiological progression and lacunar strokes over 24 months of observation.

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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.

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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.

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BACKGROUND AND PURPOSE: Natural course of cerebral small vessel disease (CSVD) has not yet been thoroughly studied. The aim of the single center study was to establish risk of vascular events or death in different manifestations of CSVD. METHODS: 150 consecutive, functionally independent patients with marked MRI features of CSVD and with recent lacunar stroke (n = 52, LS), deep hemorrhagic stroke (n = 20, HS), vascular parkinsonism (n = 28, VaP), vascular dementia (n = 50, VaD) and 55 controls (CG) with high atherothrombotic risk free of cerebrovascular events were prospectively recruited and followed for 24 months. RESULTS: Mean age and sex distribution were similar in CSVD and CG but patients with CSVD were less likely to have CAD (19% vs 40%, p = 0.02) and tended to have higher prevalence of diabetes (54% vs 37%, p = 0.11). The risk of vascular events or death was increased in any patients with moderate to severe white matter lesions at baseline MRI (HR 2.0; 95% CI 0.85-7.2), in CSVD (4.56; 95% CI 1.3-14.9) vs CG, regardless of its clinical manifestation: LS or HS (HR 4.70; 95% CI 1.3-16.2) and VaD or VaP (HR 4.59; 95% CI 1.3-15.7). Adjustment for confounders did not change the results substantially. CONCLUSIONS: Patients with symptomatic CSVD regardless of the clinical (acute or chronic) manifestation had more than fourfold the risk of vascular events or death in 24 months of observation compared with controls with high atherothrombotic risk free of cerebrovascular events.

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INTRODUCTION: The natural course of vascular parkinsonism (VaP) and dementia (VaD) due to cerebral small vessel disease (SVD) is not well known. The aim of this single-center study was to evaluate the long-term risk of vascular events, death and dependency in patients with VaP or VaD and to compare it with patients without cerebrovascular disease but with high atherothrombotic risk. MATERIAL AND METHODS: Seventy-eight consecutive, functionally independent patients with MRI features of SVD and with recently diagnosed VaD (n = 50) and VaP (n = 28) and 55 controls (control group - CG) with high 10-year risk of total cardiovascular disease (SCORE ≥ 5%) were prospectively recruited and followed for 24 months. RESULTS: Patients with SVD had lower prevalence of coronary artery disease compared with the CG (20.5% vs. 40%; p = 0.02) but similar prevalence of other atherothrombotic risk factors including mean age (73.7 ±7.3 vs. 72 ±5.9 years, p = 0.09). All outcomes were worse in SVD patients than controls. Thirty-one percent of SVD patients (34% of VaD vs. 25% of VaP, p = 0.45) experienced vascular events or died compared to 6% of controls (p < 0.01). After adjustments for potential confounders (age, sex, vascular risk factors), patients with VaP (HR = 7.5; 95% CI: 1.6-33; p < 0.01) and VaD (HR = 8.7; 95% CI: 2.1-35; p < 0.01) had higher risk of vascular events or death and death or dependency (respectively; HR = 3.9; 95% CI: 0.83-18.8; p = 0.07 and HR = 4.7, 95% CI: 1.1-19.7; p = 0.03). CONCLUSIONS: Patients with VaP or VaD due to SVD had significantly higher risk of vascular events, death and dependency compared to controls with high cardiovascular risk and without cerebrovascular disease.

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Usually limbic encephalitis (LE) is a paraneoplastic neurologic syndrome. LE symptoms can precede cancer even by a few years. Almost 50% of LE cases are connected with small cell lung carcinoma. Testis and breast cancers, granulomatous disease, thymoma, and teratomas are also often connected with LE. Other cases have infectious and autoimmunological aetiology. In LE limbic system dysfunction is observed, and it is accompanied by cerebellum and brain stem abnormalities as well as polyneuropathy. Paraneoplastic limbic encephalitis is sometimes a part of larger syndrome in which brain stem and spinal cord are involved in an inflammatory process called paraneoplastic encephalomyelitis. The main LE symptoms are: impairment of cognitive functions with subacute beginning, partial and generalised seizures, mental distress, disturbances of consciousness, and limb paresis. In MRI study hyperintensive lesions in the medial part of the temporal lobes in T2 and FLAIR sequences are present. Sharp and slow waves in electroencephalography in the temporal area are also frequent. In cerebrospinal fluid pleocytosis, elevation of protein level, intensification of immunoglobulin synthesis, and oligoclonal bands can be detected. The majority of patients with paraneoplastic LE have onconeural antibodies in the blood. The presented study is a description of the clinical course of the disease in four patients diagnosed with LE.

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Creutzfeldt-Jakob disease (CJD) is a rare syndrome of central nervous system caused by infectious protein called prion. There are four types of CJD: sporadic (sCJD), familial (fCJD), jatrogenic (jCJD) and variant (vCJD). The most frequent symptoms are rapidly progressing dementia, mioclonias, akinetic mutism and signs of cerebellum dysfunction. In sCJD, MRI often shows high signal intensity in the putamen and caudate nucleus on T2-weighted images while in vCJD pulvinar sign is often observed. 70% patients with CJD often has characteristic generalized periodic sharp wave pattern in electroencephalography. In case of 90% patients with CJD 14-3-3 protein is present in cerebrospinal fluid. Neuropathological studies play an important role in disease diagnosis. CJD incidence is 0.5-1 on 1000000 people but some cases can be undiagnosed. Presented study is a description of woman with sCJD confirmed with histopathological study. Since childhood patient had psychotic symptoms and behavior disturbances. Patient wasn't diagnosed due to this symptoms. Few months before admission to hospital her condition was getting worse. Symptoms of cerebellum, pyramidal and extrapyramidal system occurred. In cerebrospinal fluid 14-3-3 protein was detected. In EEG and MRI changes specific for sCJD was observed. After three months patient died.

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It is estimated that around 15 million people survived polio infection worldwide since early twentieth century. In 1950 effective vaccination was used for first time. Since that time number of affected people decreased. The last epidemic of Haine-Medine disease in Poland was in 1950s. Another rare cases of infections were observed till 1970s. About at least 15 years after polio virus infection, slowly progressive muscle limbs paresis with muscle atrophy, joints pain, paresthesia were observed in polio survivors. That constellation of symptoms was called post-polio syndrome (PPS). PPS frequency among people after paralytic and nonparalytic polio infectious is ranged from 30% to 80%. Fatigue that leads to physical and mental activity deterioration is another important symptom that is observed in 90% of patients with PPS. Etiology of disease remains elusive. Probably it is an effect of spine frontal horns motoneurons damage during acute virus polio infection that leads to overloading and degeneration of remaining ones. The most important risk factors of PPS are female sex and respiratory symptoms during acute polio infection. Electromyography is an important part of PPS diagnostic process. Electrophysiological abnormalities are seen in clinically affected and unaffected muscles. The most frequent are fasciculations and fibrillations during rest activity, extension of motor unit area, time duration and amplitude. In this study we described three cases of people who developed PPS years after Haine-Medine disease and correlation between their EMG results and clinical status. We also analyzed electromyography results both after one month since first PPS signs occurred as well as after few years. Presentation of dynamic changes in EMG was the most important aim of that study.

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Although mesenchymal stem cells are used in numerous clinical trials, the safety of their application is still a matter of concern. We have analysed the clinical results of the autologous adipose-derived stem cell treatment (stromal vascular fraction (SVF) containing adipose-derived stem cells, endothelial progenitors, and blood mononuclear cells) for orthopedic (cartilage, bone, tendon, or combined joint injuries) and neurologic (multiple sclerosis) diseases. Methods of adipose tissue collection, cell isolation and purification, and resulting cell numbers, viability, and morphology were considered, and patient's age, sex, disease type, and method of cell administration (cell numbers per single application, treatment numbers and frequency, and methods of cell implantation) were analysed and searched for the unwanted clinical effects. Results of cellular therapy were compared retrospectively to those obtained with conventional medication without SVF application. SVF transplantation was always the accessory treatment of patients receiving "standard routine" therapies of their diseases. Clinical experiments were approved by the Bioethical Medical Committees supervising the centers where patients were hospitalised. The conclusion of the study is that none of the treated patients developed any serious adverse event, and autologous mesenchymal stem (stromal) cell clinical application is a safe procedure resulting in some beneficial clinical effects (not analysed in this study).

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Repetitive transcranial magnetic stimulation (rTMS) is a treatment option with proved effectiveness especially in drug resist depression. It is used in functional brain mapping before neurosurgery operations and diagnostic of corticospinal tract transmission. Many studies are performed to evaluate rTMS using in treatment of obsessive - compulsive disorder, schizophrenia, autism, strokes, tinnitus, Alzheimer and Parkinson diseases, cranial traumas. Moreover rTMS was used in treatment of multiple sclerosis, migraine, dystonia. Electromagnetical field generated by rTMS penetrate skin of the scalp and infiltrate brain tissues to a depth of 2 cm, cause neurons depolarization and generating motor, cognitive and affective effects. Depending on the stimulation frequency rTMS can stimuli or inhibit brain cortex. rTMS mechanism of action remains elusive. Probably it is connected with enhancement of neurotransmitters, modulation of signals transductions pathways in Central Nervous System, gene transcription and release of neuroprotective substances. Studies with use of animals revealed that rTMS stimulation can generate brain changes similar to those seen after electric shock therapy without provoking seizures. The aim of presenting study was to analyze actual researches evaluating rTMS use in treatment of psychiatric and neurological diseases.

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Multiple sclerosis is a chronic, autoimmunological disease of central nervous system in which axonal damage in brain and spinal cord is observed. It is second most common cause of disability in young adults in West Europe and North America after injuries. There is 2.5 million people suffered from multiple sclerosis worldwide. The worse prognosis is connected with primary progressive MS in which recovery after first symptoms of central nervous system damage isn't observed. That subtype of disease is seen in case of 10-20% people with MS. MTX is a synthetic antracycline with antineoplastic, immunomodulatory and anti-inflammatory effects. Drug was allowed to treatment of leukemia. It is also used in treatment of breast, prostate, ovarian, stomach and liver cancer. Additionally MTX is used in treatment of secondary progressive SM and relapsing - remitting subtype of disease with no respond to treatment with interferon beta and glatiramer acetate. MTX inhibits topoisomerase II activity, matches to DNA molecule and damage her structure. Drug inhibits limphocyte T, B and macrophages activity and antibodies synthesis. The most dangerous side effects of MTX treatment are cardiotoxicity and induction of leukemia. There is lack of studies describing MTX effectiveness and safety in treatment of primary progressive SM.

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Multiple sclerosis (MS) is an inflammatory, demyelinating disease that affects the central nervous system. Etiology of MS is undiscovered but it is assumed that both genetic and environmental triggers play an important role in disease pathogenesis. Mitoxantrone (MTX) is an antracycline antibiotic that is used in oncologic treatment of breast, prostate, liver, ovarian and stomach cancer. MTX is also effective in treatment of primary and secondary progressive multiple sclerosis and in relapsing - remitting subtype of disease with no reaction for other drugs therapy. In treatment of MS drug is given intravenously in a dose of 12 mg/m2 in three months intervals to maximal dose of 120-140 mg/m² of body surface. MTX treatment can cause transient reduction of leukocyte, erythrocyte and thrombocyte number in blood but the most dangerous side effect of MTX treatment is therapy related acute leukemia (TRAL). The aim of this study was to evaluate influence of MTX treatment on complete blood count in multiple sclerosis patients. Seventy two patients with multiple sclerosis treated with mitoxantrone from 2002 to 2014 took part in this study. Control group comprised 60 patients with multiple sclerosis who weren't given immunomodulatory treatment. In this study, amount of leukocytes, erythrocytes and thrombocytes after MTX treatment was compared to those before treatment and in control group. Six patients were withdrawn from the study because of leucopenia. A decrease of leukocytes, erythrocytes and thrombocytes number after MTX treatment was observed in comparison to control group and value before treatment. The decrease of erythrocytes number after MTX treatment was statistically significant. The most frequent side effect of mitoxantrone treatment is transient, asymptomatic leucopenia. Therapy related acute leukemia and other life-threatening complications weren't observed in the study group.

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BACKGROUND: Mitoxanthrone (MTX) is a synthetic anthracycline antibiotic that has been used for several years in the treatment of patients with primary progressive, secondary progressive, and relapsing remitting multiple sclerosis (MS) who do not respond to other drugs. MTX has antineoplastic, immunomodulatory, and antibacterial properties. The most common adverse effects of MTX include nausea and vomiting, hair loss, increased risk of urinary and respiratory tract infections, and amenorrhea. Less frequent problems include leukopenia, thrombocytopenia, anaemia, and an increase in hepatic enzyme and bilirubin levels. Other severe sequelae of MTX treatment are drug cardiotoxicity and a potential to induce leukaemia. Drug toxicity results from its affinity to iron ions. The resulting complex strongly induces formation of free oxygen radicals and increases lipid peroxidation. Asymptomatic reduction in left ventricular ejection fraction (LVEF) by two-dimensional (2D) echocardiography, cardiomyopathy, and congestive heart failure have been observed in patients with MS at a rate of about 2.6-5%. Few studies evaluated cardiotoxicity of MTX in MS patients. Most previous studies were performed in small groups of cancer patients and cardiac evaluation was limited to physical examination. AIM: To evaluate the effect of MTX treatment on LVEF by 2D echocardiography. METHODS: We studied 72 MS patients aged 25-63 years who were treated with MTX in 2002-2014. The diagnosis of MS was made using the 2001 McDonald criteria updated in 2005. The study group included primary progressive MS in 40 (56%) patients, secondary progressive MS in 5 (7%) patients, and relapsing remitting MS in 27 (37%) patients. MTX was administered at 12 mg/m2 of body surface area every 3 months (up to the total dose of 140 mg/m2). MTX treatment was initiated in patients with no signs of heart failure on physical examination, normal electrocardiogram (ECG), normal LVEF by 2D echocardiography, and normal laboratory test findings including complete blood count and hepatic and renal function parameters. Each MTX administration was preceded by 2D echocardiography with LVEF measurement, ECG, and physical examination of the cardiovascular system. The effect of MTX treatment on LVEF was evaluated by comparing baseline LVEF with LVEF measurements before the last MTX dose. Statistical analysis was performed using the Student t test. RESULTS: The mean LVEF before administration of the first MTX dose was 65 ± 3.3%. The lowest LVEF at the final 2D echo-cardiographic examination was 60 ± 2.1%. We did not find a significant LVEF reduction during MTX treatment in MS patients compared to baseline values. Severe myocardial dysfunction manifesting with significant LVEF reduction by 2D echocardiography or clinical evidence of heart failure was not noted in any patient in the study group. CONCLUSIONS: Our study showed no significant LVEF reduction during MTX monotherapy in MS patients without a history of a cardiac disease and with normal echocardiographic findings at baseline. Long-term cardiac effects of MTX require further studies.

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UNLABELLED: Brain tumor is an abnormal growth of cells in central nervous system (CNS). The most common primary brain tumors are: gliomas, meningiomas, pituitary adenomas and craniopharyngiomas. The secondary group are metastatic tumors. About 25% patients with cancers have metastasis to CNS. AIM: The aim of this study was to evaluate the most common symptoms and localization of brain tumors, time from first symptoms to diagnosis and patients' survival rate. MATERIALS AND METHODS: In this retrospective study 106 patients with primary and metastatic brain tumors hospitalized in Military Institute of Medicine from 2007 to 2012 year were investigated. RESULTS: The most common cause of metastases to brain is non-smallcell lung carcinoma. The most frequent symptom of brain tumor is headache but very often patients have seizures, vomits, arms and legs weakness. The mean time of life for patients with gliomas was 9 month and 13 days for patients with brain metastases. CONCLUSIONS: It occurred that patients with primary and secondary brain tumors lived shorter than it is described in literature. In group of patients with metastases to brain 60% had one or two brain tumors so they could be treated with surgery and prognosis for them was better.

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Sporadic small vessel disease (sSVD) is one of the most common vascular disease of the central nervous system (CNS). It is the main cause of lacunar stokes, hemorrhages to deep brain regions and chronic CNS diseases such as vascular parkinsonism and dementia. Beside a high and growing incidence of sSVD especially in the elderly population, the knowledge of ethiopathogenesis and optimal treatment of sSVD have not been established. The article summarizes different clinical manifestations (acute and chronic) as well as heterogenous radiologic changes found in CNS neuroimaging.

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