Molecular classification of glioblastoma based on immunohistochemical expression of EGFR, PDGFRA, NF1, IDH1, p53 and PTEN proteins.

Glioblastoma (GBM) is the most common and most aggressive primary tumor of the central nervous system. Current GBM treatments have low effectiveness. This is mainly due to the high degree of heterogeneity of GBM tumors. Despite similarities in the classic microscopic image, these tumors differ significantly in molecular terms. The aim of the study was to classify GBM tumors into one of four molecular types based on the immunohistochemical expression of EGFR, PDGFRA, NF1, IDH1, p53 and PTEN proteins and find the association between individual glioma molecular types and prognostic clinical and morphological parameters. From the group of 162 patients the classical molecular type of tumor was observed in 17 (10%) patients, in 23 (14%) the tumor was mesenchymal, in 32 (20%) proneural, and in 90 (56%) neural. No significant relationship was observed between the molecular type of GBM tumors and the studied clinical and morphological parameters of prognostic significance. There were also no statistically significant correlations between the GBM tumor molecular type and survival, both in terms of overall survival and relapse-free survival. Analyzing the impact of all prognostic variables and molecular type of GBM on the probability of overall survival, statistically significant relationships were found.

Articulation recovery in ALS patients after lineage-negative adjuvant cell therapy - preliminary report.

Background: Amyotrophic lateral sclerosis (ALS) is one of the most frequently occurring neurodegenerative diseases affecting speech and swallowing. This preliminary study aimed to investigate whether an autologous lineage-negative stem/progenitor cell therapy applied to ALS patients affects the level of selected trophic and proinflammatory factors, and subsequently improves the articulation. Methods: We enrolled 12 patients with sporadic ALS, who underwent autologous bone marrow-derived lineage negative (LIN-) cells administration into cerebrospinal fluid (CSF). We evaluated patients' articulation using the Frenchay Dysarthria Assessment on days 0 and 28 following the LIN- cells administration. Concentrations of various factors (BDNF, NGF, ANGP-2, VEGF, PDGF-AA, PEDF, COMP-FH, CRP, C3, C4) in CSF were quantified by multiplex fluorescent bead-based immunoassays in the samples collected on the day of LIN- cells administration and 28 days later. On top of this, we assessed levels of BDNF and NGF in the patients' plasma on the day of the injection, three, seven days and three months after the treatment. Results: Of the 12 patients who received the LIN- cell therapy 8 showed short-termed improvement in articulatory functions (group I), which was particularly noticeable in better phonation time, lips and soft palate performance, swallowing reflex and voice loudness. Four patients (group II) did not show substantial improvement. CSF concentrations of BDNF, ANGP-2 and PDGF-AA in group I decreased significantly 28 days after LIN- cells administration. The highest concentration levels of BDNF in group II and NGF in both groups in blood plasma were observed on day 3 following the injection. Conclusions: The outcomes of the LIN- cell application in ALS treatment of articulatory organs are promising. The procedure proved to be safe and feasible. A short-lasting trophic effect of autologous LIN- administration could encourage repeated cell's application in order to sustain their beneficial effects, however this approach needs further investigation.

Free Fatty Acids and Their Inflammatory Derivatives Affect BDNF in Stroke Patients.

OBJECTIVE: The neurotrophin brain-derived neurotrophic factor (BDNF) affects poststroke functional outcome, neurogenesis, neuroprotection, and neuroplasticity. Its level is related to the diet and nutritional status, and more specifically, it is free fatty acids (FFAs) and eicosanoids that can have an impact on the BDNF level. The aim of this study was to analyze the potential impact of FFAs and eicosanoids on the BDNF level in stroke patients. Material and Methods. Seventy-three ischemic stroke patients were prospectively enrolled in the study. Laboratory tests were performed in all subjects, including the levels of FFAs, eicosanoids, and BDNF. FFAs and inflammatory metabolites were determined by gas chromatography and liquid chromatography, while BDNF was evaluated by the immune-enzymatic method (ELISA). RESULTS: The plasma level of BDNF negatively correlated with C22:1n9 13 erucic acid, C18:3n3 linolenic acid (ALA), and lipoxin A4 15-epi-LxA4. A direct association was observed in relation to BDNF and C16:1 palmitoleic acid and C20:3n6 eicosatrienoic acid (dihomo-gamma-linolenic acid (DGLA)). CONCLUSIONS: Saturated fatty acids and omega-3 and omega-9 erucic acids can affect signaling in the BDNF synthesis resulting in the decrease in BDNF. There is a beneficial effect of DGLA on the BDNF level, while the effect of ALA on BDNF can be inhibitory. Specialized proresolving lipid mediators can play a role in the BDNF metabolism. BDNF can interact with inflammation as the risk factor in the cardiovascular disorders, including stroke.

The Association of Free Fatty Acids and Eicosanoids with the Severity of Depressive Symptoms in Stroke Patients.

The study was designed to demonstrate the relationship of free fatty acids (FFAs) and eicosanoids levels with the severity of depressive symptoms in stroke. The ischemic stroke patients (n = 74) were included in the prospective study. The risk of depression was evaluated by the Beck Depression Inventory-II (BDI-II) 7 days and 6 months after the stroke onset. FFAs and inflammatory metabolites were determined by gas chromatography and liquid chromatography. In the acute phase of stroke, BDI-II and FFAs inversely correlated with C13:0 tridecanoic acid, C15:1 cis-10-pentadecanoid acid, C17:1 cis-10- heptadecanoid acid, C18:0 stearic acid, C20:3n6 eicosatrienoic acid, C22:1cis13 docosenoic acid and C22:6n3 docosahexaenoic acid (DHA). DHA level was significantly lower in patients with low vs. high BDI-II score. In the follow-up examination, BDI-II score directly correlated with C16:0 palmitic acid. The changes in BDI-II score during 6-month observation inversely correlated with lipoxin A4 and protectin D1, and directly correlated with 5-oxo-ETE. Importantly, the severity of depressive symptoms was associated with n3 PUFA level. Diet-derived FFAs were observed to potentially affect the inflammatory pathways in pathogenesis of depression in stroke and reduced DHA levels can attenuate depressive symptoms in stroke patients.

Local and Systemic Humoral Response to Autologous Lineage-Negative Cells Intrathecal Administration in ALS Patients.

Amyotrophic lateral sclerosis (ALS) remains a fatal disease with limited therapeutic options. Signaling via neurotrophins (NTs), neuroinflammation, and certain micro-RNAs are believed to play essential role in ALS pathogenesis. Lineage-negative stem/progenitor cells (Lin-) were obtained from bone marrow of 18 ALS patients and administered intrathecally. Clinical assessment was performed using ALS Functional Rating Scale (FRSr) and Norris scale. Protein concentrations were measured in plasma and cerebrospinal fluid (CSF) by multiplex fluorescent bead-based immunoassay. Gene expression in nucleated blood cells was assessed using gene microarray technique. Finally, miRNA expression was analyzed using qPCR in CSF and plasma samples. We observed a significant decrease of C-reactive protein (CRP) concentration in plasma on the seventh day from the application of cells. Gene array results revealed decreased expression of gene sets responsible for neutrophil activation. Further analysis revealed moderate negative correlation between CRP level in CSF and clinical outcome. Brain-derived neurotrophic factor (BDNF) concentrations in both plasma and CSF significantly correlated with the favorable clinical outcome. On a micro-RNA level, we observed significant increase of miR-16-5p expression one week after transplantation in both body fluids and significant increase of miR-206 expression in plasma. Administration of Lin- cells may decrease inflammatory response and prevent neurodegeneration. However, these issues require further investigations.

The Relationship between Selected Demographic Factors and Speech Organ Dysfunction in Sporadic ALS Patients.

Background and objectives: Speech disorders are observed in 30% of newly diagnosed sporadic amyotrophic lateral sclerosis (ALS) patients. Characterized by a dynamic course, dysfunction of articulation has not so far been well understood. The aim of this study was to analyze the influence of demographic factors (sex, age, duration of the disease) and concomitant diseases (degenerative spine disease, depression, hypertension, hypothyroidism, hyperthyroidism, and allergy) on the functioning of speech organs in ALS patients. Materials and Methods: The study group consisted of 65 patients with sporadic ALS. Patients were examined for articulatory functions by means of the Frenchay Dysarthria Assessment (FDA). Results: 68% of the study sample had spinal disorders. Logistic regression analysis showed that a decline in the functioning of lips, soft palate, length of phonation, and voice loudness was more common among men. Patients diagnosed with degenerative spine disease more often suffered from respiratory disorders, while younger patients (<60 years of age) significantly more often had the impairment of the sentence and spontaneous speech functions. Conclusions: The male gender in patients with ALS is associated with an increased risk of deterioration of the phonation length function. Patients under 60 years of age are associated with more often pronouncing sentences disorders and spontaneous speech disorders.

Risk factors for death by acute ischaemic stroke in patients from West-Pomerania, Poland.

AIM AND CLINICAL RATIONALE FOR STUDY: In Poland, it is widely believed that the outlook for ischaemic stroke patients is gradually improving due to the development of a network of stroke wards and other dedicated hospital units throughout the country. However, a study by Shah et al., reporting a significant increase in mortality from ischaemic stroke in several European countries including Poland, contradicts this belief. Therefore, the aim of this study was to determine the risk factors for death in patients with recent ischaemic stroke among a population of patients from Western Pomerania, a region in north-western Poland. MATERIALS AND METHODS: This retrospective study involved 2,374 patients with recent ischaemic stroke. Mortality was defined as death within 30 days of admission to hospital. Patients who died in hospital during this period were defined as deceased, while those who survived beyond this time were classified as alive. RESULTS: We found that compared to ischaemic stroke patients who survived, the group of ischaemic stroke patients who died included a higher number of patients who smoked cigarettes (OR = 6.08 in univariable model; OR = 6.22 in adjusted model), had hypertension (OR = 2.57; OR = 1.85), had a history of previous stroke (OR = 2.63; OR = 2.14), had coronary heart disease (OR = 1.78; OR=1.36), and were older (OR = 1.06; OR = 1.05). For all these factors, p-value was lower than 0.001. Females had a higher risk of death (OR = 1.48, p < 0.001; OR = 1.35, p = 0.01). For dyslipidemia, only univariable model was statistically significant (OR = 1.38, p < 0.001). CONCLUSION AND CLINICAL IMPLICATIONS: Older age, female sex, dyslipidemia, hypertension, coronary heart disease, and smoking are not only recognised risk factors for ischaemic stroke, but also risk factors associated with an unfavourable prognosis following stroke.

Secondary progressive multiple sclerosis - from neuropathology to definition and effective treatment.

INTRODUCTION: There is no single, commonly accepted, standard definition of secondary progressive multiple sclerosis (SPMS), an absence that poses a challenge for clinicians. STATE OF THE ART: SPMS is characterised by inflammation, neurodegeneration and disease progression with the presence or absence of relapses. No biochemical or radiological biomarkers are currently available to indicate the precise secondary progressive course in individual patients. The retrospective approach to identifying SPMS patients raises many difficulties, especially in terms of determining the time point of progression. Currently, the most precise diagnosis of SPMS is based on the definition proposed by Lorscheider et al., where SPMS is defined as a disability progression by 1 step on the Expanded Disability Status Scale (EDSS) in patients with EDSS ≤ 5.5 or of 0.5 EDSS steps in patients with EDSS ≥ 6 in the absence of a relapse, a minimum EDSS score of 4 and pyramidal functional system (FS) score of 2, and confirmed progression over ≥ 3 months, including confirmation within the leading FS. CLINICAL IMPLICATIONS: The need to establish criteria for the diagnosis of SPMS is currently of crucial importance due to emerging treatment opportunities including siponimod, a sphingosine 1-phosphate (S1P) receptor modulator selective for S1P1 and S1P5 receptors. It is reasonable to introduce drugs at the earliest possible stage of lesion progression to reduce inflammation a nd t o p rotect t he c entral n ervous s ystem ( CNS) a gainst i rreversible n eurodegeneration. FUTURE DIRECTIONS: Further studies with prospective, multicentre and long term follow-up design are needed to provide better insights into SP course in MS patients. This should be supported by radiological, biochemical and pathological evaluations to help establish reliable and sensitive biomarkers to guide clinical practice.

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.

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.

Comparative assessment and monitoring of deterioration of articulatory organs using subjective and objective tools among patients with amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal degenerative disease of a rapid course. In 25% of ALS sufferers, speech disorders occur as prodromal symptoms of the disease. Impaired communication affects physical health and has a negative impact on mental and emotional condition. In this study, we assessed which domains of speech are particularly affected in ALS. Subsequently, we estimated possible correlations between the ALS patients' subjective perception of their speech quality and an objective assessment of the speech organs carried out by an expert. METHODS: The study group consisted of 63 patients with sporadic ALS. The patients were examined for articulatory functions by means of Voice Handicap Index (VHI) and the Frenchay Dysarthria Assessment (FDA). RESULTS: On the basis of the VHI scores, the entire cohort was divided into 2 groups: group I (40 subjects) with mild speech impairment, and group II (23 subjects) displaying moderate and profound speech deficits. In an early phase of ALS, changes were typically reported in the tongue, lips and soft palate. The FDA and VHI-based measurements revealed a high, positive correlation between the objective and subjective evaluation of articulation quality. CONCLUSIONS: Deterioration of the articulatory organs resulted in the reduction of social, physical and emotional functioning. The highly positive correlation between the VHI and FDA scales seems to indicate that the VHI questionnaire may be a reliable, self-contained tool for monitoring the course and progression of speech disorders in ALS. TRIAL REGISTRATION: NCT02193893 .

A Novel NOTCH3 Gene Mutation in a Polish CADASIL Family.

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a genetically determined disease of the cerebral vessels, characterized by recurrent ischemic strokes, dementia, and degeneration of the cerebral white matter. The condition is caused by a mutation in the NOTCH3 gene, whose product plays a great role in the development and physiology of the cardiovascular system. Magnetic resonance imaging reveals multiple hyperintensive lesions of the white matter in the T2-weighted images also in asymptomatic carriers of CADASIL and can be detected even 10-15 years prior to clinical signs. Diagnosis is confirmed by genetic testing. We present 2 patients (mother and daughter) carrying the same mutation p.Cys212Gly in 1 allele of the NOTCH-3 gene, which has not yet been recorded in the Human Gene Mutation Database for that gene and therefore described as a new one. The clinical manifestation of the disease differs between patients -the 63-year-old mother has been suffering from severe migraine headaches since her early youth and the first vascular event occurred when she was about 50 years old, she is now presenting with impaired cognitive functions, left facial palsy, bilateral pyramidal syndrome more prominent on the left side, and four-wheel support assisted walking. The neurological deficits that her 42-year-old daughter is afflicted with are discreet. Observation to date indicates a definitely less severe clinical course of the disease. This indicates that members of the same family carrying the same mutation may produce different clinical course of the disease.

Safety and Feasibility of Lin- Cells Administration to ALS Patients: A Novel View on Humoral Factors and miRNA Profiles.

Therapeutic options for amyotrophic lateral sclerosis (ALS) are still limited. Great hopes, however, are placed in growth factors that show neuroprotective abilities (e.g., nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and vascular endothelial growth factor (VEGF)) and in the immune modulating features, in particular, the anti-inflammatory effects. In our study we aimed to investigate whether a bone marrow-derived lineage-negative (Lin-) cells population, after autologous application into cerebrospinal fluid (CSF), is able to produce noticeable concentrations of trophic factors and inflammatory-related proteins and thus influence the clinical course of ALS. To our knowledge, the evaluation of Lin- cells transplantation for ALS treatment has not been previously reported. Early hematopoietic Lin- cells were isolated from twelve ALS patients’ bone marrow, and later, the suspension of cells was administered into the subarachnoid space by lumbar puncture. Concentrations of selected proteins in the CSF and plasma were quantified by multiplex fluorescent bead-based immunoassays at different timepoints post-transplantation. We also chose microRNAs (miRNAs) related to muscle biology (miRNA-1, miRNA-133a, and miRNA-206) and angiogenesis and inflammation (miRNA-155 and miRNA-378) and tested, for the first time, their expression profiles in the CSF and plasma of ALS patients after Lin- cells transplantation. The injection of bone marrow cells resulted in decreased concentration of selected inflammatory proteins (C3) after Lin- cells injection, particularly in patients who had a better clinical outcome. Moreover, several analyzed miRNAs have changed expression levels in the CSF and plasma of ALS patients subsequent to Lin- cells administration. Interestingly, the expression of miR-206 increased in ALS patients, while miR-378 decreased both in the CSF and plasma one month after the cells’ injection. We propose that autologous lineage-negative early hematopoietic cells injected intrathecally may be a safe and feasible source of material for transplantations to the central nervous system (CNS) environment aimed at anti-inflammatory support provision for ALS adjuvant treatment strategies. Further research is needed to evaluate whether the observed effects could significantly influence the ALS progression.

The analysis of relationship between selected sociodemografic factors and disorders of speech organs in Parkinson`s patients.

BACKGROUND: Evaluation of speech disorders in PD taking into account sociodemographic conditions is not frequent. This paper aims to establish correlations between articulation disorders in PD patients and factors such as the patients' sex, age, education and residence. METHODS: The study included 92 patients with idiopathic PD diagnosed by means of multiple neurological examinations, biochemical tests, MRI and CT scanning carried out in accordance with the United Kingdom Parkinson's Disease Society Brain Bank (UKPDSBB) criteria. A speech and language test involved the assessment of the mobility of the speech organs as well as the reflexes inside the oral cavity. Frenchay Dysarthria Assessment was applied for an objective evaluation of dysarthria. RESULTS: The study revealed the existence of significant relationship between the functionality of articulators in PD patients and their education and residence. Big city dwellers demonstrated lower incidence of disorders within speech organs, particularly those affecting mobility of the soft palate while eating. Disorders of moderate intensity were more frequently found in subjects living in villages. Subjects with a university education displayed better position of the lips at rest and better performance of both lips and the mandible while speaking. CONCLUSIONS: Abnormal functioning of the articulatory organs was observed more frequently in PD patients residing in rural areas than in those inhabiting urban areas. As for education, our cohort university graduates displayed a better position of the lips at rest and better performance of the lips and jaw during speaking than those with secondary and vocational education.

The role of brain-derived neurotrophic factor and its single nucleotide polymorphisms in stroke patients.

Stroke is the main cause of motoric and neuropsychological disability in adults. Recent advances in research into the role of the brain-derived neurotrophic factor in neuroplasticity, neuroprotection and neurogenesis might provide important information for the development of new poststroke-rehabilitation strategies. It plays a role as a mediator in motor learning and rehabilitation after stroke. Concentrations of BDNF are lower in acute ischemic-stroke patients compared to controls. Lower levels of BDNF are correlated with an increased risk of stroke, worse functional outcomes and higher mortality. BDNF signalling is dependent on the genetic variation which could affect an individual's response to recovery after stroke. Several single nucleotide polymorphisms of the BDNF gene have been studied with regard to stroke patients, but most papers analyse the rs6265 which results in a change from valine to methionine in the precursor protein. Subsequently a reduction in BDNF activity is observed. There are studies indicating the role of this polymorphism in brain plasticity, functional and morphological changes in the brain. It may affect the risk of ischemic stroke, post-stroke outcomes and the efficacy of the rehabilitation process within physical exercise and transcranial magnetic stimulation. There is a consistent trend of Met alleles' being connected with worse outcomes and prognoses after stroke. However, there is no satisfactory data confirming the importance of Met allele in stroke epidemiology and the post-stroke rehabilitation process. We present the current data on the role of BDNF and polymorphisms of the BDNF gene in stroke patients, concentrating on human studies.

Early Emergency Medical Service Calls for Stroke: Was the Long-Term Education Program Based on the Experience of West Pomerania Successful?

BACKGROUND: Our objectives are to investigate whether the percentage of early emergency calls for stroke had increased and to assess current factors determining the time of deciding to seek medical help in the event of early stroke symptoms. MATERIALS AND METHODS: We analyzed data concerning the decision to call for medical help in relation to observed stroke symptoms. Group I comprised 287 people who made the decision to call emergency medical service (EMS) in the first 10 minutes after observing stroke symptoms. Group II included 275 people who called EMS after that time. Data from the current database (2013-2014) were compared with relevant data from the period 2003-2005. RESULTS: In 2013-2014, awareness of stroke signs was 2.5 times greater than in 2003-2005. Among the groups of early and delayed EMS calls during 2003-2005 and 2013-2014, there were no significant differences in the number of people who suspected stroke. Advanced patient age, young caller age, hemiparesis, facial weakness, and the severity of neurological deficit were independent factors that correlated strongly with an early EMS call, whereas feelings of numbness and dizziness correlated significantly with delayed EMS calls. CONCLUSIONS: In the West Pomeranian community, general knowledge of stroke is not a significant factor when making appropriate decisions at the onset of stroke symptoms. The education campaign regarding the initial symptoms of stroke and the possible fatal consequences appears to have been ineffective.

Association between selected gene polymorphisms and statin metabolism, risk of ischemic stroke and cardiovascular disorders.

Statins are increasingly widely used in primary and secondary prevention of cardiovascular disorders, including ischemic stroke. The initial studies regarded mainly coronary heart disease, but recently more attention has been paid to statin use in ischemic stroke, including primary and secondary prevention as well as the acute phase treatment. Besides their main hypolipemic activity, statins have been proved to have immunomodulating properties that are called a pleiotropic effect. Drug metabolism is under genetic influence, exemplified by the single nucleotide polymorphisms (SNPs). This also applies to statins. Pharmacogenetic studies are conducted in many disorders including stroke. The aim of this study was to review selected common genetic variants in lipid or statin metabolism-related genes and indicate associations with cardiovascular disorders, especially with ischemic stroke. We present available data of SNPs in regard to the most significant and promising proteins such as cytochrome P450, ATPase superfamily, organic anion transporter family, apolipoprotein E, lipoprotein-associated phospholipase A2, lipoprotein(a), LDLR, proprotein convertase subtilisin/kexin type 9, HMGCR, and CETP. A presentation of particular SNPs may help in future studies to aim for individual and thus more effective statin therapy in stroke patients.

The emotional stress and risk of ischemic stroke.

Stroke is the second leading cause of death worldwide, and the leading cause of acquired disability in adults in most regions. There have been distinguished modifiable and non-modifiable risk factors of stroke. Among them the emotional stress was presented as a risk factor. The aim of this review was to present available data regarding the influence of acute and chronic mental stress on the risk of ischemic stroke as well as discussing the potential pathomechanisms of such relationship. There is an evident association between both acute and chronic emotional stress and risk of stroke. Several potential mechanisms are discussed to be the cause. Stress can increase the cerebrovascular disease risk by modulating symphaticomimetic activity, affecting the blood pressure reactivity, cerebral endothelium, coagulation or heart rhythm. The emotional stress seems to be still underestimated risk factor in neurological practice and research. Further studies and analyses should be provided for better understanding of this complex, not fully known epidemiological problem.

Simultaneous acute shoulder arthritis and multiple mononeuropathy in a newly diagnosed type 2 diabetes patient - First case report.

Diabetes is a common disorder that leads to the musculoskeletal symptoms such as the shoulder arthritis. The involvement of peripheral nervous system is one of the troublesome for the patients as it provokes chronic sensory symptoms, lower motor neuron involvement and autonomic symptoms. In the course of the disease there has been several types of neuropathies described. A 41-year-old male patient was admitted to the internal medicine department because of the general weakness, malaise, polydypsia and polyuria since several days. The initial blood glucose level was 780mg/dl. During the first day the continuous insulin infusion was administered. On the next day when he woke up, the severe pain in the right shoulder with limited movement, right upper extremity weakness and burning pain in the radial aspect of this extremity appeared. On examination right shoulder joint movement limitation was found with the muscle weakness and sensory symptoms in the upper limbs. The clinical picture indicated on the right shoulder arthritis and the peripheral nervous system symptoms such as the right musculocutaneous, supraspinatus, right radial nerve and left radial nerve damage. We present a first case report of simultaneous, acute involvement of the shoulder joint and multiple neuropathy in a patient with newly diagnosed type 2 diabetes, presumably in the state of ketoacidosis.

Energy Metabolism of the Brain, Including the Cooperation between Astrocytes and Neurons, Especially in the Context of Glycogen Metabolism.

Glycogen metabolism has important implications for the functioning of the brain, especially the cooperation between astrocytes and neurons. According to various research data, in a glycogen deficiency (for example during hypoglycemia) glycogen supplies are used to generate lactate, which is then transported to neighboring neurons. Likewise, during periods of intense activity of the nervous system, when the energy demand exceeds supply, astrocyte glycogen is immediately converted to lactate, some of which is transported to the neurons. Thus, glycogen from astrocytes functions as a kind of protection against hypoglycemia, ensuring preservation of neuronal function. The neuroprotective effect of lactate during hypoglycemia or cerebral ischemia has been reported in literature. This review goes on to emphasize that while neurons and astrocytes differ in metabolic profile, they interact to form a common metabolic cooperation.