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.

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 .

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 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.

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.

Potential role of statins in the intracerebral hemorrhage and subarachnoid hemorrhage.

Statins are used in primary and secondary prevention of cardiovascular episodes. Most of recent studies regard ischemic stroke. There are more emerging results of studies suggesting usefulness of these drugs in the other types of stroke e.g. intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH). Searching for new methods of treatment is important, because both ICH and SAH lead to poor prognosis and severe psychomotor disability. The unquestionable role of inflammatory factors in the pathogenesis of these disorders justifies considering statin treatment. Previous results are contradictory, thus in present study we review results of studies and try to explain the potential pathomechanism of statin use in hemorrhagic strokes.

Articulation disorders and duration, severity and L-dopa dosage in idiopathic Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is one of the most common diseases of the central nervous system (CNS). It is frequently heralded by speech disturbances, which are one of its first symptoms. AIM: The aim of this paper is to share our own experience concerning the correlation between the severity of speech disorders and the PD duration, its severity and the intake of L-dopa. MATERIAL AND METHODS: The research included 93 patients with idiopathic PD, aged 26-86 years (mean age 65.1 years). Participants were examined neurologically according to the Unified Parkinson's Disease Rating Scale (UPDRS) and the Hoehn and Yahr Scale. They were also assessed by Frenchay Dysarthria Assessment. RESULTS: Considerable and severe disorders were concurrent with impairments in the mobility of the tongue, lips, the jaw as well as the pitch and loudness of the voice. The strongest correlation but at a moderate level was found to exist between the severity of labial impairment, voice loudness and the length of the disease. There was also a positive correlation between lip movement while the motions were being diversified, lip arrangement while speaking and the intake of L-dopa. CONCLUSIONS: As PD progresses a significant decline in vocal articulation can be observed, which is due to reduced mobility within the lips and the jaw. Exacerbation of articulation disorders resulting from progression of the disease does not materially influence the UPDRSS scores. L-dopa has been found to positively affect the mobility of the lips while the patient is speaking and their arrangement at rest.

Atrial fibrillation and stroke - Coexistence and attitude to preventive therapy on the basis of Szczecin and Szczecin region patients.

Atrial fibrillation (AF) is an independent factor increasing the risk of an ischemic stroke (IS) fivefold. The objective of the study was to evaluate the frequency of coexistence of non-valvular AF and IS during the acute stroke and to analyze the attitude of AF patients to treatment. The study included 3712 successive patients presenting either an IS or a transient ischemic attack. The analysis revealed a significant increase in the rate of patients with AF and IS in the years 2010-2013 (31.9%) compared with 2002-2005 (20.2%). A rise in the proportion of AF and IS patients was recorded over the course of consecutive years in group II. The proportion of newly detected AF cases during hospital stay differed significantly between the groups (16.9% vs. 31.9%). Group I and II patients differed essentially with regards to hypertension incidence and female rates. Antiplatelet medications or OACs were taken by a significantly greater number of AF patients in group II. Low number of therapeutic levels of INR was recorded in both groups. IS and AF coexist more frequently than indicated by previous assessments and demographic data from other countries. Increase in the number of IS and AF patients may result from higher detectability of AF and older age of patients affected with stroke, women in particular. Despite a well grounded knowledge about the benefits of OACs use in the prophylaxis of thrombotic-embolic events in AF patients, they are rarely used. A surprisingly low proportion of patients taking OACs reaches a therapeutic INR level.

Risk factors of stroke and -717A>G (rs2794521) CRP gene polymorphism among stroke patients in West Pomerania province of Poland.

BACKGROUND AND PURPOSE: Some of the risk factors of ischaemic stroke influence the development of atherosclerosis, which is a significant cause of vascular incidents. An inflammatory component plays a role in pathogenesis of both atherosclerosis and atrial fibrillation, the most important risk factor of embolic strokes. C-reactive protein (CRP) concentration in blood reflects the inflammatory process. Concentration of this protein depends on the CRP gene polymorphism. The aim of the study was to assess the relationship between selected risk factors of stroke and variant of -717A>G (rs2794521) CRP gene polymorphism in population of West Pomerania Province of Poland. MATERIALS AND METHODS: There were 125 consecutive patients with ischaemic stroke analysed, who met the inclusion and exclusion criteria. In all patients, -717A>G CRP gene polymorphism was genotyped and analysed in relation to selected stroke risk factors. RESULTS: Prevalence of type 2 diabetes was lower in patients with AA genotype of -717A>G CRP gene polymorphism than in patients with other alleles (p=0.017). Subjects with GG genotype had significantly higher concentration of CRP comparing to AG genotype (p=0.023). No correlation was found between -717A>G CRP gene polymorphism and the lipid profile and other selected risk factors of stroke. CONCLUSIONS: In patients with ischaemic stroke in West Pomerania Province, the GG genotype of -717A>G CRP gene polymorphism is associated with significantly higher CRP concentration in relation to AG genotype. Patients with AA genotype may be characterised by lower prevalence of type 2 diabetes.

The impact of MRI white matter hyperintensities on dementia in Parkinson's disease in relation to the homocysteine level and other vascular risk factors.

BACKGROUND: The role of white matter hyperintensities (WMH) and homocysteine (Hcy) and other vascular risk factors in the pathogenesis of Parkinson's disease (PD) dementia (PDD) remains unclear. OBJECTIVE: The aim of the study was to assess the impact of WMH, Hcy and other biochemical and vascular risk factors on PDD. METHODS: A total of 192 patients with PD and 184 age- and sex-matched healthy controls were included. A semistructured interview was used to assess demographic and clinical variables with respect to vascular risk factors (arterial hypertension, diabetes mellitus, atrial fibrillation, ischemic heart disease, obliterative atherosclerosis, hypercholesterolemia, smoking, alcohol intake). Unified Parkinson's Disease Rating Scale score, Hoehn-Yahr staging and the Schwab-England activities of daily living scale were used to assess motor abilities and activities of daily living. A complex neuropsychological examination with a battery of tests was used to classify patients into a group with dementia (PDD) and a group without dementia (PD). Neuroradiological examination of MRI scans included visual rating scales for WMH (according to the Wahlund and Erkinjunntti rating scales) and the Scheltens scale for hippocampal atrophy. Blood samples for Hcy, folate, vitamin B12, fibrinogen, lipids, glucose, creatinine, transaminases and thyroid stimulating hormone (TSH) were examined. RESULTS: Among all patients, 57 (29.7%) fulfilled the diagnostic criteria for dementia. Significantly higher Hcy plasma levels were noted in PD and PDD groups compared to controls (p < 0.05) and in PDD when compared to PD (p < 0.05). According to multivariate regression analysis, WMH (Erkinjuntti scale), high Hcy, low vitamin B12 and folate plasma levels were independent risk factors for PDD. Vascular risk factors did not play any role in the pathogenesis of PDD and WMH. CONCLUSIONS: WMH along with Hcy, folate and vitamin B12 may impact cognition in PD. Therapy with vitamin B12, folate and catechol-O-methyltransferase inhibitors may play a potential protective role against PDD.

Association of COMT, MTHFR, and SLC19A1(RFC-1) polymorphisms with homocysteine blood levels and cognitive impairment in Parkinson's disease.

INTRODUCTION: Elevated plasma homocysteine (Hcy) concentration is an independent risk factor for cardiovascular disease, and its involvement in endothelial cell dysfunction is well established. However, the role of Hcy and folate in the pathogenesis of Parkinson's disease (PD) remains controversial. OBJECTIVES: The study was aimed at evaluating the relationships between Hcy, vitamin B12, and folic acid levels in the blood and cognitive status in PD patients with the genetic polymorphisms of MTHFR (rs1801133: C>T-677C>T, rs1801131: A>C-1298A>C), COMT (rs4680: A>G-Val158Met, rs6269: A>G, rs4633: C>T, rs4818: C>G), or SLC19A1 (rs1051266: G>A-80G>A). METHODS: A total of 502 participants (248 with PD and 254 age-matched and sex-matched controls) were included in the study. The Unified Parkinson's Disease Rating Scale score, Hoehn-Yahr staging, and the Schwab-England scale were used to assess motor abilities and activity during daily life. Complex psychological examination with a battery of tests was used to classify patients into groups with (PDD) and without (nPDD) dementia. Blood samples were examined for Hcy, vitamin B12, and folic acid levels, as well as polymorphisms in genes related to Hcy metabolism, such as COMT, MTHFR, and SLC19A1(RFC-1). RESULTS: The frequency of homozygous COMT rs4680G and rs4633C allele carriers was significantly decreased in PD patients in comparison with the controls (P=0.015; odds ratio=0.60; 95% confidence interval 0.41-0.90 and P=0.020; odds ratio=0.619; 95% confidence interval 0.42-0.92, respectively). No significant differences in the distribution of MTHFR 677C>T, 1298A>C, and SLC19A1 80G>A alleles and genotypes between PD patients and the controls were found. Hcy levels were significantly increased in PD patients (18±7.8 µmol/l) as compared with the controls (14.0±9.6 µmol/l, P=10(-8)) and were significantly associated with the MTHFR 677C>T polymorphism both in PD patients and controls, in which T allele carriers were characterized by markedly elevated Hcy plasma concentrations. No association was observed between Hcy plasma level and COMT and SLC19A polymorphisms. The results of multivariate logistic regression analysis revealed age (P=0.0003) and Hcy plasma levels (P=0.07) as independent risk factors predisposing individuals to PD dementia. The studied polymorphisms were not associated with cognitive status in PD patients. CONCLUSION: The genetic factors studied were not associated with cognitive status in PD patients. Only age and Hcy plasma levels were found to be independent risk factors predisposing individuals to PD dementia. However, COMT: rs4680: A>G and rs4633: C>T polymorphisms were found to significantly affect PD risk, and the MTHFR 677C>T polymorphism helped determine plasma Hcy concentrations.

[The role of neurotrophic factors in regeneration of the nervous system]. / Rola czynników neurotroficznych w procesach regeneracji ukladu nerwowego.

Neurotrophic factors regulate survival, development, and function of nervous tissue. They act via two different classes of receptors and activation of various signaling pathways in the target cells. Illumination of their physiological role in the maintenance of central nervous system homeostasis as well as regeneration of damaged tissue have ignited expectations to heal neurodegenerative diseases, including amyotrophic late-ral sclerosis and Parkinson disease. Advances in pharmaco-therapy, gene therapy, and stem cell biology have enabled development of novel therapies with application of regenerating cell transplantation. In the foreseeable future, it may lead to the establishment of safe and effective ways of treatment of these severe and currently incurable diseases.

Atrial fibrillation risk factors in patients with ischemic stroke.

INTRODUCTION: Atrial fibrillation (AF) is the most common heart arrhythmia. The condition is known to increase the risk of ischemic stroke (IS). Classical risk factors for the development of AF include advanced age, hypertension, diabetes mellitus, coronary heart disease and lipid metabolism disorders. Importantly, these are also recognized risk factors for ischemic stroke. Therefore, the purpose of this study was to investigate AF risk factors in patients with IS. MATERIAL AND METHODS: This is single-centre retrospective study which included 696 patients with acute ischemic stroke and nonvalvular atrial fibrillation and 1678 patients with acute ischemic stroke without atrial fibrillation. RESULTS: In this study we found - based on a univariable and multivariable logistic regression model - that compared to the patients with IS without AF, the group of patients which suffered from IS with nonvalvular atrial fibrillation (NVAF) had a higher proportion of patients who smoked cigarettes (OR = 15.742, p < 0.01; OR = 41.1, p < 0.01), had hypertension (OR = 5.161, p < 0.01; OR = 5.666, p < 0.01), history of previous stroke (OR = 3.951, p < 0.01; OR = 4.792, p < 0.01), dyslipidemia (OR = 2.312, p < 0.01; OR = 1.592, p < 0.01), coronary heart disease (OR = 2.306, p < 0.01; OR = 1.988, p < 0.01), a greater proportion of female patients (OR = 1.717, p < 0.01; OR = 2.095, p < 0.01), higher incidence of diabetes mellitus (OR = 1.341, p < 0.01; OR = 1.261, p = 0.106) and more patients in old age (OR = 1.084, p < 0.01; OR = 1.101, p < 0.01). CONCLUSIONS: Our study demonstrates a need for thorough and systematic monitoring of post-ischemic stroke patients in whom AF has not been detected and who display other important risk factors. Regardless of the stroke, these factors may be responsible for development of AF.