Background: Endothelial Progenitor Cells (EPCs) are important players in neovascularization, mobilized through signalling by Angiogenic Growth Factors (AGFs) such as Vascular Endothelial Growth Factor (VEGF) and fibroblast growth factor (FGF). In vitro, inflammatory parameters impair the function and influence of EPCs on AGFs. However, this connection is not clear in vivo. To understand the mechanisms of augmented arteriogenesis and angiogenesis in acute ischemic stroke (AIS) patients, we investigated whether circulating stem cells (CD133+), early endothelial progenitor cells (CD133+/VEGFR2+), and endothelial cells (ECs; CD34¯/CD133¯/VEGFR2+) were increasingly mobilized during AIS, and whether there were correlations between EPC levels, growth factor levels and inflammatory parameters.Methods: Data on demographics, classical vascular risk factors, neurological deficit information (assessed using the National Institutes of Health Stroke Scale), and treatment were collected from 43 consecutive AIS patients (group I). Risk factor control patients (group II) included 22 nonstroke subjects matched by age, gender, and traditional vascular risk factors. EPCs were measured by flow cytometry and the populations of circulating stem cells (CD133+), early EPCs (CD133+/VEGFR2+), and ECs (CD34¯/CD133¯/VEGFR2+) were analysed. Correlations between EPC levels and VEGF and FGF vascular growth factor levels as well as the influence of inflammatory parameters on EPCs and AGFs were assessed.Results: Patient ages ranged from 54 to 92 years (mean age 75.2 ± 11.3 years). The number of circulating CD34¯/CD133¯/VEGF-R2+ cells was significantly higher in AIS patients than in control patients (p < 0.05). VEGF plasma levels were also significantly higher in AIS patients compared to control patients on day 7 (p < 0.05). FGF plasma levels in patients with AIS were significantly higher than those in the control group on day 3 (p < 0.05). There were no correlations between increased VEGF and FGF levels and the number of CD133+, CD133+/VEGFR2+, or CD34¯/CD133¯/VEGFR2+ cells. Leukocyte levels, FGF plasma levels, and the number of early EPCs were negatively correlated on day 3. High sensitivity C-reactive protein levels and the number of CD133+ and CD133+/VEGFR2+ cells were negatively correlated on day 7. In addition, there was a negative correlation between fibrinogen levels and FGF plasma levels as well as the number of early EPCs (CD133+/VEGFR2+).Conclusion: AIS patients exhibited increased numbers of early EPCs (CD133+/VEGFR2+) and AGF (VEGF and FGF) levels. A negative correlation between inflammatory parameters and AGFs and EPCs indicated the unfavourable influence of inflammatory factors on EPC differentiation and survival. Moreover, these correlations represented an important mechanism linking inflammation to vascular disease.

Epilepsy is a common neurological disorder, with approximately one-third of patients experiencing drug-resistant epilepsy (DRE), which imposes significant clinical, social, and economic burdens. Cenobamate, a novel antiseizure medication (ASM), was included to the Polish therapeutic framework in March 2023. This retrospective, multicenter study was conducted at 19 centers. Medical records of adult patients with DRE treated with cenobamate for at least six months were reviewed. Collected data included demographic characteristics, seizure frequency, treatment regimens, and adverse events (AEs). Descriptive statistical methods were employed to assess outcomes, with the primary efficacy endpoint of ≥50 % reduction in seizure frequency. The study cohort consisted of 475 patients with a median age of 37 years. Treatment with cenobamate (median maximal daily dose, 250 mg) resulted in a ≥ 50 % reduction in seizure frequency in 61.9 % of patients, with 16.5 % achieving seizure freedom during the final three months of observation, with better responses when the treatment was initiated earlier. The burden of polytherapy decreased, as 69.7 % of patients reduced or discontinued concomitant ASMs. Adverse events were reported in 48.8 % of patients, most commonly somnolence and dizziness, with no cases of severe dermatological reactions. Discontinuation of cenobamate occurred in 12 % of patients. Cenobamate demonstrated notable efficacy in patients with treatment-resistant epilepsy, and its early initiation may improve outcomes. Treatment has a large potential for significant simplification of treatment regimens. Adverse events were manageable. Cenobamate is a highly effective and well-tolerated ASM for patients with DRE, offering significant clinical benefits, including improved seizure control and reduced polytherapy.

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.

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.

Introduction Statins are widely used in stroke patients. The AHA/ASA guidelines recommend aggressive statin therapy in atherosclerotic stroke patients. Their beneficial effects are due to both their hypolipemic and pleiotropic properties. The aim of this study was to establish potential...

Background: Endothelial Progenitor Cells (EPCs) have been suggested to be a therapeutic option in Acute Ischemic Stroke (AIS). Statins modulate endothelial function and preserve blood flow to tissue exposed to an ischemic insult. We tested the hypothesis that statins therapy might augment circulating EPCs in patients with AIS. Methods: Demographic data, classical vascular risk factors, treatment and National Institutes of Health Stroke Scale data were prospectively collected from 43 consecutive AIS patients (group I), comprising – 30 treated with statins (group Statin(+)) and 13 untreated (group Statin (-)). Risk factor controls (group II) included 22 subjects matched by age, gender, and traditional vascular risk factors. EPCs were measured by flow cytometry – and the populations of circulating stem cells (CD133+), early EPCs (CD133+/VEGFR2+) and ECs CD34/CD133/VEGFR2+ cells were analyzed. Results: Patients ages ranged from 54 to 92 years (mean age 75.2 ± 11.3 years). The number of CD34/CD133/VEGF-R2+ cells was significantly lower in group I than II (p<0.05). In group Statin(+) neurological deficit on the 1st, 3rd and 7th day was significantly lower in comparison Statin(-) (p 50% or complete recovery” and less frequent death in the statin-treated group. The number of early EPCs and ECs was significantly higher in the treated group on the day 3rd (p < 0.05). Conclusions: Statins treatment is likely to have a positive effect on spontaneous CD133+/ VEGFR2+ and CD34/CD133/VEGFR2+ cell mobilization triggered by a stroke.