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Objectives: Fingolimod is indicated for the treatment of relapsing-remitting multiple sclerosis (RRMS) patients with highly aggressive disease characterized by frequent relapses and active magnetic resonance imaging. Its efficacy has been demonstrated in three large phase III trials, used in the regulatory submissions throughout the world. Fingolimod in licensed in Europe since 2011 but with a growing number of disease-modifying drugs (DMD) becoming available for RRMS, it is important to gather real-world evidence data regarding long-term effectiveness in treated patients with MS. The aim of this study was to assess fingolimod effectiveness in a real life Polish group of RRMS patients receiving fingolimod as second line treatment., Patients and Methods: The observational study with retrospective data collection was performed at 13 sites that were asked to document eligible patients in consecutive chronological order to avoid selection bias. Demographic and clinical data from 253 adult patients with RRMS treated with fingolimod were analyzed., Results: Mean treatment time with fingolimod was 42 months. Relapses reduction during 3 years treatment period was observed (2.0 v 0.2) and majority of patients were free of relapses. Mean EDSS score was stable during the time of observation. The proportion of patients who were free from any clinical disease activity, i.e. without relapses and disability progression, was over 70%. During the first and second year of observation significant reduction of new MRI lesions was observed., Conclusion: In the Polish group of patients with RRMS treated with fingolimod, the majority of them showed freedom from relapses, disability progression and reduction of new MRI lesions. Switching from injectable immunomodulatory drugs to fingolimod is associated with fewer relapses and lower disability progression., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Diseases related to DNA polymerase gamma dysfunction comprise of heterogeneous clinical presentations with variable severity and age of onset. Molecular screening for the common POLG variants: p.Ala467Thr, p.Trp748Ser, p.Gly848Ser, and p.Tre251Ile has been conducted in a large population cohort (n = 3123) and in a clinically heterogeneous group of 1289 patients. Recessive pathogenic variants, including six novel ones were revealed in 22/26 patients. Infantile Alpers-Huttenlocher syndrome and adulthood ataxia spectrum were the most common found in our group. Distinct molecular profile identified in the Polish patients with significant predominance of p.Trp748Ser variant (50% of mutant alleles) reflected strikingly low population frequency of the three remaining variants and slightly higher p.Trp748Ser allele frequency in the general Polish population as compared to the non-Finish European population., (Copyright © 2018 Elsevier B.V. and Mitochondria Research Society. All rights reserved.)

Facioscapulohumeral muscular dystrophy cases with facial weakness before the age of 5 and signs of shoulder weakness by the age of 10 are defined as early onset. Contraction of the D4Z4 repeat on chromosome 4q35 is causally related to facioscapulohumeral muscular dystrophy type 1, and the residual size of the D4Z4 repeat shows a roughly inverse correlation with the severity of the disease. Contraction of the D4Z4 repeat on chromosome 4q35 is believed to induce a local change in chromatin structure and consequent transcriptional deregulation of 4qter genes. We present early-onset cases in the Polish population that amounted to 21% of our total population with facioscapulohumeral muscular dystrophy. More than 27% of them presented with severe phenotypes (wheelchair dependency). The residual D4Z4 repeat sizes ranged from 1 to 4 units. In addition, even within early-onset facioscapulohumeral muscular dystrophy type 1 phenotypes, some cases had uncommon features (head drop, early disabling contractures, progressive ptosis, and respiratory insufficiency and cardiomyopathy)., (© The Author(s) 2014.)

Background and Purpose: The outcome in acute stroke strongly depends on patient-related issues, as well as on the availability of human and diagnostic resources. Our aim was to evaluate safety and effectiveness of intravenous alteplase for stroke according to the time of admission to the hospital., Materials and Methods: We analyzed the data of all acute stroke patients treated with alteplase between October 2003 and December 2010, contributed to the Safe Implementation of Thrombolysis for Stroke registry from 27 Polish stroke centers. According to the time of admission we distinguished between: (1) non-working days (Friday 14:30-Monday 08:00 plus national holidays); (2) out-of-office hours (non-working days plus 14:30-08:00 during working days); and (3) night hours (time from 23:00 to 06:00). Patients admitted during regular working hours (Monday 08:00-Friday 14:30, excluding national holidays) were used as the reference., Results: Of 1330 patients, 448 (32.5%) were admitted on non-working days, 868 (65.3%) at out-of-office hours, and 105 (7.9%) during night hours. In multivariate logistic regression, none of the evaluated periods showed association with symptomatic intracranial hemorrhage, 7-day mortality, and neurological improvement ≥4 points in the National Institutes of Health Stroke Scale score at day 7. Patients admitted during night hours had lower odds (OR 0.53, 95% CI: 0.29-0.95, p=0.032) for achieving favorable outcome (modified Rankin Scale score 0-2)., Conclusions: There is no bad time for thrombolysis. Stroke centers should feel confident about the treatment outside regular working hours, irrespective of equipment and staff availability. However, it may be reasonable to pay additional attention during nighttime., (Copyright © 2014 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

Background and Purpose: The aim of this study was to test the hypothesis that polymorphisms of the paraoxonase genes PON1 and PON2 may be associated with increased risk of developing multiple sclerosis (MS) in the Polish population., Material and Methods: We studied the significance of the PON gene polymorphisms C311S, A162G, Q192R and L55M in 221 patients (including 145 women) with MS and in 661 healthy controls. In the MS population, mean Expanded Disability Status Scale score was 2.92, mean age was 36.8 years, and mean disease duration was 7.7 years. PON genotyping was determined using polymerase chain reaction and restriction enzyme digestion., Results: According to our results, the PON1 and PON2 genotypes distribution did not differ between the MS patients and the controls., Conclusions: The polymorphisms of the PON genes studied are not related to increased risk of MS in the Polish population.

Facioscapulohumeral muscular dystrophy (FSHD) is a primary muscle disorder with autosomal dominant inheritance. FSHD was mapped to chromosome 4 locus q35, but the gene is not yet known. It is characterised by progressive, often asymmetric, selective muscular weakness and great clinical variability. The aim of the study was to analyze 62 FSHD cases from 44 Polish families in which the diagnosis was confirmed by DNA analyses. FSHD diagnosis was based on the clinical findings and standardized investigations confirming primary muscular involvement (EMG, muscle biopsy). DNA analysis was based on EcoRI/BlnI restriction enzyme digestion followed by hybridization with P13E-11 molecular probe. In our material, we have found a relatively large percentage (41%) of big deletions (EcoRI/BlnI fragment of 10-15 kb [kilo bases]), which in the majority of cases (67%) was present in isolated cases. In 10 families (23%) the phenotype was assessed as severe. These are cases with the onset before the age of 10 and fast progression. "Middle sized" deletions (EcoRI/BlnI fragment of 16-29 kb) were prevalent in familial cases and present in 57% of families. "Small" deletion was found in one family (EcoRI/BlnI fragment of 30 kb). Somatic mosaicism was confirmed in one case. De novo mutations were shown in 11% of the examined families. The results of this study indicate that the bigger the deletion, the more severe the FSHD course, however there are some exceptions. A similar relationship has been shown by previous research. Molecular analyses are particularly important in atypical and sporadic cases. It is the first genetic presentation of a group of patients' with this kind of dystrophy in the Polish population.