Convulsive status epilepticus management in adults and children: Report of the Working Group of the Polish Society of Epileptology

Introduction The Working Group was established at the initiative of the General Board of the Polish Society of Epileptology (PSE) to develop an expert position on the treatment of convulsive status epilepticus (SE) in adults and children in Poland. Generalized convulsive SE is the most common form and also represents the greatest threat to life, highlighting the importance of the choice of appropriate therapeutic treatment. Aim of guideline We present the therapeutic options separately for treatment during the early preclinical (>5–30min), established (30–60min), and refractory (>60min) SE phases. This division is based on time and response to AEDs, and indicates a practical approach based on pathophysiological data. Results Benzodiazepines (BZD) are the first-line drugs. In cases of ineffective first-line treatment and persistence of the seizure, the use of second-line treatment: phenytoin, valproic acid or phenobarbital is required. SE that persists after the administration of benzodiazepines and phenytoin or another second-line AED at appropriate doses is defined as refractory and drug resistant and requires treatment in the intensive care unit (ICU). EEG monitoring is essential during therapy at this stage. Anesthesia is typically continued for an initial period of 24h followed by a slow reversal and is re-established if seizures recur. Anesthesia is usually administered either to the level of the “burst suppression pattern” or to obtain the “EEG suppression” pattern. Conclusions Experts agree that close and early cooperation with a neurologist and anesthetist aiming to reduce the risk of pharmacoresistant cases is an extremely important factor in the treatment of patients with SE. This report has educational, practical and organizational aspects, outlining a standard plan for SE management in Poland that will improve therapeutic efficacy

Use of statins and the risk of dementia and mild cognitive impairment: A systematic review and meta-analysis

We conducted a systematic review and meta-analysis to investigate whether the use of statins could be associated with the risk of all-caused dementia, Alzheimer’s disease (AD), vascular dementia (VaD), and mild cognitive impairment (MCI). Major electronic databases were searched until December 27th, 2017 for studies investigating use of statins and incident cognitive decline in adults. Random-effects meta-analyses calculating relative risks (RRs) were conducted to synthesize effect sizes of individual studies. Twenty-five studies met eligibility criteria. Use of statins was significantly associated with a reduced risk of all-caused dementia (k = 16 studies, adjusted RR (aRR) = 0.849, 95% CI = 0.787–0.916, p = 0.000), AD (k = 14, aRR = 0.719, 95% CI = 0.576–0.899, p = 0.004), and MCI (k = 6, aRR = 0.737, 95% CI = 0.556–0.976, p = 0.033), but no meaningful effects on incident VaD (k = 3, aRR = 1.012, 95% CI = 0.620–1.652, p = 0.961). Subgroup analysis suggested that hydrophilic statins were associated with reduced risk of all-caused dementia (aRR = 0.877; CI = 0.818–0.940; p = 0.000) and possibly lower AD risk (aRR = 0.619; CI = 0.383–1.000; p = 0.050). Lipophilic statins were associated with reduced risk of AD (aRR = 0.639; CI = 0.449–0.908; p = 0.013) but not all-caused dementia (aRR = 0.738; CI = 0.475–1.146; p = 0.176). In conclusion, our meta-analysis suggests that the use of statins may reduce the risk of all-type dementia, AD, and MCI, but not of incident VaD

The V471A polymorphism in autophagy-related gene ATG7 modifies age at onset specifically in Italian Huntington disease patients

The cause of Huntington disease (HD) is a polyglutamine repeat expansion of more than 36 units in the huntingtin protein, which is inversely correlated with the age at onset of the disease. However, additional genetic factors are believed to modify the course and the age at onset of HD. Recently, we identified the V471A polymorphism in the autophagy-related gene ATG7, a key component of the autophagy pathway that plays an important role in HD pathogenesis, to be associated with the age at onset in a large group of European Huntington disease patients. To confirm this association in a second independent patient cohort, we analysed the ATG7 V471A polymorphism in additional 1,464 European HD patients of the “REGISTRY” cohort from the European Huntington Disease Network (EHDN). In the entire REGISTRY cohort we could not confirm a modifying effect of the ATG7 V471A polymorphism. However, analysing a modifying effect of ATG7 in these REGISTRY patients and in patients of our previous HD cohort according to their ethnic origin, we identified a significant effect of the ATG7 V471A polymorphism on the HD age at onset only in the Italian population (327 patients). In these Italian patients, the polymorphism is associated with a 6-years earlier disease onset and thus seems to have an aggravating effect. We could specify the role of ATG7 as a genetic modifier for HD particularly in the Italian population. This result affirms the modifying influence of the autophagic pathway on the course of HD, but also suggests population-specific modifying mechanisms in HD pathogenesis

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Ischemic Strokes Are More Severe in Poland Than in the United States

Case Fatality Rates for Stroke Were Ascertained Prospectively in Two Regional Catchment Hospitals in Poland and 36 Teaching Hospitals in the US University Hospital Consortium. Case Fatality Rates in Poland (23.9%) Were Higher Than in the United States (7.5%). Angina, Atrial Fibrillation, and Congestive Heart Failure Were More Frequent in Polish Stroke Patients (40%, 26%, and 25%, Respectively) Than in US Patients (17%, 12%, and 10%). Stroke Severity as Indicated by Higher Frequencies of Hemiplegia, Disordered Consciousness, Dysphagia, and Aphasia Was Greater in Poland (19%, 39%, 28%, and 42%, Respectively) Than the United States (11%, 13%, 14%, and 26%)

Self-reported quality of life in multiple sclerosis patients: preliminary results based on the Polish MS Registry

Waldemar Brola,1 Piotr Sobolewski,2 Małgorzata Fudala,1 Stanisław Flaga,3 Konrad Jantarski,4 Danuta Ryglewicz,5 Andrzej Potemkowski6 1Department of Neurology, Specialist Hospital, Końskie, 2Department of Neurology, Holy Spirit Specialist Hospital, Sandomierz, 3AGH University of Science and Technology, Krakow, 4Swietokrzyski Regional Branch of the Polish National Health Fund (NFZ), Kielce, 5First Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, 6Department of Psychology, University of Szczecin, Szczecin, Poland Background: The aim of the study was to analyze selected clinical and sociodemographic factors and their effects on the quality of life (QoL) of multiple sclerosis (MS) patients registered in the Polish MS Registry.Methods: This was a cross-sectional observational study performed in Poland. Data on personal and disease-specific factors were collected between January 1, 2011, and December 31, 2015, via the web portal of the Polish MS Registry. All patients were assessed by a physician and asked to complete the Polish language versions of the following self-evaluation questionnaires: EuroQol 5-Dimensions, EuroQoL Visual Analog Scale, and Multiple Sclerosis Impact Scale. Univariate analysis and logistic regression were performed to determine the factors associated with QoL.Results: The study included 2,385 patients (female/male ratio 2.3:1) with clinically confirmed MS (mean age 37.8±9.2 years). Average EuroQol 5-Dimensions index was 0.72±0.24, and the mean EuroQoL Visual Analog Scale score was 64.2±22.8. The average Multiple Sclerosis Impact Scale score was 84.6±11.2 (62.2±18.4 for physical condition and 23.8±7.2 for mental condition). Lower QoL scores were significantly associated with higher level of disability (odds ratio [OR], 0.932; 95% confidence interval [CI], 0.876–0.984; P=0.001), age >40 years (OR, 1.042; 95% CI, 0.924–1.158; P=0.012), longer disease duration (OR, 0.482; 95% CI, 0.224–0.998; P=0.042), and lack of disease modifying therapies (OR, 0.024; 95% CI, 0.160–0.835; P=0.024). No significant associations were found between QoL, sex, type of MS course, patient’s education, and marital status.Conclusion: The Polish MS Registry is the first national registry for long-term observation that allows for self-evaluation of the QoL. QoL of Polish patients with MS is significantly lower compared with the rest of the population. The parameter is mainly affected by the level of disability, duration of the disease, and limited access to immunomodulatory therapy. Keywords: multiple sclerosis, patient-reported outcomes, quality of life, Polan

A comparison of the costs and survival of hospital-admitted stroke patients across Europe

Background and Purpose: Policy makers require evidence on the costs and outcomes of different ways of organizing stroke care. This study compared the costs and survival of different ways of providing stroke care. Methods: Hospitalized stroke patients from 13 European centers were included, with demographic, case-mix, and resource use variables measured for each patient. Unit costs were collected and converted into US dollars using the purchasing power parity (PPP) index. Cox and linear regression analyses were used to compare survival and costs between the centers adjusting for case mix. Results: A total of 1847 patients were included in the study. After case-mix adjustment, the mean predicted costs ranged from $466 [95$8512 [7696 to 9328] in Copenhagen (Denmark), which reflected differences in unit costs, and resource use. The mean length of hospitalization ranged from 8.3 days in Menorca (Spain) to 36.8 days in Turku B (Finland). In the 3 Finnish centers at least 80% of patients were admitted to wards providing organized stroke care, which was not provided at the centers in Almada (Portugal), Menorca, or Riga. Patients in Turku A and Turku B were less likely to die than those in Riga, Warsaw (Poland), or Menorca. The adjusted hazard ratios were 0.18 [0.10 to 0.32] for Turku A, 0.18 [0.10 to 0.32] for Turku B, 0.68 [0.48 to 0.96] for Warsaw, and 0.56 [0.33 to 0.96] for Menorca, all compared with Riga. Conclusions: The cost of stroke care varies across Europe because of differences in unit costs, and resource use. Further research is needed to assess which ways of organizing stroke care are the most cost-effective