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Introduction: Although stroke patients in Slovakia had been treated according to European recommendations, no network of primary and comprehensive stroke centers had been officially established; the ESO recommended quality parameters had not been fulfilled. Therefore, the Slovak Stroke Society decided to change the stroke management concept and introduced mandatory evaluation of quality parameters. This article focuses on key success factors of the change in stroke management in Slovakia and presents the 5-year results and perspectives for the future. Material and methods: We processed data from the stroke register at the National Health Information Center, which is mandatory in Slovakia for all hospitals designated as primary and secondary stroke care centers. Results: Since 2016, we have started to change stroke management. New National Guideline for Stroke Care was prepared in 2017 and published in 2018 as a Recommendation of the Ministry of Health of the Slovak Republic. The recommendation included pre-hospital as well as in-hospital stroke care, a network of primary stroke centers (hospitals administering intravenous thrombolysis – 37), and secondary stroke centers (hospitals treating with intravenous thrombolysis + endovascular treatment (ET) – 6). A stroke priority was instituted, having equally high priority as myocardial infarction. More efficient in-hospital workflow and pre-hospital patient triage shortened the time to treatment. Prenotification became mandatory in all hospitals. Non-contrast CT, and CT angiography is mandatory in all hospitals. In patients with suspected proximal large-vessel occlusion the EMS stays at the CT facility in primary stroke centers until the CT angiography is finished. If LVO is confirmed, the patient is transported to an EVT secondary stroke center by the same EMS. From 2019 all secondary stroke centers offer endovascular thrombectomy in a 24/7/365 system. We consider the introduction of quality control one of the most critical steps in stroke management. The result of these activities is 25.2% of patients treated with IVT and 10.2% by endovascular treatment, and median DNT 30 min. Number of patients screened for dysphagia increased from 26.4% in 2019 to 85.9% in 2020. In the most of the hospitals the proportion of ischemic stroke patients discharged with antiplatelets and in case of AF with anticoagulants was >85%. Discussion: Our results indicate that it is possible to change stroke management at a single hospital and national level. For continuous and further improvement, regular quality monitoring is necessary; therefore, the results of stroke hospital management are presented regularly once a year at national and international level. Collaboration with the “Second for Life” patient organization is very important for the “time is brain” campaign in Slovakia. Conclusion: Due to the change in stroke management over the last 5 years, we have reduced the time for acute stroke treatment and improved the proportion of patients with acute treatment, and in this area, we have achieved and exceeded the goals of the Stroke Action Plan for Europe for 2018–2030. Nevertheless, we still have many insufficiencies in stroke rehabilitation and post-stroke nursing that need to be addressed.

Rationale: Direct oral anticoagulants (DOAC) are highly effective in preventing ischaemic strokes in people with atrial fibrillation (AF). However, it is unclear how soon they should be started after acute ischaemic stroke (AIS). Early initiation may reduce early risk of recurrence but might increase the risk of haemorrhagic complications. Aim: To estimate the safety and efficacy of early initiation of DOACs compared to late guideline-based initiation in people with AIS related to AF. Methods and design: An international, multicentre, randomised (1:1) controlled, two-arm, open, assessor-blinded trial is being conducted. Early treatment is defined as DOAC initiation within 48 h of a minor or moderate stroke, or at day 6–7 following major stroke. Late treatment is defined as DOAC initiation after day 3–4 following minor stroke, after day 6–7 following moderate stroke and after day 12–14 following major stroke. Severity of stroke is defined according to imaging assessment of infarct size. Sample size: ELAN will randomise 2000 participants 1:1 to early versus late initiation of DOACs. This assumes a risk difference of 0.5% favouring the early arm, allowing an upper limit of the 95% confidence interval up to 1.5% based on the Miettinen & Nurminen formula. Outcomes: The primary outcome is a composite of symptomatic intracranial haemorrhage, major extracranial bleeding, recurrent ischaemic stroke, systemic embolism or vascular death at 30 ± 3 days after randomisation. Secondary outcomes include the individual components of the primary outcome at 30 ± 3 and 90 ± 7 days and functional status at 90 ± 7 days. Discussion: ELAN will estimate whether there is a clinically important difference in safety and efficacy outcomes following early anticoagulation with a DOAC compared to late guideline-based treatment in neuroimaging-selected people with an AIS due to AF.

Aim. The aim of our study was to evaluate the results of CEA and CAS in patients with carotid artery stenosis, and their effect on long-term mortality and morbidity, as well as to identify predictors of long-term mortality in a single-centre observational study. Clinical rationale. While data on short-term morbidity and mortality after carotid endarterectomy (CEA) and carotid stenting (CAS) is robust, there is only a limited amount of literature on long-term mortality and its predictors five years-plus post these procedures. Material and methods. Consecutive patients with symptomatic and asymptomatic internal carotid artery stenosis treated with CEA or CAS in a single centre in eastern Slovakia between 2012 and 2014 were included. We recorded basic sociodemographic data, the presence of co-morbidities and periprocedural complications. Clinical and sonographic follow-up was performed three and 12 months after the procedures. Patient survival data and any stroke data was obtained at the end of a six-year follow-up. Results. We included 259 patients after CEA (mean age 67.4 ± 8.5, 64.5% men) and 321 after CAS (mean age 66.9 ± 8.4, 73.5% men). We did not identify a statistically significant difference in short-term or long-term mortality, survival times, or the presence of short-term or long-term complications between the CEA and CAS groups. Predictors of long-term mortality included age and diabetes mellitus in both cohorts. Repeated interventions were related to increased mortality only in the CAS cohort. Conclusions. The results of our study show that long-term mortality does not differ between CEA and CAS.

Background: The research is focused on sensitive biomarkers in multiple sclerosis (MS). Objective: The aim of the study was to assess the relationship between plasma neurofilament light chain (pNfL) and disease activity as defined by the concept NEDA (no evident disease activity), including brain volumetry, in a cohort of MS patients treated with disease-modifying treatment (DMT). Methods: Levels of pNfL (Single Molecule Array (SIMOA) technology) were examined in 95 RRMS (relapsing-remitting multiple sclerosis) patients and analyzed in relationship to NEDA-3 status and NEDA-BVL (brain volume loss; NEDA-3 extended by brain volumetry) during the last 12 months. The statistical model was developed using logistic regression analysis, including the independent variables: demographic, clinical, and magnetic resonance imaging (MRI) data. Dependent variables were NEDA-3 and NEDA-BVL status. Results: The mean age of the study participants ( n = 95, 62% females) was 37.85 years (standard deviation (SD) = 9.62) and the median disability score was 3.5 (2.5–4.1). Receiver operating characteristics (ROC) analysis showed that pNfL predicts NEDA-3 (the sensitivity and specificity of the model were 92% and 78%, respectively, p Conclusion: The results show that pNfL levels are a useful biomarker of disease activity determined by NEDA-BVL status, including brain MRI-volumetry in patients with RRMS.

Introduction: There is a need for blood biomarkers of disease activity in multiple sclerosis (MS). The aim of the study was to assess the relationship between plasma neurofilament light chain (pNfL) and disease activity as defined by the concept three-domain no evident disease activity (NEDA-3). Methods: Levels of pNfL (SIMOA) were examined in 159 MS patients and analyzed in relationship to NEDA-3 status (absence of relapse, disability score worsening, and brain magnetic resonance activity) during the last 12 months. The accuracy of the proposed model was evaluated by calculating the area under the receiver operating characteristics (ROC) curve. From the pNfL cutoff, we evaluated the NEDA-NfL status (no relapse, no Expanded Disability Status Scale [EDSS] worsening, and pNfL below the cutoff value). Results: Levels of pNfL were significantly higher in MS patients than in healthy controls (p p < 0.001). ROC analysis showed that pNfL predicts NEDA-3 status (sensitivity and specificity were 80.5 and 72.7%, respectively, p < 0.001), and NEDA-NfL predicts NEDA-3 status (sensitivity and specificity were 97.1 and 82.9%, respectively, p < 0.001). Conclusion: The results show that pNfL levels are a useful biomarker of disease activity determined by NEDA status in patients with MS and could be an alternative to brain magnetic resonance investigation.

BACKGROUND AND PURPOSE: A few studies using data from regional databases have recently pointed to a decreased number of patients with stroke. The aim of the present study was to describe country-level data (the number of patients with stroke, the proportion of patients with acute stroke and transient ischemic attack (TIA), the proportion of patients treated with intravenous thrombolysis [IVT] or mechanical thrombectomy [MT], the door-to-needle times [DNT], and the onset-to-needle time [ONT]) during the COVID-19 pandemic in Slovakia. METHODS: The study examined data from the stroke register at the National Health Information Centre. Data from three time periods (March to April 2020; March to April 2019; January to February 2020) were compared using an independent samples t-test and the Wilcoxon-Mann-Whitney two-sample rank-sum test. RESULTS: The number of stroke patients admitted to hospitals in Slovakia during the COVID-19 period showed a decrease (1673 vs. 2328 in period 2 and 2155 in period 3). The proportions of patients with TIA remained the same in periods 1 and 2 (9.7% vs. 11.7%) and in periods 1 and 3 (9.7 vs. 11.8%). The percentage of patients treated with IVT during the pandemic (22.4%) did not differ from period 2 (20.0%) or period 3 (21.4%). No difference was found in the rate of MT between the COVID-19 period (10.2%) and the same period in 2019 (10.7%) and in January to February 2020 (13.1%). The median DNT remained unchanged in periods 1 (30 min), 2 (35 min) and 3 (30 min), and no differences were found in median ONT in periods 1 (130 min), 2 (130 min) and 3 (140 min). CONCLUSION: We found a decreased number of stroke patients during the COVID-19 outbreak in Slovakia, but no evidence of a change in the quality of acute stroke care.

Objectives Non-motor symptoms (NMS) are commonly present along with motor impairment in patients with cervical dystonia (CD) and have a significant impact on health-related quality of life (HRQoL). However, the prevalence of NMS and their association with dystonia are still unclear. The aim of our study was to assess the prevalence of depression, anxiety, fatigue, apathy, pain, sleep problems, and excessive daytime sleepiness (EDS) in CD using different evaluation approaches and to explore their association with HRQoL relative to that of motor symptoms.Materials and Methods We enrolled 102 Slovak patients with CD. The severity of both motor and non-motor symptoms was assessed using validated scales. HRQoL was determined by the 36-item Short Form Health Survey (SF-36). Association of NMS with poor HRQoL was assessed using multiple regressions.Results The most frequent NMS in our sample were sleep impairment (67.3%), anxiety (65.5%), general and physical fatigue (57.5% and 52.9%, respectively), depression (47.1%), mental fatigue (31.4%), apathy (30.4%), reduced activity (29.4%), EDS (20.2%), and reduced motivation (18.6%). Univariate analysis showed that NMS, but not motor symptoms, were significantly linked to poor HRQoL, with EDS being most commonly associated with poor HRQoL, followed by disrupted sleep, depression, and fatigue.Conclusions The prevalence of NMS among patients with CD is high, and some NMS are strongly associated with poor HRQoL, while motor impairment was not associated with the severity of NMS or poor HRQoL. Actively diagnosing and treating NMS should therefore be a routine part of the clinical management of patients with CD.

Introduction The gene encoding myelin-associated glycoprotein (MAG) has been implicated in autosomal-recessive spastic paraplegia type 75. To date, only four families with biallelic missense variants in MAG have been reported. The genotypic and phenotypic spectrum of MAG-associated disease awaits further elucidation. Methods Four unrelated patients with complex neurologic conditions underwent whole-exome sequencing within research or diagnostic settings. Following determination of the underlying genetic defects, in-depth phenotyping and literature review were performed. Results In all case subjects, we detected ultra-rare homozygous or compound heterozygous variants in MAG. The observed nonsense (c.693C > A [p.Tyr231*], c.980G > A [p.Trp327*], c.1126C > T [p.Gln376*], and 1522C > T [p.Arg508*]) and frameshift (c.517_521dupAGCTG [p.Trp174*]) alleles were predicted to result in premature termination of protein translation. Affected patients presented with variable combinations of psychomotor delay, ataxia, eye movement abnormalities, spasticity, dystonia, and neuropathic symptoms. Cerebellar signs, nystagmus, and pyramidal tract dysfunction emerged as unifying features in the majority of MAG-mutated individuals identified to date. Conclusions Our study is the first to describe biallelic null variants in MAG, confirming that loss of myelin-associated glycoprotein causes severe infancy-onset disease with central and peripheral nervous system involvement.

Sclerosis multiplex (SM) je autoimunitne ochorenie centralneho nervoveho systemu. V sucasnosti mame k dispozicii pomerne siroku skalu ochorenie modifikujucich lieciv (Disease Modifying Therapy - DMT) s roznym mechanizmom ucinku a ucinnosťou. Na dosiahnutie co najlepsieho liecebneho ovplyvnenia ochorenia je potrebný individualny pristup pri výbere liecby. Je potrebne mať na pamati aj rizika zvolenej liecby pre daneho pacienta. Kontinualne klinicke, ako aj laboratorne monitorovanie pacientov je nevyhnutne.

Background and Purpose— Posterior circulation stroke (PCS) accounts for 5% to 19% of patients with acute stroke receiving intravenous thrombolysis. We aimed to compare safety and outcomes following intravenous thrombolysis between patients with PCS and anterior circulation stroke (ACS) and incorporate the results in a meta-analysis. Methods— We included patients in the Safe Implementation of Treatments in Stroke Thrombolysis Registry 2013 to 2017 with computed tomography/magnetic resonance angiographic occlusion data. Outcomes were parenchymal hematoma, symptomatic intracerebral hemorrhage (SICH) per SITS-MOST (Safe Implementation of Thrombolysis in Stroke Monitoring Study), ECASS II (Second European Co-operative Stroke Study) and NINDS (Neurological Disorders and Stroke definition), 3-month modified Rankin Scale score, and death. Adjustment for SICH risk factors (age, sex, National Institutes of Health Stroke Scale, blood pressure, glucose, and atrial fibrillation) and center was done using inverse probability treatment weighting, after which an average treatment effect (ATE) was calculated. Meta-analysis of 13 studies comparing outcomes in PCS versus ACS after intravenous thrombolysis was conducted. Results— Of 5146 patients, 753 had PCS (14.6%). Patients with PCS had lower median National Institutes of Health Stroke Scale: 7 (interquartile range, 4–13) versus 13 (7–18), P Conclusions— The risk of bleeding complications after intravenous thrombolysis in PCS was half that of ACS, with similar functional outcomes and higher risk of death, acknowledging limitations of the National Institutes of Health Stroke Scale for stroke severity or infarct size adjustment.

Background and Purpose— A large infarct and expanding cerebral edema (CED) due to a middle cerebral artery occlusion confers a 70% mortality unless treated surgically. Reperfusion may cause blood-brain barrier disruption and a risk for cerebral edema and secondary parenchymal hemorrhage (PH). We aimed to investigate the effect of recanalization on development of early CED and PH after recanalization therapy. Methods— From the SITS-International Stroke Treatment Registry, we selected patients with signs of artery occlusion at baseline (either Hyperdense Artery Sign or computed tomography/magnetic resonance imaging angiographic occlusion). We defined recanalization as the disappearance of radiological signs of occlusion at 22 to 36 hours. Primary outcome was moderate to severe CED and secondary outcome was PH on 22- to 36-hour imaging scans. We used logistic regression with adjustment for baseline variables and PH. Results— Twenty two thousand one hundred eighty-four patients fulfilled the inclusion criteria (n=18 318 received intravenous thrombolysis, n=3071 received intravenous thrombolysis+thrombectomy, n=795 received thrombectomy). Recanalization occurred in 64.1%. Median age was 71 versus 71 years and National Institutes of Health Stroke Scale score 15 versus 16 in the recanalized versus nonrecanalized patients respectively. Recanalized patients had a lower risk for CED (13.0% versus 23.6%), adjusted odds ratio (aOR), 0.52 (95% CI, 0.46–0.59), and a higher risk for PH (8.9% versus 6.5%), adjusted odds ratio, 1.37 (95% CI, 1.22–1.55), than nonrecanalized patients. Conclusions— In patients with acute ischemic stroke, recanalization was associated with a lower risk for early CED even after adjustment for higher rate for PH in recanalized patients.

Introduction: Sixteen subjects with biallelic WARS2 variants encoding the tryptophanyl mitochondrial aminoacyl-tRNA synthetase, presenting with a neonatal- or infantile-onset mitochondrial disease, have been reported to date. Here we present six novel cases with WARS2-related diseases and expand the spectrum to later onset phenotypes including dopa-responsive early-onset parkinsonism and progressive myoclonus-ataxia.Methods: Six individuals from four families underwent whole-exome sequencing within research and diagnostic settings. Following the identification of a genetic defect, in-depth phenotyping and protein expression studies were performed.Results: A relatively common (gnomAD MAF = 0.0033) pathogenic p.(Trp13Gly) missense variant in WARS2 was detected in trans in all six affected individuals in combination with different pathogenic alleles (exon 2 deletion in family 1; p.(Leu100del) in family 2; p.(Gly50Asp) in family 3; and p.(Glu208*) in family 4). Two subjects presented with action tremor around age 10-12 years and developed tremor-dominant parkinsonism with prominent neuropsychiatric features later in their 20s. Two subjects presented with a progressive myoclonusataxia dominant phenotype. One subject presented with spasticity, choreo-dystonia, myoclonus, and speech problems. One subject presented with speech problems, ataxia, and tremor. Western blotting analyses in patientderived fibroblasts showed a markedly decreased expression of the full-length WARS2 protein in both subjects carrying p.(Trp13Gly) and an exon-2 deletion in compound heterozygosity.Conclusions: This study expands the spectrum of the disease to later onset phenotypes of early-onset tremordominant parkinsonism and progressive myoclonus-ataxia phenotypes.

Purpose: The purpose of this study was to expand the genetic architecture of neurodevelopmental disorders, and to characterize the clinical features of a novel cohort of affected individuals with variants in ZNF142, a C 2 H 2 domain-containing transcription factor. Methods: Four independent research centers used exome sequencing to elucidate the genetic basis of neurodevelopmental phenotypes in four unrelated families. Following bioinformatic filtering, query of control data sets, and secondary variant confirmation, we aggregated findings using an online data sharing platform. We performed in-depth clinical phenotyping in all affected individuals. Results: We identified seven affected females in four pedigrees with likely pathogenic variants in ZNF142 that segregate with recessive disease. Affected cases in three families harbor either nonsense or frameshifting likely pathogenic variants predicted to undergo nonsense mediated decay. One additional trio bears ultrarare missense variants in conserved regions of ZNF142 that are predicted to be damaging to protein function. We performed clinical comparisons across our cohort and noted consistent presence of intellectual disability and speech impairment, with variable manifestation of seizures, tremor, and dystonia. Conclusion: Our aggregate data support a role for ZNF142 in nervous system development and add to the emergent list of zinc finger proteins that contribute to neurocognitive disorders.

The aim of the presented study was to reveal the frequency of insomnia spells in E200K genetic Creutzfeldt–Jakob disease (gCJD) patients. Clinical records of 22 subjects diagnosed with E200K gCJD were retrospectively reviewed. The patients w/wo insomnia (n = 4, 18%/n = 18, 82%) did not differ in age, sex and the duration of the symptomatic phase. Analysis of the clinical features in the groups yielded differences in the clinical signs in the early phase of the disorder, proportion of homozygotes (Met/Met) at codon 129, MRI changes in the thalamus and the typical EEG abnormality. The study suggests that apart from traditional clinical features, the insomnia is not a rare early symptom in phenotype of E200K gCJD based on early thalamic involvement.

Background. Neurofilament light chain is a promising biomarker of disease activity and treatment response in relapsing-remitting multiple sclerosis (MS). Its role in progressive MS is less clear. Aim: The aim of the study was to assess the relationship between plasma neurofilament light chain (pNfL) and disease activity as defined by the concept NEDA-3 (No Evident Disease Activity), and brain volumetry, in a cohort of patients with the progressive disease form (PMS). Methods. Levels of pNfL (SIMOA technology) were examined in 52 PMS patients and analysed in relationship to NEDA-3 status and annual brain volume loss (BVL) during the last 12 months. The statistical model was developed using logistic regression analysis, including demographic, clinical and magnetic resonance imaging (MRI) data as independent variables. Dependent variables were NEDA-3 status and BVL. Results. The mean age of the study participants (n=52, 50% females) was 45.85 (SD, 9.82) and the median disability score was 5.0 (IQR: 5.0-5.5). ROC analysis showed that pNfL predicts NEDA-3 (the sensitivity and specificity of the model were 77.8% and 87.6%, respectively, P

PURPOSE Multiple sclerosis (MS) is a chronic disorder with a variable course. The aim of our study was to find out whether cognitive event-related potentials are prognostic for patient disability at the 15-year follow-up. METHODS In the observed cohort of patients with MS, we examined the event-related potentials at baseline (2003). Functional status (Expanded Disability Status Scale score) was then assessed 15 years later, and the prognostic model was developed using binary logistic regression analysis. The independent variables included demographic (age, sex, and education), clinical (disability in 2003), radiologic (MRI lesion load), and event-related potentials parameters. The prognostic accuracy of the proposed model was evaluated by calculating the area under the receiver-operating characteristics curve. RESULTS The study sample consisted of 85 patients with MS. The mean age was 35.5 (SD, 11.2) years, and the median disability score was 3.0 (1-7) in 2003 and 5.0 (1.5-9.5) in 2018. The significant prognostic factors of poor Expanded Disability Status Scale are higher baseline Expanded Disability Status Scale, longer MS duration, and prolonged P300 latency. The sensitivity and specificity of the cutoff at 5.0 for the disability score were 94% and 89%, respectively, with the area under the receiver-operating characteristics curve 0.94 (95% confidence interval, 0.889-0.984; P < 0.001). CONCLUSIONS The results show that out of event-related potentials, the P300 wave latency is a prognostic of long-term disability progression in patients with MS.

Background and Purpose— The RE-SPECT ESUS trial (Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) tested the hypothesis that dabigatran would be superior to aspirin for the prevention of recurrent stroke in patients with embolic stroke of undetermined source. This exploratory subgroup analysis investigates the impact of age, renal function (both predefined), and dabigatran dose (post hoc) on the rates of recurrent stroke and major bleeding. Methods— RE-SPECT ESUS was a multicenter, randomized, double-blind trial of dabigatran 150 or 110 mg (for patients aged ≥75 years and/or with creatinine clearance 30 to Results— The trial, which enrolled 5390 patients from December 2014 to January 2018, did not demonstrate superiority of dabigatran versus aspirin for prevention of recurrent stroke in patients with embolic stroke of undetermined source. However, among the population qualifying for the lower dabigatran dose, the rate of recurrent stroke was reduced with dabigatran versus aspirin (7.4% versus 13.0%; hazard ratio, 0.57 [95% CI, 0.39–0.82]; interaction P =0.01). This was driven mainly by the subgroup aged ≥75 years (7.8% versus 12.4%; hazard ratio, 0.63 [95% CI, 0.43–0.94]; interaction P =0.10). Stroke rates tended to be lower with dabigatran versus aspirin with declining renal function. Risks for major bleeding were similar between treatments, irrespective of renal function, but with a trend for lower bleeding rates with dabigatran versus aspirin in older patients. Conclusions— In subgroup analyses of RE-SPECT ESUS, dabigatran reduced the rate of recurrent stroke compared with aspirin in patients qualifying for the lower dose of dabigatran. These results are hypothesis-generating. Aspirin remains the standard antithrombotic treatment for patients with embolic stroke of undetermined source. Registration— URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02239120.

Summary Background Dystonia is a clinically and genetically heterogeneous condition that occurs in isolation (isolated dystonia), in combination with other movement disorders (combined dystonia), or in the context of multisymptomatic phenotypes (isolated or combined dystonia with other neurological involvement). However, our understanding of its aetiology is still incomplete. We aimed to elucidate the monogenic causes for the major clinical categories of dystonia. Methods For this exome-wide sequencing study, study participants were identified at 33 movement-disorder and neuropaediatric specialty centres in Austria, Czech Republic, France, Germany, Poland, Slovakia, and Switzerland. Each individual with dystonia was diagnosed in accordance with the dystonia consensus definition. Index cases were eligible for this study if they had no previous genetic diagnosis and no indication of an acquired cause of their illness. The second criterion was not applied to a subset of participants with a working clinical diagnosis of dystonic cerebral palsy. Genomic DNA was extracted from blood of participants and whole-exome sequenced. To find causative variants in known disorder-associated genes, all variants were filtered, and unreported variants were classified according to American College of Medical Genetics and Genomics guidelines. All considered variants were reviewed in expert round-table sessions to validate their clinical significance. Variants that survived filtering and interpretation procedures were defined as diagnostic variants. In the cases that went undiagnosed, candidate dystonia-causing genes were prioritised in a stepwise workflow. Findings We sequenced the exomes of 764 individuals with dystonia and 346 healthy parents who were recruited between June 1, 2015, and July 31, 2019. We identified causative or probable causative variants in 135 (19%) of 728 families, involving 78 distinct monogenic disorders. We observed a larger proportion of individuals with diagnostic variants in those with dystonia (either isolated or combined) with coexisting non-movement disorder-related neurological symptoms (100 [45%] of 222; excepting cases with evidence of perinatal brain injury) than in those with combined (19 [19%] of 98) or isolated (16 [4%] of 388) dystonia. Across all categories of dystonia, 104 (65%) of the 160 detected variants affected genes which are associated with neurodevelopmental disorders. We found diagnostic variants in 11 genes not previously linked to dystonia, and propose a predictive clinical score that could guide the implementation of exome sequencing in routine diagnostics. In cases without perinatal sentinel events, genomic alterations contributed substantively to the diagnosis of dystonic cerebral palsy. In 15 families, we delineated 12 candidate genes. These include IMPDH2, encoding a key purine biosynthetic enzyme, for which robust evidence existed for its involvement in a neurodevelopmental disorder with dystonia. We identified six variants in IMPDH2, collected from four independent cohorts, that were predicted to be deleterious de-novo variants and expected to result in deregulation of purine metabolism. Interpretation In this study, we have determined the role of monogenic variants across the range of dystonic disorders, providing guidance for the introduction of personalised care strategies and fostering follow-up pathophysiological explorations. Funding Else Kroner-Fresenius-Stiftung, Technische Universitat Munchen, Helmholtz Zentrum Munchen, Medizinische Universitat Innsbruck, Charles University in Prague, Czech Ministry of Education, the Slovak Grant and Development Agency, the Slovak Research and Grant Agency.

We thank all SITS-ISTR investigators and their centers for their participation. We also pass on our thanks to all patients who participated in SITS-ISTR. The current SITS registry is developed, maintained and upgraded by Zitelab, Copenhagen, Denmark, in close collaboration with SITS. SITS (Safe Implementation of Treatment in Stroke) is financed directly and indirectly by grants from Karolinska Institute, Stockholm County Council, the Swedish Heart-Lung Foundation, the Swedish Order of St. John, Friends of Karolinska Institute, and private donors, as well as from an unrestricted sponsorship from Boehringer-Ingelheim. SITS has previously received grants from the European Union Framework 7, the European Union Public Health Authority and Ferrer International. SITS is currently conducting studies supported by Boehringer-Ingelheim and EVER Pharma, as well as in collaboration with Karolinska Institute, supported by Stryker, Covidien and Phenox. N Ahmed is supported by grants provided by the Stockholm County Council and the Swedish Heart-Lung Foundation. No funding sources had part in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication.

Poor sleep is a serious burden for patients with multiple sclerosis (MS). The aim of this study is to assess whether the association between sleep quality and disability in MS patients is direct or mediated by depression, pain, and fatigue. We collected data from 152 patients with MS who filled out the Pittsburgh Sleep Quality Index, the Hospital Anxiety and Depression Scale, the Multidimensional Fatigue Inventory and one item of the Short Form-36 regarding pain. The relationship between poor sleep and disability was found to be indirect, mediated by depression (p

DYT1 gene mutations lead to early-onset dystonia that begins with focal limb onset and spreads to other body regions within 5 years, with typical sparing of the oromandibular muscles. In the present study, we describe two patients with an unusual presentation of the disease.

Background Gastrointestinal symptoms are a well-recognized and common premotor feature of Parkinson's disease (PD). Moreover, multiple studies have assessed the value of colonic α-synuclein as a potential marker of prodromal PD. Recently, the International Parkinson and Movement Disorders Society (MDS) defined research criteria for prodromal PD. Objective The aim of our study was to test the MDS research criteria in patients undergoing diagnostic colonoscopies as potential candidates for inclusion in prospective trials evaluating colonic biopsies as a potential biomarker of prodromal PD. Methods We evaluated elderly patients without manifest parkinsonism undergoing diagnostic colonoscopies. During the study we assessed all risks and prodromal markers of the MDS research criteria, excluding radiotracer imaging and genetic testing. Results The mean age of the 100 enrolled patients was 61.6±9.7 years; 42 were men. The most common prodromal marker in our cohort was constipation (40%), followed by MDS-UPDRS part III scores of >6 points, excluding action tremor items (39%) and hyposmia (37%). Substantia nigra hyperechogenicity was identified in 9%, and polysomnography confirmed REM sleep behavior disorder in 2% of the patients. Five of the 100 enrolled patients (5%) fulfilled the criteria for probable prodromal PD, while another 3 patients met the 50% probability threshold. Conclusions Our findings suggest, that the prevalence of prodromal PD in patients undergoing diagnostic colonoscopies may be higher compared to the general elderly population, although this should be confirmed in further studies including also matched controls not undergoing colonoscopy. The real prevalence of prodromal PD in this cohort will have to be confirmed in longitudinal follow-up. Patients undergoing diagnostic colonoscopies may be good candidates for multistep screening and inclusion in prospective trials.

The aim of this study is to explore whether self-esteem and social participation are associated with the physical and mental quality of life (Physical Component Summary, Mental Component Summary) and whether self-esteem can mediate the association between these variables. We collected information from 118 consecutive multiple sclerosis patients. Age, gender, disease duration, disability status, and participation were significant predictors of Physical Component Summary, explaining 55.4 percent of the total variance. Self-esteem fully mediated the association between social participation and Mental Component Summary (estimate/standard error = −4.872; p

The study aimed to assess the effect of demographic and clinical features of epilepsy, anxiety, depressed mood, sleep, and quality of life on the prediction of cognitive decline in patients with epilepsy. Two hundred and six consecutive patients with epilepsy (age 41.8 ± 15.6 years, mean, SD) out of 279, were included in this cross-sectional study. We used simple linear regression to calculate the results. Objective cognitive status was predicted by anxiety and depression mood changes (Beck Anxiety Inventory (BAI), p = 0.03, Beck Depression Inventory (BDI), p = 0.005), language subdomain of Quality of Life Inventory in Epilepsy-89 (QOLIE-89) (p = 0.003), and total QOLIE-89 (p = 0.001). No significance was shown in demographic and clinical features of epilepsy (gender, age at onset, epilepsy duration, type, etiology of epilepsy, and antiepileptic treatment), except frequency of generalized epileptic seizures (p = 0.03), which also served as an independent predictor of anxiety (BAI) and depression (BDI). Our findings point at the role of mood changes in the cognitive status of patients with epilepsy, which should be used as an essential therapeutic target apart of seizure control.

Introduction: There is an ongoing debate about the use of recombinant tissue plasminogen activator in acute stroke during pregnancy. The aim of our case report is to present that even in a small stroke centre intravenous thrombolysis can be used on a pregnant woman if the benefit outweighs the risk and to summarize the diagnostic workup in a pregnant woman with stroke. Case report: Our case describes a 31-year-old woman presenting in her third trimester with a sudden onset of slurred speech, severe right hemiparesis, facial nerve central palsy, eyes deviation to the left, right side hemianopia, hemisensory loss, psychomotor agitation and pain in the right lower limb. She was successfully treated with recombinant tissue plasminogen activator with almost complete recovery (NIHSS 1 after 10 days), and 23 days after intravenous thrombolysis, she delivered in the 37th week a healthy male infant. The first documented successful outcome from thrombolysis for this condition in Slovakia supports the notion of giving intravenous recombinant tissue plasminogen activator to pregnant patients with disabling ischaemic stroke who meet the criteria for thrombolysis. Discussion: At the end of case study, a recommended diagnostic workup for acute treatment of stroke in pregnant women is presented.

Background ECHS1 encodes a mitochondrial enzyme involved in the degradation of essential amino acids and fatty acids. Recently, ECHS1 mutations were shown to cause a new severe metabolic disorder presenting as Leigh or Leigh-like syndromes. The objective of this study was to describe a family with 2 siblings affected by different dystonic disorders as a resulting phenotype of ECHS1 mutations. Methods Clinical evaluation, MRI imaging, genome-wide linkage, exome sequencing, urine metabolite profiling, and protein expression studies were performed. Results The first sibling is 17 years old and presents with generalized dystonia and severe bilateral pallidal MRI lesions after 1 episode of infantile subacute metabolic encephalopathy (Leigh-like syndrome). In contrast, the younger sibling (15 years old) only suffers from paroxysmal exercise-induced dystonia and has very mild pallidal MRI abnormalities. Both patients carry compound heterozygous ECHS1 mutations: c.232G>T (predicted protein effect: p.Glu78Ter) and c.518C>T (p.Ala173Val). Linkage analysis, exome sequencing, cosegregation, expression studies, and metabolite profiling support the pathogenicity of these mutations. Expression studies in patients' fibroblasts showed mitochondrial localization and severely reduced levels of ECHS1 protein. Increased urinary S-(2-carboxypropyl)cysteine and N-acetyl-S-(2-carboxypropyl)cysteine levels, proposed metabolic markers of this disorder, were documented in both siblings. Sequencing ECHS1 in 30 unrelated patients with paroxysmal dyskinesias revealed no further mutations. Conclusions The phenotype associated with ECHS1 mutations might be milder than reported earlier, compatible with prolonged survival, and also includes isolated paroxysmal exercise-induced dystonia. ECHS1 screening should be considered in patients with otherwise unexplained paroxysmal exercise-induced dystonia, in addition to those with Leigh and Leigh-like syndromes. Diet regimens and detoxifying agents represent potential therapeutic strategies. © 2016 International Parkinson and Movement Disorder Society

POLG2 associated disorders belong to the group of mitochondrial DNA (mtDNA) diseases and present with a heterogeneous clinical spectrum, various age of onset, and disease severity. We report a 39-year old female presenting with childhood-onset and progressive neuroophthalmic manifestation with optic atrophy, mixed polyneuropathy, spinal and cerebellar ataxia and generalized chorea associated with mtDNA depletion. Whole-exome sequencing identified an ultra-rare homozygous missense mutation located at Chr17: 062474101-C > A (p.Asp433Tyr) in nuclear POLG2 gene encoding PolγB, an accessory subunits of mitochondrial polymerase γ responsible for mtDNA replication. The healthy parents and 2 sisters of the patient were heterozygous for the variant. To our best knowledge, this is the first case of homozygous variant in the POLG2 gene resulting in mitochondrial depletion syndrome in an adult patient and its clinical manifestations extend the clinical spectrum of POLG2 associated diseases.

The aim of this study is to explore whether different coping strategies are able to mediate the association between Type D personality and quality of life. We collected information from 156 consecutive patients (response rate: 72.9%; 75.0% women; median age: 40 ± 3 years). Patients completed the Type D Scale-14, the Coping Self-Efficacy Scale and the Short-Form Health Survey for measuring physical and mental quality of life. The mediating effect of coping was analysed using correlations, linear regressions and the Sobel z-test. In the mental quality of life, all three studied coping strategies mediated the association between Type D personality and quality of life.

Objectives: An extraordinary incidence of genetic Creutzfeldt-Jakob disease (gCJD) appearing in clusters in the Slovak Republic was described in the 1990's. The aim of the study was to analyse data of CJD cases obtained from surveillance in Eastern Slovakia (ES) (2004-2016), the region outside the described geographical clusters. Methods: The database set in the project was the source for epidemiological and clinical analysis of CJD cases. Results: The incidence of CJD in ES (2004-2016) was 1.7/million person-years (95% CI 1-2.4); the incidence increase in the last five years (2012-2016) was comparable to the whole country. Twenty seven of 29 reported CJD cases were available for analysis (mean age 59 years, F/M 15/12). The proportion of gCJD (E200K mutation) cases remained dominant (78%), with 9 familiar cases originating in 4 families. Analysis of the clinical features revealed shorter duration of the symptomatic phase in sporadic CJD (sCJD) (3.4 months) versus gCJD (5.15 months). Cognitive/behavioural changes, insomnia, and sensory disturbance were more pronounced in the early symptoms of gCJD. Periodic EEG discharges were more frequent in sCJD (83%) than gCJD (56%), all 19 available MR findings were CJD specific and localisation of abnormalities varied amongst the CJD forms. Conclusions: The surveillance of CJD in ES (2004-2016) showed an increased incidence of CJD in ES, reaching the incidence rate of the whole country, with a permanent proportion of 70% gCJD cases based on the E200K mutation. Clinical, electrophysiological and MR features of sCJD and gCJD cases were in conformity with already published data. Epidemiological analysis of CJD in ES shows increasing detection of CJD but also suggests that current routine surveillance systems for CJD may underestimate the true burden of disease, especially sporadic cases in Slovakia.

The Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is a newly developed comprehensive tool to assess Parkinson's disease (PD), which covers a wider range of non-motor PD manifestations than the original UPDRS scale. The aim of this study was to assess the relationship between the MDS-UPDRS and Quality of Life (QoL) and to analyze the relationship between individual MDS-UPDRS non-motor items and QoL.A total of 291 PD patients were examined in a multicenter Slovak study. Patients were assessed by the MDS-UPDRS, HY scale and PDQ39. Data were analyzed using the multiple regression analyses. The mean participant age was 68.0 +/- 9.0 years, 53.5% were men, mean disease duration was 83 53 years and mean HY was 2.7 +/- 1.0. In a multiple regression analysis model the PDQ39 summary index was related to MDS-UPDRS parts II, land IV respectively, but not to part III. Individual MDS-UPDRS non-motor items related to the PDQ39 summary index in the summary group and in the non-fluctuating patients subgroup were pain, fatigue and features of dopamine dysregulation syndrome (DDS). In the fluctuating PD patient subgroup, PDQ39 was related to pain and Depressed mood items. Other MDS-UPDRS non-motor items e.g. Anxious mood, Apathy, Cognitive impairment, Hallucinations and psychosis, Sleep problems, Daytime sleepiness and Urinary problems were related to some PDQ39 domains.The overall burden of NMS in PD is more important in terms of QoL than motor symptoms. Individual MDS-UPDRS non-motor items related to worse QoL are-especially pain and other sensations, fatigue and features of DDS. (C) 2015 Elsevier B.V. All rights reserved.

INTRODUCTION Cardioembolic stroke (CS) in patients without thrombolytic treatment is associated with a worse clinical outcome and higher mortality compared to other types of stroke. The aim of this study was to determine the clinical outcome of CS in patients treated by intravenous thrombolysis (IVT). MATERIAL AND METHODOLOGY Data of patients from the SITS-EAST register (Safe Implementation of Treatments in Stroke) were analyzed in patients who received IVT treatment from 2000 to April 2014. The effect of the stroke etiology according to ICD-10 classification on outcome was analyzed using a univariate and multivariate analysis. The outcomes were assessed as follows: excellent clinical outcome (modified Rankin scale (mRS) 0-1) at 3 months, the rate of symptomatic intracranial hemorrhage (sICH), mortality, and improvement at 24 hours after IVT. RESULTS Data of 13 772 patients were analyzed. CS represented 30% of all strokes. The mean age of patients with CS, atherothrombotic stroke, lacunar stroke, and other stroke was 70.8, 66.7, 66.2, and 63.3 years, respectively (P

BACKGROUND: The Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) is a newly developed tool to assess Parkinson's disease (PD). Changes in scores on the scale over the course of PD, including increasing disease duration and Hoehn and Yahr (HY) stages, have not been described. The objectives of this study were to analyze MDS‐UPDRS scores on Parts I through IV and their differences based on HY stage and disease duration in a large cohort of patients with PD. METHODS: For this cross‐sectional study, demographic data and MDS‐UPDRS scores were collected, including HY stage. Subscores on MDS‐UPDRS Parts I through IV were analyzed using 1‐way analyses of variance for each HY stage and in 5‐year increments of disease duration. Part III (motor assessment) scores were analyzed separately for on and off states. RESULTS: The mean age of the 3206 patients was 65.8 ± 10.6 years, 53.3% were men, the mean disease duration was 11.5 ± 4.6 years, and the median HY stage was 2 (range, 0–5); 2156 patients were examined in an on state and 987 were examined in an off state. Scores for all MDS‐UPDRS parts increased significantly through HY stages 1 through 5, with an average increase of 3.8, 7.7, 14.6, and 2.0 points consecutively for parts I through IV, respectively. For the 5‐year increments of disease duration, MDS‐UPDRS subscores increased by an average of 1.6, 3.3, 4.2, and 1.4 points consecutively for parts I through IV, respectively. This increase was significant only during the first 15 years of disease for all 4 parts, including part III scores evaluated in both on and off states. CONCLUSIONS: MDS‐UPDRS scores for all 4 parts increase significantly with every HY stage and also with 5‐year increments of disease duration in the first 15 years of the disease.

ObjectivesFatigue and apathy are two of the most common and most disabling non-motor symptoms of Parkinson's disease (PD). They have a high coincidence and can often be confused; moreover, their relationship is not fully understood. The aim of our study was to describe the coincidence of apathy with different fatigue domains in the presence/absence of depression and to separately describe the associations of different aspects of primary and secondary fatigue with apathy and other clinical and disease-related factors.Materials and methodsA total of 151 non-demented patients with PD were examined using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Starkstein Apathy Scale, Multidimensional Fatigue Inventory (MFI), Beck Depression Inventory-II, and Epworth Sleepiness Scale.ResultsThe prevalence and severity of fatigue and apathy were significantly higher in depressed PD patients. However, our results show that depression, fatigue, and apathy can be clearly distinguished in PD. Apathy was associated with the MFI's-reduced motivation domain in both depressed and non-depressed patients. However, apathy was associated with mental fatigue aspects only in non-depressed patients, and it was not related to the physical aspects of fatigue in any of the studied groups.ConclusionsAlthough the pathophysiology of fatigue and apathy in PD is clearly multifactorial, in a proportion of PD patients, these symptoms are associated with depression, dopaminergic depletion in the mesocorticolimbic structures, and disruption of the prefrontal cortex-basal ganglia axis. Therefore, in some PD patients, adequate management of depression and optimal dopaminergic medication may improve both fatigue and apathy.

The aim of this study was to analyse whether problem-focused coping, coping focused on getting support and coping focused on stopping unpleasant emotions and thoughts are associated with different levels of physical and mental quality of life (PCS, MCS), controlling for gender, age and disease severity among MS patients.The sample consisted of 113 consecutive MS patients (response rate: 79.6%; 77.0% women; mean age 40.8 ± 9.2). Patients completed the Short-Form Health Survey (SF-36) and the Coping Self-Efficacy Scale (CSE). Disability was assessed by Expanded Disability Status Scale (EDSS). The associations between CSE and PCS and MCS were analysed using linear regression.EDSS and age were significantly associated only with PCS. The regression model for problem-focused coping, coping focused on getting support and coping focused on stopping unpleasant emotions and thoughts explained 29%, 24% and 35% of the variance in MCS, respectively. In PCS coping was not significant.Coping is significantly associated with MCS, but not with PCS. Stopping unpleasant emotions and thoughts seems to be the most important type of coping in MS patients. Thus, patients, their caregivers and their physicians should be educated about this type of coping and its positive association with MCS. Implications for Rehabilitation All types of coping are associated positively with mental component of Quality of life. Coping focused on stopping negative emotions and thoughts seems to be very adaptive for patients with MS. This type of coping can help patients with chronic conditions when problem-focused coping can not effectively solve the problem.

Bladder, bowel and sexual dysfunction are often overlooked symptoms in patients with multiple sclerosis (MS) and can be associated with lower health-related quality of life (HRQoL). The aim is to explore the association of bladder, bowel and sexual dysfunction with HRQoL in MS patients stratified by disease duration (≤5 and5 years) and controlled for clinical and sociodemographic variables.The study comprised 223 MS patients (mean age 38.9 ± 10.8 years, 67% female, mean EDSS 3.0 ± 1.5) who filled out the Short-Form-36 Health Survey, the Bladder Control Scale, the Bowel Control Scale and the Incapacity Status Scale. The relationships between the variables were analyzed with multiple linear regression using the SF36's Physical Component Summary (PCS) and Mental Component Summary (MCS) as dependent variables.More severe bladder dysfunction was associated with lower PCS in both disease duration groups (β = -0.35, p ≤ 0.001 versus β = -0.43, p ≤ 0.001), whereas more severe sexual dysfunction was associated with lower MCS in the group with shorter disease duration (β = -0.23, p ≤ 0.05).Bladder and sexual dysfunction are associated with a poorer HRQoL in MS patients even if they have had MS for a relatively short time. Recognition and proper treatment is needed to prevent the development of more severe dysfunction; this may also lead to a better HRQoL.Bladder and sexual dysfunction are associated with a poor health-related quality of life in MS patients. Sexual dysfunction may explain mental health issues among individuals with a short disease duration. Recognition and treatment may prevent the development of more severe sexual and bladder dysfunction and increase physical health-related quality of life.

Purpose: Fatigue is a frequent non-motor complaint of patients with Parkinson's disease (PD). Despite increasing knowledge on fatigue, the factors leading to its development are still not recognised. The aim of this investigation was to test, using structural equation modelling, the hypothesis that the influence of disease severity on fatigue is mediated by symptoms of depression in patients with PD. Method: The sample consisted of 190 PD patients (93 men, 48.9%, mean age 68.2 ± 9.3 years, mean disease duration 6.4 ± 4.7 years) recruited from hospitals and outpatient clinics in the East Slovakia region. The Multidimensional Fatigue Inventory, the Hospital Anxiety and Depression Scale and the Unified Parkinson's Disease Rating Scale were used. LISREL was used to analyse the data. Results: Disease severity was directly associated with symptoms of depression (β = 0.26) and directly affected fatigue in terms of increased levels of general fatigue (β = 0.35), physical fatigue (β = 0.22), reduced activity (β = 0.31) and mental fatigue (β = 0.29), but did not directly influence reduced motivation. Symptoms of depression mediated the impact of disease severity on general fatigue (β = 0.25), on reduced activity (β = 0.31) and on mental fatigue (β = 0.28), but not on physical fatigue. Reduced motivation was not mediated, but directly influenced by more symptoms of depression (β = 0.82). Discussion: Since increased symptoms of depression mediate the impact of disease severity on three domains of fatigue in PD patients, disease management should focus on the treatment of PD and symptoms of depression.

Objectives Most of the psychological and physical factors associated with poor sleep quality in patients with multiple sclerosis (MS) have a different prevalence in women and men, but whether or not these factors contribute differently to sleep quality in women and men with MS remains unclear. The aim of this study was to identify possible gender differences in factors related to poor sleep quality in MS patients.Material and Methods We collected data from 153 patients with MS. Patients filled out the Pittsburgh Sleep Quality Index (PSQI), the Hospital Anxiety and Depression Scale, and one item of the Short Form-36 regarding pain.Results The best model of predictors of poor sleep quality consisting of gender, depression, anxiety, pain, and the interaction between gender and pain showed that the only variable interacting with gender, which was significantly associated with poor sleep quality was pain (odds ratio [OR] for interaction of pain with male gender was 15.4, 95% CI: 2.4; 39.5). Separate models for men and women consisting of pain, depression, anxiety, after adjustment for age, disease duration, and disability showed that pain was the only variable associated with poor sleep quality in men (OR=12.7, 95% CI: 1.9; 29.6), whereas depression (OR=4.1, 95% CI: 1.3; 13.2) and anxiety (OR=6.8, 95% CI: 2.4; 19.1) were in women.Conclusions Factors contributing to poor sleep quality in MS patients differ by gender. Depression and anxiety are associated with poor sleep quality in women, whereas pain is in men. This highlights the need to apply gender-specific approaches to the treatment of sleep disorders.

This study explores how employment is associated with perceived physical and mental health status in people with multiple sclerosis (MS) adjusted for sociodemographic and clinical variables stratified by age. The sample consisted of 184 MS patients divided into a younger (= 45 years) age group. Respondents underwent an interview, a neurological examination on disability [Expanded Disability Status Scale (EDSS)], and completed the Short Form-36 Health Survey. Of the respondents (mean age 40.5 +/- 6.2 years), 43.5% were employed. Significant differences between younger and older patients were found in employment, EDSS, disease duration, and five Short Form-36 Health Survey dimensions. Block-step multiple regression explained 32.4% of the variance in physical health and 14.5% in mental health in the younger group. Being employed was significantly related to good physical health, whereas EDSS diminished the effect of being employed on physical health. The most important variable for mental health was employment status in the younger group. For the older age group, 19.1% of the variance in physical health and 14.0% of the variance in mental health was explained by the studied variables. Male gender and a lower EDSS were significant explanatory variables of better physical health. Male gender significantly explained mental health in the older age group. In conclusion, employment status was an explanatory variable for physical health and mental health in the younger patients. EDSS played a significant role in physical health for all patients. A vocational rehabilitation program could prevent eventual nonemployment and improve health outcomes in older MS people. International Journal of Rehabilitation Research 35: 40-47 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Objectives This systematic review focuses on the role of the intensity of fear in patient’s delay in cancer and in myocardial infarction. Methods In a search of literature published between 1990 and June 2009, 161 articles were found. After the use of inclusion and exclusion criteria, 11 articles in cancer and 4 articles in myocardial infarction remained. Results High levels of fear are associated with earlier help-seeking in both diseases; for low levels of fear, the picture is unclear. Conclusion The level of fear is an important factor, which should be taken into account when facilitating help-seeking by patients.

Madsen et al.1 reported that only the male cohort in the Greater Cincinnati/Northern Kentucky Stroke Study had a reduction in ischemic stroke incidence over time. This conclusion has relevant implications for health policy, because ischemic stroke is preventable when vascular risk factors are screened for,2 regularly monitored, and prescribed therapy regimens strictly followed.2,3 As seen in clinical practice, patients lacking a figure who continuously shadows their lifestyle and physical well-being often do not adhere to one or more of these indications. Women are more likely to be living alone throughout life, making them less likely to be screened for vascular risk factors.4 Moreover, some physicians consider vascular diseases to be male diseases, therein influencing how they counsel their female patients. In fact, only 22% of primary care physicians and 42% of cardiologists felt well-prepared to assess cardiovascular risk in women.5 In addition, only 16% of primary care physicians and 22% of cardiologists fully implemented guidelines for risk assessment. Therefore, women must be educated early in life that their overall lifetime health status depends on maintaining strong social bonds, having economic means, and seeking out vascular screening throughout life.