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Eslicarbazepine acetate (ESL), a novel sodium channel blocker, is approved for mono and adjunctive treatment of partial epileptic seizures with or without secondary generalization. Its efficacy in primary generalized seizures has not yet been evaluated.To evaluate the efficacy and safety of ESL in primary generalized tonic-clonic seizures (PGTCS) in an observational study.The data were collected from a prospective population-based register. Effectiveness was measured as relative reduction in standardized seizure frequency (SSF), responder rate (≥ 50% reduction in SSF), and seizure freedom rate at 6 and 12 months after initiation of ESL. Safety and tolerability were evaluated using patients' diaries.Fifty-six adult patients with PGTCS were treated with ESL as adjunctive therapy. Of these, 30.4% (n = 17) had myoclonic seizures in addition to PGTCS. The retention rate after 12 months was 80.4% (n = 45). After initiating ESL therapy, reduction in SSF for PGTCS on ESL was 56.0% after 6 months and 56.9% after 12 months (p lt; 0.01), whereas myoclonic seizures did not show any significant improvement in frequency. The responder rate for PGTCS was 64.3% after 6 months and 66.1% after 12 months, and seizure freedom was achieved in 32.1% and 35.7%, respectively. Forty-three patients (73.2%) reported no side effects. Among the reported side effects of ESL therapy, headache (7.1%), dizziness (8.9%), tiredness (7.1%), nausea (5.4%), and hyponatremia (5.4%) were the most prevalent.Our data suggest that ESL may provide additional benefits in the treatment of patients with PGTCS and motivate randomized controlled trials in this indication.

The aim of this study was to investigate the relevance of compartmentalized grey matter (GM) pathology and network reorganization in multiple sclerosis (MS) patients with concomitant epilepsy.From 3-T magnetic resonance imaging scans of 30 MS patients with epilepsy (MSE group; age 41 ± 15 years, 21 females, disease duration 8 ± 6 years, median Expanded Disability Status Scale [EDSS] score 3), 60 MS patients without epilepsy (MS group; age 41 ± 12 years, 35 females, disease duration 6 ± 4 years, EDSS score 2), and 60 healthy subjects (HS group; age 40 ± 13 years, 27 females) the regional volumes of GM lesions and of cortical, subcortical and hippocampal structures were quantified. Network topology and vulnerability were modelled within the graph theoretical framework. Receiver-operating characteristic (ROC) curve analysis was applied to assess the accuracy of GM pathology measures to discriminate between MSE and MS patients.Higher lesion volumes within the hippocampus, mesiotemporal cortex and amygdala were detected in the MSE compared to the MS group (all p lt; 0.05). The MSE group had lower cortical volumes mainly in temporal and parietal areas compared to the MS and HS groups (all p lt; 0.05). Lower hippocampal tail and presubiculum volumes were identified in both the MSE and MS groups compared to the HS group (all p lt; 0.05). Network topology in the MSE group was characterized by higher transitivity and assortativity, and higher vulnerability compared to the MS and HS groups (all p lt; 0.05). Hippocampal lesion volume yielded the highest accuracy (area under the ROC curve 0.80 [0.67-0.91]) in discriminating between MSE and MS patients.High lesion load, altered integrity of mesiotemporal GM structures, and network reorganization are associated with a greater propensity for epilepsy occurrence in people with MS.

ZusammenfassungKognitive Störungen sind ein häufiger Begleiter chronisch verlaufender Epilepsieerkrankungen. Neben der anfallssupprimierenden Wirkung weisen aber auch Neurostimulationsverfahren in der Behandlung von therapierefraktären Epilepsien Begleiteffekte auf die kognitive Leistung auf. Die meisten Daten liegen für die Vagusnervstimulation (VNS) vor, die eine positive Wirkung auf das verbale Gedächtnis hat. Dieser Effekt ist ausgeprägter bei Kindern als bei Erwachsenen und geht mit einer Verbesserung der Konzentration und der schulischen Leistung einher. Die tiefe Hirnstimulation (THS) des anterioren Thalamuskerns führt zu keinen anhaltenden kognitiven Störungen im Langzeitverlauf. Gleichzeitig können THS und responsive Neurostimulation (RNS) eine weitere Verschlechterung der zum Zeitpunkt der Implantation vorbestehenden Gedächtnisstörungen bewirken, so dass eine entsprechende Patientenselektion erforderlich ist. Während die Datenlage für die trigeminale Nervenstimulation und transkranielle Magnetstimulation noch unzureichend ist, scheint die transkranielle Gleichstromstimulation (tDCS) ein vielversprechendes Verfahren bezüglich positiver kognitiver Begleiteffekte zu sein. Die kathodale tDCS geht nach den aktuellsten Studiendaten nicht mit einer Verschlechterung der kognitiven Leistung einher. Insgesamt sind die neurostimulativen Verfahren bei Epilepsie hinsichtlich ihrer positiven Begleiteffekte auf die kognitive Leistung vielversprechend. Vom besonderen Interesse sind auch die neuen Verfahren der fokalen kortikalen Stimulation (z. B. „epicranial application of stimulation electrodes for epilepsy“, EASEE), die in weiteren Studien mit größeren Patientenzahlen untersucht werden sollen.

Objective: This study was undertaken to elicit patients' preferences for attributes characterizing antiseizure medication (ASM) monotherapy options before treatment consultation, and to explore the trade‐offs patients consider between treatment efficacy and risks of side effects. Further objectives were to explore how treatment consultation may affect patient preferences, to elicit physicians' preferences in selecting treatment, and to compare patient and physician preferences for treatment. Methods: This prospective, observational study (EP0076; VOTE) included adults with focal seizures requiring a change in their ASM monotherapy. Patients completed a discrete choice experiment (DCE) survey before and after treatment consultation. Physicians completed a similar survey after the consultation. The DCE comprised 12 choices between two hypothetical treatments defined by seven attributes. The conditional relative importance of each attribute was calculated. Results: Three hundred ten patients (mean [SD] age = 46.8 [18.3] years, 52.3% female) were enrolled from eight European countries, of whom 305 completed the survey before consultation and 273 completed the survey before and after consultation. Overall, this preference study in patients who intended to receive a new ASM monotherapy suggests that patient preferences were ordered as expected, with better outcomes being preferred to worse outcomes; patients preferred a higher chance of seizure freedom, lower risk of developing clinical depression, and fewer severe adverse events; avoiding moderate‐to‐severe “trouble thinking clearly” was more important than avoiding any other side effect. There were qualitative differences in what patients and physicians considered to be the most important aspects of treatment for patients; compared with patients, physicians had a qualitatively stronger preference for greater chance of seizure freedom and avoiding personality changes. Patients' preference weights were qualitatively similar before and after treatment consultation. Significance: For patients, seizure freedom and avoiding trouble thinking clearly were the most important treatment attributes. Physicians and patients may differ in the emphasis they place on specific attributes.

OBJECTIVE: To analyze satisfaction with and reliability of video-electroencephalography-monitoring systems (VEMS) in epilepsy diagnostics.; METHODS: A survey was conducted between December 2020 and January 2021 among German epilepsy centers using well-established customer satisfaction (CS) and quality assurance metrics.; RESULTS: Among 16 participating centers, CS with VEMS was low, with only 13% of customers actively recommending their system. Only 50% of users were satisfied with the overall performance of their VEMS, and a low 18% were satisfied with the manufacturer's customer service. User interface, software stability, lack of regular updates, and missing customer-oriented improvements were reported as frequent problems jeopardizing diagnosis in approximately every 10th patient. The greatest potential for improvement was identified for software and hardware stability as well as customer service.; CONCLUSION: Satisfaction with VEMS and their customer service was low, and diagnostics were regularly affected by software or hardware errors. Even if this can be partly explained by the technical complexity of VEMS, there is an urgent need for improvements with regard to the reliability and durability of system components as well as signal synchrony and data management.; SIGNIFICANCE: This analysis highlights low consumer satisfaction of users with VEMS and uncovers frequent problems and potential for improvement. Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Introduction Excessive daytime sleepiness (EDS) is a symptom of Obstructive Sleep Apnea (OSA) that can persist despite primary airway therapy and can be managed with wake-promoting agents. Solriamfetol (Sunosi®) is a wake-promoting agent approved to treat EDS associated with OSA (37.5–150 mg/day). This real-world study characterizes dosing/titration strategies among European physicians initiating solriamfetol and patient outcomes following initiation. Methods This is an ongoing retrospective chart review conducted by physicians in Germany and France. Data are reported from 52 German patients with OSA. Eligible patients (≥18 years old, diagnosed with EDS due to OSA, reached a stable solriamfetol dose, and completed ≥6 weeks of treatment) were classified into 1 of 3 groups based on solriamfetol initiation strategy: changeover (switched/switching from existing EDS medication[s]), add-on (added/adding to current EDS medication[s]), or new-to-therapy (no current/previous EDS medication). Results Patients’ mean±SD age was 50.0±13.1 years; 65% were male. All patients used primary airway therapy. Obesity was the most common comorbidity (56%). New-to-therapy was the most common initiation strategy (n=39), then add-on (n=9), and changeover (n=4). The most common starting doses of solriamfetol were 37.5 (n=34; 65%) and 75 mg/day (n=17; 33%). Solriamfetol was titrated in 30 patients (58%); the majority were titrated within 7 days. Mean±SD Epworth Sleepiness Scale (ESS) score was 15.5±3.2 (n=52) at initiation and 10.7±3.7 at follow-up (n=48), with a mean decrease of 5.0± 3.2 points. Across subgroups, mean ESS scores at initiation and follow-up ranged from 15.2–16.8 and 10.3-11.6, with mean decreases from 4.5–6.5 points. Improvements in EDS after solriamfetol initiation were reported for most patients (patient-reported, 90%; physician-reported, 88%). Most patients reported the effects of Solriamfetol to last ≥6 hours (81%) with no change in their night-time sleep quality (86%). Common adverse effects were headache, insomnia, and irritability. Conclusion These real-world data describe the use of solriamfetol in a cohort of German patients with OSA. Solriamfetol was typically initiated at 37.5 mg/day; titration was common. ESS improvements were greater than the minimum clinically important difference (MCID) of 2-3, and most patients and physicians perceived improvement in EDS. Common adverse events were consistent with those previously reported for solriamfetol. Support (if any) Axsome Therapeutics and Jazz Pharmaceuticals

Specific antiseizure medications (ASM) would improve the outcome in post-stroke epilepsy (PSE). The aim of this multicenter observational study was to compare different antiseizure monotherapies in PSE.We collected the data from 207 patients with PSE who did not change their initial antiseizure monotherapy during the period of 12 months. Efficacy was assessed by a standardized three month seizure frequency and seizure freedom. Safety was estimated by the reported side effects.The mean three month seizure frequency was 1.9 ± 3.1 on eslicarbazepine, 2.1 ± 3.2 on lacosamide, 3.4 ± 4.4 on levetiracetam, 4.3 ± 6.8 on lamotrigine, and 5.1 ± 7.3 on valproate (p 0.05 for eslicarbazepine or lacosamide in comparison with levetiracetam, lamotrigine and valproate, respectively). The lowest seizure frequency and the highest seizure freedom was observed on ASMs acting via the slow inactivation of sodium channels in comparison to other mechanisms of action (0.7 ± 0.9 vs 2.2 ± 2.4, p 0.01). Among side effects, the most frequently reported were vertigo (25%) and tiredness (15.9%). They were similar in all investigated groups of ASM. The independent factors increasing seizure frequency that were identified in multiple regression analyses were increased size of infarction, cortical involvement, hemorrhagic transformation, neurological deficits at admission and functional impairment. Administration of ASM with the mechanism of action via the slow inactivation of sodium channels was an independent factor decreasing the seizure frequency.Our data show that antiseizure medications acting via the slow inactivation of sodium channels, such as lacosamide and eslicarbazepine, are well tolerated and might be associated with better seizure control in PSE.

BackgroundFabry disease (FD) is a rare X-linked lysosomal storage disorder caused by α-galactosidase A (α-Gal A) deficiency. The progressive accumulation of globotriaosylceramide results in life-threatening complications, including renal, cardiac, and cerebrovascular diseases. In order to improve health care of FD-patients, knowledge of its predictors is important. The aim of our study was to evaluate health-related quality of life (HrQol) in FD and to identify its independent determinants by exploring a wide range of demographic, social and clinical parameters.ResultsIn this cross-sectional multicenter study, 124 adult patients with FD were recruited at three specialized European centers in Germany and Switzerland. Demographics, social status and clinical parameters as well as data on HrQol (EQ5D, EQVAS) and depression were collected by means of self-reporting questionnaires. HrQol and its predictors were evaluated by univariate and multivariate regression analyses.Study population consisted of 72 female and 52 male FD patients (median age 48yrs) of whom 87.9% (N=109) were on enzyme replacement therapy (ERT) (68.8% [N= 75] were on agalsidase α and 31.2% [N=34] on agalsidase β). Univariate analysis revealed various factors reducing HrQol, such as age>40 years, classic phenotype, organ involvement (kidney and heart disease, stroke/transient ischemic attack, gastrointestinal disturbances), depression, and burning limb pain. However, only the following factors were identified as independent predictors of decreased HrQol: classic phenotype, kidney and heart disease, stroke/TIA, depression, and burning limb pain. ERT was an independent determinant of increased HrQol.Conclusions Modifiable factors, such as burning limb pain and depression identified as independent predictors of HrQol-deterioration should be addressed in programs aiming to improve HrQol in FD. A multidisciplinary approach is essential in FD-patients since diverse organ involvement prominently compromises HrQol in affected patients. Our findings that the classic phenotype is a strong predictor of HrQol worsening.

IntroductionSolriamfetol is a dopamine/norepinephrine reuptake inhibitor approved in the EU for excessive daytime sleepiness (EDS) associated with narcolepsy. This real-world study characterises outcomes following solriamfetol initiation.MethodsSURWEY is an ongoing retrospective chart review (Germany, France, Italy). Patients (≥18 years old, EDS due to narcolepsy, stable solriamfetol dose, ≥6 weeks of treatment) were classified by solriamfe- tol initiation: changeover (from existing EDS medications), add-on (to current EDS medication), or new- to-therapy (no current/prior EDS medication). Epworth Sleepiness Scale (ESS) scores, patient/physician impressions of improvement, and adverse events (AEs) were assessed.ResultsAmong 78 German patients (36.9±13.9 years old; 56% female, 57% with cataplexy), changeo- ver was most common (n=43), followed by add-on (n=19) and new-to-therapy (n=8). Final follow-up was 15.9±7.0 weeks after initiation. Overall, ESS scores were 17.6±3.1 (n=61) at initiation and 13.6±3.8 at follow-up (n=51), indicating improvement of EDS (improvements similar across subgroups). Most patients perceived slight/strong improvements in their condition (physician report, 94%; patient report, 91%; results similar across subgroups). Common AEs: headache (9%), decreased appetite (6%), insomnia (6%).ConclusionIn this real-world cohort of German patients with narcolepsy, EDS improved across all subgroups with solriamfetol treatment. AEs were consistent with those reported in clinical trials.SupportJazz Pharmaceuticals.

Background Sleep-disordered breathing (SDB) is highly prevalent in acute ischaemic stroke and is associated with worse functional outcome and increased risk of recurrence. Recent meta-analyses suggest the possibility of beneficial effects of nocturnal ventilatory treatments (continuous positive airway pressure (CPAP) or adaptive servo-ventilation (ASV)) in stroke patients with SDB. The evidence for a favourable effect of early SDB treatment in acute stroke patients remains, however, uncertain. Methods eSATIS is an open-label, multicentre (6 centres in 4 countries), interventional, randomized controlled trial in patients with acute ischaemic stroke and significant SDB. Primary outcome of the study is the impact of immediate SDB treatment with non-invasive ASV on infarct progression measured with magnetic resonance imaging in the first 3 months after stroke. Secondary outcomes are the effects of immediate SDB treatment vs non-treatment on clinical outcome (independence in daily functioning, new cardio-/cerebrovascular events including death, cognition) and physiological parameters (blood pressure, endothelial functioning/arterial stiffness). After respiratory polygraphy in the first night after stroke, patients are classified as having significant SDB (apnoea-hypopnoea index (AHI) > 20/h) or no SDB (AHI Discussion The trial will give information on the feasibility and efficacy of ASV treatment in patients with acute stroke and SDB and allows assessing the impact of SDB on stroke outcome. Diagnosing and treating SDB during the acute phase of stroke is not yet current medical practice. Evidence in favour of ASV treatment from a randomized multicentre trial may lead to a change in stroke care and to improved outcomes. Trial registration ClinicalTrials.gov NCT02554487, retrospectively registered on 16 September 2015 (actual study start date, 13 August 2015), and www.kofam.ch (SNCTP000001521).

Background The incidence of juvenile stroke is increasing. Considering younger age of patients and the potential long-lasting disability, the consequences of juvenile stroke may have a greater societal impact than those of stroke in elder population. Methods A systematic review was performed in order to evaluate quality of life in juvenile stroke. All studies on quality of life in juvenile stroke published in PUBMED before March 1st, 2020. The search terms were “stroke”, “juvenile”, “young”, “adult”, “quality of life” and “resilience” were considered. After the abstract evaluation of 748 hits only six studies we identified as appropriate for the review. The age criterion for juvenile stroke was set as 55 years and younger. Results The studies have shown a decline of quality of life in at least 46% of patients with juvenile stroke. On average, quality of life was reduced by 37%. The following domains as measured on SF-36 were particularly impaired: physical role, physical functioning and emotional role. The factors influencing the quality of life in juvenile stroke were ability to return to work, post-stroke depression, functional outcome, level of education and age of stroke onset. Conclusions This systematic review shows a decline of quality of life in patients with juvenile stroke. Rehabilitation programs should consider the factors influencing quality of life in these patients in order to improve outcome of juvenile stroke. Patients who are unable to return to work should receive necessary social support. In addition, our data underline the importance of screening procedures for post-stroke depression in this population.

Electroencephalography (EEG) spikes and focal epileptic seizures are generated in circumscribed cerebral networks that have been insufficiently described. For precise time and spatial domain network characterization, we applied in patients with focal epilepsy dense array 256-channel EEG recordings with causal connectivity estimation by using time-resolved partial directed coherence and 3T-magnetic resonance imaging-derived cortical and thalamus integrity reconstruction. Before spike generation, significant theta and alpha bands driven information flows alterations were noted from both temporal and frontal lobes to the thalamus and from the thalamus to the frontal lobe. Medial dorsal and ventral anterior nuclei of the thalamus were delimited as possible pacemakers. Markedly reduced thalamic volumes and impaired cortical integrity in widespread areas predicted the altered information flows. Our data reveal distinct patterns of connectivity involving the thalamus and frontal cortex that are both directly and causally involved in spike generation. These structures might play an essential role in epileptogenesis and could be targeted in future therapeutic approaches.

ObjectivesBrivaracetam (BRV) is the latest approved antiepileptic drug and acts as a synaptic vesicle protein 2A ligand. The aim of the present study was to evaluate the efficacy and tolerability of BRV in the clinical setting.DesignRetrospective, observational multicentre study.SettingWe retrospectively collected clinical data of patients who received BRV in 10 epilepsy centres using a questionnaire that was answered by the reporting neurologist.ParticipantsData of 615 epilepsy patients treated with BRV were included in the study.Primary and secondary outcome measuresEfficacy regarding seizure frequency and tolerability of BRV were evaluated. Descriptive statistics complemented by X2 contingency tests and effect sizes were performed.ResultsOverall, 44% of the patients had a decreased, 38% a stable and 18% an increased seizure frequency. 17% of patients achieved seizure freedom after initiation of BRV. The seizure frequency decreased in 63% of 19 patients with BRV monotherapy. 27% reported adverse effects, but only 10% of patients with monotherapy. Brivaracetam was significantly more often associated with decreased seizure frequency in levetiracetam (LEV) naïve patients (p=0.012), but BRV also led to a decreased seizure frequency in 42% of patients who had been treated with LEV before, including 17% of patients who were completely seizure free. Adverse effects under LEV improved in 62% and deteriorated in 2% of patients after the switch to BRV. At latest follow-up (mean±SD = 26.3±6.5 months), 68% were still on BRV.ConclusionsThe present study shows that results of the phase III studies on BRV match data from real life clinical settings. Brivaracetam seems to be a useful alternative in patients who have suffered adverse effects while taking LEV.

Lyme-Borreliose-assoziierte Erkrankungen gehoren zu den haufigsten durch Zecken (Ixodes ricinus) ubertragenen Erkrankungen in Europa. Borrelieninfektionen konnen neben lokalen Entzundungsreaktionen auch das zentrale Nervensystem betreffen oder sogar zu Schlaganfallen und Hirninfarkten fuhren. Allerdings sind bei der Diagnose mehrere Faktoren zu berucksichtigen.

Study objectives In this study, we aimed to estimate the alterations of brain networks and structural integrity linked to seizure occurrence during sleep and awake states. Methods Using a graph theory approach to magnetic resonance imaging-derived volumes of cortical and subcortical regions, we investigated the topological organization of structural networks in patients with sleep seizures (n = 13), patients with awake seizures (n = 12), and age- and sex-matched healthy controls (n = 10). Abnormalities in regional structural substrates (cortical volume/surface area, subcortical volumes) associated with sleep seizures and awake seizures were further analyzed. Results Brain networks in patients with sleep seizures compared to patients with awake seizures displayed a more integrated structural organization coupled with greater networks' stability. When compared to healthy controls, networks in both patients with sleep and awake seizures were analogously compromised, exhibiting a less integrated and preserved organization. Patients with sleep seizures in contrast to awake seizures had larger volumes of bilateral insula, superior temporal, and orbitofrontal cortices but lower volumes of left postcentral and right middle temporal cortices in comparison to healthy controls. Patients with awake seizures compared to healthy controls displayed reduced volumes mainly in frontal, temporal, and parietal regions of right hemisphere. Volumes of hippocampus, amygdala, caudate, pallidum, and putamen were larger in patients with sleep seizures than in patients with awake seizures. Conclusions Despite epileptogenesis, patients with sleep and awake seizures had distinct network and structural correlates across different epilepsy types. Identified regional cortical/subcortical abnormalities can endorse the pathophysiological alterations that induce seizures during the sleep or awake states.

Eslicarbazepine acetate (ESL) is a third-generation antiepileptic drug (AED) approved as monotherapy for partial-onset seizures in adults and as adjunctive therapy in patients aged above 6 years in the European Union (EU). The prospective observational Zebinix Effects in DEpendency of BAseline Conditions (ZEDEBAC) study aimed at investigating the effectiveness of ESL in clinical practice, with ESL being administered as monotherapy (mono group), as only add-on to a current monotherapy (1 + group), or as add-on to ≥ 2 baseline AEDs (≥ 2 + group). In total, 237 patients were included, 35 in the mono group, 114 in the 1 +, and 88 in the ≥ 2 + group. Six-month retention rates were 93.9%, 78.0%, and 75.3% in the mono, 1 +, and ≥ 2 + group. There were 90.5%, 77.6%, and 48.3% of patients in the mono, 1 +, and ≥ 2 + groups who were responders (patients with a ≥ 50% reduction in seizure frequency at follow-up vs. baseline). Seizure freedom rates were 81.5%, 47.9%, and 23.4%, respectively. Adverse drug reactions (ADRs) occurred in 11.4% of patients of the mono, 19.3% of the 1 +, and 28.4% of patients of the ≥ 2 + group. Hyponatremia was reported as ADR in 3.4% of all patients. Although baseline variables differed considerably, with most elderly patients with tumor-related and vascular etiologies in the mono group and most patients with refractory epilepsies with pronounced use of concomitant sodium channel blockers (SCBs) in the ≥ 2 + group, retention as a measure of real-life effectiveness turned out not to be substantially different and favorable in all groups.

Background Lesional epilepsy is an important long-term sequela of stroke. Data on health-related quality of life (HrQoL) in patients with poststroke epilepsy are limited. We investigated HrQoL in patients with epilepsy after ischemic stroke and identified independent HrQoL-determinants. Methods and patients All patients with acute ischemic stroke, who were permanent residents in the district Marburg-Biedenkopf (Hessia, Germany, reference population 240,000 inhabitants) were recruited within 12 months in the population-based Marburg Stroke Register (MARSTREG). Follow-up visits were performed after 6, 12, and 24 months, and patients who developed poststroke epilepsy were identified. Data on demographics, antiepileptic drugs (AEDs), stroke severity (National Institute of Heath Stroke Scale (NIHSS), Barthel-Index, modified Rankin Scale), depression (Geriatric Depression Scale), and HrQoL (EQ-5D and EQ VAS) were collected. A multiple regression analysis was performed to identify HrQoL-determinants. Results Among the study participants (n = 374), 23 (6.1%) developed poststroke epilepsy. The HrQoL of patients with poststroke epilepsy was reduced in comparison with patients without seizures (24-month follow-up: EuroQol Visual Analogue Scale (EuroQol-VAS): 55.3 ± 10.7 versus 64.2 ± 11.4, p = 0.03). Seizure frequency, depression, and functional impairment (Barthel-Index) were identified as independent determinants of HrQoL. The adjustment of AEDs between 6-month and 24-month follow-ups resulted in decrease of seizure frequency by 40% and reduction of complications (dizziness by 27.8%, nausea by 52.2%, fatigue by 84.2%). Conclusion Lesional epilepsy is associated with decreased HrQoL in patients with stroke. We identified HrQoL-determinants, which would improve the management of patients with poststroke epilepsy. These determinants include proper adjustment of AEDs with reduction of seizure frequency, treatment of depression, and focused rehabilitation programs for poststroke epilepsy.

Body weight loss in late-life is known to occur at a very early stage of Alzheimer's disease (AD). Apolipoprotein E4 (ApoE4) represents a major genetic risk factor for AD and is linked to an increased cortical amyloid-β (Aβ) accumulation. Since the relationship between body weight, ApoE4, and AD pathology is poorly investigated, we aimed to evaluate whether ApoE4 allelic status modifies the association of body mass index (BMI) with markers of AD pathology. A total of 368 Aβ-positive cognitively healthy or mild cognitive impaired subjects had undergone [18F]-AV45-PET, [18F]-FDG-PET, and T1w-MRI examinations. Composite cortical [18F]-AV45 uptake and [18F]-FDG uptake in posterior cingulate cortex were calculated as surrogates of cortical Aβ load and glucose metabolism, respectively. Multiple linear regressions were performed to assess the relationships between these PET biomarkers with BMI, present cognitive performance, and cognitive changes over time. Multivariate analysis of covariance was conducted to test for statistical differences between ApoE4/BMI categories on the PET markers and cognitive scores. In carriers of the ApoE4 allele only, BMI was inversely associated with cortical amlyoid load (β= -0.193, p < 0.005) and recent cognitive decline (β= -0.209, p < 0.05), and positively associated with cortical glucose metabolism in an AD-vulnerable region (β= 0.145, p < 0.05). ApoE4/BMI category analyses demonstrated lower Aβ load, higher posterior cingulate glucose metabolism, improved cognitive performance, and lower progression of cognitive decline in obese ApoE4 carriers. The effect of ApoE4 in promoting the accumulation of cortical amyoid, which may itself be a driver for weight loss, may be moderated by altering leptin signaling in the hypothalamus.

Health economic studies in Parkinson's disease (PD) have become increasingly common in recent years. Because several methodologies and instruments have been used to assess cost and outcomes in PD, the Movement Disorder Society (MDS) commissioned a Task Force to assess their properties and make recommendations regarding their use. A systematic literature review was conducted to explore the use of those instruments in PD and to determine which should be selected for this review. We assessed approaches to evaluate cost of illness (COI), cost effectiveness, and cost utilities, which include the use of direct (standard gamble, time trade-off. and visual analogue scales) and indirect instruments to measure health status and utilities. No validated instruments/models were identified for the evaluation of COI or cost-effectiveness in patients with PD; therefore, no instruments in this group are recommended. Among utility instruments, only a few of these outcome instruments have been used in the PD population, and only limited psychometric data are available for these instruments with respect to PD. Because psychometric data for further utility instruments in conditions other than PD already exist, the standard gamble and time trade-off methods and the EQ-5D (a European quality-of-life health states instrument) and Health Utility Index instruments met the criteria for scales that are "recommended (with limitations)," but only the EQ-5D has been assessed in detail in PD patients. The MDS Task Force recommends further study of these instruments in the PD population to establish core psychometric properties. For the assessment of COI, the Task Force considers the development of a COI instrument specifically for PD, like that available for Alzheimer's disease. © 2013 Movement Disorder Society.

Neuroborreliosis affects the nervous system after systemic infection with the spirochete Borrelia burgdorferi. Previously, cerebral vasculitis has been regarded as an extremely rare complication of neuroborreliosis. The data on the long-term outcome in patients with cerebral vasculitis due to neuroborreliosis are limited. The objective of this study was to perform a longitudinal analysis of cases of neuroborreliosis-associated cerebral vasculitis. We recruited all patients (n = 11) diagnosed with neuroborreliosis-associated in three neurological departments in an East German region. Inclusion criteria were sudden neurological deficits, magnetic resonance (MR) imaging findings that conform to cerebral ischemia or brain infarction, intrathecal synthesis of borrelia-specific antibodies, and non-atherosclerotic pathology of brain supplying arteries. Vasculitic changes were detected by digital subtraction angiography, MR angiography and/or transcranial Doppler ultrasound. Outcomes were measured by the modified Rankin scale (mRS) and EuroQoL Index. Cerebral vasculitis is a rare complication of Lyme disease (0.3% of all cases in the endemic area). Ten out of 11 patients diagnosed with neuroborreliosis-associated vasculitis cerebral vasculitis using clinical, radiological and immunological criteria developed ischemic stroke or transient ischemic attacks (TIA), 7 patients had recurrent stroke. Vasculitic alterations could be demonstrated in 8 patients that all except one developed ischemic lesions. The median mRS was 3 (range 0-4) at admission and 2 (range 0-6) at discharge. The posterior circulation was affected in 8 of 11 patients; thrombosis of the basilar artery was detected in 2 patients, one died in the acute stage. Neuroborreliosis can cause recurrent stroke or TIA on the basis of cerebral vasculitis. Lumbar puncture is needed for detection of this potentially life-threatening condition. Early recognition and adequate therapy would possibly improve outcome.

Vitamin K antagonists, such as warfarin and phenprocoumon, are the first-line oral anticoagulants for primary and secondary prevention of cerebral embolism in patients with atrial fibrillation. Although vitamin K antagonists can significantly decrease the risk of stroke, their use is limited by several important drawbacks, such as a narrow therapeutic window, the risk of intracranial and gastrointestinal bleeding, interactions with a number of drugs and nutrients, and the need for regular laboratory tests for therapy adjustment. Currently, new oral anticoagulants, such as direct thrombin inhibitors (e.g., dabigatran) and direct factor Xa inhibitors (e.g., apixaban, rivaroxaban), are being developed and tested in clinical trials. Dabigatran and rivaroxaban were recently approved for prevention of cerebral embolism in patients with atrial fibrillation. The advantages of dabigatran in comparison to warfarin are a lower rate of major bleedings with dabigatran 110 mg bid, a better efficacy with dabigatran 150 mg bid, no clinically relevant interactions with other drugs and no need for routine coagulation monitoring. The disadvantages are the absence of antidote and the absence of routine laboratory tests for precise measurements of anticoagulant effect of direct thrombin/ factor Xa inhibitors. This review will focus on thrombin and factor Xa inhibitors, which are new and promising oral anticoagulants for the prevention of cerebral embolism. We will discuss their pharmacological and clinical properties and provide the most recent updates on their clinical trials.

Background: Alzheimer dementia (AD) and vascular dementia (VD) are the most common causes of dementia in the elderly. Depression is an important co-morbid disorder in these diseases, which is often challenging to recognize. We investigated the prevalence of depression in patients with AD and VD and estimated the influence of depression on the health-related quality of life (HrQoL) in these patients. Materials and Methods: We evaluated prevalence of depression in consecutively recruited patients with AD or VD (n= 98). Depression was diagnosed according to criteria of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and scored using the Geriatric Depression Scale. The EuroQol (EQ-5D and visual analogue scale) was applied to evaluate HrQoL. The severity of cognitive impairment was measured by the Mini-Mental State Examination (MMSE). Multiple regression analysis was used to identify factors predicting severity of depression. Results: The prevalence of depression in AD/VD was 87%. In comparison to the general population, HrQoL measured on the visual analogue scale was reduced by 54% in patients with AD/VD. In the dimension “anxiety/depression” of the EQ-5D, 81% of patients with AD/VD had moderate or severe problems. Depression showed significant association with reduced HrQoL (P < 0.01). Independent predictors of more severe depression were older age, male gender, better MMSE scores and being not married. Conclusions: Depression is a prevalent psychiatric co-morbidity in patients with AD/VD, which is often under-diagnosed being masked by cognitive impairment. Depression is a predictor of reduced HrQoL in elder people with AD/VD. Therefore, they should be screened for presence of depressive symptoms and receive adequate antidepressant treatment.

Neuromuscular disorders are rare diseases with a chronic and debilitating course. Unfortunately, data on the health-related quality of life (HRQoL) in neuromuscular diseases are limited. The objective of this multicentre cross-sectional study was to compare the HRQoL in patients with amyotrophic lateral sclerosis (ALS), facioscapulohumeral muscular dystrophy (FSHD) and myasthenia gravis (MG) and to identify the determinants of the HRQoL in these diseases. We recruited 91 consecutive outpatients with ALS (n = 37), FSHD (n = 17) or MG (n = 37) in seven specialized German health centres. The HRQoL was determined using the 36-Item Short Form Health Survey (SF-36) and the EuroQol (EQ-5D). Independent predictors of the HRQoL were identified using multiple regression analysis. The HRQoL in all domains of the SF-36, except for bodily pain, was significantly reduced. The domains related to physical health (physical functioning, physical role) were most affected. The EQ-5D-index score was most reduced in ALS (0.54) and least reduced in MG (0.89). Independent predictors of a reduced HRQoL were disease severity and depression in ALS, and disease severity, depression, older age and increased body-mass index in MG. The patterns of HRQoL-impairment in neuromuscular disorders share some common features, such as a more pronounced reduction in the HRQoL related to physical health, but there are a number of disease-specific features that should be considered in outcomes of clinical trials and treatment guidelines. In addition to the treatment of motor symptoms, greater attention should be paid to the treatment of depression, which was found to be among the independent predictors of the HRQoL in ALS and MG.

Objective: To determine the health economic burden on patients with Parkinson’s disease (PD) in Germany over a 12-month observation period and provide a comprehensive analysis of cost-driving factors. Methods and patients: Patients with PD (n = 145) were recruited from two clinical departments, two office-based neurologists and 12 GPs. Clinical evaluations were performed at baseline, 3, 6 and 12 months. Disease severity was measured using the Unified Parkinson’s Disease Rating Scale (UPDRS). Cost data were assessed based on a patient diary and via personal structured interviews at the respective time-points. Costs were calculated from the societal perspective (2009 €). Cost-driving factors were identified by multivariate regression analysis. Results: Mean annual costs totalled €20 095 per patient. Amongst direct costs, the highest expenditures (€13 158) were for drugs (€3526) and inpatient care including nursing homes (€3789). Indirect costs accounted for 34.5% (€6937) of total costs. Costs of home care provided by family accounted for 20% of direct costs. Cost-driving factors were identified for total costs (UPDRS, fluctuations, dyskinesia and younger age), direct costs (UPDRS, fluctuations), patient expenditures (UPDRS, depression) and drug costs (younger age). Conclusion: Parkinson’s disease has a chronic course with growing disability and considerable socioeconomic burden. Disease progression leads to an increasing number of patients who require costly institutionalized care. Home care is a major factor influencing patients’ families. Healthcare programmes aimed at reducing the burden of PD on society and individuals should consider cost-driving factors of PD.

Objective The aim of this study was to evaluate the direct and indirect costs in a cohort of German outpatients with Parkinson's disease (PD) and to identify major cost drivers in PD. Methods 91 PD patients were consecutively enrolled in the outpatient department of the neurological clinic at the University of Marburg, Germany. Patients had to fill out a standardised questionnaire at baseline and at a 3-month follow-up and report their health service resource utilisation for the past three months, retrospectively. In addition, information on clinical parameters of PD (UPDRS, Hoehn and Yahr stage) were assessed. For 86 patients, the direct and indirect cost data were analysed. Indirect costs were calculated by the human capital approach. Results Total costs per patient and 6-month period amounted to € 8,400 [95%CI 6,768-10,302]. Of these, 30% were indirect costs (€ 2,505 [95%CI 1,541-4,047]) and 70% were direct costs (€ 5,895 [95%CI 4,846-7,376]). The major parts of the direct costs were triggered by antiparkinsonian medication (€ 2,889 [95%CI 2,392-3,655]) and inpatient stays (hospital und rehabilitation, € 1,556 [95%CI 865-2,892]). A linear multivariate model with disease severity, disease duration, sleep disorders, psychosis and dystonia explained 24% of the variance of total costs and 33% of variance of direct costs, respectively. Conclusion Parkinson's disease imposes a high financial burden on both patient and society. A reduced health-related quality of life reflects the individual patient's impairment by PD.

Data on the incidence of Parkinson's disease (PD) and atypical parkinsonian syndromes (APS) in East European countries and Asia are limited. The objective of this prospective population-based study was to determine the incidence of PD and APS in the Russian population. The study area was a large district of Moscow with a population of 1,237,900 inhabitants. Multiple sources of case ascertainment were used to identify incident cases of PD and APS between July 2006 and December 2008. All incident cases were examined by a specialist and followed up prospectively to confirm the diagnosis. The age-standardized incidence rates per 100,000/year were 9.03 [95% confidence interval (CI) 8.01-10.15] for PD, 0.11 (95% CI 0.03-0.23) for multiple system atrophy, 0.14 (95% CI 0.08-0.21) for progressive supranuclear palsy, and 0.02 (95% CI 0.01-0.12) for corticobasal degeneration. The age-standardized male-to-female ratio of PD was 0.87 for all ages and 1.46 for those aged 60 and older. A high proportion of new cases with PD (34%) and APS (50%) had comorbid depressive symptoms. Given the rapid growth of the elderly population in Eastern Europe and Asia, the epidemiology of PD and APS in these regions should be investigated in greater depth. The incidence of PD in our study was slightly lower than in studies of Western populations and the male-to-female ratio was closer to those reported in studies from Asia. The clinical implication of our study is that it highlights the need for better diagnosis and treatment of depression in early stages of PD.

Life expectancy is increasing worldwide and the burden of Parkinson's disease (PD) is growing. There are several cost-of-illness studies for PD from Western Europe and the USA, however, data about the costs associated with PD in Eastern Europe are still lacking. The objective of this study was to evaluate direct and indirect costs in a cohort of Czech patients with idiopathic PD and to identify cost-driving factors. Study participants (n=100) were recruited from the neurological department of the Charles University in Prague. Health-economic data were collected using a "bottom-up" approach. Costs were calculated from the societal perspective and the human capital approach was used to estimate indirect costs. Czech currency was converted into 2004 Euros (EUR) and inflated to 2008 prices. Independent cost-driving factors were identified in multivariate regression analysis. Total semi-annual costs of PD were EUR 5510 (95% CI: 4470-7090) per patient. Direct costs accounted for 60% of the total costs and indirect costs for 40%. Patients' expenditures accounted for 40% of their income. Independent cost-driving factors included disease severity, motor complications, psychosis and age. In conclusion, our study demonstrates a considerable economic burden of PD in the Czech Republic. Total costs are generally lower than in Western Europe but the proportion of costs that fall on patients is higher because of lower incomes. More intensive government support for patients with chronic diseases such as PD and the development of disease-management programs that incorporate both the clinical and economic effects of PD treatment are needed.

Background/Aims: The objective of our study was to estimate the incidence of posttraumatic dissections of cervical arteries in patients with whiplash injury acquired in a car accident. Methods and Patients: We performed a retrospective analysis of medical records of 500 patients with whiplash injury acquired in car accidents between 1996 and 2005 and searched for dissections of cervical arteries occurring within 12 months after injury. Results: Eight cases of cervical arterial dissection occurred within 12 months following whiplash injury. In 7 cases (87.5%), the dissection was complicated by brain infarction. The incidence of posttraumatic dissections after whiplash injuries was much higher than the overall incidence of cervical arterial dissections in the general population (1.6 vs. 0.0041%). The risk of cerebrovascular events was still increased 4–12 months after whiplash injury (0.6 vs. 0.003075% in the general population). Conclusions: There is an increased risk of posttraumatic dissection and cerebrovascular events within 12 months after whiplash injury. Car accident is an important risk factor for arterial dissections. The victims of car accidents should be screened for arterial dissections. The results of this study should be more thoroughly investigated in a prospective trial of car accident victims as a risk factor for arterial dissections.

ZIELSETZUNG: Ziel dieser Studie war die Ermittlung der Krankheitskosten und der Versorgungssituation bei Patienten mit Parkinson-Erkrankung in Osterreich. Steigende Ausgaben im Gesundheitswesen und die Prognose der Verdopplung der Zahl der Krankheitsfalle in den nachsten 25 Jahren machen okonomische Evaluationen unerlasslich. METHODEN: Patientenbefragung von 81 Patienten mit idiopathischem Morbus Parkinson. Zur Ermittlung von direkten und indirekten Krankheitskosten wurde ein bottom up-Ansatz angewandt. Die kostentreibenden Faktoren wurden mittels multiplen Regressionsanalysen identifiziert. ERGEBNISSE: Die Gesamtkosten aus der gesellschaftlichen Perspektive belaufen sich auf 9820 € pro Patient innerhalb eines 6-Monatszeitraums. Sie bestehen zu 60% aus direkten Kosten (5910 €) und zu 40% aus indirekten Kosten (3910 €). Der groste Anteil (59%) der direkten Kosten sind Ausgaben, die die gesetzliche Krankenversicherung zu leisten hat. Der Patient hat durchschnittlich einen Selbstbehalt von ca. 810 € im 6-Monatszeitraum zu entrichten. Die jahrlichen Krankheitskosten in Osterreich werden auf ca. 320 Millionen Euro geschatzt. SCHLUSSFOLGERUNG: Morbus Parkinson stellt eine okonomische Herausforderung fur das nationale Gesundheitswesen dar. Direkte Krankheitskosten fallen zum grosten Teil zu Lasten der gesetzlichen Krankenversicherung. Bei den Patienten fallen hohe Kosten durch finanzielle Selbstbeteiligung an.

Neuromuscular disorders (NMD) are chronic devastating diseases. The aim of this multicenter cross-sectional study was to evaluate the socioeconomic impact of three NMDs in Germany. Patients (n = 107) with amyotrophic lateral sclerosis (ALS), myasthenia gravis (MG) or facioscapulohumeral muscular dystrophy (FSHD) were recruited consecutively in seven centers in Germany. The health-economic data were collected using a "bottom-up" approach consisting of comprehensive questionnaires and patient diaries. Costs were evaluated from the societal perspective in 2009 Euros (EUR). Total annual costs from the societal perspective were EUR 36,380 (95% CI 27,090-47,970) per patient in ALS, EUR 26,240 (95% CI 17,770-37,940) in FSHD and EUR 14,950 (95% CI 10,470-21,730) in MG. The main components of costs were the expenditures of health insurance and the loss of productivity of patients and their caregivers. The following independent cost-driving factors were identified: disease severity, assistance in activities of daily living (ADL), dementia and younger age in ALS, disease severity in FSHD and assistance in ADL, disease severity and assistance in ADL in MG. The socioeconomic burden of NMDs in Germany is considerable. Further studies evaluating both the health-economic and clinical effects of NMD treatment as well as disease management programs and benchmarking activities are necessary.

Background: The economic burden associated with Parkinson’s disease (PD) is increasing as the worldwide population ages. While cost-of-illness studies for PD from developed countries have recently been published, data for Eastern Europe and Asia are still lacking. Objective: To prospectively evaluate direct and indirect costs in a cohort of Russian patients with PD in order to identify cost-driving factors. Methods and Patients: We recruited 100 patients with idiopathic PD who visited the outpatient department for movement disorders of the Russian Medical State University in Moscow between October 2004 and December 2005. The Unified Parkinson’s Disease Rating Scale was used to evaluate clinical status. Economic data were collected in a ‘bottom-up’ approach and evaluated from the societal perspective. Indirect costs were estimated using a human capital approach. Russian currency was converted into €, year 2005 values, using the purchasing power parity. All costs were then inflated to €, year 2008 values, using the Medical Care Component of the Consumer Price Index. Independent cost predictors were identified by means of multivariate regression analyses. Results: From the societal perspective, total costs per patient over 6 months amounted to h2620 (95%CI 2050, 3200), with direct costs accounting for 67% and indirect costs for 33% of the total. Patients’ expenditures accounted for 43% of their private income. The primary burden on patients was due to informal care and drugs. Only 10% of home care was provided by the formal service sector. Costs for the nation are estimated at €1.1 billion per year. Conclusion: The economic burden of PD in Russia is considerable, especially when taking into account low private incomes. Further development of a formal care system and better reimbursement systems for drugs are necessary in Russia.

The costs of acute stroke care, length of hospital stay (LOS), and outcome in patients with cardioembolic stroke or cardioembolic transient ischemic attacks (TIA) were investigated with the aim of estimating the clinical and health-economic impacts of cerebral cardioembolism. The study population consisted of 511 consecutive patients with the diagnosis of ischemic stroke (n = 379) or TIA (n = 132) treated at the Department of Neurology, Philipps University, Marburg. Cerebral cardioembolism was defined according to the criteria of the Cerebral Embolism Task Force. Clinical status was assessed by means of Barthel index (BI) and modified Rankin Scale. Costs were calculated using a bottom-up approach. All costs (in Euros) were inflated to the 2008 level. Compared to non-cardioembolic stroke (n = 278) patients, patients who had suffered cardioembolic stroke (n = 101) had more severe clinical deficits on admission (BI 46.3 +/- 27.0 vs. 59.3 +/- 34.1; P0.01), worse recovery (BI on discharge 59.2 +/- 28.9 vs. 73.1 +/- 33.4; P0.01), and increased LOS (12.6 +/- 5.7 vs. 10.0 +/- 7.8 days; P0.01). The latter also required a relatively higher daily resource utilization due to increased expenses for personnel and diagnostics. Mean costs of acute care for patients with cardioembolic stroke [euro 4890 per patient (95% confidence interval 4460-5200)] were significantly higher than those for patients with non-cardioembolic stroke [euro 3550 (95% confidence interval 3250-3850); P0.01]. The clinical and health-economic impact of cardiogenic cerebral embolism on stroke care is considerable. Patients with cardioembolic stroke/TIA are more severely impaired, and they require longer hospital treatment and increased resource utilization. Costs of acute care of cardioembolic stroke/TIA patients may exceed those of non-cardioembolic stroke/TIA by up to 40%.

Der Schlaganfall verursacht nicht nur hohe Akutbehandlungskosten, sondern auch erhebliche Langzeitkosten durch bleibende Behinderung, Arbeitsausfall und Folgeerkrankungen, die bislang nur wenig untersucht wurden. An einer krankenhausbasierten Kohorte von 151 Patienten mit Schlaganfall oder transitorisch ischamischen Attacken (TIA) wurden am Ende des 4. Jahres nach Erkrankungsbeginn eine Nachuntersuchung und Befragung durchgefuhrt. Die Kostenberechnung erfolgte mithilfe eines Bottom-up-Ansatzes. Unterschieden wurden direkte medizinische und nichtmedizinische Kosten, indirekte Kosten sowie Eigenleistungen. Die schlaganfallunabhangigen Kosten (4610±9310 Euro/Person, Mittelwert ± Standardabweichung) wurden von den ubrigen Gesamtkosten getrennt. Die schlaganfallassoziierten Gesamtkosten betrugen im 4. Jahr nach Schlaganfall/TIA 7670±10250 Euro pro Patient. Davon waren den direkten Kosten 56% (4320±5740 Euro), den indirekten Kosten 31% (2350±2710 Euro) und den Eigenleistungen 13% (1000±4100 Euro) zuzuordnen. Die in Deutschland entstehenden Langzeitkrankheitskosten werden auf ca. 3 Mrd. Euro pro Jahr geschatzt. Die betrachtlichen Langzeitbehandlungskosten im 4. Jahr nach Schlaganfall/TIA werden zum grosten Teil durch direkte Krankheitskosten hervorgerufen und stellen eine okonomische Herausforderung fur unser Gesundheitswesen dar. Die Patienten sind in erheblichem Mase an den Kosten durch Eigenleistungen beteiligt.

Background Abdominal obesity is a well-recognized cardiovascular risk factor. Conflicting data concerning its significance with respect to stroke have been discussed in recent years. The objective of this study was to analyze the association between anthropometric parameters and the risk of stroke and transient ischemic attacks (TIAs) in German primary care. Methods Patient recruitment in this large-scale epidemiological study was performed in 3188 representative primary care offices in Germany. Among 6980 study participants, 1745 patients with a history of stroke or TIA were identified and matched for age and gender with 5235 regional controls. Associations between standard anthropometric measures such as body mass index (BMI), waist-to-hip ratio, waist circumference, waist-to-height ratio, and cerebrovascular risk were investigated using logistic regression analysis with adjustment for age, gender, and vascular risk factors. Results BMI showed no significant associations with the risk of stroke or TIA in any of the applied mathematical models. Markers of abdominal obesity were associated with an increased risk of stroke or TIA in the unadjusted model (waist circumference: odds ratio [OR] 1.15; 95% confidence interval [CI], 1.00-1.32; waist-to-hip ratio: OR 1.21; 95% CI, 1.05-1.38; waist-to-height ratio: OR 1.25; 95% CI, 1.09-1.44, comparisons between top and bottom tertiles). After adjustment for vascular risk factors, all associations were insignificant. Conclusions Abdominal obesity is a stronger predictor of risk of stroke or TIA than BMI. However, the association between abdominal obesity and the risk of stroke or TIA is not independent of other vascular risk factors. Stroke-related weight changes should be considered in longitudinal studies examining the role of obesity in cerebrovascular disease.

Obesity is one of the major risk factors of vascular diseases, and its prevalence is increasing worldwide. In the past decade, progress has been made in the understanding of genetic determinants of obesity and obesity-associated diseases. Genome-wide association studies identified a number of genetic variants associated with obesity. In addition to common variants, FTO and MC4R, new loci, such as TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2, and NEGR1 have been detected. In the past years, abdominal obesity has been shown to be a more important vascular risk factor than the body mass index. In the context of vascular risk assessment, identification of genetic polymorphisms associated with accumulation of visceral fat is of special importance. Some polymorphisms associated with abdominal obesity, such as variants of gene encoding microsomal triglyceride transfer protein, have been already discovered. In this chapter, we provide a review of genetic determinants of obesity and discuss their role in obesity-related vascular diseases.

Summary Background Three small trials suggest that intravenous immunoglobulin can affect biomarkers and symptoms of mild-to-moderate Alzheimer's disease. We tested the safety, effective dose, and infusion interval of intravenous immunoglobulin in such patients. Methods We did a multicentre, placebo-controlled phase 2 trial at seven sites in the USA and five in Germany. Participants with probable Alzheimer's disease aged 50–85 years were randomly assigned (by a computer-generated randomisation sequence, with block sizes of eight) to infusions every 4 weeks (0·2, 0·5, or 0·8 g intravenous immunoglobulin per kg bodyweight, or placebo) or infusions every 2 weeks (0·1, 0·25, or 0·4 g/kg, or placebo). Patients, caregivers, investigators assessing outcomes, and staff at imaging facilities and the clinical research organisation were masked to treatment allocation, but dispensing pharmacists, the statistician, and the person responsible for final PET analyses were not. Treatment was masked with opaque pouches and infusion lines. The primary endpoint was median area under the curve (AUC) of plasma amyloid β (Aβ) 1–40 between the last infusion and the final visit (2 weeks or 4 weeks depending on infusion interval) in the intention-to-treat population. The trial is registered at ClinicalTrials.gov (NCT00812565) and controlled-trials.com (ISRCTN64846759). Findings 89 patients were assessed for eligibility, of whom 58 were enrolled and 55 included in the primary analysis. Median AUC of plasma Aβ 1–40 was not significantly different for intravenous immunoglobulin compared with placebo for five of the six intervention groups (–18·0 [range −1347·0 to 1068·5] for 0·2 g/kg, −364·3 [–5834·5 to 1953·5] for 0·5 g/kg, and −351·8 [–1084·0 to 936·5] for 0·8 g/kg every 4 weeks vs −116·3 [–1379·0 to 5266·0] for placebo; and −13·8 [–1729·0 to 307·0] for 0·1 g/kg, and −32·5 [–1102·5 to 451·5] for 0·25 g/kg every 2 weeks vs 159·5 [51·5 to 303·0] for placebo; p>0·05 for all). The difference in median AUC of plasma Aβ 1–40 between the 0·4 g/kg every 2 weeks group (47·0 [range −341·0 to 72·5]) and the placebo group was significant (p=0·0216). 25 of 42 (60%) patients in the intervention group versus nine of 14 (64%) receiving placebo had an adverse event. Four of 42 (10%) patients in the intravenous immunoglobulin group versus four of 14 (29%) receiving placebo had a serious adverse event, including one stroke in the intervention group. Interpretation Intravenous immunoglobulin may have an acceptable safety profile. Our results did not accord with those from previous studies. Longer trials with greater power are needed to assess the cognitive and functional effects of intravenous immunoglobulin in patients with Alzheimer's disease. Funding Octapharma AG.

Background Clinical studies employ the Unified Parkinson’s Disease Rating Scale (UPDRS) to measure the severity of Parkinson’s disease. Evaluations often fail to consider the health-related quality of life (HrQoL) or apply disease-specific instruments. Health-economic studies normally use estimates of utilities to calculate quality-adjusted life years. We aimed to develop an estimation algorithm for EuroQol- 5 dimensions (EQ-5D)-based utilities from the clinical UPDRS or disease-specific HrQoL data in the absence of original utilities estimates. Methods Linear and fractional polynomial regression analyses were performed with data from a study of Parkinson’s disease patients (n=138) to predict the EQ-5D index values from UPDRS and Parkinson’s disease questionnaire eight dimensions (PDQ-8) data. German and European weights were used to calculate the EQ-5D index. The models were compared by R2, the root mean square error (RMS), the Bayesian information criterion, and Pregibon’s link test. Three independent data sets validated the models. Results The regression analyses resulted in a single best prediction model (R2: 0.713 and 0.684, RMS: 0.139 and 13.78 for indices with German and European weights, respectively) consisting of UPDRS subscores II, III, IVa-c as predictors. When the PDQ-8 items were utilised as independent variables, the model resulted in an R2 of 0.60 and 0.67. The independent data confirmed the prediction models. Conclusion The best results were obtained from a model consisting of UPDRS subscores II, III, IVa-c. Although a good model fit was observed, primary EQ-5D data are always preferable. Further validation of the prediction algorithm within large, independent studies is necessary prior to its generalised use.

Objective: Depressive disorders pose a major challenge to healthcare in the countries of the former Soviet Union. The objective of the current study was to evaluate health-related quality of life (HrQoL) and its determinants in outpatients with major depressive disorder in an urban Russian population. Methods: We consecutively recruited 100 urban Russian outpatients with major depression and 100 non-depressed controls who were matched for age and sex. The severity of their depression was assessed using the Hamilton Depression Rating Scale (HDRS). HrQoL was evaluated using the EuroQol (the EQ-5D and the visual analogue scale, EQ VAS). Independent determinants of HrQoL were identified using multiple regression analysis. Results: The mean EQ VAS score was 43.0 + 27.4 in patients with depression compared to 81.4 + 14.7 in the controls ( p < 0.01). Out of the domains of the EQ-5D, “anxiety/depression,” “usual activities,” and “self-care” were the most impaired. Independent determinants of reduced HrQoL were: severity of depression according to the HDRS; violent suicide attempts; suicide attempts in the past; and drug addiction. Conclusions: HrQoL is considerably reduced in Russians with major depression. The disease-specific patterns of HrQoL impairment and the independent determinants of HrQoL identified in our study could be addressed in focused healthcare programs and clinical trials. Comorbid drug addiction as a determinant of HrQoL should receive greater attention in the management of depressive disorders in urban Russian populations.

Health economic studies in Parkinson's disease (PD) have become increasingly common in recent years. Because several methodologies and instruments have been used to assess cost and outcomes in PD, the Movement Disorder Society (MDS) commissioned a Task Force to assess their properties and make recommendations regarding their use. A systematic literature review was conducted to explore the use of those instruments in PD and to determine which should be selected for this review. We assessed approaches to evaluate cost of illness (COI), cost effectiveness, and cost utilities, which include the use of direct (standard gamble, time trade-off. and visual analogue scales) and indirect instruments to measure health status and utilities. No validated instruments/models were identified for the evaluation of COI or cost-effectiveness in patients with PD; therefore, no instruments in this group are recommended. Among utility instruments, only a few of these outcome instruments have been used in the PD population, and only limited psychometric data are available for these instruments with respect to PD. Because psychometric data for further utility instruments in conditions other than PD already exist, the standard gamble and time trade-off methods and the EQ-5D (a European quality-of-life health states instrument) and Health Utility Index instruments met the criteria for scales that are "recommended (with limitations)," but only the EQ-5D has been assessed in detail in PD patients. The MDS Task Force recommends further study of these instruments in the PD population to establish core psychometric properties. For the assessment of COI, the Task Force considers the development of a COI instrument specifically for PD, like that available for Alzheimer's disease.