Kurtis M.M.,Hospital Ruber International |
Rodriguez-Blazquez C.,CIBER ISCIII |
Martinez-Martin P.,CIBER ISCIII |
Martinez-Martin P.,Carlos III Institute of Health
Parkinsonism and Related Disorders | Year: 2013
Background: The association between sleep disorders and other non-motor symptoms (NMS) in Parkinson's disease (PD) has been scarcely investigated. Objective: To describe the prevalence of insomnia and hypersomnia in PD and analyze their relationship with other NMS. Methods: Cross-sectional, multicenter study including 388 PD patients evaluated with Hoehn and Yahr, Clinical Impression of Severity Index for PD, Scales for Outcomes in Parkinson's Disease (SCOPA)-Sleep(S), SCOPA-Cognition, SCOPA-Psychiatric Complications, SCOPA-Autonomic, Hospital Anxiety and Depression Scale, and fatigue and pain visual analogue scales. Spearman correlation coefficients, Mann-Whitney test and multiple linear regression analysis were applied. Results: Mean age (54% male) was 65.9±11.2 years old, with disease duration of 8.1±6.0 years and median HY=2 (range: 1-5). Mean SCOPA-S nocturnal sleep (NS) was 5.4±4.0 (range: 0-15), daytime sleepiness (DS) was 3.76±3.04 (range: 0-15). Most of the sample declared nocturnal or daytime sleep problems (87.4%). Weak-to-moderate correlations were found between sleep disturbances and other NMS (range: 0.14-0.37). SCOPA-S subscales showed higher scores with the presence of most other NMS such as psychiatric complications and autonomic dysfunctions (p<0.05). Regression models showed that fatigue, depression, urinary, cardiovascular, and thermoregulatory dysfunctions were significant determinants of SCOPA-NS score (variance: 23%); cognitive impairment, urinary, cardiovascular, and pupillomotor disorders influenced SCOPA-DS score (variance: 14%). Conclusions: Insomnia and daytime sleepiness are extremely prevalent in PD. Depression, fatigue, cognitive impairment, cardiovascular, urinary and thermoregulatory dysfunctions may contribute to insomnia/hypersomnia. This is the first clinical study to relate cardiovascular and thermoregulatory dysfunctions with sleep in PD. © 2013 Elsevier Ltd.
Gil-Nagel A.,Hospital Ruber International |
Brodie M.J.,Epilepsy Unit |
Leroy R.,Neurological Clinic of Texas |
Cyr T.,Valeant Pharmaceuticals International |
And 4 more authors.
Epilepsy Research | Year: 2012
Interim results of two open-label extension studies assessed ezogabine/retigabine safety and tolerability for partial-onset seizures. At data cutoff, 336 (60%) patients received ≥12 months' open-label ezogabine/retigabine. The most common TEAEs included dizziness (22%), somnolence (19%), headache (14%), and fatigue (10%). Change in seizure frequency from baseline (median reduction, 53%) and responder rate (52.5%) was maintained in patients remaining on ezogabine/retigabine. Continuous 6-month and 12-month seizure-free rates for ezogabine/retigabine exposures ≥12 months were 13.1% and 7.1%, respectively. © 2012.
Brodie M.J.,Epilepsy Unit |
Lerche H.,University of Ulm |
Lerche H.,University of Tübingen |
Gil-Nagel A.,Hospital Ruber International |
And 5 more authors.
Neurology | Year: 2010
Objective: This study assessed the efficacy and safety of the neuronal potassium channel opener ezogabine (US adopted name; EZG)/retigabine (international nonproprietary name; RTG) as adjunctive therapy for refractory partial-onset seizures. Methods: This was a multicenter, randomized, double-blind, placebo-controlled trial in adults with ≥4 partial-onset seizures per month receiving 1 to 3 antiepileptic drugs. EZG (RTG) or placebo, 3 times daily, was titrated to 600 or 900 mg/d over 4 weeks, and continued during a 12-week maintenance phase. Median percentage seizure reductions from baseline and responder rates (≥50% reduction in baseline seizure frequency) were assessed. Results: The intention-to-treat population comprised 538 patients (placebo, n = 179; 600 mg, n = 181; 900 mg, n = 178), 471 of whom (placebo, n = 164; 600 mg, n = 158; 900 mg, n = 149) entered the maintenance phase. Median percentage seizure reductions were greater in EZG (RTG)-treated patients (600 mg, 27.9%, p = 0.007; 900 mg, 39.9%, p < 0.001) compared with placebo (15.9%). Responder rates were higher in EZG (RTG)-treated patients (600 mg, 38.6%, p < 0.001; 900 mg, 47.0%, p < 0.001) than with placebo (18.9%). Treatment discontinuations due to adverse events (AEs) were more likely with EZG (RTG) than with placebo (placebo, 8%; 600 mg, 17%, 900 mg, 26%). The most commonly reported (>10%) AEs in the placebo, EZG (RTG) 600 mg/d, and EZG (RTG) 900 mg/d groups were dizziness (7%, 17%, 26%), somnolence (10%, 14%, 26%), headache (15%, 11%, 17%), and fatigue (3%, 15%, 17%). Conclusions: In this dose-ranging, placebo-controlled trial, adjunctive EZG (RTG) was effective and generally well tolerated in adults with refractory partial-onset seizures. Copyright © 2010 by AAN Enterprises, Inc.
PubMed | Niguarda Hospital, University of Strasbourg, Moscow Research and Clinical Center for Neuropsychiatry, Vilnius University and 22 more.
Type: | Journal: Epilepsia | Year: 2017
We explored the current practice with respect to the neuropsychological assessment of surgical epilepsy patients in European epilepsy centers, with the aim of harmonizing and establishing common standards. Twenty-six epilepsy centers and members of E-PILEPSY (a European pilot network of reference centers in refractory epilepsy and epilepsy surgery), were asked to report the status of neuropsychological assessment in adults and children via two different surveys. There was a consensus among these centers regarding the role of neuropsychology in the presurgical workup. Strong agreement was found on indications (localization, epileptic dysfunctions, adverse drugs effects, and postoperative monitoring) and the domains to be evaluated (memory, attention, executive functions, language, visuospatial skills, intelligence, depression, anxiety, and quality of life). Although 186 different tests are in use throughout these European centers, a core group of tests reflecting a moderate level of agreement could be discerned. Variability exists with regard to indications, protocols, and paradigms for the assessment of hemispheric language dominance. For the tests in use, little published evidence of clinical validity in epilepsy was provided. Participants in the survey reported a need for improvement concerning the validity of the tests, tools for the assessment of everyday functioning and accelerated forgetting, national norms, and test co-normalization. Based on the present survey, we documented a consensus regarding the indications and principles of neuropsychological testing. Despite the variety of tests in use, the survey indicated that there may be a core set of tests chosen based on experience, as well as on published evidence. By combining these findings with the results of an ongoing systematic literature review, we aim for a battery that can be recommended for the use across epilepsy surgical centers in Europe.
Porter R.J.,University of Pennsylvania |
Burdette D.E.,Ford Motor Company |
Gil-Nagel A.,Hospital Ruber International |
Hall S.T.,Valeant Pharmaceuticals International |
And 3 more authors.
Epilepsy Research | Year: 2012
We assessed the efficacy and tolerability of retigabine (RTG; international non-proprietary name)/ezogabine (EZG; US adopted name) as adjunctive therapy in adults with partial-onset seizures in an integrated analysis of three trials. Studies 205, 301 (NCT00232596), and 302 (NCT00235755) were randomized, double-blind, placebo-controlled studies in adults having ≥4 partial-onset seizures per 28 days and receiving 1-3 antiepileptic drugs with/without vagus nerve stimulator. Patients underwent titration to RTG/EZG 600, 900, or 1200. mg/day or to placebo followed by 8 or 12 weeks maintenance. For efficacy analyses, placebo was compared with RTG/EZG 600 and 900. mg/day in Studies 205 and 302, and RTG/EZG 1200. mg/day in Studies 205 and 301. Responder rates (≥50% reduction in baseline seizure frequency) were 35% and 45% for RTG/EZG 600 and 900. mg/day, respectively (placebo = 21%; p< 0.001), and 50% for RTG/EZG 1200. mg/day (placebo = 24%, p< 0.001). Reductions in 28-day total partial-seizure frequency (medians: placebo = 14%; 600. mg/day = 26%, p= 0.003; 900. mg/day = 37%, p< 0.001; placebo = 15%; 1200. mg/day = 39%, p< 0.001) were significantly greater with all RTG/EZG doses vs. placebo from baseline to the double-blind phase, and similarly during the maintenance phase. The most commonly reported (>10%) treatment-emergent adverse events were dizziness, somnolence, headache, and fatigue. RTG/EZG demonstrated efficacy and was generally tolerated as adjunctive therapy in adults with partial-onset seizures in this integrated analysis. © 2012 Elsevier B.V..
Gil-Nagel A.,Hospital Ruber International |
Elger C.,University of Bonn |
Ben-Menachem E.,Sahlgren University Hospital |
Halasz P.,Experimental Medical Research Institute |
And 8 more authors.
Epilepsia | Year: 2013
Purpose: To evaluate the efficacy and safety profile of eslicarbazepine acetate (ESL) added to stable antiepileptic therapy in adults with partial-onset seizures. Methods: Data from 1,049 patients enrolled from 125 centers, in 23 countries, in three phase III double-blind, randomized, placebo-controlled studies were pooled and analyzed. Following a 2-week titration period, ESL was administered at 400 mg, 800 mg, and 1,200 mg once-daily doses for 12 weeks. Key Findings: Seizure frequency was significantly reduced with ESL 800 mg (p < 0.0001) and 1,200 mg (p < 0.0001) compared to placebo. Median relative reduction in seizure frequency was, respectively, 35% and 39% (placebo 15%) and responder rate was 36% and 44% (placebo 22%). ESL was more efficacious than placebo regardless of gender, geographic region, epilepsy duration, age at time of diagnosis, seizure type, and number and type of concomitant antiepileptic drugs (AEDs). Incidence of adverse events (AEs) and AEs leading to discontinuation were dose dependent. AEs occurred mainly during the first weeks of treatment, with no difference between groups after 6 weeks. Most common AEs (>10% patients) were dizziness, somnolence, and headache. The incidence of AEs in ESL groups compared to placebo was generally consistent among different subpopulations. Significance: Once-daily ESL 800 mg and 1,200 mg showed consistent results across all efficacy and safety end points. Results were independent of study population characteristics and type and number of concomitant AEDs. © 2012 International League Against Epilepsy.
Garcia-Escudero J.B.,Hospital Ruber International |
Trillos P.M.H.,Hospital Ruber International
PLoS ONE | Year: 2015
Background: Autologous conditioned serum (ACS) is an autologous blood product that has shown efficacy against knee osteoarthritis (OA) in randomized controlled trials. However, there are few reports of its effectiveness in everyday practice. Here, we report clinical efficacy results from a two-year prospective observational study of patients with highly symptomatic knee OA who received ACS in conjunction with physiotherapy. Methods: 118 patients with unilateral knee OA (Kellgren-Lawrence grades I-IV), who were candidates for surgery but instead chose conservative treatment, were treated with a combination of four intra-articular injections of ACS (2 mL each) once weekly over four weeks and subsequent physiotherapy applied 4 weeks after ACS injection. Main endpoints of the study were pain (Numeric Rating Scale [NRS]) assessed at 0, 3, 6, 12 and 24 months, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) global score, assessed at 0 and 24 months. The effect size (Cohen's d) was calculated for pain and WOMAC outcomes, with effect sizes >0.8 considered large. Results: By 3 months, there were significant improvements in pain (NRS) from baseline (-63.0%, p<0.001), which were maintained over 24 months. Mean WOMAC global score was reduced at 24 months compared to baseline (-56.9%, p<0.001), as were WOMAC subscores of pain (-86.0%, p<0.001) and function (-51.3%, p<0.001). Effect sizes for pain (>5) and WOMAC improvement (8.0-13.6) were very large. Only one patient received total knee joint replacement during the study. Clinical improvement did not correlate with gender, age, Kellgren-Lawrence grade, or body mass index. Conclusions: Treatment with ACS and physiotherapy produced a rapid decline in pain, which was sustained for the entire two years of the study. This was accompanied by a large improvement in WOMAC scores at two years. These results confirm that ACS combined with physiotherapy is an effective treatment for OA of the knee. © 2015 Baselga García-Escudero, Miguel Hernández Trillos.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
A White Paper on the medical and social needs of people with epilepsy and intellectual disability: The Task Force on Intellectual Disabilities and Epilepsy of the International League Against Epilepsy
Kerr M.,Institute of Psychiatric Medicine and Clinical Neurosciences |
Linehan C.,Trinity College Dublin |
Linehan C.,University College Dublin |
Linehan C.,University of Kent |
And 6 more authors.
Epilepsia | Year: 2014
This White Paper builds on the publication of the International League Against Epilepsy (ILAE) and International Bureau for Epilepsy (IBE) report "Listening for a change - medical and social needs of people with intellectual disability who have epilepsy" (Listening for a change the medical and social needs of people with epilepsy and intellectual disability, ILAE, 2013). The Paper presents an overview of the recommendations of the report, which aim to improve the health and social care of this important population of people with epilepsy worldwide. Actions in four domains are indicated: (1) the development of standards and initiatives that would enhance diagnosis, pathways to investigation, and treatment; (2) the development of guidelines for treatment, specifically best practice in the management of antiepileptic drugs including rescue medication; (3) the development of standards for primary care, multidisciplinary teamwork, and clinical consultations, with emphasis on the need to enhance communication and improve access to information; and (4) the enhancement of links among different stakeholders including medical services, educational establishments, employment services, organizations providing opportunities for social engagement, and family members. The breadth of needs of this population is a challenge to the epilepsy world, spanning all the professional groupings, care providers, and the research modalities in epilepsy. © Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.
PubMed | University of Bonn, Hospital Ruber International, Epilepsy Center for Children and Adolescents, Evangelisches Krankenhaus Bielefeld and 4 more.
Type: Journal Article | Journal: Brain pathology (Zurich, Switzerland) | Year: 2016
The histopathological spectrum of human epileptogenic brain lesions is widespread including common and rare variants of cortical malformations. However, 2-26% of epilepsy surgery specimens are histopathologically classified as nonlesional. We hypothesized that these specimens include also new diagnostic entities, in particular when presurgical magnetic resonance imaging (MRI) can identify abnormal signal intensities within the anatomical region of seizure onset. In our series of 1381 en bloc resected epilepsy surgery brain specimens, 52 cases could not be histopathologically classified and were considered nonlesional (3.7%). An increase of Olig2-, and PDGFR-alpha-immunoreactive oligodendroglia was observed in white matter and deep cortical layers in 22 of these patients (42%). Increased proliferation activity as well as heterotopic neurons in white matter were additional histopathological hallmarks. All patients suffered from frontal lobe epilepsy (FLE) with a median age of epilepsy onset at 4 years and 16 years at epilepsy surgery. Presurgical MRI suggested focal cortical dysplasia (FCD) in all patients. We suggest to classify this characteristic histopathology pattern as mild malformation of cortical development with oligodendroglial hyperplasia (MOGHE). Further insights into pathomechanisms of MOGHE may help to bridge the diagnostic gap in children and young adults with difficult-to-treat FLE.
PubMed | Hospital Ruber International
Type: Journal Article | Journal: PloS one | Year: 2015
Autologous conditioned serum (ACS) is an autologous blood product that has shown efficacy against knee osteoarthritis (OA) in randomized controlled trials. However, there are few reports of its effectiveness in everyday practice. Here, we report clinical efficacy results from a two-year prospective observational study of patients with highly symptomatic knee OA who received ACS in conjunction with physiotherapy.118 patients with unilateral knee OA (Kellgren-Lawrence grades I-IV), who were candidates for surgery but instead chose conservative treatment, were treated with a combination of four intra-articular injections of ACS (2 mL each) once weekly over four weeks and subsequent physiotherapy applied 4 weeks after ACS injection. Main endpoints of the study were pain (Numeric Rating Scale [NRS]) assessed at 0, 3, 6, 12 and 24 months, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) global score, assessed at 0 and 24 months. The effect size (Cohens d) was calculated for pain and WOMAC outcomes, with effect sizes >0.8 considered large.By 3 months, there were significant improvements in pain (NRS) from baseline (-63.0%, p<0.001), which were maintained over 24 months. Mean WOMAC global score was reduced at 24 months compared to baseline (-56.9%, p<0.001), as were WOMAC subscores of pain (-86.0%, p<0.001) and function (-51.3%, p<0.001). Effect sizes for pain (>5) and WOMAC improvement (8.0-13.6) were very large. Only one patient received total knee joint replacement during the study. Clinical improvement did not correlate with gender, age, Kellgren-Lawrence grade, or body mass index.Treatment with ACS and physiotherapy produced a rapid decline in pain, which was sustained for the entire two years of the study. This was accompanied by a large improvement in WOMAC scores at two years. These results confirm that ACS combined with physiotherapy is an effective treatment for OA of the knee.