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Hospital de Órbigo, Spain

Benito-Leon J.,University Hospital 12 Of Octubre | Benito-Leon J.,CIBER ISCIII | Benito-Leon J.,Complutense University of Madrid | Louis E.D.,Yale University | And 10 more authors.
Medicine (United States) | Year: 2015

Essential tremor (ET) has been associated with a spectrum of clinical features, with both motor and nonmotor elements, including cognitive deficits. We employed resting-state functional magnetic resonance imaging (fMRI) to assess whether brain networks that might be involved in the pathogenesis of nonmotor manifestations associated with ET are altered, and the relationship between abnormal connectivity and ET severity and neuropsychological function. Resting-state fMRI data in 23 ET patients (12 women and 11 men) and 22 healthy controls (HC) (12 women and 10 men) were analyzed using independent component analysis, in combination with a "dualregression" technique, to identify the group differences of resting-state networks (RSNs) (default mode network [DMN] and executive, frontoparietal, sensorimotor, cerebellar, auditory/language, and visual networks). All participants underwent a neuropsychological and neuroimaging session, where resting-state data were collected. Relative to HC, ET patients showed increased connectivity in RSNs involved in cognitive processes (DMN and frontoparietal networks) and decreased connectivity in the cerebellum and visual networks. Changes in network integrity were associated not only with ET severity (DMN) and ET duration (DMN and left frontoparietal network), but also with cognitive ability.Moreover, in at least 3 networks (DMN and frontoparietal networks), increased connectivity was associated with worse performance on different cognitive domains (attention, executive function, visuospatial ability, verbal memory, visual memory, and language) and depressive symptoms. Further, in the visual network, decreased connectivity was associated with worse performance on visuospatial ability. ET was associated with abnormal brain connectivity in major RSNs that might be involved in both motor and nonmotor symptoms. Our findings underscore the importance of examining RSNs in this population as a biomarker of disease. © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Labiano-Fontcuberta A.,University Hospital 12 Of Octubre | Mato-Abad V.,Rey Juan Carlos University | Alvarez-Linera J.,Hospital Ruber International | Hernandez-Tamames J.A.,Rey Juan Carlos University | And 7 more authors.
Medicine (United States) | Year: 2016

The unanticipated magnetic resonance imaging (MRI) detection in the brain of asymptomatic subjects of white matter lesions suggestive of multiple sclerosis has recently been named as radiologically isolated syndrome (RIS). The pathophysiological processes of RIS remain largely unknown and questions as to whether gray matter alterations actually occur in this entity are yet to be investigated in more detail. By means of a 3 T multimodal MRI approach, we searched for cortical and deep gray matter changes in a cohort of RIS patients. Seventeen RIS patients, 17 clinically isolated syndrome (CIS) patients (median disease duration from symptom onset=12 months), and 17 healthy controls underwent MRI and neuropsychological testing. Normalized deep gray matter volumes and regional cortical thickness were assessed using FreeSurfer. SIENAX was used to obtain normalized global and cortical brain volumes. Voxelwise morphometry analysis was performed by using SPM8 software to localize regions of brain tissue showing significant changes of fractional anisotropy or mean diffusivity. Although no differences were observed between CIS and healthy controls groups, RIS patients showed significantly lower normalized cortical volume (673±27.07 vs 641±35.88 [cm3±103, Tukey P test=0.009) and mean thalamic volume (0.0051±0.4 vs 0.0046±0.4 mm, P=0.014) compared with healthy controls. RIS patients also showed significant thinning in a number of cortical areas, that were primarily distributed in frontal and temporal lobes (P<0.05, uncorrected). Strong correlations were observed between T2-white matter lesion volume and regional cortical thickness (rho spearman ranging from 0.60 to 0.80). Our data suggest that white matter lesions on T2-weighted images are not the only hallmark of RIS. Future longitudinal studies with larger samples are warranted to better clarify the effect of RIS-related white matter lesions on gray matter tissue. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.

Labiano-Fontcuberta A.,University Hospital | Mato-Abad V.,Rey Juan Carlos University | Alvarez-Linera J.,Hospital Ruber International | Hernandez-Tamames J.A.,Rey Juan Carlos University | And 7 more authors.
Medicine (United States) | Year: 2016

To date, it remains largely unknown whether there is in radiologically isolated syndrome (RIS) brain damage beyond visible T2 white matter lesions. We used single- voxel proton magnetic resonance spectroscopy and diffusion tensor imaging (3 T MRI) to analyze normal-appearing brain tissue regions in 18 RIS patients and 18 matched healthy controls. T2-hyperintense lesion volumes and structural brain volumes were also measured. The absolute metabolite concentrations and ratios of total N-acetylaspartate+N-acetylaspartyl glutamate (NAA), choline-containing compounds, myoinositol, and glutamine-glutamate complex to creatine were calculated. Spectral analysis was performed by LCModel. Voxelwise morphometry analysis was performed to localize regions of brain tissue showing significant changes of fractional anisotropy or mean diffusivity. Compared with healthy controls, RIS patients did not show any significant differences in either the absolute concentration of NAA or NAA/Cr ratio in mid-parietal gray matter. A trend toward lower NAA concentrations (-3.35%) was observed among RIS patients with high risk for conversion to multiple sclerosis. No differences in the other metabolites or their ratios were observed. RIS patients showed lower fractional anisotropy only in clusters overlapping lesional areas, namely in the cingulate gyrus bilaterally and the frontal lobe subgyral bilaterally (P < 0.001). Normalized brain and cortical volumes were significantly lower in RIS patients than in controls (P = 0.01 and P = 0.03, respectively). Our results suggest that in RIS, global brain and cortical atrophy are not primarily driven by significant occult microstructural normal appearing brain damage. Longitudinal MRI studies are needed to better understand the pathological processes underlying this novel entity. © 2016 the Author(s).

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.

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..

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