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Molinuevo J.L.,Hospital Clinic iversitari Of Barcelona | Molinuevo J.L.,Institute dInvestigacio Biomedica August Pi i Sunyer | Gomez-Anson B.,Hospital Of La Santa Creu I Sant Pau | Monte G.C.,Hospital Of La Santa Creu I Sant Pau | And 4 more authors.
Archives of Gerontology and Geriatrics | Year: 2011

This study describes the cognitive profile of Prd-AD, the neuropsychological tests that may predict progression to dementia, and to study their brain structural correlates. We enrolled 24 stable amnesics who did not develop dementia after two years follow-up; 27 patients were considered as Prd-AD, in the initial visit, since they fulfilled NINCDS-ADRDA criteria after two years; 31 Alzheimer's disease (AD) patients and 27 controls (CTR). Structural magnetic resonance imaging (MRI), as well as a neuropsychological battery was performed at the initial visit. The key findings were: Prd-AD patients were characterized by prominent episodic memory dysfunction and minimal semantic memory and executive dysfunction. Semantic fluency test (Sem-Flu), delayed text memory test (Del-text-mem) and memory alteration test (M@T) (including both episodic and semantic memory), together with trail making test A (TMT-A), resulted significant predictors for dementia development in this group of amnesic patients. This optimal predictive model obtained an estimated accuracy of 53% after two years follow-up. M@T and semantic Sem-Flu test performance presented high correlation with decreased gray matter density in the left lateral temporal lobe. We conclude that Prd-AD is characterized by prominent episodic memory dysfunction and minimal semantic memory and executive dysfunction which are related with left medial, inferior and lateral temporal density loss, predominantly in the left side. © 2010 Elsevier Ireland Ltd.


Grau-Rivera O.,Hospital Clinic | Sanchez-Valle R.,Hospital Clinic | Sanchez-Valle R.,Institute dInvestigacio Biomedica August Pi i Sunyer | Saiz A.,Hospital Clinic | And 16 more authors.
JAMA Neurology | Year: 2014

IMPORTANCE: Creutzfeldt-Jakob disease (CJD) and autoimmune encephalitis with antibodies against neuronal surface antigens (NSA-abs) may present with similar clinical features. Establishing the correct diagnosis has practical implications in the management of care for these patients. OBJECTIVE: To determine the frequency of NSA-abs in the cerebrospinal fluid of patients with suspected CJD and in patients with pathologically confirmed (ie, definite) CJD. DESIGN, SETTING, AND PARTICIPANTS: A mixed prospective (suspected) and retrospective (definite) CJD cohort study was conducted in a reference center for detection of NSA-abs. The population included 346 patients with suspected CJD and 49 patients with definite CJD. MAINOUTCOMES AND MEASURES: Analysis of NSA-abs in cerebrospinal fluid with brain immunohistochemistry optimized for cell-surface antigens was performed. Positive cases in the suspected CJD group were further studied for antigen specificity using cell-based assays. All definite CJD cases were comprehensively tested for NSA-abs, with cell-based assays used for leucine-rich glioma-inactivated 1 (LGI1), contactin-associated protein-like 2 (CASPR2), N-methyl-D-aspartate (NMDA), and glycine (GlY) receptors. RESULTS: Neuronal surface antigens were detected in 6 of 346 patients (1.7%) with rapid neurologic deterioration suggestive of CJD. None of these 6 patients fulfilled the diagnostic criteria for probable or possible CJD. The target antigens included CASPR2, LGI1, NMDAR, aquaporin 4, Tr (DNER [δ/notch-like epidermal growth factor - related receptor]), and an unknown protein. Four of the patients developed rapidly progressive dementia, and the other 2 patients had cerebellar ataxia or seizures that were initially considered to be myoclonus without cognitive decline. The patient with Tr-abs had a positive 14-3-3 test result. Small cell lung carcinoma was diagnosed in the patient with antibodies against an unknown antigen. All patients improved or stabilized after appropriate treatment. None of the 49 patients with definite CJD had NSA-abs. CONCLUSIONS AND RELEVANCE: A low, but clinically relevant, number of patients with suspected CJD had potentially treatable disorders associated with NSA-abs. In contrast, none of 49 patients with definite CJD had NSA-abs, including NMDAR-abs, GlyR-abs, LGI1-abs, or CASPR2-abs. These findings suggest that cerebrospinal fluid NSA-abs analysis should be included in the diagnostic workup of patients with rapidly progressive central nervous system syndromes, particularly when they do not fulfill the diagnostic criteria of probable or possible CJD. Copyright 2014 American Medical Association. All rights reserved.


Puig O.,Hospital Clinic Universitari | Puig O.,Hospital Clinic Universitari of Barcelona | Puig O.,Research Center Biomedica En Red Of Salud Mental | Penades R.,Research Center Biomedica En Red Of Salud Mental | And 19 more authors.
European Child and Adolescent Psychiatry | Year: 2012

Cognition and clinical variables are known to be among the most predictive factors of real-world social functioning and daily living skills in adult-onset schizophrenia. Fewer studies have focused on their impact in adolescents with early-onset schizophrenia (EOS). The aim of this study is to examine the relationships and the predictive value of cognition and clinical variables on realworld daily living skills in a sample of adolescents with EOS. Cognitive, clinical and real-world everyday living skills measures were administered to 45 clinically and pharmacologically stabilized adolescent outpatients with EOS and 45 healthy control subjects matched by age and sex. Multi-variant analyses to compare cognitive and realworld functioning profiles between patients and controls and regression analysis to identify predictors of real-world functioning scores in patients were used. Adolescents with EOS showed a generalized cognitive and real-world daily living skills dysfunction. Several cognitive and clinical variables significantly correlated with real-world daily living skills functioning but only the processing speed and executive functions emerged as independent predictors of everyday living skills scores, explaining 25.1% of the variance. Slowness in processing information and executive dysfunction showed a significant impact on real-world daily living skills in EOS, independently from clinical symptoms and other cognitive variables. Nevertheless, much of the variance in the daily living skills measure remained unaccounted for, suggesting that other factors were involved as well in this young population. © 2012 Springer-Verlag.


Flamarique I.,Hospital Clinic Universitari Of Barcelona | Flamarique I.,Research Center Biomedica En Red Of Salud Mental | Baeza I.,Hospital Clinic Universitari Of Barcelona | Baeza I.,Research Center Biomedica En Red Of Salud Mental | And 14 more authors.
European Child & Adolescent Psychiatry | Year: 2014

To compare a sample of adolescents with schizophrenia spectrum disorders (SSD) treated with either ECT or antipsychotics (AP) alone at long-term follow-up. Patients diagnosed with SSD (n = 21) treated with ECT due to resistance to AP or catatonia under the age of 18 years (ECT group), were compared to a randomly selected group of patients with SSD treated only with AP (non-ECT group) (n = 21) and matched for age, gender, diagnosis and duration of illness. Baseline data were gathered retrospectively from medical records. Subjects were assessed at follow-up (mean of follow-up period = 5.5 years; range 2-9 years) using several clinical scales such as the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression Scale (CGI) and the Global Assessment of Functioning (GAF). Improvement in PANSS positive, negative, general, total and CGI and GAF scores between baseline and follow-up assessment did not differ significantly between groups. At follow-up, no differences were observed for the PANSS negative, CGI and GAF scores between groups, but patients in the ECT group still had higher PANSS total, positive and general scores. ECT treatment followed by AP medication in treatment-resistant SSD or catatonia is at least as effective in the long term as AP alone in non-resistant patients. © 2014 Springer-Verlag Berlin Heidelberg.


De La Serna E.,Research Center Biomedica En Red Of Salud Mental | De La Serna E.,Hospital Clinic Universitari | Baeza I.,Research Center Biomedica En Red Of Salud Mental | Baeza I.,Hospital Clinic Universitari | And 17 more authors.
Schizophrenia Research | Year: 2011

High rates of psychopathology and worse performance in cognitive areas have been described in high risk (HR) first degree relatives of subjects with schizophrenia. The present study aimed to examine clinical and neuropsychological characteristics in two different groups of first degree relatives of patients with schizophrenia - one of siblings (HRs), and one of offspring (HRo) - and compare them with healthy controls (HC). Methods: Participants were 30 HRo, 26 HRs and 33 HC, all aged between 7 and 16. years. Clinical and neuropsychological assessments were completed by all participants. Results: No significant differences were observed between HR groups in DSM-IV diagnoses. The most prevalent diagnosis in both HR samples was attention deficit/hyperactivity disorder (ADHD) followed by oppositional defiant disorder and generalized anxiety disorder. Both HR groups obtained worse scores than HC on prodromal symptoms, premorbid adjustment and behavioral problem scales. In cognitive areas, HRo performed worse than HC on most WISC-IV index scores, logical memory, visual memory and perceptual organization, whereas HRs only performed worse in WISC-IV indexes, logical memory and perceptual organization. Most of these differences remained stable after controlling for ADHD. The comparison between HRo and HRs showed significant differences in prodromal symptoms and working memory after controlling for ADHD. Conclusion: Similar abnormalities in HRo and HRs were found in relation to clinical and neuropsychological variables. Subtle differences were found between HR groups with HRo showing difficulties in more clinical and neuropsychological areas than HRs and HC. This suggests that, the specific kind of family relationship should to be taken into account in future HR research. © 2011 Elsevier B.V.


Flamarique I.,Hospital Clinic Universitari | Castro-Fornieles J.,Hospital Clinic Universitari | Castro-Fornieles J.,Research Center Biomedica En Red Of Salud Mental | Castro-Fornieles J.,Institute dInvestigacio Biomedica August Pi i Sunyer | And 14 more authors.
Journal of Clinical Psychopharmacology | Year: 2012

OBJECTIVE: To evaluate the safety and effectiveness of the combination of electroconvulsive therapy (ECT) and clozapine compared to ECT with other antipsychotics or benzodiazepines in a sample of adolescents diagnosed with schizophrenia spectrum disorders. METHODS: Data regarding 28 adolescent subjects aged 13 to 18 with diagnoses of schizophrenia spectrum disorders according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision and treated with ECT were retrospectively collected. Twelve subjects were also treated with clozapine and 16 with other antipsychotics or benzodiazepines during ECT course and follow-up. Electroconvulsive therapy parameters and adverse effects were assessed using a systematic protocol. Positive and Negative Syndrome Scale and Clinical Global Impression scores before ECT and after acute ECT, and rate of rehospitalization during 1-year follow-up were used to assess effectiveness. Response was defined as a 20% decrease in Positive and Negative Syndrome Scale scores. RESULTS: No differences were observed in the mean charge needed to induce seizure and electroencephalographic duration, but there was a slight difference in the current used. The nonclozapine group showed greater restlessness and agitation, although no differences were found in other adverse effects. The percentage of responders was similar: 66.7% in the clozapine group and 68.8% in the nonclozapine group. However, the rate of rehospitalization was lower in the patients treated with clozapine during 1-year follow-up (7.1%) compared to that of the nonclozapine group (58.3%) (P = 0.009). CONCLUSIONS: The main findings of this study were that combining ECT with clozapine, compared to ECT with other antipsychotics or benzodiazepines, was safe and that both treatments were equally effective. Charges needed to induce seizure were similar in both groups. Patients treated with clozapine during 1-year follow-up had a lower rate of rehospitalization. Copyright © 2012 Lippincott Williams & Wilkins.


de la Serna E.,Research Center Biomedica En Red Of Salud Mental | de la Serna E.,Hospital Clinic Universitari | Andres-Perpina S.,Research Center Biomedica En Red Of Salud Mental | Andres-Perpina S.,Hospital Clinic Universitari | And 25 more authors.
Schizophrenia Research | Year: 2013

Introduction: The concept of cognitive reserve (CR) has been defined as individual differences in the efficient utilization of brain networks which allow some people to cope better than others with brain pathology. CR has been developed mainly in the field of aging and dementia after it was observed that there appears to be no direct relationship between the degree of brain pathology and the severity of clinical manifestations of this damage. The present study applies the concept of CR to a sample of children and adolescents with a first episode of schizophrenia, aiming to assess the possible influence of CR on neuropsychological performance after two year follow-up, controlling for the influence of clinical psychopathology. Methods: 35 patients meeting DSM-IV criteria for schizophrenia or schizoaffective disorder (SSD) and 98 healthy controls (HC) matched for age and gender were included. CR was assessed at baseline, taking into account premorbid IQ, educational-occupational level and leisure activities. Clinical and neuropsychological assessments were completed by all patients at two year follow-up. Results: The CR proxy was able to predict working memory and attention at two year follow-up. Verbal memory and cognitive flexibility were not predicted by any of the variables included in the regression model. The SSD group obtained lower scores than HC on CR. CR measures correctly classified 79.8% of the sample as being SSD or HC. Conclusions: Lower scores on CR were observed in SSD than in HC and the CR measure correctly classified a high percentage of the sample into the two groups. CR may predict SSD performance on working memory and attention tasks. © 2012 Elsevier B.V.


Roura E.,University of Girona | Sarbu N.,Hospital Clinic | Oliver A.,University of Girona | Valverde S.,University of Girona | And 5 more authors.
Frontiers in Neuroinformatics | Year: 2016

Brain magnetic resonance imaging provides detailed information which can be used to detect and segment white matter lesions (WML). In this work we propose an approach to automatically segment WML in Lupus patients by using T1w and fluid-attenuated inversion recovery (FLAIR) images. Lupus WML appear as small focal abnormal tissue observed as hyperintensities in the FLAIR images. The quantification of these WML is a key factor for the stratification of lupus patients and therefore both lesion detection and segmentation play an important role. In our approach, the T1w image is first used to classify the three main tissues of the brain, white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF), while the FLAIR image is then used to detect focal WML as outliers of its GM intensity distribution. A set of post-processing steps based on lesion size, tissue neighborhood, and location are used to refine the lesion candidates. The proposal is evaluated on 20 patients, presenting qualitative, and quantitative results in terms of precision and sensitivity of lesion detection [True Positive Rate (62%) and Positive Prediction Value (80%), respectively] as well as segmentation accuracy [Dice Similarity Coefficient (72%)]. Obtained results illustrate the validity of the approach to automatically detect and segment lupus lesions. Besides, our approach is publicly available as a SPM8/12 toolbox extension with a simple parameter configuration. © 2016 Roura, Sarbu, Oliver, Valverde, González-Villà, Cervera, Bargalló and Lladó.


Molinuevo J.L.,Hospital Clinic | Molinuevo J.L.,Institute dInvestigacio Biomedica August Pi i Sunyer | Rami L.,Hospital Clinic | Rami L.,Institute dInvestigacio Biomedica August Pi i Sunyer
Medical Clinics of North America | Year: 2013

In 2007, new International Working Group research criteria introduced a new conceptualization of Alzheimer disease and created a framework for earlier diagnosis. There is increasing consensus to understand Alzheimer disease as a clinical-biologic entity, in which biomarkers, especially pathophysiologic markers revealing underlying pathology, represent the biologic counterpart of the diagnosis, and specific symptoms, such as episodic memory deficits, account for the clinical one. This article advances and moves forward on this. © 2013 Elsevier Inc.


Valls-Sole J.,University of Barcelona | Valls-Sole J.,Institute dInvestigacio Biomedica August Pi I Sunyer
Clinical Neurophysiology | Year: 2012

Excitability is probably the concept that fits better with the definition of the role of neurophysiology in the study of brainstem functions and circuits. Neurophysiological techniques are likely the best suited of all paraclinical tests for documenting the eventual excitability changes that may occur in certain physiological states and in many neurological disorders. The best known test of brainstem excitability is the blink reflex. While a single stimulus can already indicate the readiness of the interneuronal path and the facial motoneurons to fire, pairs of stimuli (conditioning and test) are suited to analyze the degree of excitability recovery after a single discharge. Another brainstem reflex circuit, which excitability testing can be of interest for physiological and clinical exams is the one involved in the startle reaction. The size of the responses and their habituation are the typical measures of excitability of the startle reflex circuit. Prepulse inhibition is a method to modulate both, the blink reflex and the startle reaction. It is defined as the inhibitory effect caused by a stimulus of an intensity low enough not to induce a response by itself on the response elicited by a subsequent stimulus. The circuits of the blink reflex, startle reaction and prepulse inhibition share some commonalities but they are different enough for the three techniques to provide unique, clinically relevant, information in certain conditions. The role of neurophysiology is not limited to testing those functions. It is important also for the assessment of many other circuits, such as those implicated in eye movements, vestibular reflexes, arousal, sleep, breathing, or autonomic reactions, which are not considered in this review. © 2011 International Federation of Clinical Neurophysiology.

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