Torralva T, Roca M, Gleichgerrcht E, Bonifacio A, Raimondi C, Manes F.  Validation of the Spanish Version of the Revised Addenbrooke’s Cognitive Examination. Neurología 2011 10.1016/j.psychres.2014.01.020

BACKGROUND: The Addenbrooke’s Cognitive Examination Revised (ACE-R) is an improved version of the earlier brief screening test which has been validated in English with high sensitivity and specificity to detect cognitive dysfunction. The aim of this study was to validate the Spanish version of the ACE-R in an Argentine population. METHODS: A group of patients with Alzheimer Disease (AD) and patients with behavioural variant Frontotemporal Dementia (bvFTD) paired by age, sex, and years of education with healthy controls were assessed using the ACE-R. Stage of dementia was measured with the Clinical Dementia Rating Scale (CDR). The English version of the ACE-R was first translated into Spanish and then back-translated into English by two blind independent experts. RESULTS: Internal reliability was very good (Cronbach’s alpha=0.89). Concurrent validity, determined by the correlation between total ACE-R and CDR was significant (P<.001) and inter-rater reliability was excellent (Cohen's kappa=0.98). Controls significantly outperformed AD and bvFTD patients on most subdomains of the ACE-R, with significant differences between the dementia groups. With a cut-off score of 85 points, sensitivity was 97.5% and specificity was 88.5%, with a likelihood ratio of 99.3 for the detection of dementia. The ACE-R showed higher sensitivity than the MMSE for the detection of dementia. CONCLUSIONS: The Spanish version of the ACE-R is a brief yet reliable screening tool for the detection of early cognitive impairment and has shown to discriminate between bvFTD and AD.

Manes F, Torralva T, Ibanez A, Roca M, Bekinschtein T, Gleichgerrcht E.  Decision-making in frontotemporal dementia: clinical, theoretical and legal implications. Dementia and Geriatric Cognitive Disorders 2011

BACKGROUND: The behavioral variant of frontotemporal dementia (bvFTD) is characterized by progressive changes in personality and social interaction, loss of empathy, disinhibition and impulsivity, most of which generally precede the onset of cognitive deficits. In this study, we investigated decision-making cognition in a group of patients with an early bvFTD diagnosis whose standard neuropsychological performance was within normal range for all variables. METHODS: The Iowa Gambling Task was administered to this group of early bvFTD patients, to a group of early bvFTD patients who had shown impaired performance on the classical neuropsychological battery and to healthy controls. RESULTS: Decision-making was impaired in both bvFTD patient groups, whether they had shown impaired or normal performance in the classical neuropsychological evaluation. CONCLUSIONS: Patients with early bvFTD may perform normally on standard cognitive tests, and yet develop severe deficits in judgment and decision-making. In many current legal systems, early bvFTD patients showing preserved cognitive functioning who commit unlawful acts run the risk of not being able to plead insane or not guilty on the grounds of diminished responsibility beyond reasonable doubt. This represents a unique legal and ethical dilemma. Our findings have important implications for medicolegal decisions relating to capacity and culpability, and regarding the philosophical concept of ‘free will’.

Rascovsky K, Hodges J R, Knopman D, Mendez MF, Kramer J, Neuhaus J, vSwieten J, Seelaar H, Dopper E, Onyike Ch,Hillis A, Josephs K, Boeve B, Kertesz A, Seeley W, Rankin K, Johnson J, Gorno-Tempini ML, Rosen H, Prioleau-Latham C,Lee A, Kipps C, Lillo P, Piguet O, Rohrer J, Rossor M, Warren JD, Galasko D, Salmon D, Mesulam M, Weintraub S, Dickerson B, Diehl-Schmid J, Pasquier F, Deramecourt V, Lebert F, Pijnenburg Y, Chow T, Manes F, Grafman J, Cappa S, Freedman M,Grossman M, Miller B.  Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain 2011 10.1523/JNEUROSCI.0114-13.2013

Based on the recent literature and collective experience, an international consortium developed revised guidelines for the diagnosis of behavioural variant frontotemporal dementia. The validation process retrospectively reviewed clinical records and compared the sensitivity of proposed and earlier criteria in a multi-site sample of patients with pathologically verified frontotemporal lobar degeneration. According to the revised criteria, ‘possible’ behavioural variant frontotemporal dementia requires three of six clinically discriminating features (disinhibition, apathy/inertia, loss of sympathy/empathy, perseverative/compulsive behaviours, hyperorality and dysexecutive neuropsychological profile). ‘Probable’ behavioural variant frontotemporal dementia adds functional disability and characteristic neuroimaging, while behavioural variant frontotemporal dementia ‘with definite frontotemporal lobar degeneration’ requires histopathological confirmation or a pathogenic mutation. Sixteen brain banks contributed cases meeting histopathological criteria for frontotemporal lobar degeneration and a clinical diagnosis of behavioural variant frontotemporal dementia, Alzheimer’s disease, dementia with Lewy bodies or vascular dementia at presentation. Cases with predominant primary progressive aphasia or extra-pyramidal syndromes were excluded. In these autopsy-confirmed cases, an experienced neurologist or psychiatrist ascertained clinical features necessary for making a diagnosis according to previous and proposed criteria at presentation. Of 137 cases where features were available for both proposed and previously established criteria, 118 (86%) met ‘possible’ criteria, and 104 (76%) met criteria for ‘probable’ behavioural variant frontotemporal dementia. In contrast, 72 cases (53%) met previously established criteria for the syndrome (P < 0.001 for comparison with 'possible' and 'probable' criteria). Patients who failed to meet revised criteria were significantly older and most had atypical presentations with marked memory impairment. In conclusion, the revised criteria for behavioural variant frontotemporal dementia improve diagnostic accuracy compared with previously established criteria in a sample with known frontotemporal lobar degeneration. Greater sensitivity of the proposed criteria may reflect the optimized diagnostic features, less restrictive exclusion features and a flexible structure that accommodates different initial clinical presentations. Future studies will be needed to establish the reliability and specificity of these revised diagnostic guidelines.

Ibanez A, Hurtado E, Lobos, Escobar J, Trujillo-Orrego N, Báez S, Huepe D, Manes F, Decety J.  Subliminal presentation of other faces (but not own face) primes behavioral and evoked cortical processing of empathy for pain. International Brain Research Organization 2011

Current research on empathy for pain emphasizes the overlap in the neural response between the first-hand experience of pain and its perception in others. However, recent studies suggest that the perception of the pain of others may reflect the processing of a threat or negative arousal rather than an automatic pro-social response. It can thus be suggested that pain processing of other-related, but not self-related, information could imply danger rather than empathy, due to the possible threat represented in the expressions of others (especially if associated with pain stimuli). To test this hypothesis, two experiments considering subliminal stimuli were designed. In Experiment 1, neutral and semantic pain expressions previously primed with own or other faces were presented to participants. When other-face priming was used, only the detection of semantic pain expressions was facilitated. In Experiment 2, pictures with pain and neutral scenarios previously used in ERP and fMRI research were used in a categorization task. Those pictures were primed with own or other faces following the same procedure as in Experiment 1 while ERPs were recorded. Early (N1) and late (P3) cortical responses between pain and no-pain were modulated only in the other-face priming condition. These results support the threat value of pain hypothesis and suggest the necessity for the inclusion of own- versus other-related information in future empathy for pain research.

Gleichgerrcht E, Flichtentrei D, Manes F. How much do physicians in Latin America know about behavioral variant frontotemporal dementia?. Journal of Molecular Neuroscience 2011

Diagnosis of behavioral variant frontotemporal dementia (bvFTD) can be especially challenging during the early stages for several reasons, including the fact that (a) behavioral disturbances in bvFTD can mimic the symptomatic profile of psychiatric disorders; (b) neuropsychological performance may be relatively spared; and (c) changes in structural neuroimaging may go undetected. Most frequently, bvFTD is not included as part of medical or residency training outside the field of cognitive neurology. The present study aimed at examining bvFTD-related practices concerning academic and professional training, diagnosis, and treatment across Latin America. We surveyed the academic and professional aspects of clinical practice related to bvFTD of 596 physicians from different fields throughout the continent. We discuss several aspects concerning Latin American physicians’ training on dementia and bvFTD, the way in which they approach the differential diagnosis of bvFTD, and their most frequent strategies for the treatment of this condition. We conclude that information about bvFTD deserves more attention in both undergraduate and postgraduate medical education in Latin America, and that understanding clinical practices related to FTD can help design more efficient training programs for physicians in this and other world regions.

Urbistondo C, Macbeth G, Kichic R, Ibanez A.  El modelo fronto-estriado del trastorno obsesivo-compulsivo: Evidencia convergente de estudios de potenciales evocados relacionados a eventos. Revista Virtual de la Facultad de Psicología y Psicopedagogía de la Universidad del Salvador 2011

El trastorno obsesivo-compulsivo es un trastorno psiquiátrico que en un 87% de los casos se vuelve crónico. Se caracteriza por una serie de síntomas que pueden ser agrupados en obsesiones y compulsiones, que pueden llegar a ser altamente invalidantes y afectar el estilo de vida de quienes lo padecen. Es importante entender los mecanismos neurológicos del trastorno obsesivo-compulsivo para poder abordar de manera más eficaz los tratamientos. Este trabajo plantea al modelo frontoestriado como aquel que provee mayor evidencia y explica de manera más acabada los fenómenos neuropsicológicos del TOC, con las áreas cerebrales que se encuentran implicadas en él córtex cingulado anterior, los ganglios basales, y la corteza órbito-frontal. Luego, se vinculan estos resultados con aquellos hallazgos de estudios de potenciales evocados relacionados a eventos (especialmente ERN, N200 y P300) con el fin de explicar más íntegramente lascaracterísticas del trastorno. Las funciones cognitivas que se pueden vincular con loshallazgos de neuroimágenes y ERPs son relativas al procesamiento de la información,decodificación, planificación, atención voluntaria, control inhibitorio, y funcionesejecutivas en general.

Sposato L, Loli PL, Esnaola y Rojas MM, Saposnik G.  Unemployment: A Social Risk Factor Associated with Early Ischemic Stroke Mortality? Results from the Argentinean National Stroke Registry (ReNACer). Journal of Stroke and Cerebrovascular Diseases 2011 10.1097/WAD.0000000000000030

Employment is an indicator of socioeconomic status. Unemployment is a worldwide social challenge, especially in emerging countries, accounting for a proportion of the overall higher mortality rates found in these nations. We assessed the relationship between employment status and in-hospital mortality among acute ischemic stroke patients participating in the Argentinean National Stroke Registry (ReNACer), a prospective, country-wide, hospital-based stroke registry aimed at improving quality of stroke care in Argentina. We compared demographic and socioeconomic characteristics, risk factors, acute treatment, and stroke severity between employed and unemployed patients with acute ischemic stroke participating in ReNACer. We developed a multiple logistic regression model to identify predictors of in-hospital mortality. Among the 726 patients with acute ischemic stroke included in the study, 39.5% were unemployed. In-hospital mortality was higher in the patients who were unemployed at the time of the stroke compared with those who were employed (12.0% vs 5.0%; P = .003). On multivariate analysis, being unemployed (odds ratio [OR], 3.58; 95% confidence interval [CI], 1.36-7.37; P = .005), stroke severity (OR, 3.54; 95% CI 1.11-10.40; P = .018), and infarct size >15 mm (OR, 2.80; 95% CI, 1.18-6.60; P = .019) were associated with in-hospital mortality after adjusting for relevant covariates. Social factors may influence poor outcomes after stroke. In the present study, unemployment was associated with a higher risk of adjusted in-hospital mortality. Strategies targeting individuals at high risk of cardiovascular diseases and poorer outcomes should be implemented to reduce stroke impact.

Ibanez A, Toro P, Cornejo C, Urquina H, Manes F, Weisbrod M, Johannes Schroeder.  High contextual sensitivity of metaphorical expressions and gesture blending: A video ERP design. Psychiatry Research 2011

Human communication in a natural context implies the dynamic coordination of contextual clues, paralinguistic information and literal as well as figurative language use. In the present study we constructed a paradigm with four types of video clips: literal and metaphorical expressions accompanied by congruent and incongruent gesture actions. Participants were instructed to classify the gesture accompanying the expression as congruent or incongruent by pressing two different keys while electrophysiological activity was being recorded. We compared behavioral measures and event related potential (ERP) differences triggered by the gesture stroke onset. Accuracy data showed that incongruent metaphorical expressions were more difficult to classify. Reaction times were modulated by incongruent gestures, by metaphorical expressions and by a gesture-expression interaction. No behavioral differences were found between the literal and metaphorical expressions when the gesture was congruent. N400-like and LPC-like (late positive complex) components from metaphorical expressions produced greater negativity. The N400-like modulation of metaphorical expressions showed a greater difference between congruent and incongruent categories over the left anterior region, compared with the literal expressions. More importantly, the literal congruent as well as the metaphorical congruent categories did not show any difference. Accuracy, reaction times and ERPs provide convergent support for a greater contextual sensitivity of the metaphorical expressions.

Glatstein M, Sulowski C, Waisburg CG, Gideon Koren, Garcia-Bournissen F. Severe Extrapiramidal Symptoms After Nonintentional Risperidone Exposure in a Child: Case Report and Review of the Literature. American journal of therapeutics 2011

Increase in use of atypical antipsychotics has been paralleled by an increase in the incidence of intentional and nonintentional overdose. Pediatric cases are uncommon, but may be severe. We describe a case of a child presenting with severe extrapiramidal symptoms, initially interpreted as seizures, caused by a nonintentional intoxication with risperidone, and review management options and the literature.

Gershanik O, Gómez Arévalo G.  Typical and atypical neuroleptics. Handbook of clinical neurology 2011

Neuroleptics having dopamine receptor-blocking properties are frequently responsible for the development of movement disorders. This has been known for many years as these adverse events were identified soon after the introduction of these drugs for the treatment of psychiatric disorders. Parkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesias are the different clinical presentations of these disorders. Tardive dyskinesia is the most problematic among them as it may persist even after discontinuation of the offending drug, and become an irreversible phenomenon. The term «tardive dyskinesia » encompasses a variety of clinical phenomena including stereotypic behaviors, dystonia, myoclonus, and tics. Stereotypies and orobuccolingual dyskinesias are the most frequently observed tardive disorders, particularly in the elderly population exposed to neuroleptics, while dystonic phenomena are more prevalent in younger individuals. The development of these disorders is dependent on the potency of the drug, duration of exposure, and a number of predisposing factors, including age, gender, and presence of organic brain disease. The pathophysiology is rather complex and involves changes in the dopamine synapse both at the pre- and postsynaptic level, as well as plastic changes involving transcription factors and activation of different molecular cascades downstream of the dopamine receptor. The introduction of more novel pharmacological agents, like the so-called atypical neuroleptics, has significantly reduced the incidence of these disorders; however, the prescribing physician has to be aware that a lower risk is not synonymous with absence of risk.