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The objective of this paper is to evaluate available evidence for each step in autoimmune encephalitis management and provide expert opinion when evidence is lacking. The paper approaches autoimmune encephalitis as a broad category rather than focusing on individual antibody syndromes. Core authors from the Autoimmune Encephalitis Alliance Clinicians Network reviewed literature and developed the first draft. Where evidence was lacking or controversial, an electronic survey was distributed to all members to solicit individual responses. Sixty-eight members from 17 countries answered the survey. The most popular bridging therapy was oral prednisone taper chosen by 38% of responders while rituximab was the most popular maintenance therapy chosen by 46%. Most responders considered maintenance immunosuppression after a second relapse in patients with neuronal surface antibodies (70%) or seronegative autoimmune encephalitis (61%) as opposed to those with onconeuronal antibodies (29%). Most responders opted to cancer screening for 4 years in patients with neuronal surface antibodies (49%) or limbic encephalitis (46%) as opposed to non-limbic seronegative autoimmune encephalitis (36%). Detailed survey results are presented in the manuscript and a summary of the diagnostic and therapeutic recommendations is presented at the conclusion.

The only recommended pharmacological treatments for specific dementias are donepezil, galantamine, rivastigmine, and memantine (recommended drugs, RD). However, other drugs without recommendations (not recommended drugs, NRD) are often used to treat patients with cognitive impairment (CI) in Argentina. The INSSJyP is the largest health insurance in Argentina. The objective of this study is to analyze the prescription pattern, cost, and implications of NRD used for the treatment of CI in the INSSJyP.This is a retrospective, population-based study of the INSSJyP outpatients' prescriptions database for drugs usually prescribed for CI during 2015. These data were compared with the same database in 2009. The number of "prescriptions" always refers to dispensed packages.A total of 3 255 438 packages of drugs usually indicated for CI were prescribed during 2015: 1 912 476 packages of RD (59%) and 1 342 962 packages of NRD (41%).Comparing the results with those obtained in 2009, there is a 148% gross increase in the prescription of both RD and NRD for CI, although the rates/1000 affiliates/year show a lesser rise for NRD (70.1%) compared to RD (103.9 %).The expenditure on CI drugs prescribed during 2015 was 77 million USD. NRD cost represented approximately 20 million USD.Inappropriate drug use increases health costs in developing countries. We found a high number of patients with a probable diagnosis of CI treated with NRD. It is extremely relevant that all the healthcare professionals can update their knowledge and modify behavioral insights about appropriate prescription for specific dementias.

Background: Immunological causes of atypical parkinsonisms linked to neuronal specific antibodies have been recently reported. As these are potentially treatable disorders, it is desirable to identify which clinical features may suggest an autoimmune etiology. Case Report: A 60-year-old-man with progressive supranuclear palsy associated with anti-LGI-1 antibodies presented with rapidly progressive dementia and moaning. Treatment with steroids and immunoglobulin resulted in temporary clinical improvement and disease stabilization. Discussion: Anti-LGI-1 antibodies interfere with normal synaptic activity and maturation in the central nervous system. We suggest that an immune-mediated mechanism might be considered in atypical parkinsonisms with unusual features such as rapidly progressive dementia. Highlights: We present a case of rapidly evolving progressive supranuclear palsy-like parkinsonism associated with anti-LGI-1 antibodies, suggesting that immune-mediated mechanisms might be involved in rapid progression of some atypical parkinsonisms. This case also contributes to the expanding spectrum of moaning-associated disorders.

Introduction Mutations in presenilin-1 (PSEN1) account for the majority of cases of familial autosomal dominant early-onset Alzheimer's disease (AD) as well as in sporadic forms. Atypical presentations are reported including extrapyramidal signs. In the last years, a pleiotropic effect of some PSEN1 variants has been reported in Parkinson's disease (PD). Objective to report a new PSEN1 mutation characterized by early-onset Parkinsonism (EOPD) without dementia or classical AD biomarkers phenotype. Patient and methods An Argentinian 46 years old woman was diagnosed with EOPD at 35 years old with no family history of neurodegenerative disorders. Her medical history included iron deficiency and anemia since childhood. A brain MRI showed moderate frontal atrophy. 18FDG-PET and PiB-PET as well as CSF biomarkers were inconclusive for AD. Two neuropsychological examinations were compatible with a mild non amnestic cognitive impairment. Whole blood DNA was extracted and whole exome sequencing and analysis was performed. Results and conclusion A heterozygous novel missense PSEN1 mutation (position 14:73637540, A > T, pArg41Ser) was identified as a likely causative mutation in this patient. To the best of our knowledge, this case is the first PSEN1 mutation with a l -dopa responsive Parkinsonism lacking distinctive classical AD biomarkers. This case opens a new window to explore the pathophysiological link among PSEN1 and EOPDs and contributes to increase the phenotypes of PSEN1 variants.

To examine the effect of cognitive rehabilitation therapy (CRT) on psychosocial outcomes in Argentinean patients with acquired brain injury (ABI), in connection with the time elapsed between injury and treatment initiation.Self-reported data from patients in a naturalistic setting was collected before and after CRT.An outpatient sample of 75 Spanish-speaking patients with cognitive disturbances secondary to ABI (49 male/26 female, age: 50.2 ± 20.1 years; education 14.3 ± 3.2 years) completed a set of scales on their daily living activities, memory self-perception, quality-of-life and mood. Single and multi-group analyses were conducted, considering pre- and post- responses and the time elapsed between injury and treatment initiation. The influence of socio-demographic moderators was controlled during comparisons.Results suggest an improvement in several psychosocial indicators after treatment. Additionally, correlations and group comparisons showed greater improvement in subjective memory and quality-of-life self-reports in patients who began treatment earlier than those who began treatment after a longer time period.Overall, results suggest that CRT is associated with positive results in different areas of the psychosocial domain and that post-injury time can mediate this effect.

between adiposity and brain structure has not yet been fully elucidated. We aimed to evaluate the association of body fat composition with cortical thickness in cognitively normal subjects. Methods: In total, 1,777 (887 men and 890 women) cognitively normal subjects, aged 45 years or older, were enrolled from Health Promotion Center in Korea. Normal cognition was determined by the results of an interview conducted by a qualified neurologist and scores on the Mini-Mental Status Exam that were above the 16th percentile for age-, gender-, and education-matched norms. Medical records including 3D magnetic resonance imaging, body fat percentage, waist-hip ratio (WHR), and other factors were reviewed. The WHR was categorized into six groups based on gender-specific percentile, and surface-based morphometric analysis was used to estimate cortical thickness. Multiple linear regressions and generalized additive models were used to investigate the linear and non-linear relationship of fat percentage and WHR with cortical thickness. Results: In men, the percentage of fat was positively associated with cortical thickness and the highest WHR group showed significant cortical thinning; in imaging analysis, cortical thinning was observed in the bilateral paracentral lobule, posterior cingulate gyrus, and left medial frontal areas. The WHR showed an inverted U-shaped association with total cortical thickness and frontal lobe thickness in men. Among women, there was no significant association of body fat percentage andWHRwith cortical thickness.Conclusions:Our finding suggests that in men, body fat percentagemight have a beneficial effect, while abdominal fat might have a harmful effect on cortical thickness.

Background: Mild cognitive impairment (MCI) is a transitional state between normal aging and dementia. Identifying this condition would allow early interventions that may reduce the rate of progression to Alzheimer's disease (AD). We examined the efficacy of a six-month cognitive intervention program (CIP) in patients with MCI and to assess patients’ condition at one-year follow-up.Methods: Forty-six MCI participants assessed with neuropsychological, neurological, neuropsychiatry, and functional procedures were included in this study and followed up during a year. The sample was randomized into two subgroups: 24 participants (the “trained group”) underwent the CIP during six months while 22 (control group) received no treatment. Sixteen participants dropped out of the study. The intervention focused on teaching cognitive strategies, cognitive training, and use of external aids, in sessions of two hours, twice per week for six months. Cognitive and functional measures were used as primary outcome and all were followed up at one year.Results: The intervention effect (mean change from baseline) was significant (p < 0.05) on the Mini-Mental State Examination (1.74), the Clinical Dementia Rating Scale (0.14), the Boston Naming Test (2.92), block design (−13.66), matrix reasoning (−3.07), and semantic fluency (−3.071) tasks. Four patients (one trained and three controls) progressed to dementia after one year of follow-up.Conclusions: These results suggest that persons with MCI can improve their performance on cognitive and functional measures when provided with early cognitive training and it could persist in a long-term follow-up.

Pathologic expansion of the G4C2 repeat in C9orf72 is the main genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). To evaluate the frequency of the G4C2 expansion in a Latin American cohort of FTD and ALS patients, we used a 2-step genotyping strategy. For FTD, we observed an overall expansion frequency of 18.2% (6 of 33 unrelated cases). Moreover, the C9orf72 expansion accounted for 37.5% of all familial FTD cases (6 of 16 families). The expansion frequency in sporadic ALS cases was 2% (1 of 47 unrelated patients), whereas we observed the expansion in 1 of 3 families with a positive history for ALS. Overall, the expansion frequency in our FTD group was similar to that reported for patients in Europe and North America, whereas the frequency in our sporadic ALS group was significantly lower. To our knowledge, this is the first report on the frequency of the C9orf72 expansion in a Latin American population. Fil: Itzcovich, Tatiana. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina Fil: Xi, Zhengrui. University of Toronto; Canadá Fil: Martinetto, Horacio Enrique. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina Fil: Chrem Mendez, Patricio Alexis. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina Fil: Russo, María Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina Fil: de Ambrosi, Bruno. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina Fil: Uchitel, Osvaldo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina Fil: Nogués, Martín. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina Fil: Silva, Emanuel. Provincia de Misiones. Hospital Escuela de Agudos Dr. Ramon Madariaga; Argentina Fil: Rojas, Zenón Galeno. Hospital Británico de Buenos Aires; Argentina Fil: Bagnatti, Pablo. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina Fil: Amengual, Alejandra. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina Fil: Campos, Jorge. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina Fil: Rogaeva, Ekaterina. University of Toronto; Canadá Fil: George-Hyslop, Peter St.. University of Toronto; Canadá. University of Cambridge; Reino Unido Fil: Allegri, Ricardo Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina Fil: Sevlever, Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina Fil: Surace, Ezequiel Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina

Janus Kremer, Gerardo Tiezzi, Gustavo Albanese, Marco Tozzola, Miryam Bukler, Mauricio Bosch, Galeno Rojas, Alejandro Anerson, Ricardo Klein, Marta Torres, Christiane Ponteville, Instituto Kremer, Cordoba, Argentina; Fundacion Rosarina de Neuro-Rehabilitacion, Rosario, Argentina; Hospital Argerich, Buenos Aires, Argentina; Instituto Tozzola de Neurociencias, Buenos Aires, Argentina; Centro Integral de Psicologia, Martinez, Argentina; ACeR, Rosario, Argentina; ANMAT, Buenos Aires, Argentina; Instituto de Neurologia Buenos Aires, Buenos Aires, Argentina; Hospital Borda, Buenos Aires, Argentina; ACeR, Olivos, Argentina; Facultad de Farmacia y Bioquimica Universidad de Buenos Aires, Buenos Aires, Argentina.

O (donepezil) 21 9 0 30 21.16 1.89 I (rivastigmine) 25 9 2 36 17.42 1.73 A (gallantamine) 9 3 0 12 20.66 2 E (memantine) 14 3 1 18 18.10 0.66 OME 40 1 2 43 18.52 3.75 IME 21 9 1 31 15.85 2.26 AME 5 2 0 7 17.83 3 e (cerebrolysin) 20 4 1 25 19.47 4.68 otal 155 40 7 202 18.54 2.76 Diana Pollock, Vikram Atit, George Brewer, Steven Kanzer, Lara Guzman, David Newsome, Ptak Alzheimer’s Research Center, Clearwater, Florida, United States; Atit Neurology Institute, Holiday, Florida, United States; Adeona, Ann Arbor, Michigan, United States.

Background: The economic cost of dementia is high and can be predicted by cognitive and neuropsychiatric profiles. The differential costs of the various subtypes of dementia are unknown in Argentina, and this study therefore aimed to compare these costs.Methods: Patients with a diagnosis of dementia of Alzheimer-type (DAT), frontotemporal dementia (FTD) and vascular dementia (VaD), and their primary caregivers, were evaluated between 2002 and 2008.Results: 104 patients with dementia (DAT = 44, FTD = 34, VaD = 26) were screened and matched by age and educational level with 29 healthy subjects. Demographic variables showed no significant differences among dementia patients. The annual direct costs were US$4625 for DAT, US$4924 for FTD, and US$5112 for VaD (p > 0.05 between groups). In the post hoc analysis VaD showed higher hospitalization costs than DAT (p < 0.001). VaD exhibited lower medication costs than FTD (p < 0.001). DAT exhibited higher anti-dementia drug costs; FTD had higher psychotropic costs. In the multivariate analysis, depression, activities of daily living, and caregiver burden were correlated with direct costs (r2 = 0.76).Conclusions: The different dementia types have different costs. Overall, costs increased with the presence of behavioral symptoms, depression and functional impairment of activities of daily living.

Objective: To identify early clinical predictors of sustained DAF status in patients with relapsing-remitting multiple sclerosis (RRMS) treated with Interferon Beta (IFN) and Glatiramer Acetate (GA). Background The novel concept of sustained disease activity free (DAF) status could be a viable goal of therapy based on clinical and radiological measures, yet applicable to immunomodulators currently in use. Design/Methods: DAF status was defined as absence of gadolinium-enhancing lesions, new/enlarging T2 lesions, confirmed relapses and 3-month confirmed disability progression. We assessed clinical predictors and their potential influence on the proportion of DAF patients receiving IFN and GA therapies in the long term. Categorical predictors based on baseline data were age (≤40 or >40 years), disease duration previous treatment ( 10 years), number of relapses in the previous 12 months (≤1 or ≥2), basal EDSS score (≤3.0 or ≥3.5), and treatment duration (years). Patients subgroups were stratified by baseline demographic and disease characteristics. Results: This is a retrospective, observational study of 245 naive and RRMS patients who received immunomodulators over 10 ( 9.77±3.28) years of follow up. Freedom from clinical and radiological activity was observed in 26 (28.3%) of 92 patients taking IFN and 40 (37%) of 108 taking GA ([OR]0.67, 95% CI 0.36–1.21; p=0.18). After multivariate analysis we found that the only independent predictive factor for DAF status was Conclusions: Both IFN and GA induced DAF status in patients with RRMS, sustained in the long term. Early treatment initiation could be an important predictor of that status. Disclosure: Dr. Rojas has nothing to disclose. Dr. Vrech has nothing to disclose. Dr. Rojas has nothing to disclose. Dr. Rojas has nothing to disclose. Dr. Carra has nothing to disclose.

Objective: To examine the effects of Interferon beta (IFNb) and Glatiramer Acetate (GA) on sustained disease activity free (DAF) status. Background IFNb and GA provide similar levels of efficacy in patients with relapsing-remitting multiple sclerosis (RRMS). However, they have not been demonstrated to induce disease remission. The sustained DAF status is a novel concept and viable goal of therapy based on clinical and radiological measures. Design/Methods: DAF status was defined as no activity on clinical measures (relapses and change in EDSS),and radiological measures (gadolinium-enhancing lesions and new/enlarging T2 lesions on cranial MRI). We assessed the impact of IFNb and GA on the proportion of DAF patients based on individual and combined components. All patients were matched according to baseline characteristics and treatment exposure. Results: This is a retrospective, observational study of 245 naive and RRMS patients who received immunomodulators over 10 (9.77+-3.28) years of follow up. 41 (35%) of 117 patients taking IFNb and 46 (35.9%) of 128 taking GA were free of clinical disease activity ([OR]0.96, 95% CI 0.56-1.62; p=0.8). 73 (77.7%) of 94 and 86 (81.9%) of 105 patients receiving IFNb and GA, respectively, were free of radiological disease activity ([OR]0.76 95% CI 0.38-1.53; p=0.45). Freedom from combined activity was observed in 26 (28.3%) of 92 patients taking IFNb and 40 (37%) of 108 taking GA ([OR]0.67, 95% CI 0.36-1.21; p=0.18). Although no differences were found between group treatments, subgroups analysis demonstrated a greater proportion of patients free from clinical disease activity among those on >=5 years of GA therapy ([OR] 0.32, 95% CI 0.12-0.82; p Conclusions: Both IFNb and GA induced DAF status in patients with RRMS, sustained in the long term. DAF status could be an important measure of therapeutic response in MS, yet applicable to immunomodulators currently in use. Disclosure: Dr. Carra has received personal compensation for activities with Biogen Idec, Merck Serono, Bayer Schering, Novartis, and Teva Neuroscience. Dr. Rojas has nothing to disclose. Dr. Vrech has nothing to disclose. Dr. Lindembaum has nothing to disclose.

Com a finalidade de avaliar a eficácia de um procedimento terapêutico, os autores realizaram uma análise crítica dos vários métodos para produção experimental de aneurismas e elaboraram um método próprio, baseado em uma técnica pré-existente, no qual aneurismas saculares foram produzidos na bifurcação da artéria carótida comum de cães, com enxertos de fragmentos de veias. Os aneurismas assim produzidos apresentaram uma baixa incidência de trombose e uma tendência em aumentar de tamanho e em tornarem-se esféricos. As características desses aneurismas em muito se assemelham àquelas dos aneurismas de ocorrência natural nas artérias cerebrais do homem, o que os tornam modelos úteis para fins experimentais. The authors present a critical analysis of the various methods of experimental production of aneurysms and report their own method in which saccular aneurysms were produced at the bifurcation of the common carotid artery in dogs with vein patch grafts. The objective point of this study was the creation of an experimental model to evaluate the efficacy of a therapeutic procedure. These aneurysms have a low incidence of thrombosis and a tendency to enlarge and to become spherical. They closely simulate the saccular aneurysms developing spontaneously in the cerebral arteries of man, and as such are useful models for experimental purposes.

Background: “Forgetfulness” is frequent in normal aging and characteristic of the early stages of dementia syndromes. The episodic memory test is central for detecting amnestic mild cognitive impairment (MCI). The Memory Binding Test (MBT) is a simple, easy and brief memory test to detect the early stage of episodic memory impairment. Objective: To validate the Argentine version of the MBT in a Latin American population and to estimate the diagnostic accuracy as a tool for early detection of MCI. Methods: 88 subjects (46 healthy controls and 42 patients with amnestic MCI) matched for age and educational level were evaluated by an extensive neuropsychological battery and the memory binding test. Results: A significantly better performance was detected in the control group; all MBT scales were predictive of MCI diagnosis (p