Quality of life, mood, and cognitive performance in older adults with cognitive impairment during the first wave of COVID 19 in Argentina.

BACKGROUND AND OBJECTIVES: In Argentina, government has established lockdown on 19 March 2020 to decrease SARS-COV-2 infection. The study aim was to understand how mandatory quarantine imposed due to COVID-19 pandemic has affected quality of life, mood, and cognitive performance of older adults with cognitive impairment. DESIGN: Longitudinal descriptive-observational study. PARTICIPANTS: Patients with cognitive impairment attending to online cognitive training sessions. MEASUREMENTS: Participants have completed by themselves Quality of Life in Alzheimer's Disease scale (QOL-AD), Beck Depression Inventory (BDI-II), Test your Memory (TYM), and an attention and executive task created by our institution. Same assessments were done at the beginning of the lockdown and 7 months later. RESULTS: Fifty-one adults were included. An increase in BDI-II score (p = 0.049) and worse performance in one of the executive attention tests (p = 0.012) have been found. No significant differences in QOL-AD, TYM, verbal fluency, or memory tests total scores have been observed. Reviewing scales subitems, differences in changes in sleep habits (p = 0.021), energy level decrease (p = 0.004), worse subjective record of memory capacity (p = 0.028), and decrease in ability to do housework (p = 0.007) have been shown. In those who lived alone, BDI and TYM higher scores in BDI-II (p = 0.030) (p = 0.022) have been found. CONCLUSION: Mandatory quarantine imposed due to COVID-19 pandemic was associated with worsening of mood, some quality-of-life variables, and decrease in attention in older adults with cognitive impairment in Argentina.

Autoimmune encephalitis: proposed recommendations for symptomatic and long-term management.

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.

Autoimmune encephalitis: proposed best practice recommendations for diagnosis and acute management.

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. Corticosteroids alone or combined with other agents (intravenous IG or plasmapheresis) were selected as a first-line therapy by 84% of responders for patients with a general presentation, 74% for patients presenting with faciobrachial dystonic seizures, 63% for NMDAR-IgG encephalitis and 48.5% for classical paraneoplastic encephalitis. Half the responders indicated they would add a second-line agent only if there was no response to more than one first-line agent, 32% indicated adding a second-line agent if there was no response to one first-line agent, while only 15% indicated using a second-line agent in all patients. As for the preferred second-line agent, 80% of responders chose rituximab while only 10% chose cyclophosphamide in a clinical scenario with unknown antibodies. Detailed survey results are presented in the manuscript and a summary of the diagnostic and therapeutic recommendations is presented at the conclusion.

What is happening with not recommended drugs for dementia in Argentina? Prescription patterns and direct costs analysis.

OBJECTIVES: 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. MATERIALS: 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. RESULTS: 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. CONCLUSION: 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.

[Head turn sign as a marker of dementia diagnosis]. / Signo del giro de la cabeza como marcador para el diagnóstico de demencia.

Due to the phenomenon of ageing population, cognitive impairment has become more prevalent, and any marker able to improve its detection becomes of significant importance. With that objective in mind, a prospective observational study was performed in a medical consultation related to cognitive impairment. 150 subjects (58% women) were included with an average age of 76 years (SD 8.6). The Head Turn sign was positive for 32 subjects with a sensitivity of 41.7% for dementia, a specificity of 93.7% and a negative predictive value of 64.4%. This study shows the semiologic value of a simple clinical sign, easy to spot in the daily practice and most helpful to alert physicians about a likely dementia diagnosis.

[Practice recommendations for the detection and diagnosis of patients with Alzheimer's disease dementia in the City of Buenos Aires]. / Recomendaciones para la detección y diagnóstico de pacientes con demencia debida a Enfermedad de Alzheimer en la Ciudad de Buenos Aires.

Alzheimer's disease is the most frequent cause of cognitive disorders and dementia in older adults and is considered a new epi- demic. Due to its different cognitive, behavioral and functional manifestations, the detection, and diagnosis of patients with Alzheimer's Disease Dementia can represent a challenge. In this Clinical Practice Recommendation, management are given with levels based on the best scientific evidence available. Likewise, indications for study, or referral to a higher level of sanitary assistance are presented, according to the complexity of each clinical case. In this way, a set of practical recommendations of support is provided for decision making by health professionals at each sanitary level, from primary care to medical specialists. Through an operational and dynamic approach, this recommendations propose a global strategy based on evidence for patients, family members and health agents involved in this pathology, of great social relevance.

[Rational use of psychotropic medications and sedative load in older adults with and without dementia]. / Uso de psicofármacos y carga sedativa en pacientes adultos con y sin demencia.

Sedative drugs use has been associated with more cognitive impairment and increased mortality. Sedative load refers to cumulative exposure to multiple drugs with sedative properties. OBJECTIVE: Describe the use of psychotropic drugs and sedative load in older adults with and without dementia. MATERIAL AND METHODS: We conducted a cross-sectional study from 2014-2015 (Sanatorio Trinidad Mitre), in hospitalized patients older than 65 years old. Drugs were classified according to the WHO ATC system. The sedative load of drugs was calculated using the Linjakumpu model. RESULTS: 152 PsD and 35 PcD patients were registered, mean age 80.8±8.42. Polypharmacy was present in 44.39% being higher in patients with dementia than without dementia (62.80% vs 40.13%, p=0.0147). In 40.64% at least one psychotropic/sedative medication was used, greater in PcD (60% vs 36.18%, p=0.0097). The CS was: 1.32±1.59; 2.14 in PcD and 1.13 in PsD (p<0.001). Atypical antipsychotics and benzodiazepines were the most common (51.43 and 40% respectively) in patients without dementias. CONCLUSION: we evidenced a high level of prescription psychotropic or sedative drugs, mostly in patients with dementia. In those, the sedative load was greater. This finding highlights the importance of implementing strategies to optimize sedative drug use among older people.

Cognitive rehabilitation therapy after acquired brain injury in Argentina: psychosocial outcomes in connection with the time elapsed before treatment initiation.

PRIMARY OBJECTIVE: 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. RESEARCH DESIGN: Self-reported data from patients in a naturalistic setting was collected before and after CRT. METHODS AND PROCEDURE: 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. MAIN RESULTS: 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. CONCLUSIONS: 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.

Treatment of Alzheimer's Disease in the New Era of Monoclonal Antibodies Against Cerebral Amyloid-ß: Pharmacological Prescription and Knowledge in Argentina.

Background: Alzheimer's disease (AD) presents a significant global health challenge. Understanding the current and upcoming treatment landscape is crucial for effectively managing patients. Objective: The aim of this study was to assess the pattern of prescription and knowledge about new therapies by physicians who treat AD patients in Argentina. Methods: A cross- sectional and analytic study was conducted. A survey was elaborated about pharmacological treatment in AD. Statistical analysis of answers of specialists in cognitive disorders (SCD), non-specialists in cognitive disorders (NSCD), recommended treatment, non-recommended treatment (NRT), and off-label treatment was performed. Results: 155 physicians answered the survey. A 19.35%prescribed at least one NRT for dementia. 78.06%prescribed at least an off-label treatment or an NRT for mild cognitive impairment (MCI). 31%would prescribe monoclonal antibodies (MABs) against cerebral amyloid-ß (Aß) to AD patients, and 42.6%responded that they were not aware of any adverse effect of these. Quetiapine was the most frequent treatment for psychotic symptoms (88.4%) and escitalopram (32.3%) for apathy. A 70%of potential prescribers of MABs (n = 100) would request biomarkers of cerebral Aß in the initial assessment. There were significant differences between the responses of SCD and NSCD regarding the prescription of MABs (52.17%versus 23.08, respectively) and knowledge about adverse events (76.09%versus 38.46%, respectively). Conclusions: A considerable percentage of physicians indicated NRT and off-label medication in MCI and dementia. In Argentina, there are many physicians who would indicate a MABs for AD, but many are not completely aware of its safety profile.

Efficacy of a cognitive intervention program in patients with mild cognitive impairment.

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.

[Drugs used for cognitive impairment. Analysis of 1.5 million prescriptions in Argentina]. / Medicamentos utilizados para trastornos cognitivos. Análisis de un millón y medio de prescripciones en la Argentina.

Cognitive impairment and dementia treatment costs are significant for health systems. According to national and international guidelines, recommended drugs for treatment of dementias are cholinesterase inhibitors (donepezil, galantamine, rivastigmine) and memantine. Despite these guidelines recommendations, other nootropics, vasodilators and antioxidants are often used in Argentina. The purpose of this study was to describe and compare the prescription pattern of commonly used drugs for the treatment of cognitive disorders and dementia in different regions of Argentina. An observational, retrospective study of 1814108 recipes prescribed to National Institute of Social Services for Retired and Pensioners outpatients during the during the second half of 2008 and the first and second half of 2009 was performed, taking in count the whole country and also different Argentina's regions. Demographic variables, quantity and rate of prescriptions, dosage forms and strengths were analyzed. Considering the entire country, memantine was the most prescribed drug in these periods (570893 packages). An increase in the memantine, donepezil, rivastigmine and idebenone rates of prescription was observed. Prescription rate of memantine increased in the North-West and North-East regions, that of idebenone in the North-East region and Patagonia and donepezil in the North-East region. Non recommended drugs were highly prescribed in all the analyzed regions. Some of them were indicated to young and middle-aged patients.

Triphasic waves and brain atrophy in patients with acute encephalopathy.

Introduction: Triphasic waves (TW) constitute an electroencephalographic pattern associated with certain kinds of encephalopathy. Brain atrophy may be a predisposing factor linked with TW. Objective: To compare the degree of brain atrophy and white matter disease between patients with acute encephalopathy with and without TW. Methods: A retrospective observational study including adult patients with encephalopathy, with and without TW, hospitalized between 2016 and 2017. The degree of brain atrophy and white matter lesion were defined using the Global Cortical Atrophy and Age Related White Matter Changes (ARWMC) scales, respectively. Scores were compared between groups. Mortality rates were registered. Results: Sixteen patients with TW were identified matched by age and sex with 30 patients without TW. The mean age was 80 years in the TW group. Women represented 87.5%. Multifactorial encephalopathy was the most frequent diagnosis followed by metabolic encephalopathy. Patients with TW had more brain atrophy (10.43 vs 6.9, p= 0.03). Mean ARWMC was 9.43±6.5 and 8.5 ±7.89 in patients with and without TW respectively (p= 0.5). Mortality rate was higher in the TW group (31.25 vs 6.66% p= 0.02). Conclusions: Patients with acute encephalopathy and TW had higher degree of cerebral atrophy. It is possible that this structural alteration predisposes to the appearance of TW. There was no significant difference in white matter lesion degree. The mortality of the TW group was high, so future studies are necessary to determine their prognostic value.

Introducción: Las ondas trifásicas (OT) constituyen un patrón electroencefalográfico asociado con diversas encefalopatías. La atrofia cerebral podría predisponer a su aparición. Objetivo: Comparar el grado de atrofia cerebral y de lesión de sustancia blanca en pacientes con encefalopatía aguda con y sin OT. Métodos: Estudio observacional retrospectivo, incluyó pacientes adultos con encefalopatía aguda con y sin OT internados entre 2016 y 2019. El grado de atrofia cerebral y de lesión de sustancia blanca se definieron según las escalas Global Cortical Atrophy y Age Related White Matter Changes (ARWMC), respectivamente. Se compararon los puntajes entre grupos. Se registró la mortalidad. Resultados: Se identificaron 16 pacientes con OT y 30 sin OT pareados según edad y sexo. La edad promedio del grupo con OT fue 80 años. El 87.5% fueron mujeres. La encefalopatía multifactorial fue el diagnóstico más frecuente seguido de la encefalopatía metabólica. El grado de atrofia fue mayor en pacientes con OT (10.43 vs 6.9, p= 0.03). El puntaje ARWMC fue 9.43 ±6.5 y 8.5 ±7.89 en pacientes con y sin OT respectivamente (p= 0.5). La mortalidad fue mayor en el grupo con OT (31.25 vs 6.66% p= 0.02). Conclusiones: Pacientes con encefalopatía aguda y OT tuvieron mayor grado de atrofia cerebral. Dicha alteración estructural podría relacionarse con la aparición de OT. No hubo diferencias significativas en el grado de lesión de sustancia blanca. La mortalidad del grupo con OT fue elevada. Son necesarios estudios para determinar su valor pronóstico.

Clinical and economic characteristics associated with direct costs of Alzheimer's, frontotemporal and vascular dementia in Argentina.

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.

[Analysis of advertising on neurological drugs received during the medical consultation]. / Análisis de publicidades sobre medicamentos neurológicos recibidos durante la consulta médica.

Drug promotion and advertisement by pharmaceutical industry influence medical prescription and, in some cases, the information provided is incomplete or biased. The objective was to analyze the advertisements delivered by medical representatives and determine if the information was appropriate for rational prescribing. It is a prospective study (March to November 2018) by collecting print advertisements randomly received in neurology centers. It was evaluated if they met the ethical criteria established by the WHO, using as a reference leaflets from Administración Nacional de Medicamentos, Alimentos y Tecnología Médica (ANMAT), Food and Drugs Administration (FDA) and pharmacology books. A committee of pharmacology physicians analyzed if the content of the pamphlets was misleading according to the WHO. Sixty advertisements were analyzed, being anti-epileptics and antidepressants the most advertised drugs. The 33.3% (n = 20) of them included leaflets in accordance to ANMAT. One case presented an "off-label" indication. Drug action was presented in 31.7% (n = 19) of the pamphlets, adverse reactions in 40% (n = 24), posology in 45% (n = 27), contraindications in 38.3% (n = 23) and the necessary precautions in 36.7% (n = 22) of them. The information provided was false in 80% (n = 48) and 53.3% (n = 32) contained misleading images; and 69.2% (n = 18) of the graphics were false. The information provided by medical advertisements analyzed in this study would be insufficient to know and prescribe a new drug. Lack of information in posology, contraindication, drug action and adverse reactions do not contribute to rational use of medications.

La publicidad y promoción de medicamentos por parte de la industria farmacéutica ejerce influencia sobre la prescripción médica y, en algunos casos, la información provista es incompleta o sesgada. El objetivo fue analizar las publicidades entregadas por representantes médicos y determinar si la información era apropiada para la prescripción racional. Es un estudio prospectivo (marzo a noviembre 2018) mediante la recolección de publicidades impresas recibidas aleatoriamente en centros de neurología. Se evaluó si cumplían los criterios éticos establecidos por la OMS, utilizando como referencia prospectos de la Administración Nacional de Medicamentos, Alimentos y Tecnología médica (ANMAT), la Food and Drugs Administration (FDA) y libros de farmacología. Un comité de médicos farmacólogos analizó si el contenido de los folletos era engañoso según la OMS. Se analizaron 60 publicidades, siendo antiepilépticos y antidepresivos los más publicitados. El 33.3% (n = 20) incluían prospectos acordes según ANMAT. Un caso presentaba indicación off-label. Los folletos exponían el mecanismo de acción en el 31.7% (n = 19), las reacciones adversas medicamentosas 40% (n = 24), la posología en el 45% (n = 27), las contraindicaciones 38.3% (n = 23) y en 36.7% (n = 22) las precauciones necesarias. La información brindada era falaz en el 80% (n = 48) y el 53.3% (n = 32) tenían imágenes capciosas. El 69.2% (n = 18) de los gráficos eran capciosos. En el presente trabajo, la información brindada por la publicidad médica sería insuficiente para conocer y prescribir nuevos fármacos. La falta de información en la posología, contraindicaciones, mecanismos de acción y reacciones adversas no contribuyen al uso racional de medicamentos.

[Use and abuse of drugs in cognitive impairment patients]. / Usos y abusos de fármacos en pacientes con deterioro cognitivo.

INTRODUCTION: Irrational use of drugs for the treatment of cognitive impairment can increase health costs in developing countries. OBJECTIVE: to analyze the pattern of drug prescription related to the treatment of patients with dementia and to compare them with the income of patients. PATIENTS: 313 community-based outpatients that seeked medical advice for memory problems, in the Memory Center of Zubizarreta General Hospital (Buenos Aires, Argentina), were prospectively assessed during a period of a year. RESULTS: Patients' mean income was 502.81 "Pesos Argentinos" which is equivalent to US$152 per month (2007). Fourty one point fifty five percent (41.55%) of the patients had dementia, 15.65% psychiatric diseases, 15.01% mild cognitive impairment and 27.79% were normal. Patients received an average of 2.84 drugs/day, 20% of the patients took at least one drug for cognitive impairment (9.85% memantine, 6.38% donepezil and 4% nootropics, cerebral vasodilators or antioxidants), and 39.3% received psychotropic medication (28.11% benzodiazepines and 9.26 % atypical antipsychotics). Twelve point seventy six percent (12.76%) of the patients with mild cognitive impairment were treated with antidementials, 5.74% of normal subjects received antidementials. 4% of patients were exclusively treated with free samples. CONCLUSION: In our sample irrational degree of using antidemential drugs and psychotropic agents was found.

Moaning Phenomenon and Rapidly Progressive Dementia in Anti LGI-1 Associated Progressive Supranuclear Palsy Syndrome.

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.

A novel mutation in PSEN1 (p.Arg41Ser) in an Argentinian woman with early onset Parkinsonism.

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.

Triphasic waves and brain atrophy in patients with acute encephalopathy / Ondas trifásicas y atrofia cerebral en pacientes con encefalopatía aguda

Abstract Introduction: Triphasic waves (TW) constitute an electroencephalographic pattern associated with certain kinds of encephalopathy. Brain atrophy may be a predisposing factor linked with TW. Objective: To compare the degree of brain atrophy and white matter disease between patients with acute encephalopathy with and without TW. Methods: A retrospective observational study including adult patients with encephalopathy, with and without TW, hospitalized between 2016 and 2017. The degree of brain atrophy and white matter lesion were defined using the Global Cortical Atrophy and Age Related White Matter Changes (ARWMC) scales, respectively. Scores were compared between groups. Mortality rates were registered. Results: Sixteen patients with TW were identified matched by age and sex with 30 patients without TW. The mean age was 80 years in the TW group. Women represented 87.5%. Multifactorial encephalopathy was the most frequent diagnosis followed by metabolic encephalopathy. Patients with TW had more brain atrophy (10.43 vs 6.9, p= 0.03). Mean ARWMC was 9.43±6.5 and 8.5 ±7.89 in patients with and without TW respectively (p= 0.5). Mortality rate was higher in the TW group (31.25 vs 6.66% p= 0.02). Conclusions: Patients with acute encephalopathy and TW had higher degree of cerebral atrophy. It is possible that this structural alteration predisposes to the appearance of TW. There was no significant difference in white matter lesion degree. The mortality of the TW group was high, so future studies are necessary to determine their prognostic value.

Resumen Introducción: Las ondas trifásicas (OT) constituyen un patrón electroencefalográfico asociado con diversas encefalopatías. La atrofia cerebral podría predisponer a su aparición. Objetivo: Comparar el grado de atrofia cerebral y de lesión de sustancia blanca en pacientes con encefalopatía aguda con y sin OT. Métodos: Estudio observacional retrospectivo, incluyó pacientes adultos con encefalopatía aguda con y sin OT internados entre 2016 y 2019. El grado de atrofia cerebral y de lesión de sustancia blanca se definieron según las escalas Global Cortical Atrophy y Age Related White Matter Changes (ARWMC), respectivamente. Se compararon los puntajes entre grupos. Se registró la mortalidad. Resultados: Se identificaron 16 pacientes con OT y 30 sin OT pareados según edad y sexo. La edad promedio del grupo con OT fue 80 años. El 87.5% fueron mujeres. La encefalopatía multifactorial fue el diagnóstico más frecuente seguido de la encefalopatía metabólica. El grado de atrofia fue mayor en pacientes con OT (10.43 vs 6.9, p= 0.03). El puntaje ARWMC fue 9.43 ±6.5 y 8.5 ±7.89 en pacientes con y sin OT respectivamente (p= 0.5). La mortalidad fue mayor en el grupo con OT (31.25 vs 6.66% p= 0.02). Conclusiones: Pacientes con encefalopatía aguda y OT tuvieron mayor grado de atrofia cerebral. Dicha alteración estructural podría relacionarse con la aparición de OT. No hubo diferencias significativas en el grado de lesión de sustancia blanca. La mortalidad del grupo con OT fue elevada. Son necesarios estudios para determinar su valor pronóstico.

Sertraline-induced Hemichorea.

Background: Hemichorea-hemiballism is a syndrome secondary to different etiologies. Drug-induced hemichorea is a rare syndrome related to selective serotonin reuptake inhibitors. To the best of our knowledge, no previous cases of hemichorea associated with sertraline have been reported. Case Report: A 65-year-old female noticed hemichorea 1 week after initiation of sertraline. After extensive investigations, other causes of hemichorea were excluded. Hemichorea remitted after sertraline withdrawal. Discussion: In our patient, temporal association and the negative clinical assessment supported a diagnosis of likely drug-induced involuntary movement. We hypothesized that enhanced serotonergic transmission in the ventral tegmental area or nigrostriatum may be involved in sertraline-induced hemichorea.

Validation of the Argentine version of the Memory Binding Test (MBT) for Early Detection of Mild Cognitive Impairment.

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<.01). The MBT showed high sensitivity (69%) and high specificity (88%), with a PPV of 93% and a NPV of 55% for associative paired recall. A statistically significant difference (c2=14,164, p<.001) was obtained when comparing the area under the curve (AUC) of the MBT (0.88) and the MMSE (0.70). CONCLUSION: The Argentine version of the MBT correlated significantly with the MMSE and the memory battery and is a useful tool in the detection of MCI. The operating characteristics of the MBT are well suited, surpassing other tests commonly used for detecting MCI.

"Esquecimento" é queixa frequente no envelhecimento normal e também ocorre nos primeiros estágios de síndromes demenciais. Testes de memória episódica são fundamentais para detectar comprometimento cognitivo amnéstico (CCL). O teste de Memória Associativa (Memory Binding Test-MBT) é um teste fácil e breve para detectar a fase inicial de perda de memória episódica. OBJETIVO: Validar a versão argentina do MBT e estimar a sua acurácia como instrumento diagnóstico para a detecção precoce do CCL. MÉTODOS: 88 indivíduos (46 controles saudáveis ​​e 42 pacientes com CCL amnéstico), emparelhados por idade e nível educacional, foram avaliados com extensa bateria neuropsicológica e o MBT. RESULTADOS: Um desempenho significativamente melhor foi detectada no grupo controle; todas as escalas do MBT foram preditivas do diagnóstico de CCL (p<0,01). O MBT apresentou alta sensibilidade (69%) e alta especificidade (88%), com valor preditivo (VP) positivo de 93% e e VP negativo de 55% para a recordação dos itens associados (associative paired recall). Diferença estatisticamente significativa (c2=14,164, p<0,001) foi obtida quando foram comparadas as áreas sob as curvas (AUC) do MBT (0,88) e o Mini-Exame do Estado Mental (MEEM) (0,70). CONCLUSÃO: A versão argentina do MBT correlacionou-se significativamente com o MEEM e com a bateria de memória e é uma ferramenta útil na detecção de CCL. As características operacionais do MBT são bem adequadas, superando outros testes usualmente utilizados para a detecção de CCL.