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.

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.

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.

Discharges With Triphasic Morphology as Marker of the Risk of Death in Acute Encephalopathy.

Introduction. In clinical practice, it is difficult to define the prognosis of patients with acute encephalopathy; a syndrome characterized by cognitive dysfunction and altered sensorium. Discharges with triphasic morphology (DTM) are an electroencephalographic pattern that might be useful to establish the risk of death. The aim of this study was to define the prognostic value of DTM regarding mortality in patients with acute encephalopathy. Methods. We conducted an observational retrospective cohort study including patients with acute encephalopathy with and without DTM paired by age and gender in a 1:2 ratio. We calculated the odds ratio (OR) to determine the association between DTM and mortality. In addition, we calculated sensibility, specificity, and predictive values. Results. We included 72 patients, 24 with DTM and 48 without DTM. Mortality was higher in patients with DTM (41.6% vs 14.5%, P = .01). Factors associated with a higher risk of death were DTM (OR = 4.1, 95% confidence interval [CI] 1.3-13, P = .01) and sequential organ failure assessment score (OR = 1.3, 95% CI 1.04-1.67, P = .02). A higher Glasgow coma scale score was associated with a lower risk of death (OR = 0.65, 95% CI 0.51-0.83, P = .001). The sensibility and specificity of DTM were 59% and 75%, respectively. Positive and negative likelihood ratios were 2.36 and 0.55. Discussion. Our results revealed high mortality in patients with acute encephalopathy and DTM. This electroencephalographic pattern was associated with 4 times higher risk of death. However, its usefulness for predicting death was limited.

Análisis video-electroencefalográfico de crisis epilépticas con inicio ictal de difícil lateralización, en epilepsia temporal mesial / Video-electroencephalographic analysis of epileptic seizures with ictal onset of difficult lateralization, in mesial temporal epilepsy

El propósito del trabajo fue analizar las características clínicas y electrofisiológicas de pacientes que presentaron crisis originadas en ambas regiones temporales en los registros de Video- EEG de scalp. Del total de la población con epilepsia temporal mesial (ET), resistente a las drogas, que ingresó a la Unidad de Video-EEG del Hospital Municipal Ramos Mejía y del Hospital de Alta Complejidad en Red El Cruce Dr. Néstor C. Kirchner, desde marzo de 2009 a marzo de 2014 (n=150), se seleccionaron 9 pacientes con crisis originadas en ambas regiones temporales (40 crisis focales con compromiso de la conciencia). Del total de los pacientes con epilepsia del lóbulo temporal fármaco-resistente, candidatos a cirugía de la epilepsia, en un 6% de los casos resultó difícil lateralizar la zona epileptógena con el registro de Video-EEG de scalp.

Frecuencia de crisis y eventos adversos en pacientes medicados con drogas antiepilépticas genéricas u originales / Frequency of seizures and adverse events in patients treated with generic or original antiepileptic drugs

NTRODUCCIÓN Las epilepsias son el trastorno neurológico crónico más común. Las drogas antiepilépticas (DAE) necesarias no siempre están disponibles o son muy caras. Las variantes genéricas son una estrategia para mejorar el acceso. OBJETIVOS Investigar si la utilización de DAE genéricas mantiene la efectividad para el paciente, con igual control de crisis y perfil de seguridad que los medicamentos originales. MÉTODOS Se realizó un estudio observacional de casos y controles, que comparó la reducción en la frecuencia de crisis y el perfil de seguridad en pacientes epilépticos de reciente diagnóstico de 15 a 85 años, medicados a dosis estable y adecuada durante al menos un año en el Hospital Ramos Mejía de la ciudad de Buenos Aires. Se comparó a pacientes medicados con DAE genéricas (casos) y con DAE originales (controles). RESULTADOS De 139 pacientes, 61 llegaron al año desde su incorporación 45 tomaban DAE genéricas, y 16, originales. De ellos, 23 (51,1%) con DAE genéricas y 10 (62,5%) con originales presentaron una reducción de crisis igual o mayor al 50% (OR: 0,6273; IC95%: 0,1949-2,0186; Z: 0,782; p: 0,4342). Por otra parte, 15 (33,3%) con DAE genéricas y 5 (31,2%) con originales presentaron eventos adversos (OR: 0,9091; IC: 0,2669-3,0961; Z: 0,152; p 0,8788). DISCUSIÓN Tanto en el porcentaje de reducción de crisis como en la presencia de eventos adversos, las diferencias no fueron significativas, aunque esto podría deberse a la baja cantidad de pacientes incluidos en el estudio.

Risk factors associated with DRESS syndrome produced by aromatic and non-aromatic antipiletic drugs.

PURPOSE: DRESS (drug reaction with eosinophilia and systemic symptoms) is an idiosyncratic entity associated with the use of drugs. Its pathophysiology is not known, but is associated with immunological or genetic factors. The incidence is 0.4 cases per 1,000,000 general population. The syndrome usually develops at the beginning of treatment and is characterized by the presence of rash, fever, eosinophilia and systemic manifestations. The aim of our study was to describe the clinical manifestation and treatment of patients with DRESS associated with antiepileptic drugs (AEDs). METHODS: This is a descriptive study with the aim of describing the clinical manifestation and treatment associated with DRESS produced by aromatic and non-aromatic AEDs. RESULTS: Eight patients treated with AEDs developed DRESS between January 2007 and May 2010 at our hospital. All had dermatological manifestations, eosinophilia and systemic (haematological and hepatic) manifestations that could be attributed to treatment with aromatic AEDs (carbamazepine, 2 patients; lamotrigine, 3 patients; phenytoin, 3 patients). Therapeutic management included removal of the drug from the therapeutic regime, symptomatic management, life support and use of corticosteroids. There was no mortality associated with the syndrome. Reversion of systemic manifestations was very slow: between 1 and 6 months. CONCLUSIONS: DRESS is a severe cutaneous reaction, with high morbidity and mortality, whose development seems to be associated with individual susceptibility, type of antiepileptic drug used (more common with aromatic drugs), titration rate and concomitant medications.

ApoE epsilon4 is not associated with posictal confusion in patients with mesial temporal lobe epilepsy with hippocampal sclerosis.

A previous report found an association between ApoE isoforms and postictal confusion in medically intractable temporal lobe epilepsy (TLE). We performed a molecular epidemiology study in an independent sample of 77 TLE patients. We failed to replicate the original allelic association between ApoE epsilon4 allele and postictal confusion in our population (chi(2)=1.67; d.f.=1; p=0.2). Thus, the association between ApoE epsilon4 allele and postictal confusion still needs to be fully investigated in different and independent populations.