Alteraciones genéticas asociadas a la enfermedad de Parkinson y Alzheimer: evolución y respuesta al tratamiento / Genetic Alterations Associated with Parkinson's and Alzheimer's Disease: Evolution and Response to Treatment

La enfermedad de Parkinson y Alzheimer son las enfermedades neurodegenerativas más frecuentes a nivel mundial. Tienen etiología multifactorial, entre ellas, la genética; y son motivo de interés en la investigación científica actual. Se realizó una revisión narrativa con el objetivo de determinar las alteraciones genéticas asociadas a estas patologías, además su influencia en la evolución y respuesta al tratamiento de ellas. Se consultaron artículos originales, revisiones bibliográficas, sistemáticas, metaanálisis en inglés y español, con fecha de publicación entre el 1 enero de 2018 y el 20 de mayo de 2023, en bases como PubMed y Medline. Se utilizaron los términos MeSH «Alzheimer Disease¼, «Parkinson Disease¼, «Drug Therapy¼ y «Mutations¼. El riesgo hereditario para la enfermedad de Parkinson suele ser poligenético, sin embargo, existen genes relacionados con mutaciones monogénicas. Se identifican alteraciones en genes de α-sinucleína, glucocerebrosidasa y quinasa 2 rica en leucina que se relacionan con mayor riesgo de desarrollar Parkinson, además de variaciones en el cuadro clínico y edad de inicio de síntomas. En cuanto a la enfermedad de Alzheimer, las alteraciones en los genes de la proteína precursora amiloide, presenilina 1 y 2 se relacionan con la forma familiar de la enfermedad; por otra parte, las de apolipoproteína E4 se han identificado en la forma esporádica, por lo que se consideran como el factor de riesgo genético más importante para su desarrollo

Parkinson's and Alzheimer's are the most frequent neurodegenerative diseases worldwide. They have a multifactorial etiology, including genetics, and are of interest in current scientific research. A narrative review was carried out with the aim of determining the genetic alterations associated with these pathologies, as well as their influence on their evolution and response to treatment. Original articles, literature reviews, systematic reviews, meta-analyses in English and Spanish, with publication date between January 1, 2018 and May 20, 2023, were consulted in databases such as PubMed and Medline. MeSH terms "Alzheimer Disease", "Parkinson Disease", "Drug Therapy" and "Mutation" were used. Hereditary risk for Parkinson's disease is usually polygenetic, however, there are genes related to monogenic mutations. Alterations in α-synuclein, glucocerebrosidase and leucine-rich kinase 2 genes have been identified that are related to an increased risk of developing Parkinson's disease, in addition to variations in the clinical picture and age of symptom onset. As for Alzheimer's disease, alterations in the genes of the amyloid precursor protein, presenilin 1 and 2 are related to the familial form of the disease; on the other hand, those of apolipoprotein E4 have been identified in the sporadic form, and are therefore considered to be the most important genetic risk factor for its development

A novel self-expanding shape memory polymer coil for intracranial aneurysm embolization: 1 year follow-up in Chile.

BACKGROUND: Aneurysm recurrence remains a challenge when coiling cerebral aneurysms. Development of next generation coils has focused on accelerating thrombus maturation and increasing coil packing density. Ultra low density shape memory polymer is a novel embolic material designed for this purpose. The polymer is crimped over a platinum-tungsten coil for catheter delivery and self-expands to a predefined volume on contact with blood. METHODS: This prospective study in humans evaluated aneurysms 5-16 mm (inclusive) in diameter that were indicated for endovascular coil embolization. At least 70% coil volume was required to be shape memory polymer coils. Patients were followed-up according to standard of care for 12 months. RESULTS: Nine patients (89% women, mean age 55.8±11.7 years) were treated with shape memory polymer coils and completed 12 months of follow-up. Aneurysms were all unruptured and were in the ophthalmic segment of the internal carotid artery (n=7), posterior communicating artery, and anterior cerebral artery A1-A2 segment. Aneurysms were a mean of 7.8±2.9 mm in diameter (range 5.2-14.9 mm). The mean packing density based on unexpanded polymer was 17±6%. Packing density based on expanded polymer was 43±13%. At 12 months, no recurrence had occurred, and a Raymond-Roy occlusion classification of 1 (n=5) or 2 (n=4) was observed. No serious adverse events related to the study device occurred over the 12 months after the procedure. CONCLUSIONS: Shape memory polymer coils were safe and effective in treating intracranial aneurysms over 12 months in this first study in human subjects.

Predicting and Characterizing Neurodegenerative Subtypes with Multimodal Neurocognitive Signatures of Social and Cognitive Processes.

BACKGROUND: Social cognition is critically compromised across neurodegenerative diseases, including the behavioral variant frontotemporal dementia (bvFTD), Alzheimer's disease (AD), and Parkinson's disease (PD). However, no previous study has used social cognition and other cognitive tasks to predict diagnoses of these conditions, let alone reporting the brain correlates of prediction outcomes. OBJECTIVE: We performed a diagnostic classification analysis using social cognition, cognitive screening (CS), and executive function (EF) measures, and explored which anatomical and functional networks were associated with main predictors. METHODS: Multiple group discriminant function analyses (MDAs) and ROC analyses of social cognition (facial emotional recognition, theory of mind), CS, and EF were implemented in 223 participants (bvFTD, AD, PD, controls). Gray matter volume and functional connectivity correlates of top discriminant scores were investigated. RESULTS: Although all patient groups revealed deficits in social cognition, CS, and EF, our classification approach provided robust discriminatory characterizations. Regarding controls, probabilistic social cognition outcomes provided the best characterization for bvFTD (together with CS) and PD, but not AD (for which CS alone was the best predictor). Within patient groups, the best MDA probabilities scores yielded high classification rates for bvFTD versus PD (98.3%, social cognition), AD versus PD (98.6%, social cognition + CS), and bvFTD versus AD (71.7%, social cognition + CS). Top MDA scores were associated with specific patterns of atrophy and functional networks across neurodegenerative conditions. CONCLUSION: Standardized validated measures of social cognition, in combination with CS, can provide a dimensional classification with specific pathophysiological markers of neurodegeneration diagnoses.

First multicenter experience using the Silk Vista flow diverter in 60 consecutive intracranial aneurysms: technical aspects.

BACKGROUND: The aim of this study was to assess the technical success and procedural safety of the new Silk Vista device (SV) by evaluating the intraprocedural and periprocedural complication rate after its use in several institutions worldwide. METHODS: The study involved a retrospective review of multicenter data regarding a consecutive series of patients with intracranial aneurysms, treated with the SV between September 2020 and January 2021. Clinical, intra/periprocedural and angiographic data, including approach, materials used, aneurysm size and location, device/s, technical details and initial angiographic aneurysm occlusion, were analyzed. RESULTS: 60 aneurysms were treated with SV in 57 procedures. 66 devices were used, 3 removed and 63 implanted. The devices opened instantaneously in 60 out of 66 (91%) cases and complete wall apposition was achieved in 58 out of 63 (92%) devices implanted. In 4 out of 66 (6%) devices a partial opening of the distal end occurred, and in 5 (8%) devices incomplete apposition was reported. There were 3 (5%) intraprocedural thromboembolic events managed successfully with no permanent neurological morbidity, and 4 (7%) postprocedural events. There was no mortality in this study. The initial occlusion rates in the 60 aneurysms were as follows: O'Kelly-Marotta (OKM) A in 34 (57%) cases, OKM B in 15 (25%) cases, OKM C in 6 (10%) cases, and OKM D in 5 (8%) cases. CONCLUSIONS: Our study demonstrated that the use of the new flow diverter Silk Vista for the treatment of intracranial aneurysms is feasible and technically safe.

Treatments used for obsessive-compulsive disorder-An international perspective.

OBJECTIVE: The objective of this study was to characterise international trends in the use of psychotropic medication, psychological therapies, and novel therapies used to treat obsessive-compulsive disorder (OCD). METHODS: Researchers in the field of OCD were invited to contribute summary statistics on the characteristics of their samples. Consistency of summary statistics across countries was evaluated. RESULTS: The study surveyed 19 expert centres from 15 countries (Argentina, Australia, Brazil, China, Germany, Greece, India, Italy, Japan, Mexico, Portugal, South Africa, Spain, the United Kingdom, and the United States) providing a total sample of 7,340 participants. Fluoxetine (n = 972; 13.2%) and fluvoxamine (n = 913; 12.4%) were the most commonly used selective serotonin reuptake inhibitor medications. Risperidone (n = 428; 7.3%) and aripiprazole (n = 415; 7.1%) were the most commonly used antipsychotic agents. Neurostimulation techniques such as transcranial magnetic stimulation, deep brain stimulation, gamma knife surgery, and psychosurgery were used in less than 1% of the sample. There was significant variation in the use and accessibility of exposure and response prevention for OCD. CONCLUSIONS: The variation between countries in treatments used for OCD needs further evaluation. Exposure and response prevention is not used as frequently as guidelines suggest and appears difficult to access in most countries. Updated treatment guidelines are recommended.

Experiencia en el tratamiento endovascular del accidente cerebrovascular isquémico agudo en un centro chileno / Emergency endovascular management of ischemic stroke: experience in 104 patients

Background: Recently, five randomized controlled trials confirmed the efficacy and safety of endovascular treatment with or without intravenous thrombolysis in acute ischemic stroke with large-vessel occlusion. Aim: To report patients with ischemic stroke treated with endovascular methods. Material and Methods: Retrospective analysis of 104 patients aged 61 ± 15 years (54% males) with ischemic stroke who received endovascular treatment at a single medical center between 2009 and 2017. Results: Sixty one percent were treated with intravenous thrombolysis plus endovascular procedures and 39% with endovascular procedures alone. The median door-to needle time was 61 minutes and door-to femoral puncture was 135 minutes. The median National Institute of Health Stroke Scale (NIHSS) scores on admission, 24 hours later and at discharge were 12,4 and 1 points, respectively. Middle cerebral artery was occluded in 60% of cases. Other frequent localizations where distal carotid artery in 17% and vertebro-basilar artery in 14%. Thrombolysis in cerebral infarction (TICI) scale flow score after the procedure was 3 or 2b in 58% of cases and significantly correlated with NIHSS scores at 24 hours and discharge. Fifty percent of patients had a mRankin score < = 1 and ten patients died (9.6%). Eight percent had a symptomatic intracerebral hemorrhage. Conclusions: The clinical improvement of these patients 24 hours after the procedure and at discharge demonstrate the effectiveness of endovascular treatment in ischemic stroke. The presence neurologists able to interpret multimodal images at the emergency room, the use of local guidelines, the availability of an experienced neuro-interventional team engaged with the workflow and the use of stent retrievers are strongly associated with good outcomes.

Accuracy of ASGE criteria for the prediction of choledocholithiasis.

BACKGROUND/AIMS: Few studies have validated the performance of guidelines for the prediction of choledocholithiasis (CL). Our objective was to prospectively assess the accuracy of the American Society for Gastrointestinal Endoscopy (ASGE) guidelines for the identification of CL. METHODS: A two-year prospective evaluation of patients with suspected CL was performed. We evaluated the ASGE guidelines and its component variables in predicting CL. RESULTS: A total of 256 patients with suspected CL were analyzed. Of the 208 patients with high-probability criteria for CL, 124 (59.6%) were found to have a stone/sludge at endoscopic retrograde cholangiopancreatography (ERCP). Among 48 patients with intermediate-probability criteria, 21 (43.8%) had a stone/sludge. The performance of ASGE high- and intermediate-probability criteria in our population had an accuracy of 59.0% (85.5% sensitivity, 24.3% specificity) and 41.0% (14.4% sensitivity, 75.6% specificity), respectively. The mean ERCP delay time was 6.1 days in the CL group and 6.4 days in the group without CL, p = 0.638. The presence of a common bile duct (CBD) > 6 mm (OR 2.21; 95% CI, 1.20-4.10), ascending cholangitis (OR 2.37; 95% CI, 1.01-5.55) and a CBD stone visualized on transabdominal US (OR 3.33; 95% CI, 1.48-7.52) were stronger predictors of CL. The occurrence of biliary pancreatitis was a strong protective factor for the presence of a retained CBD stone (OR 0.30; 95% CI, 0.17-0.55). CONCLUSIONS: Irrespective of a patient's ASGE probability for CL, the application of current guidelines in our population led to unnecessary performance of ERCPs in nearly half of cases.

Unusual origin of the left ophthalmic artery from the basilar trunk.

The formation of the ophthalmic artery (OA) is a complex process with two different proposed embryological steps for its development. Several anatomical variants have been described. We present a very unusual origin of the ophthalmic artery from the basilar trunk, in a 45-year-old male with a history of pontine hemorrhagic stroke. MRI and CTA showed evidence of previous hemorrhage in the pons and several intracranial arterial dysplastic dilatations. DSA confirmed several fusiform dilatations of the basilar trunk. In the left ICA, no ophthalmic artery was seen arising from the carotid siphon. The left ophthalmic artery arises from the basilar trunk and runs lateral to the cavernous sinus through the middle cranial fossa, entering the left orbit at the superior orbital fissure. The patient was treated conservatively. Two main theories for this anomaly are known, one from Lasjaunias and the other from Paget. To our knowledge, this basilar origin of the OA has only been described three times in the literature. For its origin, we propose a partial persistence of the trigeminal artery together with a dominance of the dorsal ophthalmic artery.

Descripción de los cambios en la velocidad media de flujo sanguíneo cerebral en posición supino y sedente, en pacientes con hemorragia subaracnoidea aneurismática con vasoespasmo asintomático o sin vasoespasmo: Serie de casos / Changes in cerebral blood flow velocity in supine and sitting position in patients with aneurysmal subarachnoid hemorrhage

Background: Early mobilization in intensive care units (ICU) provides respiratory, neurological and cardiovascular benefits in hospitalized patients. However, the orthostatic effects of changing from a supine to a sitting position may interfere with cerebral hemodynamics of patients with aneurysmal subarachnoid hemorrhage (aSAH). Aim: To describe the changes in mean cerebral blood flow velocity (MCBFV) in supine and sitting position, in adult patients with aSAH, with asymptomatic vasospasm (AVS) or without vasospasm (VS) at a neurosurgical ICU. Material and Methods: Descriptive case series study in 21 patients with aSAH, both with and without VS. They were positioned in a supine 30° position and then seated at the edge of bed for six minutes. MCBFV was measured by transcranial Doppler (TCD), and hemodynamic variables in both positions were registered. After this basal assessment and for 21 days after the episode of SAH, patients were seated once a day and signs of VS were recorded. Results: No significant changes in MCBFV or hemodynamic variables were detected during position changes, except for an increase in heart rate in the sitting position. No patient with AVS at the onset, had symptomatic VS during the 21 days of follow up when patients were seated. Among patients with a normal MCBFV at baseline, five patients (24%) had VS at a mean of three days after the first time that they were seated on the edge of bed. Conclusions: Sitting patients at the edge of the bed is a safe mobilization alternative for patients who suffered aSAH who did not have VS or had AVS.

Níveis comparativos de estresse oxidativo em camundongos em duas situações do limite orgânico: overreaching induzido por treinamento de natação e câncer / Comparative oxidative stress levels in mice submitted to two situations of organic limit: overreaching induced by swimming training and cancer

O objetivo deste trabalho foi comparar concentrações de estresse oxidativo em camundongos da linhagem Balb-C submetidos a duas condições severas de alterações orgânicas: treinamento exaustivo de natação (overreaching - grupo OVER; n = 10) e inoculação por tumor ascítico de Ehrlich (grupo TAE; n = 10). A proposta foi analisar como as duas situações comprometiam o equilíbrio entre os sistemas oxidantes e antioxidantes. Foram investigados alguns marcadores de estresse oxidativo, tais como as substâncias reativas ao ácido tiobarbitúrico (TBARS) e concentrações da atividade da enzima antioxidante catalase (CAT) no hemolisado. Como marcadores de lesão celular, quantificaram-se concentrações plasmáticas das enzimas creatina quinase (CK) e aspartato transferase (AST); complementado; também se observaram padrões de alterações fisiológicas por meio da quantificação plasmática de creatinina e uréia. Como resultados mais importantes, pôde-se observar que, nas duas situações de limite orgânico, seja por exercício exaustivo (OVER) ou pela inoculação de TAE, houve queda abrupta na concentração da enzima CAT (decréscimos de 30 por cento; p < 0,01 e 72 por cento; p < 0,001, respectivamente, comparando-se com o grupo treinado - T). Quanto à concentração de peroxidação lipídica (TBARS), detectaram-se aumentos significativos para os grupos OVER e TAE em relação ao grupo T (52 por cento, p < 0,01; 90 por cento, p < 0,001, respectivamente). Níveis liberados de CK foram mais proeminentes no grupo OVER, enquanto que a quantidade de AST no plasma foi mais elevada no grupo TAE. Chegou-se à conclusão de que os organismos estudados possuem um mesmo perfil de estresse oxidativo em situações limites que envolvem exercício físico e doença. Tais resultados permitirão profissionais envolvidos com elaboração das cargas de treinamento físico a se preocuparem com os períodos recuperativos, o que impede a instalação do quadro de overreaching, o qual se mostrou tão severo...

The aim of this study was to compare oxidative stress levels in mice (Balb-C) submitted to two severe organic conditions: exhaustive swimming training (overreaching - OVER group; n = 10) and inoculation of the Ehrlich's Ascitic Tumor (EAT group; n = 10). Lipid peroxidation, quantified by thiobarbituric acid reactive substances (TBARS), and levels of antioxidant enzyme (catalase- CAT) were used as indicators of oxidative stress. Muscle damage levels were measured through plasma creatine kinase (CK), aspartate transaminase (AST) as well as blood creatinine and urea activities samples. As main results, it has been observed that in both situations, whether by exhaustive exercise (OVER) or inoculation of EAT, dramatic decrease in the catalase activity levels was present when compared with the training group (T) (30 percent; p < 0.01 and 72 percent; p < 0.001, respectively) with concomitant increase in plasma TBARS concentration (52 percent; p < 0.01 and 90 percent p < 0.001, respectively). Plasma CK levels were more prominent in the OVER group, while the amount of AST plasma was higher in the EAT group. We concluded that the same profile of oxidative stress was found in situations involving exhaustive exercise and pathology. These results will allow professionals involved with load training manipulation to be concerned with the rest periods, preventing hence the installation of overreaching, which in terms of oxidative stress, was as severe as a pathological conditions.

Reticulócitos e hematócrito de cães pré e pós esplenectomia parcial / Reticulocytes and hematocrit of dogs before and after partial splenectomy

Os reticulócitos são células eritróides que exibem RNA residual e são liberados da medula óssea em resposta à hipoxia tecidual. Após sua liberação da medula óssea, ficam temporariamente seqüestrados no baço, onde adquirem forma de eritrócitos maturos. Além disso, o baço também é responsável pelo armazenamento do sangue e seus elementos. A esplenectomia é indicada para casos de torção ou ruptura esplênica, esplenomegalia sintomática e massas esplênicas. Este estudo tem como objetivo avaliar a resposta dos reticulócitos e do hematócrito em cães submetidos à remoção parcial do baço. Para isso, foram utilizados nove cães, sem raça definida, machos e fêmeas. As coletas foram feitas uma hora antes e 48, 96, 144 e 168 horas após o procedimento cirúrgico. Os resultados demonstraram que o hematócrito diminuiu significativamente após a esplenectomia parcial. O valor máximo de reticulócitos foi alcançado 96 horas após a cirurgia, a partir daí houve um declínio na quantidade de reticulócitos na corrente sangüínea, permanecendo, porém, em número superior à condição pré-esplenectomia parcial.

The reticulocytes are erythroid cells that exhibit residual RNA, being released from bone marrow by erythropoietin stimulus in response to tissue hypoxia. After its release from bone marrow, they are temporarily sequestred in the spleen, where they acquire form of mature erythrocytes. Besides, the spleen is also responsible for storage of the blood and their elements. The splenectomy is indicated in cases of splenic torsion or rupture, symptomatic splenomegaly, and splenic masses. This study aimed to evaluate the response of reticulocytes and of hematocrit in dogs submitted to partial splenectomy. Nine mongrel males and female dogs were used. The samples were obtained one hour before the surgery and 48, 96, 144 and 168 hours after this procedure. The findings demonstrated that the hematocrit decreases significantly after the partial splenectomy. Highest values reticulocytes were reached 96 h after the surgery, followed by a decline in number, nevertheless, the counting was higher than moments before of the partial splenectomy.

Terapias biológicas en psiquiatría: IV. Benzodiazepinas / Biological therapies in psichiatry: IV. Benzodiazepines

Hace 25 años fue comercializada la primera benzodiazepina: el clorodiazepóxido. Desde esa fecha la utilidad de estos medicamentos se ha confirmado en diversas áreas de la medicina. Con el fin de aumentar la especificidad de sus efectos se ha sintetizado numerosos derivados. Su amplio uso se debe a su eficacia su potencial empleo en una gran variedad de situaciones y su seguridad. Se analizan sus características clínicas y farmacológicas

Terapias biológicas en psiquiatria: II. Antidepresivos / Biological therapy in psychiatry: II. Antidepressive agents

Desde que la imipramina comenzó a ser utilizada en el tratamiento de diversos cuadros depresivos se han sintetizado numerosos derivados de este antidepresivo tracíclico. A pesar de su utilidad terapéutica todos ellos presentan efectos secundarios. En los últimos años se han introducido nuevos fármacos antidepresivos de diversas estructuras, los cuales tendrían menos efectos secundários tanto en el sistema cardiovascular como en los colinérgicos. Son los llamados antidepresivos de nueva generación. Se analizan las características psicofarmacológicas, indicaciones, contraindicaciones y efectos adversos de ambos grupos y se presenta una nómina de los medicamentos antidepresivos existentes en el país