Holmes Tremor‐Like Phenotype in DYT1 Dystonia

Holmes tremor is characterized by a combination of a flexion‐extension resting postural and action tremor, most often due to mesencephalic lesions affecting the nigrostriatal and cerebello‐thalamo‐cortical pathways. On the other hand, dystonic tremor represents a jerky postural and action tremor, which if severe enough may include a resting component and may arise from cerebellar and nigrostriatal dysfunction. Here, we present a patient with a four‐decade history of progressive tremor, initially interpreted as Holmes tremor with a dystonic (pseudospastic) gait, in whom whole exome sequencing (WES) demonstrated a pathogenic TOR1A deletion. This case highlights two important clinical points, (1) the need for proper semiologic interpretation: direct DYT1 testing could have been entertained if tremor was properly categorized as dystonic rather than cerebellar at the outset; and (2) the phenotypic variability of DYT1 dystonia, with tremor as a presenting and disabling feature separate from the body part affected by dystonia (“tremor associated with dystonia”).Fil: Rodríguez Quiroga, Sergio Alejandro. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: González Morón, Dolores. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Espay, Alberto J. University of Cincinnati; Estados UnidosFil: Kauffman, Marcelo Andres. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; Argentin

A Family with Late-Onset and Predominant Choreic Niemann Pick Type C: A Treatable Piece in the Etiological Puzzle of Choreas

Niemman Pick type C (NPC) is a treatable neurodegenerative lysosomal disorder characterized by the widespread age of onset and clinical presentation. The adult NPC phenotype frequently includes ataxia, supranuclear gaze palsy, and cognitive and behavioral problems.1 Movement disorders are also often observed in these patients. Among them, chorea has been rarely described as a dominant sign.1, 2 On the other hand, a phenotype dominated by chorea and cognitive and behavioral manifestations is suggestive of Huntington's disease (HD).3, 4 The rare cases showing this phenotype proved to be negative for the CAG expansion in HTT and are categorized as Huntington-like disorders (HDL).5 Although the list of HDL genetic etiologies has grown considerably during the past few years, the diagnostic yield for these conditions is still limited.3, 5 Noteworthy, NPC is neither routinely considered in the differential diagnosis of chorea nor among the HDL disorders. We present 2 siblings presenting with a late onset and predominate choreic phenotype, where the final diagnosis was NPC.Fil: Rodriguez Quiroga, Sergio. Universidad de Buenos Aires. Facultad de Medicina. Centro Universitario de Neurología "Dr. José María Ramos Mejía".; ArgentinaFil: Zavala, Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Centro Universitario de Neurología "Dr. José María Ramos Mejía".; ArgentinaFil: Perez Maturo, Josefina. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Centro Universitario de Neurología "Dr. José María Ramos Mejía".; ArgentinaFil: González Morón, Dolores. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Centro Universitario de Neurología "Dr. José María Ramos Mejía".; ArgentinaFil: Garretto, Nelida Susana. Universidad de Buenos Aires. Facultad de Medicina. Centro Universitario de Neurología "Dr. José María Ramos Mejía".; ArgentinaFil: Kauffman, Marcelo Andres. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Centro Universitario de Neurología "Dr. José María Ramos Mejía".; Argentin

ApoE ε4 might modify the silent interval of mesial temporal lobe epilepsy with hippocampal sclerosis

El gen de la apolipoproteína E (ApoE) presenta polimorfismos en su secuencia odificante que modulan distintos mecanismos de regeneración neuronal. La epilepsia mesial temporal con esclerosis del hipocampo (EMT-EH) frecuentemente se desarrolla años después de una injuria cerebral, habiéndose sucedido fenómenos plásticos neuro-regenerativos potencialmente epileptogénicos durante este intervalo denominado «período silente». Estudios previos han sido controversiales en cuanto al rol de esta variante genética en la EMT-EH. En particular, podría modificar la edad de comienzo de la patología. Objetivos: Nuestro objetivo fue explorar en mayor profundidad el rol de la variación genética de ApoE en el intervalo silente de la epileptogenesis de la EMT-EH. Pacientes y Métodos: Se realizó un estudio de epidemiología molecular que incluyó 78 pacientes con EMT-EH, investigando el efecto del polimorfismo sobre la edad de comienzo de la patología. La genotipificación fue hecho mediante PCR-RFLP. Se realizó un análisis limitado a nuestra población y un meta-análisis de la evidencia acumulada incluyendo nuestros datos (574 pacientes en total). Resultados: En nuestra población, los sujetos portadores de la variante ApoE E4 evidenciaron una tendencia a comenzar sus crisis a más temprana edad. En el meta-análisis se confirmó esta tendencia, aquellos sujetos portadores de la variante ApoE ε4 comienzan sus crisis casi 4 años antes que los sujetos portadores de las isoformas 2 y 3 de ApoE (p=0,005). Conclusión: ApoE ε4 es un factor genético que modifica la edad de comienzo de la EMT-EH, pudiendo estar implicado en los procesos epileptogénicos que se suceden en el período silente del desarrollo de la Epilepsia Mesial Temporal con Esclerosis del Hipocampo.Background: ApoE has a role in the maintenance and repair of neurons, but its three isoforms have different efficiency for these tasks. MTE-HS typically begins many years after an early cerebral insult. During this so called “silent interval” different epileptogenic proccesses occur that might involve the damage and repairing of neurons. Previous studies have evaluated the role of ApoE variants as modifiers of the clinical features of MTE-HS, but the results obtained have been controversial so far. Specifically, ApoE ε4 isoform might modulate the epileptic syndrome age of onset, suggesting a shorter “silent interval”. Aims: Our aim was to explore the role of Apolipoprotein E (ApoE) ε4 isoform as a modifier of the “silent interval” of Mesial temporal lobe epilepsy with hippocampal sclerosis (MTE-HS) development. Patients and Methods: We included a population of 78 MTE-HS patients in a molecular epidemiology study that investigated the effect of ApoE ε4 in the syndrome age of onset. Genotyping was done by a PCR-RFLP assay. In order to better estimate the role of this variant as a modifier of this clinical feature, we performed a systematic review of the literature, incorporating into a meta-analysis our results along data available (6 studies; 574 patients) in published studies that have investigated the role of ApoE ε4 in Temporal lobe epilepsy (TLE). Results: In our population, ApoE ε4 carriers showed a trend to begin their epilepsy at a shorter age than non-carriers. The meta-analysis confirmed this trend, where ApoE ε4 carriers had an onset of habitual seizures almost 4 years earlier than non-carriers (mean difference 3.7 years; CI 95% 1.66-5.74; p=0.0001). Conclusions: ApoE ε4 is a genetic modifier of the age of onset of MTE-HS syndrome, that might have a role in the epileptogenic processes that occur during the «silent interval» of this pathology development.Fil: Kauffman, Marcelo Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Consalvo, Damian. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: González Morón, Dolores. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Pujol, Virginia. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Solis, Patricia Cristina Lourdes. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Oddo, Silvia Andrea. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lomlomdjian, Carolina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Kochen, Sara Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentin

Adjuvant Effect of Titanium Brushes in Peri-Implant Surgical Treatment: A Systematic Review

Background: the prognosis of peri-implant surgery can be affected by poor decontamination of the implant surface, which could be improved with the use of titanium brushes. The objectives of this systematic review were to evaluate the effectiveness of titanium brushes in the decontamination of the implant surface in terms of plaque index, probing depth, bleeding on probing and bone loss/gain; as well as its effectiveness according to the type of peri-implant bone defect. Methods: an electronic search was carried out in the PubMed, Scopus, Cochrane and Embase databases, as well as a manual search. The search strategy included four keywords: “Peri-implantitis”, “Periimplantitis”, “Implant Surface Decontamination” and “Titanium Brush”. Randomized controlled studies published in the last 10 years were included and systematic reviews, in vitro studies and animal studies were excluded. Results: 142 references were found, from which only four articles met the inclusion criteria. All of the studies included in the present review reported beneficial results in terms of probing depth, gingival index and radiographic bone loss and gain after implant surface decontamination adjuvated by titanium brushes. Conclusions: titanium rotary brushes show improvements in the evolution and prognosis of peri-implant surgery, although more long-term studies are needed to draw more solid conclusionsOdontologí

Genetic Structure of the Spanish Population

<p>Abstract</p> <p>Background</p> <p>Genetic admixture is a common caveat for genetic association analysis. Therefore, it is important to characterize the genetic structure of the population under study to control for this kind of potential bias.</p> <p>Results</p> <p>In this study we have sampled over 800 unrelated individuals from the population of Spain, and have genotyped them with a genome-wide coverage. We have carried out linkage disequilibrium, haplotype, population structure and copy-number variation (CNV) analyses, and have compared these estimates of the Spanish population with existing data from similar efforts.</p> <p>Conclusions</p> <p>In general, the Spanish population is similar to the Western and Northern Europeans, but has a more diverse haplotypic structure. Moreover, the Spanish population is also largely homogeneous within itself, although patterns of micro-structure may be able to predict locations of origin from distant regions. Finally, we also present the first characterization of a CNV map of the Spanish population. These results and original data are made available to the scientific community.</p

Long-Term Real-World Effectiveness and Safety of Ustekinumab in Crohn’s Disease Patients: The SUSTAIN Study

Background Large real-world-evidence studies are required to confirm the durability of response, effectiveness, and safety of ustekinumab in Crohn’s disease (CD) patients in real-world clinical practice. Methods A retrospective, multicentre study was conducted in Spain in patients with active CD who had received ≥1 intravenous dose of ustekinumab for ≥6 months. Primary outcome was ustekinumab retention rate; secondary outcomes were to identify predictive factors for drug retention, short-term remission (week 16), loss of response and predictive factors for short-term efficacy and loss of response, and ustekinumab safety. Results A total of 463 patients were included. Mean baseline Harvey-Bradshaw Index was 8.4. A total of 447 (96.5%) patients had received prior biologic therapy, 141 (30.5%) of whom had received ≥3 agents. In addition, 35.2% received concomitant immunosuppressants, and 47.1% had ≥1 abdominal surgery. At week 16, 56% had remission, 70% had response, and 26.1% required dose escalation or intensification; of these, 24.8% did not subsequently reduce dose. After a median follow-up of 15 months, 356 (77%) patients continued treatment. The incidence rate of ustekinumab discontinuation was 18% per patient-year of follow-up. Previous intestinal surgery and concomitant steroid treatment were associated with higher risk of ustekinumab discontinuation, while a maintenance schedule every 12 weeks had a lower risk; neither concomitant immunosuppressants nor the number of previous biologics were associated with ustekinumab discontinuation risk. Fifty adverse events were reported in 39 (8.4%) patients; 4 of them were severe (2 infections, 1 malignancy, and 1 fever). Conclusions Ustekinumab is effective and safe as short- and long-term treatment in a refractory cohort of CD patients in real-world clinical practice

Using Interpretable Machine Learning to Identify Baseline Predictive Factors of Remission and Drug Durability in Crohn’s Disease Patients on Ustekinumab

Ustekinumab has shown efficacy in Crohn's Disease (CD) patients. To identify patient profiles of those who benefit the most from this treatment would help to position this drug in the therapeutic paradigm of CD and generate hypotheses for future trials. The objective of this analysis was to determine whether baseline patient characteristics are predictive of remission and the drug durability of ustekinumab, and whether its positioning with respect to prior use of biologics has a significant effect after correcting for disease severity and phenotype at baseline using interpretable machine learning. Patients' data from SUSTAIN, a retrospective multicenter single-arm cohort study, were used. Disease phenotype, baseline laboratory data, and prior treatment characteristics were documented. Clinical remission was defined as the Harvey Bradshaw Index <= 4 and was tracked longitudinally. Drug durability was defined as the time until a patient discontinued treatment. A total of 439 participants from 60 centers were included and a total of 20 baseline covariates considered. Less exposure to previous biologics had a positive effect on remission, even after controlling for baseline disease severity using a non-linear, additive, multivariable model. Additionally, age, body mass index, and fecal calprotectin at baseline were found to be statistically significant as independent negative risk factors for both remission and drug survival, with further risk factors identified for remission

Global data on earthworm abundance, biomass, diversity and corresponding environmental properties

Publisher Copyright: © 2021, The Author(s).Earthworms are an important soil taxon as ecosystem engineers, providing a variety of crucial ecosystem functions and services. Little is known about their diversity and distribution at large spatial scales, despite the availability of considerable amounts of local-scale data. Earthworm diversity data, obtained from the primary literature or provided directly by authors, were collated with information on site locations, including coordinates, habitat cover, and soil properties. Datasets were required, at a minimum, to include abundance or biomass of earthworms at a site. Where possible, site-level species lists were included, as well as the abundance and biomass of individual species and ecological groups. This global dataset contains 10,840 sites, with 184 species, from 60 countries and all continents except Antarctica. The data were obtained from 182 published articles, published between 1973 and 2017, and 17 unpublished datasets. Amalgamating data into a single global database will assist researchers in investigating and answering a wide variety of pressing questions, for example, jointly assessing aboveground and belowground biodiversity distributions and drivers of biodiversity change.Peer reviewe

Global data on earthworm abundance, biomass, diversity and corresponding environmental properties

Earthworms are an important soil taxon as ecosystem engineers, providing a variety of crucial ecosystem functions and services. Little is known about their diversity and distribution at large spatial scales, despite the availability of considerable amounts of local-scale data. Earthworm diversity data, obtained from the primary literature or provided directly by authors, were collated with information on site locations, including coordinates, habitat cover, and soil properties. Datasets were required, at a minimum, to include abundance or biomass of earthworms at a site. Where possible, site-level species lists were included, as well as the abundance and biomass of individual species and ecological groups. This global dataset contains 10,840 sites, with 184 species, from 60 countries and all continents except Antarctica. The data were obtained from 182 published articles, published between 1973 and 2017, and 17 unpublished datasets. Amalgamating data into a single global database will assist researchers in investigating and answering a wide variety of pressing questions, for example, jointly assessing aboveground and belowground biodiversity distributions and drivers of biodiversity change

Cerebrotendinous Xanthomatosis Revealed in Drug-Resistant Epilepsy Diagnostic Workup

Cerebrotendinous xanthomatosis (CTX) is a treatable disorder of bile acid production caused by mutations in the mitochondrial enzyme sterol 27-hydroxilase. This inborn error of bile acid metabolism results in lipid pathologic accumulation in multiple tissues. Progressive neuropsychiatric disturbances are a frequent manifestation of this disease. Although seizures have been frequently noticed as part of CTX manifestations, there have not been reports of CTX being diagnosed in drug-resistant epilepsy diagnostic workup nor of seizure response to chenodeoxycholic acid treatment. Here, the authors present a case of a drug-resistant epilepsy patient with a complex phenotype where a diagnosis of CTX was done and showed a significant reduction in seizure frequency after chenodeoxycholic acid supplementation. This report illustrates the importance of considering treatable neurometabolic disorders in epileptic patients showing complex phenotypes. © Copyright 2012 Southern Society for Clinical Investigation.Fil: Kauffman, Marcelo Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina. Centro Universitario de Neurología JM Ramos Mejia; ArgentinaFil: González Morón, Dolores. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina. Centro Universitario de Neurología JM Ramos Mejia; ArgentinaFil: Consalvo, Damian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina. Centro Universitario de Neurología JM Ramos Mejia; ArgentinaFil: Kochen, Sara Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina. Centro Universitario de Neurología JM Ramos Mejia; Argentin