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INTRODUCTION: Cognitive impairment has a substantial impact on the daily function of people living with demyelinating diseases. However, the study of cognitive failures and their association with clinical variables in people suffering from neuromyelitis optica spectrum disorder (NMOSD) has been scarce, especially in the latin american (Mexican) population at early and middle stages of the disease. METHOD: We applied the Rao's Brief Repeatable Battery of Neuropsychological tests and obtained data of lesion burden through magnetic resonance imaging (MRI), expression of AQPQ4-IgG antibodies, and degree of disability in 30 patients with NMOSD and 30 healthy participants as a control group. RESULTS: About half of the NMOSD patients (47%) showed some degree of cognitive impairment, especially in the executive domain compared to the control group. Executive function scores were positively associated with the degree of physical disability. We found no associations between cognitive dysfunction and disease duration, AQPQ4-IgG antibodies, lesion burden, nor depression. CONCLUSIONS: Executive functioning impairment is present in NMOSD and may predict the degree of functional disability in patients. Cognitive failures were not associated with immunological or radiological data, which emphasizes the relevance of applying systematic neuropsychological assessments in this clinical population.
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Disfunção Cognitiva , Função Executiva , Imageamento por Ressonância Magnética , Neuromielite Óptica , Humanos , Neuromielite Óptica/diagnóstico por imagem , Neuromielite Óptica/fisiopatologia , Feminino , Adulto , México , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Masculino , Pessoa de Meia-Idade , Função Executiva/fisiologia , Testes Neuropsicológicos , Aquaporina 4/imunologiaRESUMO
It is well known that as part of their response to infectious agents such as viruses, microglia transition from a quiescent state to an activated state that includes proinflammatory and anti-inflammatory phases; this behavior has been described through in vitro studies. However, recent in vivo studies on the function of microglia have questioned the two-phase paradigm; therefore, a change in the frequency of in vitro studies is expected. A systematic review was carried out to identify the microglial cytokine profile against viral infection that has been further evaluated through in vitro studies (pro-inflammatory or anti-inflammatory), along with analysis of its publication frequency over the years. For this review, 531 articles published in the English language were collected from PubMed, Web of Science, EBSCO and ResearchGate. Only 27 papers met the inclusion criteria for this systematic review. In total, 19 cytokines were evaluated in these studies, most of which are proinflammatory; the most common are IL-6, followed by TNF-α and IL-1ß. It should be pointed out that half of the studies were published between 2015 and 2022 (raw data available in https://github.com/dadriba05/SystematicReview.git ). In this review, we identified that evaluation of pro-inflammatory cytokines released by microglia against viral infections has been performed more frequently than that of anti-inflammatory cytokines; additionally, a higher frequency of evaluation of the response of microglia cells to viral infection through in vitro studies from 2015 and beyond was noted.
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Citocinas , Viroses , Humanos , Microglia , Fator de Necrose Tumoral alfa , Anti-InflamatóriosRESUMO
BACKGROUND: Anti-N-methyl-D-aspartate receptor encephalitis (ANMDARE) is a neuroimmunological disorder that frequently improves with immunotherapy. Symptomatic treatment with antipsychotics is common in the early stages when psychiatric symptoms predominate, and their use has been associated with serious side effects including neuroleptic malignant syndrome (NMS). The observation of an adverse response to antipsychotics, raising the suspicion of NMS, has been included as a criterion for possible autoimmune psychosis. METHODS: This case-control study included patients who received antipsychotics before referral to the National Institute of Neurology and Neurosurgery of Mexico, where they were diagnosed as having definite ANMDARE, and patients with ANMDARE who did not receive antipsychotics before referral. The neurologic and systemic features that are used to measure an adverse response to antipsychotics, raising the suspicion of NMS, were measured in both groups, including akinesia, autonomic instability, generalized rigidity, elevated concentrations of creatine phosphokinase, and hyperthermia. A logistic regression analysis was used to determine the relationship between the previous use of antipsychotics and the occurrence of NMS-like reactions. RESULTS: A total sample of 112 patients with definite ANMDARE were included in the study. Fifty patients received antipsychotics before being referred to our institution. In this group, thirty-six patients (72%) were initially classified as having an adverse response, raising the suspicion of NMS, with the following features: akinesia (64%), autonomic instability (58%), generalized rigidity (52%), elevated concentrations of creatine phosphokinase (50%), and hyperthermia (14%). Six patients fulfilled the criteria for NMS (12%). The comparison with patients who did not receive antipsychotics before the clinical assessment did not show a significant difference between groups regarding the frequency of akinesia, autonomic instability, generalized rigidity, elevated concentrations of creatine phosphokinase, or hyperthermia. Among different antipsychotics, only haloperidol was significantly associated with generalized rigidity as compared to patients who did not receive antipsychotics. CONCLUSIONS: Our study supports previous observations about the high frequency of autonomic dysfunction, hyperthermia, tachycardia, rigidity, and elevated creatine phosphokinase levels in patients with anti-NMDAR encephalitis following the administration of antipsychotic medications. Nevertheless, our study does not suggest a causal link between atypical antipsychotics and the onset of these neurological symptoms, as they were equally frequent among the group of patients who did not receive antipsychotic treatment.
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Encefalite Antirreceptor de N-Metil-D-Aspartato , Antipsicóticos , Síndrome Maligna Neuroléptica , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Encefalite Antirreceptor de N-Metil-D-Aspartato/complicações , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Estudos de Casos e Controles , México/epidemiologia , Síndrome Maligna Neuroléptica/tratamento farmacológico , Síndrome Maligna Neuroléptica/etiologiaRESUMO
Introduction: The study of food addiction (FA) has become relevant due to its high prevalence, the negative impact on quality of life, and its association with neuropsychological and psychiatric symptoms. Several studies have provided scientific support for these associations, however, the results are contradictory. Additionally, studies have unsuccessfully elucidated the true nature of the failures in executive functioning in people with FA symptomatology, particularly when it comes to executive deficits. Therefore, the purpose of this research was to establish whether the presence of executive dysfunction, depressive symptoms and binge eating problems, as well as high reward sensitivity entails a greater severity in FA traits and high body mass index (BMI) in a sample of Mexican adults. Methods: The sample consisted of Mexican men and women between 21-59 years (n = 36); who completed self-report questionnaires and performance tests to measure the study variables. Additionally, BMI was estimated with self-reported height and weight. Results: Our results showed that a high number of FA symptoms were associated with higher executive dysfunction scores, greater reward sensitivity, and more severe depressive and binge eating problems. Furthermore, factors that are more strongly associated with higher scores of FA include severe executive deficits, greater activation of the punishment avoidance system, and persistence in the search for reward when the depressive symptoms increased. The factors that best explained changes in the estimated BMI of women were a decreased crystallized intellectual capacity and the inability to control food intake as the number of FA symptoms increased. Discussion: In summary, the cognitive functioning profile characterized by general failure of the executive functioning, as well as a greater activation of the Punishment Avoidance System and persistence in the search for reward, were associated with greater severity of FA symptoms, especially when the depressive symptomatology was severe. In parallel, the psychopathology in participants associated with FA confirms the contribution of anxious and depressive symptomatology and borderline personality traits which could facilitate the expression of clinically relevant FA symptoms in women. Finally, we found that decreased crystallized intellectual capacity and inability to control food intake were linked to higher BMI when the number of FA symptoms increased.
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Bulimia , Dependência de Alimentos , Adulto , Masculino , Humanos , Feminino , Dependência de Alimentos/epidemiologia , Dependência de Alimentos/psicologia , Depressão/epidemiologia , Depressão/psicologia , Prevalência , Qualidade de Vida , Função Executiva/fisiologia , Bulimia/psicologiaRESUMO
Resumen Se reconoce la participación de la oxitocina en el control de la alimentación, pero su mecanismo de acción no se ha establecido totalmente. Por tanto, el objetivo de esta investigación fue evaluar el efecto del acceso intermitente a una solución de sacarosa, sobre la expresión de las neuronas del núcleo paraventricular (PVN) y del núcleo supraótico (SON) que producen oxitocina (Oxt), y caracterizar la microestructura de la conducta de beber en ratas saciadas. Se tuvieron tres grupos de ratas macho Wistar saciadas, y en la primera hora al inicio del periodo de luz, el grupo Control tuvo agua, el grupo Restringido 5g de una solución de sacarosa al 20% y el grupo Ad libitum acceso libre a la solución de sacarosa. Los sujetos incrementaron el consumo de la solución de sacarosa a pesar de estar saciados; debido a la interrupción del estado de saciedad y la demora de la satisfacción. La actividad de las neuronas de Oxt se incrementó en ambos núcleos, en el grupo Restringido la mayor expresión se observó en el SON y en el grupo Ad libitum en el PVN. No se encontró correlación entre la cantidad de bebida ingerida y la actividad de las neuronas Oxt.
Abstract The role of oxytocin in feeding control is recognized, but its mechanism of action has not been fully established. Therefore, the aim of this research was to evaluate the effect of intermittent access to a sucrose solution on the expression of paraventricular nucleus (PVN) and supraotic nucleus (SON) neurons that produce oxytocin (Oxt), and to characterize the microstructure of drinking behavior in satiated rats. Three groups of male Wistar rats satiated were used, and in the first hour at the beginning of the light period, a Control group had water, a Restricted group 5g of a 20% sucrose solution and Ad libitum group with free access to sucrose solution. The experimental subjects increased the consumption of the sucrose solution despite being satiated, due to the interruption of the state of satiety and the delay of the satiation process. Oxt neurons increased their activity in both nuclei, in the Restricted group the highest expression was observed in the SON and in the Ad libitum group in the PVN. No correlation was found between the amount of drink ingested and the activity of Oxt neurons.
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[This corrects the article DOI: 10.3389/fnins.2018.00074.].
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Sugar solutions promote hedonic feeding and increase the risk of obesity and binge-type behavior. In rodents, ingestion of sugar solutions enhances dopamine release to mesolimbic regions, suggesting changes in hedonic intake and brain reward processes. Moreover, dopaminergic D2R/D3R receptors contribute to the hedonic intake of palatable solutions. Although the experimental evidence indicate that the dopaminergic D4 receptor (D4R) modulates feeding at homeostatic levels, it is currently unknown whether D4R also regulate the hedonic intake of sugar solutions. In this study, we evaluated the effect of the central blockade of D4R on the consumption of a 20% sucrose solution, the drinking microstructure parameters, and levels of locomotor activity in sated rats. In the first experiment, male Wistar rats were daily exposed to a 20% sugar solution in the first hour of the light phase of the light:dark cycle. On day 10, rats received i.c.v injections of the D4R antagonist, L-745870 (0, 1 or 2 µg/5 µl) and sucrose consumption and drinking microstructure parameters (latency to start drinking, bouts, drinking duration, bout size, inter-bout interval, time in activity and time in resting) were evaluated. In the second experiment, rats were trained to receive the 20% sucrose solution as described in experiment 1. On day 10, after the 1 h of sucrose access, the rats were placed in the open field for 5-min (habituation phase). Then, rats received i.c.v injections of L-745870 (0, 1 or 2 µg/ 5 µl), and were placed again in the open-field test for 10-min (pharmacological phase). The number or crosses trough squares and number of rears were scored for both the habituation and pharmacological phase. Here we found that administration of L-745870 decreased the consumption of sucrose in a dose-depended manner. Moreover, L-745870-treated rats displayed microstructural changes, including greater number of bouts and reduced drinking duration, bout size and inter-bout intervals. Furthermore, the number of crosses and number of rears in the open field test remained unchanged for habituation and pharmacological phase. Finally, present findings suggest that D4R modulates the consumption of sugar solutions by alteration of hedonic responses, but the contribution of homeostatic systems is discussed. These results open perspectives for the potential use of the D4R antagonists for treating obesity or binge-eating behavior.
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Introducción: Las anomalías de la forma, en niños y niñas, son en gran medida frecuentes, por ello su estudio es importante para precisar diagnósticos, dado que pueden tener diferentes implicancias odontológicas. A la altura de la cúspide mesiopalatina de los segundos molares superiores temporarios, primeros molares superiores permanentes, y con menor frecuencia en los segundos molares superiores permanentes, es posible reconocer una cúspide accesoria o tubérculo denominada de Carabelli (TC).Objetivos: Determinar la prevalencia del TC en pacientes del Hospital de Odontología Infantil (HOI) "Don Benito Quinquela Martín" de Buenos Aires, Argentina. Asimismo, comprender, con respecto a su etiología, si existe alguna relación con el origen étnico de la familia. Para ello se incorporó la variable nacionalidad de los padres para examinar el posible vínculo entre la presencia del TC y la procedencia étnica del paciente.Materiales y Métodos: Se evaluó una muestra de 363 niños que ingresaron por primera vez al Servicio de Clínica y Orientación del HOI durante el período comprendido entre agosto 2019 y marzo 2020.Resultados: La prevalencia del TC observada fue del 34 %, por lo menos en alguna de las piezas dentarias, con una mayor tendencia en el sexo masculino en un 55%, y un 45% en el sexo femenino.Conclusiones: La hipótesis propuesta fue que la prevalencia del TC en los pacientes que acuden al del HOI es inferior al 50 % y fue validada debido a que el 34% de los pacientes presentan el TC.
Introdução: As anomalias de forma em meninos e meninas são bastante frequentes, por isso seu estudo é importante para especificar diagnósticos, pois podem ter diferentes implicações odontológicas. Na altura da cúspide mesiopalatina dos segundos molares superiores temporários, primeiros molares superiores permanentes e, menos frequentemente, nos segundos molares superiores permanentes, é possível reconhecer uma cúspide ou tubérculo acessório, denominado Carabelli (TC). Objetivos: Determinar a prevalência de TC em pacientes do Hospital de Odontologia Infantil "Don Benito Quinquela Martín" (HOI) de Buenos Aires, Argentina. Materiais e métodos: Uma amostra de 363 crianças entre dois e quinze anos de idade foi avaliada por inspeção visual direta realizada com instrumentos de exploração, considerando admissões, na Clínica HOI e Serviço de Orientação durante o período abrangido. agosto de 2019 e março de 2020. Resultados: 34% dos pacientes apresentaram TC em um dos dentes, com maior tendência para o sexo masculino em 55%. Conclusões: Embora a prevalência de DC nos pacientes que compareceram ao HOI tenha sido inferior a 50%, ter observado o traço em 34% sugere a importância de sua detecção precoce, pois é fundamental informar ao paciente que o traço o acompanhará durante todo o sua vida e exige maior higiene bucal. Além disso, avise ao paciente que a cúspide não está relacionada a uma doença, mas corresponde à herança genética
Introduction: Shape abnormalities in children are recurrent, so their study is important to make an accurate diagnosis because they can have several dental implications. This anatomical structure is generally found on the mesial palatal side of the tooth, just below the mesial palatal cusp, specifically on the upper first deciduous molars, less frequently in the upper second permanent molars, it is possible to recognize an accessory cusp or a tubercle identified as Carabelli. Aim: To determine the prevalence of the Carabelli Ìs tubercle (CT) in patients of the Clinical Service and Orientation from the Quinquela Martín Hospital of Pediatric dentistry (HOI) Government of Buenos Aires City- Aires, Argentina. Materials and methods: A sample of 363 children, between two and fifteen years of age, was evaluated by direct visual inspection carried out with exploration instruments, taking into account admissions and readmissions, to the HOI Clinic and Orientation Service during the period covered between August 2019 and March 2020. Results: The prevalence of CT observed was 34% in at least some teeth, with a greater tendency in the male gender of 55% and 45% in the female. Conclusions: Although the prevalence of CT in patients who attended the HOI was less than 50%, having observed the trait in 34% suggests the importance of its early detection, since it is essential to inform the patient that the trait it will accompany you throughout his life and requires effective oral hygiene. Also, warn the patient that the cusp is not related to a disease, but corresponds to genetic inheritance.
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Humanos , Masculino , Feminino , Criança , Anormalidades Dentárias , Higiene Bucal , Odontopediatria , Dente Canino , Dente MolarRESUMO
RESUMEN La uretrografía retrógrada es la técnica de referencia (gold standard) utilizada clásicamente para hacer diagnóstico de lesiones de uretra. En este contexto se presenta un caso en el que se realizó tomografía computarizada con reconstrucción 3D con contraste intravenoso y endouretral, pudiendo reconstruir la uretra en toda su extensión en forma tridimensional. De esta manera se arribó al diagnóstico de certeza de la lesión de uretra. Como ventaja del método se menciona la posibilidad de diagnosticar ‒ con un solo estudio por imágenes‒ lesiones de todo el tracto urinario, órganos sólidos, huecos y lesión del anillo pélvico asociados al traumatismo, con una alta sensibilidad y especificidad sin necesidad de requerir otros estudios complementarios.
ABSTRACT Retrograde urethrography is the gold standard method for the diagnosis of urethral injuries. In this setting, we report the use of computed tomography with intravenous injection and urethral administration of contrast medium and 3D reconstruction of the entire urethra. The definitive diagnosis of urethral injury was made. The advantage of this method is the possibility of making the diagnosis of traumatic injuries of the entire urinary tract, solid organs, hollow viscera and of the pelvic ring within a single imaging test, with high sensitivity and specificity, with no need to perform other complementary tests.
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Humanos , Masculino , Adolescente , Uretra/lesões , Ferimentos e Lesões/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Uretra/cirurgia , Cistostomia , Acidentes de Trânsito , Tomografia Computadorizada por Raios X/métodosRESUMO
Abstract In Argentina there are no reports on Aspergillus fumigatus fumagillin-producingstrains. In this study we describe the isolation and mycotoxin production capacity of ten A.fumigatus strains isolated from farm and clinical samples. Farm strains were isolated frommilk samples taken from dairy cows in Córdoba province, some of which were associated withsubclinical mastitis. A culture medium was defined to optimize fumagillin production and adetection method was developed by HPLC chromatography. It is known that in addition to thehost immune status, strain virulence is a fundamental characteristic that will determine itspathogenicity and, in this sense, fumagillin is considered to be among the virulence factors. Inthe present work, all the strains tested for the production of fumagillin were able to synthesizeit, highlighting that the strain A. fumigatus RC2243, from a milk sample from a cow with clinicalmastitis, was the most productive. The existence of fumagillin-producing strains represents apotential risk of mycotoxins being transferred to raw milk, constituting a public health risk.
Resumen En Argentina no existen reportes sobre cepas de Aspergillus fumigatus productoras de fumagilina. En este trabajo se describe el aislamiento y la producción de dicha micotoxina clínicaspor 10 cepas, provenientes del medioambiente rural y aisladas de muestras clínicas. Las cepasde origen rural fueron aisladas de vacas lecheras en tambos de la provincia de Córdoba, yalgunas de esas cepas se asociaron a casos de mastitis subclínica. Se definió la composición deun medio de cultivo para optimizar la producción de fumagilina y se desarrolló un método decromatografía HPLC para su determinación. Es conocido que, además del estado inmunitario delhuésped, la virulencia de la cepa es una de las características fundamentales que determinansu potencial patogénico y, en este sentido, la fumagilina es considerada un factor de virulencia. En el presente trabajo todas las cepas estudiadas fueron capaces de sintetizarla y la cepa A.fumigatus RC2243, proveniente de leche de una vaca con mastitis subclínica, se destacó comola cepa más productora. La existencia de cepas productoras de fumagillina representa un riesgopotencial por el pasaje de dicha micotoxina a la leche, lo cual constituye un problema para lasalud pública.
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In Argentina there are no reports on Aspergillus fumigatus fumagillin-producing strains. In this study we describe the isolation and mycotoxin production capacity of ten A. fumigatus strains isolated from farm and clinical samples. Farm strains were isolated from milk samples taken from dairy cows in Córdoba province, some of which were associated with subclinical mastitis. A culture medium was defined to optimize fumagillin production and a detection method was developed by HPLC chromatography. It is known that in addition to the host immune status, strain virulence is a fundamental characteristic that will determine its pathogenicity and, in this sense, fumagillin is considered to be among the virulence factors. In the present work, all the strains tested for the production of fumagillin were able to synthesize it, highlighting that the strain A. fumigatus RC2243, from a milk sample from a cow with clinical mastitis, was the most productive. The existence of fumagillin-producing strains represents a potential risk of mycotoxins being transferred to raw milk, constituting a public health risk.
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Mastite Bovina , Micotoxinas , Animais , Argentina , Aspergillus fumigatus/química , Bovinos , Cicloexanos , Ácidos Graxos Insaturados , Feminino , Humanos , Leite , Sesquiterpenos , Fatores de VirulênciaRESUMO
BACKGROUND: Multiple Sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS). B cells have an essential role in the disease pathogenesis and therefore selective B-cell depletion are commonly used to treat the disease. Rituximab (RTX), a chimeric anti-CD20 monoclonal antibody had demonstrated reduced inflammatory activity and radiological activity in MS patients. Due to economic constrains and treatment access limitations, RTX is often used as a treatment alternative in these patients. Here, we described our center experience in RTX -treated MS patients. METHODS: A single-center observational retrospective study was conducted in a Mexican cohort MS during 2010 to 2020. All patients had a confirmed MS diagnosis.All patients received fixed scheme involving induction with 1 g on day one and day 15, followed by 500 mg-1 g every six months for maintenance. Annual Relapse Rate (ARR), Progression index (PI), Expanded Disability Status Scale (EDSS) and MRI activity of the disease were evaluated. Comparison between naïve and non-naïve patients was also conducted. RESULTS: A total of 85 patients were included. The mean age at diagnosis was 33.13 (±8.90) years with 73 (85.9%) being RRMS. 39 (34.1%) were treatment-naïve. While treated with RTX, 62(72.9%) patients reached a free-of-relapse status, with statistically significant decrease in the mean ARR from 0.82 to 0.36 [0.14 (95%CI: 0.09-0.20), p = 0.0001 and EDSS [0.25 CI 0-0.5 (p = 0.034)] and a decrease in their T1 Gd-enhancing MRI lesions (1.64 vs. 0.12 CI 0.70-2.30, p = 0.004. 29 (29.4%) patients achieved NEDA-3. Among all patients, only 2 (2.4%) experienced infusion-related mild adverse events. No serious adverse events were reported. CONCLUSION: We found significant clinical and radiological improvement in naïve and non-naïve MS patients treated with RTX.
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Antineoplásicos , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Antineoplásicos/uso terapêutico , Humanos , Fatores Imunológicos/efeitos adversos , Esclerose Múltipla/induzido quimicamente , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Estudos Retrospectivos , Rituximab/efeitos adversosRESUMO
Neuromyelitis Optica Spectrum Disorder (NMOSD) is a demyelinating autoimmune disease of the central nervous system, more prevalent in individuals of non-European ancestry. Few studies have analyzed genetic risk factors in NMOSD, and HLA class II gene variation has been associated NMOSD risk in various populations including Mexicans. Thymopoietin (TMPO) has not been tested as a candidate gene for NMOSD or other autoimmune disease, however, experimental evidence suggests this gene may be involved in negative selection of autoreactive T cells and autoimmunity. We thus investigated whether the missense TMPO variant rs17028450 (Arg630Cys, frequent in Latin America) is associated with NMOSD, and whether this variant shows an interaction with HLA-class II rs9272219, previously associated with NMOSD risk. A total of 119 Mexican NMOSD patients, 1208 controls and 357 Native Mexican individuals were included. The HLA rs9272219 "T" risk allele frequency ranged from 21 to 68%, while the rs17028450 "T" minor allele frequency was as high as 18% in Native Mexican groups. Both rs9272219 and rs17028450 were significantly associated with NMOSD risk under additive models (OR = 2.48; p = 8 × 10-10 and OR = 1.59; p = 0.0075, respectively), and a significant interaction between both variants was identified with logistic regression models (p = 0.048). Individuals bearing both risk alleles had an estimated 3.9-fold increased risk of NMOSD. To our knowledge, this is the first study reporting an association of TMPO gene variation with an autoimmune disorder and the interaction of specific susceptibility gene variants, that may contribute to the genetic architecture of NMOSD in admixed Latin American populations.
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BACKGROUND: Multiple sclerosis affects more than 2 million people. Clinical decisions are performed under evidence-based medicine. The appearance of new disease-modifying therapies and changes in diagnostic criteria complicates the decision-making process in clinical practice. OBJECTIVES: To characterize the criteria for radiologically isolated syndrome (RIS), clinically isolated syndrome (CIS), and relapsing-remitting multiple sclerosis (RRMS) by Mexican neurologists in a real-world setting. METHODS: A two-round modified Delphi method (RAND/UCLA) was applied. RESULTS: In RIS, LP, spinal cord MRI and VEP should be included in diagnostic testing; DMT initiation is not necessary. A follow-up MRI within 3 months are recommended. In CIS, corticosteroid therapy should be initiated at first relapse; both simple and Gd-enhanced MRI is mandatory. LP, selective blood tests, and NMO-IgG/AQP4 antibodies should be performed as complementary. IFN beta or GA were the most suitable DMTs for treating high-risk CIS. Patients with RRMS should begin with DMT at diagnosis, include a follow-up MRI if a patient had 2 relapses within 6 months. GA and oral DMTs are the most eligible DMTs for mild RRMS. Monoclonal antibodies-based therapy is chosen when disability is present. Radiological criteria for switching DMT included >1 Gd+ lesion and >2 new T2 lesions. CONCLUSIONS: Although many coincidences, there are still many hollows in the medical attention of MS in Mexico. This consensus recommendation could be helpful to implement better evidence-based recommendations and guidelines in a real-world setting.
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Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Consenso , Humanos , México , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Padrões de Prática MédicaRESUMO
BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSDs) are a group of chronic immune-mediated demyelinating diseases of the central nervous system. Their pathophysiology dependent on humoral mediated responses caused by autoreactive IgG antibodies against aquaporin-4 water channels (AQP4-IgG) or myelin oligodendrocyte glycoprotein (MOG-IgG). Plasma exchange (PLEX) has proved to be a beneficial therapy in patients with severe relapses. We present the largest series of Latin American patients treated with PLEX for acute NMOSDs relapses. METHODS: A retrospective study was conducted. Selection included patients diagnosed with NMOSDs who received PLEX between 2010-2019, irrespective of their AQP4-IgG serostatus. All patients received 5 grams of IV methylprednisolone. PLEX therapy could be initiated simultaneously or after IV steroids. Baseline and post-PLEX therapy Expanded Disability Status Scale (EDSS) was measured to identify acute response to therapy. Comparison between responders and non-responders was also conducted. Subgroup analysis stratified response by serostatus, type of clinical relapse and time to PLEX. RESULTS: A total of 89 patients were included. Mean age at onset was 38 ± 12.97 years. 49 (55.1%) patients were AQP4-IgG seropositive. Most patients had unilateral optic neuritis (34.8%) or longitudinally extensive transverse myelitis (33.7%). Mean time from onset to PLEX initiation was 20.9 ± 18.1 days. Response rate was 39.3% and mean decline in EDSS was 0.7 ± 0.9 (p <0.001). Decline in EDSS and response rate were independent of serostatus, type of clinical relapse or time to PLEX initiation. CONCLUSION: PLEX appears to be an effective therapy for NMOSDs relapses even in limited resources setting where treatment initiation may be delayed. The benefit seems to be independent of the type of clinical relapse and AQP4 IgG serostatus.
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Neuromielite Óptica , Aquaporina 4 , Autoanticorpos , Humanos , México , Recidiva Local de Neoplasia , Neuromielite Óptica/terapia , Troca Plasmática , Estudos RetrospectivosRESUMO
INTRODUCTION: Multiple sclerosis (MS) is a chronic neurological autoimmune condition and the leading non-traumatic cause of neurological disability worldwide. Disease-modifying therapies (DMT) directly impact on the long-term prognosis of patients with MS preventing relapses and the associated disability progression. Here, we analyzed the impact of socioeconomic status (SES) on DMT access in Mexican patients. METHODS: We evaluated the association between SES and DMT access using the MS registry from the National Institute of Neurology and Neurosurgery in Mexico City. We included 974 patients with MS (McDonald 2010 criteria). We categorized SES according to the 2018 Mexican Association of Market Research Agencies (AMAI) SES classification. We analyzed DMT type, MS phenotype, educational level, symptomatic onset to diagnosis, EDSS at arrival, as well as the progression index. Chi-squared and Wilcoxon tests were used, and multivariable analysis performed for DMT access. RESULTS: When comparing the lower versus higher levels of SES, a significant association was found on the percentage of patients with higher levels of disability (EDSS >6) at arrival, the proportion of patients not receiving any DMT and a higher proportion of secondary progressive MS (p=0.006, p<0.001and p=0.004, respectively). We also found that lower educational levels had a significance and inverse association with EDSS on first visit (p=0.019), symptomatic onset to diagnosis (p<0.001) and a higher disability status at arrival (EDSS >6, p=0.010). CONCLUSIONS: Our study suggests that SES is an important factor determining not only prompt but overall access to highly effective DMT. Lower SES are associated with greater levels of disability at the first clinic visit and a higher proportion of patients not receiving DMT up to 12 months of follow-up.
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Esclerose Múltipla Crônica Progressiva , Esclerose Múltipla , Humanos , México , Recidiva , Classe SocialRESUMO
Background: The neutrophil-to-lymphocyte ratio (NLR) has been investigated in many autoimmune conditions as a biomarker of inflammation and/or disease activity. The role of NLR in AQP4-IgG-positive neuromyelitis optica spectrum disorders (NMOSD) is far from clear. In this study, NLR was evaluated in patients with AQP4-IgG-positive NMOSD at disease onset and its prognostic impact was subsequently assessed. Methods: In this multicenter study, we retrospectively included all recent/newly diagnosed treatment-naïve patients with AQP4-IgG-positive NMOSD (n=90) from three different countries in Latin America (LATAM): Argentina, Ecuador, and Mexico. NLR was compared between AQP4-IgG-positive NMOSD and healthy controls (HC, n = 365). Demographic, clinical, paraclinical (including imaging), and prognostic data at 12 and 24 months were also evaluated. Multivariate regression analysis was used to describe and identify independent associations between the log-transformed NLR and clinical (relapses and EDSS) and imaging (new/enlarging and/or contrast-enhancing MRI lesions) outcomes. Results: NLR was higher in NMOSD patients during the first attack compared with HC (2.9 ± 1.6 vs 1.8 ± 0.6; p<0.0001). Regardless of immunosuppressant's initiation at disease onset, NLR remained higher in NMOSD patients at 12 (2.8 ± 1.3; p<0.0001) and 24 (3.1 ± 1.6; p<0.0001) months. No association was found at 12 and 24 months between the log-transformed NLR and the presence of relapses, new/enlarging and/or contrast-enhancing MRI lesions, and/or physical disability. Conclusions: In this cohort of LATAM patients with AQP4-IgG-positive NMOSD, NLR was abnormally high in attacks but also during follow-up. However, a high NLR was not an independent predictor of clinical or imaging outcomes in our models.
Assuntos
Aquaporina 4/imunologia , Autoanticorpos/sangue , Linfócitos/imunologia , Neuromielite Óptica/imunologia , Neutrófilos/imunologia , Adulto , Argentina , Equador , Feminino , Humanos , Imunoglobulina G/sangue , Imunossupressores/uso terapêutico , Contagem de Linfócitos , Masculino , México , Pessoa de Meia-Idade , Neuromielite Óptica/sangue , Neuromielite Óptica/diagnóstico por imagem , Neuromielite Óptica/tratamento farmacológico , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Testes SorológicosRESUMO
Epilepsia partialis continua (EPC) has changed in its clinical and pathophysiological definition throughout time. Several etiologies have been described in addition to classic causes of EPC. The following case depicts a young woman who had a peculiar onset of epilepsy with a continuous visual aura becoming a form of chronic recurrent and non-progressive EPC. The patient was initially misdiagnosed as a non-neurological entity (assumed psychiatric in origin), but finally, an immune-mediated epilepsy was diagnosed, and EEG showed focal status epilepticus during evolution. Once the diagnosis was achieved and immune treatment was established, the patient is seizure free. Early identification of an immune basis in patients with epilepsy is important because immunotherapy can reverse the epileptogenic process and reduce the risk of chronic epilepsy. To date, this is the only case reported with EPC manifesting as a continuous visual aura associated with antiglutamic acid decarboxylase 65 (anti-GAD65) and anti-N-methyl-d-aspartate (anti-NMDA) antibodies.
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Resumen La obesidad y el sobrepeso son problemas de origen multifactorial, la interacción de los factores ambientales, genéticos y conductuales parecen ser la clave en el desarrollo de esta patología. Los receptores MC3 (rMC3) y MC4 (rMC4), participan en la regulación del balance energético (consumo de alimento, gasto energético y peso corporal), su mutación genética está asociada con el incremento de la adiposidad y el desarrollo de la obesidad. El conocimiento que se tiene de estos receptores y su función aún es limitado, principalmente con respecto a los rMC3 y, aunque los rMC4 se están posicionando como un blanco terapéutico potencial para el tratamiento de la obesidad, se requiere de mayor investigación clínica. Por lo tanto, el propósito de este documento es presentar evidencia de la participación de los receptores MC3 y MC4 en el desarrollo de la obesidad, a través de los resultados encontrados en algunas investigaciones, tanto en modelos animales como en humanos.
Abstract Obesity and overweight are problems of multifactorial origin, the interaction of environmental, genetic, and behavioral factors seems to be the key in the development of this pathology. The MC3 (rMC3) and MC4 (rMC4) receptors participate in the regulation of energy balance (food intake, energy expenditure and body weight), their genetic mutation is associated with increased adiposity and the development of obesity. Knowledge of these receptors and their function is still limited, mainly with respect to rMC3 and, although rMC4 are positioning themselves as a potential therapeutic target for the treatment of obesity, further clinical research is required. Therefore, the purpose of this document is to present the participation of MC3 and MC4 receptors in the development of obesity, through the results found in some investigations, both in animal and in human´s models.
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BACKGROUND: NMOSD is an inflammatory disorder of the central nervous system that primarily affects the optic nerves and spinal cord. Rituximab (RTX) is a monoclonal antibody directed against CD20, an epitope expressed on pre-B and mature B cells. It has of wide use in several antibody-mediated autoimmune diseases. OBJECTIVES: To demonstrate RTX clinical efficacy at different initial and maintenance doses administered in patients with NMOSD. METHODS: In this retrospective/observational study we recruited subjects with NMOSD with at least one RTX infusion. Annual relapse rates (ARR) were compared in several induction and maintenance regimens with RTX in 66 patients with NMOSD. RESULTS: Fifty-four (81.8%) were female and two thirds (66.7%) had positive anti-AQP4 antibodies. The most prevalent induction and maintenance regimens were 1000 mg on days 1 and 15 (51.5%) and 1000 mg every 6 months (40.9%), respectively. Overall, the annual relapse rate (ARR) decreased from 1.15 to 0.46 with RTX (p < 0.001). In patients with persistent relapses, the ARR decreased from 1.66 to 1.22, representing a relative risk reduction of 24%. Treatment with RTX decreased the ARR from 1.36 to 0.4 in the 500 mg induction and maintenance dose subgroup, and from 0.7 to 0.4 in the 1000 mg induction and maintenance dose subgroup. CONCLUSION: RTX treatment in patients with NMOSD demonstrated a marked and sustained reduction in the ARR, regardless of induction and maintenance regimens. EDSS stability was observed, even in patients with active and severe NMOSD.