RESUMEN
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.
Asunto(s)
Neuromielitis Óptica , Femenino , Humanos , Factores Inmunológicos/uso terapéutico , Masculino , México , Neuromielitis Óptica/tratamiento farmacológico , Estudios Retrospectivos , Rituximab/uso terapéuticoRESUMEN
BACKGROUND: Delirium has important etiological, prognostic, and therapeutic implications. The study of neurochemical markers in this condition is relevant to the understanding of its pathophysiology. The assessment of the dopamine system is particularly relevant, as dopamine antagonists are the most used drugs in delirium. AIM: To analyze neurotransmission markers in patients with delirium, focusing in the dopamine metabolite, homovanillic acid. METHODS: A case-control study was performed at the National Institute of Neurology and Neurosurgery, Mexico, including hospitalized patients in which lumbar puncture was obtained for diagnostic purposes. Cases were selected if they fulfilled DSM-5 criteria for delirium. Age-paired controls were patients in which delirium was ruled out, selected at the same clinical scenario, during the same period. Neurological and systemic diagnoses were registered. Delirium was assessed using the DRS-98-R instrument. The dopamine metabolite, homovanillic acid (HVA), was measured by means of high-performance liquid chromatography. Other neurotransmission markers were also measured (5-hydroxyindoleacetic acid, glutamate, aspartate, GABA, glycine, arginine, citrulline, nitrites, and nitrates). A logistic regression model was used to determine pathogenic factors associated with the presence of delirium. RESULTS: 68 neurological patients with delirium and 68 patients without delirium were included. Higher homovanillic acid levels in cerebrospinal fluid were significantly associated with delirium. This result was significant after a subanalysis in patients without exposure to antipsychotics. Male gender and autoimmune limbic encephalitis were also associated with the presence of delirium. CONCLUSIONS: In hospitalized neurological patients, dopaminergic hyperactivity and autoimmune limbic encephalitis are pathogenic factors associated with the presence of delirium.
Asunto(s)
Delirio/patología , Dopamina/metabolismo , Ácido Homovanílico/líquido cefalorraquídeo , Ácido Homovanílico/metabolismo , Transmisión Sináptica/fisiología , Adulto , Enfermedades Autoinmunes/patología , Biomarcadores/metabolismo , Estudios de Casos y Controles , Delirio/diagnóstico , Delirio/tratamiento farmacológico , Antagonistas de Dopamina/uso terapéutico , Femenino , Humanos , Ácido Hidroxiindolacético , Encefalitis Límbica/patología , Masculino , MéxicoRESUMEN
INTRODUCTION: Neuromyelitis optica (NMO) and Multiple Sclerosis (MS) have been reported in different populations. NMO is more frequent in non-Caucasians, and clinical phenotype differences between populations are likely influenced by genetic susceptibility. In Brazil, it has been reported that NMO patients have a mainly European ancestry background. Like other autoimmune diseases, NMO has a multifactorial origin (i.e., genetics, environmental and infectious factors). Regarding the genetics of NMO, epidemiological findings suggest that a polygenic background has an important role in the development of this type of disease. In this context, various genes have been studied, such as those involved in the synthesis of the T cell beta chain receptor, the VH2-5 gene, myelin basic protein, the CTLA-4 gene, and the interleukin-1 gene. MATERIALS AND METHODS: We performed a study with the main objective of identifying candidate genes involved in the susceptibility to develop NMO in a Mexican population. RESULT: We included 35 patients with an NMO diagnosis according to the Wingerchuk 2006 criteria. The mean age of the patients was 43.3 years old (20-67), and 80 percent of the patients were women. The presence of HLA-DRB1*03 and HLA-DRB1*10 alleles were more frequent in NMO patients than in controls (n=198; p=0.03 and 0.005, respectively). CONCLUSION: There were no differences in the other alleles that have been described in MS subjects, such as HLA-DRB1*04, HLA-DRB1*08 and HLA-DRB1*13. These findings may support the hypothesis that implicated immune-genetics as a key factor in development of this type of disease.