Neurologia最新文献

Parkinson's disease is a neurodegenerative disorder that affects more than 7 million people worldwide. Its aetiology is unknown, although the hypothesis of a genetic susceptibility to environmental agents is accepted. These environmental agents include fungi, bacteria, and viruses. Three microorganisms are directly associated with a significantly increased risk of developing Parkinson's disease: the fungal genus Malassezia, the bacterium Helicobacter pylori, and the hepatitis C virus. If the host is vulnerable due to genetic susceptibility or immune weakness, these microorganisms can access and infect the nervous system, causing chronic neuroinflammation with neurodegeneration. Other microorganisms show an epidemiological association with the disease, including the influenza type A, Japanese encephalitis type B, St Louis, and West Nile viruses. These viruses can affect the nervous system, causing encephalitis, which can result in parkinsonism. This article reviews the role of all these microorganisms in Parkinson's disease.

Introduction

Neuromyelitis optica (NMO) is an inflammatory disease of the central nervous system characterised by attacks of optic neuritis and longitudinally extensive transverse myelitis. The discovery of anti–aquaporin-4 (anti-AQP4) antibodies and specific brain MRI findings as diagnostic biomarkers have enabled the recognition of a broader and more detailed clinical phenotype, known as neuromyelitis optica spectrum disorder (NMOSD).

Objective

This study aimed to determine the demographic and clinical characteristics of patients with NMO/NMOSD with and without seropositivity for anti-AQP4 antibodies, in 2 quaternary-level hospitals in Bogotá.

Methods

Our study included patients > 18 years of age and diagnosed with NMO/NMOSD and for whom imaging and serology results were available, assessed between 2013 and 2017 at the neurology departments of hospitals providing highly complex care. Demographic, clinical, and imaging data were gathered and compared in patients with and without seropositivity for anti-AQP4 antibodies.

Results

The sample included 35 patients with NMO/NMOSD; the median age of onset was 46.5 years (P25-P75, 34.2-54.0); most patients had sensory (n = 25) and motor manifestations (n = 26), and a concomitant autoimmune disease was identified in 6. Twenty patients were seropositive for anti-AQP4 antibodies. Only age and presence of optic nerve involvement showed statistically significant differences between groups (p = .03).

Conclusions

Clinical, imaging, and laboratory variables showed no major differences between patients with and without anti-AQP4 antibodies, with the exception of age of onset and presence of optic nerve involvement (uni- or bilateral); these factors should be studied in greater detail in larger populations.

Objective

To determine if there is a relationship between environmental exposure to pesticides and the prevalence of Amyotrophic Lateral Sclerosis (ALS) in Andalusia.

Method

We carried out a case–control study using the logistic regression method to verify the relationship between the prevalence of ALS in the area exposed to pesticides versus the unexposed area, through the Odds Ratio statistical test.

Results

The study population consisted of 519 individuals diagnosed with ALS between January 2016 and December 2018 according to the CMBD (Minimum Basic Data Set) as cases. In the control group, we have 8,384,083 individuals obtained from data from the National Institute of Statistics (INE). The Odds Ratio (OR) was used as a measure of association between cases and controls, obtaining an OR between 0.76 and 1.08 for the confidence interval of the CI (95%).

Conclusions

Despite the existence of various studies that suggest a possible association between environmental exposure to pesticides and the risk of Amyotrophic Lateral Sclerosis, our analysis of the Andalusian population did not find significant evidence of this association.

Introduction

Mir-146a-5p has been widely recognized as a critical regulatory element in the immune response. However, recent studies have shown that miR-146a-5p may also be involved in the development of Alzheimer disease (AD). Regrettably, the related mechanisms are poorly understood. Here, we investigated the effects of miR-146a in mice models and SH-SY5Y cells treated with amyloid β (Aβ)_1–42.

Methods

To create a model of AD, SH-SY5Y cells were treated with Aβ_1–42 and mice received intracerebroventricular injections of Aβ_1–42. Then, the transcriptional levels of miR-146a were estimated by real-time PCR. We transiently transfected the miR-146a-5p mimic/inhibitor into cells and mice to study the role of miR-146a. The role of signaling pathways including p38 and reactive oxygen species (ROS) was studied by using specific inhibitors. Aβ and amyloid-beta precursor protein (APP)levels were measured by immunoblotting. Furthermore, Aβ expression was analyzed by immunofluorescence and histochemical examinations.

Results

Aβ_1–42-stimulated SH-SY5Y cells displayed increased transcriptional levels of miR-146a and APP. Moreover, the p38 MAPK signaling pathway and ROS production were activated upon stimulation with a miR-146a-5p mimic. However, treatment with a miR-146a-5p inhibitor decreased the levels of APP, ROS, and p-p38 MAPK. A similar phenomenon was also observed in the animals treated with Aβ_1–42, in which miR-146a upregulation increased the expression of Aβ, p-p38, and ROS, while the inhibition of miR-146a had the opposite effect. This suggests that miR-146a increases Aβ deposition and ROS accumulation via the p-p38 signaling pathway.

Conclusions

Our research demonstrates that miR-146a-5pa increases Aβ deposition by triggering oxidative stress through activation of MAPK signaling.

Late-onset neutropaenia is defined as an absolute neutrophil count of <1.5 × 10³ cells/μL starting > 4 weeks after the last dose of rituximab, in the absence of other identifiable causes.

Late-onset neutropaenia is a rare adverse reaction to rituximab (observed in approximately 5% of patients). Rheumatic diseases constitute the main indication for rituximab; in these patients, neutropaenia appears after a mean of > 28 days.

Ocrelizumab is another monoclonal antibody that binds to CD20 (a glycosylated phosphoprotein mainly expressed on the membranes of B-lymphocytes); in January 2018, it was approved for the treatment of relapsing-remitting and primary progressive multiple sclerosis.

We present a case of neutropaenia following intravenous infusion of ocrelizumab in a patient with primary progressive multiple sclerosis who presented with neutropaenic fever, herpetic stomatitis, and ecthyma gangrenosum only 20 days after infusion.