Westbean5382

Several genetic and environmental factors have been reported in progressive supranuclear palsy (PSP), although none were identified as a definitive cause. We aimed to explore potential gene-environment interactions in PSP. Two hundred and ninety two PSP cases and 292 controls matched for age, sex, and race from the ENGENE-PSP were analyzed to determine the association between PSP and minor alleles of 5 single nucleotide polymorphisms (SNPs) in 4 genes (MAPT, MOBP, EIF2AK3, and STX6), which were previously associated with PSP risk. Interactions between these SNPs and environmental factors, including previously reported occupational and agricultural risk factors for PSP, were assessed for PSP odds and age of symptom onset. Minor alleles of MAPTrs242557 and EIF2AK3rs7571971 were individually associated with increased odds; MAPTrs8070723 minor alleles were associated with lower PSP odds. There were several gene-environment interactions for PSP odds and age of symptom onset, however, they did not remain significant after FDR-correction. Larger scale studies are required to determine potential interactions.Background Reports vary on the incidence of vestibular dysfunction and dizziness in patients following cochlear implantation (CI). Disequilibrium may be caused by surgery at the cochlear base, leading to functional disturbances of the vestibular receptors and endolymphatic duct system (EDS) which are located nearby. Here, we analyzed the three-dimensional (3D) anatomy of this region, aiming to optimize surgical approaches to limit damage to the vestibular organ. Material and Methods A total of 22 fresh-frozen human temporal bones underwent synchrotron radiation phase-contrast imaging (SR-PCI). One temporal bone underwent micro-computed tomography (micro-CT) after fixation and staining with Lugol's iodine solution (I2KI) to increase tissue contrast. We used volume-rendering software to create 3D reconstructions and tissue segmentation that allowed precise assessment of anatomical relationships and topography. Macerated human ears belonging to the Uppsala collection were also used. Drilling and insertion of CI electrodes was performed with metric analyses of different trajectories. Results and Conclusions SR-PCI and micro-CT imaging demonstrated the complex 3D anatomy of the basal region of the human cochlea, vestibular apparatus, and EDS. Drilling of a cochleostomy may disturb vestibular organ function by injuring the endolymphatic space and disrupting fluid barriers. The saccule is at particular risk due to its proximity to the surgical area and may explain immediate and long-term post-operative vertigo. Round window insertion may be less traumatic to the inner ear, however it may affect the vestibular receptors.Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal postures, repetitive movements, or both. Research in dystonia has been challenged by several factors. First, dystonia is uncommon. Dystonia is not a single disorder but a family of heterogenous disorders with varied clinical manifestations and different causes. The different subtypes may be seen by providers in different clinical specialties including neurology, ophthalmology, otolaryngology, and others. These issues have made it difficult for any single center to recruit large numbers of subjects with specific types of dystonia for research studies in a timely manner. The Dystonia Coalition is a consortium of investigators that was established to address these challenges. Since 2009, the Dystonia Coalition has encouraged collaboration by engaging 56 sites across North America, Europe, Asia, and Australia. Its emphasis on collaboration has facilitated establishment of international consensus for the definition and classification of all dystonias, diagnostic criteria for specific subtypes of dystonia, standardized evaluation strategies, development of clinimetrically sound measurement tools, and large multicenter studies that document the phenotypic heterogeneity and evolution of specific types of dystonia.Alternating hemiplegia of childhood is a rare neurological disease characterized by paroxysmal movement disorders and chronic neurological disturbances, with onset before 18 months of age. Mutations in the ATP1A3 gene have been identified in up to 80% of patients. Thirty-nine patients [20 females, 19 males, mean age 25.32 years (7.52-49.34)] have been recruited through the Italian Biobank and Clinical Registry for Alternating Hemiplegia of Childhood. Demographic data, genotype, paroxysmal movement disorders, chronic neurological features, and response to flunarizine have been analyzed. ATP1A3 gene mutations have been detected in 92.3% of patients. Patients have been divided into three groups-p.Asp801Asn mutation patients (26%), p.Glu815Lys cases (23%), and patients with other ATP1A3 mutations-and statistically compared. The Italian cohort has a higher percentage of ATP1A3 gene mutation than reported in literature (92.3%). Our data confirm a more severe phenotype in patients with p.Glu815Lys mutation, with an earlier age of onset of plegic (p = 0.02 in the correlation with other mutations) and tonic attacks. read more P.Glu815Lys patients most frequently present altered muscle tone, inability to walk (p = 0.01 comparing p.Glu815Lys and p.Asp801Asn mutations), epilepsy, and a more severe grade of dystonia (p less then 0.05 comparing p.Glu815Lys and p.Asp801Asn mutations). They have moderate/severe intellectual disability and severe language impairment (p less then 0.05). Interestingly, flunarizine seems to be more efficacious in patients with p.Glu815Lys mutation than p.Asp801Asn. In conclusion, our research suggests a genotype-phenotype correlation and provides information on this disorder's features, clinical course, and treatment.In the last decade, notable progresses have been observed in chronic migraine preventive treatments. According to the European Headache Federation and national provisions, onabotulinumtoxin-A (BTX-A) and monoclonal antibodies acting on the pathway of calcitonin gene-related peptide (CGRP-mAbs) should not be administered in combination due to supposed superimposable mechanism of action and high costs. On the other hand, preclinical observations demonstrated that these therapeutic classes, although operating directly or indirectly on the CGRP pathway, act on different fibers. Specifically, the CGRP-mAbs prevent the activation of the Aδ-fibers, whereas BTX-A acts on C-fibers. Therefore, it can be argued that a combined therapy may provide an additive or synergistic effect on the trigeminal nociceptive pathway. In the present study, we report a case series of 10 patients with chronic migraine who experienced significant benefits with the combination of both erenumab and BTX-A compared to each therapeutic strategy alone.