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Autoimmune Cerebellar Ataxia Associated with Anti-Glutamate Receptor δ2 Antibodies: a Rare but Treatable Entity.

We report two novel cases of autoimmune cerebellar ataxia (ACA) associated with anti-glutamate receptor δ2 antibodies (Gluδ2-Abs). The first case was confirmed by indirect immunofluorescence and cell-based assays: a 29-year-old woman presented after 5 days of headache and vomiting, a pancerebellar syndrome, downbeat nystagmus, decreased visual acuity linked to bilateral retrobulbar optic neuritis (RON), and lymphocytic pleocytosis in the cerebrospinal fluid (CSF) without any abnormality detected using cerebral magnetic resonance imaging (MRI). Second-line immunotherapy allowed progressive clinical improvement, with full recovery achieved after a 4-year follow-up. Thereafter, we retrospectively tested Gluδ2-Abs in 350 patients with a suspicion of autoimmune encephalitis without characterized autoantibody. We identified a second case, a 12-year-old boy who developed 10 days after a respiratory infection, a static cerebellar syndrome with lymphocytosis in the CSF, and right cerebellum hyperintensity in MRI. Five days of corticosteroid treatment allowed a quick clinical improvement. No tumor was identified in both cases, whereas laboratory analyses revealed autoimmune stigma. The present cases suggested that ACA associated with Gluδ2-Abs is an extremely rare but treatable disease. Therefore, testing for Gluδ2-Abs might be considered in the setting of suspected ACA and no initial antibody identification. The visual deficits and ocular motility abnormalities observed in the first reported case might be part of the clinical spectrum of Gluδ2-Abs ACA. Young age, infectious prodromes, lymphocytic pleocytosis, and autoimmune background usually appear together with this syndrome and should lead to discuss the initiation of immunotherapy (after ruling out differential diagnosis, especially infectious causes).

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Ketorolac Tromethamine Loaded Nano-Spray Dried Nanoparticles: Preparation, Characterization, Cell Viability, COL1A1 Gene Simulation and Determination of Anti-inflammatory Activity by In Vivo HET-CAM Assay.

Ketorolac tromethamine (KT) is a non-steroidal anti-inflammatory drug from the heteroaryl acetic acid derivatives family. The most widely used new nanotechnological approaches for topical drug delivery are polymeric nanoparticles (NPs).

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Posttranscriptional Regulation of Gene Expression Participates in the Myelin Restoration in Mouse Models of Multiple Sclerosis: Antisense Modulation of HuR and HuD ELAV RNA Binding Protein.

Neuropathic pain is the most difficult-to-treat pain syndrome in multiple sclerosis. Evidence relates neuropathic pain to demyelination, which often originates from unresolved neuroinflammation or altered immune response. Posttranscriptional regulation of gene expression might play a fundamental role in the regulation of these processes. The ELAV RNA-binding proteins HuR and HuD are involved in the promotion of inflammatory phenomena and in neuronal development and maintenance, respectively. Thus, the aim of this study was to investigate the role of HuR and HuD in demyelination-associated neuropathic pain in the mouse experimental autoimmune encephalomyelitis (EAE) model. HuR resulted overexpressed in the spinal cord of MOG-EAE and PLP-EAE mice and was detected in CD11b + cells. Conversely, HuD was largely downregulated in the MOG-EAE spinal cord, along with GAP43 and neurofilament H, while in PLP-EAE mice, HuD and neuronal markers remained unaltered. Intranasal antisense oligonucleotide (ASO) delivery to knockdown HuR, increased myelin basic protein expression, and Luxol Fast Blue staining in both EAE models, an indication of increased myelin content. These effects temporally coincided with attenuation of pain hypersensitivity. Anti-HuR ASO increased the expression of HuD in GAP43-expressing cells and promoted a HuD-mediated neuroprotective activity in MOG-EAE mice, while in PLP-EAE mice, HuR silencing dampened pro-inflammatory responses mediated by spinal microglia activation. In conclusion, anti-HuR ASO showed myelin protection at analgesic doses with multitarget mechanisms, and it deserves further consideration as an innovative agent to counteract demyelination in neuropathic pain states.

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Cerium Oxide Nanoparticles Ameliorate Oxidative Stress, Inflammation, And Pain Behavior In Neuropathic Rats.

Neuropathic pain originating from a dysfunction in the nervous system is often intractable and chronic. Recently, several studies using nanoparticles suggested a new way to control neuropathic pain. This study intended to explore the potential neuroprotective effect of Cerium Oxide Nanoparticles (CNPs) synthesized by pullulan in neuropathic pain in rats.

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Xanthogranuloma of the sellar region: a systematic review.

Knowledge of xanthogranuloma (XG) of the sellar region comes from short series or single cases. We performed a systematic review, using the PubMed, Web of Science, Embase, Scopus, eLibrary, and BIOSIS Preview databases, of all cases reported from 2000 to the present. We also describe one unreported patient treated in our institution. A search of the literature revealed that of 71 patients 50.7% were male and that mean age at diagnosis was 34.7 ± 19.2 years old. Median time from clinical onset until diagnosis was 7 (3-21) months. Hypopituitarism (70.4%), visual disorders (64.7%), headache (53.5%), and polyuria-polydipsia (28.2%) were the most common symptoms. On MRI, median tumor size was 20 (16-29) mm, while 71.8% were sellar/suprasellar and less frequently exclusively suprasellar (15.5%) or sellar (12.7%). On T1-weighted imaging, XG was hyperintense in 76.3% of patients, while it showed variable appearance on T2-weighted imaging. The tumor showed cystic features in 50.7%, gadolinium enhancement in 45.1%, and calcification in 22.5% of patients. All patients underwent surgery (77.4% transphenoidal approach and 18.3% craniotomy), with hypopituitarism (56.4%), diabetes insipidus (34.5%), and visual defects (7.3%) being the most common complications. Total/subtotal resection was achieved in 93.5%, while the tumor was partially removed in 6.6%. Median follow-up was 24 (6-55) months and no tumor recurrence or remnant growth was reported in 97.5% of cases. In conclusion, XG affects the younger population, manifested by hormonal deficit and mass effect symptoms. Surgery is safe and offers excellent outcomes, though hypopituitarism is frequent post-surgery. Tumor recurrence or remnant growth is rare and radiological surveillance is a good option for patients with remnant lesions.

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How do common conditions impact health-related quality of life for children? Providing guidance for validating pediatric preference-based measures.

There is increasing interest in the validation of pediatric preference-based health-related quality of life measurement instruments. It is critical that children with various degrees of health-related quality of life (HRQoL) impact are included in validation studies. To inform patient sample selection for validation studies from a pragmatic perspective, this study explored HRQoL impairments between known-groups and HRQoL changes over time across 27 common chronic child health conditions and identified conditions with the largest impact on HRQoL.

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The medial prefrontal cortex and the cardiac baroreflex activity: physiological and pathological implications.

The cardiac baroreflex is an autonomic neural mechanism involved in the modulation of the cardiovascular system. It influences the heart rate and peripheral vascular resistance to preserve arterial blood pressure within a narrow variation range. This mechanism is mainly controlled by medullary nuclei located in the brain stem. However, supramedullary areas, such as the ventral portion of medial prefrontal cortex (vMPFC), are also involved. Particularly, the glutamatergic NMDA/NO pathway in the vMPFC can facilitate baroreflex bradycardic and tachycardic responses. In addition, cannabinoid receptors in this same area can reduce or increase those cardiac responses, possibly through alteration in glutamate release. This vMPFC network has been associated to cardiovascular responses during stressful situations. Recent results showed an involvement of glutamatergic, nitrergic, and endocannabinoid systems in the blood pressure and heart rate increases in animals after aversive conditioning. Consequently, baroreflex could be modified by the vMPFC neurotransmission during stressful situations, allowing necessary cardiovascular adjustments. Remarkably, some mental, neurological and neurodegenerative disorders can involve damage in the vMPFC, such as posttraumatic stress disorder, major depressive disorder, Alzheimer's disease, and neuropathic pain. These pathologies are also associated with alterations in glutamate/NO release and endocannabinoid functions along with baroreflex impairment. Thus, the vMPFC seems to play a crucial role on the baroreflex control, either during pathological or physiological stress-related responses. The study of baroreflex mechanism under such pathological view may be helpful to establish causality mechanisms for the autonomic and cardiovascular imbalance found in those conditions. It can explain in the future the reasons of the high cardiovascular risk some neurological and neurodegenerative disease patients undergo. Additionally, the present work offers insights on the possible contributions of vMPFC dysfunction on baroreflex alterations, which, in turn, may raise questions in what extent other brain areas may play a role in autonomic deregulation under such pathological situations.

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Eye movement characteristics are not significantly influenced by psychiatric comorbidities in people with visual snow syndrome.

Visual snow syndrome (VSS) is a neurological disorder primarily affecting the processing of visual information. Using ocular motor (OM) tasks, we previously demonstrated that participants with VSS exhibit altered saccade profiles consistent with visual attention impairments. We subsequently proposed that OM assessments may provide an objective measure of dysfunction in these individuals. However, VSS participants also frequently report significant psychiatric symptoms. Given that that these symptoms have been shown previously to influence performance on OM tasks, the objective of this study was to investigate whether psychiatric symptoms (specifically: depression, anxiety, fatigue, sleep difficulties, and depersonalization) influence the OM metrics found to differ in VSS. Sixty-one VSS participants completed a battery of four OM tasks and a series of online questionnaires assessing psychiatric symptomology. We revealed no significant relationship between psychiatric symptoms and OM metrics on any of the tasks, demonstrating that in participants with VSS, differences in OM behaviour are a feature of the disorder. This supports the utility of OM assessment in characterising deficit in VSS, whether supporting a diagnosis or monitoring future treatment efficacy.

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Differences in chronic pain care receipt among veterans from differing racialized groups and the impact of rural versus urban residence.

The current study aimed to identify differences in Veterans Affairs (VA) chronic pain care for Black, Asian, and Hispanic Americans, compared to non-Hispanic White Americans, and examine the intersection of race and rurality.

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Cross-cultural adaptation of the Dizziness Handicap Inventory – child/adolescent to Spanish version. Analysis of its application in children.

The Dizziness Handicap Inventory (DHI) is a questionnaire to assess self-perception of disability produced by the effects of vestibular system disorders. It is a tool used by professionals who treat patients with balance disorders, although it is not widely used in children. The aim of this study is to carry out a cross-cultural and linguistic adaptation of the DHI children/adolescent in the Argentine population from a version already published in Portuguese and to evaluate it in a group of patients.

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