The "gut-brain axis" provides a theoretical foundation for the connection between intestinal and neurological diseases, but whether this reflects a shared genetic etiology or causal relationships exist remains unclear. We used genome-wide association study summary data from FinnGen and UK Biobank to investigate the genetic correlations and causal relationships between three intestinal diseases and six neurological diseases. We observed positive global genetic correlations between irritable bowel syndrome and epilepsy (rg = 0.429, p = 1.53 × 10-2), and stroke (rg = 0.368, p = 2.56×10-2). Upon dividing the whole genome into 1703 independent regions, local genetic correlations were identified in a region between ulcerative colitis and multiple sclerosis (Chr6: 31571218-32682664). We also identified 12 novel pleiotropic SNPs shared between intestinal and neurological diseases, as well as a functional gene shared between ulcerative colitis and multiple sclerosis. SNP heritability enrichment analysis indicated that ulcerative colitis and multiple sclerosis have enrichment in several immune cells. Two-sample Mendelian randomization indicated the causal effect of Crohn's disease on Parkinson's disease (FDR = 1.34 × 10-2, OR = 1.092). The methylome Mendelian randomization analysis also showed causal relationships between several intestinal and neurological diseases. Through comprehensive and systematic statistical analysis, we identified the global and local genetic correlations and causal relationships between several intestinal and neurological diseases and discovered shared pleiotropic loci and genes between them. Furthermore, the consistent SNP heritability enrichment observed in immune cells also indicated the crucial role of the immune system in the "gut-brain axis."

Paediatric-onset multiple sclerosis comprises approximately 1·5% of prevalent multiple sclerosis cases and is associated with higher disease burden, early and progressive motor and cognitive disability in young adulthood, and high levels of depression and fatigue. Observational data and randomised controlled trials have shown marked effects of multiple sclerosis disease-modifying therapies on MRI activity and long-term outcomes, including disease progression, in the paediatric population. We present a comprehensive review of published literature focused on issues of access to therapy in children and adolescents with paediatric-onset multiple sclerosis. In this Review, we identify regional variability in availability of multiple sclerosis therapies and examine issues, such as differences in access to care and time to diagnosis, criteria for regulatory approval, availability of insurance, and government supports. Finally, we outline specific future directions that should be taken to address these barriers and ensure better and equal therapy access for all children and adolescents with multiple sclerosis.

Vacuoles, E1 enzyme, X-linked (Xp11.3), autoinflammatory, somatic (VEXAS) syndrome is a novel acquired disorder of adulthood, discovered in 2020. Neurological symptoms and sequelae of this new disease are underreported and rarer than their systemic counterparts. We aim to shed light upon the neurological manifestations of this disease by reporting a complex case of a 58-year-old male with a biopsy supporting tumefactive demyelination in the setting of VEXAS syndrome. A 58-year-old male with a history of VEXAS syndrome (diagnosed in 2020 as only myelodysplastic syndrome (MDS)), diabetes mellitus, and relapsing polychondritis presented to our institution's emergency department with an acute onset of right lower extremity weakness and headache in April 2022. His weakness progressed to right lower extremity hemiparesis with extinction in sensory modality. He was evaluated for acute stroke, with initial differential diagnosis favoring acute venous infarct from cerebral venous thrombosis (CVT) secondary to MDS. However, brain magnetic resonance imaging (MRI) suggested tumefactive demyelination or acute disseminated encephalomyelitis (ADEM) with a left parietal focus, and diagnostic catheter cerebral angiogram found no evidence of CVT. The patient then developed partial status epilepticus without a history of seizures and later became obtunded with global aphasia upon eventual awakening. Subsequent MRI substantiated tumefactive demyelination or glioma. The lesion was biopsied, displaying no neoplastic cells, supporting diagnosis of tumefactive demyelination. The patient received 1 g of daily solumedrol for 5 days and a few months of prednisone taper, with resolution of mental status despite persistence of right-sided hemiplegia and global aphasia. In March 2023, the patient's genetic testing revealed a UBA1 gene mutation, solidifying a diagnosis of VEXAS syndrome. At this time, the patient exhibited Broca's aphasia with intact comprehension. He was neurologically stable in a wheelchair. To our knowledge, this case is the first reported in the literature of a VEXAS syndrome-associated central demyelination. Further research into the molecular mimicry and pathogenesis of VEXAS syndrome and its neurobiological involvement is strongly encouraged. A growing body of literature will increase comprehension of this novel disease and its role in cerebral pathology.

Multiple sclerosis (MS) is a chronic neurologic disorder with significant implications for public health as being the first cause of nontraumatic neurologic disability in young adults. Although the global prevalence of MS has been increasing, recent temporal trends in incidence remain unclear. We aimed to evaluate current MS incidence trends in France over 11 years using the Système National des Données de Santé, a nationwide administrative database covering 99% of the French population. We used a published algorithm that incorporates multiple data sources, including benefits from long-term diseases, specific disease-modifying treatment prescriptions, and hospital discharge, to identify incident MS cases from January 1, 2011, to December 31, 2021. Sex-standardized and age-standardized incidence and prevalence were estimated using a "specific" and a "sensitive" definition providing bounds on the evolution of recent incidence. We used multivariable Poisson regression models to estimate temporal trends in incidence rates, calculating incidence rate ratios (IRRs) along with corresponding 95% CIs. In a sensitivity analysis, the time lag between past visits to neurologists and the database recording of MS was analyzed to ensure that the diagnosis extraction date was reliable. A total of 67,311 individuals with suspected MS were identified between 2011 and 2021, with 50,320 individuals classified as incident MS using the specific definition. The sensitive definition identified 56,918 individuals with incident cases. The median age at diagnosis was 40.6 years for the specific definition and 41.5 years for the sensitive definition. The study found stable incidence of MS over the 11-year period (adjusted IRR: 0.998 [95% CI 0.996-1.001] for the specific cohort). The female-to-male ratio of incident MS cases remained stable while sex-standardized and age-standardized prevalence of MS continued to rise. The median time lag between probable diagnosis and database recording was estimated to be less than 18 months, with variations depending on age and method of patient identification. This study provides a comprehensive analysis of MS epidemiology in France, demonstrating stable incidence and sex ratio. The increase in prevalence suggests improved management and survival and highlights the ongoing need for health care systems to support the growing population of individuals with MS.

This study retrospectively analyzed children admitted to the Fourth Affiliated Hospital of Guangxi Medical University for CO (carbon monoxide) poisoning from January 2018 to December 2022 and followed up on their neurological sequelae for a long time. The study was approved by the Ethics Committees of the Fourth Affiliated Hospital of Guangxi Medical University (the identification code was KY2023131) and informed consent was obtained from all participants and/or their legal guardians. The study complied with the Declaration of Helsinki. Through Global Deterioration Scale [GDS], we further compared the differences between children with and without cognitive impairment, and identified some risk factors for long-term cognitive impairment in children after CO poisoning. The GDS score of the patient was based on the follow-up score, and we only conducted one follow-up and recorded the GDS score throughout the entire study period. The follow-up time interval is defined as the time from the first discharge of the patient to our follow-up. A total of 113 children were encompassed in the study, with an average follow-up of 3.6 years (3.6 ± 1.5 years). Among them, 13 children (11.5%, 13/113) had cognitive abnormalities. The utilization of gas water heaters in enclosed bathrooms (101 cases, 89.4%) constituted the most frequent cause of CO poisoning among children in this study, followed by heating with fire (11 cases, 9.7%). Furthermore, one child was left by his father in a running car, thereby resulting in poisoning. The clinical manifestations of CO poisoning in children were mainly consciousness disorders (67 cases, 59.3%), dizziness or headache (37 cases, 32.7%), and other manifestations including irritability, crying, vomiting, limb weakness, and limb twitching, a total of 9 cases. The duration of consciousness disorders in children with cognitive abnormalities was mostly more than one day, with a median of 5 days, and the hospitalization time was longer. Children with cognitive abnormalities had higher C-reactive protein (CRP) levels, higher D-dimer levels, and higher liver enzyme levels. The most common imaging change after CO poisoning in children was cerebral edema, with two cases of subarachnoid hemorrhage observed and one case of demyelinating changes observed. For children with coma time less than one hour, there were few abnormal changes in cranial imaging. Children with cognitive abnormalities were more likely to develop epilepsy (38.5%, 5/13) and other system damage (53.8%, 7/13) during hospitalization, including pulmonary infection (3 cases), stressful gastrointestinal bleeding (2 cases), electrolyte imbalance (2 cases), dysfunction of liver, kidney or myocardial (3 cases), and some children had multiple system damage at the same time. There were statistical differences in the admission CO hemoglobin level, fibrinogen, D-dimer, high-sensitivity CRP, neuron enolase, alanine aminotransferase or aspartate aminotransferase (ALT or AST), lactate dehydrogenase, length of hospital stay, discharge and admission Glasgow Coma Scale (GCS), seizure frequency, duration of consciousness disorders more than one day, cranial imaging changes, use of ventilators, presence of other system damage, the number of hyperbaric oxygen (HBO) treatments, and whether the patients were transferred to another hospital between the two groups of children. Multivariate logistic regression analysis showed that head imaging changes and consciousness disorders lasting for more than a day were statistical differences. For children with unconsciousness lasting for more than one hour, it is advisable to contemplate conducting a head imaging examination as soon as possible within 3 days after CO exposure to guide the treatment during the acute phase.Characteristic alterations in cranial imaging and a longer duration of consciousness disorders (exceeding one day) might be correlated with subsequent neurological sequelae. For children with CO poisoning presenting these characteristics, active treatment can be implemented, encompassing but not restricted to HBO treatments, to minimize subsequent damage to the greater extent possible. So, for children who were unconscious for more than one day or presented characteristic changes in cranial imaging, long-term follow-up should be carried out to determine whether delayed encephalopathy or subsequent cognitive impairment occurs.