Autoimmune Neurological Disorders Research Articles

The Immunoregulatory Role of CMKLR1 within the CNS During WNV Encephalitis

Abstract West Nile Virus (WNV)-induced neuroinvasive disease (WNND) has been a public health concern in North America since its introduction in 1999. In recent years, severe neurological illness has been reported much more frequently, together with neuromuscular manifestations. Previous studies have shown that dendritic cells (DCs) within the central nervous system (CNS) are required to restrict WNV replication and immunopathology by regulating anti-viral T-cell responses. In this study, we examined the role of CMKLR1 within the CNS during WNV encephalitis. CMKLR1-expressing microglial cells and CNS-infiltrating myeloid DCs have been shown to have an inflammatory role during autoimmune neurological disorders, yet their contribution to WNND remains unknown. In addition, chemerin, the ligand for CMKLR1, was upregulated in the CNS of WNV-infected mice. To evaluate the role of CMKLR1, we infected CMKLR1-deficient (CMKLR1−/−) and wild-type (WT) mice with WNV. WNV-infected CMKLR1−/− mice exhibited increased susceptibility to WNV, loss of virologic control, and more severe clinical signs of disease. Proinflammatory chemokine expression, including CCL5, CXCL9, and CXCL10, was significantly decreased in the absence of CMKLR1 suggesting reduced leukocyte trafficking into the CNS. For future studies, we will determine the numbers and type of infiltrating leukocytes and their role in virologic control within the WNV-infected CNS. Taken together, these data will help clarify the immunoregulatory role of CMKLR1 during WNV encephalitis. NIH-SC3GM130472

Nonparaneoplastic anti-NMDA receptor encephalitis in an adolescent girl: a case report.

A 17-year-old female presented to the hospital with an 11-day history of fever, altered behavior, abnormal body movements, and altered sensorium. Upon examination, she was found to be febrile, tachycardic, and tachypneic, with a Glasgow Coma Scale score of 8. The diagnosis of anti-NMDA receptor encephalitis is usually confirmed by the presence of anti-NMDA receptor antibodies in the cerebrospinal fluid. The first-line treatment options include steroids, intravenous immunoglobulin, and plasmapheresis, while second-line therapies such as rituximab and cyclophosphamide may be necessary for some patients. While most patients respond well to treatment, complications can arise, and as in this case, death can occur. New onset symptoms like alteration in behavior, abnormal body movement, altered sensorium, and psychiatric symptoms in a young female should raise suspicion of this disease. Immunotherapy is promising; however, anticipation and management of complication are essential in reducing mortality.

Overactive bladder and multiple sclerosis in the University Hospital of Oujda

BackgroundMultiple sclerosis (MS) is the most frequent autoimmune neurological disease in the young population. Vesico-sphincter disorders are frequent in the course of the disease; it has been reported that 90% of MS patients will develop a lower urinary tract disorder within 18 years of the diagnosis.MethodsThe aim of this study is to identify the frequency, severity, diagnosis, and treatment of overactive bladder (OAB) in MS patients at the Mohammed VI hospital university in Oujda-Morocco. It is a cross-sectional study. The population was collected in neurology department of Mohammed VI hospital university in Oujda-Morocco. The population cohort consisted of patients diagnosed with multiple sclerosis, which were invited to the urology department where they underwent urinary screening and completed a form of questions regarding the frequency and severity of OAB and its influence on quality of life.ResultIn our study, the mean age of the patients was 43 years, and our sample was composed of 48% males and 52% females, and the most frequent lower urinary tract symptom was urgency (57%), followed by urinary frequency (29%) and urge incontinence (14%). The recurrent-remittent form was the most frequent (62%), followed by the primary progressive form (24%) and the secondary progressive recurrent form (14%). Among the patients, 33% presented a mild symptomatology, 48% moderate, and 19% severe. In this study, it was found that the intensity of urinary symptoms and the MS disability score were positively correlated with quality of life and disease duration.ConclusionThe urgency was the major symptom of the lower urinary tract, and the MS disability score and the severity of OAB were associated with the quality of life of the patients. The urological evaluation of patients with multiple sclerosis should be performed routinely to identify OAB and to treat this condition appropriately.

Clinical Manifestation, Auxiliary Examination Features and Prognosis of GFAP Autoimmunity: a Chinese Cohort Study (P5-5.029)

<h3>Objective:</h3> To report the clinical manifestation and auxiliary examination features of 15 Chinese patients with glial fibrillary acidic protein (GFAP) autoimmunity. <h3>Background:</h3> GFAP astrocytopathy is a corticosteroid responsive inflammatory central nervous system (CNS) disorder spectrum predominantly affecting meninges, brain, spinal cord, and optic nerve mimics infectious meningoencephalitis. IgG antibodies binding to GFAP are specific biomarkers with diagnostic significance. <h3>Design/Methods:</h3> From June 2016 to December 2019, patients with suspected neurological autoimmune disease were scanned for autoantibodies by immunohistochemistry. Samples showed a characteristic immunoreactive pattern reminiscent of GFAP of astrocytes were selected and confirmed by cell-based assay. <h3>Results:</h3> Fifteen patients (8 male, 7 female) with a median age at onset of 53 years were identified as GFAP-IgG positive. Eleven of 15 patients presented with an acute monophasic course, of which 10 had antecedent flu-like symptoms. The predominant phenotype was meningoencephalitis (46.7%), followed by meningoencephalomyelitis in 40% of cases. Magnetic resonance imaging revealed enhancement in 10 of 13 patients. Inflammatory CSF showed mild lymphocyte-predominant pleocytosis with a median of 51/μl, elevated protein with a median of 87.5mg/dl. Five of six patients tested for CSF specific oligoclonal bands were positive. Five patients had coexisting antibodies, including NMDAR-IgG in 3 patients, Yo and MOG-IgG in one each patient. One patient underwent stereotactic brain biopsy and neuropathology diagnosis was diffuse large B-cell lymphoma with normal reactive fibrillary astrocytes. One patient had ovarian teratoma. Eleven of 15 patients received both intravenous immunoglobulin and steroids. Among them, 3 patients also received immunosuppressive agents later. During 2-year follow-up, nine of 15 patients achieved complete clinical remission. <h3>Conclusions:</h3> The clinical presentation of GFAP astrocytopathy is heterogeneous, including acute monophasic course or chronic relapsing courses. Patients with an acute monophasic course with antecedent infection symptoms responded well to immunotherapy. In case of primary central nervous system lymphoma, GFAP autoimmunity doesn’t equal to autoimmune GFAP astrocytopathy. <b>Disclosure:</b> Dr. Liu has nothing to disclose. Dr. Zhang has nothing to disclose.

Best practices in the use of human immunoglobulin preparations for intravenous administration in the treatment of rare neurological diseases

Aim. To describe best practices in using human normal immunoglobulin in patients with immune-mediated neurological disorders according to the data of one clinical center.Materials and methods. From 2016 to 2021, 20 patients with various autoimmune disorders of the peripheral and central nervous system were treated with human normal immunoglobulin at the Neurology Unit No.1 of Pavlov First Saint Petersburg State Medical University. Treatment efficacy was assessed by changes in the neurological examination data according to specialized scales for specific diseases or clinical manifestations (INCAT, QMGS, MoCA, EDSS). Safety of the therapy was assessed considering the instructions to the drug.Results. In the vast majority of patients, treatment allowed to stabilize the course of the disease or was accompanied by pronounced regression.Conclusion. The considered clinical cases of the use of human normal immunoglobulin preparations demonstrate the possibility of their use in the treatment of a number of autoimmune neurological diseases for unregistered indications.

Novel Immunotherapies for Myasthenia Gravis.

Myasthenia gravis (MG), a prototype autoimmune neurological disease, had its therapy centred on corticosteroids, non-steroidal broad-spectrum immunotherapy and cholinesterase inhibitors for several decades. Treatment-refractory MG and long-term toxicities of the medications have been major concerns with the conventional therapies. Advances in the immunology and pathogenesis of MG have ushered in an era of newer therapies which are more specific and efficacious. Complement inhibitors and neonatal Fc receptor blockers target disease-specific pathogenic mechanisms linked to myasthenia and have proven their efficacy in pivotal clinical studies. B cell-depleting agents, specifically rituximab, have also emerged as useful for the treatment of severe MG. Many more biologicals are in the pipeline and in diverse stages of development. This review discusses the evidence for the novel therapies and the specific issues related to their clinical use.

Immunomodulatory Aspects of Therapeutic Plasma Exchange in Neurological Disorders—A Pilot Study

Therapeutic plasma exchange (TPE) is used for drug-resistant neuroimmunological disorders, but its mechanism of action remains poorly understood. We therefore prospectively explored changes in soluble, humoral, and cellular immune components associated with TPE. We included ten patients with neurological autoimmune disorders that underwent TPE and assessed a panel of clinically relevant pathogen-specific antibodies, total serum immunoglobulin (Ig) levels, interleukin-6 (IL-6, pg/mL), C-reactive protein (CRP, mg/dL), procalcitonin (PCT, µg/L) and major lymphocyte subpopulations (cells/µL). Blood was collected prior to TPE (pre-TPE, baseline), immediately after TPE (post-TPE), as well as five weeks (follow-up1) and 130 days (follow-up2) following TPE. Pathogen-specific antibody levels were reduced by -86% (p < 0.05) post-TPE and recovered to 55% (follow-up1) and 101% (follow-up2). Ig subclasses were reduced by -70-89% (p < 0.0001) post-TPE with subsequent complete (IgM/IgA) and incomplete (IgG) recovery throughout the follow-ups. Mean IL-6 and CRP concentrations increased by a factor of 3-4 at post-TPE (p > 0.05) while PCT remained unaffected. We found no alterations in B- and T-cell populations. No adverse events related to TPE occurred. TPE induced a profound but transient reduction in circulating antibodies, while the investigated soluble immune components were not washed out. Future studies should explore the effects of TPE on particular cytokines and assess inflammatory lymphocyte lineages to illuminate the mode of action of TPE beyond autoantibody removal.

The Coexistence of Antibodies to Neuronal Cell and Synaptic Receptor Proteins, Gangliosides and Selected Neurotropic Pathogens in Neurologic Disorders in Children

Various primarily non-autoimmune neurological disorders occur synchronously with autoantibodies against tissues in the nervous system. We aimed to assess serum and cerebrospinal fluid (CSF) autoantibodies in children with neurologic disorders. To find new diagnostic tools, we compared the laboratory and clinical findings between the distinguished groups. Retrospectively, 508 patients were divided into six subgroups: neuroinfections, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections, neurologic autoimmune and demyelinating diseases, epilepsy, pervasive developmental disorders and other patients. We analysed serum anti-aquaporin-4, antiganglioside, neuronal antinuclear and cytoplasmic antibodies, as well as antibodies against surface neuronal and synaptic antigens in the CSF and serum. We involved available demographic and clinical data. Autoantibodies appeared in 165 (32.3%) children, with 24 showing multiple types of them. The most common were anti-neuroendothelium (anti-NET), anti-N-Methyl-D-Aspartate receptor (anti-NMDAr), anti-glial fibrillary acidic protein and anti-myelin antibodies bothering 46/463 (9.9%), 32/343 (9.4%), 27/463 (5.8%) and 27/463 (5.8%), respectively. Anti-NET and anti-NMDAr antibodies appeared more frequently in children with autoimmunity (p = 0.017; p < 0.001, respectively), increasing the autoimmune disease risk (OR = 2.18, 95% CI 1.13-13.97; OR = 3.91, 95% CI 1.86-8.22, respectively). Similar pathomechanisms appeared in diseases of different aetiology with clinical spectrums mimicking each other, so we proposed the model helping to diagnose autoimmune disease. We proved the influence of age, living place and medical history on the final diagnosis.

Relationship between vitamin D deficiency and metabolic disorders

The relationship between vitamin D deficiency and the metabolic syndrome has recently been revealed. Vitamin D deficiency was hypothesized to cause increased insulin resistance and decreased insulin secretion, which can result in the development of diabetes mellitus and obesity. Cardiovascular diseases are also closely related to the metabolic syndrome. Vitamin D has been shown to have complex multistep metabolism and act as a hormone at many extraskeletal targets. In this literature review, a comprehensive analysis of publications from Scopus, Web of Science, MedLine, The Cochrane Library, EMBASE, Global Health databases, as well as scientific libraries of Ukraine, European Union, Great Britain, USA and other countries was performed. Our goal is to identify and analyze scientific publications discussing various biological effects of vitamin D and its use in the comprehensive treatment of various diseases. In addition to the previously known role of vitamin D in calcium metabolism and the musculoskeletal system functionality, a wide range of its pleiotropic effects has been discovered recently. Modern studies have shown a relationship between low levels of vitamin D and development of neurocognitive dysfunction, mental and neurological disorders, infertility, immune reactivity and autoimmune disorders, various types of cancer, and cardiovascular pathologies. More recent data also revealed a relationship of vitaminD deficiency with practically all aspects of metabolic syndrome, namely diabetes mellitus type 2 and type 1, hyperglycemia, dyslipidemia, obesity, hypertension, and insulin resistance. It was concluded that the data of the modern literature regarding the effectiveness of vitamin D in the treatment and prevention of metabolic disorders and structural and functional changes of the liver in diabetes and non-alcoholic fatty liver disease are quite contradictory: at the same level as the numerous publications on the effective use of vitamin D, there are studies with unconfirmed effectiveness of therapy and even its toxicity for the indicated pathologies.

Ravulizumab for the treatment of myasthenia gravis

Introduction Myasthenia gravis (MG) is a neurological B-cell mediated autoimmune disorder affecting the neuromuscular junction. MG therapeutics have always relied on non-selective immunosuppression with oral steroids and non-steroidal immunosuppressants, mainly with good clinical response. However, clinical stabilization is often reached at the cost of many troublesome side effects and up to 15% of MG patients are deemed as refractory to conventional immunosuppression. This highlights the need of a more targeted and efficacious therapeutic approach. Results from the randomized-controlled period of the CHAMPION study demonstrate a good safety, tolerability, and efficacy profile of ravulizumab compared to placebo. Like eculizumab, ravulizumab is an anti-C5 monoclonal antibody, but with an enhanced pharmacokinetic profile, that allows dosing every 8 weeks. Areas covered We provide an overview of ravulizumab biological features and results from the phase III CHAMPION MG (NCT03920293) study. Expert opinion Data of the CHAMPION MG trial demonstrate that ravulizumab is effective and safe in the treatment of generalized MG. Having a rapid clinical effect, with long-term clinical response, ravulizumab could represent a selective immunosuppressive drug of choice in the future therapeutic algorithm of MG, where conventional immunosuppressants slowly leave room for newer drugs with a more targeted mechanism of action.

Inherited Chromosomally Integrated Human Herpesvirus 6: Laboratory and Clinical Features

Inherited chromosomally integrated human herpesvirus 6 (iciHHV-6) is a condition in which the complete HHV-6 genome is integrated into the chromosomes of the host germ cell and is vertically transmitted. The aims of this study were to identify iciHHV-6 prevalence in hospitalized patients and clinical features in individuals carrying this integration. HHV-6 PCR on hair follicles was used to confirm iciHHV-6 status when the blood viral load was more than 5 Log10 copies/mL. From January 2012 to June 2022, HHV-6 DNAemia was investigated in 2019 patients. In particular, 49 had a viral load higher than 6 Log10 copies/mL and HHV-6 DNA in hair follicles was positive. A viral load between 5.0 and 5.9 Log10 copies/mL was observed in 10 patients: 6 infants with acute HHV-6 infection and 4 patients with leukopenia and HHV-6 integration. Therefore, the iciHHV-6 prevalence in our population was 2.6% (53/2019). Adult patients with integration presented hematological (24%), autoimmune (11%), autoimmune neurological (19%), not-autoimmune neurological (22%), and other diseases (19%), whereas 5% had no clinically relevant disease. Although in our study population a high percentage of iciHHV-6 adult hospitalized patients presented a specific pathology, it is still unknown whether the integration is responsible for, or contributes to, the disease development.

Immune-related adverse events after immune checkpoint inhibitor exposure in adult cancer patients with pre-existing autoimmune diseases.

Immune checkpoint inhibitor (ICI) therapy can predispose patients to immune-related adverse events (irAEs) and autoimmune disease (AD) flare-ups, but the characteristics of irAEs among patients with pre-existing ADs are largely unknown. We conducted this study to determine the clinical courses, irAEs, AD flares, treatment, and outcomes of patients with AD on ICIs. This was a retrospective study of adult cancer patients at a large cancer center who were diagnosed with ADs before undergoing ICI therapy. Patients' clinical courses, complications, treatments, and outcomes related to both ADs flares and irAEs were collected and analyzed. The study included 197 patients. Most (55.4%) were women. Melanoma comprised the highest proportion (28.4%) of malignancies, and most (83.8%) patients received PD-1/PD-L1 inhibitors. Fifty (25.3%) patients developed a new irAE after starting ICI therapy, while 29 (14.7%) patients had an AD flare-up. Patients with inflammatory bowel disease had the highest incidence of AD flare-ups (31.7%), while patients with Hashimoto hypothyroidism had the highest incidence of new irAEs (39.2%). Patients with inflammatory bowel disease had more severe adverse events. In our cohort, patients with a new diagnosis of irAE were treated with immunosuppressive therapy. AD flares were managed similarly. With regard to irAE manifestations, the most common presentations were colitis (24 [12.1%] patients), hepatic transaminase elevations (8 [4%] patients), and pneumonitis (7 [3.5%] patients). Our findings suggest that patients with gastrointestinal and rheumatologic ADs had a higher incidence of AD flare-ups, while patients with Hashimoto hypothyroidism and neurologic ADs had a higher incidence of new irAEs. Patients with prior ADs experiencing flare-ups or new irAEs after ICI therapy tend to require aggressive immunosuppressive treatment. Thorough evaluation of baseline disease status, appropriate medical management before ICI therapy, and early recognition of inflammatory exacerbation may help ensure long-term success in treating and improving outcomes in these patients.

Single-cell mass cytometry on peripheral cells in Myasthenia Gravis identifies dysregulation of innate immune cells.

Myasthenia Gravis (MG) is a neurological autoimmune disease characterized by disabling muscle weaknesses due to anti-acetylcholine receptor (AChR) autoantibodies. To gain insight into immune dysregulation underlying early-onset AChR+ MG, we performed an in-depth analysis of peripheral mononuclear blood cells (PBMCs) using mass cytometry. PBMCs from 24 AChR+ MG patients without thymoma and 16 controls were stained with a panel of 37 antibodies. Using both unsupervised and supervised approaches, we observed a decrease in monocytes, for all subpopulations: classical, intermediate, and non-classical monocytes. In contrast, an increase in innate lymphoid cells 2 (ILC2s) and CD27- γδ T cells was observed. We further investigated the dysregulations affecting monocytes and γδ T cells in MG. We analyzed CD27- γδ T cells in PBMCs and thymic cells from AChR+ MG patients. We detected the increase in CD27- γδ T cells in thymic cells of MG patients suggesting that the inflammatory thymic environment might affect γδ T cell differentiation. To better understand changes that might affect monocytes, we analyzed RNA sequencing data from CD14+ PBMCs and showed a global decrease activity of monocytes in MG patients. Next, by flow cytometry, we especially confirmed the decrease affecting non-classical monocytes. In MG, as for other B-cell mediated autoimmune diseases, dysregulations are well known for adaptive immune cells, such as B and T cells. Here, using single-cell mass cytometry, we unraveled unexpected dysregulations for innate immune cells. If these cells are known to be crucial for host defense, our results demonstrated that they could also be involved in autoimmunity.

Hematopoietic Stem Cell Transplantation for the Treatment of Autoimmune Neurological Diseases: An Update.

Over the last two decades, haematopoietic stem cell transplantation (HSCT) has been explored as a potential therapeutic strategy for autoimmune diseases refractory to conventional treatments, including neurological disorders. Although both autologous (AHSCT) and allogeneic HSCT (allo-HSCT) were investigated, AHSCT was preferentially developed due to a more favourable safety profile compared to allo-HSCT. Multiple sclerosis (MS) represents the most frequent neurological indication for AHSCT, but increasing evidence on the potential effectiveness of transplant in other autoimmune neurological diseases is emerging, although with a risk-benefit ratio overall more uncertain than in MS. In the present work, the rationale for the use of HSCT in neurological diseases and the experimental models that prompted its clinical application will be briefly covered. Case series and prospective studies exploring the use of HSCT in autoimmune diseases other than MS will be discussed, covering both frequent and rare neurological disorders such as myasthenia gravis, myopathies, and stiff-person syndrome. Finally, an updated summary of ongoing and future studies focusing on this issue will be provided.

Rational Development of Live-Attenuated Zika Virus Vaccines.

Zika virus (ZIKV), a re-emerging mosquito-borne flavivirus, has caused outbreaks in Africa, Asia, the Pacific, and, more recently, in the Americas. ZIKV has been associated with the neurological autoimmune disorder Guillain-Barre syndrome in adults and congenital Zika syndrome in fetuses and infants, including microcephaly, spontaneous abortion, and intrauterine growth restriction. It is considered to be a major threat to global public health due to its unprecedented clinical impact on humans. Currently, there are no specific prophylactics or therapeutics available to prevent or treat ZIKV infection. The development of a safe and efficacious ZIKV vaccine remains a global health priority. Since the recent outbreak, multiple platforms have been used in the development of candidate ZIKV vaccines. The candidate vaccines have been shown to elicit strong T cell and neutralization antibody responses and protect against ZIKV infection in animal models. Some candidates have progressed successfully to clinical trials. Live-attenuated vaccines, which induce rapid and durable protective immunity, are one of the most important strategies for controlling flavivirus diseases. In this review, we discuss recent progress in the development of candidate live-attenuated ZIKV vaccines.

Abnormal Hyperphosphorylation of Tau in Canine Immune-mediated Meningoencephalitis.

Tau is a microtubule-associated protein involved in the assembly and stabilization of microtubules. In human medicine, hyperphosphorylation of tau is associated with microtubule instability and is considered to play a role in the progression of multiple sclerosis (MS). MS is an autoimmune neurological disease that shares many characteristics, including pathological mechanisms, with canine meningoencephalitis of unknown etiology (MUE). With this background, this study investigated the presence of hyperphosphorylated tau in dogs with MUE and experimental autoimmune encephalomyelitis (EAE). In total, eight brain samples were examined from two neurologically normal dogs, three dogs with MUE, and three canine EAE models. Anti-(phospho-S396) tau antibody was used for immunohisto-chemistry, which stained hyperphosphorylated tau. In normal brain tissues, hyperphosphorylated tau was not found. In all the dogs with EAE and one of the dogs with MUE, immunoreactivity for S396 p-tau was observed in glial cell cytoplasm and the background in the periphery of the inflammatory lesion. These results suggest for the first time that tau pathology may be involved in the progression of neuroinflammation in dogs, similar to that in human MS.

Comparison of IVIg and TPE efficacy in the treatment of neurological disorders: a systematic literature review.

Intravenous immunoglobulin (IVIg) and therapeutic plasma exchange (TPE) are among the main immunotherapies for neurological disorders. Their benefit is greatest in immune-mediated conditions, but their distinct efficacy cannot be simply explained. This review aimed to systematically identify studies comparing the efficacy of TPE and IVIg treatments for selected autoimmune neurological disorders and identify optimal therapies for each condition. PubMed, MEDLINE and Embase databases were searched for original publications from 1990 to 2021. Additional publications were identified via expert recommendations. Conference abstracts older than 2017, review articles and articles without information on TPE and IVIg comparison in title and abstract were excluded. Risks of bias were descriptively addressed, without a meta-analysis. Forty-four studies were included on Guillain-Barré syndrome (20 studies - 12 adult, 5 paediatric, 3 all ages), myasthenia gravis (11 studies -8 adult, 3 paediatric), chronic immune-mediated polyradiculoneuropathy (3 studies -1 adult, 2 paediatric), encephalitis (1 study in adults), neuromyelitis optica spectrum disorders (5 studies -2 adult, 3 all ages) and other conditions (4 studies - all ages). TPE and IVIg were mostly similarly efficacious, measured by clinical outcomes and disease severity scores. Some studies recommended IVIg as easy to administer. TPE procedures, however, have been simplified and the safety has been improved. TPE is currently recommended for management of neuromyelitis optica spectrum disorder relapses and some myasthenia gravis subtypes, in which rapid removal of autoantibodies is crucial. Despite some limitations (e.g. the low evidence levels), this review provides an extensive 30-year-long overview of treatments for various conditions. Both IVIg and TPE are usually comparably efficacious options for autoimmune neurological disorders, with few exceptions. Treatment choices should be patient-tailored and based on available clinical resources. Better designed studies are needed to provide higher-level quality of evidence regarding clinical efficacy of TPE and IVIg treatments.

Correlation and differences of patient-reported outcomes vs. Likert-Rating of MS symptoms in a real-world cohort using a digital patient app.

Multiple Sclerosis (MS) is a chronic and progressive neurological autoimmune disease currently affecting 250,000 individuals in Germany. Patients suffering from the disease can be severely impaired in their day-to-day activities. BRISA is a digital app specifically designed to help MS patients monitor their disease by regularly tracking symptoms. Lengthy and time-consuming questionnaires for patient-reported outcomes (PRO) are the standard method to assess the patients' current condition. Here, we examine whether simplified versions of these questionnaires can provide comparable information regarding individual symptom presentations in BRISA users. 828 users were included in the analysis. Patients who provided onboarding information and answered at least one questionnaire and the corresponding simplified smiley symptoms assessment were included. Correlation of questionnaire and symptom scores was calculated using Pearson's correlation. Our analysis cohort predominantly consisted of female, 26-55-year-olds. Relapsing-remitting MS (RRMS) was the most common MS type recorded. Most patients were diagnosed 2-5 years ago. Questionnaires regarding fatigue and vision impairment were among the most answered, those regarding bowel movement and sexual satisfaction received fewest responses. Overall, the scores from questionnaires and symptoms correlated positively. Scoring correlation could also be shown across the subgroups divided by gender, age groups, type of MS, and time since diagnosis of the disease. Scores recorded from traditional PRO questionnaires can be reflected more easily as a trend in a simplified scale using smileys. Nevertheless, traditional questionnaires are needed to also maintain a more objective assessment. In conclusion, the patient will benefit most from an adaptive combination of regular traditional PRO questionnaire assessments and simplified symptom recording.

Screening tests for the evaluation of cognitive impairment in multiple sclerosis patients

Multiple sclerosis (MS), the most common autoimmune neurological disease of young people, is a significant burden for the patient, significantly decreasing the quality of life. Besides motor deficits, sensory problems, and vision loss, in recent years, neurologists have focused also on the cognitive impairment related to this condition. The early detection of cognitive disturbances is currently an essential part of MS patients’ follow-ups, as any worsening suggests the inefficiency of the applied treatment and the need for a therapeutic switch. In this regard, this review aims to highlight the importance of cognitive screening tests in the periodical evaluation of MS patients. While in the first part, the most frequently used cognitive screening tests in Romania are presented in a detailed manner, in the second part of the article, the clinical impact of these tests is highlighted, based on the results of the most relevant randomized clinical trials published during the last 10 years. Finally, the authors suggest future research directions to improve cognitive screening testing in MS patients after exposing the limitations of currently used screening batteries.

Autoimmune diseases and new-onset atrial fibrillation: a UK Biobank study.

The underlying mechanisms of atrial fibrillation (AF) are largely unknown. Inflammation may underlie atrial remodelling. Autoimmune diseases, related to increased systemic inflammation, may therefore be associated with new-onset AF. Participants from the population-based UK Biobank were screened for rheumatic fever, gastrointestinal autoimmune diseases, autoimmune diseases targeting the musculoskeletal system and connective tissues, and neurological autoimmune diseases. Between 2006 and 2022, participants were followed for incident AF. Cox proportional hazards regression analyses were performed to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) to quantify associations. 494 072 participants free from AF were included (median age 58.0 years, 54.8% women). After a median of 12.8 years, 27 194 (5.5%) participants were diagnosed with new-onset AF. Rheumatic fever without heart involvement (HR, 95% CI: 1.47, 1.26-1.72), Crohn's disease (1.23, 1.05-1.45), ulcerative colitis (1.17, 1.06-1.31), rheumatoid arthritis (1.39, 1.28-1.51), polyarteritis nodosa (1.82, 1.04-3.09), systemic lupus erythematosus (1.82, 1.41-2.35), and systemic sclerosis (2.32, 1.57-3.44) were associated with a larger AF risk. In sex-stratified analyses, rheumatic fever without heart involvement, multiple sclerosis, Crohn's disease, seropositive rheumatoid arthritis, psoriatic and enteropathic arthropathies, systemic sclerosis and ankylosing spondylitis were associated with larger AF risk in women, whereas only men showed a larger AF risk associated with ulcerative colitis. Various autoimmune diseases are associated with new-onset AF, more distinct in women. Our findings elaborate on the pathophysiological differences in autoimmunity and AF risk between men and women.