Autoimmune Neurological Disorders Research Articles

The Anti-Inflammatory Roles of Vitamin D for Improving Human Health

Vitamin D receptors (VDRs) are present in almost all cells of the immune system, including B cells, T cells, NK (Natural Killer) cells, dendritic cells, and monocytes, as well as the epithelial cells of many organs such as the intestine, pancreas, prostate, lungs, and cardiomyocytes. In addition, some immune cells, including dendritic cells, macrophages, and B and T cells, can synthesize calcitriol by expressing 1α-hydroxylase. Upon binding to VDRs, vitamin D (Vit D) regulates the expression of genes involved in immune responses, including those encoding for cytokines. It modulates the production of pro-inflammatory cytokines while promoting the synthesis of anti-inflammatory cytokines. Vit D also affects the differentiation and maturation of cells of the immune system. By inhibiting the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways, Vit D reduces the expression of pro-inflammatory genes. These effects highlight the potential of Vit D as a therapeutic agent in the management of inflammatory diseases, including autoimmune disorders, cardiovascular diseases, diabetes, metabolic syndrome, cancer, neurological diseases, depression, and inflammatory bowel disease.

Thymoma-associated paraneoplastic encephalitis resolved by robotic-assisted radical thymectomy: a case report

BackgroundWe present a rare case of autoimmune encephalitis associated with an incidentally discovered thymoma. Limited case reports exist of thymoma-associated paraneoplastic encephalitis. The unique clinical presentation and subsequent surgical intervention offer valuable insights into the management of similar cases.Case presentationA 41-year-old female presented with irritability, personality changes, fatigue, and seizures. Physical examination and bloodwork on first encounter were unremarkable. Neurological evaluation was done, and a brain magnetic resonance imaging (MRI) with and without contrast demonstrated numerous hyperintensity foci within bilateral cerebral cortices on T2-/FLAIR-weighted images affecting only the supratentorial brain, findings highly suggestive of encephalitis. A chest computed tomography (CT) revealed an anterior mediastinal mass compatible with a thymoma. Cerebrospinal fluid from a lumbar puncture was unremarkable. Paraneoplastic autoantibody evaluation was positive, and the patient was diagnosed with autoimmune encephalitis believed to be associated with an incidentally discovered thymoma. Given her rapid neurological deterioration, the thoracic surgery team was urgently consulted.Patient underwent robotic-assisted radical thymectomy with prompt resolution of symptoms. During her 2-week postoperative visit, she was neurologically intact with no residual deficits. Follow-up MRI at 6 months demonstrated resolution of abnormal signal intensities, with continued improvement noted 1-year post-operation. Chest CT scans at 6 and 12 months revealed no residual or recurrent thymic tissue.ConclusionsThis case illustrates the connection between thymoma and autoimmune neurological disorders like encephalitis. It emphasizes the significance of comprehensive neurological and oncological assessments for patients with unexplained neurological symptoms. Prompt diagnosis and treatment led to positive outcomes in this case, underscoring the potential for full recovery in similar cases.

Prevalence of autoantibodies neuromyelitis optica (NMO igg) and myelin oligodendrocyte glycoprotein (MOG) in NMOSD and the relationship between them in the general population

Neuromyelitis optica spectrum disorder (NMOSD) and anti-myelin oligodendrocyte glycoprotein (anti-MOG) syndromes are inflammatory conditions of the central nervous system that often involve the optic nerves and spinal cord. They can be mistaken for MS due to their similar symptoms. Therefore, we investigated the relationship between NMO antibody (NMO-Ab) and anti-MOG antibody (MOG-Ab) and the positivity of these antibodies in the general Indian population.: This retrospective study analyzed 40186 patients for Neuromyelitis Optica Antibodies serum and Myelin Oligodendrocyte Glycoprotein antibodies serum. Additionally, 5762 patients were analyzed specifically for these antibodies in their cerebrospinal fluid. The study included patients of all ages, unaccounting for their clinical history, and was conducted between January 2019 and July 2023 at the Global Reference Lab.: Overall, it was observed that MOG serum antibodies were more prevalent (18.59%) than NMO serum antibodies (8.12%). Females had a higher prevalence of NMO serum antibodies (13.23%) than males (2.16%), whereas the prevalence of MOG serum antibodies was similar in females (14.27%) and males (14.59%). The highest percentage of MOG serum positivity (31.40%) was observed in 1-12 years age group, and for NMO, it was 9.44% in the 19-30 years age group. The overlap in the positivity between NMO serum and CSF was 6.09% while for MOG serum and CSF, it was 3.86%. A concordance of 92.04% was observed for samples tested negative for NMO in serum as well as CSF. Only 2 cases of 259 cases tested for MOG antibodies showed negativity in serum but positivity in CSF.The study highlights the prevalence of MOG and NMO antibodies in serum and CSF among patients with suspected or known autoimmune neurological disorders, with notable difference in positivity rates between genders for NMO antibodies. These findings underscore the importance of comprehensive antibody testing in the diagnosis and management of demyelinating diseases such as MOG-Ab NMOSD and AQP4-Ab NMOSD. Further research is warranted to explore the clinical implications of these antibodies and their role in guiding therapeutic interventions for affected individuals.

Tryptophan-immunoadsorption plasmapheresis regulates polymorphonuclear-myeloid-derived suppressor cells and pro-inflammatory cytokines.

Immunoadsorption plasmapheresis (IA) has been reported to have immunoregulatory effects, in addition to the removal of autoantibodies. This study aimed to investigate the effects of IA on the proportion of myeloid-derived suppressor cells (MDSCs) that potentially suppress autoimmune responses and regulate immunity. The study included 21 patients with autoimmune neurological diseases and 8 healthy participants. We measured polymorphonuclear (PMN)-MDSCs (CD14-CD11b+CD33+) and inflammation-related mediators before and after a single session of tryptophan-IA. We also investigated whether an increase in PMN-MDSCs after initial IA was a predictor of clinical efficacy in nine patients with myasthenia gravis based on the Quantitative Myasthenia Gravis score. For a total of 36 times of IA procedures, the number of PMN-MDSCs significantly increased after IA. Interleukin-10, monocyte chemoattractant protein-1 and macrophage inflammatory protein-1β levels showed significant increases after IA. Despite similar severity at admission, the Quantitative Myasthenia Gravis scores at discharge were significantly lower in the group in which IA increased PMN-MDSCs to a level of 20% of peripheral blood mononuclear cells or more. Tryptophan-IA regulates PMN-MDSCs and pro-inflammatory cytokines, possibly leading to suppression of autoimmune responses and tissue damage in neuroimmunological disorders.

Effectiveness and safety of therapeutic plasma exchange in neurological diseases: An 11-year report from a tertiary care center.

Therapeutic plasma exchange has been a well-known treatment method for many years and is widely available. It leads to the improvement of neurological symptoms in autoimmune neurological diseases by the removal of antibodies. The aim of this study was to present therapeutic plasma exchange responses and procedure-related adverse events in patients with autoimmune neurological diseases based on our 11-year experience. A retrospective evaluation was conducted on adult patients who underwent a therapeutic plasma exchange procedure due to neurological diseases between January 2013 and January 2024. Data were gathered from electronic and written hospital and apheresis unit records. A total of 265 patients underwent 1274 procedures with a preliminary diagnosis of autoimmune neurological disease. Five patients were excluded from the analysis due to their final diagnoses. The most common clinical indications were Guillain-Barré syndrome (45.4%), myasthenia gravis (26.1%), and multiple sclerosis (19.2%). The overall response rate was 81.3%, with 21.7% exhibiting a complete response and 59.6% demonstrating a partial response. With the exception of one patient (hypertensive crisis), no complications necessitating the termination of the procedure were observed. The most prevalent complication was an easily manageable allergic reaction. Therapeutic plasma exchange has been demonstrated to be an efficacious and safe treatment option in autoimmune neurological diseases, with a favorable overall response rate and a manageable mild-to-moderate side effect profile.

Cost-effectiveness of oral versus injectable disease modifying therapies in relapsing multiple sclerosis: a systematic review analysis

BackgroundMultiple sclerosis (MS) is a chronic and progressive neurological autoimmune disease that affects the central nervous system. There are two types of drugs used to treat this disease: injectable and oral drugs. The present study aimed at systematically reviewing the cost effectiveness of oral versus injectable drugs.MethodsThe researchers searched the PubMed, Scopus, and Web of Science databases to find relevant studies. After removing the duplicates, two authors independently assessed the records. The studies that had conducted full economic evaluations of oral versus injectable drugs in MS patients were included. The Quality of Health Economic Studies (QHES) tool was also used to assess the quality of the studies.ResultsThirty studies that had conducted the economic analysis of oral versus injectable therapies in MS patients were included in this review. The QHES scores for all records were generally high (≥ 77) and they were of good quality. The lowest and highest levels of incremental net monetary benefit were respectively obtained through the comparison of Fingolimod and Alemtuzumab (-1,419,333) and the comparison of Teriflunomide and Interferon β-1a (1,792,810). The amount of INMB (incremental net monetary benefit) in the comparisons between oral and injectable drugs showed that the highest and lowest amount of INMB calculated between) Fingolimod and injectable drugs, respectively, compared to (interferon β-1a) 98,253 and (Ocrelizumab) -212,417, the highest amount in dimethyl fumarate is also against (peginterferon β-1a) 191,470 and the lowest against (alemtuzumab) -124,333, Teriflunomide against injectable drugs is the highest against (peginterferon β-1a) 89,956 and the lowest (Ocrelizumab) − 194,169, as well as Cladribine compared to injectable drugs, the highest was compared to (interferon β-1a) 236,430 and the lowest (Ocrelizumab) was 23,965.ConclusionA large number of health economic evaluations of disease-modifying therapies (DMTs) in MS were available at the international level, the comparison of which was difficult and sometimes contradictory. However, despite the difference in the results, Cladribine tablets were cost-effective in all studies compared with injectable drugs. In addition, the present study could be of great importance for policymakers and other beneficiaries regarding the cost-effectiveness of the aforementioned drugs.

Evaluation of autoimmune neurology testing clinical utility and stewardship initiatives

Abstract Testing for neural autoantibodies associated with autoimmune neurological diseases has an important role in clinical care. However, as they are niche tests for relatively rare diseases, they often have longer turn-around-times and more expensive costs than many other laboratory tests. In addition, due to the low yield of positive results, they often appear as attractive stewardship targets. Our objective was to review current utilization and ordering patterns and evaluate the impact of ongoing stewardship efforts to inform next steps regarding stewardship of these tests. Methods: Data on utilization and ordering patterns of autoimmune and paraneoplastic neural autoantibody panels from January 1 to December 31, 2023, was obtained from reference laboratory and electronic medical record (EMR) data. Additional data on best practice advisories from the most recent six months was obtained from the EMR. Results: Overall, we observed that providers tested 2270 patients both from our defined test menu (five total tests, ~89% of total orders) and through the miscellaneous route (12 total tests, ~11% of total orders), which allows providers to place orders for tests not currently on our menu. Just under one third of the orders were in cerebrospinal fluid (CSF) (n=725), while the remaining were for serum (n=1545). The percent positivity was generally higher in serum specimens, ranging from 0 to 50% per test (n=227 total positive specimens). The percent positivity in CSF specimens ranged from 0 to 40% per test (n=29 total positive specimens), which is generally consistent with previously published literature. Most of the orders were placed by neurology providers (56%). The best practice advisories (BPAs) currently in use are soft stops that target repeat tests in the same specimen type within thirty days of a previous order. Of note, these BPAs can only catch orders placed through the defined process. In six months, the BPA for repeat serum orders fired 104 times for 42 unique patients; the BPA for repeat CSF orders fired 96 times for 38 unique patients. The serum BPA resulted in elimination of the repeat order for 43% of patients (n=18), while the CSF BPA resulted in elimination of the repeat order for 24% of patients (n=9). We observed some situations in which the BPA appeared to be firing when previous orders were incorrectly collected and so not able to be sent out. Conclusion: Based on these data, we plan three main steps to continue to refine autoimmune neurology testing: 1) update our test menu to offer the most clinically useful orders through the defined route, 2) pilot review of tests ordered through the miscellaneous route, and 3) optimize BPAs to target situations with inappropriate utilization rather than technical issues.

Successful generation of fully human, second generation, anti-CD19 CAR T cells for clinical use in patients with diverse autoimmune disorders

BackgroundB-cell targeting chimeric antigen receptor (CAR) T-cell therapies, which lead to profound B-cell depletion, have been well-established in hematology-oncology. This deep B-cell depletion mechanism has prompted the exploration of their use in B-cell driven autoimmune diseases. We herein report on the manufacturing of KYV-101, a fully human anti-CD19 CAR T-cell therapy, derived from patients who were treated across a spectrum of autoimmune diseases. MethodsKYV-101 was manufactured from peripheral blood-derived mononuclear cells of 20 patients across 7 autoimmune disease types (neurological autoimmune diseases, n=13; rheumatological diseases, n=7). Patients ranged from 18–75 years of age. Duration of disease ranged from <1–23 years since diagnosis. Patients were heavily pretreated, and most were refractory to prior immunosuppressive treatments. Apheresis was collected across 9 sites, cryopreserved, and shipped to the manufacturing facility. Healthy donor apheresis samples were collected for manufacturing comparison. Manufacturing was performed using the CliniMACS Prodigy system. Cells were enriched for CD4+/CD8+ T cells, transduced with a 3rd generation lentiviral vector encoding the CAR, expanded in vitro, and harvested. Percent cell viability, T-cell purity, cellular expansion, and transduction efficiency were assessed. Activity was assessed using cytokine release assays for KYV-101 CAR T cells co-cultured with different CD19+/– target cell lines. ResultsKYV-101 was successfully manufactured for 100% of patients. Transduced cell populations were highly viable, with expansion ranging from 11–66 fold at Day 8, and were comparable across disease types. Healthy donor-derived controls displayed similar expansion ranges. High CAR expression and transduction rates were observed, ranging between 37–84% with low variation in transgene copy number (2 to 4 per cell). Cell viability of the final KYV-101 drug product ranged from 87–97%. KYV-101 displayed robust CD19-dependent and effector dose-related release of the pro-inflammatory cytokine IFN-γ. ConclusionsKYV-101 manufacturing yielded a CAR T-cell product with high viability and consistent composition and functionality, regardless of disease indication, pre-treatment, and heterogeneity of the incoming material. Cryopreservation of the apheresis and final drug product enabled widespread distribution. These results support the robustness of the manufacturing process for the fully human KYV-101 anti-CD19 CAR T-cell therapy drug product for patients across diverse autoimmune disease types.

The cost-of-illness of multiple sclerosis in Jordan

ABSTRACT Background Multiple Sclerosis (MS) imposes a significant financial burden on health-care systems. This study aims to determine the cost-of-illness (COI) for MS in Jordan, a country where data on the economic impact of MS are scarce. Methods Data were collected for one year, annual COI was estimated using a cross-sectional snowball sampling design. Eligible patients completed a self-reported questionnaire to provide sociodemographic, physician visit, and diagnostic and laboratory test data. Indirect costs were estimated using an adjusted Human Capital Approach. Results This study included 383 patients, (73% females, 61% between 26-45). Eighty % took disease-modifying therapies (DMTs), and 40% had relapses in that year. One-third use non-DMTs and equipment for assistance. The average annual cost per patient was $11,719 (direct costs=$11,252, indirect costs=$467). The total annual cost for all participants was $748,299. The estimated cost of non-DMT, medical tools, diagnostic tests, and hospitalization per patient was $53, 51, 99, and 235 respectively. Conclusion High costs of DMTs state the necessity of resource optimization in Jordan public healthcare facilities. Such findings yield policy-informing actionable insights, suggesting strategic investments in more cost-effective DMTs with potential improvement in accessibility and reduction in the overall economic burden faced by both patients and governments.

A Suspected case of COVID-19 Vaccine (Covishield) Induced Guillain Barre Syndrome - A Case Report

The global effort to combat the COVID-19 pandemic has witnessed the rapid development and widespread distribution of various vaccines, including adenovirus-based vaccines such as COVISHIELD. While these vaccines have demonstrated safety and efficacy, rare adverse events have emerged, raising concerns about their use. We present a case report of a 45-year-old female patient who experienced Guillain-Barré Syndrome (GBS) shortly after receiving the COVISHIELD vaccine. The patient's clinical presentation was characterized by the abrupt onset of symptoms within days of vaccination, including weakness, fatigue, and throat discomfort. Her condition deteriorated rapidly, leading to respiratory failure and paralysis, necessitating intensive care unit (ICU) admission. A comprehensive examination revealed cranial nerve involvement, cardiovascular symptoms, and progressive motor weakness. Nerve conduction studies confirmed the diagnosis of GBS, while cerebrospinal fluid analysis demonstrated elevated protein levels. This case report delves into the clinical course, diagnostic challenges, and treatments administered during the patient's hospitalization. We discuss the potential link between COVISHIELD vaccination and GBS, an autoimmune neurological disorder. While the pathophysiology of vaccine-induced GBS remains a subject of debate, this case highlights the importance of early diagnosis and prompt initiation of treatment. In conclusion, this case underscores the significance of vigilance regarding potential adverse events associated with COVID-19 vaccination, such as GBS. Timely recognition and comprehensive management are pivotal in mitigating the impact of such complications. The reporting and monitoring of vaccine-related adverse events continue to be vital components of the ongoing global vaccination campaign.

Sleep Disturbances in Autoimmune Neurological Diseases: Mechanisms, Clinical Characteristics, Assessment, and Treatment Strategies.

Sleep disturbances are a hallmark feature of various autoimmune neurological diseases (AINDs). However, limited awareness of these sleep manifestations exists among clinicians. We provide a comprehensive overview of assessment methods, characteristic sleep disturbances, the impact of specific antibodies on sleep patterns, and treatment strategies for sleep disturbances in AINDs. Research advancements in sleep disturbances in autoimmune neurological disease focus primarily on four areas: mechanisms, clinical characteristics, assessment, and treatment. Regarding mechanisms, animal models for AINDs, particularly those involving specific antibodies like anti-NMDAR, anti-LGI1, and anti-IgLON5, have become more comprehensive. Recent advancements in animal models have led to the establishment of numerous models for AINDs; these models include a wide range of antibodies, including anti-NMDAR, anti-LGI1, and anti-IgLON5. Several studies using these models have revealed common mechanisms underlying sleep disturbances in these diseases. In terms of clinical characteristics, the identification of antibodies associated with recently discovered AINDs has expanded the spectrum of sleep disturbance symptoms observed compared to prior findings. A comprehensive evaluation system for the assessment of sleep disturbances has been established, including questionnaires, polysomnography, functional magnetic resonance imaging, and 18F-FDG PET/CT. Additionally, cardiopulmonary coupling shows promise as a novel assessment tool. Currently, no universally effective treatment exists for sleep disturbances in autoimmune neurological diseases, either through symptomatic treatment or immunosuppressive therapy. Further studies are needed to confirm the efficacy of new therapies and validate the benefits of existing treatments. Sleep disturbances are a hallmark feature of AINDs. Recent advancements have significantly expanded our understanding of their assessment and treatment. However, further studies are needed to address the remaining uncertainties in sleep disturbance management.

Assessment of long-term psychosocial outcomes in N-methyl-D-aspartate receptor encephalitis – the SAPIENCE study protocol

BackgroundN-methyl-D-aspartate-receptor (NMDAR) encephalitis is a rare neurological autoimmune disease with severe neuropsychiatric symptoms during the acute phase. Despite good functional neurological recovery, most patients continue to experience cognitive, psychiatric, psychological, and social impairments years after the acute phase. However, the precise nature and evolving patterns over time of these long-term consequences remain unclear, and their implications for the well-being and quality of life of predominantly young patients have yet to be thoroughly examined.MethodsSAPIENCE is a European multi-center (n = 3) prospective observational cohort study studying the long-term cognitive, psychiatric, psychological, and social outcome in patients with NMDAR encephalitis. The study consists of three interconnected levels. Level 1 comprises a qualitative interview and focus groups with patients and their caregivers. Level 2 consists of a condensed form of the interview, standardized questionnaires, and a detailed neuropsychological examination of patients. Level 3 involves an online survey that will be open to patients world-wide and explores patient-reported outcomes (PROMs), and patient-reported experiences (PREMs) in association with clinical and cognitive outcomes. Levels 1 to 3 will progressively contribute developing of structured interviews, survey questions, and treatment guidelines by informing one another.DiscussionSAPIENCE is an in-depth study of the long-term effects of NMDAR encephalitis and bridges the gap between standardized assessments and individual patient experiences, intending to improve patient care and to increase awareness of the psychosocial long-term consequences of the disease. Through collaboration of experts in clinical neurology and social and health psychology across Europe, SAPIENCE aims to create online assessment tools and formulate guidelines for patient-centered post-acute care that will help enhance the quality of life for patients and caregivers.

Temporal trends and regional variations in mortality related to Guillain-Barré syndrome in the United States: a retrospective study from 1999 to 2020

Aim Guillain-Barré syndrome (GBS) is an autoimmune neurological disorder, with an estimated 6.4% increase in cases worldwide from 1990 to 2019. We aim to identify the GBS-related mortality trends in the US stratified by age, sex, race, and region. Methods We used data from the CDC-WONDER database to calculate crude (CMR) and age-adjusted mortality rates (AAMRs) per 1,000,000 people. We examined the temporal trends through annual percent change (APC) and the average annual percent change (AAPC) in rates using Joinpoint regression. Results From 1999 to 2020, a total of 10,097 GBS-related deaths occurred in the US. The AAMR decreased till 2014 (APC: −1.91) but increased back to initial levels by 2020 (APC: 3.77). AAMR was higher in males (1.7) than females (1.1), decreasing till 2015 for females and 2014 for males, but increasing thereafter only for females. Non-Hispanic (NH) American Indians or Alaska Natives displayed the highest AAMR (1.8) while NH Asians or Pacific Islanders displayed the lowest (0.6). AAMRs also varied by region (West: 1.5; South: 1.5; Midwest: 1.4; Northeast: 1.1). Rural regions exhibited a higher AAMR (1.7) than urban regions (1.3). Most deaths occurred in medical facilities (60.99%). The adults aged ≥85 years exhibited an alarmingly high CMR (14.0). Conclusions While the mortality rates for GBS initially declined till 2014, they climbed back up afterwards. Highest mortality was exhibited by males and NH American Indians or Alaska Natives, residents of rural regions, and adults ≥85 years. Equitable efforts are needed to reduce the burden on high-risk populations.

Exploring the diverse therapeutic benefits of metformin: from anti-cancer to anti-inflammation and PCOS management

Background: Metformin is widely prescribed for type 2 diabetes mellitus and is recognized for its therapeutic benefits beyond glycemic control. This review summarizes current data on metformin's diverse roles in various therapeutic contexts, including treating polycystic ovarian syndrome (PCOS), anti-inflammatory effects, and cancer prevention. Method: This comprehensive examination highlights the multifaceted applications of metformin in modern medicine and its potential to enhance the treatment of inflammatory diseases, cancer, and reproductive disorders. Results and Discussion: Metformin's anti-inflammatory properties may benefit autoimmune disorders, neurological diseases, and cardiovascular illnesses. In women with PCOS, metformin aids in restoring menstrual regularity, inducing ovulation, and improving reproductive outcomes by enhancing insulin sensitivity, modulating ovarian function, and reducing hyperandrogenism. Additionally, emerging evidence suggests that metformin may reduce cancer incidence and mortality in diabetic individuals by modulating cellular metabolism, inducing apoptosis, and inhibiting tumor cell proliferation. Conclusion: Our review suggests promising evidence for metformin's role in cancer prevention, reducing inflammation, and managing PCOS. However, further research is required to identify patient subgroups that will benefit most from metformin therapy, elucidate its mechanisms of action, and optimize dosing regimens.

Early Diagnosis of CNS Virus Infections from Neurological Autoimmune Diseases: A Cross-Sectional Study from China in ER Setting.

It is challenging to differentiate between central nervous system (CNS) virus infections and neurological autoimmune diseases in the emergency department. Considering their different pathogenesis, we assume they differ in neuropsychiatric symptoms and laboratory results. A total of 80 patients were included in this study, 50 with CNS virus infections and 30 with CNS autoimmune diseases, confirmed by a polymerase chain reaction (PCR) of cerebrospinal fluid (CSF). A binary logistic regression model and receiver operating characteristic (ROC) curve were employed to examine the discrimination between the two types of diseases based on neuropsychiatric symptoms and laboratory results. Compared to patients with neurological autoimmune diseases, patients with CNS virus infections had a higher incidence of abnormal behavior (p = 0.026) and abnormal sensation/thought (p = 0.029); higher total (p = 0.005), direct (p = 0.004), and indirect bilirubin (p = 0.004); and increased CSF cell (p = 0.01) and CSF white cell counts (p = 0.01). Patients with disturbance of consciousness and abnormal sensation/thought were 7.79-fold and 5.07-fold more likely to be diagnosed with CNS virus infections (OR = 7.79, p = 0.008; OR = 5.07, p = 0.032). Each unit increase in blood indirect bilirubin concentration and CSF white cell counts increased the risk of developing CNS virus infections by 1.25-fold and 1.01-fold (OR = 1.25, p = 0.016; OR = 1.01, p = 0.011). ROC analysis showed that the area under the curve was 88.0% (p < 0.001). Our study found that patients with CNS viral infections tend to have higher blood indirect bilirubin concentration, CSF leukocyte count, frequency of disorders of consciousness, and abnormal sensation and thought, which may help differentiate them from those with neurological autoimmune diseases.

Pediatric Chronic Inflammatory Demyelinating Polyneuropathy: Challenges in Diagnosis andTherapeutic Strategies.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare autoimmune neurological disorder seen in both pediatric and adult populations. CIDP typically presents with progressive and persistent weakness over at least 4 weeks in addition to sensory symptoms in the extremities. Although CIDP shares common clinical features between children and adults, it sometimes presents as a distinct clinical entity in children that requires close attention and recognition. A major caveat when diagnosing a child with CIDP is the clinical and diagnostic overlap with inherited neuropathies, most commonly Charcot-Marie-Tooth disease (CMT). Demyelinating CMT (dCMT) and CIDP might share similar clinical presentations, and sometimes it might be difficult to differentiate them on the basis of the electrodiagnostic findings or cerebrospinal fluid (CSF) albumino-cytological dissociation. This indeed merits early consideration for genetic testing in patients who do not respond to conventional CIDP therapies. Current treatment options for CIDP include intravenous immunoglobulins (IVIG), corticosteroids (CS), and plasmapheresis (PLEX). The need for novel therapies is essential in instances where patients continue to have symptoms despite the standard therapies or due to adverse effects of long-term use of standard therapies such as CS. This paper reviews the challenges in the diagnosis of CIDP in children and the current as well as novel therapies for CIDP.

Therapeutic Approach to Autoimmune Neurologic Disorders.

Autoimmune neurologic disorders encompass a broad category of diseases characterized by immune system attack of the central, peripheral, or autonomic nervous systems. This article provides information on both acute and maintenance immunotherapy used to treat autoimmune neurologic disorders as well as a review of symptomatic management and special considerations when caring for patients with these diseases. Over the past 20 years, more than 50 antibodies have been identified and associated with autoimmune neurologic disorders. Although advances in diagnostic testing have allowed for more rapid diagnosis, the therapeutic approach to these disorders has largely continued to rely on expert opinion, case series, and case reports. With US Food and Drug Administration (FDA) approval of biologic agents to treat neuromyelitis optica spectrum disorder (NMOSD) and myasthenia gravis as well as ongoing clinical trials for the treatment of autoimmune encephalitis, the landscape of immunotherapy options continues to expand. Consideration of the unique pathogenesis of individual autoimmune neurologic disorders as well as the mechanism of action of the diverse range of treatment options can help guide treatment decisions today while evidence from clinical trials informs new therapeutics in the future. Recognizing patients who have a clinical history and examination findings concerning for autoimmune neurologic disorders and conducting a thorough and directed imaging and laboratory evaluation aimed at ruling out mimics, identifying specific autoimmune syndromes, and screening for factors that may have an impact on immunotherapy choices early in the clinical course are essential to providing optimal care for these patients. Providers must consider immunotherapy, symptomatic treatment, and a multidisciplinary approach that addresses each patient's unique needs when treating patients with autoimmune neurologic disorders.

Pediatric Autoimmune Neurologic Disorders.

This article discusses common principles in diagnosing and managing autoimmune neurologic conditions in children. The key to improving outcomes in all patients with autoimmune neurologic diseases is making an early diagnosis, promptly initiating treatment, and identifying patients who will benefit from long-term maintenance treatment. Some neuroinflammatory syndromes can be diagnosed with an antibody biomarker (eg, aquaporin-4 antibodies, N-methyl-d-aspartate [NMDA] receptor antibodies), whereas others require clinical diagnostic criteria (eg, multiple sclerosis, opsoclonus-myoclonus syndrome). A proportion of children will be labeled as seronegative, and further investigations for other inflammatory or monogenetic etiologies need to be carried out in parallel with treating the central nervous system inflammation. Time to treatment and treatment escalation were shown to correlate with outcomes in many patients with these disorders. The choice and duration of treatment should be evaluated considering side effects and risks in the short and long terms. The presence of a highly inflammatory disease process in children supports the use of highly effective disease-modifying therapies in pediatrics. The phenotypes of pediatric autoimmune neurologic conditions may change across different age groups, as the brain is still actively developing. In general, the presentation in children is more inflammatory, but overall disability is lower, likely because of better neuroplasticity and repair. Convincing evidence has increasingly emerged to support the biological rationale that effective immunosuppressive therapies used in adult neuroimmunology are equally effective in children.

Stiff-Person Syndrome: Results of the First Nationwide Survey in Japan

Stiff-person syndrome (SPS) is a rare autoimmune neurological disorder characterized by progressive axial muscle stiffness, central nervous system hyperexcitability, and painful stimulus-sensitive muscle spasms. A nationwide survey performed in 2018 showed the estimated prevalence of SPS was 0.2 per 100,000 population. Most patients with SPS had antibodies against glutamic acid decarboxylase 65, followed by antibodies to the glycine receptor α-subunit. Usually, patients with SPS showed favorable outcomes; however, some studies have reported intractable SPS. Early diagnosis and aggressive immunotherapy are necessary for management of patients with SPS.

Therapeutic plasma exchange in autoimmune neurological disorders: A comprehensive evaluation of clinical outcomes, safety, and long-term disability using the modified Rankin scale.

Autoimmune neurological diseases (ANDs) involve the immune system attacking the nervous system, leading to various symptoms. Therapeutic plasma exchange (TPE) is used to remove pathogenic autoantibodies, aiming to improve clinical outcomes. This ambispective observational study included 99 patients with ANDs who underwent TPE from January 2018 to June 2022 at a tertiary care center in India. Clinical outcomes were measured using the modified Rankin Scale (mRS) scores at admission, post-TPE, at 3-months, 6-months, and 1-year follow-up post-discharge. Data were analyzed using Epi Info version 7.0. The median mRS score improved significantly from 5 (IQR 4-5) before TPE to 3 (IQR 2-4) post-TPE (p < 0.001). Complications occurred in 5.95% of procedures, with allergic reactions being the most common. The in-hospital mortality rate was 9%. TPE is a safe and effective treatment modality for autoimmune neurological diseases, especially in resource-constrained settings. It aids in both symptomatic relief and reducing long-term functional disability.