Search Results (42)

Introduction/Aims: Myopathies with Tubular Aggregates (TAM) are rare, chronic neuromuscular disorders that may be inherited or acquired. The aim of this report is to present the diagnostic pathway and the challenges encountered in a family with three members affected by TAM caused by a rare ORAI1 variant. Case report: Two siblings (15 and 11 years old) developed severe rhabdomyolysis triggered by a viral respiratory infection. Histopathological analysis demonstrated numerous tubular aggregates with mild focal secondary inflammatory changes and no immunophenotypic evidence of autoimmune inflammatory myopathy. Whole-exome sequencing identified a likely pathogenic heterozygous missense variant, NM_032790.3(ORAI1):c.319G>A (p.Val107Met), in the ORAI1 gene, in both children and their asymptomatic mother. Conclusions: The identification of a rare ORAI1 variant in this family supports the association with TAM, broadens the spectrum of phenotypic presentation, and illustrates the phenotypic variability that may exist even among affected members of the same family. Careful interpretation of inflammatory changes in muscle biopsy, together with immunohistochemical and genetic findings, is essential to avoid misclassification of hereditary tubular aggregate myopathy as autoimmune inflammatory myopathy. Full article

Acquired myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction caused by antibodies against the acetylcholine receptor, leading to generalized muscle weakness and, in severe cases, respiratory muscle paralysis. While MG is well described in dogs, it is rarely reported in cats, and fulminant cases with rapid progression have a poor prognosis. An 11-year-old neutered female Persian cat presented with acute hindlimb weakness, which progressed to tetraplegia within 4 days. The clinical course initially resembled acute polyradiculoneuritis, and electromyography revealed positive sharp waves and fibrillation potentials. Diagnostic imaging identified a cystic cranial mediastinal mass without megaesophagus. Worsening respiratory muscle paralysis prompted surgical excision of the mass via left intercostal thoracotomy. Postoperatively, the cat developed persistent respiratory failure requiring re-intubation, mechanical ventilation, and temporary tracheostomy. Histopathological and immunohistochemical examination confirmed a thymoma, and serum acetylcholine receptor antibody levels were markedly elevated, establishing the diagnosis of thymoma-associated fulminant MG. Despite tumor excision and medical therapy with pyridostigmine and prednisolone, the cat remained ventilator-dependent and was euthanized on postoperative day 3. This case emphasizes early recognition of respiratory compromise, prompt diagnostic confirmation, intensive ventilatory support, and consideration of adjunctive immunomodulatory therapies. Full article

Alzheimer’s disease (AD) is a neurodegenerative disorder, whereas myasthenia gravis (MG) is an autoimmune neuromuscular disease. Despite their distinct clinical manifestations, both disorders involve immune dysregulation and cholinergic dysfunction, and epidemiological evidence for an association remains inconclusive. Here, we investigated the genetic architecture underlying the AD–MG relationship using large-scale European-ancestry genome-wide association study (GWAS) data, including early- and late-onset MG, within a multi-resolution analytical framework. Genome-wide analyses indicated modest polygenic overlap between AD and MG, supported by nominally significant and directionally consistent correlations across datasets, SNPeffect concordance in the primary GWAS, and robust gene-level overlap. Evidence for genome-wide correlation was weaker and non-significant across AD-MG subtypes. Local genetic correlation analyses revealed that shared AD-MG signals were largely locus-specific and heterogeneous, with regions showing both concordant and discordant effects, particularly across MG subtypes. Subtype-specific analyses indicated broader and more heterogeneous overlap for AD–late-onset MG, including both major histocompatibility complex (MHC) and non-MHC loci, whereas AD–early-onset MG showed more restricted patterns largely confined to the MHC. Cross-trait meta-analysis and colocalisation further refined these findings, identifying a limited number of loci with evidence of shared AD-MG association, while most regions were consistent with distinct causal variants. A chromosome 16 locus showed the most consistent shared cross-trait AD-MG signal across multiple analytical frameworks. Mendelian randomisation analyses provided no evidence of a causal effect of AD liability on MG and yielded only suggestive, and inconclusive evidence for the reverse direction. Gene-level and expression-informed analyses prioritised immune-related genes, as well as regulators of transcription, chromatin organisation, and synaptic processes, without implying concordant causal variants across traits. Tissue and pathway analyses suggested shared immune involvement, with differential emphasis on innate immune processes in AD and adaptive immune pathways in MG. Notably, heterogeneity of effects within the MHC and across loci suggests that overlap reflects a complex, context-dependent architecture rather than a uniform immune-driven signal. Overall, our findings indicate that the AD–MG relationship is characterised by modest genome-wide polygenic overlap, substantial locus-specific heterogeneity, and partial convergence on immune-related genetic architecture, rather than a uniformly shared mechanism. Full article

Myasthenia gravis (MG) is a rare autoimmune disorder characterized by muscle weakness and fatigue, caused by autoantibodies produced by B-cells that target proteins in the postsynaptic membrane of the neuromuscular junction. Clinical manifestations are heterogeneous and may include diplopia, ptosis, dysarthria, dysphagia, and limb muscle weakness, with severity ranging from mild symptoms to life-threatening myasthenic crisis. Despite advances in diagnostic approaches and the availability of immunomodulatory and biological therapies, there remains a need for an improved understanding of the disease mechanisms and biomarker development in MG. Blood-derived exosomes are small extracellular vesicles that carry proteins, lipids, nucleic acids, and glycoconjugates, and are involved in intercellular communication and the transfer of biological material between cells. Circulating exosomes may reflect aspects of cellular and immune status and have been proposed as a minimally invasive source of biomarkers in various diseases. In this review, we summarize current evidence on the potential role of exosomes in MG, with a focus on their involvement in disease-associated processes and their possible utility as biomarkers, as well as directions for future research. Full article

Myasthenia gravis (MG) is a prevalent autoimmune disorder affecting neuromuscular junctions, typically characterized by muscle weakness due to autoantibodies targeting acetylcholine receptors (AChR) or muscle-specific kinase (MuSK). Generalized MG is a more severe form of the condition than ocular MG. Although MG can strike at any age, young adult women are typically affected, especially in their reproductive years. MG is rare during pregnancy, with the first trimester and the postpartum period being the most common times for exacerbations. The influence of MG on pregnancy outcomes remains ambiguous, with some studies finding larger prevalence of issues such as preterm birth and small-for-gestational-age babies, while others indicate results similar to the general population. Management of MG during pregnancy necessitates careful monitoring and drug adjustments. Teratogenic concerns make several immunosuppressive drugs, such mycophenolate mofetil and methotrexate, contraindicated. In contrast, medications like prednisolone and pyridostigmine are generally recognized as safe. Women with MG may have flare-ups after giving birth, and infants may have transient neonatal myasthenia gravis. Comprehensive prenatal treatment and multidisciplinary assistance are crucial for promoting maternal and fetal health during pregnancy in women with MG. This paper examines the relevance of immunological biomarkers, RNAs, and other novel biomarkers in myasthenia gravis (MG). It emphasizes the need for more investigation to determine their role in the pathogenesis of MG, evaluate biomarker profiles across subgroups, and look at changes after treatment. The study also underlines the significance of high-throughput investigations to detect new biomarkers and reveal genetic variables impacting MG pathogenesis. Full article

Multiple sclerosis (MS) is a chronic immune-mediated demyelinating disorder of the central nervous system, traditionally considered distinct from neuromuscular diseases, which primarily affect the peripheral nervous system, neuromuscular junction, or skeletal muscle. Growing clinical and experimental evidence, however, indicates that certain neuromuscular disorders may coexist with MS or shared overlapping pathophysiological, immunological, and metabolic mechanisms. This narrative review summarizes reported associations between MS and neuromuscular diseases, with particular focus on well-characterized overlaps such as Leber hereditary optic neuropathy (LHON)-associated MS (Harding’s disease), combined central and peripheral demyelination (CCPD), and myasthenia gravis (MG) co-occurring with MS. Additional associations with Charcot–Marie–Tooth disease, mitochondrial disorders with MS-like phenotypes, inherited and autoimmune myopathies, and rare syndromes such as Guillain–Barré syndrome are also discussed. This review highlights proposed mechanisms potentially linking these conditions, including immune dysregulation, T- and B-cell-mediated autoimmunity, antibody-driven demyelination, mitochondrial dysfunction, impaired neuromuscular transmission, and molecular mimicry. Limitations of the current literature are acknowledged, particularly the predominance of case reports for rare associations and the frequent lack of systematic screening for coexisting disorders. By integrating evidence from case series, cohort studies, and mechanistic research, this review provides a comprehensive overview of the biological and clinical intersections between MS and neuromuscular diseases. Enhanced understanding of these overlaps may improve diagnostic accuracy, guide individualized management strategies, and inform future research on shared neuroimmunological and neurodegenerative pathways. Full article

Introduction: Myasthenia gravis (MG) is a chronic autoimmune disorder in which fatigue represents one of the most burdensome symptoms. This multidimensional manifestation extends beyond neuromuscular fatigability and has a substantial impact on daily functioning, mental health, and quality of life. The present study aimed to evaluate the perception of fatigue in patients with MG, with particular emphasis on its interference with everyday activities and the extent to which it is understood by others. Methods: The study included 67 MG patients (61.2% women, mean age 53 years) treated at the Neurology Outpatient Department of the University Clinical Center in Gdańsk. Data were collected using an author-developed survey and standardized instruments: Chalder Fatigue Scale (CFQ), MG-ADL, MG-QoL15, HADS-M, Mini-COPE, and ACDS. Results: More than 70% of patients reported constant or frequent fatigue. Higher fatigue severity was positively associated with functional impairment (MG-ADL) and lower quality of life (MG-QoL15). More than 70% of patients reported constant or frequent fatigue. Higher fatigue severity was moderately associated with greater functional impairment and poorer quality of life. The extent to which fatigue interfered with daily life was associated with higher levels of depressive symptoms, poorer self-rated health, and less favorable disease-related perceptions (acceptance and influence). In contrast, perceiving fatigue as being better understood by others was associated with lower anxiety and depression and more favorable disease-related perceptions (acceptance, control, understanding), while it was not significantly related to fatigue severity, functional status, or quality of life. Conclusions: Fatigue in myasthenia gravis is a prevalent symptom, closely related to functional impairment and reduced quality of life. Different aspects of fatigue perception show distinct psychosocial correlates, highlighting the importance of considering subjective and social dimensions of fatigue alongside its severity. These findings support the relevance of psychosocial factors in the comprehensive care of patients with MG. Full article

Myasthenia gravis, chronic inflammatory demyelinating polyneuropathy, and idiopathic inflammatory myopathies are among the most widely recognized autoimmune neuromuscular disorders. Although they differ in clinical presentation, shared immunopathogenic mechanisms place them at a molecular crossroads. Evidence of overlapping pathways has led to the development of targeted strategies including complement inhibition, FcRn antagonism, B-cell depletion, and the CAR-T cell approach. In this review, we analyze current knowledge regarding pathogenic mechanisms and their link to immunotherapy, extensively outlining both similarities and distinctions. We further discuss existing challenges, including diagnostic limitations and refractory disease variants, how technological advances have already addressed some of these issues, and where further progress is still needed. Full article

Background. PMP22-related neuropathies comprise a spectrum of predominantly demyelinating disorders, most commonly Charcot–Marie–Tooth type 1A (CMT1A; 17p12 duplication) and hereditary neuropathy with liability to pressure palsies (HNPP; 17p12 deletion), with rarer phenotypes due to PMP22 sequence variants (CMT1E, Dejerine–Sottas syndrome [DSS]). Methods. We conducted a PRISMA-compliant systematic review (PROSPERO ID: 1139921) of PubMed and Scopus (January 2015–August 2025). Eligible studies reported genetically confirmed PMP22-related neuropathies with clinical and/or neurophysiological data. Owing to heterogeneous reporting, we synthesized pooled counts and proportions without meta-analysis, explicitly tracking missing denominators. Results. One hundred twenty-seven studies (n = 4493 patients) were included. Sex was available for 995 patients (males 53.8% [535/995]; females 46.2% [460/995]); mean age at onset was 23.7 years in males and 16.4 years in females. Phenotypic classification was reported for 4431/4493 (75.4% CMT1A, 20.9% HNPP, 2.6% CMT1E, 1.2% DSS). Across phenotypes, weakness/foot drop was the leading presenting symptom when considering only cohorts that explicitly reported it (e.g., 65.3% in CMT1A; 76.0% in HNPP); sensory complaints (numbness, paresthesia/dysesthesia) were variably documented. Neurophysiology consistently showed demyelinating patterns, with median and ulnar nerves most frequently abnormal among assessed nerves; in HNPP, deep peroneal and sural involvement were also common in evaluated subsets. Comorbidities clustered by phenotype: orthopedic/neuromuscular features (pes cavus/hammer toes, scoliosis/kyphosis, tremor) in CMT1A and DSS; broader metabolic/autoimmune and neurodevelopmental associations in HNPP; and higher syndromic/ocular/hearing involvement in CMT1E. Genetically, 75.6% (3241/4291) had 17p12 duplication, 19.6% (835/4291) 17p12 deletion, and 4.8% (215/4291) PMP22 sequence variants with marked allelic heterogeneity. Among 2571 cases with available methods, MLPA was most used (41.9%), followed by NGS (20.4%) and Sanger sequencing (17.8%). Main limitations include heterogeneous and incomplete reporting across studies (especially symptoms and nerve-specific data) and the absence of a formal risk-of-bias appraisal, which preclude meta-analysis and may skew phenotype proportions toward more frequently reported entities (e.g., CMT1A). Conclusions. Recent literature confirms that PMP22 copy-number variants account for the vast majority of cases, while sequence-level variants underpin a minority with distinct phenotypes (notably CMT1E/DSS). Routine MLPA, complemented by targeted/NGS, optimizes diagnostic yield. Standardized reporting of nerve-conduction parameters and symptom denominators is urgently needed to enable robust cross-study comparisons in both pediatric and adult populations. Full article

Introduction: Juvenile myasthenia gravis (JMG) is a rare autoimmune disorder with a variable clinical course and limited pediatric-specific treatment guidelines. Objective clinical scales, such as the Quantitative Myasthenia Gravis (QMG) Score and the Pediatric Myasthenia Gravis Quality of Life 15 (PM-QOL15), may support individualized management, but their role in routine practice remains underexplored. Methods: We retrospectively reviewed 10 seropositive JMG patients followed at a single tertiary neuromuscular clinic between 2014 and 2024. All patients underwent a systematic assessment with QMG at each visit, while PM-QOL15 was administered at the final visit. Clinical data, comorbidities, antibody status, treatment modalities, and outcomes were analyzed. Associations between treatment strategies, comorbidities, and scale scores were explored using appropriate statistical methods. Results: Seven patients (70%) underwent thymectomy, resulting in a reduction in mean QMG scores from 7.7 to 2.4, though residual relapses were observed. Chronic intravenous immunoglobulin (IVIG) therapy, administered to 70% of patients, did not significantly reduce relapse rates or steroid exposure and was associated with higher QMG scores in the second year, suggesting use in more severe phenotypes rather than therapeutic efficacy. Prolonged corticosteroid therapy did not improve remission time or relapse frequency and was complicated by major adverse effects in two patients. Timing of azathioprine initiation showed no significant correlation with relapse frequency. PM-QOL15 correlated strongly with mean QMG (r = 0.88, p < 0.001), reflecting cumulative disease burden. Patients with comorbidities required longer stabilization, although differences were not statistically significant. Conclusions: The routine integration of QMG and PM-QOL15 into follow-up may facilitate the earlier recognition of subclinical deterioration, provide objective measures of treatment response, and guide personalized management in JMG. Thymectomy showed benefit in selected patients, while the long-term roles of IVIG and corticosteroids remain uncertain. Larger multicenter prospective studies are warranted to confirm these findings and refine evidence-based strategies for pediatric JMG. Full article

Background: Generalized myasthenia gravis (gMG) is a heterogeneous autoimmune disorder marked by antibody-mediated disruption of neuromuscular transmission. Despite advancements in immunosuppressive therapies and biologics, a subset of patients remains refractory, necessitating more targeted and personalized treatment strategies. Objective: This review aims to synthesize current knowledge of the immunopathological mechanisms across gMG subtypes and to explore emerging therapeutic targets tailored to these diverse disease phenotypes. Methods: A narrative review was conducted, integrating recent findings from clinical trials, immunogenetic studies, and preclinical research to describe subtype-specific immune mechanisms and corresponding therapeutic innovations. Results: gMG subtypes—characterized by autoantibody profiles (AChR, MuSK, LRP4, or seronegative), thymic histopathology, and age of onset—demonstrate distinct immunological pathways. Early-onset MG is associated with thymic hyperplasia and Th17-driven inflammation; thymoma-associated MG involves central tolerance breakdown; late-onset MG shows immune senescence and altered T-cell regulation. MuSK- and LRP4-positive MG exhibit unique cytokine and antibody signatures. Novel therapeutic strategies include B cell- and T cell-targeted therapies (e.g., anti-CD19, anti-CD38, JAK inhibitors), cytokine inhibitors (IL-6, IL-17, IL-23), FcRn antagonists, complement inhibitors, and gene- or cell-based therapies such as CAR-T and CAAR-T cells. Conclusion: The evolving landscape of gMG treatment reflects a shift toward immunopathology-based precision medicine. Better characterization of subtype-specific molecular signatures and immune dysfunctions is essential to guide clinical decision-making and improve outcomes for treatment-refractory patients. Full article

Acute transverse myelitis (ATM) is a rare, immune-mediated disorder of the spinal cord characterized by sensory, motor, and autonomic dysfunction. Although the human papillomavirus (HPV) vaccine is widely regarded as safe, isolated reports have suggested a potential temporal association with autoimmune neurological events, including ATM. We present a case of a 21-year-old woman who developed ATM two weeks following administration of the first dose of the HPV vaccine (Cervarix). The clinical presentation included rapid-onset paraparesis, sensory deficits, and sphincter dysfunction. An MRI revealed a T2-hyperintense lesion at the Th10–Th12 level. A cerebrospinal fluid analysis showed elevated protein levels. The patient underwent corticosteroid therapy, plasmapheresis, and IVIG, followed by a comprehensive, individualized rehabilitation program. This included balance and stability training, Redcord-based neuromuscular activation, electrostimulation, and pelvic floor therapy. Although no causal link between HPV vaccination and ATM has been established, this case emphasizes the importance of considering post-vaccinal autoimmune phenomena. More importantly, it illustrates the critical role of early, targeted rehabilitation—particularly pelvic floor re-education and neuromodulation—in improving outcomes in patients with significant motor and autonomic deficits. Full article

This review aims to explore the role of immunotherapeutic strategies—primarily intravenous immunoglobulin (IVIG), plasma exchange (PLEX), and selected immunomodulatory agents—in the treatment of neurological and psychiatric disorders with suspected or confirmed autoimmune mechanisms. A central focus is placed on understanding the immunopathology of these conditions through the identification and characterization of disease-associated autoantibodies. Disorders such as autoimmune encephalitis, myasthenia gravis, limbic epilepsy, neuropsychiatric systemic lupus erythematosus (NPSLE), and certain forms of schizophrenia have shown clinical responses to immunotherapy, suggesting an underlying autoimmune basis in a subset of patients. The review also highlights the diagnostic relevance of detecting autoantibodies targeting neuronal receptors, such as NMDA and AMPA receptors, or neuromuscular junction components, as biomarkers that guide therapeutic decisions. Furthermore, we synthesize findings from published randomized controlled trials (RCTs) that have validated the efficacy of IVIG and PLEX in specific diseases, such as Guillain–Barré syndrome, and myasthenia gravis. Emerging clinical evidence supports expanding these treatments to other conditions where autoimmunity is implicated. By integrating immunological insights with clinical trial data, this review offers a comprehensive perspective on how immunotherapies may be tailored to target autoimmune contributors to neuropsychiatric disease. Full article

Stem cells are unique, undifferentiated cells that have the ability to both replicate themselves and develop into specialized cell types. This dual capability makes them valuable in the development of regenerative medicine. Current development in stem cell research has widened their application in cell therapy, drug discovery, reproductive cloning in animals, and cell models for various diseases. Although there are substantial studies revealing the treatment of human degenerative diseases using stem cells, this is yet to be explored in livestock animals. Many diseases in livestock species such as mastitis, laminitis, neuromuscular disorders, autoimmune diseases, and some debilitating diseases are not covered completely by the existing drugs and treatment can be improved by using different types of stem cells like embryonic stem cells, adult stem cells, and induced pluripotent stem cells. This review mainly focuses on the use of stem cells for disease treatment in livestock animals. In addition to the diseases mentioned, the potential of stem cells can be helpful in wound healing, skin disease therapy, and treatment of some genetic disorders. This article explores the potential of stem cells from various sources in the therapy of livestock diseases and also their role in the conservation of endangered species as well as disease model preparation. Moreover, the future perspectives and challenges associated with the application of stem cells in livestock are discussed. Overall, the transformative impact of stem cell research on the livestock sector is comprehensively studied which will help researchers to design future research work on stem cells related to livestock diseases. Full article

Myasthenia gravis (MG) is an antibody-mediated autoimmune disorder characterized by altered neuromuscular transmission, which causes weakness and fatigability in the skeletal muscles. The etiology of MG is complex, being associated with multiple genetic and environmental factors. Over recent years, progress has been made in understanding the immunological alterations implicated in the disease, but the exact pathogenesis still needs to be elucidated. A pathogenic interplay between innate immunity and autoimmunity contributes to the intra-thymic MG development. Epigenetic changes are critically involved in both innate and adaptive immune response regulation. They can act as (i) pathological factors besides genetic predisposition and (ii) co-factors contributing to disease phenotypes or patient-specific disease course/outcomes. This article reviews the role of non-coding RNAs (ncRNAs) as epigenetic factors implicated in MG. Particular attention is dedicated to microRNAs (miRNAs), whose expression is altered in MG patients’ thymuses and circulating blood. The long ncRNA (lncRNA) contribution to MG, although not fully characterized yet, is also discussed. By summarizing the most recent and fast-growing findings on ncRNAs in MG, we highlight the therapeutic potential of these molecules for achieving immune regulation and their value as biomarkers for the development of personalized medicine approaches to improve disease care. Full article