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Neurology(R) Neuroimmunology &... May 2024Relapses occur in 15%-25% of patients with leucine-rich glioma-inactivated 1 antibody (LGI1-Ab) autoimmune encephalitis and may cause additional disability. In this...
BACKGROUND AND OBJECTIVES
Relapses occur in 15%-25% of patients with leucine-rich glioma-inactivated 1 antibody (LGI1-Ab) autoimmune encephalitis and may cause additional disability. In this study, we clinically characterized the relapses and identified factors predicting their occurrence.
METHODS
This is a retrospective chart review of patients with LGI1-Ab encephalitis diagnosed at our center between 2005 and 2022. Relapse was defined as worsening of previous or appearance of new symptoms after at least 3 months of clinical stabilization.
RESULTS
Among 210 patients, 30 (14%) experienced a total of 33 relapses. The median time to first relapse was 23.9 months (range: 4.9-110.1, interquartile range [IQR]: 17.8). The CSF was inflammatory in 11/25 (44%) relapses, while LGI1-Abs were found in the serum in 16/24 (67%) and in the CSF in 12/26 (46%); brain MRI was abnormal in 16/26 (62%) relapses. Compared with the initial episode, relapses manifested less frequently with 3 or more symptoms (4/30 patients, 13% vs 28/30, 93%; < 0.001) and had lower maximal modified Rankin scale (mRS) score (median 3, range: 2-5, IQR: 1 vs 3, range: 2-5, IQR: 0; = 0.001). The median mRS at last follow-up after relapse (2, range: 0-4, IQR: 2) was significantly higher than after the initial episode (1, range: 0-4, IQR: 1; = 0.005). Relapsing patients did not differ in their initial clinical and diagnostic features from 85 patients without relapse. Nevertheless, residual cognitive dysfunction after the initial episode (hazard ratio:13.8, 95% confidence interval [1.5; 129.5]; = 0.022) and no administration of corticosteroids at the initial episode (hazard ratio: 4.8, 95% confidence interval [1.1; 21.1]; = 0.036) were significantly associated with an increased risk of relapse.
DISCUSSION
Relapses may occur years after the initial encephalitis episode and are usually milder but cause additional disability. Corticosteroid treatment reduces the risk of future relapses, while patients with residual cognitive dysfunction after the initial episode have an increased relapse risk.
Topics: Humans; Autoantibodies; Encephalitis; Magnetic Resonance Imaging; Recurrence; Retrospective Studies
PubMed: 38603771
DOI: 10.1212/NXI.0000000000200228 -
Digital Journal of Ophthalmology : DJO 2024We report 2 cases of pediatric ocular myasthenia gravis. The first case was a 7-year-old girl who presented with bilateral ophthalmoplegia and ptosis that correlated...
We report 2 cases of pediatric ocular myasthenia gravis. The first case was a 7-year-old girl who presented with bilateral ophthalmoplegia and ptosis that correlated with the onset of upper respiratory symptoms. Neuroimaging and acetylcholine receptor antibody testing were unremarkable. The ice pack test was positive. Symptoms greatly improved with pyridostigmine, with full resolution of ophthalmoplegia achieved by 8-month follow-up. The second case was a 4-year-old girl who presented emergently with ptosis and bilateral ophthalmoplegia. Acetylcholine receptor antibodies testing was positive. The patient was started on pyridostigmine and intravenous immunoglobulin and is scheduled to follow-up with pediatric ophthalmology in the outpatient setting.
Topics: Female; Child; Humans; Child, Preschool; Pyridostigmine Bromide; Myasthenia Gravis; Blepharoptosis; Ophthalmoplegia; Receptors, Cholinergic; Autoantibodies
PubMed: 38601901
DOI: 10.5693/djo.02.2023.09.002 -
Frontiers in Neurology 2024Voltage gated calcium channels (VGCCs) play a critical role in neural transmission. Antibodies that target these ion channels can disrupt cellular signal transmission...
Voltage gated calcium channels (VGCCs) play a critical role in neural transmission. Antibodies that target these ion channels can disrupt cellular signal transmission resulting in various clinical presentations. VGCC antibodies are most commonly associated with paraneoplastic syndromes such as Lambert-Eatons myasthenic syndrome. Here, we report a 47-year-old female with Stage IV appendiceal adenocarcinoma status post appendectomy and right hemicolectomy, who presented with progressive memory impairment, aphasia, ataxia, weakness, and headache. Neurologic exam was notable for right-sided parietal drift, decreased right arm swing, and ataxia of the bilateral upper extremities, more prominent on the right side. MRI of the brain with and without contrast was unremarkable. Cerebrospinal fluid (CSF) was notable for an elevated myelin basic protein (4.9 ng/mL, normal reference 0.0-3.7 ng/mL) with normal cell count, flow cytometry, and cytology. An extensive serum autoimmune neurology antibody evaluation revealed elevated VGCC autoantibodies (observed value: 96.1 pmol/L, normal range 0.0-30.0 pmol/L). A diagnosis of paraneoplastic voltage gated calcium channel antibodies secondary to appendiceal adenocarcinoma was made. The patient was treated with five exchanges with plasmapheresis over 10 days with significant clinical improvement in her symptoms. Upon literature review, this would be the first reported case of VGCC antibodies associated with appendiceal adenocarcinoma.
PubMed: 38601338
DOI: 10.3389/fneur.2024.1355437 -
Anais Brasileiros de Dermatologia 2024
Topics: Humans; Female; Lymphoma, Large-Cell, Anaplastic; Breast Implants; Ichthyosis; Paraneoplastic Syndromes; Breast Neoplasms; Middle Aged
PubMed: 38584024
DOI: 10.1016/j.abd.2022.12.009 -
Revue Neurologique May 2024The European literature has reported high variability in the incidence and prevalence rates of myasthenia gravis (MG), but no specific epidemiological data for France...
BACKGROUND
The European literature has reported high variability in the incidence and prevalence rates of myasthenia gravis (MG), but no specific epidemiological data for France have been published. This study aimed to assess the incidence and prevalence rates of myasthenia gravis in France based on data extracted from the French National Health Insurance Claims Database (the SNIIRAM database).
METHODS
We conducted a retrospective repeated cross-sectional population study from 2008 to 2018 using a representative sample of the French population (Échantillon généraliste des bénéficiaires) covered by health insurance. We calculated the incidence, prevalence, and sex ratio of MG and screened for comorbidities associated with MG (standardized to the general population).
RESULTS
In total, 331 MG patients were identified between 2008 and 2018. The average incidence of MG in France was 50 per million person-years, while the mean prevalence was 465 per million people. The female-to-male ratio was 1.33. The Incidence of MG gradually increased from 40years of age for women and 60 for men. Thymoma was present for 5.1% of MG patients and a thymectomy was performed for 4.7%. Thyroid disease was the most prevalent autoimmune comorbidity, affecting approximately 8.5% of cases. MG patients had an increased cancer risk, with a standardized rate ratio of 2.38 (95% CI: 1.64-3.46).
CONCLUSION
The incidence and prevalence rates of MG are significantly higher than those previously reported in the literature and the incidence increases with age. The excess risk of cancer raises concerns for MG patients, in particular, concerning the management of immunosuppressive drugs.
Topics: Humans; Myasthenia Gravis; France; Male; Female; Middle Aged; Incidence; Prevalence; Adult; Comorbidity; Aged; Retrospective Studies; Young Adult; Cross-Sectional Studies; Adolescent; Child; National Health Programs; Aged, 80 and over; Infant; Child, Preschool; Databases, Factual; Infant, Newborn
PubMed: 38582663
DOI: 10.1016/j.neurol.2024.02.392 -
Neurology(R) Neuroimmunology &... May 2024Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is a rare autoimmune neurologic disorder, the genetic etiology of which remains poorly understood. Our study aims...
BACKGROUND AND OBJECTIVES
Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is a rare autoimmune neurologic disorder, the genetic etiology of which remains poorly understood. Our study aims to investigate the genetic basis of this disease in the Chinese Han population.
METHODS
We performed a genome-wide association study and fine-mapping study within the major histocompatibility complex (MHC) region of 413 Chinese patients with anti-NMDAR encephalitis recruited from 6 large tertiary hospitals and 7,127 healthy controls.
RESULTS
Our genome-wide association analysis identified a strong association at the IFIH1 locus on chromosome 2q24.2 (rs3747517, = 1.06 × 10, OR = 1.55, 95% CI, 1.34-1.80), outside of the human leukocyte antigen (HLA) region. Furthermore, through a fine-mapping study of the MHC region, we discovered associations for 3 specific HLA class I and II alleles. Notably, HLA-DQB1*05:02 ( = 1.43 × 10; OR, 2.10; 95% CI 1.70-2.59) demonstrates the strongest association among classical HLA alleles, closely followed by HLA-A*11:01 ( = 4.36 × 10; OR, 1.52; 95% CI 1.29-1.79) and HLA-A*02:07 ( = 1.28 × 10; OR, 1.87; 95% CI 1.50-2.31). In addition, we uncovered 2 main HLA amino acid variation associated with anti-NMDAR encephalitis including HLA-DQβ1-126H ( = 1.43 × 10; OR, 2.10; 95% CI 1.70-2.59), exhibiting a predisposing effect, and HLA-B-97R ( = 3.40 × 10; OR, 0.63; 95% CI 0.53-0.74), conferring a protective effect. Computational docking analysis suggested a close relationship between the NR1 subunit of NMDAR and DQB1*05:02.
DISCUSSION
Our findings indicate that genetic variation in IFIH1, involved in the type I interferon signaling pathway and innate immunity, along with variations in the HLA class I and class II genes, has substantial implications for the susceptibility to anti-NMDAR encephalitis in the Chinese Han population.
Topics: Humans; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Genome-Wide Association Study; Histocompatibility Antigens Class I; Histocompatibility Antigens Class II; HLA-A Antigens; HLA-DQ beta-Chains; Interferon-Induced Helicase, IFIH1
PubMed: 38579189
DOI: 10.1212/NXI.0000000000200221 -
Journal of Neuromuscular Diseases 2024Myasthenia Gravis (MG) is an autoimmune disorder characterized by pathogenic autoantibodies (AAbs) targeting nicotinic acetylcholine receptors (AChR), disrupting...
Detection of Autoantibodies Against the Acetylcholine Receptor, Evaluation of Commercially Available Methodologies: Fixed Cell-Based Assay, Radioimmunoprecipitation Assay and Enzyme-Linked Immunosorbent Assay1.
BACKGROUND/OBJECTIVE
Myasthenia Gravis (MG) is an autoimmune disorder characterized by pathogenic autoantibodies (AAbs) targeting nicotinic acetylcholine receptors (AChR), disrupting neuromuscular communication. RadioImmunoPrecipitation Assay (RIPA) is recommended to detect AChR AAbs, but its complexity and radioactive requirements limit widespread use. We compare non-RIPA anti-AChR immunoassays, including Cell-Based Assay (CBA) and two ELISA kits, against the gold standard RIPA.
METHODS/RESULTS
145 samples were included with medical indication for anti-AChR testing. By the RIPA method, 63 were negative (RIPA-Neg < 0.02 nmol/L), 18 were classified as Borderline (≥0.02 -1 nmol/L), and 64 were positive (RIPA-Pos > 1 nmol/L). The competitive ELISA showed poor agreement with RIPA (Kappa = 0.216). The indirect ELISA demonstrated substantial agreement with RIPA (Kappa = 0.652), with ∼76% sensitivity and ∼94% specificity for MG diagnostic. The CBA, where fixed cells expressing clustered AChR were used as substrate, exhibited almost perfect agreement with RIPA (Kappa = 0.984), yielding ∼98% sensitivity and 96% specificity for MG. In addition, a semiquantitative analysis showed a strong correlation between CBA titration, indirect ELISA, and RIPA levels (r = 0.793 and r = 0.789, respectively).
CONCLUSIONS
The CBA displayed excellent analytical performance for MG diagnostic when compared to RIPA, making it a potential replacement for RIPA in clinical laboratories. Some solid-phase assays (such as the indirect ELISA applied here), as well as CBA titration, offer reliable options to estimate anti-AChR AAb levels after confirming positivity by the CBA.∥.
Topics: Humans; Enzyme-Linked Immunosorbent Assay; Autoantibodies; Radioimmunoprecipitation Assay; Myasthenia Gravis; Sensitivity and Specificity; Receptors, Cholinergic; Female; Male; Middle Aged; Adult; Aged; Young Adult
PubMed: 38578899
DOI: 10.3233/JND-230210 -
Orphanet Journal of Rare Diseases Apr 2024Myasthenia gravis (MG), a rare chronic neuromuscular disorder, is characterized by progressive physical decline and requires long-term pharmacological treatment. Due to...
BACKGROUND
Myasthenia gravis (MG), a rare chronic neuromuscular disorder, is characterized by progressive physical decline and requires long-term pharmacological treatment. Due to the decline of physical and social abilities, MG patients are in great need of social support, including tangible and emotional support. This study aims to examine the association between social support and medication adherence and the possible mediating effects of mental health and self-efficacy among MG patients.
METHODS
A cross-sectional analysis of a nationwide MG registry was conducted on 865 patients under oral medication treatment in China between June and July 2022. Validated scales were used to measure the respondent's mental distress (Four-item Patient Health Questionnaire), social support (Modified Medical Outcomes Study Social Support Scale), self-efficacy for medication use (Self-efficacy for Appropriate Medication Use Scale), and medication adherence (Morisky Medication Adherence Scale, MMAS).
RESULTS
The association between social support and medication adherence and possible mediating effects of mental distress and self-efficacy were tested by structural equation model, with significant demographic and disease-related factors adjusted. The respondents showed a very low level of medication adherence (71.2% poor adherence; 1.4% high adherence; mean MMAS = 4.65). The level of social support was positively associated with medication adherence, and such association was fully mediated by two indirect pathways: through self-efficacy (β = 0.07, proportion mediated = 63.8%); and through mental distress and then self-efficacy (β = 0.01, proportion mediated = 6.7%).
CONCLUSION
Provision of social support and interventions on mental health with emphasis on improving self-efficacy for medication use may effectively improve medication adherence among MG patients.
Topics: Adult; Humans; Mental Health; Self Efficacy; Cross-Sectional Studies; Medication Adherence; Social Support; Myasthenia Gravis; China; Surveys and Questionnaires
PubMed: 38576038
DOI: 10.1186/s13023-024-03145-6 -
Annals of Clinical and Translational... May 2024Eculizumab and ravulizumab are complement protein C5 inhibitors, showing efficacy and tolerability for patients with anti-acetylcholine receptor-positive (AChR+)...
OBJECTIVE
Eculizumab and ravulizumab are complement protein C5 inhibitors, showing efficacy and tolerability for patients with anti-acetylcholine receptor-positive (AChR+) generalized myasthenia gravis (gMG) in phase 3 clinical trials and subsequent analyses. The purpose of the present study was to evaluate the clinical significance of eculizumab and switching to ravulizumab for refractory AChR+ gMG patients in the real-world experience.
METHODS
Among the database of Japan MG registry survey 2021, we studied AChR+ gMG patients who received eculizumab. We also evaluated these patients who switched from eculizumab to ravulizumab. Responder was defined as an improvement of at least 3 points in MG-ADL. We performed a questionnaire of preference between eculizumab and ravulizumab.
RESULTS
Among 1,106 patients with AChR+ gMG, 36 patients (3%) received eculizumab (female 78%, mean age 56.0 years). Eculizumab was preferentially used in severe and refractory MG patients. The duration of eculizumab treatment was 35 months on average. MG-ADL improved from 9.4 ± 4.9 to 5.9 ± 5.1, and 25 (70%) of the 36 gMG patients were responders. Postintervention status was markedly improved after the eculizumab treatment. Of 13 patients who did not continue eculizumab, 6 showed insufficiencies. Early onset MG was most effective. However, 15 patients switching from eculizumab to ravulizumab kept favorable response and tolerability. Questionnaire surveys showed preference for ravulizumab over eculizumab.
INTERPRETATION
Eculizumab and switching to ravulizumab showed to be effective for refractory AChR+ gMG patients in clinical settings.
Topics: Humans; Myasthenia Gravis; Antibodies, Monoclonal, Humanized; Female; Male; Middle Aged; Aged; Adult; Complement Inactivating Agents; Drug Substitution; Registries; Japan
PubMed: 38572524
DOI: 10.1002/acn3.52051 -
Cell Communication and Signaling : CCS Apr 2024More than 80% of patients with myasthenia gravis (MG) are positive for anti-acetylcholine receptor (AChR) antibodies. Regulatory T cells (Tregs) suppress overproduction...
More than 80% of patients with myasthenia gravis (MG) are positive for anti-acetylcholine receptor (AChR) antibodies. Regulatory T cells (Tregs) suppress overproduction of these antibodies, and patients with AChR antibody-positive MG (AChR MG) exhibit impaired Treg function and reduced Treg numbers. The gut microbiota and their metabolites play a crucial role in maintaining Treg differentiation and function. However, whether impaired Tregs correlate with gut microbiota activity in patients with AChR MG remains unknown. Here, we demonstrate that butyric acid-producing gut bacteria and serum butyric acid level are reduced in patients with AChR MG. Butyrate supplementation effectively enhanced Treg differentiation and their suppressive function of AChR MG. Mechanistically, butyrate activates autophagy of Treg cells by inhibiting the mammalian target of rapamycin. Activation of autophagy increased oxidative phosphorylation and surface expression of cytotoxic T-lymphocyte-associated protein 4 on Treg cells, thereby promoting Treg differentiation and their suppressive function in AChR MG. This observed effect of butyrate was blocked using chloroquine, an autophagy inhibitor, suggesting the vital role of butyrate-activated autophagy in Tregs of patients with AChR MG. We propose that gut bacteria derived butyrate has potential therapeutic efficacy against AChR MG by restoring impaired Tregs.
Topics: Humans; Receptors, Cholinergic; T-Lymphocytes, Regulatory; Butyric Acid; Gastrointestinal Microbiome; Myasthenia Gravis; Autoantibodies
PubMed: 38570836
DOI: 10.1186/s12964-024-01588-9