Myasthenia Gravis Foundation Of America Research Articles

Systemic Inflammatory Response Index, a Potential Inflammatory Biomarker in Disease Severity of Myasthenia Gravis: A Pilot Retrospective Study.

Myasthenia gravis (MG) is a chronic autoimmune disease caused by neuromuscular junction (NMJ) dysfunction. Our current understanding of MG's inflammatory component remains poor. The systemic inflammatory response index (SIRI) presents a promising yet unexplored biomarker for assessing MG severity. This study aimed to investigate the potential relationship between SIRI and MG disease severity. We conducted a retrospective analysis of clinical data from 171 MG patients admitted between January 2016 and June 2021. Patients with incomplete data, other autoimmune diseases, or comorbidities were excluded. Disease severity was evaluated using the Myasthenia Gravis Foundation of America (MGFA) classification and Myasthenia Gravis Activities of Daily Living (MG-ADL) on admission. The association between SIRI and disease severity was assessed through logistic regression analysis, along with receiver operating characteristic (ROC) curve and decision curve analysis (DCA) comparisons with established inflammation indicators. After exclusion, 143 patients were analyzed in our study. SIRI levels significantly differed between patients with higher and lower disease severity (p < 0.001). Univariate logistic regression showed that SIRI had a significant effect on high disease severity (OR = 1.376, 95% CI 1.138-1.664, p = 0.001). This association remained significant even after adjusting for age, sex, disease duration, history of MG medication and thymoma (OR = 1.308, 95% CI 1.072-1.597, p = 0.008). Additionally, a positive correlation between SIRI and MG-ADL was observed (r = 0.232, p = 0.008). Significant interactions were observed between SIRI and immunosuppressor (p interaction = 0.001) and intravenous immunoglobulin (p interaction = 0.005). DCA demonstrated the superior net clinical benefit of SIRI compared to other markers when the threshold probability was around 0.2. Our findings indicate a strong independent association between SIRI and disease severity in MG, suggesting SIRI's potential as a valuable biomarker for MG with superior clinical benefit to currently utilized markers.

Intravenous methylprednisolone therapy for ocular myasthenia gravis: A retrospective study

AbstractBackgroundAlthough intravenous methylprednisolone pulse (IVMP) therapy has been recommended for ocular myasthenia gravis (OMG), the evidence is limited.AimWe aimed to investigate the efficacy and safety of IVMP for OMG.MethodsThe patients with OMG were chosen retrospectively from May 2010 to December 2022. The therapeutic effects between IVMP‐treated and non‐IVMP‐treated groups were determined by ∆ocular quantitative MG (QMG) score and the ∆ocular MG activities of daily living profile (MG‐ADL) score, which is the disparities of the scores between before and after 1 month of drug administration; and Myasthenia Gravis Foundation of America post‐intervention status at 1, 3, 6, and 12 months.ResultsThere were 26 patients with OMG included, with the mean age of 67.2 ± 13.1 years. 13 of the 26 people with OMG received IVMP and subsequent low‐dose immunotherapies. The ∆ocular QMG and ∆ocular MG‐ADL scores were significantly higher in the IVMP group of 3 (1.5, 4) and 3 (2, 4.5) than in the non‐IVMP group of 1.5 (0, 3) and 1 (0, 2), p = 0.038 and p = 0.0027, respectively. The rates of minimal manifestation or better status in post‐intervention status at 1 and 12 months were also considerably higher in the IVMP group of 77% and 92% compared with the non‐IVMP group of 0% and 23%, p = 0.0001 and 0.001. There were no serious side effects discovered.ConclusionIVMP induction therapy can quickly and safely improve symptoms of OMG, and subsequent low‐dose immunotherapy can keep symptoms at bay for 12 months.

Juvenile Myasthenia Gravis in North Texas: Clinical Features, Treatment Response, and Outcomes

BackgroundJuvenile myasthenia gravis (JMG) is a rare autoimmune disease that causes fatigable muscle weakness in children aged <18 years. There is currently no curative treatment or internationally accepted standard of care for JMG. The objective is to investigate relationships between clinical presentation, antibody status, severity of disease onset, electrodiagnostic evaluation, and response to therapy in JMG. MethodsThis study was a retrospective chart review. Congenital myasthenic syndromes were excluded. Data on demographics, treatments, and outcomes were collected. Disease severity was evaluated using Myasthenia Gravis Foundation of America (MGFA) clinical classifications. ResultsWe identified 84 patients with JMG at Children's Medical Center Dallas between January 2014 and February 2022. It was found that 52% of patients presented with ocular JMG (median onset age 4.5 years) and 48% with generalized JMG (median onset age 11.5 years); 81% tested positive for acetylcholine receptor antibodies. Patients were 17% non-Hispanic white, 29% Hispanic, 39% black, and 12% Asian. There was a significant difference in average MGFA scores between ethnicities (P = 0.047) and age groups (P = 0.004), with postpubertal patients having higher average MGFA scores than prepubertal patients. Seventy-one percent of patients who underwent thymectomy experienced a decrease in MGFA scores postprocedure. ConclusionsOur study showed that there were significant differences in disease severity between ethnicities and age groups and that most patients who underwent thymectomy showed clinical improvement. These outcomes highlight the need for additional therapies in the treatment of JMG and the importance of extending clinical trials to the pediatric population.

Comparative effectiveness of azathioprine and mycophenolate mofetil for myasthenia gravis (PROMISE-MG): a prospective cohort study

Myasthenia gravis is an autoimmune disorder of the neuromuscular junction. Treatment typically includes symptomatic oral cholinesterase inhibitors, immunosuppression, and immunomodulation. In addition to corticosteroids, azathioprine and mycophenolate mofetil are the most frequently used immunosuppressants in North America. We aimed to evaluate the comparative effectiveness of these two drugs, and to assess the effect of the dose and duration of treatment. We did a prospective cohort study at 19 academic centres in Canada and the USA. We included patients (aged ≥18 years) with autoimmune myasthenia gravis, who were never treated with immunosuppressants. Treating clinicians determined the choice of medication, dose, follow-up intervals, and drug monitoring. Outcome measures and adverse events were recorded at each visit. We assessed two co-primary outcomes. The first was the patient-reported Myasthenia Gravis-Quality of Life 15-revised (MGQOL-15r) score, measured as the mean change from treatment initiation to the follow-up visit with the lowest score. A clinically meaningful reduction (CMR) in MGQOL-15r was defined as a 5-point decrease. The second was a composite clinical outcome of disease improvement (Myasthenia Gravis Foundation of America Post-Intervention Status Minimal Manifestations or better) and low adverse event burden (defined as grade ≤1 Common Terminology Criteria for Adverse Events). We also compared these outcomes in patients receiving an adequate dose and duration of azathioprine (≥2 mg/kg per day for at least 12 months) or mycophenolate mofetil (≥2 g per day for at least 8 months) and a lower dose or shorter duration of these agents. We used propensity score weighting with generalised linear regression models. This study is registered with ClinicalTrials.gov (NCT03490539). Between May 1, 2018, and Aug 31, 2020, 167 patients were enrolled; 85 did not receive azathioprine or mycophenolate mofetil and were excluded. Four were excluded from outcome analyses because they had scores of 0 on an outcome measure at treatment initiation. Of the 78 patients included in analyses, 47 received mycophenolate mofetil (median follow-up 25 months [IQR 13·5-31·5]) and 31 received azathioprine (median follow-up 20 months [IQR 13-30]). The mean change in MG-QOL15r was -10·4 (95% CI -18·9 to -1·3) with mycophenolate mofetil and -6·8 (-17·2 to 3·6) with azathioprine (mean difference -3·3, 95% CI -7·7 to 1·2; p=0·15). 38 (81%) of 47 patients receiving mycophenolate mofetil and 18 (57%) of 31 receiving azathioprine had a CMR in MG-QOL15r (risk difference 24·0%; 95% CI -0·2 to 48·0; p=0·052). The clinical composite outcome was achieved in 22 (47·7%) of 47 patients who received mycophenolate mofetil and nine (28·1%) of 31 who received azathioprine (risk difference 19·6%, 95% CI -4·9 to 44·2; p=0·12). Descriptive analysis did not find a difference in the proportion of patients reaching a CMR in MG-QOL15r between the adequate dose and duration group and the lower dose or shorter duration group. Adverse events occurred in 11 (32%) of 34 patients who received azathioprine and nine (19%) of 48 who received mycophenolate mofetil. The most frequent adverse events were hepatotoxicity with azathioprine (five [15%] of 34) and gastrointestinal disturbances (seven [15%] of 48) with mycophenolate mofetil. There were no study-related deaths. More than half of patients treated with azathioprine and mycophenolate mofetil felt their quality of life improved; no difference in clinical outcomes was noted between the two drugs. Adverse events associated with azathioprine were potentially more serious than those with mycophenolate mofetil, although mycophenolate mofetil is teratogenic. Lower than recommended doses of azathioprine might be effective, with reduced dose-dependent adverse events. More comparative effectiveness studies are required to inform treatment choices in myasthenia gravis. Patient-Centered Outcomes Research Institute, Myasthenia Gravis Foundation of America.

Constructing and Validating a Nomogram Model for Short-Term Prognosis of Patients with AChR-Ab+ GMG.

This study aimed to establish and validate a nomogram prognostic model for predicting short-term efficacy of acetylcholine receptor antibody-positive (AChR-Ab+) generalized myasthenia gravis (GMG). A retrospective observational study was conducted at the First Hospital of Shanxi Medical University, enrolling patients diagnosed with AChR-Ab+ GMG from May 2020 to September 2022. The primary outcome was the change in the Myasthenia Gravis Foundation of America (MGFA) post-intervention status after 6months of standard treatment. Predictive factors were identified through univariate and multivariate logistic regression analyses, with significant factors incorporated into the nomogram. The bootstrap test was used for internal validation of the nomogram model. Model performance was assessed using calibration curves, receiver-operating characteristic curve analysis, and decision curve analysis (DCA). A total of 90 patients were enrolled, of whom 30 achieved unchanged or worse status after 6months of standard therapy. Univariate logistic regression analysis showed that quantitative myasthenia gravis score, gender, body mass index, course of disease, hemoglobin levels, and white blood cell counts were six potential predictors. These factors were used for multivariate logistic regression analysis, and a nomogram was constructed. The calibration curve showed that the predicted value was in good agreement with the actual value (p = 0.707), and the area under the curve value (0.792, 95% CI 0.686-0.899) indicated good discrimination ability. DCA suggests that this model has potential clinical application value. The constructed nomogram, based on key patient indicators, shows promise as a clinically useful tool for predicting the short-term efficacy of treatment of AChR-Ab+ GMG. Validation in larger, multicenter cohorts is needed to further substantiate its applicability.

The impact of myasthenia gravis severity on work and daily activities.

People with myasthenia gravis (MG) experience impaired quality of life. However, the impact of MG symptoms on work productivity has not been well-studied. We aimed to evaluate this impact and to examine associations between disease severity and the degree of impairment. Data were drawn from the Adelphi MG Disease-Specific Programme™, a multinational (USA, France, Germany, Italy, Spain, UK) survey completed by physicians and their patients with MG in 2020. Patient-reported measures included the Work Productivity and Activity Impairment (WPAI): Specific Health Problem questionnaire. The WPAI questionnaire was completed by 330 patients. Among those currently employed, the mean percentage of work time missed (absenteeism) was 13.3% (N = 116), percentage impairment of productivity at work (presenteeism) was 26.7% (N = 121), and overall work impairment was 30.0% (N = 110). Across all patients, impairment of non-work-related activities due to health problems (ADL impairment) was 39.2% (N = 330). Regression analysis indicated that impairment differed according to MG Foundation of America (MGFA) class (p = .0147, p < .0001, p < .0001 and p < .0001 for absenteeism, presenteeism, overall work impairment and ADL impairment, respectively). Being MGFA class III/IV was a predictor of presenteeism, overall work impairment and ADL impairment in a predictor model. Patients with MG experience substantial work impairment particularly those with more severe symptoms, highlighting an important way in which patient quality of life is negatively affected. More effective treatment strategies would enable patients to lead more productive lives and could impact decisions relating to work and career.

The Impact Of Thymectomy In Thymomatous And Nonthymomatous Myasthenia Gravis - The Experience Of A Tertiary Center.

Thymectomy remains a mainstay of treatment in Thymomatous (T) and Nonthymomatous (nT) Myasthenia Gravis (MG), with improved clinical outcomes and reduced need for medical treatment, however, there is little research regarding long-term follow-up. We aim to assess the impact of surgery on the long-term outcome of patients with MG at our center. Retrospective analyses of MG patients submitted to thymectomy between 2007 and 2017 at the thoracic surgery department of CHUC. Clinical assessment was performed according to the MG Foundation of America (MGFA) Clinical Classification (cMGFA). The follow-up was categorized according to the MGFA Post-intervention Status (MGFA-PIS) and cMGFA. Statistical analysis was performed with SPSS, to a significance level of 5%. Thirty-seven patients underwent extended thymectomy and 67.6% were female. Median age at diagnosis was 46.68±19.2 years. Most patients (83.8%) had anti-acetylcholine receptor antibodies and 81.1% had generalized forms of MG. Many patients (67.6%) had surgery less than 12 months after the clinical diagnosis. TMG was present in 19 (51.4%) patients. Compared to nTMG, these patients were older (54.06±17.9 vs 40.17±19.4 years) and most were men (52.9% vs 16.7%). We obtained a good outcome in most patients in the first (81.1%), second (86.1%), and fifth (84.8%) year of follow-up. There was a shift towards better prognosis categories in the good outcome group: 9.1% CSR, 3.0% PR, and 66,7% MM in the fifth year. Preoperative medical treatment did not influence the long-term follow-up outcome. A shorter time to surgery (< 12 months) correlated with better outcomes at year 5 (p=0.016). Thymectomy led to a sustained clinical improvement in our cohort, allowing for a reduced need for medication. A shorter time to surgery seems to have a positive influence on long-term prognosis. We expect that an extended follow-up would improve our results.

Efgartigimod Alfa (Vyvgart)

&#x0D; CADTH recommends that Vyvgart be reimbursed by public drug plans for the treatment of adult patients with generalized myasthenia gravis (gMG) if certain conditions are met.&#x0D; Vyvgart should only be covered to treat patients who have a diagnosis of class II to IV gMG based on the Myasthenia Gravis Foundation of America (MGFA) system, tested positive for anti–acetylcholine receptor (AChR) antibodies, and have a Myasthenia Gravis Activities of Daily Living (MG-ADL) scale score of at least 5. Vyvgart should only be covered to treat patients if their symptoms persist despite a stable dose of conventional therapy with acetylcholinesterase inhibitors (AChEIs), corticosteroids (CSs), and/or nonsteroidal immunosuppressants (NSISTs).&#x0D; Vyvgart should not be reimbursed when given during a gMG exacerbation (i.e., moment when patient experience weakness in some or all muscles, without needing assistance to breath) or crisis (i.e., moment when respiratory muscles are too weak, limiting air flow in and out of lungs, and as a result, patient is unable to breathe), or within 3 months of thymectomy (i.e., surgical removal of thymus gland). Vyvgart should only be reimbursed if prescribed by or in consultation with a neurologist with expertise in managing patients with gMG, and the cost of Vyvgart is reduced. Vyvgart should not be used concomitantly with rituximab or complement inhibitors.&#x0D;

Study on the clinical and electrophysiological characteristics of nerve function in myasthenia gravis patients in Vietnam.

In Vietnam, there is limited research on the role of nerve conduction in myasthenia gravis and its association with clinical features. This study aims to describe the electrophysiological features in patients with myasthenia gravis. This descriptive study was conducted from September 2019 to December 2021. The study included 33 myasthenia gravis patients who sought medical consultation or received inpatient treatment during this period. The Myasthenia Gravis Foundation of America classifies myasthenia gravis into five groups: I, IIa, IIb, IIIa, IIIb, IVa, IVb, and V. Notably, Group I involves pure ocular weakness, whereas Group a primarily impacts limb and axial muscles, and Group b mainly affects bulbar and respiratory muscles. The study revealed that motor and sensory nerve conduction in the upper and lower limbs were within normal limits for the patient group under evaluation. Repetitive nerve stimulation testing at a frequency of 3 Hz showed positive results in 66.7% of myasthenia gravis patients. Myasthenia gravis patients displayed distinct clinical symptoms, with ptosis being the most common (87.9%). Myasthenia Gravis Foundation of America classification indicated the highest proportion in subgroup IIa (24.2%), with myasthenia gravis predominating in limb and axial muscles (Group a) observed in 51.5% of cases. Needle electromyography showed no abnormalities in myasthenia gravis patients. There was an association between acetylcholine receptor antibody titers and the results of the 3 Hz repetitive nerve stimulation test in myasthenia gravis patients, with a significance of p = 0.002. Nerve conduction studies should be performed in patients with suspected neuromuscular disorders to aid in differential diagnosis and definitive diagnosis of myasthenia gravis.

Há declínio na fala de pacientes com Miastenia Gravis ao longo de 4 anos?

ABSTRACT Purpose To compare the speech and voice patterns of myasthenia gravis (MG) patients over four years, and correlate the results with clinical aspects of the disease. Methods Data was collected for 4 years. The clinical assessment tools included the Quantitative Myasthenia Gravis (QMG) score, the Myasthenia Gravis Foundation of America (MGFA) clinical classification, and the Myasthenia Gravis Quality of Life 15-item Scale (MG-QoL). To assess speech, the recorded speaking tasks were analyzed acoustically and given auditory-perceptual ratings. Sex (equal distribution) and age (p=0.949) were used as matching criteria in the final sample, which consisted of 10 individuals in the MG group (MGG) and 10 individuals in the control group (CG). Results After 4 years, the MG participants presented stable health status, increased mild and moderate dysarthria (from 40% to 90% of the subjects), and a significant deterioration in the respiration, phonation, and articulation subsystems. The acoustic analysis showed a decline in articulatory patterns (speech rate p=0.047, articulation rate p=0.007, mean syllable duration p=0.007) and vocal quality (increased jitter p=0.022). In the follow-up comparison, there was a significant difference between the phonation variables (shimmer and harmonic-to-noise ratio) of the MGG and CG. Conclusion The MG patients presented a decline in speech over four years and an increase in mild and moderate dysarthria. Despite presenting stable health status, their respiratory, phonatory, and articulatory subsystems worsened. There was no correlation between speech patterns and clinical characteristics of the disease (severity and motor scale).

Unveiling Myasthenia Gravis: A Comprehensive Analysis of Diagnostic Tools and Clinical Insights

Objective: This research offers a comprehensive analysis of Myasthenia Gravis (MG), uncovering the remarkable accuracy of spinal accessory, ulnar, and facial nerve repetitive nerve stimulation (RNS), along with the precision of single fiber electromyography (SF-EMG) in MG diagnosis. We also embark on an exploration of clinical features and autoantibody test results in generalized MG patients.&#x0D; Methods: In this prospective study, we welcomed 31 individuals definitively diagnosed with generalized MG into our quest. The categorization of patients was conducted in accordance with the criteria set by the Myasthenia Gravis Foundation of America (MGFA). We examined patients' trapezius, nasalis, and abductor digiti minimi (ADM) muscles using RNS. We meticulously recorded the presence of MG autoantibodies, clinical subtypes based on affected muscle groups, and SF-EMG jitter rates.&#x0D; Results: The mean age of the 31 patients of whom 19 (61.3%) were male, was 64 ± 13.9 years. Among them, 20 showed positivity in the Anti-AChR antibody test. In 28 patients, accounting for 90.3% of the study group, single fiber electromyography (EMG) displayed increased jitter. There were 4 (12.9%), 24 (77.4%) and 12 (38.7%) patients featuring a decremental response of exceeding 10% in ADM, trapezius and nasalis muscles, respectivelyOur investigation revealed notable findings, such as the absence of substantial correlations between decremental response rates and age, gender, duration of complaints, antibody test results, thymus abnormalities, affected muscle types, familial history, or increased jitter rates in SF-EMG (p&gt;0.05).&#x0D; Conclusion: As our findings clearly show, we can confidently attest to the remarkable sensitivity of RNS in MG diagnosis when muscle selection is precise. A gem discovered on our study is the high sensitivity of the spinal accessory nerve, a revelation that should guide the course of routine RNS studies, particularly for those facing ocular-onset myasthenia.

Promising efficacy of Low-Dose rituximab in Muscle specific kinase antibody positive Myasthenia Gravis

AimsThe study aims to evaluate the efficacy of low dose rituximab (RTX) in patients with muscle-specific kinase antibody positive myasthenia gravis (MuSK-MG). MethodsThis is a single-center, retrospective study. A total of 10 patients with MuSK-MG were admitted to the Department of Neurology, First Hospital, Shanxi Medical University, between April 2021 to April 2023. Of them, 9 patients had been treated with low dose RTX (500 mg every 6 month) and recruited in this study. The clinical information, including the severity before and after RTX treatment, were collected from the medical records. Clinical effectiveness was assessed by Myasthenia Gravis Foundation of America (MGFA)-postintervention status (PIS), MG-related activities of daily living (MG-ADL), Quantitative Myasthenia Gravis (QMG) scores, Myasthenia Gravis Quality of Life 15-item revised (MG-QOL15r), dosage of steroid at the end of follow up. ResultsAll nine patients showed clinical improvement at the final follow-up after low-dose RTX treatment. The mean dose of prednisolone decreased significantly from 50 mg at baseline to 18.33 mg at the last follow-up (z = -3.417, p = 0.001). The administration of low-dose RTX treatment led to significant improvements in ADL levels (Z = -2.675, P < 0.01), QMG score levels (Z = -2.371, P < 0.05) and QOL-15r levels (Z = -2.547, P < 0.01) at last visit. ConclusionLow-dose RTX is effective for treating MuSK-MG patients. Longer-term follow-up and larger-scale studies are needed to provide further evidence.

Home Noninvasive Ventilation in Myasthenia Gravis.

Noninvasive ventilation (NIV) plays an important role in avoiding endotracheal intubation during myasthenic crisis, yet there are few published data concerning long-term home NIV in stable out-patients with myasthenia gravis (MG). The aim of this study was to describe the prevalence of NIV in a cohort of subjects with stable MG and to analyze contributing factors that could predict the need of NIV. We performed a cross-sectional study that included subjects diagnosed with MG managed in the respiratory care unit over the previous year. Subjects underwent clinical analysis including demographic, clinical, and functional respiratory data. Of the 50 subjects included, 35 (70%) were positive for nicotinic acetylcholine receptor antibodies, and 68% had a diagnosis of generalized MG. Bulbar symptoms developed in 16 (32%), and 10 (20%) subjects needed long-term home NIV. The only variable predicting the need for long-term NIV was MG severity measured with Myasthenia Gravis Foundation of America (MGFA), mainly grades IIB (odds ratio 0.14 [95% CI 0.02-0.85], P = .03) and IIIB (odds ratio 0.02 [95% CI 0.01-0.34], P = .01). Home NIV was needed in a substantial percentage of medically stable subjects with MG, mainly in those with generalized type and with oropharyngeal and/or respiratory muscle involvement (MGFA grades IIB and IIIB).

Clinical characteristics and outcomes of COVID-19 infection among myasthenia gravis patients in a national referral hospital in Indonesia

Introduction. Due to their immunocompromised state from immunosuppressive therapy and respiratory efficiency, patients with Myasthenia Gravis (MG) are more likely to get infected with COVID-19. Currently, reports on MG patients exposed with COVID-19 in Indonesia are still limited. Therefore, this study was conducted to determine the clinical characteristics and outcomes of MG patients infected with COVID-19, especially in Jakarta, Indonesia. Methods. It is a retrospective study of MG patients in a National Referral Hospital in Indonesia from September 2021 to December 2022. The data obtained includes demographics, medical history, clinical characteristics, and severity of MG assessed by MG composite scale (MGCS), Myasthenia Gravis Foundation of America (MGFA) classification, symptoms, and therapy. Results. Of the 8 patients, 7 patients were female. The range of age at COVID-19 onset was 28-62 years old. On admission to the hospital, 2 patients were mild MG, 2 patients were moderate MG, 3 patients with severe MG, and one patient could not be identified because the patient came in an unconscious state. Five patients were classified as moderate COVID-19, two patients had severe COVID-19, and one patient was classified as critical COVID-19. Most patients experience MG exacerbation or require oxygen support during hospitalization. Only one patient deceased while receiving treatment at the emergency room, while the rest improved and were discharged home. Conclusion. MG patients exposed with COVID-19 tend to experience moderate, severe, and critical COVID-19 symptoms. However, with proper management of the infection and other comorbidities, MG patients with COVID-19 may achieve favorable outcome.

Remission of severe myasthenia gravis after autologous stem cell transplantation.

Myasthenia gravis (MG) is an autoantibody-mediated neuromuscular junction disorder involving the acetylcholine receptors on the motor endplate. The safety and response to high-dose chemotherapy (HDIT) and autologous hematopoietic cell transplantation (HCT) were assessed in a patient with severe refractory MG. As part of a pilot study of HDIT/HCT for patients with treatment-resistant autoimmune neurological disorders, a patient with severe refractory MG underwent treatment. After mobilization of hematopoietic stem cells with rituximab, prednisone, and G-CSF, the patient had HDIT consisting of carmustine, etoposide, cytarabine, melphalan, and rabbit antithymocyte globulin, followed by autologous HCT. The effect of treatment on the autoantibody to the acetylcholine receptor (AChR) was assessed. The patient had been diagnosed with AChR antibody-positive MG 14 years before HDIT/HCT and had failed thymectomy, therapeutic plasma exchange, and multiple immunomodulatory agents. The Myasthenia Gravis Foundation of America (MGFA) clinical classification was IVb before HDIT/HCT. She tolerated HDIT/HCT well and started to improve clinically within days of treatment. At both 1 and 2 years after HDIT/HCT, patients remained symptom-free. After HDIT/HCT, AChR-binding autoantibodies persisted, and the relative frequency of immune cell subtypes shifted. HDIT/HCT induced a complete response of disease activity in a patient with severe refractory MG. This response may suggest that a cell-mediated etiology may be a significant contributing factor in refractory MG cases. A phase 2 clinical trial is warranted to establish if HDIT/HCT can be an effective therapy for severe refractory MG and to gain a further understanding of disease pathogenesis.

Long-term efficacy and safety of tacrolimus in young children with myasthenia gravis

ObjectiveThis study was performed to evaluate the efficacy and long-term safety of tacrolimus for young children with myasthenia gravis (MG). MethodsChildren with corticosteroids (CSs)-ineffective, CSs-dependent or CSs-intolerable MG treated with tacrolimus for at least one year were recruited. The Myasthenia Gravis Foundation of America (MGFA) clinical classification and MGFA post-intervention status (MGFA-PIS) were used to evaluate before tacrolimus administration and at the last visit, respectively. MG Activities of Daily Living (MG-ADL) score and the dose of prednisone were recorded. Patients were divided into responders and poor responders based on changes in MG-ADL score to investigate the factors that affected tacrolimus efficacy. Unfavorable events were recorded. ResultsTwenty-one patients with MG were enrolled. The median age of starting tacrolimus was 8.7 (range 2.2–15.1) years old. At the last visit, 15 patients (71.4%) achieved minimal manifestation (MM) or better status. The symptoms evaluated by MG-ADL improved significantly one month after initiating tacrolimus (p＜0.05) and the dose of prednisone decreased significantly three months later (p＜0.05), and it continued to improve throughout the study. Thirteen patients (61.9%) were ultimately weaned off prednisone. Compared with 16 responders, 5 poor responders had lower MG-ADL scores. MG-ADL score was the only clinical factor of tacrolimus efficacy. Intraocular pressure and transient urine microprotein were present in one patient. ConclusionA course of tacrolimus of more than one year was effective and well-tolerated in young children with MG, and tacrolimus improved MG symptoms and reduced the dose and adverse events of oral prednisone.

Myasthenia gravis treatment in the elderly presents with a significant iatrogenic risk: a multicentric retrospective study.

Myasthenia gravis (MG) is an autoimmune disease treated with acetylcholinesterase inhibitors and immunosuppressant/immunomodulatory drugs. MG is frequently diagnosed in elderly patients, a fragile population in which treatment adverse effects (TAE) have not been evaluated until now. We retrospectively analysed the files of all MG patients with disease onset after age 70years in four French University Hospitals, including clinical, electrophysiological, biological, and treatment data, with an emphasis on TAE. MG outcomes were assessed using the Myasthenia Gravis Foundation of America (MGFA) status scale. We included 138 patients (59% of men) with a mean follow-up of 4.5years (range 1-19). Mean age at diagnosis was 78years (70-93). Anti-acetylcholine receptor antibodies were found in 87% of cases, electrophysiological abnormalities in 82%, and thymoma in 10%. MG outcome was good in a majority of cases, with 76% of treated patients presenting with alleviated symptoms at follow-up. TAE were observed in 41% of patients, including severe TAE in 14% of cases. Seven patients (5.1%) died, including four (2.9%) from MG-related respiratory failure, and three (2.2%) from MG treatment-related complications, i.e., sepsis in 2 cases and brain toxoplasmosis in 1 case. TAE were observed in 53% of patients treated with azathioprine, 23% of patients treated with corticosteroids, and 15% of patients treated with mycophenolate mofetil. This retrospective study demonstrates MG in the elderly presents with a significant iatrogenic risk, including fatal immunosuppressant-related infections.

Alterations in short-term blood pressure variability related to disease severity and autonomic symptoms in myasthenia gravis patients

ObjectivesWe aimed to evaluate beat-to-beat blood pressure variability (BPV) during head-up tilt test (HUTT) in patients with mild and moderate myasthenia gravis (MG) compared to healthy controls (HCs), and its association with the severity of autonomic symptoms.MethodsA total of 50 MG patients and 30 HCs were evaluated. Patients were stratified into 2 groups regarding Myasthenia Gravis Foundation of America (MGFA) classification: mild (I,II MGFA), moderate form (III MGFA). Autonomic symptoms were assessed by COMPASS-31 questionnaire. Cardiovascular parameters, indices of very short-term systolic (SBPV), and diastolic blood pressure (BP) variability (DBPV) were assessed at rest, and during HUTT.ResultsModerate MG patients were characterized by an overall shift of sympathovagal balance toward sympathetic predominance, either at rest and during HUTT, as well as lower values of high frequency (HFnu) of DBPV during HUTT, compared to HCs and mild MG. Similarly, moderate MG showed higher resting low frequency (LFnu) of DBPV (p=0.035), higher COMPASS-31 score (p=0.031), and orthostatic intolerance sub-score (p=0.019) than mild MG patients. Compared to HCs, mild MG patients showed lower Δmean BP (p=0.029), Δdiastolic BP (p=0.016). Autonomic symptoms were associated with lower BP values, at rest and during HUTT, and lower LF BPV parameters during HUTT.ConclusionMG patients present significant alterations in BPV, both at rest and in response to orthostatic stress, which are related to autonomic symptoms and disease severity. This study confirms the importance of monitoring BPV when evaluating cardiovascular autonomic function and its evolution over the course of MG disease.

Lymphoplasmapheresis versus plasma exchange in severe myasthenia gravis: a retrospective cohort study.

Lymphoplasmapheresis (LPE) is a new therapy developed on the basis of traditional plasma exchange (PE) in combination with leukapheresis. Currently, it remains unclear whether PE and LPE show differences in efficacy for severe MG. A retrospective analysis was conducted on 198 MG patients, 75 in the PE group and 123 in the LPE group, and the patients' Myasthenia Gravis Foundation of America (MGFA) Clinical Classification was Class IV. The treatment outcome was the change in Quantitative Myasthenia Gravis Score (QMGS) from baseline to the end of treatment. Propensity score matching (PSM) was applied for the balance of confounders between the two groups. In this study cohort, the safety profile of LPE and PE was good and no serious adverse events were observed. Based on PSM, 62 patients treated with LPE and 62 patients treated with PE were entered into a comparative efficacy analysis. In the PE group, patients underwent a total of 232 replacements, with a mean of 3.74. PE significantly improved the patients' QMGS performance, with the mean QMGS decreasing from 22.98 ± 4.03 points at baseline to 18.34 ± 5.03 points after treatment, a decrease of 4.68 ± 4.04 points (p < 0.001). A decrease of ≥3 points in QMGS was considered a significant improvement, with a treatment response rate of 67.7% in the PE group. In the LPE group, patients received a total of 117 replacements, with a mean of 1.89. The patients' mean QMGS was 23.19 ± 4.11 points at baseline and was 16.94 ± 5.78 points after treatment, a decrease of 6.26 ± 4.39 points (p < 0.001). The improvement in QMGS was more significant in patients treated with LPE compared to the PE group (p = 0.039). The treatment response rate in the LPE group was 79%, which was not significantly different compared to the PE group (p = 0.16). The LEP group had a shorter mean length of stay compared to the PE group (10.86 ± 3.96 vs. 12.14 ± 4.14 days), but the difference was not statistically significant (p = 0.13). During the 2-month follow-up period, LPE may be associated with better functional outcomes for patients, with lower QMG score and relapse rate. LPE and PE were both effective in reducing the levels of inflammatory cytokines (TNF-α, IL-1β, and IL-6) and AChR-Ab. Compared to PE, LPE was superior in the reduction of AChR-Ab titer. In severe MG, LPE may be a more preferred treatment option than PE. It achieves treatment outcomes that are not inferior to or even better than PE with fewer replacements. This study provides further evidence to support the application of LPE as a new treatment option for MG.

Safety and clinical activity of autologous RNA chimeric antigen receptor T-cell therapy in myasthenia gravis (MG-001): a prospective, multicentre, open-label, non-randomised phase 1b/2a study

Chimeric antigen receptor (CAR) T cells are highly effective in treating haematological malignancies, but associated toxicities and the need for lymphodepletion limit their use in people with autoimmune disease. To explore the use of CAR T cells for the treatment of people with autoimmune disease, and to improve their safety, we engineered them with RNA (rCAR-T)-rather than the conventional DNA approach-to target B-cell maturation antigen (BCMA) expressed on plasma cells. To test the suitability of our approach, we used rCAR-T to treat individuals with myasthenia gravis, a prototypical autoantibody disease mediated partly by pathogenic plasma cells. MG-001 was a prospective, multicentre, open-label, phase 1b/2a study of Descartes-08, an autologous anti-BCMA rCAR-T therapy, in adults (ie, aged ≥18 years) with generalised myasthenia gravis and a Myasthenia Gravis Activities of Daily Living (MG-ADL) score of 6 or higher. The study was done at eight sites (ie, academic medical centres or community neurology clinics) in the USA. Lymphodepletion chemotherapy was not used. In part 1 (phase 1b), participants with Myasthenia Gravis Foundation of America (MGFA) disease class III-IV generalised myasthenia gravis received three ascending doses of Descartes-08 to determine a maximum tolerated dose. In part 2 (phase 2a), participants with generalised myasthenia gravis with MGFA disease class II-IV received six doses at the maximum tolerated dose in an outpatient setting. The primary objective was to establish safety and tolerability of Descartes-08; secondary objectives were to assess myasthenia gravis disease severity and biomarkers in participants who received Descartes-08. This trial is registered with clinicaltrials.gov, NCT04146051. We recruited 16 individuals for screening between Jan 7, 2020 and Aug 3, 2022. 14 participants were enrolled (n=3 in part 1, n=11 in part 2). Ten participants were women and four were men. Two individuals did not qualify due to low baseline MG-ADL score (n=1) or lack of generalised disease (n=1). Median follow-up in part 2 was 5 months (range 3-9 months). There was no dose-limiting toxicity, cytokine release syndrome, or neurotoxicity. Common adverse events were headache (six of 14 participants), nausea (five of 14), vomiting (three of 14), and fever (four of 14), which resolved within 24 h of infusion. Fevers were not associated with increased markers of cytokine release syndrome (IL-6, IL-2, and TNF). Mean improvements from baseline to week 12 were -6 (95% CI -9 to -3) for MG-ADL score, -7 (-11 to -3) for Quantitative Myasthenia Gravis score, -14 (-19 to -9) for Myasthenia Gravis Composite score, and -9 (-15 to -3) for Myasthenia Gravis Quality of Life 15-revised score. In this first study of an rCAR-T therapy in individuals with an autoimmune disease, Descartes-08 appeared to be safe and was well tolerated. Descartes-08 infusions were followed by clinically meaningful decreases on myasthenia gravis severity scales at up to 9 months of follow-up. rCAR-T therapy warrants further investigation as a potential new treatment approach for individuals with myasthenia gravis and other autoimmune diseases. Cartesian Therapeutics and National Institute of Neurological Disorders and Stroke of the National Institutes of Health.