Safety, efficacy and steroid-sparing effect of amifampridine in Lambert-Eaton myasthenic syndrome patients - real world data.

INTRODUCTION: Lambert-Eaton myasthenic syndrome (LEMS) is an ultrarare neuromuscular disease with a triad of symptoms: muscle paresis, dysautonomy, and areflexia. Amifampridine is the symptomatic treatment of LEMS. AIM OF STUDY: To assess the effectiveness and safety of treatment in the real world. MATERIAL AND METHODS: 14 patients with non-neoplastic LEMS treated with amifampridine were enrolled in the study (female 42.9%, mean age 48.8 ± 11.4 years). The patients were assessed using the Quantitative Myasthenia Gravis (QMG) scale, QMG limb domain (LD) score, spirometry, Hand Grip Strength (GRIP) test, and repetitive nerve stimulation study (RNS) at baseline and at the end of follow-up. Diagnostic delay since first symptoms was from seven months up to 22 years. Treatment delay ranged from one to 26 years. The patients were treated and reevaluated after 21.1 ± 12.0 weeks (range 13-48). RESULTS: All of the patients improved in QMG score. Mean improvement was 5.1 ± 2.0 (range 1-8) points (p < 0.001) and this showed no correlation with the duration of the disease before treatment (p = 0.477). 85.7% of patients (N = 12) improved ≥ 3 points (clinically meaningful) in QMG. 78.6% of the patients improved in QMG LD (mean 2.2 ± 1.6 points (p < 0.001)). Also, forced vital capacity (FVC) improved after treatment (p = 0.031). Mean improvement in GRIP test was 7.0 ± 7.1 kg in the right hand and 5.2 ± 7.5 kg in the left hand (p < 0.001). In RNS before treatment, facilitation ( > 100%) was observed in 78.6% (N = 11) of patients, and was higher before treatment (p < 0.001). Compound muscle action potential (CMAP) amplitude was higher after treatment (p < 0.001). Mean increase of CMAP amplitude was 2.1 ± 1.6 times. In 64.3% (N = 9) of patients lowering of corticosteroid dose was achieved. CONCLUSIONS: Amifampridine is an effective treatment in non-neoplastic LEMS patients, regardless of disease duration. The treatment is well-tolerated and allows to reduce dose of corticosteroids in the majority of patients.

Myasthenia gravis-treatment and severity in nationwide cohort.

INTRODUCTION: Myasthenia gravis (MG) is a rare autoimmune disorder of neuromuscular junction. MG healthcare burden has not been studied in Poland before. METHODS: Data were drawn from the National Health Fund database; MG patient was defined as a person who received at least once medical service with ICD-10 code MG (G70) and at least two reimbursed prescriptions for pyridostigmine bromide or ambenonium chloride in two consecutive years. We have analyzed treatment: immunosuppression, intravenous immunoglobulins (IVIg), plasma exchange (PE), the number and length of hospitalizations (LOS), intensive care unit (ICU) care, and deaths between 2013 and 2018. RESULTS: In 2018, there were 9012 MG patients (F:M 1.62:1), and 30.6% had early -onset MG (<50 years). 66.3% received symptomatic treatment only, 33.7%-glucocorticoids (CS) and/or other immunosuppressants (IS), 64.6%-CS only, 17.5%-azathioprine plus CS, 11%-azathioprine only, 4.6%-CS plus other IS (methotrexate, mycophenolate mofetil, cyclosporine, or tacrolimus), and 2%-other IS only. In 2018, 42.3% of patients were hospitalized at least once (mean 2.05/year), 13.7% due to MG (1.47/year). In 2018, 1.63% patients received PE, 2.33% IVIg. In 2013-2018, 2.7%-3.2% of MG patients required hospitalization in ICU. ICU mean LOS 2013-2018 was 11.5-15.0 days/per patient/year. 2.1% of all MG patients had myasthenic crisis. Mean age at death was 75.7 years for MG and 73.9 for general population (p = .006). All-cause mortality was higher for men (4.1%-5.1%) than for women (2.5%-3.1%), p < .01. CONCLUSIONS: Our findings confirm significant healthcare burden of MG, comprising a tool to plan resources needed for MG patients.

Lower BAFF Levels in Myasthenic Patients Treated with Glucocorticoids.

B-cell activating factor (BAFF), a member of tumor necrosis factor family, activates B cells, promotes their survival and proliferation. BAFF is considered to have an influence on development of autoimmune diseases including myasthenia gravis (MG). We aimed to evaluate BAFF serum levels in MG patients, their potential connection with therapy and course of MG. Cross-sectional study. Two hundred eighteen adult patients with MG (67% women, age: 18-89 years, 82.6% AChR antibody seropositive (AChRAb(+)). Serum BAFF levels, their relationship with severity of clinical symptoms, therapy conducted, clinical and demographic features and other factors were analyzed. Patients with AChRAb(+) MG demonstrated significantly higher BAFF levels than MuSK-MG patients (831.2 ± 285.4 pg/ml vs. 745.6 ± 633.4 pg/ml, respectively; p = 0.030). Serum BAFF levels in women were significantly higher than in men (855.9 ± 302.5 vs. 756.6 ± 289.4, respectively; p = 0.017). Mean serum BAFF level was significantly decreased in patients who were ever treated with corticosteroids (CS) (770.4 ± 327.8 pg/ml vs. 891.3 ± 246.1 pg/ml, respectively; p = 0.001). Thymoma-MG patients demonstrated significantly lower BAFF levels (671.2 ± 244.9 vs. 833.5 ± 302.4, respectively; p = 0.044). Thymectomized patients did not differ in BAFF levels from the MG patients who had not undergone thymectomy. In multiple linear regression model, recent CS therapy and male sex were found to be independent predictors of lower BAFF levels. Serum BAFF level is decreased in patients treated with CS, which may suggest inhibiting influence of CS on BAFF-a potential mechanism contributing to the effectiveness of such therapy.

High incidence and clinical characteristics of fibromuscular dysplasia in patients with spontaneous cervical artery dissection: The ARCADIA-POL study.

The association between fibromuscular dysplasia (FMD) and spontaneous cervical artery dissection (SCeAD) has been recognized, but the available evidence on this relationship is scant. Therefore, the main goal of our study was to systematically evaluate FMD frequency, clinical characteristics and vascular bed involvement in patients with SCeAD. Among 230 patients referred to the ARCADIA-POL study, 43 patients (mean age 44.1 ± 8.9 years; 15 men and 28 women) with SCeAD were referred. Also, 135 patients with FMD were compared to patients with and without SCeAD. Patients underwent: ambulatory blood pressure measurements, biochemical evaluation, echocardiographic examination, and whole body computed tomographic angiography. FMD changes were found in 39.5% of patients with SCeAD. There were no differences in clinical characteristics between patients with SCeAD and FMD and those without FMD, except for a tendency towards a higher female ratio in SCeAD patients with FMD. There were no differences in other parameters describing target organ and SCeAD characteristics. Patients with SCeAD and FMD compared to those without SCeAD were characterized by a lower frequency of hypertension and a higher frequency of hyperlipidemia and history of contraceptive hormone use. Our study indicates a high incidence (39.5%) of FMD in subjects with SCeAD. Since there are no distinctive discriminating factors between patients with SCeAD and FMD and those without FMD, FMD should be suspected in all patients with SCeAD.

Serum interleukin 15 levels in patients with seropositive myasthenia gravis do not correlate with disease severity.

AIM: To assess interleukin 15 (IL-15) serum levels in patients with seropositive myasthenia gravis (MG); searching for potential relationship between IL-15 levels and clinical features such as gender, age at onset, clinical presentation or treatment received. BACKGROUND: IL-15 plays pivotal role in T-cell dependent autoimmunity. Increased IL-15 serum levels have been reported in several autoimmune diseases including MG patients from Japan. PATIENTS AND METHODS: Sera of 42 seropositive MG patients (66.7% women), mean age 50.6±23.7 years) have been tested by ELISA for IL-15 levels. RESULTS: There were no statistically significant differences between IL-15 serum levels in MG patients in comparison with controls as well as between subgroups of MG patients (early vs. late onset and thymoma MG). Mean/median IL-15 serum levels were similar in MG patients treated with corticosteroids (CS) and CS naïve. Outliers (very high values) were seen only in untreated generalized MG patients. CONCLUSIONS: Serum interleukin 15 levels in patients with seropositive myasthenia gravis do not correlate with disease severity.

Prevalence and impact of autoimmune thyroid disease on myasthenia gravis course.

OBJECTIVES: Autoimmune thyroid diseases (ATDs) frequently accompany myasthenia gravis (MG) and may influence its course. We aimed to determine the association and impact of ATD with early- (<50 years), late-onset MG, or thymoma-MG. MATERIALS AND METHODS: Prevalence of ATD was measured in a cross-sectional study of 343 consecutive patients with MG (236 F, 107 M) aged 4-89 years; 83.8% were seropositive, in 2.9%, anti-MuSK antibodies were detected. Concentrations of antithyroid peroxidase antibodies, antithyroglobulin antibodies, antithyrotropin receptor antibodies, and TSH level were measured in all patients. MG clinical course, treatment received, and treatment results were evaluated. RESULTS: Autoimmune thyroid diseases were diagnosed in 92 (26.8%) of MG patients including 4.4% with Graves (GD), 9% with Hashimoto thyroiditis (HT), and 13.4% with antithyroid antibodies only. GD patients had ocular symptoms more often than patients with antithyroid antibodies or HT (p = .008). ATD prevalence was comparable in MG with early and late onset, while non-ATDs were more frequent in thymoma-MG (p = .049). Immunosuppressive therapy was less frequently needed in the patients with MG and ATD, indirectly indicating milder MG course (p = .005). Risk of myasthenic crisis and the results of treatment did not differ between patients with and without ATD. CONCLUSIONS: Autoimmune thyroid diseases are frequently accompanied by early-and late-onset MG, while thymoma-MG is related to higher risk of non-ATD. Myasthenia coexisting with ATD follows milder course than MG alone.

Common carotid artery access for transcatheter aortic valve implantation.

Transcatheter aortic valve implantation (TAVI) is an alternative method of treatment for severe symptomatic aortic stenosis in patients who are at high risk of surgical aortic valve replacement (AVR). In randomised clinical trials TAVI was shown to be superior to standard medical therapy in a cohort of inoperable patients and non-inferior to AVR in high-risk operable patients. Additionally, in a recent trial with self-expandable prosthesis use, TAVI was associated with lower mortality compared with surgery. Usually, femoral arteries are the most common vascular access to deliver the bioprosthesis; however, in some cases (up to 20%) this route may not be applied because of significant peripheral artery disease or tortuosity. In this article, we present the first two TAVI procedures in Poland performed via the left common carotid artery.