[Myasthenia Gravis - Update]. / Myasthenia gravis ­ Update.

Myasthenia gravis - still a challenge for sufferers and doctors in 2023. But which therapy is best suited? Our clinically experienced experts have summarized the current guidelines for diagnosis and treatment in order to provide optimal support for those affected. Find out how you can carry out a quick and targeted diagnosis and which treatment options are available to alleviate the course of the disease.

Suitability of the Respicheck questionnaire and Epworth sleepiness scale for therapy monitoring in myotonic dystrophy type 1.

Myotonic dystrophy type 1 (DM1) is an autosomal dominant trinucleotide disorder that often leads to respiratory dysfunction resulting in hypoventilation symptoms, reduced quality of life and causing premature death if untreated. To early identify symptoms of hypoventilation, the Respicheck questionnaire was developed as a screening tool. Symptomatic therapies like inspiratory muscle training (IMT) are recommended to strengthen respiratory muscles and reduce or even prevent hypoventilation symptoms. Our study aimed to evaluate the Respicheck questionnaire's suitablility to monitor the efficacy of IMT. Patients with genetically confirmed DM1 were randomly assigned to either IMT - endurance or strength training, or control group. At baseline, end of study and four interim visits, pulmonary function tests, Respicheck questionnaire and Epworth sleepiness scale were assessed. While patients in training groups achieved a substantial improvement after nine months of regular IMT in pulmonary function tests, the Respicheck score did not improve likewise. Similarly, the ESS score did not change significantly in both training and control groups. Consequently, we conclude that either improvement of respiratory function is not necessarily associated with clinical improvement, or respiratory muscle weakness was not the only reason for hypoventilation syndrome, or both questionnaires are not sensitive enough to detect slight clinical changes.

Evaluation of myotonometry for myotonia, muscle stiffness and elasticity in neuromuscular disorders.

Neuromuscular disorders show extremely varied expressions of different symptoms and the involvement of muscles. Non-invasively, myotonia and muscle stiffness are challenging to measure objectively. Our study aims to test myotonia, elasticity, and stiffness in various neuromuscular diseases and to provide reference values for different neuromuscular disease groups using a novel handheld non-invasive myometer device MyotonPRO®. We conducted a monocentric blinded cross-sectional study in patients with a set of distinct neuromuscular diseases (NCT04411732, date of registration June 2, 2020). Fifty-two patients in five groups and 21 healthy subjects were enrolled. We evaluated motor function (6-min walk test, handheld dynamometry, Medical Research Council (MRC) Scale) and used ultrasound imaging to assess muscle tissue (Heckmatt scale). We measured muscle stiffness, frequency, decrement, creep, or relaxation using myotonometry with the device MyotonPRO®. Statistically, all values were calculated using the t test and Mann-Whitney U test. No differences were found in comparing the results of myotonometry between healthy and diseased probands. Furthermore, we did not find significant results in all five disease groups regarding myotonometry correlating with muscle strength or ultrasound imaging results. In summary, the myometer MyotonPRO® could not identify significant differences between healthy individuals and neuromuscular patients in our patient collective. Additionally, this device could not distinguish between the five different groups of disorders displaying increased stiffness or decreased muscle tone due to muscle atrophy. In contrast, classic standard muscle tests could clearly decipher healthy controls and neuromuscular patients.

Prediction of respiratory impairment in myotonic dystrophies using the 'Respiratory involvement symptom checklist' (Respicheck).

Chronic hypoventilation due to involvement of respiratory muscles is a frequent symptom in autosomal dominant inherited myotonic dystrophies, especially in type 1 (DM1), leading to a severely reduced quality of life, an early need for ventilatory support, or premature death. Thus, early knowledge of respiratory muscle weakness is essential to initiate further diagnostic and therapeutic measures. To get early, simple, and reliable information about respiratory impairment in DM patients, we performed a prospective controlled cohort study with DM1 and DM2 patients analysing the suitability of 'Respiratory involvement symptom checklist (Respicheck) as a clinically meaningful screening questionnaire for ventilatory impairment in patients with DM1 or DM2. Clinical assessments included a one-time pulmonary function test (spirometry and manometry) and the completion of the Respicheck. 172 participants were enrolled in this study (74 DM1, 72 DM2, 26 healthy controls). With a cut-off RespicheckCAT score of 4, the Respicheck can distinguish between patients with and without respiratory impairment with higher sensitivity and positive predictive value for DM1 than DM2 patients (DM1: sensitivity 77-87; positive predictive value 50-94%; DM2: sensitivity 67-80%; positive predictive value 14-38). In summary, our results confirm a clinically meaningful use of the Respicheck to detect respiratory impairments predominantly in DM1 patients.

The impact of interrupting enzyme replacement therapy in late-onset Pompe disease.

BACKGROUND: Late-onset Pompe disease (LOPD) is a rare autosomal recessive disorder caused by mutations in the GAA gene, leading to progressive weakness of locomotor and respiratory muscles. Enzyme replacement therapy (ERT), administered every second week, has been proven to slow down disease progression and stabilize pulmonary function. Due to the COVID-19 pandemic in Germany, ERT was interrupted at our centre for 29 days. As reports on ERT discontinuation in LOPD are rare, our study aimed to analyse the impact of ERT interruption on the change in clinical outcome. METHODS: We performed a prospective cohort study in 12 LOPD patients. Clinical assessments were performed after ERT interruption and after the next three consecutive infusions. We assessed motor function by muscle strength testing, a 6-minute-walk-test, pulmonary function tests, and adverse events. For statistical analysis, an estimated baseline was calculated based on the individual yearly decline. RESULTS: The mean time of ERT interruption was 49.42 days (SD ± 12.54). During ERT interruption, seven patients reported 14 adverse events and two of them were severe. Frequent symptoms were reduced muscle endurance/increased muscle fatigability and shortness of breath/worsening of breathing impairment. After ERT interruption, significant deterioration was found for MIP%pred (p = 0.026) and MRC%pred, as well as a trend to clinical deterioration in FVC%pred and the 6MWT%pred. CONCLUSION: Interruption of ERT was associated with a deterioration in the core clinical outcome measures. Therefore, an interruption of ERT should be kept as short as possible.

Associations Between Variant Repeat Interruptions and Clinical Outcomes in Myotonic Dystrophy Type 1.

OBJECTIVE: To assess the association between variant repeat (VR) interruptions in patients with myotonic dystrophy type 1 (DM1) and clinical symptoms and outcome measures after cognitive behavioral therapy (CBT) intervention. METHODS: Adult patients with DM1 were recruited within the OPTIMISTIC trial (NCT02118779). Disease-related history, current clinical symptoms and comorbidities, functional assessments, and disease- and health-related questionnaires were obtained at baseline and after 5 and 10 months. After genetic analysis, we assessed the association between the presence of VR interruptions and clinical symptoms' long-term outcomes and compared the effects of CBT in patients with and without VR interruptions. Core trial outcome measures analyzed were: 6-minute walking test, DM1-Activ-C, Checklist Individual Strength Fatigue Score, Myotonic Dystrophy Health Index, McGill-Pain questionnaire, and Beck Depression inventory-fast screen. Blood samples for DNA testing were obtained at the baseline visit for determining CTG length and detection of VR interruptions. RESULTS: VR interruptions were detectable in 21/250 patients (8.4%)-12 were assigned to the standard-of-care group (control group) and 9 to the CBT group. Patients with VR interruptions were significantly older when the first medical problem occurred and had a significantly shorter disease duration at baseline. We found a tendency toward a milder disease severity in patients with VR interruptions, especially in ventilation status, mobility, and cardiac symptoms. Changes in clinical outcome measures after CBT were not associated with the presence of VR interruptions. CONCLUSIONS: The presence of VR interruptions is associated with a later onset of the disease and a milder phenotype. However, based on the OPTIMISTIC trial data, the presence of VR interruptions was not associated with significant changes on outcome measures after CBT intervention. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov NCT02118779.

STIG study: real-world data of long-term outcomes of adults with Pompe disease under enzyme replacement therapy with alglucosidase alfa.

BACKGROUND: Pompe disease is one of the few neuromuscular diseases with an approved drug therapy, which has been available since 2006. Our study aimed to determine the real-world long-term efficacy and safety of alglucosidase alfa. METHODS: This multicenter retrospective study (NCT02824068) collected data from adult Pompe disease patients receiving ERT for at least 3 years. Demographics and baseline characteristics, muscle strength, lung function (FVC), walking capability (6MWT), and safety were assessed once a year. Evaluation was done on the group and individual levels, using quantitative linear models (t test) and general univariate linear models (ANOVA). FINDINGS: Sixty-eight adult Pompe disease patients from four countries (Spain, Taiwan, Italy, Germany (STIG)) participated. The mean follow-up was 7.03 years ± 2.98. At group level in all outcome measures, an initial improvement followed by a secondary decline was observed. After 10 years, the 6MWT%pred showed the most sustained positive effect (p = 0.304). The MRC%max remained stable with a mild decline (p = 0.131), however, FVC%pred deteriorated significantly (p < 0.001) by 14.93% over 10 years of ERT. The progression rate of FVC%pred under ERT could be explained in most of the patients (83.5%) by the disease severity at baseline. Furthermore, our study shows a decline in the FVC combined with an increase in non-invasive and invasive ventilation requirements in adult Pompe disease patients over time. CONCLUSIONS: The STIG real-world study confirms an initial efficacy of ERT in the first years with a secondary sustained decline in multiple outcome measures. Further efforts are required to establish a more valid long-term monitoring and improved therapies.