Stadtroda

The prerequisite for participation in this observational study is the independent decision of the treating physician and patient to start an approved injectable or oral DMT for RMS as routine medical treatment. This decision must have been made prior to enrollment in this study. Cohort 1: The prospective observational period per patient in the core part will be up to approx. two years from the time of consent (2 years +2 months visit window). If a patient re-consents to the extension part, then the prospective extension observational period will be additional approx. two years, resulting in a total observational period (prospectively for the core and extension part \& retrospectively for the potential gap between core and extension part) of approx. 4 years (+ 2 month visit window). Cohort 2: The prospective observational period per patient will be up to approx. two years from the time of consent (2 years + 2 months visit window). The observational period will not be dictated by the protocol. The follow-up documentation will take place at a frequency defined as per investigator's discretion. The diagnostic or monitoring procedures are only those ordinarily applied to the therapeutic strategy and to routine clinical care, can be performed as telemedicine visits and will take place as per investigator's discretion.

Prospective, primary data will be collected from patients with sNfL outcomes in the context of switching to ofatumumab or continuing their current therapy. Data collection will cover a maximum period of 24 months. The observational period will not be dictated by the protocol. Baseline and follow-up visits will take place at a frequency defined as per Investigator´s discretion following clinical routine. The diagnostic or monitoring procedures are only those ordinarily applied to therapeutic strategy and routine clinical care. During the observation phase of the study, data will be collected according to standard of care as recommended by KKNMS (Competence Network Multiple Sclerosis in Germany). Eligible participants for the study are patients who have received treatment with category 1 DMTs and those who have included sNfL into their treatment decision-making process. These patients have the option to either continue their current DMT or switch to ofatumumab. According to local treatment guidelines, DMT category 1 include dimethylfumarate/diroximelfumarate, glatirameroids, Interferon beta and teriflunomide. The decision to switch to ofatumumab or to continue the current DMT category 1 therapy must be made by the treating physician independently of the decision to enroll the patient in the study.

Parkinson's disease (PD) is a neurological condition, which affects the brain. PD gets worse over time, but how quickly it progresses varies a lot from person to person. Some symptoms of PD are tremors, stiffness, and slowness of movement. This study will assess how effective foscarbidopa/ foslevodopa is in treating German adult participants at initial stages of advanced Parkinson's disease under routine clinical practice. Foslevodopa/Foscarbidopa is an approved drug for the treatment of Parkinson's Disease. Approximately 125 adult participants who are prescribed Foslevodopa/Foscarbidopa by their doctors will be enrolled across approximately 20 sites in Germany. Participants will receive Foslevodopa/Foscarbidopa subcutaneous infusion as prescribed by their physician. Participants will be followed for up to 12 months. There is expected to be no additional burden for participants in this trial. Participants will attend regular visits during the study at a hospital or clinic according to their routine clinical practice.

Neurodegenerative disorders are associated with a high prevalence of neurogenic dysphagia. Depending on the underlying disease, the prevalence can affect up to 80% of patients. Dysphagia is associated with dehydration, malnutrition, facilitates aspiration pneumonia and thereby determines the prognosis of neurodegenerative diseases. For most of them, dysphagia-associated complications are the leading cause of death. Multiple system atrophy (MSA) is a sporadic progressive neurodegenerative disorder caused by oligodendroglial aggregation of α-synuclein affecting predominantly the nigrostriatal, olivo-ponto-cerebellar, and autonomic systems,resulting in a clinical presentation of dysautonomia combined with either predominantly parkinsonian (MSA-P) or cerebellar (MSA-C) symptoms of varying severity.In its early stage, the diagnosis of MSA according to the second consensus criteria can be challenging. Therefore, the Movement Disorders Society MSA study group recently addressed the importance of developing valuable diagnostic tools for securing an early diagnosis in patients with MSA not only to estimate disease prognosis but also to early initiate novel, potentially disease-modifying treatments in clinical trials. Despite laryngopharyngeal dysfunction being associated with decreased life expectancy and quality of life, systematic assessment of these functions in MSA is scarce. Previously, an easy-to-implement MSA-FEES task-protocol was suggested to systematically assess laryngopharyngeal function. A pilot study on 8 patients with MSA not only showed that the task protocol was feasible and well tolerated, but also that laryngopharyngeal symptoms where highly prevalent despite the lack of clinical presentation (Warnecke et. al 2019). Moreover, irregular arytenoid cartilages movements where present in all MSA-patients when performing this task protocol, suggesting this symptom could serve as a clinical marker to identify MSA-patients. Following this pilot study, an observational two center study assessed 57 MSA patients with this protocol and compared findings to an age-matched cohort of PD-patients (Gandor et al. 2020). While only 43.9% of MSA patients had clinical symptoms of laryngeal dysfunction, 93% showed laryngeal abnormalities during FEES performing the task-protocol. 91.2% of MSA-patients showed irregular arytenoid cartilages movements. In contrast, only one PD patient showed laryngeal abnormalities with vocal fold motion impairment, but not irregular arytenoid cartilages movements. This study suggests that irregular arytenoid cartilages movements allow differentiating MSA from PD with a sensitivity of 0.9 and a specificity of 1.0. 4repeat tauopathies (4RT) are caused by an intraneuronal accumulation of 4repeat tau. 4RT, also known as progressive supranuclear palsy (PSP) with all its clinical subtypes, is a rapidly progressive neurodegenerative disease that leads to increasing impairment of cortical and subcortical function in the affected person due to the accumulation of tau protein in the brain (Höglinger 2017). Due to the clinical variability of the presentation, early diagnostic certainty is desirable. Depending on the affected area in the central nervous system, different clinical phenotypes result. The most commonly described and researched entity is Progressive Supranuclear P, also known as Richardson Syndrome, or PSP-RS. Further clinical presentations include a Parkinsonian variant (PSP-P), corticobasal syndrome (PSP-CBS), pure akinesia with gait freezing (PSP-PAGF), speech/language dominant presentations (PSP-SL), frontotemproal dementia variants (PSP-FTD), and cerebellar presentations (PSP-C) (Höglinger 2017). 4RT is also associated with swallowing and speech problems, and aspiration pneumonia is one of the most common causes of death in this disease entity (Tilley 2016). In addition, dystonic dysinnervation of laryngeal muscles can lead to laryngeal motion abnormalities (Panegyres 2007). Equally, patients with motor neurone disease (MND) are affected by dysphagia early in the disease. In a FEES study by Steven B. Leder and colleagues (2004), which included 17 ALS patients subjectively complaining of dysphagia, fluid aspiration or an increased risk of fluid aspiration was found in almost 60% of cases, regardless of whether the disease initially mainly affected the bulbar musculature or the limb musculature. As the disease progressed, the depth of penetration of fluids into the hypopharynx prior to triggering the swallowing reflex increased, so these patients were advised to thicken fluids. Initially, residues of solid food consistencies were detected in the valleculae, piriform sinus and/or laryngeal inlet in three patients after swallowing. As a result of progressive paresis of the pharyngeal muscles, the residuals increased in the ALS patients examined during the course of the disease. If this disorder pattern was detected, it was advised to reduce the size of the food bolus and to clear the pharynx by swallowing water or reswallowing several times. In a further small case series (n = 11), the FEES showed that dysphagic ALS patients are particularly at risk of penetration/aspiration when swallowing liquids. Penetration and aspiration occur particularly frequently intradeglutitively (D'Ottaviano et al. 2013). A recent publication reports on FEES examinations in 202 ALS patients (w/m 95/107; bulbar/spinal onset 66/136; mean age 64.68 +/- 11.12 years). A close positive correlation with disease severity (measured using the ALSFRS-R) was found for all FEES parameters (leaking, aspiration, residuals), regardless of the three consistencies tested (liquid, semi-solid, solid) (Fattori et al. 2017). The aim of this FEEMSA trial is to continue recruitment of patients with neurodegenerative diseases and systematically assess laryngopharyngeal function in large cohorts, to categorise the dysphagia phenotypes and better correlate them with the disease subtypes (MSA Parkinson vs cerebellar; PSP variants, MND variants, etc). If available, laryngeal EMG will also be recorded.