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Levodopa is the gold standard for the symptomatic treatment of Parkinson's disease (PD). There are well documented motor and non-motor fluctuations, however, that occur almost inevitably once levodopa is started after a variable period in people with PD. Whilst brain neurodegenerative processes play a part in the pathogenesis of these fluctuations, a range of barriers across the gastrointestinal (GI) tract can alter levodopa pharmacokinetics, ultimately contributing to non-optimal levodopa response and symptoms fluctuations. GI barriers to levodopa transport and absorption include dysphagia, delayed gastric emptying, constipation, Helicobacter pylori infection, small intestinal bacterial overgrowth and gut dysbiosis. In addition, a protein-rich diet and concomitant medication intake can further alter levodopa pharmacokinetics. This can result in unpredictable or sub-optimal levodopa response, 'delayed on' or 'no on' phenomena. In this narrative review, we provided an overview on the plethora of GI obstacles to levodopa transport and absorption in PD and their implications on levodopa pharmacokinetics and development of motor fluctuations. In addition, management strategies to address GI dysfunction in PD are highlighted, including use of non-oral therapies to bypass the GI tract., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background and Purpose: Idiopathic inflammatory myopathy (IIM) can present with dysphagia as a leading or only symptom. In such cases, diagnostic evaluation may be difficult, especially if serological and electromyographical findings are unsuspicious. In this observational study we propose and evaluate a diagnostic algorithm to identify IIM as a cause of unexplained dysphagia., Methods: Over a period of 4 years, patients with unexplained dysphagia were offered diagnostic evaluation according to a specific algorithm: The pattern of dysphagia was characterized by instrumental assessment (swallowing endoscopy, videofluoroscopy, high-resolution manometry). Patients with an IIM-compatible dysphagia pattern were subjected to further IIM-focused diagnostic procedures, including whole-body muscle magnetic resonance imaging, electromyography, creatine kinase blood level, IIM antibody panel and, as a final diagnostic step, muscle biopsy. Muscle biopsies were taken from affected muscles. In cases where no other muscles showed abnormalities, the cricopharyngeal muscle was targeted., Results: Seventy-two patients presented with IIM-compatible dysphagia as a leading or only symptom. As a result of the specific diagnostic approach, 19 of these patients were diagnosed with IIM according to the European League Against Rheumatism (EULAR) criteria. Eighteen patients received immunomodulatory therapy as a result of the diagnosis. Of 10 patients with follow-up swallowing examination, dysphagia improved in three patients after therapy, while it remained at least stable in six patients., Conclusions: Idiopathic inflammatory myopathy constitutes a potentially treatable etiology in patients with unexplained dysphagia. The diagnostic algorithm presented in this study helps to identify patients with an IIM-compatible dysphagia pattern and to assign those patients for further IIM-focused diagnostic and therapeutic procedures., (© 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background and Purpose: Neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) are demyelinating disorders that typically affect the optic nerves and the spinal cord. However, recent studies have demonstrated various forms of brain involvement indicating encephalitic syndromes, which consequently are included in the diagnostic criteria for both. Swallowing is processed in a distributed brain network and is therefore disturbed in many neurological diseases. The aim of this study was to investigate the occurrence of oropharyngeal dysphagia in NMOSD and MOGAD using flexible endoscopic evaluation of swallowing (FEES) as a surrogate parameter of brain involvement., Methods: Thirteen patients with NMOSD and MOGAD (mean age 54.2 ± 18.6 years, six men) who received FEES during clinical routine were retrospectively reviewed. Their extent of oropharyngeal dysphagia was rated using an ordinal dysphagia severity scale. FEES results were compared to a control group of healthy individuals. Dysphagia severity was correlated with the presence of clinical and radiological signs of brain involvement, the Expanded Disability Status Scale (EDSS) and the occurrence of pneumonia., Results: Oropharyngeal dysphagia was present in 8/13 patients, including six patients without other clinical indication of brain involvement. Clinical or subclinical swallowing impairment was significantly more severe in patients with NMOSD and MOGAD compared to the healthy individuals (p = 0.009) and correlated with clinical signs of brain involvement (p = 0.038), higher EDSS (p = 0.006) and pneumonia (p = 0.038)., Conclusion: Oropharyngeal dysphagia can occur in NMOSD and MOGAD and might be associated with pneumonia and disability. FEES may help to detect subclinical brain involvement., (© 2020 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of NeurologyEuropean Academy of Neurology.)

Background: Dysphagia frequently occurs in patients with Parkinson's disease (PD) and is associated with severe complications. However, the underlying pathology is poorly understood at present. This study investigated the effect of cognitive and motor dual-task interference on oropharyngeal swallowing in PD., Methods: Thirty PD patients (23 men, mean age 65.90 ± 9.32 years, mean Hoehn and Yahr stage 2.62 ± 0.81, mean UPDRS 18.00 ± 7.18) were examined using flexible endoscopic evaluation of swallowing (FEES). FEES was performed during three paradigms: at baseline without interference, during a cognitive dual-task, and during a motor dual-task. Oropharyngeal swallowing function was rated using a score which was validated to detect changes in PD related dysphagia. The three paradigms were compared using a two-way-repetitive-measures-ANOVA and a post-hoc-analysis., Results: Mean swallowing score in baseline FEES was 10.67 ± 5.89. It significantly increased (worsened) to 15.97 ± 7.62 (p < 0.001) in the motor dual-task and to 14.55 ± 7.49 (p < 0.001) in the cognitive dual-task. Premature bolus spillage and pharyngeal residue both significantly increased during both of the dual-task conditions whereas penetration/aspiration events did not change., Conclusion: Oropharyngeal swallowing in patients with PD is not purely reflexive but requires mental capacity. Additional allocation of attentional resources in the central control of swallowing seems to be an effective compensatory mechanism in PD-related dysphagia: The proposed dual-task protocol may be useful to challenge swallowing functional reserve. Conversely, as a therapeutic strategy, it could be beneficial to focus attention on swallowing and to avoid dual-task situations., (© 2020 European Academy of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)