Faculty Bibliography

Background and aims: Dementia is considered a nonsupportive diagnostic feature for multiple system atrophy (MSA). Nevertheless, post-mortem verified dementia with Lewy bodies and Parkinson's disease masquerade as MSA. Cognitive impairment (CI), especially executive dysfunction, may occur in MSA patients. It is, however, unclear whether CI manifests in early disease stages.
Objective(s): To compare the prevalence of CI in MSA versus other Lewy Body disorders (LBD), including dementia with Lewy bodies and Parkinson's disease, in early (<3 years from symptom onset) versus more advanced disease stages (>=3 years from symptom onset).
Method(s): A total of 364 patients (LBD: n=83; MSA: n=281) of the natural history study of synucleinopathies register have been analysed. Consensus diagnostic criteria for dementia with Lewy bodies, Parkinson's disease and MSA were applied. To assess CI, the Montreal Cognitive Assessment (MoCA) has been used.
Result(s): In early disease stages, median MoCA scores did not differ significantly between MSA and LBD. In advanced disease stages, MSA patients had a significantly higher median MoCA score compared to LBD patients (27 versus 25, p=0.006). Comparison of the median MoCA Scores of LBD versus MSA patients at early and advanced disease stages
Conclusion(s): In patients with longer disease duration severity of CI helps to differentiate LBD from MSA

Background and aims: Inadequate norepinephrine (NE) release in neurogenic orthostatic hypotension (nOH) causes fall in standing blood pressure. Ampreloxetine, a novel, long-acting NE reuptake inhibitor may improve symptoms of nOH. The objective of this study was to explore durability of effect and safety of once-daily oral ampreloxetine for symptomatic treatment of nOH.
Method(s): In an open-label, phase 2, exploratory study, subjects received ampreloxetine (3-20mg) once-daily for up to 20 weeks, with 4-week follow-up after ampreloxetine withdrawal and restarting alternative pressor agents. Assessments included Orthostatic Hypotension Symptom Assessment Item 1 (OHSA#1; dizziness, lightheadedness, feeling faint), OHSA/Orthostatic Hypotension Daily Activities Scale (OHDAS) composite scores, and change in Patient Global Impression of Severity (PGI-S).
Result(s): Seventeen symptomatic subjects (baseline OHSA#1 score >4) were enrolled (mean age, 65 years). At Weeks 4 and 20, mean (SD) improvement on OHSA#1 was -3.8 (3.1) and -3.1 (3.0) point, and ~77% and ~86% of subjects reported >=1-point improvement, respectively. Improvement, seen as early as Week 1, was sustained throughout the study. Deterioration to baseline severity was observed after ampreloxetine withdrawal. Similar trends were seen in OHSA/OHDAS composite scores, and change in PGI-S. Most common adverse events (AEs) were urinary tract infection (24%), hypertension (19%) and headache (14%), with no study-drug-related serious AEs. Ampreloxetine showed durable symptom improvement over 20 weeks, with return to baseline severity after ampreloxetine withdrawal. Ampreloxetine was well tolerated.
Conclusion(s): These encouraging findings of durable symptom improvement with open-label ampreloxetine treatment are being evaluated in ongoing Phase 3, doubleblind, confirmatory studies in subjects with nOH