Clinical Features in a Danish Population-Based Cohort of Probable Multiple System Atrophy Patients

Abstract

Background: Multiple system atrophy (MSA) is a rare, sporadic and progressive neurodegenerative disorder. We aimed to describe the clinical features of Danish probable MSA patients, evaluate their initial response to dopaminergic therapy and examine mortality. Methods: From the Danish National Patient Registry, we identified 782 patients diagnosed with conditions potentially compatible with probable MSA (International Classification of Diseases, version 10 (ICD-10) codes G23.2, G23.8 and G23.9) during 1994-2009. Through medical record review, we narrowed our sample to 115 patients who fulfilled the criteria for probable MSA. We recorded clinical features, examined differences by MSA subtype and used Kaplan-Meier survival analysis to examine mortality. Results: The mean age at onset of patients with probable MSA was 60.2 years (range 36-75 years) and mean time to wheelchair dependency was 4.7 years (range 0-15 years). One-third of patients experienced a transient improvement in motor symptoms with use of levodopa. Median survival from disease onset was 6.9 years (range 1-16 years, 95% CI 6.3-7.5) with no apparent variation according to gender or subtype. Conclusions: Our nationwide approach corroborated that MSA is associated with diverse and grave symptoms, only limited response to levodopa, and poor prognosis.

Utility of the new Movement Disorder Society clinical diagnostic criteria for Parkinson's disease applied retrospectively in a large cohort study of recent onset cases

“…A good l -dopa response was present in those classified as clinically established PD (around 80%), but a significant proportion of cases (almost two-thirds) classified as non-PD also showed a good l -dopa response. This may reflect the known early-stage dopa-responsiveness in disorders such as PSP [13] , [14] and MSA [15] , which wanes over time. Absence of the l -dopa response by MDS criteria involved very few cases (0.2%), largely because the required daily l -dopa dose of at least 600 mg for this criterion was rare at this early disease stage.…”

Stridor in multiple system atrophy

“…47 Seven studies did not find an association between the presence of stridor during the disease course and shortened survival. 8,9,11,14,48–50 In most of these studies, stridor was clinically suspected without instrumental confirmation. In contrast, 1 study showed shorter survival in patients with MSA with stridor after VPSG recording, but not from disease onset.…”

“…Statements regarding the effect of stridor on survival in MSA are based on core literature consisting of Class II/III level studies, 8–11,14,31,48–50 a systematic review, 47 and expert opinion.Whether stridor affects survival is uncertain.Stridor within 3 years of motor or autonomic symptom onset may shorten survival. However, identification of stridor onset may be difficult.Whether specific features of stridor affect survival remains to be determined.Stridor during wakefulness is widely considered to reflect a more advanced stage of the disease than stridor occurring during sleep.…”

Multiple System Atrophy: Recent Developments and Future Perspectives

“…Prospective longitudinal cohorts of the European and North American MSA Study Groups have provided unprecedented information about the natural history of MSA during the past decade, in particular by describing the progression of UMSARS scores . These studies have also confirmed the poor prognosis, with median survival ranging between 6 and 10 years across published studies . Of note, some MSA patients show survival as short as 2 years, whereas a few have considerably longer disease duration, up to 20 years .…”

“…114,115 These studies have also confirmed the poor prognosis, with median survival ranging between 6 and 10 years across published studies. [82][83][84][114][115][116][117][118][119] Of note, some MSA patients show survival as short as 2 years, whereas a few have considerably longer disease duration, up to 20 years. 82,120 The latter can show a relatively benign clinical course with sustained L-dopa response and may even be considered as having PD for many years.…”