This is a population-based observational retrospective study, from January 2012 to December 2021, which covered the population of Navarre, one of the 17 Autonomous Communities (AC) in northern Spain. The population of Navarre in 2022 was 664,117 inhabitants (49.5% women), comprising the 1.4% of the Spanish population [9].

The Spanish National Health System (S-NHS) is based on the principles of universality, free access, equity, and fairness of financing, and is mainly funded by taxes [10]. Over 98% of Navarre’s citizens have an individual health card with a unique 8-digit personal identification code (called CIPNA), which allows them to have access to the public health system. It contains information on birth date, sex, and other socio-demographic conditions, and enables linking across databases through a unique identifier.

Neurologist ratio per inhabitant in Navarre is 4.65/100,000 inhabitants [11]. Since 2010, movement disorders consultations attended by specialized neurologists have been implemented in the Navarre University Hospital, the single large tertiary referral hospital for the entire region, which receives referrals from the entire community. A multidisciplinary care strategy has been in place for the management of atypical Parkinsonism since 2019.

Navarre has hosted a population-based Rare Disease Registry (RERNA) since 2013 [12], which uses all available Health Information Systems (HIS), in addition to medical reporting, to record both retrospectively and prospectively, prevalent cases from 2000. The HIS used by RERNA to collect MSA cases were: Minimum Basic Data Set at Hospital Discharge, Temporary Work Disability Registry, and Mortality Statistics [13,14,15]. To get the maximum sensitivity in identifying MSA cases, all International Classification diseases-10 diagnostic codes used for any type of MSA were included: G23.2 (striatonigral degeneration), G23.8 (other specified degenerative diseases of basal ganglia), G23.9 (degenerative disease of basal ganglia, unspecified) and G90.3 (multisystem degeneration). In addition, the Electronic Clinical Records from all Neurology hospital Departments (including inpatients, outpatients, and all private hospitals) and from the Navarre Biobank were explored and reviewed, and MSA diagnosed patients were selected to be included in RERNA. Information on the date of death was accessible and linked to MSA patients in the registry.

The procedures carried out were in accordance with the Helsinki Declaration of 1975, as revised in 2000, and the study was approved by the Navarre Ethical Committee of Clinical Research.

The information from the various data sources was reviewed in order to identify all potential diagnoses of MSA during the study period. Databases were cross-checked to identify duplicate patients, included in more than one data source. Case validation was performed using information from medical records by a neurologist expert in movement disorders. A detailed chart review was carried out, and pertinent information was extracted from each chart. We collected demographic data, date of clinical symptom onset and date of MSA diagnosis. Time to diagnosis was defined as the duration from clinical symptom onset to diagnosis. Detailed clinical features were reviewed that included symptom onset, first diagnosis established by neurologist, and the presence or absence and time of onset of: parkinsonism and levodopa resistant parkinsonism, gait and limb ataxia, cerebellar dysarthria and oculomotor cerebellar features, unexplained voiding difficulties with post-void urinary residual volume ≥ 100 mL, unexplained urinary urge incontinence, orthostatic decrease of blood pressure within 3 min of standing by at least 20 mm Hg systolic or 10 mm Hg diastolic and erectile dysfunction. Additional clinical features were collected that included rapid progression within 3 years of motor onset, moderate to severe postural instability within 3 years of motor onset, cranio-cervical dystonia, severe speech impairment or dysphagia within 3 years of motor onset, pyramidal signs, myoclonic tremor, postural deformities, stridor, cold discoloured hands and feet and pathologic laughter or crying, date of magnetic resonance imaging and radiological findings.

Patients were included if they fulfilled the new Movement Disorder Society (MDS) criteria for the diagnosis of clinically established or clinically probable MSA (Online Resource 1). Diagnosis date was defined as the date on which MSA diagnosis was first recorded. We classified MSA subtype depending on the predominant motor variant in MSA-P and MSA-C.

The exclusion criteria of the new MDS MSA diagnostic criteria were applied (Online Resource 1).

Point prevalence (global and sex-specific) of MSA was calculated annually using the number of MSA individuals per 100,000 inhabitants, resident in Navarre, on December 31. Incidence and mortality rates were defined as the number of newly diagnosed MSA cases and the number of MSA-registered deaths, respectively, per 100,000 inhabitants per year. Mean annual incidence and mortality rates per 100,000 were analysed for two periods: 2012–2016 and 2017–2021. For annual age-adjusted mortality rates, we used the 2013 European Standard Population (ESP) [16] and the 2016 Spanish and Navarre Population [9]. Overall trends were analysed for the three epidemiologic indicators.

Demographic and clinical characteristics were summarized using descriptive statistics, such as median and ranges for continuous variables and absolute and relative frequencies for categorical variables. Continuous variables were compared by sex or MSA subtype using t-test, U Mann–Whitney test for median comparisons and Chi-square test and Fisher’s test for categorical variables. Median survival time and 95% CI were computed using Kaplan–Meier estimators, and comparisons between sexes were performed using the logrank test.