Sources

Multiple sources were combined for the best coverage (figures 1 and ​and22):

The Danish National Patient Registry, established in 1977, has collected data on all admissions and outpatient visits since 1995. It includes information about the hospital department, admission and discharge dates, and discharge diagnoses, according to the ICD-10.¹⁴ We included all patients registered with NMO/Devic disease (DG36.0), ON (DH46.9), and acute TM (DG37.3) between January 1, 2007, and December 31, 2014.

The Danish Multiple Sclerosis Registry has been collecting data on MS since 1948.^15,16 All Danish citizens diagnosed with MS or suspected MS by a neurologist are notified in the Danish Multiple Sclerosis Registry and reclassified by an MS expert at the time of data entry, based on the medical records. Patients with MS who had ON or TM as the presenting symptom were reevaluated for possible NMO/NMOSD.

Laboratories providing AQP4-Ab detection tests in Denmark supplied the list of patients tested for this Ab. These laboratories are the Statens Serum Institute (SSI), the Department of Clinical Immunology at Odense University Hospital (OUH), and the Neuroimmunology Laboratory at the Danish Multiple Sclerosis Center, Rigshospitalet, University of Copenhagen (RH). In total, 4,067 samples from 3,397 patients were tested within the study period.

All departments of neurology were asked to report any NMOSD and possible NMOSD cases.

Flowchart demonstrates the strategy of patient selection and validation in the Danish population of age 16 years and older. AQP4 = aquaporin-4; IPND = International Panel for Neuromyelitis Optica Diagnosis; MS = multiple sclerosis; NMOSD = neuromyelitis optica spectrum disorder.

Venn diagram shows that we were able to identify all cases from the departments and laboratories. The NPR (National Patient Registry) and DMSR (Danish Multiple Sclerosis Registry) did not contribute with unique cases. Capture-recapture analysis requires that notification by a second source is independent of notification by the first source. Because both DMSR and NPR are strongly mutually dependent and also dependent with the departments, we treated them as a single source.

To ensure the highest possible quality of data, we excluded patients who had never been seen at any public neurology departments or if crucial clinical information was missing. The minimum data required for seronegative NMOSD cases were clinical features and brain and spinal cord MRI once, respectively. For seropositive cases, clinical data and AQP4-Ab seropositivity were required, but practically all patients had brain and spinal MRI at least once. We also excluded foreign citizens who had left Denmark.