Short summary

NMOSD and MOGAD are rare autoimmune inflammatory conditions of the CNS with uncertain prognosis and scarce evidence for the best treatment practice. Therefore, this national project aims to analyse data obtained from the first comprehensive research database and biomarkers of possible NMOSD and MOGAD patients in Denmark to improve the understanding and treatment strategy of these diseases.

Rationale

NMOSD and MOGAD include a clinically overlapping spectrum of patients with different demyelinating inflammatory CNS diseases. Both diseases can affect any age group. About 70-80% of cases fulfilling the latest international diagnostic criteria for NMOSD are associated with the pathogenic antibody (Ab) against AQP4 water channel (AQP4) located on astrocytes end-plates at the blood-brain barrier and causing primary inflammatory astrocytopathy with secondary demyelination.

Before the identification of this specific antibody, NMOSD was considered to be a severe subtype of multiple sclerosis. NMOSD may present with optic neuritis, myelitis, encephalitis or the combination of these. The AQP4-Ab seropositive cases have high risk to develop repeated relapses resulting in permanent and devastating disability. Thus, rapid and accurate diagnosis and treatment initiation are crucial to prevent further relapses and long-term handicap.

About one-third of NMOSD patients without AQP4-Ab have antibodies against myelin oligodendrocyte glycoprotein (MOG-Ab). In contrast to AQP4, MOG is expressed in oligodendrocytes, and antibodies cause oligodendrocytopathy with primary demyelination. Furthermore, MOG-Ab has also been detected in a broad spectrum of patients with inflammatory CNS condition such as isolated or recurrent optic neuritis, isolated or recurrent myelitis, and encephalitis, especially with cortical involvement. The associated spectrum of symptoms has been called MOGAD, and is just recently started to be considered as a separate disease entity.

There is limited information on the long-time prognosis of these patients, although it seems to be less severe than NMOSD. It may have a monophasic disease course raising an essential question regarding the necessary length of immunosuppressive treatment. Neither specific medication nor evidence-based treatment strategy is available for MOGAD. Besides the pressing and urgent clinical issues e.g. prognosis, start and suspension of long immunosuppression, future research should also focus on early biomarkers in order to distinguish NMOSD and MOGAD from MS (especially in the double seronegative cases), allow prompt recognition and treatment. Clinical and paraclinical data along with soluble biomarkers may help to predict the prognosis of these conditions, obtain a better understanding of diseases course, and establish/improve the treatment regime for NMOSD and MOGAD suspected cases.

Furthermore, data on patients previously diagnosed with NMOSD could be used to estimate the mortality and social burden of NMOSD.

Description of the cohort

All Danish adults tested positive for AQP4 or MOG-antibody.

Data and biological material

Data sources are the followings: patient journals, national registries, and laboratories that provide AQP4 or MOG antibody tests.

Collaborating researchers and departments

Dansk Multipel Sklerose Center, Rigshospital

• Melinda Magyari assoc. prof.
• Finn Sellebjerg prof.
• Jette Frederiksen prof.

Department of Neurology

• Kristina Svendsen MD, PhD

Department of Clinical Immunology

• Anna Christine Nilsson MD, PhD