The challenges of diagnosing neuromyelitis optica spectrum disorders without antibodies to aquaporin-4

Abstract

Neuromyelitis optica spectrum disorders (NMOSD) are rare autoimmune diseases of the central nervous system (CNS) that often lead to severe disability. Early diagnosis of NMOSD allows effective treatment to be started as soon as possible. Errors in the diagnosis of NMOSD, which can lead to delayed treatment of patients, may be due, among other things, to incorrect interpretation of diagnostic criteria.

Objective: to investigate the frequency and causes of misdiagnosis of seronegative NMOSD (without antibodies to aquaporin-4 – AQP4-IgG). Material and methods. A retrospective and prospective analysis of data from 144 patients who were referred to the Russian Сenter of Neurology and Neurosciences with a diagnosis of NMOSD without antibodies to aquaporin-4 (AQP4) was conducted. This cohort of patients was tested for compliance with the 2015 NMOSD diagnostic criteria.

Results. NMOSD without AQP4 antibodies was confirmed in 10 patients (6.94%). Alternative diagnoses were: multiple sclerosis – 42 patients (29.17%), non-inflammatory CNS diseases – 29 (20.14%), diseases associated with antibodies to myelin oligodendrocyte glycoprotein – 19 (13.19%), myelitis – 18 (12.5%), optic neuritis – 14 (9.72%), clinically isolated syndrome – 12 (8.33%). Reasons for misdiagnosis: failure to take into account spatial dissemination, non-compliance with additional MRI criteria, ignoring 'red flags' and underestimating anamnestic data.

Conclusion. The frequency of misdiagnosis of NMOSD without AQP4 antibodies was 93.06%. The diagnosis of NMOSD should be established in strict accordance with diagnostic criteria, provided that all alternative causes have been ruled out.