Expanding the spectrum of NMOSD: New cases of autoimmune epilepsy and meningoencephalitis

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease that mainly affects the optic nerves, spinal cord, and area postrema (AP). ¹ Most NMOSD patients test positive for a specific and pathogenic serum antibody called aquaporin-4-IgG (AQP4-IgG). ²

With the identification of a higher number of confirmed AQP4-IgG–positive cases, it became possible to broaden the spectrum of NMO to include atypical and limited forms of this condition, thereby introducing the concept of NMOSD. ¹ The complexity of clinical presentations and the wide range of potential differential diagnoses commonly lead to a significant challenge in diagnosing NMOSD, occasionally requiring a biopsy for a definitive diagnosis.^3,4 Consequently, some individuals with NMOSD may experience other uncommon cerebral syndromes like epilepsy (including status epilepticus due to epilepsia partialis continua) ⁵ and meningoencephalitis (including limbic encephalitis-like), ⁶ as reported in this edition of Multiple Sclerosis Journal. Despite the presence of a specific biomarker for NMOSD (AQP4-IgG), the diagnosis of NMOSD may be missed in patients presenting uncommon symptoms such as epilepsy/status epilepticus and meningoencephalitis, resulting in delays in receiving appropriate treatment.^3,4 It is crucial for neurologists to contemplate NMOSD as a potential underlying cause of epilepsy and meningoencephalitis, particularly in individuals with a history or association of clinical and imaging core characteristics such as optic neuritis, myelitis, or AP syndrome. Given that dual positivity for myelin oligodendrocyte glycoprotein (MOG)-IgG and AQP4-IgG is extremely rare, ⁷ MOG-IgG–associated diseases in addition to autoimmune encephalitis (including glial fibrillary acidic protein antibodies) should be strongly considered as important causes of central nervous system (CNS) autoimmune diseases involving cerebral and meningeal regions. ⁸ In this context, differential diagnosis should also contemplate a broaden list of non-demyelinating alternative diseases, as were ruled out in published cases.^5,6 Many attempts have been performed to revise and enhance diagnostic criteria to enable earlier diagnosis of NMOSD by utilizing more clearly defined clinical, radiological, and serostatus information. ¹ However, confirming an NMOSD diagnosis can be challenging in clinical practice.^3,4 Early detection and diagnosis of NMOSD are crucial for improving long-term patient outcomes. ² Therefore, neurologists should consider the possibility of diagnosing NMOSD in patients with epilepsy and meningoencephalitis of unknown origin.