Disease Course and Outcomes in Patients With the Limited Form of Neuromyelitis Optica Spectrum Disorders and Negative AQP4-IgG Serology at Disease Onset: A Prospective Cohort Study

Abstract

Background and Purpose Patients presenting with clinical characteristics that are strongly suggestive of neuromyelitis optica spectrum disorders (NMOSD) have a high risk of developing definite NMOSD in the future. Little is known about the clinical course, treatment, and prognosis of these patients with likely NMOSD at disease onset. Methods This study prospectively recruited and visited 24 patients with the limited form of NMOSD (LF-NMOSD) at disease onset from November 2012 to June 2021. Their demographics, clinical course, longitudinal aquaporin-4 immunoglobulin G (AQP4-IgG) serology, MRI, therapeutic management, and outcome data were collected and analyzed. Results The onset age of the cohort was 38.1±12.0 years (mean±standard deviation). The median disease duration was 73.5 months (interquartile range=44.3–117.0 months), and the follow-up period was 54.2±23.8 months. At the end of the last visit, the final diagnosis was categorized into AQP4-IgG-seronegative NMOSD ( n =16, 66.7%), AQP4-IgG-seropositive NMOSD ( n =7, 29.2%), or multiple sclerosis ( n =1, 4.2%). Seven of the 24 patients (29.2%) experienced conversion to AQP4-IgG seropositivity, and the interval from onset to this serological conversion was 37.9±21.9 months. Isolated/mixed area postrema syndrome (APS) was the predominant onset phenotype (37.5%). The patients with isolated/mixed APS onset showed a predilection for conversion to AQP4-IgG seropositivity. All patients experienced a multiphasic disease course, with immunosuppressive therapy reducing the incidence rates of clinical relapse and residual functional disability. Conclusions Definite NMOSD may be preceded by LF-NMOSD, particularly isolated/mixed APS. Intensive long-term follow-up and attack-prevention immunotherapeutic management is recommended in patients with LF-NMOSD.

Case report: Overlap syndrome of neuromyelitis optica spectrum disorder with anti-Argonaute antibodies

“…Most individuals with NMOSD have serum antibodies that target AQP4 ( 3 ). However, a subgroup of patients test negative for AQP4-Abs, especially those with asymptomatic manifestations or a temporal course with only a single clinical attack, making the diagnosis difficult ( 14 – 16 ). Similarly, although the patient in this study presented with acute brainstem syndrome at the first clinical attack with negative AQP4-Abs in the serum or CSF, the diagnosis was pending until a relapse of brainstem encephalitis with AQP4-Abs in the serum.…”

“…Patients with negative AQP4-Abs onset and clinical manifestations that do not meet the diagnostic criteria, including isolated area postrema syndrome (APS), isolated optic neuritis, isolated longitudinally extensive transverse myelitis, simultaneous short-segment transverse myelitis, and other core clinical manifestations, are diagnosed with the inaugural limited form of NMOSD (LF-NMOSD), which precedes future definite NMOSD ( 15 , 17 ). A prospective cohort study found that the mean interval conversion from AQP4-Abs seronegativity to seropositivity was >36 months ( 16 ). In our patient, the time interval from the onset of the first episode to antibody conversion was 4 years.…”

Genetics behind Cerebral Disease with Ocular Comorbidity: Finding Parallels between the Brain and Eye Molecular Pathology

“…Currently, an open-label phase I clinical trial is ongoing, using T lymphocytes with genetic modification of chimeric antigen receptors (CAR) targeting B cell maturation antigen (BCMA) in AQP4-IgG-positive patients, and the first results are expected in 2023 ([ 361 ]). However, since the molecular mechanisms of pathology in AQP4-IgG-negative disease remain unclear [ 444 ], initiation of immunosuppressive therapy is recommended [ 445 ].…”