Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: A multicentre study of 175 patients

Abstract

BackgroundThe diagnostic and pathophysiological relevance of antibodies to aquaporin-4 (AQP4-Ab) in patients with neuromyelitis optica spectrum disorders (NMOSD) has been intensively studied. However, little is known so far about the clinical impact of AQP4-Ab seropositivity.ObjectiveTo analyse systematically the clinical and paraclinical features associated with NMO spectrum disorders in Caucasians in a stratified fashion according to the patients' AQP4-Ab serostatus.MethodsRetrospective study of 175 Caucasian patients (AQP4-Ab positive in 78.3%).ResultsSeropositive patients were found to be predominantly female (p < 0.0003), to more often have signs of co-existing autoimmunity (p < 0.00001), and to experience more severe clinical attacks. A visual acuity of ≤ 0.1 during acute optic neuritis (ON) attacks was more frequent among seropositives (p < 0.002). Similarly, motor symptoms were more common in seropositive patients, the median Medical Research Council scale (MRC) grade worse, and MRC grades ≤ 2 more frequent, in particular if patients met the 2006 revised criteria (p < 0.005, p < 0.006 and p < 0.01, respectively), the total spinal cord lesion load was higher (p < 0.006), and lesions ≥ 6 vertebral segments as well as entire spinal cord involvement more frequent (p < 0.003 and p < 0.043). By contrast, bilateral ON at onset was more common in seronegatives (p < 0.007), as was simultaneous ON and myelitis (p < 0.001); accordingly, the time to diagnosis of NMO was shorter in the seronegative group (p < 0.029). The course of disease was more often monophasic in seronegatives (p < 0.008). Seropositives and seronegatives did not differ significantly with regard to age at onset, time to relapse, annualized relapse rates, outcome from relapse (complete, partial, no recovery), annualized EDSS increase, mortality rate, supratentorial brain lesions, brainstem lesions, history of carcinoma, frequency of preceding infections, oligoclonal bands, or CSF pleocytosis. Both the time to relapse and the time to diagnosis was longer if the disease started with ON (p < 0.002 and p < 0.013). Motor symptoms or tetraparesis at first myelitis and > 1 myelitis attacks in the first year were identified as possible predictors of a worse outcome.ConclusionThis study provides an overview of the clinical and paraclinical features of NMOSD in Caucasians and demonstrates a number of distinct disease characteristics in seropositive and seronegative patients.

Present and Future Therapies in Neuromyelitis Optica Spectrum Disorders

“…There are probably no differences in relapse rates and clinical features between AQP4-IgG-positive patients with classical NMO and NMOSD, but AQP4-IgG-negative patients more often have bilateral ON or simultaneous ON and myelitis at disease onset than AQP4-IgG-positive patients [11,58]. While 1 study reported that a monophasic disease course is more common in AQP4-IgG-negative patients [11], this was not found in another study [58].…”

“…Only every 2. to 5. NMOSD attack shows complete recovery [11,32]. In particular, bilateral ON and myelitis have low remission rates [33].…”

“…Most patients with NMOSD have a relapsing disease course, and the median time between first and second attack is <1 year [11]. Natural history cohorts describing the annual relapse rate (ARR) in untreated patients do not exist for NMOSD; however, it is noteworthy that AQP4-IgG-positive patients with late-onset have attacks even in the oldest age categories [57].…”

“…Furthermore, NMO and NMOSD can be associated with myopathy and occur in the context of systemic autoimmune disease or cancer [9]. The case for AQP4-IgG-negative NMO is more complex, as these patients form a heterogeneous group with demographic and clinical characteristics different from seropositive patients [11]. Autoantibodies targeting the myelin oligodendrocyte glycoprotein have been reported in some AQP4-IgG-negative patients with a classical clinical presentation of NMO [12,13], however, anti-myelin oligodendrocyte glycoprotein-antibodies are not specific for NMO and occur in a variety of other demyelinating diseases [14].…”

Neuromyelitis optica does not impact periventricular venous density versus healthy controls: a 7.0 Tesla MRI clinical study

“…Prior to the discovery of a serum immunoglobulin G antibody targeting the aquaporine-4 water channel [5,6], it was often considered a variant of multiple sclerosis (MS) as the clinical presentation of these two distinct central nervous system (CNS) diseases may overlap [1]. Indeed, patients with NMOSD are still often misdiagnosed with MS in clinical practice [7,8].…”