Abstract
Objective: To summarize the
clinical characteristics, radiological features, treatments, and
prognosis of patients with myelin
oligodendrocyte glycoprotein (MOG) antibody associated disease (MOGAD)
overlapped with NMDA receptor (NMDAR) encephalitis.
Methods: We retrospectively analyzed patients who exhibited
dual positivity for MOG antibodies and NMDAR antibodies in serum/CSF
from Jan 2018 to Jun 2023
Results: Ten patients with MOGAD and NMDAR encephalitis were
enrolled. The median age of initial attacks was 23 (range: 10-43) years
old. Common symptoms were cortical
encephalopathies (8/10), focal
neurological deficits (4/10), as well as other presentations including
headache, fever, optic neuritis, and transverse myelitis. CSF
pleocytosis was general (9/10, median 63.9 cells/μl). Lesions on brain
MRI included brainstem (37.5%), cerebral cortex (33.3%), basal ganglia
(25.0%), hippocampus (20.8%). The average follow-up duration was 25.4
months. 10/10 patients developed more than one relapse attacks, with MOG
positivity before (10%), simultaneous (40%) or after anti-NMDAR
encephalitis (50%). Most patients (7/10) had good response to
first-line therapy, but experienced next relapse with an average
interval of 6.7 (range: 2-14) months. We conducted initial analysis of
lymphocyte subsets in these patients, which revealed CD3+ and CD4+ T
cells increased after immunosuppressants medication (p < 0.01
and p < 0.05, respectively).
Conclusion: MOGAD
overlapping with NMDAR encephalitis presents a distinct clinical
phenotype which differs from either MOGAD or NMDAR encephalitis.
Brainstem in combination with
cortical lesions might be warning signs for this overlapping syndrome.
Due to the high recurrent rates, we recommend early diagnosis and timely
treatment with high-efficiency
immunosuppressants at onset.
Introduction
Myelin oligodendrocyte glycoprotein (MOG) antibody–associated disease
(MOGAD) is an inflammatory demyelinating disease of the central nervous
system (CNS) [1]. Following the detection of a distinctive
autoantibody against MOG in patients with specific clinical and imaging
features, MOGAD was regarded as an isolated disease spectrum
differentiating from aquaporin-4 seropositive neuromyelitis optica
spectrum disorder (NMOSD) and multiple sclerosis [2]. Optic neuritis
(ON) and transverse myelitis (TM) are typical clinical presentations of
MOGAD in adults, while acute disseminated encephalomyelitis (ADEM) is
common in children [3]. Cerebral cortical encephalitis and brainstem
or cerebellar demyelination is less common in MOGAD [4].
The anti-N-methyl-d-aspartate receptor (NMDAR) antibody mainly binds to
the GluN1 subunit of the neuronal surface [5], which induces
autoimmune encephalitis (AE). The defining features of NMDAR receptor
encephalitis are abnormal mental behavior, epileptic seizures, altered
consciousness, and central hypoventilation [6]. In a cohort study,
patients with NMDAR encephalitis were tested for concurrent glial and
neuronal surface antibody [7]. Of them, 4% exhibited co-existence
with glia-antibodies, among which MOG-antibody was most frequently
present. Another study showed that 3.3% of patients with anti-NMDAR
encephalitis develop demyelinating disorders, either separately or
simultaneously. Among these NMDAR antibody-positive patients, 12
(16.4%) tested positive for MOG antibody [8].
Apart from the phenomena of NMDAR encephalitis in combination with
MOG-antibody positivity, an increasing number of cases have recently
been reported in MOG antibody positive patients presenting with seizures
or cortical and brainstem encephalitis [9, 10], indicating clinical
entity distinct from typical MOGAD. These patients have episodes of
encephalopathy and demyelination concomitantly or sequentially, in which
dual positivity of anti-NMDAR and anti-MOG abs were detected [3,
11]. Other case reports and systematic reviews also revealed that
prevalence of the overlapping syndrome may be underestimated [12].
Thus, it is considered important to identify
serum MOG-positive patients
overlapping with anti-NMDAR antibodies.
Data on the clinical and radiological features of MOGAD overlapping with
NMDAR encephalitis are scarce, and the scope of published literature is
mainly restricted to case reports [13-15]. Distinct clinical spectra
were present in these patients, indicating that the overlapping syndrome
is an independent disease entity that differs from patients with single
antibody positivity. Hence, this study is aimed to provide a long-term
retrospective analysis of MOGAD overlapping with NMDAR encephalitis in
the last 5 years by summarizing clinical characteristics, imaging
features, and evaluating treatments and prognosis.