Clinical Characteristics of Anti- N-Methyl-d-Aspartate Receptor Encephalitis Overlapping with Demyelinating Diseases: A Review

Abstract

Anti-N-methyl-d-aspartate receptor encephalitis (NMDARe), a common autoimmune encephalitis, can be accompanied by demyelinating disorders, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). To compare the clinical characteristics of patients with different overlapping syndromes, we searched the PubMed database and performed a systematic review. Of the 79 patients with overlapping syndromes, 15 had MS, 18 had aquaporin-4-antibody-positive NMOSD (AQP4-Ab-positive NMOSD), and 46 had MOGAD. Compared with classical NMDARe, overlapping syndromes showed atypical symptoms, such as limb weakness, sensory disturbance, and visual impairments in addition to the main symptoms of NMDARe and a lower ratio of ovarian teratoma. Patients with MOGAD overlap were the youngest, while patients with MS and AQP4-Ab-positive NMOSD overlap tended to be older than patients with classical NMDARe. A majority of patients with NMDARe who overlapped with MS or AQP4-Ab-positive NMOSD were female, but this was not the case for patients overlapped with MOGAD. When NMDARe and demyelinating diseases occurred sequentially, the interval was the longest in patients with NMDARe overlapped with MS. A favorable outcome was observed in patients overlapping with MOGAD, but no robust comparison can be drawn with the patients overlapping with AQP4-Ab-positive NMOSD and MS regarding the small number of available data. The long-term prognosis of overlapping syndromes needs further investigation.

Keywords: aquaporin-4-antibody-positive neuromyelitis optica spectrum disorder; demyelinating diseases anti-N-methyl-D-aspartate receptor encephalitis; multiple sclerosis; myelin oligodendrocyte glycoprotein antibody-associated disease; overlapping syndromes.

Figure 1

Flowchart of the study. *Reviews and articles describing patients with a single disease were excluded. **Articles describing patients without key information or aquaporin-4-antibody-negative NMOSD were excluded. There were 15, 18, and 46 NMDARe patients overlapped with MS, AQP4-Ab-positive NMOSD, and MOGAD, respectively.

Figure 2

Details of the sequence of onset in patients with overlapping AQP4-Ab-positive NMOSD or MOGAD. NMDARe, anti-N-methyl-d-aspartate receptor encephalitis; AQP4-Ab-positive NMOSD, aquaporin-4-antibody-positive neuromyelitis optica spectrum disorder; MOGAD, myelin oligodendrocyte glycoprotein antibody-associated disease; NMOSD, neuromyelitis optica spectrum disorder.

Figure 3

Frequencies of atypical symptoms. Sensory disturbance was the most common atypical symptom in patients overlapping with AQP4-Ab-positive NMOSD; limb weakness was the most common atypical symptom in patients overlapping with MOGAD.

Figure 4

Frequencies of MRI lesions in overlapping syndromes. *No basal ganglia involvement in patients overlapped with MS, p = 0.016. Unclassified meant no specific details of MRI abnormalities in original references. White matter refers to all parts of the brain except the paraventricular white matter. Multifocal, infratentorial, and spinal cord involvement all were common in the three overlapping syndromes. Periventricular white matter was the most common lesion site in NMDARe overlapping with MS; periventricular white matter and the temporal lobe were the most common lesion sites in NMDARe overlapping with AQP4-Ab-positive NMOSD; the temporal lobe was the most common lesion site in NMDARe overlapping with MOGAD.