FLAMES overlaying anti-N-methyl-D-aspartate receptor encephalitis: a case report and literature review

Abstract

Background: In recent years, simultaneous or sequential occurrence of MOG antibody disease and anti-NMDAR encephalitis in the same patient has been reported with increasing frequency. Scholars refer to the overlapping occurrence of these two disorders as MOG antibody disease and anti-NMDAR encephalitis overlap syndrome (MNOS). Cortical T2-weighted fluid-attenuated inversion recovery (FLAIR) -hyperintense lesions in anti-MOG-associated encephalitis with seizures (FLAMES) is a rare clinical phenotype of MOGAD in which cortical FLAIR high-signal lesions are unilateral, with little spread to the cortex and meninges bilaterally. Although cases of FLAMES have been consistently reported. However, to our knowledge, such cases of FLAMES combined with NMDARE are rare.

Case presentation: Here, we describe a case of FLAMES combined with anti-NMDARE. The patient was a young male, 29 years old, admitted to our hospital with isolated seizures, whose MRI showed unilateral thalamic and bilateral frontal and parietal leptomeningeal involvement. Since we were unaware of the possibility of bilateral meningo-cortical MOGAD manifestations, the case was initially diagnosed as viral encephalitis and was given antiviral therapy. The diagnosis was not clarified until anti-NMDAR-IgG and MOG-IgG positivity was detected in the cerebrospinal fluid and serum. The patient was then treated with high-dose corticosteroids and his symptoms responded well to the steroids. Therefore, this case expands the clinical spectrum of MNOS overlap syndrome. In addition, we describe the clinical features of MNOS by summarizing the existing literature and exploring the possible mechanisms of its immune response.

Conclusions: Our case serves as a reminder to clinicians that when patients present with atypical clinical manifestations such as seizures, consideration should be given to MNOS and conduct testing for various relevant autoantibodies (including MOG abs) and viruses in both serum and cerebrospinal fluid, as it is easy to misdiagnose the disease as other CNS diseases, such as viral meningoencephalitis. This syndrome exhibits a high responsiveness to steroids, highlighting the critical importance of recognizing the clinical and neuroimaging features of this overlap syndrome for prompt diagnosis and treatment. Furthermore, it enriches the disease spectrum of MNOS.

Keywords: Anti-N-methyl-D-aspartate receptor; Autoimmune encephalitis; FLAMES; Seizures.

Fig. 1

Brain MRI performance. A-B The MRI data of the patient 6 days after the symptom onset showed hyperintensity of the right thalamus on T2-weighted imaging (red arrows), and the pia mater is strengthened( yellow arrows). C-D Brain MRI scan performed 168 days after the initial symptom onset depicted a significant improvement in the imaging abnormality

Fig. 2

Examination of NMDAR and MOG antibodies in cerebrospinal fluid and serum of our patient. Positive antibodies were confirmed by HEK293 transfected cells via the indirect immunofluorescence method (fixed cell-based assay). MOG-ab uses full-length human MOG to detect MOG-IgG (secondary antibody: IgG Fc). A-D CSF NMDAR and MOG antibodies were positive (titer 1:10 and 1:3.2, respectively) while serum NMDAR and MOG antibodies were positive (titer 1:10 and 1:32, respectively) on day 8. E-L Recheck the antibody on day 168. CSF (E, F) and serum (G, H) NMDAR antibodies were positive (titer 1:1 and 1:10, respectively) while CSF (I, J) and serum (K, L) MOG antibodies were negative and positive (titer 1:10), respectively. All images have a scale of 40X

Fig. 3

Timeline with clinical manifestation, treatment progression, and diagnosis time. EEG: Electroencephalograph; MRI: Magnetic Resonance Imaging; IVMP: Intravenous methylprednisolone; Abs, antibodies; WBC: white blood cell; CSF: cerebrospinal fluid; NMDAR: Anti-N-methyl-D-aspartate receptor; MOG: Myelin oligodendrocyte glycoprotein

Fig. 4

Ilustrates the potential pathogenesis of anti-NMDAR and MOG biantibody-positive autoimmune encephalitis. When immune cells directly attack oligodendrocytes, immune reconstitution resulting from withdrawal or dosage reduction as well as virus destroy the blood–brain barrier, NMDAR and MOG antigens are exposed and presented by antigen presenting cells, followed by T and B cell activation, leading to the production of anti-NMDAR and MOG double antibodies, resulting in demyelination and NMDAR invagination degradation, and eventually neuronal death