Cortical encephalitis with overlapping anti-N-methyl-D-aspartate receptor and anti-myelin oligodendrocyte glycoprotein antibodies: report of two cases
Autoimmune brain diseases can be complex—especially when two distinct conditions overlap. A 2020 study from Shanghai Jiao Tong University’s Renji Hospital details two rare cases where patients tested positive for antibodies linked to both anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis (a serious immune attack on brain cells) and anti-myelin oligodendrocyte glycoprotein (MOG) antibodies (which damage the protective coating around nerve fibers). The findings shed light on how these diseases interact and why diagnosis can be challenging.
The study was led by Mei-Chun Gao, Xiao-Ying Yao, Jie Ding, Ying Zhang, and Yang-Tai Guan from the Department of Neurology at Renji Hospital, School of Medicine, Shanghai Jiao Tong University, and published in the Chinese Medical Journal.
What Are These Antibodies?
To understand the cases, it helps to break down the key terms:
- Anti-NMDAR encephalitis (NMDARE): A potentially life-threatening autoimmune disease where antibodies attack NMDARs—proteins in the brain that regulate memory, mood, and movement. Symptoms often include psychosis, memory loss, uncontrollable movements, or trouble breathing.
- Anti-MOG antibodies: These target MOG, a protein made by oligodendrocytes (cells that produce myelin, the “insulation” for nerve fibers). High MOG antibody levels are linked to inflammatory demyelinating diseases (IDDs), like optic neuritis (eye nerve inflammation) or brain lesions.
Case 1: A 32-Year-Old Man with Demyelinating Attacks
A 32-year-old Chinese man was admitted to Renji Hospital with sudden headache, fever, and a seizure. Brain MRI showed high-intensity lesions (abnormal signals indicating inflammation) in his right temporal (memory), parietal (sensation), and occipital (vision) lobes. His spinal fluid (CSF)—a clear liquid that surrounds the brain and spinal cord—had elevated pressure, more white blood cells than normal, and high protein levels: all red flags for brain inflammation.
Tests ruled out common viruses (herpes simplex, Epstein-Barr, cytomegalovirus) and initial cell-based assays (lab tests to detect specific antibodies) found no signs of autoimmune encephalitis, demyelinating diseases, or cancer-linked neurological syndromes. He was treated with antiviral medication (acyclovir) and a steroid (dexamethasone), which temporarily improved his CSF and symptoms. But his headache and fever returned 3 weeks later.
A second round of steroids (methylprednisolone, 80 mg/day for 5 days) cleared his MRI abnormalities and normalized his CSF. Six months later, he came back with numbness in his right side and left arm. New MRI lesions appeared in his medulla oblongata (brainstem, which controls vital functions like breathing) and right temporal lobe. He received three months of intravenous immunoglobulin (IVIG)—a therapy that uses healthy antibodies to calm the immune system—plus azathioprine (an immunosuppressant), and stabilized.
Six months later, he developed orbital pain and vision loss in his left eye. MRI revealed new inflamed lesions in his brainstem and left optic nerve. This time, tests showed:
- High MOG antibody levels: 1:320 in his blood, 1:32 in his CSF.
- Low NMDAR antibody levels: 1:1 in his CSF (none in his blood).
He received more IVIG and steroid injections near his eye (retrobulbar methylprednisolone). Over a year, his vision partially recovered—from counting fingers at 30 cm to 0.6—but never returned to normal. He had no more seizures.
Case 2: A 50-Year-Old Man with 15 Years of Seizures
A 50-year-old Chinese man had a 15-year history of headaches, fever, and seizures, originally diagnosed as viral encephalitis. His seizures were well-controlled until 2011, when they returned. MRI showed abnormal signals in his left insula (a brain region for emotion and taste) and parietal lobe (sensation). He also had brief visual and auditory hallucinations, which stopped after taking anti-seizure drugs (carbamazepine and levetiracetam). A neurosurgeon suspected gray matter heterotopia (abnormal brain cell placement) and performed a parietal lobotomy (surgical removal of part of the parietal lobe).
In 2017, he was admitted to Renji Hospital’s CNS demyelinating disease registry with new symptoms: progressive memory loss, extreme sleepiness, visual hallucinations, and abnormal behavior. MRI revealed multiple enhancing lesions (areas that lit up with contrast dye, indicating active inflammation) in his left temporal lobe (memory), hippocampus (learning), and right basal ganglia (movement).
Tests found:
- NMDAR antibodies: 1:100 in his blood, 1:32 in his CSF.
- MOG antibodies: 1:32 in his blood, 1:10 in his CSF.
- Past viral exposure: IgG antibodies to cytomegalovirus and Epstein-Barr virus in his CSF (signs of prior infection, not active disease).
Cancer screening and autoimmune disease tests were negative. He received pulse intravenous methylprednisolone (1000 mg/day for 5 days)—a high-dose steroid to reduce inflammation—plus IVIG (0.4 g/kg daily for 5 days). His symptoms gradually improved. He now takes maintenance medications: oral prednisone (steroid), azathioprine (immunosuppressant), olanzapine (antipsychotic), and anti-seizure drugs (oxcarbazepine, levetiracetam) with no adverse effects.
Why These Cases Matter
NMDARE and MOG-related IDDs usually occur separately, but these two cases show they can overlap—and that diagnosis is often delayed. Here’s what we learned:
- Antibody tests aren’t always positive at first: Patient 1’s NMDAR and MOG antibodies weren’t detected until his third admission. Patient 2’s tests weren’t available until 2014 (when cell-based assays for autoimmune encephalitis became standard in Shanghai).
- Viruses may trigger autoimmunity: Studies show ~30% of herpes simplex encephalitis patients without tumors develop NMDAR antibodies. This suggests viruses could “prime” the immune system to attack the brain.
- Antibody levels may match symptoms: Patient 1 had higher MOG antibodies (linked to his demyelinating attacks, like optic neuritis). Patient 2 had higher NMDAR antibodies (linked to his NMDARE-like symptoms: memory loss, hallucinations).
- Oligodendrocytes have NMDARs: The cells that make myelin (oligodendrocytes) also express NMDARs. This means an immune response targeting one could accidentally hit the other—explaining why both antibodies might appear together.
Key Takeaways for Patients and Doctors
These cases highlight the complexity of autoimmune brain diseases. For doctors, the message is clear: test for both NMDAR and MOG antibodies in patients with unclear encephalitis or demyelination—even if initial results are negative. For patients, it’s a reminder that rare overlapping conditions exist, and persistence in diagnosis can lead to better care.
The study, “Cortical encephalitis with overlapping anti-N-methyl-D-aspartate receptor and anti-myelin oligodendrocyte glycoprotein antibodies: report of two cases,” was published in the Chinese Medical Journal in 2020 by Mei-Chun Gao, Xiao-Ying Yao, Jie Ding, Ying Zhang, and Yang-Tai Guan from the Department of Neurology at Renji Hospital, School of Medicine, Shanghai Jiao Tong University.
For more details, access the original study here: doi.org/10.1097/CM9.0000000000000894
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