Anti-NMDA Receptor Encephalitis Presenting with Prosopagnosia

A Caucasian male in his 60s with a history of hypertension, hyperlipidemia, and coronary artery disease presented to the emergency department with a 2-week history of altered mental status, headache, and memory loss. His wife also reported mild forgetfulness, headaches, worsening recently with consistent headaches, severe memory loss, and excessive sleeping (12–18 h/day). Magnetic resonance imaging (MRI) showed increased fluid attenuated inversion recovery signal abnormalities in the bilateral mesial temporal lobes, thalamus, and anterior pons, along with patchy contrast enhancement. Electroencephalogram revealed mild diffuse encephalopathy and intermittent focal slowing over the left frontal–temporal–central region. Positron emission tomography (PET) scan done was unremarkable for any underlying neoplasm. A brain biopsy indicated encephalitis, and a lumbar puncture showing mild pleocytosis of white blood cell counts confirmed anti-N-methyl-D-aspartate (NMDA) receptor encephalitis (NMDARE). All the alternative causes of the encephalitis were ruled out. This satisfies the Graus et al.[1] 2016 criteria for autoimmune encephalitis diagnosis. He received intravenous immunoglobulin and plasmapheresis as acute treatment. For maintenance, he was discharged on oral prednisone and several rituximab infusions for a year before he relapsed and started complaining about face recognition.

Following 1 year after the diagnosis with NMDARE, he complained of difficulty recognizing faces (prosopagnosia), along with persistent moderate forgetfulness. Mental status examination showed moderate cognitive impairment. A repeat MRI of the brain [Figure 1a–c] revealed persistent enhancement and marked atrophy in the bilateral temporal lobes, including the hippocampal gyrus, fusiform gyrus, and inferior temporal gyrus, and also enlargement of ventricles because of atrophy. Hence, prednisone dose was increased and mycophenolate mofetil was added, but there was not any improvement initially. Later, we started on cyclophosphamide infusions. Thereafter, he reported cognitive improvement, but struggled with face recognition. Hence, he was continued on mycophenolate mofetil; he showed better recognition and memory of known faces on follow-up now at almost 4 years after the onset of autoimmune encephalitis.

Figure 1.

(a): Coronal section T2 FLAIR MRI shows atrophy in the bilateral temporal lobes including the fusiform gyrus (yellow * mark). (b) Transverse T1 MRI shows atrophy of the temporal lobe including the hippocampal gyrus (yellow * mark), fusiform gyrus (pink * mark), and inferior temporal gyrus (blue * mark), with the expansion of ventricles. (c) Sagittal T1 FLAIR abnormality atrophy of the temporal lobe including the hippocampal gyrus (yellow * mark), fusiform gyrus (blue * mark), and inferior temporal gyrus (violet * mark). FLAIR: fluid attenuated inversion recovery, MRI: magnetic resonance imaging

Prosopagnosia typically involves the fusiform gyrus, anterior temporal cortex, or both as was seen in our case.[2] The fusiform gyrus, part of Brodmann area 37, is crucial for high-level visual functions like face perception, object recognition, and reading.[3] Therefore, it is imperative to address this imaging finding within the context of anti-NMDA receptor encephalitis, given its exceptionally rare presentation in this form of autoimmune encephalitis. Typically, anti-NMDA receptor encephalitis does not manifest with atrophy of the fusiform gyrus. However, the observed atrophy in our case underscores the necessity of regular MRI monitoring specifically targeting this region.

Upon comparing Figure 1c sagittal section reveals three distinct regions dividing the temporal lobe: the hippocampal gyrus, fusiform gyrus, and inferior temporal gyrus, each highlighted in Figure 1c with distinct asterisk (*) markers. Attention should particularly focus on the area marked for the fusiform gyrus, demonstrating pronounced atrophy associated with the patient’s prosopagnosia.

As such, there are only three reported cases of prosopagnosia associated with anti-NMDA autoimmune encephalitis in the literature, all occurring in females aged 19, 20, and 23 years.[4,5,6] The presence of prosopagnosia in this encephalitis is exceedingly rare. This condition is attributed to abnormalities in the temporal lobes and fusiform gyrus, as observed in our case. Notably, our case involves a male in his 60s, contrasting with the young female demographic reported in the literature, highlighting another aspect of its rarity. In addition, there were no associated tumors in our patient, as confirmed by a PET scan, which contrasts with the literature cases where neoplasms were present.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.