Four weeks later, the patient's visual acuity was 20/25, right eye, and 20/20, left eye. Panel D-15 testing revealed random crossing in both eyes (Fig. 2B). The patient lacked all stereo perception with the Titmus stereo test and was still unable to recognize faces (VPTA score 12/16), even her family members. Voice recognition allowed her to recognize her family and distinguish men from women. The patient demonstrated partially impaired visual object recognition (VPTA score 7/16), but could recognize an object correctly when holding it in her hands (VPTA score 1/16). Kinetic perimetry revealed small paracentral scotomas in each eye, and optical coherence tomography (3D-OCT 2000; Topcon Corp., Tokyo, Japan) revealed no abnormal findings of the macula or optic nerve. Fourteen weeks after her referral to our institution, the patient's visual acuity was 20/20 in both eyes, and kinetic perimetry was normal. She could recognize colors, faces, and objects. Panel D-15 testing revealed a normal minor transpositional error in the right eye and normal perfect arrangement in the left eye (Fig. 2C). Titmus tests revealed that her stereo acuity had improved to 40 seconds of arc. VPTA results were in the normal range for object recognition, face recognition, reading, and describing topography. Over 1 year of follow-up, the patient has remained stable and brain MRI findings remained unchanged.
Anti-NMDAR encephalitis has characteristic clinical features of memory disturbance, psychiatric symptoms, seizures, involuntary movements, abnormal eye movements, central hypoventilation, and dysautonomia (1,2,6). Recent reports have suggested that the pathogenesis of anti-NMDAR encephalitis involves antibodies against the GluN1 subunit of the NMDAR, which deplete the NMDAR clusters on neurons, resulting in dysfunction of signal transmission mediated by glutamatergic synapses (1,2,7–10). Involvement of cortical or subcortical structures is postulated to cause specific clinical symptoms: memory disturbances, psychiatric symptoms, and seizures are likely due to dysfunction in the cortical frontal and/or temporal lobes (1,2,11,12), and involuntary movements and central hypoventilation due to dysfunction in the subcortical structures of the basal ganglia or brainstem (3,13,14).
Our patient demonstrated a variety of visual impairments. Color sensation, face recognition, object recognition, and stereopsis are higher-order visual functions in which information is processed in distinct regions of occipital, occipitotemporal, and occipitoparietal cortices and segregated dorsal and ventral streams (15–19). Damage to these cortical visual processing regions causes specific clinical findings depending on which part of the cortex is involved (20,21). For example, loss of stereopsis is caused by bilateral occipitoparietal lesions (21), while prosopagnosia and cerebral dyschromatopsia are caused by bilateral lesions of the fusiform gyri (16,21). Our patient may have developed complex visual impairments due to prolonged dysfunction of signal transmission in occipitotemporal and occipitoparietal cortices. PET revealed hypometabolism in both occipital lobes, a pattern previously reported in anti-NMDAR encephalitis (22). We postulate that the hypometabolic regions included the fusiform gyri bilaterally contributing to our patient's visual impairment. The white matter hyperintensity detected on MRI is unlikely a cause of visual dysfunction as it remained unchanged throughout the clinical course.
Tumor removal and immunotherapy are proposed treatments for anti-NMDAR encephalitis in patients with neoplastic disease (2,23). Early tumor removal results in a better clinical outcome (2,11), especially within 4 months of the appearance of neurological symptoms (1). In our case, removal of the ovarian teratoma and retroperitoneal ganglioneuroma was performed within 2 months of symptoms onset. In patients that lack response to first-line therapy or failure to detect a tumor, additional management options include rituximab (2,24,25).
We thank Professor Josep Dalmau (Institució Catalana de Recerca I Estudis Avançats (ICREA), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Service of Neurology, Hospital Clinic, University of Barcelona and Department of Neurology, University of Pennsylvania) for analysis of the antibodies against NMDA receptor. We also thank Ms. S Umezaki (occupational therapist) for conducting repeated VPTA.
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