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Table of Contents    
Year : 2020  |  Volume : 68  |  Issue : 2  |  Page : 474-477

Optic Neuritis Associated with Anti-NMDA Receptor Antibody in the Remission Phase of Anti-NMDA Receptor Encephalitis

1 Department of Pediatric Neurology, Sichuan Provincial Hospital for Women and Children, Chengdu 610045, People's Republic of China
2 Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, People's Republic of China
3 Department of Pediatrics, Sichuan Provincial Hospital for Women and Children, Chengdu 610045, People's Republic of China
4 Department of Neurology, Children's Hospital of Chongqing Medical University, Chongqing 400014, People's Republic of China

Date of Web Publication15-May-2020

Correspondence Address:
Tingsong Li
Department of neurology, Children's Hospital of Chongqing Medical University, 136 Zhongshan 2 Road, Chongqing 400014
People's Republic of China
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.283754

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 » Abstract 

Optic neuritis is an inflammatory demyelinating disorder of the central nervous system. Anti-NMDA receptor (NMDAR) antibodies encephalitis is also mediated by the inappropriate immunological response. We report a girl who was readmitted because of unilateral eye pain and vision impairment in the remission period of anti-NMDAR encephalitis. Based on the limited available literature on the treatment of optic neuritis associated with anti-NMDA receptor antibody, she was treated with a combination of corticosteroids and intravenous immunoglobulin with clinical improvement. Optic neuritis in the remission phase of anti-N-methyl-D-aspartate receptor encephalitis remains relatively uncommon. It is important to document and follow these patients to understand the pathogenesis of optic neuritis in the setting of anti-NMDAR encephalitis and formulate effective therapeutic strategies.

Keywords: Anti-NMDAR antibodies, children, encephalitis, optic neuritis

How to cite this article:
Liu X, Giri M, Ling W, Li T. Optic Neuritis Associated with Anti-NMDA Receptor Antibody in the Remission Phase of Anti-NMDA Receptor Encephalitis. Neurol India 2020;68:474-7

How to cite this URL:
Liu X, Giri M, Ling W, Li T. Optic Neuritis Associated with Anti-NMDA Receptor Antibody in the Remission Phase of Anti-NMDA Receptor Encephalitis. Neurol India [serial online] 2020 [cited 2022 May 17];68:474-7. Available from: https://www.neurologyindia.com/text.asp?2020/68/2/474/283754

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a newly recognized antineuronal antibody-mediated inflammatory brain disease characterized by psychosis, seizures, various movement disorders, and autonomic system disturbances.[1] Optic neuritis (ON) is an acute inflammatory demyelinating disorder of the central nervous system.[2] ON and anti-NMDA encephalitis shares similar pathophysiology which is based on immune-mediated neuronal dysfunction. It has been reported that anti-NMDAR encephalitis can occur followed by ON subsequently or simultaneously.[1],[2] A patient with both diseases, separately or simultaneously, is rare as a clinical phenomenon but cannot be ignored. Till date, only six cases have been reported in the literature [Table 1]. Here, we report a rare case of a 7-year-old girl presenting solely with ON associated with anti-NMDAR antibody at the remission phase of anti-NMDA receptor encephalitis.
Table 1: Reported cases of optic neuritis associated with anti.NMDA receptor antibody including the current case

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 » Case History Top

A 7-year-old girl was admitted to the hospital because of cognitive impairment, psychiatric symptoms, and involuntary limb movements without vision impairment and limb paralysis (March 2017). At the time of her initial examination, she manifested irritability and limb trembling followed by dyssomnia, paroxysmal acousma and photism, and athetosis. On her admission, disturbance in consciousness and involuntary limb movement was prominent. Cerebro spinal fluid (CSF) cell count and chemistry evaluation were within the normal range. No abnormal signals were found in the cranial MRI (magnetic resonance imaging) [Figure 1]a. Electroencephalography (EEG) study revealed excessive β activities. The anti-NMDARIgG (immunoglobulin G) in both serum and CSF sample of patient was positive [Table 2].
Figure 1: Cranial magnetic resonance imaging (MRI).(a) Showing normal right optic nerve during first admission. (b) Showing right optic nerve edema during second admission

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Table 2: Titres of anti.NMDAR antibody in two episodes

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Serum tumor markers were within the normal range. The patient was diagnosed as anti-NMDAR encephalitis. Once the diagnosis was established, the patient was treated simultaneously with intravenous IgG (0.5 g/kg/day) and methylprednisolone (20 mg/kg/day) for 4 days, then followed by oral prednisone (1.5 mg/kg/day) and, subsequently demonstrated gradual improvement in cognitive function, psychiatric, and neurological symptoms. One month later, the patient was symptom-free. After three months of full dose, oral prednisone was tapered gradually. Five months after the initial diagnosis of anti-NMDAR encephalitis, when the dose of prednisone was reduced to 0.5 mg/kg/d, she was readmitted to the hospital because of visual loss in the right eye for four days, preceded by pain with the eye movement for six days. At this episode, the patient had no signs and symptoms of limbic system involvement. The visual acuity in the right eye was 4.0 at 0.5 m in the standard logarithmic visual acuity chart and that in the left eye was 5.0 at 5 m. Visual field examination demonstrated central scotoma in the right eye and peripheral constriction in the left eye. Intraocular pressure (IOP) was 18 mmHg in the right eye and 16 mmHg in the left eye. Ophthalmoscopy showed marked right optic disc swelling, tortuosity, and dilation of retinal veins [Figure 2]. Visual evoked potential (VEP) demonstrated abnormalities as a prolonged latent period without the alteration of amplitude in the right eye [Figure 3]. Neuromyelitis optica spectrum disorder and multiple sclerosis-associated demyelinated disorders were ruled out.
Figure 2: Fundus examination by ophthalmoscope showing right optic disc edema

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Figure 3: Patterns of visual evoked potential (a) Showing the peak time of the right eye is prolonged and the amplitude is decreased. (b) Showing the peak time of the left eye is normal and the amplitude is decreased

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Tests were performed to rule out infectious disease, auto-immune diseases, and tumor. The cranial MRI [Figure 1]b revealed the right optic nerve edema. Meanwhile, the titre of anti-NMDAR antibody (Ab) was reevaluate and the results showed that it increased higher in CSF than in the first episode with anti-NMDAR encephalitis, on the contrary, the titer in the serum decreased [Table 2]. Based on the unilateral visual loss, eye pain, swollen optic disc, absence of anti-aquaporin-4 (AQP4) Ab, anti-myelin oligodendrocyte glycoprotein (MOG) Ab and abnormal signal in MRI, the patient was diagnosed as typical ON.[1] Therefore, the patient received intravenous IgG and methylprednisolone in the same dose as the first event, followed by oral prednisone (1.5 mg/kg/day). Five days later, her visual acuity in the right eye recovered to 5.0 at 5 m. The patient felt better and could feel the existence of physical surroundings. The eyes and vision were completely free from the symptom in 1-month post initial immunotherapy. The fundus examination and VEP both recovered fully at that time [Figure 4]. After 12 months of follow-up, the visual acuity in the eyes was 5.0 at 5 m. Until now, the prednisone has been withdrawn for 18 months and had no relapse of ocular and psychiatric symptoms.
Figure 4: Fundus examination by ophthalmoscope showing bilateral optic papilla is normal

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 » Discussion Top

Our patient presented ON in the setting of anti-NMDAR antibodies encephalitis leading us to discuss a possible involvement of anti-NMDAR antibodies in the genesis of optic neuritis. According to the diagnosis criteria, the patients were diagnosed with typical optic neuritis.[2] Multiple sclerosis-associated with ON (MS-ON) and ON associated with neuromyelitis optica (NMO-ON) were excluded. Good response to immunosuppressive drugs also supported this diagnosis. To our knowledge, there have been six reported cases of patients with NMDA encephalitis with concomitant ON [Table 1].

Our case is unique because this is the first case of ON occurring in the remission period of anti-NMDAR encephalitis. It has been suggested that pediatric ON can be a manifestation of an underlying systematic demyelination disorder harboring acute disseminated encephalitis (ADEM), neuromyelitis optica (NMO), and multiple sclerosis.[3] In our patient, the normal MRI of the brain and spinal cord excluded the diagnoses of ADEM and NMO. One retrospective study from North Korea demonstrated that the risk of developing multiple sclerosis after pediatric ON was low (7.7%).[4] Meanwhile, abnormal MRI, age of10 years or greater and bilateral simultaneous or sequential ON were a significant risk factor for progression to multiple sclerosis.[3],[5] In contrast, no such risk factors were found in our patient. Previous reports[6],[7] have described two cases diagnosed with ON superimposed on the typical symptoms of NMDAR encephalitis, while the present case manifested with ocular symptoms only, without presentation of psychiatric symptom, seizure, and involuntary movements. Kruer et al.[8] described a girl aged 15 years diagnosed with NMDAR encephalitis, initially suffered relapses with longitudinally extensive transverse myelitis (LETM) as well as ON with negative findings of AQP4 antibody. Similarly, the study of AQP4 in serum and CSF, as well as white matter lesions in our patient were both negative indicating that the anti-NMDAR Ab may play a role in the inflammatory demyelination in the optic nerve.

Recently, Yang et al. reported that encephalitis associated with anti-NMDAR Ab can mimic neuromyelitis optica involving ON and transverse myelitis.[9] In line with previous reports,[6],[7],[8],[9],[10] steroid pulse therapy was effective for the treatment of ON accompanied by encephalitis in our patient. Moreover, Ran et al. also described a male patient with anti-NMDAR encephalitis followed by seropositive neuromyelitis optica spectrum disorder which responded well to the intravenous corticosteroid combined with plasma exchange.[11]

Nevertheless, the exact pathophysiology of anti-NMDAR Ab involving the clinical manifestations of anti-NMDAR encephalitis and ON sequentially is to be explored. The six previous reports described that ON resolved only with corticosteroid pulse therapy [Table 1]. Although there are no approved guidelines for the treatment of pediatric ON, corticosteroids and intravenous immunoglobulin are still recommended as acute treatment options.[2],[5] In the present study, our patient responded well to the immunotherapy and showed favorable prognosis, as other cases were mediated by non-anti-NMDAR.[4] In patients who experience adverse reactions to or in whomfirst-line treatment options fail, second-line line immunotherapy therapy, most commonly rituximab and/or cyclophosphamide may be potentially attractive immunosuppressive agents of choice.[2]

In conclusion, the anti-NMDAR Ab may play an important role in the pathogenesis of ON in the setting of anti-NMDAR encephalitis. Immunotherapy is an effective option as an acute treatment, and the prognosis is favorable.

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Conflicts of interest

There are no conflicts of interest.

 » References Top

Dalmau J, Lancaster E, Martinez-Hernandez E, Rosenfeld MR, Balice-Gordon R. Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurol 2011;10:63-74.  Back to cited text no. 1
Toosy AT, Mason DF, Miller DH. Optic neuritis. Lancet Neurol 2014;13:83-9.  Back to cited text no. 2
Collinge JE, Sprunger DT. Update in pediatric optic neuritis. Curr Opin Ophthalmol 2013;24:448-52.  Back to cited text no. 3
Kim YM, Kim HY, Cho MJ, Kwak MJ, Park KH, Yeon GM, et al. Optic neuritis in Korean children: Low risk of subsequent multiple sclerosis. Pediatr Neurol 2015;53:221-5.  Back to cited text no. 4
El-Dairi MA, Ghasia F, Bhatti MT. Pediatric optic neuritis. Int Ophthalmol Clin 2012;52:29-49.  Back to cited text no. 5
Ishikawa N, Tajima G, Hyodo S, Takahashi Y, Kobayashi M. Detection of autoantibodies against NMDA-type glutamate receptor in a patient with recurrent optic neuritis and transient cerebral lesions. Neuropediatrics 2007;38:257-60.  Back to cited text no. 6
Motoyama R, Shiraishi K, Tanaka K, Kinoshita M, Tanaka M. Anti-NMDA receptor antibody encephalitis with recurrent optic neuritis and epilepsy. Rinsho Shinkeigaku 2010;50:585-8.  Back to cited text no. 7
Kruer MC, Koch TK, Bourdette DN, Chabas D, Waubant E, Mueller S, et al. NMDA receptor encephalitis mimicking seronegative neuromyelitis optica. Neurology 2010;74:1473-5.  Back to cited text no. 8
Yang HK, Kim JH, Park YH, Park KS, Kim JS, Hwang JM. Anti-NMDA-receptor optic neuritis in a patient with a history of encephalitis. Can J Ophthalmol 2017;52:e216-8.  Back to cited text no. 9
Mugavin M, Mueller BH, Desai M, Golnik KC. Optic neuropathy as the initial presenting sign of N-methyl-d-aspartate (NMDA) encephalitis. Neuroophthalmology 2017;41:90-3.  Back to cited text no. 10
Ran Y, Wang L, Zhang F, Ao R, Dong Z, Yu S. Anti-NMDAR encephalitis followed by seropositive neuromyelitis optica spectrum disorder: A case report and literature review. Clin Neurol Neurosurg 2017;155:75-82.  Back to cited text no. 11


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

  [Table 1], [Table 2]

This article has been cited by
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Neuro-Ophthalmology. 2022; : 1
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2 A Pediatric Case of Anti-N-methyl-D-aspartate Receptor Encephalitis Associated With Optic Neuritis
Jia Yue You, Caroline Lacroix, Daniela Toffoli
Journal of Neuro-Ophthalmology. 2022; 42(1): e289
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