- Email: [email protected]
Optic perineuritis with anti-myelin oligodendrocyte glycoprotein antibody
Multiple Sclerosis and Related Disorders 38 (2020) 101444
Contents lists available at ScienceDirect
Multiple Sclerosis and Related Disorders journal homepage: www.elsevier.com/locate/msard
Case report
Optic perineuritis with anti-myelin oligodendrocyte glycoprotein antibody a,⁎
a
b
T
b
Mitsugu Yanagidaira , Takaaki Hattori , Hirofumi Emoto , Motohiro Kiyosawa , ⁎ Takanori Yokotaa, a b
Department of Neurology and Neurological Sciences, Tokyo Medical and Dental University, Graduate School of Medical and Dental Sciences, Japan Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University, Graduate School of Medical and Dental Sciences, Japan
A R T I C LE I N FO
A B S T R A C T
Keywords: Myelin oligodendrocyte glycoprotein MOG Optic perineuritis Disc swelling
A 25-year-old male presented with blurred peripheral vision and movement pain in his right eye. Fundus examination revealed unilateral disc swelling in his right eye with normal intracranial pressure. MRI showed remarkably high intensity in the optic nerve sheath and slightly high intensity in the optic nerve, indicating optic perineuritis (OPN). Anti-myelin oligodendrocyte glycoprotein (MOG) antibody was positive in both serum and cerebrospinal fluid. The patient responded promptly to corticosteroid treatment. OPN can be associated with the presence of anti-MOG antibody.
1. Case description A previously healthy 25-year-old male experienced 5 days of pain on eye movement and blurred peripheral vision in his right eye. On examination, relative afferent pupillary defect (RAPD) was positive in his right eye. His neurological signs were otherwise normal. He had no history of preceding infection or recent vaccination. His best corrected visual acuity was 1.5 in both eyes. A fundus examination and optical coherent tomography revealed disc swelling in his right eye (Figure 1A) but a normal disc and retina in the left eye. A visual field test showed inferonasal visual field loss with spared central vision. In a pattern-reversal visual evoked potential study, P100 latency was bilaterally normal. IgG4, anti-aquaporin 4 (AQP4) antibody, anti-nuclear antibody, anti-neutrophil cytoplasmic antibody, anti-Sjögren-syndrome-related antigen A/B, Treponema pallidum–specific antibody, angiotensin-converting enzyme, C-reactive protein, erythrocyte sedimentation rate, and D-dimer were all negative or within normal limits. Cerebrospinal fluid (CSF) opening pressure was normal (15.5 cm H2O) with the patient in the recumbent position. Cell count (3/mm2), total protein (44 mg/dL), and myelin basic protein were within normal limits. CSF was negative for oligoclonal bands. The IgG index was 0.82. CSF was negative for herpes simplex virus type 1 and 2, varicella zoster virus, cytomegalovirus, and Epstein-Barr virus by PCR. In a cell-based assay, anti-myelin oligodendrocyte glycoprotein (MOG) antibody was positive in the serum at 1:4096 dilution (normal is less than 1:64) and in the CSF at 1:8 (normal is less than 1:2). AntiAQP4 antibody was negative in CSF. ⁎
Orbital MRI with short tau inversion recovery (STIR) sequence demonstrated remarkably high intensity in the right optic nerve sheath and mildly high intensity in the optic nerve (Figure 2), suggesting optic perineuritis (OPN). No other abnormal findings were observed on brain and cervical spine MRIs. The patient was diagnosed with OPN on the basis of the spared central vision and high intensity in the optic nerve sheath on MRI with STIR sequence (1A). Intravenous methylprednisolone (1 g/day) was administered for 3 days from day 5 after onset, followed by oral prednisolone treatment (1 mg/kg/ day). Two days after the start of corticosteroid administration, the patient's pain on eye movement had dramatically improved and the RAPD became negative. By day 6 after treatment initiation, the disc swelling had disappeared (Figure 1B) but inferonasal visual loss remained. The corticosteroid dosage was tapered to 10 mg/day over 3 months, with no relapse in the following 4 months. 2. Discussion Here, we have reported an unusual case of OPN associated with anti-MOG antibody. Previously optic neuritis (ON) associated with antiMOG antibody were reported. The distinction between ON and OPN is important in terms of both understanding pathogenesis and predicting treatment response and prognosis: patients with OPN less frequently develop multiple sclerosis and are more responsive to steroid treatment than those with ON (Osborne BJ, 2009). Although ON patients with anti-MOG antibody can have contrast enhancement in the optic nerve sheath concurrent with predominant contrast enhancement in the optic nerve, our patient had predominantly high intensity in the right optic
Corresponding author. E-mail address: [email protected] (T. Yokota).
https://doi.org/10.1016/j.msard.2019.101444 Received 17 January 2019; Received in revised form 9 October 2019; Accepted 12 October 2019 2211-0348/ © 2019 Elsevier B.V. All rights reserved.
Multiple Sclerosis and Related Disorders 38 (2020) 101444
M. Yanagidaira, et al.
Figure 1. Fundus examination revealed disc swelling in the right eye before treatment (A), but it had disappeared by day 6 after treatment initiation (B).
in OPN remains unknown. Here, we consider 3 possibilities for the pathogenesis of this case. First, although anti-MOG antibody causes inflammation targeting MOG protein expressed in oligodendrocytes in the optic nerve, the inflammation may have extended to the optic nerve sheath, leading to high intensity of the optic sheath on MRI with STIR sequence. Second, 2 cases of aseptic meningitis with anti-MOG antibody have been reported (Ram et al., 2019); thus, anti-MOG antibodies may react with the meninges, possibly via unknown antigens. Third, another antibody or type of pathogenesis may have caused the OPN, and the presence of anti-MOG antibodies was an epiphenomenon secondary to the inflammation of the optic nerve sheath. Further studies are needed to clarify the pathognomonic role of anti-MOG antibody in OPN. Although an association between anti-MOG antibody and ON has been reported, anti-MOG antibody is not usually associated with OPN. Our case shows that anti-MOG antibody positivity should be considered as a possible etiology for OPN, especially when the OPN is accompanied by disc swelling on fundus examination and shows good response to corticosteroid treatment.
Figure 2. Coronal MRI with STIR sequence showed remarkably high intensity in the right optic nerve sheath and mildly high intensity in the optic nerve.
nerve sheath with only slightly high intensity in the right optic nerve on MRI with STIR sequence, indicating OPN. Ramanathan et al. recently reported a male patient with anti-MOG antibody positive OPN, who had peripheral visual impairment, as in our case (Ramanathan et al., 2019). His MRI showed contrast enhancement in both of the optic nerve and the optic sheath, whereas in our case, MRI with STIR sequence showed high intensity only in the optic sheath. Disc swelling is commonly caused by intracranial hypertension or ischemic optic neuropathy. However, this patient had no mass lesion restricting CSF flow and had normal intracranial pressure, ruling out papilledema. He was unlikely to have had ischemic optic neuropathy, because no retinal hemorrhage was present and he had no remarkable vascular risks. Therefore, we surmise that the pathogenesis of the disc swelling in this case was inflammation in the optic nerve sheath related to the anti-MOG antibody, rather than intracranial hypertension or ischemia. A previous biopsy study of OPN showed marked thickening of the optic nerve sheath with inflammatory infiltration, but the adjacent optic nerve was largely spared, with little lymphocyte infiltration (Purvin V1 et al., 2001). Therefore, we speculate that inflammation and thickening of the optic nerve sheath surrounding the optic nerve focally elevated pressure in the subarachnoid space, resulting in disc swelling. Serum from patients positive for anti-MOG antibody caused myelin loss when injected into mouse brain (Saadoun S et al., 2014). This finding suggests that anti-MOG antibodies play a pathognomonic role in damaging MOG-expressing cells such as oligodendrocytes. However, the optic nerve sheath is anatomically equivalent to the meninges, which do not express MOG. Therefore, the role of anti-MOG antibodies
Declaration of Competing Interest The authors state that they have no Conflict of Interest (COI). This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The patient has given informed consent for publication of this case. References Osborne, B.J., Volpe, N.J., 2009. Optic neuritis and risk of MS: Differential diagnosis and management. Cleve Clin. J. Med. 76, 181–190. Ramanathan, S., Fraser, C., Curnow, S.R., et al., 2019. Uveitis and optic perineuritis in the context of myelin oligodendrocyte glycoprotein antibody seropositivity. Eur. J. Neurol. 26 (8), 1137-e75. Purvin, V1, Kawasaki, A., Jacobson, D.M., et al., 2001. Optic perineuritis. Arch. Ophthalmol. 119, 1299–1306. Saadoun, S., Waters, P., Owens, G.P., et al., 2014. Neuromyelitis optica MOG-IgG causes reversible lesions in mouse brain. Acta Neuropathol. Commun. 2, 35. Ram, N., Cynthia, W., Peter, S., et al., 2019. Atypical Anti-MOG syndrome with aseptic meningoencephalitis and pseudotumor cerebri-like presentations. Mult. Scler. Relat. Disord. 27, 30–33.
2
Contents lists available at ScienceDirect
Multiple Sclerosis and Related Disorders journal homepage: www.elsevier.com/locate/msard
Case report
Optic perineuritis with anti-myelin oligodendrocyte glycoprotein antibody a,⁎
a
b
T
b
Mitsugu Yanagidaira , Takaaki Hattori , Hirofumi Emoto , Motohiro Kiyosawa , ⁎ Takanori Yokotaa, a b
Department of Neurology and Neurological Sciences, Tokyo Medical and Dental University, Graduate School of Medical and Dental Sciences, Japan Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University, Graduate School of Medical and Dental Sciences, Japan
A R T I C LE I N FO
A B S T R A C T
Keywords: Myelin oligodendrocyte glycoprotein MOG Optic perineuritis Disc swelling
A 25-year-old male presented with blurred peripheral vision and movement pain in his right eye. Fundus examination revealed unilateral disc swelling in his right eye with normal intracranial pressure. MRI showed remarkably high intensity in the optic nerve sheath and slightly high intensity in the optic nerve, indicating optic perineuritis (OPN). Anti-myelin oligodendrocyte glycoprotein (MOG) antibody was positive in both serum and cerebrospinal fluid. The patient responded promptly to corticosteroid treatment. OPN can be associated with the presence of anti-MOG antibody.
1. Case description A previously healthy 25-year-old male experienced 5 days of pain on eye movement and blurred peripheral vision in his right eye. On examination, relative afferent pupillary defect (RAPD) was positive in his right eye. His neurological signs were otherwise normal. He had no history of preceding infection or recent vaccination. His best corrected visual acuity was 1.5 in both eyes. A fundus examination and optical coherent tomography revealed disc swelling in his right eye (Figure 1A) but a normal disc and retina in the left eye. A visual field test showed inferonasal visual field loss with spared central vision. In a pattern-reversal visual evoked potential study, P100 latency was bilaterally normal. IgG4, anti-aquaporin 4 (AQP4) antibody, anti-nuclear antibody, anti-neutrophil cytoplasmic antibody, anti-Sjögren-syndrome-related antigen A/B, Treponema pallidum–specific antibody, angiotensin-converting enzyme, C-reactive protein, erythrocyte sedimentation rate, and D-dimer were all negative or within normal limits. Cerebrospinal fluid (CSF) opening pressure was normal (15.5 cm H2O) with the patient in the recumbent position. Cell count (3/mm2), total protein (44 mg/dL), and myelin basic protein were within normal limits. CSF was negative for oligoclonal bands. The IgG index was 0.82. CSF was negative for herpes simplex virus type 1 and 2, varicella zoster virus, cytomegalovirus, and Epstein-Barr virus by PCR. In a cell-based assay, anti-myelin oligodendrocyte glycoprotein (MOG) antibody was positive in the serum at 1:4096 dilution (normal is less than 1:64) and in the CSF at 1:8 (normal is less than 1:2). AntiAQP4 antibody was negative in CSF. ⁎
Orbital MRI with short tau inversion recovery (STIR) sequence demonstrated remarkably high intensity in the right optic nerve sheath and mildly high intensity in the optic nerve (Figure 2), suggesting optic perineuritis (OPN). No other abnormal findings were observed on brain and cervical spine MRIs. The patient was diagnosed with OPN on the basis of the spared central vision and high intensity in the optic nerve sheath on MRI with STIR sequence (1A). Intravenous methylprednisolone (1 g/day) was administered for 3 days from day 5 after onset, followed by oral prednisolone treatment (1 mg/kg/ day). Two days after the start of corticosteroid administration, the patient's pain on eye movement had dramatically improved and the RAPD became negative. By day 6 after treatment initiation, the disc swelling had disappeared (Figure 1B) but inferonasal visual loss remained. The corticosteroid dosage was tapered to 10 mg/day over 3 months, with no relapse in the following 4 months. 2. Discussion Here, we have reported an unusual case of OPN associated with anti-MOG antibody. Previously optic neuritis (ON) associated with antiMOG antibody were reported. The distinction between ON and OPN is important in terms of both understanding pathogenesis and predicting treatment response and prognosis: patients with OPN less frequently develop multiple sclerosis and are more responsive to steroid treatment than those with ON (Osborne BJ, 2009). Although ON patients with anti-MOG antibody can have contrast enhancement in the optic nerve sheath concurrent with predominant contrast enhancement in the optic nerve, our patient had predominantly high intensity in the right optic
Corresponding author. E-mail address: [email protected] (T. Yokota).
https://doi.org/10.1016/j.msard.2019.101444 Received 17 January 2019; Received in revised form 9 October 2019; Accepted 12 October 2019 2211-0348/ © 2019 Elsevier B.V. All rights reserved.
Multiple Sclerosis and Related Disorders 38 (2020) 101444
M. Yanagidaira, et al.
Figure 1. Fundus examination revealed disc swelling in the right eye before treatment (A), but it had disappeared by day 6 after treatment initiation (B).
in OPN remains unknown. Here, we consider 3 possibilities for the pathogenesis of this case. First, although anti-MOG antibody causes inflammation targeting MOG protein expressed in oligodendrocytes in the optic nerve, the inflammation may have extended to the optic nerve sheath, leading to high intensity of the optic sheath on MRI with STIR sequence. Second, 2 cases of aseptic meningitis with anti-MOG antibody have been reported (Ram et al., 2019); thus, anti-MOG antibodies may react with the meninges, possibly via unknown antigens. Third, another antibody or type of pathogenesis may have caused the OPN, and the presence of anti-MOG antibodies was an epiphenomenon secondary to the inflammation of the optic nerve sheath. Further studies are needed to clarify the pathognomonic role of anti-MOG antibody in OPN. Although an association between anti-MOG antibody and ON has been reported, anti-MOG antibody is not usually associated with OPN. Our case shows that anti-MOG antibody positivity should be considered as a possible etiology for OPN, especially when the OPN is accompanied by disc swelling on fundus examination and shows good response to corticosteroid treatment.
Figure 2. Coronal MRI with STIR sequence showed remarkably high intensity in the right optic nerve sheath and mildly high intensity in the optic nerve.
nerve sheath with only slightly high intensity in the right optic nerve on MRI with STIR sequence, indicating OPN. Ramanathan et al. recently reported a male patient with anti-MOG antibody positive OPN, who had peripheral visual impairment, as in our case (Ramanathan et al., 2019). His MRI showed contrast enhancement in both of the optic nerve and the optic sheath, whereas in our case, MRI with STIR sequence showed high intensity only in the optic sheath. Disc swelling is commonly caused by intracranial hypertension or ischemic optic neuropathy. However, this patient had no mass lesion restricting CSF flow and had normal intracranial pressure, ruling out papilledema. He was unlikely to have had ischemic optic neuropathy, because no retinal hemorrhage was present and he had no remarkable vascular risks. Therefore, we surmise that the pathogenesis of the disc swelling in this case was inflammation in the optic nerve sheath related to the anti-MOG antibody, rather than intracranial hypertension or ischemia. A previous biopsy study of OPN showed marked thickening of the optic nerve sheath with inflammatory infiltration, but the adjacent optic nerve was largely spared, with little lymphocyte infiltration (Purvin V1 et al., 2001). Therefore, we speculate that inflammation and thickening of the optic nerve sheath surrounding the optic nerve focally elevated pressure in the subarachnoid space, resulting in disc swelling. Serum from patients positive for anti-MOG antibody caused myelin loss when injected into mouse brain (Saadoun S et al., 2014). This finding suggests that anti-MOG antibodies play a pathognomonic role in damaging MOG-expressing cells such as oligodendrocytes. However, the optic nerve sheath is anatomically equivalent to the meninges, which do not express MOG. Therefore, the role of anti-MOG antibodies
Declaration of Competing Interest The authors state that they have no Conflict of Interest (COI). This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The patient has given informed consent for publication of this case. References Osborne, B.J., Volpe, N.J., 2009. Optic neuritis and risk of MS: Differential diagnosis and management. Cleve Clin. J. Med. 76, 181–190. Ramanathan, S., Fraser, C., Curnow, S.R., et al., 2019. Uveitis and optic perineuritis in the context of myelin oligodendrocyte glycoprotein antibody seropositivity. Eur. J. Neurol. 26 (8), 1137-e75. Purvin, V1, Kawasaki, A., Jacobson, D.M., et al., 2001. Optic perineuritis. Arch. Ophthalmol. 119, 1299–1306. Saadoun, S., Waters, P., Owens, G.P., et al., 2014. Neuromyelitis optica MOG-IgG causes reversible lesions in mouse brain. Acta Neuropathol. Commun. 2, 35. Ram, N., Cynthia, W., Peter, S., et al., 2019. Atypical Anti-MOG syndrome with aseptic meningoencephalitis and pseudotumor cerebri-like presentations. Mult. Scler. Relat. Disord. 27, 30–33.
2