Optic Perineuritis in Behçet Disease

The intrinsic abilities and limits of the nervous system to repair itself after damage may be assessed using a model of optic chiasmal compression, before and after a corrective surgical procedure.; ; Visual fields (VFs), multifocal visual evoked potentials (mfVEP), retinal nerve fiber layer (RNFL) thickness, and diffusion tensor imaging were used to evaluate a patient before and after removal of a meningioma compressing the chiasm. Normally sighted individuals served as controls. The advantage of each modality to document visual function and predict postoperative outcome (2-year follow-up) was evaluated.; ; Postsurgery visual recovery was best explained by critical mass of normally conducting fibers and not associated with average conduction amplitudes. Recovered VF was observed in quadrants in which more than 50% of fibers were identified, characterized by intact mfVEP latencies, but severely reduced amplitudes. Recovery was evident despite additional reduction of RNFL thickness and abnormal optic tract diffusivity. The critical mass of normally conducting fibers was also the best prognostic indicator for functional outcome 2 years later.; ; Our results highlight the ability of the remaining normally conductive axons to predict visual recovery after decompression of the optic chiasm. The redundancy in anterior visual pathways may be explained, neuroanatomically, by overlapping receptive fields.

Original Contribution Optic Perineuritis in Behçet Disease Chuntao Lai, MD, Yanbin Sun, MD, Jiawei Wang, MD, PhD, Valerie A. Purvin, MD, Yunhong He, MD, Qinglin Yang, MD, Yun Jing, MD, Hongxia Yin, PhD, Jing Zhu, MD Background: Optic perineuritis (OPN), an uncommon optic neuropathy, has previously not been described in patients with Behçet disease (BD). We conducted this study to describe the clinical features, response to treatment, and outcome of OPN due to BD, with particular emphasis on those features that might distinguish this from the idiopathic variety. Methods: This is a retrospective, case series review of all patients with a diagnosis of OPN seen in a hospital-based neurology department from 2008 to 2014 who also met the international criteria for the diagnosis of BD. Results: Twenty-one patients with OPN were identified, of whom 10 (12 eyes) met the criteria for BD. OPN developed 2-10 years (mean, 4 years) after onset of BD, but the diagnosis of BD was made only after onset of OPN in 6. Nine of 12 eyes (75%) had severe visual loss (#20/200), and 80% of patients progressed over several days from onset. After high-dose corticosteroid treatment, all patients experienced relief of pain, and 5 patients (50%) showed improved visual acuity. At last follow-up (mean, 25 months) 7 of 11 (64%) of affected eyes had good visual outcome ($14/20), and no patient experienced a subsequent neurological event. Conclusions: OPN may occur as a manifestation of BD and, in non-Western countries, this may be more common than the idiopathic variety. In contrast to idiopathic cases, OPN in BD is more likely to demonstrate initial rapid progression of visual loss and more severe loss at presentation. Patients show less recovery of vision in response to corticosteroids but carry a lower rate of subsequent relapse. Patients with OPN should be specifically questioned regarding symptoms of BD. Journal of Neuro-Ophthalmology 2015;35:342-347 doi: 10.1097/WNO.0000000000000264 © 2015 by North American Neuro-Ophthalmology Society Department of Neurology (CL, YS, JW, YH, QY, YJ, JZ), Beijing Tongren Hospital, Capital Medical University, Beijing, China; Departments of Ophthalmology and Neurology (VP), Indiana University, Indianapolis, Indiana; and Department of Radiology (HY), Beijing Tongren Hospital, Capital Medical University, Beijing, China. The authors report no conflicts of interest. Address correspondence to Chuntao Lai, MD, Department of Neurology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China; E-mail: [e-mail] 342 O ptic perineuritis (OPN) is an uncommon inflammatory disease affecting the optic nerve sheath. Patients present with acute optic neuropathy usually accompanied by pain and optic disc edema. Orbital magnetic resonance imaging (MRI) demonstrates circumferential enhancement around the optic nerve with sparing of the nerve itself (1). This is best visualized on fat-suppressed, contrasted coronal sequences. MRI also may show streaky enhancement of orbital fat and mild enlargement of extraocular muscles (2). Specific etiologies of OPN include syphilis (3), herpes zoster (1), tuberculosis (4), sarcoidosis (5), Wegener granulomatosis (6), giant cell arteritis (7), Crohn's disease (8), and acute retinal necrosis (9). However, in most patients with OPN, no specific etiology is identified. A biopsy specimen of the optic nerve lesion in 2 patients with idiopathic OPN showed acute and chronic inflammatory changes of the perioptic meninges without granulomas or vasculitis (2). In a case study of 14 patients, Purvin et al (2) defined the clinical features that help to distinguish OPN from demyelinating optic neuritis (isolated idiopathic or associated with multiple sclerosis), a more common cause of acute, painful optic neuropathy. In contrast to demyelinating optic neuritis, OPN often spares central vision, shows a more dramatic response to corticosteroids, and is more likely to recur after discontinuing treatment (2). In addition, OPN may be accompanied by ocular motility deficits, ptosis, and chemosis. Because the target tissue is not the myelin sheath, OPN is not associated with an increased risk of multiple sclerosis and thus does not preclude initial treatment with oral corticosteroids. The possibility of an underlying systemic disease should be carefully investigated before making a diagnosis of idiopathic OPN. We reviewed the charts of 10 Chinese patients with OPN who fulfilled the criteria of Behçet disease (BD) to characterize the clinical features, response to treatment, and outcomes, especially focusing on the features that might distinguish it from idiopathic OPN. Lai et al: J Neuro-Ophthalmol 2015; 35: 342-347 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution METHODS This was a restrospective case series of in-patients with OPN seen from 2008 to 2014 in the Department of Neurology, Beijing Tongren Hospital, Capital Medical University, China. We reviewed the medical history and laboratory tests of 21 Chinese patients with OPN. Among them, 10 patients (12 eyes) satisfied the criteria for BD. We also studied treatment response to corticosteroids and outcome. Our protocol was approved by Institute Review Board of Beijing Tongren Hospital, Capital Medical University, and patients gave informed consent. The diagnosis of OPN was made in patients who presented with acute or subacute visual loss; eye and/or head pain; visual field defect; enhancement of optic nerve sheath on MRI (Fig. 1). We excluded patients in whom the clinical and/or radiographic findings indicated prominent involvement of the optic nerve or other orbital structures. We also excluded patients with multiple sclerosis, neuromyelitis optica, sarcoidosis, and other vasculitis, based on the history, clinical presentation, investigations, and disease course. BD was defined by the International Criteria for Behçet Disease (ICBD) (Table 1) (10). Compared with the International Study Group criteria (11), ICBD were validated to have improved sensitivity (94.8%) while maintaining reasonable specificity (90.5%). A patient scoring 4 points or above was classified as having BD. All patients underwent laboratory testing which included complete blood cell count, erythrocyte sedimentation rate (ESR), C-reactive protein, rheumatoid factor, anti-nuclear antibodies (ANA), extractable nuclear antigens, antineutrophil cytoplasmic antibodies (ANCA), anticardiolipin antibody (ACA), angiotensin-converting enzyme (ACE), antivascular endothelial cell antibodies (AECA), anti- aquaporin-4 antibody, and syphilis serologic testing. All TABLE 1. International criteria for BD: point score system Sign/Symptom Ocular lesions Genital aphthosis Oral aphthosis Skin lesions Neurological manifestations Vascular manifestations Points 2 2 2 1 1 1 Score $4 indicates BD Modified from Ref. (10). BD, Behçet disease. patients had a purified protein derivative skin test, chest radiography, and underwent MRI of the brain and orbits with fat suppression and contrast infusion within 1 week of admission to hospital. Six patients underwent a lumbar puncture. RESULTS Clinical Profile OPN developed 2-10 years (mean, 4 years) after onset of BD. The age of onset of BD ranged from 20 to 59 years (mean, 38 years) (Table 2). Four patients (patients 3, 4, 9, and 10) were diagnosed with BD before they developed OPN, and the remaining patients satisfied the ICBD when they developed OPN. All patients had eye pain. Six patients had headache but no other sign suggesting meningeal irritation. Nine eyes (75%) had severe visual loss (visual acuity #20/200). Most patients (80%, 8 of 10) progressed over days. Only 1 patient progressed for more than 2 weeks. All patients had a history of recurrent mouth ulcers, and this was the first symptom of BD in 9 patients (11 eyes). None of the patients had uveitis. Three patients had an attack accompanied by systemic symptoms, specifically mouth ulcers, acne, and/or arthralgias. Magnetic Resonance Imaging Findings All patients showed enhancement of the affected optic nerve sheath. MRI revealed bilateral optic nerve sheath involvement in 1 patient (patient 2) with unilateral clinical findings, meningeal enhancement in 2 patients (patients 7 and 8) (Fig. 2), basal ganglia "black hole" in 1 patient (patient 3), and multiple white matter lesions in 2 patients (patients 2 and 6). Cerebrospinal Fluid Analysis FIG. 1. Postcontrast T1 coronal magnetic resonance imaging shows enhancement of the right optic nerve sheath (arrow) and "streakiness" of the orbital fat. Lai et al: J Neuro-Ophthalmol 2015; 35: 342-347 Six patients (patients 2, 3, 5, 6, 8, and 9) underwent lumbar puncture which showed normal cerebrospinal fluid (CSF) pressure in all, including 2 patients (patients 2 and 8) with bilateral optic nerve sheath enhancement. One patient (patient 8) had leukocytosis, 2 patients (patients 6 and 8) 343 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Patient Number/ Sex/Age, yr Eye Pain/ Headache Onset and Progress VAAN VF Optic Disc Medical History RMU and acne for 4 yr. Anemia for 2 yr Lai et al: J Neuro-Ophthalmol 2015; 35: 342-347 1/F/30 Yes/Yes Onset 4 d apart; both eyes progressed over 7 d 8/20 (R); 8/20 (L) IAVFD constriction Edema bilaterally 2/F/39 Yes/Yes Progression over 5d 16/20 (L) Normal Edema 3/F/52 Yes/No Progression for 3 d CF (R) Not done Normal 4/F/42 Yes/Yes Progression for 3 d NLP (L) Not done Edema 5/F/61 Yes/No Abrupt CF (L) Constriction Edema 6/F/47 Yes/No Abrupt CF (L) Constriction Normal 7/F/23 Yes/Yes Progression for 1 d NLP (L) Not done Edema 8/F/48 Yes/Yes Central scotoma bilaterially Normal 9/M/36 Yes/Yes NLP (R); CF Onset 7 d apart; both (L) eyes progressed over 20 d Progression for 3 d NLP (L) Not done Normal 10/M/47 Yes/No Progression for 10 d Not done Normal CF (R) MRI Finding Enhancement of ONS bilaterally; mild ON enhancement bilaterally RMU, acne, arthralgias, Enhancement of ONS and fat bilaterally dry eye and thirsty for 4 yr RMU, RGU, and EN for Enhancement of ONS 10 yr. HBP for 30 yr and fat and stroke for 12 yr RMU and RGU for 5 yr. Enhancement of ONS Acne for 1 yr and fat; mild ON enhancement RMU, acne, and Enhancement of ONS arthralgias for 2 yr and fat RMU, acne, and Enhancement of ONS arthralgias for 2 yr and fat RMU and acne for 3 yr Enhancement of ONS and fat with intracranial extension RMU, acne, and Enhancement of ONS arthralgias for 5 yr bilaterally with intracranial extension RMU, RGU, and Enhancement of ONS arthralgias for 5 yr and fat RMU and ance for 3 yr. Enhancement of ONS HBP for 10 yr and fat BD, Behçet disease; CF, counting finger; EN, erythema nodosum; HBP, high blood pressure; IAVFD, inferior altitudinal visual field defect; MRI, magnetic resonance imaging; NLP, no light perception; ON, optic nerve; ONS, optic nerve sheath; OPN, optic perineuritis; RGU, recurrent genital ulcers; RMU, recurrent mouth ulcers; VAAN, visual acuity at nadir; VF, visual field. Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution 344 TABLE 2. Demographic, clinical features, and MRI findings of patients with OPN and BD Original Contribution FIG. 2. A. Postcontrast T1 axial MRI reveals perineural enhancement of the prechiasmal left optic nerve (arrow). B. Postcontrast T1 coronal MRI reveals meningeal enhancement (arrows). MRI, magnetic resonance imaging. had modestly raised CSF protein, and 1 (patient 2) had positive oligoclonal bands. Serology Results The ESR was slight elevated in 3 patients (range, 24-31 mm/h). ANCA, ACA, ACE, and ANA were negative in all patients. Two patients (patients 9 and 10) had a negative AECA. Response to Corticosteroids All but 1 patient (patient 10) received intravenous methylprednisolone (1,000 mg/d for 3 days) followed by oral methylprednisolone (1 mg$kg21$d21), slowly tapered over 2 months (Table 3). All patients experienced dramatic relief of eye pain and headache, usually within 2 days. In 5 patients, visual acuity improved, but the others had no response to corticosteroid therapy. Two patients (patients 3 and 8) were maintained on low-dose oral methylprednisolone (4 or 8 mg/d) for more than 1 year for continued systemic symptoms. No patient experienced a relapse of their visual loss during or after completion of treatment. Outcomes We followed 9 patients (11 eyes) for mean 25 months after onset of OPN. Seven of 11 (64%) of affected eyes had good visual outcomes (#14/20). The remainder had severe visual loss (visual acuity #20/200). No neurological events occurred. Two patients (patients 3 and 7) developed recurrent mouth ulcers after stopping oral corticosteroids. Two patients (patients 8 and 9) had attacks of genital ulcers. One patient (patient 10) intermittently developed mouth ulcers and acne. DISCUSSION We documented an association of OPN with BD in our patient population. This is in contrast to previous reports of OPN from North America in which most cases are categorized as idiopathic. Based on the clinical features described here, we compared OPN with other manifestations of BD and also to idiopathic cases of OPN. The interval between onset of BD and development of OPN is similar to that of other neurological manifestations although the age at onset of BD (mean, 38 years) was slightly older than in patients with other neurologic involvement (usually in the third decade) (12). Central nervous system involvement in BD is usually categorized as parenchymal (12-14) or nonparenchymal (meningeal) (15-18). In 2 of our patients (patients 7 and 8), the disease process involved the TABLE 3. Response to corticosteroids and clinical outcome in patients with OPN and BD Patient 1 2 3 4 5 6 7 8 9 10 Steroids Therapy Response Final VA IV MP IV MP IV MP IV MP IV MP IV MP IV MP IV MP IV MP PO MP Resolved Resolved No No Better Better No No No Resolved 20/20; 20/20 20/20 20/20 NLP 14/20 20/20 Lost NLP; CF CF 16/20 Follow-up Interval, mo 12 60 27 24 6 48 36 5 4.5 BD, Behçet disease; IV MP, intravenous methylprednisolone (500 mg/d or 1,000 mg/d for 3-5 days) followed by oral methylprednisolone (1 mg$kg21$d21), typically, tapered for at least 2 months; OPN, optic perineuritis; PO MP, oral methylprednisolone (64 mg/d for 7 days and tapered for 2 months). Lai et al: J Neuro-Ophthalmol 2015; 35: 342-347 345 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution TABLE 4. Clinical features of OPN Feature Severe visual loss Progression RMU Response to corticosteroid Relapsing off corticosteroid Good visual outcome OPN in BD Idiopathic OPN Common Rare Abruptly or days Weeks Yes No Variable Dramatic improvement No Common after brief treatment Common More common Good visual outcome: visual acuity $10/20. BD, Behçet disease; OPN, optic perineuritis. optic nerve sheath and meninges, and in 2 patients (patients 1 and 4), MRI showed enhancement of optic nerve sheath and the optic nerve, demonstrating overlapping features. We found a lower rate of CSF pleocytosis (20%) compared with previous reports of patients with BD with parenchymal involvement. It would appear that the area of inflammation is less extensive in OPN compared with other forms of BD with neurologic involvement. Our patients share some clinical features with cases of idiopathic OPN including age, subacute onset, presence of eye pain/headache, and MRI appearance (2). However, there are also some significant differences. In contrast to idiopathic OPN, OPN in BD is more likely to demonstrate severe visual loss, rapid progression, and a more variable response to high-dose corticosteroids. In addition, patients with OPN due to BD appear to have a lower relapse rate after completing treatment (Table 4). The degree of visual loss in our series was greater when compared with that of idiopathic OPN. Visual acuity was less than 20/200 in 9 of 12 eyes (75%) vs only 3 of 15 eyes (20%) in idiopathic OPN (2). All affected eyes had some loss of visual acuity in our series, whereas 8 of 15 (53%) of eyes with idiopathic OPN maintained acuity of 20/20 or better (2). Idiopathic OPN generally progresses for several weeks before patients are diagnosed (2). In our series, OPN usually occurred abruptly or over several days, similar to the time course seen in demyelinative optic neuritis (19). Characteristic MRI changes provide the most accurate means of distinguishing OPN from optic neuritis. All patients in our series experienced dramatic relief of pain, but only 5 showed improvement of vision. In a report of 14 patients with idiopathic OPN (2), all experienced prompt improvement of vision and eye pain within days of initiating corticosteroid therapy. At the end of follow-up, 64% (7 of 11) of affected eyes in our series had visual acuity #14/20 compared with 20/25 or better in 12 (80%) of 15 eyes with idiopathic OPN (2). This finding is surprising since our patients with OPN were given high-dose intravenous 346 steroids vs patients with idiopathic OPN were being treated with a lower steroid dose taken orally (2). After discontinuation of corticosteroids in 7 of our patients and dosage reduction in 2 patients, there were no episodes of recurrent OPN. Among those with idiopathic OPN (2), 4 patients had relapse when the corticosteroid dose was reduced within a mean follow-up of 12.5 months. This difference suggests a tendency toward chronic/recurrent disease in idiopathic OPN vs OPN in BD. We acknowledge the limitation of this conclusion because of the variability in corticosteroid treatment dose and duration, our small patient sample size, and retrospective nature of our study. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: C. Lai, J. Wang, V. Purvin; b. Acquisition of data: C. Lai, Y. Sun, Y. He, Q. Yang, Y. Jing, H. Yin, J. Zhu; c. Analysis and interpretation of data: C. Lai, Y. Sun, J. Wang, Y. He, Q. Yang, Y. Jing, H. Yin, J. Zhu. Category 2: a. Drafting the manuscript: C. Lai, Y. Sun, J. Wang, V. Purvin, Y. He, Q. Yang, Y. Jing, H. Yin, J. Zhu; b. Revising it for intellectual content: C. Lai, J. Wang, V. Purvin. Category 3: a. Final approval of the completed manuscript: C. Lai, Y. Sun, J. Wang, V. Purvin, Y. 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