Orbit, 2014; 33(1): 13–16 ! Informa Healthcare USA, Inc. ISSN: 0167-6830 print / 1744-5108 online DOI: 10.3109/01676830.2013.841716
ORIGINAL ARTICLE
Wegener Granulomatosis-associated Optic Perineuritis Takanori Takazawa1, Ken Ikeda1, Tetsuro Nagaoka1, Takehisa Hirayama1, Tatsuhiro Yamamoto2, Masaru Yanagihashi1, Tetsuo Tochikubo3, and Yasuo Iwasaki1 Department of Neurology, 2Department of Rheumatology, and 3Department of Ophthalmology, Toho University Omori Medical Center, Japan
ABSTRACT Introdunction: We report two patients with optic perineuritis (OPN) and hypertrophic pachymeningitis in Wegener granulomatosis (WG). Case report: Patient 1: a 74-year-old man developed blurred vision in each eye, sequentially, over a year. In the first episode, visual acuity in the right eye was reduced to no light perception, and in the second episode, the vision in the left eye fell to 20/100. Brain and orbital magnetic resonance imaging (MRI) revealed abnormal enhancement in the meninges and the ipsilateral optic nerve sheath. T2-hyperintense lesions were found along the outer rim of the ipsilateral optic nerve. Seropositive proteinase-3-antineutrophil cytoplasmic antibody (PR3ANCA), microhematuria and multiple pulmonary nodules suggested the diagnosis of WG. Steroid therapy was initiated 3 months after the first onset, but with no clinical response. At the 2nd episode, rapid administration of steroid ameliorated visual disturbance and MRI lesions markedly. Patient 2: a 72-year-old man developed blurred vision in each eye. Visual acuity measured no light perception in OD and 6/12 in OS. Gadoliniumenhanced MRI disclosed enhancement in the meninges and both optic nerve sheaths. T2-weighted imaging displayed hyperintense lesions along the outer rims of optic nerves. Otolaryngologic examination, seropositive PR3-ANCA and pulmonary nodules supported the diagnosis of WG. Steroid and cyclophosphamide treatment improved visual dysfunction and MRI lesions in the meninges and the optic nerve sheaths. Comment: The morphological similarity and the anatomical continuity between the meningeal and the perioptic tissues suggest that extension of granulomatous inflammation along such tissue planes accounted for visual loss in these two patients with WG. Keywords: Doughnut-shaped sign, hypertrophic pachymeningiti, MRI, optic perineuritiss, Wegener granulomatosis, granulomatosis with polyangiitis
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1
INTRODUCTION
immunosuppressive therapy in two WG patients with OPN and hypertrophic pachymeningitis, and also discuss the common pathogenesis of pachymeningitis and OPN.
Granulomatosis with polyangiitis, Wegener granulomatosis (WG) is a systemic necrotizing granulomatous inflammation with vasculitis in the upper and the lower respiratory tract, and the kidney. This disease can involve the orbit, including the optic nerve. However, apparently isolated optic nerve involvement rarely occurs in WG, and little is known about the radiological feature of optic perineuritis (OPN) in such patients.1,2 Herein we report the clinicoradiological changes after
PATIENT PRESENTATION Patient 1 A 74-year-old man developed blurred vision in the right eye. He had a prior history of interstitial
Received 10 January 2013; Revised 11 June 2013; Accepted 30 August 2013; Published online 18 October 2013 Correspondence: Ken Ikeda, Department of Neurology, Toho University Omori Medical Center, 6-11-1, Omorinishi, Otaku, Tokyo, 143-8541, Japan. Tel: +81-3-3762-4151, Fax: +81-3-3768-2566, E-mail: [email protected]
13
14 T. Takazawa et al. optic nerve (Figure 2C). Methylprednisolone pulse and subsequently prednisolone (40 mg/day. po) treatment started from 6 days after the 2nd visual onset. Steroid treatment improved visual acuity of 20/20 and scotomas in the left eye. Three months later, the meningeal and the left orbital lesions had regressed on further MRI (Figure 2D–F).
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Patient 2
FIGURE 1. Fat-suppression orbital MRI at visual deficit in the right eye. (A, B) Sagittal and coronal contrast MRI showing abnormal enhancement in the right optic nerve sheath (ONS) [arrow]. (C) Coronal T2-weighted MRI showing doughnutshaped T2-hyperintense lesion in the right optic nerve (arrowhead).
pneumonitis. Ophthalmologic examination showed visual acuity of no light perception and visual field of diffuse constriction in oculus dexter (OD). Ocular fundus was unremarkable. Routine laboratory studies identified a white blood cell (WBC) count of 13,800/ mm3, C-reactive protein (CRP) of 8.9 mg/dL (normal 50.2) and microhematuria. Serum proteinase-3-antineutrophil cytoplasmic antibody (PR3-ANCA) was positive. Gallium scintigraphy of whole body revealed abnormal accumulation in the nasal cavity and throat. Chest computed tomography (CT) disclosed diffuse nodular lesions in the lung. Orbital fat-suppression magnetic resonance imaging (MRI) displayed abnormal enhancement in the right optic nerve sheath and T2-hyperintense lesions along the outer rim of the right optic nerve (Figure 1). He was diagnosed as WG. Methylprednisolone pulse therapy (1000 mg/day for 3 days, iv) was performed at 3 months after clinical onset. Steroid treatment did not respond to visual dysfunction, leading to the right optic nerve atrophy. One year later, blurred vision was appeared in oculus sinister (OS). Visual acuity of 20/ 100 and paracentral scotomas were present in the left eye. Brain and orbital MRI revealed abnormal enhancement and thickening in the frontal meninges and the left optic nerve sheath (Figure 2A, B). T2hyperintense lesion was found in the left superficial
A 72-year-old man noticed blurred vision for 1 month. Physical examination showed body mass index of 15.4 kg/m2. Ophthalmologic examination revealed visual acuity of no light perception in the right eye and 6/12 in the left. Goldmann visual field test identified diffuse constriction in OD and nasal constriction in OS. Ocular fundus was not remarkable. Otolaryngologic examination showed rhinitis, sinusitis and otitis media. Routine laboratory studies revealed WBC count of 13,800/mm3, CRP of 8.9 mg/ dL and erythrocyte sedimentation rate more than 100 mm/hour (normal of 3–15). Serum PR3-ANCA was positive. Chest CT disclosed multiple nodular lesions in the lower lung. Brain and orbital fat-suppression T1-weighted imaging disclosed abnormal enhancement and thickening in the meninges and the bilateral optic nerve sheaths (Figures 3A,B). Doughnut-shaped T2-hyperintense lesions were found in the optic nerves (Figure 3C). Clinical and laboratory findings supported the diagnosis of WG. Methylprednisolone (1000 mg/day for 3 days, iv) and subsequently prednisolone (40 mg/day, po) was administered. Cyclophosphamide (500 mg/day, iv) was given over the following 2 months, this leading to complete resolution of the visual acuity and field defects on each side, in addition to a reduction of the meningeal and orbital signs on MRI (Figures 3D–F).
COMMENT We describe the clinicoradiological hallmark of two patients with WG who had hypertrophic pachymeningitis and visual loss due to OPN. OPN is an uncommon inflammatory disorder in the optic nerve sheath, and can be due to syphilis, herpes zoster, sarcoidosis, tuberculosis, giant cell arteritis and WG. All patients with OPN complain of visual symptoms, and the characteristic finding on orbital MRI includes circumferential enhancement of the perioptic tissue, with relative sparing of the optic nerve parenchyma. With respect to WG-associated OPN, coronal views of fat-suppressed gadolinium-enhanced T1-weighted images identified doughnut-shaped enhancement in the optic nerve sheath.1,2 Orbit
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Optic Perineuritis in Wegener Granulomatosis
15
FIGURE 2. Fat-suppression MRI at visual deficit in the left eye. (A, B) MRI showing abnormal enhancement in the meninges and the left ONS (arrow). (C) T2-weighted MRI showing doughnut-shaped T2-hyperintense lesion in the left optic nerve (arrowhead). (D–F) After steroid therapy, meningeal and orbital enhancement, and T2-hyperintense lesions were regressed.
FIGURE 3. (A, B) Fat-suppression T1-weighted MRI showing enhancement in the meninges and the bilateral ONS (arrows). (C) Fatsuppression T2-weighted MRI showing doughnut-shaped T2-hyperintense lesions in both optic nerves (arrowheads). (D–F) After immunosuppressive therapy, meningeal and orbital enhancement, and T2-hyperintense lesions were vanished.
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2014 Informa Healthcare USA, Inc.
Orbit Downloaded from informahealthcare.com by University of Sydney on 01/31/14 For personal use only.
16 T. Takazawa et al. In addition, fat-suppressed T2-weighted imaging of the present patients displayed hyperintense lesions inferior to the enhancing optic nerve sheath. The frequency of neurological involvement was reported as 20–50% in WG patients.3,4 In general, three underlying mechanisms of optic nerve damage have been proposed in WG: (1) vasculitic ischemia; (2) spread inflammation of the adjacent sinuses; and (3) compression by the intraorbital granuloma. However, such mechanisms would not explain the visual deficits in the present described above. A previous pathological report demonstrated fibrosis and necrosis of the optic nerve sheath in a WG patient.2 The histological similarity and the anatomical continuity between the meninges and the optic nerve sheath, together with the MRI findings, suggest that perioptic granulomatous proliferation could play a role in the pathogenesis of optic nerve involvement in the present patients with WG. Rapid diagnosis of WG has a crucial implication for treatment of visual impairment because steroid therapy usually responds to orbital inflammation in WG patients. Thus, physicians should attend the distinct doughnutshaped sign of WG-associated OPN characterized by
abnormal enhancement in the optic nerve sheath and T2-hyperintense lesions in the superficial optic nerve on coronal MRI.
DECLARATION OF INTEREST The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
REFERENCES 1. Purvin V, Kawasaki A. Optic perineuritis secondary to Wegener’s granulomatosis. Clin Experiment Ophthalmol 2009;37:712–717. 2. Shunmugam M, Morley AM, Graham E, et al. Primary Wegener’s granulomatosis of the orbital apex with initial optic nerve infiltration. Orbit 2011;30:24–26. 3. Nishino H, Rubino FA, DeRemee RA, et al. Neurological involvement in Wegener’s granulomatosis: an analysis of 324 consecutive patients at the Mayo Clinic. Ann Neurol 1993;33:4–9. 4. de Groot K, Schmidt DK, Arlt AC, et al. Standardized neurologic evaluations of 128 patients with Wegener granulomatosis. Arch Neurol 2001;58:1215–1221.
Orbit
ORIGINAL ARTICLE
Wegener Granulomatosis-associated Optic Perineuritis Takanori Takazawa1, Ken Ikeda1, Tetsuro Nagaoka1, Takehisa Hirayama1, Tatsuhiro Yamamoto2, Masaru Yanagihashi1, Tetsuo Tochikubo3, and Yasuo Iwasaki1 Department of Neurology, 2Department of Rheumatology, and 3Department of Ophthalmology, Toho University Omori Medical Center, Japan
ABSTRACT Introdunction: We report two patients with optic perineuritis (OPN) and hypertrophic pachymeningitis in Wegener granulomatosis (WG). Case report: Patient 1: a 74-year-old man developed blurred vision in each eye, sequentially, over a year. In the first episode, visual acuity in the right eye was reduced to no light perception, and in the second episode, the vision in the left eye fell to 20/100. Brain and orbital magnetic resonance imaging (MRI) revealed abnormal enhancement in the meninges and the ipsilateral optic nerve sheath. T2-hyperintense lesions were found along the outer rim of the ipsilateral optic nerve. Seropositive proteinase-3-antineutrophil cytoplasmic antibody (PR3ANCA), microhematuria and multiple pulmonary nodules suggested the diagnosis of WG. Steroid therapy was initiated 3 months after the first onset, but with no clinical response. At the 2nd episode, rapid administration of steroid ameliorated visual disturbance and MRI lesions markedly. Patient 2: a 72-year-old man developed blurred vision in each eye. Visual acuity measured no light perception in OD and 6/12 in OS. Gadoliniumenhanced MRI disclosed enhancement in the meninges and both optic nerve sheaths. T2-weighted imaging displayed hyperintense lesions along the outer rims of optic nerves. Otolaryngologic examination, seropositive PR3-ANCA and pulmonary nodules supported the diagnosis of WG. Steroid and cyclophosphamide treatment improved visual dysfunction and MRI lesions in the meninges and the optic nerve sheaths. Comment: The morphological similarity and the anatomical continuity between the meningeal and the perioptic tissues suggest that extension of granulomatous inflammation along such tissue planes accounted for visual loss in these two patients with WG. Keywords: Doughnut-shaped sign, hypertrophic pachymeningiti, MRI, optic perineuritiss, Wegener granulomatosis, granulomatosis with polyangiitis
20 14
Orbit Downloaded from informahealthcare.com by University of Sydney on 01/31/14 For personal use only.
1
INTRODUCTION
immunosuppressive therapy in two WG patients with OPN and hypertrophic pachymeningitis, and also discuss the common pathogenesis of pachymeningitis and OPN.
Granulomatosis with polyangiitis, Wegener granulomatosis (WG) is a systemic necrotizing granulomatous inflammation with vasculitis in the upper and the lower respiratory tract, and the kidney. This disease can involve the orbit, including the optic nerve. However, apparently isolated optic nerve involvement rarely occurs in WG, and little is known about the radiological feature of optic perineuritis (OPN) in such patients.1,2 Herein we report the clinicoradiological changes after
PATIENT PRESENTATION Patient 1 A 74-year-old man developed blurred vision in the right eye. He had a prior history of interstitial
Received 10 January 2013; Revised 11 June 2013; Accepted 30 August 2013; Published online 18 October 2013 Correspondence: Ken Ikeda, Department of Neurology, Toho University Omori Medical Center, 6-11-1, Omorinishi, Otaku, Tokyo, 143-8541, Japan. Tel: +81-3-3762-4151, Fax: +81-3-3768-2566, E-mail: [email protected]
13
14 T. Takazawa et al. optic nerve (Figure 2C). Methylprednisolone pulse and subsequently prednisolone (40 mg/day. po) treatment started from 6 days after the 2nd visual onset. Steroid treatment improved visual acuity of 20/20 and scotomas in the left eye. Three months later, the meningeal and the left orbital lesions had regressed on further MRI (Figure 2D–F).
Orbit Downloaded from informahealthcare.com by University of Sydney on 01/31/14 For personal use only.
Patient 2
FIGURE 1. Fat-suppression orbital MRI at visual deficit in the right eye. (A, B) Sagittal and coronal contrast MRI showing abnormal enhancement in the right optic nerve sheath (ONS) [arrow]. (C) Coronal T2-weighted MRI showing doughnutshaped T2-hyperintense lesion in the right optic nerve (arrowhead).
pneumonitis. Ophthalmologic examination showed visual acuity of no light perception and visual field of diffuse constriction in oculus dexter (OD). Ocular fundus was unremarkable. Routine laboratory studies identified a white blood cell (WBC) count of 13,800/ mm3, C-reactive protein (CRP) of 8.9 mg/dL (normal 50.2) and microhematuria. Serum proteinase-3-antineutrophil cytoplasmic antibody (PR3-ANCA) was positive. Gallium scintigraphy of whole body revealed abnormal accumulation in the nasal cavity and throat. Chest computed tomography (CT) disclosed diffuse nodular lesions in the lung. Orbital fat-suppression magnetic resonance imaging (MRI) displayed abnormal enhancement in the right optic nerve sheath and T2-hyperintense lesions along the outer rim of the right optic nerve (Figure 1). He was diagnosed as WG. Methylprednisolone pulse therapy (1000 mg/day for 3 days, iv) was performed at 3 months after clinical onset. Steroid treatment did not respond to visual dysfunction, leading to the right optic nerve atrophy. One year later, blurred vision was appeared in oculus sinister (OS). Visual acuity of 20/ 100 and paracentral scotomas were present in the left eye. Brain and orbital MRI revealed abnormal enhancement and thickening in the frontal meninges and the left optic nerve sheath (Figure 2A, B). T2hyperintense lesion was found in the left superficial
A 72-year-old man noticed blurred vision for 1 month. Physical examination showed body mass index of 15.4 kg/m2. Ophthalmologic examination revealed visual acuity of no light perception in the right eye and 6/12 in the left. Goldmann visual field test identified diffuse constriction in OD and nasal constriction in OS. Ocular fundus was not remarkable. Otolaryngologic examination showed rhinitis, sinusitis and otitis media. Routine laboratory studies revealed WBC count of 13,800/mm3, CRP of 8.9 mg/ dL and erythrocyte sedimentation rate more than 100 mm/hour (normal of 3–15). Serum PR3-ANCA was positive. Chest CT disclosed multiple nodular lesions in the lower lung. Brain and orbital fat-suppression T1-weighted imaging disclosed abnormal enhancement and thickening in the meninges and the bilateral optic nerve sheaths (Figures 3A,B). Doughnut-shaped T2-hyperintense lesions were found in the optic nerves (Figure 3C). Clinical and laboratory findings supported the diagnosis of WG. Methylprednisolone (1000 mg/day for 3 days, iv) and subsequently prednisolone (40 mg/day, po) was administered. Cyclophosphamide (500 mg/day, iv) was given over the following 2 months, this leading to complete resolution of the visual acuity and field defects on each side, in addition to a reduction of the meningeal and orbital signs on MRI (Figures 3D–F).
COMMENT We describe the clinicoradiological hallmark of two patients with WG who had hypertrophic pachymeningitis and visual loss due to OPN. OPN is an uncommon inflammatory disorder in the optic nerve sheath, and can be due to syphilis, herpes zoster, sarcoidosis, tuberculosis, giant cell arteritis and WG. All patients with OPN complain of visual symptoms, and the characteristic finding on orbital MRI includes circumferential enhancement of the perioptic tissue, with relative sparing of the optic nerve parenchyma. With respect to WG-associated OPN, coronal views of fat-suppressed gadolinium-enhanced T1-weighted images identified doughnut-shaped enhancement in the optic nerve sheath.1,2 Orbit
Orbit Downloaded from informahealthcare.com by University of Sydney on 01/31/14 For personal use only.
Optic Perineuritis in Wegener Granulomatosis
15
FIGURE 2. Fat-suppression MRI at visual deficit in the left eye. (A, B) MRI showing abnormal enhancement in the meninges and the left ONS (arrow). (C) T2-weighted MRI showing doughnut-shaped T2-hyperintense lesion in the left optic nerve (arrowhead). (D–F) After steroid therapy, meningeal and orbital enhancement, and T2-hyperintense lesions were regressed.
FIGURE 3. (A, B) Fat-suppression T1-weighted MRI showing enhancement in the meninges and the bilateral ONS (arrows). (C) Fatsuppression T2-weighted MRI showing doughnut-shaped T2-hyperintense lesions in both optic nerves (arrowheads). (D–F) After immunosuppressive therapy, meningeal and orbital enhancement, and T2-hyperintense lesions were vanished.
!
2014 Informa Healthcare USA, Inc.
Orbit Downloaded from informahealthcare.com by University of Sydney on 01/31/14 For personal use only.
16 T. Takazawa et al. In addition, fat-suppressed T2-weighted imaging of the present patients displayed hyperintense lesions inferior to the enhancing optic nerve sheath. The frequency of neurological involvement was reported as 20–50% in WG patients.3,4 In general, three underlying mechanisms of optic nerve damage have been proposed in WG: (1) vasculitic ischemia; (2) spread inflammation of the adjacent sinuses; and (3) compression by the intraorbital granuloma. However, such mechanisms would not explain the visual deficits in the present described above. A previous pathological report demonstrated fibrosis and necrosis of the optic nerve sheath in a WG patient.2 The histological similarity and the anatomical continuity between the meninges and the optic nerve sheath, together with the MRI findings, suggest that perioptic granulomatous proliferation could play a role in the pathogenesis of optic nerve involvement in the present patients with WG. Rapid diagnosis of WG has a crucial implication for treatment of visual impairment because steroid therapy usually responds to orbital inflammation in WG patients. Thus, physicians should attend the distinct doughnutshaped sign of WG-associated OPN characterized by
abnormal enhancement in the optic nerve sheath and T2-hyperintense lesions in the superficial optic nerve on coronal MRI.
DECLARATION OF INTEREST The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
REFERENCES 1. Purvin V, Kawasaki A. Optic perineuritis secondary to Wegener’s granulomatosis. Clin Experiment Ophthalmol 2009;37:712–717. 2. Shunmugam M, Morley AM, Graham E, et al. Primary Wegener’s granulomatosis of the orbital apex with initial optic nerve infiltration. Orbit 2011;30:24–26. 3. Nishino H, Rubino FA, DeRemee RA, et al. Neurological involvement in Wegener’s granulomatosis: an analysis of 324 consecutive patients at the Mayo Clinic. Ann Neurol 1993;33:4–9. 4. de Groot K, Schmidt DK, Arlt AC, et al. Standardized neurologic evaluations of 128 patients with Wegener granulomatosis. Arch Neurol 2001;58:1215–1221.
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