A 38-year-old Asian man with a history of sinusitis status presented at the Ophthalmology outpatient department following a surgical intervention at another hospital 3 months previously, with complaints of gradual painless blurred vision and proptosis for 6 months. There was no periocular sensory change or recent trauma. His family history was unremarkable.\nOn ophthalmic examination, best-corrected visual acuity (BCVA) was 20/30 on the right eye (OD) and 20/40 on the left eye (OS). Slit-lamp and funduscopic examination results were normal. The pupil reacted sluggishly without a relative afferent pupillary defect. Color vision was normal. Ocular motility was intact without diplopia, but exophthalmometry measurements were 21.5 mm with base 112 mm using one accurately calibrated Inami exophthalmometer (Hertel K-0161; Inami & Co., Ltd., Bunkyo-ku, Tokyo, Japan) on both eyes (OU). There was neither periocular sensory change nor palpated mass in the lower eyelid.\nThyroid function tests revealed normal free thyroxine and thyroid-stimulating hormone levels, but serological studies showed extremely high serum concentrations of IgG4 (2650 mg/dL; normal range < 135 mg/dL); elevated serum concentrations of IgG (2630 md/dL; normal range 751.0–1560.0 mg/dL); abnormal erythrocyte sedimentation rate (31 mm/h; normal range < 15 mm/1 h); and high levels of total IgE (1903.00 IU/dL; normal range < 87.00 IU/mL). The calculated serum IgG4/IgG ratio was 100% (normal range < 6%). No eosinophilia was found in the blood.\nPostcontrast T1-weighted fat-saturated magnetic resonance imaging (MRI) images showed a “doughnut” sign encircling the right optic nerve, and inferior sheath enhancement surrounding the left optic nerve was visible on the coronal MRI images (Fig. a). Bilateral “tram-track” signs were evident on the axial images (Fig. b). Bilateral enhancing lesions at the pterygoid plate, pterygomaxillary fissure, and sella region, with involvement of both maxillary nerves, were visualized using gadolinium-enhanced T1-weighted MRI (Fig. c, d). Bilateral infraorbital nerve involvement was also evident on the MR images (Fig. d, e). Enlargement of extraocular muscles, especially severe at the bilateral inferior rectus, right medial rectus, bilateral superior rectus, and bilateral lateral rectus muscles, was noted on coronal MRI images (Fig. e). Mucosal thickening in the ethmoid, maxillary, sphenoid, and frontal sinuses was also visible.\nWe referred this patient to the Department of Otolaryngology in our hospital for surgical biopsy. Biopsy with functional endoscopic sinus surgery was performed, and a tissue specimen measuring 0.5 × 0.3 × 0.2 cm was sent to the Department of Pathology for further testing. The result revealed chronic sinusitis with dense infiltrate of lymphocytes and plasma cells. Chronic inflamed granulation tissue, aggregates of foamy histiocytes, and fibrosis of sinonasal tissue were also noted (Fig. a–c). Organisms were not identified in the Periodic Acid-Schiff stain and the Acid-fact stain tests. Immunhistochemistry revealed CD138 accentuated plasma cells (Fig. d) and highlighted numerous IgG4-positive plasma cells (> 50 IgG4-positive plasma cells per high-power field), of which over 40% were IgG-positive plasma cells (Fig. e, f).\nThe patient underwent a treatment regimen comprising oral systemic corticosteroids (prednisolone 1 mg per kg body weight daily) for 2 weeks followed by slow tapering. Visual acuity improved to 20/25 (OU) 1 month after initiating treatment. Four months after the initial treatment, the vision got worse again, with the BCVA dropping to 20/30 (OD) and 20/50 (OS), respectively. Visual field test showed parafoveal scotoma (OD) and an enlarged blind spot (OS). Visual evoked potentials indicated bilateral delayed P100 latency (Fig. f). No active lesions were found after systemic screening. Based on the combined clinical, radiographic, and histopathologic findings, the final diagnosis was IgG4-RD with bilateral optic perineuritis, branches of trigeminal nerves involvement, and pansinusitis.\nThe patient underwent another course of oral prednisolone daily for 2 weeks with gradually tapering of dosage. This was followed by treatment with the immunosuppressive agent azathioprine (50 mg, twice daily). The final BCVA was 20/20 (OD) and 20/25 (OS) during the follow-up period of 2 years.
A 38-year-old male patient presented with horizontal diplopia, divergent strabismus and ptosis of the left eyelid. He also had an intense stabbing/throbbing headache predominantly in the left temporal and periorbitary regions. Headache was continuous and demonstrated little response to common analgesics and nonsteroidal anti-inflammatories (NSAIDs). There was no complaint of nausea, vomiting, phonofobia or photophobia. The patient also complained of numbness in his left frontal and upper face (territory of ophthalmic and maxillary divisions of the trigeminal nerve).\nThere was a previous history of right-sided focal motor seizures, and a previous brain surgery 10 years ago for resection of a low grade tumour of the left frontal lobe (there was no pathological or immunohistochemistry report of that surgery available).\nOn examination the patient had complete third nerve palsy, sixth nerve palsy and loss of pinprick and thermic sensations in the territories of the Ophtalmic (V1) and Maxillary (V2) divisions of the trigeminal nerve on the left side. Other parts of the neurological examination, including cognition, motricity, reflexes and coordination were normal. There was no papilledema.\nA clinical diagnosis of cavernous sinus syndrome was made, and the patient was started on prednisone 60 mg/day, with significant improvement of headache intensity, resolution of ptosis and improvement in adduction, elevation and partial improvement in abduction of the left eye. An additional movie file shows this in more detail [see Additional file ].\nBrain magnetic resonance imaging (MRI) revealed an asymmetry of the cavernous sinuses, with the left cavernous sinus being larger than the right (Fig. ). There were also four meningeal lesions with contrast enhancement and without calcification in the upper convexity adjacent to the left and right frontal lobes, in the left cerebellopontine angle and left posterior temporal region (Fig. ).\nA biopsy of the meningeal lesion in the frontal convexity was performed, and resulted in a meningeal fragment with histiocytic proliferation (Fig. ). Immunohystochemical profile was negative for CD1a and ALK-1 and was positive for S100, CD68 (KP1 clone) and EMA (E29 clone), compatible with Rosai-Dorfman disease. Whole body computerized tomography (CT) scans did not reveal any other masses or lymphadenomegalies, characterizing an isolated CNS Rosai-Dorfman disease.\nThe patient was treated with intravenous methylprednisolone 1 g/kg daily for five days, with significant improvement of the cavernous sinus syndrome. Maintenance treatment consisted of prednisone 10 mg/day after tapering. He is asymptomatic and has remained seizure-free for two years. Follow-up brain MRI has showed a decrease in size of meningeal lesions and of cavernous sinus asymmetry (Fig. ).