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. ).
A 54-year-old man with a 4-month history of recurrent sinusitis, 100-lb unintentional weight loss, gait instability, and generalized weakness presented with headache and painless, bilateral visual loss. Bilateral temporal artery biopsies were performed and showed no arteritis. Magnetic resonance imaging (MRI) of the brain revealed mild meningeal enhancement and a chronic subdural hematoma causing mild midline shift. Following surgical drainage, visual acuity remained unchanged, and his headaches worsened. Pertinent clinical findings were no light perception in both eyes, amaurotic pupils, and bilateral mild, temporal optic disc pallor. Ocular coherence tomography (OCT) of both optic nerves demonstrated normal nerve fiber layer thickness. Laboratory tests failed to suggest an etiology of his vision loss. Lumbar puncture showed lymphocytic pleocytosis but cytology and flow cytometry were negative for lymphoma. Repeat brain MRI was performed and demonstrated diffuse pachymeningeal enhancement (Fig. a) with possible involvement of the optic nerve sheath (Fig. b); a dural biopsy was performed.\nHistopathology demonstrated a dense infiltrate of lymphocytes and plasma cells, with no definite vasculitis or granulomatous inflammation (Fig. c, d). The possibility of marginal zone lymphoma was considered but was ruled out by immunohistochemistry, with T cells (CD3-positive) outnumbering B cells (CD20-positive), and with in situ hybridization revealing a kappa:lambda ratio of <4:1 among the plasma cells (not shown). In situ hybridization for Epstein-Barr virus was negative (not shown). Additionally, molecular genetic studies did not show any evidence of a clonal IgH gene rearrangement by polymerase chain reaction (PCR). However, IgG4 immunostain was markedly positive, with 40 IgG4-positive cells per high-power field (HPF), comprising over 40 % of the total plasma cell population (Fig. e, f). (The total plasma cell population was assessed with CD138 immunostain, and IgG immunostain was also obtained, showing that all IgG-positive cells were also IgG4-positive, i.e., IgG4:IgG ratio of 1, not shown). Subsequent bone marrow biopsy also showed no evidence of lymphoma (small CD19-positive B-cell population with normal kappa:lambda light chain ratio), and fine-needle aspiration biopsy of a left supraclavicular lymph node showed similar findings negative for lymphoma.\nOn his systemic work-up, p-ANCA was borderline positive, and serum IgG showed elevated IgG4 subclasses (148.0; normal range 2.4–121.0). Accordingly, the diagnosis of IgG4-related meningeal disease was made. The patient was started on aggressive immunosuppression with high-dose corticosteroids to be followed by either cyclophosphamide or rituximab. However, due to insurance issues, he was able to receive only methotrexate. There was near-total resolution of meningeal enhancement on repeat MRI, but his visual acuity improved to only bare light perception in both eyes. He remains stable on methotrexate almost 1 year from his diagnosis.