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.
A 43-year-old woman with a history of recurrent headaches and associated vision disturbances for the past 4 years presented to our emergency department with a 4-week history of progressive left-eye pain that radiated to the back of her head, swelling around the left eye, double vision, and a unilateral left-sided headache. There were no factors that worsened or improved her symptoms. She first developed this 4 years ago while living in another state. At that time, she was admitted to a hospital, given intravenous (IV) then oral steroids which helped suppress the pain and swelling, but she did not recall a specific diagnosis. Since that time, she has had three separate flare-ups, each resolving after steroid treatment, with the current episode being the most recent and severe. On physical exam she had left periorbital swelling and edema, 20/25 vision in her right eye and 20/30 in her left eye, and extra ocular muscles were intact, but she reported left-eye pain when at extreme medial and lateral gaze. She did not have temporal lobe tenderness on examination. There was normal muscle tone, range of motion, and sensation in all four extremities bilaterally. Laboratory results at admission were as follows: erythrocyte sedimentation rate (ESR) of 30 mm/h and normal complete blood count, renal function, hepatic function, and transaminases. Computed tomography (CT) of the head without contrast, CT of the orbits with contrast (), CT angiogram of the head, and an electrocardiogram (EKG) were performed. All were normal aside from the CT angiogram of the head which suggested a varix versus aneurysm involving the anterior cerebral arteries in the region of the inferior sagittal sinus (). Ophthalmology was consulted, excluded acute angle closure glaucoma, retinal disorders, diagnosed her with recurrent idiopathic orbital inflammation syndrome and possibly Tolosa-Hunt syndrome, and recommended treatment with methylprednisolone 80 mg IV daily for 3 days. Within 24 h she noted a 50% reduction in pain and had complete resolution of her symptoms within 48 h. Magnetic resonance imaging (MRI) of the brain with and without contrast conducted the next day was normal and did not confirm the presence of a vascular anomaly suggested by the CT scan. At this point she was discharged on 60 mg oral prednisone daily with a taper over the course of 2 weeks. One week after discharge she was seen at her ophthalmologist’s office and remained asymptomatic.