Case Presentation

A 33-year-old woman with a history of recurrent hospitalization due to headaches with blurred vision was admitted to our neurology department. In January 2018, she had cerebral vein thrombosis (CVT) in the left transverse sinus with left mastoiditis, treated with anticoagulants and antibiotics. Extensive work-ups for finding the etiology produced negative results, including acquired and genetic thrombophilia tests. In December 2020, she was diagnosed with a new CVT in the sigmoid sinus. Again she was discharged with a 5mg daily dose of Warfarin. In March 2021, she presented horizontal binocular diplopia, blurry vision, and hemicranial headache in the last hospitalization. The patient also complained of right eye proptosis, which developed in a period of 3 months. She did not report any fever, seizures, neck stiffness, or weight loss. Except for the history of recurrent CVTs, the patient did not have any specific diseases. She had stopped using her drugs individualistically four months ago due to the improvement of her symptoms.
The patient had a smoke-free life and never used illicit drugs. Also, there was no history of drugs that induced a hyper coagulated state (e.g., Oral Contraceptive Pill or OCPs). On physical examination, the vital sign was stable (Blood Pressure:133/78 mmHg, Pulse Rate: 92 pr/min, Respiratory Rate: 18 pr/min, Temperature: 37.6 C), and the mental status was not impaired (Glasgow Coma Scale:15/15). An ophthalmometer established a 5mm protrusion from the temporal orbital rim in the right eye. On ophthalmoscopy, bilateral papilledema was detected. Except for a right sixth nerve palsy, other cranial nerve examinations were not involved. Sensory and motor examinations were unremarkable, the muscle tones were normal, and the forces were 5/5. Deep Tendon Reflexes were not impaired, and the plantar reflexes were downward. Also, the patient had a normal gait.
Brain Magnetic Resonance Imaging (MRI), Magnetic Resonance angiography (MRA), Magnetic Resonance Venography (MRV), and a Computed Tomography (CT) scan was performed. The T1 weighted MRI with Gadolinium contrast demonstrated diffuse pachymeningeal thickening (Figure 1A, B) and an enhanced intra-orbital mass measuring 9*15*24mm, which seems to be originated from right lateral and superior rectus muscles (Figure 2A, B) . Compared to the previous neuroimaging of the patient admissions in 2018 and 2020, this mass was defined as a new finding. MRV revealed CVT within the left transverse sinuses and superior sagittal sinus (Figure 3) . In addition to confirming the intra-orbital mass presence and size, Orbit MRI disclosed the tortuous appearance of both optic nerves with dilation in nerve sheets and superior ophthalmic veins were dilated. Laboratory test findings were unremarkable, except for hemoglobulin (Hgb:11.9 g/dl), high serum C-reactive protein (CRP:52 mg/L), Erythrocyte Sedimentation Rate (ESR:76mm/h), serum IgG (34,6 g/L;normal range:7-16) and serum IgG4 (141 mg/dl) was above the upper limit of the normal range (4–90 mg/dl). Other specific serum rheumatological or vasculitis markers include P-ANCA, C-ANCA, ANA, Anti-dsDNA, anti-Smith, Anti-RNP, anticardiolipin antibodies, β2-glycoprotein, C3, C4, RF, Anti-CCP, Anti-SSA/ Ro, Anti-SSB/ La were normal in the results. In addition, Acquired and genetic thrombophilia tests findings (e.g., protein C deficiency, protein S deficiency, Antithrombin III deficiency, Factor V Leiden mutation, Homocysteine level, and Prothrombin 20210 mutation) were negative. The tumor marker assessment demonstrated negative results for CA5.3, CA19.9, CA125, α-fetoprotein (α-FP), and carcinoembryonic antigen (CEA)). Lumbar puncture (LP) indicated a low elevation in opening pressure (30 cm H2O), absence of WBC and RBC, a normal protein level (33 mg/dl), and an average glucose level (63 mg/dl). CSF isoelectric focusing showed an oligoclonal IgG banding pattern. There was no evidence of bacterial growth in CSF gram staining and culture. A surgical biopsy from the intra-orbital mass was accomplished. In the pathology report, microscopic examination of the specimen revealed fragments of fibroconnective tissue containing inflammatory cells infiltration, composed mostly lymphoplasmacytic admixed with histiocytes and polymorphonuclears (PMNs). Foci of necrosis fibrosis and lymphoid follicles formation were also seen. Special stainings for acid-fast bacilli and fungi were negative. Immunohistochemistry showed approximately 60 IgG4-positive plasma cells per high-power field (HPF), of which almost more than 40 of the IgG+ plasma cells were IgG4+. Also, the IgG4+/IgG+ plasma cell ratio was more than 40%(Figure 4) . For other organ work-ups, CT-scan from chest and MRI from abdomen and pelvic were conducted, but they didn’t have any specific findings. The patient received Prednisolone (1 mg/kg/day) for three months and a 5mg daily dose of Warfarin. She felt a rapid improvement after initiating the treatment. Azathioprine (2 mg/kg/day) was also prescribed without any interval. After eight months, all neurological symptoms had resolved.