Case report
We describe a case of a 25-year-old South Asian gentleman with no past medical history who suffered a seizure during an air flight and brought to the hospital. The event started with jerky movements on the left side of his body and numbness followed by secondarily generalized tonic-clonic seizure (GTCs)and loss of consciousness lasting for a few minutes. According to the patient, these attacks started one year ago, with the last episode being two months prior. He also had a mild nonspecific headache with right frontal swelling for the last two months without any fever, cough, weight loss, and night sweats. There was no history of focal weakness, vision problems, or balance problems. He did not give a history of any myalgias, joint pain, dry eyes or mouth, skin rash, or oral ulcers. A review of the system was negative for any respiratory, gastrointestinal, and urinary symptoms. He did not take any medical treatment for these events. He was a nonsmoker, nonalcoholic, and denied any use of illicit recreational drugs. He was unmarried, and his family history was negative for epilepsy or any other neurological disease. He works as a cobbler in a leather factory. There is no sick contact history.
He was vitally stable. His neurological and systemic exam was unremarkable. He was started on phenytoin as an anti-seizure agent. Initial blood work including complete blood count, coagulation profile, blood chemistry, and renal and liver function tests did not show any significant abnormality. His chest x-ray showed hazy ill-defined shadows present in the right upper zone and to a lesser extent at the left upper zone and the right base. CT scan head non-contrast showed right side extra-axial hyperdensity along frontoparietal convexity of 12 to 13 mm in maximum thickness with effacement of the adjacent sulci and 5 mm midline shift to the left (fig1-a, b ) and was reported as Subdural hematoma. However, there was no history of any trauma or bleeding disorder. An osteolytic lesion in the right frontal bone (fig1-b, c ). There was no history of trauma and no clinical signs or laboratory abnormality indicative of bleeding diathesis for spontaneous subdural bleeding. MRI of the head with contrast was done after admission and the results showed: a right side intracranial extra-axial hemispheric crescentic shaped mass lesion showing low signal in T2, FLAIR, and T1 sequences with intense postcontrast enhancement and underlying dural involvement having a maximum thickness of 13 mm, extending along the surface of the right cerebral hemisphere more at the higher cuts, reaching the ventral part of the interhemispheric fissure with mild left frontal dural enhancement as well. There was the associated irregularity of the adjacent inner skull table with right frontal focal full-thickness bony defect, underlying diploic and extracranial enhancing swelling as well as right frontal bone marrow signal abnormality bright in T2. Partial effacement of the right cerebral frontoparietal cortical sulci with mild compression of the right lateral ventricle and midline shift to the left side of about 5 mm was seen (fig2-a-e ).
The working differential diagnosis at the stage based on the clinical and imaging findings was an infective process (TB, fungal infections), neoplastic lesion (carcinomatosis, lymphoma, leukemia), histiocytosis, and inflammatory granulomatous processes like Sarcoidosis and Wegner granulomatous. Further work-up was tailored accordingly based on the differential. CT scan of chest, abdomen, and pelvis showed multiple enhancing pulmonary nodules of both lungs, in the upper lung lobe with no other abnormality in abdomen and pelvis (fig3-a, c ). Erythrocyte sedimentation rate was high 67 (reference 5 to 28), C - reactive protein (CRP)
129 (reference 1to 5), procalcitonin was normal whilst TB PCR was negative. The serum and urine protein electrophoresis were unremarkable. The flow cytometry indicated no definitive immunophenotypic evidence of a monotypic B-cell population. ANA and ANCA were negative.
He underwent right side craniotomy and had a right frontal skull osteolytic lesion with dural thickening. Resection of the thickened dural area and repair of skull defect were done. A Frozen Section Diagnosis of the skull lesion with intracranial subdural collection showed aggregates of chronic inflammatory cells, plasma cells, and lymphocytes, while that of thickened dura had dense fibrous tissue with a focal aggregate of chronic inflammatory cells. Histopathology Sections show sclerosed fibrous tissue in storiform pattern and patchy chronic inflammatory cell infiltrate, including lymphocytes, plasma cells, and few histiocytes and eosinophils. Few neutrophils were also noted. The inflammatory cells predominantly aggregated around blood vessels with no granuloma, necrosis, or atypia. Ancillary Immunohistochemistry studies with appropriate controls show the following results: CD138: Positive and highlighting an enormous number of plasma cells. IgG: Positive in plasma cells. IgG4: Positive in plasma cells (more than 10 positive cells/HPF). Kappa and Lambda: Polyclonal. Alk-1: Negative. S-100: Negative. Based on these findings definite diagnosis was an Inflammatory sclerosing pseudo tumoral lesion compatible with IgG4-related meningeal disease. Histopathology from CT-guided right lung biopsy was also consistent with Ig4 related disease.
Serum immunoglobulin measurement was positive for elevation in total IgE with a level 263 k units/L (reference range between 0 and 114) and in IgG4 (223mg/dL with a reference range of 3–201). C3 and C4 194 and 193 were also elevated. Final cultures were negative for mycobacterium, fungal, and any other bacterial organism.
During his hospital stay, our patient had experienced episodes of sudden left side jerky movement with facial twitches followed by loss of consciousness. Levetiracetam was added. After the diagnosis of IG4 related disease, He was treated on oral steroids 60mg OD dose and IV 1g rituximab dose was given to be followed by 2nd dose in 14 days in his home country. On discharge, azathioprine 100 mg OD was also prescribed He did not have further GTCs but reported episodic mild numbness of the left side with minor jerky movements. Inflammatory markers show CRP decrease to 53. He was repatriated to his home country as he was a transit passenger.