Case Presentation:
A 69 year old right-handed Asian male presented with 2 episodes of right sided focal seizures. He has a past medical history significant for chronic headaches of 4 year duration and was being treated for presumed tuberculous meningitis based on lymphocytic pleocytosis with elevated protein in Cerebrospinal Fluid (CSF) analysis, leptomeningeal enhancement in Magnetic Resonance Imaging (MRI), a positive quantiferon gold and endemic country of origin; but his CSF gram stain and cultures were negative for Acid Fast Bacilli (AFB), Bacteria and Fungi. On examination he was afebrile with stable vitals and didn’t have any focal neurological deficit. Initial lab evaluation showed a normal Complete Blood Count (CBC), Comprehensive Metabolic Panel (CMP) and Urinalysis. His repeat MRI showed new left pareito-occipital cortical infarcts and extensive pachymeningeal and leptomeningeal enhancement along bilateral parieto-occipital regions. As the lesions were not improving with the treatment, he underwent left parietal craniotomy and dural / subarachnoid biopsy. Evaluation for tuberculous meningitis remained negative and the brain and dural biopsy specimen failed to demonstrate granulomas or organisms, but had diffuse lymphocytic and plasmacytic infiltrates, involving vessels. His autoimmune panel and Rheumatoid factor were negative and Serum and Urine Immunoelectrophoresis were normal. He had negative hepatitis serologies and HIV testing was non-reactive. Immunohistology of the meninges revealed extensive high density staining of the meninges with IgG4 (Immunoglobulin-G4) consistent with IgG4 related disease. The serum quantitative IgG4 was also found to be elevated. The patient had dramatic clinical and radiographic improvement with steroids, which is consistent with IgG4 disease. He was eventually discharged on high dose steroids, antiepileptics and was continued on INH and Rifampin therapy, as he anyways needed prophylaxis for latent TB infection and was tolerating those medications.
Discussion:
The diagnosis of IgG4-related disease is based on clinical examination showing characteristic diffuse / localized swelling or masses in single or multiple organs; hematological examination showing elevated serum IgG4 concentrations and histopathologic examination revealing marked lymphocyte and plasmacyte infiltration and fibrosis, and infiltration of IgG4+ plasma cells. Immunoglobulin G4 (IgG4) – related hypertrophic pachymeningitis is an increasingly recognized manifestation of IgG4-related disease, a fibro inflammatory condition that can affect virtually any organ. Immunosuppressants, such as steroids, azathioprine, and methotrexate are considered the main treatment options and are highly effective.
Conclusions:
IgG4-related hypertrophic pachymeningitis can present with symptoms including headaches with or without increased intracranial pressure, and cranial neuropathy. Meningeal biopsy is the most confirmatory diagnostic tool in these cases.