Case Presentation:
A 69-year-old right-handed Asian male was referred to our hospital for evaluation of chronic headache of 4 months duration. On examination, he was afebrile with stable vitals and did not have any focal neurological deficits. Initial laboratory evaluation, including complete blood counts, a comprehensive metabolic panel, and urinalysis were within normal limits. Cerebrospinal Fluid (CSF) analysis showed lymphocytic pleocytosis with elevated protein and normal glucose. CSF gram stain and cultures were negative for acid fast bacilli, bacteria and fungi. However, quantiferon gold was positive, Magnetic Resonance Imaging (MRI) showed leptomeningeal enhancement, and the patient was from a country in which tuberculosis is endemic. Therefore, a presumptive diagnosis of tuberculous meningitis was considered and anti-tuberculous therapy was initiated. One month later, he developed two episodes of seizures with right-sided motor symptoms. Repeat MRI showed new left parieto-occipital cortical infarcts and extensive pachymeningeal and leptomeningeal enhancement along the left parieto-occipital region. He underwent left parietal craniotomy for dural and subarachnoid biopsy. Pathologic examination of the brain and dural specimens failed to demonstrate granulomas or organisms, but instead showed diffuse lymphocytic and plasmacytic infiltrates involving vessels. His autoimmune panel and rheumatoid factor were negative. 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) and serum quantitative IgG4 was elevated. Hence a diagnosis of IgG4-related hypertrophic pachymeningitis (IgG4 RHP) was made and patient was started on high dose steroids. He had dramatic clinical and radiographic improvement, in keeping with this diagnosis. He was eventually discharged on high dose steroids and was asymptomatic on a 2 month follow up.
Discussion:
It is estimated that IgG4-RHP may account for a high proportion of cases of hypertrophic pachymeningitis once considered idiopathic. The diagnosis of IgG4 RHP should rely primarily on MRI, CSF analysis, and meningeal biopsy. Hallmark histopathological features are a lymphoplasmacytic infiltration of IgG4-positive plasma cells, storiform fibrosis and obliterative phlebitis. The most commonly used treatment is steroids. Immunosuppressants such as azathioprine and methotrexate may be considered if the patient does not respond to steroids.
Conclusions:
IgG4-RHP is an extremely rare disease that may exhibit parenchymal invasion and cause focal neurological deficits. It poses a diagnostic challenge because of its rarity and clinical presentation that mimics other meningeal diseases. Clinicians should become familiar with this alternative diagnosis because early recognition and prompt treatment may avoid long-term neurological complications.