Hypertrophic pachymeningitis and choroid plexitis in IgG-4 related disease

Abstract

A 64-year-old male presented with a 6-month history of headache, progressive hearing loss, vertigo, nausea/vomiting, diplopia, and gait instability. Past medical history was significant for hypertension. He was treated with several courses of antibiotics (doxycycline and ceftriaxone) for recurrent sinusitis. Neurological examination was notable for horizontal nystagmus, left facial weakness, bilateral sensorineural hearing loss, hyperreflexia in bilateral upper and lower extremities, and gait ataxia. Extensive serum laboratory workup for infectious and inflammatory disorders was non-revealing, except for a slightly elevated IgG4 level of 87.5 mg/dL (normal range: 3.9 to 86.4 mg/dL). CT examination of chest, abdomen, and pelvis was unremarkable. Cerebrospinal fluid (CSF) analysis revealed the following: protein 112 mg/dl, glucose 66 mg/dl, and white blood cell 41/µl with a lymphocytic predominance. CSF cytology and comprehensive infectious workup including meta-genomic next-generation sequencing was negative. Brain MRI with gadolinium contrast showed diffuse pachymeningeal thickening with enhancement, an enhancing mass in the choroid plexus of the posterior left lateral ventricle and focally enlarged choroid plexus within the fourth ventricle extending through the bilateral foramen of Luschka into the cerebellopontine cisterns (Figure 1). A right frontal dural biopsy showed prominent fibrosis and inflammation with CD3 positive T lymphocytes, CD20 positive B lymphocytes, and CD138 positive plasma cells (Figure 2). Strong IgG4 staining was observed with >100 IgG4 staining cells in one high power microscopic field and an IgG4/IgG staining ratio of >40% (Figure 2). A diagnosis of IgG4-related central nervous system (CNS) disorder involving predominantly the pachymeninges and choroid plexus was made. Treatment of intravenous methylprednisolone, followed by oral prednisone 60 mg and rituximab was initiated, which led to clinical and radiographic improvement at 2 months. At 14 months follow-up, he was asymptomatic with a normal neurological examination, and repeat brain MRI revealed significant improvement of pachymeningeal and choroidal thickening and enhancement (Figure 1).