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Immunoglobulin G4-related disease (IgG4-RD) is a multi-organ, relapsing fibroinflammatory disorder that can rarely involve the central nervous system (CNS). It manifests as hypertrophic pachymeningitis, hypo-physitis, and cranial neuropathies. MITIGATE Trial studied Inebilizumab's (Uplizna) efficacy for treatment of IgG4-RD and was recently approved by the Food and Drug Administration (FDA).

We managed three patients with histo-pathological confirmation of neurologically predominant IgG4-RD seen in the Neuroimmunology Clinic. Retrospective extraction of data from electronic medical records included demographics, symptomatology, neuroimaging, workup, histopathology, treatment regimens, and clinical outcomes. A comprehensive literature review was performed through PubMed, Embase, Scopus and Cochrane using keywords reporting CNS presentations and therapeutic outcomes with IgG4-RD. Data synthesis was qualitative due to heterogeneity among studies and limited sample size.

Patient 1 was a 64-year-old female presenting with monocular blurry vision, pachymeningeal enhancement and subdural hematoma. All workup was unrevealing. Biopsy demonstrated lymphoplasmacytic inflammation with IgG4-positive plasma cells. The patient was started on Inebilizumab after steroids and surgical resection ensuring symptomatic improvement. Patient 2 was a 61-year-old male with a history of pituitary IgG4-RD complicated by recurrent pituitary masses and multiple cranial neuropathies. Surgical resection and maintenance of low-dose corticosteroids achieved control. Patient 3 was a 23-year-old female with a rapidly progressive pituitary mass causing panhypopituitarism and diabetes insipidus. Histopathology demonstrated granulomatous inflammation with >100 IgG4-positive plasma cells/hpf. Post-surgical recovery was favorable, with stable postoperative imaging. Across cases, neuroimaging commonly revealed sellar/suprasellar or pachymeningeal involvement, and pathology confirmed dense IgG4+ plasma cell infiltrates. Literature review corroborated these findings, showing that early recognition and immunosuppression improve prognosis, though standardized treatment guidelines remain lacking.

Recognition of IgG4-RD requires high clinical suspicion and histopathologic confirmation. Corticosteroids remain the cornerstone of management but the emergence of Inebilizuamb poses a treatment dilemma in neurological-confined IgG4 since now there is an effective FDA approved drug available.