Neurological manifestations of immunoglobulin G4related disease: a systematic review of 393 cases

Background Immunoglobulin G 4 (IgG 4 ) related disease (RD) is a multisystem, immunologically mediated disease discovered within the last two decades. Within the nervous system, a broad range of both central and peripheral nervous system involvement has been reported. We aimed to systematically review the neurological manifestations of IgG 4 -RD. Aim To identify the clinical presentation, radiological findings, diagnostic methods, treatment and outcomes for neurological manifestations of IgG 4 -RD. Methods We systematically reviewed the literature to identify all reports of neurological manifestations of IgG 4 -RD. Data on neurological manifestations, non-neurological manifestations, clinical presentation, radiological findings, diagnostic methods, treatment modalities and outcomes were extracted. Results We identified 393 cases from 297 publications meeting the inclusion criteria. Hypertrophic pachymeningitis, IgG 4 -related orbital disease and hypophysitis are the most common neurological manifestations of IgG 4 -RD. Diagnostic evaluation involves testing for concomitant non-neurological manifestations, an MRI with gadolinium contrast, measurement of serum IgG 4 levels and a biopsy with specific staining for IgG 4 positive plasma cells. Treatment with corticosteroids leads to favourable outcomes. Conclusions IgG 4 -RD is an emerging neurological disease that can manifest in multiple ways within the nervous system. It is important to recognise as treatment is often successful.