Neurological Manifestations of IgG4-Related Disease

Abstract

IgG4-related disease (IgG4-RD) is a multisystem inflammatory disorder. Early recognition of IgG4-RD is important to avoid permanent organ dysfunction and disability. Neurological involvement by IgG4-RD is relatively uncommon, but well recognised-hypertrophic pachymeningitis and hypophysitis are the most frequent manifestations. Although the nervous system may be involved in isolation, this more frequently occurs in conjunction with involvement of other systems. Elevated circulating levels of IgG4 are suggestive of the condition, but these are not pathognomonic and exclusion of other inflammatory disorders including vasculitis is required. Wherever possible, a tissue diagnosis should be established. The characteristic histopathological changes include a lymphoplasmacytoid infiltrate, storiform fibrosis and obliterative phlebitis. IgG4-RD typically responds well to treatment with glucocorticoids, although relapse is relatively common and treatment with a steroid-sparing agent or rituximab may be required. Improved understanding of the pathogenesis of IgG4-RD is likely to lead to the development of more specific disease treatments in the future.

Keywords: Hypophysitis; IgG4-related disease; Neuropathy; Pachymeningitis; Pseudotumour.

Fig. 1

MR imaging (a, b) demonstrated an enhancing soft tissue mass involving the right posterior nasopharynx with infiltration laterally and posteriorly into the right prevertebral strap muscles and through the pharyngobasilar fascia to involve the medial and lateral pterygoids. The right carotid and internal carotid artery was ensheathed and abnormal tissue was seen in the right carotid canal and jugular foramen. The right cavernous sinus was involved via perineural spread through the foramen ovale. Basal pachy- and leptomeningitis were noted along the floor of the right middle cranial fossa with high signal in the overlying temporal lobe (c). Progressive changes were noted in the pterygomaxillary fissure, the muscles of the masticator compartment and throughout the temporalis muscle on the right at the time of representation (d). e–g A diffuse plasma cell-rich, chronic inflammatory cell infiltrate with prominent stromal fibrosis/hyalinization, fat necrosis and focal granulation tissue was evident on biopsy of the anterior temporalis and posterior maxilla (e). Immunocytochemistry demonstrated numerous IgG- and IgG4-positive plasma cells (f, g). Reproduced with permission from Rice et al. [95].