Autoimmune Encephalopathy

Eoin P. Flanagan, M.B.B.Ch.; Richard J. Caselli, M.D.

Disclosures

Semin Neurol. 2011;31(2):144-157. 

In This Article

Abstract and Introduction

Abstract

Autoimmune encephalopathy represents a complex category of disease with diverse immunologic associations, clinical manifestations, and therapeutic outcomes. Three main subgroups include autoimmune encephalopathies without cancer but with neural nonspecific serologic evidence of autoimmunity (encompassing "Hashimoto's encephalopathy") that is the main focus of this review, paraneoplastic encephalopathies, and central nervous system (CNS) vasculitis (primary or secondary). Diagnosis of autoimmune encephalopathy can be suspected based on the clinical course, serologic evidence of autoimmunity, severe but nonspecific slowing on electroencephalography, and evidence of intrathecal inflammation in the cerebrospinal fluid. Rarely, there will be evidence of meningeal enhancement or increased fluid attenuated inversion-recovery signal in symptomatic regions on magnetic resonance imaging, but diagnosis may require brain biopsy demonstration of perivascular lymphocytic infiltrates. Nonspecific autoimmune encephalopathies are generally much more therapeutically responsive than paraneoplastic and vasculitic encephalopathies, so that high-dose corticosteroids may produce dramatic improvement within as little as a few days, although exceptional patients can require months of therapy. Paraneoplastic syndromes typically require tumor removal and often prove fatal. CNS vasculitides may respond to steroid therapy, but often require a second agent such as cyclophosphamide.

Introduction

In 1966 Brain et al[1] described a 49-year-old man with Hashimoto's thyroiditis who presented with stroke-like episodes and subsequently delirium. The patient did not respond to prednisone, but eventually recovered, leading Brain to suggest that autoimmune mechanisms might be responsible. Since that time, there have been many further cases reported in the literature of Hashimoto's encephalopathy. The continued use of this term despite the now abundant evidence of its nonspecificity has provoked some controversy,[2] as it implies causality which is no longer tenable.[3] Indeed, Brain himself felt that the serologic association reflected a propensity to neurologic autoimmunity rather than a specific pathogenic relationship, and since his description, many patients with autoimmune encephalopathies have been reported with multiple other autoimmune disorders.[4] Other descriptions have included nonvasculitic autoimmune inflammatory meningoencephalitis (NAIM), to distinguish it from a similar presentation of central nervous system (CNS) vasculitis;[5] steroid responsive encephalopathy associated with autoimmune thyroiditis (SREAT), highlighting its immunotherapy responsiveness;[4] neural specific autoantibody syndromes (such as autoantibodies to the voltage gated potassium channel complex);[6–8] and autoimmune dementia,[9] highlighting a frequent clinical presentation.

Ultimately, the continued discovery of new pathogenic neural specific autoantibodies will permit more-precise classification, enhance our insight into the clinical and pathologic spectrum associated with each specific autoantibody, and better guide therapeutic decisions. To simplify clinical conceptualization and avoid terminologic confusion, we have opted for the general term autoimmune encephalopathy, and will focus primarily on that subset that are not known to be associated with a defining pathogenic autoantibody, tumor, or CNS vasculitis. For a comparison of autoimmune, paraneoplastic, and vasculitis-associated encephalopathy, please see Table 1.

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