Recognizing Autoimmune-Mediated Encephalitis in the Differential Diagnosis of Limbic Disorders

Abstract

SUMMARY: Limbic encephalitis is far more common than previously thought. It is not always associated with cancer, and it is potentially treatable. Autoantibodies against various neuronal cell antigens may arise independently or in association with cancer and cause autoimmune damage to the limbic system. Neuroimaging plays a key role in the management of patients with suspected limbic encephalitis by supporting diagnosis and excluding differential possibilities. This article describes the main types of autoimmune limbic encephalitis and its mimic disorders, and emphasizes their major imaging features.ABBREVIATIONS: AME ϭ autoimmune-mediated encephalopathy; AMPAR ϭ ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; CASPR2, contactin-asso-

Autoimmune Encephalitis: Pathophysiology and Imaging Review of an Overlooked Diagnosis

“…[1][2][3] Despite this increased recognition, it has yet to become an established diagnostic consideration outside of large tertiary referral centers. [1][2][3][4][5] The term "autoimmune encephalitis" generally refers to a family of closely related disease processes that share overlapping clinical features and neuroimaging findings but are ultimately differentiated by the specific antibody subtypes driving the underlying immune-mediated attack on different CNS structures. [6][7][8] This antibody-mediated attack on neuronal structures results in a localized inflammatory response.…”

“…While limbic dysfunction is the single most consistent finding in autoimmune encephalitis, varying degrees of involvement are seen within the neocortex, striatum, hindbrain, spine, and peripheral nervous system based on the unique antibody profile. 3,[9][10][11][12] In addition, certain antibody subtypes consistently lack imaging manifestations, while others characteristically demonstrate prominent "extralimbic" involvement. 3,7,[13][14][15] Although it was initially thought to be relatively rare, there is growing consensus that autoimmune encephalitis is responsible for a subset of altered mental status previously considered idiopathic.…”

“…3,[9][10][11][12] In addition, certain antibody subtypes consistently lack imaging manifestations, while others characteristically demonstrate prominent "extralimbic" involvement. 3,7,[13][14][15] Although it was initially thought to be relatively rare, there is growing consensus that autoimmune encephalitis is responsible for a subset of altered mental status previously considered idiopathic. [3][4][5] Despite its growing recognition as a rare cause of altered mental status, autoimmune encephalitis remains a diagnosis of exclusion with more common causes often identified during the standard diagnostic evaluation.…”

“…3,7,[13][14][15] Although it was initially thought to be relatively rare, there is growing consensus that autoimmune encephalitis is responsible for a subset of altered mental status previously considered idiopathic. [3][4][5] Despite its growing recognition as a rare cause of altered mental status, autoimmune encephalitis remains a diagnosis of exclusion with more common causes often identified during the standard diagnostic evaluation. 16,17 However, more complex presentations of altered mental status may display atypical features without a clear etiology identified after routine testing.…”

“…16,17 In these situations, recognition of potential cases of autoimmune encephalitis by the radiologist can be the first step to optimizing clinical outcomes through ensuring that a prompt and appropriate clinical work-up is performed, including the use of specialized serum/CSF antibody panels, with the ultimate goal of establishing an effective treatment regimen before the onset of devastating complications. 3,5,8,18 The purpose of this article is to discuss the subset of immunemediated CNS conditions with features of autoimmune encephalitis (ie, antibody-mediated inflammation of the brain), provide a framework for radiologists to understand the relevant neuroimmunology, review the major antibody subtypes, and describe the constellation of clinical and imaging features that are most suggestive of this diagnosis.…”