A critical review and update on autoimmune encephalitis: understanding the alphabet soup

Abstract

Autoimmune encephalitis (AE) comprises a group of diseases mediated by antibodies against neuronal cell surface or synaptic antigens, such as ion channels or neurotransmitter receptors. New clinical syndromes and their associated antibodies were and are still being characterized over the last two decades. The fact that their main clinical features are interdisciplinary, - encompassing neuropsychiatric symptoms, cognitive dysfunction, epileptic seizures, movement and sleep disorders - has led to a surge of interest in this field. Some of these diseases present with a well-defined syndrome, being recognizable on clinical grounds. Correct diagnosis is important since AE are potentially treatable diseases, despite their severity. On the other hand, an increasing number of neuronal antibodies being described casts doubt upon the way we should utilize antibody testing and interpret results. In this article we review, summarize and update the current knowledge on antibody mediated encephalitis.

An Autopsy-proven Case-based Review of Autoimmune Encephalitis

“…Anti-DPPX (Dipeptidyl-peptidase-like protein-6) antibodies, albeit infrequent, may be linked to encephalitis and gastrointestinal manifestations [ 13 , 29 , 30 ]. The presence of anti-mGluR5 (metabotropic glutamate receptor 5) antibodies is indicative of Ophelia syndrome, a specific subtype of limbic encephalitis [ 12 ].…”

“…Anti-glycine receptor antibodies predominantly correlate with stiff person syndrome and PERM (Progressive Encephalomyelitis with Rigidity and Myoclonus) [ 12 ]. Anti-MOG-associated AIE is associated with ADEM, optic neuritis, transverse myelitis, and cerebral cortical encephalitis with epilepsy [ 31 ].…”

“…Due to its rarity, AIE can be misdiagnosed as psychiatric or neurological disorders or even drug abuse [ 10 , 11 ]. However, AIE is considered a treatable disease, and early diagnosis is crucial to prevent severe complications [ 12 ].…”

“…AIE presents a diagnostic challenge as an inflammatory brain disease, with relatively few reported cases in the literature that have undergone brain biopsy or autopsy [ 4 , 12 ]. Recently, a distinct form of CNS immune reconstitution inflammatory syndrome (IRIS) known as ‘CD8 encephalitis’ has been recognized [ 14 , 15 ].…”

Clinical analysis of 173 pediatric patients with antibody-mediated autoimmune diseases of the central nervous system: a single-center cohort study

“…Clinical application of antineural antibodies has been increasing and new anti-neural antibodies continue to be discovered. The antibody spectrum of CNS autoimmune diseases is also rapidly expanding with the growing understanding of their etiology, pathogenesis, and treatment (2)(3)(4)(5)(6).…”