A clinical approach to diagnosis of autoimmune encephalitis

Abstract

Encephalitis is a severe inflammatory disorder of the brain with many possible causes and a complex differential diagnosis. Advances in autoimmune encephalitis research in the past 10 years have led to the identification of new syndromes and biomarkers that have transformed the diagnostic approach to these disorders. However, existing criteria for autoimmune encephalitis are too reliant on antibody testing and response to immunotherapy, which might delay the diagnosis. We reviewed the literature and gathered the experience of a team of experts with the aims of developing a practical, syndrome-based diagnostic approach to autoimmune encephalitis and providing guidelines to navigate through the differential diagnosis. Because autoantibody test results and response to therapy are not available at disease onset, we based the initial diagnostic approach on neurological assessment and conventional tests that are accessible to most clinicians. Through logical differential diagnosis, levels of evidence for autoimmune encephalitis (possible, probable, or definite) are achieved, which can lead to prompt immunotherapy.

N‐methyl‐D‐aspartate receptor antibody production from germinal center reactions: Therapeutic implications

“…Because NR1‐IgG has proven pathological relevance in NMDAR‐antibody encephalitis,2, 8, 13 next we explored factors related to its production. The total amount of NR1‐IgG generated in vitro for an individual patient correlated with their serum NR1‐IgG levels (r 2  = 0.88; p  < 0.0001; Supplementary Fig 1), and not with parameters including total IgG production in vitro (r 2  = 0.38; p  = 0.08), time since disease onset (r 2  < 0.01; p  = 0.83), time since immunotherapy initiation (r 2  = 0.10; p  = 0.40), or types of immunotherapy (data not shown).…”

“…A prospectively assessed consecutive cohort of 10 patients were recruited with known CSF NR1‐IgG antibodies who met diagnostic guidelines for definite NMDAR‐antibody encephalitis 13. From these 10 patients, clinical details, including treatments (Table and Supplementary Table 1), peripheral blood mononuclear cells (PBMCs; sampled at 1–112 months after symptom onset [median, 16; mean, 25]), and longitudinal sera, were obtained.…”

Bortezomib treatment for severe refractory anti‐NMDA receptor encephalitis

“…Possible infectious etiologies were excluded according to a protocol previously described 5. Diagnosis of anti‐NMDAR encephalitis was made according to the expert consensus criteria 16. All patients fulfilled criteria for probable anti‐NMDAR encephalitis and a definite diagnosis was confirmed by the detection of anti‐NMDAR antibodies in serum and CSF.…”

A bridge between evidence-based laboratory diagnostics and research in neuroimmunology: why standardizations and guidelines matter

“…Many reports recommend expertise in neuroimmunology diagnostic tests and their implementation in specialized laboratories [3,[8][9][10][11]. Nevertheless, laboratory medicine of autoimmune diseases is being increasingly conducted in large generalist laboratories that, differently from small specialized laboratories, can comply with the certification rules requested by regional agencies and national healthcare system in Italy.…”

“…Such antibody reactivities are associated with particular forms of Bautoimmune encephalitis,^potentially treatable diseases representing an expanding area in neurology [2,3] (see the guideline article in this supplementum). Table 1 shows a list of antigens targeted by these new autoantibodies together with other most common antigens involved in autoantibody-related neurological diseases.…”