Table 1.
Warning signs of autoimmune encephalitis in patients with psychotic symptoms and step-by-step diagnosis (31, 56, 58).
| Subacute onset (rapid progression within <3 months) despite therapy plus: | |
| • Disturbed consciousness | |
| • Movement disorder (dystonia or dyskinesia) or unsteadiness of stance and gait | |
| • Autonomic instability | |
| • Disorganized thinking/behavior | |
| • Catatonia/suspected malignant neuroleptic syndrome | |
| • Hyponatremia that cannot be explained by side effects of existing medication (SSRI, carbamazepine, etc.) | |
| • Epileptic seizures / faciobrachial dystonic seizures (the latter is common in LGI1 encephalitis) | |
| • Focal neurological deficits, including aphasia, dysarthria, or paresthesias | |
| • Newly developed headache or clinically relevant change in headache pattern | |
| • Prodromal flu-like symptoms | |
| • History of malignant tumor disease | |
| • Other autoimmune diseases (e.g., systemic lupus erythematosus, thyroiditis) | |
| |
| Further obligatory diagnostics | |
| cMRI (MRI is unremarkable in ~50% of cases with autoimmune encephalitis) | • Hyper-intense signal in T2 or FLAIR sequences, mesiotemporally accentuated (limbic encephalitis), or multifocal in white and/or gray matter |
| EEG | • Epileptic or slow-wave activity, possibly temporally accentuated, extreme delta brush (beta-delta complexes consisting of bilateral delta activity at 1–3 Hz and superimposed beta activity at 20–30 Hz; this pattern is fairly typical for NMDAR encephalitis) |
| Lumbar puncture/CSF analysisBasic CSF diagnostics (cell count, albumin CSF/serum ratio, immunoglobulin index, oligoclonal bands) | • Lymphocytic pleocytosis (>5 cells/μl), specific oligoclonal bands, albumin CSF/serum ratio (blood-CSF-barrier disturbance). No evidence of infection but secondary autoimmune encephalitis may occur after viral encephalitis |
| |
| Measurement of antineuronal autoantibodies in cerebrospinal fluid and serum | |
| Basic antibody screening minimally should include the most common IgG antibodies to the following antigens: | |
| • NMDA-R, CASPR2, LGI1, AMPA-R, GABAB-R, and GAD65 (determination in serum and CSF) | |
| • Hu, Ri, Yo, CV2/CRMP5, Ma2 [Ta], amphiphysin (determination in serum, CSF tests can be added if the serum is positive) | |
| In the second step (in cases of negative screening and reasonable suspicion), IgG antibodies can be detected against the following antigens: | |
| • GABAA-R, DPPX, mGluR5, Neurexin-3-alpha, IgLON5, and Glycin-R (determination in serum and CSF). | |
| Immunofluorescence screening tests on rodent brain sections (tissue-based assays) can also detect previously unknown antineuronal antibodies | |
| in specialized laboratories | |