How should the possibility of more chronic forms of autoimmune encephalitis influence our neuronal antibody testing thresholds for patients with slower progressive cognitive decline?

I will disclose that I am not a cognitive/behavioral neurology specialist nor a neuroimmunologist per se, but I would exercise caution in interpreting the conclusions of the paper that was cited.

I went over the paper briefly, and I realized that 28 patients were diagnosed with "autoimmune dementia", many of which showed a "chronic course": 7 had anti-TPO antibodies, 5 had GAD65 antibodies in serum, but NOT in CSF, and 5 had NMDA antibodies in serum, of which 2 were CSF negative, and in one, CSF was not tested.

Those facts alone raise some skepticism. Anti-TPO antibodies are very non-specific, and most patients with those antibodies do NOT have Hashimoto encephalopathy. GAD65 antibodies in serum are also not specific in low titers, especial...

I am a behavioral neurologist, and when the clinical picture is typical for a neurodegenerative condition and confirmed by atrophy on MRI or vascular disease, then I wouldn't test.

However, for younger patients or those who don't fit the typical picture, I would order labs for autoimmune encephalitis.

Sometimes serum is positive and not CSF. Usually the titers are high, but there is no harm in a trial of immunotherapy instead of labeling someone with a chronic, progressive illness and giving them, let's say, antiamyloid therapy because they meet what I think are premature and way too broad clinical criteria for Alzheimer's disease (just biomarker-positive according to the 2024 Alzheimer's Association criteria, which I don't agree with - see...

I think the main message is to consider testing for slower (>3 months) progressive cognitive decline when the syndrome is atypical for neurodegeneration or has neuropsychiatric, sleep, seizure, relapsing/fluctuating, inflammatory, or imaging clues pointing to an autoimmune process. I would not send an AE panel to everybody with cognitive decline otherwise.