Autoimmune encephalopathies presenting as dementia of subacute onset and rapid progression

Abstract

The terms autoimmune dementia and autoimmune encephalopathy may be used interchangeably; autoimmune dementia is used here to emphasize its consideration in young-onset dementia, dementia with a subacute onset, and rapidly progressive dementia. Given their potential for reversibility, it is important to distinguish the rare autoimmune dementias from the much more common neurodegenerative dementias. The presence of certain clinical features [e.g. facio-brachial dystonic seizures that accompany anti-leucine-rich-glioma-inactivated-1 (LGI1) encephalitis that can mimic myoclonus] can be a major clue to the diagnosis. When possible, objective assessment of cognition with bedside testing or neuropsychological testing is useful to determine the degree of abnormality and serve as a baseline from which immunotherapy response can be judged. Magnetic resonance imaging (MRI) head and cerebrospinal fluid (CSF) analysis are useful to assess for inflammation that can support an autoimmune etiology. Assessing for neural autoantibody diagnostic biomarkers in serum and CSF in those with suggestive features can help confirm the diagnosis and guide cancer search in paraneoplastic autoimmune dementia. However, broad screening for neural antibodies in elderly patients with an insidious dementia is not recommended. Moreover, there are pitfalls to antibody testing that should be recognized and the high frequency of some antibodies in the general population limit their diagnostic utility [e.g., anti-thyroid peroxidase (TPO) antibodies]. Once the diagnosis is confirmed, both acute and maintenance immunotherapy can be utilized and treatment choice varies depending on the accompanying neural antibody present and the presence or absence of cancer. The target of the neural antibody biomarker may help predict treatment response and prognosis, with antibodies to cell-surface or synaptic antigens more responsive to immunotherapy and yielding a better overall prognosis than those with antibodies to intracellular targets. Neurologists should be aware that autoimmune dementias and encephalopathies are increasingly recognized in novel settings, including post herpes virus encephalitis and following immune-checkpoint inhibitor use.

Keywords: autoimmune cognitive impairment; autoimmune encephalitis; central nervous system autoimmunity; immune check point inhibitors; limbic encephalitis/encephalopathy.

Figure 1.

MRI examples of autoimmune dementia. (a) Bilateral T2-hyperintensities in the mesial temporal lobe are shown in a patient with autoimmune limbic encephalitis associated with GAD65 autoantibodies. (b) Radial perivascular enhancement is shown in a patient with GFAP autoantibodies. (c) Bilateral mesial temporal T2-hyperintensities consistent with limbic encephalitis and occurring after immune checkpoint inhibitor use with an accompanying unclassified neural autoantibody detected with follow-up MRI 1 month later revealing bilateral temporal lobe atrophy (d). MRI, magnetic resonance imaging.