There is increasing recognition in the neurological and psychiatric literature of
patients with so-called isolated psychotic presentations (ie, with no, or minimal,
neurological features) who have tested positive for neuronal autoantibodies (principally
N-methyl-D-aspartate receptor antibodies) and who have responded to immunotherapies.
Although these individuals are sometimes described as having atypical, mild, or attenuated
forms of autoimmune encephalitis, some authors feel that that these cases are sufficiently
different from typical autoimmune encephalitis to establish a new category of so-called
Neuronal antibodies can cause encephalopathy syndromes often presenting with subacute cognitive impairment, sometimes resembling neurodegenerative dementias. We searched Medline and Embase for studies reporting associations between neuronal surface antibodies in all-cause dementia versus controls. Random-effects meta-analysis was used to pool adjusted estimates across studies. Six studies were included, all reporting frequency of serum NMDAR antibodies in dementia with four also reporting frequency in atypical dementias. Both IgG [OR = 8.09 (1.51; 56.85), p = 0.036] and IgA/IgM NMDAR antibodies [OR = 42.48 (11.39; 158.52), p < 0.001] were associated with atypical dementia, but neither were associated with all-cause dementia. In the first meta-analysis to explore this literature, serum IgG and IgA/IgM NMDAR antibodies were significantly more common in atypical dementias. However, methodological issues and small-sample sizes necessitate caution interpreting this result. Further studies measuring both serum and CSF antibodies are needed to investigate the role of neuronal antibodies in dementia, since evidence of pathogenicity in even a subset of patients could pave the way for novel treatment options.
Cognitive dysfunction is a common feature of autoimmune encephalitis. Pathogenic neuronal surface antibodies are thought to mediate distinct profiles of cognitive impairment in both the acute and chronic phases of encephalitis. In this review, we describe the cognitive impairment associated with each antibody-mediated syndrome and, using evidence from imaging and animal studies, examine how the nature of the impairment relates to the underlying neuroimmunological and receptor-based mechanisms. Neuronal surface antibodies, particularly serum NMDA receptor antibodies, are also found outside of encephalitis although the clinical significance of this has yet to be fully determined. We discuss evidence highlighting their prevalence, and association with cognitive outcomes, in a number of common disorders including cancer and schizophrenia. We consider mechanisms, including blood-brain barrier dysfunction, which could determine the impact of these antibodies outside encephalitis and account for much of the clinical heterogeneity observed.
Transient epileptic amnesia (TEA) is an underrecognized form of late-onset temporal
lobe epilepsy, generally occurring between the ages of 50 and 70, and manifesting
as ictal episodes of transient amnesia, either retro- and/or anterograde, of variable