Evaluation of Incidence and Clinical Features of Antibody-Associated Autoimmune Encephalitis Mimicking Dementia

Abstract

Background. Anti-neuronal autoimmunity may cause cognitive impairment that meets the criteria for dementia. Objective. Our aim was to detect the incidence and clinical features of autoimmune encephalitis imitating clinical findings of primary dementia disorders and to delineate the validity of anti-neuronal antibody screening in dementia patients. Methods. Fifty consecutive patients fulfilling the clinical criteria for primary dementia, 130 control patients, and 50 healthy controls were included. Their sera were investigated for several ion channel and glutamic acid decarboxylase (GAD) antibodies by a cell-based assay, radioimmunoassay, and ELISA, as required. Results. Sixteen patients satisfying dementia criteria had atypical findings or findings suggestive of autoimmune encephalitis. N-methyl-D-aspartate receptor (NMDAR) antibody was detected in a patient with dementia, Parkinsonism, and REM sleep behavior disorder (RBD) fulfilling the criteria for dementia with Lewy bodies (DLB). One control patient with bipolar disease displayed low anti-GAD antibody levels. Conclusions. Our study showed for the first time the presence of parkinsonism and RBD in an anti-NMDAR encephalitis patient mimicking DLB. Although autoimmune encephalitis patients may occasionally present with cognitive decline, most dementia patients do not exhibit anti-neuronal antibodies, suggesting that routine analysis of these antibodies in dementia is not mandatory, even though they display atypical features.

Clinically Relevant Anti-Neuronal Cell Surface Antibodies in Schizophrenia Spectrum Disorders

“…Results have been less compelling for anti-AMPAR antibodies, as the majority of studies have been negative [10, 15, 18, 20, 23, 26, 28, 29]. Moreover, in each of the two positive studies, antibodies were found in only one patient (<1% of the samples) [11, 24], and the only study that included a healthy control group also found antibodies in 0.2% of controls [11].…”

“…A number of studies that tested for IgG, IgA, or IgM anti-CASPR2 antibodies found seropositivity in a small percentage (2.5% or less) of patients [11, 15, 24, 29, 36], although numerous other studies were negative [16, 18, 20, 26, 28]. Of note, all of the positive studies that included a healthy control group, however, also found antibodies in a small number of controls (up to 2.9%), and no group differences were found [11, 15, 36].…”

“…Only three studies found anti-LGI1 antibodies in a small subset of schizophrenia spectrum disorder patients (2.0% or less) [11, 15, 36], whereas six studies were negative [16, 18, 20, 24, 26, 29]. All of the positive studies included a healthy control group for comparison, two of which found anti-LGI1 antibodies in a small number of healthy controls (2% and <0.1%, respectively), and no group differences were found [11, 36].…”

Rapid Eye Movement Sleep Abnormalities in Children with Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS)

“…[8][9][10] A recent case presentation of two female patients with breast cancer and paraneoplastic cerebellar disease also presenting with RBD showed clinical resolution and restoration of atonia during REM sleep after immunotherapy with intravenous immunoglobulin.…”

Reduced serum orexin-A levels in autoimmune encephalitis and neuromyelitis optica patients

“…Likewise, sleep problems of antibody-mediated CNS disorders have often been associated with reduced cerebrospinal fluid (CSF) orexin levels [1][2][3][4]. Sleep disorders in autoimmune encephalitis have been mostly associated with Ma2, N-methyl-D-aspartate receptor (NMDAR) and leucine-rich glioma inactivated 1 (LGI1)-antibodies [1][2][3][4][5]7]. Our current knowledge on sleep disorders in antibody-mediated CNS diseases is mostly limited to case reports [1,2,7] and a systemic screening of sleep-related clinical and laboratory findings is not available.…”