Antibodies to neuronal surface antigens in patients with a clinical diagnosis of neurodegenerative disorder.

• Neuronal surface antibodies are relatively frequent in patients with neurodegenerative disorders. • An unclassified diagnosis and an irregular progression predicted seropositivity. • Seropositivity was associated with ataxia, reflex myoclonus and sleep disorders. • Less than a half of seropositive cases met a priori the current criteria for autoimmune encephalitis. • There may be a proportion of cases of neurodegenerative diseases who could respond to immunotherapies. Autoimmune encephalitis due to antibodies against neuronal surface antigens (NSA-Ab) frequently presents with cognitive impairment, often as the first and prevalent manifestation, but few studies have systematically assessed the frequency of NSA-Ab in consecutive patients with established neurodegenerative disorders. We studied sera of 93 patients (41F, 52 M), aged 69.2 ± 9.4 years, with neurodegenerative conditions, and of 50 population controls aged over 60 years. Specific NSA-Abs were investigated by antigen-specific cell-based assays (CBAs). After testing, we evaluated the association between the NSA-Abs and clinical, CSF and radiological features. The patients included 13/93 (13.8%) who had specific antibodies to neuronal surface antigens: 6 GlyR, 3 GABA A R (1 also positive for AMPAR), 2 LGI1, 1 CASPR2 and 1 GABA B R. One of the 50 controls (2%) was positive for NMDAR antibody and the others were negative on all tests (P = 0.020). No difference was observed in antibody frequency between patients presenting with parkinsonism and those presenting with dementia (P = 0.55); however, NSA-Ab were more frequent in those with unclassified forms of dementia (5/13, 38.5%) than in those with unclassified parkinsonism (2/9, 22.2%) or with classified forms of dementia (4/43, 9.3%) or parkinsonism (2/28, 7.1%) (P = 0.03). A logistic regression analysis demonstrated that an unclassified diagnosis (P = 0.02) and an irregular progression (P = 0.024) were predictors of seropositive status. NSA-Abs are relatively frequent in patients with neurodegenerative disorders, particularly in those with an irregular disease progression of atypical clinical features, inconsistent with a recognized diagnosis. The significance of these antibodies and their possible primary or secondary roles need to be investigated in prospective studies. [ABSTRACT FROM AUTHOR]