Maria Pia Giannoccaro1, Matteo Gastaldi2, Giovanni Rizzo3, Leslie Jacobson4, Veria Vacchiano5, Giulia Perini6, Sabina Capellari5, Diego Franciotta6, Alfredo Costa7, Rocco Liguori5, Angela Vincent8. 1. Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK; IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy; Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Italy. Electronic address: mariapia.giannoccar2@unibo.it. 2. Neuroimmunology Laboratory, IRCCS Mondino Foundation, Pavia, Italy. 3. IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy. 4. Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK. 5. IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy; Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Italy. 6. IRCCS Ospedale Policlinico San Martino, Genoa, Italy. 7. Unit of Behavioral Neurology, IRCCS Fondazione Mondino, and Department of Brain and Behavioral Sciences, University of Pavia, Italy. 8. Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK. Electronic address: angela.vincent@ndnc.ox.ac.uk.
Abstract
OBJECTIVES: 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. METHODS: 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. RESULTS: The patients included 13/93 (13.8%) who had specific antibodies to neuronal surface antigens: 6 GlyR, 3 GABAAR (1 also positive for AMPAR), 2 LGI1, 1 CASPR2 and 1 GABABR. 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. CONCLUSIONS: 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.
OBJECTIVES: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. METHODS: 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. RESULTS: The patients included 13/93 (13.8%) who had specific antibodies to neuronal surface antigens: 6 GlyR, 3 GABAAR (1 also positive for AMPAR), 2 LGI1, 1 CASPR2 and 1 GABABR. 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. CONCLUSIONS: 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.