Objective:

To evaluate the frequency and spectrum of autoantibodies targeting the central nervous system (CNS) in patients clinically diagnosed with atypical parkinsonism, including progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and multiple system atrophy (MSA). 

Background:

Anti-CNS autoantibodies have not been systematically evaluated in patients with atypical parkinsonism.

Design/Methods:

A retrospective observational study was conducted on 135 patients clinically diagnosed with PSP, CBS, or MSA who met clinical features defined by the Movement Disorder Society (MDS)-PSP criteria, Armstrong’s criteria or MDS-MSA criteria, respectively. We examined anti-CNS immunoglobulin G (IgG) in the cerebrospinal fluid (CSF) using paraformaldehyde-fixed tissue-based assays with indirect immunofluorescence on frozen rat brain sections.

Results:

Anti-CNS IgGs were examined in 48 PSP patients (mean age 69.2 ± 10.1 years; 32 males, 16 females), 45 CBS patients (mean age 70.0 ± 9.4 years; 12 males, 33 females), and 42 MSA patients (mean age 67.0 ± 11.0 years; 24 males, 18 females). Patients who had anti-CNS IgGs were as follows: PSP, three patients (6.3%, astrocytes 3/3, neuronal cytoplasm 1/3, myelin 1/3); CBS, two patients (4.4%, neuronal cytoplasm 1/2, myelin 1/2); and MSA, six patients (14.3%, astrocytes 3/6, neuronal cytoplasm 3/6, neuronal surface 2/6). Among these patients, two (one with PSP and one with MSA) experienced a subacute course, and the other patients experienced a chronic progressive course. None of the patients showed brain magnetic resonance imaging findings suggestive of autoimmune encephalitis or CSF pleocytosis. All patients tested negative for anti-immunoglobulin-like cell adhesion molecule 5 (IgLON5) antibodies and did not receive immunotherapy on evaluation.

Conclusions:

The study findings revealed that approximately 5–10% of patients with atypical parkinsonism have anti-CNS IgGs that target neurons, astrocytes, and myelin in the CSF. Patients with atypical parkinsonism may have a wider range of anti-CNS autoantibodies than previously reported, although the pathological significance of these antibodies remains unknown.