To report two cases of anti-glycine antibody-positive syndromes mimicking progressive supranuclear palsy (PSP) and to emphasize the role of autoimmune antibodies in movement disorders.

Autoimmune movement disorders comprise treatable and possibly reversible conditions. Over the years, a growing number of autoimmune syndromes with a multifaceted and ever-expending phenotype has been described. 

We describe a patient with neuropsychiatric symptoms, eyelid-opening apraxia, vertical gaze restriction, severe axial rigidity, and frequent falls developing over six months. Our diagnostic tests revealed positive serum anti-glycine antibodies, although he was only mildly responsive to immunotherapy. The second patient experienced progressive gait dysfunction with unilateral weakness who further developed vertical gaze restriction, severe rigidity, and apraxia. Her workup also revealed positive serum anti-glycine antibodies and she experienced a mild improvement with plasmapheresis, maintenance therapy intravenous immunoglobulins, and rituximab.

Anti-glycine antibody syndromes take on a broad syndromic spectrum, which includes stiff person syndrome, progressive encephalomyelitis, and epilepsy. We propose our cases may expand the spectrum of anti-glycine autoimmune phenotypes. At the same time, we underscore the existence of autoantibodies of unknown significance and the growing need for accurate biomarkers to differentiate autoimmune from neurodegenerative disorders.