An autoimmune disorder of the central nervous system, stiff person syndrome, frequently presents with increased titers of 65KD anti-glutamic acid decarboxylase (anti-GAD) antibodies. The clinical phenomenology of this syndrome includes stiffness, ataxia, vertigo due to horizontal gaze-evoked and downbeat vertical nystagmus, and dysmetria of saccades and reaching movements. Here, we describe a novel phenomenology of syndrome of anti-GAD antibody, non-position-dependent upbeat nystagmus and superimposed horizontal gaze-evoked nystagmus. Lack of gravity dependence of primary position upbeat nystagmus, intense nystagmus on up-gaze, relatively stable gaze on downward orientation, and the exponentially decaying waveform suggests neural integrator dysfunction. The titer of anti-GAD in our patient (30 U/ml) was consistent with a variant called “low-titer anti-GAD syndrome”. In addition of presenting as an unusual manifestation of a rare neurological syndrome, this case presents a neurochemical correlate of upbeat nystagmus in GABA-mediated control system involving horizontal and vertical neural integrators. Furthermore, the variant of “low-titer anti-GAD syndrome” suggests that GABAergic system may be affected at lower level or antibodies, and/or the epitopes of antibody in those with full-blown clinical syndrome, but low titers of anti-GAD may be different.
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AS is supported by career development award from the American Academy of Neurology, George C. Cotzias Memorial Fellowship from the American Parkinson’s Disease Association, and Dystonia Medical Research Foundation neural network in dystonia grant.
JO-M is covered by NIH K99 EY027846.
Conflict of Interest
The authors declare that they have no conflict of interest.
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Feldman, D., Otero-Millan, J. & Shaikh, A.G. Gravity-Independent Upbeat Nystagmus in Syndrome of Anti-GAD Antibodies. Cerebellum 18, 287–290 (2019). https://doi.org/10.1007/s12311-018-0972-z
- Stiff person syndrome