Session Information
Date: Saturday, October 6, 2018
Session Title: Pathophysiology (Other Movement Disorders)
Session Time: 1:45pm-3:15pm
Location: Hall 3FG
Objective: Delineate pathophysiology of gaze-holding function in stiff person syndrome (SPS).
Background: Glutamic acid decarboxylase (GAD) catalyzes conversion of glutamate to gamma-aminobutyric acid (GABA). Anti-GAD antibodies, as seen in SPS, can compromise this function. Proof of this mechanism comes from peculiar eye movements in SPS such as downbeat nystagmus, dysmetria, impaired pursuit, and impaired vestibulo-ocular reflex cancellation. It is possible that eye movement dysfunction in SPS is multifactorial, due to deficiency in GABA and excess of glutamate.
Methods: We measured gaze holding in 11 SPS patients using high-resolution oculography to capture horizontal and vertical eye positions. Patterns of deficits were dissected via offline analysis of eye position. Specific waveforms and known principles of eye movement control systems were then applied to determine the role of GABA versus glutamate in gaze holding behaviors.
Results: Downbeat nystagmus and horizontal gaze-evoked nystagmus were the most common deficits identified. Downbeat nystagmus presented in 9 patients, while 6 had horizontal gaze-evoked nystagmus. They were co-existent in some patients. Universally, horizontal gaze-evoked nystagmus had velocity-decreasing waveform, and the slow-phase eye velocity reduced as the desired eye position reached central null position. Null position for vertical nystagmus varied in patients: in 2 it was downward, while in 7 it was in the upward position. Seven patients with downbeat nystagmus had velocity-increasing waveform, and 2 had velocity-decreasing waveform. Two patients had opsoclonus. Visually guided saccades were slow in 2 patients with opsoclonus and 1 with normal gaze holding.
Conclusions: Gaze-holding deficits in SPS causes dysfunction of cerebellar neural integrator, which explains the mechanism of eye-in-orbit position dependence of slow-phase velocity of horizontal and vertical nystagmus, null position and velocity-increasing/decreasing waveforms of downbeat nystagmus. However, opsoclonus is not explained. Excessive glutamate causes reverberations of saccadic burst neurons in the reciprocally innervating circuit. Glutamatergic excess explains the opsoclonus in SPS patients.
To cite this abstract in AMA style:
F. Wang, L. Neilson, H. Wang, G. Wilmot, A. Shaikh. Ocular motor function in stiff person syndrome – Role of GABA and beyond [abstract]. Mov Disord. 2018; 33 (suppl 2). https://www.mdsabstracts.org/abstract/ocular-motor-function-in-stiff-person-syndrome-role-of-gaba-and-beyond/. Accessed May 9, 2025.« Back to 2018 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/ocular-motor-function-in-stiff-person-syndrome-role-of-gaba-and-beyond/