Abstract
Syndrome of oculopalatal tremor (OPT) causes pendular nystagmus of the eyes and its disabling consequence on the visual system. Classic pharmacotherapeutic studies revealed reduction in the eye velocity of the oscillatory waveforms. Subjective improvement in vision, however, remains out of proportionately low. Elegant models depicting quasi-sinusoidal coarse oscillations of the eyes highlighted two distinct oscillators; one at the inferior olive causing primary 2 Hz oscillations, while the second, independent oscillator, at the cerebellum adding the randomness to the waveform. Here we examined whether pharmacotherapy affects the randomness of the oscillatory waveform. Horizontal, vertical, and torsional angular eye positions were measured independently from both eyes as six subjects with OPT directed gaze toward a straight-ahead target. The measurements were performed before administration of alpha-2-delta calcium channel blocker (gabapentin) or NMDA receptor antagonist (memantine) and after the subjects were treated with each of these drugs for at least 8 days. Amplitude and velocity of eye oscillations were reduced by gabapentin and memantine, but there was an increase in the waveform randomness. We found that the increase in randomness was proportionate to the amount of reduction in the waveform velocity or amplitude. Hierarchical clustering revealed distinct patterns of oscillatory waveforms, with each subject belonging to a specific cluster group. The pharmacotherapy changed the waveform clustering pattern of the waveform in each subject. We conclude that in addition to incomplete resolution of the oscillation intensity, increased randomness could be one of the reasons why there is not enough clinical difference in the patients’ visual quality.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Averbuch-Heller, L., Tusa, R. J., Fuhry, L., Rottach, K. G., Ganser, G. L., Heide, W., Büttner, U., & Leigh, R. J. (1997). A double-blind controlled study of gabapentin and baclofen as treatment for acquired nystagmus. Annals of Neurology, 41(6), 818–825. https://doi.org/10.1002/ana.410410620.
Birbamer, G., Gerstenbrand, F., Aichner, F., Buchberger, W., Chemelli, A., Langmayr, J., Lo Presti, R., Pollicino, P., & Bramanti, P. (1994). MR-imaging of post-traumatic olivary hypertrophy. Functional Neurology, 9(4), 183–187.
Deuschl, G., Mischke, G., Schenck, E., Schulte-Monting, J., & Lucking, C. H. (1990). Symptomatic and essential rhythmic palatal myoclonus. Brain, 113(Pt 6), 1645–1672. https://doi.org/10.1093/brain/113.6.1645.
Deuschl, G., Toro, C., & Hallett, M. (1994). Symptomatic and essential palatal tremor. 2. Differences of palatal movements. Movement Disorders, 9(6), 676–678. https://doi.org/10.1002/mds.870090615.
Goyal, M., Versnick, E., Tuite, P., Cyr, J. S., Kucharczyk, W., Montanera, W., Willinsky, R., & Mikulis, D. (2000). Hypertrophic olivary degeneration: Metaanalysis of the temporal evolution of MR findings. AJNR. American Journal of Neuroradiology, 21(6), 1073–1077.
Hong, S., Leigh, R. J., Zee, D. S., & Optican, L. M. (2008). Inferior olive hypertrophy and cerebellar learning are both needed to explain ocular oscillations in oculopalatal tremor. Progress in Brain Research, 171, 219–226. https://doi.org/10.1016/S0079-6123(08)00631-6.
Kang, S., & Shaikh, A. G. (2017). Acquired pendular nystagmus. Journal of the Neurological Sciences, 375, 8–17. https://doi.org/10.1016/j.jns.2017.01.033.
Kim, Y. S., Chang, H. K., Lee, J. W., Sung, Y. H., Kim, S. E., Shin, M. S., Yi, J. W., Park, J. H., Kim, H., & Kim, C. J. (2009). Protective effect of gabapentin on N-methyl-D-aspartate-induced excitotoxicity in rat hippocampal CA1 neurons. Journal of Pharmacological Sciences, 109(1), 144–147. https://doi.org/10.1254/jphs.08067sc.
Kornhuber, J., Weller, M., Schoppmeyer, K., & Riederer, P. (1994). Amantadine and memantine are NMDA receptor antagonists with neuroprotective properties. Journal of Neural Transmission. Supplementum, 43, 91–104.
Leigh, R. J., Averbuch-Heller, L., Tomsak, R. L., Remler, B. F., Yaniglos, S. S., & Dell'Osso, L. F. (1994). Treatment of abnormal eye movements that impair vision: Strategies based on current concepts of physiology and pharmacology. Annals of Neurology, 36(2), 129–141. https://doi.org/10.1002/ana.410360204.
Leigh, R. J., Rushton, D. N., Thurston, S. E., Hertle, R. W., & Yaniglos, S. S. (1988). Effects of retinal image stabilization in acquired nystagmus due to neurologic disease. Neurology, 38(1), 122–127. https://doi.org/10.1212/wnl.38.1.122.
Leigh, R. J., & Zee, D. S. (2015). The neurology of eye movements (6th ed.). New York: Oxford.
Nishie, M., Yoshida, Y., Hirata, Y., & Matsunaga, M. (2002). Generation of symptomatic palatal tremor is not correlated with inferior olivary hypertrophy. Brain, 125(Pt 6), 1348–1357. https://doi.org/10.1093/brain/awf126.
Shaikh, A. G., Hong, S., Liao, K., Tian, J., Solomon, D., Zee, D. S., Leigh, R. J., & Optican, L. M. (2010). Oculopalatal tremor explained by a model of inferior olivary hypertrophy and cerebellar plasticity. Brain, 133(Pt 3), 923–940. https://doi.org/10.1093/brain/awp323.
Shaikh, A. G., Thurtell, M. J., Optican, L. M., & Leigh, R. J. (2011). Pharmacological tests of hypotheses for acquired pendular nystagmus. Annals of the New York Academy of Sciences, 1233, 320–326. https://doi.org/10.1111/j.1749-6632.2011.06118.x.
Sperling, M. R., & Herrmann Jr., C. (1985). Syndrome of palatal myoclonus and progressive ataxia: Two cases with magnetic resonance imaging. Neurology, 35(8), 1212–1214. https://doi.org/10.1212/wnl.35.8.1212.
Thorpe, A. J., & Offord, J. (2010). The alpha2-delta protein: An auxiliary subunit of voltage-dependent calcium channels as a recognized drug target. Current Opinion in Investigational Drugs, 11(7), 761–770.
Thurtell, M. J., Joshi, A. C., Leone, A. C., Tomsak, R. L., Kosmorsky, G. S., Stahl, J. S., & Leigh, R. J. (2010). Crossover trial of gabapentin and memantine as treatment for acquired nystagmus. Annals of Neurology, 67(5), 676–680. https://doi.org/10.1002/ana.21991.
Availability of data, material, and code
Deidentified data/material and code will be provided upon request to interested parties.
Funding
This work was supported by American Academy of Neurology Career Award (Shaikh), American Parkinson’s Disease Association George C Cotzias Memorial Fellowship (Shaikh), Dystonia Medical Research Foundation Research Grant (Shaikh), and philanthropic funds to the Department of Neurology at University Hospitals (The Allan Woll Fund). Dr.Shaikh has Penni and Stephen Weinberg Research Chair in Brain Health.
Author information
Authors and Affiliations
Contributions
WT: analyzed data, conceptualized analysis and interpretation, wrote paper, edited paper.
MT: collected data, edited paper.
KL: conceptualized analysis and interpretation, edited paper.
AS: analyzed data, conceptualized analysis and interpretation, wrote paper, edited paper.
Corresponding author
Ethics declarations
Conflict of interest
The authors have no conflicts of completing interests.
Ethics approval, consent to participate
The institutional review board at Louis Stokes Cleveland VA Medical Center approved the study protocol, and consent material. Subjects signed informed consent form prior to participation.
Additional information
Action Editor: Jeffrey Schall
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This article belongs to the Topical Collection: Vision and Action
Guest Editors: Aasef Shaikh and Jeffrey Shall
Rights and permissions
About this article
Cite this article
Theeranaew, W., Thurtell, M.J., Loparo, K. et al. Gabapentin and memantine increases randomness of oscillatory waveform in ocular palatal tremor. J Comput Neurosci 49, 319–331 (2021). https://doi.org/10.1007/s10827-020-00753-6
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10827-020-00753-6