Eye Movement Abnormalities in Amyotrophic Lateral Sclerosis

Xintong Guo, Xiaoxuan Liu, Shan Ye, Xiangyi Liu, Xu Yang, Dongsheng Fan, Xintong Guo, Xiaoxuan Liu, Shan Ye, Xiangyi Liu, Xu Yang, Dongsheng Fan

Abstract

It is generally believed that eye movements are completely spared in amyotrophic lateral sclerosis (ALS). Although a series of eye movement abnormalities has been recognized in recent years, the findings are highly controversial, and bulbar disabilities should be considered in relation to eye movement abnormalities. The present study aimed to determine whether eye movement abnormalities are present in ALS and, if so, to investigate their characteristics and their association with bulbar disability in ALS patients. A total of 60 patients and 30 controls were recruited and underwent the standardized evaluations of the oculomotor system using videonystagmography. Square-wave jerks (OR: 16.20, 95% CI: 3.50−74.95, p < 0.001) and abnormal cogwheeling during smooth pursuit (OR: 14.04, 95% CI: 3.00−65.75, p = 0.001) were more frequently observed in ALS patients than in the control subjects. In subgroup analyses, square-wave jerks (OR: 26.51, 95% CI: 2.83−248.05, p = 0.004) and abnormal cogwheeling during smooth pursuit (OR: 6.56, 95% CI: 1.19−36.16, p = 0.031) were found to be more common in ALS patients with bulbar involvement (n = 44) than in those without bulbar involvement (n = 16). There were no significant differences in the investigated eye movement parameters between bulbar-onset (n = 12) and spinal-onset patients (n = 48). ALS patients showed a range of eye movement abnormalities, affecting mainly the ocular fixation and smooth pursuit systems. Our pioneering study indicates that the region of involvement could better indicate the pathophysiological essence of the abnormalities than the type of onset pattern in ALS. Eye movement abnormalities may be potential clinical markers for objectively evaluating upper brainstem or supratentorial cerebral lesion neurodegeneration in ALS.

Keywords: amyotrophic lateral sclerosis; bulbar involvement; eye movement abnormalities.

Conflict of interest statement

The authors have no conflict of interest to declare.

Figures

Figure 1
Figure 1
Examples of eye movement abnormalities in our ALS patients. Abbreviations: OD, oculus dexter; OS, oculus sinister. (A) Square-wave jerks, (B) abnormal cogwheeling during smooth pursuit, and (C) saccadic hypometria.

References

    1. Brooks B.R., Miller R.G., Swash M., Munsat T.L. El Escorial Revisited: Revised Criteria for the Diagnosis of Amyotrophic Lateral Sclerosis. Amyotroph. Lateral Scler. Other Mot. Neuron Disord. 2000;1:293–299. doi: 10.1080/146608200300079536.
    1. Chen L., Zhang B., Chen R., Tang L., Liu R., Yang Y., Yang Y., Liu X., Ye S., Zhan S., et al. Natural History and Clinical Features of Sporadic Amyotrophic Lateral Sclerosis in China. J. Neurol. Neurosurg. Psychiatry. 2015;86:1075–1081. doi: 10.1136/jnnp-2015-310471.
    1. Chiò A., Logroscino G., Hardiman O., Swingler R., Mitchell D., Beghi E., Traynor B.G. Prognostic Factors in Als: A Critical Review. Amyotroph. Lateral. Scler. 2009;10:310–323. doi: 10.3109/17482960802566824.
    1. Robberecht W., Philips T. The Changing Scene of Amyotrophic Lateral Sclerosis. Nat. Rev. Neurosci. 2013;14:248–264. doi: 10.1038/nrn3430.
    1. Mandrioli J., Faglioni P., Nichelli P., Sola P. Amyotrophic Lateral Sclerosis: Prognostic Indicators of Survival. Amyotroph. Lateral. Scler. 2006;7:211–220. doi: 10.1080/17482960600947648.
    1. Jacobs L., Bozian D., Heffner R.R., Jr., Barron S.A. An Eye Movement Disorder in Amyotrophic Lateral Sclerosis. Neurology. 1981;31:1282–1287. doi: 10.1212/WNL.31.10.1282.
    1. Leveille A., Kiernan J., Goodwin J.A., Antel J. Eye Movements in Amyotrophic Lateral Sclerosis. Arch. Neurol. 1982;39:684–686. doi: 10.1001/archneur.1982.00510230010003.
    1. Mizuno M. Neurotological Findings in Amyotrophic Lateral Sclerosis. Auris Nasus Larynx. 1986;13((Suppl 2)):S139–S146. doi: 10.1016/S0385-8146(86)80067-0.
    1. Saito S., Yamamoto H. Analysis of Oculomotor Disorders in Motor Neuron Disease. Rinsho Shinkeigaku. 1989;29:969–975.
    1. Gizzi M., DiRocco A., Sivak M., Cohen B. Ocular Motor Function in Motor Neuron Disease. Neurology. 1992;42:1037–1046. doi: 10.1212/wnl.42.5.1037.
    1. Okuda B., Yamamoto T., Yamasaki M., Maya K., Imai T. Motor Neuron Disease with Slow Eye Movements and Vertical Gaze Palsy. Acta Neurol. Scand. 1992;85:71–76. doi: 10.1111/j.1600-0404.1992.tb03999.x.
    1. Marti-Fàbregas J., Roig C. Oculomotor Abnormalities in Motor Neuron Disease. J. Neurol. 1993;240:475–478. doi: 10.1007/BF00874116.
    1. Ohki M., Kanayama R., Nakamura T., Okuyama T., Kimura Y., Koike Y. Ocular Abnormalities in Amyotrophic Lateral Sclerosis. Acta Otolaryngol. Suppl. 1994;511:138–142. doi: 10.3109/00016489409128318.
    1. Shaunak S., Orrell R.W., O’Sullivan E., Hawken M.B., Lane R.J., Henderson L., Kennard C. Oculomotor Function in Amyotrophic Lateral Sclerosis: Evidence for Frontal Impairment. Ann. Neurol. 1995;38:38–44. doi: 10.1002/ana.410380109.
    1. Palmowski A., Jost W.H., Prudlo J., Osterhage J., Käsmann B., Schimrigk K., Ruprecht K.W. Eye Movement in Amyotrophic Lateral Sclerosis: A Longitudinal Study. Ger. J. Ophthalmol. 1995;4:355–362.
    1. Donaghy C., Pinnock R., Abrahams S., Cardwell C., Hardiman O., Patterson V., McGivern R.C., Gibson J.M. Ocular Fixation Instabilities in Motor Neurone Disease. A Marker of Frontal Lobe Dysfunction? J. Neurol. 2009;256:420–426. doi: 10.1007/s00415-009-0109-x.
    1. Donaghy C., Pinnock R., Abrahams S., Cardwell C., Hardiman O., Patterson V., McGivern R.C., Gibson J.M. Slow Saccades in Bulbar-Onset Motor Neurone Disease. J. Neurol. 2010;257:1134–1140. doi: 10.1007/s00415-010-5478-7.
    1. Moss H.E., McCluskey L., Elman L., Hoskins K., Talman L., Grossman M., Balcer L.J., Galetta S.L., Liu G.T. Cross-Sectional Evaluation of Clinical Neuro-Ophthalmic Abnormalities in an Amyotrophic Lateral Sclerosis Population. J. Neurol. Sci. 2012;314:97–101. doi: 10.1016/j.jns.2011.10.016.
    1. Proudfoot M., Menke R.A., Sharma R., Berna C.M., Hicks S.L., Kennard C., Talbot K., Turner M.R. Eye-Tracking in Amyotrophic Lateral Sclerosis: A Longitudinal Study of Saccadic and Cognitive Tasks. Amyotroph Lateral Scler Front. Degener. 2015;17:101–111. doi: 10.3109/21678421.2015.1054292.
    1. Kang B.H., Kim J.I., Lim Y.M., Kim K.K. Abnormal Oculomotor Functions in Amyotrophic Lateral Sclerosis. J. Clin. Neurol. 2018;14:464–471. doi: 10.3988/jcn.2018.14.4.464.
    1. Abel L.A., Williams I.M., Gibson K.L., Levi L. Effects of Stimulus Velocity and Acceleration on Smooth Pursuit in Motor Neuron Disease. J. Neurol. 1995;242:419–424. doi: 10.1007/BF00873543.
    1. Liu X., Zhang S., Huang X., Zhang Y., Fan D. Vestibular Evoked Myogenic Potentials and Their Clinical Utility in Patients with Amyotrophic Lateral Sclerosis. Clin. Neurophysiol. 2019;130:647–654. doi: 10.1016/j.clinph.2019.01.023.
    1. Neumann M., Sampathu D.M., Kwong L.K., Truax A.C., Micsenyi M.C., Chou T.T., Bruce J., Schuck T., Grossman M., Clark C.M., et al. Ubiquitinated Tdp-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis. Science. 2006;314:130–133. doi: 10.1126/science.1134108.
    1. Braak H., Brettschneider J., Ludolph A.C., Lee V.M., Trojanowski J.Q., Del Tredici K. Amyotrophic Lateral Sclerosis--a Model of Corticofugal Axonal Spread. Nat. Rev. Neurol. 2013;9:708–714. doi: 10.1038/nrneurol.2013.221.
    1. Brettschneider J., Del Tredici K., Toledo J.B., Robinson J.L., Irwin D.J., Grossman M., Suh E., Van Deerlin V.M., Wood E.M., Baek Y., et al. Stages of Ptdp-43 Pathology in Amyotrophic Lateral Sclerosis. Ann. Neurol. 2013;74:20–38. doi: 10.1002/ana.23937.
    1. Gorges M., Müller H.P., Lulé D., Del Tredici K., Brettschneider J., Keller J., Pfandl K., Ludolph A.C., Kassubek J., Pinkhardt E.H. Eye Movement Deficits Are Consistent with a Staging Model of Ptdp-43 Pathology in Amyotrophic Lateral Sclerosis. PLoS ONE. 2015;10:e0142546. doi: 10.1371/journal.pone.0142546.
    1. Leigh R.J., Zee D.S. The Neurology of Eye Movements. Contemporary Neurology; Columbia, MD, USA: 2015.
    1. Swinnen B., Robberecht W. The Phenotypic Variability of Amyotrophic Lateral Sclerosis. Nat. Rev. Neurol. 2014;10:661–670. doi: 10.1038/nrneurol.2014.184.
    1. Kaufmann P., Levy G., Thompson J.L., Delbene M.L., Battista V., Gordon P.H., Rowland L.P., Levin B., Mitsumoto H. The Alsfrsr Predicts Survival Time in an Als Clinic Population. Neurology. 2005;64:38–43. doi: 10.1212/01.WNL.0000148648.38313.64.
    1. Kimura F., Fujimura C., Ishida S., Nakajima H., Furutama D., Uehara H., Shinoda K., Sugino M., Hanafusa T. Progression Rate of Alsfrs-R at Time of Diagnosis Predicts Survival Time in Als. Neurology. 2006;66:265–267. doi: 10.1212/01.wnl.0000194316.91908.8a.
    1. McCaslin D.L. Electronystagmography and Videonystagmography (Eng/Vng) Plural Publishing; San Diego, CA, USA: 2019.
    1. Herishanu Y.O., Sharpe J.A. Normal Square Wave Jerks. Invest. Ophthalmol. Vis. Sci. 1981;20:268–272.
    1. Anagnostou E., Karavasilis E., Potiri I., Constantinides V., Efstathopoulos E., Kapaki E., Potagas C. A Cortical Substrate for Square-Wave Jerks in Progressive Supranuclear Palsy. J. Clin. Neurol. 2020;16:37–45. doi: 10.3988/jcn.2020.16.1.37.
    1. Otero-Millan J., Macknik S.L., Serra A., Leigh R.J., Martinez-Conde S. Triggering Mechanisms in Microsaccade and Saccade Generation: A Novel Proposal. Ann. N. Y. Acad. Sci. 2011;1233:107–116. doi: 10.1111/j.1749-6632.2011.06177.x.
    1. Carasig D., Paul K., Fucito M., Ramcharan E., Gnadt J.W. Irrepressible Saccades from a Tectal Lesion in a Rhesus Monkey. Vision Res. 2006;46:1161–1169. doi: 10.1016/j.visres.2005.05.024.
    1. Munoz D.P., Wurtz R.H. Fixation Cells in Monkey Superior Colliculus. Ii. Reversible Activation and Deactivation. J Neurophysiol. 1993;70:576–589. doi: 10.1152/jn.1993.70.2.576.
    1. Averbuch-Heller L., Helmchen C., Horn A.K., Leigh R.J., Büttner-Ennerver J.A. Slow Vertical Saccades in Motor Neuron Disease: Correlation of Structure and Function. Ann. Neurol. 1998;44:641–648. doi: 10.1002/ana.410440410.

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