Skip to main content

Advertisement

SpringerLink
Log in

Slow saccades in bulbar-onset motor neurone disease

  • Original Communication
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Historical studies of eye movements in motor neurone disease (MND) have been conflicting although current findings suggest that eye movement abnormalities relate to frontal lobe impairment. Numerous case reports, however, describe slow saccades and supranuclear gaze palsies in patients with MND often associated with bulbar-onset disease. We performed a study of saccades and smooth pursuit in a large group of patients with MND to examine for any differences between bulbar-onset and spinal-onset patients. Forty-four patients (14 bulbar-onset and 30 spinal-onset patients) and 45 controls were recruited. Reflexive saccades, antisaccades and smooth pursuit were examined using infra-red oculography and all subjects then underwent neuropsychological evaluation. Reflexive saccades were found to be slower in bulbar-onset compared to spinal-onset patients and controls (p = 0.03, p = 0.05). Antisaccade latency (p = 0.01) and antisaccade type 1 errors (p = 0.03, p = 0.04) were increased in patients compared to controls. ‘Proportion of time spent in smooth pursuit’ and smooth pursuit ‘velocity gain’ were reduced in patients compared to controls (p = 0.000, p = 0.001). Antisaccade errors and velocity gain correlated with neuropsychological measures sensitive to lesions of the frontal lobes. This is the first study to highlight the presence of slow saccades in bulbar-onset MND. These findings suggest that slow saccades may be due to increased brainstem pathology in bulbar-onset disease that involves burst cell neurons. Furthermore these observations highlight the potential for overlap between bulbar-onset MND and progressive supranuclear palsy (PSP) as both can have a bulbar palsy and slowed saccades.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Abe K, Fujimura H, Toyooka K, Sakoda S, Yorifuji S, Yanagihara T (1997) Cognitive function in amyotrophic lateral sclerosis. J Neurol Sci 148:95–100

    Article  CAS  PubMed  Google Scholar 

  2. Abel LA, Williams IM, Gibson KL, Levi L (1995) Effects of stimulus velocity and acceleration on smooth pursuit in motor neuron disease. J Neurol 242:419–424

    Article  CAS  PubMed  Google Scholar 

  3. Abrahams S, Goldstein LH, Al-Chalabi A, Pickering A, Morris RG, Passingham RE, Brooks DJ, Leigh PN (1997) Relation between cognitive dysfunction and pseudobulbar palsy in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 62:464–472

    Article  CAS  PubMed  Google Scholar 

  4. Abrahams S, Goldstein LH, Kew JJ, Brooks DJ, Lloyd CM, Frith CD, Leigh PN (1996) Frontal lobe dysfunction in amyotrophic lateral sclerosis. A PET study. Brain 119(Pt 6):2105–2120

    Article  PubMed  Google Scholar 

  5. Abrahams S, Leigh PN, Harvey A, Vythelingum GN, Grise D, Goldstein LH (2000) Verbal fluency and executive dysfunction in amyotrophic lateral sclerosis (ALS). Neuropsychologia 38:734–747

    Article  CAS  PubMed  Google Scholar 

  6. Averbuch-Heller L, Helmchen C, Horn AK, Leigh RJ, Buttner-Ennerver JA (1998) Slow vertical saccades in motor neuron disease: correlation of structure and function. Ann Neurol 44:641–648

    Article  CAS  PubMed  Google Scholar 

  7. Baloh RW, Konrad HR, Sills AW, Honrubia V (1975) The saccade velocity test. Neurology 25:1071–1076

    CAS  PubMed  Google Scholar 

  8. Brooks BR (1994) El Escorial World Federation of Neurology criteria for the diagnosis of amyotrophic lateral sclerosis. Subcommittee on Motor Neuron Diseases/Amyotrophic Lateral Sclerosis of the World Federation of Neurology Research Group on Neuromuscular Diseases and the El Escorial “Clinical limits of amyotrophic lateral sclerosis” workshop contributors. J Neurol Sci 124(Suppl):96–107

    Article  PubMed  Google Scholar 

  9. Cedarbaum JM, Stambler N, Malta E, Fuller C, Hilt D, Thurmond B, Nakanishi A (1999) The ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of respiratory function. BDNF ALS Study Group (Phase III). J Neurol Sci 169:13–21

    Article  CAS  PubMed  Google Scholar 

  10. Condy C, Rivaud-Pechoux S, Ostendorf F, Ploner CJ, Gaymard B (2004) Neural substrate of antisaccades. Role of subcortical structures. Neurology 63:1571–1578

    CAS  PubMed  Google Scholar 

  11. Donaghy C, Pinnock R, Abrahams S, Cardwell C, Hardiman O, Patterson V, McGivern RC, Gibson JM (2009) Ocular fixation instabilities in motor neurone disease: a marker of frontal lobe dysfunction? J Neurol 256:420–426

    Article  CAS  PubMed  Google Scholar 

  12. Evdokimidis I, Constantinidis TS, Gourtzelidis P, Smyrnis N, Zalonis I, Zis PV, Andreadou E, Papageorgiou C (2002) Frontal lobe dysfunction in amyotrophic lateral sclerosis. J Neurol Sci 195:25–33

    Article  CAS  PubMed  Google Scholar 

  13. Frank B, Haas J, Heinze HJ, Stark E, Munte TF (1997) Relation of neuropsychological and magnetic resonance findings in amyotrophic lateral sclerosis: evidence for subgroups. Clin Neurol Neurosurg 99:79–86

    Article  CAS  PubMed  Google Scholar 

  14. Gallassi R, Montagna P, Ciardulli C, Lorusso S, Mussuto V, Stracciari A (1985) Cognitive impairment in motor neuron disease. Acta Neurol Scand 71:480–484

    CAS  PubMed  Google Scholar 

  15. Gallassi R, Montagna P, Morreale A, Lorusso S, Tinuper P, Daidone R, Lugaresi E (1989) Neuropsychological, electroencephalogram and brain computed tomography findings in motor neuron disease. Eur Neurol 29:115–120

    Article  CAS  PubMed  Google Scholar 

  16. Garbutt S, Harwood MR, Kumar AN, Han YH, Leigh RJ (2003) Evaluating small eye movements in patients with saccadic palsies. Ann N Y Acad Sci 1004:337–346

    Article  PubMed  Google Scholar 

  17. Gizzi M, DiRocco A, Sivak M, Cohen B (1992) Ocular motor function in motor neuron disease. Neurology 42:1037–1046

    CAS  PubMed  Google Scholar 

  18. Guitton D, Buchtel HA, Douglas RM (1985) Frontal lobe lesions in man cause difficulties in suppressing reflexive glances and in generating goal-directed saccades. Exp Brain Res 58:455–472

    Article  CAS  PubMed  Google Scholar 

  19. Jacobs L, Bozian D, Heffner RR Jr, Barron SA (1981) An eye movement disorder in amyotrophic lateral sclerosis. Neurology 31:1282–1287

    CAS  PubMed  Google Scholar 

  20. Kew JJ, Goldstein LH, Leigh PN, Abrahams S, Cosgrave N, Passingham RE, Frackowiak RS, Brooks DJ (1993) The relationship between abnormalities of cognitive function and cerebral activation in amyotrophic lateral sclerosis. A neuropsychological and positron emission tomography study. Brain 116(Pt 6):1399–1423

    Article  PubMed  Google Scholar 

  21. Kobayashi M, Ikeda K, Kinoshita M, Iwasaki Y (1999) Amyotrophic lateral sclerosis with supranuclear ophthalmoplegia and rigidity. Neurol Res 21:661–664

    CAS  PubMed  Google Scholar 

  22. Leigh RJ, Zee DS (2006) The neurology of eye movements. Oxford University Press, New York

    Google Scholar 

  23. Leveille A, Kiernan J, Goodwin JA, Antel J (1982) Eye movements in amyotrophic lateral sclerosis. Arch Neurol 39:684–686

    CAS  PubMed  Google Scholar 

  24. Ludolph AL, Langen KJ, Regard M, Herzog H, Kemper B, Kuwert T, Bottger IG, Feinendegen L (1992) Frontal lobe function in amyotrophic lateral sclerosis: a neuropsychologic and positron emission tomography study. Acta Neurol Scand 85:81–89

    Article  CAS  PubMed  Google Scholar 

  25. Marti-Fabregas J, Roig C (1993) Oculomotor abnormalities in motor neuron disease. J Neurol 240:475–478

    Article  CAS  PubMed  Google Scholar 

  26. Massman PJ, Sims J, Cooke N, Haverkamp LJ, Appel V, Appel SH (1996) Prevalence and correlates of neuropsychological deficits in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 61:450–455

    Article  CAS  PubMed  Google Scholar 

  27. McDowell JE, Brown GG, Paulus M, Martinez A, Stewart SE, Dubowitz DJ, Braff DL (2002) Neural correlates of refixation saccades and antisaccades in normal and schizophrenia subjects. Biol Psychiatry 51:216–223

    Article  PubMed  Google Scholar 

  28. McKenna P, Warrington E (1983) The graded naming test. NFER-Nelson, Oxford

    Google Scholar 

  29. Mizuno M (1986) Neurotological findings in amyotrophic lateral sclerosis. Auris Nasus Larynx 13(Suppl 2):S139–S146

    PubMed  Google Scholar 

  30. Mort DJ, Perry RJ, Mannan SK, Hodgson TL, Anderson E, Quest R, McRobbie D, McBride A, Husain M, Kennard C (2003) Differential cortical activation during voluntary and reflexive saccades in man. Neuroimage 18:231–246

    Article  PubMed  Google Scholar 

  31. Muri RM, Heid O, Nirkko AC, Ozdoba C, Felblinger J, Schroth G, Hess CW (1998) Functional organisation of saccades and antisaccades in the frontal lobe in humans: a study with echo planar functional magnetic resonance imaging. J Neurol Neurosurg Psychiatry 65:374–377

    Article  CAS  PubMed  Google Scholar 

  32. Neary D, Snowden JS, Gustafson L, Passant U, Stuss D, Black S, Freedman M, Kertesz A, Robert PH, Albert M, Boone K, Miller BL, Cummings J, Benson DF (1998) Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 51:1546–1554

    CAS  PubMed  Google Scholar 

  33. Nelson H, Willison J (1991) Restandardisation of the NART against the WAIS-R. NFER-Nelson, Windsor

    Google Scholar 

  34. Ohki M, Kanayama R, Nakamura T, Okuyama T, Kimura Y, Koike Y (1994) Ocular abnormalities in amyotrophic lateral sclerosis. Acta Otolaryngol Suppl 511:138–142

    Article  CAS  PubMed  Google Scholar 

  35. Okuda B, Yamamoto T, Yamasaki M, Maya K, Imai T (1992) Motor neuron disease with slow eye movements and vertical gaze palsy. Acta Neurol Scand 85:71–76

    Article  CAS  PubMed  Google Scholar 

  36. Palmowski A, Jost WH, Osterhage J, Prudlo J, Kasmann B, Schimrigk K, Ruprecht KW (1995) Disorders of eye movement in amyotrophic lateral sclerosis––report of 2 patients. Klin Monatsbl Augenheilkd 206:170–172

    Article  CAS  PubMed  Google Scholar 

  37. Palmowski A, Jost WH, Prudlo J, Osterhage J, Kasmann B, Schimrigk K, Ruprecht KW (1995) Eye movement in amyotrophic lateral sclerosis: a longitudinal study. Ger J Ophthalmol 4:355–362

    CAS  PubMed  Google Scholar 

  38. Pierrot-Deseilligny CM, Muri RM, Ploner CJ, Gaymard B, Demeret S, Rivaud-Pechoux S (2003) Decisional role of the dorsolateral prefrontal cortex in ocular motor behaviour. Brain 126:1460–1473

    Article  CAS  PubMed  Google Scholar 

  39. Pierrot-Deseilligny CR, Rivaud S, Gaymard B, Agid Y (1991) Cortical control of reflexive visually guided saccades. Brain 114:1473–1485

    Article  PubMed  Google Scholar 

  40. Rivaud S, Muri RM, Gaymard B, Vermersch AI, Pierrot-Deseilligny C (1994) Eye movement disorders after frontal eye field lesions in humans. Exp Brain Res 102:110–120

    Article  CAS  PubMed  Google Scholar 

  41. Saito S, Yamamoto H (1989) Analysis of oculomotor disorders in motor neuron disease. Rinsho Shinkeigaku 29:969–975

    CAS  PubMed  Google Scholar 

  42. Shaunak S, Orrell RW, O’Sullivan E, Hawken MB, Lane RJ, Henderson L, Kennard C (1995) Oculomotor function in amyotrophic lateral sclerosis: evidence for frontal impairment. Ann Neurol 38:38–44

    Article  CAS  PubMed  Google Scholar 

  43. Tanaka M, Lisberger SG (2001) Regulation of the gain of visually guided smooth-pursuit eye movements by frontal cortex. Nature 409:191–194

    Article  CAS  PubMed  Google Scholar 

  44. Tanaka M, Lisberger SG (2002) Enhancement of multiple components of pursuit eye movement by microstimulation in the arcuate frontal pursuit area in monkeys. J Neurophysiol 87:802–818

    PubMed  Google Scholar 

  45. Thier P, Ilg UJ (2005) The neural basis of smooth-pursuit eye movements. Curr Opin Neurobiol 15:645–652

    Article  CAS  PubMed  Google Scholar 

  46. Trenerry M, Crosson B, DeBoe J, Leber W (1989) STROOP Neuropsychological Screening Test Manual. Psychological Assessment Resources, Inc, Lutz

    Google Scholar 

  47. Ushio M, Iwasaki S, Sugasawa K, Murofushi T (2009) Atypical motor neuron disease with supranuclear vertical gaze palsy and slow saccades. Auris Nasus Larynx 36:85–87

    Article  PubMed  Google Scholar 

  48. Warrington EJ, James M (1991) The visual object and space perception battery. Thames Valley Test Company, Bury St Edmunds

    Google Scholar 

  49. Zigmond AS, Snaith RP (1983) The hospital anxiety and depression scale. Acta Psychiatr Scand 67:361–370

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We would like to thank all the patients and volunteers who gave of their time to participate in this study. We would also like to thank Mrs. Carol Montgomery and the Neurophysiology department in the Royal Victoria Hospital, Belfast, for their assistance.

Author information

Authors and Affiliations

  1. Department of Neurology, Royal Victoria Hospital, Belfast, BT12 6BA, Northern Ireland, UK

    Colette Donaghy, Victor Patterson & J. Mark Gibson

  2. Northern Ireland Regional Medical Physics Agency, Royal Victoria Hospital, Belfast, Northern Ireland, UK

    Ralph Pinnock & R. Canice McGivern

  3. Department of Psychology, School of Philosophy, Psychology and Language Sciences, University of Edinburgh, Edinburgh, Scotland, UK

    Sharon Abrahams

  4. School of Medicine and Dentistry, Royal Victoria Hospital, Queens University of Belfast, Belfast, Northern Ireland, UK

    Chris Cardwell

  5. Department of Neurology, Beaumont Hospital, Dublin, Ireland

    Orla Hardiman

Authors
  1. Colette Donaghy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ralph Pinnock
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sharon Abrahams
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chris Cardwell
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Orla Hardiman
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Victor Patterson
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. R. Canice McGivern
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. J. Mark Gibson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Colette Donaghy.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Donaghy, C., Pinnock, R., Abrahams, S. et al. Slow saccades in bulbar-onset motor neurone disease. J Neurol 257, 1134–1140 (2010). https://doi.org/10.1007/s00415-010-5478-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-010-5478-7

Keywords

Search

Navigation