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Journal of Neurology

, Volume 262, Issue 3, pp 585–592 | Cite as

Esophoria or esotropia in adulthood: a sign of cerebellar dysfunction?

  • Katharina HüfnerEmail author
  • Claudia Frenzel
  • Olympia Kremmyda
  • Christine Adrion
  • Stanislavs Bardins
  • Stefan Glasauer
  • Thomas Brandt
  • Michael Strupp
Original Communication

Abstract

Convergent strabismus is a common diagnosis in early childhood, when it is mostly considered benign. If it develops later in life, strabismus can, however, be a sign of neurological disease. In these cases the underlying pathophysiological mechanisms are largely unknown. In this retrospective case–control study we analyzed the neuro-ophthalmological examination reports of 400 adult patients who presented at the German Center for Vertigo and Balance Disorders to determine an association between ocular misalignment and cerebellar dysfunction. Patients with cerebellar signs (i.e., cerebellar ataxia and/or cerebellar ocular motor signs) had a 4.49 (95 % CI [1.60; 13.78]) times higher frequency of ocular misalignment and specifically a 13.3 (95 % CI [3.80; 55.73]) times increased frequency of esophoria/esotropia (ESO) during distant gaze than patients without cerebellar dysfunction. ESO when looking into the distance was associated with saccadic smooth pursuit, dysmetria of saccades, and downbeat nystagmus (DBN) (χ 2 test, p < 0.0001 for all associations). Patients with cerebellar dysfunction also showed mildly impaired eye abduction (χ 2 test, left eye and right eye: p < 0.0001), associated with horizontal gaze-evoked nystagmus (χ 2 test, p < 0.0001). The association of ESO and DBN implicates a pathophysiological involvement of the cerebellar flocculus, while the association with dysmetric saccades suggests involvement of the oculomotor vermis. This is compatible with animal studies showing that the pathways of the flocculus/posterior interposed nucleus and vermis/nucleus fastigii are both involved in vergence movements and static binocular alignment. From a clinical point of view, a newly diagnosed esophoria/esotropia only during distant gaze may be a sign of a cerebellar disease.

Keywords

Esophoria Esotropia Distant gaze Cerebellar dysfunction 

Notes

Acknowledgments

This study was not industry sponsored. The study was supported by the German Federal Ministry of Education and Research (BMBF 01EO0901). We thank Judy Benson and Katie Ogston for carefully copy-editing the manuscript.

Conflicts of interest

None declared.

Ethical standard

The study was approved by the ethics committee of the Ludwig-Maximilians University, Munich, Germany and was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Written informed consent was obtained for the videooculography recordings.

References

  1. 1.
    Anderson WD, Lubow M (1970) Astrocytoma of the corpus callosum presenting with acute comitant esotropia. Am J Ophthalmol 69:594–598CrossRefPubMedGoogle Scholar
  2. 2.
    Baier B, Bense S, Dieterich M (2008) Are signs of ocular tilt reaction in patients with cerebellar lesions mediated by the dentate nucleus? Brain 131:1445–1454CrossRefPubMedGoogle Scholar
  3. 3.
    Balaban CD, Watanabe E (1984) Functional representation of eye movements in the flocculus of monkeys (Macaca fuscata). Neurosci Lett 49:199–205CrossRefPubMedGoogle Scholar
  4. 4.
    Buttner-Ennever JA (1999) A review of otolith pathways to brainstem and cerebellum. Ann N Y Acad Sci 871:51–64CrossRefPubMedGoogle Scholar
  5. 5.
    Chaudhuri Z, Demer JL (2013) Divergence insufficiency esotropia is a misnomer-reply. JAMA Ophthalmol 131:547–548PubMedCentralCrossRefPubMedGoogle Scholar
  6. 6.
    Das VE (2012) Responses of cells in the midbrain near-response area in monkeys with strabismus. Invest Ophthalmol Vis Sci 53:3858–3864PubMedCentralCrossRefPubMedGoogle Scholar
  7. 7.
    Dufosse M, Ito M, Miyashita Y (1977) Functional localization in the rabbit’s cerebellar flocculus determined in relationship with eye movements. Neurosci Lett 5:273–277CrossRefPubMedGoogle Scholar
  8. 8.
    Defoort-Dhellemmes S, Denion E, Arndt CF, Bouvet-Drumare I, Hache JC, Dhellemmes P (2002) Resolution of acute acquired comitant esotropia after suboccipital decompression for Chiari I malformation. Am J Ophthalmol 133:723–725CrossRefPubMedGoogle Scholar
  9. 9.
    Gomez CR, Gomez SM, Selhorst JB (1988) Acute thalamic esotropia. Neurology 38:1759–1762CrossRefPubMedGoogle Scholar
  10. 10.
    Graham PA (1974) Epidemiology of strabismus. Br J Ophthalmol 58:224–231PubMedCentralCrossRefPubMedGoogle Scholar
  11. 11.
    Hain TC, Luebke AE (1990) Phoria adaptation in patients with cerebellar dysfunction. Invest Ophthalmol Vis Sci 31:1394–1397PubMedGoogle Scholar
  12. 12.
    Holmes G (2007) The Croonian Lectures on the clinical symptoms of cerebellar disease and their interpretation. Lecture II. 1922. Cerebellum 6:148–153PubMedGoogle Scholar
  13. 13.
    Hoyt CS, Good WV (1995) Acute onset concomitant esotropia: when is it a sign of serious neurological disease? Br J Ophthalmol 79:498–501PubMedCentralCrossRefPubMedGoogle Scholar
  14. 14.
    Hufner K, Barresi D, Glaser M, Linn J, Adrion C, Mansmann U, Brandt T, Strupp M (2008) Vestibular paroxysmia: diagnostic features and medical treatment. Neurology 71:1006–1014CrossRefPubMedGoogle Scholar
  15. 15.
    Ito M, Nisimaru N, Yamamoto M (1977) Specific patterns of neuronal connexions involved in the control of the rabbit’s vestibulo-ocular reflexes by the cerebellar flocculus. J Physiol 265:833–854PubMedCentralCrossRefPubMedGoogle Scholar
  16. 16.
    Jacobson DM (2000) Divergence insufficiency revisited: natural history of idiopathic cases and neurologic associations. Arch Ophthalmol 118:1237–1241CrossRefPubMedGoogle Scholar
  17. 17.
    Jones GM, Berthoz A, Segal B (1984) Adaptive modification of the vestibulo-ocular reflex by mental effort in darkness. Exp Brain Res 56:149–153PubMedGoogle Scholar
  18. 18.
    Joshi AC, Das VE (2013) Muscimol inactivation of caudal fastigial nucleus and posterior interposed nucleus in monkeys with strabismus. J Neurophysiol 110:1882–1891PubMedCentralCrossRefPubMedGoogle Scholar
  19. 19.
    Joshi AC, Das VE (2011) Responses of medial rectus motoneurons in monkeys with strabismus. Invest Ophthalmol Vis Sci 52:6697–6705PubMedCentralCrossRefPubMedGoogle Scholar
  20. 20.
    Kestenbaum A (1961) Clinical methods of neuro-ophthalmologic examination. Grune & Stratton, New YorkGoogle Scholar
  21. 21.
    Kheradmand A, Zee DS (2011) Cerebellum and ocular motor control. Front Neurol 2:53PubMedCentralCrossRefPubMedGoogle Scholar
  22. 22.
    Kirchner H, Kremmyda O, Hufner K, Stephan T, Zingler V, Brandt T, Jahn K, Strupp M (2011) Clinical, electrophysiological, and MRI findings in patients with cerebellar ataxia and a bilaterally pathological head-impulse test. Ann N Y Acad Sci 1233:127–138CrossRefPubMedGoogle Scholar
  23. 23.
    Kono R, Hasebe S, Ohtsuki H, Kashihara K, Shiro Y (2002) Impaired vertical phoria adaptation in patients with cerebellar dysfunction. Invest Ophthalmol Vis Sci 43:673–678PubMedGoogle Scholar
  24. 24.
    Leigh RJ, Zee DS (1999) The neurology of eye movements. Oxford University Press, New YorkGoogle Scholar
  25. 25.
    May PJ, Porter JD, Gamlin PD (1992) Interconnections between the primate cerebellum and midbrain near-response regions. J Comp Neurol 315:98–116CrossRefPubMedGoogle Scholar
  26. 26.
    Mays LE (1984) Neural control of vergence eye movements: convergence and divergence neurons in midbrain. J Neurophysiol 51:1091–1108PubMedGoogle Scholar
  27. 27.
    Milder DG, Reinecke RD (1983) Phoria adaptation to prisms. A cerebellar-dependent response. Arch Neurol 40:339–342CrossRefPubMedGoogle Scholar
  28. 28.
    Miles FA, Fuller JH, Braitman DJ, Dow BM (1980) Long-term adaptive changes in primate vestibuloocular reflex. III. Electrophysiological observations in flocculus of normal monkeys. J Neurophysiol 43:1437–1476PubMedGoogle Scholar
  29. 29.
    Mittelman D (2013) Divergence insufficiency esotropia is a misnomer. JAMA Ophthalmol 131:547CrossRefPubMedGoogle Scholar
  30. 30.
    Musazadeh M, Hartmann K, Simon F (2004) Late onset esotropia as first symptom of a cerebellar tumor. Strabismus 12:119–123CrossRefPubMedGoogle Scholar
  31. 31.
    Pathai S, Cumberland PM, Rahi JS (2010) Prevalence of and early-life influences on childhood strabismus: findings from the Millennium Cohort Study. Arch Pediatr Adolesc Med 164:250–257CrossRefPubMedGoogle Scholar
  32. 32.
    Pokharel D, Siatkowski RM (2004) Progressive cerebellar tonsillar herniation with recurrent divergence insufficiency esotropia. JAAPOS 8:286–287Google Scholar
  33. 33.
    Radtke A, Bronstein AM, Gresty MA, Faldon M, Taylor W, Stevens JM, Rudge P (2001) Paroxysmal alternating skew deviation and nystagmus after partial destruction of the uvula. J Neurol Neurosurg Psychiatry 70:790–793PubMedCentralCrossRefPubMedGoogle Scholar
  34. 34.
    Repka MX, Downing E (2014) Characteristics and surgical results in patients with age-related divergence insufficiency esotropia. JAAPOS 18:370–373Google Scholar
  35. 35.
    Richter HO, Costello P, Sponheim SR, Lee JT, Pardo JV (2004) Functional neuroanatomy of the human near/far response to blur cues: eye-lens accommodation/vergence to point targets varying in depth. Eur J Neurosci 20:2722–2732CrossRefPubMedGoogle Scholar
  36. 36.
    Sander T, Sprenger A, Neumann G, Machner B, Gottschalk S, Rambold H, Helmchen C (2009) Vergence deficits in patients with cerebellar lesions. Brain 132:103–115CrossRefPubMedGoogle Scholar
  37. 37.
    Simon JW, Waldman JB, Couture KC (1996) Cerebellar astrocytoma manifesting as isolated, comitant esotropia in childhood. Am J Ophthalmol 121:584–586CrossRefPubMedGoogle Scholar
  38. 38.
    Takagi M, Tamargo R, Zee DS (2003) Effects of lesions of the cerebellar oculomotor vermis on eye movements in primate: binocular control. Prog Brain Res 142:19–33CrossRefPubMedGoogle Scholar
  39. 39.
    Umetani T (1992) Efferent projections from the flocculus in the albino rat as revealed by an autoradiographic orthograde tracing method. Brain Res 586:91–103CrossRefPubMedGoogle Scholar
  40. 40.
    Versino M, Hurko O, Zee DS (1996) Disorders of binocular control of eye movements in patients with cerebellar dysfunction. Brain 119(Pt 6):1933–1950CrossRefPubMedGoogle Scholar
  41. 41.
    Watson AP, Fielder AR (1987) Sudden-onset squint. Dev Med Child Neurol 29:207–211CrossRefPubMedGoogle Scholar
  42. 42.
    Westheimer G, Blair SM (1973) Oculomotor defects in cerebellectomized monkeys. Invest Ophthalmol 12:618–621PubMedGoogle Scholar
  43. 43.
    Williams AS, Hoyt CS (1989) Acute comitant esotropia in children with brain tumors. Arch Ophthalmol 107:376–378CrossRefPubMedGoogle Scholar
  44. 44.
    Yamada J, Noda H (1987) Afferent and efferent connections of the oculomotor cerebellar vermis in the macaque monkey. J Comp Neurol 265:224–241CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Katharina Hüfner
    • 1
    • 2
    • 5
    Email author
  • Claudia Frenzel
    • 1
  • Olympia Kremmyda
    • 1
    • 2
  • Christine Adrion
    • 2
    • 3
  • Stanislavs Bardins
    • 2
  • Stefan Glasauer
    • 2
    • 4
  • Thomas Brandt
    • 2
    • 4
  • Michael Strupp
    • 1
    • 2
  1. 1.Department of NeurologyUniversity Hospital Munich, Ludwig-Maximilians UniversityMunichGermany
  2. 2.German Center for Vertigo and Balance DisordersUniversity Hospital Munich, Ludwig-Maximilians UniversityMunichGermany
  3. 3.Institute for Medical Informatics, Biometry und EpidemiologyUniversity Hospital Munich, Ludwig-Maximilians UniversityMunichGermany
  4. 4.Institute for Clinical NeurosciencesUniversity Hospital Munich, Ludwig-Maximilians UniversityMunichGermany
  5. 5.Department of PsychiatryMedical University of InnsbruckInnsbruckAustria

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