Consult the medical resource doctors trust

UpToDate is one of the most respected medical information resources in the world, used by over 360,000 doctors and thousands of patients to find answers to medical questions.

  • Content written by a faculty of over 4,000 physicians from leading medical institutions
  • Unbiased: free of advertising or pharmaceutical funding
  • Evidence-based treatment recommendations
  • Continuously updated to incorporate new medical findings

Internuclear ophthalmoplegia

INTRODUCTION

Internuclear ophthalmoplegia (INO) is a specific gaze abnormality characterized by impaired horizontal eye movement with weak adduction of the affected eye and abduction nystagmus of the contralateral eye. It is one of the most localizing brainstem syndromes, resulting from a lesion in the medial longitudinal fasciculus (MLF) in the dorsomedial brainstem tegmentum of either the pons or the midbrain [1].

OCULOMOTOR CIRCUITRY

Foveation or visual targeting with binocular fusion and stereoscopy (depth perception) requires highly synchronous eye movements that place objects of visual interest on the corresponding points of both retinas. This process is dependent upon the precise coordination between cranial nerves III, IV, and VI and their interneuronal pathways that project through the medial longitudinal fasciculus (MLF) (figure 1).

The paramedian pontine reticular formation (PPRF) is often referred to as the conjugate gaze center for horizontal eye movements. During horizontal eye movement, the PPRF burst cells innervate the abducens nucleus, which contains two distinctive sets of neurons. Axons from the abducens motorneurons innervate the ipsilateral lateral rectus muscle. Axons of the abducens interneurons cross the midline to become the MLF and subsequently innervate the medial rectus subnucleus of the oculomotor complex (cranial nerve nucleus III) and finally the medial rectus muscle.

The MLF exists as a pair of white matter fiber tracts that lie near the midline just under the fourth ventricle and cerebral aqueduct and extend through the dorsomedial pontine and midbrain tegmentum. Because of their close physical proximity, bilateral injury is common.

An internuclear ophthalmoplegia (INO) results from injury to the MLF within the dorsomedial pontine or midbrain tegmentum. The side of the INO is named by the side of the adduction deficit, which is ipsilateral to the medial longitudinal fasciculus (MLF) lesion.

To continue reading this article you need to subscribe.

Read the rest of this article and others like it

The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use (click here) ©2010 UpToDate, Inc.
References Top
  1. Frohman, EM, Zhang, H, Kramer, PD, et al. MRI characteristics of the MLF in MS patients with chronic internuclear ophthalmoparesis. Neurology 2001; 57:762.
  2. Kim, JS. Internuclear ophthalmoplegia as an isolated or predominant symptom of brainstem infarction. Neurology 2004; 62:1491.
  3. Mills, DA, Frohman, TC, Davis, SL, et al. Break in binocular fusion during head turning in ms patients with ino. Neurology 2008; 71:458.
  4. Frohman, EM, Frohman, TC, Zee, DS, et al. The neuro-ophthalmology of multiple sclerosis. Lancet Neurol 2005; 4:111.
  5. Zee, DS, Hain, TC, Carl, JR. Abduction nystagmus in internuclear ophthalmoplegia. Ann Neurol 1987; 21:383.
  6. Baloh, RW, Yee, RD, Honrubia, V. Internuclear ophthalmoplegia. I. Saccades and dissociated nystagmus. Arch Neurol 1978; 35:484.
  7. Flipse, JP, Straathof, CS, Van der, Steen J, et al. Binocular saccadic eye movements in multiple sclerosis. J Neurol Sci 1997; 148:53.
  8. Zee, DS. Internuclear ophthalmoplegia: pathophysiology and diagnosis. Baillieres Clin Neurol 1992; 1:455.
  9. Bronstein, AM, Rudge, P, Gresty, MA, et al. Abnormalities of horizontal gaze. Clinical, oculographic and magnetic resonance imaging findings. II. Gaze palsy and internuclear ophthalmoplegia. J Neurol Neurosurg Psychiatry 1990; 53:200.
  10. Evinger, LC, Fuchs, AF, Baker, R. Bilateral lesions of the medial longitudinal fasciculus in monkeys: effects on the horizontal and vertical components of voluntary and vestibular induced eye movements. Exp Brain Res 1977; 28:1.
  11. Ranalli, PJ, Sharpe, JA. Vertical vestibulo-ocular reflex, smooth pursuit and eye-head tracking dysfunction in internuclear ophthalmoplegia. Brain 1988; 111 ( Pt 6):1299.
  12. Bolanos, I, Lozano, D, Cantu, C. Internuclear ophthalmoplegia: causes and long-term follow-up in 65 patients. Acta Neurol Scand 2004; 110:161.
  13. Cremer, PD, Migliaccio, AA, Halmagyi, GM, Curthoys, IS. Vestibulo-ocular reflex pathways in internuclear ophthalmoplegia. Ann Neurol 1999; 45:529.
  14. Zwergal, A, Cnyrim, C, Arbusow, V, et al. Unilateral INO is associated with ocular tilt reaction in pontomesencephalic lesions: INO plus. Neurology 2008; 71:590.
  15. Keane, JR. Internuclear ophthalmoplegia - a reply. Arch Neurol 2006; 63:626.
  16. Jung, DS, Park, KP. Posttraumatic bilateral internuclear ophthalmoplegia with exotropia. Arch Neurol 2004; 61:429.
  17. Keane, JR. Internuclear ophthalmoplegia: unusual causes in 114 of 410 patients. Arch Neurol 2005; 62:714.
  18. Muri, RM, Meienberg, O. The clinical spectrum of internuclear ophthalmoplegia in multiple sclerosis. Arch Neurol 1985; 42:851.
  19. Meienberg, O, Muri, R, Rabineau, PA. Clinical and oculographic examinations of saccadic eye movements in the diagnosis of multiple sclerosis. Arch Neurol 1986; 43:438.
  20. Frohman, EM, Frohman, TC, O'Suilleabhain, P, et al. Quantitative oculographic characterisation of internuclear ophthalmoparesis in multiple sclerosis: the versional dysconjugacy index Z score. J Neurol Neurosurg Psychiatry 2002; 73:51.
  21. Eggenberger, E, Golnik, K, Lee, A, et al. Prognosis of ischemic internuclear ophthalmoplegia. Ophthalmology 2002; 109:1676.
  22. Gray, M, Forbes, RB, Morrow, JI. Primary isolated brainstem injury producing internuclear ophthalmoplegia. Br J Neurosurg 2001; 15:432.
  23. Constantoyannis, C, Tzortzidis, F, Papadakis, N. Internuclear ophthalmoplegia following minor head injury: a case report. Br J Neurosurg 1998; 12:377.
  24. Matsumoto, H, Ohminami, S, Goto, J, Tsuji, S. Progressive supranuclear palsy with walleyed bilateral internuclear ophthalmoplegia syndrome. Arch Neurol 2008; 65:827.
  25. Flint, AC, Williams, O. Bilateral internuclear ophthalmoplegia in progressive supranuclear palsy with an overriding oculocephalic maneuver. Mov Disord 2005; 20:1069.
  26. al-Din, SN, Anderson, M, Eeg-Olofsson, O, Trontelj, JV. Neuro-ophthalmic manifestations of the syndrome of ophthalmoplegia, ataxia and areflexia: a review. Acta Neurol Scand 1994; 89:157.
  27. Davis, TL, Lavin, PJ. Pseudo one-and-a-half syndrome with ocular myasthenia. Neurology 1989; 39:1553.
  28. Korkmaz, A, Topaloglu, H, Kansu, T. Wall eyed bilateral internuclear ophthalmoplegia in chronic inflammatory demyelinating polyneuropathy. Eur J Neurol 2002; 9:691.
  29. Lifshitz, M, Gavrilov, V, Sofer, S. Signs and symptoms of carbamazepine overdose in young children. Pediatr Emerg Care 2000; 16:26.
  30. Atlas, SW, Grossman, RI, Savino, PJ, et al. Internuclear ophthalmoplegia: MR-anatomic correlation. AJNR Am J Neuroradiol 1987; 8:243.
  31. Solingen, LD, Baloh, RW, Myers, L, Ellison, G. Subclinical eye movement disorders in patients with multiple sclerosis. Neurology 1977; 27:614.
  32. Frohman, TC, Frohman, EM, O'Suilleabhain, P, et al. Accuracy of clinical detection of INO in MS: corroboration with quantitative infrared oculography. Neurology 2003; 61:848.
  33. Smith, JL, David, NJ. Internuclear ophthalmoplegia. Two new clinical signs. Neurology 1964; 14:307.
white circle LOG IN
white circle DEMO