What are the variants of internuclear ophthalmoplegia (INO) in multiple sclerosis (MS)?

Answer

Wall-eyed internuclear ophthalmoplegia

Patients with unilateral INO do not typically have significant exotropia (outwardly deviating eye) in primary gaze because convergence tone is intact.^[40]In contrast, bilateral MLF lesions can cause exotropia in wall-eyed bilateral INO (WEBINO) syndrome. WEBINO syndrome differs from paralytic pontine exotropia of one-and-a-half syndrome, which is characterized by a unilateral horizontal gaze palsy and INO due to a pontine lesion involving the paramedian pontine reticular formation and MLF.^[47]

One-and-a-half syndrome

One-and-a-half syndrome is a clinical disorder characterized by a conjugate horizontal gaze palsy in one direction with an associated INO. The syndrome usually results from a single unilateral lesion of the paramedian pontine reticular formation or the abducens nucleus on one side (causing the conjugate gaze palsy), with interruption of internuclear fibers of the ipsilateral MLF (causing failure of adduction of the ipsilateral eye). Consequently, the single preserved horizontal eye movement is the abducting eye contralateral to the MLF lesion.^{[40, 48]}

Skew deviation

Skew deviation refers to a vertical ocular misalignment caused by supranuclear lesions disrupting inputs to the ocular motor nuclei.^[48]Skew deviation may cause vertical diplopia or misalignment in patients with INO because the MLF contains utricular pathways that maintain vertical eye position in addition to interneurons from the abducens nucleus to the medial rectus subnucleus.^[40]

In skew deviation caused by a pontine lesion, the ipsilateral eye is lower, whereas, with a midbrain lesion, the ipsilateral eye is higher.^[40]

Ocular tilt reaction

Ocular tilt reaction consists of skew deviation, ocular torsion, head tilt, and deviation of the subjective visual vertical, which are all tilted toward the lower or hypotropic eye.^[49]The side of the tilt is named for the lower eye.^[49]Static ocular tilt reactions from hypofunction are ipsiversive (lower eye on the side of the lesion) with peripheral vestibular and pontomedullary lesions and contraversive with pontomesencephalic lesions.^[49]Paroxysmal ocular tilt reaction is rare but has been described in MS.^[49]

Did this answer your question?

Yes No

Additional feedback? (Optional)

Thank you for your feedback!

Compston A, Coles A. Multiple sclerosis. Lancet. 2008 Oct 25. 372(9648):1502-17. [Medline].
Costello F. The afferent visual pathway: designing a structural-functional paradigm of multiple sclerosis. ISRN Neurol. 2013. 2013:134858. [Medline]. [Full Text].
McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001 Jul. 50(1):121-7. [Medline].
Polman CH, Reingold SC, Edan G, Filippi M, Hartung HP, Kappos L. Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria". Ann Neurol. 2005 Dec. 58(6):840-6. [Medline].
Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011 Feb. 69(2):292-302. [Medline].
Ruck T, Bittner S, Wiendl H, Meuth SG. Alemtuzumab in Multiple Sclerosis: Mechanism of Action and Beyond. Int J Mol Sci. 2015 Jul 20. 16 (7):16414-39. [Medline].
Milo R. The efficacy and safety of daclizumab and its potential role in the treatment of multiple sclerosis. Ther Adv Neurol Disord. 2014 Jan. 7 (1):7-21. [Medline].
Sørensen PS, Bertolotto A, Edan G, Giovannoni G, Gold R, Havrdova E. Risk stratification for progressive multifocal leukoencephalopathy in patients treated with natalizumab. Mult Scler. 2012 Feb. 18(2):143-52. [Medline].
Disease Modifying Therapies. Multiple Sclerosis Society of Canada. Available at https://mssociety.ca/managing-ms/treatments/medications/disease-modifying-therapies-dmts. Accessed: July 24, 2016.
Miller D, Barkhof F, Montalban X, Thompson A, Filippi M. Clinically isolated syndromes suggestive of multiple sclerosis, part I: natural history, pathogenesis, diagnosis, and prognosis. Lancet Neurol. 2005 May. 4(5):281-8. [Medline].
Hickman SJ, Dalton CM, Miller DH, Plant GT. Management of acute optic neuritis. Lancet. 2002 Dec 14. 360(9349):1953-62. [Medline].
Beck RW, Cleary PA, Anderson MM Jr, Keltner JL, Shults WT, Kaufman DI. A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. The Optic Neuritis Study Group. N Engl J Med. 1992 Feb 27. 326(9):581-8. [Medline].
Beck RW. Optic Neuritis. Walsh & Hoyt’s Clinical Neuro-Ophthalmology. 5th ed. Williams & Wilkins; 1998. Vol. 5: 12.
Costello F. Inflammatory optic neuropathies. Continuum (Minneap Minn). 2014 Aug. 20(4 Neuro-ophthalmology):816-37. [Medline].
Davis FA, Bergen D, Schauf C, McDonald I, Deutsch W. Movement phosphenes in optic neuritis: a new clinical sign. Neurology. 1976 Nov. 26 (11):1100-4. [Medline].
Selhorst JB, Saul RF. Uhthoff and his symptom. J Neuroophthalmol. 1995 Jun. 15 (2):63-9. [Medline].
Keltner JL, Johnson CA, Cello KE, Dontchev M, Gal RL, Beck RW. Visual field profile of optic neuritis: a final follow-up report from the optic neuritis treatment trial from baseline through 15 years. Arch Ophthalmol. 2010 Mar. 128(3):330-7. [Medline].
Volpe NJ. The optic neuritis treatment trial: a definitive answer and profound impact with unexpected results. Arch Ophthalmol. 2008 Jul. 126 (7):996-9. [Medline].
Balcer LJ, Miller DH, Reingold SC, Cohen JA. Vision and vision-related outcome measures in multiple sclerosis. Brain. 2015 Jan. 138 (Pt 1):11-27. [Medline].
Wingerchuk DM, Banwell B, Bennett JL, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology. 2015 Jul 14. 85 (2):177-89. [Medline].
Rostasy K, Mader S, Schanda K, Huppke P, Gärtner J, Kraus V, et al. Anti-myelin oligodendrocyte glycoprotein antibodies in pediatric patients with optic neuritis. Arch Neurol. 2012 Jun. 69 (6):752-6. [Medline].
Heussinger N, Kontopantelis E, Gburek-Augustat J, et al. Oligoclonal bands predict multiple sclerosis in children with optic neuritis. Ann Neurol. 2015 Jun. 77 (6):1076-82. [Medline].
Balcer LJ. Clinical practice. Optic neuritis. N Engl J Med. 2006 Mar 23. 354 (12):1273-80. [Medline].
Costello F. Optical coherence tomography in neuro-ophthalmology. Neurology Clinics (in press).
Yeh EA, Marrie RA, Reginald YA, Buncic JR, Noguera AE, O'Mahony J, et al. Functional-structural correlations in the afferent visual pathway in pediatric demyelination. Neurology. 2014 Dec 2. 83 (23):2147-52. [Medline].
Costello F, Burton JM. An approach to optic neuritis: the initial presentation. Expert Rev Ophthalmol. 2013. 8(6):539–551.
Martinelli V, Rocca MA, Annovazzi P, Pulizzi A, Rodegher M, Martinelli Boneschi F. A short-term randomized MRI study of high-dose oral vs intravenous methylprednisolone in MS. Neurology. 2009 Dec 1. 73(22):1842-8. [Medline].
Burton JM, O'Connor PW, Hohol M, Beyene J. Oral versus intravenous steroids for treatment of relapses in multiple sclerosis. Cochrane Database Syst Rev. 2009 Jul 8. CD006921. [Medline].
Kaufman DI, Trobe JD, Eggenberger ER, Whitaker JN. Practice parameter: the role of corticosteroids in the management of acute monosymptomatic optic neuritis. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2000 Jun 13. 54(11):2039-44. [Medline].
Shams PN, Plant GT. Optic neuritis: a review. Int MS J. 2009 Sep. 16(3):82-9. [Medline].
Kupersmith MJ, Gal RL, Beck RW, Xing D, Miller N,. Visual function at baseline and 1 month in acute optic neuritis: predictors of visual outcome. Neurology. 2007 Aug 7. 69(6):508-14. [Medline].
Raz N, Dotan S, Benoliel T, Chokron S, Ben-Hur T, Levin N. Sustained motion perception deficit following optic neuritis: Behavioral and cortical evidence. Neurology. 2011 Jun 14. 76(24):2103-11. [Medline].
Rodriguez M, Siva A, Cross SA, O'Brien PC, Kurland LT. Optic neuritis: a population-based study in Olmsted County, Minnesota. Neurology. 1995 Feb. 45(2):244-50. [Medline].
Multiple sclerosis risk after optic neuritis: final optic neuritis treatment trial follow-up. Arch Neurol. 2008 Jun. 65(6):727-32. [Medline].
Kaya D, Kaya M, Özakbaş S, İdiman E. Uveitis associated with multiple sclerosis: complications and visual prognosis. Int J Ophthalmol. 2014. 7 (6):1010-3. [Medline].
Gordon LK, Goldstein DA. Gender and uveitis in patients with multiple sclerosis. J Ophthalmol. 2014. 2014:565262. [Medline].
Jain N, Bhatti MT. Fingolimod-associated macular edema: incidence, detection, and management. Neurology. 2012 Feb 28. 78(9):672-80. [Medline].
McClelland C, Galetta S. Eye Symptoms, Signs, and Therapy in Multiple Sclerosis. Rae-Grant A, Fox R, Bethoux F. Multiple Sclerosis and Related Disorders: Diagnosis, Medical Management, and Rehabilitation. Demos Medical Publishing; 2013. 179-86.
Balak D, Hajdarbegovic E. PML in Patients Treated with Dimethyl Fumarate. N Engl J Med. 2015 Aug 6. 373 (6):582-3. [Medline].
Prasad S, Galetta SL. Eye movement abnormalities in multiple sclerosis. Neurol Clin. 2010 Aug. 28(3):641-55. [Medline].
Straube A, Bronstein A, Straumann D. Nystagmus and Oscillopsia. Gilhus NE, Barnes MP, Brainin M. European Handbook of Neurological Management. 2nd ed. Blackwell Publishing Ltd; 2011. Vol. 1:
Brazis PW. Isolated palsies of cranial nerves III, IV, and VI. Semin Neurol. 2009 Feb. 29 (1):14-28. [Medline].
Kirkpatrick C. Facial Colliculus Syndrome. The University of Iowa Health Care: Ophthalmology and Visual Sciences. Available at http://webeye.ophth.uiowa.edu/eyeforum/atlas/pages/facial-colliculus-syn/index.htm.
Available at http://mastersofmedicine.com/midbrain-and-pontine-syndromes/. Accessed: July 28, 2016.
Wong AM. Understanding skew deviation and a new clinical test to differentiate it from trochlear nerve palsy. J AAPOS. 2010 Feb. 14(1):61-7. [Medline].
Frohman TC, Galetta S, Fox R, Solomon D, Straumann D, Filippi M, et al. Pearls & Oy-sters: The medial longitudinal fasciculus in ocular motor physiology. Neurology. 2008 Apr 22. 70(17):e57-67. [Medline].
Kim JS, Jeong SH, Oh YM, Yang YS, Kim SY. Teaching NeuroImage: Wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) from midbrain infarction. Neurology. 2008 Feb 19. 70 (8):e35. [Medline].
Walsh RD, McClelland CM, Galetta SL. The Neuro-ophthalmology of Multiple Sclerosis. Future Neurology. 2012. 7(6):679-700. [Full Text].
Rodriguez AR, Egan RA, Barton JJ. Pearls & Oy-sters: paroxysmal ocular tilt reaction. Neurology. 2009 Apr 14. 72(15):e67-8. [Medline].
Han BI, Song HS, Kim JS. Vestibular rehabilitation therapy: review of indications, mechanisms, and key exercises. J Clin Neurol. 2011 Dec. 7 (4):184-96. [Medline].
National MS Society. Disease-Modifying Therapies for MS. National MS Society. Available at http://www.nationalmssociety.org/NationalMSSociety/media/MSNationalFiles/Brochures/Brochure-The-MS-Disease-Modifying-Medications.pdf. July 2016; Accessed: July 28, 2016.

Media Gallery

Magnetic resonance imaging (MRI) scan of the head of a 35-year-old man relapsing-remitting multiple sclerosis. MRI reveals multiple lesions with high T2-signal intensity and 1 large white matter lesion. In some cases, these demyelinating lesions mimic brain tumors because of the associated edema and inflammation.
Normal-appearing right optic nerve and mild left optic disc edema.
The evolution of temporal optic disc pallor (arrow) after left optic neuritis.
Cranial MRI study showing typical white matter lesions (arrows).
Optical coherence tomography (OCT) and fluorescein angiography (FA) showing cystoid macular edema in fingolimod-associated macular edema (FAME).
Examining for internuclear ophthalmoplegia (INO) (1 of 5).
Examining for internuclear ophthalmoplegia (INO) (2 of 5).
Examining for internuclear ophthalmoplegia (INO) (3 of 5).
Examining for internuclear ophthalmoplegia (INO) (4 of 5).
Examining for internuclear ophthalmoplegia (INO) (5 of 5).

of 10

Author

Fiona Costello, MD, FRCP Associate Professor, Department of Clinical Neurosciences, Neuro-opthalmologist, Clinical Neurologist and Clinical Investigator, Hotchkiss Brain Institute, University of Calgary Faculty of Medicine, Canada

Fiona Costello, MD, FRCP is a member of the following medical societies: Alberta Medical Association, American Academy of Neurology, American Academy of Ophthalmology, American Medical Association, Canadian Medical Protective Association, College of Physicians and Surgeons of Alberta, North American Neuro-Ophthalmology Society, Ontario Medical Association, Royal College of Physicians and Surgeons of Canada

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Clene; Prime; EMD Serono.

Coauthor(s)

J M Burton, MD, MSc, FRCPC Assistant Clinical Professor, Departments of Clinical Neurosciences and Community Health Sciences, University of Calgary Faculty of Medicine, Canada

Disclosure: Received honoraria from Novartis for speaking and teaching; Received honoraria from TEVA Neuroscience for speaking and teaching.

Andrew G Lee, MD Chair, Department of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital; Clinical Professor, Associate Program Director, Department of Ophthalmology and Visual Sciences, University of Texas Medical Branch School of Medicine; Clinical Professor, Department of Surgery, Division of Head and Neck Surgery, University of Texas MD Anderson Cancer Center; Professor of Ophthalmology, Neurology, and Neurological Surgery, Weill Medical College of Cornell University; Clinical Associate Professor, University of Buffalo, State University of New York School of Medicine

Andrew G Lee, MD is a member of the following medical societies: American Academy of Ophthalmology, American Geriatrics Society, Houston Neurological Society, Houston Ophthalmological Society, International Council of Ophthalmology, North American Neuro-Ophthalmology Society, Texas Ophthalmological Association

Disclosure: Received ownership interest from Credential Protection for other.

Chief Editor

Hampton Roy, Sr, MD Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Hampton Roy, Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.

Acknowledgements

Cecil L Berlie, MD, Consulting Staff, Department of Ophthalmology, Luther Midelfort Eye Clinic

Disclosure: Nothing to disclose.

Andrew W Lawton, MD Medical Director of Neuro-Ophthalmology Service, Section of Ophthalmology, Baptist Eye Center, Baptist Health Medical Center

Andrew W Lawton, MD is a member of the following medical societies: American Academy of Ophthalmology, Arkansas Medical Society, and Southern Medical Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Reference Salary Employment

Brian R Younge, MD Professor of Ophthalmology, Mayo Clinic School of Medicine

Brian R Younge, MD is a member of the following medical societies: American Medical Association, American Ophthalmological Society, and North American Neuro-Ophthalmology Society

Disclosure: Nothing to disclose.

What are the variants of internuclear ophthalmoplegia (INO) in multiple sclerosis (MS)?

Answer

Related Questions:

References

Tables

Contributor Information and Disclosures