1. Grand Rounds Conference Jinghua Chen, MD, PhD University of Louisville Department of Ophthalmology and Visual Sciences July 17, 2015

2. History CC: Double vision for three days. HPI: 56 year old African American male presented to PCC with double vision for 3 days. Three days ago he woke up in the morning with right eye deviated to the right side. He denied vision change, numbness, weakness, tingling or speech problems. 56 year old African American male presented to PCC with double vision for 3 days. Three days ago he woke up in the morning with right eye deviated to the right side. He denied vision change, numbness, weakness, tingling or speech problems.

3. Past Medical History POH: None PMH: Hypertension, Type 2 diabetes on insulin Allergy: NKDA FH: Non contributory Medication: Aspirin 81 mg, amlodipine 10 mg, and Humalog 20 units with meals (? compliance) SH: Smokes 1 pack per day and drinks 6 packs of beer up to 3 times a week.

4. Exam ODOS ODOS BCVA: 20/20 20/20 Pupils: 4  34  3 No APD OU No APD OU IOP: 1311 EOM Limited adduction OD(-4) CVF:Full OU Anterior segment: Mild Cataract OU DFE: Normal OU

5. Eye Movement Exam Video

6. MRI DWI ADC

7. Assessment Assessment Impression: 56 year old African American male presented to PCC with double vision for 3 days. Exam shows adduction deficit in OD. Impression: 56 year old African American male presented to PCC with double vision for 3 days. Exam shows adduction deficit in OD. Differential Diagnosis of Causes: Differential Diagnosis of Causes: Stroke Stroke Demyelination Demyelination Other Other Trauma Trauma Infection Infection Tumor Tumor Hemorrhage Hemorrhage Vasculitis Vasculitis Diagnosis: Right internuclear ophthalmoplegia (INO) Diagnosis: Right internuclear ophthalmoplegia (INO)

8. Management The patient was admitted to Stroke Service The patient was admitted to Stroke Service Diagnosis: Right midbrain acute ischemic stroke Diagnosis: Right midbrain acute ischemic stroke in the posterior brainstem in the posterior brainstem CTA and TEE were negative CTA and TEE were negative Plavix and IV fluids were started in the ER. Plavix and IV fluids were started in the ER.

9. Follow up Visit after Two Weeks Patient states doing better. Patient states doing better. Improved adduction of OD (-2) and diplopia. Improved adduction of OD (-2) and diplopia. VA: 20/20 OU VA: 20/20 OU

10. Follow up Video

11. Internuclear Ophthalmoplegia Internuclear ophthalmoplegia (INO) is an eye movement disorder characterized by adduction impairment due to a lesion involving the medial longitudinal fasciculus (MLF).

12. History 1859 Foville’s landmark study of pontine gaze palsy 1859 Foville’s landmark study of pontine gaze palsy The CN VI nucleus- gaze center The CN VI nucleus- gaze center Yoked eye muscles Yoked eye muscles A crossed pathway connecting the pons and midbrain to coordinate horizontal gaze A crossed pathway connecting the pons and midbrain to coordinate horizontal gaze 1873 medial longitudinal fasciculus (MLF) was identified as the connecting pathway 1873 medial longitudinal fasciculus (MLF) was identified as the connecting pathway 1921 Lhermitte named INO 1921 Lhermitte named INO

13. The Third and Sixth Nucleus Ophthalmology 2 nd. 2004: 1324

14. Internuclear Ophthalmoplegia in 410 Patients Arch Neurol. 2005;62(5):714-717. doi:10.1001/archneur.62.5.714 Infarction 38% Multiple sclerosis 34% Unusual causes 28% Medications: Adalimumab-anti-TNFα

15. Internuclear Ophthalmoplegia in 410 Patients

16. Unilateral INO Decreased saccadic velocity in adducting eye Decreased saccadic velocity in adducting eye Abducting nystagmus of the fellow eye Abducting nystagmus of the fellow eye Convergence may be spared or disrupted Convergence may be spared or disrupted Skew deviation Skew deviation INO is named for the side of limited adduction INO is named for the side of limited adduction

17. Bilateral INO

18. One-and-a-Half Syndrome A horizontal gaze palsy and ipsilateral INO

19. Eight-and-a-Half Syndrome One and a half syndrome plus facial nerve palsy One and a half syndrome plus facial nerve palsy http://archneur.jamanetwork.com.echo.louisville. edu/article.aspx?articleid=2279877

20. Prognosis of Ischemic Internuclear Ophthalmoplegia. 78.8% demonstrated resolution of diplopia in primary position with an average time to resolution of 2.25 months. 78.8% demonstrated resolution of diplopia in primary position with an average time to resolution of 2.25 months. The presence of associated neurologic symptoms (vertigo, ataxia, dysarthria, facial palsy, pyramidal tract signs) correlated with a worse prognosis for resolution of diplopia. The presence of associated neurologic symptoms (vertigo, ataxia, dysarthria, facial palsy, pyramidal tract signs) correlated with a worse prognosis for resolution of diplopia. Ophthalmology.Ophthalmology. 2002 Sep;109(9):1676-8.

21. References BSCS 2014-2015 Book 5, Neuro-Ophthalmology: 209-211 BSCS 2014-2015 Book 5, Neuro-Ophthalmology: 209-211 James R. Keane. Internuclear Ophthalmoplegia: Unusual Causes in 114 of 410 Patients. Arch Neurol. 2005;62(5):714-717. James R. Keane. Internuclear Ophthalmoplegia: Unusual Causes in 114 of 410 Patients. Arch Neurol. 2005;62(5):714-717. Shanzer S Neuro-ophthalmology in 19th century Paris: pioneering work on conjugate gaze. In: Rose FC, ed. Neuroscience Across the Centuries. London, England: Smith-Gordon & Co Ltd; 1989:151-156 Shanzer S Neuro-ophthalmology in 19th century Paris: pioneering work on conjugate gaze. In: Rose FC, ed. Neuroscience Across the Centuries. London, England: Smith-Gordon & Co Ltd; 1989:151-156 Freeman W Paralysis of associated lateral movements of the eyes: a symptom of intrapontile lesion. Arch Neurol Psychiatry 1922;7454- 487 Freeman W Paralysis of associated lateral movements of the eyes: a symptom of intrapontile lesion. Arch Neurol Psychiatry 1922;7454- 487 Michael Strupp, Katharina Hüfner, etc. Central Oculomotor Disturbances and Nystagmus. Dtsch Arztebl Int. 2011 Mar; 108(12): 197–204. Michael Strupp, Katharina Hüfner, etc. Central Oculomotor Disturbances and Nystagmus. Dtsch Arztebl Int. 2011 Mar; 108(12): 197–204. Michael StruppKatharina Hüfner Michael StruppKatharina Hüfner Bocos-Portillo J, Ojeda JR, etc. Eight-and-a-Half Syndrome. JAMA Neurol. 2015 May 11. doi: 10.1001/jamaneurol.2015.0255. Bocos-Portillo J, Ojeda JR, etc. Eight-and-a-Half Syndrome. JAMA Neurol. 2015 May 11. doi: 10.1001/jamaneurol.2015.0255. Bocos-Portillo JOjeda JRJAMA Neurol. Bocos-Portillo JOjeda JRJAMA Neurol. Drury J, Hickman SJ. Internuclear ophthalmoplegia associated with anti-TNFα medication. Strabismus. 2015 Mar;23(1):30-2. Drury J, Hickman SJ. Internuclear ophthalmoplegia associated with anti-TNFα medication. Strabismus. 2015 Mar;23(1):30-2. Drury JHickman SJ Strabismus. Drury JHickman SJ Strabismus. Eggenberger E, Golnik K, etc. Prognosis of ischemic internuclear ophthalmoplegia. Ophthalmology. 2002 Sep;109(9):1676-8. Eggenberger E, Golnik K, etc. Prognosis of ischemic internuclear ophthalmoplegia. Ophthalmology. 2002 Sep;109(9):1676-8. Eggenberger EGolnik K Ophthalmology. Eggenberger EGolnik K Ophthalmology.