1. Clinical Case Challenges In Neuro-Optometry III Thomas J. Landgraf, O.D., F.A.A.O.

2. Before We Get Started…..  On our LAST hour together  Foundations & Support Groups  Myasthenia Gravis  Multiple Sclerosis

3. Case #6: Don’t Assume Anything  Or “The Case Of The Chronic Sixth Nerve Palsy”  70 yo male  Diplopia with isolated abduction deficit OS  Other eye movements intact  No other significant neuro-eye findings

4. Case #6: Don’t Assume Anything  Or “The Case Of The Chronic Sixth Nerve Palsy”  Most likely a case of ischemic sixth nerve palsy  Patient of vasculopathic age  Sixth nerve palsy is isolated  May follow the patient without neuro-imaging  Expectation of improvement or resolution in 8-12 weeks

5. Case #6: Don’t Assume Anything  Or “The Case Of The Chronic Sixth Nerve Palsy”  No expected recovery in 6-8 weeks upon re- exam  Refer to neurologist  MRI with gadolinium  DDx includes: a mass lesion  Pons, along the clivus, in the nasopharynx, at the base of the brain, in the cavernous sinus, in the orbit

6. Case #6: Don’t Assume Anything  Or “The Case Of The Chronic Sixth Nerve Palsy”  MRI with gadolinium  Large pontine mass consistent with glioma  A death sentence in a young person  Elderly, grows very slowly

7. Case #6: Don’t Assume Anything  Or “The Case Of The Chronic Sixth Nerve Palsy”  Neurosurgical consult  Monitor without intervention  Prismatic correction

8. CN VI Palsy  Background  Common cause of horizontal diplopia  Most commonly affected of the ocular motor nerves

9. CN VI Palsy  Background  Most emergent  Age 40 and under  If non-isolated  Think microvascular in elderly  If isolated, most patients recover fully and may not require referral

10. CN VI Palsy  Background: Anatomy  Longest subarachnoid course  Nucleus in the pons  Innervates the ipsilateral lateral rectus  T2-weighted MRI in a patient with a chronic CN VI palsy shows a left pontine glioma 

11. CN VI Palsy  Diagnosis: Who?  Any age  Variety of causes  Ischemia most common in adults  Elderly with DM and HTN

12. CN VI Palsy  Diagnosis: Who?  Variety of causes  Neoplasm  Mass lesion of CNS most common in children and young adults  MRI of large posterior fossa tumor associated with hydrocephalus and CN VI palsy in a 6 yo  Inflammation  Post-viral and ear infections in kids  Aneurysm  Trauma

13. CN VI Palsy  Diagnosis: Symptoms  Diplopia  Binocular or monocular?  Horizontal or vertical?  Pain, especially if growing lesion in the cavernous sinus  Additional neurologic signs  Depends on the etiology

14. CN VI Palsy  Diagnosis: Signs  Abduction deficit  Esotropia  Maximum on gaze to the side of the palsy  Head turn

15. CN VI Palsy  Diagnosis: additional signs dependent on etiology  Papilledema with nausea, vomiting, tinnitus, HA’s  Proptosis  Ptosis  Increased ESR with HA and jaw claudication  Retraction of globe and narrowing of lid fissure on attempted abduction

16. CN VI Palsy  Differential Diagnosis  Ischemia  Inflammation  Neoplasm  Aneurysm  Trauma

17. CN VI Palsy  Ancillary Tests: Optometric In-Office  Visual fields  Forced duction?

18. CN VI Palsy  Ancillary Tests: Referral  Indications for Neuro-Imaging  Emergent if age < 30 years  Head trauma  Pain  Non-isolated  Other etiologies besides microvascular, myasthenia gravis, thyroid, Giant Cell, congenital

19. CN VI Palsy  Ancillary Tests: Referral  Indications for Neuro-Imaging  Consult with neuro-eye doc or neurologist reassures:  “that level of comfort thing again”  Workup if microvascular: DM, HTN

20. CN VI Palsy  Management  Microvascular, trauma, idiopathic  Resolve spontaneously within 6 months  Comfort: patch, blur, block, Botox for temporary treatment  If need long-term: prism, surgery

21. CN VI Palsy  Management  Follow-up  CN VI  every 6 weeks over 6 months  If you expect improvement?  Neuro consult if no improvement

22. CN VI Palsy  My Clinical Experience  All isolated (majority) have been:  Elderly  Microvascular  If it all makes sense, I hold off on the “Neuro-massage”  All non-isolated:  Younger  Poor prognosis

23. Case #7: A Quickie  On-call Resident  Ptosis OD  Several months prior Ptosis OS  Seen by another resident  Don’t assume you are smarter than another resident  Documentation was correct  What is really going on?

24. Myasthenia Gravis  Background  Autoimmune Disease  Autoantibodies against acetylcholine receptors  Abnormal fatigueability of muscles under voluntary control  Usually orbital and facial muscles

25. Myastenia Gravis  Background  Prevalence: 1:20,000  But we see it!  Ocular involvement: 90%  Account for initial complaint in 75%

26. Myasthenia Gravis  Diagnosis: Who?  Females under 50 / 7:3  Males peak in late 50’s  Associated conditions: thymoma, thyroid disease, diabetes, lupus, rheumatoid

27. Myasthenia Gravis  Diagnosis: Symptoms  Majority present with ocular symptoms  Ptosis: asymmetric  Diplopia: any motility defect  And spread  Variability of ocular fatigue  Worse at the end of the day  Hx, Hx, Hx!

28. Myasthenia Gravis  Diagnosis: Symptoms  Non-Ocular  Within two years of ocular  Limb fatigue  Facial muscle weakness  Difficulty breathing, chewing, talking, swallowing

29. Myasthenia Gravis  Diagnosis: Signs  Ptosis & EOM involvement  Cogan’s lid twitch  Exposure keratitis  Ophthalmoplegia  Orbicularis oculi weakness

30. Myasthenia Gravis  Differential Diagnosis  Pupils are never affected  No eye pain  Thyroid ophthalmopathy,  INO (Internuclear Ophthalmoplegia), orbital pseudotumor, botulism, myotonic dystrophy, Chronic Progressive External Ophthalmoplegia

31. Myasthenia Gravis  Ancillary Tests: Optometric In-Office  Measure palpebral apertures  Pupil center to upper lid margin  Sustained up gaze  Squeezing of eyelids closed  Initial VF

32. Myasthenia Gravis  Ancillary Tests: Optometric In- Office  Ice Pack Test  5 minutes  Improves neuromuscular transmission  ptosis  Safe, speedy, easy and with relatively high sensitivity and specificity  Sleep Test: eyes closed for 30 minutes  FAT (Family Album Topography) Scan

33. Myasthenia Gravis  Ancillary Tests: Referral  Tensilon (Endrophonium HCL) Test  IV 10 mg of Tensilon  Why refer in Tennessee?  Rate of complications low but life-threatening  Hypotension, bradycardia, cardiac arrest, respiratory arrest, seizures, vomiting  Improves eyelid / motility defect  Anticholinesterase

34. Myasthenia Gravis  Ancillary Tests: Referral  EMG (Electomyography)  Acetylcholine antibody receptor test

35. Myasthenia Gravis  Management  Referral  Neurologist, neuro-eye doc  Internist or PCP  Lab testing for associated conditions  CT scan of chest / mediastinum for thymoma

36. Myasthenia Gravis  Management: Medical  Anticholinesterases, steroids, immunosuppressants  Thymectomy  Plasmapharesis  IV gammaglobulin

37. Myasthenia Gravis  Management: Optometric  Lid crutches, tape  Occlusion  Rarely prism, ptosis or strabismus surgery  Follow-up as needed post-diagnosis  Monitor for steroid side effects

38. Myasthenia Gravis  My Clinical Experience  Am I missing this?  Teaching about it may help…..

39. Case #8: OK To Not Refer?  History  2006 68 yo Caucasian female  My patient since 1997  “my glaucoma drops are too expensive”  Alphagan-P bid OU  H/O thinner that normal pachymetry OU  H/O highest tonometry 20 mm Hg OU

40. Case #8: OK To Not Refer?  History: Of interest to us today…..  1997: first visit  Referred for pupil and glaucoma work-up  Anisicoria noted over 10 years ago

41. Case #8: OK To Not Refer?  History  HTN, hypercholesterolemia  H/O bypass  Hyzarr, Metiprolol, Lipitor, Aspirin, Lyrica, vitamins  No wonder the glc drop is too expensive  POAG, Horner’s Syndrome, ERM

42. Case #8: OK To Not Refer?  Exam  BVA: 20/25+, 20/25+  Pupils: anisocora  Dim illumination: 4, 6 mm  Bright illumination: 3, 4 mm  Ptosis: 1 mm upper lid OD  EOM’s: FROM  Confrontation fields: FTFC OU

43. Case #8: OK To Not Refer?  Exam  SLX: essentially normal OU, mild NS OU  T(a): 16, 15  DFE .7/.7 OD,.6/.6 OS  Macular pigmentary changes  periphery clear OU  Yearly HRT, VF

44. Case #8: OK To Not Refer  Latest VF OD

45. Case #8: OK To Not Refer  Latest VF OS

46. Case #8: OK To Not Refer  Latest HRT OD

47. Case #8: OK To Not Refer  Latest HRT OS

48. Case #8: OK To Not Refer?  Assessment  1. POAG OU  Stable HRT, VF, ONH appearance, IOP  Alphagan-P too expensive  2. H/O Horner’s Syndrome OD  Benign and stable  3. Macular pigmentary changes

49. Case #8: OK To Not Refer?  Plan:  1. Switch Alphagan-P to Brimonidine, RTC 1 month IOP check, Education potential side effects of Brimonidine  2,3. To monitor

50. Case #8: OK To Not Refer?  After preparing this lecture  Looked way back in the record again  10/5/83: “Anisocoria noted 1-2 years ago; neuro- opthalmology work-up with no known causes”  I never got the cocaine in ‘97  Good idea eventually:  Iopidine  Paredrine or Pholedrine

51. Horner’s Syndrome  Background  1852: Claude Bernard first noted experimentally  1869: Swiss ophthalmologist Johann Friedrich Horner noted  Should be called?  Bernard’s Syndrome  Bernard-Horner’s Syndrome

52. Horner’s Syndrome  Background: Sympathetic Anatomy of Eye & Face  First order sympathetic neuron  Begins in ipsilateral hypothalamus  Descends through midbrain, pons, and medulla  Ends at ciliospinal center of Budge at levels of C8-T1 in the spinal cord

53. Horner’s Syndrome  Background: Sympathetic Anatomy of Eye & Face  Second order pre- ganglionic fibers  Leave the ciliospinal center of Budge  Pass the pulmonary apex  Travel up along carotid artery sheath  End in superior cervical ganglion near bifurcation of common carotid

54. Horner’s Syndrome  Background: Sympathetic Anatomy of Eye & Face  Third order post-ganglionic neuron  Travels along internal carotid artery to the cavernous sinus  Leave the internal carotid, travel with the abducens and join the ophthalmic division of the trigeminal  Enter the orbit with the naso-ciliary branch

55. Horner’s Syndrome  Background: Sympathetic Anatomy of Eye & Face  In the orbit, the sympathetic fibers pass through the ciliary ganglion  Join the two long ciliary branches of the nasociliary nerve and innervate the iris dilator muscle  Other sympathetic branches travel with branches of the ophthalmic artery to innervate the lacrimal gland, Muller’s muscles, and orbital vessels  Sympathetic fibers controlling facial sweating travel with the external carotid artery

56. Horner’s Syndrome  Why?  Dysfunction of the sympathetic innervation to eye and parts of face  Interruption of oculosympathetic nerve supply somewhere between hypothalamus and the eye

57. Horner’s Syndrome  Diagnosis: Who?  No predilection  Age, race, gender, geographics  Congenital  Presents by age two with heterochromia

58. Horner’s Syndrome  Diagnosis: Signs  Ptosis  Mullers muscle  1-2 mm upper eyelid  Reverse ptosis  Slight elevation lower eyelid  Miosis  iris dilator muscle

59. Horner’s Syndrome  Diagnosis: Signs  Anisicoria > darkness  Dilator iris muscle normally more active  Dilation lag: prolonged redilation of the pupil after dimming the light  Hypochromia Iridis: typical if congenital  Anhidrosis

60. Horner’s Syndrome  Differential Diagnosis: not limited to…..  Pre-Ganglionic ( First and Second- Order)  LESS COMMON BUT MORE OMINOUS  Pancoast Tumor  Tuberculosis  Aortic dissection  Internal carotid artery dissection   MRA (MR angiography)  Trauma  Stroke, syphilis, tumor, MS, lymphadenopathy

61. Horner’s Syndrome  Differential Diagnosis  Post-Ganglionic (Third-Order)  Aneurysm  Atherosclerosis  Herpes Zoster  Trauma  Sinusitis  Painful Horner’s  Carotid dissection until proven othewise

62. Horner’s Syndrome  Differential Diagnosis  Vs Third Nerve Palsy  Ptosis  Anisicoria exaggerated in dim illumination  Horner’s

63. Horner’s Syndrome  Ancillary Tests: Optometric In-Office?  Pupil Testing 1: Horner’s?  Cocaine blocks reuptake of norepinephrine at the sympathetic nerve endings  Dilates normal eye after an hour  No dilation in Horner’s due to lack of norepinephrine at nerve endings  Availability of cocaine 10% solution?

64. Horner’s Syndrome  Ancillary Tests: Optometric In-Office  Pupil Testing 1: Horner’s?  Alternative: Iopidine (Apraclonidine)  Weak, direct action on alpha-1 receptors  Normal: no dilation  Horner’s: dennervation supersensitivity to norepinephrine  increase in alpha-1 receptors in iris stroma  dilation

65. Horner’s Syndrome  Ancillary Tests: Optometric In-Office  Pupil Testing 2: pre- or post- ganglionic?  Paredrine 1% (Hydroxyamphetamine) releases norepinephrine from stores in nerve endings  Mydriasis in a normal pupil  No mydriasis in a post- ganglionic Horner’s due to destroyed nerve endings  “Fail-safe”?  Postive Paredrine Test  OD did not dilate

66. Horner’s Syndrome  Ancillary Tests: Optometric In-Office  Pupil Testing 2: pre- or post-ganglionic?  Alternative: Pholedrine 5%  With third neuron damage  Horner’s pupil will not dilate  Post-ganglionic lesion  If dilates 

67. Horner’s Syndrome  Management: Referral unless congenital  Neurologist, Neuro-Eye Doc  PCP, Internist  Cardiologist, Oncologist, Vascular Surgeon  No treatment to improve or reverse the condition

68. Horner’s Syndrome  My Clinical Experience  Some pharmacist in Memphis is upset with me!  Glad we have Iopidine now