Back to Basics: Diplopia Michael Dollin PGY2 University of Ottawa Eye Institute University of Ottawa Meds Year 4 LMCC review course April 2, 2009

Outline What is diplopia? Important questions to ask Important causes of diplopia Monocular Binocular Investigations Management Summary

What is diplopia? Double vision

Important questions Does the diplopia resolve when 1 eye is covered? (i.e. monocular vs. binocular) Is it the same in all fields gaze (comitant) or does it vary with gaze direction (incomitant)? Is it horizontal, vertical, or oblique? Is it constant, intermittent, or variable?

Causes of diplopia Monocular causes Binocular causes Start with question #1: Does the diplopia resolve when 1 eye (either eye) is covered? (If not, the diplopia is monocular)

Monocular causes (1) Abnormalities of the refractive media High astigmatism Corneal irregularity (e.g. scar, k’conus) Lens opacities (e.g. cataract) (2) Retinal pathology Maculopathy (fluid, Hgb, fibrosis) The diplopia will persist when the unaffected eye is covered, but resolve when the affected eye is covered

Binocular diplopia will resolve by covering either eye Binocular causes Binocular diplopia will resolve by covering either eye Now question #2: Is the diplopia the same in all fields gaze (comitant) or does it vary with gaze direction (incomitant)?

Comitant deviations Characteristic of congenital or early-onset strabismus Typically do not cause diplopia although diplopia may develop later in life e.g. patient with long-standing exophoria whose accommodation and convergence capacities wane in 5th decade of life Divergence insufficiency Manifests as esodeviation greater at distance than at near; comitant in right and left gaze Benign syndrome, resolves spontaneously Rule out incipient or resolving U/L CN6 palsy or highly symmetric B/L CN6 palsy (consider MRI)

Incomitant deviations More likely acquired and usually cause diplopia Think of… Paretic etiologies Neural (CN 3, 4, and 6 palsies) Neuromuscular junction (MG) Restrictive etiologies Trapped or fibrotic EOM

Incomitant deviations Approach to these etiologies… Question #3: Is it horizontal, vertical, or oblique? Tells you which extra-ocular muscle(s) might be involved Question #4: Is it constant, intermittent, or variable? Constant: paretic (neural) or restricted Intermittent, variable: paretic (neuromuscular; MG)

Way back to basics! Let’s review the actions and innervations of the extra-ocular muscles (EOM)

EOM “LR6SO4” 4 rectus muscles 2 oblique muscles Innervation: Lateral (LR), Medial (MR), Superior (SR), Inferior (IR) 2 oblique muscles Superior (SO), Inferior (IO) Innervation: CN3  SR (+ levator), MR, IR, IO CN4  SO CN6  LR “LR6SO4”

AAO, Neuro-Ophthalmology EOM 10 action 20 action 30 action LR MR SR IR SO IO ABduction ADduction Elevation Depression Intorsion Extorsion None

Back to incomitant deviations…

Neural (paretic) causes Oculomotor nerve palsies CN3 (Oculomotor) CN4 (Trochlear) CN6 (Abducens) Internuclear ophthalmoplegia (INO)

AAO, Neuro-Ophthalmology

CN3 palsy Exits ventrally from midbrain Motor innervation to levator, SR, IR, MR, IO Parasympathetic innervation to pupillary sphincter (constrictor) and ciliary muscles Reference 3

Causes of 3rd nerve palsy Ischemic (DM, HTN) – most common Brain stem lesion (infarct, MS) Compression (P comm aneurysm, uncus) Tumour Inflammation (Sarcoid, vasculitis) Infection (meningitis) Infiltration (lymphoma, carcinoma) Trauma

AAO, Neuro-Ophthalmology Complete 3rd nerve palsy Severe ptosis Eye positioned “down and out” Dilated pupil that responds poorly to light Partial 3rd nerve palsy Mild or moderate limitation AAO, Neuro-Ophthalmology

Always check pupils! “Pupil-involving” Dilated pupil that responds poorly to light Due to loss of parasympathetic input These fibers travel along the medial superficial surface of CN3 Susceptible to direct compression by an aneurysm of the posterior communicating artery (P comm) Assumed to be secondary to an aneurysm until proven otherwise  must image Gold standard is catheter angiography CTA or MRA can reliably detect 2-3 mm aneurysms

AAO, Neuro-Ophthalmology

Always check pupils! “Pupil-sparing” Normal pupillary function but complete loss of lid and ocular motor function Almost always ischemic (DM) May be painful Resolves within 3 months (if not  image) If partial w/o pupillary involvement or young and no ischemic risk factors  follow closely (may evolve) Older patients  consider GCA

CN4 palsy Crosses in the brainstem Exits dorsally Nucleus innervates contralateral SO Exits dorsally Longest intracranial course Reference 3

Palsy typically causes diplopia that is worse in downgaze “Double vision is worse while reading” Motility testing often appears normal Identify using Parks-Bielchowsky 3-step test Look for: ipsilateral hypertropia and compensatory contralateral head tilt

Left 4th nerve palsy

Causes of 4th nerve palsy Congenital Asymptomatic until 40-60yo (↓ fusional amplitudes) Chronic head tilt – check old photographs Ischemic Patients older than 50yo with ischemic risk factors Expect resolution within 3 months Trauma MS, tumour, hydrocephalus, aneurysm Idiopathic Consider Graves and Myasthenia

Investigations Neuroimaging Medical work-up Usually of little diagnostic value Lack of recovery after 3 months  MRI Medical work-up Patients in vasculopathic age group BP, fasting BG, lipid profile

CN6 palsy Exits brainstem at ponto-medullary junction Travels ventrally up the clivus Crosses over the apex of the petrous bone Enters the cavernous sinus Reference 3

AAO, Neuro-Ophthalmology Typically presents as horizontal diplopia that worsens on ipsilateral gaze and when viewing at a distance Patient appears esodeviated AAO, Neuro-Ophthalmology

Causes of 6th nerve palsy Ischemic – most common Patients older than 50yo with ischemic risk factors Expect resolution within 3 months CPA tumours (e.g. acoustic neuroma) CN 5, 6, 7, and 8 usually also affected Trauma Raised intracranial pressure Gradenigo syndrome (mastoiditis) Consider leukemia or brain stem glioma (children) Consider MS (adolescents and young adults)

Investigations Adults > 50yo Patients < 50yo Medical work-up (BP, fasting BG, lipid profile) Lack of recovery after 3 months  MRI Patients < 50yo Rarely ischemic  must image (MRI/FLAIR) Consider LP, Tensilon test

INO Secondary to brainstem lesion of the medial longitudinal fasciculus (MLF) Bundle of fibers connecting 6th nerve nucleus on one side to the MR (3rd nerve) subnucleus on the opposite side

AAO, Neuro-Ophthalmology Cardinal feature: slowed ADducting saccadic velocity in eye ipsilateral to lesion INO = Insufficient Nasal Output Associated ABducting nystagmus of contralateral eye Most common causes: Adults: MS, brain stem stroke Children: post-viral, brain stem tumour Myasthenia gravis: pseudo-INO AAO, Neuro-Ophthalmology

Neuromuscular (paretic) causes Problem at the neuromuscular junction (e.g. Myasthenia Gravis) www.colorado.edu

Myasthenia Gravis Immunologic disorder characterized by weakness which worsens with use (end of day) and improves with rest Pathophysiology: anti-acetylcholine receptor antibodies Hallmark features: fluctuation and fatiguability Common clinical presentation: Ptosis (worsens with sustained upgaze) Diplopia (especially changing pattern of diplopia) Cogan eyelid twitch Pseudo-INO Absence of pupil or sensory abnormalities

Why is this diagnosis important to make? Systemic involvement: Dyspnea, dysphagia  life-threatening! Muscle weakness (masticators, extensors) Hoarseness Dysarthria

Diagnosing MG Clinical exam Tensilon test Edrophonium chloride (Ach-esterase inhibitor) Document baseline deficit (e.g. ptosis) 2 mg test dose (observe 60 sec) 4 mg  4 mg Positive response dramatic if deficit was severe Potential side effects: bradycardia, respiratory arrest, bronchospasm, syncope, cholinergic crisis Pulse and BP monitoring; Atropine and crash cart ready Alternatives: sleep test, ice test

Other diagnostic tests: Serology: Anti-Ach receptor antibodies Anti-muscle specific kinase Test for thyroid dysfunction (5%) and Lupus Single fiber EMG: decremental response CT chest: malignant thymoma (10%) Treatment: Mestinon (Pyridostigmine) +/- Thymectomy

Restrictive causes Most common causes: Thyroid-Associated Orbitopathy (Graves) Orbital trauma (blow-out fracture) Other causes: Orbital inflammation (myositis) Orbital infection (orbital cellulitis) Orbital tumour (EOM infiltration or metastases)

Thyroid-Associated Orbitopathy (Graves’ disease) Autoimmune inflammatory disorder Usually hyperthyroid (can be euthyroid) Eye disease does not necessarily parallel thyroid gland activity Clinical signs: Eyelid retraction Lid lag Proptosis (exophthalmos) Restrictive EOM ( diplopia) Compressive optic neuropathy

Orbital wall (blow-out) fracture Typically orbital floor or medial wall Mechanism: blunt trauma Diplopia 20 EOM or fascia entrapment

Check motility (esp. up and lateral gaze) Other signs: Enophthalmos (affected eye sunken in) V2 numbness (over cheek bone) Subcutaneous emphysema

Summary Remember the 4 questions Determine onset and course Check pupils in CN3 palsy Pupil-involving needs imaging (CTA or MRI) Other indications for imaging Non-resolving (presumed ischemic) CN palsy Younger patients (< 50yo) Value of a Tensilon test in MG In older patients, consider GCA (ESR, CRP)

References AAO BCSC 2007-2008 Section 5, Neuro-Ophthalmology. Kanski JJ. Clinical Ophthalmology: A Systematic Approach, 6th ed. Philadelphia, PA: Elsevier Limited; 2007. Patel V. Efferent Neuroanatomy. Neuro-Ophthalmology teaching block, 2009, University of Ottawa Eye Institute. www.colorado.edu (March 17, 2009)

Thank you Any questions?

Good luck on the exam! (Enjoy your summer)