2. Grand Rounds Presentation By Scott Belliston DO PGY2 10/12/12

3. Dysphagia Elderly. right handed male with PMH of HTN, HLD, aneurysm in stomach 3cm, and GERDwas transferred from OSH for further evaluation of dysphagia Hx of dysphagia 3 years ago improved after esophageal dilatation No pain with swallowing

4. Where? Corticobulbar Tracts – Motor strip – Medulla – Nuclei of Lower Cranial Nerves Esophagus C-Spine Neuromuscular Junction – Presynaptic – Postsynaptic

5. What? Stroke ischemic or hemorrhagic Intracerebral mass (tumor, abscess, lesion, aneurysm) Amyotrophic lateral sclerosis Myasthenia Gravis Lambert-Eaton Myasthenic syndrome Multiple sclerosis Parkinson’s disease Toxins/Drugs (Botulism, snake venom, anticholinergics, antimuscarinics, tetrodotoxin…) Foreign body internal or external compression

6. More history 3 years ago developed dysphagia was diagnosed with allergies to ragweed. GI procedure improved symptoms. One week before admission was eating and choked on a sandwich hasn’t been able to eat or drink since. GI doctor told him no stricture that he had ALS. OSH neurology workup – MRI brain no stroke, EMG of facial muscles and tongue negative. Acetylcholine receptor antibodies pending. Video swallow failed. Pt on TPN refusing PEG tube.

7. Labs Hbg 16.5 WBCs 7.4 Platelets 166 INR 1.1 UDS positive benzos Sodium 132 Potassium 3.8 Chloride 106 CO2 22 BUN 12 Creatinine 0.72 Glucose 85 HgbA1c 5.3 TSH 1.980 CPK 297

8. Exam General exam unremarkable Neuro exam Mental status alert and oriented x 4 Speech moderate to severe flaccid dysarthria and dysphonia Dysphagia to solids and liquids CN mild right eye ptosis, Obicularis oculi 3/5 Obicularis oris 2/5, unable to protrude tongue or place in cheek Motor Neck flexor 4/5 wrist flexors and hip flexors 4+/5

9. Edrophonium test Tensilon test (No longer available in US) – Edrophonium a short acting IV acetylcholinesterace inhibitor Risks/Side effects

10. Edrophonium Test (cont) Prior to injection After second dose of 5 mg

11. EMG/NCS

13. Other studies Acetylcholine receptor antibodies – Acetylcholine Binding AB 37.0, Acetylcholine Blocking AB 29, Acetylcholine Modulating AB 34 – 85% of MG MuSK antibodies not checked – 40-70% of AChR-Ab negative CT chest for thymoma negative – 10–15% have a thymoma

14. Myasthenia Gravis 10 to 125 of every 1 million people worldwide Bimodal distribution 2 nd and 3 rd decades (mainly women) and 6 th through 8 th decades (mainly men). Antibodies to the muscle type of nicotinic cholinergic receptors Increased incidence of RA, SLE, and polymyositis

15. Common Presenting Symptoms Occular symptoms Ptosis and or diplopia over 50% Bulbar symptoms Dysarthria, dysphagia and fatigable chewing about 15% Proximal limb weakness alone less than 5% May get other isolated muscle weakness but are much less common Myasthenia crisis is when the respiratory muscles are involved

16. Neuromuscular Junction

17. Physiology

18. Watch out for! Crisis! When to intubate? – VC < 20ml/kg or NIF <-30ccH2O – ABGs insensitive for respiratory weakness Drugs to avoid in MG – Antibiotics (aminoglycosides, erythromycin, and azithromycin) – Cardiac drugs (beta-blockers, procainamide, and quinidine) – Magnesium – Glucocorticoids

19. Treatment Symptomatic Anticholinesterace (Mestinon) Chronic immunomodulating Glucocorticoids Immunosuppression Rapid immunomodulating Plasmapheresis IV immune globulin Surgical Thymectomy (reduction in symptoms of 70% of pts without thymoma)

20. Questions

21. References Balzer, KM, PharmD, “Drug-Induced Dysphagia”, International Journal of MS Care, page 6, Volume 2 Issue 1, March 2000. (http://www.mscare.com/a003/page_06.htm)http://www.mscare.com/a003/page_06.htm Barohn, RJ, “Update on Myasthenia Gravis: Diagnosis, Measurement, and Treatment”, PowerPoint, Accessed October 07, 2012. Bird, SJ. Myasthenic Crisis. In: UpToDate, Dashe, JF (Ed), UpToDate, Waltham, MA, 2012. Brunton LL, Chabner BA, Knollmann BC: Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12 th Edition: www.accessmedicine.com National Institute of Mental Health, Electron micrograph of neuromuscular junction: http://commons.wikimedia.org/wiki/File:Electron_micrograph_of_neuromuscular_junction_(cross- section).jpg http://commons.wikimedia.org/wiki/File:Electron_micrograph_of_neuromuscular_junction_(cross- section).jpg Ropper AH, Samuels MA. Chapter 53. Myasthenia Gravis and Related Disorders of the Neuromuscular Junction. In: Ropper AH, Samuels MA, eds. Adams and Victor's Principles of Neurology. 9th ed. New York: McGraw-Hill; 2009. http://www.accessmedicine.com.proxy.kumc.edu:2048/content.aspx?aID=3642849. Accessed October 11, 2012. Taylor P. Chapter 10. Anticholinesterase Agents. In: Brunton LL, Chabner BA, Knollmann BC, eds. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 12th ed. New York: McGraw- Hill; 2011. http://www.accessmedicine.com.proxy.kumc.edu:2048/content.aspx?aID=16660859. Accessed October 11, 2012.