Neuromuscular Disorders

1. Neuromuscular Disorders Ping-Wei Chen PGY – 2 Emergency Medicine Resident April 8, 2010 Thanks: Dr. Walker, Dr. Burton-MacLeod, Dr. Oster, Dr. Brownell

2. Weakness • Non-Neuromuscular • Cardiovascular • Respiratory • Infectious • Metabolic • Endocrine • Toxicologic • Neuromuscular • Brain • Spinal Cord • Anterior Horn Cell • Peripheral Nerve • Neuromuscular Junction • Muscle

3. Localizing the Lesion: UMN vs LMN • Upper motor neuron • Unilateral symptoms • If bilateral symptoms, associated • Altered mental status • Cranial nerve abnormalities • If bilateral symptoms and normal mental status • THINK spinal cord

4. Localizing the Lesion: UMN vs LMN

5. Myelopathy • Pathology of the spinal cord • Clinically: • UMN signs • Ascending weakness • Bowel/Bladder involvement • Sensory involvement (define level)

6. Anterior Horn Cell • UMN synapses with LMN here • Clinically: • Both UMN/LMN signs • Little/No sensory involvement • Bulbar symptoms (ALS) • Speech • Swallowing • Chewing

7. Neuropathy • Peripheral nerve pathology • Clinically: • LMN signs • Distal to proximal involvement • “glove and stocking” pattern • Varied sensory involvement

8. Neuromuscular Junction • Connection between CNS and muscles • Clinically: • Variable presentations of weakness • Fatigability • Proximal • Ascending vs Descending • No sensory involvement

9. Myopathy • Muscle pathology • Clinically: • LMN signs • Proximal > Distal • ±muscle tenderness

10. Case • 65M with weakness. • 2x visits to GP in last 3 months for same. • Notices: • sometimes chokes on food • Blurry vision when tired • Generalized fatigue • “Enough is enough” • O/E: • Normal PERL • Rapid neurological exam otherwise normal. • Any thoughts?

11. Myasthenia Gravis • RARE • Rarely diagnosed in ED • Bi-modal age of onset • Women 20-40 • Men 50-70

12. Neuromuscular Junction

13. Myasthenia Gravis • Autoantibodies against Nicotinic ACh receptors • Decreased number of post-synaptic ACh receptors • Compete for binding on ACh receptors with ACh

14. Myasthenia Gravis • Clinically: • Fatigability of voluntary muscles • BEWARE – respiratory muscles • Ocular symptoms first • Ptosis, diplopia, blurred vision • Normal sensation • No pain

15. Myasthenia Gravis • Diagnosis • Clinical + Further Testing • Edrophonium/Ice Bag Test • Anti-ACh Receptor Antibody • Muscle Specific Receptor Tyrosine Kinase Antibody • Electrophysiologic Tests

16. Myasthenic Crisis • MG + Respiratory failure requiring intubation • 15%-20% MG patients • Precipitants • Infection (most common) • Medication changes • Surgery • Pregnancy/Childbirth • Unidentified (30%)

17. Back to our patient • When to intubate? • Caution:Don’t rely on work of breathing! • Spirometry • FVC ≤ 1L = intubate • Rate of decrease in FVC • “sooner rather than later”

18. Cholinergic Crisis • Excessive anticholinesterase medication • Too much Acetylcholine Acetylcholine Succinylcholine

19. Myasthenic VS Cholinergic Crisis • May be difficult to differentiate • Response to Edrophonium/Ice Bag Test • Presence of muscarinic symptoms • Cholinergic crisis rare unless >> dose ingested • ie: pyridostigmine >120mg every 3 hours • Assume weakness 2o worsening MG

20. Edrophonium/Tensilon Test • Edrophonium • 135mg IV • Response 30-90s? • Adverse effect? • Max dose 10mg IV • Caution • Asthmatics/COPD • Atropine at bedside!! • Measure distance between upper and lower eyelid in most affected eye

21. Ice Bag Test • Apply ice to most affected eye X 2 mins • Measure distance between upper and lower eyelid in most affected eye

22. Myasthenia Gravis • Management • Emergency Department • Identify • Supportive • Early intubation for respiratory failure • Neurology/ICU • Anti-cholinesterase Medications • Pyridostigmine • Immunomodulation • Plasmapheresis, IVIG • Glucocorticoids, Azathioprine, MycophenolateMofetil, Cyclosporine • Thymectomy

23. Clinical Pearls • Do spirometry! • Insidious respiratory failure • FVC ≤1L = ICU consult, FVC≤500cc • Sick Myasthenia Gravis patient? • *Continue acetylcholinesterase inhibitor meds* • Admitting Myasthenia Gravis patient? • Neurology consult

24. Case • 62M with known small cell lung Ca • Generalized leg weakness • Difficulty climbing stairs • Could this be Lambert-Eaton Syndrome?

25. Lambert-Eaton Syndrome • RARE • Strong association with neoplasm (SCLC) • Auto-antibodies to Voltage Gated Ca channels • Decreased release of ACh from pre-synaptic terminal

26. Lambert-Eaton Syndrome • Clinically: • Proximal muscle weakness (<MG) ± soreness • Autonomic dysfunction (anti-cholinergic) • Variable bulbar involvement • Differentiation from MG • Weakness improves with use of muscle • Autonomic involvement

27. Case • 41yo male with nausea and diarrhea X 24 hrs • “really weak” • Difficulty holding head up for long periods • Arms weak • Blurred vision, dry mouth • ? “food poisoning” • moloha • Any thoughts?

28. Botulism • Clostridium botulinum • Obligate anaerobe • Spore forming • Toxin producing • Mechanism of Action • Irreversible binding to presynaptic membrane of peripheral and cranial nerves • inhibiting ACh release • Disperses widely via vascular system regardless of portal of entry

29. Botulism • Clinical Entities • Food-borne • Infantile • Wound • Adult Enteric Infectious Botulism/Adult Infectious Botulism of Unknown Source • Inhalational

30. Botulism • Clinically: • Both voluntary and autonomic involvement • Symptom onset 6-48hrs post-ingestion of toxin • Descending, symmetrical paralysis • ±GI tract symptoms (N/V/D, abdo cramps, constipation) • ±Anti-cholinergic symptoms • Pupils dilated and non-reactive to light* • No sensory involvement • No pain • No fever *differentiates from myasthenia gravis

31. Infantile Botulism • Clinically: • Constipation • Weak Cry • Feeding difficulties/Anorexia • Descending/Global Hypotonia • Lethargy

32. Botulism • Diagnosis • Clinical Diagnosis (exclude other pathology) • Home canned foods, contaminated aquatic products, honey (infants) • Vegetables • Centre for Disease Control and Prevention 1998 • Suspect in • Adult with acute onset dysfunction of • GI tract • Autonomic nervous system (anticholinergic symptoms) • Cranial nerve dysfunction • Infant with acute onset of • Poor feeding • Diminished crying ability • Weakness • Respiratory distress

33. Botulism • Diagnosis • Laboratory tests rarely helpful in initial management • Toxin/Spore Analysis • Serum, Stool, Vomitus, Food • Wound Cultures

34. Management • Supportive Care • Early intubation for respiratory failure • Equine Trivalent Anti-toxin • >1 year old • Decrease mortality, disease duration (if given early) • Unclear effect on ventilator dependence • Side effects: serum sickness, anaphylaxis • Human Botulism Immune Globulin (BIG-IV) • <1 year old • Antibiotics in Wound Botulism • Penicillin G or Metronidazole (allergy)

35. Case • 9yo male • 1 day history of: • Tripping when walking • Legs “feeling tight” • Seen by GP earlier; clinic note faxed • Neuro exam abnormalities • 4+/5 strength bilaterally in lower extremities • Sensation grossly normal • Able to ambulate but “clumsy” • Bloodwork normal • Go to ED if gets worse

36. Case • Now back: can’t walk or sit up independently • “A cold” 3 weeks ago • Otherwise healthy, IUTD • O/E: • Normal cranial nerves • No sensory level • Decreased DTRs

37. Video Exam

38. Case • Bloodwork unremarkable • Electrolytes normal • No increased WBC • Other investigations? • Any thoughts?

39. Guillain-Barre Syndrome • Most common cause of acute symmetrical weakness in developed countries • 1-2 per 100,000 worldwide • All ages affected • Peaks in young adults and elderly

40. Guillain-Barre Syndrome • Heterogeneous syndrome with several variant forms • Acute Inflammatory DemyelinatingPolyneuropathy • Miller-Fisher Syndrome • Acute Motor Axonal Neuropathy • Acute Sensorimotor Axonal Neuropathy • Autoimmune response to preceeding infection • Molecular mimicry • Campylobacter • HIV, EBV, CMV, H. influenza, E. coli

41. Guillain-Barre Syndrome • Clinically: • Progressive, relatively symmetric muscle weakness • Usually ascending, then generalized • Distal paresthesias • Decreased/Absent deep tendon reflexes • Dysautonomia • Variable involvement • Facial muscles • Bulbar muscles • Cranial Nerves • Investigations: • Increased protein in CSF; normal white cell count

42. Guillain-Barre Syndrome • Management • Emergency Department • Supportive • Early intubation for respiratory failure (15-30%) • Hemodynamic monitoring (autonomic dysfunction) • Neurology/ICU • Plasmapheresis • IVIG • No role for steroids

43. Tick Paralysis • Summer months • Tick Endemic Areas • Pacific Northwest (BC) • Rocky Mountains • Injection of ixovotoxin with tick feeding • Diminish release of ACh • Slow nerve conduction velocity • Clinically: • Early: restless, irritable, hand/feet paresthesia • 24-48hrs: • ascending, symmetrical, flaccid paralysis • ±cerebellar dysfunction

44. Tick Paralysis • Diagnosis: • Clinical; no diagnostic laboratory measure • Management: • Supportive Care • Early intubation for respiratory failure • Tick Removal

45. Case • 46yo woman with ALS • 5 days of productive cough (clear, now green) • Fever 38.9oC today • No GI/GU symptoms • O/E: • HNT – normal • CV – tachycardic (115bpm) • Resp – RR46, SCM use, crackles R lung field • Abdo – soft, nontender, no CVA tenderness • MSK – no rashes

46. Intubate?

47. Amyotrophic Lateral Sclerosis • 1-3 per 100,000 • Sporadic and Familial forms • Increasing incidence after 40yo; peaks 70-80yo • Clinically: • Progressive UMN/LMN symptoms (months/years) • Asymmetric weakness (distal to proximal) • No sensory findings

48. Amyotrophic Lateral Sclerosis • Management • Supportive Care • Advanced Directive? • Moss et al. Chest. 1996 • Case Series (n=75) • 72% ALS patients aware of disease progression to respiratory failure • 48% ALS patients learned this from MD • 42% ALS patients made decision re: long term ventilation prior to crisis

49. Questions?