1. Morning Report
Palak Kachhadia
08/31/2017

2. Scenario
Patient is a 32 year female who comes into your clinic complaining of generalized weakness and right eyelid droop. Her symptoms started 5 days prior and have gotten progressively worse…..

3. What do you want to know?

4. History
PMH: HTN
SH: smokes 1 pack a day for the past 8 years. Drinks alcohol occasionally. Works as a secretary at a local family practitioner’s office.
FH: Has a history of RA on her mother’s side along with HTN, CAD and CVA
Medications: Hydrochlorothiazide, OCPs
Allergies: none
Filler slides, go through this quickly.

5. Physical Exam General? HEENT? CV? Respiratory? Abdomen? Skin?
Extremities?
Neurological?
General: Mild distress, increased work of breathing
HEENT: R eyelid droop noted. Pupils symettical , round and reactive to night.
CV: Normal S1 and S2. No murmurs noted.
Abdomen: Soft, nontender, non-distended.
Skin: No rashes, lesions or wounds.
Extremities: No edema or chronic venous stasis.
Neurological: 5/5 motor strength in the LE. UE have 4/5 strength bilaterally. No sensory deficits noted. Finger to nose normal. Heel to shin normal. Gait normal. Diplopia on extreme horizontal gaze to the left and right.
Differentials: Thyroid opthalmopathy
Oculopharngeal dystrophy
Mitochondrial myopathy
Intracranial mass lession
ALS (though it also has upper motor neuron deficits. Usually no ocular involvement)
Lambert – Eaton (also has autonomic dysfunction such as erectile dysfunction, BP problems – RNS causes improvement in symptoms)
Penicillamine (used for RA and Wilsons) causes increased in ach R antibodies that can cause MG)
What are your differentials?
What labs would you like to order?

6. MYASTHENIA GRAVIS

7. Epidemiology Incidence: 10-20 new cases/million individuals
Prevalence: /million
Increased recognition and survival
Bimodal:
2nd and 3rd decades: women
6th to 8th decades: men

8. Q1: What is the pathophysiology?
Antibody mediation dysfunction of post-synaptic transmission
Autoimmune antibodies on post-synaptic membrane leads to AChR cross-linking and internalization in the post-synaptic membrane
A) Anti-AChR (70-90%)
B) Anti-MuSK (5-8%)
C) Sero-negative to AChR and MuSK (5-25%)
Added animation.

9. Explain this slide verbally while presenting.

10. Q2: What are the most common Signs and Symptoms?
Muscular: fluctuating muscle weakness with repetitive movement, neck flexion and extension weakness, proximal limb weakness
Ocular: Ptosis, diplopia
Bulbar: dysarthria, dysphagia, chewing difficulty

11. Q3: How do you make the Diagnosis?
History taking + PE + Bedside/EP tests!
Bedside maneuvers: Ice pack test, Tensilon (edrophonium test)
Serologic testing for AChR-Ab and/or MuSK-Ab
AChR-Ab and MuSK-Ab correlate poorly with disease severity
CT: Thymoma?
Electrophysiological tests:
A) RNS (Repetitive Nerve Stimulation)
B) SFEMG (single fiber electromyography)
RNS – positive if incremental decrease in motor response 10%. Not specific for myasthenia gravis!
What is the ice pack test? How does it work?
Initially
Dosing: 2 mg of edrophonium is administered intravenously as a test dose
Monitoring heart rate: Bradycardia or ventricular fibrillation may develop
Follow-up
After observing for about 2 minutes, if no clear response develops
Up to 8 additional mg of edrophonium is injected
A double-blind protocol with a saline injection as placebo has been advocated
Testing should be performed with patient free of all cholinesterase-inhibitor medications
Cholinergic side effects of edrophonium
May include increased salivation and lacrimation, mild sweating, flushing, urgency & perioral fasciculations.
Atropine should be readily available to reverse effects of edrophonium in case of hemodynamic instability
Extra precautions are especially important in elderly patients

12. Decrease greater than 10%
2-3 Hz – 8-10 stimulations

13. Single Fiber EMG
SFEMG is more technically demanding than RNS and is less widely available, but it is the most sensitive diagnostic test for myasthenia gravis. This technique allows simultaneous recording of the action potentials of two muscle fibers innervated by the same motor axon. The variability in time of the second action potential relative to the first is called "jitter." Any disorder, such as myasthenia gravis, that reduces the safety factor of transmission at the neuromuscular junction will produce increased jitter. To maximize the sensitivity, a limb and facial muscle may be studied.
Simultaneous recording of AP of two muscle fibers innervated by the same motor axon.
Records variability in time (jitter)

14. Ice Pack Testing
test+video&view=detail&mid=6AC6FEA5367A7 B756CA46AC6FEA5367A7B756CA4&FORM=VI RE
Clinicians have observed that sunlight may aggravate the ptosis of myasthenic patients and that hot liquids (vs. cold liquids) may provoke myasthenic dysphagia. 22 Based on these observations and that results of electromyography in myasthenia are temperature dependent, Salvedra devised the ice pack test in as a test for ptosis. In this test the clinician places a surgical glove filled with crushed ice for 2 minutes over the patient’s closed eye and then compares the ptosis before application of the ice (by measuring the palpebral fissure, i.e., the vertical height of eye opening, to the nearest 0.5 mm) to that after application of the ice. Digital pressure is applied on the forehead just above the eyebrow to avoid contributions from the frontalis muscle in elevating the lid. Because cold temperature improves the weakness of myasthenia, the positive result is diminished ptosis after application of the ice (i.e., the palpebral fissure increases 2 mm or more).

15. Evidence Based Medicine

16. Evidence Based Medicine

17. Q4: Name 5 differences between Lambert-Eaton Syndrome and MG
Myasthenia Gravis
Lambert -Eaton
Association
Thymoma
Small-cell lung cancer
Pathophysiology
Post-synaptic
Pre-synaptic
Ocular Involvement
Common
Not-Common, but can occur!
Symptoms
Weakness worsens with activity
Weakness improves with activity
Physical Exam
Deep tendon reflexes normal
Deep tendon reflexes normal or decreased
Autonomic dysfunction
Other differences: LE: Autonomic dysfunction: dry mouth, constipation, blurred vision, impaired sweating, orthostatic hypotension

18. Lambert Eaton Syndrome
Antibodies against P/Q type calcium channels
Impaired release of ACh from nerve terminals
Ask them what LE syndrome is before giving answer.

19. Q5: What Treatments can you offer?
Acetyl cholinesterase inhibitors (pyridostigmine)
Rapid Induction Immunotherapy (IVIG, plasmapheresis): bridge therapy, myasthenic crisis, maintenance treatment in refractory MG
Steroids: low dose vs. high dose?
Azathioprine
Mycophenolate Mofetil
Cyclosporine and Tacrolimus
Rituximab
Cyclophosphamide
Thymectomy
Pyridostigmine has rapid onset (15-30 min) and lasts 3-4 hours. Normally take it as 60 mg starting dose TID

20. Steroids Mild to moderate MG: Oral 20-40 mg of prednisone/day
Myasthenic Crisis: high dose steroids receiving concurrent induction immunotherapy (1mg/kg/day) over 3-4 weeks
Taper: slowly to avoid relapse (5-10 mg/month decrease)
Supplement with Calcium (1500 mg/day) and Vitamin D ( U/day)

21. Azathioprine Interferes with DNA synthesis of T & B lymphocytes
Delayed onset: 6-12 months
Start with 50 mg/day with increase of 50 mg every 2 weeks
Goal: 2-3 mg/kg/day
Labs: check liver function and CBC every week for 2 months and then monthly for a year
Mutant allele in thiopurine methyltransferase gene could lead to life threatening bone marrow suppression
Add in what meds do you need lab monitoring for?

22. Mycophenolate Mofetil
Inhibits purine synthesis and therefore B and T lymphocytes
Start with 500 mg BID and increase to mg BID within 3-6 months
Fewer side effects, well tolerated
Labs: cbc, cmp monthly for 6 months and then yearly
Leukopenia, LFT elevation

23. Cyclosporine and Tacrolimus
Inhibits calcineurin and blocks synthesis of IL-2 and Interferon
Faster onset (1-2 months)
Maintenance dose of 5mg/kg/day with serum level between ng/mL
T: mg/kg/day with levels between 2-9 ng/mL
Renal Toxicity: Cyclosporine >> Tacrolimus

24. Rituximab Monoclonal antibody against CD-20 on B cells
Used more with refractory MG
Particularly effective for MG-MuSK
Minimal reactions, well tolerated!

25. Cyclophosphamide Used sparingly Lots of side effects Myelosuppression
Hemorrhagic Cystitis
Skin/bladder/blood malignancies

26. Thymectomy for Tumors
75% prevalence in those with Ach-R antibody positive MG
85% Thymic Hyperplasia
15% Primarily Thymoma

27. Great chart!

28. Q6: What autoimmune diseases are associated with MG?
Autoimmune thyroid disease (3-8%)
Rheumatoid Arthritis
Systemic Lupus Erythematosus
Added animation to make it interactive.

29. Q7: What medications should you avoid if you have MG?
Really key slide. Would ask them the question before showing this slide.

30. Q7: What medications should you avoid if you have MG?

31. Q8: What parameters are used for intubation?
Vital Capacity < 20mL/kg
NIF (negative inspiratory force) < 30 cm H2O
Physical exam – how does the patient look? What are the respiratory rates? Is the patient tiring out?
DO NOT USE ABGs OR VBGs
Added in animation to make more interactive.

32. MKSAP
A 24-year-old woman comes to the office for a follow-up evaluation of myasthenia gravis that was diagnosed 1 year ago after frequent episodes of double vision and muscle weakness occurring at the end of the day or after exercise. Symptoms have become less frequent with the use of prednisone and pyridostigmine. The patient has had no shortness of breath or other medical issues. Her mother has rheumatoid arthritis.
On physical examination, temperature is 37.4 °C (99.3 °F); other vital signs are normal. Diplopia is noted in all directions with disconjugate gaze and is exacerbated after sustained upgaze for 1 minute. Muscle strength is 4/5 in the deltoids, biceps, triceps, quadriceps, and hamstrings bilaterally. Weakness is more pronounced after she keeps the arms upright while sitting and standing five times; she needs to use her arms to stand from a seated position on her last attempt. No shortness of breath, dysarthria, or dysphagia is noted. Sensory examination and reflex testing are normal.
Results of laboratory studies show high titers of antiacetylcholine receptor antibodies.
No evidence of myopathy or neuropathy is found on an electromyogram or during nerve conduction studies; repetitive stimulation of the motor nerves showed a decrement in amplitude. A CT scan of the chest shows no thymoma.
Was there only 1 MKSAP question on MG? Maybe we could add 1-2 more? Even do Lambert-Eaton question?

33. C) Mycophenolate Mofetil D) Plasmapheresis E) Thymectomy
According to a recently completed randomized clinical trial, which of the following is the most appropriate treatment?
A) Azathioprine
B) IVIG
C) Mycophenolate Mofetil
D) Plasmapheresis
E) Thymectomy
Answer: E
Lead to lower rate of hospitalizations, need for steroids, use of azathioprine and overall symptoms

34.
What is the purpose of this slide? Are you going to tell us about the article?

35. Alternate day prednisone vs. prednisone + thymectomy
Primary outcomes:
Quantitative MG score over 3 years
Average dosage of prednisone used over 3 years

36. MKSAP
A 62-year-old man is admitted to the hospital for a 6-week history of progressive cough, hemoptysis, and shortness of breath. Prior to the onset of symptoms, he reports feeling well except for some difficulty rising out of a chair and walking up a flight of stairs because of lower extremity weakness. He has a 50-pack-year history of cigarette smoking. He has no other medical problems and takes no medications.
On physical examination, temperature is 37.6 °C (99.7 °F), blood pressure is 140/84 mm Hg, pulse rate is 102/min, respiration rate is 14/min, and oxygen saturation is 90% breathing ambient air; BMI is 30. Cardiovascular and pulmonary examination findings are unremarkable. On neurologic examination, he has symmetric proximal muscle weakness in both his upper and lower extremities. There is no palpable peripheral lymphadenopathy.
Chest radiograph shows a right hilar mass. Chest CT confirms an 8-cm right hilar mass adjacent to the mediastinum with bulky bilateral mediastinal lymphadenopathy.

37. Which of the following is the most likely diagnosis?
A) Adenocarcinoma of the lung
B) Atypical bronchial carcinoid tumor
C) Small cell lung cancer
D) Squamous cell carcinoma of the lung
Answer C

38. References JAMA evidence – The Rational Clinical Examination Uptodate
Dynamed
MKSAP 17
Evidence Based Physical Diagnosis, McGee

39. Questions?