Beruflich Dokumente
Kultur Dokumente
Erin O’Ferrall
Colin Chalk
March 11, 2009
Objectives
To identify key features of the history & physical
exam of a patient with Myasthenia Gravis (MG)
To learn how to elicit a history of fatigable weakness
Learn what investigations to order if you suspect a
diagnosis of MG
Describe what are MUSK antibodies and their significance
Discuss the potential therapies and evidence for
each
To describe the approach and management to refractory
MG
To describe the role of thymectomy
Outline
Case
History & Physical exam
Investigations
Treatment
Case
Neuromuscular Junction
(NMJ)
Case 1
57yr old female with 3 month history of
fatigue, ptosis, dysphagia
Clinical Course of MG
Ptosis
Describe (%complete, mm below upper pupil
margin)
Compensation: head tilt, frontalis contraction
Worse with upgaze; better with rest/ cooling
Curtain sign aka enhanced ptosis or paradoxical
ptosis
Lid twitch sign
Physical Exam: what do you see here?
IVIG -Class I -First line therapy for short term use in worsening of moderate
to severe MG. See Zinman et al Neurology 2007; 68: 837
Thymectomy
How many MG patients have a thymic tumour?
10% of MG patients have a thymic tumour
20% of patients with MG whose symptoms began between
30 and 60 yrs had thymoma
lower incidence of thymoma if symptoms began after age 60
And the rest?
70% of MG patients have hyperplastic changes (germinal
centers) …indicate as active immune response
thymic tumours are usually benign, well-
differentiated, encapsulated and can be completely
removed
Thymectomy
Mandatory if you have a thymoma but if not...
AAN practice parameter (2000)
For patients with nonthymomatous autoimmune
MG, thymectomy is recommended as an option to
increase the probability of remission or
improvement (Class II).
Often done in generalized MG patients <50
yrs within 1-2 yr of disease onset (expert
opinion)
Trial underway: Dr Chalk...
Multicenter, single blind RCT (thymectomy or not)
Ab positive, < 60 yr
Refractory MG
Is this really refractory MG or is this under treated
MG?
Adequate doses & duration of medications
Did you try all the options we already discussed?
Compliance
Is the thymoma gone or did you miss one?
Is this really MG?
Comorbidities? Check thyroid
Could this be a congenital form of MG?
Is the risk worth the potential benefit if you want to
resort to experimental therapies:
Rituximab (Ab to Cd20): case series
Tacrolimus (suppresses T cell activation)
Stem cell transplant???
Case 1: HPI
57 yr F with 3 month history of fatigue, ptosis,
dysphagia
3 months:
Fatigue & “weak all over”
Ptosis:
right side, better in am (for first 5-10 minutes);
needed to tape her eye open; did not note
recovery with rest; progressively worse
Blurred vision
1 mo: progressive dysphagia
Case1: PMHx
Graves disease
Coincidence?
Headaches
All: sulfa
Med: synthroid, prn ibuprofen, sudafed
Case 1
On exam...
Ptosis
Proximal weakness of the limbs
What to do?
Case 1: Investigations
Tensilon test
EMG
sfEMG
CT chest: thymic mass
What now?
Case 1: Mngmt
Thymectomy: thymoma
IVIG
Prednisone
Mestinon
D/c home 10 postop
Conclusion
Signs & symptoms of MG can be elicited by
the history and physical exam--> clinical
diagnosis
The diagnosis of MG can be confirmed by
electrophysiological & serological tests
Anti-Musk patients are probably different
Treatment consists of symptomatic &
immune modulatory therapies
Thymectomy is mandatory for thymoma and
should be considered for non-thymomatous
patients (consider enrolling in a trial)
References
Continuum Feb 2009; 15(1): 13-82
See Ethics chapter by K Brownell & Phil!
Bradley 4th & 5th Ed
www.utdol.com: comprehensive list of drugs to avoid
in MG
Good reviews:
Muscle & Nerve Apr 2004
Lancet June 30, 2001
AAN guideline on thymectomy 2000
Evidence for treatments & good review of
pathophysiology:
Nat Clin Prac Neurol Jun 2008
Important papers:
L Zinman Neurol Mar 13, 2007 (IVIG RCT)
‘Seroneg MG’ Brain May 31, 2008