ZSFG AM report pearls: Myasthenia Gravis mechanism, exam, triggers, therapy

Thanks to Paul, Jesse, and Kendra for pioneering neurology morning report and discussing the case of a 67W h/o HIV, COPD, and myasthenia gravis who presented with SOB, found to be in myasthenia crisis.

Paul, our stellar neurology night resident, noted the main aspects of his (non-pulmonary) physical exam for a patient with myasthenia gravis (MG)…

  • Ptosis
  • Bifacial weakness
  • Inability to sustain upward gaze
  • Motor exam looking for proximal >distal muscle weakness

We reviewed the mechanism for myasthenia gravis (MG)…

  • Autoimmune disorder of neuromuscular transmission, usually caused by antibodies to postsynaptic nicotinic acetylcholine receptors (AchRs)
  • ~15% of patients with MG don’t have detectable AChR antibodies
    • A portion (<40%) of these “sero-negative” patients have other immune factors detected, including IgG antibodies to muscle-specific tyrosine kinase (MuSK)
  • In some circles, MG is approached as a paraneoplastic process given that thymomas are found in 10-30% of patients with MG

mg pic

Triggers for MG crisis (crisis=weakness from MG severe enough to consider or necessitate invasive respiratory support):

  • Recent surgery/procedure
  • Infection
  • Medications: new ones or changes in old one i.e. Fluroquinolones, beta-blockers, succinylcholine, magnesium, steroids** see below
  • Pregnancy/childbirth

What to monitor in patients with concern for MG crisis?

  • Vital capacity (VC) and Mean inspiratory force (MIF); Paul described the 20-30 rule about VC and MIF
  • VC: deep breath and exhalation maximally into spirometer; goal is at least 20cc/kg
  • MIF: inhalation against a closed valve with negative force recorded; goal is “more negative” than -30 cmH20. -60cmH20 is expected or what is associated with weak cough in NL person

How do we treat MG? IVIg***, plasma exchange (exchange and IVIg are the rapid go-to therapies), immunosuppressants, pyridostigmine, thymectomy.
Immunosuppressant drugs come in three flavors:

  • Inhibition of the cell cycle (azathioprine, cyclophosphamide, methotrexate and mycophenolate mofetil)
  • Immunosuppression of T cells (steroids**, ciclosporin and tacrolimus)
  • B-cell depletion (rituximab)

 

**There was concern in this case that steroid therapy for COPD may have contributed to worsening or precipitation of patient’s myasthenia crisis. Interesting comments about use of steroids in MG therapy…

  • About 50% of patients with MG receiving treatment with high-dose corticosteroids have an early MG exacerbation
  • This ‘steroid dip’ usually occurs after 4–10 days and can precipitate a MG crisis
  • Mechanism of this worsening/early MG crisis:
    • potentiation of the effects of muscle relaxants
    • direct effect on neuromuscular transmission including depolarization of nerve terminals, reduced Ach release, altered MEPPs, alteration of choline transport, and intracellular potassium depletion
    • immune-mediated (hand-wave)
  • To overcome the problem with the steroid dip, treatment on alternate days has been recommended by some

***Pearls from ICU fellow extraordinaire, Lekshmi, about IVIg in Myasthenia gravis***

  • Time course: IVIG starts to work within several days, but benefits only last a few weeks
  • Mechanism: Unknown mechanism – pooled immunoglobulins from thousands of donors
  • Dose: 2grams/kg over 2-5 days (consider spreading out dose with patients who can’t tolerate high volume such as CHF or ESRD)
  • Evidence: No RCT placebo-controlled trials for myasthenic crisis
  • Alternatives: consider plasma exchange for IVIG – a systematic review showed no difference in therapies
  • Side effects: Always check IgA levels before IVIG – patients with IgA deficiency can have an anaphylactic reaction to IVIG! Other common side effects are HA, flushing, myalgia, nausea/vomiting, tachycardia.
  • Prognosis: Prognosis has improved from 75% mortality in 1950s to 5% mortality by 1990s
  • Early role of BiPAP: 20% of patients in one study could be supported with NIV and initial NIV use was associated with shorter duration of ventilatory support and spend less time in the ICU and hospital
  • Other principles of treatment: Admit to ICU early, frequently monitor MIFs/NIFs and FVC, electively intubate if impending respiratory failure, stop pyridostigmine for myasthenic crisis, begin therapy with high-dose steroids/azathioprine/cellcept/cyclosporine

 

References:

  • Pascuzzi, M. Medications and Myasthenia Gravis (A Reference for Health Care Professionals). Updated 2007. Indiana Univeristy, School of Medicine. http://www.myasthenia.org/LinkClick.aspx?fileticket=JuFvZPPq2vg%3D
  • Sathasivam S. Steroids and immunosuppressant drugs in myasthenia gravis. Nature Clinical Practice Neurology (2008) 4, 317-327 doi:10.1038/ncpneuro0810
  • Mao Z-F, Mo X-A, Qin C, Lai Y-R, Hackett ML. Incidence of Thymoma in Myasthenia Gravis: A Systematic Review. Journal of Clinical Neurology (Seoul, Korea). 2012;8(3):161-169. doi:10.3988/jcn.2012.8.3.161.

Evernote link: https://www.evernote.com/shard/s354/sh/0bb141a7-19cf-4d0e-b8bb-1065623e42d4/998da0a82894697a410e1a02ac68c52e

 

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