Myasthenia Crisis Secondary to… a Thymoma! 12/26/2018

Our case today is a 49 year old woman with no medical history, presenting with 1 month of difficulty swallowing, voice changes, and more recently dysphagia with liquids and solids, and shortness of breath. Her symptoms are worse during the night time to the point that she couldn’t swallow her own spit/secretions. She presented with respiratory failure requiring intubation, and on CXR/CT she was found to have an anterior mediastinal mass concerning for a… thymoma!


Let’s first briefly review Myasthenia Gravis before moving onto Myasthenia Crisis, and lastly, Thymomas.

Myasthenia Gravis

Epidemiology

  • Bimodal: Early peak in 2-3rd decades (female predominance) and late peak 60-80s (male predominance).
  • F in post-partum period have inc risk.
  • Possible association with: neuromyelitis optical, autoimmune thyroid disorders, SLE, RA.

Diagnosis

  • Bedside
    • Ice-pack test: Improvement of ptosis after application of an ice pack = positive. Sensitivity around 80ish %, limited to patients with ptosis and not helpful for those with extraocular muscle weakness.
      • myastheniagravis-myasthenia-diagnosis-clinical-icepack-original.jpeg Source: NEJM, Grepmed
    • Edrophonium test is no longer used very often, in a nut shell, it is a Acetylcholinesterase inhibitor with rapid onset (within 30-45 seconds), produces improvement of affect muscles after injection.
      • 80-90% sensitivity but high rates of false positive. Not very specific.
  • Serology (seropositive in 90% of MG patients).
    • AChR Ab
      • Titers do not correlate with disease activity
      • 85% positive in generalized MG
      • Highly specific, extremely low false positives (LE, certain motor neuro dz, polymyositis)
    • MuSK-Ab
      • Seen in 38-50% with generalized MG who are AChR Ab negative.
    • Thymoma patients with MG: 98-100% will have positive AChR-Ab.
      • NPPV for thymoma in the absence of AChR-Ab is 99.7%
    • Seronegative: 6-12%, more likely to have purely ocular myasthenia.
  • EMG: Can help confirm diagnosis
    • Single fiber EMG
      • Abnormal in > 90% of those with generalized MG, less so in ocular MG
      • Most sensitive diagnostic test for MG, 90-95% sensitivity (les for ocular MG), 91% specific.
    • Repetitive nerve stimulation
      • Readily available but less sensitive vs SFEMG
      • Nerve is stimulated multiple times, and the compound muscle action potential is recorded, test is considered positive if progressive decline in CMAP readings with the first 4-5 stimuli.
      • Sensitivity 75-80%

Management

  • Symptomatic: Pyridostigmine, max daily dose 7mg/kg
    • Too much pyridostigmine can cause cholinergic crisis, leading to—weakness. Chances of this dec by limit daily dose of pyridostigmine to less than 960mg daily
  • Chronic immunotherapy: Required for those with sx on pyridostigmine or recurrence of sx on pyridostigmine after initial improvement.
    • Steroids or immunosuppressives i.e. azathioprine, mycophenolate, cyclosporine.
  • Thymectomy: Recommended for age < 60, has been considered beneficial even without presence of a thymoma.

Myasthenic Crisis

Definition: Weakness severe enough to impair muscles of respiratory requiring mechanical ventilation.

  • 10-20% of pts with MG will experience at least one crisis, annual risk 2-3%
  • For 13-20% of pts with MC, the crisis is their first clinical manifestation of MG and initial diagnosis.
  • Most occur in the first few years after diagnosis of MG.

Presentation

  • Progressive generalized or bulbar weakness leading to respiratory failure.
  • Variable presentation in terms of degree of weakness (general vs respiratory)
  • May be precipitated by: infection, surgery, pregnancy, childbirth, medication tapering, certain drugs (beta blockers, antibiotics), magnesium

Evaluation

  • Airway/Breathing: Monitor respiratory muscle strength frequently, should be admitted to MICU
  • Indications for intubation:
    • FVC < 15 – 20 mL/kg
    • NIF < -25 to -30 cmH2O (i.e. 0 to -24)
    • Respiratory fatigue
    • PCO2 > 50
    • Difficulty with secretions

Management

  • Intubation if signs of impending respiratory failure.
    • Elective intubation, rather than emergent, is preferred.
  • Rapid IVIG or plasma exchange, FAST
    • Plasmapheresis directly removes acetylcholine receptor ab in the circulation
  • High dose glucocorticoids, azathioprine, cyclosporine, or mycophenolate
  • Wean as respiratory muscle strength improves after completing or IVIG or plasma exchange.
  • Aggressive pulmonary toilet.
  • Pyridostigmine generally avoided after intubation temporarily since it might increase secretions, leading to more complex pulmonary care.
    • Can be resumed after extubation.

Thymoma

Epidemiology

  • Median age 40-60
  • Men ~ Women
  • No known risk factors but strong association with myasthenia gravis

Presentation

  • Local thoracic symptoms
  • Asx
  • Paraneoplastic symptoms
  • Up to ½ of pts with thymoma will have MG like sx.
  • MG is common with thymomas but rare in thymic carcinoma

Paraneoplastic presentation

  • Neuro: MG, polymyositis, Lambert Eaton, Isaac’s syndrome, stiff person syndrome
  • Heme: Pure red cell aplasia, hemolytic anemia, pernicious anemia, agranulocytosis
  • Derm: Alopecia areata, pemphigus, scleroderma, vitiligo, oral lichen planus
  • Endo: Addison’s disease, Cushing syndrome, panhypopit, thyroiditis
  • Other: Nephrotic syndrome, RA, sarcoid, hepatitis, hypogammaglobulinemia, myocarditis

Diagnosis

  • CT and/or MRI
  • Carcinoma findings: Necrotic, cystic, or calcified, irregular contour
  • Definitive dx requires tissue biopsy

Staging

  • Masaoka staging system vs American Joint Committee on Cancer (AJCC), with the former being more commonly used.

Capture.JPG

Management

  • Surgical resection: as much as possible, including complete resection of the thymus. Potentially curative.
  • If extensive disease, can consider chemo followed by radical resection +/- RT for potentially resectable cases.
  • If complete resection cannot be done, maximal debulking followed by post-op RT.
  • Potential phrenic nerve damage due to tumor expansion or surgery. Can sacrifice one for surgical resection but if both are involved, then it’s a more complicated discussion.

Prognosis

  • Main determinant = staging and complete resectability of the tumor
  • Most commonly used staging system = Masaoka Staging System
  • Masaoka stage I and II: Favorable
  • Masaoka stage III: 27% recurrence after complete resection, 62% with incomplete resection. 10yr survival 83%
  • Masaoka stage IV: 10-yr survival is 47%

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