Background

Autoantibody degradation, dysfunction, and blockade of acetylcholine receptor at the NMJ

Thymus is abnormal in 75% of patients Thymectomy resolves or improves symptoms in most patients, especially those with a thymoma

No sensory, reflex, pupillary, or cerebellar deficits

[1] Drugs that may unmask or worsen myasthenia gravis

Drugs Usually well-tolerated in myasthenia gravis but occasionally associated with an exacerbation

See also: https://neurology.uams.edu/wp-content/uploads/sites/49/2018/03/Drugs-that-may-worsen-Myasthenia-Gravis.pdf

Clinical Features

Cranial nerve palsy and ptosis in a patient with myasthenia gravis

Differential Diagnosis

Drug-induced myasthenia

Evaluation

Right partial ptosis (left picture) with left lid showing compensatory pseudo lid retraction because of equal innervation of the levator palpabrae superioris (Hering's law of equal innervation): Right picture: after an edrophonium test, note the improvement in ptosis.

A chest CT-scan showing a thymoma (red circle).

Ice Pack Test- should improve symptoms temporarily (usually ptosis; high specificity) Place ice-pack on eyes for 2 mins, if ptosis decreases by ≥2mm the test is positive

Acetylcholine receptor antibodies (AcHR-Ab). Positive in 80-90% of generalized MG and 40-55% in Ocular MG.

Flaccid paralysis resulting from cholinergic crisis can be distinguished from myasthenia gravis by the use of the drug edrophonium, which worsens the paralysis caused by cholinergic crisis, but strengthens the muscle in the case of myasthenia gravis. (Edrophonium is an cholinesterase inhibitor hence increases the concentration of acetylcholine present).

Myasthenic Crisis Respiratory failure is feared complication Much more common Due to medication non-adherence, infection, surgery, tapering of immunosuppressants, meds

Cholinergic Crisis Excessive anticholinesterase medication may cause weakness and cholinergic symptoms Rarely if ever seen with dose limitation of pyridostigmine to less than 120mg q3hr If on usual dose of meds assume exacerbation due to MG even with cholinergic side effects

Edrophonium (Tensilon) test to distinguish the two is controversial Give 1-2mg IV slow push. If any fasciculations, respiratory depression, or cholinergic symptoms within a few minutes, problem is likely cholinergic crisis (no more edrophonium). If no evidence of cholinergic excess, give total of 10mg and observe improvement in case of myasthenic crisis. Side effects of Edrophonium: Arrhythmias, Hypotension, Bronchospasm Thus, need to be on a monitor, with atropine on hand Treatment: Atropine



Management

Always evaluate:[5]

Tidal volume

Forced Vital capacity (normal is >25cc/kg in MG)

FEV

Negative inspiratory force (NIF) (normal is -80 to -100 and greater than +20 respiratory support indicated)

Ability to handle secretions

ACh-R antibody testing: first-line investigation. Indication for thymectomy if < 45 years. MuSK antibody testing: for patients negative for ACh-R antibodies

Thyroid function

Neurophysiology: Repetitive nerve stimulation is the initial test; if negative, consider single-fibre electromyography.

MR scan of brain: Patients with negative serology and neurophysiology, and symptoms compatible with ocular myasthenia may have structural brain disease.

Thymus scanning: All patients with suspected myasthenia, irrespective of distribution (ocular/generalised) or serology (seropositive/negative), should undergo thymus imaging. The modality (CT or MRI) should be decided locally.

Edrophonium/Tensilon test

Medications

Pyridostigmine and neostigmine primarily used for symptomatic relief but does not alter course of crisis[7]. Consider avoiding pyridostigmine/neostigmine in ICU ventilated patients, as these may increase secretions. Continued use of these meds also prevents assessment of other treatment modalities and can increase muscle weakness if used in excess

Pyridostigmine: Titrate up to find the lowest effective dose Initially 30 mg four times daily for 2–4 days Then 60 mg (1 tablet) four times daily for 5 days and experiment with timing Then increase to 90 mg four times daily over 1 week if required. If patient's usual dose has been missed the next dose is usually doubled IV route: 1/30th of the PO dose (2-3mg) by slow IV infusion

Neostigmine 0.5mg IV



Prednisolone: If symptomatic despite Pyridostigmine. Monitor diabetes mellitus.

Ocular myasthenia gravis Start 5 mg on alternate days for three doses and increase by 5 mg every three doses until symptoms improve. The maximum dose is 50 mg on alternate days or 0.75 mg/kg/alternate day

Generalised myasthenia gravis Start 10 mg on alternate days for three doses and increase by 10 mg every three doses until symptoms improve. Maximum dose is 100 mg alternate days or 1.5 mg/kg



Plasmapheresis

Effect lasts 15-20 days

IVIG

0.4 g/kg/die for 5 days

Effect lasts 30-45 days

In Myasthenic Crisis :

Acetylcholinesterase inhibitors are discontinued to avoid excessive bronchial secretions

Intubation If possible avoid depolarizing AND non-depolarizing agents If patient requires paralysis use non-depolarizing agent at smaller dose If must use depolarizing agents, will need higher doses

IVIG and plasmapheresis

Disposition

Typically MICU or neuro ICU, consideration for thymectomy if not done already

Consideration for corticosteroids or other immunosuppressants (i.e. corticosteroids, azathioprine, mycophenolate mofetil, cyclosporine)

See Also

References