Ver el código de «Myasthenia gravis»

==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

===Drugs Associated with Exacerbations===
====May Unmask or Worsen<ref>https://neurology.uams.edu/wp-content/uploads/sites/49/2018/03/Drugs-that-may-worsen-Myasthenia-Gravis.pdf</ref>====
*Antimicrobials ([[Aminoglycosides]], [[clindamycin]], [[erythromycin]], [[tetracycline]], [[doxycycline]], [[azithromycin]], [[fluoroquinolones]], [[vancomycin]], [[chloroquine]], [[hydroxychloroquine]], )<ref> UpToDate Clinical manifestations of myasthenia gravis may 2016</ref>
*Cardiovascular drugs ([[beta blockers]], [[procainamide]], [[quinidine]])
*Neuro/psych meds ([[chlorpromazine]], [[lithium]], [[prochlorperazine]], [[phenytoin]], [[risperidone]], 
*Other (Botox, [[quinine]]s, [[magnesium]])
 
====Usually Well-tolerated, but Occasionally Associated====
*Local anesthetics
*Antibiotics ([[Tetracycline]]/[[doxycycline]], [[macrolides]], [[metronidazole]], [[nitrofurantoin]])
*Anticonvulsants ([[carbamazepine]], [[ethosuximide]], [[gabapentin]], [[phenobarbital]], [[phenytoin]])
*Butyrophenones ([[haloperidol]])
*Phenothiazines ([[chlorpromazine]]/[[prochlorperazine]])
*[[Calcium channel blockers]]
*[[Steroids]]
*Ophthalmic drugs (betaxolol/timolol/proparacaine)
*Other (Iodinated contrast agent)

==Clinical Features==
[[File:DiplopiaMG1.jpg|thumb|Cranial nerve palsy and ptosis in a patient with myasthenia gravis]]
*Muscle [[weakness]]
**Proximal extremities
**Neck extensors
**Facial/bulbar muscles ([[dysphagia]], [[dysarthria]], [[dysphonia]])
*Ocular weakness
**Ptosis
**[[Diplopia]]
**[[cranial nerve palsies|CN III, IV, or VI weakness]]
*Symptoms worsen with repetitive use / as the day progresses<ref>Tintinalli's Emergency Medicine: A Comprehensive Study Guide, 7e (2010), Chapter 167. Chronic Neurologic Disorders</ref>

==Differential Diagnosis==
{{Weakness DDX}}

==Evaluation==
[[File:Myasthenia gravis ptosis reversal.jpg|thumb|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.]]
[[File:Tumor Thymoma1.jpg|thumb|A chest CT-scan showing a thymoma (red circle).]]
===Workup===
====ED Workup====
Always evaluate:<ref>Emergency Medicine Practice -- Weakness: A systemic approach to acute non-traumatic neurologic and neuromuscular causes Dec 2002</ref>
*Tidal volume
*Forced Vital capacity (normal is >25cc/kg in MG)
*FEV
*Negative inspiratory force (NIF) (normal is -80 to -100; respiratory support is indicated for -20 to 0)
*Ability to handle secretions 

====Neuro Workup====
The following may be considered for neurologic workup, but are not typically indicated in the ED:<ref>Myasthenia gravis: Association of British Neurologists’ management guidelines [https://pn.bmj.com/content/15/3/199]</ref>
*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

{{Myasthenic vs cholinergic crisis}}

===Diagnosis===
*Prolonged upward gaze test<ref>Ptosis in myasthenia gravis: Extended fatigue and recovery bedside test. Klaus V. Toyka. Neurology Oct 2006, 67 (8) 1524.</ref>
**Have the patient gaze upward at examiner's finger for 30 seconds
**Diplopia or ptosis that develops is suggestive of MG
*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.

==Management==
;Avoid medications that can cause/worsen exacerbations (see Background), including [[magnesium]] (which can cause [[respiratory failure]])
===Myasthenic Crisis===
*Acetylcholinesterase inhibitors are discontinued to avoid excessive bronchial secretions
*[[Intubation]] (if needed)
**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]]
**0.4 g/kg/day for 5 days
**Effect lasts 30-45 days
*[[Plasmapheresis]]
**Effect lasts 15-20 days

===Other Medications===
''[[Pyridostigmine]] and [[neostigmine]] primarily used for symptomatic relief but does not alter course of crisis<ref>Wendell LC and Levine JM. Myasthenic Crisis. Neurohospitalist. 2011 Jan; 1(1): 16–22.</ref>. Consider avoiding 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
**Generalized 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

==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==
*[[Weakness]]

==References==
<references/>


[[Category:Neurology]]