View source for Myasthenia gravis

==Epidemiology==
*Most common disorder of neuromuscular transmission; prevalence ~20 per 100,000<ref name="PMC7489768">Suresh AB, Asuncion RMD. Myasthenia Gravis. StatPearls. 2023.</ref>
*Bimodal age distribution: women peak in 2nd–3rd decade; men peak in 6th–7th decade<ref name="Pascuzzi">Pascuzzi RM, Bodkin CL. Myasthenia Gravis and Lambert-Eaton Myasthenic Syndrome: New Developments in Diagnosis and Treatment. Neuropsychiatric Disease and Treatment. 2022;18:3001-3022.</ref>
*15–20% of patients with MG will experience myasthenic crisis, most commonly within the first 2 years<ref name="Wendell">Wendell LC and Levine JM. Myasthenic Crisis. Neurohospitalist. 2011 Jan; 1(1): 16–22.</ref>
*~20% of myasthenic crises are the initial presentation of MG<ref name="emcrit">EMCrit - Myasthenia gravis & myasthenic crisis. https://emcrit.org/ibcc/myasthenia/</ref>

==Background==
*Autoantibody degradation, dysfunction, and blockade of acetylcholine receptor (AChR) at the neuromuscular junction (NMJ)
*Thymus is abnormal in ~75% of patients (85% hyperplasia, 15% thymoma)
**Thymectomy resolves or improves symptoms in most patients, especially those with a thymoma
*No sensory, reflex, pupillary, or cerebellar deficits
*Key distinguishing feature from other NMJ disorders: normal reflexes, normal sensation, no autonomic symptoms, no fasciculations, worsening weakness with repetitive motion<ref name="Roper">Roper J, Fleming ME, Long B, Koyfman A. Myasthenia Gravis and Crisis: Evaluation and Management in the Emergency Department. J Emerg Med. 2017;53(6):843-853.</ref>

===Drugs Associated with Exacerbations===
;Critical: Review the medication list of every MG patient presenting to the ED, regardless of chief complaint
====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]], iodinated contrast agents)

====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]] (may transiently worsen symptoms upon initiation; see Management)
*Ophthalmic drugs (betaxolol/timolol/proparacaine)

===Precipitants of Myasthenic Crisis===
Identify and treat the trigger in every crisis presentation:<ref name="Roper"/><ref name="emcrit"/>
*Infection (most common cause, >30–40% of crises; respiratory infections #1, aspiration pneumonitis #2)
*Medication changes (see above; also includes tapering or abrupt discontinuation of immunosuppressants)
*Non-adherence with pyridostigmine or immunosuppressants
*Surgery/anesthesia
*Initiation or discontinuation of corticosteroids
*Emotional or physical stress, heat
*Electrolyte abnormalities (Ca, Phos, Mg)
*Thyroid disease (hyper- or hypothyroid; associated with autoimmune thyroid disease)
*Pregnancy/postpartum
*No identifiable trigger found in ~50% of patients

==Clinical Features==
[[File:DiplopiaMG1.jpg|thumb|Cranial nerve palsy and ptosis in a patient with myasthenia gravis]]
*Muscle [[weakness]]
**Proximal extremities
**Neck extensors ("dropped head")
**Facial/bulbar muscles ([[dysphagia]], [[dysarthria]], [[dysphonia]])
*Ocular weakness (presenting symptom in ~50% of patients; eventually involved in >80%)
**Ptosis (often asymmetric)
**[[Diplopia]]
**[[cranial nerve palsies|CN III, IV, or VI weakness]]
*Symptoms worsen with repetitive use and as the day progresses<ref>Tintinalli's Emergency Medicine: A Comprehensive Study Guide, 7e (2010), Chapter 167. Chronic Neurologic Disorders</ref>
*Respiratory weakness: dyspnea (especially supine/orthopnea), weak cough, inability to clear secretions, pausing mid-sentence to breathe, tachypnea with shallow breathing

===MGFA Clinical Classification===
{| class="wikitable"
|-
! Class !! Description
|-
| I || Ocular MG only
|-
| II || Mild generalized (IIa = predominantly limb/axial; IIb = predominantly bulbar)
|-
| III || Moderate generalized (IIIa = predominantly limb/axial; IIIb = predominantly bulbar)
|-
| IV || Severe generalized (IVa = predominantly limb/axial; IVb = predominantly bulbar)
|-
| V || Requiring intubation (myasthenic crisis)
|}

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

===Myasthenia Gravis vs Lambert-Eaton Myasthenic Syndrome===
{| class="wikitable"
|-
! Feature !! Myasthenia Gravis !! Lambert-Eaton (LEMS)
|-
| Mechanism || Postsynaptic AChR antibodies || Presynaptic P/Q-type VGCC antibodies
|-
| Initial symptoms || Ocular (ptosis/diplopia) in ~60% || Proximal leg weakness in ~95%
|-
| Pattern of weakness || Craniocaudal (eyes → bulbar → limbs) || Caudocranial (legs → arms → cranial)
|-
| Effect of repetition || Weakness ''worsens'' || Weakness initially ''improves'' (Lambert's sign)
|-
| Deep tendon reflexes || '''Normal''' || '''Depressed''' (may improve post-exercise)
|-
| Autonomic dysfunction || Absent || Common (dry mouth, constipation, impotence)
|-
| Cancer association || Thymoma (10–15%) || Small cell lung cancer (~60%)
|-
| Respiratory crisis || Common || Rare
|-
| RNS pattern || Decremental response || Initial decrement then ''incremental'' post-exercise
|}
<ref name="Pascuzzi"/><ref>Wirtz PW et al. Difference in distribution of muscle weakness between myasthenia gravis and the Lambert-Eaton myasthenic syndrome. J Neurol Neurosurg Psychiatry. 2002;73(6):766-768.</ref>

==Evaluation==
[[File:Myasthenia gravis ptosis reversal.jpg|thumb|Right partial ptosis (left picture) with left lid showing compensatory pseudo lid retraction (Hering's law): Right picture: after edrophonium test, note improvement in ptosis.]]
[[File:Tumor Thymoma1.jpg|thumb|A chest CT showing a thymoma (red circle).]]

===ED Workup===
Always evaluate respiratory function serially (q2hr or more frequently if deteriorating):<ref>Emergency Medicine Practice -- Weakness: A systemic approach to acute non-traumatic neurologic and neuromuscular causes Dec 2002</ref><ref name="Wendell"/>
*Forced Vital Capacity (FVC): normal ≥60 mL/kg; <20 mL/kg indicates impending respiratory failure
*Negative Inspiratory Force (NIF): normal is −80 to −100 cmH₂O; values closer to 0 indicate weaker effort
*Tidal volume
*Ability to handle secretions
*Continuous capnography (best early indicator of ventilatory deterioration)<ref name="NUEM">Management of Myasthenia Crisis in the ED — NUEM Blog. https://www.nuemblog.com/blog/myasthenia 2019.</ref>

;'''Intubation Triggers (Consider when ANY of the following present):'''
{| class="wikitable" style="background:#fff3f3;"
|-
| FVC < 20 mL/kg (or < 1 L, or rapidly declining) || NIF weaker than −30 cmH₂O (i.e., closer to 0)
|-
| Significant bulbar dysfunction with aspiration risk || Hypercapnia (pCO₂ > 45 mmHg)
|-
| Inability to handle secretions || Orthopnea with rapid shallow breathing
|-
| Serial decline in respiratory parameters || Clinical respiratory distress
|}
<ref name="MGFA">Myasthenia Gravis Foundation of America. Emergency Management of Myasthenia Gravis. 2024. https://myasthenia.org/wp-content/uploads/2024/09/MGFA-brochure-Emergency-Mgt-First-Responders.pdf</ref>

;Do NOT rely on SpO₂ alone—MG causes hypercarbic respiratory failure; hypoxemia is a late finding that may suggest atelectasis or aspiration<ref name="emcrit"/>

===Bedside Tests===
*Prolonged upward gaze test<ref>Toyka KV. Ptosis in myasthenia gravis: Extended fatigue and recovery bedside test. Neurology Oct 2006, 67(8):1524.</ref>
**Have the patient gaze upward at examiner's finger for 30–60 seconds
**Diplopia or ptosis that develops is suggestive of MG
*Ice Pack Test (high specificity for MG)
**Place ice-pack on closed eyes for 2 mins; positive if ptosis decreases by ≥2 mm
*Single breath count test
**Have patient take a deep breath and count aloud as high as possible; <20 suggests respiratory compromise

===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. Positive in 80–90% of generalized MG and 40–55% in ocular MG. (Results take days—do not delay treatment while awaiting)
**MuSK antibody testing: for patients negative for ACh-R antibodies
*Thyroid function
*Neurophysiology: Repetitive nerve stimulation (RNS) 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 imaging (CT or MRI): All patients with suspected myasthenia, regardless of distribution or serology
*Edrophonium/Tensilon test (sensitivity ~50% overall, ~80% in crisis; generally not used in ED due to risk of bradycardia/bronchospasm)

===Myasthenic Crisis vs Cholinergic Crisis===
{| class="wikitable"
|-
! Feature !! Myasthenic Crisis !! Cholinergic Crisis
|-
| Cause || Exacerbation of MG (infection, medication, stress) || Excessive acetylcholinesterase inhibitor use
|-
| Pupils || Normal || Miotic (constricted)
|-
| Secretions || Normal or mildly increased || Markedly increased (SLUDGE: Salivation, Lacrimation, Urination, Defecation, GI distress, Emesis)
|-
| Fasciculations || Absent || Present
|-
| Bradycardia || Absent || May be present
|-
| Diaphoresis || Absent || Present
|-
| Response to edrophonium || Improvement || Worsening
|-
| Modern relevance || Common || Exceedingly rare with modern dosing (pyridostigmine < 120 mg q3hr)<ref name="emcrit"/>
|}

==Management==
;Avoid medications that can cause/worsen exacerbations (see Background), including [[magnesium]] (which can precipitate [[respiratory failure]])

===Myasthenic Crisis===
;Priorities: (1) Secure the airway, (2) Identify/treat the precipitant, (3) Immunomodulatory therapy, (4) Neurology consultation early
====Respiratory Support====
*'''Noninvasive ventilation (BiPAP)''' may be used as initial support or bridge to intubation<ref name="Wendell"/>
**Can be successful even in patients with bulbar weakness
**Predictors of NIV ''failure'': hypercapnia (pCO₂ >45 mmHg), APACHE II ≥6, serum bicarb ≥30
**Monitor closely—these patients often need definitive airway management
*'''Intubation''' (if needed)—favor elective intubation over emergent<ref name="Wendell"/>
**If possible, intubate without paralytic agents (use adequate sedation alone)
**If paralysis is required, use a nondepolarizing agent at reduced dose (preferred):
***Rocuronium 0.5–0.6 mg/kg (roughly half the standard dose)<ref name="Poremba">Poremba M. UMEM Educational Pearls: Myasthenia Gravis and Neuromuscular Blockers. University of Maryland. 2023.</ref><ref name="roccase">Billups K et al. Extreme Paralysis Following Rocuronium Administration in a Myasthenia Gravis Patient. West J Emerg Med. 2023;24(4):735-738.</ref>
***MG patients are extremely sensitive to nondepolarizing agents—standard doses can cause prolonged paralysis (case reports of >4 hours)<ref name="roccase"/>
***'''Sugammadex''' can reverse rocuronium/vecuronium (dose 2–4 mg/kg, or 16 mg/kg for immediate reversal); have available<ref>StatPearls: Anesthesia for Patients With Myasthenia Gravis. 2025.</ref>
**If depolarizing agents must be used:
***Succinylcholine 1.5–2.0 mg/kg (roughly double the standard dose)<ref name="Levitan">Levitan R. Safety of succinylcholine in myasthenia gravis. Ann Emerg Med. 2005;45(2):225-226.</ref>
***MG patients are resistant to succinylcholine (fewer functional AChRs); may require up to 2.6× normal dose
***Not contraindicated in MG (unlike other neuromuscular diseases, no risk of hyperkalemia from receptor upregulation)<ref name="Levitan"/>
***Response may be unpredictable; avoid defasciculating dose of nondepolarizer
**'''Avoid''' benzodiazepines and opioids pre-intubation if possible (respiratory depressant effects exaggerated in MG patients)

====Pharmacologic Management in Crisis====
*Discontinue acetylcholinesterase inhibitors (pyridostigmine/neostigmine) to reduce bronchial secretions<ref name="Wendell"/>
**Exception: if patient is NOT intubated, continue home pyridostigmine—abrupt cessation can worsen crisis<ref name="emcrit"/>
**Restart pyridostigmine as patient approaches extubation
*Plasmapheresis (PLEX) — generally preferred in crisis for faster onset<ref name="emcrit"/>
**Usually improvement by 2nd–3rd session
**Effect lasts 15–20 days
**Contraindicated in sepsis, hemodynamic instability
**Requires central venous access
*[[IVIG]]
**0.4 g/kg/day for 5 days (total 2 g/kg)
**Effect lasts 30–45 days
**May take days to weeks for full effect
**Contraindicated in renal failure, hypercoagulability, IgA deficiency
*PLEX and IVIG are considered equivalent for exacerbations overall, but PLEX may have faster onset; choice depends on patient factors and local availability<ref>Gajdos P et al. Treatment of myasthenia gravis exacerbation with intravenous immunoglobulin. Arch Neurol. 2005;62:1689-1693.</ref>

====Corticosteroids in Crisis====
*Use with caution in the acute setting<ref name="emcrit"/>
**Steroid initiation can ''cause'' transient worsening (in ~50% of patients), typically 5–10 days after initiation
**Generally defer initiation until after PLEX/IVIG has been started and patient is stabilized
**If patient was previously on steroids, continue the same dose

===Outpatient / Non-Crisis Management===
''[[Pyridostigmine]] and [[neostigmine]] provide symptomatic relief but do not alter the course of crisis<ref name="Wendell"/>. Consider avoiding in ICU ventilated patients due to increased secretions.''
*[[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 (2–3 mg) by slow IV infusion
*[[Neostigmine]]
**0.5 mg IV
*[[Prednisolone]]: If symptomatic despite pyridostigmine. Monitor for diabetes mellitus.
**''Ocular myasthenia gravis''
***Start 5 mg on alternate days for three doses, increase by 5 mg every three doses until symptoms improve
***Maximum dose: 50 mg on alternate days (or 0.75 mg/kg/alternate day)
**''Generalized myasthenia gravis''
***Start 10 mg on alternate days for three doses, increase by 10 mg every three doses until symptoms improve
***Maximum dose: 100 mg alternate days (or 1.5 mg/kg)

==Disposition==
===Admit (ICU/Neuro ICU)===
*Any myasthenic crisis (respiratory failure or impending)
*FVC < 20 mL/kg or NIF weaker than −30 cmH₂O
*Rapidly declining serial respiratory parameters
*New-onset or worsening bulbar symptoms with aspiration risk
*Consideration for thymectomy if not previously done

===Admit (Floor/Stepdown)===
*MG exacerbation without respiratory failure but requiring IV medications, monitoring, or initiation of PLEX/IVIG
*New diagnosis of MG with significant symptoms

===Consider Discharge with Close Follow-up===
*Known MG with mild exacerbation, stable respiratory parameters, adequate oral intake, and reliable follow-up with neurology
*Ensure medication list has been reviewed and offending agents discontinued
*Patient education on signs of respiratory compromise and when to return

;Key Consult Points for Neurology:
*Current medication regimen (pyridostigmine dose, immunosuppressants)
*FVC, NIF, and trend over ED visit
*Suspected precipitant (infection, medication change, non-adherence)
*Prior crisis history and treatments (PLEX vs IVIG preference, thymectomy status)


==Medication Dosing==
===Myasthenic Crisis===
*{{MedicationDose|drug=IVIG|dose=0.4 g/kg/day x5 days (or 1 g/kg/day x2 days)|route=IV|context=Immunomodulatory therapy for crisis|indication=Myasthenia gravis|population=Adult|notes=Alternative to plasmapheresis; preferred if sepsis or hemodynamic instability}}

===Outpatient/Symptomatic===
*{{MedicationDose|drug=Pyridostigmine|dose=60 mg QID (titrate to effect)|route=PO|context=Acetylcholinesterase inhibitor (symptomatic)|indication=Myasthenia gravis|population=Adult|notes=Provides symptomatic relief; does not alter disease course}}

==See Also==
*[[Weakness]]
*[[Guillain-Barré syndrome]]
*[[Botulism]]
*[[Lambert-Eaton myasthenic syndrome]]
*[[Organophosphate toxicity]]

==References==
<references/>

[[Category:Neurology]]