Myasthenia gravis: Difference between revisions

(Created page with "Harwood Nuss p.1002 Differential Diagnosis 1. Toxin Induced - Botulism - Tick Paralysis - Envenomation (coral snake, black widow spider), paralytic shellfish 2. Autoimm...")
 
(Strip excess bold)
 
(85 intermediate revisions by 18 users not shown)
Line 1: Line 1:
Harwood Nuss p.1002
==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>


Differential Diagnosis
===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)


1. Toxin Induced
====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)


- Botulism
===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


- Tick Paralysis
==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


- Envenomation (coral snake, black
===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)
|}


widow spider), paralytic shellfish
==Differential Diagnosis==
{{Weakness DDX}}


2. Autoimmune - Eaton Lambert
===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>


3. Drug-Induced - aminogly, dilantin
==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).]]


procainamide, chloroquine
===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>


4. Poisoning - Organophosphates
;'''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>


Carbamates
;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"/>


5. Miller Fisher Variant Guillen Barre
===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


6. Causes of oculomotor palsy - DM
===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)


MS, aneurysm.
===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]])


Pathophys
===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)


- thymus abnl in most - thymoma,
====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>


thymitis, B cells sensitized to Ach
====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


receptors here.
===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


Epi
===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


- mostly women in 20s
===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


- peak incid in men is 60-70s
;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)




History
==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}}


- pts report worse sxs as day progr
===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}}


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


- insidious onset, can develop over
==References==
<references/>


wks to months.
[[Category:Neurology]]
 
- precipitated by stress, preg, infec
 
 
Symptoms
 
- diplopia, ptosis (later in day)
 
- weakness in eye closure, swallowing
 
muscles of facial expression,
 
difficulty chewing, dysarthria, dys-
 
phagia.
 
 
Physical Exam
 
- Provocative tests - ptosis with pro-
 
longed upward gaze, hold arms up,
 
clench tongue blade, dysarthria w/
 
loud counting
 
- sensation, reflexes usually normal
 
- always eval tidal volume, FEV &
 
ability to handle secretions
 
 
Testing
 
1. Always test FEV, consider ABG
 
Look for infections (resp) or
 
meds, electrolyte problems that
 
may have induced problem.
 
2. Edrophonium - use caution in try-
 
ing to test for crisis vs. cholinergic
 
crisis
 
3. Ach receptor antibodies - found 90%
 
4. CT of thymus, TFTs, search for
 
other immun dz
 
 
Treatment
 
- Plasmapherisis or plasma exchenge
 
in acute setting
 
- Anticholinesterase agent such as
 
Pyridostigmine 60 mg tid
 
- Corticosteroids produce good results in >80% but are reserved for
 
those who don't respond to anti-
 
cholinesterases and thymectomy
 
due to adverse effects. Decreases
 
levels of antiAch receptor Ab. Also
 
may initially aggravate muscle
 
weakness so usually begun in hosp
 
& at low doses
 
 
Myasthenic Crisis vs. Cholinergic
 
1. Cholinergic - usually present w/
 
signs of cholinergic overactivity
 
(miosis, sweats, salivation, GI dis-
 
tress-musc) & cramps, fascicula-
 
tions (nicotinic)
 
2. Myasthenic - more common, caused by noncompliance, drug interaction, infection, stress
 
- aminoglycosides, flouroquinolones
 
clinda, sulfas, erythro, ampicillin
 
Dilantin, phenobarb, B blockers
 
Ca channel Blk, procainamide
 
steroids, lithium, phenothiazines
 
MSO4, benzos, antihistamines
 
 
VERY DANGEROUS & UNRELIALE to
 
use Tensilon Test to distinguish betw
 
the two.
 
 
OTHER NM TRANSMISSION D/O
 
1. Botulism - toxin binds to presyn
 
prevents AcH release. Wound may be benign in appearance
 
GI source - neuro sxs w/in 72 hrs of ingestion usually. Aticholinergic effects include dry mouth, mydriasis
 
ileus, urine retention then fluctuat-
 
ing but rapidly progressive weakness
 
- send cx blood, food, stool or wound
 
- only 33% of food borne source have
 
positive blood cx
 
- may actually see pos Tensilon test
 
in botulism.
 
Wound Botulism - high dose PCN &
 
debridement.
 
2. Eaton Lambert - rare, defect in
 
release of AcH from presynapse
 
Usually paraneoplastic (part. small
 
cell Ca of lung)
 
- Clinically proximal weakness of limb
 
muscles, hyporeflexia, dry mouth,
 
impotence.
 
- Extraocular & facial muscles usually
 
spared.
 
3. Tick Paralysis - acsending flaccid paralysis caused by neurotoxin
 
- block acH release
 
- late spring, summer in Rockies & NW
 
- female wood tick or common dog tick
 
- paralysis progresses over 1-2 days
 
to involve bulbar, extraocular muscles.
 
- Resp paralysis can follow
 
- Ataxia may be early finding
 
- normal sens exam usually
 
- DTRs decreased markedly as in GB
 
- fatal in 10% if tick not removed
 
- CHECK for ticks in someone you
 
think has Guillen Barre
 
 
TAKE HOME
 
- don't treat Myasthenic with meds
 
that may exacerbate weakness
 
- search for source of infection or
 
electrolyte problem w/ weakness
 
 
 
 
[[Category:Neuro]]

Latest revision as of 09:26, 22 March 2026

Epidemiology

  • Most common disorder of neuromuscular transmission; prevalence ~20 per 100,000[1]
  • Bimodal age distribution: women peak in 2nd–3rd decade; men peak in 6th–7th decade[2]
  • 15–20% of patients with MG will experience myasthenic crisis, most commonly within the first 2 years[3]
  • ~20% of myasthenic crises are the initial presentation of MG[4]

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[5]

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[6]

Usually Well-tolerated, but Occasionally Associated

Precipitants of Myasthenic Crisis

Identify and treat the trigger in every crisis presentation:[5][4]

  • 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

Cranial nerve palsy and ptosis in a patient with myasthenia gravis
  • Muscle weakness
  • Ocular weakness (presenting symptom in ~50% of patients; eventually involved in >80%)
  • Symptoms worsen with repetitive use and as the day progresses[8]
  • 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 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

Myasthenia Gravis vs Lambert-Eaton Myasthenic Syndrome

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

[2][9]

Evaluation

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

ED Workup

Always evaluate respiratory function serially (q2hr or more frequently if deteriorating):[10][3]

  • 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)[11]
Intubation Triggers (Consider when ANY of the following present):
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

[12]

Do NOT rely on SpO₂ alone—MG causes hypercarbic respiratory failure; hypoxemia is a late finding that may suggest atelectasis or aspiration[4]

Bedside Tests

  • Prolonged upward gaze test[13]
    • 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:[14]

  • 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

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)[4]

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[3]
    • 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[3]
    • 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)[15][16]
      • MG patients are extremely sensitive to nondepolarizing agents—standard doses can cause prolonged paralysis (case reports of >4 hours)[16]
      • Sugammadex can reverse rocuronium/vecuronium (dose 2–4 mg/kg, or 16 mg/kg for immediate reversal); have available[17]
    • If depolarizing agents must be used:
      • Succinylcholine 1.5–2.0 mg/kg (roughly double the standard dose)[18]
      • 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)[18]
      • 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[3]
    • Exception: if patient is NOT intubated, continue home pyridostigmine—abrupt cessation can worsen crisis[4]
    • Restart pyridostigmine as patient approaches extubation
  • Plasmapheresis (PLEX) — generally preferred in crisis for faster onset[4]
    • 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[19]

Corticosteroids in Crisis

  • Use with caution in the acute setting[4]
    • 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[3]. 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

  • IVIG 0.4 g/kg/day x5 days (or 1 g/kg/day x2 days) IV — Alternative to plasmapheresis; preferred if sepsis or hemodynamic instability

Outpatient/Symptomatic

  • Pyridostigmine 60 mg QID (titrate to effect) PO — Provides symptomatic relief; does not alter disease course

See Also

References

  1. ↑ Suresh AB, Asuncion RMD. Myasthenia Gravis. StatPearls. 2023.
  2. ↑ 2.0 2.1 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.
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 Wendell LC and Levine JM. Myasthenic Crisis. Neurohospitalist. 2011 Jan; 1(1): 16–22.
  4. ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 EMCrit - Myasthenia gravis & myasthenic crisis. https://emcrit.org/ibcc/myasthenia/
  5. ↑ 5.0 5.1 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.
  6. ↑ https://neurology.uams.edu/wp-content/uploads/sites/49/2018/03/Drugs-that-may-worsen-Myasthenia-Gravis.pdf
  7. ↑ UpToDate Clinical manifestations of myasthenia gravis May 2016
  8. ↑ Tintinalli's Emergency Medicine: A Comprehensive Study Guide, 7e (2010), Chapter 167. Chronic Neurologic Disorders
  9. ↑ 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.
  10. ↑ Emergency Medicine Practice -- Weakness: A systemic approach to acute non-traumatic neurologic and neuromuscular causes Dec 2002
  11. ↑ Management of Myasthenia Crisis in the ED — NUEM Blog. https://www.nuemblog.com/blog/myasthenia 2019.
  12. ↑ 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
  13. ↑ Toyka KV. Ptosis in myasthenia gravis: Extended fatigue and recovery bedside test. Neurology Oct 2006, 67(8):1524.
  14. ↑ Myasthenia gravis: Association of British Neurologists' management guidelines [1]
  15. ↑ Poremba M. UMEM Educational Pearls: Myasthenia Gravis and Neuromuscular Blockers. University of Maryland. 2023.
  16. ↑ 16.0 16.1 Billups K et al. Extreme Paralysis Following Rocuronium Administration in a Myasthenia Gravis Patient. West J Emerg Med. 2023;24(4):735-738.
  17. ↑ StatPearls: Anesthesia for Patients With Myasthenia Gravis. 2025.
  18. ↑ 18.0 18.1 Levitan R. Safety of succinylcholine in myasthenia gravis. Ann Emerg Med. 2005;45(2):225-226.
  19. ↑ Gajdos P et al. Treatment of myasthenia gravis exacerbation with intravenous immunoglobulin. Arch Neurol. 2005;62:1689-1693.
Retrieved from "https://www.wikem.org/w/index.php?title=Myasthenia_gravis&oldid=389104"