ACUTE MYASTHENIC CRISIS

Under the guidance of : Presented by:

Dr. H.D. Meena Sir Dr. Harleen Bhatia
Dr. Ibraheem Sir PG Second Year
Dr. N.K. Maheshwari Sir Medicine Unit - 7
Dr. Manoj Sir
 Introduction
• Myasthenia Gravis is a chronic
autoimmune disorder.
• It affects transmission at the
neuromuscular junction.
• It is characterised by fluctuating
weakness of skeletal muscles.
• Friedrich Jolly first coined the term
myasthenia gravis.
Friedrich Jolly
 Epidemiology
• Prevalence (worldwide) – around 20/100,000.
• Sex – F:M = 3:2
• Age – Bimodal distribution :
• 2nd – 3rd decade – women affected more than men.
• 6th – 8th decade – men affected more than women.
Epidemiology Of Acute Myasthenic Crisis

10 to 20 percent patients
Annual risk : 2 to 3
experience at least one
percent.
myasthenic crisis.

Most myasthenic crisis First manifestation of

occur in the first few myasthenia gravis in 13
years. to 20 percent.
 Pathogenesis
Action potential at the presynaptic
nerve terminal.

Opening of voltage-dependent Ca 2+
Agrin binds to the channels.
complex formed by LRP4
and MuSK, causing
Release of acetylcholine and agrin into
AChR clustering.
the synaptic cleft.

Stabilization of NMJ Acetylcholine binds to AChRs, & Muscle

promotes sodium channel opening. contraction.
Normal Neuromuscular Junction
 Autoantibodies Involved In Myasthenia Gravis

A. Anti-AChR Antibodies :
• Blockade of receptor function: Antibodies bind to AChR and prevent acetylcholine
(ACh) from binding.
• Accelerated internalization and degradation: Crosslinking of AChRs by
antibodies leads to increased receptor turnover.
• Complement-mediated lysis: Antibody binding activates the complement cascade
→ damages the postsynaptic membrane → loss of folds → reduced surface area and
fewer receptors.
B. Anti-MuSK Antibodies (10–15% of patients) :
• MuSK is critical for the clustering and maintenance of AChRs.
• These are mostly IgG4 antibodies, which do not activate complement,
but disrupt receptor clustering via a different immune mechanism.

C. Anti-LRP4 Antibodies (rare) :

• LRP4 interacts with agrin and MuSK to maintain NMJ structure.
• Disruption impairs signal transduction needed for AChR maintenance.
 Role of Thymus
• Thymic hyperplasia in ~70% of AChR-positive MG patients.
• Thymoma found in ~ 10–15%.
• The thymus may provide the environment for abnormal T-cell
education and the development of autoreactive T cells that stimulate
antibody-producing B cells

Net Effect At Neuro Muscular Junction

• ↓ Number of functional AChRs.
• Flattening/loss of postsynaptic membrane folds.
• Inefficient transmission of nerve impulses → muscle weakness and
fatigability.
 Clinical Features

• Myasthenic weakness increases during repeated use or late in the day

and may improve following rest or sleep - Myasthenic Fatigue.
• More than 50% patients present with ocular symptoms of ptosis and/or
diplopia.
• About half will progress to generalized disease in 2 years.
• 15% patients will present with bulbar weakness, c/o dysarthria
dysphagia and fatigable chewing.
• Less than 5% will present with proximal limb muscle weakness.
Common presentations :
1. Ocular myasthenia :
• Most common presentation.
• Includes ptosis, diplopia, etc.
2. Generalised Myasthenia
3. Oculopharyngeal Myasthenia e.g. dysarthria, dysphagia.
4. Isolated muscle group myasthenia e.g. neck extensors (rare).

• Often patient can present in emergency department in Acute

Myasthenic crisis.
 Acute Myasthenic Crisis

Myasthenic crisis is a life-threatening exacerbation of myasthenia gravis that is

defined as worsening of myasthenic weakness (respiratory muscle and/or bulbar
muscle weakness) requiring intubation or noninvasive ventilation.
 Risk Factors

1. Greater disease severity at diagnosis.

2. Presence of thymoma.
3. Association with Anti-MuSK antibodies.
 Precipitants
 Infection (Most common cause)
 Surgical intervention
 Pregnancy
 Tapering of immune therapeutic medications
 Drugs
 Clinical Presentation
• Increasing generalized or bulbar weakness as a warning.
• Respiratory insufficiency out of proportion to limb or bulbar
weakness.
• In rare cases, respiratory failure is the only clinically overt
manifestation.
• Generalized weakness can mask the usual signs of respiratory
distress, such as accessory muscle use.
• Bulbar weakness may cause aspiration.
 Diagnosis
1. Simple bedside tests
2. Lab investigations
3. Electromyographic studies
 1. Bedside Tests :
A. Ice pack test :
• In patient with ptosis, a small cube of ice is placed over the eyelid for about 2
minutes.
• Improvement of the ptosis suggests a disorder of NMJ.
• Ptosis due to other conditions will not improve.
• Local cooling provides symptomatic relief possibly by slowing the kinetics of
acetylcholinesterase

Ptosis Before and After Ice Pack Test

B. Edrophonium (Tensilon test) :
• Edrophonium is a short acting Acetylcholine Esterase Inhibitor.
• 0.Iml of a 10 mg/ml edrophonium solution is administered as a test
• If no unwanted effects are noted (i.e. sinus bradycardia), the remainder
of the drug is injected.
• Evaluate weakness (i.e. ptosis and ophthalmoplegia) before and after.
• Rapid improvement of weakness over next 2 minutes is positive.
• False positive - occurs in ALS, poliomyelitis, etc.
• False negative - should consider long acting neostigmine that gives
more time for evaluation
• Require cardiac monitoring, ICU setup is needed.
 2. Laboratory Investigations :
A. Anti-acetylcholine receptor B. Anti MuSK antibodies :
antibodies : • Present in 40% of AChR-ab negative
• Most sensitive and highly specific. pts with generalized MG.
• Positive in 80%-90% of generalized & • Mostly in women, predominantly
50%-60% of patients with ocular MG. bulbar, facial , neck muscle
• The degree of "positivity" does not involvement.
correlate with the severity of disease. C. Anti-striated muscle antibodies :
• But fall during treatment correlates • Present in 30% of MG pts
with clinical improvement • Present in 84% of patients with
thymoma who are younger than 40
years
3. Electrodiagnostic Testing :

A. Repetitive nerve stimulation.

B. Single fiber electromyography (SFEMG)

• SFEMG is more sensitive than RNS in MG.

 Differential Diagnosis
1. Non-autoimmune congenital myasthenia
2. Lambert-Eaton myasthenic syndrome (LEMS)
3. Neurasthenia
4. Hyperthyroidism (Graves’ disease)
5. Botulism
6. Various types of myopathy
7. Treatment with immune checkpoint inhibitors for cancer
 Myasthenic Crisis Vs. Cholinergic Crisis
• Paradoxical weakening with excessive anticholinesterase medications
is called "cholinergic crisis."
• Cholinergic crisis is so rare that it should not be the presumed cause of
increasing weakness unless the doses taken are known to be
significantly high.
• The possibility that deterioration could be due cholinergic crisis is best
excluded by temporarily stopping anticholinesterase drugs.
 MYASTHENIC Vs CHOLINERGIC CRISIS

PARAMETERS MYASTHENIC CRISIS CHOLINERGIC CRISIS

Muscle weakness, dyspnea, sweating, agitation,

SHARED SYMPTOMS disorientation, drowsiness

PUPIL Normal Miosis

FASCICULATIONS None Present

HEART RATE Tachycardia Bradycardia

SKIN Cold and faint Warm and flushed

BRONCHIAL SECRETIONS Normal Increased

 Management Of Acute Myasthenic Crisis
• Admit to intensive care unit.
• Frequently monitor respiratory muscle strength.
• Electively intubate if impending respiratory failure suspected.
• Rapid therapy with plasma exchange or IVIG.
• Immunotherapy.
• Weaning from mechanical ventilation.
• Treat intercurrent infections.
• Stop Acetylcholine inhibitors.
 Maintenance Of Respiration

Symptoms and signs that should alert the clinician to respiratory

failure include :
• Dyspnea that worsens in supine position.
• Severe dysphagia with weak cough and difficulty clearing secretions.
• Low baseline vital capacity (VC)< 30mL/kg of ideal body weight, even
if the patient is breathing without distress.
• Signs of respiratory muscle weakness.
• Progressive respiratory acidosis despite therapy.
 Objective Indicators Of Muscle Weakness
( In Acute Myasthenic Crisis )

Maximal Expiratory Maximal Inspiratory

Vital Capacity (VC) Pressure (MIP)
Pressure (MEP)

• Measure of • For expiratory • For inspiratory muscle

Inspiratory and muscle strength strength.
expiratory muscle • Important for cough • MIP below one-third of
strength. and secretion normal (eg, 0 to -30 cmH
clearance O) predicts severe
respiratory muscle
weakness.
 On serial measurements, if:

MIP is less
VC falls negative than
below 15 -25 to -30
cm H20 (i.e.,
to 20 between 0 and
mL/kg -30 cm H20)

Indications for elective intubation.

• In general, we use assist control modes of volume-controlled
ventilation and low levels of positive end-expiratory pressure (PEEP)
with subsequent adjustments to achieve adequate gas exchange.

Role Of Non-invasive Ventilation

• Noninvasive ventilation (NIV) may be used in patients who are
expected to improve quickly, who have adequate cough and can
tolerate the mask.
 Supportive Respiratory Therapies

• Use of suction for secretions.

• Intermittent positive pressure breathing.
• Bronchodilators.
• Chest physiotherapy.
 Management of Myasthenia Gravis

Symptomatic • Acetylcholine Esterase Inhibitors

Short Term / Rapid Therapy • Plasmapheresis

• Immunoadsorption
• Intra Venous Immuno Globulins
Long Term Therapy / • 1st line : Glucocorticoids
Immunomodulators • 2nd line : Other e.g., Azathioprine,
cyclophosphamide, mycophenolate mofetil,
rituximab, eculizumab, etc.
Surgical Thymectomy
 Rapid Therapy
The main therapies for myasthenic crisis are :
• Plasma exchange, and
• IVIG.
A. Plasmapheresis :

• Mechanism : Removes autoantibodies from the circulation leading to reduction in

antibody levels.
• Indications : Myasthenic crisis, preoperative, pre-immunomodulator therapy.
• Method : Patients usually undergo a 2-week course of 5-6 exchanges (2-
3.5L each). Removed plasma is replaced with albumin and saline.
• Drawbacks :
• Beneficial clinical effect usually lasts only three to four weeks.
• Risk of infection, DVT, fluid imbalance and hypercoagulation.
Plasmapheresis
 B. Intra Venous Immuno Globulins :

• IVIG is the pooled immunoglobulins from thousands of donors and acts in

myasthenia via uncertain mechanisms.
• The total dose of IVIG is 2 g/kg, usually over two to five days.
• Spreading the IVIG dose over more days may be preferable in those who
have renal disease or heart failure and in older adults.
• Only few adverse effects, although headache, chills, and fever have been
reported.
• Other rare adverse events include aseptic meningitis and renal failure.
Choosing Rapid Therapy :

• Some evidence suggests that plasma exchange works more quickly

than IVIG and might shorten ICU length of stay.
• Others prefer IVIG because :
a) easier to administer
b) lower incidence of serious side effects
c) similar efficacy, compared with plasma exchange
 Immunotherapy
1. Glucocorticoids :
• For most patients with myasthenic crisis, start oral or nasogastric
glucocorticoids at moderate to high doses (e.g., prednisone 60 to 80
mg daily).
• The onset of benefit with glucocorticoids for myasthenia gravis
generally begins within two to three weeks and peaks after a mean of
5.5 months.
2. Second Line Therapies :
• These agents are typically used in MG for long term glucocorticoid-
sparing immunotherapy or when glucocorticoids are contraindicated.
• These include - azathioprine, mycophenolate mofetil, cyclosporine,
tacrolimus, and rituximab, eculizumab, etc.
• However, these agents may not provide immediate benefit during a
myasthenic crisis since many take weeks to months to take effect.
 Weaning From Ventilatory Support
• Daily spontaneous breathing trials (SBTs) is the preferred method of
weaning.
• An SBT refers to a patient spontaneously breathing through the
endotracheal tube (ETT) for a set period of time (usually 30 minutes to
two hours) either with or without a small amount of ventilator support.
• SBTs should only begin after the patient has resumed
anticholinesterase medications and started treatment with plasma
exchange or IVIG and the patient shows evidence of improving
respiratory muscle strength.
• When a patient successfully passes an SBT and no contraindication to
extubation is present, the ETT is typically removed.

• Weaning should proceed in a manner that prevents respiratory muscle

fatigue and allows for adequate rest between weaning trials.

• Close monitoring following extubation for early failure using VC and

MIP measurements to detect those who may need reintubation.

• Early tracheostomy is an option if prolonged intubation is anticipated.

Drugs Used In Myasthenia Gravis
 Complications Of Myasthenia Crisis
• Pneumonia, bronchitis, urinary tract infection, colitis
• Bacteraemia, and sepsis.
• Vascular complications : including deep vein thrombosis.
• Heart failure, acute myocardial infarction, arrhythmias,
• There are also several case reports of stress-induced cardiomyopathy
(takotsubo cardiomyopathy).
 Prognosis
• Myasthenic crisis is associated with an in-hospital mortality rate of
5 to 12 percent with modern therapies and specialized neurologic
intensive care.
• The most common causes of death are multiorgan failure due to
sepsis and respiratory failure despite maximal care.
 References
Bradley's Harrisons Current Medical
Neurology in principles of Diagnosis &
Clinical Practice Internal Medicine Treatment 2025
8th edition 21st edition