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Myasthenia gravis

Updated : September 5, 2023





Background

The most prevalent condition impacting the NMJ (neuromuscular junction) of the skeletal musculature is MG (myasthenia gravis). The traditional presentation is a variable weakness, more pronounced in the late afternoon. Usually, the muscles in the throat, extremities, or eyes are involved.

Muscle weakness results from the diminished electric signal transmission across the NMJ caused by the production of antibodies, even against particular postsynaptic protein complexes. MG can be triggered by a numerous range of factors, including medication, vaccinations, operations, and infections. Several difficulties are brought on by MG.

Acute respiratory paralytic, known as an MG, which necessitates critical care, along with side effects from long usage of pharmaceuticals, such as secondary infections & lymphoproliferative tumors, are among them. For improved patient care & outcomes, a complete analysis of the pathophysiological processes, clinical symptoms, therapeutic options, & consequences of MG is required.

Epidemiology

Across the Us, there are 20 cases of myasthenia gravis per 100,000 people. It shows a feminine predominance in people under the age of 40 as well as a men predominance in people beyond the age of 50.

While child MG is relatively uncommon in western communities, it is common in Asian nations, affecting over 50 percent of children under the age of 15. They typically exhibit signs of weak extraocular muscles when they first appear.

Anatomy

Pathophysiology

The type of antibodies present affects the pathophysiologic processes in MG. IgG1 & IgG3 subclass antibodies are present in nicotinic acetylcholine receptors MG. In the postsynaptic membrane of skeletal muscles, they connect to the nicotinic acetylcholine receptors binding site & stimulate the complement system, causing the MAC (membrane attack complex) to form.

The receptors’ final breakdown is caused by MAC. They could work by boosting the endocytosis of the n-ACh ligand that is attached to an antibody or by functionally inhibiting the binding of ACh to its receptor. The antibodies in muscle-specific kinase MG & LPR4 MG are of the IgG4 subclass and lack the complement stimulating function.

They attach to the Agrin- lipoprotein-related protein 4- muscle-specific kinase receptor complex in the neuromuscular junction, which is primarily responsible for maintaining the neuromuscular junction, including the distribution and clustering of nicotinic acetylcholine receptors. The complex is inhibited, which results in fewer nicotinic acetylcholine receptors synapses.

Due to a deficiency in nicotinic acetylcholine receptors sensors, the ACh produced at the nerve ending cannot produce the postsynaptic potential necessary to trigger a nerve impulse in muscle, which results in the symptoms of muscular weakness. Because frequent usage of a specific muscle depletes the ACh storage in the NMJ, the weakening is more obvious.

Etiology

Similar to other autoimmune diseases, myasthenia gravis develops in people who are genetically predisposed to it. Conditions like infections, vaccinations, surgeries, and medications are examples of precipitating factors.

The n- AChR’s (nicotinic acetylcholine receptors), MuSK (muscle-specific kinase), & LPR4 (lipoprotein-related protein 4) are among the proteins that are frequently implicated in the NMJ and against which autoantibodies are formed. Thymomas are found in 10 percent or less of MG patients, and they are thought to contribute to the creation of autoantibodies.

  • Classification of Myasthenic Gravis:

MG can be divided into a number of subgroups based on the type of clinical characteristics or the kind of antibodies associated. Every group has a prognosis value since they respond to treatment differently:

  • Initial MG: Thymic hyperplasia and onset age of fewer than fifty years
  • Age of onset of more than fifty years with thymic atrophy defines delayed MG.
  • MG related to thymoma
  • Anti-MuSK autoantibodies in MG
  • Ophthalmic MG: Only periocular musculature can cause symptoms
  • MG lacking AChR & MuSK autoantibodies that can be detected

Genetics

Prognostic Factors

With the available treatment options, the majority of MG patients live close to normal lives. In myasthenic crises, the death rate used to range from 50 percent to 80 percent; today, it is only 4.47 percent.

The occasional muscle pain that causes aspiration pneumoniae and the negative drug side effects cause morbidity. A number of clinical & imaging/laboratory abnormalities in MG are also predictive.

Research has revealed the following: 

Second generalizations risk: Delayed age of onset, strong AChR antibodies titers, and the existence of thymoma are all related to this. According to a recent survey, the sort of clinical signs present at the time of admission can predict this probability.

In comparison to ptosis and diplopia separately, the risk of subsequent generalization is higher when both conditions are present from the outset. However, there is a reduction in risk with early use of immunosuppressive medications, including corticosteroids & azathioprine.

MG relapse risk: Prednisolone treatment, earlier thymectomy, and beginning age (40 years) are all linked to a lower likelihood of relapse. Patients with concurrent autoimmune illness and anti-Kv1.4 autoantibodies, however, exhibited a significant rate of relapse.

Clinical History

Physical Examination

Age group

Associated comorbidity

Associated activity

Acuity of presentation

Differential Diagnoses

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

Medication

 

pyridostigmine

600

mg

Tablet

Orally 

once a day

or 180-540 mg tablet ER orally once a day



pyridostigmine

600

mg

Tablet

Orally 

once a day

or 180-540 mg tablet ER orally once a day



ephedrine

25 mg-50 mg IM or subcutaneously or 5 mg-25 mg IV administered slowly repeat the dose in 5-10 minutes as needed



eculizumab 

Dosages 1-4: 900 mg Intravenous every week for the first four weeks, then
Dosage 5: 1200 mg Intravenous one week later, following
1200 mg Intravenous every two weeks thereafter
Give at or within two days of the recommended dosage regime time points



efgartigimod/hyaluronidase SC 

Administer 1008mg/112000 units subcutaneously every week for 4 weeks
Safety of starting future cycles before 50 days from the prior treatment cycle is not established.



Dose Adjustments

Renal Impairment
Mild (eGRF 60 to 89 mL/min/1.72 m2): No need to change the dose, but patients were exposed to 22% more of the drug than people with normal kidney function.
Moderate to severe (eGFR less than 59 mL/min/1.73 m2): Insufficient facts are provided.

Hepatic impairment
There hasn't been specific pharmacokinetic research done.
efgartigimod pharmacokinetics are not anticipated to be impacted by hepatic impairment.

edrophonium 

Initial dose-2mg
If there is a significant improvement after 90 seconds, the test is declared positive and can be discontinued. If the symptoms return, another 2 mg dosage may be given.
If there isn't a noticeable difference after the first dosage, you may give the patient another dose of 3 mg and watch them for another 90 seconds. If the test is negative, give them the last dose of 5 mg and watch them for another three to five minutes.

Assessment of myasthenia gravis therapy needs:
Administer 1 to 2 mg Intravenously given 1 hour after oral anticholinesterase dosage.
Intravenously administer 1 mg; repeat after 1 minute to differentiate cholinergic from myasthenic crises. If the patient is experiencing a cholinergic crisis, intubation, and controlled breathing may be necessary.
Nondepolarizing neuromuscular blockers are reversed.
Administer 0.5 to 1 mg/kg intravenously as the usual dosage.



huperzine A 

Indicated for Prevention of muscle weakness in myasthenia gravis
Administer 400 mcg intramuscularly every day



rozanolixizumab 


Indicated for Myasthenia Gravis
Body weight <50 kg
420 mg subcutaneously infused every week for six weeks
Body weight 50-100 kg
560 mg subcutaneously infused every week for six weeks
Body weight >100 kg
840 mg subcutaneously infused every week for six weeks
Depending on clinical evaluation, administer the subsequent therapy cycles



ipidacrine 

and myasthenic syndrome:

10-20 mg of ipidacrine (1/2 - 1 tablet) 1 to 3 times daily. The duration of treatment lasts for 1 to 2 months and can be repeated often with a 1 to 2 months gap between courses



neostigmine 

Administer dose of 0.5 to 2.5 mg subcutaneously/intramuscularly/ intravenously every day
Take a maintenance dose of 15 to 375 mg daily orally divided every 6 to 8 hours
Administer injectable containing 0.6 to 1.2 mg of atropine intravenously to counteract the muscarinic effects



ambenonium 

It is utilized to treat myasthenia gravis
Initial oral administration of 5 mg at intervals of 6–8 hours is the recommended dosage
The recommended daily dosage for maintenance is between 15 and 100 milligrams, with 40 mg being the usual quantity
The dosage may be raised to a maximum of 50–75 mg administered orally every 6–8 hours if necessary



Dose Adjustments

Limited data is available

tubocurarine 

Single IV dose of 4-33 mcg/kg is recommended



Dose Adjustments

Limited data is available

tubocurarine 

Single IV dose of 4-33 mcg/kg is recommended



Dose Adjustments

Limited data is available

efgartigimod alfa 

Patients with anti-acetylcholine receptor antibody positive.
Weight less than 120kg:10mg per kg iv every week for a month.
Weight more than 120 kg:1200mg iv every week for a month.



Dose Adjustments

Renal impairment-Insufficient data are available.

 

pyridostigmine

Age: children
7 mg/kg tablet orally 4 times a day
0.05-0.15 mg/kg solution IV/IM 4times a day
Age: Newborn:
5 mg tablet orally 4times a day
0.05-0.15 mg/kg IV/IM 4 times a day



ephedrine

Body surface area (BSA): 0.5 mg/kg or 16.7 mg/m2 IM or SC every 4-6 hours



edrophonium 

Infants-Administer 0.5mg intravenously
Children and Adults:
>34kg- Administer 2 mg. If there is no reaction after 45 seconds, the dose can be increased by 1 mg every 30 to 45 seconds, up to a maximum of 10 mg.
Administer 5mg intramuscularly.
<34 kgs- Administer 1 mg. If there is no reaction after 45 seconds, the dose can be increased by 1 mg every 30 to 45 seconds, up to a maximum of 10 mg.
Administer 2 mg intramuscularly.
Neutralization of nondepolarizing neuromuscular blockers
Usual dose: Administer 0.5 to 1 mg/kg/dose intravenously;
minimum dose: Administer 0.3 mg/kg/dose intravenously



neostigmine 

Use this with atropine drug
Administer dose of 0.01 to 0.04 mg/kg subcutaneously/intramuscularly/ intravenously every 2 to 3 hours as needed
Take a dose of 2 mg/kg daily orally divided every 4 hour and maximum dose up to 375 mg in a day



ambenonium 

It is utilized to treat myasthenia gravis
The first dose should be divided and taken orally every 6 to 8 hours at a rate of 0.3 mg/kg/day
1.5 mg/kg/day, split and administered orally every 6–8 hours, is the recommended dosage for maintenance



 

Media Gallary

References

https://www.ncbi.nlm.nih.gov/books/NBK559331/

Myasthenia gravis

Updated : September 5, 2023




The most prevalent condition impacting the NMJ (neuromuscular junction) of the skeletal musculature is MG (myasthenia gravis). The traditional presentation is a variable weakness, more pronounced in the late afternoon. Usually, the muscles in the throat, extremities, or eyes are involved.

Muscle weakness results from the diminished electric signal transmission across the NMJ caused by the production of antibodies, even against particular postsynaptic protein complexes. MG can be triggered by a numerous range of factors, including medication, vaccinations, operations, and infections. Several difficulties are brought on by MG.

Acute respiratory paralytic, known as an MG, which necessitates critical care, along with side effects from long usage of pharmaceuticals, such as secondary infections & lymphoproliferative tumors, are among them. For improved patient care & outcomes, a complete analysis of the pathophysiological processes, clinical symptoms, therapeutic options, & consequences of MG is required.

Across the Us, there are 20 cases of myasthenia gravis per 100,000 people. It shows a feminine predominance in people under the age of 40 as well as a men predominance in people beyond the age of 50.

While child MG is relatively uncommon in western communities, it is common in Asian nations, affecting over 50 percent of children under the age of 15. They typically exhibit signs of weak extraocular muscles when they first appear.

The type of antibodies present affects the pathophysiologic processes in MG. IgG1 & IgG3 subclass antibodies are present in nicotinic acetylcholine receptors MG. In the postsynaptic membrane of skeletal muscles, they connect to the nicotinic acetylcholine receptors binding site & stimulate the complement system, causing the MAC (membrane attack complex) to form.

The receptors’ final breakdown is caused by MAC. They could work by boosting the endocytosis of the n-ACh ligand that is attached to an antibody or by functionally inhibiting the binding of ACh to its receptor. The antibodies in muscle-specific kinase MG & LPR4 MG are of the IgG4 subclass and lack the complement stimulating function.

They attach to the Agrin- lipoprotein-related protein 4- muscle-specific kinase receptor complex in the neuromuscular junction, which is primarily responsible for maintaining the neuromuscular junction, including the distribution and clustering of nicotinic acetylcholine receptors. The complex is inhibited, which results in fewer nicotinic acetylcholine receptors synapses.

Due to a deficiency in nicotinic acetylcholine receptors sensors, the ACh produced at the nerve ending cannot produce the postsynaptic potential necessary to trigger a nerve impulse in muscle, which results in the symptoms of muscular weakness. Because frequent usage of a specific muscle depletes the ACh storage in the NMJ, the weakening is more obvious.

Similar to other autoimmune diseases, myasthenia gravis develops in people who are genetically predisposed to it. Conditions like infections, vaccinations, surgeries, and medications are examples of precipitating factors.

The n- AChR’s (nicotinic acetylcholine receptors), MuSK (muscle-specific kinase), & LPR4 (lipoprotein-related protein 4) are among the proteins that are frequently implicated in the NMJ and against which autoantibodies are formed. Thymomas are found in 10 percent or less of MG patients, and they are thought to contribute to the creation of autoantibodies.

  • Classification of Myasthenic Gravis:

MG can be divided into a number of subgroups based on the type of clinical characteristics or the kind of antibodies associated. Every group has a prognosis value since they respond to treatment differently:

  • Initial MG: Thymic hyperplasia and onset age of fewer than fifty years
  • Age of onset of more than fifty years with thymic atrophy defines delayed MG.
  • MG related to thymoma
  • Anti-MuSK autoantibodies in MG
  • Ophthalmic MG: Only periocular musculature can cause symptoms
  • MG lacking AChR & MuSK autoantibodies that can be detected

With the available treatment options, the majority of MG patients live close to normal lives. In myasthenic crises, the death rate used to range from 50 percent to 80 percent; today, it is only 4.47 percent.

The occasional muscle pain that causes aspiration pneumoniae and the negative drug side effects cause morbidity. A number of clinical & imaging/laboratory abnormalities in MG are also predictive.

Research has revealed the following: 

Second generalizations risk: Delayed age of onset, strong AChR antibodies titers, and the existence of thymoma are all related to this. According to a recent survey, the sort of clinical signs present at the time of admission can predict this probability.

In comparison to ptosis and diplopia separately, the risk of subsequent generalization is higher when both conditions are present from the outset. However, there is a reduction in risk with early use of immunosuppressive medications, including corticosteroids & azathioprine.

MG relapse risk: Prednisolone treatment, earlier thymectomy, and beginning age (40 years) are all linked to a lower likelihood of relapse. Patients with concurrent autoimmune illness and anti-Kv1.4 autoantibodies, however, exhibited a significant rate of relapse.

pyridostigmine

600

mg

Tablet

Orally 

once a day

or 180-540 mg tablet ER orally once a day



pyridostigmine

600

mg

Tablet

Orally 

once a day

or 180-540 mg tablet ER orally once a day



ephedrine

25 mg-50 mg IM or subcutaneously or 5 mg-25 mg IV administered slowly repeat the dose in 5-10 minutes as needed



eculizumab 

Dosages 1-4: 900 mg Intravenous every week for the first four weeks, then
Dosage 5: 1200 mg Intravenous one week later, following
1200 mg Intravenous every two weeks thereafter
Give at or within two days of the recommended dosage regime time points



efgartigimod/hyaluronidase SC 

Administer 1008mg/112000 units subcutaneously every week for 4 weeks
Safety of starting future cycles before 50 days from the prior treatment cycle is not established.



Dose Adjustments

Renal Impairment
Mild (eGRF 60 to 89 mL/min/1.72 m2): No need to change the dose, but patients were exposed to 22% more of the drug than people with normal kidney function.
Moderate to severe (eGFR less than 59 mL/min/1.73 m2): Insufficient facts are provided.

Hepatic impairment
There hasn't been specific pharmacokinetic research done.
efgartigimod pharmacokinetics are not anticipated to be impacted by hepatic impairment.

edrophonium 

Initial dose-2mg
If there is a significant improvement after 90 seconds, the test is declared positive and can be discontinued. If the symptoms return, another 2 mg dosage may be given.
If there isn't a noticeable difference after the first dosage, you may give the patient another dose of 3 mg and watch them for another 90 seconds. If the test is negative, give them the last dose of 5 mg and watch them for another three to five minutes.

Assessment of myasthenia gravis therapy needs:
Administer 1 to 2 mg Intravenously given 1 hour after oral anticholinesterase dosage.
Intravenously administer 1 mg; repeat after 1 minute to differentiate cholinergic from myasthenic crises. If the patient is experiencing a cholinergic crisis, intubation, and controlled breathing may be necessary.
Nondepolarizing neuromuscular blockers are reversed.
Administer 0.5 to 1 mg/kg intravenously as the usual dosage.



huperzine A 

Indicated for Prevention of muscle weakness in myasthenia gravis
Administer 400 mcg intramuscularly every day



rozanolixizumab 


Indicated for Myasthenia Gravis
Body weight <50 kg
420 mg subcutaneously infused every week for six weeks
Body weight 50-100 kg
560 mg subcutaneously infused every week for six weeks
Body weight >100 kg
840 mg subcutaneously infused every week for six weeks
Depending on clinical evaluation, administer the subsequent therapy cycles



ipidacrine 

and myasthenic syndrome:

10-20 mg of ipidacrine (1/2 - 1 tablet) 1 to 3 times daily. The duration of treatment lasts for 1 to 2 months and can be repeated often with a 1 to 2 months gap between courses



neostigmine 

Administer dose of 0.5 to 2.5 mg subcutaneously/intramuscularly/ intravenously every day
Take a maintenance dose of 15 to 375 mg daily orally divided every 6 to 8 hours
Administer injectable containing 0.6 to 1.2 mg of atropine intravenously to counteract the muscarinic effects



ambenonium 

It is utilized to treat myasthenia gravis
Initial oral administration of 5 mg at intervals of 6–8 hours is the recommended dosage
The recommended daily dosage for maintenance is between 15 and 100 milligrams, with 40 mg being the usual quantity
The dosage may be raised to a maximum of 50–75 mg administered orally every 6–8 hours if necessary



Dose Adjustments

Limited data is available

tubocurarine 

Single IV dose of 4-33 mcg/kg is recommended



Dose Adjustments

Limited data is available

tubocurarine 

Single IV dose of 4-33 mcg/kg is recommended



Dose Adjustments

Limited data is available

efgartigimod alfa 

Patients with anti-acetylcholine receptor antibody positive.
Weight less than 120kg:10mg per kg iv every week for a month.
Weight more than 120 kg:1200mg iv every week for a month.



Dose Adjustments

Renal impairment-Insufficient data are available.

pyridostigmine

Age: children
7 mg/kg tablet orally 4 times a day
0.05-0.15 mg/kg solution IV/IM 4times a day
Age: Newborn:
5 mg tablet orally 4times a day
0.05-0.15 mg/kg IV/IM 4 times a day



ephedrine

Body surface area (BSA): 0.5 mg/kg or 16.7 mg/m2 IM or SC every 4-6 hours



edrophonium 

Infants-Administer 0.5mg intravenously
Children and Adults:
>34kg- Administer 2 mg. If there is no reaction after 45 seconds, the dose can be increased by 1 mg every 30 to 45 seconds, up to a maximum of 10 mg.
Administer 5mg intramuscularly.
<34 kgs- Administer 1 mg. If there is no reaction after 45 seconds, the dose can be increased by 1 mg every 30 to 45 seconds, up to a maximum of 10 mg.
Administer 2 mg intramuscularly.
Neutralization of nondepolarizing neuromuscular blockers
Usual dose: Administer 0.5 to 1 mg/kg/dose intravenously;
minimum dose: Administer 0.3 mg/kg/dose intravenously



neostigmine 

Use this with atropine drug
Administer dose of 0.01 to 0.04 mg/kg subcutaneously/intramuscularly/ intravenously every 2 to 3 hours as needed
Take a dose of 2 mg/kg daily orally divided every 4 hour and maximum dose up to 375 mg in a day



ambenonium 

It is utilized to treat myasthenia gravis
The first dose should be divided and taken orally every 6 to 8 hours at a rate of 0.3 mg/kg/day
1.5 mg/kg/day, split and administered orally every 6–8 hours, is the recommended dosage for maintenance



https://www.ncbi.nlm.nih.gov/books/NBK559331/