yasthenia Gravi

Pramodhiya Sanduni Perera

Grp 10
 Introduction
It is an acquired Autoimmune Disorder mediated by Antibodies
against the Acetylcholine-Receptor (AChR) at the Neuromuscular
Junction(NMJ).
It can be characterized by varying degrees of Weakness of the
Voluntary Muscles.
Simply, “A defect in the transmission of impulses from nerve
endings in the muscle fibers result in the development of skeletal
muscle weakness.”
Scientists have not yet been able to determine the exact cause of the
development of autoimmune diseases, in which the immune system of the
human body begins to produce antibodies against its own healthy cells.
Researchers believe the thymus could be one of the factors responsible for the
condition by producing antibodies to block acetylcholine (a neurotransmitter)
Furthermore, antibodies may block a receptor protein called tyrosine kinase.
Myasthenia gravis can exacerbate by i) viral infection, ii) severe stress and c
iii) certain types of medication like statins
Autoimmune form is not contagious and is not inherited.
The disease is most common in young women (under 40 years of age), but
can develop at any age, in addition, it affects men over 60 years of age.
 Types of Myasthenia Gravis
1) Congenital myasthenia – not autoimmune disease but a defect in the genes which result in abnormal
proteins, inherited as an autosomal recessive disease

2) Transient neonatal myasthenia gravis - relatively rare form of myasthenia gravis may develop in a child
immediately after birth. The reason for this are the mother's antibodies, suffering from a disease
transmitted through the placenta. It is necessary to distinguish the neonatal form of another type of
myasthenia gravis associated with a genetic mutation COLQ, and inherited

3) Juvenile myasthenia gravis - Develops in childhood and adolescence, usually girls, occurs in approximately
10% of Myasthenia gravis cases

4) Generalized myasthenia gravis - the most common form of the disease. The most characteristic
occurrence of the disease in women aged 20-30 and men aged 50-60 years

5) Ocular myasthenia gravis – around 10-15% of people only experience problems with the muscles that
control eye
 The Myasthenia Gravis Foundation of America Clinical Classification divides
MG into 5 main classes and several subclasses:
 Class I: Any ocular muscle weakness; may have weakness of eye closure; all other muscle strength is normal

 Class II: Mild weakness affecting other than ocular muscles; may also have ocular muscle weakness of any severity
 Class IIa: Predominantly affecting limb, axial muscles, or both; may also have lesser involvement of oropharyngeal muscles
 Class IIb: Predominantly affecting oropharyngeal, respiratory muscles, or both; may also have lesser or equal involvement of limb, axial
muscles, or both

 Class III: Moderate weakness affecting other than ocular muscles; may also have ocular muscle weakness of any severity
 Class IIIa: Predominantly affecting limb, axial muscles, or both; may also have lesser involvement of oropharyngeal muscles
 Class IIIb: Predominantly affecting oropharyngeal, respiratory muscles, or both; may also have lesser or equal involvement of limb, axial
muscles, or both

 Class IV: Severe weakness affecting other than ocular muscles; may also have ocular muscle weakness of any severity
 Class IVa: Predominantly affecting limb, axial muscles, or both; may also have lesser involvement of oropharyngeal muscles
 Class IVb: Predominantly affecting oropharyngeal, respiratory muscles, or both; may also have lesser or equal involvement of limb, axial
muscles, or both

 Class V: Defined by the need for intubation, with or without mechanical ventilation, except when used during routine postoperative
 Myasthenia Gravis Symptoms
1) Visual problems - ptosis (drooping of the upper eyelid), diplopia (double vision)
2) Weakness of the muscles of the upper and lower extremities.
- Patients often describe the following symptoms of myasthenia gravis:
Difficulties in the transition from a sitting to a standing position, as well as climbing the
stairs, the inability to raise his hands above his head, reduced tolerance to previously
routine physical activity
3) Violations of speech(Dyrathria) and swallowing(Dysphagia)
4) Extreme weakness of the neck muscles
5) Facial expressions (mask-like face), altered speech (nasal-sounding), difficulty chewing
and swallowing
 The symptoms of myasthenia gravis usually worsen when muscles are overly used during the day, while at
rest symptoms improve. However over time, progressive autoimmune disease gradually leads to significant
functional impairment (including secondary muscle atrophy), and can cause severe disability. Myasthenic
crisis, for example, occurs in severe, progressive forms of Myasthenia gravis, where the muscles that control
breathing are affected – this is a life-threatening situation and requires immediate attention.
Myasthenia Gravis Weakness
Why does Myasthenia Gravis causes Muscle Weakness.
 DIAGNOSIS
AChR Antibody Test
Positive in 85% of MG patients
Antibody level does NOT correlate with disease severity between patients
In an individual patient, changes in antibody levels do correlate

“Antibody negative” - Myasthenia Gravis

40-50% of patients with ocular MG
MuSK antibodies in 40% of AChR negative, generalized MG
“Low-affinity” antibodies in “double negatives” ??
Others
 Anti-lipoprotein-related protein 4 (LRP4) antibody
 Anti-agrin antibody
 Antistriational antibody (present in almost all patients with thymoma and MG, as well as in
half of MG patients with onset of MG at 50 years or older)
 Anti-cortactin antibody
 Plain chest radiographs may identify a thymoma as an anterior mediastinal mass
 Chest computed tomography is important to identify or rule out thymoma or thymic
enlargement in all cases of MG
 In strictly ocular MG, magnetic resonance imaging of the brain and orbit is helpful to
evaluate for mass lesions compressing the cranial nerves or a brainstem lesion that may
masquerade as ocular MG
 Electrodiagnostic studies (repetitive nerve stimulation and single-fiber electromyography)
 Obstacles
 Treatment of autoimmune disease occurs months or even years
after the onset of the disease process
 Autoimmune response becomes more complex as disease
progresses
 Benefit achieved by interfering with the immune system’s defense
mechanisms

Before After
 Myasthenia Gravis Treatment
Therapy for MG includes the following:
Symptomatic therapy
•Anticholinesterase (AchE) inhibitors
•Pyridostigmine is used for maintenance therapy
•Neostigmine is generally used only when pyridostigmine is unavailable
•Rapidly acting or short-term immunomodulating agents:
•Intravenous immune globulin (IVIg)
•Plasmapheresis
•Efgartigimod alfa is a human IgG1 antibody fragment that binds to neonatal Fc receptor (FcRn).

Long-term immunosuppression
•Prednisone is the most important immunosuppressant and provides short- and long-term benefit
•Azathioprine (AZA) is a first-line steroid-sparing agent
•Mycophenolate mofetil (MMF) is also a first-line steroid-sparing agent.
•Cyclosporine (CyA) is used as a steroid-sparing agent in patients who are intolerant to
azathioprine.
•Tacrolimus is used as a steroid-sparing agent in patients intolerant or unresponsive to AZA, MMF,
or CyA
•Methotrexate is used as a steroid-sparing agent and has similar efficacy and tolerability to AZA
•Rituximab may be an effective intervention in refractory MG, both for anti-AChR and anti-MuSK-
 Management of neonatal myasthenia gravis
 Transient neonatal myasthenia gravis (MG), in which MG is transmitted vertically from an affected mother to her fetus,
occurs in 10-30% of neonates born to myasthenic mothers. It may occur any time during the first 7-10 days of life, and
infants should be monitored closely for any signs of respiratory distress.

 The syndrome of neonatal myasthenia is caused by transplacental transfer of maternal autoantibodies against the
acetylcholine receptor (AChR).

 Infants affected by this condition are floppy at birth, and they display poor sucking, muscle tone, and respiratory
effort.

 They often require respiratory support and intravenous (IV) feeding, as well as monitoring in a neonatal ICU. As the
transferred maternal antibodies are metabolized over several weeks, symptoms abate and the infants develop normally.

 Treatment with cholinesterase inhibitors is effective in this age group as well. However, the dosage must be carefully
titrated to the clinical effect.
 Complications
Myasthenic Crisis
 A myasthenic crisis is an exacerbation of the myasthenia gravis process characterised by severe generalised
muscle weakness and respiratory and bulbar weakness that may result in respiratory failure.
 Treatment
i) Neostigmine methylsulfate -IM/IV
ii) Plasmapharesis and IVIG
iii) Endotracheal intubation and mechanical ventilation

Cholinergic Crisis
 Anticholinergic overmedication leads to cholinergic crisis. The symptoms are similar to myasthenic crisis.
 Treatment
i) Withdraw the anticholinergic medication and administer Atropine sulfate (antidote to
anticholinesterase drugs)
ii) Endotracheal intubation and mechanical ventilation.
Differential Diagnoses
 Amyotrophic Lateral Sclerosis in Physical Medicine and Rehabilitation
 Botulism
 Brainstem Gliomas
 Cavernous Sinus Syndromes
 Chronic Myelogenous Leukemia (CML)
 Congenital Myasthenic Syndrome
 Multiple Sclerosis
 Myocardial Infarction
 Neurosarcoidosis
 Organophosphate Toxicity
 Polymyositis
 Pulmonary Embolism (PE)
 Tetrodotoxin Toxicity
 Thyroid Ophthalmopathy
 Tick-Borne Disease
References
https://www.ninds.nih.gov/health-information/disorde
rs/myasthenia-gravis
https://emedicine.medscape.com/article/1171206-over
view

https://www.nhs.uk/conditions/myasthenia-gravis/trea
tment/
https://myasthenia.org/

Thank you!