Myasthenia gravis is an either autoimmune or congenital neuromuscular disease that leads to fluctuating muscle weakness and fatigue. In the most common cases, muscle weakness is caused by circulating antibodies that block acetylcholine receptors at the postsynaptic neuromuscular junction, inhibiting the excitatory effects of the neurotransmitter acetylcholine on nicotinic receptors at neuromuscular junctions. Alternatively, in a much rarer form, muscle weakness is caused by a genetic defect in some portion of the neuromuscular junction, that is inherited at birth as opposed to developing it through autoimmunity later in life or through passive transmission by the mother's immune system at birth.
2. Myasthenia gravis was first described by Thomas Willis in 1672.
An uncommon chronic autoimmune disorder, literally meaning
‘muscle weakness’.
Prevalence of MG is about 20 per 100,000 population in U.S
(Department of Neurology, University of Virginia, Charlottesville,
Virginia 22908, USA. lhp3n@virginia.edu)
A neuromuscular disease, defect in the transmission of nerve
impulse.
Women are affected more than men.
3. Pediatric myasthenia gravis
Neonatal group
Juvenile group
Adult myasthenia gravis
Group1: Ocular
Group2A: Mild generalized disease
Group2B: Moderately similar generalized disease
Group3: Acute fulminating disease
Group4: Late severe disease
4. Pediatric myasthenia gravis
Neonatal
Infants born of myasthenic mothers.
Self limited
Transplacental transfer of AchR
antibodies
Juvenile
Non-myasthenic mother
Tends to be permanent
Onset anytime from birth to puberty.
6. Group3: Acute fulminating disease
• Severe symptoms
• Thymoma relatively frequent
• High mortality
Group4: Late severe disease
• High incidence of thymoma
• Poor response to anticholinesterase
7. Autoantibodies block the receptors of acetylcholine in
neuromuscular junction.
Autoantibodies against MuSK protein- tyrosine kinase receptor
which helps in neuromuscular junction formation.
Thymoma- enlargement of thymus.
Rare hereditary form of myasthenia gravis.
9. Eye muscles
Drooping of one or both eyelids (ptosis).
Double vision (diplopia)
Face and throat muscles
Altered speaking(dyasarthria)
Difficulty swallowing(dysphagia)
Problems chewing
Limited facial expressions
Neck and limb muscles
Weakness in arms, legs, neck, fingers etc.
Weakness in the chest muscles sometimes
occurs. If this is severe, myasthenic crisis
may result .
10. Multiple sclerosis (MS)- MS effects central nervous system while
MG effect peripheral nervous system. Symptoms- problem in speech,
swallowing, visual problems etc.
Hyperthyroidism- Symptoms include bulging eyes, weight loss, rapid
heart rate, weakness in arms and thighs, muscle fatigue.
Myalgic encephalomyelitis (ME)- 'chronic fatigue syndrome’.
Symptoms- muscle weakness, joint pain, sore throat, cardiac and
respiratory problem.
Lambert-Eaton myasthenic syndrome- Symptoms are similar.
Double vision is less common. Symptoms also include impaired
sweating, difficulties in urination etc.
11. Ice Pack Test
Blood Test
Serology is performed to identify antibodies against
Achr and MuSK protein.
Single fibre electromyography
EMG measures the electrical activity travelling between
brain and muscles.
Endrophonium Test
Intravenous administration of endrophonium chloride.
12. Imaging
MRI and CT scan of chest is performed.
Pathological finding
Muscle biopsy is performed if the diagnosis remains in doubt and
clinical suspicion of MG persists.
13. Medications
Acetylcholinesterase inhibitors: Neostigmine and pyridostigmine
Corticosteroids: prednisone
Immunosuppressive drugs: azathioprine, cyclosporin,
mycophenolate mofetil, tacrolimus.
Therapy
Plasmapheresis can be used to remove the putative antibodies
from the circulation.
Intravenous immunoglobulins (IVIGs) can be used to bind the
circulating antibodies.
Surgery
Thymectomy
14. Pathophysiology of myasthenia gravis with antibodies to the acetylcholine
receptor, muscle-specific kinase and low-density lipoprotein receptor-related
protein 4.
Verschuuren JJ, Huijbers MG, Plomp JJ, Niks EH, Molenaar PC, Martinez-
Martinez P, Gomez AM, De Baets MH,Losen M,
DOI: 10.1016/j.autrev.2013.03.001
Abstract
Myasthenia gravis is caused by antibodies to the acetylcholine receptor, muscle-
specific kinase, low-density lipoprotein receptor-related protein 4, or possibly yet
unidentified antibodies. The mechanisms by which these antibodies interfere with
the function of postsynaptic proteins include complement activation, antigenic
modulation by crosslinking of the target proteins, competition with ligand binding
sites, or steric hindrance which inhibits conformational changes or binding to
associated proteins. Screening for auto-antibodies to different postsynaptic targets,
and also for low-affinity antibodies, is contributing to a more accurate diagnosis
of MG patients. Further studies into the specific pathophysiological pathways of
the several MG subforms might help to develop new, more antigen specific,
therapies.
15. Disturbed B cell subpopulations and increased plasma cells in
myasthenia gravis patients
Siegfried Kohler, Thomas Oskar Philipp Keil, Marc Swierzy, Sarah
Hoffmann DOI: 10.1016/j.jneuroim.2013.09.006.
Abstract
Whether there is a general perturbation of B and plasma cell subsets in
myasthenia gravis (MG) has not been investigated so far. Here we
performed a detailed flow cytometric analysis of blood and if available
thymic tissue in order to detect MG-specific and therapy-induced changes.
We observed significant differences in the distribution of B cell subsets in
MG patients, yet these were mainly attributable to medical treatment.
Furthermore MG is associated with significantly increased frequencies of
plasma cells that were especially activated in purely ocular disease
manifestation. In contrast to thymoma, B cell subset distribution in
hyperplastic thymus could be distinguished from peripheral blood,
however both tissues were not significantly enriched with plasma cells.
Thus B cell differentiation in general is not defective in MG, but modified
by therapy and enhanced frequencies of plasma cells can be detected in
MG patients.
16. An autoimmune neuromuscular disorder caused by auto
antibodies against AchR .
Myasthenia gravis is an immune-mediated post-synaptic
disorder of neuromuscular transmission, most commonly
presenting as oculobulbar and proximal muscle weakness
associated with easy fatigability.
The typical main symptom is weakness of muscles that gets
worse with activity and improves with rest.
Once diagnosed, proper treatment is necessary for living a
normal life.
17. BOOKS
Owen J.A, Punt J, Stranford S.A (Seventh edition,2013) Kuby
Immunology
Kenneth S. Saladin (Third edition) Anatomy & Physiology :The
unit of form and function
LINKS
http://www.medicinenet.com/myasthenia_gravis/article.htm
http://www.nlm.nih.gov/medlineplus/myastheniagravis.html
http://www.healthline.com/health/myasthenia-gravis
http://www.niams.nih.gov/Health_Info/myasthenia_gravis/
http://www.medicalnewstoday.com/info/myasthenia-gravis/