Myasthenia gravis (MG) is a disease of skeletal muscle acetylcholine receptors. The neurotransmitter, acetylcholine (ACh) is unable to bind to the receptors (AChR) on the postsynaptic membrane to transmit the nerve impulse to muscle fibers to produce a muscle contraction.

1. Rajendra Dev Bhatt (PhD Scholar)
Asst. Professor
Clinical Biochemistry & Laboratory Medicine
Fellow: Translational Research (2018-2022) in CVD in Nepal, NHLBI & NIH, USA
Myasthenia Gravis

2. INTRODUCTION
 Myasthenia gravis (MG) is a disease of skeletal muscle
acetylcholine receptors. The neurotransmitter,
acetylcholine (ACh) is unable to bind to the receptors
(AChR) on the postsynaptic membrane to transmit the
nerve impulse to muscle fibers to produce a muscle
contraction.
 This is a relatively rare autoimmune disorder in which
antibodies form against acetylcholine nicotinic
postsynaptic receptors at the neuromuscular junction of
skeletal muscles.
 Causes problems with the nerves that communicate
with muscles. Affects the voluntary muscles of the body,
especially the eyes, mouth, throat, and limbs.

3.  Characterized by weakness and rapid fatigue of any
of the muscles under the voluntary control.
 The major cause of myasthenia gravis is a
breakdown in the normal communication between
nerves and muscles.
 No cure for myasthenia gravis, but treatment can
help relieve signs and symptoms – such as weakness
of arm or leg muscles, double vision, drooping
eyelids, and difficulties with speech, chewing,
swallowing and breathing.
 While myasthenia gravis can affect people of any
age from neonatal to above 60 and more common
in women younger than 40 and in men older than
60.

5. MG occurs at any age, involves either sex
and begins insidiously .
Second and third decades commonest age
of onset in women. Seventh and eighth
decades in men.
Patients complain of specific muscle
weakness, not generalized fatigue.

6. Ptosis or diplopia – initial symptoms in 65%
of patients.
Oropharyngeal muscle weakness – difficulty
in swallowing and talking initial symptoms
in 17% of patients.
Limb weakness presenting symptom in only
10% of cases

7. Characteristically, severity of weakness
fluctuates during the day, least in the
morning, worsening as the day progresses,
especially after prolonged use of affected
muscles.
In the era before corticosteroid treatment,
approximately one-third of patients
improved spontaneously, one third became
worse and one third died.

8. Ocular myasthenia – if progressing to
generalized MG usually does so within the first
two years after onset.
After 15 to 20 years, weakness becomes fixed.
The Burnt-Out-Stage is muscle atrophy.

9. The defect in neuromuscular transmission in
Myasthenia Gravis is due to The muscle end-
plate membrane is distorted.
Acetylcholine receptors are lost from the tips of
the folds, and antibodies attach to the
postsynaptic membrane.
Ach is released normally but absence of
receptors prevents the transmitter binding to the
muscle membrane

10. Acetylcholine Receptor Antibodies
• 75% of cases generalized MG have serum
antibodies (Ab) that bind to huma AChR.
• 54% with ocular MG have antibodies and
10% MG cases with no binding antibodies
have other antibodies.
• The AChR Ab varies widely among patients
with similar degrees of weakness. The
amount of Ab in the serum does not predict
the severity of the disease in individual
patients

11. • The Ab level may be low at onset on MG and
gradually become elevated in late stage.
• Worthwhile to repeat test when initial values
normal

12. The Presence of AChR Antibody is
not diagnostic for MG, also may
present in:
Systemic lupus erythematosus
Inflammatory neuropathy
Rheumatoid arthritis
In cases of thymoma without MG

13. Association of MG with other
diseases
• Hyperthyroidism 6%
• Rheumatoid arthritis, less than 2%
• Systemic lupus erythematosus 2%
• Diabetes mellitus 7%
• Non thymus neoplasm 3%

14. Thymus gland, a part of your immune system located in the
upper chest beneath the breastbone, may trigger or
maintain the production of antibodies that result in the
muscle weakness common in MG.

15. COMPLICATIONS
 Myasthenic crisis: A life-threatening condition,
which occurs when the muscles that control
breathing become too weak to do their jobs.
Emergency treatment is needed to provide
mechanical assistance with breathing.
 Thymus tumors: About 15 percent of the people
who have myasthenia gravis have a tumor in their
thymus, a gland under the breastbone that is
involved with the immune system. Most of these
tumors are noncancerous.

16. PARKINSON’S DISEASE
Parkinson's Disease is a medical disorder
whose primary symptom is excessive muscle
contraction. It is characterised by muscle
rigidity, a slowing of physical movements, and
in many cases tremor. At its worst it can affect
every system in the body.

17. • Parkinson’s disease was first described by
Dr. James Parkinson in 1817 as “shaking
palsy.”
• Parkinson’s disease is a slowly progressive
degenerative neurologic disease
characterized by: (TRABP)
• tremor,
• rigidity,
• akinesia (difficult in initiation movements)
• bradykinesia (sluggish neuromuscular
responsiveness),
• postural instability.

18. • It is one of the most common hypokinetic
disorders occurred after age 50 (with an
incidence of 100~150/100,000 population).
Onset generally occurs between ages 50 and
65.

19. BIOCHEMISTRY OF PARKINSON'S
DISEASE
• Dopamine is produced in the dopaminergic
neurons, one of dozens of cell types in the
brain.
• The term dopaminergic neuronal groups
refers to collections of neurons in the
central nervous system that have been
found to contain dopamine.
• The primary fault in Parkinson's disease is
that, whatever the cause, there is
insufficient dopamine.

22. Organophosphate (OP) Poisining
Organophosphate (OP) compounds are a diverse
group of chemicals used in both domestic and
industrial settings.
Organophosphorus (OP) compounds are usually
esters, amides or thiol derivatives of phosphonic
acid and form a large family of chemical agents.
A large group of chemicals used for protecting
crops, livestock, human health and as warfare
agents.

23. • The first OPs were synthesised in the 19th
century, used widely in the 1930s.
• The German chemist Gerhard Schrader
synthesised many commercial OPs of which
parathion is still used as a common pesticide.
• At the beginning of the Second World War the
development of OP substances switched to
highly toxic compounds employed as nerve
warfare agents, e.g. sarin, soman and tabun.

24. MECHANISM OF TOXICITY
• The toxicity of OPs depends on their chemical
structure, metabolism in target organism,
concentration (i.e. dose), mode of application
etc.
• Acute organophosphorus poisoning occurs
after dermal, respiratory, or oral exposure to
either low volatility pesticides (e.g.,
chlorpyrifos, dimethoate) or high volatility
nerve agents (e.g., sarin, tabun).

25. • Acetylcholinesterase inhibition by
organophosphorus pesticides or organophosphate
nerve agents can cause acute parasympathetic
system dysfunction, muscle weakness, seizures,
coma, and respiratory failure.

26. • Normally the cholinesterases rapidly
hydrolyze the neurotransmitter
acetylcholine into inactive fragments of
choline and acetic acid after the completion
of neurochemical transmission.
• In human beings, the two principal
cholinesterases are RBC, or true
cholinesterase (acetylcholinesterase), and
serum cholinesterase
(pseudocholinesterase).

27. • The major toxicity of organophosphate
compounds is the covalent binding of
phosphate radicals to the active sites of the
cholinesterases, transforming them into
enzymatically inert proteins.
• Organophosphates thus act as irreversible
cholinesterase inhibitors because the
organophosphate-cholinesterase bond is not
spontaneously reversible without
pharmacological intervention.

28. • The inhibition of cholinesterase activity leads
to the accumulation of acetylcholine at
synapses, causing overstimulation and
subsequent disruption of transmission in both
the central and peripheral nervous systems.

30. Thank You