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Myasthenia gravis
1.
2.
INTRODUCTION
GROSS ANATOMY OF ARM
HISTO-ANATOMY OF ARM
PHYSIO OF SKELETAL MUSCLE
SIGNS & SYMPTOMS
PATHOPHYSIOLOGY OF MG
DIAGNOSIS
MANAGEMENT
PROGNOSIS
REFERENCES
3. The
word MYASTHENIA GRAVIS is derived from
Greek & Latin
Greek: myasthenia: muscle weakness
Latin:gravis: serious
4. Mg
is an autoimmune neuromuscular disease,
leading to fluctuating muscle weakness &
fatigue
5. In
MG 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 throughout
neuromuscular junctions.
6. Myasthenia
gravis:
It affects people of any age, it's
more common in women younger than 40 and
in men older than 60
The disease incidence is 3–30 cases per
million per year and rising as a result of
increased awareness.
7. NEONATAL
MYASTHENIA:
If a woman with myasthenia gravis
gives birth, the baby may have some
temporary, and potentially life-threatening,
muscle weakness (neonatal myasthenia)
because of antibodies that have transferred
from the mother's bloodstream.
8. Typically,
during the baby's first weeks of
life, the antibodies are cleared from the
baby's circulation and the baby develops
normal muscle tone and strength.
11. Origin
•
•
short head: coracoid process of the scapula
long head: supraglenoid tubercle of the scapula
Insertion
•
tuberosity of the radius
Action
flexes the forearm, flexes arm (long head), supinates
13. Origin
•
anterior surface of the lower one-half of the
humerus and the associated intermuscular septa
Insertion
•
coronoid process of the ulna
Action
flexes the elbow, assists in pronation &
supination
17. Triceps Brachii
Origin
•long head: infraglenoid tubercle of the scapula
•lateral head: posterolateral humerus & lateral
intermuscular septum
•medial head: posteromedial surface of the inferior 1/2 of
the humerus
Insertion
•olecranon process of the ulna
Action
extends the forearm, the long head extends and adducts
arm
19. Anconeus
Origin
•lateral epicondyle of the humerus
Insertion
•lateral side of the olecranon and
the upper one-fourth of the ulna
Action
•extends the forearm
21.
Nerves that supply the arm are branches of the
brachial plexus.
There are five main nerves from the brachial
plexus, these nerves are;
Axillary
Ulnar
Median
Musculocutaneous
Radial
22.
However, there are two main nerves that supply
the Arm. These nerves are;
Musculocutaneous nerve
Radial Nerve
23. It’s a mixed nerve , it has both sensory and
motor function.
Its root value is C5,C6,C7
It arises from the lateral cord
The musculocutaneous nerve leaves the brachial
plexus sheath high in the axilla at the level of
the lower border of the teres major muscle and
passes into the coracobrachialis muscle.
It innervates the muscles in the flexor
compartment of the arm and carries sensation
from the lateral (radial) side of the forearm
Its responsible for the biceps jerk (C5,C6)
(Stephen et al, 2013)
25.
It is derived from the posterior cord
Its root value is C5,C6,C7,C8,C9,T1
The nerve passes out of the axilla posteriorly
and supplies branches to the long and medial
heads of the triceps brachii.
It has both sensory and motor function
26.
Sensory; Innervates most of the skin of the
posterior side of forearm, and the dorsal surface
of the lateral side of the palm, and lateral three
and a half digits
Motor; Innervates the triceps brachii,
responsible for extension at the elbow.
Innervates the majority of the extensor muscles
in the forearm, responsible for extension of wrist
and fingers and supination of the forearm
(Oliver, 2013)
28. A skeletal muscle consists of muscle
fibres held together by connective
tissue (collagenous fibres).(Hill,2013)
Skeletal muscle constitutes the muscle
that is attached to the skeleton and
controls motor movements and posture.
There are a few instances where this type
of muscle is restricted to soft tissues: the
tongue, pharynx, diaphragm and upper
part of the esophagus
31. Skeletal
muscle fibres (cells) are actually a
multinucleated syncytium formed by the fusion of
individual small muscle cells(myoblasts), during
development. They’re filled with longitudinally arrayed
subunits(myofibrils). The myofibrils are made up of
the myofilaments myosin (thick filaments)
and actin (thin filaments).
The striations reflect the arrangement of actin and
myosin filaments and support structures. The individual
contractile units are called sarcomeres.
A myofibril consists of many sarcomeres arranged end to
end. The entire muscle exhibits cross-striations because
sarcomeres in adjacent myofibrils and muscle fibers are in
register
32. .
The most obvious feature in longitudinal
sections of skeletal muscle is the alternating
pattern of dark and light bands, A
(anisotropic) and I (isotropic) band.
The I band is bisected by a dense zone
called the Z line, to which the thin filaments
of the I band are attached. The nuclei are
located peripherally, immediately under the
plasma membrane (sarcolemma),(mark,2013)
33. .
Individual muscle fibres are surrounded by
a delicate layer of reticular
fibres(endomysium). Groups of fibres are
bundled into fascicles by a thicker CT
layer(perimysium). The collection of
fascicles that constitutes one muscle is
surrounded by a sheath of dense
CT(epimysium) which continues into the
tendon. Blood vessels and nerves are found
in the CT associated with muscle. The
endomysium contains only capillaries and the
finest neuronal branches.(mark,2013)
34. Extremely
elongated
Unbranched cylindrical cells
Each muscle cell is called muscle fibre
Numerous flattened nuclei located just
beneath the sarcolemma
Shows regular striations .(Hill,2013)
Sarcolemma – plasma membrane of muscle
cell
Sarcoplasm (cytoplasm of muscle cell) myofibrils,mitochondria, T-tubules,
sarcoplasmic ( smooth endoplasmic)
reticulum.(HILL,2013)
Sarcosomes – mitochondria of muscles
35. The
structural subunit of the muscle fibre
is the myofibril.
Myofilaments are individual filamentous
polymers of myosin ( thick filaments) and
actin ( thin filaments ) and its associated
proteins.(Hill,2013)
Thin filaments – composed primarily of the
protein actin .
each thin filament of fibrous actin ( Factin) is a polymer formed from globular
actin molecules ( G- actin)
Tropomyosin , troponin also present.
Thick filaments – composed of protein
myosin.(Hill,2013)
Myoglobin – is oxygen- binding protein.
Numerous in red muscle.)
37. Dark
bands / A bands – anisotropic i.e.
birefringent in polarised light.
Light band / I bands – isotropic i.e. do not
alter the plane of light. (Hill,2013)
The functional subunit of the myofibril is
the sarcomere , the segment of the
myofibril b/w Light I band is bisected by a
dense line Z line / Z disk.
Dark A band is bisected by a light region
called H band.
Bisecting the light H band is a narrow dense
line called M line(Hill,2013)
40. Autoimmune
disease
Extreme muscle
weakness(Leite et.al,
2008)
In this disease , Ach
receptors on
sarcolemma are
blocked by antibodies
to the receptor
protein.(Leite
et.al,2008)
No. of receptor sites are
reduced – weakening of
muscle fiber response
to nerve stimuli
41.
42. Under
voluntary control.
Each skeletal muscle is innervated by a branch of
motorneurons.
Action potentials are propogated along motorneurons,
leading to release of Ach at the nuromuscular
junction,depolarisation of the motor end plate and
initiation of action potential in the muscle fiber.
Events occuring between action potential and
contraction in muscle fiber are called excitationcontraction coupling(mechanism that translates the
muscle action potentialinto the production of
tension).
43.
44.
45.
46.
47. Step 1
A nerve impulse travels down an axon and
causes the release of acetylcholinein the
neuro muscular junction. Acetylecholine
causes the impulse to spread across the
surface of the sarcolemma.
48. Depolarisation of sarcolemma-influx of Na+
and efflux of k+. The nerve impulse enters
the T Tubules and Sarcoplasmic Reticulum,
stimulating the release of calcium ions.
49. Release of Ca ions into actin filaments.
Calcium ions combine with Troponin, shifting
troponin and exposing the myosin binding
sites on the actin.
50. Head of myosin binds with ATP and makes way
for forming cross- bridges to actin
filament.In this process ATP breaks down to
ADP + Pi. The released energy activates the
myosin cross bridges and results in the sliding
of thin actin myofilament past the thick
myosin myofilaments.
51. The sliding of the myofilaments draws the Z
lines towards each other, the sarcomere
shortens, the muscle fibers contract and
therefore muscle contracts.
52. ACh is inactivated by Acetylcholinesterase, inhibit the
nerve impulse conduction across the sarcolemma.
Nerve impulse is inhibited, calcium ions are actively
transported back into the Sarcoplasmic Reticulum,
using the energy from the earlier ATP breakdown.
The low calcium concentration causes the myosin cross
bridges to separate from the thin actin myofilaments
and the actin myofilaments return to their relaxed
position.
57. Myasthenia
gravis is caused by a problem
with the transmission of nerve signals to
the muscles.
It is an autoimmune condition, which means
the body's immune system attacks its own
tissues.
58.
59.
60.
61.
62. Genetic
factors also may be associated with
myasthenia gravis.
Rarely, mothers with myasthenia gravis have
children who are born with myasthenia gravis
(neonatal myasthenia gravis). If treated
promptly, children generally recover within
two months after birth.
63.
64. Diagnosis
MG can be a difficult diagnosis, as the symptoms
can be subtle and hard to distinguish from both
normal variants and other neurological disorders
A thorough physical examination can reveal easy
fatigability
A good response to medication can also be
considered a sign of autoimmune pathology.
65. Physical examination
Muscle fatigability can be tested for many muscles. A thorough
investigation includes:
•looking upward and sidewards for 30 seconds: ptosis
(DROOPING OF EYELIDS) and diplopia(DOUBLE VISION)
•looking at the feet while lying on the back for 60 seconds
•keeping the arms stretched forward for 60 seconds
•ten deep knee bends
•walking 30 steps on both the toes and the heels
66. •five sit-ups, lying down and sitting up completely
•"Peek sign": after complete initial apposition of the
lid margins, they quickly (within 30 seconds) start
to separate and the sclera starts to show
67. Blood test
If the diagnosis is suspected, serology can be performed in
a blood test to identify certain antibodies:
•One test is for antibodies against the acetylcholine receptor]The
test has a reasonable sensitivity of 80–96%, but in MG limited to
the eye muscles (ocular myasthenia) the sensitivity falls to 50%
(negative in up to 50% who have MG).
•A proportion of the patients without antibodies against the
acetylcholine receptor have antibodies against the Muscle protein.
68. •In specific situations (decreased reflexes which
increase on facilitation, coexisting autonomic features,
suspected presence of neoplasm, especially of the
lung, presence of increment or facilitation on repetitive
EMG (electromyography) testing) testing is performed
for
•Lambert-Eaton syndrome, in which other antibodies
(against a voltage-gated calcium channel) can be
found.
69. Electrodiagnostics
Muscle fibers of patients with MG are easily fatigued,
and thus do not respond as well as muscles in healthy
individuals to repeated stimulation.
By stimulating a nerve-muscle motor unit with short
sequences of rapid, regular electrical impulses, before
and after exercising the motor unit, the fatiguability of
the muscle can be measured.
This is called the repetitive nerve stimulation test. In
single fiber electromyography (SFEMG), which is
considered to be the most sensitive (although not the
most specific) test for MG,
70. Ice test
Applying ice to weak muscle groups characteristically
leads to improvement in strength of those muscles.
Applying ice for 5 minutes to the muscles reportedly has
a sensitivity and specificity of 76.9% and 98.3%,
respectively, for the identification of MG.
It is thought that acetylcholinesterase is inhibited at the
lower temperature and that this is the basis for this
diagnostic test.
71. Edrophonium test
The "edrophonium test" is infrequently performed to identify MG;
its application is limited to those situations in which other
investigations have failed to yield a conclusive diagnosis.
This test requires the intravenous administration of edrophonium
chloride (Tensilon, Reversol) or neostigmine (Prostigmin), drugs
that block the breakdown of acetylcholine
by cholinesterase (acetylcholinesterase inhibitors) and temporarily
increases the levels of acetylcholine at the neuromuscular
junction.
In people with myasthenia gravis involving the eye muscles,
edrophonium chloride will briefly relieve weakness.
72. Edrophonium test
Photograph of a patient showing right partial ptosis (left picture),
Right picture: after an edrophonium test, note the improvement in
ptosis.
73. Imaging
A chest X-ray is frequently performed; it may point
towards alternative diagnoses (e.g., Lambert-Eaton
syndrome due to a lung tumor) and comorbidity.
It may also identify widening of
the mediastinum suggestive of thymoma, but computed
tomography (CT) or magnetic resonance imaging (MRI)
are more sensitive ways to identify thymomas and are
generally done for this reason.
MRI of the cranium and orbits may also be performed to
exclude compressive and inflammatory lesions of the
cranial nerves and ocular muscles.
75. Pulmonary function test
Spirometry (lung function testing) may be performed to assess
respiratory function if there are concerns about breathing
adequacy.
The forced vital capacity may be monitored at intervals to detect
increasing muscular weakness.
Acutely, negative inspiratory force may be used to determine
adequacy of ventilation.
Severe myasthenia may cause respiratory failure due to
exhaustion of the respiratory muscles.
76. Pathological finding
Muscle biopsy is only performed if the diagnosis remains in doubt
and clinical suspicion of MG persists.
Immunofluorescence shows IgG antibodies on the neuromuscular
junction. (The antibody which causes myasthenia gravis does not
fluoresce, but rather a secondary antibody directed against it.)
Muscle electron microscopy shows receptor infolding and loss of
the tips of the folds, together with widening of the synaptic clefts.
Both these techniques are currently used for research rather than
diagnostically.
77.
78.
Specific treatment to age, overall health, and
medical history and extent of the condition
No cure for MG, but the symptoms can be
controlled.
MG is a life-long medical condition and the key to
medically managing MG is early detection.
The goal of treatment is to prevent respiratory
problems and provide adequate nutritional care to
the child since the swallowing and breathing
muscles are affected by this condition.
79. TREATMENT OF MYASTHENIA GRAVIS
SHORT TERM
ANTICHOLESTERASE
S
eg : Neostigmine
Pyridostigmine
EPHEDRINE
PLASMAPHERESIS
LONG TERM
IMMUNOSUPPRESSIVE
AGENTS
Eg : PREDNISONE
AZATHIOPRINE
CYCLOPHOSPHAMIDE
CYCLOSPORINS
IMMUNOGLOBULIN
G
80. Cholinesterase inhibitors
neostigmine and pyridostigmine can improve
muscle function by slowing the natural enzyme
cholinesterase that degrades acetylcholine in the
motor end plate.
the neurotransmitter is therefore around longer
to stimulate its receptor
Side effects, such as perspiration and diarrhea,
can be countered by adding atropine
Pyridostigmine is a short-lived drug, with a halflife of about four hours.
81. CORTICOSTEROIDS
Produce rapid improvement in many
Produce total remission / marked
improvement in > 75 % of patients
Used as initial definite therapy
Used as secondary treatment in who do not
respond to thymectomy /
immunosuppressive therapy
Initial dose prednisone 15 – 25 mg/day
increased until maximal improvement is
seen or upto 50 – 60 mg/day
82. Immunosuppressants
eg:prednisone, cyclosporin, mycophenolate and
azathioprine
Patients are commonly treated with a
combination of these drugs with an
acetylcholinesterase inhibitor.
Treatments with some immunosuppressives take
weeks to months before effects are noticed.
Other immunomodulating substances, such as
drugs that prevent acetylcholine receptor
modulation by the immune system, are currently
being researched.
83. Plasmapheresis
This procedure is done in serious case of
myasthenia gravis
This procedure uses a filtering process
similar to dialysis.
Blood is routed through a machine that
removes the antibodies that are blocking
transmission of signals from nerve endings to
muscles' receptor sites.
However, the beneficial effects usually last
only a few weeks .
84. Intravenous immune globulin
This therapy provides body with normal
antibodies, which alters immune system
response.
It has a lower risk of side effects than do
plasmapheresis and immune-suppressing
therapy.
But it can take a week or two to start
working and the benefits usually last less
than a month or two.
86. Thymectomy
The surgical removal of the thymus.
Thymectomy is recommended for most young
patients.
It improves the disease course and can improve
remission.
Thymectomy is thought to remove an antigen
source and reduce an anti-AChR antibody source.
Thymectomy is performed when the disease is in
control.
But in the presence of myasthenia gravis,
thymoma is the most likely diagnosis.
Thymectomy may result in cure or great
improvement in the myasthenia.
87. Diet
Patients may experience difficulty chewing and
swallowing due to oropharyngeal weakness
• Thickened liquids are preferred, when dysphagia arises to
counteract the fear of aspiration.
• Asparagus should be taken as it contains steroid-like
substance.
•
Activity
•
Patients should be as active as possible but should take rest
in between.
• Yoga exercises to stretch the weakened muscles should be
done.
• This not only strengthens the muscles but also provides
oxygen & removes carbon dioxide from them.
88. Teach patient/family disease process,
complications, and treatments
Teach patient about their medications uses
dosage etc
Teach medications to use with caution d/t
muscle exacerbation
Beta blockers, calcium channel blockers, quinine,
quinidine, procainamide, some antibiotics,
neuromuscular blocking agents
Avoid certain medications
D-penicillinamine, A-interferon, botulinum toxin
89. In
patients with generalized MG, there is
some evidence that a partial home program
including training in diaphragmatic breathing
, pursed lip breathing , and interval based
IMT may improve respiratory muscle
strength, chest wall mobility, respiratory
pattern, and respiratory endurance
90.
91. Not all patients have adverse effects
Streptomycin
Ciprofloxacin
Levofloxacin
Ofloxacin
Gatifloxacin
Propanol
Atenolol
Local
anaesthetic
xylocaine
Erythromycin
Azithromycin
Non depolarizing muscle
relaxants –
DTC,pancuronium
Myasthenic
Weakness
exaggerated
Quininine
Magnesium
penicilliamine
92. With effective treatment, patients have high possibility of a normal life
expectancy, but anexception would be the presence of a malignant
thymoma (whose lesser life expectancy is on account of the thymoma
itself and is otherwise unrelated to the myasthenia).
Quality of life can vary depending on the severity and the cause.
93. Drugs used to control MG either diminish in
effectiveness over time (acetylcholinesterase inhibitors)
or can possibly cause severe side effects of their own
(immunosuppressants).
About 10% of MG patients are found to have tumors in
their thymus glands, in which case a thymectomy is a
very effective treatment with long-term remission.
However, most patients need treatment for the
remainder of their lives, and their abilities vary greatly.
MG is not usually a progressive disease; the symptoms
may fluctuate, but do not always get worse as the
patient ages. For some, the symptoms decrease after a
span of three to five years ( costanzo, 2012).
94.
95. Oliver Jones (2013), The Radial nerve, from; http://teachmeanatomy.info/upperlimb/nerves/the-radial-nerve/
Stephen k, Jeffrey MV, Julia L (2013) The Anatomy of brachial plexus. From;
http://emedicine.medscape.com/article/1877731-overview#showall
Hill, M.A. (2013) Skeletal Muscle Histology. Retrieved October 1,
2013,
from http://php.med.unsw.edu.au/embryology/index.php?title=Skeleta
l_Muscle_Histology
Dr Mark Hill 2013, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW
CRICOS Provider Code No. 00098G
Leite MI, Jacob S, Viegas S, et al. (July 2008). "IgG1 antibodies to
acetylcholine receptors in 'seronegative' myasthenia
gravis" . Brain 131 (Pt 7): 1940–
52.doi:10.1093/brain/awn092 . PMC 2442426.PMID 18515870
96.
Hill, M.A. (2013) Skeletal Muscle Histology. Retrieved
October 1, 2013,
from http://php.med.unsw.edu.au/embryology/index.p
hp?title=Skeletal_Muscle_Histology
Dr Mark Hill 2013, UNSW Embryology ISBN: 978 0 7334
2609 4 - UNSW CRICOS Provider Code No. 00098G
Leite MI, Jacob S, Viegas S, et al. (July 2008). "IgG1
antibodies to acetylcholine receptors in 'seronegative'
myasthenia gravis" . Brain 131 (Pt 7): 1940–
52.doi:10.1093/brain/awn092 . PMC 2442426.PMID 1851
5870