DIAGNOSIS AND TREATMENT OF MYASTHENIA

GRAVIS

Lecturer Adviser :
Dr.Donny H Hamid.SpS

Relanfa Farando
110201234

Clinical Science of Neurology

General Hospital Pasar Rebo East Jakarta
11 September 2017 16 October 2017
 Definition

Myasthenia gravis (MG) is the most common primary disorder

of neuromuscular transmission. It is characterised clinically by
fluctuating painless muscle weakness, which worsens with
exercise and towards the end of the day, and improves with
rest. It is usually caused by antibodies to postsynaptic
proteins, of which three namely nicotinic acetylcholine
receptor (AChR), muscle-specific tyrosine kinase (MuSK) and
low-density lipoprotein receptor-related protein 4 (LRP4)
 Epidemiology

200/
200/ Million
Million case
case Young
Young Adult
Adult ::
Male/Females
Male/Females Females
Females
Risk
Risk Increase
Increase with
with
Age
Age
 Classification

Subtypes of MG According to
Antibodies

1. early-onset MG: age at onset <50 years. Thymic hyperplasia,

usually
2. late-onset MG: age at onset >50 years. Thymic atrophy, mainly
3. thymoma-associated MG (10%15%)
4. MG with anti-MUSK antibodies
5.ocularMG (oMG): symptoms only affecting extraocular muscles
6.MG with no detectable AChR and muscle-specific tyrosine kinase
(MuSK)
 Other
Classification

Osserman
Osserman Classification
Classification of of Myasthenia
Myasthenia Gravis
Gravis (modified
(modified from
from MGFA)
MGFA)
Class
Class II pure
pure ocular
ocular

Any
Any ocular
ocular weakness,
weakness, may
may have
have weakness
weakness ofof eye
eye closure;
closure;
Strength of all other muscles is
Strength of all other muscles is normal. normal.
Class
Class II II ocular
ocular plus
plus other
other deficits
deficits

IIa Mild weakness aff ecting limbsbulbar muscles;

IIa Mild weakness aff ecting limbsbulbar muscles;

IIb
IIb Predominantly
Predominantly aff aff ecting
ecting limbs
limbs oropharyngeal.
oropharyngeal.
Class
Class IIIIII moderate
moderate generalized
generalized

IIIa Moderate weakness Predominantly

IIIa Moderate weakness Predominantly aff aff ecting
ecting limb,
limb, axial
axial muscles,
muscles, or
or both;
both;
IIIb Moderate generalized weakness predominantly aff ecting
IIIb Moderate generalized weakness predominantly aff ecting oropharyngeal, oropharyngeal,
respiratory
respiratory muscles,
muscles, oror both.
both.
Class
Class IV IV severe
severe generalized
generalized

IVa
IVa Severe
Severe weakness
weakness affaff ecting
ecting limbs;
limbs;

IVb
IVb Severe
Severe weakness
weakness affaff ecting
ecting limbs.
limbs. Predominantly
Predominantly affaff ects
ects bulbar
bulbar muscles.
muscles.
Class
Class V V

Ventilator
Ventilator dependent
dependent except
except when
when used
used during
during routine
routine postoperative
postoperative management
management
Etiopathogenesis

Autoantibodies

Thymus

Genetic

Enviromental
Pathofisiologi

Antibodies to AChR protein:

85 % of patients with
generalized myasthenia and
60% of those with ocular
myasthenia shows AChR
Antibodies
Anti-MuSK Ab(40% of
seronegative cases)

An immune response to muscle-

specific kinase (MuSK) can also
result in myasthenia gravis,
possibly by interfering with AChR
clustering
1.
1. Anti-AChR
Anti-AChR antibodies
antibodies bind
bind and
and
crosslink
crosslink the
the AChRs,
AChRs, resulting
resulting in
in
increased
increased endocytosis
endocytosis andand degradation
degradation
of AChRs by the muscle
of AChRs by the muscle cell. cell.
2.anti-AChRs
2.anti-AChRs bind
bind complement
complement factors
factors
at
at the
the post
post -- synaptic
synaptic membrane,
membrane,
leading
leading to
to focal
focal lysis
lysis of
of the
the postsynaptic
postsynaptic
folds
folds at
at the
the neuromuscular
neuromuscular junction
junction by
by
the membrane attack complex.
the membrane attack complex.
3.the
3.the destruction
destruction of of other
other AChR-
AChR-
associated
associated proteins, such as utrophin,
proteins, such as utrophin,
rapsyn
rapsyn and
and voltage-gated
voltage-gated sodium
sodium
channels,
channels, impairs
impairs neuromuscular
neuromuscular
transmission
transmission as these proteins
as these proteins are
are
involved in neuromuscular junction
involved in neuromuscular junction
formation
formation and
and maintenance
maintenance
 Clinical Manifestastion
Levator
Levator palpebrae
palpebrae weakness,
weakness, may
may bebe
Ptosis unilateral,
unilateral, N III,IV,V1 weakness, Difficulty with
N III,IV,V1 weakness, Difficulty with
eye closure
eye closure

Facial muscle
an expressionless face,
an expressionless face, or
or a
a snarl
snarl when
when the
the
& Jaw patient
patient tries
tries to
to smile,
smile, mastication,
mastication,
Weakness
dysphagia,
dysphagia, weakness
weakness of
of the
the pharyngeal
pharyngeal and
and tongue
tongue
dysarthria
dysarthria musculature, laryngeal weakness
musculature, laryngeal weakness
,choking,
,choking,
dysphonia
dysphonia

Upper commoner than lower extremity

extremity weakness
weakness
Ocular involvement (A), myasthenic snarl (B)
 Diagnosis

Physical Examination :
Anamnesis : Ocular
Ocular (Ptosis,
(Ptosis, Peek
Peek sign)
sign)
Insidious onset Frontalis
Frontalis (Worried/surprised look,
(Worried/surprised look, Unilateral)
Unilateral)
Symptoms may be worsened Oropharyngeal (Chewing and swallowing,
Oropharyngeal (Chewing and swallowing,
changes
changes inin the
the voice
voice
by some agents Laryngeal
Laryngeal (hoarseness,
(hoarseness, choking,
choking, dysphagia,
dysphagia,
Slowly progressive course respiratory dysfunction)
respiratory dysfunction)
Symptoms often fluctuate in Facial
Facial appearance
appearance (myasthenic
(myasthenic snarl)
snarl)
intensity during the day Weak
Weak trunk or limb muscle (Neck flexors
trunk or limb muscle (Neck flexors ,,
triceps
triceps and
and extensors
extensors of of the
the wrist
wrist and
and
fingers
fingers and
and ankle
ankle dorsiflexors
dorsiflexors ))
Muscle weakness in MG can be exacerbated by emotional upset, hot
temperature, infection, menstruation, physical exertion, pregnancy,
surgery, thyroid disease (hyperthyroidism or hypothyroidism) and
many classes of drugs
Diagnostic investigations

Ice Pack Test

Edhorphonium
Neurophysiology
Antibodies Test
Differential
Diagnosis
Treatment
 Emergency in
Myasthenia Gravis

Myasthenic Crisis (MC)

Severe weakness of the bulbar (innervated by cranial nerves) and/or
respiratory muscles, enough to cause inability to maintain adequate
ventilation and/or permeability of upper airways, causing respiratory
failure that requires artificial airway or ventilatory support.
 Epidemiology

15-20%
Women
< 50 years
Patients
The :ofMen
median inmyasthenic
old affect
crisis
time woman
patients
requiring
to first :endotracheal
man
myasthenicare affected
4 form
crisis :1 onset
by myasthenic
intubation
of MG ranges crisis
spend a median
form 8-12 months of 1
 Warning Symptoms !!

1.Abdominal muscle paradox 11.Orthopnea

2.Accessory muscle use 12.Pausing during speech to
3.Cough after swallowing take a breath
4.Difficulty in clearing secretions 13.Rapid shallow breathing
5.Dysphagia 14.Staccato speech or a nasal
6.Hypophonia quality to speech
7.Inability to raise the head due to 15.Single breath count of < 15
neck muscle weakness 16.Stridor
8.Forehead sweating 17.Tachypnea
9.Jaw weakness (jaw closure 18.Tongue weakness
weaker than jaw opening) 19.Weak cough
10.Nasal regurgitation 20. Wet, gurgling voice
 Diagnosis

FVC <1 L, negative inspiratory force of 20 cm H2O or less, and the

need for ventilatory support
Arterial blood gas analysis commonly shows hypercarbia before
hypoxia
Patients with previous diagnosed Myasthenia gravis
Patients without a previous diagnosis of Myasthenia gravis. Suddenly
show a severe respiratory distress, facial weakness, airway collapse,
and muscle failure. Initially, oxygenation is preserved.
Treatment
1.Admit to ICU
2.Assessment of respiratory
function
3.Elective intubation
4.Rapid therapy IV IG ,
5.Plasmapheresis
6.Immunomodulating therapy
7.Careful weaning
8.Taking care of complications
9.Anticholinesterase inhibitors
10.Thymectomy