MYASTHENIA GRAVIS
BY
DR. S.O ITODO
INTRODUCTION:
An autoimmune disease condition
characterized by a fluctuating
pathological weakness with remission
and exacerbation involving one or
several skeletal muscle groups mainly
caused by antibodies to acetylcholine
receptor (AChR) at the post-synaptic
site of the neuromuscular junction.
The Neuromuscular Junction
It is a heterogenous group of disease
affecting any age group.
It is a chronic but rare disease in our
environment.
PREVALENCE
MG has a prevalence of 85-125 per
million, and annual incidence of 2-4
per million.
Generally, MG affects women more
than men esp. btw 20 and 40 years,
above this men are more affected.
20 % of patients present before
20years
AETIOLOGY
Genetic predisposition ( 30% of MG
patients have one maternal relative
with MG or other autoimmune
disorders).
Infections ( bacteria and herpes
simplex virus infection, usually due to
a cross reaction of the antibodies to
these antigens with AChR)
Midsize Neurofilament NF-M
CLASSIFICATION
MG being heterogenous disease is
classified into different subgroups:
Early onset subgroup (<50 years)
*AChR antibodies positive
*Non-thymoma
*Generalised symptoms
*Thymus hyperplasia
*Largest subgroup
*Predominant female patient with M/F of 1:4
*High frequency of concomitant autoimmune
diseases
Late Onset MG subgroup (>50yrs)
* Predominant male patients
Osserman classification
I ocular myasthenia
iia Mild generalised, slow progression, no
crisis
iibModerate generalised, severe skeletal and
bulbar involvement , no crisis
iiiAcute fulminant- rapid progression of
severe symptoms with respiratory crisis
iv Late severe myasthenia, symptom as in
(iii)but with steady progression over 2years.
Clinical Presentations
The hallmark of myasthenia gravis is fatigability.
Muscles become progressively weaker during
periods of activity and improve after periods of rest.
Voluntary muscles especially those innervated by
the motor nuclei of the brainstem are affected.
(ocular, masticatory, facial, deglutional, lingual)
Themuscles that control breathing and neck and
limb movements can also be affected
Snarl smile, diplopia, chewing tough food is difficult
Proximal muscles more affected than distal ones-
inability to comb hair, climb stairs.
Tendon reflexes not affected
Facial
muscles may be slack, facial mobility and
expression are altered.
Thepatient may be unable to support his or her
head, which will fall onto the chest while the
patient is seated.
Jawis slack, Voice fades and becomes nasal after
sustained conversation. Body is limp.
Gag reflex is often absent, and such patients are
at risk for aspiration of oral secretions.
Respiratory distress
The patient's ability to generate adequate
ventilation and to clear bronchial secretions
may be impaired in severe exacerbations of
myasthenia gravis.
Inability to cough leads to an accumulation
of secretions; therefore, rales, rhonchi, and
wheezes may be auscultated.
Eye signs characteristic of MG
Sustainedupgaze for 30sec or more will
induce ptosis
Cogan (lid twitch sign) – twitching of the
upper eyelid that appear after moving the
eyes from downward to a primary position
Ptosis of the left eye
16
Ptosis
Diplopia
Difficulty in swallowing
Difficulty in speaking
Weakness
N:B: The muz of respiration can be affected.
These patients are sensitive to curariform
drugs and other agents affecting neuro-
muscular transmitters.
Diagnosis:
Electrophysiologic testing:
• Decremental response in the amplitude of
compound muscle Action Potential evoked
during a series of repetitive stimulation of
a peripheral nerve
Single fiber electromyography: variability in
firing of muscle fibres from same motor
unit (“jitter)
Edrophonium (tensilon) test:
Anticholinesterase inhibitors exaggerate the
effect of ACH in the synapse and thereby
provide an increment in muscle power.
Procedure:
A baseline measurement of the muscle
strength of the patient is taken.
2mg dose of Edrophonium is injected
intravenously into the pt.
If no reaction is noticed after
45seconds, another 8mg of same drug
is given iv
An improvement in the mus. strength
lasting for about 5minutes indicates
MG.
Receptor antibody in blood, anti – ACHR
antibodies sensitive and highly specific
USE OF EDROPHNIUM IN MG
Diagnosis
Assessing the adequacy of treatment with long
standing cholinesterase Inhibitors
N:B: Edrophonium is not used in the treatment of
MG.
TREATMENT MODALITY
1. Pharmacological approach
2. Non-pharmacological approach
A. Pharmacological approach:
I. Acetylcholinerase Inhibitors ( 1st line
treatment)
II. Immunosuppressive drugs ( 2nd line
treatment)
Acetylcholinerase Inhibitors:
Pyridostigmine
Neostigmine
Immunosuppressive Drugs:
Corticosteroids
Azathioprine
Cyclosporin
Cyclophosphomide
Methotrexate
Myophenolate mofetil( new immuno-
suppresant)
Tacrolimus (new imm.)
Rituximab (monoclonal antibody against B-
cell)
B. Non-pharmacological Approach
Thymectomy (surgery)
Plasmapheresis
Therapeutic recommendations
It
is not easy to give specific therapeutic
guidelines in MG as MG is a
heterogeneous disease and not all the
patients can be treated following a
single recommendation.
However,the following recommen-
dations may facilitate the therapeutic
approach to an MG patient.
After
the diagnosis of MG is establi-shed, an
acetylcholinesterase inhibitor should be
introduced, such as pyri-dostigmine 60mg
three times a day.
At
this early stage, the patient should be
investigated for thymoma, and if proven the
patient should undergo surgery.
If
a thymoma is not found and the
patient belongs to the early onset MG
subgroup and is AChR antibody
positive with generalized MG,
thymectomy should be considered
within 1 year after MG diagnosis,
especially if the response to
pyridostigmine therapy is poor and
the disease is progressive.
Immunosuppressive drug treatment should be
considered as an add on to pyridostigmine in
thymectomized and non-thymectomized
patients with progressive MG symptoms
Insuch a case, steroids such as prednisolone
should be chosen and given on alternate days,
usually by increasing the dose to 60–80 mg
initially and then with a gradual and slow
reduction to 20 mg or lower.
Non-steroid immunosuppressants,
such as azathioprine, should be
introduced (usually 100–150 mg/day)
in addition if long-term treatment
with steroids is regarded necessary.
Side effects of drugs used
They include muscarinic symptoms:
Abdominal cramps
Diarrhoea
Increased salivation
Excess brochosecretions
Miosis
Bradycardia
Myaesthenic crisis
Rapidsevere deteroriation of the myaesthenia
leading to respiratory failure and
quadriparesis
May be precedded by respiratory infection,
excessive use of medications with potentials
to block the Neuromuscular junction
Precipitating factor may not be evident 31
Often accompanied by restlessness, anxiety,
diaphoresis and tremor
Rx
-Manage in ICU
-Timely and careful intubation followed by
mechanical
ventilation
-Plasma exchange – may hasten improvement
and weaning
off ventilation 32
Cholinergic crisis
Relatively
rapid increase in muscular
weakness usually coupled with adverse
muscarinic effects of anticholinesterase drugs
Nausea,vomiting, pallor, sweating, salivation,
bronchoconstriction,colic,diarrhea, miosis)
33
MYASTHENIA CRISIS/CHOLINERGIC
CRISIS
Both can present with muscle weakness
Differentiating both is therefore very
important becos of the different line of
management.
While the weakness seen in MC is due to
the disease itself, the weakness in CC
usually results from excessive use of the
longer-acting cholinesterase inhibitors and
presents later after other cholinergic
symptoms .
In CC there is hx of previous excessive use of
the longer-acting cholinesterase inhibitors
e.g Neostigmine.
In CC, there are cholinergic symptoms such as
sweating, salivation, bradycardia, diarrhoea
e.t.c
Injection of 1-2mg of IV Edrophonium
produces no effects or worsens the
weakness in CC while it improves that of MG.
Some medications that may cause exacerbations of
myasthenia gravis include
◦ Antibiotics - Macrolides, fluoroquinolones,
aminoglycosides, tetracycline, and chloroquine
◦ Antidysrhythmic agents - Beta-blockers, calcium channel
blockers, quinidine, lidocaine, procainamide, and
trimethaphan
◦ Miscellaneous - Diphenylhydantoin, lithium,
chlorpromazine, muscle relaxants, levothyroxine,
adrenocorticotropic hormone (ACTH), and, paradoxically,
corticosteroids
36
Associations
Myasthenia
Gravis is associated with various
autoimmune diseases, including:
Thyroiddiseases, including Hashimoto’s thyroiditis and
Graves' disease
Diabetes mellitus type 1
Rheumatoid arthritis
Lupus erythematosus
37
Prognosis
In the past untreated myasthenia gravis carried a mortality rate of
30-70%.
In the modern era, patients with myasthenia gravis have a near-
normal life expectancy.
Morbidity results from intermittent impairment of muscle strength,
which may cause aspiration, increased incidence of pneumonia,
falls, and even respiratory failure if not treated.
In addition, the medications used to control the disease may
produce adverse effects.
With prompt diagnosis and treatment, the mortality rate of
myasthenic crisis is less than 5%.
38
Thank you
39
