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 111

but with steady progression over 2years from
1 to 11
 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

Facialmuscles may be slack, facial mobility and expression
are altered.

The patient 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

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 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 and IV immunoglobulin
 Therapeutic recommendations
 It
is not easy to give specific thera-
peutic 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, thymec-
tomy should be considered within 1
year after MG diagnosis, especially if
the response to pyridostigmine thera-
py 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)

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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 inhibitiors 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

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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

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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%.

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Thank you

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