common neurological problem. public can clear their doubts

1. Dr. K. Vasantha M.S.,F.R.C.S
Director RIO Chennai Rtd

2.  The basic part of this disease is fatigability of muscles
 Mya asthenia gravis = muscle weakness serious
 This is due to decrease in the availability of acetylcholine
receptors at neuro muscular junctions

3. This decrease in acetylcholine receptors is due to
antibodies against the receptors which act by
 a. blocking the receptors
 b. complement mediated membrane damage
 c. accelerated degradation of the receptors

4.  Peak incidence is more in young women less than 40 and
old men more than 60
 Neonatal myasthenia affects infants born to myasthenic
mothers. This is due to passive transfer of the
immunoglobulins from the mother. The disorder
disappears in 2 to 3 weeks as the immunoglobulin
depletes fro the system. Immunosuppression during
pregnancy will prevent this
 Till then supportive therapy with oral anticholinestrase
must be given

5.  This occurs due to inherited defect in the neuromuscular
junction

6.  When D- penicillamine and statins are used anti ACh
antibodies may be produced. When the drug is stopped
the symptoms will disappear.
 Aminoglycosides, nitrofurantoin, beta- blockers and
quinidine will exacerbate myasthenia
 Exacerbated by respiratory infection, stress, surgery, in
vitro fertilization (due to hormone induced fluctuation)

7.  If you see random involvement of extra ocular muscles,
levator palpebrae superioris along with orbicularis oculi
– suspect myasthenia
 The main feature in the involvement of muscles in this
disorder is its variability
 Weakness of the muscles increase after prolonged
activity
 The involved muscles will not be uniformly weak
 It varies during day time, worsening during the evening
 After physical exertion also it will be worse

8.  Proximal limb muscles like triceps, deltoids and
iliopsoas
 Muscles of facial expression, mastication and speech
 Extensors of the neck

9.  ? Fetal form of acetylcholine receptors are found in the
receptors of extra ocular muscles but not in the skeletal
muscles. But Levator muscle does not have fetal AC
receptors
 Even a mild involvement of the extra ocular muscle will
cause diplopia and the patient becomes symptomatic
 High firing frequencies make them more susceptible
 These muscles are warmer
 May be there is a specific antibody affecting these
muscles

10.  The amount of ACh released in myasthenia is normal
 But transmission is impaired
 Normally the amount of Ach released is reduced when
there is sustained muscle contraction
 Because of this reduction added to less number of
receptors, in myasthenia the muscle is fatigued
 This is seen more in bright light

11.  The anti Ach receptor antibody is due to T-cell dependent
B-cell response.
 The thymus in a myasthenic patient contain more B-cells
and produce more antibodies against Ach receptors
 If a patient is over 30 years and a male, thymoma must
be suspected
 2/3rds of myasthenia patients have hyperplasia of the
thymus
 About 10% have thymoma

12.  Ptosis is the most common presentation
 It is usually binocular. It may shift from one eye to the
other especially when it is asymmetric.
 Prolonged upward gaze will result in gradual lowering of
the lids worsening the ptosis.
 If you hold one eyelid up, then that eye will not have
worsening as no effort is needed to keep the eye open.

13.  If the ptosis is unilateral the other eye may show lid
retraction as more effort will be used to keep the ptotic
eye lid elevated
 When the ptotic lid is held up the other lid will droop.
This is called curtaining
 This is due to Hering’s law
 The pupils are normal there by differentiating it from
Horner’s, third nerve palsy and botulism

14.  Cogan’s lid twitch sign:- when the patients are made to
look down for 10 to 20 seconds and then asked to look
up the upper lid will overshoot upward and twitch a few
times before settling down. This upshoot is due to build
up of ACh when the lid is resting and, easy weakening of
the muscle after rapid elevation.
 This may occur in brain stem lesions and other oculo
motor nerve lesions also
 Sometimes transient eye lid retraction also can occur

15.  These muscles are involved more due to the presence of
fetal receptors
 Minimal involvement of these muscles are symptomatic
due to diplopia unlike other muscle involvement
 The nerve connections to these muscles are very high
and hence more sensitive to nerve stimulation and
fatigue
 These muscles are warmer compared to limb muscles
 ? More accessible to antibodies

16.  There is no set pattern. It is haphazard
 One or more muscles may be involved. Even complete
external ophthalmoplegia can occur. So one may mistake
it for pupil sparing third nerve palsy
 Must be differentiated from III , IV and VI nerve palsies,
supra nuclear palsy and gaze palsies

17.  Hypermetric saccades – in an attempt to overcome the
weakness created by myasthenia the central nervous
system increases the pulse
 Hypometric saccade – starts with normal movement and
then slows down
 Small jerky quivering movements
 Gaze evoked nystagmus

18.  On gentle closure of the eye, lids will be apposed. But
after sometime the eye will start opening. This looks like
as if the person is trying to peek.
 While washing the face with soap they will experience
irritation as the eye will open up after sometime
 Ectropion of lower lid also may occur towards the
evening
 Because of ptosis orbicularis involvement will not be
apparent

19.  Pupil is not involved in myasthenia
 But accommodation fatigue can occur. This will cause
blurring of near vision

20.  Because of weakness of extensors of the neck the head
will hang forward – called head ptosis
 Speech, swallowing and chewing becomes difficult
 Inability to smile
 Nasal regurgitation of food
 The jaw is likely to hang down, and has to be physically
closed

21.  Protrusion of the tongue may become weak
 Involvement of stapedius causes hyperacusis. Less
intensity will be needed to elicit acoustic reflex
 There is no loss of reflexes, or coordination.
 Sensory system also remains normal
 Mental status is not affected

22.  In women weakness may increase during menstruation
 This may be due to estrogen induced regulation of
antigen presenting cells
 There is also a decrease in cytokine secretion and
increase in the level of interleukin-10
 Temporary stoppage of oral contraceptives will also
exacerbate the condition

23.  Steroids can paradoxically induce myasthenia
 This is due enhanced proliferation of sensitized
lymphocytes
 Highly activated cholinesterase in neuromuscular
junctions
 Decrease in acetylcholine release
 Increase in immune response
 Even myasthenic crisis can occur.

24.  If the patient sleeps for 30 minutes an improvement in
ptosis is seen when the patient wakes up. This lasts for
about 3 – 4 minutes
 Ice pack test: when a small pack of ice cubes is kept on
the eye lid for 2 minutes there is an improvement of
ptosis by 2 mm. This lasts only for about a minute. The
other eye if involved, serves as a control

25.  In these tests acetyl cholinesterase inhibitors are given
to the patient and improvement in the signs are noted
 Edrophonium (tensilon)test: acts very quickly i.e.
within30 seconds and the effect disappears within 5
minutes.10 mg of tensilon is taken and a test dose of
2mg is first injected. If no adverse events occur, further 8
mg is injected slowly. If there is no improvement within 3
minutes, the test is considered negative.
 Diplopia if present may not disappear completely. So the
physician has to carefully note the improvement in the
movement of the eyes before giving the injection

26.  The positive nicotinic response causes improvement in
myasthenic symptoms
 But the muscarinic effect on other muscles will cause a
brief over stimulation of the parasympathetic system
 Bradycardia, loss of consciousness, apnea, dizziness,
involuntary defecation, twitching of eye lids can occur.
 Serious complication- abnormal heart rhythms

27.  Slow heart rate, irregular heart beat
 Asthma
 Low BP
 Obstruction in the urinary tract or intestines
 Sleep apnea

28.  To prevent complications, intra muscular Atropine
sulphate is given as it will annul the muscarinic activity
 It should not be performed in patients with known
cardiac disease
 False positive and false negative results has been found
 The response is also transient
 Tensilon test is also used to find out whether you are
over dosed with pyridostigmine

29.  Because of the serious complications and the transient
effect prostigmine is used
 If 0.6 mg of atropine and 1.5 mg of neostigmine are given
intra muscularly
 The signs of myasthenia start improving in 15 minutes
and peaks in 30 minutes
 May be positive in brain stem tumors, multiple sclerosis
and sometimes even in congenital ptosis
 Negative results also have been seen

30. Seen in
 Thymoma
 Lambert Eaton syndrome
 Lung cancer
 Rheumatoid arthritis patients on Penicillamine

31.  Supramaximal electric stimuli are given to the muscle to
be tested. Rapid reduction in action of 10 to 15% is
considered abnormal
 Single fiber EMG test is considered very sensitive in
generalized myasthenia. Very useful in pulmonary
muscle involvement

32.  If the weakness is confined to the extra ocular muscles
antibodies are detected only in 35 to 75%
 False positive results can be seen in amyotrophic lateral
sclerosis
 Other anti bodies like anti musk antibodies (muscle
specific kinase). These patients will have more of tongue
and facial muscle weakness. This is more difficult to
treat

33.  Antibodies against low density lipoprotein 4 (LRP4) is
sometimes seen in ocular myasthenia
 Antibodies against Agrin and Titin proteins are also
rarely involved

34.  Myotonic dystrophy
 Oculopharyngeal dystrophy – seen in French, Spanish
and Jewish people. Autosomal dominant or recessive.
Males and females are affected. Age 40 to 50 years.
Aspiration pneumonia is common. Muscle biopsy
needed
 Mitochondrial dystrophy- Kearns Sayre syndrome.
Cardiac abnormalities are seen. Ragged red fibers due to
accumulation of mitochondria

35.  As this is an autoimmune disease, other autoimmune
diseases like SLE, pemphigus, ulcerative colitis,
sarcoidosis, Sjogren’s, diabetes and hepatitis may be
seen
 All types of thyroid diseases can be found. Even sub
clinical involvement of thyroid gland must be ruled out
 Rheumatoid arthritis, ankylosing spondilitis
 Aplastic anemia with thymic tumor, pernicious anemia

36.  Cholinesterase inhibitors
 Thymectomy
 Immunosuppressives
 Specific therapy for ocular complications
 Diabetes and tuberculosis must be ruled out as steroids
and immuno suppressives may have to be used

37.  Thymus tumor (thymoma)must be ruled out with CT or
MRI
 If present thymectomy must be done regardless of
patient’s age
 If the patient is below 50 even without tumor thymectomy
can be tried. Beyond that age thymus would have
involuted. So thymectomy will not be useful
 The effect will be seen only after minimum of 6 months
and may take even 2 to 5 years

38.  Injury to phrenic nerve or recurrent laryngeal nerve
 Atelectasis
 Pleural effusion
 Pneumonia
 Intercurrent pulmonary embolism
 Sternal instability
 Myasthenic crisis. Plasmapheresis may have to be done
before surgery to prevent this

39.  Drugs like pyridostigmine will prolong the action of ACh
by slowing its degradation at the neuromuscular junction
 Onset of action happens within 30 minutes and peaks at
about 2 hours. So one tablet 30 mg is taken every 3 to 4
hrs. It can be increased up to 150 mg every 4 hrs.
 Side effects- diarrhea, watering of eyes, increased
salivation, cramping and fasciculations. Loperamide,
glycopyrrolate or diphenoxylate with atropine will help in
this condition

40.  Tachyphylaxis and over medication can cause
cholinergic crisis
 Excessive use will cause weakness of muscles
 To differentiate this from low dosage Edrophonium is
used. If it gets better with Edrophonium it means the
dosage is low

41.  If the patients are intolerant to pyridostigmine steroids
can be given
 The side effects of steroids like osteoporosis, peptic
ulcer and diabetic status of the patient must be kept in
mind
 Low doses like 10 mg on alternate days must be tried
first

42.  Short term –
 By doing plasmapheresis the circulating antibodies are
removed. There is a temporary improvement (days to
weeks) in the symptoms. Used mainly in myasthenic
crisis and before thymectomy
 Intra venous human immunoglobulin can be given to
when rapid improvement of symptoms is needed. It takes
around five days for the response and lasts for weeks to
even months. Very expensive

43.  Azathioprine. Patients must be screened for thiopurine
methyltransferase gene mutation before starting therapy
 Cyclosporine
 Methotrexate
 Mycophenolate mofetil?, Tacrolimus?

44.  Ocular problems especially ptosis is relieved with
neostigmine.
 Crutch glasses can also be used if ptosis is not fully
relieved
 If ptosis is the only problem or if it is refractory to
treatment ptosis surgery can be done

45.  If diplopia is severe and not relieved with drugs or if the
patient is intolerant to medicines, one eye can be
occluded.
 It is difficult to prescribe prisms as the muscle imbalance
is not fixed
 Extra ocular muscle surgery is not usually performed for
the same reason
 10 to 20% of ocular myasthenia patients experience a
remission. This may even be permanent. Or else
relapses occur after a few years

46.  Weakness of muscles similar to myasthenia is seen
 No antibodies
 Genetic abnormalities in the
 pre synaptic – defect in acetylcholine resynthesis,
 synaptic -- end plate acetyl cholinesterase deficiency
 post synaptic – slow channel syndrome, end plate acetyl
cholinesterase deficiency, fast closure of Ach receptor
channel. Defect in neuro muscular junction is the cause

47.  Slow channel syndrome is autosomal dominant
 Other syndromes are autosomal recessive

48.  Lambert-Eaton syndrome which rarer than myasthenia is
a presynaptic neuro transmission disorder
 It may primary autoimmune or paraneoplastic(Eg. Small
cell ca of lung)
 Unlike myasthenia only ptosis will be there. No
ophthalmoplegia. After sustained up gaze the ptosis may
improve due to accumulation of calcium in the
neuromuscular junction
 Diagnosis is by EMG

49.  Pathology is in the calcium channels in the presynaptic
area affected by antibodies.
 Acetylcholine which is calcium dependant is not
released properly
 Autonomic symptoms like dry eyes, dry mouth, blurred
vision, impotence and constipation
 Proximal muscle weakness
 Other auto immune diseases also may be seen

50.  To find out if there is any malignancy and treat that
 Acetyl cholinesterase inhibitors
 Immunomodulation with prednisolone, Azathioprine or
Rituximab