Myasthenia Gravis And Lambert–eaton 

Myasthenic Syndrome

Disorder of neuromuscular junction

PHYSIOLOGY OF MUSCLE CONTRACTION

 Depolarisation of nerve terminal.

 Voltage gated Na channels open.

 Voltage gated Ca channels open.

 Influx of Ca+ triggers release of acetylcholine.

 Acetylcholine binds receptors on muscle membrane.

 Allows influx of Na+

 Generate endplate potential. Activates muscle fibres VGNa + to create

action potential.
 Triggers muscle contraction.
 PATHOLOGY
 Initiated by an autoimmune
response which ultimately
disrupts transmission at
neuromuscular junction.

 Antibodies are directed against

acetylcholine receptors.
They directly block AChR.

• Auto antibodies cause damage to post synaptic membrane altering

AChR shape, thus inhibiting Ach binding and disrupting synaptic
transmission.

• Auto antibodies cause increased turnover of AChR thru endocytosis.

• Normally life of an AChR is seven days. In MG patients, it is one day.

INCIDENCE: 5 – 10 per 1 lakh population.

SEX:
Female-Male (6:4)
Mean age of onset (Male-42, Female-28)
INCIDENCE PEAKS-
Male- 6-7th decade
Female- 3rd decade

MORTALITY/MORBIDITY:
Recent decrease in mortality rate due to
advances in treatment
3-4% (as high as 30-40%)
Risk factors
Age > 40
Short history of disease
Thymoma
MAJOR CLINICAL FEATURES:

• Weakness.
• Excessive fatigability.
FOUR MAJOR GROUPS

1. Onset in early adult life

 Commonly females.
 antiAChR antibody titres are high.
 Thymus shows hyperplasia.

2. Late onset
 Commonly males.
 antiAChR antibody titres are low.
 Thymus atrophy.
3. Late onset equal ratio
 Intermediate levels of antiAChR antibodies.
 Thymoma present.

4. Any age
 Male predominance.
 antiAChR antibody not detected by standard array.
 Thymus atrophy.
 Often restricted to ocular involvement.
 Progression of disease
◦ Mild to more severe over weeks to months
 Usually spreads from ocular to facial to bulbar to
trunkal and limb muscles
 Often, symptoms may remain limited to EOM and
eyelid muscles for years
 The disease remains ocular in 16% of patients

 Remissions
◦ Spontaneous remissions rare
◦ Most remissions with treatment occur within the first three
years
CLINICAL FEATURES
1. Ocular involvement
2. Muscle weakness and fatigue
3. Characteristic feature is excessive fatigability.

4. Facial and bulbar muscle weakness causes dysarthria and

dysphagia.

5. Dysarthria increases with speaking.

6. Respiratory muscle weakness severe enough to cause ventilatory

problems.

7. Selective weakness of neck extensors common feature in older

typically male patients, - cause head drop.

8. Weakness varies during course of the day and during activity.

Eased with rest.
8. Weakness is increased by emotion, heat, menstruation and
infection.

9. In small proportion, disease remain only to extraocular

muscles

11. If untreated, gradually spreads to involve more muscles.

When severe may even cause respiratory failure.

12. Sensation is normal.

13. No loss of coordination.
14. can produce isolated finger weakness.

15. Muscle shrinking (atrophy) is not part of Myasthenia Gravis,

but some patients with severe weakness for many years
may have some atrophy (muscle wasting).
 Facialmuscle weakness is almost always present
◦ Ptosis and bilateral facial muscle weakness
◦ Sclera below limbus may be exposed due to weak
lower lids

 Bulbar muscle weakness

◦ Palatal muscles
 “Nasal voice”, nasal regurgitation
 Chewing may become difficult
 Severe jaw weakness may cause jaw to hang open
 Swallowing may be difficult and aspiration may occur
with fluids—coughing and choking while drinking

◦ Neck muscles
 Neck extensors affected more than flexors
 Limbmuscle weakness
◦ Upper limbs more commonly affected than lower limbs

Upper Extremities Lower Extremities

Deltoids Hip flexors (most common)
Wrist extensors Quadriceps
Finger extensors Hamstrings
Triceps > Biceps Foot dorsiflexors
Plantar flexors
Ocular muscle weakness

◦ Asymmetric
 Usually affects more than one extraocular muscle and is
not limited to muscles innervated by one cranial nerve

 Weakness of lateral and medial recti may produce a

pseudointernuclear opthalmoplegia
Limited adduction of one eye with nystagmus of the
abducting eye on attempted lateral gaze

◦ Ptosis caused by eyelid weakness

◦ Diplopia is very common

Myasthenia Gravis does not cause true tremors.
Medications used to treat MG, like Prednisone and Cyclosporine,
may cause tremors. The weakness of muscles can make a Myasthenic
have difficulty with movement and feel uncoordinated.

MG does not cause seizures, cramping, weakness only on one side of

the body, burning of the tongue or bottom of feet, hot flashes (these
could be related to Prednisone therapy), numbness or tingling.

Mestinon frequently causes muscle spasms and twitching of the

muscles. Mestinon may produce, or worsen, cramps
Myasthenia Gravis crisis
Symptoms of a Myasthenia Gravis crisis

A crisis is defined as being unable to breathe to the point that one

needs a ventilator.

A Myasthenia Gravis crisis involves several breathing difficulties

(shortness of breath) due to muscle weakness.

Usually occurs over days to weeks, not suddenly, as the term

suggests. Often induced by another medical condition, such as an
infection.
In a crisis, the most dangerous signs are breathing and throat
muscle weakness.
Problems with swallowing (coughing and choking frequently
while eating) from throat muscle problems may lead to aspiration
of food into the lungs, which will lead to pneumonia.
It is important for MG patients to notify the symptoms of
shortness of breath.
If the problem is not identified and treated correctly, it could lead
to death.
INVESTIGATIONS/DIAGNOSTIC CRITERION

◦ Anti-acetylcholine receptor antibody

 Positive in 74%
 80% in generalized myasthenia
 50% of patients with pure ocular myasthenia

◦ Anti-striated muscle
Present in 84% of patients with thymoma who are younger
than 40 years

◦ Interleukin-2 receptors
 Increased in generalized and bulbar forms of MG
 Increase seems to correlate to progression of disease
o Imaging studies
Chest x-ray
Plain anteroposterior and lateral views may
identify a thymoma as an anterior mediastinal
mass
Chest CT scan to identify thymoma

o Electrodiagnostic studies
Repetitive nerve stimulation

Single fiber electromyography (SFEMG)

SFEMG is more sensitive than RNS in MG

 Repetitive Nerve Stimulation

Low frequency RNS (1-5Hz)

◦ Locally available Ach becomes depleted at all NMJs and
less available for immediate release
Results in smaller EPSP’s (Excitatory postsynaptic
potential)
 AchR’s are reduced and during RNS EPSP’s
may not reach threshold and no action
potential is generated

 Results in a decremental decrease in the

compound muscle action potential

 Any decrement over 10% is considered

abnormal

 Proximal muscles are better tested than

unaffected distal muscles

AChE inhibitors prior to testing may mask

the abnormalities and should be avoided for
atleast 1 day prior to testing
 Single-fiber electromyography
Findings suggestive of NMF transmission
defect
 Increased jitter and normal fiber
density
 SFEMG can determine jitter
 Variability of the interpotential
interval between two or more
single muscle fibers of the same
motor unit

◦ Generalized MG
 Abnormal extensor digiti minimi found in 87%
 Examination of a second abnormal muscle will increase
sensitivity to 99%
◦ Ocular MG
 Frontalis muscle is abnormal in almost 100%
 More sensitive than EDC (60%)
Edrophonium (Tensilon test)
◦ Patients with MG have low numbers of AChR at the NMJ

◦ Ach released from the motor nerve terminal is metabolized

by Acetylcholine esterase

◦ Edrophonium is a short acting Acetylcholine Esterase

Inhibitor that improves muscle weakness

◦ Evaluate weakness (i.e. ptosis and opthalmoplegia) before

and after administration

◦ Edrophonium can improve weakness in diseases other than

MG such as ALS, poliomyelitis, and some peripheral
neuropathies
TREATMENT
 If thymoma present: thymectomy or radiotherapy or chemotherapy.
Immunosuppresant drug therapy should continue following
thymectomy, gradually tapered as patient’s condition improves

 Medications:
Anti cholinesterase (pyridostigmine 60mg 6times a day/Neostigmine-
15 mg)
For pure ocular myasthenia-
Steroids (prednisolone- 1.5mg/kg body wt/alternate day).
Gradually decreased to minimum effective dose.
Being long term therapy consider side effects like osteoporosis.

Azathioprine-2.5mg/kg body wt/day added as steroid sparing agent.

PHYSIOTHERAPY ASSESSMENT
 Muscle strength: MMT .

 Fatigue assessment: 10 point single item fatigue scale (0 – no

fatigue and 10 – greatest possible fatigue).

 Range of motion.

 Respiratory assessment: auscultation and chest expansion.

 Speech and swallowing

 Functional evaluation
 Endurance assessment
GOALS OF MANAGEMENT
 Improve strength in the muscles.

 Prevent respiratory muscle weakness.

 Improve respiratory function.

 To reduce fatigue.

 To improve cardiovascular and muscular endurance.

 To improve quality of Gait and balance.

DYSPHAGIA
◦ Patients may experience difficulty chewing and swallowing due to
oropharyngeal weakness

 If dysphagia develops, liquids should be thickened as they decrease

risk for aspiration.

 Refer for dietary consultation for choice and progression of solid

and liquid foods and supplements.

 Teach swallowing techniques.

 Change eating position, head position, texture or viscosity of food.

 Severe dysphagia requires nasogastric feeding tube.

MUSCLE STRENGTHENING

 All proximal muscles.

 Resisted exercises – PRE with adequate rest.
 Generalised lower limb exercises.
 Straight leg raise, hip abductn in standing, half squats and calf
raises.

 To improve aerobic capacity – treadmill training for 6 minutes at

2.5 kph. Progress to 30 min at 3.0 kph along with warm up and
cool down exs.

 Home walking programme: 1400meter 4 times a week, progress

to twice daily 4 times a week. Gradual progression to 1600 meter
4 times a week.

 Low impact aerobic exs can help to manage symptoms of fatigue

in MG patients.
RESPIRATORY TRAINING
 Diaphragmatic and intercostal breathing exs.
 Severe respiratory failure – ventilatory management.
BALANCE AND GAIT
 Balance exercises (start with exs within BOS, progress to out of
BOS).

 Pertubation exs.

 Gait training in parallel bars.

 Train individual components of gait.

FATIGUE (ENERGY CONSERVATION TECHNIQUES)

 Managing fatigue is an important aspect of managing disease.

 Fatigue: Generalised exhaustion of the entire body related to
central nervous system function rather than localised muscle
fatigue.

 Two main concepts:

Preserving energy

 Energy conservation : balance between rest and activity.

 Effective means to increase functional endurance : take 5 to 10

minutes break before getting tired or exhausted.
1. Need to identify ways that your own daily activities can be
simplified.
a. Think of the task thoroughly.
b. Decide when and where the job best done.
c. Plan out the simplest approach to the job.
d. Gather all supplements before you begin.
e. Arrange step sequence so that it moves in one direction.
f. Use fewer, more efficient movements to complete task.

2. Eliminate extra trips

a. Organise your shopping list
b. Clean one area at a time

3. Do not fight gravity

a. Use wheeled cart, trolleys
b. Use light weight equipment.
4. Use good posture and body mechanics
a. Sit to work.
b. Use large strong muscles
c. Lift with your knees bent, back straight.
d. Carry object close to the body
e. Push objects rather than pull.

5. Pace yourself
a. Get plenty of night rest.
b. Plan several rest periods during the day.
c. Rest before you get tired.
d. Avoid risk
e. Develop a rhythm to your movements.

6. Use energy saving device or adaptive equipment.

Thank you
 A randomized controlled trial wherein the training group underwent interval-
based IMT associated with BR (diaphragmatic breathing [DB] and pursed-
lips breathing [PLB]) three times a week for 8 weeks. The sessions included
10 min each of DB, interval-based IMT, and PLB.
 Interval-based IMT consisted of training series interspersed with recovery
time. The threshold load was increased from 20 to 60% of maximal
inspiratory pressure (Pimax) over the 8 weeks.
 Study concluded the partial home program of interval-based IMT associated
with BR is feasible and effective in patients with generalized MG.
Improvements in respiratory muscle strength, chest wall mobility, respiratory
pattern, and respiratory endurance were observed. (Guilherme et al 2005)
Extraocular muscle surgery may be beneficial in selected cases of
myasthenia gravis (J f Acheson, 1995).

 Difficulties in the pre-oral phase of swallowing were encountered

primarily.

 A limitation in the ability to open the mouth was also noted.

 Posterior swallowing time is especially affected.

 A better understanding of the swallowing problems associated with

these disorders may help in choosing treatment possibilities,
technical aids, adaptation of the consistency of foods, swallowing
rehabilitation, and nutritional support by the non-oral route.
(Willig T N, Arch Phys Med Rehabil. 1994 Nov;75(11):1175-81).