By Dr.Walid Reda Ashour

Myasthenia GravisMyasthenia Gravis

• Definition:Definition:

• It is a chronic disorder in NMJ It is a chronic disorder in NMJ characterized by easy muscle characterized by easy muscle fatiguability on repetition of fatiguability on repetition of movement & relieved by rest.movement & relieved by rest.

Etiology :Etiology : • It is due to impairment of conduction at the It is due to impairment of conduction at the

neuromuscular junction. neuromuscular junction.

Pathogenesis :Pathogenesis :

Unknown. theories: Unknown. theories: 1- Acetyl choline deficiency. 1- Acetyl choline deficiency. 2- Choline esterase in excess. 2- Choline esterase in excess. 3- Curare- like substance at the N.M.J. 3- Curare- like substance at the N.M.J.

increasing the threshold of motor end plate to increasing the threshold of motor end plate to Acetyl Choline . the thymus gland is blamed for Acetyl Choline . the thymus gland is blamed for secretion of such substance. secretion of such substance.

• 4- Recently the disease is considered as an 4- Recently the disease is considered as an auto-immune disorderauto-immune disorder, antibodies against A.ch , antibodies against A.ch receptors in NMJ. receptors in NMJ.

• Age: 20-40 . Age: 20-40 .

• Sex : female > male. Sex : female > male.

• Gradual onset.Gradual onset.

• Progressive course.Progressive course.

• Skeletal muscles only.Skeletal muscles only.

C/PC/P* Most characteristic feature is * Most characteristic feature is Easy FatiguabilityEasy Fatiguability on on

repetition of movement. repetition of movement.

• Characteristic Characteristic descending march course:descending march course:

A) Ocular:A) Ocular: ptosis is the earliest symptom. Later ptosis is the earliest symptom. Later ophthalmoplegia & diplopia. pupillary reaction are normal.ophthalmoplegia & diplopia. pupillary reaction are normal.

B) Facial:B) Facial: expressionless expressionless (mask face)(mask face). On smiling. On smiling

(myasthenic snarl).(myasthenic snarl).

C) Jaw muscles: C) Jaw muscles: mouth hanging open.mouth hanging open.

D) Bulbar:D) Bulbar: dysarthria, dysphagia, nasal regurgitation & nasal dysarthria, dysphagia, nasal regurgitation & nasal tone of voice.tone of voice.

E) Other muscles:E) Other muscles: neck muscles neck muscles (head lolling),(head lolling), upper limbs upper limbs more than lower limbs (prox. > distal), respiratory muscles more than lower limbs (prox. > distal), respiratory muscles leading to dyspnea. leading to dyspnea.

* Diurnal variation:* Diurnal variation:

After night rest the patient wakes up in the After night rest the patient wakes up in the

morning nearly normal but as the day goes on morning nearly normal but as the day goes on

with its activity the muscle gradually become with its activity the muscle gradually become

weaker.weaker.

* Tendon reflexes: normal but after repeated * Tendon reflexes: normal but after repeated

tapping tapping lost . lost .

* Muscles atrophy: may occur in long standing * Muscles atrophy: may occur in long standing

cases.cases.

* Some cases may be associated with * Some cases may be associated with

thyrotoxicosis or enlarged thymus gland . thyrotoxicosis or enlarged thymus gland .

DIAGNOSIS

DiagnosisDiagnosis : :

1- Clinically:1- Clinically: a ) The a ) The descending marchdescending march character character

and the and the diurnal variationdiurnal variation..

b) Induction of fatigue by repetition of b) Induction of fatigue by repetition of

movements.movements.

c) c) Walker's test:Walker's test: sphygmomanometer is sphygmomanometer is

applied to the arm. The pressure is raised above applied to the arm. The pressure is raised above

the systolic. The patient is asked to do rapid the systolic. The patient is asked to do rapid

repetitive movements with his hand till exhaustion repetitive movements with his hand till exhaustion

occurs. The cuff is then released. In case of occurs. The cuff is then released. In case of

myasthenia myasthenia ptosis will occur within a few ptosis will occur within a few

seconds .seconds .

2- Pharmacological tests:2- Pharmacological tests:

a) Prostigmine test :a) Prostigmine test : I.M injections of 2.5 mg I.M injections of 2.5 mg prostigmine + one ampoule atropine ( to prostigmine + one ampoule atropine ( to counteract the action of prostigmine on the counteract the action of prostigmine on the smooth muscles of intestine), improvement smooth muscles of intestine), improvement occurs within 1/2 h in myasthenia.occurs within 1/2 h in myasthenia.

b) Tensilon test: b) Tensilon test: 8 mg I.V improvement occurs 8 mg I.V improvement occurs within 1 min.within 1 min.

3- EMG:3- EMG:

Reduction in amplitude of the motor action Reduction in amplitude of the motor action potentials on successive motor activity potentials on successive motor activity (decrementing response).(decrementing response).

Tensilon test

AfterBefore

4) CT & Plain X-ray4) CT & Plain X-ray

chest may show thymic enlargement. chest may show thymic enlargement.

5) Serological tests: 5) Serological tests:

Anti-AchR Ab in serum of 85-90% pt.Anti-AchR Ab in serum of 85-90% pt.

N.BN.B. seronegative myasthenia gravis refers to . seronegative myasthenia gravis refers to

disease without detectable (anti-AChR) Ab. In disease without detectable (anti-AChR) Ab. In these patients, IgG antibodies against the muscle-these patients, IgG antibodies against the muscle-

specific kinase (MuSK)specific kinase (MuSK) have been described.have been described.

6) Muscle biopsy:6) Muscle biopsy:

increased lymphocytes.increased lymphocytes.

• TreatmentTreatment

1 ) Rest:1 ) Rest: avoid excessive exercise and avoid excessive exercise and exhaustion.exhaustion.

2 ) Medical:2 ) Medical:

I) Anticholinesterase drugs:I) Anticholinesterase drugs:

* Prostigmine. * Pyridostigmine.* Prostigmine. * Pyridostigmine.

II) Steroids: II) Steroids: Prednisolone in pt. not Prednisolone in pt. not responding to I) may give remission up to 5 responding to I) may give remission up to 5 years.years.

III) Other immunosuppressant drugs:III) Other immunosuppressant drugs: e.g. e.g. Azathioprine in pt. not responding to Azathioprine in pt. not responding to steroids.steroids.

3) Plasmapharesis:3) Plasmapharesis: Pt.’s plasma exchanged for Pt.’s plasma exchanged for albumin to reduce AchR ab level. Repeated every albumin to reduce AchR ab level. Repeated every 2-3 weeks2-3 weeks

4) Surgical: 4) Surgical:

a) Thymectomy:a) Thymectomy: May be needed in severe cases May be needed in severe cases especially in young patient with duration less especially in young patient with duration less than 3 years . the prognosis is better if no than 3 years . the prognosis is better if no thymoma. In pt. with thymoma irradiation should thymoma. In pt. with thymoma irradiation should be tried before operation .be tried before operation .

b) Thyroidectomy:b) Thyroidectomy: If there is associated If there is associated thyrotoxicosis.thyrotoxicosis.

Secondary MyastheniaSecondary Myasthenia Easy fatiguability secondary to known diseases:Easy fatiguability secondary to known diseases:

1) Bronchogenic carcinoma.1) Bronchogenic carcinoma.

2) Polymyositis.2) Polymyositis.

3) Lupus erythematosis.3) Lupus erythematosis.• In this condition there:In this condition there:

- No descending march.- No descending march.

- Not responding to prostigmine but to guanidine - Not responding to prostigmine but to guanidine Hcl.Hcl.

- E.M.G after repetitive movement - E.M.G after repetitive movement increase increase amplitude of motor action potential amplitude of motor action potential (incrementing (incrementing response). response). Eaton- Lambert phenomenon.Eaton- Lambert phenomenon.

Neonatal MyastheniaNeonatal Myasthenia

Myasthenic women's infants show Myasthenic women's infants show myasthenic manifestations at birth. myasthenic manifestations at birth.

• Due to transplacental passage of AchR Due to transplacental passage of AchR Ab.Ab.

• Poor crying, suckling & floppy infant.Poor crying, suckling & floppy infant.

• They recover spontaneously within 2 – They recover spontaneously within 2 – 6 weeks.6 weeks.

• We may use We may use AnticholinesteraseAnticholinesterase drugs. drugs.

Congenital MyastheniaCongenital Myasthenia

* Very rare.* Very rare.

* Starts in infancy.* Starts in infancy.

* Structural abnormality in the * Structural abnormality in the AchR at NMJ.AchR at NMJ.

* persists for life.* persists for life.

* No treatment.* No treatment.

• Crisis in myastheniaCrisis in myasthenia : : It is of two types :It is of two types :

1 ) Myasthenic crisis 1 ) Myasthenic crisis :: due to increase of the due to increase of the

severity of myasthenia with sudden deterioration in severity of myasthenia with sudden deterioration in

pt.'s conditionpt.'s condition..

2) Cholinergic crisis :2) Cholinergic crisis : due to over dosage in ttt due to over dosage in ttt

(choline esterase intoxication ).(choline esterase intoxication ).

• C/P.C/P.

I) weakness of the muscles which simulate I) weakness of the muscles which simulate

myasthenic crisis .myasthenic crisis .

II) Fasciculations , pallor , sweating , small pupils II) Fasciculations , pallor , sweating , small pupils

and excessive salivation.and excessive salivation.

THANK YOU