MYAESTHENIA GRAVIS

 MYASTHENIA GRAVIS

• Myasthenia gravis is an autoimmune disease in which antibodies mediate damage and destruction of acetylcholine receptors in striated muscle.
• The resultant impairment of neuromuscular conduction causes weakness and fatigability of skeletal musculature, but not of cardiac and involuntary muscles.
• Myasthenia gravis is an uncommon disorder characterized by weakness and fatigability of voluntary musculature due to impaired transmission at the neuromuscular junction.
• The disease affects females twice as commonly as males. The female to male ratio is 2:1. (2F:M)

PATHOGENESIS-

Antibodies → damage Ach receptors→ impaired neuromuscular contraction→ weakness & fatiguability of skeletal muscles [not cardiac / involuntary muscles]

Myasthenia may be  

 (a) ocular 

(b) bulbar 

(c) generalized. 

Clinical features  

• Presentation is typically during the third and fourth decades with excessive fatiguability of  ocular, bulbar and skeletal muscles. 
• Symptoms are typically worse in the evenings, although some patients may be troubled on  first waking 

Systemic myasthenia 

1. Presentation is usually in the 3rd decade, but may be at any time after the first year of life, most  frequently with ptosis or diplopia. 

Patients with generalized involvement may develop painless fatigue, often brought on by exercise, which may be worse towards the end of the day, and provoked by infection or stress. 

2. Signs. The most important feature is fatigability, affecting musculature of the limbs and that  involved in facial expression, ocular movements, mastication and speech. 

(a) Peripheral 

• Weakness, particularly of the arms and proximal muscles of the legs. 
• Limb muscle weakness which is increased by repetitive movements.  
• Permanent myopathic wasting may occur in long-standing cases. 

(b) Facial. Lack of expression and ptosis (myopathic facies) 

(c) Bulbar. Difficulties with swallowing (dysphagia), speaking (dysarthria) and chewing. 

(d) Respiratory. Difficulty with breathing is rare but serious. 

3. Investigations include the following: 

• Edrophonium test  
• Raised serum acetylcholine receptor antibody levels. 
• Thoracic CT or MR to detect thymoma, which is present in 10% of patients.  Patients under the age of 40 years without thymoma generally have a hyperplastic thymus;  in older patients the thymus is usually normal (atrophic). 
• (Chest X-ray of the anterior mediastinum may show a thymic enlargement in 10-20% of patients (usually  males).  
• CT scan (or preferably MR scan) of the anterior mediastinum should be performed in all patients to rule out the  possibility of a thymoma.) 
• Electromyography may be very helpful in confirming fatigue with repetitive stimulation.

4. Treatment options include: 

1.  Long-acting Anticholinesterase drugs (pyridostigmine, neostigmine) 
2. Systemic Steroids 
3. Immunosuppressive drugs (azathioprine, ciclosporin, cyclophosphamide) 
4. Plasma exchange (Plasmapharesis to remove antibodies in severely affected cases) 
5. Intravenous immunoglobulins  
6. Thymectomy.  
• Thymectomy may be helpful in some patients. 
• Young women with generalized symptoms of recent onset are most likely to benefit. Thymectomy should also be performed if a thymoma is suspected 
• Patients with pure ocular myasthenia are usually not helped by thymectomy. 

Ocular myasthenia 

• Ocular involvement occurs in 90% of cases and is the presenting feature in 60%. ∙ Two-thirds of patients have both ptosis and diplopia. 
• Less than 10% of patients have ptosis alone and less than 30% have diplopia alone.   

1. Ptosis 

• insidious, bilateral and frequently asymmetrical. 
• It is worse at the end of the day and least on awakening. 
• Ptosis is worse on prolonged upgaze due to fatigue. 
• If one eyelid is elevated manually as the patient looks up, the fellow eyelid will show fine  oscillatory movements. 
• Cogan twitch sign is a brief upshoot of the eyelid as the eyes saccade from depression to the  primary position. 
• Positive ice test demonstrates an improvement in the severity of ptosis improves after an ice  pack is placed on the eyelid for 2 minutes as cold improves neuromuscular transmission. The  test is negative in non-myasthenic ptosis. 

2. Diplopia is frequently vertical, although any or all of the extraocular muscles may be  affected. 

• A pseudo-internuclear ophthalmoplegia may be seen. 
• Patients with stable deviations may  benefit from muscle surgery, botulinum toxin injection or a combination of both. 

3. Nystagmoid movements may be present on extremes of gaze. 

• Bizarre defects of ocular motility may also occur so that myasthenia should be considered in  the differential diagnosis of any ocular motility disorder that does not fit with a recognized pattern. 

Edrophonium test 

 Edrophonium is a short-acting anticholinesterase agent which increases the amount of acetylcholine  available at the neuromuscular junction. In myasthenia this results in transient improvement of symptoms  and signs.  

The estimated sensitivity is 85% in ocular and 95% in systemic myasthenia. Potential but uncommon  complications include bradycardia, loss of consciousness and even death. 

 The test should therefore never be performed without an assistant, and a resuscitation trolley should also be  close at hand in case of sudden cardiorespiratory arrest.  

The test is performed as follows: 

• (a) Objective baseline measurements are made of the ptosis, or of the diplopia with a Hess test. 
• (b) Intravenous injection of atropine 0.3 mg is given to minimize muscarinic side-effects. 
• (c) Intravenous test dose of 0.2 mL (2 mg) edrophonium hydrochloride is given. If definite symptomatic  improvement is noted, the test is terminated forthwith. 
• (d) The remaining 0.8 mL (8 mg) is given after 60 seconds, provided there is no hypersensitivity. 
• (e) Final measurements/repeat Hess testing are made and the results compared, remembering that the effect lasts  only 5 minutes.

Treatment

1. Anticholinesterase drugs-Pyridostigmine 60mg qid

                                            -Neostigmine

2.  Steroids.[ may precipitate respiratory crisis],so close monitoring is a must

3. Immunosuppressive – Azathioprine [1-3mg/kg/day]-OD /BD

                                     _  Cyclosporin [2-5mg/kg/day]

4. Plasma exchange

5. Intravenous immunoglobulins

6. Thymectomy

7. For ptosis- B/L  Frontalis sling

Diff from Eaton Lambert syndrome -

• Eaton Lambert syndrome -
• Affects pre-synaptic receptor [ MG- postsynaptic]
• Power is increased following exercise
• Reduced tendon reflex [ normal in MG]
• Seen in oat cell carcinoma