1. Neuromuscular disorders
Myasthenia gravis
Eaton Lambert syndrome
Botulism

2. MYASTHENIA GRAVIS AUTOIMMUNE DISORDER
ANTIBODIES DIRECTED TOWRDS THE ACETYLCHOLINE RECPTORS AT POST SYNAPTIC MEMBRANE
AFFECTS ANY AGE
BUT MAINLY AGE YEARS
2 FEMALE >1 MALE
ROLE OF THYMUS

3. Role of the thymus
Abnormalities of the thymus in 80 %
Production of T-cell lymphocytes which participate in the immune responses

4. Pathophysiology III-postsynpatic membrane:Ach receptors
Neuromuscular junction is composed of
I-Presynaptic nerve ending which contains the synaptic vesicles(Ach)
II.Synaptic cleft
III-postsynpatic membrane:Ach receptors
Reuptake of the Ach by choline-estetrase

5. Clinical features I
Fatigability

6. DEFINITION
FAILURE TO SUSTAIN A MAINTAINED OR REPEATED CONTRACTION OF STRIATED MUSCLES

7. Clinical features II Onset usually insidious Fluctuating weakness
Weakness at the end of the day
Extraocular muscles (ptosis)
Bulbar muscles
Limbs
generalized

8. Clinical features III Onset can be fulminant
With involvement of respiratory muscles
Weakness may be provoked by :
Infection, hypo k., hypocalcemia
Drugs :
Quinine.betablockers,phenytoin
Sedatives (diazepam)
Antibiotics
Surgery,pregnancy

9. Clinical exam I Look for fatigability
Examine motor power :first movement is normal
Repeat movements; weakness will appear
All muscles should be examined
Induce fatigue (no change of power in normal individual)

10. Clinical exam II Every thing else is normal Reflexes unaffected
No wasting
No deformity
Tone is normal
No sensory change

11. Clinical exam III May be associated with diseases Malignancy
Autoimmune disorders.
Then look for associated features

12. Test to be used in the clinic :Tensilon test
Technique:
Inject edrophonium (10 mg in 1cc)
First 2 mg (0.2 cc)
If no hypotension or hypersensitivity
Inject the rest (8mg)
Result:
Weakness improves within 1-2 minutes

13. CRISiS
I- Myasthenic crisis
II-Cholinergic crisis

14. I.Myasthenic Crisis Precipitating factors Infections Changes of drugs
Pregnancy
Surgery

15. II-cholinergic crisis
Excessive use of anticholinergic medication
Myosis,diarrhea,
increased salivation
Abdominal cramps
bradycardia

16. Investigations I Logical (immune disorder)
Look for antibodies in serum
EMG
Repetetive stimulation test
Technique :
Exert repetetive stimulation o nerve (ulnar) at 3,10,30-50 (tetanization) and look for response -> decremential response
Single fiber EMG :increased jitter.=delayed NMJ transmision

17. Investigations II Biopsy of the neuromuscular joint
And electron microscope study
Severe Loss of receptors
Look for the thymus by CXR,CT,MRI

18. Neonatal MG
12-16 % of infant born to myasthenic mother have myasthenic features (ptosis,weakness,poor cry and suck)
Last up to 6 weeks
Due to transplacental transfer of maternal circulating anti-Ach receptor antibodies
Temporary administration of anti choline esterase agents may be needed

19. Treatment I 1-Anticholine esterase agents
A-Short acting :neostigmine (Prostigmine)
B-Long acting : pyridostigmine (Mestinon)
20.60 and 180 mg
2-4 times a day
SE : increased bronchial secretions bronchspasm,miosis,diarrhea,abdominal cramps,bradycardia

20. Treatment II
Reduce circulating antibodies
Plasmpheresis

21. Treatment III :immunemodulation
Steroids
Immunosupressants
IVIG

22. Treatment VI Thymus
Thymectomy
Thymic hyperplasia ? More common :70%

23. EATON LAMBERT SYNDROME I
Male > female
Later onset
Associated with oat cell carcinoma of the lung in 70%
Affects mainly lower extremities
Clinically initial fatigability-weakness which improves on continuing the effort
Due to impairment of the Ach release in the presynaptic part

24. E-L syndrome II Neurophysilogy:incremental response
Treat the underlying cause

25. Botulism
Bacterial :clostridium botilinum an anaerobic spore forming bacteria -> very strong toxin
May be present in improperly canned food
In raw meat
Toxin impairs pre-synaptic Ach release
Leads to severe weakness and autonomic features

26. Botulism Supportive treatment Tracheostomy Death in about 15 %
Botulinum toxin (Botox) is used in dystonia, spasticity and for cosmetic purposes