This document discusses neuromuscular junction disorders, focusing on Myasthenia Gravis. Myasthenia Gravis is an autoimmune disorder causing muscle weakness and fatigue. It results from antibodies destroying acetylcholine receptors at the neuromuscular junction, reducing signal transmission. Symptoms include drooping eyelids, facial weakness, difficulty swallowing and limb weakness. Diagnosis involves tests like repetitive nerve stimulation and response to medication like pyridostigmine. Treatment includes pyridostigmine, steroids, immunosuppressants and sometimes plasma exchange or IV immunoglobulin for severe cases. Thymectomy may also help by removing the source of antibody production in the thymus.

1. Neuromuscular junction disorders
Dr Mohamed Rizk Khodair
Lecturer of neurology
Faculty of medicine

2. Introduction
Diseases of the neuromuscular junction can be classified as either presynaptic (e.g., Lambert-Eaton
syndrome, botulism) or postsynaptic (e.g., myasthenia gravis).

3. Disorders of Neuromuscular Junctions
Myasthenia
Gravis
Lambert Eaton
Syndrome
Congenital Myasthenic
Syndromes
Botulism

4. Myasthenia gravis
It is a disorder of neuromuscular junction
(NMJ) causing easy fatigability of skeletal
muscles. There is no weakness or atrophy.

5. Etiology
 Autoimmune production of antibodies against acetylcholine (nicotinic) receptors (AChR) in the NMJ.
 Antibodies are produced from B cells and helped by T cells in cultures of hyperplastic thymus.
The production of these antibodies will lead to:
a) Accelerating internalization of Acetyl choline receptor molecules.
b) Destruction of junctional folds.
c) Blocking binding of Acetyl choline to Acetyl choline receptor
d) Reduction of postsynaptic Acetyl choline receptors
e) Inefficient neuromuscular transmission.
Patients become symptomatic when the number of AChRs is reduced to approximately 30% of normal.

6. Other autoimmune conditions associated with MG:
Thyroiditis, Graves ’Disease, Rheumatoid Arthritis, SLE, Pernicious Anemia, Addison’s Disease, Vitiligo, NMO.

7. Clinical picture
Age: at any age (20-40 years).
Sex: females more than males = 3: 2
 Easy fatigability on repetition of movement, but without weakness. Fluctuation of symptoms and diurnal variation; patient is better in the
morning
 Temporary increase weakness occurs after:
Vaccination, Menstruation, And Extremes of Temperature.
 The disease affects the skeletal muscle in a descending march:
- Ocular muscles:
Ptosis and diplopia (muscles affected are levator palpebrae superioris, (superior rectus, lateral rectus), usually asymmetric.
- Facial muscles:
Expressionless face, Myasthenic snarl on smiling (lip retractors are affected more than elevator's).
- Bulbar muscles:
Dysphagia, Nasal Intonation of Voice, And Nasal Regurgitation.
- Upper limbs and Lower limbs weakness:
(Proximal more than distal).
In UL, deltoids, and extensors of the wrist' and fingers are affected most. Triceps > biceps.
In LL, hip flexors, quadriceps, and hamstrings.
- Respiratory muscles (more. with cholinergic crisis}.
Recognize imminent respiratory failure.
- Neck muscles and erector spinae muscles.
o sensory, normal DTRs, no sphincteric manifestation.

8. Complications
Myasthenic crisis (rapid respiratory deterioration and
failure) Aspiration pneumonia.

9. Bedside tests
 Provoke weakness by repetitive or
sustained use of muscles involved 
fatigue.
 Walker test: apply the
sphygmomanometer, raise the pressure
and the patient
 does repetitive movements with his hand
 ptosis appear.
 Ice pack test (i.e., placing ice over the
lids)  improvement in ptosis
 Counting test: it is a bed side test for
follow up.

10. 1) Pharmacological Tests:
• Prostigmine test: give atropine sulfate I.M. 9 (to guard against muscarinic side
effects), plus prostigmine 2.5 mg IM (20 minutes later) à improvement of
myasthenic symptoms after 20 minutes (improvement must be > 50%,
sustained for 1 hour at least).
• Tensilon {edrophonium) test: 1 mg test dose is given first then 8 mg Tensilon
IV à improvement in one minute.
2) Neurophysiological Studies:
• Repetitive Nerve Stimulation: low amplitude of action potentials with
repetition. of movements, or decrement response; supramaximal, repetitive
stimulation. Of the nerve (3 Hz) decreases in amplitude of the action potentials
(compare 5th with 1st if > 10- 15% à MG)
• Single Fiber EMG: more sensitive but difficult à increased jitter.
• Routine NCS: normal.

11. 3) laboratory Tests:
• Anti-acetylcholine receptor (AChR) antibody "most specific": positive in 90% with generalized MG, and 50-70%
with pure ocular MG.
• Anti-striated muscle antibody (in about 84% of with thymoma who< 40 years).
• Anti-MuSK antibody (present in .1/2 of patients with negative results for antiAChR antibody}. MuSK plays a
critical role in postsynaptic differentiation and clustering of AChRs.
• Antistriational antibody (present in almost all patients with thymoma and MG, as well as in half of MG patients
with. onset of MG at SO years or older).
• Lab for associated thyrotoxicosis, thyroiditis, SLE, rheumatoid.
4) Muscle biopsy:
• Widening of myoneural junction.
• Normal presynaptic membrane.
• Flattening of postsynaptic membrane.
• Marked reduction of post synaptic proteins.
• Increase lymphocytes.
5) Radiology:
• X-ray (lateral view), CT chest to detect thymic enlargement (thymic hyperplasia in young, or malignant thymoma
in old).

12. Treatment
Initial Treatment Plan
Choose inpatient care: For significant bulbar symptoms early on, low vital capacity, respiratory symptoms, or
progressive deterioration.
Choose outpatient care: For ocular symptoms, mild-to moderate limb weakness and mild bulbar symptoms.
A. Pharmacological:
1) Acetylcholine esterase. (AChE) inhibitors:
Pyridostigmine (mestinon): 60 mg tab 3-6 times/day long-acting effect, decrease by 4-6 hours
Action: they inhibit the cholinesterase enzyme responsible for the destruction of Ach  increase Ach in the MNJ.
Side effects:
a. Fasciculation, pupillary constriction.
b. Increase secretions, lacrimation, salivation, bronchial, and diarrhea.
c. Increase muscle contraction: bronchial asthma, incontinence to urine.
d. Cardiac arrhythmias·; and cholinergic crisis.

13. 2) Prednisolone
- Steroids indicated in patients who are not adequately controlled with cholinesterase inhibitors and are
unsuitable for thymectomy.
3)Azathioprine
- Azathioprine, with its actions predominantly on T cells.
- It is prescribed for:
- Those in whom corticosteroids are contraindicated.
- Those with an insufficient response to corticosteroids as a steroid-sparing agent.

14. 4) Rituximab (anti-CD20 B-cell monoclonal antibody) 375 mg/m2 IV four times weekly reports of benefit in resistant
cases.
5) Plasma exchange and IV immunoglobulin
- Both may be used for patients in myasthenic crisis with severe bulbar and respiratory compromise.
- Patients may also be pre-treated prior to thymectomy.
- Patients with seronegative MG may also respond. The effects last 4–6 weeks.
- Plasma exchange: five exchanges, 3–4 L per exchange over 2 weeks.
- IV immunoglobulin: 0.4 g/kg/day for 5 days.
6) Thymectomy
- Therapeutic benefit in MG (generalized and less often in ocular myasthenia): results in complete remission in some
patients or a reduction in immunosuppressive medication in others.

15. Thank you
Mohamedrizk.med@o6u.edu.eg