DISORDERS OF

NEUROMUSCULAR
JUNCTION
By- Well wisher
 DISORDERS OF NEUROMUSCULAR
JUNCTION
• Myasthenia gravis
• Lambert- Eaton Syndrome
 Myasthenia Gravis
 Myasthenia gravis is an autoimmune neuromuscular disease characterized
by generalized muscle weakness.
 When acute life threatening exacerbation of myasthenic symptoms occur,
a myasthenic crisis occurs that leads to respiratory failure.
 Epidemiology
• It is the most common neuromuscular junction disorder.
• It is more commonly seen in females when compared to males.
• Peak incidence in males is between 40-70 years and in females is between
20-40 years.
 Etiology
• Autoreactive antibodies target against the postsynaptic Ach receptor at the
NMJ.
• It is associated with other autoimmune diseases like Hashimoto thyroiditis
or rheumatoid arthritis.
• It is also associated with thymic hyperplasia or thymoma.
 Classification
• Ocular myasthenia- Only extraocular or eyelid muscles.
• Generalized myasthenia- All skeletal muscles are involved like ocular,
bulbar, limb and respiratory muscles.
 Pathophysiology
• Acetylcholine receptor antibodies are responsible for inhibition of signal
transduction in the NMJ.
• Antibodies target postsynaptic AchRs of normal muscles and leads to the
competitive inhibition of Ach.
• AchR decay occurs due to decreased receptor density at the postsynaptic
membrane and activation of complement which leads to skeletal muscle
weakness and fatigue.
 Clinical features
• Muscle weakness that worsens with use and improves with rest.
• Eye muscle weakness like ptosis or diplopia, bulbar muscle weakness,
proximal limb weakness and respiratory muscle weakness.
 Diagnostics
 AChR antibody test
 Electromyography
 Chest CT
 Prognosis
• Prognosis of ocular MG is good.
 Treatment
• Cholinesterase inhibitors like pyridostigmine is used to improve
symptoms.
• Supplemental immunosuppressants like glucocorticoids can be used if
symptoms persist after using cholinesterase inhibitors.
• Thymectomy and plasmapheresis can also be done.
 LAMBERT- EATON SYNDROME
• It is a rare autoimmune disease that reduces neuromuscular transmission,
leading to muscle weakness.
 Etiology
• It arises due to a paraneoplastic syndrome, most commonly due to small
cell carcinoma.
• It can also be associated with other autoimmune diseases.
 Pathophysiology
 Autoantibodies are directed against presynaptic calcium channels at the
NMJ.
 This leads to a decreased calcium influx which results in decreased
presynaptic vesicle fusion.
 As a result of the above steps, an impaired acetylcholine release in the
NMJ occurs.
 Clinical features
• Proximal muscle weakness improves with use , eyes are usually spared.
• Dry mouth or constipation can also be seen.
 Diagnostics
• Physical examination
1) Active muscle contraction or repeated muscle tapping increases reflex
activity.
2) Lambert sign- Muscle strength improves with repetitive or ongoing
use.
 Prognosis
• It is worse when compared to myasthenia gravis.
 Treatment
• Paraneoplastic LEMS- Therapy of the underlying malignancy.
• Drugs like amifampridine can also be used to improve neuromuscular
transmission.
• A 42 year old woman comes to the physician because of progressive weakness. She has
noticed increasing difficulty performing household chores and walking her dog over the past
month. Sometimes she feels to fatigued to cook dinner. She has noticed that she feels better
after sleeping. She does not have chest pain, shortness of breath or a history of recent illness.
She has no personal history of serious illness and takes no medications. She appears fatigued.
Her temperature is 37 C, pulse is 88/min and blood pressure is 148/80 mm Hg. Pulse
oximetry shows an oxygen saturation of 98% on room air. Bilateral expiratory wheezes are
heard at both lung bases. Examination shows drooping of the upper eyelids. There is
diminished motor strength in her upper extremities. Her sensation and reflexes are intact. A
treatment with which of the following mechanisms of action is the most appropriate next step
in the management?
1) Inhibition of acetylcholinesterase
2) Stimulation of beta 2 adrenergic receptors
3) Removing autoantibodies, immune complexes and cytotoxic constituents
from serum.
4) Reactivation of acetylcholinesterase
5) Competitive blocking of the muscarinic receptor
Cholinesterase inhibitors are used to manage the symptoms of myasthenia
gravis because they increase the availability of endogenous acetylcholine in
the NMJ, which competes with the Ach receptor antibodies that would
otherwise block Ach receptors. Pyridostigmine and neostigmine are the
prefered drugs since they act only on the peripheral Ach receptors and do not
cross the BBB, thereby limiting the adverse effects.
 References
• Robbins basic pathology 10 th edition
• Amboss
• Medscape