Diseases of Neuromuscular junction Flashcards
How are diseases of the neuromuscular junction characterised
By impaired transmission of impulses at the neuromuscular junction
What is the anatomy of the neuromuscular junction
Presynaptic terminal (synaptic vesicle, Ca+2 channel)
Synaptic cleft (ACh, AChE)
Postsynaptic membrane (Fold, AChR)
What is the function of the NMJ
site of transmission of action potential from nerve to muscle
What is myasthenia gravis (MG)
is chronic autoimmune disorder of the NMJ in which antibodies destroy the communication between nerves and muscle, resulting in weakness of the skeletal muscles.
What is the etiology of MG
AChR antibodu –> Decrease of AChRs, postsynaptic folds flatten –> weakness of muscle contraction
- Thymus plays a role in thsi process, 75% of patients have germinal hyperplasia , 10% have thymomas
List the clinical manifestations of MS
- can occur at any age; females are more prone than males (3:2)
- provoked or worsened by infection, fatigue, psychic trauma, pregnancy
- insidious onset, slow progression
- cardinal features
- extraocular muscles: ptosis of eyelid, diplopia, strabismus
*pharyngolaryngeal muscles: difficulty in chewing and swallowing, speech in lower voice - limb muscles: difficulty in lifting objects, walking and running
*respiratory muscles: dyspnoea, even respiratory muscle paralysis
How is MG diagnosed?
Tests:
- clinical features
- Jolly/fatigue test (+)
- Anticholinesterase test (+)
- neostigmine: 0.5-1mg im/tensilon: 2mg + 8mg iv
- EMG: repetitive electrical stimulation test: decrement
- AChR antibody titre test
Clinical pearls of MG:
- variable muscle weakness
- weakness in cranial nerve distribution
- normal reflexes and sensation
- response to anticholinesterase drugs
What is the differential diagnosis for MG
Lambert-Eaton myasthenic syndrome (LEMS)
- autoimune disorder of NMJ that can causes weakness similar to that of MG
- most patients have associated malignancy (small-cell carcinoma of lung) –> thought to trigger the autoimmune disease
- proximal muscles of lower limbs are most commonly affected
- AChR antibody titre test (-)
- Anticholinesterase test (+/-)
How is MG treated
- avoid over-fatigue and other induced causes
- anticholinesterase drugs
- thymectomy
- immunosuppresants
- corticosteroid therapy
- plasmapheresis and IVIG
- management of crisis
What is meant by “management of crisis” for the treatment of MG
Crisis: rapidly progressive weakness of medulla oblongata and respiratory muscles leading to dyspnoea and respiratory failure (life-threatening event)
What are the 3 types of crises?
1.Cholinergic crisis
- overdosage of the anti-AChE
- paradoxic worsening in tensilon test
2. Myasthenic crisis
- underdosage of anti-AChE
- tensilon test is (+)
3. Brittle crisis
- poor response to anti-AChE
- tensilon test is negative
How is crises in MG managed?
- keep the respiratory tract unobstructed
- differentiate the types and treat them in time
What is meant by periodic paralysis
group of rare inherited disorders that cause temporary episodes of muscle weakness or paralysis
What is the etiology of hypokalaemic periodic paralysis
autosomal-dominant inheritance
What are the clinical features of hypokalaemic periodic paralysis
- attacks begin in 1st/2nd decade
- overfatigue, high carb meal –> may induce attacks
- symptoms noticed after rest or sleep –> four limbs may have flaccid paralysis (not involving cranial muscles)
- serum potassium is decreased <3.5mmol/L
- ECG: U waves appear
- attacks last from several hours to one weeks
