Muscle and neuromuscular junction disease

Question 1

What are 2 pre-synaptic muscle disorders?

Answer 1

Botulism

Lambert-eaton myaesthenic syndrome

Question 2

what is botulism?

• what is this cause by?
• what is the pathophysiolofy

Answer 2

Clostridium botulinum. Found in soil. Food and woulds can become infected. Intravenous drug users – black tar heroin.

 Botulinum toxin cleave presynaptic proteins involved in vesicle formation and block vesicle docking with the presynaptic membrane. Rapid onset weakness without sensory loss. Some medical (and cosmetic) uses of toxin

Question 3

What is Lambert eaton myaesthenic syndrome? what is this strongly associated with?

Answer 3

Lambert Eaton Myasthenic Syndrome -antibodies to presynaptic calcium channels leads to less vesicle release. Strong association with underlying small cell carcinoma.

Presynaptic problem that is the sequelae to cancer

Question 4

What is myaesthenia gravis?

Answer 4

Postsynaptic autoimmune disorder:

• antibodies to acetyl choline receptors (AchR)
• reduced no. of functioning receptors leads to muscle weakness and fatiguability

Question 5

What is the pathophysiology of myaesthenia gravis?

Answer 5

• reduced number of ACh receptors and flattening of endplate folds
• even with normal amounts of ACh transmission becomes inefficient
• symptoms start when ACh receptors reduced to 30% of normal
• as the Ach receptors are blocked they die and grow back, but less and less do grow back
• ACh antibodies are found in 80 - 90% patients
• Antibodies block binding of ACh but also trigger inflammatory cascades that damage the folds of the postsynaptic membraneThymus plays a role, 75% patients have hyperplasia or thymoma

Question 6

At what age does myaesthenia gravis affect people?

Answer 6

May occur at any age but two peaks of incidence

females in 3rd decade 

males in 6th or 7th decade 

female:male ratio - 3:2

Question 7

describe the clinical features of myaesthenia gravis

Answer 7

Weakness typically fluctuating - worse through the day

Most common presentation with extraocular weakness, facial and bulbar weakness 

Weakness fluctuates and repetitive motions are hardest e.g. speaking/swallowing 

Limb weakness typically proximal 

Ptosis – extraocular weakness most common 

Bilateral facial weakness

Question 8

What is the treatment of myaesthenia gravis?

Answer 8

acetylcholinesterase inhibitor – pyridostigmine

increase concentration of Ach in cleft initiallyy 

thymectomy 

immunomodulating 

ultimately autoimmune so use immunosupression 

steroids / azathioprine 

emergency treatment with plasma exchange or immunoglobulin

Question 9

What is the typical history for inclusion body myositis?

Answer 9

Historically thought to be inflammatory but little response to steroid

Typically slowly progressive weakness in 6th decade of life with characteristic thumb sparing

Question 10

What is myotonic dystrophy?

-what are the clinical features?

Answer 10

Commonest muscular dystrophy

Autosomal dominant 

Multisystem involvement 

Myotonia, weakness, cataracts, ptosis, frontal balding, cardiac defects 

Trinucleotide repeat disorder with anticipation

Question 11

What is the triad for rhadomyolysis?

• what causes rhabdomyolysis?
• what are the complications?

Answer 11

“dissolution of muscle”

damage to skeletal muscle causes leakage of large quantities of toxic intracellular contents into plasma. 

Many potential causes – crush injuries, toxins, post convulsions 

Triad of myalgia, muscle weakness and myoglobinuria 

Complications of acute renal failure and DIC