Neuromuscular Disorders

Question 1

Explain the key steps in muscular contraction and spread of impulse from NM junction

Answer 1

• Transmission at the NMJ is mediated by quantal release of ACh which acts on post-junctional nicotinic ACh receptors (nAChRs) to increase membrane cation conductance generating an e.p.p.
• The e.p.p. initiates a muscle action potential (AP) that invades the T-tubule system causing contraction by electromechanical coupling
• The action of ACh is terminated its hydrolysis by acetylcholinesterase (AChE)

Question 2

What is the action of Ach terminated by?

Answer 2

hydrolysis by acetylcholinesterase (AChE)

Question 3

What are 2 presynaptic disorders of the neuromuscular junction?

Answer 3

Botulism

Lambert eaton myasthenic syndrome

Question 4

Describe Lambert Eaton Myasthenic syndrome?

Answer 4

antibodies to presynaptic calcium channels leads to less vesicle release. Strong association with underlying small cell carcinoma. Treatment with 3- 4 diaminopyridine.

Question 5

Describe Botulism?

Answer 5

Organism present in soil. Food and wounds can become infected. IV drug users – black tar heroin.
Botulinum toxin cleaves presynaptic proteins involved in vesicle formation and blocks vesicle docking with the presynaptic membrane. Rapid onset weakness without sensory loss. Some medical (and cosmetic) uses of toxin.

Question 6

What is myasthenia gravis?

Answer 6

Auto-immune disorder of NMJ transmission, affects post synaptic transmission.

Question 7

Describe pathogenesis of myasthenia gravis?

Answer 7

Antibodies to acetylcholine receptor protein are present and these form complexes causing destruction of acetylcholine receptors blocking binding of Ach to post synaptic membrane. As Ach is the NT at the NMJ this means signals don’t get through to the muscle. Symptoms start when acetylcholine receptors are reduced to 30% of normal.

Question 8

What is found in 70% of MG patients under 40 yo?

Answer 8

thymic hyperplasia

Question 9

What ages tend to get MG?

Answer 9

peaks for females in the 3rd decade

peaks for males in the 6th or 7th decade

Question 10

Males or females get MG more?

Answer 10

females

Question 11

Describe some presenting symptoms of MG?

Answer 11

Weakness, worsen through the day > FATIGUABLE!
Most commonly extra ocular weakness, facial and bulbar weakness
proximal limb weakness
drooping eye lids
eye movement abnormalities > double vision that comes and goes

Question 12

Describe investigations for MG?

Answer 12

Serum anti AchR and anti-MuSK antibodies
repetitive nerve stimulation test shows characteristic decrements in evoked muscle action potential during repetitive stimulation
Imaging to look for thymomas

Question 13

Describe the prognosis of MG?

Answer 13

Use to be quite bad but now actually only mortality of 3-4%, the disease fluctuates in severity

Question 14

Describe acute treatment of MG?

Answer 14

acetylcholinesterase inhibitors (this allows persistence of Ach so get transmission through) Intravenous immunoglobulin

Question 15

Describe long term treatment of MG?

Answer 15

Steroids initially then move slowly to steroid sparing agents e.g. azathioprine and mycophenolate
potentially thymectomy

Question 16

Describe drugs that should be avoided in MG?

Answer 16

There is a long list, big one to know about is gentamicin, sometimes patients with MG are actually picked up because they are given gentamicin for a UTI and then get dramatic MG symptoms when before their MG was so mild they didn’t notice.

Question 17

Define myotonia and explain what someone might complain of?

Answer 17

Failure of muscle relaxation after use

Someone may notice a slow to release grip

Question 18

What is inclusion body myositis?

Answer 18

idiopathic inflammatory myopathy that occurs in men over 50 yo, CK only slightly elevated, slowly progressive weakness of the distal muscles, poor response to steroids

Question 19

What is polymyositis and dermatomyositis?

Answer 19

Idiopathic inflammatory myopathy that causes symmetrical, proximal muscle weakness. Dermatomyositis is same but has typical cutaneous manifestations.

Question 20

Who is polymyositis and dermatomyositis more common in?

Answer 20

More common in women than men, usually affects adults older than 20 yrs especially 45-60 yrs.

Question 21

Presentation of poly and dermatomyositis?

Answer 21

Muscle weakness-insidious onset, worsening over months, usually symmetrical and proximal muscles (hips, thighs, shoulders etc)
Often specific issues e.g. brushing hair
Sometimes myalgia but this is usually mild
In Dermato Gottron’s sign, heliotrope rash and shawls sign

Question 22

Describe gottrons sign, heliotrope rash and shawls sign?

Answer 22

Occurs in dermatomyositis: gottrons sign is flat red rash over back of fingers, heliotrope rash is reddish purple rash around the eyelids and shawls sign is widespread redness on the upper back, shoulders and neck. Lesions can worsen with UV exposure.

Question 23

Describe involvement of other organs in Dermato and polymyositis?

Answer 23

Lungs- resp muscle weakness and interstitial disease
Oesophageal- dysphagia
Cardiac- myocarditiis
Fever, weight loss, raynauds, inflammatory arthritis
Increased risk of malignancy- ovarian, breast, stomach, lung, bladder and colon. Greatest in Dermatology and greatest in men over 45 years.

Question 24

What is the definitive test for poly and dermatomyositis?

Answer 24

Muscle biopsy- perivascular inflammation and muscle necrosis

Question 25

Exam of poly and dermatomyositis?

Answer 25

Muscle wasting, skin, test muscle power with direct test *(test against own strength) or isotonic testing 30s sit to stand test

Question 26

Blood tests in poly and dermatomyositis?

Answer 26

First to become abnormal is CK, also test inflammatory markers, calcium, PTH, electrolytes and TSH to exclude other causes. Auto antibodies - ANA, Anti-Jo and other myositis specific antibodies.

Question 27

Describe electromyography?

Answer 27

Good for investigating poly and dermatomyositis. Put fine needle into muscle and pass electrical current through muscle to see how it reacts. This is unpleasant as feels like electric shock but shows good patterns for diseases.

Question 28

Treatment of poly and dermatomyositis?

Answer 28

Corticosteroids short term, immune suppression long term. Methotrexate usually first (others azathioprine, cyclosporin, IV immunoglobulin, ritixumab)
Need big dose of steroid to start