Muscle diseases - just learn Duchenne's and myasthenia

Question 1

Symptoms (3) /signs (5) of muscle disorders in general

Answer 1

Symptoms:

• Dyspnoea (respiratory muscles not getting enough O2)
• Dysphagia (–> aspiration)
• Muscle cramp/pain/stiffness

Signs:

• Motor weakness
• Myoglobinuria (myoglobin in urine; usually present inside muscle but released into blood as a result of muscle destruction) –> dark brown urine
• Muscle wasting OR hypertrophy
• Normal/reduced tone + reflexes
• Cardiomyopathy (diseases of skeletal muscle can affect cardiac muscle)

Question 2

2 classifications of muscle diseases/disorders

Answer 2

Congenital/genetic

Acquired

Question 3

Name 4 subcategories of congenital muscle diseases + give an example for each category

Answer 3

Structural: muscular dystrophies
Contractile: congenital myopathies
Coupling: channelopathies
Energy: enzyme defect or mitochondrial defect

Question 4

Name 4 subcategories of acquired muscle diseases

Answer 4

Metabolic muscle diseases
Endocrine muscle diseases
Inflammatory muscle diseases
Iatrogenic muscle diseases - induced by medication

Question 5

Investigation of muscle diseases (4)

Answer 5

History and examination

Bloods - Creatine Kinase (CK) (increased in muscle degeneration)

EMG (electromyography) - inserting a small needle into the muscle, to view and listen to the electrical activity generated within the muscle

Muscle biopsy

Question 6

Name 2 types of muscular dystrophy (congenital muscle disease)

Answer 6

Duchenne’s

Becker’s

Question 7

What is muscular dystrophy (congenital muscle disease)

Answer 7

PROGRESSIVE degeneration and re-generation of muscle fibres

Question 8

Pathophysiology of muscular dystrophies

Answer 8

GENETIC CAUSE:

Gene deletion or mutation –> defective or specifically absent glycoproteins (e.g., dystrophin) in the muscle membrane

Question 9

Clinical features of muscular dystrophies (6)

Answer 9

Muscle weakness
Muscle wasting
Decreased muscle tone (flaccidity)
Walking on toes/heel
Imbalance of lower limbs 
Respiratory difficulty

Question 10

Clinical features of muscle disease in babies (3)

Answer 10

Failure to thrive
Poor feeding/latching
Floppy/weak

Question 11

Describe channelopathies (congenital muscle disease)

Answer 11

Disorders of Ca, Na, K and Cl channels on the muscle membrane

Question 12

Duchenne’s muscular dystrophy treatment (not curative)

Answer 12

Steroids

Supportive care - treating respiratory distress, swallowing issues, physio

Question 13

Relationship of dystrophin and duchenne’s (congenital muscle disease)

Answer 13

Absent dystrophin which usually provides structural stability to cell membranes

Question 14

Main treatment for muscle diseases

Answer 14

Supportive care/symptomatic care

Question 15

Metabolic/energy deficient muscle diseases* pathophysiology

*congenital muscle disease

Answer 15

Enzyme defect or mitochondrial defect due to genetic mutations

Question 16

Name the 2 types of *inflammatory muscle disease (myositis) + describe them

*acquired muscle disease

Answer 16

Polymyositis - uncommon inflammatory disease that causes muscle weakness affecting both sides

Dermatomyositis - additional rash + muscle weakness; rash appears before the onset of muscle symptoms

Question 17

Cause of polymyositis and dermatomyositis (inflammatory muscle disease)

Answer 17

Autoimmune - immune system starts attacking healthy tissue

Question 18

Clinical features of inflammatory muscle disease (4) + identify the sign suggestive of dermatomyositis

Answer 18

Muscle weakness
Muscle atrophy
Frequent falls
Fatigue after standing/walking

Rash specifically in dermatomyositis

Question 19

Definitive investigation for inflammatory muscle disease, e.g. polymyositis, dermatomyositis

Answer 19

Muscle biopsy

Question 20

Definitive investigation for duchenne’s

Answer 20

DNA testing for specific mutation

Question 21

What is myasthenia gravis

Answer 21

An AUTOIMMUNE disorder of the neuromuscular junction

Question 22

Pathophysiology of myasthenia gravis

-involves 1 main autoantibody + another in minority

Answer 22

End plate potential (EPP) fails to effectively activate the muscle fibre due to an AUTOIMMUNE reaction against acetylcholine receptors on the muscle

• ACh RECEPTOR AUTOANTIBODY binds to acetylcholine receptor on the muscle membrane surface preventing ACh from binding to it so can’t activate muscle
• minority of people produce MUSCLE SPECIFIC TYROSINE KINASE RECEPTOR AUTOANTIBODY (Anti MuSK ab) which attacks proteins INSIDE muscle cell rather on muscle membrane surface

Question 23

Symptoms/signs of myasthenia gravis (7)

+ does it affect sensation

Answer 23

Fatiguable weakness of skeletal muscle:
– Proximal limb weakness
– Ptosis
– Facial weakness - facial expression muscles + muscles of mastication
– Dysphagia
– Dysarthria 
– Diplopia
– Dyspnoea  (less common) --> resp failure if severe

NO SENSORY SIGNS

Question 24

List the 3 main clinical features of myasthenia gravis

Answer 24

Muscle weakness
Fatigue
Normal sensation

Question 25

Myasthenia gratis investigations (4)

Answer 25

AChR ab (ACh receptor auto- antibody)

Anti MuSK ab (muscle-specific tyrosine kinase auto-antibody)

Neurophysiology

• Repetitive nerve stimulation (similar to nerve conduction study) - shows slowed response
• Single fibre EMG - shows increased Jitter

Question 26

What result does an EMG show in myasthenia gravis

Answer 26

INCREASED Jitter

Question 27

Myasthenia gravis treatment
-1st line
+/- (3)

Answer 27

Acetylcholinesterase inhibitor - Pyridostigmine

+/- prednisolone/other immunosuppressant

+/- plasma exchange OR IV immunoglobulin

+/- thymectomy

Question 28

What tumour is myasthenia gravis associated with

Answer 28

Thymoma

-causes myasthenia to present as a paraneoplastic syndrome where thymoma secretes ACh receptor autoantibodies