MSK Muscle disorders

Question 1

Types of muscle disorder:

Answer 1

1. Intrinsic diseases of muscle (myopathies)
   a. Genetically determined
   b. Acquired
2. Neurological diseases
3. Fatigue or effort syndrome
4. Tumours (rare)

Question 2

Muscular Dystrophies: Characterised by

Answer 2

Progressive muscle weakness, defects in muscle prteins, fibre atrophy, and necrosis of muscle cells

Question 3

Muscular Dystrophies: Types

Answer 3

9

Question 4

Muscular Dystrophies: Most common and severe

Answer 4

Duchenne muscular dystrophy (DMD), which involves mutations of dystrophin gene.

Question 5

Muscular Dystrophies: Becker

Answer 5

Less severe form of DMD

Question 6

Muscular Dystrophies: Dystrophin

Answer 6

• Forms part of transmembrane “dystrophin – glycoprotein complex” that represents the costamere
• Prevents excessive stress on cell membrane during muscle contraction
• Stabilises sarcolemma and protects muscle fibre from disruption during contraction
• Possible role in regulating calcium levels

Question 7

Muscular Dystrophies: Lack of Dystrophin in studies showed

Answer 7

• Increases susceptibility to membrane damage and allows excess calcium to penetrate cell membrane

Question 8

Metabolic Myopathies: Includes disorders of

Answer 8

Glycogen metabolism, lipid metabolism or phosphagen system

Question 9

Metabolic Myopathies: Cause

Answer 9

Impaired energy supply via affected pathways

Question 10

Mitochondrial Myopathies: Involves

Answer 10

Structural abnormalities of mitochondria

Question 11

Mitochondrial Myopathies: Cause

Answer 11

Dysfunction of mitochondrial pathways → impaired aerobic metabolism

Question 12

Mitochondrial Myopathies: Often linked to

Answer 12

Mutations in mtDNA; mutations of nuclear DNA may cause dysfunction in respiratory chain

Question 13

Disorders of muscle membranes (channelopathies) Periodic paralysis due to

Answer 13

Inexcitability of muscle that causes temporary paralysis or weakness

Question 14

Disorders of muscle membranes (channelopathies) Myotonic dystrophy characterised by

Answer 14

Abnormal resting membrane potential

Question 15

Congenital Myopathies: Definition

Answer 15

Myopathies that are present at birth or begin during infancy

Question 16

Congenital Myopathies: Transmission

Answer 16

Usually hereditary and progress slowly

Question 17

Congenital Myopathies: Characterised by

Answer 17

Specific morphologically abnormalities that cause muscle weakness and loss of muscle tone in infancy and delayed motor development during childhood

Question 18

Diagnosis and investigation of muscle disease:

Answer 18

1. DNA analysis
2. Muscle biopsy
3. Exercise testing
4. Electromyography
5. Plasma creatine kinase analysis

Question 19

DNA Analysis:

Answer 19

1. Used to investigate disorders with major genetic component
2. Single gene disorders (caused by mutation in one gene) are easiest to identify
3. Possible to predict gene involved from the aberrant protein (e.g. dystrophin in DMD)

Question 20

Muscle Biopsy: Enzymes of glycolysis

Answer 20

Stain for enzymes involved in glycolysis e.g. PFK and myophospharylase → used to identify such as myophosphorylase defiency (McArdle’s disease)

Question 21

Muscle Biopsy: Storage Products

Answer 21

Periodic acid-Schiff Stains for Glycogen

Demonstrates abnormal glycogen storage in patients with glycogenesis

Question 22

Muscle Biopsy: Enzymes of oxidative metabolism

Answer 22

Oxidative enzymes e.g. NADH, cytochrome C oxidase, SDH used in diagnosis of mitochondrial myopathies
CCO used to demonstrate respiratory chain abnormalities
SDH used as marker enzyme for mito
→ Indicates abnormalities in mit distribution e.g. in mito myopathies, core disease, MD

Question 23

Ischaemic exercise disease: Used to investigate

Answer 23

Certain metabolic myopathies

Question 24

Ischaemic exercise disease: Process

Answer 24

• Baseline blood sample taken at rest
• Circulation of forearm occluded whilst subject exercises forearm for fixed time or t o exhaustion
• Circulation restored, blood samples taken immediately after exercise and during recovery
• Blood analysed for lactate and ammonia

Question 25

Ischaemic exercise disease: Failure to produce lactate

Answer 25

• Disorders of glycogen metabolism e.g. myophosphorylase defiency

Question 26

Ischaemic exercise disease: Impaired ammonia production indicative

Answer 26

Of myoadenylate deaminase defiency (MADD)

Question 27

Incremental/steady state exercise test: Aids

Answer 27

Diagnosis/assessment of mito myopathies

Question 28

Incremental/steady state exercise test: Process

Answer 28

1. Baseline blood sample taken at rest 2. Subject exercises at series of incremental loads on bicycle ergometer or treadmill 3. At each load, blood samples taken for lactate analysis, further samples taken during recovery

Question 29

Incremental/steady state exercise test: Elevated lactate levels for

Answer 29

Given workload indicates increased conversion of pyruvate to lactate

Question 30

Electromyography:

Answer 30

1. Intramuscular (needle) EMG used to investigate alterations in muscle activity as a result of disease 2. Most commonly studied features are: a. Insertional activity b. Spontaneous activity c. MUAP characteristics d. Recruitment patterns 3. EMG changes occur as a result of membrane disorders that affect excitability of cell membrane, or as result of marked atrophy or necrosis.

Question 31

Plasma Creatine kinase analysis:

Answer 31

1. Plasma CK levels may rise temporailiy in healthy subjects in healthy subjects following eccentric exercise (as shown in figure) 2. Elevated plasma CK levels indicate damage to muscle cell membrane, and are common feature of DMD.