Muscle and nerve diseases

Question 1

Where does the UMN synapse first?

Answer 1

The anterior horn

Question 2

What are the 4 components of muscle contraction?

Answer 2

Structural components

Contractile mechanism – myosin fibrils embedded in membrane and it shortens as it contracts

Excitation-contraction coupling (ion channels)

Energy system – can’t contract muscle without energy

Question 3

Symptoms of muscle disease? (7)

Answer 3

Weakness of skeletal muscle

Short of breath (respiratory muscles)

Poor swallow / risk of aspiration (bulbar muscles)

Cardiomyopathy

Cramp (repetitive!)

Pain and stiffness

Myoglobinuria

Question 4

What is myoglobinuria?

Answer 4

Muscle breaks down and is excreted in urine – makes urine black, looks like blood

Question 5

Symptoms of muscle disease in babies?

Answer 5

Poor suck / feeding / failure to thrive / floppy

Question 6

Signs of muscle disease?

Answer 6

Wasting / hypertrophy

Normal or reduced tone and reflexes (usually loss
of muscle tone)

Motor weakness…NOT sensory

Question 7

Why might hypertrophy result from a muscle disease?

Answer 7

Muscle cannot relax

Question 8

Investigations for muscle disease (5)

Answer 8

History and examination

Creatine Kinase (CK)

EMG - electromyography

Muscle biopsy - look at structure, biochem and inflammation

Genetic testing

Question 9

What is significant about creatine levels?

Answer 9

sign of muscle fibre degeneration - chewing up muscle

Question 10

Genetics and muscle disease

Answer 10

Most congenital diseases are genetic however this doesn’t mean they are present at birth – can come up later on in life

Genetics can affect all 4 components of muscle contraction

Question 11

How do congenital / genetic muscle diseases affect each component

Answer 11

Structural: muscular dystrophies

Contractile: congenital myopathies - hypotonia and weakness, usually present from birth, with a static or slowly progressive

Coupling: channelopathies - diseases caused by disturbed function of ion channel subunits or the proteins that regulate them

Energy: enzymes / mitochondria

Question 12

How do acquired muscle diseases affect muscles

Answer 12

Metabolic (increased or low Ca2+, K+) – severe illness

Endocrine (thyroid, adrenal, vit D- rickets?)

Inflammatory muscle disease

Iatrogenic: medication (steroids / statins) - ie steroids used to treat myopathy then result in further myopathy

Question 13

What is Myopathy?

Answer 13

Myopathy is a disease of the muscle in which the muscle fibers do not function properly.

This results in muscular weakness.

Question 14

Describe what Muscular dystrophies are

Answer 14

Gradually cause the muscles to weaken, leading to an increasing level of disability.

Young or older onset
progressive, variable severity

Cell degeneration (often high CK)

No specific treatments yet

Question 15

Give examples of some muscular dystrophies

Answer 15

Duchenne’s/Becker’s
Duchenne’s - aggressive and will limit life where as becker’s has milder symptoms and has a later onset. They are 2 alterations of same gene/protein

Facioscapulohumeral

limb girdle

Myotonic dystrophy - ong-term genetic disorder that affects muscle function - muscles contract and can’t relax - cataracts is common symptom - multi-system disease

Question 16

What are channelopathies

Answer 16

disorders of Ca2+, Na+, K+ and Cl- channels

often paroxysmal symptoms e.g. periodic paralysis / myotonia

partially treatable

Question 17

Metabolic myopathy

Answer 17

Exercise induced:
early = disorders of carbohydrate metabolism
late = disorders of lipid metabolism

Mitochondrial problems

Partially treatable

Question 18

Inflammatory muscle disease

Answer 18

Polymyositis

It can be associated with a skin rash and is then called ‘dermatomyositis’

Can occur at any age, acute or subacute

painful, weak muscles

symptoms can be a sign of existing cancer or may also increase the risk of malignancy - tumour screen done

High CK levels

Question 19

Tests for inflammatory muscle diseases

Answer 19

EMG

Biopsy - polymyositis - CD8 T cells
Dermato - humeral-mediated, B cells and CD4 cells

Question 20

Treatment for inflammatory muscle diseases

Answer 20

immunosuppression

Question 21

What are the classifications of muscle disease?

Answer 21

Muscular dystrophies - usually genetic - to do with structure of the muscle

Channelopathies - usually episodic

Metabolic muscle disease - an issue with the way the muscle uses energy, usually due to enzymes

Inflammatory muscle disease

Congenital myopathies

Iatrogenic - medication - statins cause inflammation or degeneration of the muscles

Question 22

What is Myasthenia Gravis

Answer 22

Disorder of the neuromuscular junction - long-term neuromuscular disease

Question 23

Investigations for Myasthenia Gravis

Answer 23

Antibodies

If negative do Neurophysiology (Repetitive stimulation, Jitter)

CT chest (thymoma about 10% have underlying)

Question 24

Treatment for Myasthenia Gravis (4)

Answer 24

Symptomatic
- Acetylcholinesterase inhibitor (pyridostigmine)

Immunosuppression

• Prednisolone
• Steroid saving agent (e.g. azathioprine)

Immunoglobulin / plasma exchange

Thymectomy - antibody production can be as a result of an over active thymus - even in the case where there is no thymoma

Question 25

What is peripheral nerve disease (neuropathy)?

Answer 25

disease of the nerves beyond the brain and spinal cord

Question 26

What does a peripheral nerve consist of? (4)

Answer 26

Sensory axons - Small fibres (pain + temperature) - Large fibres (joint position sense + vibration) Motor axons Autonomic axons Nerve sheath (myelin)

Question 27

Generalised peripheral neuropathy affect

Answer 27

Motor / sensory / both | +/- autonomic features

Question 28

A lesion of individual peripheral nerve will cause what?

Answer 28

Compressive / entrapment neuropathy - direct pressure on a nerve - causes pain, tingling, numbness Vasculitic (mononeuritis multiplex) - If nerve doesn’t receive blood from the vasovasorum there is mononeuritis multiplex

Question 29

Causes of generalised peripheral neuropathy (6)

Answer 29

Hereditary Metabolic: diabetes, alcohol, renal failure, B12 Toxic: drugs Infectious: Lyme, HIV, leprosy Malignancy: paraneoplastic Inflammatory demyelinating: Acute = Guillain Barre syndrome Chronic = chronic inflammatory demyelinating polyneuropathy

Question 30

Nerve disease can be of which 3 types?

Answer 30

Root disease Lesion of individual peripheral nerve Generalised peripheral neuropathy

Question 31

Symptom and signs: | Nerve root disease (3)

Answer 31

Myotomal wasting and weakness Reflex change Dermatomal sensory change

Question 32

``` Symptom and signs: Individual nerve (2) ```

Answer 32

Wasting and weakness of innervated muscle Specific sensory change

Question 33

Symptom and signs: | Generalised peripheral neuropathy

Answer 33

Sensory and motor symptoms, usually starting distally and moving proximally

Question 34

Investigations for nerve disease (5)

Answer 34

Blood tests Genetic analysis Nerve Conduction Studies Lumbar puncture (CSF analysis) – invasive , not done much Nerve biopsy (nb sensory nerve)

Question 35

Treatment of nerve diseases?

Answer 35

Treat the cause eg stop drug, surgery, immunoglobulin

Question 36

What is solely affected in spinal muscular atrophy?

Answer 36

anterior horn cell

Question 37

Motor neuron disease: | Disease progression and signs

Answer 37

Usually starts with limb → bulbar → respiratory ``` combination of UMN and LMN signs LMN = muscle fasciculations, wasting, weakness UMN = increased tone, brisk reflexes No sensory involvement 10%+ have cognitive decline ``` Doesn't affect sensory just the motor part

Question 38

Prognosis of Motor Neuron disease?

Answer 38

Median 3-5 years from symptom onset 2-3 years from diagnosis 50% die within 14 months of diagnosis

Question 39

What do you usually see in an atrophic tongue

Answer 39

fasciculations, wasting and weakness (LMN signs), while spasticity causes slow tongue movements

Question 40

Treatment of motor neuron disease

Answer 40

Supportive - PEG feed, non invasive ventilation, physio, OT, SALT, care Riluzole - delays the onset of ventilator-dependence or tracheostomy in some people and may increase survival by two to three months Anticipatory / palliative care

Question 41

Diagnosis of motor neuron disease

Answer 41

unique combination of UMN and LMN signs with no sensory signs Electromyography

Question 42

What is the presentation of disorders of the neuromuscular junction?

Answer 42

Fatiguable weakness: –Limbs –Eyelids (ptosis) –Muscles of mastication (chewing), swallow –Talking –SOB - Affects all NMJ’s so can cause respiratory failure –diplopia Clear feature of NMJ problems is fatigue – muscles start strong and then get weaker. As day goes on – progressive problem with muscle weakness – diplopia because of muscle weakness in the eye.

Question 43

Which antibodies are searched for in Myasthenia Gravis?

Answer 43

AChR, Anti MuSK antibodies

Question 44

What is the other name for motor neuron disease?

Answer 44

Amyotrophic lateral sclerosis