Neuromuscular disorders (Muscular & NMJ)

Question 1

Which muscles do neuromuscular auto-immune conditions tend to affect?

Answer 1

Muscles that are larger and have higher activity, e.g. shoulders, thigh, cardiac, and eye muscles (Myathenia!)

Question 2

Define and explain the pathophysiology of myasthenia gravis and why it causes 1) muscle weakness and 2) fatigability of muscles.

Answer 2

It is an autoimmune neuromuscular disorder characterised by weakness and fatigue of voluntary muscles caused by autoantibodies targeting the NMJ.

Muscle weakness: reduced endplate potential of the post-synaptic membrane, causing reduced transmission.

Fatigability: Repeated use of the affected muscles leads to worsening weakness due to the depletion of available ACh.

Question 3

Which two antibodies are commonly implicated myasthenia gravis?

Answer 3

Antibodies of: **Acetylcholine receptors (AChR) **or, less commonly, **muscle-specific tyrosine kinase (MuSK) **at the neuromuscular junction.

Question 4

Which other organ is commonly associated with myasthenia gravis?

Answer 4

Thymus

The thymus gland is often implicated, with 80% of patients showing some form of thymic abnormalities, including hyperplasia or thymomas.

Question 5

Clinical presentation of myasthenia gravis— list 4 locations that are commonly affected.

What are two major risks associated with it that may be life-threatening?

Answer 5

• Ocular: Ptosis and diplopia are often the initial and most common symptoms.
• Bulbar: Dysphagia, dysarthria, and difficulty chewing, neck weakness.
• Limb: Symmetrical proximal muscle weakness affecting the arms more than the legs.
  Patients report difficulty getting out of chairs, climbing stairs etc.
• Respiratory: Severe cases can lead to respiratory muscle involvement and myasthenic crisis.

Question 6

What is myasthenia gravis called when it just affects the eyes/an eye?

Answer 6

Ocular myasthenia

Question 7

What is the time course? What are some exacerbating factors?

Answer 7

Worse after use and in the evening, and can be exacerbated by stress, infection, or medications.

Question 8

What is a condition that presents with descending paralysis and autonomic symptoms (e.g., dry mouth, blurred vision).

Answer 8

Botulism

Question 9

What are tips of examining a patient with myasthenia gravis? Especially if they don’t present with any symptoms?

Answer 9

Ask them to stare up for a minute. Notice ptosis or diplopia.

Question 10

Complications of myasthenia gravis. Consider the organs that are affected.

Answer 10

• Impaired Swallowing: Can lead to myasthenic crisis/ aspiration and may necessitate mechanical ventilation or feeding tubes.
• Cardiac Complications: Includes myocarditis, arrhythmias, and sudden death.
• Thyroid Disorders: MG is associated with thyroid disorders like Graves’ disease and Hashimoto’s thyroiditis.
• Thymoma: Requires monitoring as it may be associated with malignant transformation.

Question 11

What is a myasthenia crisis?

(Happens in people with MG with an exacerbating factor e.g. Infection, surgery, certain medications (e.g., antibiotics, beta-blockers), emotional stress, or abruptly stopping anticholinesterase medications.)

Answer 11

A life-threatening exacerbation of myasthenia gravis, characterised by severe muscle weakness leading to respiratory failure, requiring immediate medical intervention.

Signs and Symptoms: Sudden worsening of muscle weakness, particularly in the respiratory muscles, leading to difficulty breathing, shortness of breath, inability to clear secretions, and possible cyanosis.

Question 12

How might a myasthenic crisis be managed?

Answer 12

• ITU/ventilation
• Plasmapheresis or Intravenous Immunoglobulin (IVIG)

Question 13

Causes and epidemiological risk factors for myasthenia gravis?

Answer 13

Auto-immune condition

Younger women, pregnant women, and older men.

Question 14

First line diagnostic investigations for myasthenia gravis.

Answer 14

1. Acetylcholine receptor (AChR) Antibody: Detectable in 80-90% of patients.
2. Muscle Specific Tyrosine Kinase (MuSK) Antibody: Detectable in 70% of patients that are seronegative for AChR antibodies.
3. Serial Pulmonary Function Tests: Will be considered for patients with myasthenic respiratory compromise.

Second-line: nerve conduction studies/ single fibre EMG

Question 15

What is the main risk with a thymoma and what screening scan is required?

Answer 15

Thymoma –> malignant transformation.

CT scan required.

Question 16

What are three components of managing myasthenia gravis?

Answer 16

1. Patient-led management: avoiding triggers
2. Pharmacological management
3. Surgical management for thymus

Question 17

Pharmacological management of myasthenia gravis

Answer 17

For those with AchR antibodies: Anticholinesterase Inhibitors (Pyridostigmine): Increases acetylcholine at the neuromuscular junction → improved muscle strength.

Corticosteroids (e.g. prednisolone): Low dose then gradually increased
Immunosuppressant (e.g. azathioprine): Considered if initial therapy is ineffective

Question 18

Which surgery is considered for patients with myasthenia gravis, especially with they are younger e.g. 18-50 years old

Answer 18

Thymectomy

Question 19

List a group of congential conditions that cause progressive, ascending muscle weakness, including the Gower’s sign.

Answer 19

Muscular dystrophy (MD)

A group of genetic disorders characterized by progressive muscle weakness and degeneration.

The most common types include Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD).

Question 20

What is the inheritance of muscular dystrophies?

Answer 20

X-linked inheritance – affected males of carrier mothers.

Question 21

When is the onset of Duchenne/Becker muscular dystrophy?

Answer 21

DMD: The lack of functional dystrophin leads to severe muscle degeneration and weakness, with symptoms typically appearing in early childhood (around ages 2-5).

BMD: The presence of some functional dystrophin results in a milder phenotype with later onset of symptoms, often during adolescence or adulthood.

Question 22

List 3 diagnostic tests are used to confirm muscular dystrophy?

Answer 22

• genetic testing to identify mutations in the DMD gene,
• muscle biopsy to examine dystrophin levels, and
• elevated serum creatine kinase (CK) levels indicating muscle damage.

Question 23

What is the role of corticosteroids in the management of Duchenne muscular dystrophy (DMD)?

Answer 23

Corticosteroids, such as prednisone and deflazacort, are used to slow the progression of muscle weakness and improve muscle strength and function in patients with DMD.

Question 24

What are some potential complications associated with muscular dystrophy?

• impact in quality of life, reduced life expectancy

Answer 24

Complications can include respiratory failure, cardiomyopathy, scoliosis, and contractures.

Regular monitoring and supportive care are essential to manage these complications.

Question 25

What is Guillain-Barré Syndrome (GBS)? What is it characterised by?

Answer 25

An acute, immune-mediated polyradiculoneuropathy (affecting nerve roots and peripheral nerves), often triggered by an infection.

It is characterised by rapidly progressive, symmetrical weakness, typically starting in the lower limbs and ascending to involve the arms and, sometimes, respiratory muscles. Reflexes are usually diminished or absent.

Question 26

What are the two common initial symptoms of Guillain-Barré Syndrome?

Answer 26

• Paresthesia
• Weakness
• Ascending pattern from lower limbs

affects sensory and motor nervous system

Question 27

What is the pattern of illness in Guillain-Barre Syndrome?

Answer 27

Symmetrical and progressive

Question 28

Apart from peripheral motor and sensory symptoms, what other problems may Guillain-Barré Syndrome patients experience?

Answer 28

Autonomic dysfunction and cranial nerve involvement.

Autonomic dysfunction e.g. Fluctuations in BP, bowel and bladder dysfunction. Cranial nerve involvement e.g. bilateral facial weakness, difficulty swallowing, impaired eye movements.

Question 29

What exam findings might you find in Guillain-Barré Syndrome?

Answer 29

• Weakness/ paralysis
• Reduced sensation in a gloves-stocking distribution
• reduced reflexes

Question 30

What would make you increase in suspicion o Guillain-Barré Syndrome based on the onset and recent medical history of a patient? What should you make sure to ask about?

Answer 30

Acute onset,
Recent infection e.g. C. jejuni, CMV, EBV, influenza

• Have you had any gastroenteritis or flu-like illness in the weeks leading up to your current presentation?. *

Question 31

What is the most common trigger for Guillain-Barre Syndrome?

Answer 31

Campylobacter jejuni is the most common trigger

Question 32

Why might infection trigger Guillain-Barre Syndrome? Think about its pathophysiology.

Answer 32

1. Molecular mimicry: Following infection, antibodies mistakenly target the myelin sheath or axons of peripheral nerves.
2. Causing an acute inflammatory demyelination and motor axonal damage

Question 33

Although Guillain-Barre Syndrome is rare, who is more at risk?

Answer 33

• GBS can occur at any age but is slightly more common in age ranged 15-35 and 50-75 years
• Gender: Slight male predominance (1.78:1 male to female ratio)

Seasonality: Higher incidence in winter and spring, possibly linked to viral infections.

Question 34

What is a major complication of Guillain-Barre Syndrome?

Answer 34

Respiratory failure (restrictive)

Question 35

What is the typical disease progression of Guillain-Barré Syndrome? How long might it last?

Answer 35

GBS typically progresses over a few days to weeks, reaching its peak within four weeks. Recovery can take weeks to years, with some patients experiencing long-term residual weakness.

Question 36

How is Guillain-Barré Syndrome diagnosed? What tests would you order and what are their results?

Answer 36

• Nerve conduction studies (slower transmission) and
• CSF analysis showing elevated protein levels with normal white cell count.

Question 37

What are the main treatment option for Guillain-Barré Syndrome?

Answer 37

Treatment options include intravenous immunoglobulin (IVIG) and plasma exchange (plasmapheresis), which help reduce the severity and duration of the symptoms.

Question 38

What is the prognosis for patients with Guillain-Barré Syndrome?

Answer 38

Most patients recover fully, but some may have residual weakness or other neurological deficits. The prognosis is generally good with appropriate treatment, though recovery can be slow.

Question 39

As with any patient in the hospital with prolonged rest, what risk should be prevented in Guillain-Barré Syndrome?

Answer 39

VTE risk - use anticoagulants.

Question 40

What is a chronic, fluctuating form of Guillain-Barré Syndrome?

Answer 40

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)

GBS= AIDP

Question 41

Case study of Guillain-Barré Syndrome:

A 55-year-old man presents with a 4-day history of progressive weakness in both legs, which started as difficulty climbing stairs and has now spread to his arms. He reports mild tingling in his toes and fingers. He also mentions a recent diarrhoeal illness one week prior.

On examination, there is symmetrical flaccid paralysis in the lower limbs, with reduced reflexes. He also has bilateral facial weakness and mild difficulty swallowing. His respiratory function appears to be mildly impaired.