Zero To Finals Flashcards
Describe Motor Neurone Disease / (ALS)
Motor neurone disease is a term that encompasses a variety of specific diseases affecting the motor nerves. Motor neurone disease is a progressive, eventually fatal condition where the motor neurones stop functioning. There is no effect on the sensory neurones. Sensory symptoms suggest an alternate diagnosis.
Amyotrophic lateral sclerosis (ALS) is the most common and well-known type of motor neurone disease. Stephen Hawking had amyotrophic lateral sclerosis.
Progressive bulbar palsy is the second most common form of motor neurone disease. It primarily affects the muscles of talking and swallowing (the bulbar muscles).
Other types to be aware of are progressive muscular atrophy and primary lateral sclerosis.
Pathophysiology of motor neurone disease
Pathophysiology
Motor neurone disease involves a progressive degeneration of both the upper and lower motor neurones due to a damage to the ventral horn as a result of autoimmune attacking them. The sensory neurones are spared (dorsal horns).
The exact cause is unclear, although several mechanisms have been considered. Many genes have been linked with an increased risk of developing the condition. Family history is important as around 5-10% of cases are inherited. There seems to be an increased risk with smoking and exposure to heavy metals and certain pesticides.
Presentation of motor neurone disease
Presentation
The typical patient is a late middle-aged (e.g., 60) man, possibly with an affected relative. There is an insidious, progressive weakness of the muscles throughout the body, affecting the limbs, trunk, face and speech. The weakness is often first noticed in the upper limbs. There may be increased fatigue when exercising. They may complain of clumsiness, dropping things more often or tripping over. They can develop slurred speech (dysarthria).
Signs of lower motor neurone disease:
• Muscle wasting
• Reduced tone
• Fasciculations (twitches in the muscles)
• Reduced reflexes
Signs of upper motor neurone disease: ○ Increased tone or spasticity ○ Brisk reflexes ○ Upgoing plantar reflex
Management of MND
Management
There are no effective treatments for halting or reversing the progression of the disease.
Riluzole can slow the progression of the disease and extend survival by several months in ALS.
Non-invasive ventilation (NIV) can be used to support breathing when the respiratory muscles weaken.
Management of the condition involves supporting the person and their family:
• Breaking bad news effectively and supportively
• Multidisciplinary team (MDT) input to support and maintain their quality of life
• Symptom control (e.g., baclofen for muscle spasticity and antimuscarinic medical for excessive saliva)
• Benzodiazepines may help breathlessness worsened by anxiety
• Advanced directives to document their wishes as the disease progresses
• End-of-life care
Patients with motor neurone disease tend to die of respiratory failure or pneumonia.
Diagnosis of MND
Investigations
Though the diagnosis of ALS remains largely clinical, investigations can be helpful both in ruling out other disease processes as well as providing supportive findings.
Electrophysiology
Electromyography: findings consistent with both acute and chronic denervation can be found. Also helps in the identification of fasciculation.
Nerve conduction studies: motor conduction can be normal or demonstrate abnormalities that reflect denervated muscles. Sensory conduction is normal
Prognosis of MND
Prognosis
Death most commonly results from respiratory failure, with a median survival of 3-5 years after symptom onset.
The speed of disease progression varies between individuals. Male and younger patients tend to have a better prognosis, those with limb onset have longer survival than those with bulbar onset. Certain familial forms show more rapid progression.
Around 5-10% of patients live 10 years and rarely they may live 20 years or more following symptom onset.
What is myesthina gravis?
Myasthenia gravis is an autoimmune condition affecting the neuromuscular junction. It causes muscle weakness that progressively worsens with activity and improves with rest.
Myasthenia gravis affects men and women at different ages, typically affecting women under 40 and men over 60.
There is a strong link with thymomas (thymus gland tumours). 10-20% of patients with myasthenia gravis have a thymoma. 30% of patients with a thymoma develop myasthenia gravis.
Pathophysiology of myasthenia gravis
Pathophysiology
Motor neurones communicate with muscles via the neuromuscular junction. On one side of the synapse is the presynaptic membrane of the axon terminal of the motor neurone. On the other side is the postsynaptic membrane of the motor end plate of the muscle cell.
The axons release a neurotransmitter called acetylcholine from the presynaptic membrane. Acetylcholine travels across the synapse and attaches to receptors on the postsynaptic membrane, simulating muscle contraction.
Acetylcholine receptor (AChR) antibodies are found in most patients with myasthenia gravis. These antibodies bind to the postsynaptic acetylcholine receptors, blocking them and preventing stimulation by acetylcholine. The more the receptors are used during muscle activity, the more they become blocked. There is less effective stimulation of the muscle with increased activity. With rest, the receptors are cleared, and the symptoms improve.
These antibodies also activate the complement system within the neuromuscular junction, leading to cell damage at the postsynaptic membrane, further worsening symptoms.
Two other antibodies can cause myasthenia gravis:
• Muscle-specific kinase (MuSK) antibodies
• Low-density lipoprotein receptor-related protein 4 (LRP4) antibodies
MuSK and LRP4 are important proteins for the creation and organisation of the acetylcholine receptor. Destruction of these proteins leads to inadequate acetylcholine receptors.
Presentation of myasthenia gravis
Presentation
Symptoms vary dramatically between patients, ranging from mild to life-threateningly severe. The critical feature is weakness that worsens with muscle use and improves with rest. Symptoms are typically best in the morning and worst at the end of the day.
The symptoms most affect the proximal muscles of the limbs and small muscles of the head and neck, with:
• Difficulty climbing stairs, standing from a seat or raising their hands above their head
• Extraocular muscle weakness, causing double vision (diplopia)
• Eyelid weakness, causing drooping of the eyelids (ptosis)
• Weakness in facial movements
• Difficulty with swallowing
• Fatigue in the jaw when chewing
• Slurred speech
There are a few ways to elicit fatiguability in the muscles: ○ Repeated blinking will exacerbate ptosis ○ Prolonged upward gazing will exacerbate diplopia on further testing ○ Repeated abduction of one arm 20 times will result in unilateral weakness when comparing both sides Further examination steps include: § Checking for a thymectomy scar § Testing the forced vital capacity (FVC)
Investigations for myasthenia gravis
Investigations
Antibody tests look for:
• AChR antibodies (around 85%)
• MuSK antibodies (less than 10%)
• LRP4 antibodies (less than 5%)
A CT or MRI of the thymus gland is used to look for a thymoma. The edrophonium test can be helpful where there is doubt about the diagnosis. Edrophonium Test Patients are given intravenous edrophonium chloride (or neostigmine). Normally, cholinesterase enzymes in the neuromuscular junction break down acetylcholine. Edrophonium blocks these enzymes, reducing the breakdown of acetylcholine. As a result, the level of acetylcholine at the neuromuscular junction rises, temporarily relieving the weakness. A positive result suggests a diagnosis of myasthenia gravis.
Treatment options for myasthenia gravis
Treatment options
Treatment options include:
○ Pyridostigmine is a cholinesterase inhibitor that prolongs the action of acetylcholine and improves symptoms
○ Immunosuppression (e.g., prednisolone or azathioprine) suppresses the production of antibodies
○ Thymectomy can improve symptoms, even in patients without a thymoma
○ Rituximab (a monoclonal antibody against B cells) is considered where other treatments fail
Myasthenic crisis
Myasthenic Crisis
Myasthenic crisis is a potentially life-threatening complication of myasthenia gravis. It causes an acute worsening of symptoms, often triggered by another illness, such as a respiratory tract infection. Respiratory muscle weakness can lead to respiratory failure. Patients may require non-invasive ventilation or mechanical ventilation.
Treatment is with IV immunoglobulins and plasmapheresis.
Guillain-Barré syndrome
Guillain-Barré syndrome is an “acute paralytic polyneuropathy” that affects the peripheral nervous system. It causes acute, symmetrical, ascending weakness and can also cause sensory symptoms. It is usually triggered by an infection and is particularly associated with to campylobacter jejuni, cytomegalovirus and Epstein-Barr virus.
Pathophysiology of Guillain-Barré syndrome
Pathophysiology
Guillain-Barré is thought to occur due to a process called molecular mimicry. The B cells of the immune system create antibodies against the antigens on the pathogen that causes the preceding infection. These antibodies also match proteins on the nerve cells. They may target proteins on the myelin sheath of the motor nerve cell or the nerve axon.
Presentation of Guillain-Barré
Presentation
• Symmetrical ascending weakness (starting at the feet and moving up the body)
• Reduced reflexes
• There may be peripheral loss of sensation or neuropathic pain
• It may progress to the cranial nerves and cause facial nerve weakness
