Myasthenia Gravis + Trigeminal neuralgia Flashcards
What is myasthenia gravis?
An autoimmune condition that causes muscle weakness that gets worse with activity and improves with rest.
Myasthenia gravis preferentially affects:
- Young women 20s and 30s
- Older men 60s and 70s
Describe the link between myasthenia gravis and a thymoma
10-20% of patients with myasthenia gravis have a thymoma
20-40% of patients with a thymoma develop myasthenia gravis
Which auto-antibodies cause myasthenia gravis?
- Acetylcholine receptor antibodies (85%)
- Muscle-specific kinase (MuSK) antibodies (10%)
- Low-density lipoprotein receptor-related protein 4 (LRP4) antibodies (<5%)
How do acetylcholine receptor antibodies cause myasthenia gravis?
These bind to the postsynaptic neuromuscular junction receptors. This blocks the receptor and prevents the acetylcholine from being able to stimulate the receptor and trigger muscle contraction. As the receptors are used more during muscle activity, more of them become blocked up. This leads to less effective stimulation of the muscle with increased activity.
These antibodies also activate the complement system within the neuromuscular junction, leading to damage to cells at the postsynaptic membrane. This further worsens the symptoms.
How do MuSK and LRP4 antibodies cause myasthenia gravis?
MuSK and LRP4 and important proteins for the creation and organisation of the acetylcholine receptor. Destruction of these proteins by autoantibodies leads to inadequate acetylcholine receptors. This causes the symptoms of myasthenia gravis.
Symptoms of myasthenia gravis
The characteristic feature is weakness that gets worse with muscle use and improves with rest. Symptoms are typically minimal in the morning and worst at the end of the day.
- Diplopia
- Ptosis
- Weakness in facial movements
- Difficulty with swallowing
- Fatigue in the jaw when chewing
- Slurred speech
- Progressive weakness with repetitive movements
The symptoms of myasthenia gravis most affect which muscles?
The proximal muscles and muscles of the head and neck
How do the symptoms of myasthenia gravis fluctuate throughout the day?
Symptoms are typically minimal in the morning and worst at the end of the day.
How severe are the symptoms of myasthenia gravis?
The severity of symptoms can vary dramatically between patients. They can be mild and subtle or life threateningly severe.
How would you examine someone with myasthenia gravis?
- There are a few ways to elicit fatiguability in the muscles:
- Repeated blinking will exacerbate ptosis
- Prolonged upward gazing will exacerbate diplopia on further eye movement testing
- Repeated abduction of one arm 20 times will result in unilateral weakness when comparing both sides
- Check for a thymectomy scar.
- Test the forced vital capacity (FVC)
What tests are used to diagnose myasthenia gravis?
- Testing directly for the relevant antibodies:
- Acetylcholine receptor (ACh-R) antibodies (85% of patients)
- Muscle-specific kinase (MuSK) antibodies (10% of patients)
- LRP4 (low-density lipoprotein receptor-related protein 4) 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
Treatment options for myasthenia gravis
- Reversible acetylcholinesterase inhibitors (usually pyridostigmine or neostigmine) increases the amount of acetylcholine in the neuromuscular junction and improves symptoms
- Immunosuppression (e.g. prednisolone or azathioprine) suppresses the production of antibodies
- Thymectomy can improve symptoms even in patients without a thymoma
- Monoclonal antibodies - Rituximab is a monoclonal antibody that targets B cells and reduces the production of antibodies
What is a myasthenic crisis?
A severe complication of myasthenia gravis. It can be life threatening. It causes an acute worsening of symptoms, often triggered by another illness such as a respiratory tract infection. This can lead to respiratory failure as a result of weakness in the muscles of respiration.
Treatment for myasthenic crisis
Patients may require non-invasive ventilation with CPAP or full intubation and ventilation.
Medical treatment of myasthenic crisis is with immunomodulatory therapies such as IV immunoglobulins and plasma exchange.
What is trigeminal neuralgia?
Trigeminal neuralgia is a pain syndrome which describes severe unilateral pain in the distribution of one or more trigeminal branches.
How frequently does the pain in trigeminal neuralgia occur?
May occur infrequently, with periods of remission lasting years, or with a frequency up to hundreds of times a day.
Give some specific triggers of trigeminal neuralgia.
Light touch such as washing, shaving, talking and brushing teeth.
Symptoms of trigeminal neuralgia
- Pain
- trigeminal distribution
- severe
- unilateral
- electirc shock-like sensation
- seconds to minutes
- episodic
- provoked eg touch, cold
- Autonomic symptoms; such as lacrimation, facial swelling, rhinorrhoea or ptosis
First line treatment of trigeminal neuralgia
Carbamazepine
Dose is titrated up every 2 weeks until the pain in controlled
What is motor neurone disease?
Motor neurone disease is a disorder or both upper and lower motor neurones that rarely presents before 40 years old.
What is the most common pattern of motor neurone disease?
Amyotrophic lateral sclerosis (ALS): 50% of cases
Amyotrophic lateral sclerosis
The familial form is associated with mutations in what?
What type of signs are seen?
The familial form is associated with mutations in superoxide dismutase (SOD1)
Overall, mixed UMN/LMN signs may be seen
UMN signs: predominantly affects the corticospinal tracts
LMN signs: also affects anterior horn cells
Symptoms of motor neurone disease
- Progressive weakness
- Falls
- Speech and swallow issues (particularly in progressive bulbar palsy)
Signs of motor neurone disease
- Mixed UMN and LMN signs
- Spastic paraparesis with brisk reflexes
- Fasiculations, especially on the tongue
- Dysarthria and dysphagia: particularly in progressive bulbar palsy
- Muscle wasting: particularly of small hand muscles and tibialis anterior
Certain features characteristically absent:
- No sensory abnormalities
- No extraocular involvement
- No cerebellar involvement
- Sphincter dysfunction is rare and would only present as a late feature
- Abdominal reflexes are usually preserved
MND is a clinical diagnosis but investigations can be conducted to rule out other pathology
- Electromyography: in MND there will be evidence of fibrillation potentials
- Nerve conduction studies: at show modest reductions in amplitude
- MRI spine: imaging can help exclude spinal pathology which may mimic MND, such as cervical cord compression and myelopathy
- Pulmonary function tests: patients with MND are at risk of respiratory failure
Management of motor neurone disease
- Riluzole: prolongs survival by 2-4 months
- Respiratoy support: patients with reduced FVC can use non-invasive ventilation at home, usually BiPAP; prolongs survival by 7 months
- Supportive treatment:
- antispasmodics: such as baclofen
- feeding support: many patients require nutritional support, often with a PEG tube
- speech and language therapy
- physiotherapy
Motor neurone disease prognosis
Most patients die within 3 years from the onset of symptoms.
The majority of patients die from respiratory complications.
What kind of genetic condition is Duchennes muscular dystrophy?
An X-linked recessive condition
Presentation of Duchennes muscular dystrophy
Boys with Duchennes muscular dystrophy present around 3-5 years with weakness in the muscles around their pelvis. The weakness tends to be progressive and eventually all muscles will be affected.
They are usually wheelchair bound by the time they become a teenager. They have a life expectancy of around 25-35 years with good management of cardiac and respiratory complications.
Management of Duchennes muscular dystrophy
Oral steroids slow the progression of muscle weakness by as much as 2 years. Creatine supplementation can give a slight improvement in muscle strength.
- Occupational therapy
- Physiotherapy
- Surgical and medical management of complications such as spinal scoliosis and heart failure
Children with proximal muscle weakness use a specific technique to stand up from a lying position. What is this called?
Gower’s sign
