QuestionSBA
QuestionChoice
A lumbar puncture can be used to help diagnose a variety of neurological conditions. It has no role in the diagnosis of myasthenia gravis and so would only be considered if previous investigations were negative and the diagnosis was unknown
33087
e
Lumbar puncture
QuestionChoice
MRI brain can be used to help diagnose a variety of neurological conditions. For myasthenia gravis, it can be used to exclude compressive and inflammatory lesions of the cranial nerves and ocular muscles but is less likely to be diagnostic
33086
d
MRI brain
QuestionChoice
Anti-VGCC antibodies can be seen in Lambert-Eaton myasthenic syndrome. Given the patient is not complaining of proximal arm or leg weakness, but predominantly facial weakness, this favours myasthenia gravis as the most likely diagnosis
33085
c
Anti-voltage-gated calcium channels (Anti-VGCC) antibodies
QuestionChoice
This patient is experiencing progressive facial weakness, bilateral ptosis, and diplopia - worse on progressive use, suggestive of myasthenia gravis. The first-line investigation is serum AChR antibodies (present in 85% of patients)
33083
a
Acetylcholine receptor (AChR) antibodies
QuestionChoice
Thyroid function tests should be done in patients with suspected myasthenia gravis as they can often co-exist together. The best diagnostic test for myasthenia gravis, however, are AChR antibodies
33084
b
Thyroid function tests
Concept
Chapter
# Summary

Myasthenia gravis is an autoimmune disease characterised by the production of antibodies against the postsynaptic nicotinic acetylcholine receptors at the neuromuscular junction, leading to muscle weakness. Primary symptoms include fatigable muscle weakness, bilateral ptosis, and bulbar features. Key investigations include blood tests for serum acetylcholine receptor antibody, imaging investigations like CT of the chest, and nerve conduction studies with repetitive nerve stimulation. Management strategies involve a multi-disciplinary approach, medical management with immunosuppressive therapy and anticholinesterase inhibitors, and surgical management with thymectomy in select cases.

# Definition

Myasthenia gravis is an autoimmune disease marked by the production of antibodies that target tthe postsynaptic nicotinic acetylcholine receptors at the neuromuscular junction. This immune-mediated interference reduces the ability of acetylcholine to trigger muscle contraction, resulting in muscle weakness.

# Epidemiology

Myasthenia Gravis affects both genders and all age groups, but there is a bimodal distribution with a higher incidence in women under 40 and men over 60.


# Signs and symptoms

The key feature of weakness in patients with myasthenia gravis is **fatigability**.

Patients with myasthenia gravis commonly present with:

- **Fatiguable** limb muscle weakness
- Ptosis
- Diplopia
- Facial palsy
- Bulbar weakness e.g. dysphagia, dysphonia
- Proximal muscle weakness

These signs and  typically worsen with prolonged movement or by the end of the day.

A number of drugs can exacerbate Myasthenia Gravis, including:

- Beta blockers
- Lithium
- Penicillamine
- Gentamicin
- Quinolones
- Phenytoin


# Differential Diagnosis

The following conditions may present with similar symptoms and should be considered in the differential diagnosis:

- Lambert-Eaton syndrome is a fluctuating weakness that improves with exercise, differentiating it from MG. This is usually due to underlying malignancy, most commonly small-cell lung cancer. It affects voltage-gated calcium channels in the presynaptic membrane.
- Multiple sclerosis can present with any neurological sign that may fluctuate or persist over hours to days to weeks secondary to demyelination in the central nervous system. 
- Botulism presents with ptosis, double vision, progressive weakness, and pupillary abnormalities accompanied by systemic symptoms. Ingestion of honey or contaminated foods may be elicited in the patient's history.
- Polymyositis and dermatomyositis cause proximal muscle weakness and is usually associated with pain. The pathology is the inflammation of the muscle itself.
- Graves ophthalmopathy presents with eyelid retraction and widened palpebral fissure. These are caused by autoantibodies targeted toward the structures of the eye.

# Investigations

Key investigations in the diagnosis of myasthenia gravis include:

- Bedside tests: Ice-pack test
	- Eye is placed over the eye for 2-5 minutes to assess for improvements in ptosis
- Blood tests: Testing for serum acetylcholine receptor (anti-AChR) antibody and muscle-specific tyrosine kinase (anti-MusK) antibodies and (rarely) anti-LRP4 antibodies
- Imaging investigations: CT scan of the chest to identify thymic hyperplasia or thymoma
	- Approximately 10% of patients with MG have a thymoma, and it is implicated in the production of autoantibodies
- Nerve Conduction Studies/EMG: Repetitive nerve stimulation testing

In a myasthenic crisis, serial pulmonary function tests (spirometry) are performed. 

If the forced vital capacity is 15 mL/kg or less, the patient should be considered for mechanical ventilation.

# Management

The management of myasthenia gravis involves:

- Regular review in neurology outpatients
- Multidisciplinary team involvement as required (including occupational therapist, physiotherapist, speech and language therapist)
- Medical management with immunosuppressive therapy (such as **steroids**) and anticholinesterase inhibitors (such as **pyridostigmine** or neostigmine). 
- Acute cases may require intravenous immunoglobulin (IVIG) or plasmapheresis in severe, steroid-refractory, cases.
- Surgical management with thymectomy is indicated in patients with evidence of thymoma AND in patients with non-thymomatous antibody positive n-AChR MG

# References

1. Gilhus, N. E., & Verschuuren, J. J. (2015). Myasthenia gravis: subgroup classification and therapeutic strategies. The Lancet Neurology, 14(10), 1023-1036.
2. Meriggioli, M. N., & Sanders, D. B. (2009). Autoimmune myasthenia gravis: emerging clinical and biological heterogeneity. The Lancet Neurology, 8(5), 475-490.
3. Sanders, D. B., & Wolfe, G. I. (2021). Myasthenia Gravis and Lambert-Eaton Myasthenic Syndrome. In Harrison's Principles of Internal Medicine (21st edition). McGraw-Hill Education.

226
221
Myasthenia Gravis
Topic
34
Neurology
Video
Concept
221
Myasthenia Gravis
234
ULMFWnv
images/videos/neurology.png
Myasthenia Gravis
Video
Concept
221
Myasthenia Gravis
304
XBigS3j
images/videos/neurology.png
Quesmed Tutorial: Advanced Neurology
6617
Myasthenia gravis is an autoimmune neuromuscular disorder characterized by weakness and fatigue of voluntary muscles, often associated with the presence of acetylcholine receptor (AChR) antibodies that disrupt nerve signal transmission at the neuromuscular junction.
Picture
James Heilman, MD, CC BY-SA 3.0 <https://creativecommons.org/licenses/by-sa/3.0>, via Wikimedia Commons
373
Diplopia.jpeg
images/7rmqakoq1639016687003.jpg
images/7rmqakoq1639016687003_256.jpg
images/7rmqakoq1639016687003_512.jpg
4WkGC4IMuVZ9ePZ4DHiYQIg=
Topic
34
Neurology
A 71-year-old woman presents to the GP with progressive bilateral facial weakness and diplopia for the past two months, worst in the evenings.

External examination findings are below:

[lightgallery]

Which of the following investigations is most likely to confirm the diagnosis?
a