13th February 2025

Muscular and neuromuscular junction

Myasthenia gravis

Myasthenia gravis (MG) is an autoimmune disease affecting the neuromuscular junctions of skeletal muscles. Pathophysiology includes the presence of autoantibodies to acetylcholine receptors (AChR).

MG typically presents with fatigable weakness and often affects the extraocular muscles. Patients can present with a spectrum of symptom severity from mild blurred vision to variable ptosis to severe diplopia. Examination characteristically reveals a fatigable muscle weakness not confined to a specific muscle or nerve and which is variable and asymmetrical in nature. Importantly, there is no associated eye pain and no pupil involvement. The tongue can also be affected, resulting in atrophy and a rare but distinctive ‘triple-groove’ appearance.

Occasionally, manifestations of MG are limited to the levator palpebrae superioris, orbicularis oculi and extraocular muscles, which is known as ‘ocular MG’. Unlike generalised MG where more females are affected, males are more likely to be affected by ocular MG. Furthermore, patients with ocular MG are more likely to be seronegative for AChR antibodies than those with generalised MG.

Diagnosis can be confirmed through various tests:

Table 7 Investigations to confirm a diagnosis of myasthenia gravis

Treatment with AChE inhibitors, such as pyridostigmine, improves symptoms but does not alter disease activity. Tapering courses of corticosteroids and immunosuppressants, such as azathioprine, are also used.

Thyroid eye disease

Thyroid eye disease is an autoimmune disorder. It is most commonly associated with thyrotoxicosis secondary to Graves’ disease and occurs due to shared autoantigens between the thyroid and the orbit. However, rarely, the patient can be euthyroid or hypothyroid. Common symptoms include altered periocular appearance, eye surface discomfort or lacrimation and diplopia at extremes of gaze. Diplopia occurs due to inflamed extraocular muscles and connective tissues and affects the inferior rectus, medial rectus and superior rectus in that order. The diplopia is worse in the direction opposite the affected muscle. Hence, hypertropia occurs if the inferior rectus is affected.

Diagnosis can be made clinically, but if required CT or MRI are the most valuable tests. Imaging demonstrates enlarged extraocular muscles with tendon sparing.

Management options include:

• Conservative: controlling exacerbating factors, e.g. smoking cessation, correction of thyroid dysfunction, lubricants, prisms
• Medical: steroids
• Surgical: orbital decompression

The natural course of thyroid eye disease is progression for 1-2 years, followed by a stable chronic phase. Complications include corneal ulceration precipitated by impaired eyelid closure and optic nerve compression.

Differential diagnoses include myasthenia gravis, allergic conjunctivitis and orbital tumours.

Miller Fisher syndrome

Guillain-Barré syndrome is an acute inflammatory demyelinating polyneuropathy which can affect extraocular muscles, when it is known as Miller Fisher syndrome (MFS). It is characterised by a triad of ophthalmoplegia, ataxia and areflexia. Approximately 85-90% of patients are positive for GQ1b antibodies. Pathophysiology includes a T-cell-mediated inflammatory response and destruction of myelin.

References

• Bienfang DC. Overview of diplopia. In: Brazis PW, Wilterdink JL, editors. UpToDate. [Internet]. Waltham (MA): UpToDate Inc; 2021 [updated September 9 2021; cited May 3 2023]. Available from: https://www.uptodate.com/contents/overview-of-diplopia 
• Suleiman AO. Basic Approach to Diplopia. American Academy of Ophthalmology, EyeWiki. [Internet]. February 2023 [cited May 3 2023]. Available from: https://eyewiki.aao.org/w/index.php?title=Basic_Approach_to_Diplopia&oldid=89879
• Factor SA, Esper CD. Progressive Supranuclear Palsy (PSP). In: Hurtig HI, Eichler AF, editors. UpToDate. [Internet]. Waltham (MA): UpToDate Inc; 2022 [cited May 12 2023]. Available from:
• https://www.uptodate.com/contents/progressive-supranuclear-palsy-psp-clinical-features-and-diagnosis
• Feroze KB, Wang J. Internuclear Ophthalmoplegia. [Updated 2022 Jun 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441970/
• Nair AG, Patil-Chhablani P, Venkatramani DV, Gandhi RA. Ocular myasthenia gravis: a review. Indian J Ophthalmol. 2014 Oct;62(10):985-91. doi: 10.4103/0301-4738.145987. PMID: 25449931; PMCID: PMC4278125.
• Perros P, Neoh C, Dickinson J. Thyroid eye disease. Bmj. 2009 Mar 6;338.