We had a really interesting discussion about this case. Here is Dr Hewett’s summary:
This presentation of fatigable ophthalmoplegia, ptosis, facial weakness and proximal limb weakness is most in keeping with generalised myasthenia gravis (MG).
A subjective sensation of ‘numbness’ is not uncommonly reported by those with facial weakness and can confuse the picture, though no actual sensory deficit is detected on formal examination.
The intermittent speech difficulty may be due to the facial weakness or bulbar dysfunction.
MG is associated with other autoimmune disorders, in this case the hypothyroidism (previous Hashimoto’s thyroiditis).
Important differential diagnoses to consider:
Guillain Barre syndrome (Acute Inflammatory Demyelinating Polyradiculoneuropathy) or the variant Miller Fisher Syndrome can present acutely with ophthalmplegia, ptosis and proximal weakness. In the early stages some cases can retain their reflexes, though after 1-2 weeks of symptoms you would expect areflexia.
The acute inflammatory myopathies such as polymyositis and dermatomyositis present with proximal limb and bulbar dysfunction though almost never involve the ocular muscles. A high ESR and CK would also be expected.
Others would include:
Lambert-Eaton Myasthenic syndrome – Reflexes normally depressed except after repeated muscle contraction, in older patients and associated with paraneoplastic autonomic features (dry mouth and skin, constipation etc…).
Multiple Sclerosis – the lack of objective sensory involvement leans away from MS, but if this young woman came to my clinic in Scotland, it’s always on the differential!
Botulism – should always be considered, though faster acting normally.
Anything else on examination?
The muscle weakness may only be apparent with repetitive or sustained use of the muscles e.g. maintaining upgaze whilst counting out loud to fifty may reproduce the diplopia, ptosis or dysarthria. Testing arm abduction bilaterally before and after exercising one arm can elicit fatiguability – though sometimes the weakness is asymmetrical.
There is a battery of tests/investigations, but the first with this patient should be to check at regular intervals her respiratory function with vital capacity or formal spirometry – with ITU involvement if any concerns as mentioned.
Antibodies against acetylcholine receptors would confirm the diagnosis but are positive in approximately 80% of generalised MG and only 50% in ocular myasthenia. Another 10% maybe positive for antibodies against muscle-specific kinase (MuSK).
Repetitive nerve stimulation (detecting a decremental repsonse) and single fibre electromyography (detecting jitter and blocking) are used to detect a defect in neuromuscular transmission. This is very helpful to support the diagnosis but can depend on the skill of the neurophysiologist, patient compliance and environmental factors.
The ‘Tensilon’ test uses edrophonium as a short-acting acetylcholine esterase inhibitor to improve muscle weakness in patients with MG. This test can show impressive results has fallen out of favour due to the false-positive and false-negative results even if blinded appropriately and cardiac adverse events. A resuscitation trolley nearby is required!
Once a diagnosis is made, a CT or MRI thorax is obligatory to exclude a thymoma, especially in older patients.
Other tests mentioned -
Cranial MRI – not usually necessary especially if the blood tests and EMG/NCS support the diagnosis, but if there is a strong suspicion of MS or the is only atypical cranial involvement then it should certainly be considered.
Muscle biopsy would only be performed if the other tests were negative.