History.
Mr. Shek was a 60-year-old non-smoker who presented with a 1-month history of subacute onset, variable bilateral ptosis (left followed by right) with binocular diplopia.
He had bilateral sensorineural hearing loss since age 40. There was no apparent family history of neuromuscular diseases.
Physical examination.
Bilateral fatigable ptosis (RE almost complete ptosis, LE partial ptosis); curtain sign and Cogan lid twitch positive; rest test and LE ice pack test positive.
RE impaired elevation and adduction; LE impaired adduction and abduction; right LMN type facial weakness.
No chemosis or proptosis.
Normal neck and limb power with preserved reflexes.
Investigations.
Anti-AChR elevated.
RNS: progressive reduction in CMAP to >10% upon stimulating the left facial nerve.
SFEMG not done: variability timing of a second muscle fiber action potential relative to the first one within a single motor unit potential, AKA jitter.
Contrast CT thorax: no thymoma.
Contrast MRI brain: no brainstem lesion / extra-ocular muscle enlargement.
LP was not suggestive of CNS inflammation.
Thought process.
Syndrome:
- Subacute onset, variable bilateral ptosis with complex ophthalmoplegia.
Localization:
- Neuromuscular junction
- Peripheral nerve
- Meninges: GQ1b syndrome or thiamine deficiency; fixed or progressive symptoms
- Cavernous sinus or orbital apex: fixed or progressive symptoms; absence of proptosis or chemosis
- Muscle (oculopharyngeal muscular dystrophy; fatiguability is possible in myopathy; focal ocular onset in the absence of bulbar or limb weakness is atypical)
- Less likely midbrain or pons (central 3rd nerve palsy classically presents with unilateral complete 3rd nerve palsy with bilateral superior rectus weakness or bilateral incomplete ptosis; absence of long tract signs i.e., pyramidal weakness, cerebellar ataxia, or choreoform movements)
Etiology
- Ocular onset myasthenia gravis
- Paraneoplastic (thymoma or thymic carcinoma)
- Iatrogenic (immune checkpoint inhibitor; with myositis and myocarditis)
- Less likely Lambert-Eaton Myasthenic syndrome (classical triad of lower extremity weakness, areflexia or hyporeflexia, autonomic dysfunction; some display ataxia; facilitation present; P/Q type VGCC or SOX1 antibodies; marked (>100%) increase in the CMAP amplitude after high-frequency (10-50 Hz) repetitive nerve stimulation or after 10- to 12-second maximal isometric muscle activation or exercise.
- Less likely botulism (no exposure history; classically presenting with acute, symmetrical, descending flaccid paralysis starting with oculobulbar weakness, associated with autonomic dysfunction).
Learning points
- Myasthenia gravis is a great micmicker. This patient presented subacutely with a 1-week history of LE partial ptosis and left 6th nerve palsy. He was thus worked-up for suspected GQ1b syndrome initially. A chronic presentation would be less likely (c.f. a young lady with fatiguable neck and limb weakness for >10 years, thought to have a myasthenic syndrome but later diagnosed with mitochondrial myopathy).
- It may take time for immunotherapy to take effect (c.f. treatment response monitoring in CIDP). This patient was readmitted twice for myasthenic symptom flare while on escalating steroids. Alternative diagnoses including mitochondrial disease (noting the bilateral SNHL) due to the initial slow response to immunotherapy. However, response to IVIg has been clear-cut though short-lived.
Progress.
Started on low-dose steroids.
Readmitted 1 month later for generalized myasthenia gravis (ocular, bulbar, neck weakness).
Close clinical monitoring for differential diagnoses (slow clinical response to escalating immunotherapy).
Symptomatic control was achieved with repeated IVIg courses and high-dose steroids.
Outcome.
Bridged over to MMF as the steroid-sparing agent.