How NMJ disorders are tested on Step 1

Presynaptic or postsynaptic? Improves or worsens with use?

Myasthenia gravisAntibodies to postsynaptic AChREyes and bulbar muscles earlyWorse with repeated useReflexes normalThymoma; decremental RNSLambert-EatonAntibodies to presynaptic Ca²⁺ channelsProximal limbs firstImproves with repeated useReduced reflexes; dry mouthSmall cell lung cancer; incremental RNSvs
MG vs Lambert-Eaton. Lambert-Eaton is a paraneoplastic syndrome; look for a smoking history.

Diagnosis of myasthenia gravis

Confirm with antibodies and electrodiagnostics, then image the chest.

TestResult in myasthenia gravis
AChR antibodiesPositive in most generalized disease; MuSK antibodies in some negative cases
Repetitive nerve stimulationDecreasing response (decrement)
Single-fiber EMGIncreased jitter; most sensitive test
Ice pack testCooling improves ptosis
Chest CTThymoma or thymic hyperplasia

The edrophonium (Tensilon) test is of historical interest.

Treatment and myasthenic crisis

Boost acetylcholine, suppress antibodies, and avoid triggers.

  • Symptomatic: pyridostigmine, a cholinesterase inhibitor that does not cross into the CNS.
  • Immunotherapy: corticosteroids, azathioprine, mycophenolate, complement and FcRn inhibitors; thymectomy for thymoma and many generalized cases.
  • Myasthenic crisis: respiratory or bulbar failure; monitor vital capacity, intubate if needed, and give IVIG or plasma exchange.
  • Drugs that worsen MG: aminoglycosides, fluoroquinolones, macrolides, β blockers, magnesium, neuromuscular blockers.

Other neuromuscular junction problems

Toxins and drugs act at the same synapse.

BotulismToxin cleaves SNARE proteins → no ACh release;descending paralysis, dilated pupilsLambert-EatonFewer Ca²⁺ channels → less ACh release; improveswith useMyasthenia gravisFewer AChRs → weak endplate response; worsens withuseOrganophosphatesInhibit acetylcholinesterase → excess ACh, thenparalysis
NMJ disorders. Infant botulism follows ingestion of spores (honey); adults ingest preformed toxin from improperly canned food.

Worked example

Link the weakness to a chest finding.

functions Worked example — drooping eyelids by evening

A 35-year-old woman has double vision and drooping eyelids that are worse at the end of the day and better after sleep. Strength fades with repeated arm raises. Reflexes and sensation are normal. What test confirms the diagnosis, and what imaging is needed?

  1. Fatigable ocular and limb weakness with normal reflexes and sensation points to myasthenia gravis.
  2. Serum acetylcholine receptor antibodies confirm it in most patients.
  3. Myasthenia gravis is associated with thymic disease.
  4. Chest CT looks for a thymoma, which would be removed.

Answer. AChR antibody testing; chest CT for thymoma.