What causes muscle twitches apart from pyridostigmine and neostigmine?

Causes of Muscle Twitches Beyond Pyridostigmine and Neostigmine

Nerve agent (organophosphate) poisoning causes muscle fasciculations and twitches through irreversible acetylcholinesterase inhibition, leading to nicotinic receptor overstimulation at the neuromuscular junction. 1

Organophosphate and Nerve Agent Toxicity

Nerve agents cause involuntary skeletal muscle contractions (fasciculations) followed by complete depolarization-like block through constant activation of nicotinic receptors. 1 This occurs because:

• Organophosphates and nerve agents (such as sarin) irreversibly block acetylcholinesterase activity, causing rapid accumulation of acetylcholine at muscarinic and nicotinic receptors 1
• The resultant nicotinic hyperstimulation generates involuntary skeletal muscle contractions that precede muscle weakness and flaccid paralysis 1
• Clinical manifestations include musculoskeletal fasciculations as an early sign, followed by weakness 1

The mechanism differs fundamentally from pyridostigmine/neostigmine in that nerve agents create irreversible acetylcholinesterase blockade, whereas pyridostigmine creates slowly reversible blockade 1

Immune Checkpoint Inhibitor-Related Myasthenia Gravis

IR-myasthenia gravis syndrome from immune checkpoint inhibitors causes exercise-dependent fluctuating weakness and can present with myasthenic symptoms including muscle twitching. 1 Key features include:

• Estimated incidence of neurological immune-related adverse events is 1-5%, with neuromuscular disorders accounting for approximately 50% 1
• Typical symptoms include exercise-dependent fluctuating weakness of proximal extremities or bulbar muscle groups and ocular symptoms 1
• This represents an increasingly recognized ICI-related complication that can rapidly progress 1

Cholinergic Crisis from Anticholinesterase Overdose

Overdosage of any anticholinesterase agent (not just pyridostigmine/neostigmine) causes cholinergic crisis characterized by muscle twitching and fasciculations. 2 This includes:

• Muscarinic symptoms (nausea, vomiting, increased secretions, bradycardia) combined with nicotinic effects 2
• The possibility of iatrogenic overdose can be lessened by carefully monitoring muscle twitch response to peripheral nerve stimulation 2
• Cholinergic crisis is characterized by increasing muscle weakness that can progress to respiratory muscle involvement 2

Important Clinical Pitfall

Administering neostigmine when TOF ratio is already ≥0.9 paradoxically causes muscle weakness and impaired neuromuscular transmission rather than typical fasciculations. 3 This represents a critical distinction:

• Neostigmine 40 mcg/kg given when TOF ratio >0.9 may decrease the TOF ratio and impair neuromuscular function for 17-52 minutes 3
• This paradoxical effect occurs because excessive acetylcholine accumulation can impair rather than enhance transmission 3

Other Anticholinesterase Agents

Edrophonium, another acetylcholinesterase inhibitor, can cause muscle twitches through the same mechanism as neostigmine and pyridostigmine but with different receptor activity profiles. 4, 5 Edrophonium is more effective at presynaptic (fade) receptors compared to neostigmine, which in turn is more effective than pyridostigmine 4