2025年10月18日 星期六

Poisoning Induced Myoclonus

 

1. Definition and Clinical Description

  • Myoclonus refers to sudden, brief, involuntary muscle jerks caused by abnormal central nervous system excitation. Poisoning-induced myoclonus can be multifocal or generalized, irregular or rhythmic. [1]
  • It includes positive myoclonus (sudden contraction) and negative myoclonus (brief loss of tone, e.g., asterixis).[1]
  • It is often mistaken for tremor or clonus, but differs in rhythm, mechanism, and duration.Clonus is rhythmic and stretch-reflex–driven, usually sustained.
  • Myoclonus is irregular, brief (<100 ms), and cannot be voluntarily controlled.
  • Differential: Tremor is rhythmic and often partially suppressible.

🔹 2. Mechanisms in Toxicology

  • Loss of GABAergic inhibition
    • Many toxins block GABA_A or GABA_B receptors, leading to decreased CNS inhibition. Examples include β-lactam antibiotics, isoniazid, theophylline, caffeine, diphenhydramine, cyclobenzaprine, and TCAs.
    • Mechanism: reduced GABA activity increases neuronal excitability, resulting in myoclonus or seizures.
  • Serotonergic overactivity (serotonin syndrome) [2]
    • Caused by SSRIs, MAOIs, linezolid, meperidine, tramadol, or fentanyl.
    • Myoclonus (59.5%) appears with hyperreflexia, agitation, tremor, and diaphoresis.
  • Metabolic or toxic accumulation
    • Occurs in uremia, hepatic encephalopathy, or drug accumulation in renal or hepatic failure.
    • Common agents include cefepime [3] and morphine.[4]
  • Excess excitatory amino acids (glutamate pathway)
    • Some toxins enhance NMDA or AMPA receptor activity.
    • Examples include domoic acid and organophosphates. [5]
  • Opioid toxicity or withdrawal
    • Certain opioids (meperidine, tramadol, fentanyl, morphine) produce neurotoxic metabolites such as normeperidine.
    • Presents with multifocal myoclonus and altered mental status.

 

🔹 3. Common Poisons and Drugs Causing Myoclonus

  • Antibiotics: cefepime, ceftriaxone, penicillin G.
  • Antidepressants: SSRIs, MAOIs, TCAs.
  • Analgesics: tramadol, meperidine, fentanyl, morphine (via metabolites).
  • Stimulants: amphetamines, cocaine [6], theophylline, caffeine.
  • Others: isoniazid, lithium, baclofen withdrawal [7], organophosphates [5], heavy metals.

 

🔹 4. Diagnostic Clues

  • EEG may show diffuse cortical spikes or polyspike–wave discharges.
  • Clinical pattern shows abrupt, arrhythmic, and sometimes stimulus-sensitive jerks.[1]
  • Myoclonus differs from seizures by being briefer and often without loss of consciousness. Always consider drug exposure, renal or hepatic impairment, and polypharmacy / Poisoning.

🔹 5. Management

  • Identify and discontinue the offending toxin or drug.
  • Correct metabolic abnormalities such as uremia, hypoxia, or electrolyte imbalance.
  • Perform hemodialysis if due to a renally excreted neurotoxic agent (e.g., cefepime, lithium, isoniazid).
  • Use benzodiazepines (clonazepam, diazepam, lorazepam) to enhance GABAergic inhibition.[1]
  • Valproate or levetiracetam can be used in persistent cases.[1]
  • Avoid serotonergic or excitatory agents.
  • Cyproheptadine is useful for serotonin syndrome.
  • Pyridoxine (vitamin B6) should be given in isoniazid toxicity.[8]

🔹 6. Summary

Myoclonus is an important warning sign of neurotoxicity in poisoning. Always assess renal function and cumulative neurotoxic drug exposure. EEG monitoring helps identify subclinical epileptiform activity. Main management principle: stop the toxin and enhance GABAergic inhibition.

References

[1]. https://www.ncbi.nlm.nih.gov/books/NBK537015/

[2]https://pubmed.ncbi.nlm.nih.gov/31688388/

[3]https://pubmed.ncbi.nlm.nih.gov/39068595/

[4]. https://pubmed.ncbi.nlm.nih.gov/9204657/

[5]. https://pubmed.ncbi.nlm.nih.gov/36609395/

[6]. https://pubmed.ncbi.nlm.nih.gov/116267/

[7]. https://pubmed.ncbi.nlm.nih.gov/12736874/

[8].https://pubmed.ncbi.nlm.nih.gov/2796112/

 

 Edited by Yu-Jang Su Oct 18, 2025  

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Poisoning Induced Myoclonus

  1. Definition and Clinical Description Myoclonus refers to sudden, brief, involuntary muscle jerks caused by abnormal centr...