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/
