How is clonus typically managed?

Management of Clonus

Clonus management depends critically on the underlying etiology: when clonus occurs as a symptom of serotonin syndrome or drug toxicity, immediately discontinue the offending agent and administer benzodiazepines; for chronic clonus from upper motor neuron lesions (stroke, spinal cord injury, multiple sclerosis), initiate baclofen as first-line pharmacotherapy. 1, 2, 3

Acute Management: Drug-Induced Clonus

Serotonin Syndrome

When clonus presents with agitation, diaphoresis, tremor, or hyperreflexia in the context of serotonergic medication use, this represents a medical emergency requiring immediate intervention:

• Discontinue all serotonergic agents immediately (SSRIs, TCAs, tramadol, amphetamines) 1, 2
• Administer benzodiazepines as first-line treatment for neuromuscular symptoms, agitation, and tremor 1, 2
• Provide IV fluids for dehydration and autonomic instability 2
• Implement external cooling measures (cooling blankets) for hyperthermia; avoid antipyretics as they are ineffective since fever results from muscular hyperactivity rather than hypothalamic dysregulation 2
• Avoid physical restraints as they exacerbate isometric contractions, worsening hyperthermia and lactic acidosis 4, 2

Critical pitfall: Serotonin syndrome has an 11% mortality rate and approximately 25% of patients require intubation and ICU admission, making rapid recognition essential 2. Clonus and hyperreflexia are highly diagnostic when occurring with serotonergic drug exposure 2.

Additional Pharmacotherapy for Severe Cases

• Cyproheptadine (serotonin 2A antagonist): 12 mg orally initially, then 2 mg every 2 hours until symptom improvement, followed by maintenance of 8 mg every 6 hours 4, 2
• Monitor for cyproheptadine side effects including sedation and hypotension 2

Chronic Management: Upper Motor Neuron Lesion-Related Clonus

For clonus resulting from stroke, spinal cord injury, multiple sclerosis, or other permanent descending motor neuron lesions:

First-Line Pharmacotherapy

• Baclofen is the primary treatment for chronic clonus 3
• Mechanism: GABA-B agonist that reduces spasticity and pathological stretch reflexes

Alternative Pharmacological Options

• Cold application to the affected limb 3
• Botulinum toxin injections for focal, disabling clonus 3, 5
• Phenol injections for localized severe clonus 3

Antimyoclonic Agents for Severe Cases

When clonus is particularly disabling and refractory:

• Levetiracetam is especially useful for posthypoxic myoclonus 5
• Clonazepam has demonstrated efficacy for myoclonic movements 5
• Valproate sodium can be effective as an antimyoclonic agent 4
• Avoid phenytoin as it is typically ineffective for myoclonus and clonus 4

Important note: Combination therapy is often required to achieve adequate symptom control 5

Special Populations

Infants and Children

• Evaluate for developmental delay and upper motor neuron dysfunction when clonus is detected, as 7.1% of infants with ankle clonus develop mental retardation and 1.2% have motor delay 6
• Perform thorough neuromotor examination including postural tone, extremity tone, primitive reflexes, and antigravity movement 6
• Consider measuring creatine phosphokinase (CK) and thyroid-stimulating hormone (TSH) if low tone with weakness is present 6
• For startle-induced clonic attacks in infants with encephalopathy: myorelaxing drugs produce dramatic improvement, while antiepileptic drugs are typically unsuccessful 7

Patients with Encephalopathy

• Myorelaxing drugs rather than antiepileptic drugs for severe, prolonged startle-induced clonic episodes 7
• Video-EEG may be necessary to distinguish non-epileptic clonic attacks from true seizures 7

Monitoring for Complications

When managing acute drug-induced clonus (particularly serotonin syndrome):

• Monitor for rhabdomyolysis with creatine kinase elevation 4, 2
• Watch for metabolic acidosis 4, 2
• Check for elevated transaminases 4, 2
• Assess renal function for acute kidney injury 4, 2
• Screen for disseminated intravascular coagulation 4, 2
• Consider continuous EEG monitoring if seizures are suspected 4

Clinical Pearls

Mechanism understanding: Clonus represents involuntary, rhythmic muscle contractions at 5-8 Hz frequency, with ankle clonus oscillations occurring approximately every 160-200 ms 3. While traditionally attributed to hyperactive stretch reflexes from self-excitation, evidence suggests central generator activity interacting with peripheral events may contribute, as clonic EMG patterns occur across varied kinematic conditions and are not consistently related to muscle-tendon stretch 8.

Common mistake: Do not confuse clonus with epileptic seizures, particularly in children with encephalopathy where startle-induced clonic attacks can closely mimic clonic seizures but require entirely different management 7.