What is clonus and how is it diagnosed in an elderly patient with a history of fluoxetine (selective serotonin reuptake inhibitor) overdose and suspected serotonin syndrome?

What is Clonus and How to Diagnose It

Clonus is a rhythmic, involuntary muscular contraction characterized by repetitive, oscillating movements that occur when a muscle is suddenly stretched, and in the context of serotonin syndrome from fluoxetine overdose, it represents one of the most specific and diagnostic neuromuscular findings you should actively elicit during physical examination. 1

Definition and Clinical Significance

Clonus is a neuromuscular abnormality that manifests as rhythmic, involuntary muscle contractions triggered by sudden passive stretch of a muscle group. 1 In serotonin syndrome, clonus is considered highly diagnostic when occurring with serotonergic drug use, making it a critical finding to identify. 1, 2

The presence of clonus has higher specificity for serotonin toxicity compared to other clinical features, which is why it forms the cornerstone of the Hunter Criteria diagnostic algorithm. 3

Types of Clonus to Assess

You must systematically evaluate for three distinct types of clonus during your physical examination:

1. Spontaneous Clonus

• Rhythmic muscle contractions that occur without any stimulus or provocation 1
• This is the most severe form and alone meets Hunter Criteria for serotonin syndrome diagnosis when a serotonergic agent is involved 1, 2
• Observe the patient at rest for any spontaneous rhythmic movements of the extremities 4

2. Inducible Clonus

• Elicited by rapidly dorsiflexing the patient's foot at the ankle (similar to testing for ankle clonus) or by briskly extending the knee 1
• Diagnostic for serotonin syndrome when present with either agitation OR diaphoresis 1, 2
• More common than spontaneous clonus and often more prominent in the lower extremities 1

3. Ocular Clonus

• Horizontal eye movements that are rhythmic and jerky 1
• Diagnostic when present with either agitation OR diaphoresis 1, 2
• Assess by having the patient track your finger horizontally across their visual field 4

Diagnostic Approach Using Hunter Criteria

The American Academy of Pediatrics specifically recommends using the Hunter Criteria for diagnosis, which has 84% sensitivity and 97% specificity (superior to older Sternbach criteria). 2

To diagnose serotonin syndrome in your elderly patient with fluoxetine overdose, you need:

Confirmed exposure to a serotonergic agent (fluoxetine) PLUS one of the following:

• Spontaneous clonus (alone is sufficient) 1, 2
• Inducible clonus PLUS agitation or diaphoresis 1, 2
• Ocular clonus PLUS agitation or diaphoresis 1, 2
• Tremor AND hyperreflexia 1, 2
• Hypertonia AND temperature >38°C AND (ocular clonus OR inducible clonus) 1, 2

Physical Examination Technique

How to Elicit Inducible Clonus:

1. Lower extremity assessment (most sensitive location): 1

   • Have the patient lie supine with knee extended
   • Rapidly dorsiflex the foot at the ankle with a brisk, sustained stretch
   • Observe for rhythmic, repetitive beats (≥3 beats is abnormal)
   • Clonus is more prominent in the lower extremities in serotonin syndrome 1

2. Upper extremity assessment: 1

   • Rapidly extend the wrist
   • Observe for rhythmic oscillations

3. Assess for hyperreflexia concurrently: 1

   • Test deep tendon reflexes (patellar, Achilles, biceps, triceps)
   • Hyperreflexia frequently accompanies clonus in serotonin syndrome 1, 2

Complete Neuromuscular Assessment:

Beyond clonus, examine for the full spectrum of neuromuscular abnormalities: 1

• Myoclonus (present in 57% of serotonin syndrome cases) - brief, shock-like involuntary movements 2
• Muscle rigidity - particularly in severe cases 1
• Tremor - often coarse and bilateral 1
• Hyperreflexia - exaggerated deep tendon reflexes 1, 2

Clinical Context for Your Patient

In an elderly patient with fluoxetine overdose, symptoms typically develop within 6-24 hours after ingestion. 1, 5 The clinical presentation follows a triad: 1, 2

1. Mental status changes: Agitated delirium, confusion, or altered consciousness 1
2. Autonomic hyperactivity: Hyperthermia (up to 41.1°C), tachycardia, hypertension, diaphoresis, mydriasis 1
3. Neuromuscular abnormalities: Clonus, hyperreflexia, myoclonus, rigidity 1

Critical Pitfalls to Avoid

• Do not rely on laboratory tests - there are no pathognomonic laboratory findings for serotonin syndrome 1
• Do not confuse with neuroleptic malignant syndrome (NMS) - NMS presents with "lead pipe" rigidity rather than hyperreflexia and clonus, and occurs with antipsychotics rather than serotonergic agents 1
• Mild cases are easily missed due to variable presentation - maintain high clinical suspicion with any serotonergic drug exposure 1
• Physical restraints worsen the condition by exacerbating isometric contractions, leading to increased hyperthermia and lactic acidosis 2, 5

Severity Assessment

Once clonus is identified and serotonin syndrome diagnosed, classify severity: 1

• Mild: Clonus and hyperreflexia without significant autonomic instability
• Moderate: Requires hospitalization with continuous cardiac monitoring 5
• Severe: Medical emergency with hyperthermia >41.1°C, severe muscle rigidity, multiple organ failure - mortality rate approximately 11% 1, 2

In severe cases with prominent rigidity and hyperthermia, approximately 25% of patients require intubation, mechanical ventilation, and ICU admission. 2, 5