What causes clonus (involuntary, rhythmic muscle contractions)?

From the Guidelines

Clonus is primarily caused by hyperexcitability of the stretch reflex, resulting from damage to the descending motor pathways that normally inhibit spinal reflexes, and can also be triggered by certain medications, particularly those that enhance serotonergic activity, such as SSRIs, as seen in cases of serotonin syndrome 1. This neurological sign typically occurs due to lesions in the upper motor neurons, such as those found in the brain or spinal cord.

• Common conditions that cause clonus include:
  • Multiple sclerosis
  • Stroke
  • Traumatic brain injury
  • Spinal cord injury
  • Cerebral palsy
  • Metabolic disorders like liver or kidney failure The mechanism involves interruption of the normal inhibitory signals from the brain to the spinal cord, leading to exaggerated reflex responses when a muscle is suddenly stretched. This creates the characteristic rhythmic, involuntary muscle contractions when a joint is rapidly flexed or extended. The severity of clonus often correlates with the extent of the underlying neurological damage, and its presence helps clinicians localize and assess the severity of central nervous system lesions. In some cases, clonus can be a symptom of a life-threatening condition, such as serotonin syndrome, which can be caused by the simultaneous use of multiple serotonergic drugs, including SSRIs, and requires immediate medical attention 1. Additionally, myoclonus, a clinical phenomenon consisting of sudden, brief, involuntary jerks caused by muscular contractions or inhibitions, can also be a predictor of poor outcome in comatose survivors of cardiac arrest, particularly when it occurs as a status myoclonus starting within 48 hours from return of spontaneous circulation (ROSC) 1.

From the Research

Causes of Clonus

• Clonus is involuntary and rhythmic muscle contractions caused by a permanent lesion in descending motor neurons 2
• It may occur in any muscle with a frequency of 5-8 Hz and the average period of oscillations of the ankle clonus is approximately 160-200 ms 2
• Two different hypotheses have been asserted regarding the development of clonus:
  • Hyperactive stretch reflexes in clonus are caused by self-excitation 2
  • Central generator activity that arises as a consequence of appropriate peripheral events and produces rhythmic stimulation of the lower motor neurons 2, 3
• Clonus can be attributed to increased reflex gain and enlarged tissue viscoelasticity 4
• It is part of the upper motor neurone syndrome manifesting as increased tone, clonus, spasms, spastic dystonia and co-contractions 5

Related Conditions

• Spasticity is common in many neurological disorders, such as stroke and multiple sclerosis, and can cause clonus 5
• Clonus can occur secondary to spinal cord injury (SCI) and other neurological disabilities 3
• Tizanidine is an imidazoline central alpha(2)-adrenoceptor agonist widely used to manage spasticity secondary to conditions such as multiple sclerosis (MS), stroke, and spinal cord injury (SCI) 6

Mechanism

• The exact mechanism of clonus remains unclear 2
• The interaction of central mechanisms and peripheral events may be responsible for clonus 3
• Reflex gains were largest in patients with the largest tissue viscoelasticity 4