Introduction 

Clonus or clonus reflex, is an abnormal neurological reflex causing involuntary muscle contractions, spasms, pulsing, tightness, and pain, resulting from central nervous system (CNS) (brain and spinal cord) damage. This is often associated with stroke, spinal cord injuries (SCI), cerebral palsy (CP), and amyotrophic lateral sclerosis (ALS).¹ While the exact cause of clonus is still not known, exploring its neurological basis, mechanisms, and pathophysiology could aid our understanding of the condition. This will help us facilitate its accurate diagnosis, evaluation, and management among healthcare professionals, thus improving the quality of life of those affected. 

Neurological basis 

What is clonus?

Clonus is a rhythmic, oscillating reflex induced by brisk muscle stretch.^1,2 It is often a sign of permanent upper (descending) motor neuron lesion, associated with hyperreflexia, spasticity, and muscle weakness.^1,3

Subtypes of clonus 

Stretch reflex, reflex arc, and clonus generation 

Stretch (deep tendon or myotatic) reflex is a pre-programmed body response to sudden muscle stretch in postural control, maintenance and overstretching prevention. A reflex arc is like an electrical pathway, allowing impulses to travel from our muscles to the spinal cord and back. Once the stretch reflex is activated, changes in muscle length are detected in the muscle spindles as specialised sensors, where impulses are sent to the spinal cord. As motor neurons split, a contracting signal is sent to the stretched muscle, while a relaxing one is sent to the antagonist muscles, facilitating an immediate muscle contraction within 1-2 milliseconds. However, due to exaggerated spinal signalling, rhythmic, repetitive muscle contractions are seen in clonus.^4,5 

Mechanisms 

Upper motor neuron (UMN) involvement 

Upper motor neuron (UMN) syndrome refers to descending motor pathways from the brain.⁶ This could disrupt the inhibitory control among lower motor neurons (LMNs), lower its activation threshold, and trigger hyperexcitability.^3,6 The involuntary, repetitive muscle contraction in clonus can thus be observed among UMN syndrome. 

Spinal cord mechanisms 

The spinal cord mechanism of clonus involves the disrupted inhibitory signals and an imbalance of excitatory-inhibitory output that descends from the brain, resulting in hyperexcitability and exaggerated spinal reflexes. This loss of normal muscle activity modulation and control thus contributes to the trigger of involuntary, repetitive muscle contractions seen in clonus.^3,4,6  

Excitatory and inhibitory neurotransmitters

A complex excitatory and inhibitory neurotransmitter interplay is also involved in clonus. While excitatory neurotransmitters such as glutamate and acetylcholine promote muscle contractions, inhibitory neurotransmitters like gamma-aminobutryric (GABA) and glycine regulate and suppress excessive muscular excitability. Imbalances between the two, either an increased excitatory signalling or reduced inhibitory control, can trigger hyperactivated spinal reflexes, thus the emergence of clonus.^4,7 

Feedback loop dysfunction 

Feedback loops are crucial in muscle activity regulation for smooth and coordinated movements. As disrupted among clonus, the processing and interpretation of sensory signalling triggered by muscle contractions in transmission to the central nervous system are altered. This leads to abnormal muscular responses instead of appropriate muscle activity. This disrupted, positive feedback loop in turn reinforces and sustains the muscle contractions, perpetuating the repetitive, uncontrollable clonic muscle contractions, among clonus.^3,6

Signs or characteristics of clonus 

Clonus is a neuropathological reflex, either temporary, acute, or chronic. There are several defining characteristics for distinguishing from other motor abnormalities. 

Rhythmic, involuntary and repetitive muscle contractions

Clonus happens in response to a sudden stretch or stimulation, with muscle spindles unloading among spastic muscles, often triggered by external factors such as tapping or passive movement.⁶ 

A series of alternating muscle spasms or jerking motions

Clonus can be observed visually and felt through palpation, commonly affecting specific muscle groups, such as the ankle, wrist, patellar or other muscles attached to joints, depending on the underlying condition.³ 

Variability in duration and intensity among episodes 

While clonus can last from several seconds to minutes, the severity also differs among individuals and underlying conditions. Some individuals may experience milder clonic episodes, meanwhile others have more pronounced and disruptive episodes interfering with their gait, posture, and daily life activities.¹ 

Diagnosis and assessment

Physical examination 

Clonus is primarily tested clinically as part of a neurological exam, induced by stretching the affected muscles or tapping the corresponding tendon, most commonly in the ankle joint by briskly flexing the foot towards the shin when supine. Generally pathological in adults, positive clonus is recorded when involuntary oscillations (bouncing up-and-down) are seen more than 5 beats against the pressure. While it may stop spontaneously or continue a long time, its duration and intensity is also recorded to determine its severity, with more than 10 beats considered as “sustained.” For even more severe cases, simply sitting or walking can trigger ankle clonus.^1,2,8 

Thorough medical history review and medical tests 

A clonus is usually a sign of a descending motor pathway lesion, whether it is temporary, acute or chronic. A thorough medical history review and a number of medical tests, such as blood tests, MRI scanning of the brain and/or spinal cord, nerve conduction studies, electromyogram, and lumbar puncture to differentiate clonus from other motor abnormalities, as well as identify its underlying cause.¹ 

Conditions associated with clonus 

Stroke and cerebral palsy 

Stroke and cerebral palsy(CP) could damage corticospinal tract integrity and disrupt the reflex arc, motor control, and muscle tone. The resulting hyperreflexia, spasticity, and weakness can contribute to clonus development.^1,9

Spinal cord injury (SCI)

While Spinal cord injuries would interrupt the normal functioning of the spinal circuit, reflex arc, and thus spinal reflexes and motor function. The hyperreflexia and impaired motor control could also trigger sustained, involuntary clonic muscle contractions among SCI individuals.^1,3 

Amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders 

Progressive motor neuron loss among amyotrophic lateral sclerosis (ALS) can disrupt the balance between excitatory and inhibitory signals within the spinal cord. The diminished motor neuronal inhibitory inputs could further exacerbate muscular hyperexcitability, resulting in hyperreflexia and thus sustained and involuntary clonic muscular contractions. 

Other neurodegenerative conditions like multiple sclerosis (MS), Parkinson's disease and Spinal muscular atrophy (SMA) can also involve motor neuron dysfunction that interrupts signalling transmission between the brain, spinal cord, and muscle, triggering abnormal reflexes and clonus onset. ^{10,11,12,13,14} 

Treatment and management  

Medications

While muscle relaxants (e.g., baclofen or tizanidine) and antispasmodic drugs (e.g., diazepam or dantrolene) can be prescribed to target and reduce muscle hyperexcitability, thus helping to alleviate and control clonus occurrence.¹  

Physical therapy

Customised physical exercises are crucial in preserving and improving muscle strength, endurance, flexibility, and coordination. Therapeutic techniques incorporating stretching, range-of-motion (ROM) exercises and functional training are also used to optimise motor control, reducing spasticity, and minimising clonic movements. 

Functional electrical stimulation (FES)

Functional electrical stimulation can stimulate nerves and activate specific muscles with electrical currents to modulate muscle activities, reduce clonic spasms, and improve motor function.¹⁵ 

Occupational therapy 

Occupational therapists can provide strategies, such as daily task modifications and ergonomic adjustments, to enhance function and adapt activities upon clonus management. 

Assistive devices and orthotic devices 

Assistive devices and orthoses such as braces, splints, and ankle-foot orthoses (AFOs) can provide support, stabilisation, and better alignment of weakened muscles and joints to reduce clonus occurrence. Adaptive utensils, mobility aids, and environmental modifications can further aid motor deficits, thus minimising the daily impact brought by clonus and improving mobility.  

Botulism toxin injections

In certain cases, botulism toxin can be locally injected, temporarily paralysing the affected muscle(s), as it cannot contract involuntarily, thus relieving muscle hyperactivity, spasticity, and the development of clonus.^1,3 

Intrathecal baclofen pump

An intrathecal baclofen pump can be applied to cases with severe spasticity and clonus to manage muscle tone and alleviate clonus through direct baclofen delivery into the spinal fluid.¹⁶ 

Prognosis and long-term outlook 

Clonus itself is not a specific condition, but a symptom of an underlying neurological disorder or injury. Its prognosis and long-term outlook mainly depend on the underlying causes and effectiveness of treatment interventions.

Those associated with reversible conditions or injuries, such as temporary nerve compression or medication side effects, are more favourable, where treating the underlying causes or discontinuing medications can already resolve or significantly improve clonus. 

Those secondary to progressive neurodegenerative disorders like ALS, multiple sclerosis, or spinal cord injury, involving ongoing motor neuron loss and degeneration, result in persistent or worsening clonus and can therefore have a more challenging long-term prognosis. 

Regarding the variations among individuals, it may be difficult to completely eliminate clonus. Regular monitoring, management, timely adjustments, and ongoing healthcare support are crucial for symptomatic management and control, thus daily functioning and quality of life optimisation.¹ 

Summary 

Clonus is a neuropathological sign characterised by involuntary, rhythmic, repetitive muscle contractions. It mainly arises from disrupted normal muscular activities control and modulation due to upper motor neuron lesion or dysfunction, among stroke, cerebral palsy, spinal cord injuries, and neurodegenerative diseases like ALS. The loss of inhibitory signals, excitatory and inhibitory imbalances, spinal reflexes' hyperexcitability, and a dysfunctional feedback loop can contribute to clonus occurrence. A comprehensive understanding of the neurological mechanisms of clonus is vital for the accurate identification of underlying causes. It is also beneficial to the targeted therapeutic intervention development for proper management in order to improve the quality of life among the affected population.

FAQs 

What’s the difference between clonus and myoclonus?

Clonus is an abnormal reflex response to muscle stretch involving rhythmic movement, whereas myoclonus is a brief, involuntary, irregular twitching of a muscle or group of muscles.  

How is clonus differentiated from tremor?

Clonus is a rhythmic muscle contraction from a sudden stretch, associated with upper motor neuron lesions, typically in the ankles; while tremor is involuntary rhythmic oscillations involving alternating muscle contractions, among various body parts, and frequencies from diverse causes.