Clinical manifestations

Presentation and course

Spasticity is a common symptom of upper motor neuron disease. It can be seen in various conditions affecting the central nervous system, including cerebral palsy, stroke, traumatic brain injury, multiple sclerosis, and spinal cord injury. Spasticity can manifest in various ways in terms of location and severity due to this variation in etiology and localization.

Spasticity is assessed by attempts to measure resistance to passive movement. The most commonly used assessments of passive movement are the Modified Ashworth Scale (05) and the Tardieu Scale (67). The Modified Ashworth Scale grades spasticity on a scale from 0 to 4 (03). A joint is passively moved, testing the corresponding muscle’s resistance to stretch and where the resistance is felt in the range of motion. In cases of mild spasticity, the muscles will only resist when stretched at a higher velocity. In the case of severe spasticity, movement of the muscle may be difficult to impossible (12). The Tardieu Scale also assesses resistance to passive movement but notes an angle at which the catch is appreciated and compares the angles when the muscle is stretched at different velocities. It also factors clonus into the assessment.

Table 1. The Modified Ashworth Scale

Table 2. Tardieu scale

The examination can begin with the patient relaxed and lying down, with the head in a neutral position and arms resting to the sides. It can be easier to determine the extent of spasticity in this position. Observing a patient’s level of function, such as movement of limbs, standing, or walking, can be especially valuable, and video cameras can assist in providing more objective comparisons of movement and function before and after treatment.

The amount of function the patient derives from spasticity can be evaluated by doing a functional examination and testing motor strength and control. It is essential to evaluate the advantages and disadvantages that spasticity in individual muscles gives the patient so that treatment strategies and goals can be identified. Disadvantages of spasticity may include interference with activities of daily living, inhibition of good sleep, contractures, dislocations, skin breakdown, bowel and bladder dysfunction, impairment of respiratory function, pain with stretching, and masking of the return of voluntary movement. However, given that many people with spasticity have underlying weakness and decreased motor control, patients may rely on a certain amount of spasticity for maintaining muscle tone and managing activities of daily living.

Related clinical manifestations should also be evaluated, such as resistance to passive stretch, decreased range of motion, increased deep tendon reflexes, positive Babinski sign, or a more subtle reduction of the plantar withdrawal reflex. Motoneuronal overactivity, or overflow movement, where input to motoneurons produces excessive and prolonged muscle activity and contractions of many limb muscles, can also be observed (79). Reduction in the tonic vibration reflex can also be tested.

Prognosis and complications

Spasticity results in limited functional capacity and increased inactivity. The sequelae of this inactivity may include decubiti, cardiovascular problems, thrombophlebitis, respiratory infections, fixed contractures, osteoporosis, bladder and bowel problems, and social isolation. Ultimately, these consequences of inactivity may lead to a further decrease in strength and function (19). The patient’s quality of life may be compromised as spasticity negatively impacts mobility, hygiene, self-care, sleeping patterns, self-esteem, mood, and sexual function.

Early treatment of spasticity and preventative measures can help to prevent many of these complications.

Clinical vignette

Patient A. Patient A was a 5-year-old African-American boy with a history of developmental delay and a diagnosis of cerebral palsy of the spastic-diplegic type. He first presented at 18 months with severe spasticity in both lower extremities. The patient walked on tiptoes and had hip and knee flexion. There was some scissoring of the legs. On examination, exaggerated deep tendon reflexes were elicited, as were sustained clonus and bilateral Babinski signs. Brain MRI showed findings that may be secondary to previous hypoxic injury, compatible with cerebral palsy. Prior treatments included physical therapy, bilateral ankle-foot orthosis, serial casting, and oral baclofen. Before treatment with botulinum toxin injections, the patient was a tiptoe walker.

With treatment the patient’s gait has improved; he is flat-footed and presently wears bilateral ankle-foot orthosis.

His hygiene and positioning have also improved and he returns every 6 to 9 months for reinjection.

Patient B. Patient B was a 7-year-old African-American boy with a history of cerebral palsy of the spastic-diplegic type. On primary examination, he presented with tightness of both hamstrings and heel cords, in the right more involved than the left. The patient had good toe standing, especially on the right side, and good sitting balance with a kyphotic sacral-type sitting due to the tight hamstring. He uses a walker to ambulate and walks on tiptoes. The EEG was abnormal, indicating the presence of epileptiform activity from the left central parietal head region and diffuse background disorganization, which indicates underlying neuronal dysfunction. Treatments before intrathecal baclofen pump implantation included bilateral ankle-foot orthoses, tendon releases, alcohol block, and botulinum toxin injections. Before treatment with intrathecal baclofen, the patient was dependent on a caregiver and used a walker to ambulate.

With the intrathecal baclofen pump, the patient has gained function, does not use a walker to ambulate, and performs activities of daily living independently.

Patient C. Patient C was a 61-year-old man with a history of chronic cerebrovascular accident with left spastic hemiparesis. He was ambulatory with the use of an ankle foot orthosis and used his left hand as a holder for activities of daily living. The patient had never received prior treatment for spasticity and presented due to stiffness contributing to low back pain. On primary examination, fingers were flexed with hypertonia, worst at proximal interphalangeal and metacarpophalangeal joints. Ambulation revealed a stiff knee gait with reduced passive dorsiflexion of the ankle, worse with knee extension. Standing elicited toe flexion and tenderness in the lumbar paraspinals. The patient’s goal was to reduce back stiffness and enhance the functional use of his hand. The treatment plan included physical and occupational therapy, oral therapy, and chemodenervation. He was started on oral tizanidine and received botulinum toxin injection in the finger flexors, hand intrinsics, ankle plantar flexors, and toe flexors. Following these interventions, the patient had improved hand function and reduced knee stiffness. Back pain began resolving with tizanidine and continued to improve as gait became less effortful. With physical, oral, and focal therapies, he could take longer walks with his wife and increase the ease of performing activities of daily living.

Biological basis

Etiology and pathogenesis

Spasticity may result from diffuse or localized pathology of the cerebral cortex, brainstem, or spinal cord. Possible causes of such injuries include cerebral palsy, traumatic brain injury, stroke, multiple sclerosis, spinal cord trauma, or diseases such as genetic neurodegenerative disorders and anoxic insults. The neurologic localization of the lesion causing spasticity may result in different clinical manifestations. Thus, it is essential to consider whether the spasticity results from cerebral or spinal cord pathology and whether it is diffuse or localized.

Diffuse cerebral injury or diseases would include anoxia or toxic or metabolic encephalopathies, whereas localized cerebral injury would include tumors, abscesses, cysts, arteriovenous malformations, cystic degeneration of the brain, hemorrhage, or trauma. Causes of cerebral palsy include generalized hypoxic ischemic injuria and anoxia or localized periventricular leukomalacia, encephalomalacia, and cortical abnormalities, such as porencephaly or congenital malformations of gyri (eg, micropolygyria). Spinal cord injury or disease caused by trauma, inflammatory or demyelinating disease, degenerative disorders, or compression such as is caused by a tumor or cyst (12; 21; 03) are also causes of spasticity but are less common than cortical causes.

Because of this, more than one mechanism may be responsible for the disturbance in muscle tone, and the mechanisms may vary between patients. The neuropathophysiologic processes involved in spasticity are complex and not fully understood. Still, there is a widely accepted hypothesis that spasticity depends on hyperexcitability of spinal alpha motor neurons, which is due to the interruption of descending modulatory influences carried by the corticospinal, vestibulospinal, and reticulospinal tracts and other possible tracts (18). Ia afferent fibers provide segmental input from muscle spindles to alpha motor neuron pools. They synapse on segmental inhibitory interneurons that then inhibit alpha motor neurons innervating antagonist muscles in the Ia reciprocal inhibition pathway. Ib afferents inhibit alpha motor neurons through the Golgi tendon organs via the Ib inhibitory interneuron in another pathway known as nonreciprocal inhibition (76; 18). Increased excitation of these afferents does not seem to be the cause of spasticity. Instead, evidence supports that reduced reciprocal inhibition of antagonist motor neuron pools by Ia afferents, decreased presynaptic inhibition of Ia afferents, and decreased nonreciprocal inhibition by Ib terminals are all possible pathophysiologic mechanisms of spasticity (76). The pathophysiology of traumatic brain injury involves a complex combination of forces that has been a subject of substantial debate (14).

Epidemiology

Spasticity is a frequently observed consequence among patients who have experienced neurologic insults. However, incidence and prevalence are difficult to quantify, primarily due to a lack of reliable measures and variability of definitions and clinical manifestations (46).

Stroke. Spasticity is most commonly seen following a stroke. Globally, the incidence of stroke is 12.2 million with over 101 million prevalence (23), and spasticity occurs in 40% of stroke patients with paresis (77).

Cerebral palsy. The incidence of cerebral palsy is 1.5 to 3.0/1000 live births, depending on risk factors (59), and about 81% of those diagnosed with cerebral palsy experience spasticity (75).

Traumatic brain injury. The incidence of traumatic brain injury is 500/100k, though 80% of these are categorized as mild head injuries (24). Spasticity occurs in about 18% to 53% of individuals who have sustained traumatic brain injuries (46). The significant variability in occurrence rates among patients with brain injury is attributed to the varying degrees of severity, which includes those affected by concussions.

Multiple sclerosis. The global incidence of multiple sclerosis is 2.1/100k, and the prevalence is 44/100k (70). Spasticity manifests in 84% of patients with multiple sclerosis (58; 52).

Spinal cord injury. The incidence of spinal cord injury in the United States is 17,000, with 282,000 prevalence (04). In the spinal cord injury population, 65% to 78% of patients who are more than 1-year post-injury experience spasticity (02).

Considering the above statistics, a significant population is affected by spasticity each year.

Prevention

Spasticity can occur from any CNS trauma or insult. In the case of CNS trauma, safety precautions, such as helmets and seatbelts, are advised. Safety measures should be taken in individuals with conditions that make them susceptible to brain or spinal cord injury or both (ie, helmets for patients with frequent seizures).

To prevent cerebral palsy and the resulting spasticity in infants, mothers must receive prenatal care during pregnancy, measures must be taken to avoid premature labor, and special consideration should be given to pregnancies involving multiple gestations. When appropriate, antenatal magnesium sulfate and corticosteroids (64), neonatal use of caffeine, and hypothermia (63), as well as early resuscitation and access to acute care can help with risk factors for cerebral palsy. When combined with therapies, umbilical cord blood has been shown to improve motor skills over therapies alone (51). There is increasing evidence for erythropoietin's effects on neuroregeneration (63).

Noxious stimuli, such as constipation, urinary retention, infection, or sources of pain, all relatively common in this patient population, can worsen underlying spasticity. It is recommended to monitor changes in spasticity and address any underlying causes of worsening spasticity.

To prevent or minimize secondary complications of spasticity, including contractures, nerve entrapment, and skin breakdown, treatment of problematic spasticity should be initiated on recognition. Ongoing clinical reassessment is critical to ensure that treatment efforts are maximized. Early and frequent range of motion in a paretic limb and using splints for positioning can also help prevent skin breakdown and contracture.

Differential diagnosis

Confusing conditions

Conditions that are sometimes confused with spasticity and can co-occur with spasticity include:

Rigidity. In rigidity, a generalized high tone throughout a joint range of motion is not velocity-dependent. Rigidity is also more likely to relax through repeated stretching (12; 76).

Volitional movement. Purposeful movement (eg, purposeful resistance to movement) can include guarding or tensing a muscle due to anxiety, pain, or fear of pain. This can cause resistance to movement and may even appear to be velocity-dependent as greater velocity may elicit more pain/fear of pain and, thus, more purposeful resistance. In children, this can also be due to resisting the examiner, not wanting to participate in the examination, or not understanding how to relax muscles.

Dystonia. In dystonia, an involuntary pattern of muscle contractures leads to repetitive movement and abnormal posturing.

Contracture. In contracture, a joint is fixed due to muscle, ligament, tendon, and skin tightening and cannot be moved.

Associated or underlying disorders

Spasticity is due to injury to the upper motor neuron unit and can develop in many neurologic disorders. Associated conditions depend on the underlying neurologic diagnosis and may include deep vein thrombosis, heterotopic ossification, and autonomic dysreflexia, which can be severe and potentially life-threatening (13; 11). Many orthopedic problems may result from a spastic limb, including spontaneous fracture, dislocation of the hip or knee, heterotopic ossification, and scoliosis. Spasticity can also cause impingement of peripheral nerves, for example, causing cubital or carpal tunnel syndrome.

Because children are still growing, those with spasticity due to any cause are at high risk for bony deformity, including increased risk for hip subluxation or dislocation (which can result in pain and prevent sitting or standing) as well as scoliosis (which can cause restrictive lung disease). Vigilance in treating spasticity in children is, thus, especially critical, and close hip surveillance, including x-rays, is critical as physical examimation alone can not reliably identify hip subluxation. For children with cerebral palsy, there are specific guidelines; one of the most established in the United States is that published by the American Academy of Cerebral Palsy and Developmental Medicine: https://www.aacpdm.org/publications/care-pathways/hip-surveillance-in-cerebral-palsy.

Diagnostic workup

Spasticity is a clinical diagnosis of velocity-dependent resistance to movement due to a neurologic cause. When clinically identified, testing can be done to establish the underlying cause, such as any lesions of brain or spinal cord injury. History and physical examination are used to help localize the lesion and guide further workup, which most commonly includes MRI of the brain or spine or genetic studies.

Signs of spasticity can also be seen in EMG or nerve conduction studies. On EMG, the jerks show greater amplitudes than are normal and are followed by after-discharge of the motor units that is often slightly longer-lasting than normal. The size of tendon jerks can be measured by either EMG response or by recordings of mechanical events. H-reflex studies are electrically elicited tendon jerks and are mainly restricted to the soleus and flexor carpi radialis muscles in normal adults. In cases of upper motor neuron lesions, the H-reflex may be elicited in muscles where it is not normally seen, such as the intrinsic hand muscles, tibialis anterior, or peroneal muscles (79). Neurophysiological studies, such as the H-reflex study, may be performed in patients with neurodegenerative disease.

Basic laboratory studies can help identify metabolic derangement. Enzymatic assays, EMG or nerve conduction study, and genetic testing can help identify neurodegenerative diseases or other genetic causes of neurologic abnormalities. A baseline EEG to establish underlying seizure activity can also be done to determine any seizure activity associated with the underlying condition.

Table 3. Useful Tests for Diagnosis

Management

Pharmacological management

Oral therapy. Oral medications can decrease spasticity; however, many have unwanted side effects, such as drowsiness, sedation, confusion, and fatigue.

Baclofen. Baclofen is a GABA-B agonist acting centrally in the brain and spinal cord. Baclofen binds with GABA-B receptors, restricting calcium influx into presynaptic nerve terminals, thereby reducing spasticity (19). The clinical effects include decreased resistance to passive motion, decreased hyperreflexia, and reduced painful spasms and clonus. Baclofen can be administered intrathecally and orally. When taken orally, it is absorbed in the upper small intestine. There is no rectal or colonic absorption. Due to the relatively small area for absorption, there is a potential for a saturation phenomenon to be observed, where escalating doses do not increase effectiveness after a certain point. Oral preparations include tablets, granules, and liquid suspension.

Tizanidine. Tizanidine is an alpha-2 adrenergic agonist acting centrally in the brain and spinal cord. It prevents the release of excitatory neurotransmitters (norepinephrine), resulting in reduced spasticity and hyperreflexia. Animal studies with tizanidine demonstrate antinociceptive activity under specific conditions with increased dose titration (10; 08; 69; 45). Potential side effects include drowsiness, dry mouth, weakness, hypotension, and elevation of liver function tests. Literature suggests that tizanidine may be better tolerated than other antispasticity agents as measured by the global tolerance rating scale (39). In placebo-controlled studies, tizanidine has been shown to be effective in multiple sclerosis and spinal cord injury. It is also helpful for spasticity of spinal pathology when weakness is of concern. Tizanidine may also prove effective in managing spasticity of cerebral origin (47). Monitoring of liver function is recommended with tizanidine use.

Clonidine. Clonidine belongs to the same class as tizanidine (alpha-2 adrenergic agonist), although clonidine has some alpha-1 agonist activity. Clonidine can be given orally and also transdermally. Hypotension is a potential side effect.

Dantrolene. Dantrolene is unique in that it acts peripherally at the muscle fiber level. It does not affect neuromuscular transmission but works by hindering calcium release from the sarcoplasmic reticulum, thereby preventing the excitation-contraction coupling mechanism. This affects both intrafusal and extrafusal fibers by decreasing the force of muscle contraction. This mechanism is not selective for muscles with increased tone, and generalized muscle weakness may result and could potentially weaken respiratory muscles. Dantrolene is indicated for treating spasticity secondary to cerebrovascular accident and cerebral palsy and has possible applications for traumatic brain injury, spinal cord injury, and multiple sclerosis. Clinical effects of dantrolene sodium include decreased resistance to passive range of motion, decreased hyperreflexia and tone, and reduced spasms and clonus. Like tizanidine, dantrolene can raise liver function tests and requires periodic monitoring of liver function.

Benzodiazepines. Benzodiazepines, such as diazepam, are not FDA-approved for spasticity but are commonly used. These authors do no generally recommend them as a first line due to their wide array of potential adverse effects as well as the potential for dependence. However, in children with cerebral palsy, diazepam, in particular, can be considered a first-line treatment (51). Benzodiazepines are effective in spinal cord injury, multiple sclerosis, cerebral palsy, and stroke-related spasticity. Benzodiazepines are generally avoided in traumatic brain injury due to cognitive side effects but can be useful in withdrawal from intrathecal baclofen scenarios. Clinical effects include sedation, reduced anxiety, decreased resistance to passive range of motion, decreased hyperreflexia, and reduced painful spasms. Side effects of all benzodiazepines include sedation, weakness, hypotension, gastrointestinal symptoms, memory impairment, incoordination, confusion, depression, and ataxia. Also, benzodiazepines are controlled substances with the potential for dependency. Diazepam is the most widely used benzodiazepine for spasticity management. If nocturnal spasticity is the presenting problem, the patient should be started with a single dose at night.

Secondary oral agents. Secondary oral agents include cyproheptadine, lamotrigine, and gabapentin (25). Additional studies have confirmed the benefit of gabapentin in multiple sclerosis (09) and spinal cord injury (28; 50; 55).

Cyproheptadine. Cyproheptadine is an antihistamine and a serotonin antagonist. Although not approved for spasticity, it has been described to be helpful with spasticity in patients with spinal cord injury or multiple sclerosis without side effects of weakness. Adverse effects include sedation and dry mouth.

Cannabis or cannabinoids. The active alkaloid of the cannabis plant is delta-9-tetrahydrocannabinol (THC). This is available as a dronabinol or as a synthetic cannabinoid nabilone. Although anecdotally reported to be associated with reducing spasticity in multiple sclerosis, stroke, and spinal cord injury, it has been studied more recently in patients with multiple sclerosis. In a meta-analysis of 14 studies with 2280 participants (2,138 with multiple sclerosis and 142 with spinal cord injury), cannabinoids were associated with improvements in spasticity, but this failed to reach statistical significance in most studies (72). There were no clear differences based on the type of cannabinoid. Only studies in patients with multiple sclerosis reported sufficient data to generate summary estimates. Cannabinoids (nabiximols, dronabinol, and THC/CBD) were associated with a greater average improvement on the Ashworth scale for spasticity compared with placebo, although this did not reach statistical significance.

Other muscle relaxants. Some drugs, such as cyclobenzaprine, metaxalone, and methocarbamol, are prescribed as skeletal muscle relaxants, but they have not been shown to be effective in spasticity. They are centrally acting, but the exact mechanism of action is poorly understood. They do not directly affect skeletal muscle, motor end plates, or peripheral nerves.

Intrathecal baclofen therapy. It has been established that oral baclofen has a limited area of absorption in the small intestine, does not effectively cross the blood-brain barrier (where it has its site of action in the GABA-B receptors of the brain and spinal cord), and is associated with serious side effects at higher doses (19). Intrathecal baclofen results in a greater decrease in spasticity by allowing higher concentrations of baclofen in the cerebrospinal fluid at about 1% of the daily oral dosage (32). Intrathecal baclofen therapy involves the infusion of baclofen from a pump implanted in the abdominal wall through a catheter that is surgically positioned in the intrathecal space. An external radiotelemetry hand-held device programs infusion settings. The intrathecal baclofen pump can be programmed to deliver baclofen continuously throughout the day or only during specific periods whenever the spasticity interferes with comfort or function (20).

Before implantation of an intrathecal baclofen pump, an intrathecal baclofen trial, in which a test dose of 50 to 100 µg of baclofen is delivered via lumbar puncture or spinal catheter, is recommended (20). After implantation, the pump is periodically refilled by percutaneous access to the central reservoir.

Intrathecal baclofen will circulate throughout the CSF but tends to affect muscles below the level of the catheter tip to a greater degree, often providing relatively more benefit to the lower limbs than the upper limbs. Intrathecal baclofen therapy can significantly improve function and quality of life and offers the most precise delivery control. Additionally, intrathecal baclofen therapy is cost-effective when one considers cumulative medical costs relative to anticipated costs without a pump implant (61).

Complications associated with intrathecal baclofen are rare but include pump mechanical failure, including rotor stall and battery failure, catheter migration or disruption, human errors such as programming or refill error, and surgical complications such as cerebrospinal fluid leakage, pump pocket seroma, hematoma, infection, and soft tissue erosion. Both abrupt withdrawal from intrathecal baclofen and overdose are life-threatening conditions that require immediate medical attention in the hospital setting. Best practice guidelines are available to guide the management of these conditions (62).

Intrathecal clonidine. Although clonidine's primary route of administration is oral or transdermal, there have been reports of its off-label use via intrathecal delivery to relieve spasticity. Case studies and reports have suggested that intrathecal clonidine, either used as single or adjuvant therapy, can modulate the transmission of pain signals by inhibiting the release of excitatory neurotransmitters. In one review, 24 patients received intrathecal clonidine for 5 or more years, with relief in spasticity and pain and no significant adverse effects (29). Another case described significant relief of anal sphincter spasms in a tetraplegic patient after clonidine was added to her intrathecal baclofen pump (48). In the event of withdrawal, management would include antihypertensive therapy and consideration of cardiac monitoring.

Pharmacologic focal treatments. There is no single algorithm for treatment of spasticity. Focal therapies are appropriate first-line therapies for focal problems, but a combination of therapies is often needed to achieve optimal results.

Focal therapy options for spasticity management can be divided broadly into pharmacologic and nonpharmacologic treatments. Pharmacologic options include chemoneurolysis with ethyl alcohol or phenol and chemodenervation with botulinum neurotoxin. Local anesthetic nerve blocks are sometimes used diagnostically as a prelude to additional treatments. An emerging but currently off-label pharmacologic focal therapy is the injection of hyaluronidase. Nonpharmacologic options include surgeries such as tendon lengthening, tendon transfers, tendon release, functional neurotomy, and nerve transfers. An emerging but currently off-label nonpharmacologic focal treatment for spasticity is cryoneurolysis.

Local anesthetic blocks. Local anesthetic blocks produce a temporary block via Na+ channel inactivation. Temporary nerve blocks with local anesthetic can distinguish the relative contribution of spasticity versus contracture. They can be useful to see what range is possible and determine whether additional procedures, such as chemodenervation, will effectively achieve the desired outcome. For instance, in severe spasticity, when passive movement is difficult or impossible, it can be challenging to determine if a joint is completely contracted or if the spasticity is too severe for the limb to be passively moved. A temporary block can paralyze the muscles innervated by the branch of the nerve block, allowing the examiner to determine how much range of motion a patient has if the spastic portion is removed. Local anesthetic nerve blocks are typically performed with bupivacaine, which has an onset of action of 5 to 10 minutes and a duration of 4 to 8 hours, or lidocaine, which has an onset of 1 to 2 minutes and a duration of 2 hours.

Chemoneurolysis. Chemoneurolysis is performed similarly to nerve blocks, except phenol or ethyl alcohol are used. Unlike the effects of local anesthetics, the effects of injection of phenol or ethyl alcohol are immediate and permanent. Proper training is necessary to perform this procedure safely. Nerves are localized through the use of electrical stimulation (76; 19). The nerve and surrounding supportive connective tissue structures are lysed by protein denaturation, but sprouting and regeneration can ultimately allow the recurrence of muscle overactivity, necessitating repeating the procedure in the future, often months to years later.

If neurolysis is performed on whole nerves, both afferent and efferent fibers will be disrupted. All muscles innervated by that nerve will be paralyzed, and anesthesia will occur in the skin supplied by the sensory branches. Incomplete lysis of sensory fibers can result in painful dysesthesias. Neurolysis can also be performed on motor branches, which is more selective (49). With selective motor branch neurolysis, dysesthesias are rare.

Chemodenervation. Chemodenervation with botulinum neurotoxin is a first-line option for focal treatment of spasticity. First clinically introduced in the United States in the early 1980s, botulinum neurotoxin is derived from the anaerobic bacteria Clostridium botulinum, the same organism responsible for botulism. There are seven serotypes of botulinum neurotoxin, types A, B, C, D, E, F, and G, but only types A and B are commercially available in the United States. Other serotypes are available in Europe.

Botulinum neurotoxin is delivered to spastic muscles via percutaneous injection and is then taken up into the axon terminal, where it has its site of action. Botulinum neurotoxin works by cleaving the SNARE proteins, which allow the synaptic vesicles containing acetylcholine to fuse with the membrane of the axon terminal to release acetylcholine into the neuromuscular junction. Botulinum neurotoxin type A cleaves the SNARE protein SNAP-25, and botulinum neurotoxin type B cleaves the SNARE protein synaptobrevin. Individual brands may vary, but botulinum neurotoxin types A and B reach peak effectiveness by about 2 weeks post-injection and last approximately 12 weeks.

Effects are reversible, and patients who enjoy the effects of botulinum neurotoxin will require re-injection once the effects wear off. The main potential side effect is weakness. Adverse effects are not common and are usually associated with the site of injection, such as bleeding, bruising, injection site soreness, or diffusion to nearby muscle groups. Botulinum neurotoxin is contraindicated during pregnancy, lactation, and in individuals with known allergies to the drug. Caution is advised in patients with neuromuscular junction disorders, such as myasthenia gravis, and in patients taking certain drugs that could potentiate the effects, such as aminoglycoside antibiotics or paralytic agents (eg, vecuronium). Though poorly studied, long-term use of chemodenervation has been linked to muscle atrophy, which may be related to toxin serotype, lipid accumulation, changes in blood flow, mitochondrial dysfunction, and muscle fiber type (60). Using injection guidance, such as EMG amplifier guidance, electrical stimulation, ultrasound, or a combination of these methods, is recommended with strong evidence (27). Dosing is based on the muscle size and its relative involvement in the spastic position, and dosing guidelines are available for each commercially available botulinum neurotoxin agent.

Hyaluronidase. Hyaluronidase injection is an emerging and off-label treatment for spasticity, which targets muscle's abnormal elasticity (stiffness) (57). The theory behind its effectiveness is that paralysis and immobility lead to atrophy of muscle fibers, a relative increase in the extracellular matrix, and an increase in hyaluronan. At high concentrations, hyaluronan can dramatically increase the viscosity of the extracellular matrix and decrease the sliding of muscle fibers, leading to shortening and fibrosis of muscles. In a study of spastic muscles of the upper limbs of 20 patients, 75 units of hyaluronidase were injected per site, up to 600 units. This intervention was paired with exercise, and a resultant increased range of motion was observed, which persisted for at least 3 months (57).

Nonpharmacological management

Therapies. Therapies are fundamental to gaining strength, maintaining and increasing range of motion, and, most importantly, improving function. Although it does not seem to affect spasticity directly, it is a critical part of treating people with spasticity (35; 51). There are many beneficial therapies, including muscle strengthening and stretching, the practice of functional tasks, sensory integration, targeted muscle training, constraint-induced movement therapy, treadmill training, aqua therapy, and hippotherapy. Many more therapies exist that improve function and quality of life in individuals with spasticity.

Modalities, alternative medicine, and stem cell treatments. A systematic review of the nonpharmacologic treatment of spasticity for adults concluded that there was moderate evidence for electroacupuncture combined with conventional routine care (pharmacological or rehabilitation) (35). Evidence also shows that traditional acupuncture decreases spasticity (51). The mechanism is unknown, but theories with limited studies include that acupuncture or electroacupuncture may break the pain-spasm-pain cycle, decrease the hyperexcitability of gamma and alpha motor neurons or increase the inhibition of interneurons, or increase GABA levels and decrease levels of excitatory neurotransmitters in the brain and spinal cord (81). There is also moderate evidence for neuromuscular electric stimulation combined with other interventions (35).

There is some low-quality evidence for extracorporeal shock wave therapy, transcranial direct current stimulation for stroke, and transcranial magnetic stimulation and transcutaneous electrical nerve stimulation for other neurologic conditions, as well as repetitive magnetic stimulation in multiple sclerosis and vibration therapy (35). Further studies are needed to understand the effect of these interventions on spasticity; however, they show some promise in the temporary relief of spasticity.

A systematic review showed some support for increased objective measures of spasticity with pregnancy, posture, cold, circadian rhythm, and skin conditions (54). Additionally, increased self-reports of spasticity included bowel- and bladder-related issues, menstrual cycle, mental stress, and tight clothing (54).

Hyperbaric oxygen does not treat spasticity, nor has it shown functional benefits for patients with spasticity (07; 51).

Looking to the future, stem cell therapy shows promise in treating various central nervous system conditions causing spasticity, but more research is needed (17; 42; 53; 80).

Cryoneurolysis. Cryoneurolysis is an emerging treatment for focal spasticity (73). Presently, cryoneurolysis is FDA-approved for pain but is currently off-label for spasticity. Unlike chemoneurolysis with phenol, which is not selective to neural tissue and destroys surrounding connective tissue, cryoneurolysis selectively targets neural tissue, causing Wallerian degeneration. As the surrounding connective tissue is not lysed, cryoneurolysis is potentially safer than chemoneurolysis (06; 31; 73), and subsequent procedures performed in the same area, should spasticity recur, are said to be less technically challenging in terms of nerve localization than they are with repeat chemoneurolysis.

Surgical interventions. Surgical interventions include peripheral procedures (rhizotomy, neurectomies, stereotactic radiosurgery) and central procedures (cordectomy, myelotomy, or cerebellar or spinal electrode stimulators) as well as combined surgical and pharmacological treatment of intrathecal baclofen pump discussed above.

There is the most evidence for selective dorsal rhizotomy, especially in children with cerebral palsy, which will be covered in detail below. There is also some evidence for the success of selective neurectomy (26; 40; 44). For severe, intractable cases of spasticity, there have been some papers looking at the use of cordectomies (37) and myelotomies (65; 43) as well as some experimentation on stereotactic radiosurgery of peripheral nerves (56). Implantation of cerebellar or spinal stimulators (66) and deep brain stimulators may show some benefit for spasticity, although more research is needed.

Nerve transfer to improve spasticity and function also shows promise. One randomized control trial studied the effect of a C7 nerve transfer from the unaffected side to the affected spastic arm from chronic cerebral injury (78). Significant improvements in power, function, and reduced spasticity at 12 months post-surgery were seen compared to the control group that only received physical therapy.

Selective dorsal rhizotomy. Selective dorsal rhizotomy is a treatment used to alleviate spasticity, specifically in children with cerebral palsy. Generally, this is best performed between the ages of 3 and 10 years to treat a patient before they develop joint contractures or hip subluxation or dislocation while simultaneously waiting until they are mature enough to participate in inpatient rehabilitation therapy after selective dorsal rhizotomy (22). Factors that make a child a good candidate for selective dorsal rhizotomy include having a General Motor Functional Classification System (GMFCS) I, II, and II, spastic diplegia, and gross motor function measure (GMFM) over 60 (15). Poor candidates are patients with poor motor control, those who depend on their spasticity for function due to underlying weakness, and those with underlying dystonia. This neurosurgery is meticulous and generally requires a neurophysiologist and a physiatrist or therapist to help identify the the percentage of nerve rootlets and which nerve root levels are to be severed based on the degree and location of spasticity limiting function. Studies have shown that performing selective dorsal rhizotomy at a young age can reduce the need for orthopedic surgery and botox injections (15). Side effects include sensory deficits and bladder incontinence (34). There also may be an increased risk of scoliosis and lordosis an average of 4 to 11 years after selective dorsal rhizotomy (68; 33).

A summary of spasticity interventions is provided in Table 4.

Treatment of contractures. The best treatment is the prevention of contractures via treating spasticity (as outlined above) and regular stretching of joints via therapies, bracing, splints, and all movement activities. Most contractures can be prevented when treatments are started immediately after spasticity starts, which is why early identification and treatment are critical. Once contractures have developed, the main treatments are serial casting and orthopedic procedures.

Serial casting. Serial casting, where a cast is placed on a joint and replaced weekly, each time intensifying the stretch, has been shown to be beneficial for increasing the range of motion. Serial casting combined with botulinum toxin injections is the gold standard for contracture treatment in children with cerebral palsy (51) and has also shown to be successful in adult patients with spasticity, including stroke and brain injury (74; 41). Serial casting is generally started about 1 to 2 weeks after botox is given to maximize the benefits of botox in facilitating the stretch achieved during serial casting and tolerance. Serial casting can also be done without botulinum toxin. Most commonly, the ankle joint is done, and weight bearing is allowed while in the cast.

Orthopedic procedures for contractures. Orthopedic procedures are performed for contractures not responsive to more conservative measures restricting function or quality of life. The targets of these operations are tendons or bones. Muscle tendons may be released, lengthened, or transferred. The goals of surgery are to increase the range of motion, improve access for hygiene, improve the ability to tolerate braces, or reduce pain.

Tendon release. In this procedure, the tendon of a muscle that has a contracture is partially or completely cut. The joint is then positioned at a more normal angle, and a cast is applied. Regrowth of the tendon to a new length occurs over several weeks. Another example of a tendon release surgery is an operation known as a slide procedure used to lengthen the supraspinatus muscle in a shoulder abduction contracture. The surgeon can release all four muscles that typically cause this deformity.

Tendon transfer. A tendon from a spastic muscle is cut and then transferred to a different site, changing the direction that the joint is pulled. In some situations, the transfer allows improved function. In others, the joint retains passive but not active function. Ankle-balancing procedures are among the most effective interventions.

Osteotomy. In an osteotomy, a small wedge is removed from a bone to allow it to be repositioned or reshaped. It is often accompanied by operations to lengthen or split tendons to allow for fuller correction of the joint deformity. A cast is applied while the bone heals in a more natural position. Osteotomy procedures are commonly used to correct hip subluxation or dislocation and foot deformities.

Arthrodesis. In arthrodesis, bones are fused to limit movement. This fusion limits the ability of a spastic muscle to pull the joint into an abnormal position but also prevents joint movements. This is done when the spastic pull of a muscle on the bone cannot be controlled, and it is deemed best to prevent movement at the joint to attain functional or preventative goals. Most often, arthrodesis is performed on the ankle and foot. In triple arthrodesis, the three joints of the foot are exposed, the cartilage is removed, and screws are inserted into the bones, fixing the joints into position. With a short walking cast in place for 6 weeks or until the bones have fully healed, the patient may bear weight immediately after the operation (WE MOVE 2007).

Special considerations in children. Other principal treatments in children with cerebral palsy include single-event multilevel surgery, where multiple orthopedic surgeries are combined into one and carefully planned and timed, given that children are growing.

Table 4. Therapeutic Interventions for Spasticity

Special considerations

Pregnancy

The patient with spasticity may expect to have a difficult pregnancy and delivery as well as difficulty managing and caring for an infant.