Introduction

Spasticity is a common complication after spinal cord injury (SCI) that occurs in the context of an upper motor neuron injury syndrome, and may develop even years after the acute injury leading to further loss of function ( ; ).

Spasticity was defined by as “a motor disorder characterized by a velocity dependent increase in tonic stretch reflexes (muscle tone) with exaggerated tendon jerks, resulting from hyper excitability of the stretch reflex, as one component of the upper motoneuron syndrome.” Dynamic phenomena were not included, so the Ability Network (an international panel of clinical experts to develop management algorithms to guide and standardize assessment, treatment and outcomes in SCI people with disabling spasticity) recommends Pandyan definition ( ): “Disordered sensorimotor control, resulting from an upper motor neuron injury, presenting as intermittent or sustained involuntary activation of muscles.”

Considering every SCI people regardless of the time of evolution, neurological level or extent, the prevalence of spasticity is approximately 65% according to the studies of . Some studies have been conducted on SCI complications; demonstrated an incidence of 25%–37% in acute traumatic SCI, showed an incidence of 15%–36% in acute nontraumatic SCI, and in papers by or , incidence of chronic SCI is estimated about 65%–93%. There is no significant correlation among neurological level, ASIA Impairment Scale (AIS) grade, and spasticity, but related severe spasticity with cervical levels and grade A, and a highest prevalence of spasticity among people with grade C.

Pathophysiology of spasticity

The stretch reflex is a monosynaptic reflex that originates in the muscle spindles with any stimulus (not just stretch) and travels through an afferent pathway to the spinal cord (SC) where it synapses with the corresponding alpha motor neuron and contracts the muscle fibers where it is has produced the stimulus. If the stimulus is prolonged, the Golgi tendon organs are activated, and via interneurons Ib, the previous contraction can be relaxed. Studies by show that spasticity is generally due to a lowered threshold of phasic or tonic stretch reflexes; when inhibitory signals are lost due to spinal cord damage, the segmental reflexes are released and become hyperactive. In addition, other spinal mechanisms are postulated, such as fusimotor hyperexcitability, axonal sprouting, reduction of presynaptic inhibition, and reduction of reciprocal inhibition.

described that clinical features of spasticity depend on the greater or lesser loss of the ability to voluntarily modulate the level of activity of a given motor pool and the capacity of the interneurons that project to these motor pools to recruit the appropriate combination of them.

Besides, there are plastic alterations in affected muscles. Basically, spasticity causes fibrosis, atrophy of muscle fibers, decrease in the elastic properties, decrease in the number of sarcomeres, accumulation of connective tissue, and alteration of contractile properties toward tonic muscle characteristics.

Manifestations of spasticity in spinal injuries

According to , two classification criteria can be used: the place where the stimulus for spasticity is located, which differentiates between intrinsic if the stimulus emerges within the central nervous system, and extrinsic if the afferences come from other structures such as the skin, muscles, and joints; also if there is no resultant movement, a tonic or static component is described, and if there is any movement, a phasic or dynamic component is described. So, we can distinguish three main types of spasticity:

• (a)
  

  Intrinsic tonic spasticity: hypertonia.

  
  
• (b)
  

  Intrinsic phasic spasticity: clonus and osteotendinous hyperreflexia.

  
  
• (c)
  

  Extrinsic spasticity: spasms.

The presence of triggers was described by ; these exacerbating factors can cause a patient with a SCI and a normal or decreased tone to present intense or frequent spasms. The most important triggers are neurogenic bowel (constipation) and bladder problems (hyperreflexia). The supine position is associated with more intense hypertonia and increased likelihood to provoke spasms, and according with , the most frequent clinical sign is usually spasms when making any transfer. Other factors such as pregnancy, cold, circadian rhythm, pressure ulcers, menstrual cycle, stress, and even tight clothing also increase spasticity, while acute and severe infections (sepsis) and syringomyelia can cause both an increase of spasticity as a sudden absence of spasticity.

The ability to achieve functional goals may be impaired due to spasticity and can even make the length of hospital stay last longer, according to .

Assessment of spasticity and its consequences

Treatment of spasticity

Modalities of treatment in spinal injury

Since the intensity of spasticity can vary in intensity throughout the same day and eradication treatment is not possible, the management of spasticity should focus on EDUCATION; the patient must learn what spasticity is, its signs and symptoms and its consequences, and how they can be prevented, starting with avoiding exacerbating factors.

• (a)
  

  Control of triggers . The first point in treatment is to eliminate the triggering factors, since although they do not cause spasticity, they are usually present when it appears or worsens.

  
  
• (b)
  

  Positioning . The most appropriate posture is sitting; in the wheelchair, the patient must have hips, ankles, and knees flexed at 90 degrees and a slight inclination of the seat, in bed it is recommended lateral decubitus with more forced flexion of the hip and knee of the lower limb located just above the bed. You may improve spasticity using standing devices.

  
  
• (c)
  

  Physical modalities . Studies by have shown that most of them have a short-lasting effect to be significant, and is based on the maintenance of the myotatic reflex by prolonging a stimulus (stretching, cold) and therefore the stimulation of the Golgi reflex.

  
  
  
  
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    Stretching. It should be held for at least 1 min to achieve muscle relaxation and increase ranges of motion. It can be done through self-stretching, casting, splinting, or within a physical therapy protocol.

    
    
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    Cold or heat application.

    
    
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    Orthotics and splints. They are used to allow long-term stretching, but they should only be used in moderate spasticity or to maintain outcomes from another previous treatment.

    
    
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    Muscle-strengthening. In this way, we mitigate the functional repercussions that traction of the antagonist spastic muscle can have on any muscle.

    
    
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    Electrical stimulation. The repeated application of tetanic contractions by high frequencies > 2500 Hz can fatigue the spastic muscle, but this effect is short-lasting, and even long-term may lead to increase spasticity, especially in incomplete injuries. Functional electrical stimulation (FES) is used to strengthen antagonist muscles.

    
    
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    Robotic systems can work both by causing prolonged stretching and by strengthening antagonists, showed by .

    
    
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    Passive cycling is postulated as a treatment for strengthening weak muscles. In a study by , it is shown that there may be improvement in spasticity but the significance is demonstrated with FES compared to passive cycling. The rest of the studies collected in the metaanalysis by show that passive cycling can only achieve subjective improvement but objectively there are no effects or there is even a worsening in spasticity.

    
    
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    Other modalities. performed a randomized controlled trial on kinesiotaping for spasticity in stroke patients resulting in short-lasting improvement, but there are no trials within SCI people. Shockwaves have been used in poststroke spasticity, and a systematic review by confirms moderate improvement, but it has not been studied in SCI either.

  
  
  
  
• (d)
  

  Oral drugs . Its characteristics have been studied by , and its specific use for SCI patients has been described by .

  
  
  
  
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    Baclofen. It is considered the gold standard drug because it acts by binding to receptors just in the spinal cord, since it is a structural analog of gamma-amino-butyric acid (GABA, an inhibitory neurotransmitter) and an agonist of GABA-B receptors. In adults, you can start with 15 mg daily in 3 doses and increase every 4–7 days 15 mg daily. Start dosage can be 15 mg/day divided in 3 doses and titration may be 15 mg each 4–7 days; in older patients or with comorbidities, the titration should be slower, and in children, dosage starts with 2.5 mg/day to a maximum dose of 30 mg/day in children 2–7 years and 60 mg/day in children older than 7. Side effects are dose-dependent; the most frequent are fatigue and drowsiness, it can also cause muscle weakness, confusion, dizziness, hypotension, or constipation.

    
    
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    Diazepam. It binds to GABA-A receptors and causes presynaptic inhibition in the spinal cord. Side effects include sedation and cognitive impairment. Its main indication would be night spasms, prescribing 5 mg daily.

    
    
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    Clonazepam. It is another benzodiazepine that is typically used when spasms predominate, the starting dose is 0.5 mg daily and requires a slower titration because of its side effects (withdrawal syndrome may be more dangerous).

    
    
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    Tizanidine. It is an α2 agonist that acts by inhibiting the release of excitatory amino acids in SC interneurons. The most frequent side effects are drowsiness, dizziness, hypotension, or xerostomia, the starting dose is 4 mg daily. The effectiveness of tizanidine, usually considered as a second-line drug, is backed by the largest study.

    
    
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    Clonidine. It is also an α2 agonist, but it causes hypotension more frequently, so it is not recommended in tetraplegic patients.

  
  
  
  
• (e)
  

  Intrathecal medication . Studies by and show that baclofen pumps may be considered when high dosages of baclofen are required or there is no response with any other treatment. A programmable pump is implanted into the abdomen, from where a catheter conveys the baclofen into the intrathecal space, usually at the lumbar level since there is greater concentration of GABA receptors in the lumbar spinal cord. Prior to implantation of the pump, all candidates undergo a trial via lumbar puncture, with a dose of 50 μg of baclofen; tone and spasms are measured each 2 h, and if there is positive outcome (spasticity improves), we proceed to gradually withdraw oral drugs and then increase the dose of baclofen in the pump up to the optimum dose (average is 400–500 μg/day), which is kept refilling the reservoir pump at regular intervals (3–6 months). Most adverse effects occur during the titration phase and include drowsiness, headache, nausea, weakness, and hypotension; other complications may be due to mechanical problems (dislodgment, disconnection, kinking, blockage), pump failure, or infection. Any interruption of intrathecal baclofen delivery may result in a severe baclofen withdrawal syndrome that is usually characterized by a sudden increase of spasticity, pruritus, hyperthermia, autonomic dysregulation, seizures, coma, rhabdomyolysis, disseminated intravascular coagulation, and multisystem organ failure.

  
  
• (f)
  

  Local injections . They are indicated in focal spasticity. Local phenol injections are discussed in the corresponding chapter. Studies by have shown that focal spasticity is described in some cases of AIS C or D injuries. Botulinum toxin serotype A is produced by the Clostridium botulinum bacterium, and is a metalloprotease which, in nerve endings, proteolitically cleaves synaptosomal associated protein (SNAP-25) to inhibit the fusion of the synaptic vesicle with the presynaptic membrane of the axon terminal, and thus ultimately relax the muscle Botulinum toxin can also be used if there are muscles that cause worse functional repercussions (e.g., hip adductors to allow bladder indwelling).

  
  
• (g)
  

  Surgery . In SCI, it is not used as an etiological treatment, but it can be applied as a correction of complications (tenotomies and tendon transfers).

  
  
• (h)
  

  Other treatments . Studies by have reported that repetitive magnetic stimulation at the lumbar nerve roots can decrease lower limbs spasticity in SCI patients, and found that repetitive transcranial magnetic stimulation may be effective against spasticity in SCI patients, even more than against cerebral spasticity.

Outcome measures after treatment

It is performed by means of comparison with previous measurements, the global tolerance to the treatment, and a subjective assessment by the patient. It is also possible to assess the achievement of the objectives set before the treatment, or Patient Global Impression of Change scale, as stated in protocol by .

Management protocol for spasticity in spinal cord injury

There are studies on the application of one or other treatments such as that of but there are no specific protocols or algorithms of management nowadays for spasticity in SCI. Most of the systematic reviews and metaanalysis have been performed on spasticity due to stroke or several mixed pathologies, so no evidence can be shown for any technique for SCI as stated by and . A protocol for this treatment is then proposed:

• (a)
  

  Positioning and exercise : The first step is to promote an adequate positioning and educate the patient in the need to exercise daily; during acute in-patient phase, this exercise will be performed in the context of physical therapy, and then in chronic phase perform only mobilizations or stretching as maintenance.

  
  
• (b)
  

  Control of triggering factors : It can be considered as the first part of the treatment because it is the first factor to be taken into account when spasticity appears or is decompensated.

  
  
• (c)
  

  Baclofen : If spasticity must be treated, the first-line drug is baclofen. We start with a dosage of 15 mg/day divided into 3 doses (lower dosage for children, elderly people or concomitant drugs), and in 3–4 days, it can be increased to 30 mg/day; we must wait 2 weeks to significantly evaluate the effect.

  
  
  
  
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    If the response to treatment is partial, we increase to 45 mg/day and if now the response is complete, the same dosage is maintained.

    
    
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    If there is no response for 4 weeks, we can go directly to next point by withdrawing baclofen.

    
    
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    If there is a partial response after 3 weeks with baclofen at 45–60 mg/day and spasticity remains with much functional interference, a second-line drug is added, and this depends on the spasticity features.

  
  
  
  
• (d)
  

  Second-line drugs :

  
  
  
  
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    Only phasic spasticity. If the only symptom not controlled by baclofen is night spasms diazepam is added in a single nightly dose. If there are spasms or other dynamic phenomena all day long then clonazepam is added.

    
    
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    Predominance of hypertonia. In general, the drugs preferred as adjuvants to baclofen are tizanidine or clonidine, considering that if the patient has a cervical SCI, we only choose tizanidine.

    
    
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    Focal spasticity. If there are less than four muscle groups involved in spasticity, botulinum toxin is used. If spasticity is initially generalized but after administration of baclofen or others only focal spasticity persists, botulinum toxin is also indicated.

  
  
  
  
• (e)
  

  Third – line treatment . If we are using two of the drugs mentioned earlier with a dose close to the maximum allowed or effective, we can add one of the others as third drug (e.g., if we use baclofen and tizanidine, we can associate diazepam). If one of the drugs mentioned earlier cannot be added as a third drug (elderly patients, prevention of adverse events), we can test other drugs with less recognized efficacy or focus on physical modalities (e.g., hydrotherapy).

  
  
• (f)
  

  Failure of all the treatments . If we are using three or four oral drugs, we have every exacerbating factor controlled, the patient performs physical activity, and despite everything spasticity is still intense or disabling, we will consider the intrathecal baclofen pump. We must perform a previous baclofen test dose (positive if instillation of a 50 μg bolus produces improvement of spasticity), there must be permeable intrathecal flow, the patient must be motivated and psychologically stable, and there must have been a minimum time of evolution of the lesion (usually 9–12 months).

Applications to other areas of neuroscience

Differences between spasticity of cerebral and spinal origin ( ; ).

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  The most frequent presentation of spasticity when the origin is spinal is generalized and diffuse, while focal spasticity is more frequent when the origin is cerebral.

  
  
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  Regarding hypertonia, patients with SCI develop a more intense spasticity, and the clasp knife phenomenon is more frequent.

  
  
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  The most affected muscles in SCI are extensors (antigravity muscles), especially in the lower extremities, while people with stroke or cerebral palsy show specific synergies (hemiparesis, diparesis) with greater involvement of flexor muscles.

  
  
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  Regarding intrinsic phasic spasticity, clonus of the plantar flexors is more frequent when the origin is spinal, and patellar clonus is rare if the origin of the spasticity is not cerebral.

  
  
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  Extrinsic spasticity is more common in SCI; lower limb extensor spasms are the most prevalent spastic sign in SCI. The most important stimulus in SCI is the extension of the hip (especially the last 20 degrees). The highest concentration of mechanoreceptors in people with cerebrovascular diseases is in the knees.

  
  
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  Spinal spasticity is further exacerbated by visceral diseases.

  
  
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  SCI patients show shortening of muscles due to prolonged postures, and the most frequent affected muscles are hamstrings that are shortened by keeping the sitting in the wheelchair. However, stroke patients can maintain a posture due to spasticity when they develop spastic dystonia, whose principal example is elbow flexion posture.

Mini-dictionary of terms

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  Antagonist muscle produces an opposite movement. Since antagonist muscles produce an opposing joint torque to the agonist muscles, this torque can be used to control the motion.

  
  
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  Antigravity muscle acts to counterbalance the pull of gravity and to maintain an upright posture. Most important antigravity muscles are quadriceps femoris and triceps surae.

  
  
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  Catch is a sudden appearance of increased muscle activity as a response to a fast passive stretch, which provokes an abrupt stop.

  
  
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  Clasp knife phenomenon occurs when there is an initial resistance to passive movement of a joint and this tone reduces suddenly and then the limb can move quite freely through its range of motion.

  
  
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  Clonus is an involuntary rhythmic muscle contraction that can cause distal joint oscillation.

  
  
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  Hypertonia is an involuntary increase in muscle resistance to passive stretching.

  
  
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  Osteotendinous hyperreflexia is an exaggerated muscular response to percussion of the tendons.

  
  
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  Spasms are abrupt, involuntary muscle contractions.

  
  
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  Spinal shock is the temporary loss of spinal reflex activity that appears as an initial phase when SCI starts abruptly (as occurs in traumatic or vascular injuries).

  
  
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  Tonus (muscle tone) is a continuous and passive partial contraction of the muscles that works as preparatory for voluntary movement.

Key facts of “diagnosis of spasticity in spinal cord injury”

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  When a traumatic SCI is starting, the appearance of spasticity means the ending of the spinal shock.

  
  
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  Spasticity cannot be found in lower motoneuron syndromes. The clinical course of cauda equina or conus medullaris syndromes is like a second motoneuron syndrome, and therefore they never develop spasticity.

  
  
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  When the cause of the SCI is vascular, the duration of spinal shock is usually longer.

  
  
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  The presence of neurogenic bladder or bowel is associated with normal or even flaccid tone but frequent and spontaneous spasms.

  
  
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  We must make a differential diagnosis between spasticity and other tone disorders; resistance to passive movement found in extrapyramidal stiffness, paratonia, or simulation is velocity-independent.

Key facts of “treatment of spasticity in spinal cord injury”

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  Physical modalities are often considered the mainstay of treatment for spasticity, but the duration of the effect is too short, so these treatments are useless. It may be beneficial to strengthen the muscles antagonistic to the spastic ones.

  
  
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  Although there is only one trial with only six SCI patients that compared oral baclofen with placebo, baclofen has been reported to be effective for reducing spasticity (particularly spasms) and is considered the first-line treatment for spasticity.

  
  
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  Since the proportion of elderly SCI patients is increasing, the dosage of baclofen is becoming more difficult due to its effects on cognitive abilities.

  
  
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  Tizanidine is the drug with the most important and reliable studies but it is usually associated with the treatment of stroke spasticity, where it is the only drug allowed.

  
  
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  Clonazepam has not been supported by any published study (not even observational), but it is found in all spasticity treatment protocols when the clinical features are spasms.

Summary points

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  Spasticity is defined as a disordered sensorimotor control, resulting from an upper motor neuron injury, presenting as intermittent or sustained involuntary activation of muscles. It occurs in 65% of SCI patients.

  
  
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  Spinal cord damage breaks the connection between the brain and the lower areas, so inhibitory signals are not received, and this causes a release and hyperactivity of segmental reflexes.

  
  
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  Spasticity in spinal cord injuries is characterized by being generalized and very intense.

  
  
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  The diagnosis of spasticity is eminently clinical and is made by confirming the clinical symptoms and signs.

  
  
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  The assessment is carried out by means of the measurements of the tone (Modified Ashworth Scale), dynamic phenomena (Spinal Cord Assessment Tool for Spastic reflexes), and of the functional repercussions.

  
  
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  Treatment is required only if the spasticity causes functional disadvantage and the main point is the education of the patient as to the recognition of the factors that can exacerbate the spasticity and the interventions to reduce its intensity.

  
  
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  Baclofen is the first-choice drug for the treatment of spasticity in spinal cord injuries.