CHAPTER 91 Management of Spasticity by Central Nervous System Infusion Techniques
Chronic intrathecal infusion of baclofen has been extremely successful in the treatment of spasticity.1,2 Because baclofen does not cure spasticity, most treated patients need to take baclofen intrathecally for the rest of their lives. This long-term commitment to treatment is similar to maintaining shunt function in hydrocephalics and may be equally rewarding or frustrating. To make proper use of this powerful tool, neurosurgeons need to understand the pharmacology and distribution of intrathecal baclofen and how pumps are used to infuse the drug. Proper selection of patients requires an understanding of the physiology of spasticity and its clinical manifestations. Other neurosurgical methods for reducing spasticity are considered elsewhere; in particular, dorsal rhizotomy for spastic cerebral palsy in children is discussed in Chapter 90.
Definition of Spasticity
Spasticity is a term that refers to a wide variety of motor problems and has numerous associated definitions.3 It has been used to connote difficulty with coordinated movements, spasms, rigidity, abnormal primitive reflexes, and hyperactive reflexes. Researchers studying spasticity tend to stress definitions that emphasize abnormal reflex responses, whereas clinicians tend to stress more global definitions, primarily related to impairment of movement. To further complicate the issue, many clinical syndromes associated with spasticity are caused by injuries at multiple sites in the neuraxis, and the pathologic mechanisms producing motor dysfunction are equally varied.
For the sake of clarity, a narrow physiologic definition is used in this chapter, with note made when more general meanings arise in clinical situations. According to the definition of Lance, spasticity is “a motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes (i.e., muscle tone) with exaggerated tendon jerks, resulting from hyperexcitability of the stretch reflex, as one component of the upper motoneuron syndrome.”4 The important point to stress about this definition is that spasticity is a velocity-dependent phenomenon. This dependence on velocity differentiates spasticity from other, non–velocity-dependent forms of rigidity that can be caused by contractures, dystonias, or Parkinson’s disease. In addition to hyperactive reflexes, spasticity can be associated with various symptoms that can be viewed in terms of positive and negative categories.5 Positive signs are produced by overactivity (i.e., disinhibition) of certain pathways as a result of injury to a specific part of the motor system; negative symptoms are caused by lack of function of the injured area. In spasticity, an increase in deep tendon reflexes and resistance to passive stretch of the limb are positive signs. Negative symptoms are weakness and loss of dexterity. It is the negative symptoms that usually create the clinically significant problems that are disabling for the patient. Occasionally, increased muscle tone, clonus, and hyperactive reflexes can interfere with initiation and smooth completion of a movement.6 Spasms, although often associated with hyperactive reflexes, are not a necessary concomitant of hyperreflexia and should be considered separately.
The relationship between physiologic abnormalities and motor disability is a major area of investigation and of more than academic interest. It is uncertain how or to what extent the velocity-dependent increase in stretch reflex activity interferes with movement.7 Therapies that reduce reflex excitability may not necessarily improve the symptoms of spasticity.3,8,9 To evaluate and treat patients with spasticity, the physician must have a basic understanding of its pathophysiology and knowledge about scales of measurement and different types of treatment.
Physiologic Basis of Spasticity
The final common pathway to the muscle is the alpha motoneuron. Many mechanisms influence the output of the alpha motoneuron and may therefore exaggerate this neuron’s response to stretch. The muscles contain receptors called spindles, which are diagrammed in the center portion of Figure 91-1. A spindle is made up of intrafusal fibers attached to primary sensory endings. The primary sensory endings, which are extensions of the large, myelinated Ia afferents, attach at the noncontractile equatorial region of the intrafusal fibers. The spindle organs are attached at both ends of the muscle mass and consist of extrafusal fibers. Because the spindles are attached in this way, they undergo the same changes in length as the overall muscle and monitor changes in muscle length. The spindles themselves are under control of the fusimotor efferents (i.e., gamma system).
When a muscle is stretched, it contracts in an attempt to regain its original length. This response can be broken down into five events, four of which are diagrammed in Figure 91-1:
Mechanisms Underlying Reflex Function
To understand how changes in these mechanisms lead to spasticity, we must trace the events that occur when a muscle is stretched. In a closed loop system, it is impossible to identify the beginning and end of a sequence of events. For simplicity of presentation, the various mechanisms are discussed in the following order: Ia monosynaptic connection, Ia excitatory polysynaptic pathways, reciprocal Ia inhibition, group II pathways, decreased recurrent inhibition, alpha motoneuron hyperexcitability, gamma motoneuron hyperactivity, and group Ib inhibition. A detailed discussion of these mechanisms has been presented by Pierrot-Deseilligny,11,12 Pierrot-Deseilligny and Mazieres,13 and Sehgal and McGuire.14 Sehgal and McGuire also provided a detailed explanation of the different electrophysiologic testing procedures that are used to deduce which mechanisms are underlying the spasticity.14
Ia Monosynaptic Connection
When a muscle is stretched, the Ia afferent neuron transmits excitatory messages from its receptor, the muscle spindle, to the alpha motoneuron of the same muscle by means of a monosynaptic connection. It has been suggested that Ia discharge is normally reduced by presynaptic inhibition and that reduced levels of presynaptic inhibition could lead to an increased stretch reflex.13 For example, Calancie and colleagues argued that presynaptic inhibition is enhanced in patients in the acute stage of spinal cord injury but is reduced in the chronic stage.15 This reduction in presynaptic inhibition could give rise to an increased reflex response. There is also evidence of a decrease in presynaptic inhibition in paraplegic patients but not in hemiplegic patients.16
Ia Excitatory Polysynaptic Pathways
The alpha motoneuron can also be affected by the Ia excitatory polysynaptic pathway (Fig. 91-2).17 This can be shown by producing vibration-induced activity in group Ia fibers to generate tonic contraction of the vibrated muscle through Ia excitatory polysynaptic pathways, the tonic vibration reflex. This reflex can be increased or decreased, or both, in spastic patients.18 Facilitation of this pathway leads to increased stretch reflexes.
Reciprocal Ia Inhibition
When a muscle is stretched, the reflex evoked in that muscle is normally accompanied by inhibition of the opposing muscle. This finding of reciprocal inhibition has had a pervasive influence on our understanding of movement control.19 It has been assumed that as a movement is made, stretch-related activation in the antagonist muscle is suppressed by reciprocal inhibition. Lack of reciprocal inhibition can lead to unwanted activation of the antagonist muscle and impede movement. The Ia inhibitory interneuron receives excitatory synaptic input from numerous descending pathways, including the corticospinal tract.20 Input from the descending tracts is combined with output from the Ia afferent of the contracting agonist muscle.21 If the Ia interneuron does not receive input from the corticospinal tract, reciprocal inhibition may become ineffective, a phenomenon observed in some spastic patients.22
Decreased Recurrent Inhibition
Motor axons give off recurrent collaterals that activate Renshaw cells, which in turn inhibit alpha motoneurons,11 thereby creating a recurrent inhibitory circuit. Renshaw cells are influenced by supraspinal control, which can facilitate or inhibit them. At rest, a complicated picture emerges with respect to recurrent inhibition.23 In about 40% of spastic patients tested, there is no evidence of abnormal recurrent inhibition at rest. In patients with hemiplegia (most often from stroke) and in patients with spinal cord injury (most often from trauma), recurrent inhibition increases. In contrast, patients with progressive paraparesis caused by hereditary spastic paraparesis or amyotrophic lateral sclerosis exhibit reduced recurrent inhibition.
During active movements in spastic patients, an increased reflex response may be caused by lack of inhibition of Renshaw cells. In healthy subjects, Renshaw cells are inhibited, thereby inhibiting the Ia inhibitory interneuron directed to the antagonist motoneuron. This prevents decreased inhibition of the Ia inhibitory interneuron by Renshaw cells and allows reciprocal inhibition to function to suppress a stretch reflex in the antagonist muscles.24 Lack of descending control of Renshaw cells leads to impaired voluntary movements and prevents modulation of control of the antagonist muscle, as has been shown by Katz and Pierrot-Deseilligny.25
Alpha Motoneuron Hyperexcitability
The alpha motoneuron receives excitatory input from the segmental and descending pathways. Lesions at numerous levels of the central nervous system may upset the delicate balance between excitatory and inhibitory input influencing the alpha motoneuron. There may also be a change in the intrinsic properties of motoneurons in spasticity.12 However, the influence of alpha hyperexcitability is impossible to assess in humans because it requires knowledge of the firing level of motoneurons deprived of any sensory input.11 There is no evidence for or against the involvement of alpha hyperexcitability in spasticity, although Noth has argued that it does play a role.26
Gamma Motoneuron Hyperactivity
The gamma system modulates the length of the intrafusal fibers and is therefore responsible for establishing the firing thresholds for group Ia and group II neurons (Fig. 91-3). Incorrect threshold settings for the afferent neurons could lead to a hyperactive response. Evidence to support gamma hyperactivity is derived from analogy with the decerebrate cat, from selective blockade of the fusimotor system with local anesthetics, from the Jendrassik maneuver, and from comparison of the tendon jerk reflex and the H-reflex. Selective blockade of the fusimotor system has been used clinically in spastic patients. Injection of dilute procaine into the motor points of spastic and rigid muscles decreases muscle tone.27 This effect seems to support the view that spasticity is related to an imbalanced fusimotor system in that stretch reflexes are abolished as a result of block of the gamma system but voluntary muscle power is maintained by the output of unaffected larger alpha motoneurons. However, at a different site, intrathecal and epidural injections of local anesthetic did not show a link between increased fusimotor activity and spasticity.28 The strongest evidence against the gamma hyperactivity hypothesis comes from the finding that the discharge rate of primary spindle endings is the same in spastic and normal individuals.29 Increased gamma activity should lead to increased sensitivity of the discharge rate of primary spindle endings in spastic patients. Although the gamma hyperactivity hypothesis has been influential, the evidence to support it is indirect, inconclusive, and circumstantial.30
FIGURE 91-3 Muscle spindle afferents and fusimotor innervation. Ia pathways are described in Figure 91-2. Two pathways from group II afferents (dotted line) to homonymous motoneurons are represented: synapses are angle signs if excitatory and small filled circles if inhibitory. Interneurons are open circles if excitatory and filled circles if inhibitory. Notice that alpha (α) and gamma (γ) motoneurons are controlled by descending pathways.
(Redrawn from Pierrot-Deseilligny E. Pathophysiology of spasticity. Triangle. 1983;22:165-174.)
Decreased Ib Inhibition
Golgi tendon organs are sensitive to stretch because they lie in series with the muscle. On muscle stretch, impulses from Ib fibers are transmitted to homonymous motoneuron pools and heteronymous pools acting synergistically to inhibit stretch.31 Lack of inhibition can result in an increased response to stretch and thereby contribute to spasticity. This has been demonstrated by Delwaide and Oliver, who showed that Ib inhibition was markedly reduced in spastic patients.32
Summary of Mechanisms
Contributions of the different spinal mechanisms to hyperreflexia are summarized in Table 91-1. The information in this table should be treated with caution because of considerable variability in the tests used and in the types of spasticity in the different studies. Under the column “Mechanism” we have listed the putative mechanism by which hyperreflexia could occur. The evidence is strong that decreased presynaptic inhibition, decreased inhibition from supraspinal centers, and decreased Golgi tendon organ inhibition can each play a role in hyperreflexia. However, the importance of each mechanism may vary in the different types of injuries that cause hyperreflexia. Research conducted over the past 20 years makes it strikingly clear that different causes of spasticity can have opposing effects on the patterns of inhibition and excitation observed in various spinal pathways.
Why Do Spinal Circuits Malfunction?
Abnormal Descending Control
One way to consider the diminished motor control in patients with spasticity is from a developmental perspective.39,40 It is well known that babies demonstrate a mass of uncontrolled reflexes. Before a baby can stand, the flexor reflexes in the lower limbs must be inhibited and the extensor reflexes enhanced to brace the limbs against gravity, a function of the vestibulospinal and facilitatory reticulospinal tracts. After the child has learned how to stand, the next step is walking. For the child to walk, the extensor pattern of reflex standing in the lower limbs must be inhibited, and the flexor synergy of the lower limbs must be integrated into a walking pattern. This requires involvement of the motor cortex to inhibit extensor activity and facilitate flexor activity.
As maturity is reached, the pyramidal tract exerts control over the direct connections to the anterior horn cells, in conjunction with the basal ganglia, cerebellum, and brainstem. If the motor cortex or its projections are damaged, the brainstem exerts primary control. If the brainstem assumes complete control, a decorticate posture consisting of flexion of the upper limbs and extension of the lower limbs develops. In cerebral spasticity, there is enhancement of the stretch reflexes in the upper limb flexors and lower limb extensors. If the spinal cord is damaged, even brainstem control is disrupted such that flexor reflexes and stretch reflexes are released. This can lead to any or all of the following physical signs40:
Transection of the spinal cord results acutely in spinal shock, abolition of reflexes, and muscle flaccidity.41 Slowly, over a period of weeks, muscle tone and reflex activity reappear and then become excessive. These increases may be caused by loss of descending control, but this loss cannot explain the reflex exaggeration as time proceeds. This is best explained by reorganization of the spinal cord circuitry and alterations in levels of presynaptic inhibition.15 A detailed review of the neurophysiology of spinal spasticity has been provided by Ashby and McCrea.42
Local Changes at the Spinal Level
Most evidence for plastic changes at the spinal level is based on experience with spinal cord hemisection.43,44 Changes in the spinal cord may be structural or functional, or both. Collateral sprouting of peripheral afferents has been shown to occur. In a hemisected spinal cord, a greater number of dorsal root fibers are eventually found on the hemisected side than on the intact side. Ia fibers may eventually constitute 10% of the synapses on motoneurons instead of the normal 1%, which may account for exaggerated tendon reflexes.41
There is evidence that changes can occur in the spinal circuitry of humans who have suffered perinatal injuries to the immature nervous system.45–47 In adults who suffered birth-onset injuries, rapid stretch of the soleus muscle elicits a reflex in the soleus and tibialis anterior muscles. This phenomenon of reciprocal excitation is in marked contrast to the normal occurrence of reciprocal inhibition in the nonstretched muscle, thus suggesting that some disorders (e.g., cerebral palsy) may be characterized by abnormal spinal cord circuitry and brain damage.
Changes in Muscle Fiber and Connective Tissue
Neural mechanisms initiate spasticity. However, these altered neural mechanisms lead to numerous secondary changes in muscle that may be partially responsible for the symptoms of spasticity. The mechanical properties of muscles and joints in spastic limbs can change in several ways.48 The degree of abnormality of the muscles of children with cerebral palsy depends on which muscle groups are involved.49 Examples have been found of atrophy, hypertrophy, and myopathy. During long-term spastic hemiplegia in human patients, some motor units develop increased fatigability and prolonged twitch-contraction times, which causes changes in the dynamic properties of muscle.50 Several studies on locomotion and interlimb coordination have suggested that when hypertonia is present without concomitant changes on electromyography, the hypertonia must be caused by altered muscle properties.51–57 For example, histochemistry and morphometry of the spastic muscle of four individuals revealed increased atrophy of muscle fibers (especially type II) and a predominance of type I fibers.58
In some patients, another likely explanation for spastic hypertonia is that some muscle fibers are replaced by connective tissue. In the more severely atrophic muscles, an increase in the amount of perimysial-endomysial connective and interstitial tissue and an increase in the number of internal nuclei have been found.49 Summarizing many studies, Dietz and Sinkjaer have recently argued that the degree of hyperreflexia found in patients does not correlate with functional loss and that treatment of spasticity should be directed at improving movement and not simply decreasing overactive reflexes.9 They also point out that changes in muscles are important in producing rigidity and that abnormal spinal circuits interfere with voluntary movements and are a major cause of disability in spastic patients.
Measurement of Spasticity
Clinical Evaluation
Clinically, spasticity is graded qualitatively. Muscle response to stretch is judged by the deep tendon reflexes elicited by a reflex hammer and by the spread of the response to other muscle groups. Symmetry of response is more important than the strength of the response, and even a few beats of clonus in both ankles may be normal. Resistance to passive stretch can be a gauge of spasticity but often reflects other problems, such as contractures or ankylosis of the joint being tested. Spasticity may vary because of factors such as fatigue and emotional stress. Normal individuals may even experience sustained clonus under these conditions.59 Position (i.e., vestibular input) dramatically changes spasticity. For example, patients with partial cord injuries, when tested in the upright position or in a wheelchair, may demonstrate much less resistance than when supine. Voluntary movement is assessed by analysis of gait and the ability to generate rapid successive movements.
To provide a simple grading system that would be useful for repeated clinical examinations, Ashworth devised the scale shown in Table 91-2.60 A graded scale is appropriate because the response of a muscle to stretch can vary considerably in a normal individual, and a spastic patient’s increased response represents the higher end of a continuum. In general, the categories are distinct enough that changes in spasticity can be judged accurately during repeated examinations. However, one problem with the scale is that the scores of many patients cluster in the middle. Thus, it is worth considering the modified Ashworth scale, which tries to account for this problem by adding an extra scoring category.61 Another problem with the scale is that factors that affect the response of a muscle to stretch are not differentiated (i.e., reflex abnormalities versus contractures). Numerous other outcome measures can be used to facilitate effective management of spasticity and are summarized by Pierson.62 Objective tests should be used whenever possible because placebo effects have been noted in up to 50% of patients.63
| SCORE* | CHARACTERISTIC |
|---|---|
| 1 | No increase in tone |
