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.

FIGURE 91-2 In addition to monosynaptic Ia excitatory pathways, polysynaptic pathways also converge on the alpha motoneuron. Interneurons interposed in these pathways (shaded circles) are controlled by descending pathways. Excitatory synapses are represented as angle signs and inhibitory synapses as dots.

(Redrawn from Pierrot-Deseilligny E. Pathophysiology of spasticity. Triangle. 1983;22:165-174.)

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

Group II Pathways

Group II endings (i.e., secondary endings), like Ia endings, are located on intrafusal muscle fibers and are most sensitive to dynamic stretch. Their role in spasticity is not well understood.

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.

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:

Lack of descending control is the initial cause of the hyperexcitability of the stretch reflex, which is the cardinal sign of spasticity. Any lesion that affects upper motoneurons can cause spasticity. However, there are numerous factors to consider in trying to establish the effect of such a lesion (e.g., age, precise location of the lesion, time since the lesion, cause of the lesion). These lesions upset the delicate balance between excitation and inhibition in the spinal cord.

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.

Direct Interference in Movement Capability

Deficits in the ability to generate movements can be tested and analyzed in numerous ways. The most common methods have been studies of unidirectional or reciprocal movements, use of ergometers, and evaluation of gait.^53,71–73 The definition of spasticity presented at the beginning of this chapter suggests that a reflex can be elicited in the muscle antagonistic to a movement. The evidence for this assertion, however, is contradictory. It has been suggested that there is no relationship between hyperactive reflexes and movement deficits,^9,73 but it has also been shown that reflexes in patients with mild spasticity are suppressed during voluntary movement.⁷⁴ It has been suggested that abolition of hyperactive stretch reflexes does not necessarily improve motor performance.^3,8,28 However, direct evidence showing the effect of reflex involvement in movement impairment has also been observed.^5,72,75,76 Boorman and colleagues found loss of supraspinal control over spinal inhibitory mechanisms during cycling movements in patients with spinal cord injury.⁷⁷

Studies of gait in spastic patients have described abnormal features of locomotion with the use of force plate recordings, accelerometry, and photography, alone or in conjunction with electromyography. The findings emphasize large interindividual variations in the underlying mechanisms. For instance, a specific clinical entity (e.g., footdrop) can be caused by diverse mechanisms.⁷⁸ Frequently, the observed paralysis of the foot is caused by pull of the hypertonic triceps surae muscle.

Indirect Interference in Movement Capability

For patients with spasticity associated with paraplegia, even though the full range of movement is available in the upper limbs, spasms and contractures in the lower limbs can make such movements very unpleasant or impossible. The spasms and contractures can also severely limit the ability of these individuals to bend or stretch during everyday reaching movements, such as when tying shoelaces. Movements of the upper limbs indirectly stretch the muscles of the lower limbs and trigger the spasms or contractures. Any treatment that can effectively reduce the frequency or severity of these events indirectly influences the individual’s ability to move.

Physiologic Effects of Baclofen

Baclofen was designed to be a lipophilic γ-aminobutyric acid (GABA) agonist that could pass through the blood-brain barrier.⁸⁰ However, baclofen only partially permeates from blood to brain and does not fully resemble GABA in its physiologic actions.⁸¹ Several types of receptors for GABA are found in the brain and spinal cord, and baclofen affects only the B type. This receptor has been identified and sequenced.⁸² It is a transmembrane protein that affects calcium and potassium channels. Immunohistologic staining of the spinal cord has shown a high concentration of GABA_B receptors in layer II of the dorsal gray matter.⁸³ Physiologic experiments on isolated perfused spinal cords have demonstrated that baclofen produces a profound reduction in monosynaptic and polysynaptic spinal reflexes.⁸⁴ This effect is caused by activation of the GABA_B receptors, which reduces the influx of calcium into the presynaptic terminals of afferent fibers, the result being a reduction in the release of excitatory transmitters. Baclofen can also affect the postsynaptic membrane by increasing potassium influx, thereby stabilizing or increasing the membrane potential and inhibiting neuronal firing.^85,86

The sum of these presynaptic and postsynaptic effects is to decrease drive on the motoneurons. Diazepam, the other centrally active antispastic medication, works differently. It binds to the presynaptic membrane and facilitates GABA-mediated presynaptic inhibition. Unlike baclofen, which directly activates the receptor, diazepam works only when GABA is released, and it enhances response to the transmitter (Fig. 91-5).⁸⁷

FIGURE 91-5 Enlargement of the left half of Figure 91-1. Synaptic mechanisms at the spinal level are responsible for excitatory postsynaptic potential (EPSP) and two types of inhibition: inhibitory postsynaptic potential (IPSP), and presynaptic inhibition. The sites of action of γ-aminobutyric acid (GABA), baclofen, and diazepam at the spinal level are schematically illustrated.

(Redrawn from Young RR, Delwaide PJ. Drug therapy: spasticity. Part 2. N Engl J Med. 1981;304:96-99.)

The physiologic effects of baclofen have been studied most frequently in the normal spinal cord. After spinal cord injury, spasticity develops slowly and is related to plastic changes in the spinal cord circuitry. The physiology of the damaged spinal cord is significantly changed, and so is its response to medications. Tests have shown that after a cervical injury the rat lumbar cord increases the number of its GABA_B receptors by 30%.⁸⁸ Other experiments in rats and cats have demonstrated that bladder reflexes change after cord injury and that the modified reflexes are inhibited by morphine and baclofen.⁸⁹ These animal findings are supported by clinical observations. Intrathecal baclofen given to normal patients does not interfere with movement or decrease strength, but the same dose given to a spastic patient markedly decreases spasticity and muscle tone. Ninety-six percent or more of patients with spasticity from multiple sclerosis or spinal cord injury have responded to intrathecal baclofen in double-blind studies.⁹⁰ The reason that baclofen is so effective in reducing spasticity is that the same changes in the spinal cord that produce spasticity increase sensitivity to baclofen.

Kinetics and Distribution of Intrathecal Baclofen

Baclofen, like morphine, is primarily water soluble, which means that only a small amount crosses the blood-brain barrier.⁸¹ Similarly, little of the drug that is introduced into cerebrospinal fluid is lost by movement across membranes into the systemic circulation. Therefore, cerebrospinal fluid flow is the only distribution source of intrathecal baclofen to the spinal cord. When a bolus of baclofen is delivered via lumbar puncture, it mixes rapidly in the lumbar subarachnoid space and is gradually carried upward along the spinal cord.⁹¹ In 3 to 6 hours it reaches the brainstem and then travels over the convexities, where it is eliminated into the systemic circulation at the arachnoid granulations. Bolus administration leads to transient but very high drug levels at the spinal cord and, later, at the brainstem. The half-life of a bolus of baclofen in cerebrospinal fluid is about 90 minutes.⁹² It is stable in cerebrospinal fluid and does not become metabolized by tissue.

If baclofen is given by slow infusion, a different distribution is achieved. The concentration gradually reaches a steady state in which the same amount of baclofen is being removed from cerebrospinal fluid as is being infused; this occurs at about 12 to 18 hours (i.e., seven times the half-life). As has been measured in patients, the final steady-state concentration is directly proportional to the drug infusion rate.⁹³ Other measurements in patients have demonstrated that in the steady state, the concentration of baclofen is decreased to one quarter from the lumbar cistern to the high cervical region. The manner in which the concentration varies along the spinal cord is indicated by indium 111 flow studies of cerebrospinal dynamics in patients with implanted pumps.⁹¹ These tests indicate that the decrease in concentration is gradual and almost linear along the cord (Fig. 91-6).

FIGURE 91-6 Decline in ¹¹¹In-diethylenetriamine pentaacetic acid concentration as the compound ascends the thoracic spinal column after slow intrathecal infusion. The 0-cm point is at the T12 vertebra, and the 20-cm point is at the T2 vertebra. The percentage of maximal concentration is the ratio of counts at points along the spinal canal to the level measured at T12. Data are presented as means ± standard deviation for four patients.

(Adapted from Kroin J, Ali A, York M, et al. The distribution of medication along the spinal canal after chronic intrathecal administration. Neurosurgery. 1993;33:226-230.)

The results of these kinetic and distribution studies have practical consequences:

Another point of considerable clinical significance is that to have its physiologic effect, baclofen must travel from cerebrospinal fluid to the spinal cord receptors, a distance of 2 to 5 mm through cord tissue. Diffusion is a very slow process. This accounts for the 45- to 60-minute delay from the time that a bolus dose is injected until spasticity is reduced. After the receptors have been reached, diffusion back to cerebrospinal fluid is equally slow. A single bolus dose may reduce spasticity for 4 to 12 hours; its maximal effect occurs when the level in cerebrospinal fluid has decreased to almost zero.⁹⁴ This slow diffusion from tissue also means that a large, single overdose causes long-lasting respiratory depression and coma, even after cerebrospinal fluid levels have been reduced. When giving medication intrathecally, the physician must always be aware that the clinical effects are slow to appear and equally slow to clear because the drug requires time for diffusion into the spinal cord, and the cord tissue acts as a reservoir after it is loaded.

Efficacy of Intrathecal Baclofen for Spinal Spasticity

The most effective use of oral baclofen has been for the treatment of spasticity caused by spinal cord injury or multiple sclerosis. The initial studies of intrathecal delivery were conducted in these patient groups after oral medications showed limited success or had unacceptable side effects such as drowsiness. In this well-defined patient population, a bolus of 50 to 100 µg of intrathecal baclofen reduced abnormal muscle tone 2 or more points on the Ashworth scale for almost all patients. If patients had spasms, they were also significantly reduced. The short-term effect could be maintained with constant delivery. Individual and multicenter studies in the United States and Europe have demonstrated that control of spasticity and spasms can be achieved over a period of years by using implanted drug pumps to deliver baclofen (Table 91-3 and Fig. 91-7).

FIGURE 91-7 Effects of chronic intrathecal baclofen administration in 47 patients with spinal cord injury (SCI) and in 27 patients with multiple sclerosis (MS). Values are expressed as means ± standard deviation. A, Ashworth scale scores over time after pump implantation. B, Spasm frequency scores over time after pump implantation.

(Adapted from Coffey JR, Cahill D, Steers W, et al. Intrathecal baclofen for intractable spasticity of spinal origin: results of a long-term multicenter study. J Neurosurg. 1993;78:226-232.)

The efficacy of chronic intrathecal administration of baclofen is clear and unequivocal, but several questions need to be answered. What are the drug’s side effects? How difficult is it to maintain long-term baclofen treatment? What other patient groups can benefit from this treatment?

Drug Side Effects

The side effects of intrathecal baclofen are similar to those of oral baclofen and are dose related. Although some protection from central side effects is afforded by the fact that the baclofen concentration is higher in the lumbar region than at the brainstem, increasing dosage can lead to adverse effects. Common problems from high dosage include drowsiness, mental confusion, lightheadedness, and ataxia. Weakness can be induced in some patients, as can loss of function because of reduced muscle tone. A 10% to 20% reduction in dosage usually eliminates these symptoms. Bolus administration, used for testing before implantation of a pump, is more frequently associated with these side effects and occasionally produces hypotension, nausea, and respiratory depression. A large overdose, in the range of 1 to 20 mg, results in coma, flaccidity, hypotension, and respiratory depression.⁹⁹ If an overdose occurs, the patient must be kept under surveillance with apnea monitoring and, if necessary, be provided with ventilatory support. No deaths from overdose have been reported, but the intrathecal route of drug administration can result in potent and serious side effects. Treatment of a moderate overdose with physostigmine (0.5 to 2 mg) often reverses the somnolence and respiratory effects.¹⁰⁰ This treatment does not work for large overdoses and should not be given to patients with heart conduction defects. The central effects of an overdose should clear in 24 to 48 hours.

Tolerance to baclofen develops in most patients. Over the first 6 to 12 months, the dose of baclofen required to achieve a given clinical effect usually doubles and then eventually stabilizes.⁹⁰ In a few patients, tolerance may be a significant problem that necessitates “drug holidays” for several weeks or a switch to intrathecal morphine, which shares some of the antispastic effects of baclofen. Most often, the need for increasing dosage after the first year is related to a problem with drug delivery through the catheter rather than true tolerance.

Seizures and hallucinations can occur if baclofen is withdrawn suddenly. After intrathecal treatment has been initiated, oral baclofen should be withdrawn gradually over a period of several weeks. Baclofen may change the seizure threshold in some patients and has been associated with the onset of seizures in a few patients. It may make established seizure conditions more difficult to control. Sudden withdrawal of intrathecal baclofen produces a rebound phenomenon consisting of spasticity and spasms that may be worse than those that occurred before baclofen therapy was initiated. This increased spasticity gradually dissipates over several days. It also frequently causes a tickling and dysesthetic sensation.

A rare life-threatening baclofen withdrawal syndrome of high fever, altered mental state, and profound muscular rigidity that can lead to fatal rhabdomyolysis has been described. The most effective treatment is rapid reinstatement of intrathecal baclofen. Oral and intravenous medications, including high-dose benzodiazepines, and supportive care can help,¹⁰¹ but in severe cases intrathecal baclofen should be given by lumbar puncture or external catheter. Patients with preexisting autonomic dysreflexia are particularly at risk for this withdrawal syndrome.¹⁰¹

Delivery Systems

Intrathecal baclofen therapy depends completely on proper function of the pump and catheter system used to deliver the drug. Pump designs, catheter systems, and implantation procedures have been discussed for delivery of morphine and are the same as for baclofen. The incidence of pump failure is low, approximately 0.5% to 1% per year, and the only common failures are stalling or stopping. Overdosing is rare, except for iatrogenic causes such as misprogramming.

The major cause of disruption of drug delivery is catheter malfunction. The implanted catheters are thin walled and small caliber so that they can be passed easily into the subarachnoid space without causing injury to the nerve roots.⁹⁰ Despite anchoring devices, the flimsy catheters can pull out of position because of movement. The catheters can also tear, disconnect, or occlude. Frequently, the problem can be diagnosed by plain radiography. If the cause is not obvious, indium 111 can be placed in the pump and the patient scanned at 24 and 48 hours to check catheter patency.¹⁰² The indium 111 study has the advantage of showing the flow of cerebrospinal fluid, and it can demonstrate a subarachnoid block caused by arachnoiditis or fibrosis around the catheter tip. Sometimes, a pinhole leak in a catheter cannot be seen on any study and the cause is found only when the catheter is replaced. An alternative is to inject a radiopaque dye under fluoroscopic guidance into the pump’s side port and look for blockage or a leak outside the subarachnoid space.

As with any implanted device, infection is a potential problem. The bacteriostatic filter within the pump blocks any contamination in the pump reservoir from reaching the cerebrospinal fluid. However, localized infection in the pump pocket or meningitis from the catheter in cerebrospinal fluid has occurred in a few patients (<3%). Infection usually requires removal of the hardware, although intrathecal antibiotics delivered by pump can sometimes successfully treat an infection of cerebrospinal fluid.

Long-term management of patients requires regular pump refills, dose adjustments, and diagnosis and treatment of complications.¹⁰³ Despite these requirements, the dropout rate of implanted patients is quite low. In a 7-year study, no patients were lost because of medication side effects, and although more than 30% had pump or catheter problems requiring operative repair, only 10% decided to not continue long-term treatment.⁹⁰ The key to management is a well-trained nurse practitioner who can help with patient education, pump refills, and dose adjustments.

Patient Selection

The U.S. Food and Drug Administration first approved pump implantation and intrathecal baclofen treatment of spasticity caused by multiple sclerosis or spinal cord injury on the basis of several double-blind, multicenter studies. Approval was then extended to patients with spasticity of cerebral origin, including those with cerebral palsy. These and other conditions in which spasticity may be reduced with baclofen are listed in Table 91-4. In general, if a patient has the classic signs of spasticity, baclofen can decrease them. Athetosis and generalized dystonia do not usually improve, although exceptions are found.^103,111 Focal, painful lower limb dystonias may be helped considerably.¹¹⁴ Stiff man syndrome, in which spinal GABA-producing neurons are thought to be lost and the patient suffers from episodes of severe axial and limb spasms and rigidity, is markedly improved.¹¹³

TABLE 91-4 Conditions Responding to Intrathecal Baclofen

In patients with clinically typical spasticity, intrathecal baclofen will almost always be effective. However, if the patient wants to know what the effect will be like or if the physician has any question about the diagnosis or the contribution of spasticity to the patient’s clinical problems, a test of intrathecal baclofen should be performed. A single trial dose of 50 to 100 µg given by lumbar puncture is usually adequate. This easy test, done under observation in the hospital, has few side effects and provides the physician and the patient a good chance to understand what baclofen can accomplish in this particular situation. The only caveat is that a bolus frequently reduces spasticity so much that motor function may be lost transiently if some rigidity is required. Patients must be warned about this possibility. For most patients, careful dosage adjustment after implantation allows titration to a level that improves spasticity without significantly interfering with motor function.

The indications for intrathecal treatment of spasticity are straightforward for most patients: spasticity that has not responded to oral antispastic medications and a successful trial of intrathecal baclofen (50 to 100 µg). The drug should be used in patients whose spasticity is severe enough to cause significant disability, difficulty in self-care, or pain from spasms. The use of destructive neurolytic or neurosurgical procedures should be limited to the few patients who cannot be maintained on intrathecal baclofen or who have no useful motor function. The most difficult decisions involve patients for whom it is unclear whether a reduction in spasticity will improve motor function and for those in whom baclofen treatment decreases functionally useful rigidity. This group includes many patients with spastic cerebral palsy. The results of dorsal rhizotomy are difficult to compare with intrathecal baclofen because rhizotomy is generally performed on young children and pumps are implanted in older children who weigh more than 50 pounds. Both procedures reduce spasticity. A pump requires continuous treatment and many dose adjustments; however, it is reversible, and the degree of reduction in spasticity can be titrated to meet the patient’s needs, whereas rhizotomy is irreversible and requires a long recovery period. In many cerebral palsy patients, regardless of the method used to reduce spasticity, motor function improves only slightly because of widespread damage to the nervous system, but care may become much easier.