Pathogenesis of Spastic Cerebral Palsy

Spastic CP is the most common subtype of cerebral palsy. Spastic diplegia and spastic quadriplegia affect approximately 60% of patients, but spasticity may also occur with dyskinesia or ataxia, or both, in mixed subtypes of CP. Thus, in total, spasticity afflicts 80% to 90% of all patients with CP.^3,4 A distinctive epidemiologic feature of spastic CP—and spastic diplegia in particular—is its correlation with premature birth and low birth weight.^5–7 This relationship does not exist with other subtypes of the disease, such as athetoid or dyskinetic CP.

Periventricular leukomalacia (PVL) is the most common finding on brain magnetic resonance imaging (MRI) in children with spastic CP.^8,9 Histologically, PVL is characterized by ischemic necrosis of the periventricular and subcortical white matter (Fig. 227-1), areas that are predisposed to hypoperfusion during hypotension.¹⁰ Reperfusion injury resulting from oxygen free radicals, cytokines, and excitatory amino acids such as glutamate probably mediate PVL.¹⁰ The high incidence of spastic diplegia in infants with PVL has led many to speculate that PVL is the neuropathologic basis for spastic CP.¹¹ The neurological deficits in spastic CP may be explained in part by the topographic arrangements of projection fibers descending from the motor homunculus in the white matter. As seen in Figure 227-2, the leg fibers traverse the white matter closer to the ventricle than the arm fibers do. Thus, PVL is more likely to injure the leg fibers and spare the arm fibers. However, extensive leukomalacia will also injure other projection fibers and result in spastic quadriplegic CP.

FIGURE 227-1 Coronal section of the brain showing periventricular leukomalacia with markedly reduced white matter adjacent to the posterior lateral ventricle. A subcortical infarct is also seen.

FIGURE 227-2 Schematic drawing of projection fibers from the motor cortex in relation to the lateral ventricle. The topographic arrangement of the descending motor tracts, with the leg fibers located medially, explains the high incidence of spastic diplegia in the setting of periventricular leukomalacia.

Spinal cord ventral horn alpha motor neuron output is a primary determinant of muscle tone. The activity of alpha motor neurons is modulated by excitatory influences (e.g., Ia fibers from muscle spindles, descending input from the corticospinal and reticulospinal pathways) and inhibitory influences (e.g., descending GABAergic [γ-aminobutyric acid] pathways from the cerebellum and basal ganglia). Although the neural pathways involved in CP spasticity remain speculative, it is believed that spasticity results from an imbalance in these excitatory and inhibitory influences that creates hyperactive alpha and gamma neurons with exaggerated stretch reflex activity compounded by loss of inhibitory control (reviewed by Koman and colleagues¹²). Thus, excessive alpha motor neuron activity of the target muscles, coupled with decreased inhibition of antagonistic muscles, results in the co-contraction of agonist and antagonist muscle groups.¹³ Clinically, this results in a velocity-dependent, increased resistance to passive stretch.¹²

Deleterious Effects of Cerebral Palsy Spasticity

CP spasticity has harmful, long-term effects on growing children and thus requires optimal treatment at an early age. When untreated, inhibition of motor activity and limitation of voluntary movement result in decreased muscle and bone development, which ultimately causes deformities of the affected extremities.¹⁴ Long-lasting improvements in motor function are observed after SDR, thus supporting the argument for early intervention in the disease.¹⁵ Indeed, the spasticity-induced inhibition of motor activities does not abate if the spasticity is left untreated. Normally, longitudinal muscle growth proceeds as new myofilaments and sarcomeres are added to the ends of the muscle fibers.¹⁶ The greatest increase in sarcomere numbers occurs at an early age, with the increase taking place much more actively during development than after maturation. In parallel with the addition of sarcomeres, longitudinal muscle growth occurs rapidly during development. The increase in sarcomere number is not under neural control but is induced mainly by the amount of tension that the muscle is subjected to (i.e., repeated muscle stretch).^17,18 Thus, when muscles are immobilized, there is a rapid decrease in the number of already existing sarcomeres, as well as a decrease in the number of new sarcomeres that should increase with normal development.¹⁹ Because CP spasticity in developing children limits muscle stretch in daily activities, it could cause loss of sarcomeres and inhibition of longitudinal muscle growth. In fact, the effect of spasticity on muscle growth was clearly shown in an experimental study in which longitudinal muscle growth was reduced by 45% in spastic mice as compared with control animals.²⁰ The loss of sarcomeres accompanies a significant decrease in elasticity in the muscles²¹ and makes them resistant to passive stretch.²² Additionally, atrophy of type I and II muscle fibers compounds the slowed muscle growth.²³ Recent work has implicated both shorter muscle (decreased sarcomere length, myocyte length, and fascicle length)²⁴ and an increased extracellular elastic modulus²⁵ in the clinical finding of stiffness. These pathologic events in the muscle cells cause abnormally shortened muscles, long tendons, and muscle contracture (i.e., increased resistance of the muscle to passive stretch in the absence of muscle contraction).^22,26,27 The muscle contractures typically worsen as a child grows²⁶ and produce various bone and joint deformities in the extremities.¹⁴

Treatment of Spastic Cerebral Palsy

Spasticity is commonly treated with oral medications, including the GABA_B receptor agonist baclofen (Lioresal), benzodiazepines such as diazepam (Valium), the anticholinergic trihexyphenidyl, dantrolene, and tizanidine (Zanaflex).^28,29 In general, oral medications are moderately effective in treating spasticity but frequently have significant adverse effects (sedation, confusion, dependence).

Intramuscular injections of alcohol and phenol for chemodenervation have been performed for many years. The introduction of intramuscular injection of Botox was a major advance in the treatment of CP spasticity, with predictable benefits and fewer adverse effects.²⁹ Botox is injected directly into the affected muscle, and relaxation is generally seen within several days. Maximal benefit occurs approximately 4 weeks following injection, after which the effect declines and repeated injection is required in approximately 3 to 4 months.

Selective Dorsal Rhizotomy

SDR has been shown in several controlled trials to reduce spasticity and increase range of motion.^15,38–41 In conjunction with physical therapy, SDR produces significant improvements in gross motor function and gait.^15,41 SDR also decreases the rate of subsequent orthopedic surgeries.⁴²

Indications

Indications for SDR vary among medical centers. Our current indications for SDR are summarized in Table 227-1. Primary beneficiaries of SDR are children with spastic diplegia secondary to premature birth; however, children with spastic quadriplegic CP can also benefit from SDR. In spastic hemiplegic CP, spasticity is not a predominant cause of the motor impairment, and reduction of spasticity may not greatly improve motor function (see also Table 227-2). The optimal age for children to undergo SDR is 2 to 6 years. Because of the significant deleterious effects of spasticity outlined earlier, early treatment is recommended to reduce the chance of severe orthopedic deformities of the lower extremities. SDR is not considered for children younger than 2 years because approximately 30% of children in whom CP is diagnosed at the age of 1 year later become free of symptoms.⁴³ Adolescents and adults younger than 40 years can also enjoy good functional gains with SDR.⁴⁵ The risk associated with dorsal rhizotomy in adolescents and adults is no greater than that in young children when performed through a single-level laminectomy. It is possible that reduction of spasticity will lessen the impact of aging on the physical stress caused by CP, such as abnormal stress on bones and muscles, wear and tear on joints, and increasing joint and muscle pain.

TABLE 227-1 Indications for Selective Dorsal Rhizotomy for Spastic Cerebral Palsy

Diagnosis—spastic diplegia or quadriplegia Age—2 to 40 years History of premature birth or neonatal asphyxia Emerging locomotive functions Potential for significant postoperative functional gain

TABLE 227-2 Contraindications to Selective Dorsal Rhizotomy for Spastic Cerebral Palsy

CP associated with intrauterine encephalitis Mixed CP with predominant dystonia or ataxia CP caused by a widespread neuronal migration disorder Severe head injury and hypoxic encephalopathy, such as after drowning Familial spastic paraplegia and other progressive neurological disorders Severe basal ganglia damage in children younger than 5 years Severe thoracolumbar scoliosis Severe lumbar lordosis Multiple previous muscle and tendon releases Profound motor impairment with no head control Psychiatric disorders in adults Lack of commitment to carry out postoperative therapy

Patients should have sufficient motor function underlying the spasticity to potentially become assisted or independent ambulators. In some patients with spastic quadriplegia, SDR is recommended to improve sitting posture and upper extremity movement. Patients are not candidates when their motor impairment is severe enough to require support for sitting. In such patients, SDR often fails to reduce muscle tone because of concurrent rigidity and dystonia, and its long-term benefits are generally negligible.

When selecting patients older than 18 years for SDR, we take several additional factors into consideration: (1) independent ambulation, (2) fixed orthopedic deformities, (3) back pain, (4) level of motivation, and (5) medical comorbid conditions. Because the main goal of SDR is to improve function and quality of life, we have limited SDR to those who can walk independently or with a cane. At present, it is unclear whether SDR will benefit adults who walk with walkers or those who are unable to walk with any assistive device. Severe orthopedic deformities render functional gains unlikely, and hence they are contraindications to SDR.

Spinal deformities in independently walking adults with CP include lumbar hyperlordosis, spondylolysis, spondylolisthesis, and scoliosis. These deformities do not preclude SDR performed through a single-level lumbar laminectomy. Back pain in older adult patients may be due to degenerative diseases of the spine. Spinal abnormalities and the severity of the back pain should be taken into consideration. In patients older than 10 years, the level of motivation and desire to improve quality of life are important for postoperative rehabilitation and maximal functional benefit from SDR. With regard to medical problems, one should be alert to the possibility of depression, a common condition in disabled adults; depression may have an impact on the level of motivation for postoperative physical therapy.

Contraindications

Table 227-2 provides a partial list of contraindications to SDR. Such contraindications include a history of severe congenital hydrocephalus or severe neonatal CNS infection such as intrauterine encephalitis (e.g., toxoplasmosis or cytomegalovirus infection) or bacterial meningitis. Likewise, patients with severe head trauma or hypoxic encephalopathy may not be suitable candidates for SDR. Although SDR is contraindicated in patients with extensive neuronal migration disorders, those with limited schizencephaly involving the sensory motor area, a rare cause of spastic diplegia, may achieve a reduction in spasticity and functional improvements after SDR.

Patients with damage to the basal ganglia deserve special consideration because rigidity and dystonia may coexist with spasticity in this setting. Of particular concern is severe basal ganglia damage in children younger than 5 years. Dystonia may develop anytime in the first 5 years of life.⁴⁶ As noted earlier, patients with mixed types of CP spasticity (i.e., those with components of dystonia or athetosis) do not enjoy the same degree of functional improvement after SDR. Thus, in the setting of basal ganglia damage it is best to wait until the age of 5, when the predominance of dystonia can more reliably be ascertained. After the age of 5, however, SDR may be considered even in the presence of demonstrable basal ganglia damage if spasticity is the primary clinical symptom. Likewise, athetosis and ataxia are also relative contraindications. Similar to dystonia, if spasticity is the predominant feature in patients with concomitant athetosis, SDR may be of benefit. In these cases, SDR reduces spasticity postoperatively, but the athetosis and dystonia remain unchanged.

Severe scoliosis is a contraindication to rhizotomy when a multilevel lumbosacral laminectomy approach is used. However, patients with mild or early-stage scoliosis can undergo SDR safely if it is performed via a single-level laminectomy. When no functional gain is anticipated in a child, parents should be dissuaded from SDR. In adults, the presence of severe depression or other psychiatric disorders is considered a contraindication if they will limit motivation or participation in aggressive postoperative physical therapy.

Preoperative Evaluation

Evaluation of patients for SDR starts with a careful review of the perinatal history, including gestational age, birth weight, twin birth, hypoxic/ischemic events, intraventricular hemorrhage, neonatal infection, and seizures. A history of premature birth is among the most important factors in evaluating patients for SDR. Next, one should be certain that the patient’s motor impairment dates back to infancy and has taken a course of steady improvement rather than progressive deterioration during the preschool years. If a child had a period of normal motor development and subsequently showed signs of motor impairment, one should consider a neoplasm or neurological disorder rather than CP. One of us (T.S.P.) has seen children in whom CP was diagnosed erroneously and who were later found to have a spinal cord tumor or craniovertebral junction anomaly.

Previous treatments of spasticity and orthopedic surgeries should also be reviewed. If a child received intramuscular injection of Botox or intrathecal baclofen infusion, or both, the extent of improvements after the treatments can help assess the effect of spasticity on the child’s motor function and thus aid in predicting functional improvements after SDR. A history of orthopedic surgery should be reviewed in detail and taken into account in the physical examination.

Next, a neurologic examination is performed to evaluate the patient for signs of spasticity, such as increased muscle tone, hyperactive deep tendon reflexes, and ankle clonus. Ankle clonus is an unequivocal sign of spasticity. Spasticity increases as the child repeats movements rapidly. An effective way to elicit spasticity in a young child is to instruct the child to walk, stand, crawl, and sit. The attempted movements increase not only muscle tone but also abnormal postures. For example, equinus postures of the ankles, tiptoe walking, and scissoring of the lower extremities become prominent during the attempted movements. This will also help determine whether the spasticity is significantly inhibiting motor activities. The presence of concomitant ataxia, athetosis, and dystonia is also ascertained. Unlike athetosis and dystonia, it can be difficult to detect ataxia in a child with CP spasticity.

Motor strength can be determined by testing individual muscles. In young children, past motor milestones, speed of movement, and the ability to isolate joint movements are reliable indices of motor strength. If the motor milestone is close to normal and, for instance, the child can sit alone by the age of 2 years, the child most likely has adequate motor strength and will walk in the future. Crawling or walking in a walker and making rapid transitions between positions are also signs of relatively good motor function. As a rule, the greater the motor impairment, the slower the movement. In our experience, a neurological sign that can be an excellent predictor of gait outcome in children younger than 3 to 4 years is isolated joint movements in the lower extremities (see “Gait” in the section “Outcome”).⁴⁷

In addition, the severity of orthopedic deformities and their effect on a patient’s motor performance are assessed in detail. Neurosurgeons performing SDR should be knowledgeable about the ramifications of orthopedic deformities and standard orthopedic management for the deformities. In addition, it is particularly important to determine muscle weakness caused by previous muscle releases and the effects on walking and posture. Common problems include excessive foot dorsiflexion and consequent crouch gait after heel cord release, genu recurvatum after hamstring release, and excessive hip abduction and valgus deformities of the foot after adductor release. These problems are in general refractory to treatment.

Thorough evaluation by a physical therapist is essential and includes gross motor function measurements, determination of orthopedic deformities, assessment of braces, and a review of previous physical therapy provided to the child. Function should be assessed with and without appropriate braces and assistive devices. Videotaping is useful for measurement of gross motor function, as well as to record changes in the child’s condition over time.

Radiographs of the thoracolumbar spine may demonstrate the presence of lumbar hyperlordosis, scoliosis, spondylolysis, spondylolisthesis, and congenital anomalies. Hip radiographs reveal hip subluxation and dislocation, both of which may influence the timing of surgical interventions. Routine head or spine MRI is typically unnecessary; however, in specific situations, these studies may be helpful in identifying patients in whom SDR is contraindicated.

Gait analysis with dynamic electromyographic (EMG) studies helps confirm the presence of spasticity before SDR and also serves to assess postoperative changes in motor performance.

Surgical Considerations and Operative Technique

Between 1987 and 1991, I (T.S.P.) performed dorsal rhizotomies on 173 patients through a laminectomy at the L2-S2 levels, as described by Peacock and colleagues.⁴⁸ In 1991, however, the potential risk for late spinal deformities after the procedure led to the development of a dorsal rhizotomy procedure through an L1-2 or L1 laminectomy.⁴⁹ Aside from minor technical refinements,⁵⁰ the surgical technique described here has been performed between 1991 and 2008 on 1719 children and adults, with a single instance of cerebrospinal fluid (CSF) leakage and no other postoperative complications. Please refer to Tables 227-3 and 227-4.

TABLE 227-3 Subtypes of Spastic Cerebral Palsy Treated by Selective Dorsal Rhizotomy

SPASTIC CEREBRAL PALSY SUBTYPES	NO. OF PATIENTS	PERCENT
Diplegia	1358	78
Triplegia or quadriplegia	356	21
Hemiplegia	5	<1
Total	1719	100

Data from St. Louis Children’s Hospital, 1987 to 2008.

TABLE 227-4 Prerhizotomy Ambulatory Function in Patients Who Underwent Selective Dorsal Rhizotomy for Spastic Cerebral Palsy

AMBULATION	NO. OF PATIENTS	PERCENT
Walking with a walker	719	42
Walking with crutches or a cane	124	7
Independent walking	557	32
Some locomotion	180	11
Crawling	117	7
No independent mobility	22	1
Total	1719	100

Data from St. Louis Children’s Hospital, 1987 to 2008.

Anesthetic Considerations

The patient may be premedicated with oral midazolam in the operating room holding area if necessary. Induction and intubation are performed with thiopental, halothane, and nitrous oxide. Short-lasting muscle relaxants (e.g., atracurium or vecuronium) are sometimes used to facilitate intubation. Anesthesia is maintained with fentanyl (10 µg/kg), 1% halothane, and 70% nitrous oxide throughout the procedure. Propofol is avoided because it greatly alters EMG activities. The patient receives a dose of antibiotic before any skin incision, and a Foley catheter is placed.

Positioning

The patient is positioned prone on gel bolsters. The operating table is maintained in a slight Trendelenburg position to minimize loss of CSF from the intracranial compartment. Needle electrodes are placed bilaterally in the adductor longus, vastus lateralis, anterior tibialis, peroneus, medial hamstring, and medial gastrocnemius muscles in preparation for intraoperative EMG examinations.

Determination of the Operative Level

In children, the spinous process of the L1 vertebra is approximated by counting the lumbar spinous processes from the level of the iliac crest. The level of the conus medullaris is then identified percutaneously with ultrasound. In adolescents and adults, L1 is localized with lateral lumbosacral radiography or fluoroscopy. The lower thoracic and entire lumbar regions are exposed in the operating field.

Operative Exposure of the Conus Medullaris

An incision is made in accordance with the localization just described. Electrocautery is used to expose the spinous process and lamina. In children, ultrasound is again used to examine the intradural structures through the exposed interlaminar space. In adults, a keyhole laminotomy may be performed to improve visualization with ultrasound. The conus is easily distinguished from the cauda equina with ultrasound (Fig. 227-3). Sagittal views show the conus as a hypodense triangle tapering caudally, whereas the cauda equina appears hyperdense. On axial views, the conus appears as a hypodense circular structure centered within the dural sac. A narrow gap between the dorsal and ventral spinal roots, lateral to the conus, can also be appreciated on the axial view. In general, axial views localize the conus more reliably than do sagittal views. A single-level laminectomy is performed to visualize 5 to 10 mm of the caudal conus and provide adequate exposure to safely separate the dorsal roots from the ventral roots later in the operation. The laminectomy may be extended to include a portion of the lamina above or below to achieve this exposure. Finally, a Midas Rex craniotome with a B5 attachment (Midas Rex Pneumatic Tools, Inc., Fort Worth, TX) is used to extend the laminectomy to the medial margin of the facet. The location of the conus is confirmed with ultrasound one final time before opening the dura. A midline durotomy is then made sharply, and the dural edges are tacked back with sutures.

FIGURE 227-3 Ultrasound is used to confirm the location of the conus. Before skin incision, the ultrasound probe is inserted percutaneously to localize the conus and plan the level of the incision. A, After the soft tissue dissection is complete, ultrasound is used to localize the level of the conus through the interlaminar space or through a keyhole laminotomy, if necessary B, On ultrasound, the conus appears hypoechoic on axial (left) and sagittal (right) images.

(Reproduced with permission from Park TS, Johnson JM. Surgical techniques of selective dorsal rhizotomy for spastic cerebral palsy. Neurosurg Focus. 2006;21:E7.)

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