Pathophysiology

It is difficult to establish a precise location of neurologic lesions on the basis of etiology or clinical signs because there is no characteristic pathologic picture. In some cases, there are gross malformations of the brain. In others, there may be evidence of vascular occlusion, atrophy, loss of neurons, and laminar degeneration that produce narrower gyri, wider sulci, and low brain weight. Anoxia appears to play the most significant role in the pathologic state of brain damage, which is often secondary to other causative mechanisms.

There are a few exceptions. In some cases, the manifestations or etiology is related to anatomic areas. For example, CP associated with preterm birth is usually spastic diplegia caused by hypoxic infarction or hemorrhage with periventricular leukomalacia in the area adjacent to the lateral ventricles. The athetoid (extrapyramidal) type of CP is most likely to be associated with birth asphyxia but can also be caused by kernicterus and metabolic genetic disorders such as mitochondrial disorders and glutaricaciduria (Johnston, 2011). Hemiplegic (hemiparetic) CP is often associated with a focal cerebral infarction (stroke) secondary to an intrauterine or perinatal thromboembolism, usually a result of maternal thrombosis or hereditary clotting disorder (Johnston, 2011). Cerebral hypoplasia and sometimes severe neonatal hypoglycemia are related to ataxic CP. Generalized cortical and cerebral atrophy often cause severe quadriparesis with cognitive impairment and microcephaly.

Clinical Classification

A revision of the Winter classification was proposed in 2005 to reflect the child’s actual clinical problems and their severity, an assessment of the child’s physical and quality-of-life status across time, and long-term support needs (Bax, Goldstein, Rosenbaum, et al., 2005; Nehring, 2010). The proposed new definition has four major dimensions of classification (Bax, Goldstein, Rosenbaum, et al., 2005):

Cerebral palsy has four primary types of movement disorders: spastic, dyskinetic, ataxic, and mixed (Nehring, 2010). The most common clinical type, spastic CP, represents an upper motor neuron muscular weakness (Box 49-1). The reflex arc is intact, and the characteristic physical signs are increased stretch reflexes, increased muscle tone, and (often) weakness. Early neurologic manifestations are usually generalized hypotonia or decreased tone that lasts for a few weeks or may extend for months or even as long as 1 year.

Diagnostic Evaluation

Infants at risk according to known etiologic factors associated with CP warrant careful assessment during early infancy to identify the signs of neuromotor dysfunction as soon as possible. The neurologic examination and history are the primary means for diagnosis. Neuroimaging of the child with suspected brain abnormality and CP is now recommended for diagnostic assessment, with MRI preferred to CT scan. Metabolic and genetic testing is recommended if no structural abnormality is identified by neuroimaging; laboratory tests are no longer recommended in the diagnostic process for CP.

Early recognition is made more difficult by the lack of reliable neonatal neurologic signs. However, nurses should monitor infants with known etiologic risk factors and evaluate them closely in the first 2 years of life. Because cortical control of movement does not occur until later in infancy, motor impairment associated with voluntary control is usually not apparent until after 2 to 4 months of age at the earliest. More often, the diagnosis cannot be confirmed until the age of 2 years because motor tone abnormalities may be indicative of another neuromuscular illness. In addition, some children who show signs consistent with CP before 2 years do not demonstrate such signs after 2 years (Nehring, 2010). However, there is no consensus regarding an age cut-off for the onset of symptoms. Clinical manifestations of CP at the time of diagnosis are listed in Box 49-2; early warning signs are listed in Box 49-3, but these are not considered diagnostic.

Establishing a diagnosis may be easier with the persistence of primitive reflexes: (1) either the asymmetric tonic neck reflex or persistent Moro reflex (beyond 4 months of age); and (2) the crossed extensor reflex. The tonic neck reflex normally disappears between 4 and 6 months of age. An obligatory response is considered abnormal. This is elicited by turning the infant’s head to one side and holding it there for 20 seconds. When a crying infant is unable to move from the asymmetric posturing of the tonic neck reflex when crying, it is considered obligatory and an abnormal response. The crossed extensor reflex, which normally disappears by 4 months, is elicited by applying a noxious stimulus to the sole of one foot with the knee extended. Normally, the contralateral foot responds with extensor, abduction, and then adduction movements. The possibility of CP is suggested if these reflexes occur after 4 months.

A number of assessment instruments are now available to evaluate muscle spasticity: functional independence in self-care, mobility, and cognition; self-initiated movements over time; and capability and performance of functional activities in self-care, mobility, and social function.

Therapeutic Management

The goals of therapy for children with CP are early recognition and promotion of optimal development to enable affected children to attain normalization and their potential within the limits of their existing health problems. The disorder is permanent, and therapy is primarily preventive and symptomatic.

Therapy has five broad aims:

Ankle-foot orthoses (AFOs, braces) are worn by many children with CP and are used to help prevent or reduce deformity, increase the energy efficiency of gait, and control alignment. Wheeled go-carts that provide sitting balance may serve as early “wheelchair” experience for young children. Manual or powered wheelchairs allow for more independent mobility (Figs. 49-1 and 49-2). Strollers can be equipped with custom seats for dependent mobilization.

Orthopedic surgery may be required between the ages of 5 and 7 years to correct contracture or spastic deformities, to provide stability for an uncontrollable joint, and to provide balanced muscle power. This includes tendon-lengthening procedures, release of spastic muscles, and correction of hip and adductor muscle spasticity or contracture to improve locomotion. Hip dislocation often occurs in children with CP. Spinal fusion may be done for scoliosis. Computerized motion analysis, radiographs, and clinical findings are used to make decisions about orthopedic surgery. Selective dorsal rhizotomy provides marked improvement in some children with CP. The procedure involves selectively cutting dorsal column sensory rootlets that have an abnormal response to electrical stimulation. Achieving the benefits from the surgery requires intensive physical therapy and family commitment. Because the procedure results in flaccid muscles, the child must be retaught to sit, stand, and walk.

Surgical intervention is usually reserved for children who do not respond to the more conservative measures such as bracing, but it is also indicated for children whose spasticity causes progressive deformities. Surgery is used primarily to improve function and enable proper sitting, standing, and walking rather than for cosmetic purposes and is followed by physical therapy.

Intense pain may occur with muscle spasms in patients with CP. Pharmacologic agents given orally (dantrolene sodium, baclofen [Lioresal], and diazepam [Valium]) have had little effectiveness in improving muscle coordination in children with CP; however, they are effective in decreasing overall spasticity. The most common side effects of these agents include hepatotoxicity (dantrolene), drowsiness, fatigue, and muscle weakness; less commonly, diaphoresis and constipation may be seen with baclofen.

Botulinum toxin A (Botox) is also used to reduce spasticity in targeted muscles, primarily those of the upper and lower extremities. Botulinum toxin A is injected into a selected muscle (commonly the quadriceps, gastrocnemius, or medial hamstrings) after a topical anesthetic is applied. The drug acts to inhibit the release of acetylcholine into a specific muscle group, thereby preventing muscle movement. When it is administered early in the course of the condition, affected muscle contractures may be minimized, particularly in lower extremities, thus avoiding surgical procedures with possible adverse effects. The goal is to allow stretching of the muscle as it relaxes and permit ambulation with an AFO. The major reported adverse effects of botulinum toxin A injection are pain at the injection site and temporary weakness (Lukban, Rosales, and Dressler, 2009). Prime candidates for botulinum toxin A injections are children with spasticity confined to the lower extremities; the drug weakens spasticity so the muscles can be stretched and the child may walk with or without orthoses. The onset of action occurs within 24 to 72 hours, with a peak effect observed at 2 weeks and a duration of action of 3 to 6 months. Diazepam has proved effective on a short-term basis in reducing spasticity in children with CP (Delgado, Hirtz, Aisen, et al., 2010).

Children with CP may also experience pain as a result of surgical procedures intended to reduce contracture deformities, position and gastroesophageal reflux, and physical therapy. Therefore pain management is an important aspect of care of children with CP.

The neurosurgical and pharmacologic approach to relieving the spasticity associated with CP involves the implantation of a pump to infuse baclofen directly into the intrathecal space surrounding the spinal cord. Intrathecal baclofen therapy is best suited for children with severe spasticity that interferes with activities of daily living (ADLs) and ambulation; however, this drug and method of administration (intrathecal) have had a significant number of adverse or side effects (Delgado, Hirtz, Aisen, et al., 2010). Patients may be screened before pump placement by the infusion of a “test dose” of intrathecal baclofen delivered via a lumbar puncture, followed by close monitoring for side effects (hypotonia, somnolence, seizures, nausea, vomiting, headache). Relief of spasticity occurs for several hours after the infusion. If a positive effect is noted, the patient is considered a candidate for pump placement. The implantation procedure is done in the operating room by a neurosurgeon. The pump, which is approximately the size of a hockey puck, is placed in the subcutaneous space of the midabdomen. An intrathecal catheter is tunneled from the lumbar area to the abdomen and connected to the pump. The pump is filled with baclofen and programmed to provide a set dose using a telemetry wand and a computer. Benefits of intrathecal baclofen include fewer systemic side effects than oral baclofen, dosage titration for maximizing effects, and reversibility of therapy with removal of the pump if so desired. The patient may remain hospitalized for 3 to 7 days to adjust the dosage and ensure proper healing. Outpatient visits to refill the pump and make dosage adjustments occur about every 3 to 6 months, depending on the patient’s response to the treatment. This procedure is most suited for a multidisciplinary setting where rehabilitation specialists are readily available and consistently involved in the patient’s ongoing care. Abrupt withdrawal of intrathecal baclofen may result in adverse effects such as rebound spasticity, pruritus, hyperthermia, rhabdomyolysis, disseminated intravascular coagulation, multiorgan failure, and death; in some cases, intrathecal baclofen withdrawal may mimic sepsis.

Oral baclofen has also been widely used in children with CP to treat spasticity; however, side effects are common and include systemic toxicity, drowsiness, and sedation (Delgado, Hirtz, Aisen, et al., 2010).

Antiepileptic drugs (AEDs) such as carbamazepine (Tegretol) and divalproex (valproate sodium and valproic acid; Depakote) are prescribed routinely for children who have seizures. Gabapentin (Neurontin) has been used in adults with spinal cord injury (SCI) to decrease spasticity with success; no studies are available on the effectiveness of the drug in children. The α₂-adrenergic agonists clonidine (Catapres) and tizanidine (Zanaflex) have been used to decrease spasticity in adults with SCI and multiple sclerosis. The use of oral tizanidine in children has been limited, and only a few small studies have been conducted in children with CP specifically evaluating the reduction of spasticity (Delgado, Hirtz, Aisen, et al., 2010). Oral tizanidine given in conjunction with botulinum type A has been reported to be more effective than oral baclofen and botulinum type A in one study of children with CP (Dai, Wasay, and Awan, 2008). All medications should be monitored for maintenance of therapeutic levels and avoidance of subtherapeutic or toxic levels. Other medications include levodopa to treat dystonia; Artane for treating dystonia and for increasing the use of upper extremities and vocalizations; and reserpine for hyperkinetic movement disorders such as chorea or athetosis (Johnston, 2011).

Dental hygiene is especially important. Regular visits to the dentist and prophylaxis, including brushing, fluoride, and flossing, should be instituted as soon as the teeth erupt. Dental care is especially important for children being given phenytoin, since they often develop gum hyperplasia. Additional problems common among children with CP include constipation caused by neurologic deficits and lack of exercise, poor bladder control and urinary retention, chronic respiratory tract infections, problems with airway clearance, and aspiration pneumonia. These occur as a result of gastroesophageal reflux, abnormal muscle tone, immobility, and altered positioning, and skin problems may occur as a result of altered positioning, poor nutrition, and immobility.

A wide variety of technical aids are available to improve the functioning of children with CP. These include electromechanical toys that employ the concept of biofeedback and operate from a head unit. The toy is manipulated only when the head and trunk are in correct alignment. Eye-hand coordination can also be enhanced by computerized toys and games. Microcomputers combined with voice synthesizers help children with speech difficulties to “speak.” These and other devices print messages onto screen monitors and paper.

Many other electronic devices allow independent functioning. Sensors can be activated and deactivated by using a head-stick or tongue or other voluntary muscle movement over which the child has control. Voice-activated computer technology may also allow increased mobility and ambulation with specially designed equipment such as wheelchairs. The application of this technology makes it possible for persons with CP to function eventually in their own residences and can be extended into the workplace.

There is some evidence that neuromuscular electrical stimulation (NMES) in addition to dynamic splinting may result in increased muscle strength, range of motion, and function of upper limbs in children with CP. Further studies are needed in children with CP to support the use of botulinum toxin A in conjunction with NMES to decrease muscle spasticity and improve function (Wright, Durham, Ewins, et al., 2012).

Behavior problems may occur and often interfere with the child’s development. Attention deficit hyperactivity disorder and other learning problems require professional attention. In addition, children with CP may have vision difficulties such as strabismus, nystagmus, and optic atrophy (Johnston, 2011). Speech-language therapy involves the services of a speech-language pathologist who may also assist with feeding problems.

Physical therapy is one of the most frequently used conservative treatment modalities. It requires the specialized skills of a qualified therapist with an extensive repertoire of exercise methods who can design a program to stimulate each child to achieve his or her functional goals.

An active therapy program involves the family, the physical therapist, and often other members of the health care team, including the nurse. The most common approach uses traditional types of therapeutic exercises that consist of stretching, passive, active, and resistive movements applied to specific muscle groups or joints to maintain or increase range of motion, strength, or endurance.

Spina Bifida (Myelomeningocele)

Abnormalities that derive from the embryonic neural tube (neural tube defects [NTDs]) constitute the largest group of congenital anomalies that are consistent with multifactorial inheritance. Normally, the spinal cord and cauda equina are encased in a protective sheath of bone and meninges (Fig. 49-5, A). Failure of neural tube closure produces defects of varying degrees (Box 49-4). They may involve the entire length of the neural tube or may be restricted to a small area.

In the United States, rates of NTDs have declined from 1.3 per 1000 births in 1970 to 0.3 per 1000 births after the introduction of mandatory food fortification with folic acid in 1998. One concern is that NTD rates have not decreased among Hispanic and non-Hispanic Caucasian mothers since 1999 (Centers for Disease Control and Prevention [CDC], 2009). In 2005, the rates for spina bifida were estimated by the CDC to be 17.96 per 100,000 live births, thus making this one of the most common birth defects in the United States (Matthews, 2009; Wolff, Witkop, Miller, et al., 2009). Increased use of prenatal diagnostic techniques and termination of pregnancies have also affected the overall incidence of NTDs (see also Prevention, p. 1582).

Anencephaly, the most serious NTD, is a congenital malformation in which both cerebral hemispheres are absent. The condition is incompatible with life, and many affected infants are stillborn. For those who survive, no specific treatment is available. The infants have a portion of the brainstem and are able to maintain vital functions (e.g., temperature regulation and cardiac and respiratory function) for a few hours to several weeks but eventually die of respiratory failure.

Myelodysplasia refers broadly to any malformation of the spinal canal and cord. Midline defects involving failure of the osseous (bony) spine to close are called spina bifida (SB), the most common defect of the central nervous system (CNS). SB is categorized into two types—SB occulta and SB cystica.

Spina bifida occulta refers to a defect that is not visible externally. It occurs most frequently in the lumbosacral area (L5 and S1) (see Fig. 49-5, B). SB occulta may not be apparent unless there are associated cutaneous manifestations or neuromuscular disturbances.

Spina bifida cystica refers to a visible defect with an external saclike protrusion. The two major forms of SB cystica are meningocele, which encases meninges and spinal fluid but no neural elements (see Fig. 49-5, C), and myelomeningocele (MMC) (or meningomyelocele), which contains meninges, spinal fluid, and nerves (see Fig. 49-5, D). Meningocele is not associated with neurologic deficit, which occurs in varying, often serious, degrees in myelomeningocele. Clinically, the term spina bifida is used to refer to myelomeningocele.

Pathophysiology

The pathophysiology of SB is best understood when related to the normal formative stages of the nervous system. At approximately 20 days of gestation, a dedicated depression, the neural groove, appears in the dorsal ectoderm of the embryo. During the fourth week of gestation, the groove deepens rapidly and its elevated margins develop laterally and fuse dorsally to form the neural tube. Neural tube formation begins in the cervical region near the center of the embryo and advances in both directions—caudally and cephalically—until by the end of the fourth week of gestation, the ends of the neural tube, the anterior and posterior neuropores, close.

Most experts believe the primary defect in neural tube malformations is a failure of neural tube closure. However, some evidence indicates that the defects are a result of splitting of the already closed neural tube as a result of an abnormal increase in cerebrospinal fluid (CSF) pressure during the first trimester.

There is evidence of a multifactorial etiology, including drugs, radiation, maternal malnutrition, chemicals, and possibly a genetic mutation in folate pathways in some cases, which may result in abnormal development. There is also evidence of a genetic component in the development of SB; myelomeningocele may occur in association with syndromes such as trisomy 18, PHAVER (limb pterygia, congenital heart anomalies, vertebral defects, ear anomalies, and radial defects) syndrome, and Meckel-Gruber syndrome (Shaer, Chescheir, and Schulkin, 2007). Additional factors predisposing children to an increased risk for NTDs include prepregnancy maternal obesity, maternal diabetes mellitus, low maternal vitamin B₁₂ status, maternal hyperthermia, and the use of AEDs in pregnancy. The genetic predisposition is supported by evidence of the risk for recurrence after one affected child (3%-4%) and a 10% risk for recurrence with two previously affected children (Kinsman and Johnston, 2011).

The degree of neurologic dysfunction depends on where the sac protrudes through the vertebrae, the anatomic level of the defect, and the amount of nerve tissue involved. The majority of myelomeningoceles (75%) involve the lumbar or lumbosacral area (Fig. 49-6). Hydrocephalus is a frequently associated anomaly in 80% to 90% of the children. About 80% of patients with myelomeningocele develop a type II Chiari malformation (Kinsman and Johnston, 2011). There is some evidence that prolonged exposure of the MMC sac to amniotic fluid predisposes an infant to the development of hindbrain herniation and Chiari II malformation (Adzick, 2013).