Cerebral palsy occurs in 1.2–3.6 children per 1000 live births. Numerous cerebral palsy registries exist throughout the world [Cans et al., 2004], and population prevalence rates from four continents have remained consistent over several decades. In Denmark, there was a declining birth prevalence between the period of 1983–1986 (3.0 per 1000 live births) and the period 1995–1998 (2.1 per 1000 live births) [Ravn et al., 2009]. In the United States, the prevalence of cerebral palsy increased from 1.7 to 2.0 per 1000 live births between the mid-1970s and late 1980s [Winter et al., 2002], and was estimated to be as high as 3.6 per 1000 8-year-old children in 2002 [Yeargin-Allsopp et al., 2008]. Based on these numbers, approximately 12,000 children with cerebral palsy are born annually in the United States.

Prematurity is the single most important risk factor for cerebral palsy. The risk of cerebral palsy in very low birth weight infants is as high as 4–10 percent, whereas the risk in term infants is only 1.0–1.5 per 1000 live births [Grether et al., 1992; Hagberg et al., 2001; Topp et al., 2001; Wu et al., 2003; Ancel et al., 2006; Moster et al., 2008]. Infants born at 24–26 weeks’ gestation may have as high as a 20 percent chance of developing cerebral palsy [Ancel et al., 2006]. In most epidemiologic studies, preterm infants constitute approximately half of all infants with cerebral palsy. An increase in the prevalence rate of cerebral palsy among preterm infants during the mid-1980s was attributed to increased survival of low birth weight infants [Colver et al., 2000; Pharoah et al., 1990; Topp et al., 2001]. Subsequent longitudinal studies, however, suggest that the rate of cerebral palsy among preterm infants has remained constant or even decreased [Clark and Hankins, 2003; Hagberg et al., 2001; O’Shea et al., 1998; Winter et al., 2002; Platt et al., 2007], though this is not a consistent finding in all populations [Vincer et al., 2006].

Term infants represent more than half of all cases of cerebral palsy [Bax et al., 2006]. The prevalence of cerebral palsy among term infants, 1–1.5 per 1000 live births, has not diminished over the past three decades, despite the introduction of electronic fetal monitoring during the 1970s and the subsequent sharp rise in births by cesarean section [Clark and Hankins, 2003; Colver et al., 2000; Topp et al., 2001; Winter et al., 2002]. Although unchanged prevalence is disappointing in view of the fact that perinatal deaths, stillbirths, and birth asphyxia, as measured by low Apgar scores, all have dropped dramatically in recent decades, other data are more encouraging [Ravn et al., 2009]. Longitudinal data in the United States suggest that a slight increase in cerebral palsy prevalence among infants with normal birth weight was responsible for the significant increase in total cerebral palsy prevalence reported over a 15-year period [Winter et al., 2002]. Although the severity of cerebral palsy within an Australian population increased during this period [Blair, 2001], suggesting that perhaps more infants who would have died in previous times are being saved, workers in the United Kingdom have described a decrease in severity of cerebral palsy among term infants over a similar (18-year) period [Colver et al., 2000].

Male infants exhibit a higher risk of cerebral palsy than female infants [Platt et al., 2007; Wu et al., 2009; Johnston and Hagberg, 2007]. Twins, who constitute 2 percent of the population, also carry a higher risk, and contribute 10–12 percent to the overall prevalence of cerebral palsy [Grether et al., 1992; Bax et al., 2006]. The increased risk of cerebral palsy among infants of multiple gestation is partly due to the higher rate of prematurity, though twins born at term may also exhibit an increased risk for cerebral palsy [Petterson et al., 1993; Pharoah, 2001]. Death in utero of a co-twin, such as from twin–twin transfusion, places the surviving twin at particularly high risk for neurologic and other complications [Grether et al., 1993; Szymonowicz et al., 1986].

Blacks have an increased risk of cerebral palsy when compared with whites [Murphy et al., 1993; Yeargin-Allsopp et al., 2008]. Although this finding is due in part to an increased rate of prematurity, the risk of cerebral palsy among black infants born at term also is elevated [Wu et al., 2003]. Furthermore, several studies suggest that infants born to mothers with lower socioeconomic status exhibit an increased risk of cerebral palsy [Sundrum et al., 2005; Yeargin-Allsopp et al., 2008; Dolk et al., 2001]. In one study that adjusted for potential confounding effects of prematurity, the effect of low socioeconomic status on cerebral palsy risk was only partly accounted for by lower birth weight and gestational age [Sundrum et al., 2005].

Life expectancy of patients with cerebral palsy is related to the type of involvement and the severity of motor disability. Severe quadriplegia has been associated with a shortened life expectancy. Other significant variables include associated disabilities and availability of quality medical care. The risk of death is highest in the first 5 years of life [Blair et al., 2001]. As mortality data have become available, it has become clear that, with reasonable medical attention, a majority of affected persons will survive into adult life [Evans et al., 1990; Eyman et al., 1990; Hutton et al., 1994; Plioplys et al., 1998; Strauss et al., 1998; Plioplys, 2003].

Etiology

A wide range of causative disorders and risk factors have been identified for cerebral palsy. Box 69-1 lists some of the more common etiologic categories and risk factors, broadly classified into the following groups: perinatal brain injury, brain injury related to prematurity, developmental abnormalities, prenatal risk factors, and postnatal brain injury. These factors may coexist and interact with each other in contributing to the pathogenesis of brain injury resulting in cerebral palsy.

Perinatal Brain Injury

Intrapartum hypoxia-ischemia is a well-described cause of cerebral palsy, especially in the setting of an acute intrapartum event such as uterine rupture, placental abruption, or cord prolapse. The extent to which hypoxic-ischemic brain injury is responsible for cerebral palsy, however, has been a major source of controversy. Epidemiologic studies suggest that in a minority (between 6 and 28 percent) of affected children, cerebral palsy is due to perinatal asphyxia [Hagberg et al., 2001; Nelson and Grether 1998]. The form of cerebral palsy most often associated with hypoxic-ischemic brain injury is spastic quadriparesis.

The term perinatal asphyxia is confusing and deserves further clarification. Traditionally, this term has been defined by clinical signs and symptoms, including low Apgar scores, meconium-stained amniotic fluid, and low umbilical cord pH. Yet the clinical findings used to define this term are not specific for hypoxic-ischemic brain injury [Blair, 1993]. Although various groups of investigators have defined specific criteria that can be used to establish intrapartum hypoxia-ischemia as the underlying cause of cerebral palsy [MacLennan, 1999], a widely accepted, evidence-based standard for determining when cerebral palsy is due to hypoxia-ischemia is still lacking.

Some investigators prefer the term neonatal encephalopathy to describe the clinical syndrome of perinatal asphyxia because it is an all-embracing term that does not imply a single underlying etiologic disorder [Leviton and Nelson, 1992]. Signs and symptoms of brain dysfunction that constitute neonatal encephalopathy include low Apgar scores, failure to initiate and/or maintain respiration, depressed consciousness, abnormal tone (usually flaccidity), depression of developmental reflexes, and seizures during the first 48 hours of life. The clinical syndrome of neonatal encephalopathy may be preceded by a variety of prenatal and intrapartum risk factors [Badawi et al., 1998b], and usually is associated with acute brain injury occurring around the time of birth [Cowan et al., 2003].

Signs and symptoms of birth asphyxia or neonatal encephalopathy are strongly predictive of cerebral palsy in the child. For instance, term infants whose immediate postpartum course was comprised of a 5-minute Apgar score of 5 or less, continuing neurologic abnormalities, and seizures in the first days of life constitute a group at high risk for chronic motor disability (55 percent) and for death or disability combined (70 percent) [Ellenberg and Nelson, 1988]. The risk of cerebral palsy is increased 30-fold in infants with a 5-minute Apgar score of less than 7, and 80-fold in infants with a 5-minute Apgar score of 3 or less [Moster et al., 2001; Thorngren-Jerneck and Herbst, 2001; Wu et al., 2003].

Neonatal stroke, which encompasses ischemic perinatal infarction and sinovenous thrombosis occuring in the perinatal period (before the age of 7 days) or neonatal period (before 28 days of age), is a particularly important cause of cerebral palsy [Lynch and Nelson, 2001]. Ischemic perinatal stroke may be responsible for 28–50 percent of all cases of hemiplegic cerebral palsy in term infants [Humphreys et al., 2000; Uvebrant, 1988; Wu et al., 2003; Bax et al., 2006]. Among children with cerebral palsy who are referred for neuroimaging, 13–37 percent are diagnosed with a neonatal stroke [Ashwal et al., 2004]. Newborns with ischemic perinatal infarction either may present acutely during the neonatal period, with neurologic symptoms such as seizures, or may be clinically asymptomatic until several months of age, when pathologic handedness or seizures are first noted [Golomb et al., 2001]. The risk of cerebral palsy after ischemic perinatal infarction is especially high among infants with delayed presentation; this finding is not surprising, given the fact that hemiparesis is the most common presenting symptom in this group [Golomb et al., 2001; Wu et al., 2004b]. Involvement of the internal capsule also portends a poorer motor outcome after ischemic perinatal infarction [Mercuri et al., 1999; Wu et al., 2004b].

Neonatal sinovenous thrombosis also can lead to cerebral palsy. In a population-based study of pediatric stroke in Canada, 43 percent of all cases of sinovenous thrombosis occurred during the neonatal period [deVeber and Andrew, 2001]. Risk factors for neonatal sinovenous thrombosis include systemic illness, polycythemia, coagulation abnormalities, and extracorporeal membrane oxygen (ECMO) therapy, and motor sequelae such as cerebral palsy were more common if sinovenous thrombosis led to development of venous infarction [deVeber and Andrew, 2001; Wu et al., 2002]. Periventricular venous infarction [Takanashi et al., 2003], intraparenchymal hemorrhage, and birth trauma also may lead to cerebral palsy. (Please refer to Chapter 18 for further discussion of birth trauma.)

Brain Injury Related to Prematurity

Preterm infants constitute a disproportionate share of the cases of children who develop spastic diplegia but can manifest any cerebral palsy subtype. Both intraventricular hemorrhage and white matter necrosis seen in periventricular leukomalacia may occur before or after birth. The main pathogenetic mechanisms underlying periventricular leukomalacia are hypoxia-ischemia and inflammation [Volpe, 2009; Dammann and Leviton, 1997]. Periventricular leukomalacia and intraventricular hemorrhage are reviewed in Chapters 17–19.

Developmental Abnormalities

Brain malformations originating from intrauterine maldevelopment may underlie the neurologic impairment seen in children with cerebral palsy. As a group, children with cerebral palsy have a higher incidence of congenital malformations both within and outside of the brain [Rankin et al., 2009]. Population-based studies of cerebral palsy suggest that 9–14 percent of affected children have a brain malformation [Croen et al., 2001; Wu et al., 2003]. The most common malformations in term children are cortical dysplasia/polymicrogyria, schizencephaly, and pachygyria/lissencephaly. Complex brain malformations are the most frequent category among preterm infants with cerebral palsy [Ashwal et al., 2004].

A genetic or metabolic disorder may be associated with a specific brain malformation that causes cerebral palsy. For example, children with Zellweger’s syndrome typically have polymicrogyria and other cortical malformations. Miller–Dieker syndrome is a known cause of lissencephaly. Glutaric aciduria type I may masquerade as dyskinetic cerebral palsy [Hauser and Peters, 1998], and arginase deficiency mimics diplegic cerebral palsy [Prasad et al., 1997]. Children with cerebral palsy who demonstrate either progressive decline or atypical features such as dysmorphisms, macrocephaly, or a strong family history should be tested for an underlying genetic or metabolic disorder.

Prenatal Risk Factors

A number of maternal conditions have been associated with an increased risk of cerebral palsy in the offspring. Intrauterine inflammation, or chorioamnionitis, has received increasing attention as a potential risk factor [Grether and Nelson, 1997; Leviton et al., 1999; Wu and Colford, 2000]. Epidemiologic studies suggest that maternal intrapartum fever, a clinical or histologic diagnosis of chorioamnionitis, and serologic markers of inflammation in the fetus all confer an increased risk of cerebral palsy. In term infants, chorioamnionitis, often diagnosed by the presence of intrapartum maternal fever, is a particularly strong risk factor for spastic quadriplegia [Grether and Nelson, 1997; Wu et al., 2003]. Maternal fever during labor also increases the chance that the neonate will have low Apgar scores and characteristics of neonatal encephalopathy [Badawi et al., 1998a; Lieberman et al., 2000]. It is hypothesized that the fetal inflammatory response that occurs in the setting of an inflammatory intrauterine environment is responsible for brain injury leading to cerebral palsy [Dammann et al., 2002; Nelson et al., 1998]. Yet the mechanisms by which intrauterine inflammation might cause cerebral palsy remain controversial. It is postulated that inflammation may interact with a hypoxic-ischemic insult to injure the newborn brain in some children with cerebral palsy. A study has indicated that, in the presence of fetal acidemia, chorioamnionitis has poor predictive value and does not portend additional risk for development of neonatal encephalopathy [Shalak et al., 2005]. It has also been postulated that exposure to neurotropic viruses, such as herpes group B viruses, may also increase the risk of cerebral palsy [Gibson et al., 2006a; Djukic et al., 2009].

Intrauterine growth restriction is associated with an increased risk of cerebral palsy, especially in term infants [Jarvis et al., 2003; Topp et al., 1996]. Infants who are large for gestational age also have been reported to be at higher risk [Uvebrant and Hagberg, 1992]. Prothrombotic abnormalities, including factor V Leiden, methylenetetrahydrofolate reductase (MTHFR) C677T, and presence of anticardiolipin antibodies, have been found with increased frequency among infants with cerebral palsy and perinatal arterial infarction [Gunther et al., 2000; Hagstrom et al., 1998; Gibson et al., 2005], though not all studies have confirmed these associations [Miller et al., 2006]. A history of infertility also has been found to be associated with an increased risk of neonatal encephalopathy, developmental delay, and cerebral palsy [Badawi et al., 1998b; Ericson et al., 2002; Stromberg et al., 2002].

The pathogenesis of cerebral palsy is complex and multifactorial. For instance, among infants with perinatal ischemic infarction in the newborn period, multiple risk factors often are observed [Gunther et al., 2000; Wu et al., 2002]. When signs of hypoxia-ischemia and markers of infection both are present in a newborn, the risk for cerebral palsy is markedly heightened [Nelson and Grether, 1998]. Studies of placental abnormalities in cerebral palsy also suggest that a combination of thrombotic and inflammatory findings confers the highest risk of adverse neurologic outcome [Redline and O’Riordan, 2000].

A number of toxins have been described as causing cerebral palsy, such as benzyl alcohol preservative and in utero alcohol exposure [Benda et al., 1986; Burd et al., 2003]. Ingestion of methyl mercury by pregnant women in the Minamata Bay disaster resulted in the birth of children who were spastic, microcephalic, and cognitively impaired. Congenital infections, often referred to as TORCH infections (toxoplasmosis, rubella, cytomegalovirus, and herpes simplex infection), also can infect the fetus and produce serious encephalitides with motor sequelae [Sever, 1985].

Recent literature suggests that the risk of cerebral palsy may be modified by relatively common genetic polymorphisms. Inherited cytokine polymorphisms, including several found in the tumor necrosis factor-alpha and mannose-binding lectin genes, have been associated with increased risk of cerebral palsy in term infants [Gibson et al., 2006b, 2008]. Furthermore, a functional promotor region polymorphism in the interleukin (IL)-6 gene has been associated with cerebral palsy in term infants, as well as with the extent of brain injury and gray-matter volume in premature infants [Wu et al., 2009; Harding et al., 2004; Reiman et al., 2008; Djukic et al., 2009].

Postnatal Brain Injury

Cerebral palsy may result from brain injury occurring during the neonatal period. Neonatal meningitis from group B streptococcal and other infections may cause brain damage leading to cerebral palsy. Other types of postnatal brain injury, including hypoxia-ischemia and traumatic brain injury from nonaccidental trauma, also may cause cerebral palsy.

Bilirubin toxicity is a well-known cause of dyskinetic cerebral palsy, and continues to be a significant problem, in spite of recent progress in management of hyperbilirubinemic neonates [Shapiro, 2003]. Although bilirubin levels below 25 mg/dL rarely may be associated with kernicterus [Soorani-Lunsing et al., 2001], more commonly, bilirubin levels greater than 30 mg/dL are responsible for this problem. Symptoms of kernicterus in a jaundiced newborn usually are present by the second or third day of life. The child becomes listless and sucks poorly. Fever may be present, and crying becomes weak. The Moro and deep tendon reflexes become difficult to elicit, and general muscle tone becomes decreased. After several weeks, tone increases, and the infant manifests extension of the back with opisthotonos and marked extension of the extremities [Van Praagh, 1961].

The full clinical pattern of kernicterus infrequently is present in a single affected patient. Signs and symptoms consist of choreoathetosis, dystonia, tremors, and rigidity. Upward gaze and, on rare occasions, horizontal gaze may be impaired. Sensorineural hearing loss is common. Mental retardation, microcephaly, and spasticity may be present. A clinical score for assessing bilirubin-induced dysfunction in newborns has been recommended [Johnson et al., 1999]. Preterm infants with athetotic cerebral palsy have relatively uniform features, similar to term infants with kernicterus [Okumura et al., 2009]. Unconjugated bilirubin damages mitochondria and is toxic to neurons and to astrocytes [Ostrow et al., 2004]. Microscopic examination reveals yellow granules that are found not only in neurons, but also in the interstitial tissue. These changes occur in the first few days after injury. Neurons are grossly pyknotic, and in children who live for longer periods, large areas of cell loss, gliosis, and demyelination are evident.

The primary management problem for children affected with kernicterus is the lack of provision of the multiple services needed by affected infants and, more importantly, the failure to recognize early at-risk infants and manage severe hyperbilirubinemia in an efficient and timely fashion [Johnson et al., 2009; Maisels, 2009].

Clinical Features and Diagnosis

Delay in attaining developmental milestones is the most distinctive presenting complaint in children with cerebral palsy. A detailed history and thorough physical and neurologic examinations are crucial in the diagnostic process. Records of the mother’s pregnancy and delivery and of the infant’s early neonatal period may be invaluable. Physical and neurologic abnormalities may be subtle. The clinician should be cautious about diagnostic pronouncements unless the findings are unequivocal. Prognostic statements generally are not appropriate until after several serial examinations.

The clinical findings often change with maturation; both severity and distribution may be altered. A child with cerebral palsy who has been hypotonic may become hypertonic. A number of infants with mild abnormalities subsequently demonstrate a decrease or, in some instances, a disappearance of motor dysfunction [Nelson and Ellenberg, 1982]. The clinical picture should not include evidence of progressive disease or loss of skills previously acquired. Any suggestion of progression of disability should result in expansion of the differential diagnosis to explain the progression. The history should focus on an attempt to identify a specific cause and should especially investigate familial or metabolic disease that might have implications for treatment or family counseling [Barabas and Taft, 1986].

The diagnosis of cerebral palsy often is indicated by delayed developmental milestones, the persistence of developmental reflexes, the presence of pathologic reflexes, abnormal tone, and the failure to develop maturational reflexes, such as the traction response and the parachute response, in a timely fashion. The use of standard developmental screening tests (e.g., the Denver Developmental Screening Test II) may provide quantitative evidence of motor delay, as well as evidence of delay in acquisition of other skills.

Further Diagnostic Evaluation

A useful algorithm for the evaluation of the child with cerebral palsy has been published (Figure 69-1) [Ashwal et al., 2004]. An abnormality is documented on cranial magnetic resonance imaging (MRI; in 89 percent of cases) or computed tomography (CT; in 77 percent) in a large percentage of patients; therefore, all children with cerebral palsy should undergo a neuroimaging study, preferably MRI [Accardo et al., 2004]. Because of the reported low incidence of metabolic and genetic disorders among children with cerebral palsy, testing for these disorders is indicated only in children in whom the history or clinical examination includes atypical features, or if a specific diagnosis is not established with neuroimaging. Children with a brain malformation also warrant consideration for further testing to determine if an underlying genetic or metabolic disorder is present. The presence of microcephaly at birth, dysmorphic features, and congenital anomalies outside the nervous system suggests early developmental defects. Microcephaly is one of the most common brain malformations and is caused by mutations of a number of different genes [Ashwal et al., 2009; Mochida, 2009]. The high incidence rates for mental retardation (52 percent), epilepsy (45 percent), ophthalmologic defects (28 percent), speech and language disorders (38 percent), and hearing impairment (12 percent) [Ashwal et al., 2004] make it imperative that all children with cerebral palsy be screened for mental retardation, ophthalmologic and hearing impairments, and speech and language disorders; nutrition, growth, and swallowing also should be closely monitored. Unfortunately, although neuronal plasticity likely aids improvement in brain dysfunction, significant injury persists [Johnston, 2009].

Fig. 69-1 Algorithm for the evaluation of the child with cerebral palsy (CP).

Screening for associated conditions (mental retardation, vision/hearing impairments, speech and language delays, oral motor dysfunction, and epilepsy) is recommended. Neuroimaging (magnetic resonance imaging [MRI] is preferred to computed tomography [CT]) is recommended for further evaluation if the etiology has not been previously determined. In some children, additional metabolic or genetic testing may be indicated. EEG, electroencephalogram.

(From Ashwal S et al. Practice parameter: Diagnostic assessment of the child with cerebral palsy: Report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology 2004;62:851–863.)

Functional Classification

The validated Gross Motor Function Classification System (GMFCS) provides an easy and straightforward way to classify severity of motor impairment into one of the five levels [Palisano et al., 1997]. The GMFCS scale has been found to predict Gross Motor Function Measure (GMFM) scores [Palisano et al., 2000] and is simpler to use.

Some evidence suggests that family reporting may be utilized to enhance the use of the GMFCS [Morris et al., 2004]. In recent years, the GMFCS has been applied to develop five distinct motor development curves for use in prognostication [Rosenbaum et al., 2002]. Use of the GMFCS has indicated that there is no functional decline in levels I and II. However, in levels III, IV, and V, function peaked from 6 years 11 months to 7 years 11 months, and declined thereafter [Hanna et al., 2009]. Many other scales and inventories are in use, however [Shapiro, 2004]. These include the modified Ashworth scale, passive Range of Motion measurements, Selective Motor Control scale, and the Pediatric Evaluation of Disability Inventory [Ostensjo et al., 2004]. Adequacy of performance of everyday activities is best predicted by the child’s ability to perform gross motor tasks [Ostensjo et al., 2004].

Common Cerebral Palsy Syndromes

Cerebral palsy can be classified by the predominant type of motor abnormality – spasticity, choreoathetotic, dystonic, hypotonic, ataxic, or mixed – as well as by the distribution of limb involvement – hemiplegia, quadriplegia, or diplegia. The most common clinical cerebral palsy syndromes are discussed next.

Spastic Hemiplegia

Although children may manifest obvious hemiplegia in the second year of life, specific difficulties may not be observed during the first 3–5 months of life. After a perinatal stroke, an infant may be neurologically normal until the development of pathologic handedness at approximately 4–6 months of age. For unexplained reasons, the left hemisphere (right side of the body) is affected in two-thirds of patients, and perinatal stroke is more common on the left than on the right [Crothers and Paine, 1959; Nelson and Lynch, 2004].

During the examination, the child exhibits impaired gross and fine motor coordination, has difficulty moving the hand quickly, and frequently is unable to grasp small items with a pincer grasp. The obligate palmar grasp reflex, which usually is absent by age 6 months and frequently rudimentary after age 4 months, may remain obligate. Weakness of the wrist and forearm often is associated with limitation of range of motion of supination. The range of elbow extension may be restricted. Attempts at reaching for objects may be accompanied by athetotic posturing with flexion of the wrist and hyperextension of the fingers (avoidance reaction). Facial involvement is unusual. Only 10 percent of affected patients, including those with extensive hemiplegia, have homonymous hemianopia [Black, 1988]. Children with hemiparesis may have a circumductive gait with a variable degree of abnormality. Most commonly, the child walks on the toes and swings the affected leg over a nearly semicircular arc during the course of each step. In contrast with the leg, the affected arm usually moves less than normal and does not participate in normal reciprocal motion during ambulation. An equinovarus positioning of the foot is seen; weakness and lack of full range of motion of dorsiflexion often are present. Further evidence of upper motor neuron involvement on the hemiplegic side includes hyperreflexia of the deep tendon reflexes, ankle clonus, and extensor toe signs.

Growth retardation of the abnormal side, usually more prominent in the distal arm and hand or distal leg and foot, may be manifest. An indication of the presence of growth impairment may be obtained when the thumb and thumbnail of the affected side are compared with their normal opposite members and found to be smaller. Growth discrepancy of the leg may result in significant difficulties during walking, leading to orthopedic problems involving the proximal leg and the lower spinal vertebrae.

Although frequently overlooked, corticosensory impairment and hemineglect of the affected side are common. Examination for the integrity of stereognosis and graphesthesia usually reveals varying degrees of compromise [Brown et al., 1987; Skatvedt, 1960].

Spastic Quadriplegia

Little [1861] first described cerebral palsy. He used the term spastic rigidity in place of the modern term spasticity. As part of his original treatise, he wrote: “Spastic cerebral palsy has the characteristics of upper motor unit involvement, such as hyperreflexia and increased tone, often with ankle clonus, crossed adductor reflexes, and extensor toe signs. Both lower extremities are more or less generally involved. Sometimes the affection of one limb only is observed by the parent, but examination usually shows a smaller degree of affection in the limb supposed to be sound. The contraction in the hips, knees, and ankles is often considerable. The flexors and adductors of thighs, the flexors of knees, and the gastrocnemii, preponderate. In most cases, after a time, owing to structural shortening of the muscles and of the articular ligaments, and perhaps to some changes of form of articular surface, the thighs cannot be completely abducted or extended, the knees cannot be straightened, nor can the heels be properly applied to the ground. The upper extremities are sometimes held down by preponderating action of pectorals, teres major and teres minor, and latissimus dorsi; the elbows are semiflexed, the wrists partially flexed, pronated, and the fingers incapable of perfect voluntary direction. Sometimes the upper extremities appear unaffected with spasm or want of volition, sometimes a mere awkwardness in using them exists.”

Spastic quadriplegia is characterized by a generalized increase in muscle tone. The legs are involved more than the arms, and paucity of limb movement is characteristic. Opisthotonic posturing may be evident in early infancy and may persist through the first year of life. Movement of the head often initiates forced extension of the arms and legs, resulting in a position similar to that in decerebrate rigidity. Accompanying supranuclear bulbar palsy, the result of bilateral corticobulbar tract impairment, may produce difficulties with swallowing and articulation. The incoordination of the oropharyngeal muscles may predispose the patient to recurrent pneumonia during the first years of life.

Neurologic examination demonstrates marked spasticity and accompanying signs of corticospinal tract involvement, including hyperactive deep tendon reflexes, ankle clonus, and extensor toe signs. Weakness of dorsiflexion of the feet, associated with equinovarus deformities, is common. Marked spasticity of the hip muscles may lead to subluxation of the femur and associated acetabular pathologic conditions. Radiographs may be necessary to exclude the abnormal positioning of the head of the femur. Flexion contractures of the wrists and elbows of various degrees and spasticity of the arm muscles are readily apparent.

Ophthalmologic evaluation of children with spastic quadriplegia more commonly reveals visual impairment in these children than in children with athetoid cerebral palsy [Preakey et al., 1974]. The incidence of auditory, visual, motor, and learning disability is much higher in children with spastic quadriplegia than in children with spastic hemiplegia, spastic diplegia, and ataxic cerebral palsy [Robinson, 1973; Shevell et al., 2009].

Spastic Diplegia

Spastic diplegia is characterized by bilateral leg involvement and, commonly, some degree of upper extremity impairment. Preterm infants are particularly prone to spastic diplegia. Approximately 80 percent of preterm infants who manifest motor abnormalities have spastic diplegia [McDonald, 1963]. In recent years, the survival of very small preterm infants has resulted in a larger group of more severely neurologically impaired survivors [Hagberg et al., 1989a, b]. Diffusion tensor imaging in preterm infants has demonstrated disruption of thalamocortical connections, as well as descending corticospinal pathways [Hoon et al., 2009].

Some infants with spastic diplegia manifest ataxia after further maturation. These infants have a great increase of tone of the leg muscles and accompanying difficulties in coordination and strength. Impairment may be asymmetric. When a small child is held in the vertical position by the examiner and the plantar surfaces of the feet are lightly bounced on the examining table, adduction of the legs (scissoring) and obligatory extension (extensor thrust) are seen. The feet also are kept in an equinovarus posture. Further examination reveals weakness of dorsiflexion of the feet. In older children, this same spasticity causes them to toe-walk. As expected, signs of upper motor unit involvement are easily demonstrable in the legs (e.g., hyperactive deep tendon reflexes, bilateral ankle clonus, extensor toe signs). Striking spasticity of the hip muscles may lead to subluxation of the femur and associated acetabular pathologic conditions and further restriction of motion. Radiographs may be necessary to exclude the abnormal positioning of the femoral head.

The arms may be affected but usually only to a mild degree. The child may hold the arms in unusual fixed postures, either extended or flexed during walking, and may have clumsy, reciprocating, swinging arm movements or hold both arms flexed at the elbows. Affected children may extend their arms, pronate their hands, and clench their fists during running. Associated athetosis makes this latter posturing more likely. Vasomotor instability, often manifested by cold extremities and variable and sometimes unpredictable patterns of sweating, may prove troublesome for the patient.

After a variable period, usually 18 months to 2 years in children with moderate involvement, spasticity is increasingly accompanied by contractures that maintain the hips in flexion, knees in flexion, and the feet in an equinovarus position. For reasons that are unclear – either disuse or probably hemispheric (parietal) lobe dysfunction – marked retardation of linear growth of the legs may be a feature.

Extrapyramidal Cerebral Palsy

Extrapyramidal (dyskinetic) cerebral palsy can be divided arbitrarily into two primary clinical subtypes – choreoathetotic and dystonic. Patients are unable to perform meaningful movements smoothly because of interfering movements and involvement of inappropriate agonist and antagonist muscles (see Chapter 68). Extrapyramidal cerebral palsy involves defects of posture and involuntary movement (e.g., athetosis, ballismus, chorea, dystonia); increased tone usually is associated with these conditions and is of the “lead pipe” or rigid variety. Children with this form of cerebral palsy have more severe cognitive and motor impairments than children with bilateral spastic quadriplegia [Himmelmann et al., 2009].

Choreoathetotic cerebral palsy

Choreoathetotic cerebral palsy is characterized by large-amplitude, involuntary movements. The most obvious and dominating movement component is athetosis. Chorea is present in variable degree. Tremor, myoclonus, and even some element of dystonia also may be evident.

Athetosis usually involves the distal limbs. Athetosis results in slow, writhing involuntary movements. Other common features are finger and toe extension and rotation of the limb and its long axis. The resultant pattern of these movements culminates in bizarre transient positions of the limbs. Chorea may involve the face, limbs, and rarely the trunk. The choreiform movements can be characterized as asymmetric, fleeting, incoordinated, involuntary contractions of individual muscle groups. The combination of athetoid and choreiform movements results in a pattern of distal extremity movement, on-going hypertonia, and rotary writhing movements of the limbs.

Athetotic posturing may be evident in the first year of life when the child begins to reach for objects. The movements, as generally is true of most involuntary movements, are not present during sleep. Movements are more prominent during stress or illness, and their intensity changes from day to day.

As expected from the pathologic findings, evidence of upper motor neuron unit impairment (e.g., hyperactive deep tendon reflexes, ankle clonus, positive extensor toe signs), as well as seizures, spasticity, and mental retardation, may be present.

Children with choreoathetosis may have marked difficulty with speech, which is characterized by great variability in rate and explosive changes in volume.

Ballismus, a movement disorder in which the arms and legs are violently flung about, may be an extreme form of choreoathetotic cerebral palsy. Most of the activity takes place at the shoulders and hips. Although patients with ballismus are said to have a shortened life expectancy and do not survive beyond the second decade, few data are available, and clinicopathologic correlation is undefined.

Dystonic cerebral palsy

The dystonic form of cerebral palsy is uncommon. The extrapyramidal form of cerebral palsy is often, but not always, preceded by hypoxic-ischemic brain injury or kernicterus. Requirement for respiratory support and hypoxic-ischemic encephalopathy at birth usually are documented in the patient history. The dystonic movements are not unlike those in other conditions associated with dystonia. The trunk muscles and proximal portions of the limbs are predominantly affected. Movements may be slow and persistent, particularly of the head and neck, which may be pulled to one side or the other, or retrocollis may be present. At times, the movements may consist of rapid and repetitive retractions of the head. The trunk may be literally twisted into many fixed positions that may appear bizarre.

Corticospinal tract findings may be evident in children who have choreoathetosis. On pathologic examination, the brains of these children may reveal large areas of patchy necrosis of the cortical laminar pattern, venous congestion in the cortex, ventricular dilatation, and accompanying white-matter loss that may be related to demyelination and central necrosis. Fibrosis in the meninges also may be present. Both cortex and basal ganglia may be jointly involved in these patients. Cortical lesions associated with necrosis in areas adjacent to the ventricles may be the result of occlusion of the vein of Galen. Obstruction of this major vessel triggers a chain of events, including rupture of blood vessels, primarily veins, with ensuing multiple hemorrhages in the areas served by the branches of the internal cerebral veins. The hemorrhages result in subependymal necrosis and subsequent pathologic dilatation of the lateral ventricles and associated atrophy of the basal ganglia. If obstruction is extremely widespread, the internal capsule may be involved, and further symptoms and signs of corticospinal tract involvement arise.

In one report, patients with severe athetoid cerebral palsy originating perinatally were divided into two groups neuropathologically: the “globo-Luysian group” and the “thalamoputaminal group.” The major abnormal sites in the globo-Luysian group were the pallidum and subthalamic nucleus, and in the thalamoputaminal group, the thalamus and putamen. The causative pathologic condition in the globo-Luysian group was primarily severe perinatal jaundice, and the cause in the thalamoputaminal group was predominantly neonatal asphyxia. The patients in the thalamoputaminal group demonstrated lower mental ability and suffered from more intractable convulsions than those in the globo-Luysian group. In the globo-Luysian group, rigidity and spasticity were frequently demonstrated, with fluctuation of athetoid movements, whereas in the thalamoputaminal group, various abnormalities of muscle tone and rather restricted athetosis were observed [Hayashi et al., 1991].

MRI studies in 22 children with athetotic cerebral palsy frequently revealed high-intensity areas in the thalamus and putamen in T2-weighted images. Of 16 children with known perinatal asphyxia, 14 had lesions in the basal ganglia, thalamus, and/or cerebral white matter. MRI findings were normal in 7 of the 22 children [Yokochi et al., 1991].

Hypotonic (Atonic) Cerebral Palsy

Infants with hypotonic cerebral palsy almost always have associated leg weakness. Although hypotonic, the arms may manifest near-normal strength and coordination. In the past, this combination of clinical findings led to the use of the term atonic diplegia to describe such children.

Diagnosis is difficult because of the plethora of diagnostic possibilities. Most children with generalized hypotonia have so-called central hypotonia (see Chapter 5), resulting from inadequate control of the motor pathways and subsequent disruption of gamma loop function. Others, with absent or hypoactive deep tendon reflexes, may have involvement of the lower motor neuron unit (i.e., anterior horn cell, peripheral nerve, neuromuscular junction, muscle). Extrapyramidal (choreoathetotic and dystonic) cerebral palsy may be preceded by a hypotonic phase.

Atonic cerebral palsy is relatively uncommon, compared with other forms of cerebral palsy; it often is associated with slow attainment of motor milestones and the presence of normal or hyperactive deep tendon reflexes. Children with atonic cerebral palsy, when suspended while held under the arms, flex both legs at the hips (Förster’s sign).

Although, in the past, it has been thought that muscle tone almost always increases with maturation in this form of cerebral palsy [Ingram, 1964], experience has taught that in a sizable number of cases, spasticity does not develop, but the child remains hypotonic.

The causes leading to this condition and the associated anatomic location of brain involvement are unknown. It is through their effect on the gamma motor neuron that portions of the central nervous system (e.g., motor cortex, thalamus, basal ganglia, vestibular nuclei, reticular formation, cerebellum) modify tone, with ensuing hypotonia.

Ataxic Cerebral Palsy

The least common form of cerebral palsy is the ataxic form. It sometimes coexists with spastic diplegia [Hagberg et al., 1975]. This form usually is associated with other motor abnormalities; however, the diagnosis is applied only when the predominant manifestation is cerebellar dysfunction. Patients with ataxic cerebral palsy may have impairment of intellectual ability, but they are rarely grossly delayed [Clement et al., 1984]. Motor difficulties often are not apparent until late in the first year of life. Early manifestations include hypotonia, truncal ataxia with sitting, dysmetria, and gross incoordination. The motor involvement results in delayed attainment of motor skills; independent walking may not occur until age 3 or 4 years, and then may be performed only with great difficulty and frequent falling. Compromise of writing skills and other skills that demand good fine motor coordination often adversely affects educational endeavors.

Examination often reveals nystagmus, dysmetria, hypotonia, and a wide-based gait. The result on Romberg testing with the eyes open is positive. Likely sites of involvement are the cerebellum and adjacent brainstem.

Because of the large number of conditions associated with ataxia, the clinician must exclude conditions in which ataxia predominates in early childhood (see Chapter 67). Ataxia, especially if accompanied by mental retardation, may not be properly included among cerebral palsy conditions but may be the result of one of many inherited conditions [Hagberg et al., 1984].

The pathologic features of ataxic cerebral palsy are poorly defined and inconstant. Discussion of these features is confounded by the fact that total absence of the vermis may not give rise to cerebellar symptoms in certain congenital conditions, whereas aplasia of the vermis may be associated with nonprogressive ataxia [Bordarier and Aicardi, 1990]. Cerebellar hemispheric lesions may or may not be present in patients with ataxic cerebral palsy. The lack of correlation of evident structural changes with functional impairment is emphasized by CT studies. In one report, CT evaluation of patients with ataxic cerebral palsy revealed that the posterior fossa was normal in 38 percent and abnormal in 28 percent. By contrast, the cerebral hemispheres were abnormal in 55 percent of the patients [Miller and Cala, 1989].