Cerebral Palsy and Static Encephalopathies
Robert S. Rust and David K. Urion
By convention, the cerebral palsies (CP) are nonprogressive disorders of tone, strength, movement, and posture due to central nervous system (CNS) injury, the consequences of which become apparent in infancy. The CNS lesions variously involve pyramidal (cortical, subcortical, brainstem, spinal cord), extrapyramidal, or cerebellar motor systems. A cerebral palsy (CP) is a static encephalopathy (SE) in which motor dysfunction must be present, although individuals may also manifest disorders of intellect, attention, memory, sensory, autonomic, and other neurologic modalities. They may also be at risk for epilepsy and for dysfunction of respiratory, gastrointestinal, and other nonneural systems.1-6
Cerebral palsies are a subgroup of SE, a category that also includes individuals whose static CNS injury may involve various patterns of intellectual dysfunction unaccompanied by central motor system deficits. Where only one or a few specific relatively mild cognitive modalities are impaired, the qualifier learning disabled may be applied, whereas more severe conditions affecting many or all cognitive domains suggests the qualifier intellectually disabled rather than the older term mentally retarded. Limitations of variable degree in the social-pragmatic functions of daily life may or may not be found in individuals with CP.
The combination and degree of deficits in individuals with SE or the large subgroup comprising CP is dependant on the location and extent of underlying CNS injury. The clinical pattern is often predictive of the site of lesions and may be predictive of underlying cause. However, the deficits of most individuals with CP or SE remain of uncertain pathogenesis, although rapid progress in the elucidation of genetically determined developmental disorders is reducing this uncertainty and replacing these generic labels with specific conditions. The importance of labels is that they designate cause with increasing accuracy. The increasing specificity of labels that should be permitted to replace the generic labels of CP or SE results in increasing accuracy of formulation of heritability, risks, prognosis, and treatment.7-9 Postnatal neural development may impart a pseudoprogressive appearance to the static deficits of CP, or of conditions within the wider spectrum of SE.3,4,7 It is important to note that despite the possible infantile worsening of manifestations, most children with CP will experience, at varied rates and degrees, improvement over the course of their development.3,8,9
The incidence of CP is approximately 0.1% to 0.25% of all live births, with little international variation among countries with modern medical facilities.10,11 Modern neonatology has greatly increased the survival of very low birth weight babies, whose risk for CP is approximately eight-fold greater than for larger neonates.12 Interestingly, increases in utilization of electronic fetal monitoring and cesarean section rates, advances in neonatal management, and declining rates of acute neonatal encephalopathy have not appreciably altered CP prevalence in term infants. In fact, the prevalence and severity of CP in term infants may have increased, possibly due to increased survival of very ill neonates.11,13,14
These data place in question the magnitude of the effect of presumed perinatal hypoxic-ischemic stress in increasing risk for CP. The uncertainty is in large part the result of a lack of a reliable biological marker for any of the several possible types of hypoxic-ischemic encephalopathy (HIE) to which the neonate is potentially subjected and the difficulty that exists concerning identification of the timing, degree, and duration of such stress. Neonatal encephalopathy and other possible indices of hypoxic-ischemic encephalopathy (HIE), such as acidemia, seizures, and so forth, may result not only from HIE, but also from inherited metabolic disease, intrauterine infectious or vascular events, developmental brain anomalies, and so forth.15,16 The best available data suggest that perinatal hypoxic ischemic stress may account for 6% to 28% of all cases of CP. More than half of all term infants who experience severe neonatal encephalopathy may develop CP.12,17
Determination of the efficacy of neonatal interventions that may prevent or ameliorate CP (eg, acute mild brain cooling) will require refinement of clinical and biologic markers for the various subtypes of HIE (hypoxemic, ischemic, hypoxic-ischemic, asphyxial; each further qualified by developmental maturity at birth, time of onset, intrauterine/peripartum duration) that set specific HIE syndromes apart from other causes of neonatal encephalopathy.15,16,18 It remains particularly unclear what role HIE may play in the leukencephaloclastic or hemorrhagic forms of CNS injury that are the most commonly encountered structural abnormalities found in very low birth weight infants who develop CP.
Various other risk factors for CP have been identified. These include African-American ancestry, absence of prenatal care, and maternal smoking. The increased rate of prematurity associated with these conditions may in part explain the elevation of risk, although mechanisms of injury are otherwise little understood. Other important and incompletely understood risk factors include male sex, intrauterine growth retardation, maternal chorioamnionitis, insulin dependant diabetes, hyperthyroidism, and epilepsy. Postnatal causes of cerebral palsy include kernicterus, infection, intoxication, and trauma.2-5,17,19,20
The National Collaborative Perinatal Project (NCPP), which evaluated the outcome of 40,000 live births between 1959 and 1966, somewhat demonstrated that cerebral palsy developed in only a minority of neonates who had manifested Apgar scores of 3 or below during the first 15 minutes of life. As markers and definitions of the various forms of hypoxicischemic encephalopathy (HIE) became more refined, it remained surprising that evidence for perinatal HIE was found in less than 15% of NCPP children who ultimately developed CP. The Western Australia Cerebral Palsy register, which considered infants born between 1975 and 1980, could assign HIE as the most probable cause of CP in less than 10% of the infants. The Cummins study of all normal birth weight live-birth infants in four northern California counties from 1983 to 1995 could assign HIE as the probable cause of ensuing cerebral palsy in only 6% of cases. Thus, other, often unknown causes appear to be of greater statistical importance.
Conventionally, the cerebral palsies are sub-classified on the basis of the type and distribution of the predominant motor findings. The subgroups include hemiparetic (HP), double hemiparetic/quadriparetic (QP), diplegic (DP), extrapyramidal (EP), ataxic (ATx), and hypotonic/atonic (Hyp) cerebral palsies.2-4,19,21 The groups are not entirely discrete from one another and the terminology is not universally standardized.
HEMIPARETIC CEREBRAL PALSY
Hemiparetic cerebral palsy (HP CP) is usually found in children who have experienced large vessel (especially middle cerebral artery, left more commonly than right) strokes.3,19,22,23 In approximately half of such cases the stroke is thought to have occurred prior to delivery, while in the other half they are thought to have occurred in the perinatal interval. The latter cases may be identified perinatally upon the basis of contralateral hand or arm clonic seizure activity occurring during the first few days after birth. Weakness and encephalopathy are more likely to be present in the perinatal interval where multiple large artery territories (unilaterally or bilaterally) are found to be involved. The resulting hemiparesis is often not apparent until 4 to 8 weeks later.
The clinical course is one of spastic hemiparesis (arm > leg > face) that very gradually improves. Comparative stunting of the growth of the affected limbs (especially arm and hand) ensues in proportion to weakness. A very helpful clinical sign is the finding of a smaller thumbnail on the affected as compared to the unaffected hand. Cortical sensory abnormalities may be found in older children.24 A visual field cut may be detected (ipsilateral to the hemiparesis) although even if found this often improves within the first year of life.2,3,5 Epilepsy (usually localization related seizures, often partial-complex) develops in at least one-third of these full-term infants. Onset is typically within 2 to 10 years after birth and may be associated with mental retardation, the severity of which correlates with difficulty controlling seizures.1,5,8 In individuals who do not have epilepsy, intellect is well preserved in as many as two-thirds of children with HP CP.
DOUBLE HEMIPARETIC CEREBRAL PALSY/SPASTIC QUADRIPLEGIA
The designation quadriplegic cerebral palsy (QP CP) is the commonly employed term for infants who actually manifest double hemiparetic CP (DHP CP). Whereas all four limbs are involved, one side of the body manifests greater degree of spastic weakness than the other and on each side the arm is more involved than the leg or face. This is the form of CP that is most commonly associated with birth asphyxia of term or near-term infants. It may also be found in infants who experienced bilateral large vessel strokes. In such cases, as with bilateral asphyxial insults, epilepsy, motor, and intellectual deficits are significantly more likely and severe than in individuals with HP CP.1,3
Bilateral spastic rigidity is a characteristic finding, with associated clonus, hyperreflexia, and asymmetric scissoring of the legs. Over time contractures tend to develop, rendering care, such as diapering, difficult. In severe cases there is little movement of the limbs. Supranuclear bulbar palsy or injury to brainstem and cerebellum may result in cranial nerve abnormalities and impairments of coordination, breathing, swallowing, and vision. The deficits may be due to selective neuronal necrosis of particularly vulnerable neurons due to various forms of hypoxicischemic encephalopathy (HIE) or to acute severe hypoglycemia. Because of the large volume of brain that may be injured in DHP CP, intellectual deficits are often marked. Complications of DHP CP often include drooling, feeding problems, inanition, aspiration pneumonia, constipation, and significant risk for bedsores. Head turning may evoke opisthotonus and decerebrate posturing, which may disturb onset or maintenance of sleep.3-5,7,8 The combination of deficits results in greater risk for early death in children with QP CP.25
Epilepsy is found in at least half of these children.1,3 Intermittent irritability of unclear etiology is often encountered. Care is aimed at prevention or treatment of the complications noted above. Common surgical interventions include placement of feeding tubes and orthopedic intervention to improve function. Medical management includes treatment of epilepsy as well as prevention of aspiration, inanition, and osteopenia. Nutritional approaches should scrupulously avoid excessive weight gain, which may further compromise movement, increasing risk for aspiration, bedsores, and other complications. Muscle relaxant medications may prove useful, although they often do so at the expense of alertness. Benzodiazepines may dampen the sleep-onset dystonia or posturing that interferes with sleep. Asymmetrical leukoencephalomalacia with acquired microcephaly is the most common pathologic finding. Involvement of forebrain deep gray tissues is the cause of associated dystonia. In milder cases, sclerosis may largely be confined to the cortical mantle, whereupon the clinical findings are largely pyramidal (spastic weakness) rather than extrapyramidal.
DIPLEGIC CEREBRAL PALSY
Spastic diplegia (SD) is the most common form of cerebral palsy (CP) encountered after premature birth, accounting for as many as 80% to 90% of cases. Spastic diplegic CP prevalence has increased in association with increased survival of very low birth weight children.26 Legs are more strikingly involved than arms and ankle clonus is an early important sign of the underlying leukoencephalomalacia. In milder cases, toe walking associated with ankle clonus may be the first clues to diplegic (DP) CP. Although the motor involvement of arms tends to be of lesser degree than legs, fine motor dysfunction of the hands may impair daily living activities. Even with mild arm involvement, a forearm clasp-knife response to passive rotation is usually found.27
Periventricular leukomalacia (PVL) is the characteristic pathologic landmark of SD CP, although injuries to cerebral and cerebellar gray matter are recognized with increasing frequency. Intraventricular hemorrhage (IVH) with ventricular enlargement may be associated with SD CP of greater degree. Grade IV IVH may be associated with severe motor and intellectual abnormalities, with the combination of QP CP and SD CP.27 There is evidence that low-birth-weight (LBW) male infants are at greater risk for PVL and for IVH than LBW girls.28 There is increasing evidence that antenatal intrauterine infection and the ensuing inflammatory response may, by several mechanisms, increase the risk for SD CP as well as for associated visual defects (see Chapter 58).29
Problems associated with SD CP include abnormalities of intellect, vision, and feeding, though these tend to be milder than those encountered in children with QP CP. Drooling may be troublesome, which together with gait abnormalities may lead to underestimation of the intellect of children with SD CP, which in many instances may be normal. Orthopedic intervention may prove beneficial in improving stance and gait in children with SD CP. Spastic diplegia CP may be associated with diminished limb growth and stature and is occasionally complicated by ataxia.3,5-8,19
EXTRAPYRAMIDAL CEREBRAL PALSY
Extrapyramidal (EP) or dystonic cerebral palsy (CP) is most commonly manifested by dystonia or by involuntary and uncontrollable slow writhing movements (athetosis), particularly of the distal limbs. In more severe cases shoulder and trunk dystonia or abnormal movements may be found. Athetosis includes rotation of the limb about the long axis in association with choreic (dancelike) intermittent extension of fingers and toes. To a lesser degree, asymmetric chorea of the face and limbs, sudden, fleeting, nonrepetitive postured movements, may be intercalated with the athetosis. The various postures may at times coalesce into a sustained peculiar dystonic posture, At times, sudden shocklike myoclonus (much more rapid and less graceful than chorea) may be observed, as well as briefly sustained tremors.
Extrapyramidal system dysfunction tends to become increasingly apparent late in the first year of life, as abnormal patterns of movement tend to be activated by voluntary motor activities such as reaching, crawling, and walking. Postural stability and gait are often greatly impaired. Large scale and bizarre dystonic patterns of movement may be observed. Speech impairment may be prominent in extrapyramidal (EP) CP, probably due to the complexity of demands that speech makes on the pyramidal, extrapyramidal and cerebellar motor systems, as well as cortical speech areas. Attempted speech may have a quality of strangulation, explosive moments, and great variability in pitch and speech meter. Laughter or crying may activate complex vocal dysfunction.
The various motor abnormalities of EP CP vary in intensity over time, tending to be more prominent with stress, fatigue, anxiety, frustration, embarrassment, or intercurrent illness. Attempts of affected individuals to restrain extraneous motor activation often worsen EP abnormalities. Fine motor function and self-care skills may be difficult or impossible to perform. The EP CP movement abnormalities disappear with sleep.
Examination may disclose variable tone ranging from rigidity of the “lead pipe” variety to hypotonia as well as clonus and hyperactive muscle stretch reflexes. Associated abnormalities may include epilepsy, learning disorders, or mental retardation. Milder forms of EP CP may manifest modest degrees of choreoathetosis or effort-induced dystonia. In its severest form, EP CP may cause exceeding impairment of movement, posture, and tone. Forceful head extension (retrocollis) in association with bizarre twisted posturing of the trunk may occur. Predominantly choreoathetotic or dystonic-dyskinetic CP is the characteristic result of kernicterus with injury to the pallidum and subthalamic nucleus and a characteristic pathology, termed status marmoratus. Hearing impairment and ataxia are common concomitants.
Predominantly dystonic CP most commonly occurs as a consequence of asphyxia with injury to the thalamus and putamen. Some individuals will have a mixture of manifestations and more widespread abnormalities of brain may be found, including injuries to cerebral and cerebellar gray or white matter or brainstem.3,5,8 It is particularly important to carefully exclude genetically determined conditions such as metabolic disturbances when evaluating children thought to have EP CP.30
HYPOTONIC/ATONIC CEREBRAL PALSY
Diminished or absent muscle stretch reflexes, marked leg weakness, and arms more hypotonic than weak and displaying relatively normal coordination characterize the uncommon condition called hypotonic (Hyp) cerebral palsy (CP). This syndrome has also been termed central hypotonia, whereas infants are described as floppy. The Förster sign on examination is characteristic: evocation of hip and leg flexion by holding the infant in vertical suspension with the examiner’s hands under the armpits. Head lag is prominent when the infant is pulled from recumbency to a seated position. Sometimes this condition precedes the onset of findings of extrapyramidal (EP) CP or (rarely) double hemiparetic (DHP) CP. One anatomically specific entity that may be distinguished is that of axioproximal weakness resulting from parasagittal brain infarction, an entity that may result from marked perinatal hypotension, such as may result from placental abruption or uterine rupture. Perinatal brain imaging usually discloses the “watershed infarction” pattern, sometimes with associated hemorrhage into the ischemic parasagittal tissues. In more severe cases, brainstem hemorrhagic infarction may occur, producing cranial nerve abnormalities.3,5 Maternofetal hyperthermia during the 21st to 28th day of gestation has been associated with the development of neural tube defects and infantile manifestation of Hyp CP.
Where Hyp CP is considered, care must be taken to exclude lower motor neuron diseases (diseases involving muscular, nerve, or anterior horn cells), as well as metabolic, degenerative, or other genetic conditions. Down syndrome is among the more common causes of infantile hypotonia. Other important considerations are such syndromes as Angelman, Coffin-Lowry, Miller-Dieker, Prader-Willi, or Zellweger. Each of these has characteristic findings on physical examination. Speculation as to the cause and anatomic locus of hypotonic CP has not produced any widely accepted conclusions. Very gradual improvement to normal strength may be observed, possibly associated with a lesser degree of residual hypotonia. In other instances, the abnormalities may be quite persistent. In such cases severe developmental abnormalities of the brain may be found, in which case the diagnosis should be changed to reflect the specific type of malformation.
ATAXIC CEREBRAL PALSY
Although it is commonly associated with signs of other forms of CP, such as diplegic (DP) CP, ataxic (Atx) CP is diagnosed where the evidence of cerebellar system dysfunction is predominant. Ataxia usually becomes apparent only near the end of the first year of life, with hypotonia, axial and appendicular ataxia, and nystagmus. Gross and fine motor skill development may be markedly delayed and slow gait development may be accompanied by frustrating persistence of wide base and frequent falls. Romberg test positivity also persists for a long interval in early childhood. Ataxic CP is a diagnosis by exclusion. Important differential considerations include Angelman syndrome and ataxia-telangiectasia. Where this syndrome is associated with mental retardation, variation in severity, or progression, more likely diagnoses are various heritable developmental, degenerative and metabolic conditions. Brain imaging discloses abnormalities of forebrain in about half the cases of ATx CP, while cerebellar abnormalities are less common. As noted above, ATx CP findings may be admixed with those of DP CP in some toddlers.30
The most important neuropathologic correlates of various types of cerebral palsy (CP) have been noted above. To these observations it should be added that roughly one-third of children diagnosed with cerebral palsy are found to have some disorder of cortical migration. It is likely that additional careful studies will demonstrate that perhaps a majority of children with CP have underlying genetically determined developmental disorders.
MANAGEMENT OF CEREBRAL PALSY
The diagnosis of cerebral palsy (CP) is made in children with static central nervous system-mediated motor deficits for whom a more specific diagnosis cannot be made. Initial physician responsibilities include assuring that an appropriate range of diagnostic tests has been performed. Among these, imaging studies may be the most important tests with regard to proper classification, within the context of history and examination.2
The history and examination may suggest other appropriate tests, as is indicated in the preceding discussion. Genetic testing should be undertaken in order to provide appropriate counseling concerning risk of recurrence in subsequent pregnancies. The extent of such testing may best be defined by genetic consultation. Electroencephalograms (EEGs) are commonly helpful in evaluation of individuals with CP whose clinical evolution suggests that epilepsy may have developed, as it does in approximately one-third of individuals with CP. Other forms of testing may be required to characterize and treat as needed, problems with learning, language, coordination, mood, behavior, as well as vision, hearing, and other sensory functions.
Following diagnosis it is important to alleviate potential maternal guilt regarding potential etiologies resulting from pregnancy related events and to aid the family in adjustment to caring for a child with a chronic condition (see Chapter 123).
Issues of care including optimizing functionality and mobility, and care coordination are discussed in Chapter 124. Physical and occupational therapy should be provided on a consistent basis, with education and assistance for family members so that they can become active participants in the ongoing therapy. Variously modified recreational therapies involving activities such as sports and dancing may prove very helpful in the treatment of CP. Such activities entail enlisting the positive attitudes of patients and their families in a setting that provides fun and encouragement. The positive attitude and determination of the individual with CP is even more important than particular therapeutic approaches.
Attention should be paid to posture and seating, particularly when assistive devices are required, such as wheelchairs or standers. Adjuvant devices such as splinting, either diurnal or nocturnal, may be required in certain instances. If spasticity cannot be treated by more conservative means, other interventions may be brought to bear. The use of botulinum toxin injected into selected muscle groups has demonstrable efficacy for relieving spasticity so that physical therapy can be more successful. Other procedures, such as phenol injections, can be used in a similar fashion. The relief from these procedures is transient, but beneficial in certain instances. They should be administered by individuals well experienced with their use, particularly in light of the tendency for antibodies to botulinum to develop over time, thus limiting its efficacy.
In some individuals, continuous administration of intrathecal baclofen using an implanted pump can provide relief from spasticity. This can allow a precise titration so that a child can be left with sufficient muscle tone for ambulation but with reduced spasticity to avoid contractures. In other individuals, selective severing of the afferent dorsal rootlets in the lumbosacral region (usually L2 to S2) through a dorsal rhizotomy can produce relief, particularly when the spasticity involves legs more than it does arms. In both instances, careful selection of patients by a center well versed in the techniques is essential for good outcomes.
Attention may be directed to correcting problems with speech and drooling, and with tracheopharyngeal, pulmonary, gastrointestinal, and urinary function. These are problems that are important for the daily living, comfort, and dignity of individuals with CP. Careful collaboration between specialists, including physical and occupational therapists, orthotists, orthopedic surgeons, otolaryngologists, gastroenterologists, physiatrists, neurologists, neurosurgeons, and others, is often crucial for the achievement of the best possible outcomes.
With the diagnosis of CP, the treating physician should provide a prognostic estimation couched within appropriate limits based on adequate understanding of the breadth of possibilities for the specific CP syndrome. This estimation should be revised as the child grows and develops.
The psychological burdens of the disorder can be great for families and children alike. Appropriate psychological support, and vigilance for its implementation, is often needed. It is improper in most instances to claim to fully understand what parents are going through. This is particularly true in instances where the needs of a child are so large that institutionalization is the appropriate care choice; this can be a very difficult decision for family and child. Advocacy for access to appropriate education is part of the role of the clinician caring for a child with cerebral palsy. Federal and state laws in the United States guarantee a child a free and appropriate public education, but many factors can conspire against this. The clinician’s role of advocacy can be very useful for families.
Life expectancy for persons with CP varies in relation to the type of CP and severity of motor deficit as well as certain associated nonmotor deficits.25 Premature death, which may occur within the first 5 years of life, tends to be confined to individuals with double hemiparetic/quadriparetic CP severe enough to prevent independent rolling, and especially those infants requiring ventilatory support. Gastrointestinal reflux or epilepsy may also reduce life expectancy. Death from these various causes may result from aspiration pneumonia, bedsores, inanition, or status epilepticus. It is important to emphasize that modern approaches to care of individuals with CP has reduced the risk for premature death and that most individuals with CP, including severe forms, survive into adulthood.25 Although parents must be prepared for the possibility of serious complications in individuals with CP, it is a disservice to inappropriately suggest that a particular child “will not live long.”
See references on DVD.