What is the History of Cerebral Palsy?

Cerebral Palsy (CP) was first described by William Little, an English Physician in the 1860’s. CP was affectionately called “Little’s Disease”. He described children that are now characteristic of symptoms of ‘Spastic Diplegia’ which is due to birthing complications, specifically birth asphyxia. Birth asphyxia implies some sort of dysfunction resulting from a lack of oxygen supply to the baby's tissues during the birth process. In 1897, Sigmund Freud described CP with associated mental retardation, visual disturbances, and seizures that resulted from issues beyond birth complications. In the 1980’s, research confirmed that Freud’s description of birthing complications accounted for only a fraction of CP cases. (Cummins, Nelson, Grether &Velie, 1993; Nelson, 1996.

 What is the Etiology of CP?

Two major studies of children with cerebral palsy have been reported in which their labour, delivery and neonatal records were in agreement in finding that, for 90%-94%, their disability could not be related to intrapartum (during labor, delivery or childbirth) hypoxia. This does not mean that in 6%-10% of labours hypoxia beginning in labour is the cause of cerebral palsy (Shields & Schifrin, 1998; Nelson & Ellenberg, 1986). In cases in which severe intrapartum hypoxia was documented, it may not have been preventable and earlier delivery may not always have been possible. Pre-existing neurological deficit can contribute to intrapartum hypoxia, or be associated with chronic hypoxia (Soothill, 1987).

How do you diagnose CP?

A diagnosis of cerebral palsy is initially made by a physical examination of muscle tone, movements and reflexes (Badawi, 1998). Here physicians look at the delay in developmental milestones of motor function such as sitting up, walking, reaching and head control (Yokochi, 1993). The literature is inconsistent in diagnosing CP, however the range tends to lie between 6 to 24 months of age. A diagnosis of CP is typically based on the exclusion of other neurological diseases and disorders. For example physicians will rule out temporary motor impairments due to closed head injuries, or spinal cord injury. Diagnostic tests may include various testing methods including blood tests and chromosome analysis which is helpful in diagnosing hereditary conditions that may influence the parents' future child-bearing decisions.

What technologies are used to diagnose for CP?

Other neurological examinations include, x-rays, electroencephalogram (EEG), gait lab analysis (to evaluate the walking pattern of the child, and magnetic resonance imaging (MRI) (Nelson & Ellenberg, 1986). These tests may provide evidence of hydrocephalus (an abnormal accumulation of fluid in the cerebral ventricles), and they may be used to exclude other causes of motor problems. Typically, children with cerebral palsy do have incidences of brain scars, cysts, and other changes which tend to show up on scans more frequently than in typically developing children (Wood et al, 2000). Therefore, when a scar is seen on a CT scan of the brain of a child whose physical examination suggests he may have cerebral palsy, the scar is additional evidence indicating that the child is likely to have motor problems in the future (Wood et al, 2000).

What is the prognosis for CP?

The prognosis for CP before one year of age is often a guess. Beyond two years, a practitioner is able to make a better prognosis. For example if child is 4 years of age and not sitting, or 8 years and not walking, results tend to indicate a poor prognosis, versus a child walking by age 3 which presents with a good prognosis (Kuban & Leviton, 1994).

What exactly is CP?

Cerebral Palsy (CP) is and umbrella-like term used to describe a group of chronic motor disorders . The cerebral palsies (CP) are a heterogeneous group of non-progressive motor disorders of the developing brain(Badawi et al., 1998). Its onset is usually before five years of age . It is characterized as a non-progressive, permanent disorder that is a result of a direct insult to the cerebrum. The period from 26 to 34 weeks' gestation is critical for neurodevelopment. The patterns of brain injury, and therefore imaging features, are similar in fetuses and neonates, and late investigations cannot separate brain injury occurring in utero from perinatal or postnatal events (Ellenberg & Nelson, 1988). Magnetic resonance imaging of limited numbers of cerebral palsy patients suggests that the adverse neurodevelopmental event occurs prenatally in up to 50% of cases (Ellenberg & Nelson, 1988).

Therefore, at a critical time, either a single factor or a combination of factors can contribute to or can cause damage to the developing brain. All factors have not yet been identified. However, a large number are known, and their most influential times of occurrence are being identified.

What is understood of the Neurology of CP?

There is no single brain lesion that is distinctive of cerebral palsy, as might be anticipated from the variety of causes. Many different lesions are found, singly or in various combinations. In general, the lesions tend to be bilaterally symmetrical and are characterized by loss of neurons and increase of glial cells and fibers (gliosis) (Mutch et al., 1992). Usually there is obvious loss of tissue in one or more of four sites: the cerebral cortex (resulting in spastic CP), the central white matter of the cerebrum (resulting in spastic CP), the basal ganglia (resulting in athetoid CP), and the cerebellum (resulting in ataxic CP). In the cerebral cortex (spastic CP) the usual lesion is sclerotic microgyria (abnormal narrowness of the cerebral convolutions) (Mutch et al., 1992). This is the most frequent lesion in cases of spastic CP. In this lesion individual gyri or groups or gyri are shrunken and firm as a result of loss of neurons and an increase of glial tissue. The sulcal cortex is more severely affected than is the cortex over the gyral crests. In most but not all cases of cerebral palsy, clinically apparent abnormalities occur during the preceding pregnancy, delivery, or neonatal period (Mutch et al., 1992).

Brain injury in the premature infant consists of multiple lesions, principally germinal matrix-intraventricular hemorrhage, posthemorrhagic hydrocephalus, and periventricular leukomalacia (PVL) (Mutch et al., 1992). The last of these now appears to be the most important determinant of the neurological morbidity observed in survivors of birth weight less than 1500 g (Blair, 1993). Of these very low birth weight infants, 10% later exhibit cerebral palsy, and 50%, cognitive and behavioral deficits 1-5 The focal necrotic lesions of PVL deep in the cerebral white matter correlate well with the cerebral palsy, whereas the cognitive/behavioral deficits may relate to more diffuse white matter injury observed with PVL. (Blair, 1993)

Currently, fetal brain development cannot be monitored during pregnancy. Only examination of the brain at autopsy can identify the full extent of injury in some cases. In other cases of cerebral palsy no pathological lesion is identifiable. There are several neuropathological lesions leading to cerebral palsy which include mal-developments (cerebral dysgenesis), germinal matrix-intraventricular haemorrhage, cerebellar haemorrhages, grey matter damage, white matter damage (periventricular leukomalacia), hypoglycaemic neuronal injury, thromboembolic injury (including vasculitis that are secondary to infection) and kernicterus (disorders due to jaundice) (Blair, 1993) .

The immature brain has only a limited number of ways of responding to acute or chronic injury and these essentially consist of neuronal and white matter loss and glial proliferation. These changes occur over many days and weeks. They may later be modified by secondary changes such as post-haemorrhagic or post-inflammatory hydrocephaly or white matter atrophy (Blair, 1993; Blair & Stanley, 1988) . By the time a child presents with cerebral palsy during the first years of life, the neuropathological effects of any hypoxic-ischaemic injury or other injury will have become modified by these changes and by further postnatal brain development (Blair & Stanley, 1988) . Even if that child was to die during its first year and the brain was made available for expert examination, it would be impossible, on this basis, to determine the exact timing of the original neurological insult. Recent suggestions that the condition of the placenta could be used as a surrogate marker of antepartum (pre-labour) fetal injury are based largely on anecdotal argument and have not yet been fully evaluated; such techniques are fraught with observer and sampling bias (Blair, 1993; Blair & Stanley, 1988) .

At preconception there are several variables that can have significant affect. For example biological aging of the parents, that is if the parents are over the age of 35. Conversely, biological immaturity, that is, if the parents are very young can have an effect. It has also been found that exposure to environmental toxins can cause significant problems. The genetic background of the parent(s), including genetic disorders can have important implication. The medical state of the parent(s), including malnutrition, or the possibility of metabolic disorders is important. As well as exposure to radiation can cause significant damage (Blair & Stanley, 1988).

During the first trimester of pregnancy (0 to 3 months) , there are several factors that can affect the developing fetus. The mothers’ endocrine functioning, specifically her thyroid function, and/or whether there are issues with progesterone insufficiency.
The nutritional state of the mother includes: malnutrition; vitamin deficiencies; and amino acid intolerance. Toxins such as alcohol, drugs, poisons, and smoking can all significantly alter the developing fetus (Nelson & Ellenberg, 1986).

In the second trimester of pregnancy (3+ to 6 months) , infection such as rubella, toxoplasma (parasite), HIV, syphilis, chicken pox, or subclinical uterine infection can severely affect the developing child. Additionally, the placental pathology including any incidence of vascular occlusion, fetal malnutrition, chronic hypoxia, or growth factor deficiencies, can cause serious damage. (Nelson & Ellenberg, 1986).

In the third trimester of pregnancy (6+ to 9 months) , there is the possibility of early labor. As a result many complications arise to an infant of prematurity and low birth weight. Blood factors such as Rh incompatibility and jaundice have been implicated in cases of CP. As well as cytokines, which causes neurological tissue destruction (Nelson & Ellenberg, 1986). Other factors that have been implicated in CP include hypoxia, causing placental insufficiency and perinatal hypoxia. Other factors include infection such as listeria (bacterial infection), meningitis, streptococcus group B, septicemia, and chorioamnionitis (inflammation process) (Woods, 2000).

During the perinatal period and infancy (first 2 years post natal) , there are several incidences that can cause brain damage. Complications with the endocrine system such as hypoglycemia and/ or hypothyroidism. Also hypoxia such as perinatal hypoxia or respiratory distress syndrome (Nelson & Ellenberg, 1986). Infections can include meningitis and encephalitis. With late childbearing and the use of infertility drugs, multiple births can cause complications. Postnatal trauma such as shaky baby syndrome and accidents (falling on head) can cause brain damage.

There are several theories that speculate the etiology of CP. Nevertheless CP is secondary to prenatal, perinatal, or neonatal insult; or is secondary to neuronal damage at the cellular level in the neurotransmitter or receptor systems. The global effects are the result of impaired communication between the brain, and the muscles decreased control of movements that causes poor motor coordination, balance, and abnormal movements. As a result, these motor difficulties are secondary to brain damage or abnormal brain development.

CP is a disorder with a spectrum of severity, ranging from mild disability to severally impaired. CP frequently is associated with other deficits. For example MR is associated in 60% of cases (Stanley, 2003; McLaren & Bryson, 1987). One-third of children who have cerebral palsy are mildly intellectually impaired, one-third are moderately or severely impaired, and the remaining third are intellectually normal. Mental impairment is even more common among children with spastic quadriplegia.

As many as half of all children with cerebral palsy have seizures (Singhi et al., 2003). In the individual who has cerebral palsy and epilepsy, this disruption may be spread throughout the brain and cause varied symptoms all over the body as in tonic-clonic seizures, or may be confined to just one part of the brain and cause more specific symptoms, as in partial seizures.

Neonatal and infantile seizures suggest underlying structural brain disease with the possibility of adverse motor consequences (Singhi et al., 2003). Although structural injury increases the likelihood of infantile spasms and later seizures, the most vulnerable group of children are those with quadriplegia and hemiplegia with pre-existing cortical involvement, seizures affecting 20% of cases (Singhi et al., 2003). Diplegic children infrequently develop seizures highlighting the relative sparing of the cortex.

Additionally there have been cases of children with CP with hearing and visual deficits (10-15%) (Mutch et al., 1992). In spite of improvements in obstetrical and neonatal care, the incidence of CP has not decreased. In almost 50% of cases, the cause of brain damage cannot be identified. Birth asphyxia is responsible for CP in only a small percentage, estimated to be around 5-10% of otherwise normal newborns with no other risk factors for CP (Ellenberg & Nelson, 1979). The various risk factors for cerebral palsy are summarized in table 1.

Prenatal	Perinatal	Postnatal
Other congenital malformations of the brain	Premature separation of the placenta	Asphyxia (secondary to choking/ drowning)
Congenital infections (rubella)	Hypoxic-Ischemic encephalopathy (permanent brain injury caused by lack of oxygen)	Head injury
Exposure to toxins/chemicals (drugs)	Cord Prolapse (cord slips through the cervix before the baby)	Brain infections (mennengitis)
Prematurity LBW	Dystocia (difficult labor)
Anoxia (lack of oxygen to the brain)
Multiple births

 

What are the symptoms of CP?

There are four symptoms of cerebral palsy. (1) Spastic, (2) Ataxic, (3) Athetoid, and (4) Mixed. Each symptom of CP affects various structural areas of the developing. The first type is Spastic CP. This affects the cerebral cortex including the corticospinal tract/ motor cortex , which functions to provide inhibition to the reflex. Presently, serious birth asphyxia is the most common cause of choreoathetotic movement disorders and often is associated with spastic quadriplegia and MR (McLaren & Bryson, 1987). Approximately, 50-70% of CP is comprised of this type. Spastic CP also known as hypertonic, that is an overabundance of tone, or sclerotic microgyria. Spastic CP is caused by lesions in the cerebral cortex and underlying central white mater of cerebrum (Bax, 1964). As a result of the lesions, there is too much facilitatory input from the spinal reflex causing spasticity.Another area of lesion is sclerotic microgyria. Here, gyri or groups of gyri are shrunken and become firm (Counsell et al., 2002). As a result, there is a decrease in neurons and an increase in glial tissue.Insult to this area causes muscle tone to be too high or too tight, which results in stiff and jerky movements, the individual has a hard time moving from on and difficulty letting go of an object with their hand.

The second symptom is ataxic cerebral palsy . This affects the cerebellum. Approximately 10% of CP is comprised of this type (Counsell et al., 2002). The cerebellum is the center for coordination and movement, resulting in balance and other finely tuned movements. The cerebellum slows down nerve impulses in order to organize cerebral impulses going to the skeletal muscles and thus confer coordination and organized movements. Insult to this area causes: hypotonia, disorders of balance, poor proprioception, ataxia, tremor, dysmetria, depth perception, wide gait, jerky movements (Counsell et al., 2002).

The third symptom is athetoid Cerebral Palsy. Kernicterus due to Rh incompatibility and subsequent hyperbilirubinemia was the most common cause of athetoid CP before the introduction of exchange transfusions (Counsell et al., 2002). Athetoid CP affects the basal ganglia. Damage to both the basal ganglia and the supplementary motor area are correlated with impaired performance on sequential tasks. Dysfunction of the basal ganglia appears to be that the balance between the two major pathways is disturbed: the result is either involuntary movements or impairments to motion. Impaired motions include lack of movement (akinesia), slowness of movement (bradykinesia), and the shuffling gait of Parkinson's disease (Miyahara & Mobs, 1995).

Approximately, 20-40% of CP are comprised of this type. It is also known as diskenetic, hypotonia, or dystonia. The basal ganglia is located deep within the cerebral hemispheres in the telencephalon region of the brain. It consists of the corpus stratium, subthalamic nucleus and the substantia nigra. The basal ganglia controls cognition, movement coordination, and voluntary movement s. The basal ganglia is the center related to posture, and coordinating movements including speech. Impairment to this area can result in dyarthria (Miyahara & Mobs, 1995). Often times, individuals are said to engage in the Athetoid Dance. This describes their inability and difficulty keeping weight on their feet. Damage occurs to the extrapyramidal motor system, pyramidal tract, & basal ganglia. Insult to this area causes akinesia, which is difficulty starting or stopping motion. This results in involuntary movements, rigidity, tremor, chorea writhing, grimacing, and fine motor problems (Miyahara & Mobs, 1995).

The fourth symptom is mixed cerebral palsy. Approximately, 10% of CP is comprised of this type. It involves both low and high tone Additionally, this involves two or more types of cerebral palsy. The most common combinations are athetodic-spastic-diplegic and athetoid–spastic-hemiplegic. The least common is athetoid-ataxic. However is possible to have a mix of all three (spastic-athetoid-ataxic) (Kuban & Leviton, 1994).

What parts of the brain are affected in CP?

In addition, there are other neurological structures implicated in CP. The frontal lobe is in charge of voluntary motion. The left lobe controls the motor movements involved in language (speech and writing). The right lobe is usually involved in non-verbal activities. Damage to one frontal lobe usually results in a person's inability to move the opposite side of his body. Moreover, damage to the frontal lobes can also cause the inability to initiate or respond to speech even though language can still be understood.

The last structure is the parietal lobe. The parietal lobe is a structure where sensory information, such as touch, pressure, muscles, temperature and pain, is processed. Damage to one parietal lobe usually results in a loss of sensation in the opposite side of the body as well as being unable to feel touch, temperature, and pain.

How is CP Classified?

The most frequent clinical syndrome, caused by lesions in the cerebral cortex and underlying white matter, is spastic paralysis (spastic cerebral palsy), which accounts for approximately 50% of all cerebral pasly cases (Miyahara & Mobs, 1995). Spastic CP can be classified into five groups: monoplegia, hemiplegia, diplegia, triplegia, and quadriplegia. The usual type of CP in these patients is spastic quadriparesis, especially that associated with dyskinesia.

The first type is m onoplegia which is quite rare. This is where one limb shows signs of spastic cerebral palsy. The most common type is diplegia. This is where spastic involvement is in two extremities on the same side of the body. As a result is only one side of their body. The other side functions normally. Here the individual is able to walk and run however shows a slight limp or awkwardness in their gait. Periventricular leucomalacia (PVL) denotes destruction or wasting of the white matter (Woods et al., 2000). The susceptibility of fetal brain to PVL varies according to gestational age, peaking at 28 weeks with a steep fall in both early postnatal death and PVL thereafter. PVL presents as diplegia and accounts for about 70% of CP in babies born before 32 weeks gestation and 30% of CP in term born babies-suggesting a common antenatal origin during the period of oligodendroglial activity and resultant myelination (Woods et al., 2000). Late third trimester insults tend to affect both grey and white matter structures, resembling the typical stroke patterns encountered postnatally.

The third type is hemiplegia. This results in bilateral lesions of the cortex or lesions to the white subcortical white matter. Periventricular hemorrhagic infarction in preterm infants, usually unilateral, results in hemiparesis in which the leg typically is more involved than the arm (Woods et al., 2000). Abnormalities of the middle cerebral artery result in congenital spastic hemiplegia. This is when either both legs have spastic involvement. Here only the legs are affected. As a result walking or running may be difficult. The upper body is not affected and the individual is able to hold themselves upright and have good use of their arms and hands. Hemiplegia is associated with late third trimester injuries. By contrast, the risk of bilateral brain injury increases with prematurity (Woods et al., 2000). A knowledge of the sequences of embryonic and fetal brain development establishes the timing of brain injury. The finding of disordered migration, such as lissencephaly or grey matter heterotopias, indicates damage occurring before 22 weeks gestation that disturbs normal neuronal migration (Scott & Jankovic., 1996). For example, children with unilateral hemiplegia have only minimal cognitive deficits, if any, but a high frequency of sensory deficits such as homonymous hemianopsia (blindness for half the field of vision in one or both eyes) (Scott & Jankovic., 1996) , deficits in stereognosis (recognizing objects by touch) and position sense, and a high incidence of epilepsy.

The fourth type is triplegia, which is quite rare. Here the individual has spastic cerebral palsy in three limbs. The most debilitating is quadriplegia. Here, spastic cerebral palsy affects all four extremities. The individual thus requires a wheelchair for mobility and has trouble speaking and eating. Children with quadriplegia have more severe cognitive deficiencies and epilepsy than children with other types of CP.

Are there associated symptoms related to CP?

Children with cerebral palsy have many problems, not all of them related to the brain injury. Most of these complications are nevertheless neurological. They include epilepsy, mental retardation, learning disabilities, and attention deficit-hyperactivity disorder (Scott & Jankovic., 1996) . Problems that occur less commonly include swallowing problems in children with spastic quadriplegia. Children with cerebral palsy may also develop hip subluxation (partial dislocation) or have problems with the gait (Scott & Jankovic., 1996).

What types of therapy are available?

Medical care is fragmented into many specialties that may include: neurology, orthopedics, phychiatry, opthamalogy, OT/PT, SLP, and behavioural therapy. Medical technology and research continuously moves forward and as a result it is difficult for physicians to keep up with latest research and techniques. Objectives of early intervention commonly address mobility, stability, positioning, adaptive, balance, coordination, and strengthening.  Popular treatment philosophies include Neuro-developmental Treatment (NDT). NDT is used by Physical Therapists to decrease spasticity, strengthen underlying muscles, and teach proper or functional motor patterns. A second popular treatment paradigm is Conductive Education (CE) which t eaches motor skills and independence in an educational setting. Other common therapies include occupational therapy and speech and language therapy.

What does the research say?

Current research is looking at several questions in improving knowledge on preventing and managing cerebral palsy. The first questions looks at what children with CP have in common. Researchers have recently observed that more than one-third of children who have cerebral palsy also have missing enamel on certain teeth. This tooth defect can be traced to problems in the early months of fetal development, suggesting that a disruption at this period in development might be linked both to this tooth defect and to cerebral palsy (Mutch et al, 1992).

Another area is looking at preventing insult to the developing brain. Scientists are also scrutinizing other events such as bleeding in the brain, seizures, and breathing and circulation problems that threaten the brain of the newborn baby. Through this research, they hope to learn how these hazards can damage the newborn's brain and to develop new methods for prevention. Researchers are also looking at how to control brain insults. Here scientists are exploring how brain insults such as hypoxic-ischemic encephalopathy (brain damage from a shortage of oxygen or blood flow), bleeding in the brain, and seizures can cause the abnormal release of brain chemicals and trigger brain damage (Mutch et al, 1992).

Additionally researchers are looking at preventing neonatal stroke. In related research, some investigators are already conducting studies to learn if certain drugs can help prevent neonatal stroke. Several of these drugs seem promising because they appear to reduce the excess production of potentially dangerous chemicals in the brain and may help control brain blood flow and volume. Earlier research has linked sudden changes in blood flow and volume to stroke in the newborn. Looking at prenatal and perinatal preventative measures (Mutch et al, 1992)..

Some scientists currently investigating this serious health problem are working to understand how infections, hormonal problems, and genetic factors may increase a woman's chances of giving birth prematurely. They are also conducting more applied research that could yield: 1) new drugs that can safely delay labor, 2) new devices to further improve medical care for premature infants, and 3) new insight into how smoking and alcohol consumption can disrupt fetal development (Mutch et al, 1992).

An important thrust of such research is the evaluation of treatments already in use so that physicians and parents have the information they need to choose the best therapy. Investigators are also working to develop new drugs and new ways of using existing drugs to help relieve cerebral palsy's symptoms. In one such set of studies, early research results suggest that doctors may improve the effectiveness of the anti-spasticity drug called baclofen (Mutch et al, 1992). A large research effort is also directed at producing more effective, nontoxic drugs to control seizures.

At this time, there are no clinically meaningful interventions that are able to successfully repair the existing damage to the areas of the brain that control muscle coordination and movement . The brain is constantly reorganizing structurally and functionally as it responds to stimuli and to injury. This ability to reorganize is referred to as neuroplasticity (Mutch et al., 1992). Here, all areas of the brain adapt to a change in any one area of the brain because of the wealth of neurological connections to and from each area. The period of most dramatic plasticity is during the first 2 years of life as the infant's brain becomes organized in response to its environment. At birth, most of the nerve circuits are in place anatomically but functional connections are awaiting stimuli. Plasticity is also challenged dramatically at any age when the brain responds to an injury (for example a developmental injury; head trauma; stroke or convulsion) (Mutch et al, 1992). There is no evidence that current obstetric practices can reduce the risk of cerebral palsy. The origins of many cases of cerebral palsy are likely to be antenatal. While obstetric interventions in the presence of signs of possible hypoxia may prevent fetal death, there is no evidence that they will limit the prevalence or severity of cerebral palsy.

The immature brain has only a limited number of ways of responding to acute or chronic injury and these essentially consist of neuronal and white matter loss and glial proliferation. These changes occur over many days and weeks. They may later be modified by secondary changes such as posthaemorrhagic or postinflammatory hydrocephaly or white matter atrophy (Mutch et al, 1992). By the time a child presents with cerebral palsy during the first years of life, the neuropathological effects of any hypoxic-ischaemic injury or other injury will have become modified by these changes and by further postnatal brain development. 

References and further literature in CP

Badawi N, Watson L, Patterson B, Blair E, Slee J, Haan E, Stanley F. (1998) What constitutes cerebral palsy? Dev Med Child Neurol 40: 520-527.

Bax M. (1964) Terminology and classification of cerebral palsy. Dev Med Child Neurol 6: 295-297.

Blair E. (1993) A research definition for birth asphyxia? Dev Med Child Neurology; 35: 449-455.

Blair E, Stanley FJ. (1988) Intrapartum asphyxia: a rare cause of cerebral palsy. J Pediatrics; 112: 515-519.

Cadman D, Boyle 11, Szatmari P, Offord DR. (1987)Chronic illness, disability, and mental and social well-being: findings of the Ontario child health study. Pediatrics;79:805-13.

Counsell SJ, Allsop JM, Harrison MC, et al. Diffusion-weighted imaging of the brain in preterm infants with focal and diffuse white matter abnormality.

Cummings SK , Nelson KB, Grether JK (1993): Cerebral Palsy in four northern California Counties, births 1983 through 1985. Journal of Pediatrics ; 123: 232-237.

Ellenberg JH, Nelson KB. (1979) Birthweight and gestational age in children with cerebral palsy or seizure disorders. Am J Dis Child: 133: 1044-48.

Ellenberg JH, Nelson KB. (1988) Cluster of perinatal events identifying infants at high risk for death or disability. J Pediatrics; 113: 546-552.

Kuban CK, Leviton A (1994) Cerebral Palsy. New England Journal of Medicine; 330: 188-195.

McLaren J, Bryson S. (1987): Review of recent epidemiological studies of mental retardation: prevalence, associated disorders, and etiology. American Journal on Mental Retardation; 92: 243-254.

Miyahara M, Mobs I. (1995) Developmental dyspraxia and developmental coordination disorder. Neuropsychol Rev.5:245-268.

Mutch L, Alberman E, Hagberg B, et al. (1992) Cerebral palsy epidemiology:

where are we now & where are we going? Dev Med Child Neurol 34:547-55.

Naeye R, Peters E, Bartholomew M, Landis JR. (1989) The origins of cerebral palsy. Am J Dis Child; 143: 1154-1161.

Nelson KB, Dambrosia JM, Ting TY, Grether JK (1996). Uncertain value of electronic fetal monitoring in predicting cerebral palsy. N Engl J Med;334:613-8.

Nelson KB, Ellenberg JH. (1986) Antecedents of cerebral palsy: multivariate analysis of risk. N Engl J Med; 315: 81-86.

Rosembloom L (1994) : Dyskinetic cerebral palsy and birth asphyxia. Developmental Medicine and Child Neurology; 36: 285-289.

Scott LB, Jankovic J (1996): Delayed-onset progressive movement disorders after static brain lesions. Neurology; 46: 68-74.

Singhi P, Jagirdar S, Khandelwal N, Malhi P. (2003)Epilepsy in children with cerebral palsy. J Child Neurol. Mar;18(3):174-9

Stanley, F., (2003). Recent trends in neurodisability: Implications for research and prevention Developmental Medicine and Child Neurology London Copyright Mac Keith Press

Winter S, Autry A, Boyle C, Yeargin-Allsopp M. (2002) Trends in the prevalence of cerebral palsy in a population-based study. Pediatrics;110:1220-5.

Wood NS , Markow N, Costeloe K, Gibson AT, Wilkinson AR. (2000) Neurologic and developmental disability after extremely preterm birth. N Engl J Med. 343:378-384

Yokochi K, Shimabukuro S, Kodama M (1993) Motor function of infants with athetoid cerebral palsy. Dev Med Child Neurol Oct; 35(10): 909-16

Presentation

Biological basis of Cerebral Palsy

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