Paediatric Neuropsychiatric Disorders

Paediatric neuropsychiatric disorders. Topics covered: 

  • The developmental perspective
    • Scope of developmental neuropsychiatry
  • Clinical features
    • Neurodevelopmental disorders
    • Neurogenetic syndromes with behavioural phenotypes
    • Neurobehavioural teratology
  • Fetal alcohol syndrome
    • Clinical features
    • Behavioural phenotype
    • Natural history
    • Epidemiology
    • Aetiology
    • Treatment
  • Gestational substance abuse
    • Opiates
    • Cocaine
    • Treatment
  • Endocrinopathies
    • Congenital hypothyroidism
  • Traumatic brain injury
    • Clinical features
    • Classification—types of traumatic brain injury
    • Epidemiology
    • Aetiology
    • Course and prognosis
    • Treatment
    • Possibilities for prevention
  • Epilepsy
    • Clinical features and clinical course
    • Classification
    • Diagnosis and differential diagnosis
    • Epidemiology
    • Aetiology
    • Course and prognosis
    • Management
    • Possibilities for prevention
  • Further reading
  • References

The developmental perspective

Developmental neuropsychiatry addresses the neurobiological basis of behaviour in infancy and childhood. As a field, it includes the aetiology, diagnosis, and treatment of behavioural, emotional, interpersonal, and psychiatric disorders in children and adolescents with neurodevelopmental disorders, and in those with brain damage occurring during the developmental period. (1,2) The parent's response, adjustment to, and involvement in treatment is a critical element in outcome.

The developmental neuropsychiatrist utilizes a developmental perspective that focuses on the developing person who is active, socially oriented, and emerging rather than passively responding to the environment or maturing independently of psychosocial experience. The adaptive plasticity of the developing nervous system to change is emphasized, and the essential role of environmental experience in brain development is acknowledged. When working with the affected child, an effort is made to facilitate the mastery of age-appropriate developmental tasks while keeping in mind the child's individual capacities.

Scope of developmental neuropsychiatry

The scope of developmental neuropsychiatry is broad (2) and includes the following.

  1. Neurodevelopmental disorders that are described in other articles on this site, including attention-deficit and hyperactivity disorders, pervasive developmental disorders and childhood-onset schizophrenia, obsessive– compulsive disorder and Tourette's syndrome, and specific developmental disorders.
  2. Neurogenetic disorders with behavioural phenotypes including both cytogenetic and metabolic disorders, several of which are also reviewed here:
  3. Teratogenic exposure from both organic and inorganic toxins. In these cases, behavioural dysfunction is the result of gestational substance abuse with alcohol and other substances or exposure to inorganic metals. 
  4. Endocrinopathies.
  5. Traumatic brain injury.
  6. Other neurological disorders (e.g. epilepsy).

Clinical features

Neurodevelopmental disorders

Developmental psychopathology considers child psychopathology from a developmental perspective by applying developmental concepts to neurodevelopmental disorders. Thus, the relationship of disordered to non-disordered behaviour is considered, as are the early origins of maladaptive behaviours that do not appear in clinical form until adulthood. Knowledge of normal development is utilized to study children whose development is atypical, in order to understand the natural history of their disorder. Conversely, investigation of such deviant behaviour is considered in regard to our understanding of normal development. For example, attention-deficit hyperactivity disorder has been investigated as a disorder of executive function, and autistic disorder as a disorder of social cognition and communication. In both instances, new knowledge about brain functions has been derived from these formulations. Among the neurodevelopmental disorders, the age of onset varies, multiple causes are involved, and many transformations in behaviour may occur in determining their complex course. The goal is to understand the mechanisms and processes through which risk factors lead to the emergence of a disorder. Disordered behaviour is not viewed as a static condition, but is considered as part of a dynamic transaction. Behaviour and development are viewed within a social context, and the transactional nature of interactions is considered from infancy through adulthood to understand these processes.

Attention-deficit hyperactivity disorder, pervasive developmental disorders, obsessive–compulsive disorder, Tourette's syndrome, and childhood-onset schizophrenia are developmental neuropsychiatric disorders under active investigation and each is reviewed in the respective articles. Their developmental psychopathology is investigated by addressing the origins and course of individual patterns of behavioural maladaptation in each of these disorders and determining their genetic bases, thought to be complex, and involving more than one gene. Information derived from genetics, developmental psychology, clinical psychology, psychiatry, sociology, physiological sciences, neurosciences, and epidemiology is included in the description of each of these disorders.

The interrelationship of the various child neuropsychiatric disorders is an important consideration. Disorders may be risk factors for other conditions, so that attention-deficit disorder may be a risk factor for conduct disorder. In this instance, the child's behaviour affects the adult and the transactional interactions between child and adult may result in further disruptive behaviours. Moreover, there may be a developmental basis for disorders whose full presentation is not evident until later in life, as is the case with schizophrenia—generally considered to be a disorder of late adolescence or early adult life, but with origins in the developmental period. (3) Some disorders may have co-occurring diagnoses that influence their outcome, as in Tourette's syndrome, where co-occurring conditions may determine the behavioural presentation. In Tourette's syndrome, obsessive–compulsive symptoms may be an aspect of ‘pure' Tourette's syndrome, while co-occurring disruptive behaviour, mood, and anxiety disorder may be secondary to co-occurring attention-deficit disorder. (4) Compulsive behaviours may not only interfere with the normal routines for the affected child but also become particularly problematic for their impact on other family members.

Neurogenetic syndromes with behavioural phenotypes

Particular patterns of behaviour, temperament, and psychopathology may be associated with specific chromosomal and genetic disorders. (2,5,6) The term ‘behavioural phenotype' was introduced by Nyhan in 1972 (7) to describe patterns of unusual behaviour that are so characteristic that they suggest a specific neurogenetic disorder. He described stereotypical patterns of behaviour occurring in syndromic fashion in sizeable numbers of affected individuals with a given syndrome, and observed that these patterns seemed self-programmed. In these children, he proposed that it is reasonable to hypothesize that their behaviours are associated with an abnormal neuroanatomy and that such stereotypical patterns of unusual behaviour could reflect the presence of structural deficits in the central nervous system. Recent developments in the neurosciences provide a means to investigate the biological bases of behavioural phenotypes. Behavioural assessments, neuropsychological testing, and neuroimaging procedures, carried out in well-characterized genetic syndromes, are being utilized to understand pathways from genes to cognition and complex behaviours in these conditions.

Comprehensive study of children with different neurogenetic disorders may increase our appreciation for the relative contribution of genetic variables in the pathogenesis of specific affective and behavioural disorders. Behavioural phenotypes have been studied most extensively in Down syndrome (mimicry), (8) fragile X syndrome (gaze aversion, hyperkinesia, autistic-like behaviour), (9) Williams syndrome (sociability, hyperverbal behaviour, and visuospatial deficits), (10,11) Lesch–Nyhan syndrome (compulsive self-injury and aggression), (12,13 and 14) and Prader–Willi syndrome (hyperphagia, obsessive–compulsive behaviour). (15,16) The number of identifiable behavioural phenotypes is growing with careful observations of behaviours in neurogenetic disorders. (5) Besides behaviours, particular temperamental features have also been considered in these disorders. However, when studying temperament, the appropriate measures must be chosen. For example, when Down syndrome, proposed to be linked to a particular temperament, was studied using temperamental clusters of easy temperament, slow to warm up, and difficult temperament, Gunn et al. (17) demonstrated both easy and difficult temperament in children with Down syndrome; therefore, a typical temperamental pattern among these three categories was not demonstrated. However, when a more comprehensive assessment was carried out in other syndromes (18) (that included the personality factors of extraversion, agreeableness, conscientiousness, emotional stability, and openness, along with motor activity and irritability), specific personality phenotypes were identified. These were differentially related to parental behaviours and family context in Prader–Willi, fragile X, and Williams syndromes. Moreover, isolated special abilities, as in calculation and in music, (19) are recognizable that might be considered as phenotypes and linked to the proposed modular organization of the central nervous system. Finally, physical and behavioural phenotypes are not only identified in neurogenetic syndromes but also in those caused by environmental events, such as intrauterine exposure to alcohol: namely, the fetal alcohol syndrome. Because alcoholism is a familial disorder, there may vulnerability to its effects resulting in a more severe presentation in some individuals. (20)

Both traditional Mendelian laws of inheritance (Lesch–Nyhan syndrome) and non-traditional inheritance have been identified in conditions with behavioural phenotypes. Among the non-traditional forms of inheritance are triplet repeat amplification (fragile X syndrome), microdeletion or contiguous gene deletion (Williams syndrome), imprinting (Prader–Willi syndrome), and excessive gene dosage (Down syndrome). A key finding is the recognition that mutations of single genes can lead to complex behavioural symptoms, especially if the affected protein is essential for the expression or processing of multiple ‘downstream' genes.

Behavioural phenotypes are also discussed in relation to mental retardation in this article: 

Neurobehavioural teratology

Neurobehavioural teratology investigates abnormal development of the nervous system and of cognition and complex behaviour that results from prenatal environmental insults. Neurobehavioural research addresses the prevalence of cognitive–behavioural disorders in exposed individuals and the consequences of the brain insult on other developing brain systems, to identify risks for functional or behavioural deficits. Investigators focus on cognitive–behavioural deficits and their underlying anatomy and embryology. Assessment emphasizes not only IQ but also neuropsychological profiles, because learning disability or difficulty in visuomotor integration may be evident in children who function in the low to average range of general mental ability.

The natural history of intrauterine drug exposure on motor, cognitive, emotional, and social behaviour is an area of growing concern. Multiple drug exposures during pregnancy is common among substance-abusing mothers. Of syndromes associated with intrauterine substance abuse, alcohol abuse has been studied the most extensively. Subsequently, retinoids, anticonvulsants (lithium, tegretol, and valproic acid), and the selective serotonin-reuptake inhibitors have also been studied. Other teratogens do not lead to major malformations of the nervous systems but they do compromise its integrity (for example, lead, heroin, methadone), and are associated with neurotoxic damage or effects on neurochemical systems.

The greatest period of vulnerability to drugs in a human pregnancy is during the period of embryogenesis (days 14 to 60). During embryogenesis, many neurobehavioural teratogens (for instance, retinoids and ethanol) produce syndromes with abnormalities that involve craniofacial, neural, and major organ systems. Behavioural abnormalities without detectable physical abnormality occur when the insult occurs during the fetal period. The extent of malformation is stage specific and dose dependent, with outcomes ranging from death with malformation, malformation and survival, effects on growth, and cognitive–neuropsychological or behaviour disorder. The same exposure to alcohol needed to produce cognitive–behavioural change in the fetal period would generally cause malformation if it occurred during embryogenesis. The term ‘developmental toxicology' is sometimes used if the insult occurs in the postnatal period.

There may be a genetic vulnerability that influences the extent of expression of response to environmental toxins in an individual. A common family of regulatory genes are involved in the formation of structures of the face, head, hindbrain, parts of the heart, and thymus gland, all of which share a common origin from neural crest cells (anterior neural tube). These regulatory genes, known as HOX genes, provide rules for assembling various structures and for determining particular anatomical segments. Transgenic mice who lack certain of these HOX genes show syndromic craniofacial, hindbrain, heart, and thymus abnormalities. Because the retinoid family is involved in controlling these HOX genes, a similar pattern is produced by excessive retinoid administration, as in hypervitaminosis of vitamin A. Thus, both genetic and teratogenetic agents may produce similar developmental abnormalities. Understanding these mechanisms helps to understand how an abnormal facial appearance may suggest an abnormal brain.

Fetal alcohol syndrome

Fetal alcohol syndrome is one of the most commonly recognized causes of mental retardation; one that is preventable if recommended guidelines regarding alcohol use are followed by mothers. (21)

Clinical features

Children with the full fetal alcohol syndrome demonstrate prenatal and postnatal growth deficiency, microcephaly, infantile irritability, mild to moderate mental retardation, and a characteristic facial appearance. (21) The extent of the abnormality depends on the time of maximal exposure to alcohol and the dose. Approximately half of those affected have co-ordination problems, are hypotonic, and have attention deficits. Between 20 and 50 per cent have other birth defects, including eye and ear anomalies and cardiac anomalies. Those children who do not show growth retardation or congenital anomalies may show more subtle changes, such as attention problems, reduced speed of information processing, motor clumsiness, speech disorders, fine motor impairment, and learning problems, especially in mathematics. These findings have been documented in a prospective longitudinal study of the effects of prenatal alcohol exposure on a birth cohort of 500 offspring who were selected from 1529 consecutive pregnant women in prenatal care in community hospitals. (22) Dose-dependent effects are most clear from the neurobehavioural status of subjects with regular neurodevelopmental evaluations from birth to age 14 years. The more subtle abnormalities are referred to as ‘fetal alcohol effects', or alcohol-related neurodevelopmental disorder. Subjects with average to above-average IQ may demonstrate neuropsychological deficits in complex attention, verbal learning, and executive functioning. (23,24) Both attention-deficit disorder and autistic-like behaviour have been described (25,26) in children with fetal alcohol syndrome and fetal alcohol effects disorder who test in the moderate to severe range of mental retardation.

Behavioural phenotype

The behavioural phenotype is characterized by problems in cognitive functioning, academic problems in arithmetic, difficulty with abstractions, understanding cause and effect, and generalizing from one situation to another. Thus, inattention, poor concentration, impaired judgement, memory deficits, and problems in abstract reasoning are characteristic. Behavioural problems related to impulsivity and hyperactivity make them vulnerable to later diagnoses of oppositional defiant and conduct disorder.

Natural history

Fetal alcohol syndrome is not only a childhood disorder; the cognitive and behavioural effects and psychosocial problems may persist throughout adolescence into adulthood. (22,23 and 24,27,28 ) Although the facial features are not as distinctive after puberty and the growth deficiency is not as apparent as in the younger child, the central nervous system effects do persist throughout life. Approximately 50 per cent of those affected function as mentally retarded persons. Moreover, adaptive behavioural problems in communication skills and in socialization are apparent in those with both fetal alcohol effects and alcohol-related developmental disorder whose intelligence test scores are in the normal range.

Poor judgement, attention problems, distractibility, difficulty in recognizing common social cues, and problems in modulating mood continue as characteristic features. Family environmental problems often continue as risk factors for behavioural problems if there is a lack of stability in family life. In one follow-up study (27) that used structured interviews with non-retarded affected subjects, the most common diagnoses were alcohol or drug dependence, depression, psychotic disorders, and personality disorders (avoidant or antisocial). Further follow-up is needed to investigate the mechanisms involved in these psychiatric presentations, and particularly in determining the pathways leading to alcoholism.


Fetal alcohol syndrome is a common cause of neuropsychiatric disorders, with a worldwide incidence of approximately 1.9 in 1000 live births. When fetal alcohol syndrome and alcohol-related neurodevelopmental disorder are considered together, the combined rate in one study conducted in the United States was 9.1 in 1000. (24) Despite its frequency and severity, the syndrome may go unrecognized because physicians may not systematically enquire about alcohol use and may not recognize the spectrum of the effects of prenatal alcohol exposure on neurodevelopment.


Twin studies suggest that there are genetic risks for fetal alcohol syndrome. Microcephaly is commonly reported in fetal alcohol syndrome and suggests an underdevelopment of the brain. Neuropathological studies demonstrate the underdevelopment or absence of the corpus callosum and enlarged lateral ventricles. Ferrer and Galofre (29) observed decreased numbers of dendritic spines on the apical dendrites and abnormal morphology of the spines on the apical and basilar dendrites of cortical pyramidal cells in a 4-month-old with fetal alcohol syndrome. These neuropathological changes are of interest because dendritic spine abnormalities have been reported in mental retardation syndromes such as Down syndrome. Dendritic changes have also been observed in animals with prenatal exposure to alcohol; these changes were correlated with decreased learning ability. Magnetic resonance imaging studies have documented brain abnormalities in fetal alcohol syndrome. (30)



Mothers of children with fetal alcohol syndrome who drank more alcohol and drank excessively early in gestation have more severe clinical features. Alcohol use in late pregnancy is primarily associated with prematurity and infants who are small for gestational age, rather than with the full fetal alcohol syndrome. One prospective study of 31 604 pregnancies found that the consumption of one or two drinks a day was associated with an increased risk of giving birth to a baby who was growth retarded. (31) Because of these risks, treatment must begin with prevention. There is no clearly agreed safe dose of alcohol for pregnant women. Because there is no known safe amount of alcohol consumption during pregnancy, it is recommended that women who are pregnant or who are planning a pregnancy abstain from drinking alcohol. Special efforts for educating women of child-bearing age are required that highlight the harmful effects of alcohol; identified children must be referred for early educational services.


A comprehensive treatment programme begins with parental acknowledgement of the aetiology of fetal alcohol syndrome and treatment for the parent, as indicated, for alcohol misuse and abuse. Parental counselling should include discussion of the physical and behavioural phenotype. The family should be advised about the need for special educational programmes and assisted in behavioural management. Family therapy is often required to help family members cope with the developmental disorder. Appropriate educational and behavioural treatment resources are needed to address the social deficits, particularly in those cases where attention-deficit disorder and autistic-like behaviour are indentified. 

Gestational substance abuse


New-born infants exposed in utero to opiates such as heroin may experience severe consequences. (32) Exposure to methadone ranges from a withdrawal syndrome to less predictable long-term outcomes. Methadone effects have been associated with reduced head circumference, increased body tension, poor motor co-ordination, and delay in motor skills acquisition. However, the effects on mental development are less clear, but they do affect the child-rearing environment. Since methadone exposure produces an increased vulnerability to the effects of poor parent–infant relationships, these relationships require careful monitoring.


Cocaine is a central nervous system stimulant that inhibits nerve conduction in the peripheral nervous system. Cocaine is metabolized primarily through the plasma cholinesterase system, with the primary metabolic product being benzoylecgonine. Since cocaine rapidly crosses the placenta by simple diffusion, fetal peak blood levels are reached as quickly as 3 min. (33) Having crossed the placenta in the fetus, cocaine has the same direct actions on the fetal cardiovascular system as seen in the maternal system. These cardiac changes involve the direct effects of cocaine, as well as indirect effects such as fetal hypoxia. Cocaine may lead to placental dysfunction (via vasocontracture effects), structural changes (via vascular compromise), and neurobehavioural abnormalities (via postsynaptic junction neurotoxicity).

Infant gestational age, birth weight, head circumference, and length have been found to be decreased in affected infants, and low birth weight is a frequent finding in studies of the offspring of cocaine-using women. In addition to abnormal growth patterns, congenital anomalies involving the genitourinary tract, heart, and central nervous system as well as limb-reduction abnormalities have been reported. A potential mechanism for all these anomalies appears to be interruption of the intrauterine blood supply, with subsequent disruption of embryonic development. Although approximately 25 to 30 per cent of infants exposed to cocaine in utero may have physical difficulties, overall neurobehavioural problems may be more common. Approximately one-third of the drug-exposed children demonstrate delays in normal language development and/or difficulties with attention and self-regulation. Child abuse is closely linked to substance abuse.


These findings suggest that careful attention be paid to the postnatal home-rearing environment of children who are exposed to drugs in utero. Overall, the treatment programme must take into account physical and psychological change secondary to intrauterine drug use as well as the postnatal nurturing environment. Both substance use and psychiatric disorder in the parents must be considered, because parents with attention-deficit disorder and mood disorders may themselves self-medicate with cocaine. Without early intervention, special school programmes, behavioural management programmes, and a structured day programme will be necessary. Ongoing parent training is also required. (34)


Congenital hypothyroidism

Congenital hypothyroidism is associated with mental retardation and may be associated with decreased motor activity at birth, hoarse cry, and difficulty with feeding. It is rarely diagnosed at birth from clinical assessment alone, but it is recognized from new-born screening tests with confirmation by measurement in blood samples. Symptoms of hypothyroidism may not be clearly detected until the second month of life. The overall prevalence is 1 in 4000 live births. Neurological and learning disorders associated with untreated congenital hypothyroidism include attention-deficit disorder, hearing loss, speech defects, ataxia, and abnormal muscle tone. (35) Rapid diagnosis in infancy is essential to prevent these complications. Without treatment, severe neurological dysfunction ensues. With initiation of oral thyroid hormone treatment (levothyroxine in a single daily dose of 8 to 10 μg/kg per day) in the first 6 weeks of life, IQ is in the normal range. If treatment is delayed until 3 to 6 months, IQ drops to an average of 75, and, if initiated after 6 months, to an IQ of 55 or less.

Traumatic brain injury

Traumatic brain injury is defined as physical damage or impairment in function of the brain as a consequence of the application of acute mechanical force. Other causes of brain injury result from birth trauma, poisoning, or asphyxia. Traumatic brain injury is a major cause of death and disability among children, adolescents, and young adults, and is one of the most common causes of chronic brain syndromes in childhood. Traumatic head injury is common and becoming increasingly more so.

Clinical features

Cognitive and behavioural

The most common long-term outcomes of traumatic brain injury are cognitive and behavioural changes. Immediately after emerging from a coma, the child will be unable to form new memories. The time, from the accident to the time when new memories emerge, is referred to as post-traumatic amnesia. The length of coma and the duration of post-traumatic amnesia are especially important in regard to the extent of cognitive recovery. Moreover, there is a strong inverse relationship between subsequent IQ and duration of coma. The persistence of cognitive deficits is correlated with the duration of post-traumatic amnesia; the more persistent deficits follow more than 3 weeks of post-traumatic amnesia. Persistent verbal memory impairment is reported as long as 10 years after injury in up to one-quarter of those studied. Psychiatric symptoms in adults occur more often following focal frontal-lobe traumatic brain injury than injury to other cerebral areas. In children, Rutter (36) reported behavioural disinhibition after severe closed traumatic brain injury characterized by over-talkativeness, ignoring social conventions, impulsiveness, and poor personal hygiene.


Psychiatric outcomes can be divided into those that occur during the early phases of recovery and those that occur later. The earliest psychiatric sequelae are found before the termination of post-traumatic amnesia. During this time, behavioural and affective symptoms are linked to the neurological presentation. The most common psychiatric diagnosis is delirium. Symptoms include short attention span, agitation, hallucinations, and disturbances in the sleep–wake cycle.

Subsequent occurrence of post-traumatic psychiatric symptoms is linked to the severity of the injury, its location, the child's behavioural and emotional features prior to the accident, and the psychosocial interactions of the family members during the recovery phases. The more severe the traumatic brain injury, the greater the likelihood of psychiatric sequelae. All children in one prospective study of severely injured children who had premorbid psychiatric conditions showed post-traumatic psychiatric disorders.(37) Moreover, over half the children in this group who had no premorbid symptoms prior to the accident had developed psychiatric symptoms during a 28-month, follow-up period. The greatest premorbid risks for psychiatric disorder were previous difficulties with impulse control and disruptive behaviour. In addition, a prior history of family dysfunction increased the risk for later symptomatology. The range of disorders (38,39 and 40) includes attention-deficit hyperactivity disorder, disruptive behaviour, (41) post-traumatic mood disorders (both depressive and manic symptoms), post-traumatic stress disorder, (42) and family dysfunction.(43,44)

Classification—types of traumatic brain injury

Neurological damage associated with head trauma can be produced in several ways. Traumatic brain injury is classified as open or closed; these types differ in the pattern of injury and neurobehavioural outcome. Open refers to penetration of the skull, as in a depressed skull fracture or bullet wound, the extent depending on the regions damaged by contusion or cerebral oedema. Closed head injury results from acceleration and deceleration of the brain within the hard skull; this often leads to contusion of the brain from a sudden impact and may result in subarachnoid haemorrhage. Different parts of the brain have different densities, and therefore shearing stresses that develop during rapid brain movement cause injury. Furthermore, compression of blood vessels against the falx cerebri or tentorium may result in infarction of the areas which these blood vessels supply. Penetrating traumatic brain injury causes specific and direct loss of neural tissue.


It is estimated that 185 children per 100 000 from infancy to 14 years of age and 295 per 100 000 adolescents and young adults aged between 15 and 24 are hospitalized each year for traumatic brain injury. (45,46) The risk is highest among the 15- to 19-year-olds where the rate is 550 per 100 000. (47) The incidence in paediatric populations is similar to that in adults. A mortality rate of 10 per 100 000 makes head trauma a major cause of death in children, but the death rate is still less than that in adults. There is no difference in the death rate between boys and girls before the age of 5 years, but after this age males are four times more likely to die than females. Approximately 90 per cent of head injuries are mild. (45) Falls and transport injuries make up the majority of cases.


The causes of traumatic brain injury are different depending on the age of the child. The incidence is twice as high in males as in females, and children who live in poor psychosocial circumstances are at greater risk. Traumatic brain injury from child abuse occurs in infancy: in the preschool years the most common cause is falls; in early elementary school, it is pedestrian accidents. From 10 to 14 years of age there is an increase in sports and bicycle accidents, but by 15 years motor vehicle accidents and violent assault are the most common. Risk factors include poverty, single-parent homes, congested living arrangements, and a parental history of psychiatry disorder.

A common complication of traumatic brain injury is cerebral oedema, but there are other complications such as infection and haematoma formation both inside and outside the brain. These complications result in neurological deficits that may be extensive. Furthermore, compensatory mechanisms that are involved in recovery from head trauma may alter brain function. A child who has suffered a traumatic brain injury is likely to experience both neurological and psychiatric difficulties depending on the brain regions involved. Multiple mechanisms lead to psychological symptom formation—both psychosocial and physiological factors are involved.

Course and prognosis

The level of consciousness, degree of somatic injury, extent and duration of post-traumatic amnesia, severity of head injury, and degree of neurocognitive dysfunction in the early post-trauma period are important in determining outcome. Children who experience severe traumatic brain injury usually follow a predictable postoperative course. (48) As previously noted, landmarks for recovery are associated with the time of emergence from coma and the time of emergence from post-traumatic amnesia. The emergence from coma is most often defined as the point at which the patient is able to follow simple verbal commands. Concurrently, visual tracking of objects in the environment may be observed.

Post-traumatic amnesia ends when the child is able to form new memories. The frequency of post-traumatic amnesia is probably related to concurrent injury to the temporal lobes associated with the head trauma. However, older memories may be recalled that do not involve the temporal lobe. The hippocampus has a central role in the formation of new memories. Besides recovery from post-traumatic amnesia, another form of memory loss—retrograde amnesia—for events that took place before the accident, typically becomes shorter and shorter during the recovery process. It is important to remember that children with severe head trauma will rarely have specific memories of the accident itself. Overall, the most important milestones in recovery for future outcome are the length of coma and the duration of post-traumatic amnesia.



Complete recovery of all brain functions following brain injury is rarely accomplished. Still, if recovery is defined as a reduction in impairments in behavioural and physiological functions over time then changes do occur so that, typically, there is recovery of function together with a fair amount of substitution of function. Mechanisms include resolution of brain swelling (oedema), resolution of damage to other brain regions damaged through shock (diaschisis), changes in the structure of the nervous system (plasticity), and regrowth of neural tissue (regeneration). The extent of recovery depends on the severity of the injury, the number of times injured, the age at the time of injury, premorbid cognitive status, extent to which loss functions can be subsumed under other systems, integrity of other parts of the brain, individual brain structures, motivation, emotional considerations, and the quality of rehabilitation programme. (49,50)

Although children and adolescents tend to have a better outcome after severe traumatic brain injury than those over the age of 21, (46) the adult brain has greater plasticity than previously considered. (49) Despite this general rule, children who are younger than 7 years may have a worse outcome since they may be at increased risk of child abuse, which may be particularly traumatic. Furthermore, younger children may have a worse outcome based on the global effects of trauma on the developing brain. The duration of recovery of significant neuropsychological, behavioural, and emotional deficits may last several years following injury. These higher cognitive deficits lead to the major disability observed with traumatic brain injury.


Partial recovery of function can and does occur over time, not only in children but also in adults. (49) Intervention through retraining and the use of cognitive memory aids can lead to improvements in cognitive functioning such as memory, attention, language, and perception. (50) Even though partial recovery does occur after various types of brain injury, there is variability in the extent of recovery.

Possibilities for prevention

The most important primary injury prevention activities focus on teaching safe behaviour, the use of seatbelts in cars, and wearing helmets when riding horses, bicycles, or motorcycles. Once an injury has occurred both anticipatory guidance, which teaches the family and child what to expect, and preventive intervention strategies are necessary. Early and focused rehabilitation procedures coupled with medication for associated psychiatric disorder, behaviour management, supportive therapy for families, and appropriate school programmes are necessary to prevent behavioural and psychiatric complications.


Epilepsy refers to recurrent seizures that are idiopathic (of unknown aetiology) or due to congenital or acquired brain lesions. Epilepsy is the symptomatic expression of brain pathology or disordered brain function and is not a disease in itself. The symptom complex is episodic and associated with an excessive self-limiting neuronal discharge. The seizure is a frightening experience for parents and they require support and guidance.

Clinical features and clinical course

Complex partial seizures involving the temporal and frontal lobe is the most common condition, where complex neurological and psychiatric symptoms are seen in the same person. Complex symptoms include behavioural automatisms, perceptual alterations, changes in affect and memory, distorted thinking, and hallucinations. (51,52) Forms occurring in infancy and childhood include temporal lobe epilepsy, frontal-lobe epilepsy, infantile spasms, Lennox–Gastaut syndrome, Landau– Kleffner syndrome, and benign focal epilepsy.

Children with partial seizures and electroencephalographic evidence of frontal involvement have more severe formal thought disorders and deficits in communication discourse than those with temporal involvement. Because these seizures are rare in children, reports of symptoms are primarily found in case reports. For example, Saygi et al.(53) and Stores et al.(54) have described sexual disinhibition, pressured and tangential speech, screaming, aggression, disorganized behaviour, and nightmares in children with epilepsy.

Frontal-lobe epilepsy should be considered if there are episodes of brief sudden unresponsiveness without loss of consciousness. These episodes occur with continued understanding of spoken language and clonic or tonic motor phenomena involving the face and arms bilaterally. Laughing, crying, pedalling movements, and sexual automatisms may also suggest this diagnosis. A normal electroencephalograph does not rule out the diagnosis. Left frontal hypometabolism on positron-emission tomography scanning or reduced cerebral blood flow to the frontal area, although not diagnostic, support this diagnosis.

The Lennox–Gastaut syndrome is characterized by early onset of intractable seizures and bilateral slow spike–wave complexes on the EEG. (52) The onset is typically between the ages of 1 and 7 years. The seizure pattern includes tonic, generalized tonic–clonic, atypical absence, atonic, and myoclonic seizures. Approximately half of children with the Lennox–Gastaut syndrome test as mentally retarded. (55) Marked language delay, overactivity, and irritability are characteristic. However, these behavioural symptoms may improve with seizure control. Ultimately, the diagnosis is based on the characteristic EEG finding of interictal slow spike–wave discharges in children with the early onset of poorly controlled seizures and a developmental disorder. In some instances, there is prolonged minor status epilepticus. Such episodes may last for several weeks during which the child engages in a variety of everyday activities but is socially unresponsive, aggressive, less articulate, and has minor twitching of the face and hands. This presentation must be differentiated from a psychiatric disorder.


Classification of epileptic seizures utilizes both clinical and electroencephalographic features. The current classification divides seizures into two categories: partial and generalized. Partial seizures involve one cerebral hemisphere, in part or totally. They begin focally, although they may become generalized. Consciousness is preserved but cognitive functions may be transiently impaired: for example, speech may be impaired if the dominant hemisphere is affected. Partial seizures are further subdivided into those with simple or complex symptomatology. In children, simple complex seizures are most often simple motor or sensory phenomena. Complex partial seizures usually begin in temporal or frontal-lobe structures. It is a group that is particularly important to psychiatrists.

Diagnosis and differential diagnosis

Epilepsy is a clinical rather than a laboratory diagnosis, and diagnostic errors most commonly occur due to inadequate history and physical examination. The accuracy of diagnosis has improved with the establishment of a universally agreed upon classification. In some instances there may be confusion between sleep arousal disorders and epilepsy. (53)

The differential diagnosis includes complex partial seizures of temporal origin and pseudoseizures. (54,56) Frontal-lobe complex partial seizures differ from those of temporal lobe origin in that the amnesia of frontal-lobe seizures is more pronounced than the extent of loss of consciousness. Moreover, frontal-lobe involvement is associated with unilateral or bilateral tonic posturing and pedalling movements, partial and not complete loss of consciousness, and eye and head deviation to the contralateral side. In complex partial seizures of temporal lobe origin, oroalimentary and repetitive hand automatisms, and looking around are characteristic. Lastly, sensory, gustatory, or olfactory hallucinations in frontal-lobe epilepsy must be differentiated from psychotic disorders such as schizophrenia and manic psychosis.

The distinction between true seizures and pseudoseizures can be difficult. Children with pseudoseizures commonly also have true seizures. Emotional dysphoria can precipitate true seizures and many children with chronic seizures have psychiatric diagnoses. Frontal-lobe seizures may be confused with pseudoseizures. Frontal complex partial seizures differ from pseudoseizures in that pseudoseizures have a gradual onset and longer duration, while frontal-lobe seizures start slowly and last less than 1 min.(53) Pseudoseizures include thrusting or rolling movements rather than the rhythmic flexion and extension clonic movements seen in frontal-lobe epilepsy. Still, it may be difficult to distinguish pseudoseizures, and video and electroencephalograph monitoring with depth electrodes may be necessary to definitively diagnose frontal-lobe epilepsy.

Other features differentiating pseudoseizures are as follows.

  1. The seizure occurs when the child is observed, but not when alone.
  2. The seizures are gradual rather than of sudden onset.
  3. Uncontrolled flailing occurs, rather than true tonic–clonic movements.
  4. The seizure is accompanied by histrionics, with screaming and shouting.
  5. Painful stimuli are avoided during an attack; pain is avoided.
  6. There is a sudden cessation of the seizure, with immediate return to an alert and responsive state.
  7. There is absence of paroxysmal discharge during an attack on electroencephalography. (57)


The incidence of epilepsy ranges from 0.8 to 1.1 per cent of the general population. (51) It is the most common of the neurological diseases diagnosed in children. Approximately 50 per cent of all cases of epilepsy begin during the childhood years and about 5 per cent of children will experience repeated epileptic seizures without a known extracerebral cause. In addition, about 3 per cent of children will have febrile convulsions that are usually benign and accompany a febrile illness. The great majority of these children, approximately 98 per cent, do not go on to develop true epilepsy. Other causes include hypoglycaemic seizures in children with diabetes. In some instances, as in tuberous sclerosis complex, cognitive impairment and autistic regression with onset in the first year of life, are linked to epilepsy; and in others there is a late onset of language disorder as in the Laudau– Kleffner syndrome.


Advances in understanding epilepsy in childhood have come from the newer medical technologies. Recognition of a typical spike–wave pattern has led to the identification of benign focal epilepsy; CT scanning and high-resolution magnetic resonance imaging ( MRI) have led to the recognition of mesial temporal sclerosis, tuberous sclerosis, neuroblast migrational disorders, and small temporal lobe tumours. Positron emission tomography scanning can demonstrate lesions undetected by MRI, such as focal lesions in patients with hypsarrthymia. Advances in surgical procedures have decreased the risks associated with callosotomies and hemispherectomies used for catastrophic seizures. New understanding about neurotransmitters involved in the production and inhibition of seizures has led to advances in seizure medications.

Epileptic seizures are the result of an imbalance between inhibitory (g-aminobutyric acid ( GABA)) and excitatory (glutamate) neurotransmitter systems. Neuronal hyperexcitability leading to seizures may result from decreased inhibition or increased excitation. (58) Epilepsy has its highest incidence in childhood, suggesting that the immature brain is more vulnerable to seizures than the mature brain—a finding that is borne out by animal studies. Decreased inhibition or increased excitation may result in neuronal excitability and seizures. (58) The specific mechanisms responsible for this imbalance remain uncertain. (58) However, it is known that the binding of GABA to GABAA receptors opens a chloride channel (ionophore) leading to a flux of chloride ions and consequent membrane hyperpolarization: it is also known that there are fewer GABAA high-affinity receptors in immature animals. Similarly, there are maturational differences in the development of major ionotrophic receptors in excitatory systems and in the activation of N-methyl-D-aspartate receptors. In younger animals this results in larger excitatory post-synaptic potentials. It remains a puzzle why certain seizure types are age-specific in their onset. (59)

Epilepsy syndromes may have a genetic basis. (60) Gene localization for five epilepsy syndromes with Mendelian inheritance are recognized, and localization has been suggested in three epilepsies with complex inheritance. Those epilepsies with a single gene inheritance include symptomatic epilepsies with associated diffuse brain dysfunction and idiopathic epilepsies, where the seizures are the primary brain abnormality. Idiopathic single gene epilepsies include benign, familial neonatal convulsions, in which genetic linkage to chromosomes 20q and 8q have been demonstrated. to date, four autosomal dominant forms of epilepsy have been described. The first genetic defect described in idiopathic epilepsy is in autosomal-dominant nocturnal frontal-lobe epilepsy ( ADNFLE), where a genetic defect with two different mutations in the a4-subunit of the nicotinic acetylcholine receptor has been identified. Subsequently, it has been shown that, although the ADNFLE phenotype is clinically homogeneous, there are a variety of molecular deficits responsible for this disorder, (61) highlighting the complexity in understanding the basic mechanisms of epileptogenesis. Molecular genetic studies are expected to lead to the discovery of other epilepsy genes. Investigation of animal models of epilepsy are continuing. (62)

The aetiology of temporal lobe seizures includes mesial temporal sclerosis, tumours, and cortical dysplasia. The younger the child, the less frequent is mesial temporal sclerosis. Other factors linked to aetiology are proposed: temporal lobe hypoperfusion and hypometabolism in Landau–Kleffner syndrome, and diffuse cortical and subcortical hypoperfusion in Lennox–Gastaut syndrome.

Course and prognosis

Early-onset epilepsies are associated with cognitive, behavioural, and communication disorders. Moreover, there is evidence that both clinical and subclinical epilepsy may result in developmental deviance, which has led to earlier and more aggressive treatment to try to prevent these impairments. Psychosocial factors are important in impairment. One prospective study evaluated 220 adults with childhood-onset seizures (63,64) up to age 35. The majority of subjects were free of seizures as adults, but were at risk for social and educational problems. When compared with random control subjects, those with epilepsy demonstrated correlations between neurological and cognitive impairment and social deficits. Those with epilepsy only (100 subjects) had a fourfold risk of psychiatric disorder. The authors reported social adjustment problems, competence problems, and reduction in marriage rate and fertility.


Cognitive and behavioural findings suggest the importance of early intervention to prevent negative outcomes. The behavioural and psychiatric problems should be treated with the same approach used in children who are neurologically intact and include educational, family, and pharmacological approaches. The indications and choice of psychiatric drugs is similar; epilepsy is not a strong contraindication for the use of neuroleptic or antidepressants, even though some of these medications may increase the frequency of seizures. Dexedrine may be the treatment of choice for hyperkinetic behaviour because it may increase the seizure threshold. (57) Although caution is needed in those with more severe neurological involvement, there is no strong evidence for an increased risk for neuroleptic-induced tardive dyskinesia. When there are behavioural problems one must consider the behavioural effects associated with anticonvulsant medications. In some instances, reducing the dose or changing the medication may be helpful and this should be discussed with the referring physician.

The major drugs used for treatment include carbamazepine, valproic acid, gabapentin, vigabatrin, and topiramate. These medications are used for the various forms of epilepsy described above including temporal lobe seizures and Lennox–Gastaut syndrome. Lamotrigine is also used, but with caution because severe dermatological side-effects may occur. In some instances, temporal lobectomy has been successful in the control of behavioural dysfunction and illogical thinking when performed in children with intractable temporal lobe seizures. In tuberous sclerosis complex the seizure medication vigabatrin may be helpful (and more so than corticosteroids) for infantile spasms. (65)

Possibilities for prevention

A developmental perspective is indicated as there is increasing evidence of there being a developmental period during which a structure or function can be developed most completely.(66) For example, in tuberous sclerosis complex the cognitive impairment and autistic regression may be approached by way of early drug therapyand, in some instances, by the surgical removal of tubers. (67) A developmental understanding of epilepsy is now crucial in treatment planning. Research is continuing to clarify why, in some instances, epilepsy may have a severe developmental impact and in other instances be more benign. With greater understanding of genetic mechanisms appropriate family counselling will be needed, and perhaps, new drug treatments may emerge. An important treatment goal is to prevent adverse psychosocial outcome by correct diagnosis, early intervention for seizures, continual assessment for cognitive and behavioural disorders, appropriate schooling, as well as effective family support, guidance, and therapy. Careful prospective follow-up studies are needed to demonstrate which interventions are most appropriate to specific types of epilepsy.

Further reading

Harris, J. (ed.) (1998). Developmental neuropsychiatry: the fundamentals. Oxford University Press, New York. Harris, J. (ed.) (1998). Developmental neuropsychiatry: assessment, diagnosis and treatment of the developmental disorders. Oxford University Press, New York.


1. Harris, J. (1998). Developmental neuropsychiatry: the fundamentals. Oxford University Press, New York.

2. Harris, J. (1998). Developmental neuropsychiatry: assessment, diagnosis and treatment of the developmental disorders. Oxford University Press, New York.

3. Woods, B.T. (1998). Is schizophrenia a progressive neurodevelopmental disorder? Toward a unitary pathogenic mechanism. American Journal of Psychiatry, 155, 1661–70.

4. Spencer, T., Biederman, J., Harding, M., et al. (1998). Disentangling the overlap between Tourette's disorder and ADHD. Journal of Child Psychology and Psychiatry, 39, 1037–44.

5. Flint, J. (1998). Behavioral phenotypes: conceptual and methodological issues. American Journal of Medical Genetics, 81, 235–40.

6. O'Brien, G. and Yule, W. (ed.) (1995). Behavioural phenotypes. Clinics in developmental medicine, No. 138. MacKeith, London.

7. Nyhan, W. (1972). Behavioral phenotypes in organic genetic disease. Presidential address to the Society for Pediatric Research, May 1, 1971. Pediatric Research, 6, 1–9.

8. Holland, A.J., Hon, J., Huppert, F.A., Stevens, F., and Watson, P. (1998). Population-based study of the prevalence and presentation of dementia in Down syndrome. British Journal of Psychiatry, 172, 493–8.

9. Hagerman, R.J. (1999). Clinical and molecular aspects of fragile X syndrome. In Neurodevelopmental disorders (ed. H. Tager-Flusberg), pp. 27–42. MIT Press, Cambridge, MA.

10. Udwin, O. and Yule, W. (1991). A cognitive and behavioural phenotype in Williams syndrome. Journal of Clinical and Experimental Neuropsychology, 13, 232–44.

11. Howlin, P., Davies, M., and Udwin, O. (1998). Syndrome specific characteristics in Williams syndrome: to what extent do behavioral patterns extend into adult life? Journal of Applied Research in Developmental Disabilities, 32, 129–41.

12. Lesch, M. and Nyhan, W.L. (1964). A familial disorder of uric acid metabolism and central nervous system function. American Journal of Medicine, 36, 561–70.

13. Harris, J.C. (1998). Lesch–Nyhan disease. In Developmental neuropsychiatry: assessment, diagnosis and treatment of the developmental disorders (ed. J.C. Harris), pp. 306–19. Oxford University Press, New York.

14. Wong, D.F., Harris, J.C., Naidu, S, et al. (1996). Dopamine transporters are markedly reduced in Lesch Nyhan disease in vivo. Proceedings of the National Academy of Sciences of the United States of America, 93, 5539–43.

15. Cassidy, S.B. and Schwartz, S. (1998). Prader–Willi and Angelman syndromes: disorders of genomic imprinting. Medicine, 77, 140–51.

16. Dykens, E.M. and Kasari, C. (1997). Maladaptative behavior in children with Prader–Willi syndrome, Down syndrome and non-specific mental retardation. American Journal of Mental Retardation, 102, 228–37.

17. Gunn, P., Berry, P., and Andrews, R.J. (1981). The temperament of Down's syndrome in infants: a research note. Journal of Child Psychology and Psychiatry, 22, 189–94.

18. van Lieshout, C.F.M., DeMeyer, R.E., Curfs, L.M.G., and Fryns, J.P. (1998). Family contexts, parental behaviour, and personality profiles of children and adolescents with Prader–Willi, fragile-X, or Williams syndrome. Journal of Child Psychology and Psychiatry, 39, 699–710.

19. Hill, A.L. (1978). Savants: mentally retarded individuals with special skills. International Review of Research in Mental Retardation, 9, 277–98.

20. Beirut, L.J., Dinwiddie, S.H., Begleiter, H., et al. (1998). Familial transmission of substance dependence: alcohol, marijuana, cocaine, and habitual smoking. A report from the Collaborative Study of the Genetics of Alcoholism. Archives of General Psychiatry, 55, 982–8.

21. Jones, K.L., Smith, D.W., Ulleland, C.N., and Streissguth, A.P. (1973). Pattern of malformation in offspring of chronic alcoholic mothers. Lancet, i, 1267–71.

22. Streissguth, A.P., Barr, H.M., Sampson, P.D., and Bookstein, F.L. (1994). Prenatal alcohol and offspring development: the first fourteen years. Drug and Alcohol Dependence, 36, 89–99.

23. Streissguth, A.P., Aase, J.M., Clarren, S.K., Randels, S.P., Ladue, R.A., and Smith, D.F. (1991). Fetal alcohol syndrome in adolescents and adults. Journal of the American Medical Association, 265, 1961–7.

24. Olson, H.C., Streissguth, A.P., Sampson, P.D., et al. (1997). Association of prenatal alcohol exposure with behavioral and learning problems in early adolescence. Journal of the American Academy of Child and Adolescent Psychiatry, 36, 1187–94.

25. Nanson, J.L. (1992). Autism in fetal alcohol syndrome: a report of six cases. Alcoholism, 16, 558–65.

26. Nanson, J.L and Hiscock, M. (1990). Attention deficits in children exposed to alcohol prenatally. Alcoholism, 14, 656–61.

27. Famy, C., Streissguth, A.P., and Unis, A.S. (1998). Mental illness in adults with fetal alcohol syndrome or fetal alcohol effects. American Journal of Psychiatry, 155, 552–4.

28. Sampson, P.D., Streissguth, A.P., and Bookstein, F.L., et al. (1997). Incidence of fetal alcohol syndrome and prevalence of alcohol-related neurodevelopmental disorder. Teratology, 56, 317–26.

29. Ferrer, I. and Galofre, E. (1987). Dendritic spine anomalies in fetal alcohol syndrome. Neuropediatrics, 18, 161–3.

30. Swayze, V.M., II, Johnson, V.P., Hanson, J.W., et al. (1997). Magnetic resonance imaging of brain abnormalities in fetal alcohol syndrome. Pediatrics, 99, 232–40.

31. Mills, J.L., Graubard, B.I., Harley, E.E., Rhoads, G.G., and Berends, H.W. (1984). Maternal alcohol consumption and birth weight: how much drinking in pregnancy is safe? Journal of the American Medical Association, 252, 1875–9.

32. Hans, S.L. (1989). Developmental consequences of prenatal exposure to methadone. Annals of the New York Academy of Sciences, 562, 195–207.

33. Stewart, D.J., Inaba, T., and Lucassen, M. (1979). Cocaine metabolism: cocaine and norcocaine hydrolysis by liver and serum esterases. Clinical Pharmacology and Therapeutics, 25, 464–8.

34. Chasnoff, I.J. (1992). Cocaine, pregnancy, and the growing child. Current Problems in Pediatrics, 22, 302–21.

35. New England Congenital Hypothyroidism Collaborative (1990). Elementary school performance of children with congenital hypothyroidism. Journal of Pediatrics, 116, 27–32.

36. Rutter, M. (1981). Psychological sequelae of brain damage in children. American Journal of Psychiatry, 138, 1533–44.

37. Brown, G., Chadwick, O., Shaffer, D., Rutter, M., and Traub, M. (1981). A prospective study of children with head injuries. III: Psychiatric sequelae. Psychological Medicine, 11, 63–78.

38. Max, J.E., Koele, S.L., Smith, W.L., Jr, et al. (1998). Psychiatric disorders in children and adolescents after severe traumatic brain injury: a controlled study. American Academy of Child and Adolescent Psychiatry, 37, 832–40.

39. van Reekum, R., Bolago, I., Finlayson, M.A., Garner, S., and Links, P.S. (1996). Psychiatric disorders after traumatic brain injury. Brain Injury, 10, 319–27.

40. Max, J.E., Arndt, S., and Castillo, C.S. (1998). Attention-deficit hyperactivity symptomatology after traumatic brain injury: a prospective study. Journal of the American Academy of Child and Adolescent Psychiatry, 37, 841–7.

41. Max, J.E., Lindgren, S.D., Knutson, C., Pearson, C.S., Ihrig, D., and Welborn, A. (1998). Child and adolescent traumatic brain injury: correlates of disruptive behaviour disorders. Brain Injury, 12, 41–52.

42. Max, J.E., Castillo, C.S., and Robin, D.A. (1998). Posttraumatic stress symptomatology after childhood traumatic brain injury. Journal of Nervous and Mental Disease, 186, 589–96.

43. Max, J.E., Castillo, C.S., and Robin, D.A. (1998). Predictors of family functioning after traumatic brain injury in children and adolescents. Journal of the American Academy of Child and Adolescent Psychiatry, 37, 83–90.

44. Wade, S.L., Taylor, H.G., Drotar, D., Stancin, T., and Yeates, K.O. (1998). Family burden and adaptation during the initial year after traumatic brain injury in children. Pediatrics, 102, 110–16.

45. Kraus, J.F. and Nourjah, P. (1988). The epidemiology of uncomplicated brain injury. Journal of Trauma, 28, 1637–43.

46. Kraus, J.F., Fife, D., and Conroy, C. (1987). Pediatric brain injuries: the nature, clinical course, and early outcomes in a defined United States population. Pediatrics, 79, 501–7.

47. Jennett, B. and Teasdale, G. (1981). Management of head injuries. F.A. Davis, Philadelphia, PA.

48. Rosen, C.D. and Gerring, J.P. (1986). Head injury: educational reintegration. College Hill Press, Boston, MA.

49. Wilson, B.A. (1998). Recovery of cognitive functions following nonprogressive brain injury. Current Opinion in Neurobiology, 8, 281–7.

50. Robertson, I.H. (1998). Theory-driven neuropsychological rehabilitation: the role of attention and concentration in recovery of function after brain damage. In Attention and Performance, Vol. 17 (ed. D. Gopher and A. Koriat). MIT Press, Cambridge, MA.

51. Aicardi, J. (1992). Diseases of the nervous system in children. Clinics in developmental medicine, No. 115/118. MacKeith Press, London.

52. Commission on Classification and Terminology of the International League Against Epilepsy (1989). Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia, 30, 389.

53. Saygi, S., Katz, A., Marks, D.A., et al. (1992). Frontal lobe partial seizures and psychogenic seizures: comparison of clinical and ictal characteristics. Neurology, 42, 1274–7.

54. Stores, G., Zaiwalla, Z., and Bergel, N. (1991). Frontal lobe complex partial seizures in children: a form of epilepsy at particular risk of misdiagnosis. Developmental Medicine and Child Neurology, 33, 998–1009.

55. Ohtsuka, Y., Amano, R., Mizukawa, M., et al. (1990). Long-term prognosis of the Lennox–Gastaut syndrome. Japanese Journal of Psychiatry and Neurology, 44, 257–64.

56. Stores, G. (1991). Confusions concerning sleep disorders and the epilepsies in children and adolescents. British Journal of Psychiatry, 158, 1–7.

57. Goodman, R. (1994). Brain disorders. In Child and adolescent psychiatry: modern approaches (ed. M. Rutter, E. Taylor, and L. Hersov), pp. 172–87. Blackwell Science, Oxford.

58. Scott, R.C. and Neville, G.R. (1998). Developmental perspectives on epilepsy. Current Opinion in Neurology, 11, 115–18.

59. Holmes, G.L. (1997). Epilepsy in the developing brain: lessons from the laboratory and clinic. Epilepsia, 38, 12–30.

60. Berkovic, S.F. and Scheffer, I.E. (1997). Epilepsies with single gene inheritance. Brain Development, 19, 13–18.

61. Phillips, H.A., Sheffer, I.E., Crossland, K.M., et al. (1998). Autosomal dominant nocturnal frontal-lobe epilepsy: genetic heterogeneity and evidence for a second locus at 15q24. American Journal of Human Genetics, 63, 1101–9.

62. Buchhalter, J.R. (1993). Animal models of inherited epilepsy. Epilepsia, 34 (Supplement 3), S31–S41.

63. Jalava, M., Sillanpaa, M., Camfield, C., and Camfield, P. (1997). Social adjustment and competence 35 years after onset of childhood epilepsy: a prospective controlled study. Epilepsia, 38, 708–15.

64. Sillapanpaa, M., Jalava, M., Kaleva, O., and Shinnar, S. (1998). Long-term prognosis of seizures with onset in childhood. New England Journal of Medicine, 338, 1715–22.

65. Chiron, C., Dumas, C., Jambaque, I., Mumford, J., and Dulac, O. (1997). Randomized trial comparing vigabatrin and hydrocortisone in infantile spasms due to tuberous sclerosis. Epilepsy Research, 26, 389–95.

66. Neville, B. (1998). The reemergence of critical periods of development. Current Opinion in Neurology, 11, 89–90.

67. Bebin, E., Kelly, P., and Gomez, M. (1993). Surgical treatment for epilepsy in cerebral tuberous sclerosis. Epilepsia, 34, 651–7.