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Childhood Neuropsych..


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Childhood Neuropsych..

  1. 1. Children with Complex Neurodevelopmental and Neuropsychiatric Disorders PART I Definitions and Epidemiology RCPSC MOC Personal Learning Project Dr. Jennifer Fisher. M.B., B.S., MRCPsych, FRCP(C) Clinical Associate Professor Departments of Psychiatry and Pediatrics Faculty of Medicine The University of Calgary July 20th 2006. "Brain development in the early years sets the patterns for behaviour, learning and physical and mental health later on" Dr. J. Fraser Mustard Companion of the Order of Canada, Founding President and Fellow, The Canadian Institute for Advanced Research "The human brain is designed for life in small, relationally healthy groups. Law, policy and practice that are biologically respectful are more effective and enduring. Unfortunately, many trends in caregiving, education, child protection and mental health are disrespectful of our biological gifts and limitations, fostering poverty of relationships. If society ignores the laws of biology, there will inevitably be neurodevelopmental consequences". Dr. Bruce Perry Inaugural Margaret McCain lecture, September 23, 2004 Background The landscape of neurodevelopmental and neuropsychiatric disorders in childhood is vast and only partially explored and charted. It touches all levels of medicine, society, economics and geopolitics. "The human brain is the remarkable organ that allows us to sense, process, perceive, store and act on information from outside and inside the body to carry out the three prime directives required for the survival of our species: (1) survive, (2) affiliate and mate and then, (3) protect and nurture dependents …... This most complex of all biological systems in the known universe is a product of neurodevelopment – a long process orchestrating billions upon billions of complex chemical transactions. It is through these chemical actions that a human being is created" (Perry, 2000). 1
  2. 2. It is because of this complexity and only nascent knowledge that conceptualizing how we understand and manage such children is so challenging yet intriguing and stimulating at one and the same time. Beginning in 2003 there were a series of large meetings involving many representatives of community agencies, paediatricians (general and specialist) and Alberta Children's Hospital (ACH) Mental Health and Developmental Services. These meetings were in response to concerns, mainly from the community, about the difficulties all were facing with management of this population and to begin the process of designing specific services within the Calgary Health Region. The design of clinical delivery services for this large and varied population is not easy for a number of reasons. These include; difficulties articulating the characteristics of the population, problems estimating prevalence and other epidemiological factors, lack of clinical practice guidelines, multiple individuals and agencies are usually involved, the delivery of care is often fragmented and access to funding for specific treatments is very limited amongst many other issues. Concerns have emerged from all levels of medical practice, community agencies and, not least of all, the families. These children are complex in all aspects; medical, developmental and social. They are “expensive”, in that they require enormous amounts of clinical time and other resources. Families have identified tremendous difficulties accessing social supports particularly: day programming, respite, finding suitable in- home support staff, funding and "case management". In situations with children with complex neurodevelopmental and neuropsychiatric disorders almost all the children have extensive comorbidities associated with a very high prevalence of behavioural, psychiatric and psychosocial disturbances. A further observation by paediatricians is that it is the comorbidities that mainly influence prognosis and severely impact the management of the primary condition. The population of patients with complex neurodevelopmental and neuropsychiatric disorders is much like any other paediatric population with chronic illness (for instance diabetes, epilepsy, cystic fibrosis, asthma, arthritis and oncology) requiring long term treatment. In addition, as these are developmental problems, they are chronic and require ongoing regular management and the children graduate to adult services. Unfortunately, adult services for persons with developmental disorders face the same issues as child services. Most units are working at capacity, and are under resourced in terms of staffing and funding. Many physicians working with this population have indicated that remuneration by direct service billing from the various Provincial Health Care Insurance Plans is a barrier to efficient medical care because most of these cases require significant amounts of non- direct clinical time. 2
  3. 3. History Psychiatry, evolving from philosophical roots, became “scientific” at the beginning of the 20th century, with the work of Kraepelin, Wernicke and Hughlings Jackson. The foundations of child psychiatry were social with the emergence of child development clinics in the United States, as part of the education and social service delivery systems. There followed, during the 1960's and 1970's, a dominance of general systems theory, cybernetics and family therapy, as the primary approaches to managing children with mental health problems. Adult psychiatry, during the same period, was beginning to explore the organic associations with psychiatric disorder, particularly schizophrenia, bipolar disorder and anxiety disorders. The 1980's and early 1990's saw enormous advances in neuroanatomy, neurophysiology and psychopharmacology. However, child psychiatry lagged behind. It was not until 1980, that Michael Rutter published his book, “Scientific Foundations of Developmental Psychiatry” (London: Heinemann Medical) and then in 1984, Rutter edited the book “Developmental Neuropsychiatry” (Edinburgh: Churchill Livingston). These books were readily accepted in Europe and shortly thereafter, in the USA. Acceptance of "neuropsychiatric thinking" in Canada was patchy with some areas, notably Montreal, Toronto and Vancouver, beginning to develop neuropsychiatric services for children and youth whilst others significantly lagged behind. Baird and Santosh in 2003 noted that in the post-war years of the 20th century, the divide between neurology and psychiatry was almost complete. There was a separation between the “organic” biologically-based disorders and the “functional” mentally ill behaviorally, affectively or psychotically disturbed individuals. They also note, in the same paper for pediatric neurologists, it was rare for a psychiatrist to be a regular participant in their meetings. As well, it was rare for neurologists to be involved in teaching child psychiatrists. In the last decade, with the advent of neuroimaging, functional neuroimaging, better understanding of neurophysiology, genetics and psychopharmacology, the landscape of child psychiatry has dramatically changed. There is no doubt that there has been a paradigm shift in conceptualizing child psychiatric conditions. In 1995, Christopher Gillberg, in his book “Clinical Child Neuropsychiatry” (Cambridge University Press) stated: “A textbook specifically on clinical child neuropsychiatry has been needed for some time. To the best of my knowledge, this is the first book to be published”. Given the massive paradigm shift in the last decade within child psychiatry, particularly in neurobiology, genetic research and especially imaging technology, this has prompted a significant and extensive re-evaluation of disorders of behavior that were previously 3
  4. 4. assumed to have little biological basis. Several major “mental illnesses” are now fully understood as having significant biological bases. These include: obsessive compulsive disorder (OCD), autistic spectrum disorders, addictions, schizophrenia, attention deficit disorder (ADHD), dyslexia, non-verbal learning disability and mood disorders, amongst many others. Baird and Santosh also state “it is often commented in jest that psychiatry is one of the medical disciplines that is striving towards its own extinction, through the systemic biological research of functional disorders”. Numerous psychiatry training programs, particularly in Europe and the U.S.A. now include mandatory training in pediatric neurodevelopment and pediatric neurology. New departments of "Neurosciences" are emerging encompassing neurology, developmental paediatrics, psychiatry, neuropsychology, genetics and neuroimaging all under one umbrella. It matters little in these departments whether "the head" is a paediatrician, psychologist, neurologist or psychiatrist. Definitions A generally accepted definition of child neurodevelopmental disorders and child neuropsychiatry was provided by Gillberg in 1995. “Child neurodevelopmental and neuropsychiatric disorders includes those infancy, childhood or adolescent onset disorders, in which mental, emotional and behavioral problems predominate at one or other stage of development and for which biological factors have been shown to play a major pathogenic / contributory role”. This may appear to be a simple and unambiguous definition, however the challenges in understanding exactly what neurodevelopmental and neuropsychiatric disorders encompass are considerable. All experts agree that a thorough understanding of neurodevelopment and it's associations with genetic and environmental influences is essential. Dr. Bruce Perry in his chapter on "The Neuroarcheology of Child Maltreatment" provides a clear description of neurodevelopment and the intimate relationship of the brain and environment (Perry 2000). The book "The Synaptic Self – How Our Brains Become Who We Are" (Joseph Ledoux, 2002) is a remarkable and accessible synthesis of "cutting edge" thinking in neurodevelopment. It is also essential reading for those working in this area of social and medical practice. "Development is a breathtaking orchestration of precision micro-construction that allows the healthy development of a human being" (Perry 2000). Dr. Perry's coherent and thorough summary of neurodevelopment is attached to this report as Appendix I. 4
  5. 5. Accepted neurodevelopmental disorders include: Major "syndromes" Mental retardation, including mental retardation with major psychiatric disorder Deficits in attention, motor control and perception (DAMP) Behavioral phenotype syndromes Neurobehavioral disorder in substance-exposed fetuses Disorders of Communication and Language Disorders Developmental Learning Disorders (including coordination, gross and fine motor delays) Autistic spectrum disorders The Neurodevelopmental Impact of Child Maltreatment Neurological Disorders Brain injury Delirium, dementia, stupor and catatonia Brain infection Brain Tumours Neurodegenerative and neuromuscular disorders Seizure disorders Sleep disorders Movement disorders Specialized paediatric populations Children with chronic medical illness Organ transplantation Oncology Burns Hearing and visual impairment "The continuum of obstetric casualty” “Pure neuropsychiatric disorders” (which may or may not include developmental delay) Obsessive compulsive disorder Child and adolescent psychosis Mood disorders (including anxiety disorders, depression, post-traumatic stress disorder, regulatory disorders and adolescent bipolar disorder) Anorexia nervosa How do we define complexity? The first documented use of the word ‘complex’ occurred about 1652 and derives from the French complexe meaning “composed of parts”, which in turn derives from the Latin complexus meaning “surrounding, encompassing”. Com means to “encircle, embrace” and plectere means “to weave, braid, twine”. The adjective meaning “not easily 5
  6. 6. analyzed” was first recorded in 1715. As will become clear and obvious in the body of this report, one of the great complexities of understanding this population is the sheer range of difficulties and how they “encircle, embrace and weave” with each other and numerous other disorders. Components of Complexity With this population, defining complex can be difficult however can be conveniently broken down into the following attributes: The severity of the primary condition or conditions The number and severity of comorbid disorders The number and severity of presenting symptoms The response to previous treatments and interventions The degree of functional and adaptive impairment Difficulties navigating systems The lack of case management The number of professionals and systems involved The degree of communication between the professionals and systems The number and type of recommendations following clinical appraisal Each of these attributes has its own levels of complexity. Epidemiology Epidemiology may be defined as “the study of patterns of disease in human populations” (Kleinbaum et al 1982) Tony Earls in 1979, indicated that epidemiology was “an exact and basic science of social medicine and public health” Earls, F. (1979) Earls went on to state that epidemiology provides the scientific underpinnings for the prevention and control of disease across the spectrum of medicine and its social applications. According to Costello (2005) child and adolescent psychiatry came late to epidemiology. In one respect this was fortunate because a tremendous amount of empirical, theoretical and statistical work had been previously done in other branches of medicine and psychology, from which child psychiatry was able to benefit. In the last 30 years, and particularly in the last decade, research in child neurodevelopmental and neuropsychiatric disorder has caught up considerably, particularly in the innovative use of longitudinal epidemiological samples to study gene-environment interactions. This latter approach has moved to the forefront of epidemiological research, particularly in developmental medicine. Earls in 1979, distinguished between: 6
  7. 7. a.) “Public health epidemiology”, which he defined as, ‘whose task is to monitor and reduce the burden of disease on the community’, and b.) “Scientific epidemiology”, which uses epidemiological methods to speculate on, and attempt to understand, the causative factors. Traditionally epidemiology involved static comparisons between, “indexed populations” and “control groups”. However within in child psychiatry in the 1980s this changed dramatically with the landmark studies of Cicchetti (1984), Garber (1984), Rutter and Garmezy (1983) and Sroufe and Rutter (1984) leading to the emergence of “developmental psychopathology”. This was an integrative discipline seeking to unify, within a developmental, life-span framework, the integration of biology, developmental science and psychopathology. Rather than static differences in symptom presentation at different developmental periods, developmental psychopathology deals with: “The convergence or divergence in the organization of biological, psychological and socio-contextual systems”, as they relate to symptom manifestation and disorder" (Boyce et al.1998, Cicchetti and Toth, 1998). Developmental psychopathology has several implications for epidemiology: I. It presupposes change and novelty. II. It underscores the importance of timing in the establishment and organization of behavior. III. It expects a causal factor may have many outcomes, whereas several causal factors may have the same outcome (Cicchetti and Cohen 1995). IV. Leads us not to expect invariant relationships because causes and outcomes across the span of development (Costello and Angold 1995). In other words, “It helps disentangle how the trajectories of symptoms, environment and individual development intertwine, to produce psychopathology”. Specific Disorders There have been a number of studies in the epidemiology of child psychiatric disorder. Historically, the major figures have been Michael Rutter, author if the Isle if Wight Studies and Dan Offord of the Ontario Child Health Studies. In the United States, Costello and Costello have been prominent figures. Overall findings from community surveys indicate that the prevalence of one or more psychiatric disorders varies between 17.6% and 22.2% (Costello, 1989; Costello et al 7
  8. 8. 1996; and Boyle and Offord 1988). In a more recent article by Roberts et al (1998) which was a review of 52 separate epidemiological studies, revealed a mean prevalence for all psychiatric disorders in childhood at 5.8%. Focusing particularly on neuropsychiatric disorders, at the very least, 5% of all children in the general population, show clear signs of neuropsychiatric disorder before adult age. Depending on exactly which defining criteria are used, some studies quote as many as 9% of the general population. In Sweden, 25 to 50% of all child and adolescent psychiatry consultations are for neuropsychiatric problems (Gillberg, IC 1987). A United States Department of Education study, revealed that 13.2% of school-age children are in special education; most of them diagnosed with learning disabilities or mental retardation (Condition of Education 1997. Supplement; table 46-2). In all epidemiological studies there are significant issues of population selection, instrument design and use, as well as establishing cutoff points between “normal and abnormal”. All epidemiological studies of child psychiatric disorders reveal rates of comorbidity of child disorders far in excess of chance. In the Ontario Child Health Study, 67.8% of the children aged 6 to 16 years, with a diagnosis of at least one of the four studied psychiatric disorders, had one or more additional diagnoses (Offord et al, 1989). The Great Smokey Mountain Study (Costello et al 1996) revealed co-morbidities at 38%. The following section will outline the epidemiology of the major neurodevelopmental and neuropsychiatric conditions. Much of this information is based on the principles of “developmental epidemiology”. Mental Retardation Gillberg (1995) defined mental retardation (MR) as, “MR is not a disease or specific disability. It is an administrative cover-all, blanket term for a variety of genetic, social and medical conditions that share one common feature”. Traditionally, the classification of MR has been, Profound: I.Q below 20-25. Severe: I.Q 20-25 to 35-40. Moderate: I.Q 35-40 to 50-55. Mild: I.Q. 50-70. Borderline: I.Q.70 – 85 / 90 In recent years, the tendency has been to simply distinguish between severe MR (SMR), meaning I.Q. below 50 and mild MR (MMR) I.Q. 50-69. Borderline I.Q. is now defined as I.Q. 70-84. 8
  9. 9. In early studies, the prevalence of MR was based on I.Q. measures alone, which gave a figure of 3% of the total population. However the definition was revised in 1975, by the U.S. Rehabilitation Comprehensive Services and Developmental Disabilities Amendments (PL95-602 of 1978). Using this definition, King et al in 1999 estimated that 1% of the total population could be defined as mentally retarded. This figure is similar to Swedish studies, such as Hagberg in 1983. In all studies the male to female ratio has been found to be 2 to 1. The causes of SMR include: Prenatal 55% chromosomal/genetic factors 34% multiple congenital abnormalities and specific syndromes 10% pregnancy factors, including infection 8% Perinatal 15% fetal anoxia 12% CNS infection 3% Postnatal 12% Unknown 18% includes cases with familial loading 4% The causes of MMR include: Unknown 55% includes cases with familial loading 29% Prenatal 23% chromosomal 5% multiple congenital abnormalities and specific syndromes 10% pregnancy alcohol 8% Perinatal 18% fetal anoxia 17% CNS infection 1% Postnatal 4% Difficult to group The co-morbidities with mental retardation are very varied and extensive. Because mental retardation has, as its origins, genetic and “traumatic” etiology, the medical co- morbidities are obviously extensive. They include: Associated handicap SMR MMR (%) (%) Cerebral palsy 21 9 Epilepsy 37 12 Severe hearing impairment / deafness 8 7 Severe visual impairment / blindness 15 1 Hydrocephalus 5 2 One or more of above handicaps 40 24 Infantile autism 8 4 9
  10. 10. Other severe psychiatric abnormality 56 53 (mood, behaviour, attention, tics etc) Hagberg and Kyllerman (1983), Gillberg et al (1986) Overall, it is estimated that 45% of the total population of mentally retarded individuals has at least one associated medical disorder, as a result of conditions related to or causative of MR. The most common medical co-morbidities are cardiac, orthopedic and endocrine. Regarding behavioral and psychiatric co-morbidities, there is a high incidence of hyperactivity and attentional problems. Even though approximately 60% of MR children may have hyperactive and attentional difficulties, in many cases, it is very difficult to ascertain whether the hyperactivity is a co-morbid disorder (as some 6 to 8% of the general population have hyperactive and attention disorders) or is part of the primary MR disability. This leads to considerable difficulties in deciding whether to attempt treatment of the attention component as one would with any typical child. It is quite common practice amongst pediatricians and psychiatrists, to attempt treatment of the attentional component, as this can result in significant improvements in behavior. However, the use of stimulant medication within the MR population is associated with increased complications. About 20% of the SMR population have a history of pica. Of the total MR population, approximately 25% demonstrate the triad of social, communication and developmental delay, known as the ‘Wing triad’ (Wing 1991). Approximately 5% of the MR population present with classical autism. The psychiatric comorbidities are extensive. Of school-age children with MMR (I.Q. 50 to 69), approximately 50% have co-morbid major psychiatric and behavioral disorders. The figure for SMR (I.Q. below 50) is approximately 70 to 75% for severe psychiatric and behavioral co-morbidity. It is an unfortunate reality in the management of persons with MR, that they have a low societal and medical profile. A term of abuse frequently heard in schools, towards other children is “retard”. Unfortunately the societal attitudes permeate clinical, particularly hospital services. It is a common belief that as these children are “retarded”, then they are “untreatable”. It is extremely difficult, if not impossible, in many instances, to easily admit a mentally retarded person to inpatient services. The reality however, is that a substantial number of these individuals present with potentially treatable co-morbidities, to their primary condition. These co-morbidities would include: attention deficit disorder, mood regulatory disorders, bipolar disorder, obsessive compulsive symptoms and repetitive movements (tics). The diagnosis of a co-morbid (and possibly treatable) disorder, in a mentally retarded individual, requires considerable clinical expertise, clinical acumen and observational skills. Experts in this area of medical practice tend to be quite aggressive in looking for and treating such comorbid disorders, as if successful, this can considerably change the 10
  11. 11. degree of suffering for the individual and their family. There are numerous community-based organizations that specialize in specific behavioral approaches to these children, but without expert medical support. The use of psychopharmacology (in conjunction with specific behavioral approaches), requires considerable medical, developmental and pharmacological knowledge. Typically with these children (and adults), expert knowledgeable and regular follow up is required. Deficits in Attention, Motor Control and Perception (DAMP): The concept of the DAMP disorders emerged from the literature of the 1960's and 1970's on so-called "minimal brain damage" (MBD). Unfortunately, the concept of MBD was expanded so widely and used so frequently that it began to lack diagnostic specificity and the validity. However, in the late 1970's and 1990's Gillberg and others narrowed and redefined the concept considerably and provided diagnostic criteria. DAMP may be defined as a combination of motor coordination and perception dysfunctions and pervasive attention deficit, in any child of normal or low-normal intelligence, who does not meet the criteria for cerebral palsy. The motor coordination component is roughly equivalent to the DSM IV category “Developmental Coordination Disorder”. By using narrow criteria, the concept has considerable practical value. The concept of DAMP has been extensively accepted in Europe and is gaining momentum in Austral-Asia. However, in North America (due to the categorical approach of DSM), it has gained less acceptance. A child in Europe may be diagnosed with DAMP; in North America, the equivalent diagnoses would likely be, using the DSM classification: Axis I - Attention Deficit with disruptive or oppositional problems and on Axis II - Developmental Coordination Disorder and visual perceptual problems (as identified on cognitive assessment). As is well known, attention deficit hyperactivity disorder is common and has a prevalence of approximately 6% of the child population. In this report, although a neurodevelopmental disorder, Attention Deficit Disorder will not be discussed. Aetiology and Clinical Practice Guidelines will be discussed in Part II of this report. Approximately 1% - 2% of seven year olds present with severe DAMP and about 3 to 6% of seven year olds with mild disorder (Landgren et al 1993 - a representative study). Co-morbidities with DAMP are extensive. The depression is a frequent occurrence (approximately 30%) and peaks at age ten. About 50% of ten year olds present with features of severe oppositional defiant and conduct disorder; during the teenage years, the rates of behavioral disturbance are about 30%. One of the most interesting features of the DAMP disorders is that 50% of children with severe DAMP demonstrate autistic symptoms and traits. These include: motor 11
  12. 12. stereotypies, preoccupations, peculiar language, abnormalities of prosody, restricted non- verbal communication and semantic pragmatic language disorder. It is frequently impossible to distinguish severe DAMP and Asperger’s syndrome. A particularly worrying aspect of these disorders is the high rate of emerging personality distortion in the teenage years – up to 60%. There is a high association with forensic difficulties and emerging criminal behaviors. Approximately 80% of this population have dyslexia and dysgraphia. Overall, the outcome for DAMP is not good. Dysfunction Percentage showing dysfunction at age 7 10 13 16 Attention/hyperkinesis 100 (0) 45 (4) 19 (2) - Motor control 100 (0) 55 (4) 30 (2) 36 (5) Reading/writing 69 (0) 76 (16) 73 (8) 75 (5) Psychiatric/behavioural 69 (10) 81 (20) 64 (25) 64 (11) (Gotenberg studies) (brackets = age-matched controls) Wing (1991) considers the triad of social, communication and behavioral delay with SMR to be on a continuum with Kanner's syndrome (classical autism), Asperger’s syndrome and finally severe DAMP. Triad of social, communication, Kanner's syndrome Asperger DAMP behavioural delay and SMR (classical autism) syndrome I______________________________I____________________I__________I (extreme handicap) (mild handicap) Gillberg provided a useful diagrammatic understanding of the complexities of interaction between these disorders. 12
  13. 13. Although not included in the DSM classification, as noted, there are the categorical equivalents to diagnoses on Axis I and II. There is no doubt that these conditions have significant secondary handicap, in terms of family stress and secondary parenting problems. At a practical level, the numbers of these children are large and well-known to all front line clinicians and services. Large numbers of these children are managed by primary care pediatricians in the community. In addition, there are very large numbers of these children in the Child Welfare System, the Youth Justice System, residential homes and throughout the school systems. They are a considerable burden, in terms of resources and require aggressive medical management, of the attention deficit and mood co-morbidities. This is in addition to the extensive behavioral supports, family management (therapy) and school modifications that these children require over many years. It is well-known that these disorders have high associations with low socio-economic status, poverty, under-privileged areas and numerous other psychosocial factors. With the huge neurodevelopmental impact of child maltreatment the DAMP conditions illustrate the intimate relationship between neurodevelopment and environmental 13
  14. 14. disadvantage. Behavioral Phenotype Syndromes Within the group of mental retardation plus psychiatric co-morbidity, there are significant numbers of individuals, who suffer from specific-named genetic syndromes. As of July 9th 2006 some 16,901 genetic disorders have been identified (John Hopkins University: Online Mendelian Inheritance in Man Data Base - mimstats.html). Some 3-5% of all births result in congenital malformations (Robinson, 1993), 20-30% of all infant deaths are due to genetic disorders (Berry, 1987), 30-50% of post-neonatal deaths are due to congenital malformations (Hoekelman, 1988) and 11.1% of pediatric hospital admissions are for children with genetic disorders and 18.5% are children with other congenital malformations (Scriver, 1973). I have been unable to estimate how many surviving children of all genetic disorders have or later develop significant developmental or neurodevelopmental disability. However in my neuropsychiatric community practice the following syndromes are represented: Down’s Syndrome, William’s Syndrome, Prader-Willi Syndrome, Turner’s Syndrome, Klienefelters syndrome, Smith-Magenis Syndrome, Fragile-X Syndrome, Noonan’s Syndrome, Angleman’s Syndrome, Neurofibromatosis, Tuberous Sclerosis and Juvenile Huntington's Chorea (22 cases from a total of 248 active cases). Gillberg (1995) estimates the overall prevalence for such syndromes as exceeding 2/1000 children born. Many of these syndromes show typifying behavioral features are at least as specific as the genetic syndrome. The Genetics Education Center of the University of Kansas Medical Center has an excellent, and updated website for those interested ( Neurobehavioural Disorder in Substance Exposed Fetuses These disorders include Fetal Alcohol Spectrum Disorders (FASD) and prenatal exposure to various other substances including opiates, cocaine and marijuana. Alcohol abuse in society is very prevalent and any alcohol use is unacceptable during pregnancy. FASD and related disorders, such as alcohol-related neurodevelopmental disorder (ARND) are the most common and completely preventable form of developmental disability and birth defects in the western world. The societal cost is staggering. According to the National Institute on Alcohol Abuse and Alcoholism in 2000 Harwood estimated the cost in 1998 to the U.S.A. was $4 billion dollars in terms of lost productivity, health and educational expenses. The World Health 14
  15. 15. Organization has defined alcohol use and abuse. It is salutary to compare societal impressions of "normal" alcohol use and actual risk of harm (Appendix II). Fetal Alcohol Spectrum Disorders are a spectrum of structural abnormalities, neuro- cognitive disabilities, psychiatric and behavioral disorders. The earliest descriptions were by Aristotle (Abel EL 1999) and the Bible (Judges 13:4) describes the offspring of women drinkers. Several physician groups in England during the 1700's described children of alcoholics as “weak, feeble and distempered” and “born weak and silly - shriveled and old, as though they had numbered many years”. In 1899, Sullivan described the offspring of alcoholic women imprisoned in England. The clinical syndrome was "re-discovered" in 1968, when Lemoine et al in France published a report that described some of the common problems among 100 children of women who drank heavily. The frequency of FAS in Canada is estimated between 0.5 and 3 per thousand live births. The estimated incidence of conditions within the FASD category is 10 per thousand live births (Alberta Clinical Practice Guidelines 1999). Even despite increased public awareness of FASD, early recognition and accurate diagnosis by mental health professionals continues to be a significant and serious problem (Alberta Clinical Practice Guidelines 1999, Streissguth AP 2000). Indeed, it has been stated that mental health professionals do not routinely inquire into maternal alcohol (and other substances) use during pregnancy, nor are thorough physical examinations completed by psychiatrists, particularly in outpatient clinics. In the Aboriginal community, the rates of fetal alcohol syndrome are much greater; in an isolated B.C. community, FASD was estimated at 190 per 1000 live births. (Robinson et al 1987). Overall, the estimates for Aboriginals are between 25 and 100 per 1000 live births for FASD in Canada (Williams et al 1999, Square 1997). A very important factor with FASD is there is no ethno-cultural association and the disorder occurs across all levels of the socio-economic spectrum. However, incidents appear to be increased with higher maternal age, lower parental education level, lower socio-economic status, paternal drinking and cigarette smoking. The primary disabilities in FASD are the result of direct brain damage due to the toxic effects of alcohol. The most consistent finding is a reduction in brain weight that can result in microcephaly. Prenatal alcohol exposure is known to disrupt many areas of brain development, including the cerebellum, hippocampus, basal ganglia, and corpus callosum. Other pathologic changes within the brain and central nervous system include: enlarged ventricles, abnormal cell migration and changes in the microvascular architecture, in certain brain regions. Within the complete spectrum, I.Q. may be within normal limits, however within the FAS component, there is commonly mental retardation. In the absence of mental retardation, numerous neuro-cognitive and neuropsychological abnormalities have been described. Mental retardation may occur within 25% of persons with FAS. Other 15
  16. 16. impairments include: severely impaired learning and memory, intrusion errors and confabulation. Abnormalities in language function are typical; individuals are very good at “parroting back” verbal information they have heard, however they tend to be loquacious with their verbal communication, lacking complex meaningful content. They also have significant problems with the comprehension of complex material. Other co-morbidities include visuomotor integration problems, numerous learning disabilities, impulsivity and poor response inhibition. A common co-morbid disorder is attention deficit hyperactivity disorder. Severe dysfunction with executive functioning is usually the norm, as well as severe delays in adaptive skills. A common and misleading feature of FASD is that as many individuals appear physically typical and mature and because they seem to use relatively sophisticated language, the diagnosis is missed or significantly delayed; this is a significant issue within the practice of adult psychiatry. In addition to the typical neurodevelopmental and neuropsychological disorders, the secondary disabilities and co-existing conditions are substantial. Common secondary disabilities include: Mental health disorders - depression and suicidal ideation Disrupted school and employment experience Forensic problems Inappropriate sexual behavior and involvement in the sex trade Addictions The rates of coexisting disorders are staggering, including 90% of subjects having neuro- cognitive disturbance and 61% with a co-morbid psychiatric disorder in childhood. When one examines the adult population, the complications are equally staggering, including 44% with major depressive disorders, 40% with psychotic disorders and 20% with bipolar disorder (Famy et al 1998). Standardized diagnostic approaches have been developed; the most common are from the Institute of Medicine (Stratton et al, 1996) and the FAS Diagnostic and Prevention Network Model (Astley and Clarren, 1999). Clarke and Gibbard (Alberta Children’s Hospital) have provided excellent summary publications regarding diagnosis, complications and management of FASD. In addition to FASD, in the last number of years, there is increasing concern about prenatal exposure to opiates, marijuana and cocaine amongst other substances. Neurodevelopmental assessments are clearly indicating infants born with low birth weight, small head circumference and failure to thrive; however a complicating factor is many infants born to substance abusing mothers, are also being raised in environments of neglect, deprivation and abuse. Given what is known about the severe impact of abuse and neglect on neurodevelopment, it is difficult to tease out and weight the various factors. 16
  17. 17. Children born to substance abusing parents in later years, have high incidences of mood disorder, cognitive difficulties, learning problems and attentional issues. Quite commonly, they present with oppositional and conduct disordered behaviors. Once again, it is difficult to tease out a direct “neuro-toxic” effect from psychosocial variables. Brain Injury Childhood accidents are the most common cause of acute brain injury. Some 10 to 20% of the child population annually, have significant accidents; of these 33% are injuries to the head and neck and 1% include fractures of the skull. The rates of severity increase steadily up to about 14 years of age, with a dramatic peak occurring at 15 years. However there is also a peak of moderate to severe injuries occurring in infants younger than one year of age (much of this is as a result of child physical abuse). There are interesting demographic risk factors, including poverty, single parent households, a parental history of psychiatric disorder, drug and alcohol abuse or physical illness with the parents. Child characteristics include, risk-taking behaviors. A study in the city of Westfet found that 0.86% of children under 16 years of age sustained skull fractures or brain contusions over the course of one year, and 1% of boys and 0.5% of girls had an acute head injury with cerebral symptoms over the course of one year. These figures are echoed in more recent data from the U.S. National Pediatric Trauma Registry. Traumatic brain injury (TBI) has traditionally been assessed on the basis of the initial level of consciousness, duration of coma or extent of the post-traumatic amnesia. The Glasgow Coma Scale has become the standard measure of the initial level of consciousness. This area of practice is extremely difficult to study, given the wide variety of injuries and difficulties assessing severity. The sequelae of head injury include: “Traditional” neurological sequelae: seizures, low arousal, hyper-somnolence, headache, migraine, EEG abnormalities. Psychiatric sequelae: depression, psychotic symptoms, disinhibition, abulia, mood dysregulation, hypochondriasis, insomnia, bulimia. Cognitive sequelae: deficits in memory and attention, executive function problems. Estimating the prevalence of sequelae is almost impossible and one can only speak in generalities. In severe injury, all of the above sequelae occur and likely in the majority of cases. It is also known that symptoms can persist over months and years. Full neuropsychological assessment is recommended at one year post-injury. Diskala et al in 1991, using the Pediatric Trauma Registry estimated that 73% of children with major TBI suffered multiple functional cognitive and psychiatric symptoms. 17
  18. 18. In mild head injury, the post-concussion syndrome is common; however sound long-term data with children is lacking. However Gillberg (1995) and Gualtieri (1990) dispel the commonly held myth that “mild head injury is really of no, or at least very little, long- term consequence”. They indicate that the bulk of evidence clearly indicates otherwise. Long-term data that is available in children, even after only transient unconsciousness or confusion, without any clear anatomic evidence of brain damage, indicates problems with headache, dizziness, irritability, difficulty concentrating and in the older person, alcohol intolerance, fatigue, anergia, depression and insomnia. Memory deficits are also commonly reported features. Traditionally and historically there has been little involvement of psychiatrists in brain injury or trauma units. Indeed, Gillberg comments: "one of the most unfortunate outcomes for a survivor of closed head injury, is that he/she will be usually confronted with a less than informed attitude, on the part of psychiatrists. Only conventional psychiatric diagnoses will be applied – in spite of generally being inadequate in this field”. What Gillberg is highlighting with this statement is the traditional diagnoses do not fully encompass the subtly and pervasiveness of the multitude of symptoms that can occur following severe and mild head injury. It is clear from the literature and clinical practice that these children require long-term and regular follow up. Disorders of Communication and Language Disorders Communication problems occur commonly within mental retardation, hearing impairment and a host of behavioral phenotype syndromes, including the autistic spectrum disorders. Acquired disorders of communication can be associated with many general medical disorders, including traumatic brain injury, brain infection and a side- effect of some treatments, including radiation treatment in oncology. There is also a high incidence of communication disorders associated with pre-natal exposure to substances such as drugs and alcohol, along with parental behavior disorders. Language disorders are a frequent component in FASD. There are common environmental associations with communication disorders, including child maltreatment. Culp (1991) argued that language development is particularly vulnerable in the maltreatment situation, not only because of the disruption in social interaction maltreatment entails, but also the frequent association with neglect. Numerous studies (for example, Allen and Oliver 1982, Fox et al 1988 and Coster and Cicchetti 1993) have found a clear association between neglect and lower verbal I.Q. relative to non-verbal I.Q. on cognitive assessment (see also Perry 2000). Specific speech and language disorders include, stuttering, phonological disorders, expressive and receptive language disorders. Accurate estimates of the prevalence of specific language disorders have been difficult to come by, because of methodological differences between studies and classification issues. Rescorla and Lee (2001) estimated the prevalence during the preschool period, to be generally in the range of 10 to 15%. 18
  19. 19. Law et al (1998) noted a 6% prevalence of speech and language problems in all children of school age. These included: expressive language disorder, mixed expressive/receptive language disorder and phonological disorder. Co-morbidities with developmental language disorders are extensive with huge cross- overs in co-morbidity with severe behavioral disorders, other learning disabilities, DAMP, autistic spectrum disorders, maltreatment and mental retardation. It is estimated that there is a 50 to 80% co-morbidity of language disorders with other neurodevelopmental disorders. Developmental Learning Disorders (including coordination disorders) Developmental learning disorders include reading disorder, mathematics disorder, disorder of written expression and learning disabilities not otherwise specified according to the DSM classification. A diagnosis of a developmental learning disability is when a significant, usually two year, delay is noted on standardized testing. Learning disabilities are extremely common in the school-age population, approximately 8% of all school-age children (National Health Interview Surveys, 1997 - 1998 U.S. National Center of Health Statistics). The Behavioral Research Unit at Alberta Children's Hospital headed by Dr. Bonnie Kaplin (Professor, Department of Pediatrics) is nationally and internationally known for research in developmental learning disabilities. Reading disorder (dyslexia), is about 4% of the school-age population, math disorder (dyscalculia) is approximately 2% and disorders of written expression (dysgraphia) are about 4% of the school-age population. The overlap between the categories of learning disability is approximately 60%. As would be expected, there are huge associations with all other neurodevelopmental disorders, but particularly with DAMP and ADHD, as well as behavioral disorders, including oppositional defiant and conduct disorder. Other well-known figures reveal that 40% of children with developmental learning disabilities have ADHD and 40% of ADHD children are learning disabled. 33% of the reading disordered group also have conduct disorder and 33% of conduct disordered children have severe reading disability. The famous long-term cohort studies of Lee Robins beginning in the 1940's estimate that 80% of youth in forensic services have some form of developmental language or learning disability in addition to commonly MMR and DAMP. Closely associated with developmental, communication, language and learning disabilities are disorders of gross and fine motor development and coordination disorders. Clearly disorders of motor control are part of the DAMP complex. Barkley (1997) noted that 50% of children with developmental coordination disorder (DCD) also met the criteria for ADHD and vice versa. There are numerous secondary handicaps and co- 19
  20. 20. morbidities with DCD itself, particularly on self-esteem and self-concept in children, as well as accidents, including an increased risk of traumatic brain injury. Combinations of learning disabilities, including disorders of written expression have high correlations with DCD. Some estimates are as high as 12% of all school-age children will present with one of these neurodevelopmental learning disorders (American Academy of Child and Adolescent Psychiatry. Practice Parameter for Psychiatric Consultation to Schools. 2005). Palfrey et al examined the records of 1726 children in special education classes at five sites and found that only between 15 and 25% of the learning and speech disorders had been identified prior to school entry (age five). A further study in the United Kingdom failed to detect 38% of children with moderate learning disabilities and 94% of children with mild to moderate learning disabilities prior to school entry. The Juvenile Forensic Population Finally there needs to be brief discussion of the forensic population as there are highly significant associations with DAMP disorders, mental retardation and developmental learning disabilities (reading, math and developmental coordination disorder amongst many others). Although as many as 75% of juvenile offenders have one or more diagnosable psychiatric disorders (Teplin et al., 2002), most correctional facilities do not have the resources to provide adequate services. Autistic spectrum disorders Rutter (1978) defined the pervasive developmental disorders, as: “a group of neurodevelopmental - neuropsychiatric disorders, characterized by specific delays and deviance, in social, communicative and cognitive development, with an early onset, typically in the first years of life. Although commonly associated with mental retardation, these disorders differ from other developmental disorders, in that their developmental and behavioral features are distinctive and do not simply reflect the developmental level”. This is a fairly standard definition and there would be little disagreement. However there are significant concerns about the current situation of how we understand these disorders, particularly at the “higher end of the spectrum”. Using categorical diagnostic systems the relationships and diagnostic overlap between high functioning autism, Asperger's syndrome and "atypical autism" and approximately 50% of the DAMP population can be confusing. 20
  21. 21. Kanner's Syndrome High functioning autism ("classical" autism + SMR) (MMR or average intellect) I__________________________________________I_________ I I I I I Asperger's I "Atypical "The Wing Triad" Syndrome I Autism" + SMR I 50% of severe DAMP There are many "concerns" regarding the understanding, epidemiology and management of ASD, they include: - The apparent massive reported increase in prevalence over the last decade - The "careless" use of the DSM classification of PDD (over-inclusive diagnosis) - The pathologizing of gifted individuals - Unconventional ideas regarding etiology - Unproven and unorthodox treatments - Questions of whether the spectrum is a valid construct - A clear lack of evidence-based thinking In the Journal of Pediatrics in 2004, it is reported that “autism is a complex, behaviorally defined static disorder of the immature brain, that is of great concern to the practicing pediatrician, because of an astonishing 556% reported increase in pediatric prevalence between 1991 and 1997, to a prevalence higher than that of spina bifida, cancer or Down’s syndrome”. The first medical description of autistic disorder was by Kanner (1943) when he described 11 children with “extreme autistic aloneness", abnormal speech with echolalia and an “anxiously obsessive desire for the maintenance of sameness”. Kanner also emphasized the familial characteristics. Unfortunately Kanner's choice of the word "autism" was unfortunate, because of its previous use Bleuler (1911) to describe the withdrawal into an active fantasy adopted by schizophrenics” (Ritvo, 1976). It was not until the work of Israel Kolvin (Kolvin 1971, Kolvin I, C Ounsted et al. 1971) that autism and childhood schizophrenia were finally separated. This terminology issue delayed research into the etiology and management of autism by some 20 to 30 years and was part of emphasis on the psychodynamic aetiology prevalent during the 1950's to 1970's. [Even though the medical description was not provided until 1943 "classical" cases of autism have been described since the 18th century (a particularly interesting case is that of Hugh Blair of Borgue, 1708 – 1765 (Houston and Frith, 2000). John Haslam, in the chapter "Cases of Insane Children" in his book, “Observations on Madness and Melancholy” in 1809, describes a 7 year old boy and from the records of the Great Ormond Street Hospital Dickinson describes three children with what we would today consider "DSM autism" (Mintz 2004)] 21
  22. 22. About the same time that Kanner described autism, Hans Asperger (1943) described a group of relatively high functioning individuals with impaired social interaction, restricted range of interests and activities with the early preservation of language skills, but severe delays in communication skills (pragmatics), many these children could speak incessantly and were known as “little professors”. Motor delays were common and although they had normal intellect, they frequently had associated learning disabilities. Prior to the advent of the DSM classification, various other terms were used, such as, “autistic psychopathy”, “more able autistic people” and “high functioning autism”. It was not until 1981, that Lorna Wing coined the term, “Asperger’s syndrome” (Wing L 1981). The current DSM-IV classification of Pervasive Developmental Disorders include: Autistic disorder, Asperger's disorder (AD), Rett's Disorder, Childhood Disintegrative Disorder (CDD) and Pervasive Developmental Disorder - Not Otherwise Specified (PDD-NOS). With the advent of the DSM-IV classification it appeared that there was clarity, however the late 1980's and 1990's exploded with a host of "new diagnoses", including high functioning autism, sensory integration disorder, regulatory disorder of infancy, non-verbal learning disability, right hemisphere syndrome in children, hyperlexic syndrome, visuospatial motor disorder, multiplex developmental disorder and pragmatic language disorder. In addition autistic symptoms were described in numerous genetic disorders and syndromes, brain injury, frontal lobe syndromes, a host of neurological disorders, Gilles de la Tourette's syndrome, obsessive compulsive disorder and many others. Even with the DSM classification much confusion continues today. Not only was there an "explosion" in diagnoses and “symptoms” being observed in many other conditions, there was also an "explosion" in theories of causation – mostly of little to no validity with some being frankly wildly speculative. Numerous studies have not confirmed these assertions - an excellent paper by Herbert et al “Separating Fact from Fiction in the Etiology and Treatment of Autism: A Scientific Review of the Evidence” is essential reading (Herbert et al 2002). Such reading is essential to the current considerations of the business plan as very many families hold on to many of these alternative theories, the result being a delay in accessing evidence based treatments and management. Interested readers may access full and up to date information on autism by downloading three PowerPoint presentations presented by me for the Department of Paediatrics, Division of Developmental Paediatrics Grand Rounds (November 2005, February and April 2006). The URL is: Site/ Defining the spectrum and understanding the epidemiology has been remarkably complex, because of the shifting definitions, loose application of criteria and a very real tendency for the diagnosis to be “in vogue” over the last decade. Numerous countries including Canada, U.S. and the United Kingdom have created government and parliamentary groups, to drive research in autistic spectrum disorders and there has been much written on screening and population surveillance. Concerning diagnosis, classical autism on history and examination, is an easily 22
  23. 23. identifiable disorder, however most children are not diagnosed until age four to five years and typically two to three years after parents first seek professional help. Indeed, most children are seen by at least three professionals prior to diagnosis. Many studies however indicate that autism can be detected as early as 18 months (Baron-Cohen 1992) and the diagnosis appears robust over time (Eaves LC 2004). Interestingly, these studies indicate that early recognition is more related to the degree of developmental delay and the presence of neurological symptoms, rather than the severity of the autistic condition. Solid Practice Parameters exist for the assessment and treatment of children with autism and related disorders (Volkmar et al. J Am Acad Child Adolesc Psychiatry 1999). In recent years, there has been the introduction of standardized diagnostic instruments, including the Autism Diagnostic Interview - Revised (Lord et al 1994) and the Autism Diagnostic Observation Schedule: Generic (ADOS-G) (Lord et al 1989). Both of these are semi-structured, standardized instruments and at the “lower end of the spectrum”, have high validity and specificity. However, at the higher end of the spectrum, that is children with so-called high functioning autism, or atypical autism, the validity and specificity is much less certain (Mahoney WJ 1993, Bishop DV 2002). Because of these issues, as noted, establishing prevalence has been remarkably difficult. It has been questioned whether the increase in the numbers of autistic children represents a true increase, or is related to shifting diagnostic criteria and categories, or due to international differences in concept, as well as the diagnosis being “currently fashionable". Gurney (2003) noted that most of the increase in the prevalence could not be accounted for by diagnostic substitution, however Croen (2002) studying a cohort population in California strongly suggests that autism was being diagnosed in preference to mental retardation (likely to access services). Probably the best data on prevalence have been presented by Eric Fombonne. In 2003, he reviewed 21 epidemiological studies from 13 countries since 1987. He noted the huge methodological problems with sampling and definition and concluded that the rates for autism varied between 2.5 per 10,000 to 30.8 per 10,000 - the “best estimate” was 10 per 10,000. He noted, in studying Asperger’s syndrome and PDD from 32 studies, the same methodological issues and gave a prevalence of Asperger’s syndrome at 2.5 per 10,000 and PDD-NOS at 15 per 10,000. Taking all diagnoses together, the prevalence of autistic spectrum disorders is approximately 60 per 10,000 (or one in 165 children). A detailed review of prevalence reveals that the rates of “classical autism” have increased in the western world, but only modestly. The prevalence rates of Rett's disorder and CDD have not increased. However the rates for Asperger’s syndrome, high functioning autism, "atypical autism" and PDD-NOS have risen tremendously. It is worth noting once again, the problems with diagnosis, the ADI-R and ADOS identification at the "top end" of the spectrum. 23
  24. 24. Prevalence of PDD in Canadian children aged 0-19 This table shows the estimated number of Canadian children with PDD, by province, based on 2001 Census data and a prevalence rate of 60/10,000. Current numbers would be higher, about 48,000 Canadian children. PROVINCE POPULATION CHILDREN WITH PPD Newfoundland and Labrador 128,220 769 Prince Edward Island 36,875 221 Nova Scotia 226,775 1,361 New Brunswick 180,770 1,085 Quebec 1,753,650 10,522 Ontario 3,002,165 18,013 Manitoba 314,140 1,885 Saskatchewan 285,540 1,713 Alberta 840,550 5,043 British Columbia 976,350 5,858 Yukon 8,325 50 Northwest Territories 13,060 78 Nunavut 12,445 75 Total for Canada 7,778,865 46,673 (Chakrabarti S, Fombonne E 2001, 2004) (In Canada, there are about 8 million young people in the age group 0-19. Applying a rate of 60/10,000 (or 0.6%), we can estimate that there are currently 48,000 young people from that age group suffering from a PDD today in Canada. This count does not reflect the adult population) There are numerous medical co-morbidities and disabilities, which are summarized below Associated medical disorders and disabilities in children with autistic disorder: a population-based study Kielinen M 2004 Sample population: 152,732 children under the age of 16, 187 children DSM IV autistic disorder. (AD, Rett syndrome, CDD excluded) 19% more than one disorder 12.3% known or suspected genetic condition 18.2% seizure disorder 24
  25. 25. 13.4% impaired ability to walk 8.6% hearing impairment (1.6% severe hearing loss) 7.5% associated neurological disorder 4.3% cerebral palsy 3.7% blind 3.2% hydrocephalic 1.1% fetal alcohol syndrome In general, the proportion of cases attributable to specific medical conditions is low and identifying clear causal relationships is complex. Although previous literature suggested associations with the following disorders, recent literature does not suggest more than chance associations between autism and Down’s syndrome, congenital rubella, cerebral palsy, phenylketonuria and neurofibromatosis. However 4% of autistic children have fragile-X syndrome (Dykens and Volkmar 1997) and rates of autism are increased in tuberous sclerosis (Smaley et al 1992). There is a clear association between autism and epilepsy. In autistic children with severe mental retardation, up to 70% may have generalized seizure disorders. The degree of mental retardation in autism is predictive for the development of seizures; the highest rates are in adolescents and adults. Regarding cognitive abilities, Fombonne (2003) reported that 40% have severe MR, 30% mild to moderate MR and 30% have normal intellect (this included all subtypes of autism on the spectrum). However in classical autism, 75% have severe to profound mental retardation. There are numerous reports of associations with psychiatric and behavioral disorders, however there is less certainty whether such associations are greater than would be expected by chance alone and significant questions about whether such symptoms and behavioral manifestations are part of the primary autistic condition or the manifestation of a co-morbid condition (Tsai 1996). The psychiatric disorders associated with autism include: oppositional behavior, anxiety, depression, hyperactivity, poor attention, tics and obsessive compulsive behaviors (Volkmar et al: Practice Parameters 1999). The diagnosis of co-morbid psychiatric disorders in autism can be particularly difficult for individuals who are largely, or entirely mute, or function in the severely or profoundly mentally retarded range. Quite frequently, higher functioning autistic individuals, particularly those with Asperger’s disorder, have co-morbid problems with generalized anxiety disorder, social anxiety disorder (over and above what would be expected by the primary condition) obsessive compulsive disorder and as adults, often schizoid, schizotypal or avoidant personality disorder diagnosed. The psychiatric comorbidity likely effects 70 – 80% of the population. Gillberg (1998) provides a useful graphic of the inter-relatedness of ASD with other disorders. 25
  26. 26. Briefly there needs to be mention of aetiological factors. No other disorder in medicine has been subjected to as much “pseudo-science” and hypothesizing as autism. All experts now agree that there is compelling evidence for strong genetic influences, resulting in abnormal brain development, which in turn results in regional brain abnormalities, at the gross and micro anatomic levels and at the biochemical and neurophysiological levels. Although the precise location of the abnormalities is open to some discussion, numerous replicated studies are consistently demonstrating abnormalities in the frontal lobes, limbic system (amygdala and related structures) and the fusiform gyrus. The Neurodevelopmental Impact of Child Maltreatment Poverty, psychosocial disadvantage, neglect, and child maltreatment are the leading causes of developmental delay (physical, cognitive and emotional) in the western world. The prevalence of all types of abuse and poverty is extensive. In 1998, there were an estimated 21.52 per 1000 investigations for child maltreatment in Canada. Forty-five percent of these investigations were substantiated, 22% remained suspected, and 33% were found to be unsubstantiated. Child maltreatment investigations were divided into four primary categories: physical abuse (31% of all investigations), 26
  27. 27. sexual abuse (10% of all investigations), neglect (40% of all investigations), and emotional maltreatment (19% of all investigations). Thirty-four percent of the physical abuse investigations were found to be substantiated. This compares with 38% for sexual abuse, 43% for neglect, and 54% for emotional maltreatment. Thirty-four percent of the physical abuse investigations were found to be substantiated. This compares with 38% for sexual abuse, 43% for neglect, and 54% for emotional maltreatment. Substantiated cases of physical abuse consisted of: -Inappropriate punishment (69% of physical abuse cases) -Shaken Baby Syndrome (1%) -Other forms of physical abuse (31%) The most common forms of substantiated neglect included: -Failure to supervise leading to physical harm (48% of neglect cases) -Physical neglect (19%) -Permitting criminal behaviour (14%) -Abandonment and educational neglect (12% and 11% respectively) The most common forms of substantiated sexual abuse included: -Touching and fondling of the genitals (68% of sexual abuse cases) -Attempted and completed sexual activity (35%) -Adults exposing their genitals (12%) Substantiated cases of emotional maltreatment included: -Exposure to family violence (58% of emotional maltreatment cases) -Emotional abuse (34%) -Emotional neglect (16%) (The Canadian Incidence Study of Reported Child Abuse and Neglect (CIS) Public health Agency of Canada 1998, the second cycle of studies began in 2003, Finkelhor D. et al 1999) Belsky (1980) articulated the prevailing model of the origins of abuse. This is the ecological model which views child abuse as the consequence of interactions of parental vulnerabilities (mental illness, substance abuse), child vulnerabilities (low birth weight, difficult temperament), a particular developmental stage (adolescence, toddler), and social stressors (lack of social supports, poverty, single parenthood, minority ethnicity, lack of acculturation, presence of four or more children in a family, young parental age, stressful events, exposure to family violence). It is clear from the ecological model that there are numerous developmental and psychiatric pathways, to each of the parental, child and social vulnerabilities. The situation is so complex that no single one of these factors can be "teased out" as being 27
  28. 28. predominant over the others. Giovannoni (1998) defined child neglect as follows: “whereas abuse is considered an act of commission, neglect is considered an act of omission. Neglect is perpetrated by caretakers of children, who fail to fulfill their caretaker obligations to children”. In 1998, 53.5% (6.8 per 1000 U.S. children), of documented child maltreatment victims, suffered neglect (U.S. Department of Health and Human Services, 2000). Dr. J.W. Pearce, psychologist with the Child Abuse Program at Alberta Children’s Hospital and Dr. T.D. Pezzot-Pearce, a psychologist in private practice in Calgary, authored the book, “Psychotherapy of Abused and Neglected Children”. The book is now in press for the second edition. Chapter one is titled, “Child Maltreatment and Developmental Outcome”. The authors provide an extensive and extremely well- researched overview of the multiple developmental interactions and outcomes of child maltreatment. In context of the business plan, this chapter should be reviewed (Pearce, JW, and Pezzot-Pearce, TD, 2006 - in press). Almost every developmental delay described in this report including cognitive, language, communication, motor, attention, mood and traumatic brain injury (including sequelae), are significantly increased in the maltreated population of children. Likely the figures are in the region of 60% of all maltreated children. O’Brien (2003) reports that although child abuse causes approximately 5% of brain injuries in children between the ages of one and four years old, it results in 90% of serious brain injury. Also in the same report, she notes nearly 25% of infant and toddler TBI cases admitted to pediatric and intensive care units are caused by physical child abuse. There are clear neuroanatomic consequences of abuse. DeBellis (1999) using MRI studies compared the brains of 44 maltreated children with PTSD, with a healthy control group. The cerebral volumes of the abused children were reportedly 7% smaller than the controlled subjects. In addition, the corpus callosum was smaller and volumes of CSF were larger in the abused sample. Other studies have shown clear changes in chatecholamine metabolism, high cortisol levels and other neurophysiological abnormalities in maltreated children, particularly those with PTSD. McCrea et al (1997) notes that a common result of abuse or neglect is direct CNS injury, which is later associated with hyperactivity, emotional lability, diminished intelligence, poor judgement, impulsiveness, and very importantly it is known that injuries to the CNS, even apparently mild concussions, have accumulative neurological and cognitive effect. As an aside, other research shows that violent juveniles have often experienced multiple accidents and injuries with many of them inflected by those entrusted with their care – Ewing-Cobb et al (1998). Neuropsychological appraisals of maltreated children describe, not only reduced cognitive abilities, but severe dysfunction in executive frontal lobe functions. All of this is in addition to the emotional consequences of abuse, including heightened 28
  29. 29. vigilance, anxiety, fear, self-esteem, depression and many other responses. Dr. Bruce Perry of the Child Trauma Academy, in Texas, has concisely outlined the neurodevelopmental impact of neglect in childhood. Not only does he report similar findings to Pearce (2006), he also notes the significant neurological impact on development, including microcephaly, delayed sensory motor and cognitive abilities, along with numerous examples of other neurological and neurophysiological deficits. Neurological Disorders Neurological disorders with neuropsychiatric components, of importance to the current business plan and development of services include conditions such as delirium, dementia, stupor, catatonia, seizures, brain tumors, brain infection/encephalitis, brain irradiation factors, neuro-degeneration, neuromuscular disorders, the complications of pediatric HIV infection and sleep disorders. Given the large number of neurological disorders that present with neuropsychiatric complications or components, it is not possible to focus on all in this review. Seizure Disorder in Childhood This is probably the commonest condition where there will be liaison between neurology and psychiatry. Epilepsy is the most prevalent major childhood neurological disorder affecting 0.5 to 1.0 % of children under 16 years of age. Co-morbid conditions are common in children with epilepsy and some may even over-shadow the epileptic condition itself. The treatment of epilepsy must also take into account, the effect of anti- epileptic drugs (AEDs) on co-morbid conditions. The co-morbidities associated with epilepsy differ between children and adults, because of ongoing maturation (both CNS and systemic) and associated behavioral cognitive and structural changes. As part of the evolution, seizure type and epilepsy syndromes also change with age. The evolution of the seizure type with age complicates the diagnosis of epilepsy syndromes and their co-morbidities. Common seizure types in childhood include: complex partial (23.4%), generalized tonic clonic (18.6%), absence seizures (12.8%), other generalized seizures (11.3%) and varied others including simple partial, myoclonic and of unknown origin. Prevalence rates for neuropsychiatric co-morbidities vary widely. The incidence of ADHD has been reported from 8 to 77% (Dunn et al). Depression and anxiety is common at approximately 26% (Ettinger et al). Children with autism and developmental delay are at increased risk for epilepsy, as are children with many disabilities, including cerebral palsy and other developmental syndromes. There is a very high incidence of behavioral and school-based problems relating to learning and achievement, in children with epilepsy, however as noted above, disentangling the contributing factors is extremely difficult.An excellent summary and review of the co-morbidities affecting 29
  30. 30. children with epilepsy, has been completed by Pellock, 2004. Sleep Disorders Sleep disorders in childhood are increasingly recognized as a significant component of child psychiatric and neuropsychiatric disorder. There is no doubt that sleep disorders are very common in childhood. The prevalence of the various disorders varies depending on age and presenting symptoms. Sleep disorders can be classified as dyssomnias, including primary insomnia and circadian rhythm disorders, primary hypersomnia (excessive daytime sleepiness), breathing-related sleep disorder and parasomnias (including sleep-walking, sleep-terror disorders and nightmare disorder). There are other rarer types of sleep disorder, including narcolepsy and Kline-Levin syndrome. Traditionally, sleep disorders have been viewed as mainly “behavioral”. Although behavioral sleep disorders are common, the interaction between sleep, behavior and neuro-development is only just becoming understood in childhood. Numerous psychiatric disorders are associated with sleep problems, including autistic spectrum disorders, attention deficit hyperactivity disorder, various developmental learning disabilities, depressive disorder, bipolar disorder, generalized anxiety disorder, post-traumatic stress disorder, psychotic disorder and a host of neurological disorders. Children with mental retardation typically have disturbed sleep patterns. As well, sleep problems complicate numerous general medical disorders and substance abuse. Suffice to say, detailed questioning of sleep habit should be part of every comprehensive psychiatric history. With the growing knowledge in the area of sleep disorders, it is no longer adequate to ask a child and family, the simple question, “do you sleep well?”, without further clarification of actual pattern. Movement Disorders Movement disorders include the various tic disorders (Tourette’s disorder, chronic motor or vocal tic disorder, transient tic disorder) and various manneristic and stereotypic movements, associated with primary major syndromes, such as, autistic disorder, cerebral palsy and other neurological conditions. A further cause of movement disorders (including tremor) are toxins and medications. Tics are common in children. Community surveys indicate that between 1 to 13% of boys and 1 to 11% of girls manifest “frequent tics, twitches, mannerisms, or habit spasms” (Zohar et al, 1998). The wide variance in prevalence amongst the various studies, owes in part to the timing of the interviews and examinations, in relation the waxing and waning course of tic symptoms. Regarding the overall general population prevalence, tic disorders likely affect 1 to 2% of the general child population. Costello (1996) gives figures of 10 per 10,000 children meeting the criteria for Tourette’s syndrome. This is thought to be a significant under-estimate, indeed many consider the actual prevalence to be 300 per 10,000 (Mason et al., 1998). As isolated symptoms 30
  31. 31. motor or vocal tics are extremely common and there is a considerable overlap with DAMP and autistic spectrum disorders. Within Tourette’s disorder, neurocognitive and neuropsychological abnormalities are common. The most consistently observed deficits occur in visuomotor integration and visuographic abilities (Schultz et al., 1998). The genetic transmission of Tourette’s disorder (and many other movement and tic disorders) is not in doubt. Calgary is fortunate to have Dr. Oksana Suchowersky of the Movement Disorders Clinic, who is an international authority on the genetics of movement disorders. The concordance rate for Tourette’s syndrome among monozygotic twin pairs is greater than 50% and 10% for dizygotic twins (Hyde et al 1992). If chronic motor tics (not only Tourette’s) are included, monozygotic concordance approaches 90%. Many studies indicate the frequent occurrence of obsessive compulsive disorder (OCD) in first degree family members of patients with Tourette’s disorder. Risks can approach 50% (Pauls et al., 1991; Walkup et al., 1996). Neuro-anatomic, post-mortem, neuro-imaging and neuro-physiologic studies have clearly shown disturbance with the basal ganglia and related structures, in the mid-brain and cortex (Leckman and Riddle 2000). Studies of OCD as the index disorder are also focusing on the same brain areas. Besides genetic factors, tics and obsessions are related to stress related neuroendocrine factors and perinatal problems (such as adverse perinatal events). It is well known that the group-A beta hemolytic streptococci can trigger immune-mediated disease in genetically predisposed individuals. It has been suggested that pediatric autoimmune neuropsychiatric disorder, associated with streptococcal infection (PANDAS) is a distinct clinical entity (Swedo et al., 1998). An interesting observation with PANDAS is exacerbation of symptoms of attention problems, oppositional behavior and hyperactivity during or shortly after episodes of pharyngitis. In some cases of PANDAS, prophylactic antibiotics are required. Other common co-morbidities with tic disorders are right hemisphere learning disabilities, reading/math disability, cognitive problems, anxiety disorder, attention deficit hyperactivity disorder, motor hyperactivity, oppositional behaviors, in addition to the common occurrence of obsessive compulsive symptoms. Kadesjo and Gillberg (2000) noted that in Tourette’s disorder, attention deficit and empathy/autism spectrum problems (including Asperger’s disorder) were very common with each type of co-morbidity affecting approximately two-thirds of individuals. In these conditions, there is a marked degree of functional impairment. Tic disorders with complications and co-morbidities require sophisticated psychopharmacological and specific psychological treatment approaches. Because these disorders wax and wane and are longstanding, they require consistent management over many years and graduate to adult services. 31
  32. 32. Brain Infection Common causes of brain infection include bacterial meningitis and viral central nervous system infections including HIV infection. Bacterial meningitis is a serious childhood disease and even though the incidence has dramatically reduced in North America and Europe in recent years it is still a leading cause of disability. There has been concern about increased antibiotic resistance in recent years. According to Weilm et al (2000) possibly as high as 50% of the survivors of bacterial meningitis will have some sequelae, including cranial nerve problems, hearing loss, hemiparesis, hypertonia, ataxia, mental retardation and seizure disorders. A prospective 7-year follow up study in New Zealand discovered that of children surviving bacterial meningitis, they had mildly decreased I.Q. scores and performed less well on a broad range of neuropsychological tests (Grimwood et al 1995). There is also an increased incidence of behavior and mood problems (Grimwood et al 1996). Motor skill and attention problems have also been described. The incidence of viral meningitis ranges in different years from 1.5 to 4 cases per 100,000. The incidence of viral meningoencephalitis is greater than that of bacterial meningitis, although the morbidity is usually less. The major exception to this is infection due to herpes virus, where the morbidity and mortality can be very high (Weil et al., 2000). Depending on the virus type, location of the inflammation and neurological complications, the developmental and psychiatric sequelae can be very varied and can include, cognitive, language problems, seizures, hemiparesis, non-specific behavior difficulties and in some cases, lowering of I.Q. Human immunodeficiency virus (HIV) and its complications are becoming more prominent and psychiatrists (particularly adult psychiatrists) are more aware of the extensive neurocognitive and neuropsychiatric complications. The actual prevalence of HIV in children is difficult to estimate, but may be approximately 3 million world-wide. There have been 2,005 infants identified as perinatally exposed to HIV born between 1984 and 2004 in Canada. The number of HIV exposed infants reported per birth-year has increased steadily from 87 infants in 1993 to 163 in 2004. The overall proportion of HIV exposed infants whose mothers’ HIV status was attributed to the exposure category of heterosexual contact was 70.6% and 27.7% were attributed to injecting drug use. Although the number of HIV-exposed infants has increased for each birth-year, the proportion of infants confirmed to be HIV infected decreased from 47% in 1993 to 2% by 2004. Correspondingly, the proportion of HIV-positive mothers receiving anti-retroviral therapy has increased steadily reaching a high of 96% in 2004 (Public Health Agency of Canada, May 2005). In Approximately 80% of pediatric AIDS is due to vertical mother to child transmission, 20% to transfusion of blood products and 1% due to sexual contact with adolescents. Amongst HIV infected children, there are three patterns of abnormal neurocognitive development (Mintz et al. 1996, Woods 1998, Pao et al., 2001). The first pattern is one 32
  33. 33. of a rapidly progressive encephalopathy characterized by impaired growth (secondary microcephaly), motor weakness and various motor signs. The second pattern is one of subacute progression of encephalopathy with relatively stable periods and the third is a static encephalopathy with failure to achieve new milestones. In HIV positive adolescents, 44% present with current major depression and up to 85% have at least one Axis I DSM IV diagnosis, (Pao et al., 2001). About 60% of HIV infected children experience chronic pain and severely disturbed sleep patterns (Yaster and Schecter, 1996). Tardieu et al in 1995 found only 67% had normal school achievement, 54% had impaired performance on visuospatial function and time orientation tests and 44% had speech or language delay or articulation disorders. The psychosocial impact on children with HIV has been well publicized in the media and is extensive. Brain Tumors The incidence of intracranial tumors in youth below the age of 15 years ranges from 2 to 5 per 100,000 per year, which ranks these tumors as second only to the leukemias, as neoplasms in children. Brain tumors make up roughly half of all solid tumors in children. The presenting symptomatology of brain tumors is largely dependent upon tumor location and rate of growth. Often onset is silent with non-specific symptoms and presentation, for example; headache, deterioration in school functioning, personality change, restlessness, irritability, quietness and decreased motoric activity. Given how non-specific these presenting features are, a high index of suspicion is required. The treatment of brain tumors in childhood is often by brain radiation and surgery. Obviously the neurological and neuropsychiatric sequelae of surgery are dependent on tumor location. Several studies using global and specific measurements have shown that many surviving children can function at near normal levels however a substantial proportion of the population, possibly 40 to 60% can have intellectual and emotional disturbances (Bamford et al., 1982). The emotional disorders that have been reported include; psychotic symptoms, immaturity, depression, anxiety, oppositional and anti- social behavior, as well as the neurological sequelae and neuropsychological problems. A complicating factor in estimating co-morbidities is separating out important variables, including tumor characteristics, age of the child and treatment modalities. There is no doubt that cranial irradiation (for both primary brain tumors and leukemia), can effect neuropsychiatric functioning. All children develop a post-irradiation syndrome within four to eight weeks of treatment that includes somnolence, anorexia and lethargy. Long-term changes can consist of cerebral atrophy, distractibility, memory and attention deficits and declining I.Q. There is some evidence indicating these changes are greater with higher radiation dose and combined irradiation and chemotherapy in the younger child (Cohen and Duffner 1994). Even without radiation, CNS chemotherapy causes neurocognitive defects, especially in academic achievement that may take three to four years to appear (Brown et al., 2000). Delirium Delirium may be defined as a transient and usually reversible dysfunction in cerebral metabolism that can have an acute or subacute onset. It is usually caused by the direct 33
  34. 34. physiologic consequences of a general medical condition and can manifest clinically in a very wide array of neuropsychiatric and general medical situations. With regard to the Department of Psychiatry requests for assessing children with such disorders, can come from many outpatient clinics, inpatient clusters and the intensive care unit, they are usually directly physician to physician. It is difficult to estimate the prevalence of delirium in a general pediatric inpatient population. “Guesstimates” from asking pediatricians would place the figure at about 5% of all hospital admissions, however only a few of these are referred for psychiatric evaluation; the vast majority of the children with varying degrees of delirium are managed by the pediatric service. Severe delirium is an uncommon situation. Typical causes of delirium include infection (encephalitis, meningitis, HIV), substance withdrawal, acute metabolic disorders (acidosis, alkalosis, electrolyte disturbance, hepatic and renal failure), trauma, including heat stroke, post-operatively and severe burns. CNS pathology includes; abscesses, hemorrhage, normal pressure hydrocephalus, seizures, tumors and vasculitis. Other causes include hypoxia, carbon monoxide poisoning, hypotension and various pulmonary and cardiac conditions. Deficiencies including vitamin B12, hypovitaminosis, niacin and thiamin and endocrinopathies (hyper and hypo adrenal corticism and hyper and hypo glycemia) can also be causative. Acute vascular episodes would encompass hypertensive encephalopathies, shock and severe migraine. Toxins and drugs are well known to precipitate delirious episodes, including pesticides, solvents and medications. Rarely but still seen occasionally, particularly in rural and possibly aboriginal populations are heavy metal poisonings, including lead, manganese and mercury. Such a list highlights the extent of and intimate relationship between general paediatric medicine and neuropsychiatry. Psychiatrists because they are skilled in mental state examination, phenomenology and pharmacological management can be an important part of the general paediatric service delivery. Dementia Dementia is a condition that we usually associate with the elderly, however there are a number of childhood neuropsychiatric disorders, including brain injury and degenerative brain disorders that may cause dementia in childhood and adolescence. These disorders are rare and result in an absolute and progressive loss of skills. Usually the onset of these disorders is subacute and requires both neurology and psychiatry to work closely together. Frequent psychiatric symptoms in such conditions include: dysphoria, withdrawal, anxiety, loss of interest and insomnia along with typical cognitive disturbances (aphasia, apraxia, agnosia, memory problems and progressive disturbance in executive functioning). Although these conditions are rare, a high index of suspicion is required. Because of the subacute and vague onset to these conditions, often functional psychiatric disorders are diagnosed during the early stages of deterioration. 34
  35. 35. Stupor and Catatonia: For most neurologists, stupor means a condition of behavioral non-responsiveness, including loss of speech, markedly reduced movement (hypokinesis) and a reduced level of consciousness from which the subject can be aroused only by vigorous and repeated stimulation. Stupor is seen by most neurologists, as having diffuse organic cerebral dysfunction, hence it can occur in numerous neurological conditions. However within the psychiatric literature, stupor has been traditionally associated with conditions where there is hypokinesis and mutism, but with relative preservation of consciousness. I have been unable to find any child literature relating to the outcome of stuporous conditions, however in adult psychiatry, those diagnosed with “psychogenic stupor” have, on follow up, been shown to actually have organic pathology in the majority of cases. For example, Cutting in 1992 noted that of 100 patients, 25% had depression, 34% schizophrenia and 23% organic disorders. Only 10% had psychogenic features confirmed. Catatonia has been designated as a subtype of stupor and can have numerous organic, neurological and metabolic causes. I have been unable to estimate the prevalence of stupor and catatonia in a child general medical population. However, once more, given the diagnostic uncertainties, neuropsychiatry can play an important role. Neurodegenerative and neuromuscular disorders These are a wide range of diseases, characterized by degeneration of the nervous system diffusely or in part. Examples include; Krabbe’s disease, metachromatic leukodystrophy, multiple sclerosis, Schilder’s disease, various basal ganglia disorders, cerebella degeneration (Friedreich’s ataxia) and the various neurocutaneous diseases, including the various subtypes of neurofibromatosis, tuberous sclerosis and Sturge-Weber syndrome. Complications of these disorders are widely varied including memory, attention, cognitive, learning, language and motor co-morbidities. Specialized General Medical Populations Although almost any childhood disorder can have psychiatric complications, certain populations are prone to a higher incidence of psychiatric and neuropsychiatric disorders. Any child with a chronic paediatric illness (with frequently multiple hospitalizations) suffers because of specific illness-related factors, the age of onset, the degree of morbidity and disability (including in some cases deformity), the prognosis and course of the illness. Typical serious chronic conditions in children are: Children per 1000 Asthma 62.0 Migraine 15.2 Epilepsy 4.9 Arthritis 1.9 Diabetes 1.2 35
  36. 36. Cystic Fibrosis 0.5 Leukaemia 0.15 (Adams et al, 1996) All of these conditions are associated with neuropsychiatric complications, to a greater or lesser extent. The oncology population of children with malignancies is a highly specialized area of practice. Clearly there are the illness-related factors, but also the neurodevelopmental, educational and psychiatric complications of treatment, including chemotherapy, irradiation and the impact of multiple and often lengthy hospitalizations. The advances in solid organ, bone marrow and stem cell transplantation, have brought their own complications to psychiatry. Not only is there the psychosocial impact but many of the treatments, particularly the immunosuppressants and anti-infectious agents can cause significant complications. There are numerous central nervous system side- effects of these agents, including trauma, anxiety, delirium, ataxia, seizures, hallucinations, depression, mania, headache, confusional states, irritability and agitation. There are also the neuropsychiatric complications of the management of pain in this population. Often psychopharmacological treatment is required for the psychiatric co- morbidities and because of the complex medication regimes and factors related to transplants highly knowledgeable use of psychotropic medication is required. The care of infants, children and adolescents with burn injuries, is also a highly specialized area of practice. Essentially burns can be accidental (the majority), however some adolescents, particularly with bipolar disorder and psychosis, can self-inflect burns. Unfortunately, child neglect and maltreatment is a frequent cause of burns in younger children. The most common being scalding and burns with cigarettes, irons or radiators (Renz and Sherman 1993). Besides any issues of deformity, specialized management of pain is required. Much of the pain management comes along with various neuropsychiatric complications. In severe burns, there are physiological components, including delirium, confusional states and the effects of disturbed electrolyte balance on mental functioning. As well, there are various neuroendocrine and typically severe sleep/wake cycle problems (Lawrence et al: 1998). There are neurobiological post-burn phases and a typical disorder following a burn, is of a post-traumatic stress disorder. Traditional psychiatric thinking has considered PTSD as being "psychogenic" however extensive recent research confirms that PTSD is a neurobiological disorder that is typically chronic (Carr 1998, Stoddard and Todres, 2001). Once again, expert psychopharmacology is often indicated. Obviously, neuropsychiatric interventions need to be in concert with individual and family therapy interventions. A brief note should be made of children with visual and hearing impairments. There are numerous conditions causing these; many are associated with specific syndromes, which have their own neurodevelopmental profile. About 50% of vision loss in childhood is 36