Towards a better understanding of early atruamatic brain injury


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Towards a better understanding of early atruamatic brain injury

  1. 1. Towards a Better Understanding of Early Atraumatic Brain Injury and its Treatment Alan Challoner MA MChS
  3. 3. Ego Functions 54 Abnormal Brain Structure & Autism 56 INTRODUCTION 56 AETIOLOGY OF AUTISM SPECTRUM DISORDERS 57 AUTISM AND ITS TREATMENT 64 Management Following Early Brain Injury 68 EARLY MANAGEMENT 68 LONG-TERM MANAGEMENT 68 COGNITIVE PROBLEMS 69 PSYCHIATRIC INTERVENTION FOLLOWING EARLY BRAIN INJURY 72 Some of the Physical and Cognitive Difficulties Encountered following Atraumatic Brain Damage 74 FEEDING AND SWALLOWING DIFFICULTIES 74 DYSPRAXIA AND NON-FLUENCY 75 PRAGMATIC SKILLS 76 LANGUAGE IN CHILDREN WITH EARLY BRAIN DAMAGE 76 PROBLEMS OF GAIT AND MOVEMENT 80 Types of Emotional, Behavioural, Psychiatric and Social Problems Seen After Brain Injury in Children 84 Post-traumatic stress disorder 88 PTSD AND EMOTIONAL RESPONSES 91 Rational Drug Interventions 96 DIAGNOSIS AND TREATMENT 96 DRUG INTERVENTIONS 98 Possible Effects of Specific Cognitive Deficits on Behaviour and Social Functioning 103 BEHAVIOUR MANAGEMENT 108 SPECIAL PROVISION 111 INTERVENTIONS WITH PARENTS 112 EDUCATION OF THE FAMILY AND OF THE CARERS 113 FAMILY COUNSELLING AND FAMILY THERAPY 113 Summary and Conclusions 113 Page 3 of 116
  4. 4. Towards a Better Understanding of Early atraumatic brain injury and its treatment ___________ A General Introduction to Early Brain Injury Acquired brain injury is common and may follow traumatic and non- or atraumatic insults. It has major individual patient and public health implications. Although head trauma is the leading cause of an acquired brain injury, non-traumatic injuries are also common. Importantly, the survival rate of children who have suffered both types of brain injury continues to increase, in part reflecting the improved (and still improving), acute and resuscitative medical and surgical treatment given at the time of, and immediately following, the injury. However, the survival of these children is clearly at some cost — to both the child and their family — and this includes a corresponding increase in the morbidity rate, in which children are often left with significant difficulties. These difficulties will obviously range from mild to severe and may be transient or permanent. In addition, children may have difficulties that are limited to just one area, or more typically, the difficulties and their problems are multiple and complex and there will be major implications for physical and educational (and, subsequently, career) achievements and social interaction. Paediatric traumatic brain injury is a major cause for concern when considering both the number of children sustaining injuries and the large number of children incurring life-long difficulties that impact on quality of life. Research is continuing to investigate outcomes and predictors of recovery in both cognitive and behavioural domains. Findings have contributed to better identification of children at high risk for neurobehavioral difficulties. The challenge is to develop new intervention programs to prevent or lessen the impact of such difficulties. 1 Some brain injuries have been caused by vaccines and generally that is the result of the toxins in the vaccine passing the blood/brain barrier and causing sporadic 1 Catroppa, C. & Anderson, V. ‌ Neuro-developmental outcomes of ‌(2009) pediatric traumatic brain injury. Future Neurology November 2009, Vol. 4, No. 6, Pages 811-821. Page 4 of 116
  5. 5. damage to the nerve cells of the brain. This process and some of its results have been dealt with elsewhere.2 ATRAUMATIC OR NON-TRAUMATIC BRAIN INJURY It is important to realize that brain damage can be caused by non-traumatic or atraumatic brain injury (ABI). This may be almost as common as TBI.3 These injuries may be caused by a number of different disorders and of those the ones that are significant are: • as a complication of meningitis or encephalitis; • prolonged convulsive status epilepticus (when an epileptic convulsion lasts more than 60 minutes) • as a complication of some other toxic (e.g. alcohol, drug), metabolic or biochemical impairment These non-traumatic brain injuries are relatively common When a nerve cell is injured or diseased, it may stop functioning and the circuits to which it contributed will then be disrupted. Some circuits may eventually reac- tivate as damaged cells resume functioning or alternative patterns involving different cell populations take over. When a circuit loses a sufficiently great number of neurons, the broken circuit can neither be reactivated nor replaced. In general, when a human neuron dies, it is not replaced, except in the capacity of the dentate gyrus of the human hippocampus to generate new neurons (Eriksson et aI, 1998)4. Evidence of the generation of new neurons in response to injury or disease is still lacking. The experience at Alder Hey Hospital suggests that when one considers all causes of atraumatic brain injury together, the incidence and prevalence of significant ABI may be as high, or even higher, than TBI. This pattern seems to have been emerging over the past couple of years. 5 A great deal of the research into early brain injury has been involved with TBI. Most cases of ABI occur very early in a child’s life and therefore it is less easy to assess what changes have taken place as a result of the injury, particularly as there will be little or no pre-morbid history to take into consideration. That said, the results of insults to the brain tissue will often have the same implications whether the origins of the damage are ABI or TBI. The summary that follows will therefore include the research into TBI and will use that similarity as a means to try and identify what the 2 Challoner, A. 2009. Brain Damage caused by Vaccination. ( 3 Appleton, R. & Baldwin, T. Management of Brain Injured Children. 2nd Ed. OUP,2006. 4 Eriksson, P.S., Perfilieva, E., Bjork-Eriksson, T., et al. (1998). Neurogenesis in the adult human hippocampus. Nature Medicine, 4, 1313-1317. 5 Appleton, R. et al. 2006 idem Page 5 of 116
  6. 6. outcomes will be for those who suffer ABI. Where the research involved ABI subjects then that can be seen to support this method of analysis. THE AFTERMATH OF CONVULSIONS 6 There is an increased incidence of convulsions following head injury. Convulsions can cause a rise in inter-cranial pressure (ICP) which may adversely affect cerebral blood flow (CBF) and contribute to further neuronal damage. Acute brain injury results in death of a variable number of brain cells, both neurons and neural connective tissue. At this time, cellular energy metabolism can be restored over a period as short as 30 minutes but cell swelling still occurs. In the 'latent' phase which follows, magnetic resonance spectroscopy may indicate oxidative cerebral energy metabolism similar to normal, but the electroencephalography (EEG) is depressed and CBF reduced. It is believed that cellular ionic changes begin in the 'latent' phase and progress to apoptosis (programmed cell death). The latent phase is followed by 'secondary' deterioration after the acute event and manifests as delayed convulsions, cytotoxic oedema, extracellular accumulation of potential cytotoxins such as excitatory neurotransmitters, failure of oxidative metabolism and neuronal death. There is damage to the blood-brain barrier with escape of water and plasma as components of the oedema. This may already have been damaged in the first phase of vaccine damage to the brain when the toxins pass into the brain. Acute cell necrosis may result in the release of cellular ions, such as calcium, which may induce vascular spasm of cerebrovascular smooth muscle. These ions may damage other cells which were unaffected by the primary acute brain insult. There are physical effects related to sluggish flow of blood in small blood vessels, such as capillary sludging and platelet aggregation that may progress to critical and irreversible ischaemia and cerebral infarction. The acute changes in this late phase may take several days to resolve. _______ The Nature of Brain Injury Would that we could simply describe the results of brain damage and say, "this is how it is.” But what we see, and how we talk about it, is never based on pure, naive, veridical perception; rather, it is inextricably bound to what we already know, what we're looking for, what we're trying to prove. Just as a proper appreciation of contemporary art demands familiarity with the fashions and approaches of earlier eras, so the study of brain damage is inseparable from consideration of the hypotheses of earlier clinicians, the categories and syndromes they devised and, lamentably, the facts they distorted or overlooked. 7 ‘FIRST AID’ FOR BRAIN INJURIES 6 Appleton, R. et al. 2006 idem 7 Gardner, H. The Shattered Mind: The person after brain damage. Routledge & Kegan Paul, London, 1974. Page 6 of 116
  7. 7. When brain cells die, whether from head trauma, stroke or disease, a substance called glutamate floods the surrounding areas, overloading the cells in its path and setting off a chain reaction that damages whole swathes of tissue. Glutamate is always present in the brain, where it carries nerve impulses across the gaps between cells; but when this chemical is released by damaged or dying brain cells, the result is a flood that overexcites nearby cells and kills them. A new method for ridding the brain of excess glutamate has been developed at the Weizmann Institute of Science. This method takes a completely new approach to the problem, compared with previous attempts based on drugs that must enter the brain to prevent the deleterious action of glutamate. Many drugs, however, can’t cross the blood-brain barrier into the brain, while other promising treatments have proved ineffective in clinical trials. Prof. Vivian Teichberg, of the Institute’s Neurobiology Department, working together with Prof. Yoram Shapira and Dr. Alexander Zlotnik of the Soroka Medical Center and Ben Gurion University of the Negev, has shown that in rats, an enzyme in the blood can be activated to “mop up” toxic glutamate spills in the brain and prevent much of the damage. This method may soon be entering clinical trials to see if it can do the same for humans. In the majority of cases, the extent of a learning difficulty resulting from a head or other brain injury is related to the severity and nature of the head injury 8. For instance, in a child whose brain injury has been complicated by severe cerebral oedema (brain swelling) then blood and oxygen supply to the brain may be severely compromised. This is often termed an 'hypoxic-ischaemic encephalopathy', resulting in diffuse cerebral damage and on recovery, general cognitive functioning can be impaired. The mention of injury to the head or brain strikes a note of apprehension in most people. Similarly, reports of any injury or debilitating tragedy to children arouse widespread sympathy and feelings of indignation that the young should suffer in any way. For the head-injured child, however, such public sympathy appears to be rather short lived, despite persisting and long-term difficulties stemming from the injuries. Head injury is never an all-or-nothing phenomenon, irrespective of the cause; rather, it is a matter of degree, producing relative changes in brain structure and function. Johnson et al make it evident that the notion of greater plasticity and recovery of children who suffer head injury is not generally supported. 9 There is little age differentiation in the published reports on children's head injury: a paediatric population may range from birth to 19 years of age 10 . This has generated much confusion, especially in relation to evaluating outcome. Age demarcates stages or periods of development which reflect the underlying neurological substrate, although age alone is not a sufficient index 11 . 8 Levin, H. S., Benton, A. L., & Grossman R. G. (1982). Neurobehavioural Consequences of a Closed Head Injury. Oxford: Oxford University Press. 9 Johnson, DA.; Uttley, D. & Wyke, M. (1989) Children’s Head Injury: Who Cares? Taylor & Francis. 10 Ward, J.D. & Alberico, A.M. (1987) 'Paediatric head injuries', Brain Injury, 1, pp. 21-25 11 Jeffery, R. (1980) 'The developing brain and child development', in WITTROCK, M.C. (ed.) The Brain and Psychology, New York, Academic Press. Page 7 of 116
  8. 8. Consequently, head-injured children as a population may reasonably be expected to show quite different, within-group responses to trauma, relative to their stage of development 12. Much of the early literature, especially neurosurgical and psychological, implies that the younger child is less vulnerable and shows a greater recovery from head injury than those who are older. There have been extensive methodological criticisms of such work, however, which suggest that given adequate evaluations, particularly of cognitive function, the young head-injured child does not show a preferential recovery rate. Relatively greater impairment appears in children younger than 8 years at the time of injury, but there has been a general failure to institute longitudinal studies of infants and toddlers with sufficiently sensitive outcome measures, and parallel neuro-radiological confirmation. It appears that younger children may also be more vulnerable to a wide range of secondary factors, including nutrition and environmental stimulation. Head injury to the child occurs in the context of development and incomplete neurological maturation. Consequently, the general concepts of critical periods and vulnerability are most pertinent to the younger child sustaining head-injury. It remains speculative as to what extent normal development proceeds after head injury but, given the greater vulnerability of immature neurones to insult and their tendency for more rapid degeneration, it seems reasonable that normal maturation must be at high risk in terms of either the sequence or rate of development, or both. 13 The age at which a head injury occurs is therefore an important factor to be taken into consideration. Infants may appear to recover but if the child has been very severely brain-injured, then they may always require a great deal of intensive support. Many assessment tools are not appropriate for very young children and yet subtle deficits can be acquired in the informative years that may affect the long-term potential. Clearly, the question, 'does an early injury have a more serious effect on overall mental development than a later one?', cannot be answered easily, as many factors including the type of injury and size, extent and location of damage must be considered, as well as the specific mental activity involved and its cognitive complexity. It is within this context that complex skills may not be expected of children in their formative years, and therefore deficits acquired early on may not become apparent until much later in their lives. It is very likely that aberrant development may result from secondary factors in the recovery process, or from subsequent atrophy of damaged tissue. Secondary neural degeneration in the head-injured child, for example, has not been widely 12 Luerssen, T.G., Klauber, M.R. & Marshall, L.F. (1988) 'Outcome from head injury related to patient's age', Journal of Neurosurgery, 68, pp. 409-416. 13 Johnson, DA.; Uttley, D. & Wyke, M. (1989) Children’s Head Injury: Who Cares? Taylor & Francis. Page 8 of 116
  9. 9. reported 14, 15, 16, 17, , but this often arises even in the presence of relatively good physical ability and appearance. The Central Nervous System (CNS) possesses a finite adaptive capacity to withstand the effects of any cerebral insult. Head injury reduces that capacity and, with increasing severity of trauma and subsequent atrophy, the remaining capacity of the CNS to adapt to any further neurological insult becomes relatively limited. With a decline in capacity, new signs and symptoms may appear as critical thresholds are reached. As brain development results from complex interactions between genetic and environmental factors, it seems reasonable to suggest that the young head-injured child may be in greater need of early rehabilitation than his adult counterpart. Rehabilitation must aim to facilitate as normal a pattern of development as possible, hence the need for follow-ups throughout the period of the child's remaining development.18 Similarly, there must be a development of inter- disciplinary rehabilitation facilities specifically for the head-injured child, incor- porating neurological, educational and social factors. Rehabilitation must become more scientifically based and practised in a coherent and neurologically meaningful way, rather than the haphazard, inconsistent guesswork which characterizes rehabilitation in the UK. When someone is injured it is assumed by both public and doctors that the best treatment is provided, based on sound knowledge of the patho-physiological response to trauma 19. Recent reports challenge this complacency 20. The system of such care would be of far greater practical importance that any of its constituent parts. Trauma to the brain exerts perhaps the highest toll among all injuries, simply because it may dramatically alter the quality of future life for its survivors and their 14 Lange-Cosack, H., Wider, B., Schlfsner, H.J., Frumme, T. & Kubicki, S. (1979) 'Prognosis of brain injuries in young children (1 until 5 years of age)" Neuropaediatrie, 10, pp. 105-127. 15 Cullum, C.M. & Bigler, E.D. (1985) 'Late effects of haematoma on brain morphology and memory in closed head injury', International Journal of Neurosdenu, 28, pp. 279-283. 16 Jellinger, K. (1983) 'The neuropathology of paediatric head injury', in SHAPIRO, K. (ed.) Paediatric Head Traurna, New York, Futura. 17 Mortimer, J.A. & Pirozzolo, F.J. (1985) Remote effects of head trauma, Developmental Neuropsychology, 1, pp. 215-229. 18 Kaiser, G., Rudeberg, L., Fankhauser, L. & Zumbuhl, C. (1986) 'Rehabilitation medicine following severe head injury in infants and children', in Raimondi, A.J., Choux, M. & DiRocco, C. (eds.) Head Injury in the Newborn and Infant, New York, Springer. 19 Yates, D.W. (1988) 'Action for accident victims', British Medical Journal, 297, pp. 1419-1420. 20 Cummins, B. (1987) 'A head injury polemic', British Journal of Neurosurgery, 1, pp. 6-8. Page 9 of 116
  10. 10. families 21, 22, 23 . Nonetheless society continually fails to see the full implications of disability resulting from head injury in childhood 24 including increased educational support, lost or diminished careers, poor social and emotional adjustment, and later demands on mental health services. The long-term effects of a brain injury on a child can therefore depend upon the age at which the injury occurs and problems may not always be evident from the early stages. Unlike adults, children's brains develop rapidly both in size and complexity through the childhood years and into adolescence. Neurodevelopment is not uniform through the brain at anyone time, and areas, particularly those in the frontal lobes, do not become fully operational until adolescence and early adulthood. Making a positive long-term prognosis from what may appear a rapidly sound recovery can therefore be misleading. More subtle deficits, particularly those affecting frontal lobe functioning, may not become apparent until many years later. For a substantial number of years, there has been a strong belief that recovery from head injury is better in children than adults, due to what has been termed 'cerebral plasticity', that is, damaged skills being compensated for by areas of the brain that are not affected, and are able to take over the function of the damaged areas, at least to some degree. However, this is often not the case, and children who have a very early ABI can often have a poorer prognosis than had they sustained a somewhat similar injury as an older child or adult. Goodman 25 argued that there were limits to cerebral plasticity. Generally, research has indicated that ABI has more significant effect on the cognitive skills of young children. Typically, it is thought that children younger than seven or eight years do not improve in intellectual functioning in the same way that older children and adults do 26, 27 . Brain functioning and development occur rapidly during a child's life. The period of most rapid development occurs within the first couple of years of life, but it remains incomplete well into the teenage years, and final myelinisation 28 does not occur 21 Shapiro, K. (1985) 'Head injury in children', in Becker, D.P. & Povlishock, J.T. (eds.) Central Nervous System Traurna Status Report, Maryland, NIH. 22 Lezak, M.D. (1988) 'Brain damage is a family affair', Journal of Clinical and Experimental Neuropsychology, 10, pp. 111-123. 23 Waaland, P.K. & Kreutzer, J.S. (1988) 'Family responses to childhood brain injury', Journal of Head Trauma Rehabilitation, 3, pp.51-63. 24 Haas, J.F., Cope, D.N. & Hall, K. (1987) 'Premorbid prevalence of poor academic performance in severe head injury', Journal of Neurology, Neurosurgery and Psychiatry, 50, pp. 52-56. 25 Goodman, R. (1989). Limits to cerebral plasticity. In: Children's Head Injury: Who Cares (eds. D. A. Johnson, D. Uttley & M. Wyke). London: Taylor and Francis. 26 Stiles J. (2002). Neural plasticity and cognitive development. Developmental Neuropsychology, 18,237-72. 27 Stiles, J., Reilly, J., Paul, B., & Moses, P. (2005). Cognitive development following early brain injury: evidence for neural adaptation. Trends in Cognitive Sciences. 9, 136-43. 28 Myelinisation. The change or maturation of certain nerve cells whereby a layer of myelin forms around the axons which allows the nerve impulses to travel faster. Page 10 of 116
  11. 11. until adolescence. There is a sequential pattern of myelinisation, with the frontal lobes being the final areas to mature, usually with the onset of adolescence. The later implications that early impairment to the frontal lobes can have on the social, behavioural and cognitive functioning of children in their later years is given in two case studies reported by Williams and Mateer 29. In very recent years, neuro-imaging research has yielded important information concerning the structure, neurochemistry, and function of the amygdala, medial prefrontal cortex, and hippocampus in posttraumatic stress disorder (PTSD). A review of neuro-imaging research reveals heightened amygdala responsivity in PTSD during symptomatic states and during the processing of trauma-unrelated affective information. Importantly, amygdala responsivity is positively associated with symptom severity in PTSD. In contrast, medial prefrontal cortex appears to be volumetrically smaller and is hypo-responsive during symptomatic states and the performance of emotional cognitive tasks in PTSD. Medial prefrontal cortex responsivity is inversely associated with PTSD symptom severity. The reviewed research suggests diminished volumes, neuronal integrity, and functional integrity of the hippocampus in PTSD. 30 (See PTSD below, p85) FOCAL IDENTITY IN THE FUNCTIONAL BRAIN Thought and knowledge about the localization of mental functions in the human brain have a long and complicated history and are still evolving. There has been uncertainty about what the concept means, debate about where localization takes place and even denial that it exists. Ideas about cerebral localization have been determined primarily by the knowledge of brain anatomy existing at a particular time and by the availability of techniques for disclosing the presence and locus of brain lesions. They have also been influenced by concepts of the nature of disease and the prevailing state of psychological analysis. 31 ASSESSMENT AND THE MORE RECENT CHANGES It is often only in a neuropsychological assessment that the underlying deficits of children who have sustained a brain injury become apparent. Deficits in many cases are not global, especially in the milder cases 32 although subtle deficits do remain and can affect academic performance 33 where they may be 29 Williams, D. & Mateer, C. (1992). Developmental impact of frontal lobe injury in middle childhood. Brain and Cognition 20,196-204. 30 Shin, Lisa M.; Rauch, Scott L. & Pitman, Roger K. Amygdala, Medial Prefrontal Cortex, and Hippocampal Function in PTSD. Ann. N.Y. Acad. Sci. 1071: 67–79; 2006. 31 Benton, A. (2000). Historical aspects of cerebral localization. In Localization of Brain Lesions and Developmental Functions, D. Riva & A. Benton (eds.); John Libbey & Company Ltd, pp. 1-14. 32 Bawden, H. N., Knights, R. M., & Winogron, H. W. (1985). Speeded- performance head injury in children. Journal of Clinical Neuropsychology 7, 39-54. 33 Wrightson, P., McGinn, V., & Gronwall, D. (1995). Mild head injury in pre- school children - evidence that can be associated with a persisting cognitive defect. Journal of Neurology Neurosurgery and Psychiatry 59, 375-80. Page 11 of 116
  12. 12. misinterpreted or overlooked. Most neuropsychological assessments have an intelligence test as their core. However, the concept of intelligence tests (intelligence quotients [IQ]) is, in many respects, outdated as suggested by Lezak 34 and certainly these tests must be used with caution when making any assumptions about the brain injured child. Tests of 'intelligence' may be useful as indicators of levels of functioning and can be used as a basis from which further assessments can be undertaken, but a screening test in which a broader and more detailed neuropsychological assessment can take place will be essential and will provide a better understanding of the injury. Possibly the best source of general information about neuropsychological assessments is to be found in Lezak 35, although in recent years, a range of neuropsychological tests have been developed for use in children. These tend to be rarely used in their totality and, indeed, concern has been expressed that many of the sub-tests are not specific in detecting distinct neuropsychological processes, but rather 'g' or general cognitive ability. In addition, following ABI, sub-tests requiring more fluid performance tend to be depressed greater than those comprising what are termed 'crystallized skills', that is, verbal abilities. During the recovery phase, the discrepancy between these quotients generally decreases, and although there are a number of reasons why this may occur, it tends to indicate a general recovery. It can, of course, relate to the heavy practice effects that are possible from repeated testing, and care therefore needs to be exercised when gauging improvement through changes in test results. The tests themselves do not always measure what they intend to measure and may be significantly affected by other factors. Lezak comments: “IQ refers to a derived score used in many test batteries designed to measure a hypothesized general ability — intelligence. Because of the multiplicity of cognitive functions assessed in these batteries, IQ scores are not useful in describing cognitive test performances. IQ scores obtained from such tests represent a composite of performances on different kinds of items, on different items in the same tests when administered at different levels of difficulty, on different items in different editions of test batteries bearing the same name, or on different batteries contributing different kinds of items. If nothing else, the variability in sources from which the scores are derived should lead to serious questioning of their meaningfulness. In neuropsychological assessment in particular, IQ scores are often unreliable indices of neuropathic deterioration. Specific defects restricted to certain test modalities, for example, may give a totally erroneous impression of significant intellectual impairment when actually many cognitive functions may be relatively intact and lower total scores are a reflection of impairment of specific functional modalities. Conversely, IQs may obscure selective defects in specific tests . In fact, any derived score based on a combination of scores from two or more measures of different abilities results in loss of data. Should the levels of performance for the combined measures differ, the composite score-which will be somewhere between the highest and the lowest of the combined measures-will be misleading. Averaged scores on a Weschler Intelligence Scale battery provide just 34 Lezak, M. D. (1988). IQ. R.I.P. journal of Clinical and Experimental Neuropsychology 10, 351-61. 35 Lezak, M. D. (2004). Neuropsychological Assessment (4th edn). Oxford: Oxford University Press. Page 12 of 116
  13. 13. about as much information as do averaged scores on a school report card. In the same way, it is impossible to predict specific disabilities and areas of competency or dysfunction from averaged ability test scores (e.g., "IQ" scores). Thus composite scores of any kind have no place in neuropsychological assessment. In sum, "IQ", as a score, is inherently meaningless and not infrequently misleading as well. "IQ" — whether concept, score, or catchword-has outlived whatever usefulness it may once have had and should be discarded.” (idem) Both the Weschler Intelligence Scale for Children (WISC) and the Weschler Pre- School and Primary Scale of Intelligence (WIPPSI) have been replaced by new and updated versions. The third edition of the WIPPSI provides a much-needed update of the original WIPPSI which was last revised in 1989. In addition to the material being updated and made more contemporary and appealing to children, the tests have been extensively revised. As well as providing the original cognitive domains of verbal IQ, performance IQ and a full-scale IQ, it now provides further analysis of the updated and additional sub-tests to provide a global language score, a processing speed quotient, and a general language composite score, in addition to the original cognitive domains. It is suitable for children from the age of two years, six months to seven years, three months. The WISC Ill-UK has now been superseded by the new WISC IV-UK. This updated version provides a broadly similar assessment of general ability; however, it also incorporates significant revisions that include updated normative data, new sub- tests and an increased emphasis on composite scores which assess more discrete domains of cognitive functioning. In total, there are now 15 sub-tests available, but once more, the general test framework evaluates the four original composite indexes of verbal comprehension, perceptual reasoning, working memory and processing speed. The WISC IV is linked to the Wechsler Individual Achievement Test (second edition) which provides a comprehensive measure of academic achievements in a number of principal domains. The test can therefore be used to provide a predictive score and actual score, thereby indicating the extent to which a child may be under-functioning in a particular attribute. The child's basic educational attainments and other core attributes can therefore be judged in comparison with their general level of intellectual ability using the newer versions of Weschler Objective Numerical Dimensions (WOND) and Weschler Objective Reading Dimensions (WORD). The basis of any treatment programme must also take into account the wider range of neuropsychological deficits in children as these will influence the learning style and specific learning difficulties. The assessment of brain-injured children may therefore be more appropriately addressed using a hypothesis testing and problem solving approach looking at functional deficits. Until recently, there was a very limited range of neuropsychological tests available for children. These were well described by Strauss and Spreen 36. Unfortunately, many of the tests had been devised for adults and although normative data are available for children, they tended to be derived from very small samples, and the tests themselves may not hold an inherent interest for children. 36 Strauss, E. & Spreen, O. (1991). A Compendium of Neuropsychological Tests. Oxford: Oxford University Press. Page 13 of 116
  14. 14. A number of assessment instruments have become available since 1988. These not only provide a broader overview of a child's level of functioning, but in many respects provide very valid and functional assessments for the child, which can form the basis of an assessment upon which further neuropsychological testing can be carried out as part of an overall rehabilitation teaching strategy. Although a child's limitations can be obvious, sometimes they can be more subtle and missed. A number of general developmental scales have been used in this respect, the Vineland Social Adaptive Scales being the most notable (Sparrow et al) 37 and these can provide a detailed overview of a child's functional capabilities in a number of domains. The new Adaptive Behaviour Assessment System (ABAS) was published in two versions in 2000; one questionnaire being completed by the parents, and the other by the child's teachers. It provides a diagnostic assessment of the child who has difficulties with daily living skills and is therefore more functionally oriented. According to the manual, it provides a comprehensive diagnostic assessment for very young people with a variety of disabilities, disorders and health problems and also provides a basis upon which a rehabilitation programme can be focused. It is unfortunate that a number of the questions are American and to date there is no 'anglicized' version. It does, however, provide a standardized score which can be used in comparison with other intellectual measures, in addition to providing a profile of 'strengths and weakness'. The age range is also practical (5-21 years), and can therefore provide many years of assessment continuity. During 2004, a number of neuropsychological tests specifically devised for children became available, with the Developmental Neuropsychological Assessment ('NEPSY') being one example. This test is not often cited in the literature, but is useful in that it evaluates a range of neuropsychological functioning that provides useful insight into a child's neuropsychological status. The NEPSY is most probably the most unique test for children, because it has been specifically devised for the 3-12 years age range. It provides assessment of six complex cognitive functions: • attention; • executive functioning; • language; • sensory motor functioning; • visual-spatial processing; • memory and learning. One of its primary aims is to provide a comprehensive assessment of the neuropsychological status of children with a range of difficulties. Consequently, it 37 Sparrow, S., Balla, D., & Cichetti, D. V. (1984). Vineland Adaptive Behaviour Scales. Minnesota: American Guidance Service Inc. Page 14 of 116
  15. 15. is, for example, used for children who have cerebral palsy, epilepsy, hydrocephalus or traumatic brain injury. A number of sub-tests in the NEPSY are of particular value when assessing functional problems that may occur following a head injury. For instance, children can sometimes be left with an extremely short verbal memory. Simple tests such as 'sentence repetition' can reveal the very real problems a child can have when they are unable to retain sentences of increasing length and complexity; for example, asking a child to, 'finish their work, put the book on the table, the pencil in the drawer and line up by the door', is pointless if the child can only retain one instruction at a time. It is therefore extremely useful to provide some normalized information in order to provide an objective assessment. When considering the effects of an acquired brain injury, it must be acknowledged that neuropsychological assessments offer only moderate correlations with everyday functioning, and this is particularly relevant when providing neuropsychological reports that include comments on prognosis. It is essential that ecologically valid information is obtained and that very careful consideration is given with regard to the child's pre-injury status; the level of support that the child has received following the injury, including educational support; parental expectations and attitude etc. These issues are well discussed by Silver 38, who examined the multiple issues that exist when trying to predict functioning following traumatic brain injury (TBI) in day- to-day, real-life situations, and especially when having to consider developmental factors and the intervening variables that may increase or decrease the child's adaptive functioning over the course of recovery. Ylvisaker and Gioia 39 pointed out that children with TBI may perform poorly on unfamiliar or unappealing tests, whereas functioning in the real world with a familiar routine may exceed expectations suggested by these more formal test results. Cripe 40 emphasized the necessity for using observations or check-lists and that rating scales are needed in order to provide some valid appraisal of the child's functioning in the real world. A further point to consider is the rehabilitation of adults and how well neuropsychological assessments relate to outcomes. Leahy and Lam 41 examined the relationship between performance and neuropsychological measures, and the vocational and independent living functioning of individuals following TBI. They reported that the correlations were generally poor, with only the intelligence test and colour and word test scores differentiating individuals who did or did not require assistance with activities of daily living. Whereas neuropsychological assessments are extremely important in assessing 38 Silver, C. H. (2000). Ecological validity of neuropsychological assessment in childhood traumatic brain injury. Journal of Head Trauma Rehabilitation 15,973-88. 39 Ylvisaker, M. & Gioia, G. A. (1998). Cognitive assessment. In: Traumatic Brain Injury Rehabilitation: Children and Adolescents. 2nd edn. (ed. M. Ylvisaker), pp. 159-79. Boston: Butterworth-Heinemann. 40 Cripe, L. I. (1996). The ecological validity of executive function testing. In: Ecological Validity of Neuropsychological Testing (eds F. R. Sbordone & C. J. Long), pp. 171-202. Delray Beach, FL: GR Press/St. Lucie. 41 Leahy, B. J. & Lam, C. S. (1998). Neuropsychological testing and functional outcome for individuals with traumatic brain injury. Brain Injury 12, 1025-35 Page 15 of 116
  16. 16. children's abilities along a number of dimensions and in helping to plan remediation strategies, the translation between test scores and the skills required in everyday life in the child's real environment must be made with caution. When devising therapeutic and rehabilitative packages, great care must be taken regarding making long-term predictions from test results that, at present, would appear to be relatively poor predictors of long-term outcome; a much broader based assessment of a child's functioning, taking all factors into consideration, is essential before making important statements that may have very long-term implications to a child's future needs (Rivara et al.) 42. A broad-based assessment is therefore needed to provide an overall profile of the child's deficits. Some of this information may be derived from specific tests, but valuable information can be derived from detailed observation of the child in normal situations. A comprehensive neuropsychological evaluation should therefore sample the following range of attributes which may or may not have been provided by other professionals: 1. A consideration of the child's sensory and motor functioning; this includes vision and hearing including auditory perception, visual acuity and visual fields and depth perception. Whereas these will usually have been com- pleted by the relevant medical personnel, their functional implications are not always evaluated in the child's normal environment. 2. The child's physical skills need to be considered. At a fine motor level this includes an assessment of the child's functional living skills including dressing, feeding and, of course, writing skills - including their speed of writing. Evaluation of the child's gross motor skills includes the child's functional mobility within the home and school, and their ability to take part in recreational sports. 3. An assessment of the child's overall intellectual functioning using a standardized assessment. This would usually include an assessment to profile the child's skills, assessing areas of comparative strengths and weaknesses. 4. An evaluation of the child's ability to solve problems in real-life situations and make reasonable judgements given the information that would be available to them. 5. An examination of the child's ability to think flexibly, that is, their ability to cope with changing situations and problems. Problems with mental flexibility can reveal themselves both in coping with specific academic skills and also day-to-day living skills. 6. Memory can often be impaired following a brain injury and many tests of short- and longer-term verbal, auditory and visual memory are available. However, some formal assessment of the child's functional memory is needed. 42 Rivara, J. B., Jaffe, K. M., Fay, G. C., Polissar, N. L., Martin, K. M., Shurtleff, H. A., & Liao, S. (1993). Family functioning and injury severity as predictors of child functioning one year following traumatic brain injury. Archives of Physical Medicine and Rehabilitation, 74, 1047-55. Page 16 of 116
  17. 17. 7. In order to organize them in day-today living, it is necessary to assess the child's ability. Deficits in this skill can often be masked in children because parents usually fulfil the role for many years. It is only usually following their transfer to secondary school, that these deficits become manifest. 8. An assessment of the child's basic educational skills is essential; this includes not only reading accuracy and spelling skills, but also the child's reading comprehension, as frequently it is their comprehension skills that are impaired following a brain injury. Mathematical skills are also commonly impaired, because of difficulties in mental processing. 9. Some assessment is required of the child's ability to process information efficiently and quickly. The brain-injured child may have difficulties in the rate at which they can process many tasks. The full extent of these difficul- ties can be judged at a functional level when comparing their performance with that of their peers. 10. It is important to make some assessment of the child's ability to learn from their environment; although testing a child's ability to learn in a structured setting or teaching situation is important, it must be remembered that a great deal of information and skills will be learned incidentally from their day-to-day living. 11. Communication is a crucial skill which can frequently be impaired following a brain injury. Within the expressive (language) domain, it is necessary to assess the child's functional communications skills, including intelligibility of speech, pragmatics and word finding. Within the area of receptive language, there is a need to evaluate their ability to understand short instructions and longer, more complex conversation. 12. Some estimation should be made of the child's stamina. Fatigue is a com- mon problem following a brain injury, particularly in first few weeks and months, and whereas a child may be capable of several hours of home tuition, they may not have the ability to cope with the rigours and demands of a full or even half a school day. 13. Emotional lability is common, and it is necessary to assess the child's ability to cope with the ups and downs of everyday life, including the frustration often encountered in the classroom and other learning situations. 14. The child's ability to make valid and appropriate social judgements relating to the behaviour and intentions of others is often overlooked, and if impaired can result in behavioural difficulties and a diminished quality of life for the child. 43 There is no one overall test or method of assessment that can evaluate all these aspects of functioning. Indeed, in some cases, tests are not appropriate. Given the rapid progress some children can make, the timing of any formal assessment can be variable and, in the early stages, assessments may best be done in the form of structured observations, although some detailed assessments will be 43 Appleton, R.; Baldwin, T. Management of Brain Injured Children. 2nd Ed. OUP,2006. Page 17 of 116
  18. 18. required at some stage. With the rapid development of neuropsychological tests that are available for children, the question arises as to the nature of any assessment, and the appropriateness of administering battery after battery of test with the aim of identifying some deficits. This is not only wasting time, but it can put the child through a stressful experience. 44 It has been assumed that a fixed battery of assessments provides an assessment of all the relevant neuropsychological domains (Lezak) 45, but, of course, this is far from true. With the wide variety of tests that are now available and suitable for children, it is not possible or appropriate to give serial assessments. It can also add little to our knowledge of the child. Excess testing can often lead to fatigue and poor test performance (Strauss 46). The assessment of children's disabilities should therefore follow a hypothesis-testing approach. 47 This has long been advocated within educational psychology, but more recently eloquently explained in the book School Neuropsychology (Hale and Fiorello 2004 48 ). Clearly, some form of basic assessment is required in the first instance, but a considerable amount of information should be gathered relating the child's functioning in the real world from which it is possible to draw inferences about their neuropsychological functioning and areas of likely deficit. (Appleton, R. et al 2006 idem.) Using a hypothesis-testing approach, the amount of testing can be limited and focused on areas where deficits are identified. This obviously needs knowledge of the tests and an understanding of neuropsychology. Of course, the danger of such an approach is to risk a confirmation bias, that is, to seek only information that supports one's hypothesis. It is therefore necessary not to avoid information that may be contradictory to one's hypothesis, nor indeed to be over-restrictive in the gathering of information, but to look for supporting evidence from a number of sources. It must be recalled that ecological validity should be the main goal of an assessment, but it is not relevant just to describe a child's neuropsychological functioning, but rather this should lead on to a positive intervention strategy, generating a working hypothesis by which a teaching strategy can then evolve. Changes can then be appropriately assessed, preferably using some form of objective measure to evaluate whether or not the teaching strategies are appropriate, as again it is the functional outcome which is especially important. For these reasons, a hypothesis-testing approach has far more relevance, providing it follows the cardinal rules of objectivity. A number of tests are now available and suitable for children, many with well-produced norms, and there may be considerable overlap in the periods of neuropsychological functioning they are 44 idem 45 Lezak, M. D. (2004). Neuropsychological Assessment (4th edn). Oxford: Oxford University Press. 46 Strauss, E. & Spreen, O. (1991). A Compendium of Neuropsychological Tests. Oxford: Oxford University Press. 47 Appleton, R et al 2006 idem. 48 Hale, J. B & Fiorello, C. A. (2004). School Neuropsychology. Guildford: Guildford Press. Page 18 of 116
  19. 19. assessing. It must be appreciated that in the case of ABI, multiple areas of functioning may or will have been affected, and a number of hypotheses would therefore have to be generated and then evaluated. Information should be sought from a number of different sources and it is often necessary to provide a preferred hierarchy of intervention, depending upon the particular needs of the child, so that subsequent stages of action can take place. It is essential that all members of those working with a child, including the family, should have a consistent approach to the child. When the child is disoriented, they should say who they are, and what they are doing, talking them through all movements, clearly, calmly and positively. If the child is being taught, then they are told where and why, being careful not to overload them with information which may be too much for them to process. It is essential to keep all instructions simple. DISORDERS OF THE HORMONE AND METABOLIC SYSTEMS It is important that there is an understanding that those with the type of brain injury caused by vaccines may be particularly prone to disorders of the hormone and metabolic systems. They may also have a lack of capacity to rationalise fear and anxiety whether real or imagined or perhaps as a result of dreams. [See Cortisol and Dreams below, p27] If these failings of the system are looked upon as mental illness then there is a grave risk of causing more harm through inappropriate medication. Such medication will not only fail to solve the problems but it will exacerbate the original condition by causing more damage to the system. The Hormonal Process — Normally, cortisol levels rise during the early morning hours and are highest about 7 am, so giving the energy that is needed to begin the day. In the evening and during the early phase of sleep the cortisol level should drop by approximately 90%. Evening is generally the time when the stresses of the day are behind you, the time when you can relax and unwind. For those who are constantly under stress, the cortisol level can remain elevated over long periods of time. Research now correlates chronically elevated levels of cortisol with blood sugar problems, fat accumulation, compromised immune function, exhaustion, bone loss, and even heart disease. Memory loss has also been associated with high cortisol levels. Continual stress can indeed have a negative impact on our health. An additional problem of long-term elevations of cortisol is that the adrenal gland may wear itself out and no longer be able to produce even normal levels of cortisol. This is called "adrenal exhaustion" and is associated with many other health problems. Besides impacting the immune system, fertility, and bone health, the list of the risks of high cortisol levels grows longer. New studies demonstrate that elevated cortisol levels can lead to abdominal weight gain, loss of verbal declarative memory (see Memory below, p39) words, names, and numbers), insulin resistance, and Type 2 Diabetes. Page 19 of 116
  20. 20. Increasing scientific evidence suggests that prolonged psychological stress takes its toll on the body, but the exact mechanisms by which stress influences disease processes have remained elusive. Now, scientists report that psychological stress may exact its toll, at least in part, by affecting molecules believed to play a key role in cellular aging and, possibly, disease development. In this study 49, the UCSF-led team determined that chronic stress, and the perception of life stress, each had a significant impact on three biological factors — the length of telomeres, the activity of telomerase, and levels of oxidative stress — in immune system cells known as peripheral blood mononucleocytes, in healthy premenopausal women. Telomeres are DNA-protein complexes that cap the ends of chromosomes and promote genetic stability. Each time a cell divides, a portion of telomeric DNA dwindles away, and after many rounds of cell division, so much telomeric DNA has diminished that the aged cell stops dividing. Thus, telomeres play a critical role in determining the number of times a cell divides, its health, and its life span. These factors, in turn, affect the health of the tissues that cells form. Telomerase is an enzyme that replenishes a portion of telomeres with each round of cell division, and protects telomeres. Oxidative stress, which causes DNA damage, has been shown to hasten the shortening of telomeres in cell culture. "Numerous studies have solidly demonstrated a link between chronic psychological stress and indices of impaired health, including cardiovascular disease and weakened immune function," says lead author Elissa Epel, an assistant professor of psychiatry. "The new findings suggest a cellular mechanism for how chronic stress may cause premature onset of disease. Anecdotal evidence and scientific evidence has have suggested that chronic stress can take years off your life; the implications of this study are that this is true at the cellular level. Chronic stress appears to have the potential to shorten the life of cells, at least immune cells." Sweeping changes are needed in the organisation and ethos of the NHS’s dedicated inpatient facilities and care homes for people with learning disabilities, the health watchdog for England has said. Care at NHS facilities for people with learning disabilities falls short of modern safety and quality standards, says the Healthcare Commission in a new report, and many people live in bleak accommodation far away from their families. 50 Institutional failings mean that many people are being deprived of their human rights and dignity and have little access to advocacy services, few choices about how they live their lives, and limited activities, the report says. Services are too reliant on drug treatment to control behaviour, it says, when the evidence that this is a reasonable response is limited. Effects of Stress on the Brain — there is a need for providers and carers to understanding about how stress is generated. For everyone, those aggravating things that go wrong in the day and those irritating things that go bump in the night 49 Blackburn, Elizabeth; Herzstein, Morris & Epel, Elissa. Psychological stress and disease. Proceedings of the National Academy of Sciences. 30 November 2004. 50 Zosia Kmietowicz. People with learning disabilities are being let down by NHS. BMJ 2007;335:1177 (8 December) Page 20 of 116
  21. 21. — disrupting routines and interrupting sleep — all have a cumulative effect on the brain, especially its ability to remember and learn. As science gains greater insight into the consequences of stress on the brain, the picture that emerges is not a pretty one. A chronic overreaction to stress overloads the brain with powerful hormones that are intended only for short-term duty in emergency situations. Their cumulative effect damages and kills brain cells. The Response of the Body's Reaction to Stress — This is sometimes referred to as General Adaptation Syndrome (GAS). When a person experiences stress, the brain responds by initiating 1,400 different responses including the transmission of a variety of chemicals to our blood stream. This gives momentary boost to do whatever needs to be done to survive. Hormones rush to the adrenal glands to suppress the streaming cortisol on its way to the brain. Other hormones rush to the brain to round up all the remnants of cortisol that made it to the hippocampus. These hormones escort the cortisol remnants back to the kidneys and then on to the bladder. The body at this stage has reached metabolic equilibrium, also known as homeostasis. (see below p21) There are three stages to GAS. In the first stage — called alarm reaction, the body releases adrenaline and a variety of other psychological mechanisms to combat the stress and to stay in control. This is called fight or flight response. The muscles tense, the heart beats faster, breathing and perspiration increase, the eyes dilate, the stomach may clench. This happens as a natural process in order to protect you in case something bad happens. Once the cause of the stress is removed, the body will go back to normal. If the cause for the stress is not removed, go to a second stage called resistance or adaptation. This is the body's response and provides long term protection. It causes the secretion of more hormones that increase blood sugar levels to sustain energy and raise blood pressure. The adrenal cortex (outer covering) produces hormones called corticosteroids for this resistance reaction. Overuse by the body's defence mechanism in this phase may eventually lead to disease. If this adaptation phase continues for a prolonged period of time without periods of relaxation and rest to counterbalance the stress response, sufferers become prone to fatigue, concentration lapses, irritability and lethargy as the effort to sustain arousal slides into negative stress. The third stage of GPS is called exhaustion. In this stage, the body has run out of its reserve of body energy and immunity. Mental, physical and emotional resources suffer heavily. The body experiences "adrenal exhaustion". The blood sugar levels decrease as the adrenals become depleted, leading to decreased stress tolerance, progressive mental and physical exhaustion, illness and possibly collapse. The hypothalamus-pituitary-adrenal (HPA) chain of command has served humans well as a means of survival for thousands of years. However, for those suffering from chronic anxiety and depression this process malfunctions. Continual stress early in life disrupts the cycle. Instead of shutting off once the crisis is over, the process continues, with the hypothalamus continuing to signal the adrenals to produce cortisol. Page 21 of 116
  22. 22. Homeostasis — When a danger finally passes or the perceived threat is over, the normal brain initiates a reverse course of action that releases a different type of biochemicals throughout the body. Attempting to bring you back into balance; the brain seeks the holy grail of "homeostasis," that elusive state of metabolic equilibrium between the stimulating and the tranquilizing chemical forces in the body. When either one of the stimulating or tranquilizing chemical forces dominates the other without relief, then you will experience an on-going state of internal imbalance. This condition is known as stress; it can have serious consequences for brain cells. Parasympathetic and Sympathetic Nervous System — the sympathetic nervous system (SNS) turns on the fight or flight response. In contrast, the parasympathetic nervous system (PNS) promotes the relaxation response. Like two tug-of-war teams skilfully supporting their rope with a minimum of tension, the SNS and PNS carefully maintain metabolic equilibrium by making adjustments whenever something disturbs this balance. The vital elements in this process are the hormones, the chemical messengers produced by endocrine glands. These hormones travel through the bloodstream to accelerate or suppress metabolic functions. The trouble is that some stress hormones are not completely regulated by the body’s system. They remain active in the brain for too long – injuring and even killing cells in the hippocampus, the area of the brain needed for memory and learning. Because of this hierarchical dominance of the SNS over the PNS, it often requires conscious effort to initiate the relaxation response and re-establish metabolic equilibrium. The Emotional Brain: The Limbic System — The primary area of the brain that deals with stress is its limbic system. Because of its enormous influence on emotions and memory, the limbic system is often referred to as the ‘emotional brain’. It is also called the mammalian brain, because it emerged during evolution with our warm-blooded relatives, and marked the beginning of social cooperation in the animal kingdom. Whenever a threat is perceived, imminent or imagined, the limbic system immediately responds via the autonomic nervous system — the complex network of endocrine glands that automatically regulates metabolism. The term "stress" is short for distress, a word evolved from Latin that means "to draw or pull apart.” The Romans even used the term districtia to describe "a being torn asunder.” When stressed-out, most of us can probably relate to this description. Distress Signals from the Brain — The sympathetic nervous system does an excellent job of rapidly preparing to deal with what is perceived as a threat to one’s safety. Its hormones initiate several metabolic processes that allows one to cope in the best way with sudden danger. The adrenal glands release adrenaline (also known as epinephrine) and other hormones that increase breathing, heart rate, and blood pressure. This moves more oxygen-rich blood faster to the brain and to the muscles needed for fighting or fleeing — and, you have plenty of energy to do either, because adrenaline Page 22 of 116
  23. 23. causes a rapid release of glucose and fatty acids into your bloodstream. Also, your senses become keener, your memory sharper, and you are less sensitive to pain Other hormones shut down functions unnecessary during the emergency. Growth, reproduction, and the immune system all go on hold. Blood flow to the skin is reduced. With the mind and body in this temporary state of metabolic overdrive, you are now prepared to respond to a life-threatening situation. Getting Back to Normal — After a perceived danger has passed, the body then tries to return to normal. But this may not be so easy, and becomes even more difficult with age. Although the hyper-activating sympathetic nervous system jumps into action immediately, it is very slow to shut down and allow the tranquilizing parasympathetic nervous system to calm things down. Once the stress response has been activated, the (normal) system wisely keeps the body in a state of readiness. Not All Stress is Bad — Bear in mind that an appropriate stress response is a healthy and necessary part of life. One of the things it does is to release norepinephrine, one of the principal excitatory neurotransmitters. Norepinephrine is needed to create new memories. It improves mood. Problems feel more like challenges, which encourages creative thinking that stimulates your brain to grow new connections within it. Stress Compromises the Blood-Brain Barrier (BBB) — Stress can dramatically increase the ability of chemicals to pass through the blood-brain barrier. During the Gulf War, Israeli soldiers took a drug to protect themselves from chemical and biological weapons. Normally, it should not have crossed the BBB, but scientists learned that the stress of war had somehow increased the permeability of the BBB. Nearly one-quarter of the soldiers complained of headaches, nausea, and dizziness — symptoms which occur only if the drug reaches the brain. Stress and Noise — sudden sound is an urgent wake-up call that alerts and activates the stress response — a biological alarm that affects the brain in powerful ways. Because loud noise often heralds bad news, animals and humans have evolved a rapid response to audio stressors: the roar of a carnivore, the crack of a falling tree, the scream of a child and more recently; the explosion of a weapon, the wail of a siren, the crash of the stock market. Sudden and unexpected noise for those under stress can increase the startle response to noise. Stress and Memory — chronic over-secretion of stress hormones adversely affects brain function, especially memory. Too much cortisol can prevent the brain from laying down a new memory, or from accessing already existing memories. The renowned brain researcher, Robert M. Sapolsky, has shown that sustained stress can damage the hippocampus, the part of the limbic brain which is central to learning and memory. 51 The ‘culprits’ are "glucocorticoids," a class of steroid 51 Sapolsky, Robert M.; Krey, Lewis C.; & McEwen, Bruce S. Glucocorticoid- sensitive hippocampal neurons are involved in terminating the adreno-cortical stress response. Proc. Natl. Acad. Sci. USA. Vol. 81, pp. 6174-6177, October 1984 Page 23 of 116
  24. 24. hormones secreted from the adrenal glands during stress. They are more commonly known as corticosteroids or cortisol. During a perceived threat, the adrenal glands immediately release adrenalin. If the threat is severe or still persists after a couple of minutes, the adrenals then release cortisol. Once in the brain cortisol remains much longer than adrenalin, where it continues to affect brain cells. Cortisol Affects Memory Formation and Retrieval — Cortisol also interferes with the function of neurotransmitters, the chemicals that brain cells use to communicate with each other. Excessive cortisol can make it difficult to think or retrieve long-term memories. That's why people get befuddled and confused in a severe crisis. Their mind goes blank because "the lines are down.” They can't remember where the fire exit is, for example. Cortisol and Temporary Memory Loss – a Study — in an animal study, rats were stressed by an electrical shock, and then made to go through a maze with which they were already familiar. When the shock was given either four hours before or two minutes before navigating the maze, the rats had no problem but, when they were stressed by a shock 30 minutes before, the rats were unable to remember their way through the maze. This time-dependent effect on memory performance correlates with the levels of circulating cortisol, which are highest at 30 minutes. The same thing happened when non-stressed rats were injected with cortisol. In contrast, when cortisol production was chemically suppressed, then there were no stress-induced effects on memory retrieval. According to James McGaugh, director of the Centre for the Neurobiology of Learning and Memory at the University of California, Irvine, "This effect only lasts for a couple of hours, so that the impairing effect in this case is a temporary impairment of retrieval. The memory is not lost. It is just inaccessible or less accessible for a period of time." Cortisol and the Degenerative Cascade — normally, in response to stress, the brain's hypothalamus secretes a hormone that causes the pituitary gland to secrete another hormone that causes the adrenals to secrete cortisol. When levels of cortisol rise to a certain level, several areas of the brain, especially the hippocampus, tell the hypothalamus to turn off the cortisol-producing mechanism. This is the proper feedback response. The hippocampus, however, is the area most damaged by cortisol. In his book Brain Longevity, Dharma Singh Khalsa, M.D., describes how older people often have lost 20-25% of the cells in their hippocampus, so it cannot provide proper feedback to the hypothalamus, so cortisol continues to be secreted.52 This, in turn, causes more damage to the hippocampus, and even more cortisol production. Thus, a Catch-22, "degenerative cascade" begins, which can be very difficult to stop. Cortisol and Brain Degeneration -— Studies done by Dr. Robert M. Sapolsky, Professor of Neurology and Neurological Sciences at Stanford University, 52 Khalsa, Dharma Singh; Stauth, Cameron. Brain Longevity. Century, 1997 Page 24 of 116
  25. 25. showed that lots of stress or exposure to cortisol accelerates the degeneration of the aging hippocampus.53 And, because the hippocampus is part of the feedback mechanism that signals when to stop cortisol production, a damaged hippocampus causes cortisol levels to get out of control — further compromising memory and cognitive function. The cycle of degeneration then continues. NUTRITION AND METABOLIC DISTURBANCES Children with head injuries present a number of complex inter-related metabolic disturbances. The specific requirement for, and effects of nutritional support cannot be separated from the child's nutritional condition or the pre-injury environment and must be considered as only part of the total environment for recovery. Superimposed on the normal requirements for growth and development are the metabolic problems induced by trauma, the changes in nutrition that may directly result from focal brain injury, and the effects on neurotransmitter metabolism which are secondary to tissue damage and nutritional insufficiency. 54 The optimal milieu for recovery after head injury has been poorly investigated, and the conditions essential for maximizing further development in the head-injured child remain ill-defined. From a functional viewpoint, the effects on neurotransmitter metabolism may be considered crucial, but these are unlikely to persist solely because of dietary factors rather, they may be compounded by post- traumatic changes in sleep and behaviour, prophylactic drug use, disruption of social development or on-going social relationships, general levels of home stimulation and parental management55. A continuum of insufficiency and impairment of brain growth, development and mental ability may exist for the head-injured child. Consistent with a rational approach to rehabilitation, adequate nutritional intake may be necessary, but not of itself sufficient. Sensory activity may be essential but nutritional support a necessity in order to obtain it56. Whilst nutritional intervention may not provide a magic wand for the head-injured child, it might be possible to increase the probability of positive change by nutritional intervention. Studies of single amino acids such as tryptophan, tyrosine and choline or lecithin in relatively large doses may have little meaning in strictly nutritional terms for they are not representative of how people eat. The effects of ordinary meals on behaviour are usually smaller than those in studies of single nutrients, so that sizeable numbers of subjects, adequately sensitive measures and tight methodological controls are required57. Dose response parameters are largely unknown in this sort of 53 Sapolsky, Robert M.; Uno, Hideo; Rebert, Charles S. & Finch, Caleb E. Hippocampal Damage Associated with Prolonged Glucocorticoid Exposure in Primates. The Journal of Neuroscience, September 1990, 10(9): 2897-2902 54 Dickerson, JWT.; Johnson, DA. & Maclean, A. Food for thought: a rôle for nutrition in recovery. In Johnson, D., Uttley, D., & Wyke, M. A. (1989). Children's Head Injury: Who Cares? London: Taylor and Francis. 55 Kraemer, G.W. (1985) 'The primate social environment, brain neurochemical changes and psychopathology', Trends in Neuroscience, 8, pp. 339-340. 56 Ricciuti, H.N. (1981) ‘Adverse environmental and nutritional influences on mental development: a perspective’, Journal of the American Dietetic Associatian, 79, pp. 115-120. 57 Spreen, O., Tupper, O., Risser, A., Tuokko, H. & Edgell, D. (1984) Human Developmental Neuropsychology, Oxford, Oxford University Press. Page 25 of 116
  26. 26. investigation, making it difficult to determine portion sizes for experimental studies. Whilst less dramatic responses to food than to the pharmacologically pure forms could be expected, food effects upon brain function may still be of more significance, at least in longer term maintenance of recovery achieved. It is important to note that if the specific neurotransmitter receptors are damaged, or other neuronal populations are also destroyed which contain converting enzymes, for example, then increasing a particular class of neuro-chemical activity is unlikely to be uniformly successful, particularly in cases of severe diffuse head injury. A great deal of research is necessary before nutritional and dietary factors are implicated in recovery from paediatric head injury. If post-traumatic deficits in nutritional status persist, compounded by social, cognitive and emotional difficulties, then dietary evaluation and management may be one avenue to explore, to help maximize progress and outcome. The effects of dietary stress on an individual child will not simply be matters of nutritional pathophysiology, but rather will be moulded and modified by his genetic endowment, stage of development, home stimulation, social and emotional climates. With increasing knowledge of neurotransmission and parallel concern about subclinical nutritional deficiencies, the development of collaborative research studies in this most complex field would soon help to delineate the validity of nutritional factors in determining the optimal milieu for recovery in paediatric head- injury. Head-injured children grow up to become relatively disabled adults, with the added possibility that, in the presence of structural damage, the normal ageing process may be exacerbated. Consequently, instilling good dietary habits in childhood may at the very least be beneficial to long-term mental function. (Dickerson et al, 1989 idem) Cohen et al have researched neurological dysfunction caused by traumatic brain injury and have found that this results in profound changes in net synaptic efficacy, leading to impaired cognition. Because excitability is directly controlled by the balance of excitatory and inhibitory activity, underlying mechanisms causing these changes have been investigated using lateral fluid percussion brain injury in mice. Although injury-induced shifts in net synaptic efficacy were not accompanied by changes in hippocampal glutamate and GABA levels, significant reductions were seen in the concentration of branched chain amino acids58 (BCAAs), which are key precursors to de novo glutamate synthesis. Dietary consumption of BCAAs restored hippocampal BCAA concentrations to normal, reversed injury-induced shifts in net synaptic efficacy, and led to reinstatement of cognitive performance after concussive brain injury. All brain-injured mice that consumed BCAAs demonstrated cognitive improvement with a simultaneous restoration in net synaptic efficacy. Posttraumatic changes in the expression of cytosolic branched chain aminotransferase, branched chain ketoacid dehydrogenase, glutamate dehydrogenase, and glutamic acid decarboxylase support a perturbation of BCAA and neurotransmitter metabolism. Ex vivo application of BCAAs to hippocampal slices from injured animals restored 58 Branched Chain Amino Acids are Leucine, Isoleucine and Valine. They are available combined in a powder or as a tablet. Effectiveness of BCAAs can be increased by consuming 10mg of Vitamin B6 with every 10g of BCAA. Page 26 of 116
  27. 27. posttraumatic regional shifts in net synaptic efficacy as measured by field excitatory postsynaptic potentials. These results suggest that dietary BCAA intervention could promote cognitive improvement by restoring hippocampal function after a traumatic brain injury.59 _______ Sleep and dreaming following Brain Injury By measuring electrical activity, we are able to distinguish sleep from its unconscious imitation by other behaviours. Thus, sleep is an active state of the brain and its electrical activity continues throughout sleep and differs from that during waking. Sleep is of the brain. The research of Payne and Nadel briefly stated is that variations in cortisol (and other neurotransmitters) determine the functional status of hippocampal ↔ neocortical circuits, thereby influencing the memory consolidation processes that transpire during sleep. The status of these circuits largely determines the phenomenology of dreams, providing an explanation for why we dream and of what. As a corollary, dreams can be thought of as windows onto the inner workings of our memory systems, at least those of which we can become conscious. In addition to exploring these ideas, their paper provides some background concerning: (1) the states of sleep and the role of various neurotransmitters in switching from one sleep state to another, (2) how the characteristics of dreams vary as a function of sleep state, (3) the memory content typically associated with dreaming in different dream states, and 60 (4) the role of sleep in the consolidation of memory. We know also, that the normal brain controls itself so as to produce sleep. The clocks that turn sleep on and off are composed of networks of brain cells. These clocks not only time whether we sleep or wake but also program an elaborate and orderly sequence of brain events within sleep. In one such event, the continuously active brain becomes extraordinarily more active every 90 to 100 minutes during sleep and remains so as long as an hour. It is during such periods that we dream. 59 Cohen, Akiva S.; Cole, Jeffrey T.; Mitala, Christina M.; Kundu, Suhali; Verma, Ajay; Elkind, Jaclynn A.; & Nissim, Itzhak. Dietary branched chain amino acids ameliorate injury-induced cognitive impairment. Proceedings of the National Academy of Sciences. published online before print December 7, 2009, 60 Payne, Jessica D. & Nadell, Lynn. Sleep, dreams, and memory consolidation: The role of the stress hormone cortisol. Learning and Memory; 2004. 11: 671-678. Page 27 of 116
  28. 28. 61 Thus, dreaming, like sleep, is of the brain and by the brain. The brain is the prime beneficiary of sleep, as is made obvious by the progressive decline in our cerebral capacities when we are deprived of sleep. We first have difficulty concentrating, attending, and performing coordinated motor acts such as driving cars. Then we become irritable and suffer an almost painful sleepiness. After we go five to ten days without sleep, our brain loses its bearings altogether and madness takes over: the trusting become paranoid; the rational, irrational; and the sane begin to see and hear things that aren't there. All the dysfunctions caused by sleep deprivation are rapidly reversed when lost sleep is recovered. We don't yet know exactly how sleep ensures efficient brain function, but that it does so is beyond doubt. Thus, sleep is for the brain. Sleep is of the brain, by the brain, and for the brain. (Hobson, 1989, idem) Recognizing the connection between the brain and sleep we can better appreciate why sleep science is so new. It was not until the second quarter of our own century that a way was found to measure sleep objectively by recording the brain electrical activity. There are two combined factors that have helped to produce an observational sleep science. First, the subjective experience of nightmares and dreams shows that sleep cannot occur without intense brain activity. Secondly, while animal sleep appears tranquil, in all mammals — including humans — observable movements of the eyes, face, and fingers occur periodically during sleep. It seems inconceivable to us that those who watched sleeping cats' paws twitch, sleeping puppies' feet scamper, or sleeping babies' faces grimace and smile did not suspect intense underlying brain activity. We can infer that such outward signs of motion are related to the inward experience of dreams and therefore a strong presumptive evidence of brain activation. (Hobson, 1989, idem) When there is a chronic lack of sleep it seems likely that structures behind the medulla (see below, this page) might actively contribute to the slowing of non-REM sleep. Studies by other researchers have implied that an area just next to the hypo- thalamus, called the basal forebrain, may playa role in controlling non-REM sleep. The generation of non-REM sleep was shown to be impeded by damaging and enhanced by stimulating this area of the brain. Liu et al 62 and Madan et al 63 suggest that conditioned fear causes REMS alterations, including difficulty in initiating a REMS episode as indicated by the diminution in the number of seq-REMS episodes. Another finding, the increase in phasic activity, agrees with the inference from clinical investigations that retrieval 61 Hobson, JA. Sleep. Scientific American Library; 1989; pp3. 62 Liu, Xianling; Tang, Xiangdong & Sanford, L D. Fear-conditioned suppression of REM sleep: relationship to Fos expression patterns in limbic and brainstem regions in BALB/cJ mice. Brain Research. Volume 991, Issues 1-2, 21 November 2003, Pages 1-17 63 Madan, Vibha; Brennan, Francis X.;.Mann, Graziella L.; Horbal, Apryle A.; Dunn, Gregory A.; Ross, Richard J. & Morrison, Adrian R. Long-term Effect of Cued Fear Conditioning on REM Sleep Micro-architecture in Rats. Sleep. 2008 April 1; 31(4): 497–503. Page 28 of 116
  29. 29. of fearful memories can be associated with the long-term REMS disturbances characteristic of posttraumatic stress disorder. Michel Jouvet is perhaps the world's leading sleep and dream researcher. He discovered a dream state that he called paradoxical sleep. This third category of brain activity (distinct from sleeping and waking) is a state of very deep sleep with some specific motor events, including rapid eye movements (REM). 64 In 1959 Michel Jouvet conducted several experiments on cats regarding muscle atonia (paralysis) during REM sleep. Jouvet demonstrated that the generation of REM sleep depends on an intact pontine tegmentum65 and that REM atonia is due to an inhibition of motor centres in the medulla oblongata. 66 Cats with lesions around the locus coeruleus67 have less restricted muscle movement during REM sleep, and show a variety of complex behaviours including motor patterns suggesting that they are dreaming of attack, defence and exploration. Jouvet proposed the speculative theory that the purpose of dreaming is a kind of iterative neurological programming that works to preserve an individual's psychological heredity, the basis of personality. 68 A different brainstem structure, the pons, has been shown by Jouvet to be critical for REM sleep generation. He transected the midbrain of a cat, and then completely removed all the structures above the cut, except the hypothalamus. The resulting "pontine" cats had a periodically recurrent phase of rapid eye movements associated with a complete loss of muscle tone. This latter phe- nomenon (called postural atonia) had been shown also to characterize REM sleep in normal cats by Jouvet and Francois Michel in 1959 and was later shown to be true also of human REM sleep (Michel Jouvet et al)69. This experiment pointed to a timer and trigger for REM sleep in the pons. 64 Jouvet, Michel. The Paradox of Sleep: The Story of Dreaming. MIT Press 1999. 65 The pontine tegmentum is a part of the pons of the brain involved in the initiation of REM sleep. It includes the pedunculo-pontine nucleus and the latero-dorsal tegmental nucleus, among others, and is located near the raphe nucleus and the locus ceruleus . PET studies seem to indicate that there is a correlation between blood flow in the pontine tegmentum, REM sleep, and dreaming . 66 The medulla oblongata is the lowest part of the brain, situated at the top of the spinal cord and controlling activities such as heart beat, blood pressure and breathing. 67 The Locus coeruleus is a nucleus in a dense cluster of neurons in the dorso rostral pons of the brain stem involved with physiological responses to stress and panic. This nucleus gained prominence in the 1960s when new anatomical approaches revealed it to be the major source of norepinephrine in brain with projections throughout most central nervous system regions, including the cerebral cortex, hippocampus, thalamus, midbrain, brainstem, cerebellum, and spinal cord (Foote et al., 1983; Aston-Jones et al., 1995). These findings stimulated a great deal of research into this unusual system, resulting in a wealth of knowledge at the cellular, systems, and behavioural levels. 68 Jouvet, Michel. Paradoxical Sleep - A Study of its Nature and Mechanisms. Progress In Brain Research Vol. 18 Sleep Mechanisms 1965 69 Jouvet, M., Michel, F., & Courjon, J. (1959). Sur un stade d'activité é]ectrique cérébrale rapide au cours du sommeil physiologique C.R. Soc. Biol. (Paris), 153, 1024-1028. Page 29 of 116
  30. 30. Electromyogram (EMG) experiments show that movements are found to be abolished in REM sleep. Because we do not move our muscles in REM sleep, we cannot express the motor acts of our dreams. Of course, during their atonic-REM periods Jouvet's cats could show no cortical EEG changes (because they had no cortex), but they did have spiking EEG waves in the pons during these periods that resembled those seen in normal cats. Jouvet proposed that there was both a REM sleep clock and trigger mechanism in the pons. The clock was reliable because the episodes occurred in the cat at regular intervals of 30 minutes as in normal sleep; the trigger was effective because the episodes lasted for the normal duration of 6 to 8 minutes. It should be clear therefore that many areas of the complex brainstem are involved in the control of sleep and waking. Non-REM sleep mechanisms in the basal forebrain interact with medullary and midbrain reticular systems to produce EMG slow waves in the cortex; periodically interrupting this process is the REM sleep generator in the pons, which reactivates the brain. This then leads us to look at why brain injury can cause sleep disturbance and what parts of the sleep cycle may be affected. Glen Johnson, a Clinical Neuropsychologist of the Neuro-Recovery Head Injury Program, Traverse City, USA writes that, “…all of my head-injured patients have some form of a sleep disorder.” 70 It is enlightening to read of his experience with brain injured patients. “First, let's recognize what happens with a typical sleep disorder caused by a head injury. Typically, you may go to sleep fairly easily, although sometimes people can’t stop their thoughts in the evening and have difficulty getting to sleep. Once you have fallen asleep, you may feel that you’re waking up as often as every hour. By about 4 or 5 in the morning, you're wide awake, even though you are dead tired. In addition, many people who have head injuries are easily awakened by small noises. I've had patients who would sleep though a fire alarm prior to their head injuries, but who now wake up when a cat walks by. Sleep is very important to the healing process. If you don't sleep, you're going to be tired throughout the day. If you're tired throughout the day, your memory will get worse and you'll be more cranky and irritable. Lack of sleep makes the other head injury symptoms much worse. Sleep also has an important role in physical healing.” (idem) A wide-range study of victims of head injury often reveals disorders that are neglected by less extensive examinations, and dispels the idea that there is usually a benign outcome. Following head trauma, there is a marked increase in dreams of threatening content, despite the fact that, contrary to repression occurring in many post-traumatic victims, a comatose person with head injury has no registration of the traumatic event. The loss of self-esteem and self-confidence creates a permanent state of stress, which can be reflected in the patients’ threatening, frightening and anxiety-provoking dream content. It is reasonable to assume that dreaming is, in part, an expression of both neurological control and feedback of intention and action. 71 70 Johnson, Glen. Traumatic Brain Injury: Survival Guide. Online edition at: 71 Parker, RS. (2000) Concussive brain trauma: neurobehavioral impairment and maladaptation. Taylor & Francis Ltd. Page 30 of 116
  31. 31. _______ Information Processing A common deficit arising from a brain injury, and more commonly from a head injury, is the inability to process information at the normal rate. Whereas the child may be able to carry out a variety of mental tasks, the speed at which these are completed in a brain-injured child may be significantly slower than it would be for a normal child (Brooks 1984). 72 The deficit may involve the speed at which the child can understand the task involved, learn the material, retrieve it from memory and then carry out the mental processes involved. Deficits in this area can severely limit the ability of the child to function in many everyday situations and such deficits can arise following even a mild head injury (Wrightson et al.) 73 In specific detail, the child finds difficulty comprehending information at the normal rate, formulating their thoughts and then carrying out the required actions. They may find it difficult to understand if too much information is presented at any one occasion. They may therefore initially start off understanding what is going on but rapidly lose their way as the amount of information accumulates. This is particularly the case if the level of information becomes more complex and can occur in both the classroom and in social situations. Borod 74 found brain-injured children to be less competent at comprehending emotional information. In the teaching situation this often shows itself in the child's inability to complete written assignments or answer questions in the allotted time, and therefore never being able to answer a question directed at the class, because by the time they raise their hand someone else has already answered before them. Children who are significantly affected can find themselves severely disadvantaged at a social level. Whereas adults will give a child a sympathetic look and the necessary time to collect their thoughts, a more competitive adoles- cent group will not be so kind or so tolerant. In the playground, the conversation moves at the pace of the group and for those too slow to respond, they frequently find themselves left far behind; sometimes it is easier not to even try, and the child may find themselves becoming increasingly isolated from their peers. 75 The ability to understand, learn and then retrieve information involves a range of abilities, including attention, short-term memory and the ability to manipulate the information in order to place it into a more permanent memory system. Essential to this, is the ability to organize material into a meaningful manner so that it can be 72 Brooks, N. (1984). Cognitive deficits after head injury. In: Closed Head Injury: Psychosocial Social and Family Consequences (ed. N. Brooks), pp. 44-73. Oxford: Oxford Community Press. 73 Wrightson, P., McGinn, V., & Gronwall, D. (1995). Mild head injury in pre- school children - evidence that can be associated with a persisting cognitive defect. Journal of Neurology Neurosurgery and Psychiatry 59, 375-80. 74 Borod, J. C. (1992). Interhemispheric and intrahemispheric control of emotion. Journal of Consulting and Clinical Psychology 60, 339-48. 75 Appleton, R et al 2006 idem. Page 31 of 116