Viewpoint on the Brain Disorder in Autism

  (based on a review of research papers in the medical literature)

Viewpoint on the brain disorder(2003) (View in 2000)

The auditory system The inferior colliculus Hemoglobin & the brain

Concepts of autism Autism spectrum Social responsibility

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Conrad Simon Memorial Research Initiative
Date posted: 
© Copyright 2003
Eileen Nicole Simon
Introduction | I. Brain damage at birth | II. Auditory system | III. Language
IV.  Childhood handicaps | V. Brainstem Damage | VI.  References | Summaries
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Topics (section links):

Introduction

I. BRAIN DAMAGE AT BIRTH
1 - Asphyxia at Birth
2 - Hypoxic Birth
3 - Asphyxia Versus Hypoxia
4 - Human Conditions
5 - Stages of Asphyxia
6 - The Umbilical Cord Lifeline
7 - Developmental Delay
8 - Poor Manual Dexterity
9 - Progressive Degeneration
10 - Autism and Complications at Birth
11 - Mercury, and Other Toxic Factors

II. THE AUDITORY SYSTEM
12 - Metabolic Rank Order
13 - The Auditory System
14 - Auditory Dysfunction

III. LANGUAGE
15 - Language by Ear
16 - Verbal Auditory Agnosia
17 - Echolalic Speech
18 - Echolalic Speech is Pragmatic

IV. CHILDHOOD HANDICAPS
19 - Auditory and Motor Handicaps
20 - Increased Incidence of Autism
21 - Fetal to Postnatal Adaptation
22 - Forgotten History
23 - Worth Remembering
24 - Hemoglobin
25 - Infant Anemia
26 - Autism in Twins
27 - Male-Female Differences

V. BRAINSTEM DAMAGE
28 - Variable Vulnerability
29 - Patterns of Damage
30 - Wernicke's Encephalopathy
31 - Suffocation at the Molecular Level
32 - Thiamine Deficiency
33 - Brain-Gut Relationship

VI. REFERENCES (for all sections)
34 - Bibliography (for section IV)
35 - Autism and Complications at Birth
36 - Umbilical Cord Clamping

Summaries (for all sections)
    Summaries (for section IV)

[Site Links]


Overview (Chilldhood Handicaps):

High blood flow in the inferior colliculus supports the highest rate of aerobic metabolism in the brain. Protective mechanisms go into action under adverse conditions that preserve function in the inferior colliculus. Hemoglobin delivers oxygen in exchange for carbon dioxide, and may provide the quickest response to carbon dioxide produced by high metabolic activity in the inferior colliculus during a hypoxic episode. Hemoglobin becomes depleted of oxygen under hypoxic conditions, but the inferior colliculus can obtain enough to remain undamaged leaving nothing for other areas of the brain.

Myers (1972) demonstrated that the inferior colliculus is selectively and predictably damaged by a few minutes of total oxygen deprivation at birth; but prolonged partial hypoxia late in gestation damages the cortex and other less metabolically active areas of the brain, without involvement of the inferior colliculus. The spectrum of childhood disorders from cerebral palsy to autism may represent damage of motor cortex at one extreme, and autism at the other.


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IV. CHILDHOOD HANDICAPS

19 - Auditory and Motor Handicaps
The syndrome of autism described by Kanner (1943) did not include indications of neurological problems [123]. Children with the "core syndrome" of Kanner autism develop motor milestones on time, are toilet trained on time, and even appear to begin speaking on time. By the age of three or four however, speech development is clearly aberrant.

Delayed motor development and residual physical awkwardness are however indications of neurological impairment in many children with autism, and especially in those with a diagnosis of Asperger's syndrome. Few children fit the narrow description of Kanner autism; Kanner even commented on the individual differences he observed. To explain the autism spectrum: Impairment of function in the inferior colliculi (by asphyxia at birth) might be at one end of the spectrum and involvement of motor systems (by hypoxic birth) at the other. Most children with autism show signs of both auditory dysfunction and some delay of motor development.

Asperger's syndrome is a far more hopeful diagnosis than autism. Children with Asperger's syndrome may be late learning to speak and their speech is full of pedantic sound-bytes with often peculiar and pun-like connections to conversational context. But command of language is the tool by which children with Asperger's syndrome can learn and grow. Language disorder is the most serious impediment to human development.

Lack of manual dexterity was noted as the most common residual deficit in monkeys asphyxiated at birth. The normal climbing ability of monkeys was also never achieved. Control of wrist, ankles, and digits remained inadequate. A reduced level of spontaneous activity was observed. The asphyxiated monkeys were described as hypoactive, docile, unemotional, and not easily disturbed.

Short-term memory also appeared deficient in asphyxiated monkeys. But tests of learning involved repeated trials, and the asphyxiated monkeys were described as difficult to coax as if they gave up shortly after beginning training trials. The behaviors were compared to the condition known then as "minimal cerebral dysfunction" (MCD) in children. Clinical signs listed for MCD included problems with attention, impulse control, interpersonal relations, and hyper- or hypo-reactivity, along with lack of coordination and learning disabilities. Some children with MCD might now be viewed as having Asperger's syndrome or attention-deficit hyperactivity disorder (ADHD).
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20 - Increased Incidence of Autism
As long ago as 1975 I proposed that echolalic speech of children with autism might be the result of damage to the inferior colliculi, and that asphyxia at birth is an example of how such damage could take place [152]. But now immediate clamping of the umbilical cord has become a standard obstetric practice, whether or not the infant has begun to breathe. Unless breathing is established within seconds after cutting off umbilical circulation, asphyxia will occur and brainstem nuclei like the inferior colliculus will be damaged or impaired.

Four minutes is generally recognized as the time beyond which resuscitation becomes less likely following accidents such as drowning or cardiac arrest. It is a common belief that infant humans and animals can withstand oxygen deprivation longer than mature beings. But Myers (1972) described changes in neurons (seen only under the microscope) in the inferior colliculus of monkeys subjected to asphyxia of duration too short to cause visible damage [2]. Asphyxia had to be of seven to eight minutes duration before visible damage was seen, and Faro and Windle (1969) found progressive neuropathologic changes in monkeys kept alive for months or years following asphyxia at birth, even in monkeys without the characteristic lesions of the inferior colliculi [30].

It would seem dangerous to assume that a newborn child is more resistant to anoxia and can withstand a few minutes of asphyxia until breathing is initiated by artificial ventilation. Myers found that it is the infant heart that withstands asphyxia better than that of the adult (not the brain). Failure of attempts for prompt resuscitation after cutting the cord will result in at least some impairment of the brain.

Who has the evidence that minimal brainstem damage is not important? Research data clearly implies that damage confined to the brainstem results in developmental deficits. That early brain damage heals because of "plasticity" was disproved when Faro and Windle discovered that with time early brainstem damage leads to progressive widespread changes throughout the brain.

Delayed onset of breathing after the cord has been cut deserves consideration as a contributing factor to increased numbers of children with developmental disorders, and the increased incidence (or prevalence) of autism. A low Apgar score five minutes after birth is considered ominous, and has been correlated with later developing autism [56, 57]. Increases in autism have been noted during the same period that immediate cord clamping has become routine.

In addition to complications at birth, autism is associated with many medical conditions, which include prenatal exposure to alcohol and drugs, pre- and postnatal infections, lead poisoning, gastrointestinal disorders, neurologic (seizure) disorders, and diverse genetic predispositions [57, 83-95,153-179, 180-210]. All of these conditions are likely to have a catastrophic effect on metabolism similar to that caused by asphyxia at birth. Prenatal exposure to alcohol, drugs, and medications might be linked to the increased prevalence of autism. But genetic mutations are unlikely to be increasing at such a high rate.
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21 - Fetal to Postnatal Adaptation
Mercer and Skovgaard (2002) noted that early clamping of the umbilical cord may have been put into practice without adequate evidence of its safety [211]. They further described how clamping of the cord obstructs normal completion of transition from pre- to postnatal life. Most dangerous is the potential reduction of neonatal blood volume from 25 to 40 percent.

Ventilation alone is not sufficient to expand the lungs. Mercer and Skovgaard call attention to the need for adequate blood volume to stimulate erection of capillaries in the alveoli of the lungs, and thus to initiate oxygen transfer to the red blood cells. They point out also that activity of other organs, like the gut, is low during gestation, and capillary erection may also be involved in stimulating function of all body organs.

In the fetal state 40 percent of the cardiac output is to the placenta to obtain oxygen from the mother. Transition to postnatal life depends upon utilization of blood from the placental circuit to activate all organs for extra-uterine survival. In the fetal state the lungs secrete amniotic fluid, and according to Mercer and Skovgaard, "capillary erection may be the natural stimulus for the lung to change both structure and function immediately at birth from an organ of fluid secretion to an organ of gas exchange."

If an infant cries immediately at birth this transition has at least for the most part occurred. But it appears that the child who does not cry right away is the first to have the umbilical cord cut and be taken away for ventilation and other desperate efforts (including artificial blood volume expanders) to initiate breathing! These are the infants who could most benefit from allowing placental circulation to continue.

Mercer and Skovgaard note that, "Since the beginning of mammalian life, young have been born attached to a life-line that supports their transition to extrauterine life." They call attention to two exceptions: (1) human birth in recent times, and (2) attended births of some thoroughbred foals, which included rapid clamping of the umbilical cord, and in which a "convulsive syndrome" often occurred. Normally a mare and foal rest for about half an hour after birth, and the cord is broken only when either the mare or the foal rises.

Pathology found in foals that died of the convulsive syndrome included an absence of aeration of the alveoli. [Top]

22 - Forgotten History
Adequate blood volume is required at birth to stimulate opening of the capillaries within the lungs, gut, and other body organs that are dormant during gestation. But depriving an infant of placental blood at birth also leaves the child anemic. Wilson, Windle, and Alt (1941) investigated clamping of the umbilical cord as the cause of iron deficiency anemia in infancy [212]; they noted that the diet of an infant up to the end of the first year cannot make up for this deficiency. Infant anemia has since been found correlated with early childhood learning disorders [213-214].

It appears that during the 1930s use of anesthesia in childbirth and sluggish respiratory efforts of the newborn led to development of protocols for resuscitation, which included early clamping of the cord. The children described by Kanner in 1943 were all born during the 1930s, and at least two by cesarean. Anesthesia was first used in 1846, but obstetric textbooks through the 1930s still encouraged allowing the umbilical cord to cease pulsation before cutting it [58-65]. The teaching of older texts should be heeded, at least that the umbilical cord be left intact until the newborn infant is breathing on its own. How shocking that what was so clearly understood in the past has been disregarded and totally forgotten.


William Windle
Figure 15: William Windle (1898-1985)

The research of Windle and Myers is also already part of forgotten history. Subjecting monkeys to experimental asphyxia may never again be possible. Animal activists would object, insisting the results should be obvious. But the obvious did not happen: Damage of the cerebral cortex and ensuing cerebral palsy were not produced by asphyxia at birth, and damage in the inferior colliculi was almost overlooked.

To neglect the finding of auditory system damage caused by total asphyxia (or cortical damage caused by partial oxygen insufficiency) is to overlook the obvious. Maybe professional experts should heed what animal activists claim is already known. Genetics, toxic environment, maternal stress during pregnancy, and more are all under consideration as causes of autism. At the same time complications at birth are dismissed as mild rather than severe [88] or nonspecific [86], and without any unifying feature [91].

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But the unifying feature of mild and nonspecific complications is the likelihood of lapses in oxygen delivery during the transition from placental to pulmonary respiration. In the hierarchy of human needs nothing is more essential and of immediate urgency [215].

Interference with respiration at birth should be thoroughly re-investigated and "ruled out" before any more esoteric causes of autism are entertained. The research of Windle and Myers still provides evidence that complications at birth can have serious consequences, and their findings merit continuing consideration in the search for understanding and preventing developmental disabilities.

23 - Worth Remembering
The following quotes from Windle (1969) are points worth remembering:

  • "In any delivery it is important to keep the umbilical cord intact until the placenta has been delivered.

    To clamp the cord immediately is equivalent to subjecting the infant to a massive hemorrhage, because almost a fourth of the fetal blood is in the placental circuit at birth."

  • "Spontaneous neurological deficits are practically unknown among rhesus monkeys born in their natural habitat…

    The female squats and drops the infant on the ground. During delivery most of the blood in the placenta passes to the infant."

  • "It is no longer acceptable to assume that the human fetus or newborn infant is so resistant to oxygen deficiency that it will escape harm from a short exposure to asphyxia neonatorum.

    If the infant's brain can be compared to the monkey's, asphyxia of such duration that resuscitation was required will certainly have damaged it."

  • "The briefly asphyxiated infant monkeys with minimal brain damage lost their signs of neurological deficit… The extent of this 'recovery' was surprising.

    The residual deficits of the surviving animals are now inadequate manual dexterity…"

  • "It is commonly recognized that improvement can be expected after a distressful birth…

    We know that the brain of a 'recovered' monkey is structurally damaged, whereas we only assume on clinical grounds that the brain of a 'recovered' human infant is normal."
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24 – Hemoglobin
Respiratory gas exchange is a biochemical process mediated by the hemoglobin molecule within red blood cells. The binding and release of oxygen from hemoglobin provides an explanation for why hypoxia is so different from the effect of asphyxia. The quickest adjustment to an environment of oxygen insufficiency is that provided by the action of hemoglobin in delivering oxygen first to tissues producing the most carbon dioxide.

Myers (1972) demonstrated that while the inferior colliculi are predictably and selectively damaged by a few minutes of total oxygen deprivation at birth, they are spared during a period of prolonged partial oxygen insufficiency. It takes a catastrophic and complete obstruction of aerobic metabolism for involvement of the inferior colliculus to take place. But this can happen to an infant born not breathing if the umbilical cord is cut before respiration can be established.


Some textbooks of biochemistry attach a name to the mechanism of oxygen in exchange for carbon dioxide, the "Bohr effect" [216-217]. Binding of oxygen at different pressures of carbon dioxide was determined in experiments done by Christian Bohr and co-workers a hundred years ago [31].

Christian Bohr was the father of the Nobel Prize winning physicist, Nils Bohr; but his derivation of the mechanism of oxygen binding by hemoglobin remains as important as the contribution by his famous son to the understanding of atomic structure. The paper by Schaffarzik and Spies (1996) pays tribute to Christian Bohr as a forgotten trailblazer of respiratory physiology [35].

Even Myers (1972) spoke of "oxygen dissolved in blood," (p 250), but only cells of primitive organisms can make use of oxygen by simple absorption from environmental fluids.


Christian Bohr
Figure 16: Christian Bohr (1855-1911)

Survival of multi-cellular organisms depended upon evolution of a more efficient means for exchange of respiratory gases. As White et al (1969) commented, the active metabolism of mammalian tissues remote from the atmosphere is possible only because, "Through the action of hemoglobin, oxygen is abstracted from the air, carried within a few seconds to the most distant parts of the body, and delivered to the tissues at a pressure only slightly less than that at which it existed in the atmosphere" [216].

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25 – Infant Anemia
Windle warned that clamping the umbilical cord immediately after birth is equivalent to subjecting an infant to a massive hemorrhage. In 1941 a group of researchers including Windle reported iron deficiency anemia (low hemoglobin levels) in infants at 8 to 10 months of age whose umbilical cords had been clamped immediately at birth [212]. Hemoglobin is the iron-containing molecule of red blood cells; a deficiency of iron implies a deficiency of hemoglobin upon which oxygen delivery depends.

Deficient hemoglobin is equivalent to a hypoxic environment; less oxygen will be available for growth and development of the brain and other organs. Anemia in infancy is a state of chronic partial hypoxia, the effects of which can be compared to those produced by Myers (1972) on partial obstruction of umbilical blood flow.

Perhaps some of the on-going degeneration within the brains of monkeys asphyxiated at birth was due to anemia resulting from the way asphyxia was imposed – by clamping the umbilical cord. The residual inadequate manual dexterity of monkeys asphyxiated by umbilical cord clamping at birth could as well be the result of involvement of motor areas of the brain from postnatal anemia as from brainstem damage.

The paper by Saigal and Usher (1977) appears to have initiated the fear that delayed clamping of the umbilical cord could result in polycythemia (too many red blood cells) and jaundice [47]. But polycythemia is a physiological response to abnormalities like methemoglobinemia, which results from a genetic or drug-induced abnormality of the hemoglobin molecule [217, 218-220]. It may be time to question the opinions of modern authorities and look back again at some forgotten history.

Jellett (1910) in his Manual of Midwifery discussed the issue of polycythemia after stating, "The old dispute as to when the cord should be tied possesses now little more than an academic interest, as it is conclusively settled that this should not be done until all pulsations in the cord have ceased" [221].

Jellett cited research known at that time (but long since forgotten). White (1785) had written about the absurdity of supposing that it was possible for the change from placental to pulmonary circulation, with all that this implies, to take place in a moment, "that this wonderful alteration in the human machine should be brought about in one instant of time, and at the will of a bystander?" [222].

Jellett further cited research by Schmidt (1894) in which he found that 72 percent of children in whom immediate ligation of the cord was done were jaundiced, while only 42 percent were jaundiced when the cord was not tied until ten minutes after birth. It may be time to consider whether postnatal anemia isn't a greater risk for more infants than polycythemia and jaundice [223].

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26 – Autism in Twins
Autism is not 100 percent concordant in identical twins. The finding of even one pair of identical twins who are discordant for any disorder provides the counterexample that disproves a simple genetic etiology.

Folstein and Rutter (1977) investigated cases of autism occurring in twins [224]. Eleven pairs were identical (monozygotic), and ten fraternal (dizygotic). Concordance for autism was found in 4 of the 11pairs of monozygotic twins (36 percent) and no concordance was found in the dizygotic pairs. Thus of 21 twin pairs, 17 were discordant for autism; and in 12 of these autism was associated with an event likely to cause brain damage. Case reports are provided and worth reviewing:

  • Of the identical twin pairs concordant for autism, all four are male and complications of pregnancy were noted in each case. For example, the mother of one pair went into labor of 24 hours duration six weeks early, and each twin was a breech birth. Another mother of a concordant pair had labor induced at 39 weeks gestation because of pre-eclamptic toxemia; the second twin was born 30 minutes after the first due to uterine inertia. He suffered fetal distress, and did not breathe until 7 minutes after birth; autism and cognitive disability were more severe in this second-born twin than in his brother. The differences are more striking than the similarities in each of the four twin pairs deemed concordant for autism.
  • Three of the five identical twins discordant for autism were female. One of the female twins who became autistic was a breech birth with delayed breathing; her umbilical cord was described as very narrow and white. One of the male twins with autism also had a cleft palate, which suggests prenatal exposure to alcohol or other drugs.
  • Of the non-identical twin pairs, three of the mothers were Rh-negative. The three twin pairs of these mothers were all male. The only twins concordant for cognitive disorder were born to one of these mothers; she did not have Rh-factor antibodies but bilirubin rose to 10 mg in the neonatal period of the twin who became autistic. Exchange transfusions were performed in both twins of one Rh-negative mother. Of the third Rh-negative mother, only the twin who later became autistic had an exchange transfusion at birth.

It is difficult not to question the role of perinatal compromise in all of the cases described by Folstein and Rutter. The most obvious genetic predisposition is the occurrence of Rh-negative blood type in three of the mothers.
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Norman (1982) noted that perinatal hazards are increased for twins and suggested that therefore twins are an imperfect model for genetic versus environmental studies of things like intelligence [225]. That concordance is higher in identical than fraternal twins reflects factors such as the limited capacity of a shared placenta to withstand environmental hazards like anoxia or prenatal infections. Davis et al. (1995) found that twins who both develop schizophrenia were more likely to have shared a single placenta and chorionic sack in utero [226]. Autism becomes evident years earlier than schizophrenic disorders and is therefore even more likely related to prenatal environment, and autism may yet prove to be part of the schizophrenia spectrum

Ritvo et al. (1985) reported concordance for autism in 22 of 23 identical twin pairs (95.7 percent) and in 4 of 17 fraternal twin pairs (23.5 percent) [227]. The discordant identical twins were male, age 8, with a normal sister, one year younger. Of the 22 pairs of identical twins concordant for autism, 5 were female, comparable to the 4:1 ratio of males to females reported for autism occurring in the general population.

In the study of Ritvo et al., concordance for autism among the 17 pairs of fraternal twins was high, occurring in 4 pairs. Of the 13 pairs of fraternal twins discordant for autism, 5 were male-female twins and the autistic twin was male in 2 pairs. Both of the male-female twin pairs, in which the male was autistic, had male siblings who were autistic. Of the 8 same-sex twin pairs discordant for autism, only one was female.

Steffenburg et al. (1989) investigated occurrence of autism in same-sexed twins under the age of 25 [85]. They found 21 twin pairs, 11 monozygotic (including one set of identical triplets) and 10 dizygotic. Concordance for autism was 91 percent in the monozygotic pairs. Concordance for autism was not found in the dizygotic pairs, but concordance for cognitive disorder was 30 percent. In the twin pairs discordant for autism, autism was associated with greater perinatal stress. Steffenburg et al. concluded that autism sometimes has a hereditary component, and that perinatal stress is involved in some cases. Case reports were not provided.

Greenberg et al (2001) noted a higher concordance of autism in fraternal twins than would be expected in the general population, and this indicates environmental influences are more significant than genetic factors [93]. If environmental factors were not involved, the concordance rate for fraternal twins should not be greater than between single-born siblings in families in which autism has occurred more than once.

Autism has been found as a complication of phenylketonuria, and other genetic disorders. But some of the medical conditions associated with autism may have been mistakenly thought of as genetic. For example Migeon et al. (1995) and Subramaniam et al. (1997) described a pair of identical twin girls in which one had Rett syndrome but the other was developing normally still at the age of six [228, 229]; and Feekery et al. (1993) reported Landau-Kleffner syndrome in one but not the other of identical twins [230].

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27 – Male-Female Differences
In my own dissertation research, I with my advisor, Ladislav Volicer, investigated the long-term effects of neonatal asphyxia in laboratory rats. The major findings of this research have been published (Simon and Volicer 1976) [231].

Newborn rat pups were subjected to asphyxia by suffocation in small air-tight vials until gasping efforts ceased (45 minutes to two hours). Pups were pale and flaccid when removed from the vials; they were resuscitated using a slow stream of air to the nose and mouth and massaging the chest. Only about half of the experimental animals survived and they were lethargic during the first 24 hours following resuscitation. Most did not gain the normal amount of weight and many lost weight during the first 24 hours; animals with weight loss exceeding 0.5 to 1.0 grams or that appeared jaundiced (with yellow discoloration of the skin) often died during the first two days. Control animals gained about one gram during the first 24 hours after birth.


Male/Female weight-gain differences
Figure 17: Weight differences between control and asphyxiated male (solid line) and female (broken line) pairs during the first week after neonatal suffocation
(from Simon and Volicer 1976).

No focal lesions or visible disruption of neural pathways in the brain could be detected, although development of some reflexes was delayed. Increased synthesis of norepinephrine in the brain was found at 5 to 6 weeks of age in rats subjected to neonatal suffocation; alteration in serotonin synthesis was found in male rats only. Monoamine metabolism was just coming to the forefront during the 1970s, which is why I investigated the effect of asphyxia on these systems.

Perhaps more important, as it turns out, was the startling discovery of growth retardation that was significant for male animals only. The initial failure of weight gain may have resulted from lethargy and lack of initiative to suckle and seek nourishment.


But growth retardation persisted for the first two weeks of life, most noticeably in male rats. Figure 17 is a graph showing differences in weight between pairs of male and pairs of female animals. Brain growth was also retarded in the asphyxiated rats, and to the same degree in both males and females.
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We thought that vulnerability to asphyxia might be related to the metabolic requirements of the animal and that this might be related to birth weight and sex. Male animals were significantly heavier at birth (just over 7 grams) than females (just under 7 grams), with standard deviation 0.07 grams. Metabolism would appear to be higher in males than females. Research evidence is not abundant on this subject, but it is common knowledge that males (on average) have greater muscle mass than females and have greater muscular strength. Almost all competitive athletic events have male and female categories, or female champions and record-setters would be few and far between if at all.


Males were more prone to growth retardation than females as a consequence of asphyxia at birth. According to the Diagnostic and Statistical Manual of the American Psychiatric Association (DSM-IV) many developmental disabilities are found more frequently in males than females [232]. Perhaps oxygen insufficiency resulting from perinatal complications should be investigated as the possible cause of other developmental problems.

Metabolism is higher in males than females. Research evidence is not abundant on this subject, but it is common knowledge that males (on average) have greater muscle mass than females and have greater muscular strength. Almost all competitive athletic events have male and female categories, or female champions and record-setters would be few and far between.

Greater metabolic needs imply greater requirement for intact aerobic activity. Thus males are likely to be more vulnerable in situations in which compromise of oxygen delivery is involved.


Conrad in the lab with mom
Figure 18: Conrad in the lab with mom and newborn rat pups.

Growth retardation of male laboratory rats indicates they were more severely affected by asphyxia. The inferior colliculi and other brainstem nuclei are likely affected sooner in males than females; thus impairment should occur with a shorter period of asphyxia.

Again, before complex hypotheses are investigated in search for the brain disorder in autism, the most basic requirement for aerobic organisms deserves thorough study. Damage of the auditory system by asphyxia at birth is worth further research as cause of developmental language disorder.
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VI. REFERENCES

34 - Bibliography

Asphyxia and Hypoxia at Birth
  1. Windle, W. F. (1969). Brain damage by asphyxia at birth. Scientific American, 221(#4), 76-84.
  2. Myers RE (1972) Two patterns of perinatal brain damage and their conditions of occurrence. American Journal of Obstetrics and Gynecology 112:246-276.
    Back to: Increased incidence, Worth remembering, Hemoglobin, [Top]

    Cerebral Blood Flow
  3. Landau WM, Freygang WH, Rowland LP, Sokoloff L, Kety SS (1955) The local circulation of the living brain; values in the unanesthetized and anesthetized cat. Transactions of the American Neurological Association 80:125-129.
  4. Kety SS (1962) Regional neurochemistry and its application to brain function. In French, JD, ed, Frontiers in Brain Research. New York: Columbia University Press, pp 97-120.
  5. Reivich M, Jehle J, Sokoloff L, Kety SS (1969) Measurement of regional cerebral blood flow with antipyrine-14C in awake cats. Journal Of Applied Physiology 27:296-300.
  6. Sakurada O, Kennedy C, Jehle J, Brown JD, Carbin GL, Sokoloff L (1978) Measurement of local cerebral blood flow with iodo-14-C-antipyrine. American Journal of Physiology, 234, H59-H66.

    Measures of Aerobic Metabolism (Deoxyglucose Uptake)
  7. Sokoloff L, Reivich M, Kennedy C, Des Rosiers MH, Patlak CS, Pettigrew KD, Sakurada O, Shinohara M (1977) The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. Journal of Neurochemistry 28:897-916.
  8. Reivich M, Kuhl D, Wolf A, Greenberg J, Phelps M, Ido T, Casella V, Fowler J, Gallagher B, Hoffman E, Alavi A, Sokoloff L (1977) Measurement of local cerebral glucose metabolism in man with 18F-2-fluoro-2-deoxy-d-glucose. Acta Neurologica Scandinavica. Supplementum 64:190-1

    Correlates of High Deoxyglucose Uptake
  9. Gross PM, Sposito NM, Pettersen SE, Panton DG, Fenstermacher JD. Topography of capillary density, glucose metabolism, and microvascular function within the rat inferior colliculus. J Cereb Blood Flow Metab. 1987 Apr;7(2):154-60.
  10. Rahner-Welsch S, Vogel J, Kuschinsky, W (1995) Regional congruence and divergence of glucose transporters (GLUT1) and capillaries in rat brains. Journal of Cerebral Blood Flow and Metabolism 15:681-686.
  11. Zeller K, Rahner-Welsch S, Kuschinsky W (1997) Distribution of Glut1 glucose transporters in different brain structures compared to glucose utilization and capillary density of adult rat brains. Journal of Cerebral Blood Flow and Metabolism 17:204-209.
  12. Calingasan NY, Baker H, Sheu KF, Gibson GE (1994) Distribution of the alpha-ketoglutarate dehydrogenase complex in rat brain. Journal Of Comparative Neurology 346:461-479.

  13. Hovda DA, Chugani HT, Villablanca JR, Badie B, Sutton RL (1992) Maturation of cerebral oxidative metabolism in the cat: a cytochrome oxidase histochemistry study. Journal of Cerebral Blood Flow and Metabolism 12:1039-1048
  14. Gonzalez-Lima F, Valla J, Matos-Collazo S (1997) Quantitative cytochemistry of cytochrome oxidase and cellular morphometry of the human inferior colliculus in control and Alzheimer's patients. Brain Research 752:117-126.

    Research on Blood Flow and Glucose Uptake
  15. Sokoloff L (1981) Localization of functional activity in the central nervous system by measurement of glucose utilization with radioactive deoxyglucose. Journal of Cerebral Blood Flow and Metabolism 1:7-36.
  16. Hakim AM and Pappius HM (1981) The effect of thiamine deficiency on local cerebral glucose utilization. Annals of Neurology 9:334-339.
  17. Vingan RD, Dow-Edwards ML, Riley EP (1986) Cerebral metabolic alterations in rats following prenatal alcohol exposure: a deoxyglucose study. Alcoholism, Clinical and Experimental Research 10:22-26.
  18. Bertoni JM and Sprenkle PM (1989) Lead acutely reduces glucose utilization in the rat brain especially in higher auditory centers. Neurotoxicology 9:235-242.

  19. Nehlig A, Pereira de Vasconcelos A, Boyet S (1989) Postnatal changes in local cerebral blood flow measured by the quantitative autoradiographic [14C]iodoantipyrine technique in freely moving rats. Journal of Cerebral Blood Flow and Metabolism 9:579-588.
  20. Dow-Edwards DL, Freed LA, Fico TA (1990) Structural and functional effects of prenatal cocaine exposure in adult rat brain. Brain Research Developmental Brain Research 57:263-268.
  21. Kusumoto, M., Arai, H., Mori, K., & Sato, K. (1995). Resistance to cerebral ischemia in developing gerbils. Journal of Cerebral Blood Flow and Metabolism, 15, 886-891.

  22. Chugani HT, Hovda DA, Villablanca JR, Phelps ME, Xu, W-F (1991) Metabolic maturation of the brain: a study of local cerebral glucose utilization in the developing cat. Journal of Cerebral Blood Flow and Metabolism 11:35-47.
  23. Burchfield DJ, Abrams RM (1993). Cocaine depresses cerebral glucose utilization in fetal sheep. Developmental Brain Research 73:283-288.
  24. Grünwald F, Schröck H, Biersack HJ, Kuschinsky W (1993) Changes in local cerebral glucose utilization in the awake rat during acute and chronic administration of ethanol. Journal of Nuclear Medicine 34:793-798.

  25. Antonelli PJ, Gerhardt KJ, Abrams RM, Huang X. Fetal central auditory system metabolic response to cochlear implant stimulation. Otolaryngol Head Neck Surg. 2002 Sep;127(3):131-7.

    Early Research of Windle and Coworkers
  26. Ranck JB, Windle WF (1959). Brain damage in the monkey, Macaca mulatta, by asphyxia neonatorum. Experimental Neurology 1: 130-154.
  27. Jacobson HN & Windle WF (1960) Responses of foetal and new-born monkeys to asphyxia. The Journal of Physiology (London) 153:447-456.

    Circulatory Arrest in Adult Monkeyts
  28. Miller JR, Myers RE (1970) Neurological effects of systemic circulatory arrest in the monkey. Neurology 20:715-724.
  29. Miller JR, Myers RE (1972) Neuropathology of systemic circulatory arrest in adult monkeys. Neurology 22:888-904.

    Developmental Degeneration Following Asphyxia
  30. Faro MD & Windle WF (1969) Transneuronal degeneration in brains of monkeys asphyxiated at birth. Experimental Neurology 24:38-53.
    Back to: Increased Incidence, [Top]

    Biochemistry of Respiration
  31. Bohr C, Hasselbalch K, Krogh A (1904) Ueber einen in biologischer Beziehung wichtigen Einfluss, den die Kohlensaurespannung des Blutes auf dessen Sauerstoffbindung ubt. Skandinavishes Archiv fur Physiologie 16:402-412.
  32. Tigerstedt R (1911) Christian Bohr: Ein Nachruf. Skandinavishes Archiv fur Physiologie 25:v-xviii.
  33. Edsall JT (1980) Hemoglobin and the origins of the concept of allosterism. Federation Proceedings 39:226-35
  34. Dickerson RE, Geis I (1983) Hemoglobin: structure, function, evolution, and pathology. Menlo Park, California: Benjamin Cummings.
  35. Schaffartzik W, Spies C (1996) Christian Bohr -- ein vergessener Wegbereiter der Atemphysiologie. Anasthesiologie, Intensivmedizin, Notfallmedizin, Schmerztherapie 31:239-243
  36. Simon N (1998) Hemoglobin and the brain: a piece of the autism puzzle? Journal of Autism and Developmental Disorders 28:579-80.
    Back to: Hemoglobin, [Top]

    Brainstem Lesions in Human Infants
  37. Norman MG (1972) Antenatal neuronal loss and gliosis of the reticular formation, thalamus, and hypothalamus. A report of three cases. Neurology (Minneapolis) 22:910-916.
  38. Griffiths AD, Laurence KM (1974) The effect of hypoxia and hypoglycemia on the brain of the newborn human infant. Developmental Medicine and Child Neurology 16:308-319.
  39. Grunnet ML, Curless RG, Bray PF, Jung AL (1974) Brain changes in newborns from an intensive care unit. Developmental Medicine and Child Neurology 16:320-328.
  40. Schneider H, Ballowitz L, Schachinger H, Hanefield F, Droeszus J-U (1975) Anoxic encephalopathy with predominant involvement of basal ganglia, brain stem, and spinal cord in the perinatal period. Acta Neuropathologica (Berlin) 32:287-298.
  41. Leech RW, Alvord EC (1977) Anoxic-ischemic encephalopathy in the human neonatal period, the significance of brain stem involvement. Archives of Neurology 34:109-113.
  42. Roland EH, Hill A, Norman MG, Flodmark O, MacNab AJ (1988) Selective brainstem injury in an asphyxiated newborn. Annals of Neurology 23:89-92.
  43. Natsume J, Watanabe K, Kuno K, Hayakawa F, Hashizume Y (1995) Clinical, neurophysiologic, and neuropathological features of an infant with brain damage of total asphyxia type (Myers). Pediatric Neurology 13:61-64.

    Minimal Cerebral Dysfunction?
  44. Windle WF (1969) Asphyxial brain damage at birth, with reference to the minimally affected child. In Perinatal Factors Affecting Humn Development. Pan American Health Organization, proc. spec. session, 8th meeting, pp. 215-221
  45. Sechzer JA, Faro MD, Barker JN, Barsky D, Gutierrez S, Windle WF. Development behaviors: delayed appearance in monkeys asphyxiated at birth. Science. 1971 Mar 19;171(976):1173-5.
  46. Sechzer JA, Faro MD, Windle WF. Studies of monkeys asphyxiated at birth: implications for minimal cerebral dysfunction. Semin Psychiatry. 1973 Feb;5(1):19-34.

    Umbilical Cord Clamping
  47. Saigal S, Usher RH. Symptomatic neonatal plethora. Biol Neonate. 1977;32(1-2):62-72.
  48. American College of Obstetricians and Gynecologists Obstetric Practice Committee (1994) Utility of umbilical cord blood acid-base assessment. ACOG Committee Opinion: Committee on Obstetric Practice. Number 138--April 1994. International Journal of Gynaecology and Obstetrics 45:303-304.
  49. Wardrop CA, Holland BM. The roles and vital importance of placental blood to the newborn infant. J Perinat Med. 1995;23(1-2):139-43.
  50. Morley GM (1998) Cord Closure: Can Hasty Clamping Injure the Newborn? OBG MANAGEMENT July 1998; 29-36.
  51. Papagno L. Umbilical cord clamping. An analysis of a usual neonatological conduct. Acta Physiol Pharmacol Ther Latinoam. 1998;48(4):224-7.
  52. Rabe H, Wacker A, Hulskamp G, Hornig-Franz I, Schulze-Everding A, Harms E, Cirkel U, Louwen F, Witteler R, Schneider HP. A randomised controlled trial of delayed cord clamping in very low birth weight preterm infants. Eur J Pediatr. 2000 Oct;159(10):775-7.
  53. Mercer JS. Current best evidence: a review of the literature on umbilical cord clamping. J Midwifery Womens Health. 2001 Nov-Dec;46(6):402-14.
    Back to: Infant anemia, [Top]

    Bilirubin Only Gets into Oxygen-Deprived Tissues
  54. Lucey JF, Hibbard E, Behrman RE, Esquival FO, Windle WF (1964) Kernicterus in asphyxiated newborn monkeys. Experimental Neurology 9:43-58.

    Stages of Drowning
  55. Junger S (1998) The Perfect Storm. New York: HarperTorch/ HarperCollins, pp 179-185 (in the chapter: The Zero-Moment Point).

    Low 5-minute Apgar Score
  56. Thorngren-Jerneck K, Herbst A. Low 5-minute Apgar score: a population-based register study of 1 million term births. Obstet Gynecol. 2001 Jul;98(1):65-70.
  57. Hultman CM, Sparen P, Cnattingius S. Perinatal risk factors for infantile autism. Epidemiology. 2002 Jul;13(4):417-23.
    Back to: Increased Incidence, [Top]

    Historical Textbooks on Obstetrics
  58. Swayne JG (1856) Obstetric Aphorisms: For the use of students commencing midwifery practice. London: John Churchill.
  59. Playfair WS (1880) A Treatise on the Science and Practice of Midwifery. Philadelphia: Henry C. Lea, p 283
  60. Lusk WT (1882) The Science and Art of Midwifery. New York: D Appleton and Company, pp 214-215
  61. Williams JW (1917) Obstetrics: A Text-Book for the Use of Students and Practicioners, Fourth Edition. New York & London: D. Appleton and Company, pp 342-343
  62. Williams JD (1930) Obstetrics: A Text-Book for the Use of Students and Practicioners, Sixth Edition. New York: D. Appleton-Century, pp 418-419
  63. Stander HJ (1941) Williams Obstetrics, Eighth Edition. New York, London: D. Appleton-Century company, pp 429-430.
  64. Eastman HJ (1950) Williams Obstetrics, Tenth Edition. New York: Appleton-Century-Crofts , pp 397-398
  65. Cunningham FG, MacDonald PC, Gant NF, Leveno KJ, Gilstrap LC, Hankins GDV, Clark SL, Williams JW, (1997) Williams Obstetrics, Twentieth Edition. Stamford, Conn: Appleton & Lange, pp 336-337.
    Back to: Forgotten History, [Top]

    Sound Localization
  66. Rose JE, Gross NB, Geisler CD, Hind JE (1966) Some neural mechanisms in the inferior colliculus of the cat which may be relevant to localization of a sound source. Journal of Neurophysiology 29:288-314.
  67. Brainard MS (1994) Neural substrates of sound localization. Current Opinion In Neurobiology 4:557-562
  68. Litovsky RY, Delgutte B. Neural correlates of the precedence effect in the inferior colliculus: effect of localization cues. J Neurophysiol. 2002 Feb;87(2):976-94.

    Large Handwriting (Macrographia)
  69. Beversdorf DQ et al. (2001) Macrographia in high functioning autism. Journal of Autism and Developmental Disorders 31:97-101.

    Neurotrophic Influences on Maturation
  70. VonHungen K, Roberts S, Hill DF (1974) Developmental and regional variations in neurotransmitter-sensitive adenylate cyclase systems in cell-free preparations from rat brain. Journal of Neurochemistry 22:811-819.
  71. Kungel M and Friauf E (1995). Somatostatin and leu-enkephalin in the rat auditory brainstem during fetal and postnatal development. Anatomy and Embryology, 191, 425-443.

    Brain Abnormalities in Autism
  72. Williams RS, Hauser S, Purpura DP, deLong GR, Swisher CN (1980) Autism and mental retardation: Neuropathologic studies performed in four retarded persons with autistic behavior. Archives of Neurology 37:748-753.
  73. Ritvo ER, Freeman BJ, Scheibel AB, Duong T, Robinson H, Guthrie D, Ritvo A (1986) Lower Purkinje cell counts in the cerebella of four autistic subjects: initial findings of the UCLA-NSAC Autopsy Research Report. American Journal of Psychiatry 143:862-6
  74. Jacobson R, LeCouteur A, Howlin P, Rutter M (1988) Selective subcortical abnormalities in autism. Psychological Medicine 18:39-48.
  75. Gaffney GR, Kuperman S, Tsai LY, Minchin S (1988) Morphological evidence for brainstem involvement in infantile autism. Biological Psychiatry 24:578-586.
  76. Egaas B, Courchesne E, Saitoh O (1995) Reduced size of corpus callosum in autism. Archives of Neurology 52:794-801.
  77. Courchesne E, Yeung-Courchesne R, Press GA, Hesselink JR, Jernigan TL (1988) Hypoplasia of cerebellar vermal lobules VI and VII in autism. New England Journal of Medicine 318:1349-1354.
  78. Hashimoto T, Tayama M, Murakawa K, Yoshimoto T, Miyazaki M, Harada M, Kuroda Y (1995) Development of the brainstem and cerebellum in autistic patients. Journal of Autism and Developmental Disorders 25:1-18.
  79. Rodier PM, Ingram JL, Tisdale B, Nelson S, Romano J (1996) Embryological origin for autism: developmental anomalies of the cranial nerve motor nuclei. Journal of Comparative Neurology 370:247-261.
  80. Piven J, Bailey J, Ranson BJ, Arndt S (1997) An MRI study of the corpus callosum in autism. American Journal of Psychiatry 154:1051-1056
  81. Kemper TL, Bauman M (1998). Neuropathology of infantile autism. Journal of Neuropathology and Experimental Neurology 57:645-652 .
  82. Bailey A, Luthert P, Dean A, Harding B, Janota I, Montgomery M, Rutter M, Lantos P (1998) A clinicopathological study of autism. Brain 121:889-905.

    Autism and Complications at Birth
  83. Lobascher ME, Kingerlee PE, Gubbay SS. Childhood autism: an investigation of aetiological factors in twenty-five cases. Br J Psychiatry. 1970;117:525-529.
  84. Finegan J-A, Quarrington B. Pre-, peri- and neonatal factors and infantile autism. J Child Psychol Psychiatry. 1979;20:119-128
  85. Steffenburg S, Gillberg C, Hellgren L, Andersson L, Gillberg IC, Jakobsson G, Bohman M. A twin study of autism in Denmark, Finland, Iceland, Norway and Sweden. J Child Psychol Psychiatry. 1989 May;30(3):405-16.
    Back to: Increased Incidence of Autism, Forgotten History, Autism in twins, [Top]

  86. Lord C, Mulloy C, Wendelboe M, Schopler E. Pre- and perinatal factors in high-functioning females and males with autism. J Autism Dev Disord. 1991 Jun;21(2):197-209.
  87. Ghaziuddin M, Shakal J, Tsai L. Obstetric factors in Asperger syndrome: comparison with high-functioning autism. J Intellect Disabil Res. 1995 Dec;39 ( Pt 6):538-43.
  88. Bolton PF, Murphy M, Macdonald H, Whitlock B, Pickles A, Rutter M. Obstetric complications in autism: consequences or causes of the condition? J Am Acad Child Adolesc Psychiatry. 1997 Feb;36(2):272-81
  89. Burd L, Severud R, Kerbeshian J, Klug MG. Prenatal and perinatal risk factors for autism. J Perinat Med. 1999;27(6):441-50.
  90. Matsuishi T, Yamashita Y, Ohtani Y, Ornitz E, Kuriya N, Murakami Y, Fukuda S, Hashimoto T, Yamashita F. Brief report: incidence of and risk factors for autistic disorder in neonatal intensive care unit survivors. J Autism Dev Disord. 1999 Apr;29(2):161-6
  91. Juul-Dam N, Townsend J, Courchesne E. Prenatal, perinatal, and neonatal factors in autism, pervasive developmental disorder-not otherwise specified, and the general population. Pediatrics. 2001 Apr;107(4):E63.
  92. Bodier C, Lenoir P, Malvy J, Barthélemy C, Wiss M, Sauvage D. (2001) Autisme et pathologies associées. Étude clinique de 295 cas de troubles envahissants du developpment. [Autism and associated pathologies. Clinical study of 295 cases involving development disorders] Presse Médicale 2001 Sep 1; 30(24 Pt 1):1199-203. French.
  93. Greenberg DA, Hodge SE, Sowinski J, Nicoll D. Excess of twins among affected sibling pairs with autism: implications for the etiology of autism. Am J Hum Genet 2001 Nov;69(5):1062-7
    Back to: Increased Incidence of Autism, Forgotten History, Autism in twins, [Top]

  94. Zwaigenbaum L, Szatmari P, Jones MB, Bryson SE, MacLean JE, Mahoney WJ, Bartolucci G, Tuff L. Pregnancy and birth complications in autism and liability to the broader autism phenotype. J Am Acad Child Adolesc Psychiatry 2002 May;41(5):572-9
  95. Wilkerson DS, Volpe AG, Dean RS, Titus JB. Perinatal complications as predictors of infantile autism. Int J Neurosci. 2002 Sep;112(9):1085-98.
    Back to: Increased Incidence of Autism, Forgotten History, [Top]

    Cephalhematoma
  96. Towbin A (1970) Neonatal damage of the central nervous system. In Tedeschi CG (ed) Neuropathology: Methods and Diagnosis. Boston, Little, Brown & Co., pp 609-653.

    Controversy Over Mercury Preservatives in Vaccinge
  97. Bernard S, Enayati A, Roger H, Binstock T, Redwood L. The role of mercury in the pathogenesis of autism. Mol Psychiatry. 2002;7 Suppl 2:S42-3.
  98. Blaxill MF. Any changes in prevalence of autism must be determined. BMJ. 2002 Feb 2;324(7332):296.
  99. Borchers AT, Keen CL, Shoenfeld Y, Silva J Jr, Gershwin ME. Vaccines, viruses, and voodoo. J Investig Allergol Clin Immunol. 2002;12(3):155-68.
  100. Kimmel SR. Vaccine adverse events: separating myth from reality. Am Fam Physician. 2002 Dec 1;66(11):2113-20.
  101. Wakefield AJ. Measles, mumps, and rubella vaccination and autism. N Engl J Med. 2003 Mar 6;348(10):951-4; author reply 951-4.

    Mercury Damages the Auditory System
  102. Oyanagi K, Ohama E, & Ikuta F. (1989). The auditory system in methyl mercurial intoxication: a neuropathological investigation on 14 autopsy cases in Niigata, Japan. Acta Neuropathologica (Berlin), 77, 561-568.

    Fluoro-deoxyglucose Brain Scans
  103. Asano E, Chugani DC, Muzik O, Behen M, Janisse J, Rothermel R, Mangner TJ, Chakraborty PK, Chugani HT. Autism in tuberous sclerosis complex is related to both cortical and subcortical dysfunction. Neurology. 2001 Oct 9;57(7):1269-77.
  104. Haznedar MM, Buchsbaum MS, Wei TC, Hof PR, Cartwright C, Bienstock CA, Hollander E. Limbic circuitry in patients with autism spectrum disorders studied with positron emission tomography and magnetic resonance imaging. Am J Psychiatry. 2000 Dec;157(12):1994-2001.
  105. Schifter T, Hoffman JM, Hatten HP Jr, Hanson MW, Coleman RE, DeLong GR. Neuroimaging in infantile autism. J Child Neurol. 1994 Apr;9(2):155-61.
  106. Siegel BV Jr, Asarnow R, Tanguay P, Call JD, Abel L, Ho A, Lott I, Buchsbaum MS. Regional cerebral glucose metabolism and attention in adults with a history of childhood autism. J Neuropsychiatry Clin Neurosci. 1992 Fall;4(4):406-14.
  107. Heh CW, Smith R, Wu J, Hazlett E, Russell A, Asarnow R, Tanguay P, Buchsbaum MS. Positron emission tomography of the cerebellum in autism. Am J Psychiatry. 1989 Feb;146(2):242-5.
  108. Horwitz B, Rumsey JM, Grady CL, Rapoport SI. The cerebral metabolic landscape in autism. Intercorrelations of regional glucose utilization. Arch Neurol. 1988 Jul;45(7):749-55.
  109. De Volder A, Bol A, Michel C, Congneau M, Goffinet AM. Brain glucose metabolism in children with the autistic syndrome: positron tomography analysis. Brain Dev. 1987;9(6):581-7.
  110. Rumsey JM, Duara R, Grady C, Rapoport JL, Margolin RA, Rapoport SI, Cutler NR. Brain metabolism in autism. Resting cerebral glucose utilization rates as measured with positron emission tomography. Arch Gen Psychiatry. 1985 May;42(5):448-55.

    Cardiac Arrest Encephalopathy
  111. Neubuerger KT (1954) Lesions of the human brain following circulatory arrest. Journal of Neuropathology and Experimental Neurology 13:144-160.
  112. Brierley JB (1961) Some neuropathological contributions to problems of hypoxia. In Gastaut H & Meyer JS, eds. Cerebral Anoxia and the Electroencephalogram. Charles C. Thomas, Springfield, Illinois.
  113. Gilles FH (1963) Selective symmetrical neuronal necrosis of certain brain stem tegmental nuclei in temporary cardiac standstill. Journal of Neuropathology and Experimental Neurology 22:318-318.
  114. Lindenberg R (1963) Patterns of CNS vulnerability in acute hypoxiaemia, including anaesthesia accidents. In Schade JP & McMenemey WH, eds. Selective Vulnerability of the Brain in Hypoxaemia. Blackwell Scientific Publications, Oxford.
  115. Adams JH, Brierley JB, Connor RC, Treip CS. (1966) The effects of systemic hypotension upon the human brain. Clinical and neuropathological observations in 11 cases. Brain 89:235-268.
  116. Gilles FH (1969) Hypotensive brain stem necrosis: selective symmetrical necrosis of tegmental neuronal aggregates following cardiac arrest. Archives of Pathology 88:32-41.
  117. Janzer RC, Friede RL. Hypotensive brain stem necrosis or cardiac arrest encephalopathy? Acta Neuropathol (Berl). 1980;50(1):53-6.

    Importance of the Auditory System
  118. Fisch L (1970) The selective and differential vulnerability of the auditory system. In GEW Wolstenholm and J Knight, (Eds), Sensorineural Hearing Loss: A Ciba Foundation Symposium (pp 101-116). London: Churchill.

    General Awareness and Consciousness
  119. Denny-Brown, D. (1962). The midbrain and motor integration. Proceedings of the Royal Society of Medicine, 55, 527-538.
  120. Jane JA, Masterton RB, Diamond IT (1965) The function of the tectum for attention to auditory stimuli in the cat. Journal of Comparative Neurology 125:165-192.
  121. Sprague JM, Chambers WW, Stellar, E (1961) Attentive, affective, and adaptive behavior in the cat. Science 133:165-173.

    Fast Acting Anesthesia
  122. Roth LJ, Barlow CE (1961) Drugs in the brain. Science 134:22-31.

    Kanner's Original Description
  123. Kanner L (1943) Autistic disturbances of affective contact. Nervous Child 2:217-250.
    Back to: Auditory and Motor Handicaps, [Top]

    Auditory Evoked Potentials
  124. Student M, Sohmer H (1978) Evidence from auditory nerve and brainstem evoked responses for an organic brain lesion in children with autistic traits. Journal of Autism and Childhood Schizophrenia 8:13-20.
  125. Rosenblum SM, Arick JR, Krug DA, Stubbs EG, Young NB, Pelson RO (1980) Auditory brainstem evoked responses in autistic children. Journal of Autism and Developmental Disorders 10:215-225.
  126. Skoff BF, Mirsky AF, Turner D (1980) Prolonged brainstem transmission time in autism. Psychiatry Research 2:157-166.
  127. Taylor MJ, Rosenblatt B, Linschoten L (1982) Auditory brainstem response abnormalities in autistic children. Canadian Journal of Neurological Sciences 9:429-433.
  128. Thivierge J, Bedard C, Cote R, Maziade M. Brainstem auditory evoked response and subcortical abnormalities in autism. Am J Psychiatry. 1990 Dec;147(12):1609-13.
  129. Wong V, Wong SN. Brainstem auditory evoked potential study in children with autistic disorder. J Autism Dev Disord. 1991 Sep;21(3):329-40.
  130. McClelland RJ, Eyre DG, Watson D, Calvert GJ, Sherrard E. Central conduction time in childhood autism. Br J Psychiatry. 1992 May;160:659-63.
  131. Bruneau N, Roux S, Adrien JL, Barthelemy C. Auditory associative cortex dysfunction in children with autism: evidence from late auditory evoked potentials (N1 wave-T complex). Clin Neurophysiol. 1999 Nov;110(11):1927-34.
  132. Seri S, Cerquiglini A, Pisani F, Curatolo P. Autism in tuberous sclerosis: evoked potential evidence for a deficit in auditory sensory processing. Clin Neurophysiol. 1999 Oct;110(10):1825-30.
  133. Maziade M, Merette C, Cayer M, Roy MA, Szatmari P, Cote R, Thivierge J. Prolongation of brainstem auditory-evoked responses in autistic probands and their unaffected relatives. Arch Gen Psychiatry. 2000 Nov;57(11):1077-83.
  134. Rosenhall U, Nordin V, Brantberg K, Gillberg C. Autism and auditory brain stem responses. Ear Hear. 2003 Jun;24(3):206-14.

    Evoked Potentials in Asphyxiated Monkeys
  135. Mirsky AF, Orren MM, Stanton L, Fullerton BC, Harris S, Myers RE (1979) Auditory evoked potentials and auditory behavior following prenatal and perinatal asphyxia in rhesus monkeys. Developmental Psychobiology 12:369-379

    Auditory Tests
  136. Church MW, Eldis F, Blakley BW, Bawle EV (1997) Hearing, language, speech, vestibular, and dentofacial disorders in fetal alcohol syndrome. Alcoholism, Clinical and Experimental Research 21:227-237.

    Inhibitory Transmitters
  137. Faingold CL, Gehlbach G, Caspary DM (1991) Functional pharmacology of inferior colliculus neurons. In R.A. Altschuler et al. Neurobiology of Hearing: The Central Auditory System. New York: Raven Press, pp 223-252 (chapter 10).
  138. Zhang H, Feng AS (1998) Sound direction modifies the inhibitory as well as the excitatory frequency tuning characteristics of single neurons in the frog torus semicircularis (inferior colliculus). Journal of Comparative Physiology. A, Sensory, Neural, and Behavioral Physiology 182:725-735
  139. Caspary DM, Milbrandt JC, Helfert RH (1995) Central auditory aging: GABA changes in the inferior colliculus. Experimental Gerontology 30:349-360.

    Early Myelination and Maturation of the Auditory System
  140. Langworthy OR (1933) Development of behavior patterns and myelinization of the nervous system in the human fetus and infant. Contributions to Embryology, no. 139 24:1-57.
  141. Yakovlev PI and Lecours A-R (1967) The myelogenetic cycles of regional maturation of the brain. In A. Minkowski (Ed.), Regional Development of the Brain in Early Life (pp. 3-70). Oxford: Blackwell Scientific Publications.
  142. Moore JK, Perazzo LM, Braun A (1995). Time course of axonal myelination in the human brainstem auditory pathway. Hearing Research 87:21-31, 91:208-209.

    Stressed Syllables and Learning to Speak
  143. Brown R, Bellugi U (1964) Three processes in the child's acquisition of syntax. Harvard Educational Review 34:133-151.
  144. Brown R (1973) A First Language: The Early Stages. Cambridge, MA: Harvard University Press.
  145. Brown R (1975) A collection of words and sentences, an autistic child. In R Brown RJ Herrnstein, Psychology (pp. 444-449). Boston: Little, Brown and Company.

    Verbal Auditory Agnosia
  146. Rapin I (1997) Autism. New England Journal of Medicine 337:97-104.

    Early Aging of the Auditory System
  147. Uecker A, Gonzalez-Lima F, Cada A, Reiman EM. Behavior and brain uptake of fluorodeoxyglucose in mature and aged C57BL/6 mice. Neurobiol Aging. 2000 Sep-Oct;21(5):705-18.

    Verbal Auditory Agnosia Following Damage of the Inferior Colliculi
  148. Meyer B, Kral T, Zentner J. (1996) Pure word deafness after resection of a tectal plate glioma with preservation of wave V of brain stem auditory evoked potentials. Journal of Neurology, Neurosurgery and Psychiatry. 61:423-424.
  149. Johkura K, Matsumoto S, Hasegawa O, Kuroiwa Y. (1998) Defective auditory recognition after small hemorrhage in the inferior colliculi. Journal of the Neurological Sciences. 161:91-96.
  150. Masuda S, Takeuchi K, Tsuruoka H, Ukai K, Sakakura Y. (2000) Word deafness after resection of a pineal body tumor in the presence of normal wave latencies of the auditory brain stem response. The Annals of otology, rhinology, and laryngology. 2000 Dec;109(12 Pt 1):1107-1112.

    Irrelevant and Metaphorical Language
  151. Kanner L (1946) Irrelevant and metaphorical language of early infantile autism. American Journal of Psychiatry 103:242-246.

    The Inferior Colliculus and Echolalic Speech
  152. Simon N (1975) Echolalic speech in childhood autism, consideration of possible underlying loci of brain damage. Archives of General Psychiatry 32:1439-1446.

    Non-genetic Predispositions for Autism:
    Prenatal Exposure to Drugs
  153. Nanson JL (1992) Autism in fetal alcohol syndrome: a report of six cases. Alcoholism, Clinical and Experimental Research 16:558-565.
  154. Harris SR, MacKay LL, Osborn JA (1995) Autistic behaviors in offspring of mothers abusing alcohol and other drugs: a series of case reports. Alcoholism, Clinical and Experimental Research 19:660-5
  155. Aronson M, Hagberg B, Gillberg C (1997) Attention deficits and autistic spectrum problems in children exposed to alcohol during gestation: a follow-up study. Developmental Medicine and Child Neurology 39:583-7
  156. Church MW, Eldis F, Blakley BW, Bawle EV (1997) Hearing, language, speech, vestibular, and dentofacial disorders in fetal alcohol syndrome. Alcoholism, Clinical and Experimental Research 21:227-237.
  157. Christianson AL, Chesler N, and Kromberg JGR (1994) Fetal valproate syndrome: clinical and neuro-developmental features in two sibling pairs. Developmental Medicine and Child Neurology 36:357-369.
  158. Williams PG & Hersh JH (1997) A male with fetal valproate syndrome and autism. Developmental Medicine and Child Neurology 39:632-634.
  159. Williams G, King J, Cunningham M, Stephan M, Kerr B, Hersh JH. (2001) Fetal valproate syndrome and autism: additional evidence of an association. Developmental Medicine and Child Neurology 43:202-206.
  160. Stromland K, Nordin V, Miller M, Akerstrom B, and Gillberg C (1994) Autism in thalidomide embryopathy: a population study. Developmental Medicine and Child Neurology 36:351-356.
    Back to: Increased Incidence of Autism, [Top]
    Infectious Encephalitis
  161. Desmond MM, Montgomery JR, Melnick JL, Cochran GG, Verniaud W (1969) Congenital rubella encephalitis. Effects on growth and early development. American Journal of Diseases of Children 118:30-31.
  162. Chess S (1971) Autism in children with congenital rubella. Journal of Autism and Childhood Schizophrenia 1:33-47.
  163. Chess S, Fernandez P, Korn S. (1978) Behavioral consequences of congenital rubella. Journal of Pediatrics. 93:699-703.
  164. Townsend JJ et al. (1975) Progressive rubella panencephalistis: Late onset after congenital rubella. New England Journal of Medicine 292:990.
  165. Weil et al. (1975) Chronic progressive panencephalitis due to rubella virus simulating subacute sclerosing panencephalitis. New England Journal of Medicine 292:994
  166. deLong GR, Bean SC, Brown FR (1981) Acquired reversible autistic syndrome in acute encephalopathic illness in children. Archives of Neurology 38:191-194
  167. Gillberg C (1986) Brief report: onset at age 14 of a typical autistic syndrome. A case report of a girl with herpes simplex encephalitis. Journal of Autism and Developmental Disorders 16: 369-375.
  168. Gillberg IC (1991) Autistic syndrome with onset at age 31 years: herpes encephalitis as a possible model for childhood autism. Developmental Medicine and Child Neurology 33:920-4
  169. Ghaziuddin M, Tsai LY, Eilers L, Ghaziuddin N. (1992) Brief report: autism and herpes simplex encephalitis. Journal of Autism and Developmental Disorders. 22:107-13.
  170. Greer MK, Lyons-Crews M, Mauldin LB, Brown FR 3rd. (1989) A case study of the cognitive and behavioral deficits of temporal lobe damage in herpes simplex encephalitis. Journal of Autism and Developmental Disorders 19:317-26.
  171. Domachowske JB, Cunningham CK, Cummings DL, Crosley CJ, Hannan WP, Weiner LB (1996) Acute manifestations and neurologic sequelae of Epstein-Barr virus encephalitis in children. Pediatric Infectious Disease Journal 15:871-5
  172. Thivierge J. (1986) A case of acquired aphasia in a child. Journal of Autism and Developmental Disorders. 16:507-12.
  173. Barak Y, Kimhi R, Stein D, Gutman J, Weizman A (1999) Autistic subjects with comorbid epilepsy: a possible association with viral infections. Child Psychiatry and Human Development 1999 Spring;29(3):245-51
    Back to: Increased Incidence of Autism, [Top]

    Lead Poisoning
  174. Cohen DJ, Johnson WT, Caparulo BK. Pica and elevated blood lead level in autistic and atypical children. Am J Dis Child. 1976 Jan;130(1):47-8
  175. Accardo P, Whitman B, Caul J, Rolfe U. Autism and plumbism. A possible association. Clin Pediatr (Phila). 1988 Jan;27(1):41-4.
  176. Eppright TD, Sanfacon JA, Horwitz EA. Attention deficit hyperactivity disorder, infantile autism, and elevated blood-lead: a possible relationship. Mo Med. 1996 Mar;93(3):136-8.
    Back to: Increased Incidence of Autism, [Top]

    Seizure Disorder/ Neurologic Damage
  177. Chugani HT, Da Silva E, Chugani DC (1996) Infantile spasms: III. Prognostic implications of bitemporal hypometabolism on positron emission tomography. Annals Of Neurology 39:643-649.
  178. daSilva EA, Chugani DC, Muzik O, Chugani HT (1997) Landau-Kleffner syndrome: metabolic abnormalities in temporal lobe are a common feature. Journal of Child Neurology 12:489-495.

    Intestinal Inflammation
  179. Wakefield AJ, Murch SH, Anthony A, Linnell J, Casson DM, Malik M, Berelowitz M, Dhillon AP, Thomson MA, Harvey P, Valentine A, Davies SE, Walker-Smith JA (1998) Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. Lancet Feb 28;351(9103):637-41.
    Back to: Increased Incidence of Autism, [Top]

    Genetic/Metabolic Predispositions for Autism:
    Neurolipidosis
  180. Creak M (1963) Childhood psychosis: A review of 100 cases. British Journal of Psychiatry 109:84-89.
  181. Darby JK (1976) Neuropathologic aspects of psychosis in children. Journal of Autism and Childhood Schizophrenia 6:339-352

    Tuberous Sclerosis
  182. Fisher W, Kerbeshian J, Burd L, Kolstoe P. (1986) Tuberous sclerosis and autism. Developmental Medicine and Child Neurology 28:814-815
  183. Bolton PF, Griffiths PD (1997) Association of tuberous sclerosis of temporal lobes with autism and atypical autism. Lancet 349(9049):392-395
  184. Webb DW, Fryer AE, Osborne JP (1996) Morbidity associated with tuberous sclerosis: a population study. Developmental Medicine and Child Neurology 38:146-55
  185. Griffiths PD, Martland TR (1997) Tuberous Sclerosis Complex: the role of neuroradiology. Neuropediatrics 28:244-52
  186. Crino PB, Henske EP (1999) New developments in the neurobiology of the tuberous sclerosis complex. Neurology 53:1384-90
  187. Bolton PF, Park RJ, Higgins JN, Griffiths PD, Pickles A. (2002) Neuro-epileptic determinants of autism spectrum disorders in tuberous sclerosis complex. Brain 125:1247-1255
    Back to: Increased Incidence of Autism, [Top]

    Neurofibromatosis
  188. Gaffney GR, Kuperman S, Tsai LY, Minchin S. (1989) Forebrain structure in infantile autism. J Am Acad Child Adolesc Psychiatry. 28:534-537.
  189. Gaffney GR, Kuperman S, Tsai LY, Minchin S, Hassanein KM (1987a) Midsagittal magnetic resonance imaging of autism. British Journal of Psychiatry 151:831-3
  190. Gaffney GR, Tsai LY, Kuperman S, Minchin S (1987b) Cerebellar structure in autism. American Journal of Diseases of Children 141:1330-2
  191. Gillberg C, Coleman M (1996). Autism and medical disorders: a review of the literature. Developmental Medicine and Child Neurology 38:191-202.

    Phenyhlketonuria
  192. Lowe TL, Tanaka K, Seashore MR, Young JG, Cohen DJ (1980). Detection of phenylketonuria in autistic and psychotic children. Journal of the American Medical Association 243:126-128.
  193. Williams RS, Hauser S, Purpura DP, deLong GR, Swisher CN (1980) Autism and mental retardation: Neuropathologic studies performed in four retarded persons with autistic behavior. Archives of Neurology 37:748-753.
  194. Chen CH, Hsiao KJ (1989) A Chinese classic phenylketonuria manifested as autism. British Journal of Psychiatry 155:251-3
  195. Miladi N, Larnaout A, Kaabachi N, Helayem M, Ben Hamida M (1992) Phenylketonuria: an underlying etiology of autistic syndrome. A case report. Journal of Child Neurology 7:22-23.
  196. Leuzzi V, Trasimeni G, Gualdi GF, Antonozzi I (1995) Biochemical, clinical and neuroradiological (MRI) correlations in late-detected PKU patients. Journal of Inherited Metabolic Disease 18:624-634.
    Back to: Increased Incidence of Autism, [Top]

    Fragile X Syndrome
  197. Brown WT, Jenkins EC, Friedman E, Brooks J, Wisniewski K, Raguthu S, French J. (1982) Autism is associated with the fragile-X syndrome. Journal of Autism and Developmental Disorders. 12:303-8.
  198. Folstein SE, Rutter ML (1988) Autism: familial aggregation and genetic implications. Journal of Autism and Developmental Disorders. 18:3-30.

    Leber's Congenital Amaurosis
  199. Rogers SJ, Newhart-Larson S (1989) Characteristics of infantile autism in five children with Leber's congenital amaurosis. Developmental Medicine and Child Neurology 31:598-608
  200. Malamud N (1959) Heller's disease and childhood schizophrenia. American Journal of Psychiatry 116:215-218.
    Back to: Increased Incidence of Autism, [Top]

    Adenylosuccinate Lyase Defect
  201. Jaeken J, Van den Berghe G. (1984) An infantile autistic syndrome characterised by the presence of succinylpurines in body fluids. Lancet. Nov 10;2(8411):1058-61.
  202. Jaeken J, Wadman SK, Duran M, van Sprang FJ, Beemer FA, Holl RA, Theunissen PM, de Cock P, van den Bergh F, Vincent MF, et al. (1988) Adenylosuccinase deficiency: an inborn error of purine nucleotide synthesis. European Journal of Pediatrics. 148:126-31.
  203. Barshop BA, Alberts AS, Gruber HE. (1989) Kinetic studies of mutant human adenylosuccinase. Biochimica et Biophysica Acta. 999:19-23.
  204. Van den Berghe G, Vincent MF, Jaeken J. (1997) Inborn errors of the purine nucleotide cycle: adenylosuccinase deficiency. Journal of Inherited Metabolic Disease. 20:193-202.

    Lactic Acidosis
  205. Coleman M, Blass JP (1985) Autism and lactic acidosis. Journal of Autism and Developmental Disorders 15 1-8.
  206. Philippart M (1986) Clinical recognition of Rett syndrome. American Journal of Medical Genetics Supplement 1:111-8
  207. Lombard J (1998) Autism: a mitochondrial disorder? Medical Hypotheses 50:497-500.
    Back to: Increased Incidence of Autism, [Top]

    Krebs Cycle (aerobic metabolism) Defects
  208. Shaw W, Kassen E, Chaves E (1995) Increased urinary excretion of analogs of Krebs cycle metabolites and arabinose in two brothers with autistic features. Clinical Chemistry 41:1094-1194.

    Mitochondrial Disorders
  209. Fillano JJ, Goldenthal MJ, Rhodes CH, Marin-Garcia J (2002) Mitochondrial dysfunction in patients with hypotonia, epilepsy, autism, and developmental delay: HEADD syndrome. J Child Neurol. 2002 Jun;17(6):435-9.
  210. Graf WD, Marin-Garcia J, Gao HG, Pizzo S, Naviaux RK, Markusic D, Barshop BA,Courchesne E, Haas RH (2000) Autism associated with the mitochondrial DNA G8363A transfer RNA(Lys) mutation. J Child Neurol. 2000 Jun;15(6):357-61.
    Back to: Increased Incidence of Autism, [Top]

  211. Fetal to Postnatal Adaptation Mercer JS, Skovgaard RL. Neonatal transitional physiology: a new paradigm. J Perinat Neonatal Nurs. 2002 Mar;15(4):56-75.
    Back to: Fetal to Postnatal Adaptation, [Top]

    Infant Anemia
  212. Wilson EE, Windle WF, Alt HL (1941) Deprivation of placental blood as a cause of iron deficiency in infants. Am. J. Dis. Child. 62:320-327.
  213. Lozoff B, Jimenez E, Wolf AW (1991) Long-term developmental outcome of infants with iron deficiency. New England Journal of Medicine 325:687-694.
  214. Hurtado EK, Claussen AH, Scott KG (1999) Early childhood anemia and mild or moderate mental retardation. American Journal of Clinical Nutrition 69:115-119.
    Back to: Forgotten History, Infant Anemia, [Top]

    Hierarchy of Human Needs
  215. Maslow AH (1970) Motivation and Personality, Second Edition. New York: Harper & Row.
    Back to: Forgotten History, [Top]

    Biochemistry Textbooks
  216. White A, Handler P, Smith EL (1969) Principles of Biochemistry, Fourth Edition. New York: Blakiston Division, McGraw-Hill Book Company, Chapter 32, pp 758-776.
  217. Murray RK, Granner DK, Mayes PA, Rodwell VW (2000) Harper's Biochemistry, twenty-fifth edition. New York: McGraw-Hill Health Professions Division.
    Back to: Hemoglobin, Infant anemia, [Top]

    Polycythemia
  218. Beutler E. Genetic disorders of human red blood cells. JAMA. 1975 Sep 15;233(11):1184-8.
  219. Kohli-Kumar M, Zwerdling T, Rucknagel DL. Hemoglobin F-Cincinnati, alpha 2G gamma 2 41(C7) Phe-->Ser in a newborn with cyanosis. Am J Hematol. 1995 May;49(1):43-7.
  220. Kralovics R, Prchal JT. Congenital and inherited polycythemia. Curr Opin Pediatr. 2000 Feb;12(1):29-34.
  221. Jellett H (1910) A Manual of Midwifery for Students and Practitioners. New York: William Wood & Company.
  222. White (1785) A Treatise on the Management of Pregnant and Lying-in Women, third edition, p 109 et seq. London. (cited by Jellett 1910)
  223. Schmidt (1894) Archiv f Gyn, vol xiv. (cited by Jellett 1910)
    Back to: Infant anemia, [Top]

    Autism in Twins
  224. Folstein S, Rutter M (1977) Infantile autism: a genetic study of 21 twin pairs. Journal of Child Psychology and Psychiatry 30:405-416.
    Back to: Autism In Twins, [Top]

  225. Norman MG (1982) Mechanisms of brain damage in twins. The Canadian journal of neurological sciences 1982 Aug;9(3):339-44
  226. Davis JO, Phelps JA, Bracha HS (1995) Prenatal development of monozygotic twins and concordance for schizophrenia. Schizophrenia Bulletin 21:357-366. Published erratum appears in Schizophrenia Bulletin 21:539.
    Back to: Autism In Twins (increased risk of perinatal hazards in twins), [Top]

  227. Ritvo ER, Freeman BJ, Mason-Brothers A, Mo A, Ritvo AM (1985) Concordance for the syndrome of autism in 40 pairs of afflicted twins. American Journal of Psychiatry 142:74-7
    Back to: Autism In Twins (increased concordance in fraternal twins), [Top]

  228. Migeon BR, Dunn MA, Thomas G, Schmeckpeper BJ, Naidu S (1995) Studies of X inactivation and isodisomy in twins provide further evidence that the X chromosome is not involved in Rett syndrome. American Journal of Human Genetics 56:647-53.
  229. Subramaniam B, Naidu S, Reiss AL (1997) Neuroanatomy in Rett syndrome: cerebral cortex and posterior fossa. Neurology 48:399-407.
  230. Feekery C, Parry-Fielder B, Hopkins IJ (1993) Landau-Kleffner syndrome: six patients including discordant monozygotic twins. Pediatric Neurology 9:49-53.
    Back to: AutismInTwins, [Top]

    Neonatal Asphyxia in Laboratory Rats
  231. Simon N, Volicer L (1976) Neonatal asphyxia in the rat: greater vulnerability of males and persistent effects on brain monoamine synthesis. Journal of Neurochemistry 26:893-900.
    Back to: Male/Female differences, [Top]

    Categories of Mental Disorders
  232. American Psychiatric Association (1994) Diagnostic and Statistical Manual of Mental Disorders, DSM-IV. Washington, DC: American Psychiatric Association.
    Back to: Male/Female differences, [Top]


. . . .

SUMMARIES


IV. CHILDHOOD HANDICAPS

19 - Auditory and Motor Handicaps
Motor handicaps associated with the brainstem pattern of damage were transient and overcome except for manual dexterity in monkeys subjected to asphyxia at birth. More serious permanent disorders of movement indicate impairment of function in the basal ganglia or cerebral cortex. Most children with autism show signs of both, thus signs of damage caused by both asphyxia and hypoxia. Asphyxia is more likely to occur as the final insult of a difficult hypoxic birth. Signs of auditory dysfunction in children with autism would seem to indicate catastrophic impairment of aerobic metabolism by asphyxia at birth or by any of the other medical conditions associated with autism.

20 - Increased Incidence of Autism
The increased prevalence of autism is more likely due to increased incidence of asphyxia at birth than to increases in the medical conditions associated with autism. Textbooks on obstetrics in the late nineteenth and early twentieth centuries stressed the importance of leaving the umbilical cord intact until the newborn infant is breathing. The modern procedure of immediate umbilical cord clamping needs to be investigated as a possible cause of increased prevalence of auditory dysfunction in children.

21 - Fetal to Postnatal Adaptation
The alveoli of the lungs become functional by perfusion with blood at birth. Resuscitation by ventilation in the intensive care unit often requires use of blood volume expanders. Normal blood volume is best ensured by maintaining placental circulation through the umbilical cord.

22 - Forgotten History
Experimental asphyxiation of newborn monkeys would no longer be permissible. But the findings of past research projects remain important and merit re-examination.

23 - Worth Remembering
Comments made by Windle in 1969 are worth heeding still today, especially:
(a) To clamp the umbilical cord immediately is equivalent to subjecting the infant to a massive hemorrhage.
(b) It is no longer acceptable to assume that the human infant will escape harm from a short exposure to asphyxia at birth.
(c) Although improvement can be expected, we know that the brain of a "recovered" monkey is damaged whereas we only assume that the brain of a "recovered" human infant is normal.

24 - Hemoglobin:
The release of oxygen from hemoglobin provides an explanation for why the effects of hypoxia are so different from those of asphyxia. The quickest adjustment to an environment of oxygen insufficiency is provided by the action of hemoglobin in delivering oxygen first to tissues producing the most carbon dioxide. The inferior colliculus is spared under hypoxic conditions, but first to sustain damage during any catastrophic interference with aerobic metabolism

25 - Postnatal Anemia:
Clamping the umbilical cord at birth is equivalent to subjecting the infant to a massive hemorrhage; this loss of blood was shown over 60 years ago to lead to anemia in infancy. An anemic child is in a state of chronic hypoxia, which will impede normal growth of brain and other organs.

26 - Autism in Twins:
Concordance of autism in identical twins is not 100 percent. Differences between concordant twin pairs are greater than similarities. Twins are more vulnerable to perinatal problems, which is also evident from the larger than would be expected number of non-identical twin pairs in which both are autistic.

27 - Male-Female Differences:
Males have higher metabolic needs than females and are thus more vulnerable to any factor that interferes with aerobic energy production. Males outnumber females in most developmental disorders. Growth retardation was immediately evident in males but not females following neonatal asphyxia in laboratory rats.

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