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


Site Map Home
Conrad Simon Memorial Research Initiative /inc/docinfo.shtml
Date posted:  January 20, 2023 06:44 PM
© 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
  Scroll/Print Version

Topics (section links):


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

12 - Metabolic Rank Order
13 - The Auditory System
14 - Auditory Dysfunction

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

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

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
35 - Autism and Complications at Birth
36 - Umbilical Cord Clamping

Summaries (for all sections)
    Summaries (for section V)

[Site Links]

Overview (Brainstem Damage):

Damage to the cerebral cortex is the most common consequence of oxygen deficiency. Protective mechanisms increase blood flow in response to factors that decrease metabolism in brainstem nuclei of high metabolic rate. The inferior colliculus is often spared at the expense even of other brainstem nuclei that are slightly less active; thus the mammillary bodies are most prominently affected in the Wernicke's encephalopathy pattern of damage that occurs with chronic alcohol intoxication.

Brainstem pathology found in survivors of resuscitation from cardiac arrest, drowning, or suffocation has long been viewed as puzzling. Janzer and Friede (1980) aptly suggested this pattern of damage be referred to as "cardiac arrest encephalopathy." The brainstem pattern of damage also occurs with obstruction of aerobic metabolism by poisonous substances or deficiency of essential enzyme cofactors such as vitamin B1.

The gastrointestinal system is often affected in alcoholism and other conditions in which the brainstem pattern of damage occurs. Brainstem autonomic centers that control functions like peristalsis may become damaged and the damage compounded by non-absorption of essential nutrients like thiamine or absorption of toxic metabolites of deranged digestive processes.

. . . .



28 - Variable Vulnerability
Preservation of function in the auditory system is apparently important for survival and homeostasis. Mechanisms that increase blood flow under adverse conditions protect the auditory system in most circumstances, as shown by research using the autoradiographic methods for blood flow and deoxyglucose uptake For example the nerve gas Soman administered to laboratory animals in sub-toxic doses stimulated increased blood flow, with the greatest increase in the inferior colliculus [233-235].

Adjustment of aerobic metabolism as well as increased blood flow takes place with use of alcohol and other drugs. Research on the effects of amphetamine drugs revealed increased blood flow and metabolism in the inferior colliculus and visual cortex with metabolic depression elsewhere in the brain [236].

Grünwald et al. (1993) found that administration of one dose of alcohol to laboratory rats depressed glucose utilization throughout the brain, and this was most pronounced in the auditory system [24]. Increasing doses of alcohol given over a three week period increased deoxyglucose uptake in the inferior colliculus in dramatic contrast to lowered uptake in other areas of the brain. But an additional dose given two hours before measurement of deoxyglucose led to depressed uptake in the inferior colliculus.

If increased metabolism leads to auditory sensitivity that is diminished by an additional dose of alcohol, this might provide one explanation for addiction. In any event it provides an example of how metabolism as well as blood flow adapts to substances like alcohol.

Neuropathology caused by alcohol intoxication has long been known (as Wernicke's encephalopathy, in Wernicke-Korskoff syndrome), and the mammillary bodies are most predictably involved [237-241]. The mammillary bodies are among the brain areas of high glucose utilization as can be seen in table 2. Protective mechanisms that spare the inferior colliculi may then make slightly less active nuclei like the mammillary bodies most vulnerable to compromise.

Damage to the cerebral cortex is the most common consequence of oxygen deficiency. Clamping the carotid arteries of neonatal gerbils led to decreased blood flow to the forebrain but increased circulation in the inferior colliculi from collateral blood vessels [21]. Partial obstruction of placental blood flow to fetal monkeys produced damage in the cerebral cortex and cerebral palsy [2].

29 - Patterns of Damage

(1) Cortical and brainstem patterns
Damage caused by partial oxygen insufficiency (hypoxia) and total oxygen cutoff (asphyxia) is not a matter of degree. That brainstem damage is sometimes seen in human cases of circulatory arrest or suffocation has been a puzzle and topic of discussion in the medical literature [111-117].

Neubuerger (1954) investigated neuropathology in cases of cardiac arrest during surgery; most resulted in damage to the cerebral cortex, but Neubuerger expressed surprise that the location of lesions showed more variety than expected [111]. He made special note of one case in which there was, "...involvement of centers usually affected in Wernicke's disease, especially the mammillary bodies and posterior colliculi..." This was a person who died, at age 72, of respiratory failure during surgery. Artificial respiration and heart massage were performed with spontaneous heart beats obtained after eight minutes and spontaeous respiration after eighteen minutes. The patient, however, remained in a coma until death one week later. This can be viewed as a case of sudden catastrophic asphyxia, comparable to asphyxia at birth as produced in the experiments begun five years later by Ranck and Windle 1959 [26].

Gilles (1963) described symmetrical damage of brainstem nuclei in three individuals who survived episodes of cardiac arrest but later succumbed [113]. In two of the cases, normally expected damage was found in the cerebral cortex, thalamus, and cerebellar cortex. In addition, brainstem lesions of sensory and motor nuclei of several cranial nerves including the third (oculomotor), the inferior colliculi, cell groups in the reticular formation, and the lateral cuneate nuclei were found. The third case was an eighteen-month-old child who drowned but was resuscitated. In this case, the cerebral and cerebellar cortex remained intact.

Gilles noted the similarity of the brainstem pattern of damage to that found after experimental asphyxia of newborn monkeys and in human cases of kernicterus (bilirubin staining, or jaundice, of subcortical nuclei), and he suggested that brainstem "aphasias," such as in Moebius syndrome [242] might be related to temporary cardiac arrest in the prenatal or perinatal period. Moebius syndrome is another condition associated with Autism [243, 244], and it appears to be related to brainstem pathology [245-248], caused in some cases by prenatal exposure to the drug misoprostol [249].

(2) Wernicke-like or "circulatory arrest" encephalopathy
Brierley (1961) described, "Wernicke-like" lesions in the mammillary bodies as well as severe cell loss and gliosis in the inferior colliculi" in the brain of a two-year old child who suffered cardiac arrest of ten to fifteen minutes duration from anesthesia used for repair of a hernia [112]. Brierley also noted the striking similarity of this pattern of damage to that reported by Ranck and Windle.

Gilles (1969) reported three more cases of brainstem damage: In a 17-month-old boy who suffered cardiac arrest during a high fever, a nine-year-old child resuscitated after suffocation under a collapsed earthen bank, and a 22-year-old man who suffered cardiac arrest following a bullet wound to the abdomen [116]. Gilles referred to these cases as examples of "hypotensive brainstem necrosis." Janzer and Friede (1980) suggested "cardiac arrest encephalopathy" as a better term, and reported the brainstem pattern of damage in eight infants and seven adults for all of whom a well documented episode of cardiac arrest had occurred [117].

When circulation and oxygen delivery are completely cut off, metabolism within the brainstem nuclei of high circulatory rate comes to a sudden halt. This clearly happens far less often with survival than circulatory insufficiency or partial disruption of aerobic metabolism. Damage from both partial and total asphyxia can happen, with both cortical and brainstem patterns evident in the brain of any victim of an accident that interferes with respiration.

Asphyxia is not a more severe degree of hypoxia; asphyxia is a different kind of insult. Protective mechanisms go into effect in situations of reduced blood flow or oxygen insufficiency (hypoxia). Expansion of blood vessels (vasodilation) happens with exposure to toxic substances [233-236], and in alcohol intoxication [24]. Increased blood pressure can lead to bursting of capillaries; the "whiskey nose" of some alcoholics is a visible sign of this kind of process. Figure 19 (below) shows "flea-bite" size hemorrhages in the brainstem caused by alcohol intoxication. The "corpus quadrigeminum post" (posterior quadrigeminal body, or inferior colliculus) is indicated as a primary site in which this kind of damage occurs.

Wernicke's encephalopathy
Figure 19: Wernicke's encephalopathy: Flea-bite size hemorrhages in the brainstem from dilated blood vessels that burst (from Kant 1933, with permission from Springer-Verlag).

30 – Wernicke's Encephalopathy

(1) Hemorrhagic (or vascular) cause?
Brainstem damage caused by alcohol intoxication has long been known as Wernicke's encephalopathy [237-241]. Wernicke (1881) observed this pattern of damage in the brains of two alcoholic men and a young woman who had swallowed sulfuric acid [251]. An English translation of part of Wernicke's paper can be found in the article by Brody and Wilkins (1968) [253].

Wernicke described the damage as hemorrhagic, consisting of pin-point size burst capillaries as shown in the photograph above. Whether Wernicke's encephalopathy is always hemorrhagic has been controversial. Rosenblum and Feigin (1965) reported 41 cases of which 17 had no hemorrhages [252]. Visible petechial hemorrhages were recognized in 5 cases, and 19 revealed hemorrhages only under the microscope; five of these 19 were old hemorrhages recognized only by hemosiderin laden macrophages. Thus only 60 percent of their 43 cases showed any evidence of a hemorrhagic process.

Wernicke cited a paper by Gayet (1875) who described hemorrhagic brainstem damage in a man who survived several months following scalding of his airways in a boiler explosion [250]. Figure 20 predates use of photography, but is a drawing in color showing the areas of hemorrhagic damage in Gayet's patient.

(2) Brain structures involved
The mammillary bodies are usually noted as most severely affected in Wernicke's encephalopathy. But damage in the inferior colliculi is also often prominent [237-241].

Location and severity of the damage is variable because protective mechanisms have time to go into effect whenever a toxic insult does not immediately or totally disrupt aerobic metabolic systems.

Drawing of hemorrhagic brainstem damage (from Gayet 1875)

Figure 20: Drawing of hemorrhagic brainstem damage found by Gayet (1875) in a patient who survived eight months following scalding of the airway in a boiler explosion.

Note the involvement of the cerebellum in Wernicke's encephalopathy [254, 255]. Similar cerebellar pathology is prominent in the few investigations of brains from individuals with autism.

Damage caused by asphyxia at birth should probably be recognized as a variant of Wernicke's encephalopathy. Windle reported that the brainstem lesions caused by asphyxia at birth were not hemorrhagic in origin, which may be why he did not consider the damage caused by asphyxia at birth to be a variant of Wernicke's encephalopathy. But the brainstem structures affected are comparable.

31 - Suffocation at the Molecular Level
Circulatory arrest and suffocation have an immediate and catastrophic effect on respiratory gas exchange and thence aerobic metabolism. In these circumstances brain structures of high metabolic rate are most vulnerable, evident from experiments on asphyxia in monkeys (newborn and adult) and case reports of damage following resuscitation after cardiac arrest and accidents like drowning [1-2, 29, 111-117]. The same metabolically active brain nuclei are also susceptible to damage or impaired function by chemical substances many of which may selectively disable aerobic metabolic pathways.

(1) Selective disruption of aerobic metabolism:
Troncoso et al. (1981) introduced the substance pyrithiamine as a tool for simulating thiamine deficiency, producing Wernicke's encephalopathy, and as a shortcut for mimicking the effects of chronic alcohol consumption in laboratory animals [256]. Pyrithiamine displaces thiamine (vitamin B1) from the enzyme that activates it as a cofactor for the major (Krebs cycle) pathway of glucose metabolism. Neurological impairment and neuropathology are produced more quickly with pyrithiamine than by administering alcohol to experimental animals [257-261].

Pyrithiamine causes suffocation at the molecular level. Protective mechanisms can have no effect. Hakim (1986) found dramatic increases in cerebral circulation following pyrithiamine administration – a protective response doomed to failure [259]. Blood flow returned to normal levels following administration of thiamine except in the inferior colliculi, mammillary bodies, and thalamic nuclei – an early sign of permanent impairment in these metabolically most active brain nuclei.

Glucose metabolism is blocked by pyrithiamine, thus carbon dioxide is not produced as a stimulus for hemoglobin to release oxygen. Chen et al. (1997) found the inferior colliculi sustained damage before the mammillary bodies or any other of the brainstem nuclei of high metabolic rate in laboratory rats injected with pyrithiamine [261]. The blocking of glucose metabolism by pyrithiamine is one step beyond that of carbon monoxide or cyanide, which displace oxygen on the hemoglobin molecule [33, 34].

(2) Fast-acting anesthesia:
Roth and Barlow (1961) used an autoradiographic technique modeled after that used for measuring blood flow to investigate distribution of anesthetic agents in the brain [122]. They found distribution in the brain of fast-acting thiopental was different from that of barbiturates, which are slow to take effect but of longer duration. Thiopental was quickly distributed to the inferior colliculi and other nuclei of high blood flow. This finding lends support to the idea of Denny-Brown (1962) that the midbrain tectum (auditory and visual colliculi) is involved in maintaining the conscious state [119].

If the action of thiopental is on a specific neurotransmitter system, it would appear to be one of special importance for consciousness, and one closely coupled to aerobic energy production – the reason for high aerobic metabolism to have evolved in brain nuclei that maintain vigilance for environmental change.

(3) Brain-damaging intoxicants:
Damage of the inferior colliculus has been reported following exposure to several toxic chemicals [262-267]. Fumes from dry-cleaning fluids may reduce oxygen available to the lungs, or like thiopental be quickly distributed to areas of the brain with high blood flow. A confusional delirium afflicting two pressers in a dry-cleaning establishment was described by Bini and Bollea (1947) as comparable to alcohol intoxication [262]. Chronic intoxication lead to coma and death with focal lesions typical of Wernicke's encephalopathy found in the mammillary bodies, floor of the fourth ventricle, and inferior and superior colliculi.

Franken (1959) reported the case of a 28-year-old man exposed over a two-year period in his work filling fire extinguishers with methyl bromide [263]. He developed transient alterations in consciousness and involuntary jerking of his legs; he died two days after acute intoxication by a large amount of methyl bromide. Franken described brain lesions of the Wernicke-encephalitic type involving both posterior quadrigeminal bodies (the inferior colliculi). Goulon et sl. (1975) and Squier et al. (1992) reported additional cases of disability and death following acute exposure to methyl bromide, with Wernicke-like patterns with prominent involvement of the inferior colliculi [264, 265].

Cavanagh (1992) commented on the paper by Squier et al. and pointed out other toxic substances (6-amino-nicotinamide, misonidazole, metronidazole, and mono- and dinitro-benzene) that act by disabling the biochemical pathways of energy generation and produce symmetrical brainstem damage similar to that caused by methyl bromide [266]. Cavanagh and Nolan (1993) described the same pathology in laboratory rats caused by alpha-chlorohydrin, which was under investigation for use as a male anti-fertility agent [267]!

(4) Selective what?
Terms such as "Selective serotonin re-uptake inhibitors" have become part of the common vernacular, and are used to promote sales of drugs touted to improve mental well-being. Caution is warranted. There may be drugs, and even herbal remedies, that impair aerobic metabolism without causing visible damage; unlike alpha-chlorohydrin they may be out there on the market.

Alzheimer dementia as well as autism is on the rise. It might seem prudent to require that all pharmaceutical products be tested for their effects on the brain. The autoradiographic methods for blood flow and deoxyglucose uptake are ideally suited to investigation of metabolic effects of substances that do not produce visible damage. Auditory system and aerobic metabolic impairments have been detected in Alzheimer patients [14, 268].

(5) Mercury and lead poisoning:
Bertoni and Sprenkle (1989) used the deoxyglucose method to investigate how lead compounds affect the brain. They found decreased glucose uptake throughout the brain seven hours after administration of lead acetate, but this was most pronounced in structures of the auditory system: Inferior colliculus, superior olive, cochlear nucleus, lateral lemniscus, and auditory cortex [18]. Bertoni and Sprenkle proposed that lead may poison the energy-activating enzyme Na,K-ATPase.

Oyanagi et al. (1989) reported auditory system involvement as part of the neuropathology of mercury poisoning in 14 victims of Minamata disease (or Hunter-Russell syndrome), a condition that includes impairment of hearing and speech [102]. The evidence that mercury and lead affect the auditory system suggests that they may be disruptive to aerobic metabolism or a neurotransmitter system dependent upon a steady energy supply. How heavy metals interfere with aerobic metabolism is not as clear-cut as in the case of pyrithiamine.

The mercury preservative (Thimerosol) in vaccines is widely claimed to be a cause of autism [97-101]. The mercury theory is controversial because it has been formulated largely by parents who report having seen regression into autism following vaccination of their child. Lead poisoning has been reported as a co-morbid condition in some children with autism[174-176].

(6) Mitochondrial damage:
Aerobic metabolism takes place within the mitochondria of cells. Any substance disruptive to any component of mitochondria (cell walls, cristae, enzyme complexes, ribosomes, or DNA) will impede aerobic metabolism. Mitochondria have their own double stranded circular DNA similar to that of primitive bacteria [274, 276]. Mitochondria are thought possibly to have been a primeval infecting organism that turned out to be symbiotic for multicellular life forms because of the efficiency of their aerobic pathways for energy production [270, 277].

Mitochondrial genes encode RNA sequences for ribosomes, where peptides are assembled to become components of the enzymes that catalyze oxidative metabolism [274, 276]. Genes within chromosomes of cell nuclei encode additional RNA and peptide sub-units for the mitochondrial enzyme system. Mitochondria are duplicated from the maternal egg because sperm cells do not contain mitochondria [277]. Chromosomal genes are derived from both parents, and are far less vulnerable to mutations because protective enzymes that repair chromosomal DNA evolved later in cells with nuclei.

Mitrochondrial DNA is especially susceptible to mutagenic agents, and antibiotic drugs can damage mitochondria because of their similarity to bacterial organisms [271, 275]. Antibiotics are less and less effective against bacteria, which mutate and produce resistant strains. But damage to mitochondria may be a more urgent reason to avoid overuse of antibiotic medications. Mutations of mitochondrial DNA can lead to serious mitochondrial disorders. The kidneys and auditory system are most susceptible; nephrotoxicity and ototoxicity are common side effects of many drugs.

Matrilineal transmission of deafness induced by widespread use of streptomycin has been reported [272, 273]. Toxic chemicals used as herbicides and pesticides have long been known to cause neurodegenerative disorders; methyl bromide was used for this purpose as well as in fire extinguishers. DeJong (1944) reported the neurotoxicity of methyl bromide [269], which later was found to cause a brainstem pattern of damage similar to that caused by asphyxia [262-265]. Other chemical substances have been found to be mutagenic to mitochondrial DNA and are known to cause symptoms similar to those of Parkinsonism and Huntington’s chorea [271, 275]. [Top]

32 - Thiamine Deficiency
Suffocation at the molecular level also occurs in cases of severe thiamine (vitamin B1) deficiency. Beriberi is an illness that developed in countries where rice was a dietary staple after whole-grain rice was replaced by refined white rice [282, 284].

Causes ranging from infection, toxic contamination of water, dietary deficiency of protein, to racial predispositions were sought, but adding back to rice "polishings" containing the germ removed during refining was found to immediately ameliorate the symptoms of this illness. Diligent research finally led to isolation of thiamine as the essential molecular component that would prevent illness [281].

Thiamine is an essential cofactor for enzymes that catalyze glucose metabolism, and is now therefore classified as a vitamin. Thiamine is needed only in small amounts but it has a high turnover rate and needs to be replaced at least daily. Neurological signs gave evidence of brain involvement in beriberi. Peripheral "polyneuritis," disorders of eye movements, staggering gait, disorientation, and drowsiness were noted to be similar to the problems of chronic alcoholics, and thiamine deficiency was found to produce the same bilaterally symmetric lesions of brainstem nuclei characteristic of Wernicke's encephalopathy [283].

Inferior colliculus damage caused by thiamine (vitamin B1) deficiency
Figure 21: Damage to the inferior colliculi in a human patient maintained on prolonged parenteral feeding lacking vitamin B1 (from Vortmeyer et al. 1992).

Calingasan et al (1994) measured distribution of the major thiamine-dependent enzyme, alpha-ketoglutarate dehydrogenase, and found the highest amounts in regions of the brain that are predilection sites for Wernicke’s encephalopathy [12].

Brain damage in alcoholism is widely regarded as due to thiamine deficiency in part because alcohol damages the gastro-intestinal system, which disrupts absorption of nutrients. Thiamine is used in detoxification treatment of alcoholics, and an analogue of thiamine appears to be helpful to some children with autism. Its use should perhaps be considered in autistic children with gastrointestinal disorders. One pilot study with thiamine tetrahydrofurfuryl disulfide appears to have helped some children [285].

Figure 21 shows severe damage to the inferior colliculi in a terminally ill patient maintained on total parenteral nutrition (TPN) in which thiamine was lacking [286], and this was not a unique case [287]!

The damage in figure 21 is hemorrhagic but otherwise strikingly similar to the pattern of damage caused by asphyxia at birth. Wernicke's encephalopathy has been observed in animals inadvertently maintained on diets lacking thiamine [288, 290] and in experimental thiamine deficiency [289, 291]. Damage to the inferior colliculi was found most prominent in animals, in contrast to more severe involvement of the mammillary bodies in human cases of chronic alcohol use.

Damage caused by long-term escalating abuse of alcohol is serious, but not as catastrophic as sudden total deprivation of the essential aerobic coenzyme thiamine. Protective mechanisms spare the inferior colliculus and leave the mammillary bodies more vulnerable to repeated damage during the lifespan of a person addicted to alcohol.

33 - Brain-Gut Relationship
Chronic alcohol use damages the esophagus, intestinal tract, and liver. Liver encephalopathy or cirrhosis is the terminal stage of alcoholism. Alcohol in excess directly damages these organs. But considering the speed with which mental changes and inebriation occur following use of alcohol, it seems clear that alcohol's first target is the brain.

Toxic impairment of the brain involves brainstem centers, and involuntary functions such as intestinal peristalsis depend upon intact brainstem circuits that control the autonomic nervous system [292]. Thus the gut is as dependent upon integrity of brainstem function as the brain is on absorption of essential nutrients like thiamine.

Myers referred to the brainstem pattern of damage by asphyxia at birth as a "monotonous rank-order of brainstem nuclei." This pattern of damage did not produce cerebral palsy, but it is a pattern of damage no less serious. Impaired autonomic function caused by brainstem damage should be investigated as possibly contributive to the gastrointestinal problems of some children with autism.

Korsakoff (1889) observed the signs of neurological impairments (oculomotor, ataxia, and mental confusion) described by Wernicke not only in cases of chronic alcoholism, but also during the course of infections and cancerous cachexia (or wasting which may also have involved thiamine deficiency) [293]. Korsakoff provided description of 14 cases of non-alcoholic origin. Among these were post-partum illnesses, typhoid, tuberculosis, tapeworm, diabetes, pneumonia, jaundice, and intestinal disorders. In addition to early acute symptoms similar to those reported by Wernicke, Korsakoff is best remembered for describing the long-term course leading to memory impairment.

Neubuerger (1937) discussed the possibility that "auto-toxic" substances could be produced in senile and diseased organs, and that these auto-toxins were the reason Wernicke's encephalopathy developed in the brain [294]. The brain-gut relationship continues to be described [295-298].

Morley (2003) has noted that immediate clamping of the umbilical cord at birth can leave the infant in a state of hypovolemic shock, which in turn triggers generalized vasoconstriction that shifts blood flow from less vital organs to the heart and brain [299]. Hankins et al. (2002) provided evidence that asphyxia from placental abruption or umbilical cord prolapse during labor results in injury to the liver, kidneys, and heart as well as the brain [300]. Autism is associated with complications at birth, and some children with autism may then begin life with multiple organ injury as well as damage of brainstem autonomic centers.

. . . .


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: Variable vulnerability, Molecular suffocation, [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. Back to: Figure 1, [Top]
  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.
    Back to: Thiamine Deficiency, [Top]

  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.
    Back to: Molecular Suffocation, [Top]

    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.
    Back to: Molecular Suffocation, [Top]

  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.
    Back to: Variable Vulnerability, [Top]

  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.
    Back to: Variable Vulnerability, Patterns of Damage, [Top]

  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.
    Back to: Patterns of Damage, [Top]

    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.
    Back to: Molecular suffocation, [Top]

    Developmental Degeneration Following Asphyxia
  30. Faro MD & Windle WF (1969) Transneuronal degeneration in brains of monkeys asphyxiated at birth. Experimental Neurology 24:38-53.

    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: Molecular Suffocation, [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.

    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.

    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.

    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.
  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
  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.

  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.
    Back to: Molecular Suffocation, [Top]

    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.
    Back to: Molecular Suffocation, [Top]

    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.
    Back to: Patterns of Damage (1), [Top]

  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.
    Back to: Patterns of Damage (2), [Top]

  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.
    Back to: Patterns of Damage (1), [Top]

  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.
    Back to: Patterns of Damage (2), [Top]

  117. Janzer RC, Friede RL. Hypotensive brain stem necrosis or cardiac arrest encephalopathy? Acta Neuropathol (Berl). 1980;50(1):53-6.
    Back to: Patterns of Damage (1), Patterns of Damage (2), Molecular suffocation, [Top]

    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.
    Back to: Molecular Suffocation, [Top]

    Fast Acting Anesthesia
  122. Roth LJ, Barlow CE (1961) Drugs in the brain. Science 134:22-31.
    Back to: Molecular Suffocation, [Top]

    Kanner's Original Description
  123. Kanner L (1943) Autistic disturbances of affective contact. Nervous Child 2:217-250.

    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.

    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

    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: Molecular Suffocation, [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.

    Genetic/Metabolic Predispositions for Autism:
  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

  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.

  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.

    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.

    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. 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.

  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.

    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.

    Hierarchy of Human Needs
  215. Maslow AH (1970) Motivation and Personality, Second Edition. New York: Harper & Row.

    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.

  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)

    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.
  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.
  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
  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.

    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.

    Categories of Mental Disorders
  232. American Psychiatric Association (1994) Diagnostic and Statistical Manual of Mental Disorders, DSM-IV. Washington, DC: American Psychiatric Association.

    Adjustments Under Adverse Conditions
  233. Scremin OU, Shih TM, Corcoran KD (1991) Cerebral blood flow-metabolism coupling after administration of soman at nontoxic levels. Brain Research Bulletin 26:353-6
  234. Scremin OU, Shih TM, Li MG, Jenden DJ (1998) Mapping of cerebral metabolic activation in three models of cholinergic convulsions. Brain Research Bulletin 45:167-74
  235. Shih TM, Scremin OU (1992) Cerebral blood flow and metabolism in soman-induced convulsions. Brain Research Bulletin 28:735-42
  236. Kelly PA, Ritchie IM, McBean DE, Sharkey J, Olverman HJ (1995) Enhanced cerebrovascular responsiveness to hypercapnia following depletion of central serotonergic terminals. Journal of Cerebral Blood Flow and Metabolism 15:706-713
    Back to: Variable Vulnerability, Patterns of Damage, [Top]

    Neuropathology in Alcoholism (Wernicke's Encephalopathy)
  237. Gamper (1928) Zur Frage der Polioencephalitis haemorrhagica der chronischen Alkoholiker. Anatomische Befunde beim alkoholischen Korsakow und ihre Beziehungen zum klinischen Bild. Deutsche Zeitschrift für Nervenheilkunde 102:122-129
  238. Kant F (1933) Die Pseudoencephalitis Wernicke der Alkoholiker. (polio-encephalitis haemorrhagica superior acuta). Archiv für Psychiatrie und Nervenkrankheiten 98:702-768.
  239. Malamud N, Skillicorn SA (1956). Relationship between the Wernicke and the Korsakoff Syndrome. Archives of Neurology and Psychiatry, 76, 585-596.
  240. Torvik A (1987) Topographic distribution and severity of brain lesions in Wernicke's encephalopathy. Clinical Neuropathology 6:25-29.
  241. Victor M, Adams RD, Collins GH (1989) The Wernicke-Korsakoff syndrome and related neurologic disorders due to alcoholism and malnutrition, 2nd ed, Contemporary Neurology Series v30. Philadelphia, PA : F.A. Davis Co.
    Back to: Variable Vulnerability, Wernicke's Encephalopathy (1), or (2), [Top]

    Moebius Syndrome (Bilateral Facial Palsy)
  242. Moebius PJ (1888) Ueber angeborenen doppelseitige Abducens-Facialis-Laemung. Münchener Medizinische Wochenschrift. 35: 91-94.
  243. Gillberg C, Steffenburg S (1989) Autistic behaviour in Moebius syndrome. Acta Paediatrica Scandinavica 78:314-316.
  244. Miller MT, Stromland K. (1999) The mobius sequence: a relook. Journal of AAPOS
  245. Lipson AH, Webster WS, Brown-Woodman PD, Osborn RA (1989) Moebius syndrome: animal model--human correlations and evidence for a brainstem vascular etiology. Teratology 40:339-50
  246. Fujita I, Koyanagi T, Kukita J, Yamashita H, Minami T, Nakano H, Ueda K (1991) Moebius syndrome with central hypoventilation and brainstem calcification: a case report. European Journal of Pediatrics 150:582-3
  247. Yoon K, Yoo SJ, Suh DC, Lee YA, Kim KS, Choe G (1997) Mobius syndrome with brain stem calcification: prenatal and neonatal sonographic findings. Pediatric Radiology 27:150-2
  248. Matsunaga Y, Amamoto N, Kondoh T, Ohtsuka Y, Miyazoe H, Kamimura N, Matsumoto T, Tsuji Y (1998) A severe case of Moebius syndrome with calcification on the fourth ventricular floor. Journal of Human Genetics 43:62-4.
  249. Pastuszak AL, Schuler L, Speck-Martins CE, Coelho KE, Cordello SM, Vargas F, Brunoni D, Schwarz IV, Larrandaburu M, Safattle H, Meloni VF, Koren G (1998) Use of misoprostol during pregnancy and Mobius' syndrome in infants. New England Journal of Medicine 338:1881-1885
    Back to: Patterns of Damage, [Top]

    Wernicke-Gayet Encephalopathy
  250. Gayet M (1875) Affection encéphalique (encéphalite diffuse probable) localisée aux étages supérieurs des pédoncules cérébraux et aux couches optiques, ainsi qu’au plancher du quatrième ventricule et aux parois latérales du troisième. Archives de physiologie normale et pathologique série 2, 2:23-351.
  251. Wernicke C (1881) Die acute, haemorrhagische Poliencephalitis superior. Lehrbuch der Gehirnkrankheiten für Ärzte und Studirende,Band II. Kassel: Theodor Fischer, pp 229-242.
  252. Rosenblum WI, Feigin I. (1965) The hemorrhagic component of Wernicke's encephalopathy. Archives of Neurology 13:627-32.
  253. Brody IA, Wilkins RH. (1968) Wernicke's encephalopathy. Archives of Neurology. 19:228-32.
  254. Butterworth RF (1993) Pathophysiology of cerebellar dysfunction in the Wernicke-Korsakoff syndrome. Canadian Journal of Neurological Sciences 20 Suppl 3:S123-S126.
  255. Cavanagh JB, Holton JL, Nolan CC (1997) Selective damage to the cerebellar vermis in chronic alcoholism: a contribution from neurotoxicology to an old problem of selective vulnerability. Neuropathology and Applied Neurobiology 23:355-363.
    Back to: Wernicke's Encephalopathy, [Top]

    Pyrithiamine Enzyme Poison
  256. Troncoso JC, Johnston MV, Hess KM, Griffin JW, Price DL (1981) Model of Wernicke's encephalopathy. Archives Of Neurology 38:350-354.
  257. Irle E, Markowitsch HJ (1983) Widespread neuroanatomical damage and learning deficits following chronic alcohol consumption or vitamin B1 (thiamine) deficiency in rats. Behavioral Brain Research 9:277-284.
  258. Cogan DG, Witt ED, Goldman-Rakic PS (1985) Ocular signs in thiamine-deficient monkeys and in Wernicke's disease in humans. Archives of Ophthalmology 103:1212-1220.
  259. Hakim AM (1986) Effect of thiamine deficiency and its reversal on cerebral blood flow in the rat. Observations on the phenomena of hyperperfusion, "no reflow," and delayed hypoperfusion. Journal of Cerebral Blood Flow and Metabolism 6:79-85
  260. Leong DK, Le O, Oliva L, Butterworth RF (1994) Increased densities of binding sites for the "peripheral-type" benzodiazepine receptor ligand [3H]PK11195 in vulnerable regions of the rat brain in thiamine deficiency encephalopathy. Journal of Cerebral Blood Flow and Metabolism. 14:100-5.
  261. Chen Q, Okada S, Okeda R (1997) Causality of parenchymal and vascular changes in rats with experimental thiamine deficiency encephalopathy. Pathology International 47:748-756
    Back to: Molecular Suffocation, [Top]

    Toxic fumes, Methyl Bromide, and Alpha-chlorohydrin
  262. Bini, L. & Bollea, G. (1947). Fatal poisoning by lead-benzine (a clinico-pathologic study). Journal of Neuropathology and Experimental Neurology, 6, 271-285.
  263. Franken L (1959) Étude anatomique d'un cas d'intoxication par le bromure de méthyle. Acta Neurologica et Psychiatrica Belgica 59:375-383.
  264. Goulon M, Nouailhat R, Escourolle R, Zarranz-Imirizaldu JJ, Grosbuis S, Levy-Alcover MA (1975). Intoxication par le bromure de methyl: Trois observations, dont une mortelle. Etude neuro-pathologique d'un cas de stupeur avec myoclonies, suivi pendent cinq ans. Revue Neurologique (Paris) 131:445-468.
  265. Squier MV, Thompson J, Rajgopalan B. (1992) Case report: neuropathology of methyl bromide intoxication. Neuropathology and Applied Neurobiology 18: 579-584.
  266. Cavanagh JB (1992) Methyl bromide intoxication and acute energy deprivation syndromes. Neuropathology and Applied Neurobiology 18:575-578.
  267. Cavanagh JB, Nolan CC (1993) The neurotoxicity of alpha-chlorohydrin in rats and mice: II. Lesion topography and factors in selective vulnerability in acute energy deprivation syndromes. Neuropathology and Applied Neurobiology 19:471-479.
    Back to: Molecular Suffocation (intoxicants), (mitochondrial damage), [Top]

    Auditory System Impairment in Alzheimer Dementia
  268. Sinha UK, Hollen KM, Rodriguez R, Miller CA (1993) Auditory system degeneration in Alzheimer's disease. Neurology 43:779-85.
    Back to: Molecular Suffocation, [Top]

    Mitochondria and their vulnerability
  269. DeJong R (1944) Methyl bromide poisoning. Journal of the American Medical Association 125:702.
  270. Reijnders L (1975) The origin of mitochondria. Journal of Molecular Evolution 5:167-76
  271. Tipton KF, Singer TP. (1993) Advances in our understanding of the mechanisms of the neurotoxicity of MPTP and related compounds. Journal of Neurochemistry 61:1191-1206.
  272. Prezant TR, Agapian JV, Bohlman MC, Bu X, Oztas S, Qiu WQ, Arnos KS, Cortopassi GA, Jaber L, Rotter JI, et al (1993) Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and non-syndromic deafness. Nature Genetics 4:289-294.
  273. Pandya A, Xia X, Radnaabazar J, Batsuuri J, Dangaansuren B, Fischel-Ghodsian N, Nance WE (1997) Mutation in the mitochondrial 12S rRNA gene in two families from Mongolia with matrilineal aminoglycoside ototoxicity. J Med Genet 1997 Feb;34(2):169-72
  274. Warner TT, Schapira AH (1997) Genetic counselling in mitochondrial diseases. Current Opinion in Neurology 10:408-412.
  275. Schapira AH (1998) Inborn and induced defects of mitochondria. Arch Neurol 55:1293-1296.
  276. Wallace DC (1999) Mitochondrial diseases in man and mouse. Science 283:1482-1488.
  277. Gray MW, Burger G, Lang BF. (1999) Mitochondrial evolution. Science (Mar 5, 5407) 283:1476-1481.
    Back to: Molecular Suffocation, [Top]

    Disruption of Mitochondrial Function
  278. Cavanagh, J. B. & Harding, B. N. (1994). Pathogenic factors underlying the lesions in Leigh's disease. Tissue responses to cellular energy deprivation and their clinico-pathological consequences. Brain, 117(Pt 6), 1357-1376.
  279. 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.
  280. 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.
    Back to: Molecular Suffocation, [Top]

    Thiamine Deficiency
  281. Peters RA (1936) The biochemical lesion in vitamin B1 deficiency. Lancet, May 23, 1161-1165.
  282. Williams RR (1961) Toward the Conquest of Beriberi. Cambridge, MA: Harvard University Press.
  283. Dreyfus PM, Victor M (1961) Effects of thiamine deficiency on the central nervous system. American Journal of Clinical Nutrition 9: 414-425.
  284. Carpenter KJ (2000) Beriberi, White Rice, and Vitamin B: A Disease, a Cause, and a Cure. Berkeley: University of California Press.
    Back to: Thiamine Deficiency, [Top]

    Thiamine Treatment
  285. Lonsdale D, Shamberger RJ, Audhya T. (2002) Treatment of autism spectrum children with thiamine tetrahydrofurfuryl disulfide: A pilot study. Neuroendocrinology Letters 23:303-308.

    Thiamine Deficiency in Total Parenteral Nutrition
  286. Vortmeyer AO, Hagel C, Laas R (1992) Haemorrhagic thiamine deficient encephalopathy following prolonged parenteral nutrition. Journal of Neurology, Neurosurgery and Psychiatry 55:826-829.
  287. Hahn JS, Berquist W, Alcorn DM, Chamberlain L, Bass D. Wernicke encephalopathy and beriberi during total parenteral nutrition attributable to multivitamin infusion shortage. Pediatrics. 1998 Jan;101(1):E10.

    Thiamine Deficiency in Animals
  288. Evans CA, Carlson WE, Green EG (1942) The pathology of Chastek paralysis in foxes. A counterpart of Wernicke's hemorrhagic polioencephalitis of man. American Journal of Pathology 18:79-90.
  289. Rinehart JF, Friedman M, Greenberg LD (1949) Effect of experimental thiamine deficiency on the nervous system of the rhesus monkey. Archives of Pathology 48:129-139.
  290. Jubb KV Saunders LZ, Coates HV (1956) Thiamine deficiency encephalopathy in cats. Journal of Comparative Pathology 66:217-227.
  291. Witt ED, Goldman-Rakic PS (1983) Intermittent thiamine deficiency in the rhesus monkey. I. Progression of neurological signs and neuroanatomical lesions. Annals of Neurology 13:376-395.
    Back to: Thiamine Deficiency, [Top]

    Brainstem Control of Autonomic Functions
  292. Johnson RH, Eisenhofer G, Lambie DG. The effects of acute and chronic ingestion of ethanol on the autonomic nervous system. Drug Alcohol Depend. 1986 Dec;18(4):319-28.

    Wernicke's Encephalopathy in Gastrointestinal Disorders
  293. Korsakoff SS (1889) Psychic disorder in conjunction with multiple neuritis. Translated by Victor M & Yakovlev PI (1955) Korsakoff's psychic disorder in conjunction with peripheral neuritis: a translation of Korsakoff's original article with brief comments on the author and his contribution to clinical medicine, Neurology 5:394-405.
  294. Neubürger K (1937) Wernickesche Krankheit bei chronischer Gastritis. Ein Beitrag zu den Beziehungen zwischen Magen und Gehirn. Zeitschrift für die gesamte Neurologie und Psychiatrie 160:208-225.
  295. Albers JW, Nostrant TT, Riggs JE. Neurologic manifestations of gastrointestinal disease. Neurol Clin. 1989 Aug;7(3):525-48.
  296. Butterworth RF. Pathophysiology of alcoholic brain damage: synergistic effects of ethanol, thiamine deficiency and alcoholic liver disease. Metab Brain Dis. 1995 Mar;10(1):1-8.
  297. Kril JJ. Neuropathology of thiamine deficiency disorders. Metab Brain Dis. 1996 Mar;11(1):9-17.
  298. Holzer P, Michl T, Danzer M, Jocic M, Schicho R, Lippe IT. Surveillance of the gastrointestinal mucosa by sensory neurons. J Physiol Pharmacol 2001 Dec;52(4 Pt 1):505-21.
    Back to: Brain Gut Relationship, [Top]

    Hypovolemic Shock at Birth
  299. Morley GM (2003) Neonatal Resuscitation: Life that Failed.
  300. Hankins GD, Koen S, Gei AF, Lopez SM, Van Hook JW, Anderson GD (2002) Neonatal organ system injury in acute birth asphyxia sufficient to result in neonatal encephalopathy. Obstetrics and gynecology 99:688-91.
    Back to: Brain Gut Relationship, [Top]

. . . .



28 - Variable Vulnerability
Protective mechanisms increase blood flow to the inferior colliculus in any circumstance that leads to impairment of aerobic metabolism. This has been revealed in several experiments with toxic chemicals. Total catastrophic disruption of aerobic metabolism damages the rank order of brainstem nuclei of high metabolic rate. Partial interference with aerobic metabolism spares the inferior colliculus and leads to damage of less metabolically active brain centers.

29 - Patterns of Damage
Circulatory insufficiency most often leads to damage of the cerebral cortex. Brainstem damage with or without involvement of cortical areas has been reported in people resuscitated after drowning, suffocation, or cardiac arrest. Brainstem damage has often been compared with that found in monkeys asphyxiated at birth and also in Wernicke's encephalopathy.

30 - Wernicke's Encephalopathy
Gayet (in 1875) and Wernicke (in 1881) described damage restricted to the brainstem in cases of airway damage, alcoholism, and ingestion of sulfuric acid. This pattern of damage is associated most often with alcoholism and thiamine (vitamin B1) deficiency.

31 - Suffocation at the Molecular Level
An increasing array of toxic substances has been found to interfere partially or catastrophically with aerobic metabolism. Brainstem nuclei are affected in varying degrees.

32 - Thiamine Deficiency
Thiamine (vitamin B1) is an essential cofactor for enzymes of aerobic metabolism. Deficiency of thiamine in the diet or because of malabsorption in gastrointestinal disorders leads to Wernicke's encephalopathy or variants of this pattern of damage.

33 - Brain-Gut Relationship
Autonomic functions such as intestinal peristalsis are controlled by brainstem centers. Damage to these autonomic centers can impair intestinal function. Intestinal dysfunction in turn leads to malabsorption and/or absorption of digestional fragments that should be excluded. Toxic fragments of digestion may be toxic to the brain and further compound the effects of earlier damage.


January 20, 2023 06:44 PM

Valid HTML 4.0!