Brainstem Lesions in Autism:
Birth Asphyxia and Ischemia as Causative Factors
Nicole Simon, RN, PhD and George M. Morley, M.B., Ch. B., FACOG
Poster Presentation at the International Meeting for
Autism Research
(IMFAR) November 1, 2002
http://conradsimon.org
http://cordclamping.com
Brainstem Lesions in Autism: Birth Asphyxia and Ischemia as Causative Factors
Nicole Simon and George M. Morley
ABSTRACT
Immediate clamping of the umbilical cord at birth has become a standard procedure during the past two decades. This merits investigation as the cause of increased incidence of autism. Clamping of the umbilical cord before the lungs function induces a period of total asphyxia and produces severe hypovolemia by preventing placental transfusion - a 30% to 50% loss of blood volume - resulting in a hypoxic, ischemic neonate at risk for brain damage.
As in circulatory arrest and other factors that disrupt aerobic metabolism, damage of brainstem nuclei and the cerebellum can result. Visible damage seen in some cases of autism also involves brainstem nuclei and the cerebellum. The brainstem auditory pathway is especially vulnerable to brief total asphyxia. Impairment of the auditory system can be linked to verbal auditory agnosia, which underlies the language disorder in some children with autism.
Due to blood loss into the placenta, the immediately clamped neonate is very prone to develop infant anemia that has been widely correlated with mental deficiency and learning / behavior disorders that become evident in grade school.
We propose that increased incidence of autism, infant anemia, childhood mental disorders and hypoxic ischemic brain damage, all originate at birth from one cause - immediate umbilical cord clamping. This deserves to be investigated as extensively as genetics or exposure to toxic substances as an etiological factor for autism. Normal cord closure, with placental oxygenation and transfusion, prevents asphyxia and ischemia. Allowing physiological cord closure at every delivery could at least reduce the incidence of birth brain injuries.
Keywords:
umbilical cord clamping, placental transfusion, oxygen, aerobic, lungs, birth, asphyxia, brain damage, brainstem, cerebellum, verbal auditory agnosia, infant anemia, etiology, incidence, autism
LANGUAGE – AUDITORY
AGNOSIA – MATURATION
1 – Language development and the auditory
system
a) Inability to recognize syllable and word boundaries in rapid streams of speech has been identified as a problem in some children with autism [1, 2]. This handicap known as "verbal auditory agnosia" implies dysfunction within the auditory system.
b) The brainstem auditory system is myelinated and functional by 29 gestational weeks in the human fetus [3, 4, 5]. See FIGURE 1.
c) The language areas of the temporal and frontal lobes of the cerebral cortex are not myelinated or fully functional until a child is three or four years of age [4]. See FIGURE 2.
d) Language learning therefore begins before full maturation of cortical language areas.
e) Normal children recognize stressed syllables as a prominent feature of speech around them, which leads to a predictable first stage of language learning known as "telegraphic speech" [6, 7].
2 – Maturation and injury of brainstem
auditory nuclei
a) Neurotrophic transmitters are produced within brainstem auditory nuclei; these are thought to guide maturation of the frontal and temporal lobes of the cerebral cortex [8, 9]. Impairment of brainstem systems will prevent normal development of higher cognitive centers.
b) FIGURE 3 is a diagram of the auditory system. The auditory pathway in the brainstem is much more than a simple transmission cable. The nuclei along the way each perform important transformations on acoustic signals from the ears to their interpretation as language in the temporal lobes. [10, 11].
c) Injury of the inferior colliculus in the midbrain auditory pathway has been reported in three cases to cause "word deafness" (inability to comprehend spoken language) in previously normal adults [12, 13, 14].
d) Impairment within the auditory system is worth considering as the locus of verbal auditory agnosia in children with autism.
3 – Vulnerability of brainstem auditory
nuclei
a) The highest rates of blood flow and aerobic metabolism within the brain have been found in nuclei of the auditory system [15, 16, 17]. See FIGURE 4 and TABLES 1 and 2.
b) The auditory system is especially vulnerable to any lapse in aerobic metabolism [18-27].
c) The inferior colliculus has the highest rates of blood flow and aerobic metabolism of any structure of the brain [15-17, 28, 29].
d) The inferior colliculus is selectively damaged by a few minutes of total asphyxia at birth in newborn monkeys [30, 31]. See FIGURES 5 and 6.
e) Inferior colliculus damage has been found in the brains of human infants who died in the neonatal period [32-38]. See FIGURE 7.
f) Inferior colliculus damage occurs in adult monkeys subjected to several minutes of total asphyxia, as in the case of newborn monkeys [39].
4 – Effects of impaired aerobic metabolism
a) Myers [31] noted a "rank order" of brainstem nuclei damaged by an episode of total asphyxia.
b) Most prominent visible brain abnormalities reported in cases of autism have involved brainstem nuclei and the cerebellum [40-47].
c) Involvement of brainstem nuclei and the cerebellum is characteristic of damage caused by circulatory arrest and other factors that disrupt aerobic metabolism [21, 22, 39, 48, 49, 50].
d) Symmetric bilateral damage of brainstem nuclei, in which the cortex is largely spared, is known as Wernicke's encephalopathy [51, 52, 53].
UNNATURAL
COMPROMISE OF AEROBIC METABOLISM
5 – Immediate clamping of the umbilical
cord and asphyxia at birth
a) Immediate clamping of the umbilical cord (before the infant has breathed) has become a common practice over the past 20 years [54].
b) Immediate clamping of the cord induces a period of asphyxia until the lungs begin to function, and the inferior colliculi are therefore a prime target for damage until pulmonary oxygenation is established.
c) Immediate clamping of the umbilical cord and preventing oxygenation of the lungs were part of the experimental procedures used by both Windle and Myers in their investigations of brain damage caused by asphyxia in newborn monkeys [30, 31].
d) Myers [31] described a marked and rapid loss of blood pressure during the period of asphyxia; likewise, immediate clamping of the umbilical cord leaves the newborn human infant very hypovolemic and hypotensive due to lack of placental transfusion.[55, 56].
6 – Recovery without cord clamping
a) Myers [31] induced prenatal
partial asphyxia in some monkey fetuses, which, followed by birth asphyxia
(immediate clamping of the cord) produced lesions typical of hypoxic ischemic
encephalopathy (HIE) and spastic cerebral palsy (CP).
b) Quite remarkably in Myers' experiments, prenatal asphyxia to the point of severe depression handled by resuscitation without cord clamping resulted in full recovery of the neonate and no brain damage.
c) Following fetal distress, immediate cord clamping is routine in the resuscitation of human neonates. Resuscitation with placental circulation and oxygenation intact (no cord clamping) should prevent HIE and CP; It should also prevent damage to the inferior colliculus and thus prevent autism. [55].
IS ANY BRAIN DAMAGE MINOR?
7 – Consequences of so-called
"minor" brainstem impairment
a) Monkeys subjected to a few minutes of total asphyxia initially displayed "hypotonic" cerebral palsy. These monkeys were considered to have "minor" brainstem damage and with time recovered normal muscle tone and strength. But persistent memory and attention deficits remained. See FIGURE 8.
b) The resultant behavioral dysfunction was likened to the syndrome of minimal brain dysfunction (MBD), which would now be referred to as attention deficit disorder or perhaps even pervasive developmental disorder (PDD) [57]. Autistic disorder was not mentioned. (If autism is principally a language disorder, a precise animal model is not possible.)
c) Asphyxia at birth consistently damaged the auditory pathway while sparing the cerebral cortex. Behavior changes in cats with lesions of the lateral lemniscal tracts had been described as similar to those of children with autism [58]; loss of environmental awareness in monkeys follows ablation of parts of the inferior and superior colliculi [59, 60].
8 – Language delay, Moebius syndrome, and
Wernicke's encephalopathy
a) Gilles [48], in 1963, was first to suggest that damage of the inferior colliculi might lead to developmental language delay, such as that (Gilles suggested) observed in ocular-facial diplegia (Moebius) syndrome [61].
b) Population studies have revealed a high frequency of autistic behaviors in children with Moebius syndrome, and suggest that there may be a common site of dysfunction within the brainstem [62, 63].
c) The brainstem pattern of damage caused by asphyxia at birth is a variant of Wernicke's encephalopathy. Facial and oculomotor nuclei are involved in this pattern of pathology [64]. Lack of facial expression and diminished oculomotor activity in children with autism suggests a similar kind of brainstem impairment.
VARIANTS OF
BRAINSTEM DAMAGE
9 – Protective mechanisms and the
"rank order" of brainstem lesions
a) Impairment of aerobic metabolism results in vasodilation and increased blood flow to the inferior colliculi and other brainstem nuclei of high metabolic rate.
b) Increased blood flow under adverse conditions is one result of protective mechanisms that go into action to help preserve function in the metabolically most active components of the brain, leaving less active areas of the brain more vulnerable.
c) Preservation of function in the inferior colliculi will first lead to compromise and damage of slightly less active brain nuclei such as the mammillary bodies. See TABLE 2.
d) The mammillary bodies are the most prominently affected nuclei in Wernicke's encephalopathy caused by alcohol intoxication [53].
e) Total asphyxia damages the inferior colliculi first [65, 66]. Lesser degrees of oxygen insufficiency will produce different patterns of involvement of the vulnerable "rank order" of brainstem nuclei.
10 – Protective mechanisms and spectrum of
handicaps
a) Protective mechanisms are responsible for the wide variability of brain structures damaged by factors that disrupt aerobic metabolism.
b) Prolonged hypoxia such as that caused by hypovolemia, infant anemia, or respiratory distress syndrome (RDS) leads to damage of the cerebral cortex as shown by Myers [31].
c) In both adult and fetal monkeys damage of the cerebral cortex was produced by prolonged partial anoxia (or hypoxia).
d) A spectrum of disorders therefore results in circumstances of impaired aerobic metabolism, from auditory system damage caused by a brief period of total asphyxia to widespread involvement of the cerebral cortex under conditions of prolonged hypoxia and hypo-perfusion.
e) Cerebral palsy and severe autism are immediately apparent. Asperger syndrome, attention deficit disorder, and learning disabilities often go unnoticed until the child is evaluated in grade school.
11 – The natural shift from placental to
pulmonary respiration
a) At normal (physiological) birth, immediately following delivery, precise physiological coordination is required in the switch from placental to pulmonary respiration to ensure an uninterrupted supply of oxygen and blood to the brain. The natural transition occurs without any period of asphyxia, and with a large placental transfusion of oxygenated blood.
b) Initiation of pulmonary respiration requires:
1 – Aeration of the lungs
2 – Perfusion of the lungs (as fetal circulation changes to adult circulation)
c) The switch from fetal to adult circulation is effected by:
1. A massive transfusion of blood from the placenta (a 30% to 50% increase in blood volume) which fills the pulmonary vessels, and
2. Reflexive relaxation of pulmonary arterioles following pulmonary aeration.
d) Placental oxygenation continues until pulmonary oxygenation is established, following which the umbilical vessels close reflexively.
12 – Hazards of early clamping of the
umbilical cord
a) Most normal term babies appear to survive immediate clamping without overt difficulties, though many are slow to respond and most are pale.
b) Blood volume is reflexively switched to the lungs from other organs to establish the pulmonary circulation. Even if adequate pulmonary circulation and oxygenation are established, there still is risk of organ (and especially brain) ischemia [67].
c) Ischemia/hypovolemia is most evident in preemies and in neonates that are born already hypovolemic from intrapartum cord compression that engorges the placenta. In smaller preemies, the placenta and its blood content are disproportionately large.
d) The prevalence of neonatal hypovolemia and hypovolemic shock is mirrored by the frequency of use of blood volume expanders and blood transfusion, and the incidence of anemia in the neonatal intensive care unit (NICU).
e) Respiratory distress syndrome (RDS or shock lung) is the most common diagnosis in the NICU. Hypoxic-ischemic encephalopathy (HIE), the neuropathology of cerebral palsy [31], is the most litigated. Both correlate with immediate cord clamping and both should be virtually avoidable by physiological cord closure at birth with full placental transfusion – no cord clamp used.
ASPHYXIA – JAUNDICE
– ISCHEMIA – ANEMIA
13 – Long-term consequences of neonatal
blood loss and ischemia
a) Perinatologists and neonatologists constantly promote the concept of "placental over-transfusion" harming the neonate, especially the preemie. Yet a series of babies delivered using physiological cord closure (no cord clamp used) has never been studied and documented.
b) In experiments on asphyxia at birth in monkeys, none of the control animals (delivered naturally without cord clamp) had brain or other lesions.
c) Jaundice was found by a group of Windle's colleagues to discolor only brain areas already compromised by a brief period of asphyxia [68, 30]. See FIGURE 9.
d) Premature infants, who routinely have their cords clamped immediately, almost universally become anemic in the NICU, where the anemia is promptly corrected, sometimes by blood transfusion. However, despite prompt treatment they have poor mental achievement outcomes through young adulthood [69].
e) Infant anemia has been correlated with childhood attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), and learning disorders to the point of moderate mental deficiency that become evident only in grade school [70, 71].
f) At normal birth, no newborn has iron deficiency anemia; adequate
iron is supplied from the mother regardless of her iron status. Any newborn that receives a full placental
transfusion at birth has enough iron to prevent anemia during the first year of
life. [72] Therefore, full placental transfusion (natural cord closure) should prevent the behavioral disorders and learning disabilities that correlate with infant anemia.
14 – History of immediate cord clamping
ü
Immediate cord
clamping saw its origin in the 1950’s when early cord clamping was advocated to
reduce neonatal jaundice.
ü
In the late 1970’s, immediate clamping to facilitate resuscitation was demanded.
ü
In the 1990’s
ACOG advocated immediate clamping for medico-legal documentation [54].
ü
Despite the
procedure being universally condemned in the literature, it is practiced
routinely today without a thought of the consequences.
ü There is no clinical justification for immediate cord clamping:
1 – Neonatal resuscitation is best achieved by ventilating the lungs with the placental circulation intact [55, 56].
2 – Cord blood gases are available through a fine needle without disrupting placental function.
15
– Increased incidence of autism and related disorders
a) The increase in incidence of autism has occurred during the period
since adoption of immediate cord clamping as a standard procedure.
b) The increase in autism that has occurred over the past 10 to 20
years has also been paralleled by increases in attention deficit hyperactivity
disorder (ADD or ADHD), learning disabilities and under-achievement. All coincide with increased use of immediate
cord clamping.
c) From primate studies, it is clear a brief period of asphyxia at birth is extremely pathogenic for the brainstem nuclei. Thus lack of placental transfusion and placental oxygenation from immediate cord clamping becomes a crucial risk factor in auditory pathway damage.
d) While the time of cord clamping is seldom recorded, a history of birth difficulty that would give rise to immediate clamping is not uncommon in autistic children [75-84].
e) Impairment of brain function by immediate cord clamping at birth deserves investigation as an etiological predisposition for autism that is just as important as research on genetics and/or exposure to toxic substances.
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