2 – Complacency, the persisting interpretation
Complacency was the end result of the experiments
on asphyxia at birth, and led to the still prevalent idea
that a brief lapse in respiration is better tolerated by
newborn infants than adults. The adult victim of
drowning, choking or cardiac arrest must be
resuscitated within four to eight minutes at most, to
avoid permanent neurological handicap [1]. Visible
damage within the brains of newborn monkeys
subjected to asphyxia was found only if resuscitation
was delayed past six minutes; and then the damage
was restricted to what Myers referred to as "a
monotonous rank-order of brainstem nuclei" which he
claimed was never observed in human cases [2]. He
was wrong.
Ranck and Windle (1959) though puzzled that
brainstem rather than cortical damage was the result
of their experiments on asphyxia at birth commented,
"The human neuropathologic entity most closely
resembling the effects of asphyxia neonatorum in the
monkey is kernicterus" [3]. Kernicterus is a serious
disorder of motor control, and is classified as one
form of cerebral palsy. Kernicterus is generally
thought to be caused by toxic effects of high bilirubin
levels on the brain. However, when considering the
supposed toxicity of bilirubin, it should be noted that
bilirubin primarily affects a variable "rank order" of
brainstem nuclei, not the cerebral cortex. Bilirubin
only affects brain areas where the blood-brain barrier
has been breached. Bilirubin levels are normally high
in the neonatal period, and most infants with high
bilirubin levels do not develop kernicterus [4-7].
Neubuerger (1954) reported a brainstem pattern of
damage in an elderly patient who survived for two
weeks after being resuscitated from cardiac arrest
suffered during surgery [8]. Damage of the inferior
colliculi was a prominent part of the observed
pathology, and Neubuerger noted the similarity of this
brainstem pattern of damage to that of Wernicke's
encephalopathy, a pattern of neuropathology most
often associated with chronic alcohol intoxication.
Windle and Myers should perhaps have recognized
the brainstem pattern of damage found in
asphyxiated monkeys as a variant of Wernicke's
encephalopathy. However, Wernicke (1881) reported
hemorrhagic involvement of brainstem nuclei following
ingestion of sulfuric acid in one case and in two cases
of chronic alcohol intoxication [9]. The ischemic
brainstem damage observed by Windle and Myers in
monkeys asphyxiated at birth was not hemorrhagic.
The damage resulting from asphyxia at birth may
have been caused in large part by clamping the
umbilical cord, and thus preventing the transfer of
respiratory blood from the placenta to the lungs and
other organs of the asphyxiated monkeys. Toxic
damage on the other hand is usually associated with
vasodilation and increased blood flow as a response
to poisoning of metabolic enzymes; this has been
shown in research like that of Grünwald et al (1993)
on the metabolic effects of alcohol in the brain [10].
Gilles (1963) reported bilateral brainstem lesions that
resembled the pattern of damage found in monkeys
subjected to asphyxia at birth [11, 12]. Gilles went
further and suggested the damage in the auditory
pathway in infants might be responsible for
developmental language delay [11].
Several other reports of perinatal brainstem damage
were published during the 1970s and 1980s [13-19].
Natsume et al. (1995) reported brainstem damage of
"type Myers" found in a newborn infant; it is
heartening to realize that these researchers at least
had looked back more than 20 years to find Myers'
1972 paper [20].
- Anonymous (2004) Six
minutes to save a life.
Minutes matter when
someone collapses from a
cardiac arrest.
- Myers RE (1972) Two
patterns of perinatal brain
damage and their conditions
of occurrence.
- Ranck JB, Windle WF (1959).
Brain damage in the monkey,
Macaca mulatta, by asphyxia
neonatorum.
- Maisels, M.J. (2006). What's
in a name? Physiologic and
pathologic jaundice: the
conundrum of defining
normal bilirubin levels in the
newborn. Pediatrics, 118,
805-807.
- Levine RL et al. (1982). Entry
of bilirubin into brain due to
opening of the blood-brain
barrier.
- Valaes T, Gellis SS (1981) Is
kernicterus always the
definitive evidence of bilirubin
toxicity?
- Levine RL (1979): Bilirubin:
Worked out years ago?
- Neubuerger KT (1954)
Lesions of the human brain
following circulatory arrest.
- Wernicke C (1881) Die acute,
haemorrhagische
Poliencephalitis superior.
- Grünwald F et al (1993)
Changes in local cerebral
glucose utilization in the
awake rat during acute and
chronic administration of
ethanol.
- Gilles FH (1963) Selective
symmetrical neuronal
necrosis of certain brain
stem tegmental nuclei in
temporary cardiac standstill.
- Gilles FH (1969) Hypotensive
brain stem necrosis:
selective symmetrical
necrosis of tegmental
neuronal aggregates
following cardiac arrest.
- Norman MG (1972) Antenatal
neuronal loss and gliosis of
the reticular formation,
thalamus, and
hypothalamus. A report of
three cases.
- Griffiths AD, Laurence KM
(1974) The effect of hypoxia
and hypoglycemia on the
brain of the newborn human
infant.
- Grunnet ML et al (1974) Brain
changes in newborns from
an intensive care unit.
- Schneider H et al (1975)
Anoxic encephalopathy with
predominant involvement of
basal ganglia, brain stem,
and spinal cord in the
perinatal period.
- Smith JF, Rodeck C (1975)
Multiple cystic and focal
encephalomalacia in infancy
and childhood with brain
stem damage.
- Leech RW, Alvord EC (1977)
Anoxic-ischemic
encephalopathy in the human
neonatal period, the
significance of brain stem
involvement.
- Roland EH et al (1988)
Selective brainstem injury in
an asphyxiated newborn.
- Natsume J et al (1995)
Clinical, neurophysiologic,
and neuropathological
features of an infant with
brain damage of total
asphyxia type (Myers).
- Anonymous (2004) Six minutes to save a life. Minutes matter when someone
collapses from a cardiac arrest. Harv Heart Lett. 2004 Feb;14(6):3
- Myers RE (1972) Two patterns of perinatal brain damage and their conditions of occurrence.
American Journal of Obstetrics and Gynecology 112:246-276.
- Ranck JB, Windle WF (1959). Brain damage in the monkey, Macaca mulatta, by asphyxia
neonatorum. Experimental Neurology 1:130-154.
- Maisels, M.J. (2006). What's in a name? Physiologic and pathologic jaundice: the conundrum
of defining normal bilirubin levels in the newborn. Pediatrics, 118, 805-807.
- Levine RL, Fredericks WR, Rapoport S. Entry of bilirubin into brain due to opening of the blood-
brain barrier. Pediatrics. 1982;69:255–259.
- Valaes T, Gellis SS. Is kernicterus always the definitive evidence of bilirubin toxicity?
Pediatrics. 1981 Jun;67(6):940-1.
- Levine RL: Bilirubin: Worked out years ago? Pediatrics 64: 380, 1979.
- Neubuerger KT (1954) Lesions of the human brain following circulatory arrest. Journal of
Neuropathology and Experimental Neurology 13:144-160.
- Wernicke C (1881) Die acute, haemorrhagische Poliencephalitis superior. Lehrbuch der
Gehirnkrankheiten für Ärzte und Studirende,Band II. Kassel: Theodor Fischer, pp 229-242.
- 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.
- 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.
- Gilles FH (1969) Hypotensive brain stem necrosis: selective symmetrical necrosis of
tegmental neuronal aggregates following cardiac arrest. Archives of Pathology 88:32-41.
- 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.
- 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.
- 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.
- 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.
- Smith JF, Rodeck C (1975) Multiple cystic and focal encephalomalacia in infancy and
childhood with brain stem damage. Journal of the neurological sciences 25:377-88.
- 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.
- Roland EH, Hill A, Norman MG, Flodmark O, MacNab AJ (1988) Selective brainstem injury in
an asphyxiated newborn. Annals of Neurology 23:89-92.
- 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.