5 -  Leech & Alvord (1977) and Gilles (1963)
Leech and Alvord (1977) investigated the incidence of
brainstem damage in 16 infants who had experienced
an anoxic episode in utero, during birth, or within the
first three months of life [1].  One of these (case 15)
died at age 13; the anoxic episode was described as
abruptio placentae twice with loss of fetal movement,
but the child’s developmental course was not
provided.  Clinical features for all of the subjects
studied were briefly summarized in a table.  All but two
were full-term infants; these two (cases 7 and 9) were
born after 31 and 32 weeks gestation, and case 7
died of recurrent pneumonia after aspiration at 5
weeks of age.  Cases 10 and 16 were crib deaths at
ages 2.5 months and 3 months; nine (cases 1, 2, 3, 4,
6, 8, 9, 11, 14) suffered anoxia during labor and
delivery.  The neuropathology found is summarized in
a table.  The thalamus, reticular formation, and cranial
nerve nuclei were affected in over 90% of the cases.  
The colliculi were examined in 13 of the cases and
found damaged in 11 (85%).  In descending order
other areas involved were the cerebral cortex and
hippocampus (13/16), lateral geniculate bodies,
cerebral white matter, striatum, pallidum, substantia
nigra, dentate nuclei, and cerebellar cortex (6/16).

Leech and Alvord commented that the
neuropathological changes they found represented
both the result of prolonged partial asphyxia as
described by Myers (1972) and an acute anoxic
episode of the type inflicted in the experiments of
Ranck and Windle (1959) in each of the infants [2, 3].  
None of their cases could be classified as purely one
or the other form of anoxia.

Gilles (1963) noted involvement of the inferior colliculi
as part of a pattern of brainstem damage observed in
an eighteen month old child who died a few weeks
following resuscitation from downing [4].  He called
attention to the similarity of this pattern of damage to
that produced by experimental asphyxia in newborn
monkeys (Ranck & Windle 1959).  Gilles further
suggested that the lesions caused by anoxia in the
perinatal period might result in developmental
language disorders such as those observed in ocular-
facial diplegia syndrome described by Moebius (1888)
[5].  Gillberg and Steffenburg (1989) later reported a
high frequency of autistic behaviors in children with
Moebius syndrome, and suggested that there may be
a common site of dysfunction within the brainstem [6].  
Lipson et al. (1989) suggested a brainstem etiology
for Moebius syndrome [7].

Autism in people with Moebius syndrome continues to
be investigated, as arising from teratogenic effects of
drugs like thalidomide and misoprostol, or from
genetic factors acting during early embryogenesis
[8].  Similarities to facial and oculomotor problems in
children with fetal alcohol syndrome have been
pointed out [8].
References
  1. Leech RW, Alvord EC (1977)
    Anoxic-ischemic
    encephalopathy in the
    human neonatal period, the
    significance of brain stem
    involvement.
  2. Myers RE (1972) Two
    patterns of perinatal brain
    damage and their conditions
    of occurrence.
  3. Ranck JB, Windle WF
    (1959). Brain damage in the
    monkey, Macaca mulatta, by
    asphyxia neonatorum.  
  4. Gilles FH (1963) Selective
    symmetrical neuronal
    necrosis of certain brain
    stem tegmental nuclei in
    temporary cardiac standstill.  
  5. Moebius PJ (1888) Ueber
    angeborenen doppelseitige
    Abducens-Facialis-
    Laemung.
  6. Gillberg C, Steffenburg S
    (1989) Autistic behaviour in
    Moebius syndrome.
  7. Lipson AH et al. (1989)
    Moebius syndrome: animal
    model--human correlations
    and evidence for a
    brainstem vascular etiology.
  8. Miller MT et al (2004)
    Autism with ophthalmologic
    malformations: the plot
    thickens.
Full References
top
  1. 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.
  2. Myers RE (1972) Two patterns of perinatal brain damage and their conditions of
    occurrence.  American Journal of Obstetrics and Gynecology 112:246-276.
  3. Ranck JB, Windle WF (1959). Brain damage in the monkey, Macaca mulatta, by asphyxia
    neonatorum.  Experimental Neurology 1:130-154.
  4. 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.
  5. Moebius PJ (1888) Ueber angeborenen doppelseitige Abducens-Facialis-Laemung.  
    Münchener Medizinische Wochenschrift. 35: 91-94.
  6. Gillberg C, Steffenburg S (1989) Autistic behaviour in Moebius syndrome.  Acta
    Paediatrica Scandinavica 78:314-316.
  7. 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.
  8. Miller MT, Stromland K, Ventura L, Johansson M, Bandim JM, Gillberg C.
    Autism with ophthalmologic malformations: the plot thickens. Trans Am Ophthalmol Soc.
    2004;102:107-20; discussion 120-1.