5 -  Brain size and fetal alcohol syndrome
Guerin et al. (1996) examined the brain of a 16-year-
old girl with autism whose muscle tone had been
hypotonic from birth [1].  She never learned to walk or
talk, and remained incontinent.  In contrast to the
cases of Bailey et al. and Kemper and Bauman, her
brain was small (1000g) [2, 3]; Guerin et al. noted that
this would have been normal for an 18-month-old
child.  The third and lateral ventricles were enlarged
and thinning of the corpus callosum connecting the
hemispheres of the cerebral cortex was noted.  
Perivascular lymphocyte infiltrates in the lower
brainstem appeared to reflect an intercurrent viral
infection and perhaps the patient’s terminal illness.  
Despite her severe mental retardation, no other
macroscopic or microscopic abnormalities could be
found.

      Microcephaly (small brain) is a common feature of
fetal alcohol syndrome, and thinning of the corpus
callosum has also been noted in several cases of fetal
alcohol syndrome [4].  The corpus callosum is the
major connection between the left and right cerebral
hemispheres.  Bailey et al. (1998) observed that the
corpus callosum was thin in the brain of one of their
autistic subjects, a 23-year-old male with normal to
large head size [2].  Abnormalities of the corpus
callosum have been found in other investigations of
brain pathology in autism [5-9].

      Developmental compromise of the corpus
callosum could possibly be a long-term result of
impairment of function in the mammillary bodies.  As
discussed in preceeding chapters, the mammillary
bodies show a special vulnerability to chronic alcohol
exposure and are likely to be susceptible to damage
caused by other factors that undermine aerobic
metabolism.  The mammillary bodies are among the
brainstem nuclei of high metabolic rate, and they are
part of the limbic system, which is thought to facilitate
incorporation of recently remembered events into long-
term memory.  Neurons from the mammillary bodies
synapse with developing cortical areas adjacent to the
corpus callosum during maturation of the brain.

      When features of fetal alcohol pathology in the
brain are observed they may indicate cases of autism
caused by undocumented prenatal exposure to
alcohol.  Children with autism or autistic behaviors
have been found among clearly established cases of
fetal alcohol syndrome [10,11].  Prenatal exposure to
alcohol is likely to have been a factor in the case
reported by Rodier et al. (1996).  The mother was
hospitalized for addiction to alcohol and other drugs
during the infancy of her autistic child but stated she
could not recall whether she had problems with
alcohol and drug use during pregnancy [12].  The
brain was above average in weight, but the
dysmorphology of the brainstem found by Rodier et al.
is remarkably similar to descriptions of
neuropathology in fetal alcohol syndrome [4].  Rodier
et al. also described photos of the patient as showing
no nasolabial folds, which perhaps fits in with
descriptions of craniofacial abnormalities observed in
cases of fetal alcohol syndrome.  Facial
characteristics such as smooth or hypoplastic upper-
lip philtrum are listed in some articles on fetal alcohol
syndrome [13, 14].

References

1. Guerin P et al. (1996)
   Neuropathological study of a
   case of autistic syndrome
   with severe mental
   retardation.
   
2. Bailey A et al. (1998) A
   clinicopathological study of
   autism.
   
3. Kemper TL, Bauman M
   (1998). Neuropathology of
   infantile autism.
   
4. Roebuck TM et al. (1998) A
   review of the
   neuroanatomical findings in
   children with fetal alcohol
   syndrome or prenatal
   exposure to alcohol.
   
5. Saitoh O, Courchesne E
   (1998) Magnetic resonance
   imaging study of the brain in
   autism.
   
6. Haas RH et al. (1996)
   Neurologic abnormalities in
   infantile autism.
   
7. Egaas B et al. (1995)
   Reduced size of corpus
   callosum in autism.
   
8. Piven J et al. (1997) An MRI
   study of the corpus callosum
   in autism.
   
9. Gillberg C, Svendsen P
   (1983) Childhood psychosis
   and computed tomographic
   brain scan findings.
   
10. Nanson JL (1992) Autism in
    fetal alcohol syndrome: a
    report of six cases.
    
11. Church MW et al. (1997)
    Hearing, language, speech,
    vestibular, and dentofacial
    disorders in fetal alcohol
    syndrome.
    
12. Rodier PM et al. (1996)
    Embryological origin for
    autism: developmental
    anomalies of the cranial
    nerve motor nuclei.
    
13. Iosub S et al. (1981) Fetal
    alcohol syndrome revisited.  
    
14. Graham JM et al. (1988)
    Independent dysmorphology
    evaluations at birth and 4
    years of age for children
    exposed to varying  amounts
    of alcohol in utero.
    

Full References

top

1. Guerin P, Lyon G, Barthelemy C, Sostak E, Chevrollier V, Garreau B, Lelord G (1996)
   Neuropathological study of a case of autistic syndrome with severe mental retardation.
   Developmental Medicine and Child Neurology 38:203-211.
   
2. 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.
   
3. Kemper TL, Bauman M (1998). Neuropathology of infantile autism. Journal of
   Neuropathology and Experimental Neurology 57:645-652.
   
4. Roebuck TM, Mattson SN, Riley EP (1998) A review of the neuroanatomical findings in
   children with fetal alcohol syndrome or prenatal exposure to alcohol. Alcoholism, Clinical
   and Experimental Research 22:339-44
   
5. Saitoh O, Courchesne E (1998) Magnetic resonance imaging study of the brain in autism.
   Psychiatry And Clinical Neurosciences 52 Suppl:S219-22.
   
6. Haas RH, Townsend J, Courchesne E, Lincoln AJ, Schreibman L, Yeung-Courchesne R
   (1996) Neurologic abnormalities in infantile autism. Journal of Child Neurology 11:84-92.
   
7. Egaas B, Courchesne E, Saitoh O (1995) Reduced size of corpus callosum in autism.
   Archives of Neurology 52:794-80.
   
8. 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.
   
9. Gillberg C, Svendsen P (1983) Childhood psychosis and computed tomographic brain scan
   findings. Journal of Autism and Developmental Disorders 13:19-32.
   
10. Nanson JL (1992) Autism in fetal alcohol syndrome: a report of six cases. Alcoholism,
    Clinical and Experimental Research 16:558-565.
    
11. 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.
    
12. 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.
    
13. Iosub S, Fuchs M, Bingol N, and Gromisch DS (1981) Fetal alcohol syndrome revisited.  
    Pediatrics 68:475-479.
    
14. Graham JM Jr, Hanson JW, Darby BL, Barr HM, Streissguth AP (1988) Independent
    dysmorphology evaluations at birth and 4 years of age for children exposed to varying  
    amounts of alcohol in utero. Pediatrics 81:772-8.