Brain Development: Normal Processes and the Effects of Alcohol ...

144 ETHANOL-AFFECTE D DEVELOPMENT
(i.e., al l thre e o f the diagnosti c criteri a ar e met , in -
cluding th e combinatio n o f spécifi e dysmophi a re -
quired t o mee t FA S criteria). Therefore, individual s
with a history of prenatal alcohol exposur e and deficits
thought to be related t o the alcohol exposure , but without
th e necessar y criteria for an FA S diagnosis, would
be considere d a s nondysmorphic FASD . Th e termi -
nology use d throughou t th e presen t chapter refers to
alcohol-exposed individual s as having FAS when they
meet th e thre e majo r criteri a for the diagnosis , an d
nondysmorphic FAS D when the y do not . I t is important
to note that although there is a general consensu s
on th e wide-rangin g an d variabl e effect s o f feta l
alcohol exposure , diagnostic an d classificatio n terminology
remains controversial . Thus, honing the diag -
nostic criteri a tha t describ e feta l alcoho l effect s i s
currently a priority for the field (Riley et al., 2003).
AUTOPSY STUDIES
Dysmorphic Fetal Alcohol
Spectrum Disorde r
Autopsy, which literall y means, "t o see for oneself," in -
volves examinatio n t o determin e th e exac t caus e o f
death. Autopsies are useful i n the stud y of brain disease
processes. Postmorte m examinatio n permit s a mor e
direct study of neuroanatomy than i n vivo techniques.
Examination of expired tissue, however, presents a confound
whe n attemptin g t o generaliz e th e finding s t o
live cases. In other words, autopsies allow for a detailed
description no t possibl e with les s invasive techniques,
but the data they provide are not necessarily representative
o f living cohorts. Historically , autopsy cas e report -
ing wa s one o f th e initia l method s use d t o examin e
teratogenic effects o f alcohol on brain structure. In th e
autopsy case s o f children wit h FAS , death usuall y occurred
because of major CNS o r cardiac dysfunction.
The handfu l o f subsequent autops y report s sho w
that developing brain s sufficiently expose d t o alcoho l
have a host of structural abnormalities. These include
gross microcephaly , cellula r disorganization , an d
anomalies of specific brain structures such a s the cor -
pus callosum an d cerebellum . Th e first autops y of a
FAS case wa s o f an infan t wh o die d a t 5 days of ag e
(Jones, 1975) . The infant' s brain exhibite d enlarge d
lateral ventricles and agenesis (absence ) of the corpu s
callosum. In addition, neuroglial heterotopias, a type
of microdysplasia in which abnormal neural and glia l
tissue cover parts of the brain surface, were described.
Notably, suc h microdysplasia s ar e though t t o resul t
from aberran t cortical neural migration and ar e com -
mon i n autops y case s o f prenatal alcoho l exposure .
For instance , i n a n autops y repor t o f five cases, het -
erotopias wer e note d i n eac h case , althoug h th e
amount o f abnormal tissu e was variable among indi -
viduals (Wisniewsk i e t al. , 1983) . Anothe r autops y
study that examine d brain s from fetuses , infants, an d
one chil d corroborate d th e presenc e o f microdys -
plasias and commente d on the diversit y of malformations
observed (Peiffe r e t al., 1979) . Furthermore, th e
authors suspecte d tha t dosage , i n additio n t o tim e
course o f exposure, likely influences the degre e an d
nature of structural damag e t o the developing brain.
Recent neuropathologica l studie s associat e FA S
with specific types of complex cerebral malformations
(Coulter et al., 1993) . Evaluation o f a 2-month-old infant
expose d t o a bing e patter n o f alcoho l exposur e
during th e firs t trimeste r o f pregnancy wa s the firs t
observation associatin g feta l alcoho l exposur e wit h
midline cerebral dysgenesis. Due t o elements of septooptodysplasia,
midlin e cerebra l dysgenesi s i s a typ e
of midlin e malformatio n characterize d b y a lac k o f
the septum pellucidum, optic nerv e damage , an d endocrine
abnormalities . I n additio n t o thi s midlin e
damage, th e cas e showe d genera l microcephal y an d
cerebellar Purkinj e neuro n disruption . Specifically ,
the cerebellar neurons were unusually positioned and
had abnormal dendritic structure.
Non-Dysmorphic Feta l
Alcohol Spectrum Disorde r
An earl y case stud y that examine d th e brain s o f four
neonates include d case s o f bot h dysmorphi c an d
nondysmorphic FAS D (Clarre n et al., 1978) . Disrup -
tions t o brain structure wer e note d i n addition t o microcephaly,
includin g heterotopia s an d histologica l
structural aberration s associated wit h error s i n neu -
ronal an d glia l migration . Th e degre e o f structura l
damage t o the alcohol-expose d brain s prompted th e
authors to conclude "tha t problems of brain morpho -
genesis can occur as the predominant effec t o f ethanol
exposure in utero" (p. 67). Brain alterations may more
directly indicat e damag e fro m alcohol-relate d effect s
than facia l dysmorphia.
As th e consensu s o f initia l autops y report s indi -
cating extensiv e and diffus e damag e throughou t th e
alcohol-exposed brai n mounted , investigator s bega n