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Many clinical descriptions illustrate the natural
history of prenatal-alcohol central nervous system (CNS) dysfunction
and highlight the prevalence of inattentional-hyperactive and impulsive
symptomatology (22,53–55). Clinical features of ADHD with memory
and executive function deficits persist through the lifespan. (2,7,9,54).
Animal studies on rats and mice prenatally exposed to alcohol have
shown that physical hyperactivity tends to diminish with increasing
age and to be worse in males than in females, which appears to parallel
the situation in humans with prenatal alcohol exposure (51,56–58).
Coles has analyzed the Continuous Performance Task (CPT), as well
as a 4-factor model of attention developed by Mirsky, and has reported
a qualitative difference in patients with FAS and ADHD (59). Her
results suggest that patients with ADHD have more significant problems
in the “focus” and “sustain” factors, whereas
patients with FAS have more problems with the “encode”
and “shift” factors (60). Numerous studies have demonstrated
the complex learning disability that accompanies ADHD symptoms,
including problems in working memory, executive function, and language
(2,5,8,9,13,15,22,35, 53–55,61).
Animal researchers have demonstrated that animals prenatally exposed
to alcohol tend to show an exaggerated response to psychostimulants
(32,33,56) a medication response influenced by age, sex, and drug
dosage (30). Pychostimulants have been used to treat patients with
developmental disability, mental retardation, and ADHD. Controlled
efficacy studies have documented their benefit (13,62–68).
However, O’Malley and Hagerman recently reviewed the action
of the stimulants and their use in FAS, PFAS, ARND, and mental retardation
(31). Clinical response to stimulants varied: in Denver, patients
with ARND had an 80% response rate, whereas patients with FAS had
a 48% response rate (13,31,69). In the University of Washington
Secondary Disabilities Study, 32% of 415 patients with FAS or Fetal
Alcohol Effects (FAE) or ARND were given methylphenidate for ADHD
and had a response rate of 47% (7,31). A retrospective case series
study undertaken by O’Malley and colleagues found a higher
response rate to dextroamphetamine (79%) than to methylphenidate
(22%) in 30 children and adolescents with FAS, PFAS, or FAE (ARND)
who were followed by 3 psychiatrists in Canada and the US (70).
Only 2 controlled studies have been published regarding psychostimulant
intervention for ADHD symptomatology in patients with FASD (71,72).
Synder and colleagues studied 11 children who were known positive
responders to stimulants. They analysed 3 different types of psychostimulant
(methylphenidate, dextroamphetamine, and pemoline). The study used
short and long acting preparations with different drug dosages on
a mg-per-kg basis. Their results showed no significant effect on
sustained attention but, as expected, significant effects on parent
rating scales (72). A study by Oesterheld analyzed 4 Native American
patients. This study used a randomized double-blind crossover design
and lasted only 5 days. It employed 2 placebos and a fixed dosage
of short-acting methylphenidate (71). As measured daily, using the
Conners’ Parent Rating Scales and the Conners’ Teacher
Rating Scales, methylphenidate significantly improved scores on
the Hyperactivity Index of both measures. However, scores were not
improved on the Daydreaming-Attention Index of the Conners’
Teacher Rating Scale.
Generally, patients (including those with FASD) who have neurochemical
or structural changes in the CNS are often overly sensitive to the
effects and side effects of medication (13,31,73–75). Response
to psychostimulants may improve with age. Thus, a negative response
may occur in a child under the age of 5 years, but a subsequent
positive response may be seen when the child is 6 or 7 years of
age (20,31,69). There may also be ethnic differences in clinical
response to stimulants, and some clinicians have suggested that
methylphenidate should not be used to treat the ADHD symptoms of
Native American children with FASD, because it possibly lacks effectiveness
and may retard growth (36,71).
Studies have also indicated that attention
should be given to possible medical complications, called alcohol-related
birth defects (ARBD), that may occur in individuals with FASD. These
include cardiac, renal, eye, or skeletal problems (3,13–15,31).
(See Table
1.)
Discussion
It is important to remember that there may be no link between FASD
and ADHD, as is suggested by studies supporting hypotheses 1 and
2. ADHD is a common condition, and adults with ADHD are more likely
to drink and thereby pass the disorder on to their infants through
genetic transmission. Nevertheless, the early onset, CNS dysfunction,
complex learning disability, atypical medication response, and complicated
psychiatric and medical comorbidity have many implications for management
that distinguish children with FASD and ADHD from children with
ADHD alone.
The implications of this possible link between FASD and ADHD have
some practical consequences for clinical management. Patients often
present with early-onset ADHD resulting from prenatal brain damage,
and their reactions to medication are unpredictable. Thus, medication
may sometimes increase a patient’s impulsivity or aggressiveness,
and an increase in the dosage may actually worsen the clinical situation,
rather than alleviating it (31,34,75). Stimulant medication for
children with FASD and ADHD should be considered as part of a multimodal
treatment array. Ideally, management will include various treatment
modalities, such as sensory integration, language therapy, special
schooling, nonverbal play therapy, medication therapy, parent education,
and supportive family therapy (32–34,70,75,76). Multimodal
treatment to manage childhood ADHD has been recommended by the MTA
Cooperative Group and the American Academy of Pediatrics (77,78).
One study has indicated that it is unwise to use stimulants to help
children cope with an unsafe environment, because ADHD high arousal-vigilance
may have a protective role for the child in this environment. Therefore,
removal of the ADHD symptoms may potentially decrease the child’s
wariness and so increase the risk of abuse (75).
The clinical presentation of ADHD in children with FASD is commonly
seen with such comorbid developmental, psychiatric, and medical
conditions. The complex learning disability in children with FASD
can include an unrecognized mixed receptive-expressive language
disorder that affects their social cognition and social communication
(5,61). Children with FASD and ADHD are commonly quite talkative,
and their lack of cognitive understanding, with inappropriate answers,
can frequently be misdiagnosed as an oppositional defiant disorder.
Commonly, the child will also show problems in working memory. A
mathematics disorder is frequently seen, which may underpin an executive-function
deficit in deductive reasoning. Thus, children with FASD often do
not link cause and effect or respond to standard behavioural-management
techniques. Judgement and self-awareness are also suspect, not just
in childhood but throughout the lifespan (2,5,7,8,75). Morphological
changes in the corpus callosum have been tied to the FASD complex
learning disability (3).
The psychiatric comorbid disorders include; anxiety disorder (with
panic attacks), mood disorder or affective instability, conduct
disorder, psychotic disorder, and intermittent explosive disorder.
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Finally, comorbid medical conditions such as cardiac, renal, eye,
or skeletal problems are often present and warrant specific interventions
(1,2,5,7,8,10,11,13–15,75). Sometimes as well, there may be
a complex partial or absence seizure disorder (13,31).
Dextroamphetamine may be the more effective first-line stimulant
when treating ADHD associated with FASD (31,70). This hypothesis
is consistent with the animal work of Hannigan and Randall (30),
which demonstrated the impact of prenatal alcohol exposure on the
D1 receptors of the mesolimbic dopamine system—the area where
dextroamphretamine has been shown to act (15,79). A negative response
to methylphenidate has been reported in animals and humans with
ADHD and a history of prenatal alcohol exposure, which suggests
that the frontal-nigrostriatal dopamine pathway may not be the mechanism
involved in patients with FASD and comorbid ADHD (16,31–33,70,80–82).
FASD is a chronic neurodevelopmental and neuropsychiatric disorder,
and proper treatment of FASD with ADHD symptomatology offers an
opportunity to decrease its documented destructive secondary disabilities
(2,5,7,75,83).
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