Screening Magnetic Resonance Imaging in Autism Spectrum Disorders: EvidenceBased Guideline

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Screening Magnetic Resonance Imaging in Autism
Spectrum Disorders Evidence-Based
Guideline Bibiana Restrepo MD. Dept of
Pediatrics, Texas Tech University Health Science
Center, El Paso, TX.
BACKGROUND Autistic spectrum disorder (ASD) is
a complex disorder defined by the presence of
social deficits, abnormalities in communication,
and interaction characterized by repetitive
behaviors. ASD ranges from low functioning autism
(LFA) with mental retardation to high functioning
(HFA) with normal IQ. Many autistic individuals
have cognitive impairments, with up to 70
incidence of mental retardation (MR) of affected
individuals. In recent years promising
information about the pathogenesis and detection
of autistic spectrum disorders had been reported
using neuroimaging. The underlying neurobiology
basis remains unknown numerous studies suggest
an anatomical and developmental pathological
basis. The purpose of this systematic review is
to determine the impact of Magnetic Resonance
Imaging (MRI) assessment in the identification of
ASD in patients before three years of age.
Results Since the development of the Magnetic
Resonance Imaging there is a considerable
interest in the structural alterations in this
disorder starting in 1992. Initial researches in
autistic population older than 6 years were done
reporting increase of brain volume and increased
ventricular volume. Hashimoto in 1993 found a
smaller midbrain, pons, medulla oblongata, and
vermis lobule VIII-X areas, reproduced two years
later by the same group 1. Then a couple of
studies found increased volume only at younger
age 2, 3. In 2001 Hardan reported increased
brain and ventricular volume including children
less than 3 years of age in the sample, as well
as adult individuals 4. The increased volume
was found in white and gray matter in 2-3 years
of life in autistic children compared with
controls in early childhood 3, located in the
frontal and temporal areas 2. Sparks reported
same findings in 45 patients with ASD versus
normal controls between 3 to 4 years of life 5.
Other studies revealed abnormal increase in
white and gray matter between 2 to 4 years of
age. Cerebellum and limbic system have been
involved as well. Cerebellar abnormalities
including abnormal volumes, and increased
ventrical volumes, have been reported 4 Sparks
reported an increase of the cerebellar volume
proportional to the increased brain size
including patients since 38 months of age. In
other studies the cerebellar size appeared
increased even after correction of brain volume
4, but other studies found no differences in
older patients 3. Differences in the white
matter between cerebral regions and an increase
of the cortical white and gray matter were noted
exclusively in 2-3 year old participants 3.
Other research has showed alterations in the
basal ganglia, which are supposed to be involved
in the repetitive behaviors that characterize
this disorder increased caudate nucleus volume
in a matched sample was reported 6, no further
studies have been published involving a younger
population. It is postulated that in ASD the
cerebral connectivity may be involved, then the
corpus callosum (CC) acts connecting the two
hemispheres. Piven in 1997 reported a smaller CC
in autistic individuals, other studies have
showed persistently the same finding, but no
other reports were selected by our inclusion
criteria. A bilateral increase of the amygdala
volume was reported 7, then another study found
an increased size proportional to the brain
enlargement 5, but no abnormalities in both
hippocampal and left amygdala volumes. Other
studies performed in older individuals found no
changes in its size some even found decreased
amygdala size. Different findings were reported
in the hippocampus, some studies found a normal
size 7, 8, but others have found it increased
proportional to the brain volume 5.
Methods Electronic databases and bibliographies
were searched PubMed and Pedialink for relevant
English-language articles using the terms
"Autistic disorder", "Asperger Syndrome",
"Magnetic Resonance Imaging", "Use of MRI in
Autism", "Autistic Spectrum Disorder", Screening
MRIin various combinations. A key word search
was also done using these terms "autism",
"infantile autism", "ASD", "autistic disorder",
development, neuroanatomy, brain growth,
cerebral white matter. The evidence was
reviewed systematically when criteria was
partially meet, a detailed analysis was done.
Search Strategy A total of 397 articles were
reviewed, electronic databases and bibliographies
were searched PubMed, and Medline from 1986 to
2006 the reference lists of all the reviewed
articles. A critical review was used to support
the selected data analysis. Inclusion criteria
structural MRI, healthy children with ASD, no
comorbid conditions in the participants, studies
in vivo, including healthy controls, matched
subjects, high functioning autism, MRI slice
thickness lt 3mm, reproducible imaging technique.
Exclusion criteria functional MRI, studies not
including patient younger than 3, adult
population, comorbid conditions, case reports.
DISCUSSION The first investigator suggesting
the biologic underlying cause for autism was
Kanner in 1943 nonetheless the cause remains
unknown. Behavioral signs and symptoms of ASD are
evident during the second and third years of
life, and should start raising red flags that a
child might have autism some of them including
delayed speech, unusual social reactions, and
poor exploration to the environment. ASD is
presently diagnosed exclusively by behavioral
criteria. Multiple studies have been performed
trying to elucidate the neuroanatomical basis.
Some reported enlargement of some brain regions
such as the frontal and temporal lobes, the
cerebellum, limbic system, and brainstem. A
common finding was an initial accelerated brain
growth followed for arrest of development,
restricted to the first years of life as well as
the cerebello-thalamo-cortical pathway has been
involved in the ASD pathology. Although studies
in older population have reported a decrease in
the thalamic volumes no studies have been
performed during the first 3 years of life. We
found inconsistent findings in amygdala volume
and hippocampus. Reports of a smaller corpus
callosum were not included in this review due to
our exclusion criteria. The cingulated gyrus
involved in emotions, has not been studied trying
to elucidate its role in autism. Generalized
brain enlargement during the first 2 years of
life is the most consistent finding. The basal
ganglia were found abnormal, but only one study
has been performed in early childhood. Many
studies have found cerebral abnormalities, but
not many studies have evaluated the MRI as a
diagnostic instrument. The findings related with
brain size are not consistent, and some studies
have failed matching the individuals by age, IQ,
sex, handedness, weight, socio-economic status,
co morbid conditions, and medication use. The
analyzed studies indicated a strong association
of ASD with anatomic abnormalities supporting the
theory that ASD is a developmental
neurobiological disorder. There are many
abnormalities reported by different researches,
but no omnipresent finding has been established
to clarify further use of the MRI as a diagnostic
tool. Recent years have seen a revolution
regarding neuroanatomical findings. During the
past two decades studies have begun to clarify
the underlying changes in the development and
anatomy of the autistic brain, but further
prospective MRI studies are needed during early
ages (before 3 years of age) to find the initial
changes in the autistic brain.
References 1. Hashimoto, T., et al., Brainstem
and cerebellar vermis involvement in autistic
children. J Child Neurol, 1993. 8(2) p.
149-53. 2. Carper, R.A., et al., Cerebral lobes
in autism early hyperplasia and abnormal age
effects. Neuroimage, 2002. 16(4) p.
1038-51. 3. Courchesne, E., et al., Unusual brain
growth patterns in early life in patients with
autistic disorder an MRI study. Neurology, 2001.
57(2) p. 245-54. 4. Hardan, A.Y., et al., Brain
volume in autism. J Child Neurol, 2001. 16(6) p.
421-4. 5. Sparks, B.F., et al., Brain structural
abnormalities in young children with autism
spectrum disorder. Neurology, 2002. 59(2) p.
184-92. 6. Sears, L.L., et al., An MRI study of
the basal ganglia in autism. Prog
Neuropsychopharmacol Biol Psychiatry, 1999.
23(4) p. 613-24. 7. Howard, M.A., et al.,
Convergent neuroanatomical and behavioural
evidence of an amygdala hypothesis of autism.
Neuroreport, 2000. 11(13) p. 2931-5. 8. Piven,
J., et al., An MRI study of autism the
cerebellum revisited. Neurology, 1997. 49(2) p.
546-51.