Full text of DOI:10.1177/088307380001500206

OriginalArticle
ofthe
Quantitative Morphology
Corpus
Callosumin ChildrenWithNeurofibromatosis
andAttention-Deficit Hyperactivity
Disorder
AnneE.
Bartlett D. Moore
NormanE.
JohnM.
Kayl, PhD;
EdwardF.
III, PhD;
Slopis, MD;
MD
Jackson, PhD;
Leeds,
ABSTRACT
Neurofibromatosis-1 is
a
commonautosomal-dominant
disorder associated with numerous
anomalies
genetic
physical
childrenwithidiopathicADHD
andanincreasedincidence ofattention-deficit hyperactivity disorder
ADHD). Studies of
(
have
a
linkbetween
callosumsize and
symptomseverity. Thisstudy
examinesthecontributionofcorpus
suggested
corpus
callosum
morphologyto
drenwithneurofibromatosisunderwent
symptoms ofADHDin children with neurofibromatosis.
Eighteen control
subjects
significantlylargertotal corpus
subjects and36 chil-
withneurofibromatosis
callosumarea
magneticresonanceimagingofthebrain.
withneurofibromatosishad
Twelve
hadevidenceofADHDand24didnot.
Subjects
and
measurementsin three ofseven areas.
However, there
wereno differences betweenthe
significantly largerregional
neurofibromatosisalone andneurofibromatosis
ADHD
Increased
of
attentionproblems
wasassoci-
plus
groups.
severity
somefeaturesofADHDin childrenwithneurofibromatosis
butthenatureofthe mutationinneurofibromatosis
atedwithsmallertotalcallosalareas. Theseresults
suggestthat
quantifiabledifferencesinbrainmorphology,
couldbelinkedto
genetic
2000;15:90-96).
thatneurochemical effects also couldbeimportant.
ChildNeurol
suggests
(J
Neurofibromatosis-1 is
disorder
a
common autosomal-dominant
in the
general population,’ learning disabilities
andbehav-
disor-
1
in
3500) characterized by
iors characteristic ofattention-deficit
der
genetic
(incidence,
hyperactivity
variations in skin
pigmentation (cafe-au-lait spots), iris
and
(ADHD)occurmuchmorefrequentlyin
thesechildren
hamartomas
malignantneural
thanin the
Whilenumerousstudies
(
Lischnodules), benign
generalpopulation. 6--10
andcentralnervoussystemmanifestations, includ-
hamartomasor
haveexaminedtheassociationsbetweentheanatomicand
behavioral
individualswithneu-
tumors,
ingopticpathway
gliomas, aqueductalsteno-
abnormalitiesreportedin
sis, and dural ectasia.n2 Interestingly, an estimated 40%of
childrenwith neurofibromatosishavesomeform
rofibromatosis,’,’,’, 11-17theneuroanatomiccorrelatesofatten-
diagnosed
orbehavioral impairment.3-5
tion
problems
have not beenwell studied
among
children
of
Althoughthe fre-
withthe disorder.
Evidence to support the belief that central nervous
underlies ADHDin the
cognitive
quency ofmental retardation in children with neurofibro-
matosis
Wechsler Full-Scale IQ less than 70 and
than
(ie,
system dysfunction
general popu-
imaging
deficitinfrontostriatalcortical
impairmentsinadaptivebehavior)is onlyslightlyhigher
lation has come from several realms. Functional
studies
pointlargelyto
a
sys-
tems.18,19 Studies of brain function in both children and
adultswithADHDhavedocumenteddifferencesinthecau-
Received Feb 25, 1999. Received revised May21, 1999. Acceptedfor pub-
lication May25, 1999.
dateand
brain
regionsincomparison
withcontrol
posterior
while
Fromthe University of Texas M.D. Anderson Cancer Center (Drs Kayl,
Moore, Jackson, andLeeds), andthe University of Texas Medical School
at Houston(DrSlopis), Houston, TX.
Presentedin part at the meeting ofthe International Neuropsychological
Society, Boston, MA, February 11, 1999.
cerebral blood flow studies have
groups,2°
revealed
regional
in the striatal and
periventricular
pathophysiologic observation is
hypoperfusion
An additional
regions.21
the reduction in overall cerebral
metabolism in
glucose
adult subjects withADHDrelative to normalcontrols.22
Structuralevidence frontostriatalalterations
Addresscorrespondenceto DrBartlett D. MooreIII, DivisionofPediatrics
(
Box87), UTM.D. AndersonCancerCenter, 1515HolcombeBlvd, Houston,
TX 77030. Tel: 713-792-2454; fax: 713-794-4373; e-mail: bmoore
supporting
in individuals with ADHD has come from studies using
@
mdanderson.org.
9
0
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91
We obtained volumetric MRI studies of the brain and
mid-
computedtomography23 andmagnetic resonance imaging
Forexample, in their 1997
MRI)-based morphometry. 24-26
sagittal corpus callosum on 36 of these children.
werebetweenthe ages of and 16years, were English speaking,
had
WechslerFull-Scale IQgreaterthan70, andhadnotreceived
their
The children
(
study, Filipek et
al20 found decreased volume in the left
6
caudatenucleus, rightanterosuperiorfrontallobe, andbilat-
eralparieto-occipitalwhitematterinsubjectsdiagnosedwith
ADHD.Examinationsofspecificbrainstructuresalsohave
a
cranialirradiationorchemotherapyfor
neuropsychologicevaluation. Thesesubjectsrepresentthefirst 36
consecutive patients to receive volumetric MRIofthe brain as
abraintumorbefore
been completed. Hyndet a127 measuredtotal and
a
regional
valuesfor
callosumareasandfoundsmaller
newphaseofthe study. Noneofthe36subjectshadbeenreferred
specificallyfor attentionorothercognitiveproblems. Ofthese 36
childrenwithneurofibromatosis, 21 wereboys and 15 weregirls.
Thirty-five (97%) wereright-hand dominant.
Volumetric MRIstudies ofthe brain andmidsagittal corpus
callosumareaswerealsoobtainedon 18 controlsubjectsranging
to 16 years. This group wascomposedprimarily of
siblings ofchildrenseenin the Neurofibromatosis Clinic or other
pediatric oncologyclinics atM.D.AndersonCancerCenter. Of the
(50%) were siblings ofpatients seen in the
NeurofibromatosisClinic. Thesesubjectsweresiblings ofpatients
diagnosedwithnonfamilialneurofibromatosis (ie, resulting from
spontaneous mutation). Five (28%) ofthe 18 subjects weresib-
lings of child beingtreated for central nervous system malig-
nancy, two (11%) were siblings of patients with osteosarcoma,
andtwo(11%)werechildrenofanM.D.AndersonCenteremployee.
Thirteen of the control subjects were boys and five were girls.
Seventeen(94%) ofthecontrolsubjectswereright-handdominant.
corpus
average
ADHDrelative to normalcontrols. In
subjectswith
a
simi-
lar study, Semrud-Clikemanet a128
sumareain childrenwithADHDto
callo-
comparedcorpus
a
groupofage-matched
controls. WhiletheADHDgroupevidencedsmallersplenial
measures,nodifferenceswerefoundintheanteriorportions
ofthe corpus callosum. In
pared corpus callosum morphology in 18 patients
ADHDversusnormalcontrolsandfound smaller
a
third
Gieddet a129 com-
in age from
6
study,
with
significantly
rostrumandrostralbodyareasforpatientswithADHD.How-
Castellanos etal3l failedto
no
18 control subjects,
9
a
ever, follow-up studyby
repli-
catethe earlierresults ofthe Gieddet a129
differencesintotal or
study, finding
corpuscallosum
a
significant
regional
area. Finally,
gatedcorpus
andTourette syndrome.
tus wasobserved for rostral
a
1996 studyby
et a131 investi-
a
a
Baumgardner
callosum
in childrenwithADHD
morphology
A
significant effect ofADHDsta-
with the presence
bodyarea,
smaller areain comparisonto
ofADHDassociated with
a
normal comparison subjects and Tourette syndrome-only
groups.
Assessments
Together, these studies have suggested
basis for differences in
a
structural
For this
study,
examination conductedbythe pediatric neurologistfor the Neu-
rofibromatosisClinic (J.M.S.),
comprehensiveneuropsychologic
evaluation, and
volumetricMRIstudyofthe brain. Dataonvar-
assessments included
a
physical and
neurologic
ADHD, documenting significant
both anterior29 andposterior27 callosal
with ADHDversus normal controls.
regions in
Though
a
persons
brain abnor-
a
malities and behaviors characteristic of ADHD are fre-
ioussubjectcharacteristics, includingage, yearsofeducation, and
quently reported in
children with
no
socioeconomic status, were also collected for between-group
analyses.
neurofibromatosis,
has examined corpus callosum
morphology in that
study
population. Thus,
the
ofthisstudywasto determine
purpose
whether there are differences in corpus callosum mor-
VolumetricMagneticResonanceImaging
between children with neurofibromatosis and
a
All subjects werescannedwith
a
GeneralElectric Signa1.5-Tesla
phology
of
healthy controls and, if
such differences
scanner(GeneralElectricMedicalSystems, Milwaukee, WI)located
atM.D.AndersonCancerCenter. Sedationwasusedwhenclinically
indicatedforpatientswithneurofibromatosis. Noneofthecontrol
subjectswassedated. Inadditiontointerleaved axial protonden-
sity-weighted, TI-weighted, T 2-weighted, andfluid-attenuatedinver-
sion-recovery images, TI-weighted sagittal images were acquired
group
whether differences in
exist,
morphology are related to the
of ADHDin children with
frequently reported symptoms
neurofibromatosis.
METHODS
from2-mmthick sections
a
three-dimensional fast spoiled
using
echoacquisitionsequence. Theacquisitionparametersfor
Subjects
Overthe past
gradient
this sequencewereTE 4.2 ms, TR 13.4ms, 22-cmfield ofview,
256
192 acquisition matrix, and 60 2-mmsections. If clinically
6
years, 236 children withneurofibromatosis have
ofTexasM.D.AndersonCancerCen-
beenreferredtothe
x
University
terforneuropsychologicassessments, medicaldiagnosis, treatment,
The referrals have come from of
indicated, these scans were followed by contrast-enhanced
Tl-weighted axial imaging.
and
a wide
range
follow-up.
sources, includingpediatricians, ophthalmologists, orthopaedists,
aswellasfromtheTexasNeurofibromatosisFoun-
TheMRIdataweretransferredtoanimageprocessingwork-
station formorphometric analysis. Toobtainthecorpuscallosum
measurements,thethree-dimensionalTl-weightedimagedatawere
processed using the public domain National Institutes of Health
Imageprogram(developedattheUSNationalInstitutes ofHealth
andavailable ontheInternetathttp://rsb.info.nih.gov/nih-image/).
Foreachsubject, thesectionclosesttomidlinewaschosenformor-
and
internists,
dationandlocalneurofibromatosissupportgroups. All236children
wereenrolledin
federallyfundedresearchstudy(NationalInsti-
a
tutesofHealth, RO1NS31950)inwhichneuropsychologicassess-
mentispartofanannualevaluation. Informedconsentwasobtained
fromtheir parents or guardians in accordance with institutional
ofthe corpus callosum.
policy.
phometricanalysis
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9
2
Thecross-sectionalareaofthesevenregionsidentifiedbythe
criteria ofWitelson 32 (Figure 1) wascomputedusingpixel count-
DSM-JV33 criteria. Twelve
with neurofibromatosis had
subjects
not.
evidence
of ADHD; 24 did
andwasnormalized to the total brainvolume. In
the
Toexaminethe association ofbehaviorwithneuroanatomic
ing
corpuscallosumintoregionsforquantitative
dividing
measurement,
a
hor-
observations, parents
tention and
werealsoaskedtoratetheirchildren’sinat-
izontal line drawnbetweenthe mostanteriorandmostposterior
pointsofthecorpuscallosumdeterminedthestructure’smaximum
on two additional measures. The rat-
hyperactivity
ingsincludedinthe analysiswerethe attentionfactorscore ofthe
This areawasthen divided into seven
regions as follows:
anante-
ChildBehaviorChecklist34 andthe
hyperactivityscale
scoreonthe
length.
the
callosumwas
dividedintwo, yielding
Personality Inventory for
behavior in the school
Children.35 To
a
of
initially,
riorand
corpus
incorporate
rating
a
posteriorhalf. Thecorpuscallosumwasthendividedinto
each child’s teacherwasaskedto
setting,
thirdswithtwoadditionallines. Thespleniumwasdefinedby
drawnattheposteriorfifth ofthestructure. Todefmetherostrum,
line wasdrawnthroughthe anteriormostpointoftheinnercon-
a
line
complete TeacherReportForm.36
a
Theattentionfactorobtained
fromthat measurewasusedin statistical
analyses.
a
vexity ofthe anterior callosum.
RESULTS
Following image analysis,
the total area and seven
regional
areas ofthecorpuscallosumintheneurofibromatosisandcontrol
Thechildren includedinthis
studyrangedin age
from
6
to
werecomparedbyStudent’s t-test. Tocontrolforthepos-
16
The
average age
of children in the neurofibro-
groups
sibility of interactions between ADHD and neurofibromatosis,
mean corpus callosum measures ofthe control also were
years.
matosisgroupwas10.6years(standarddeviation, 2.8years)
an
of11.0
group
comparedto
childreninthecontrolgroup (Table 1). Thisdifferencewas
not the two neurofibro-
averageage
years (SD, 2.7years) for
comparedto subgroups ofsubjects withneurofibromatosiswith-
out ADHD (neurofibromatosis alone) and co-occurring ADHD
statistically significant. Further,
(
A
neurofibromatosisplusADHD)byanalysisofvariance (ANOVA).
series of
matosis groups (neurofibromatosis alone versus neuro-
fibromatosis not differ with
=
a
posterioritests
was
performedto clarify the results
plus ADHD) did
significantly
of the ANOVA. Frequencydatawere comparedwith X2 analyses.
to
education
orsocioeconomic
respect
status37
age(P .12),
(P .6),
=
P
=
The
didnotdifferinterms
(
X2
6.0,
.35).
groups
ParentandTeacherBehavioral Questionnaires
Tofacilitate accurateplacementofsubjectswithneurofibromatosis
intoADHDandnon-ADHDgroups, parentswereaskedto complete
ofoverallintellectual
=
MeanWechsler
functioning (P .37).
Full-ScaleIQscoreforcontrolsubjects
was100.2
(SD, 9.5),
to 97.9
for
subjects in
(SD, 14.3) forsubjectsin
the neurofibro-
compared
(SD, 17.2)
and92.5
a
questionnaire assessing thepresence and severity ofbehaviors
relatedtoADHDintheirchildren. TheBehaviorRatingScale con-
sist of18
the 18 criteriain theDiag-
matosisalone
the
group
neurofibromatosis
ADHD
MeanWechslerVer-
plus
scoreswere101.6
group.
statementscorrespondingto
nostic andStatistical Manual ofMental Disorders, 4th edition
balIQ
SD, 12.6)
neurofibromatosis
and89.9
and
(SD, 11.3), 97.8 (SD, 18.6),
for the
neurofibromatosis
(
control,
plus
alone,
to
ADHD. Statements wererated on
a
ADHD
Mean
(
DSM-W)33 used
diagnose
groups, respectively.
Likert scale from
0
(&dquo;not true at all or
to
6
(&dquo;very true or
Performance
and97.4
IQscores
were98.6
seldom&dquo;)
(SD, 10.2), J7.0 (SD, 16.2),
neurofibromatosis
A
behaviorwasconsidered
presentin
a
childifit received
forthe
always&dquo;).
(SD, 17.3)
control,
alone,
a
rating of3 (&dquo;somewhat trueor
ormore. Eachchild
andneurofibromatosis
ADHD
groups.
sometimes&dquo;)
plus
wasthenclassified as
eitherhaving
ADHDornot onthe basis of
Corpus CallosumMeasurements
Theneurofibromatosis
demonstratedatotal callosal
group
area
than that of the control
significantly larger
group
differenceswerealsodemon-
P
(
t52 = 2.91,
< .O1).
Significant
stratedforthree ofthe seven
areas
the
regional
(Figure 1):
=
rostral body(P
posterior midbody (P
.002), anterior midbody(P
.0001), and
=
with
with neuro-
.002),
subjects
fibromatosis consistently evidencinglarger areas.
Toclarifytheseresults, theneurofibromatosis
was
group
subdivided into neurofibromatosis alone and neurofibro-
matosis
ADHD
ANOVArevealed
plus
groups.
significant
differencesintotal callosalareabetweennormalcontrolsub-
neurofibromatosis
jects, subjects diagnosed with
alone,
(F(2,5 1) =
andsubjectswithneurofibromatosis
ADHD
plus
P
<
ofthe rawvaluesofthe
4.3,
.05) (Table2). Comparison
sevencallosalregionsagainrevealed
differences
significant
anteriormidbody
.01),
fortherostralbody
=
5.8,
P
<
Figure 1.
Rostrum (orbital prefrontal, inferior premotor); 2, Genu (prefrontal);
Rostral body (premotor, supplementary motor); 4, Anterior mid-
body (motor); 5, Posterior midbody(somaesthetic, posterior parietal);
Isthmus (superiortemporal, posterior parietal); 7, Splenium (occip-
ital, inferior temporal). (Adapted fromWitelson.3z)
The seven areas of the corpus callosum measured. 1,
(
F(2,51)
12.4, P <
.001), andposteriormidbody
(F(2,51) =
(
F(2,51) =
3,
P
5
.3,
< .owl).
The Scheff6 test wasusedto
the results ofthe
clarify
6,
ANOVA. Analysis revealed that meanareas of the rostral
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9
3
Table 1.
Subject Characteristics
body and anterior midbody were significantly larger
for
BehavioralAssessments
The score derived from the Behavior Rating Scale was
basedon18questions, eachwithpossibleratingsfrom
6. Thus, the total possible score on the Behavior Rating
Scale wasfrom
to 108, withhigherscorescorresponding
subjects in
the neurofibromatosis alone and neurofibro-
ADHD
matosis
groupsascomparedto
posterior midbody, only subjects in the neuro-
control
0to
plus
subjects.
For the
fibromatosisalonegroupdemonstratedsignificantly
areas thancontrol
0
larger
the dif-
area,
Fortotal callosal
to greater severity ofADHDsymptoms. Themean Behav-
ior Rating Scale score for the control subjects was 32.2
(SD, 25.8). The meanBehavior Rating Scale score for the
combinedneurofibromatosisgroupswas39.5 (SD, 31.3). Sub-
jects in the neurofibromatosis plus ADHDgroup received
subjects.
ference betweenthe neurofibromatosisplus ADHD
group
and control subjects was
with subjects in the
group evidencing larger
significant,
neurofibromatosis
ADHD
plus
areas. Differences between the neurofibromatosis alone
andneurofibromatosis
ADHD
werenotstatis-
a
meanscoreof73.6 (SD, 16.5) versus 19.1 (SD, 16.5) inthe
plus
any
groups
of the callosal measurements
for
non-ADHDgroup
-9.03,
P
<
.001).
OntheChildBehav-
tically significant
(t3o
=
obtained. To control for possible variation in brain size
withneurofibromatosis alone andthose
iorChecklist, parentsofchildrenwithneurofibromatosisplus
ADHDreportedsignificantlymoreattentionproblemsthan
did the parents of children with neurofibromatosis alone
between
subjects
withneurofibromatosisplusADHD,ratios ofcorpuscallo-
sumareatototalbrainareawerecalculatedand
(Child BehaviorChecklist-attention:
-6.00,
P
<
.001;
compared.
significant differ-
t34
This
procedure also failed to
reveal any
Table3). Similarly, onthePersonalityInventoryforChildren,
theparentsofchildrenwithneurofibromatosisplusADHD
reportedgreaterlevels of hyperactivity(PersonalityInven-
ences betweenthe neurofibromatosis
for any cor-
groups
callosum
puscallosumregion (ortotal corpus
There was correlation of
area).
and total
a
toryfor Children-hyperactivity:
-3.2,
P
<
.01).
Incon-
significant
age
plus
the association
t32
callosumareafortheneurofibromatosis
ADHD
trast to parent ratings, teacher responses on the Teacher
corpus
group (r -0.72,
of andtotalcorpuscallosumareawasnot
=
P
=
In
Formindicatedthatchildrenwithneurofibromato-
Report
.008).
comparison,
for
sisplusADHDdidnothavemoresevereattentionproblems
age
significant
=
the neurofibromatosis alone
=
.01,
P
than did children with neurofibromatosis alone (Teacher
group (r
.94).
ReportForm-attention:
P
.6).
GenderDifferences in Callosal Area
The neurofibromatosis alone and neurofibromatosis
ADHD
Relative to the girls in the sample, boys consistently
receivedhigherscoresonthebehavioralmeasuresofatten-
tion andhyperactivity (suggesting moreproblemsin these
areas), although these differences were not statistically
plus
didnotdifferwithrespectto genderdistrib-
groups
ution. Across the neurofibromatosis
groups, corpus
callo-
sumareas were
consistentlylargerforboysin
the
significant.
sample,
with statistically significant differences noted forthe ros-
Ofthe 12subjectsintheneurofibromatosisplusADHD
trum
P
<
anteriormidbody
2.5,
P
group,
8
weretakingmedication (Ritalin, Cylert, orpemo-
(t
34 = 2.1,
.05),
(tl4
=
< .05),
and
=
P
<
Total callosal
line). Noneofthe subjects in the neurofibromatosis alone
or control groups wastakingmedication.
posterior midbody (t34
2.8,
.01).
areawasalso
significantlylargerforboys(t&dquo;4
P
<
2.3,
.05).
Table 2. MagneticResonance Imaging Measurements of CorpusCallosum Regions*
*Area in mm2.
TSignificant at
P
.01.
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9
4
Table 3.
BehavioralAssessments
*
Significant at
P
<
.01.
Relation ofCorpus CallosumandBehavioralMeasures
of ADHDinchildrenwithneurofibromatosiscouldbelinked
to differences in brain or
Across the neurofibromatosis
teacher
of
groups,
ratings
andthesize of
quantifiable
both.
Theseresultsare
structure, function,
attention
(
TeacherReportForm-attention)
the spleniumwere
andnegatively, correlated
intriguing, asthey
seemcountertothe
significantly,
.03), suggesting
=
P
=
thatmore
severeattentionprob-
(
r
-.45,
results ofsimilar studies in individuals withADHD,which
lemsareassociatedwithsmallersplenial size. Forsubjects
have documented smaller
callosum areas
regional corpus
relative to normal controls.27-2s,31 Ratherthan
in the neurofibromatosis alone
a
corre-
a
group,
lation was found between Personality
significant
suggesting
these results could reflect real differences in the
for Chil-
Inventory
conflict,
dren-hyperactivityratingsandthe size ofthespleniumof
the corpus callosum
presentationandmanifestationof ADHDinindividualswith
neurofibromatosis
=
P
=
with
(r
.47,
.02),
larger splenial
hyperactivity.
ADHD
comparedto idiopathic
ADHD.
area
being associated
with
of
Someconsideration ofthe developmentofthe corpus
callosum andits influence on function be
higherratings
For
subjectsin
theneurofibromatosis
plus
group,
cognitive
might
more severe attention
problems as reported
on the Child
helpful in elucidating
these differences. Studies of brain
miniature version ofthe
BehaviorChecklistwereassociatedwithsmallertotal cor-
development have shown that a
callosum size
P
In
teacher
that
corpus
adult callosum is
present by the 17th gestational
pus
(r
-.59,
.03).
addition,
suggested
on the Teacher
Form
week. 38
Althoughthere
areno incallosal
responses
Report
significantchanges
to of andelemen-
increased attention
atedwithsmaller
in the classroom are associ-
size between
5
problems
preschool (up
years
age)
a
there is dramatic
=
P
andsmallertotal
splenial (r -.69,
-.67,
= .02)
tary
schoolchildren
(6
elementary school
to 10
yearsold),
collosal
P
.03) size.
increase between
children and adoles-
studies have doc-
(
r
cents
to 15years
(
11
old) .39 Longitudinal
DISCUSSION
umented continued
of this structure
through the
growth
seconddecadeoflife
Developmentalabnormalities
characteristicofseveral
Althoughseveralstudiescomparingchildren
withADHDand
ofthe
callosumare
also
corpus
normal children have documented functional and struc-
tural differences in the corpus callosum andrelated these
the behavioral differences betweenthese
neurologic syndromesbutare
in otherwise normal chil-
present as incidental findings
findings to
dren.38 Partial
agenesis ofthe corpus
monlyinvolves theposteriorregions, 38 butcasesinvolving
the havebeendocumented. 41,42
callosum morecom-
pop-
ulations, suchfindings mightnot holdtrue across popula-
tions of children with various
knownto affect
anteriorregions
diagnoses
central nervous system function. For example,
Neuropsy-
although
et all’ documentedsmaller
chologic impairments in patients with this developmental
Giedd et a129 and
anomaly include visuospatial deficits, 43 and it has been
Baumgardner
rostrum androstral bodyareas in subjects withADHDas
to normalsubjects, wefailed to find
argued
in neuronal resources.44
that such
impairments are
Impairments in
domain also have been documented
the result of
a
shortage
visuospatial
children with
among
compared
significant
differencesbetweenchildren withneurofibromatosis
the
plus
ADHDandthosewithneurofibromatosisalone. Volumetric
neurofibromatosis-1.~In
ourgroup
ofchildrenwithneuro-
andtotalcallosal
MRI data revealed
total and
fibromatosisplusADHD,smallersplenial
areas were associated with more severe attention
significantly larger
cross-sectional corpus callosum areas for
regional
with
subjects
prob-
neurofibromatosis
to the control
bothalone
and
withADHD)ascompared
differences were not
lems.
Althoughthechildren
withneurofibromatosisincluded
(
group. Although the
in this
donot evidence
agenesis ofthe corpus
callo-
study
the
further
revealed that subjects in the
andfunctional similarities between
significant,
analysis
sum,
morphologic
neurofibromatosisplusADHDgroupevidenced
and
largertotal
thesepatient groupsis interesting.
corpus callosum areas relative to subjects
Inthis
the
callosumwasthestructureof
corpus
regional
study,
butthe
withneurofibromatosis alone.
largersize
ofthiswhite-mattertract could
interest,
Behavioral datawerealso
Acrossthe neu-
be
a reflection of broader cortical variation in the neu-
interesting.
rofibromatosis
wefoundthatmoresevereattention
rofibromatosis
Fewstudies have
on
groups,
problems were associated with smaller splenial measure-
mentsandsmallertotal
callosumareas. The
population.
reported
the brain morphologic characteristics of subjects with
corpus
icant associations ofattentionproblems
areastrengthensthe casethatatleast someofthefeatures
signif-
neurofibromatosis. Saidand
colleagues45
found
significant
white-matter
andtotal callosal
increases in total
brainvolume, particularly
volume, in
22 children with neurofibromatosis relative to
Downloaded from jcn.sagepub.com at WESTERN OREGON UNIVERSITY on June 1, 2015

95
2
0
normalcomparisonsubjects. Wehavesinceobtainedvol-
andthosewithneurofibromatosisplusADHDthatdifferfrom
thosereportedin studiesofsubjectswithADHDwhodonot
haveneurofibromatosis. These results are not necessarily
conflicting. It couldbethatthepathophysiologyofattention
disordersin childrenwithneurofibromatosisis influenced
morebythe presence ofthe neurofibromatosis gene than
byobviousdifferencesincallosalmorphology. Furtherdef-
umetricdataon52 childrenwithneurofibromatosisand19
normal controls (unpublished data). Althoughtotal brain
volumewas
greaterin the subjectswithneu-
significantly
rofibromatosis, in contrast to Said et al, the variability is
attributableto greatergray-mattervolume. However, while
Said et al and our unpublished data suggest
significant
the research is far from con-
increases in brain
inition ofthe
uniquefeatures
ofneurofibromatosis-related
volume,
clusive and conflicting results have been reported. For
example, MacDonald and Schaefer~6 reported relative
ADHD(versusnon-neurofibromatosis-relatedADHD)could
providemorecluesto themechanismofADHDin the gen-
a
decrease in supratentorial brain size andmidline cerebel-
lumofpatients withneurofibromatosisrelative to normal
controls.
eral
population. However, a
search for
a
neu-
single
roanatomic or biochemical marker for ADHD could be
futile. It is morelikelythatthebehavioralmanifestationof
Details ofthe nature andmechanismsofattention dif-
ADHDisinfluencedbyseveralfactors. While
improvements
techniqueshaveallowedusto
ficulties inneurofibromatosisremainuncertain. It is
inneuroimaging
the
compare
possible
ofchildrenarisefrom
thatattentiondisordersinthis
brainstructuresofchildrenwithneurofibromatosiswithand
group
different mechanisms than do attention disorders in indi-
vidualswithoutneurofibromatosis. Currentstudies ofcor-
without ADHD, more extensive
biochemical factors
of the
investigation
and behavioral
underlying structural
callosum
morphologyin
children withADHD
brain
differences is needed.
pus
that
suggest
results
pathologic developmentofspecific
pathologic function. Subsequent brain growth
regions
in
is then
Acknowledgments
accompanied by impaired development of transcollosal
projectionsbetweenbilaterallyrepresentedregions.
The authors wouldlike to acknowledgethe dedicated assistance ofMurlidhar
Tekchandaniinthe acquisitionandprocessingofthemagneticresonanceimag-
ing data. Supported by grant NS-31950 fromthe National Institutes of Health,
Bethesda, MD, andbysupport fromthe Texas Neurofibromatosis Foundation,
Whether
these structural variants disrupt
remainstobeseen.
cortical function
higher
However,the differences
in
cal-
corpus
Dallas,
TX.
losumsize seeninsubjectswithneurofibromatosisrelative
to control subjects
implies that hemispheric morphologic
differencescouldbeassociatedwiththedisorder. Ourfind-
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