Pediatr Radiol (2003) 33: 334–345

DOI 10.1007/s00247-003-0891-z ORIGINAL ARTICLE

Gustavo Soto-Ares
Béatrice Joyes
MRI in children with mental retardation
Marie-Pierre Lemaı̂tre
Louis Vallée
Jean-Pierre Pruvo

Received: 29 August 2002

Accepted: 17 January 2003
Published online: 11 March 2003

Springer-Verlag 2003
G. Soto-Ares (&) Æ B. Joyes Æ J.-P. Pruvo
Department of Neuroradiology,
Hôpital Roger Salengro, CHRU Lille,
59037 Lille, France
E-mail: gsotoares@chru-lille.fr
Tel.: +33-3-20446468
Fax: +33-3-20446488
M.-P. Lemaı̂tre Æ L. Vallée
Department of Paediatric Neurology,
Hôpital Roger Salengro,
CHRU Lille, Lille, France
Abstract Background: In mental re-
tardation (MR) an aetiological
diagnosis is not always obtained
despite a detailed history, physical
examination and metabolic or
genetic investigations. In some of
these patients, MRI is recommend-
ed and may identify subtle abnor-
mal brain findings. Objective: We
reviewed the cerebral MRI of
children with non-specific mental
retardation in an attempt to estab-
lish a neuroanatomical picture of
this disorder. Materials and
methods: Thirty children with
non-specific MR were selected to
undergo cerebral MRI. The exam-
ination included supratentorial axi-
al slices, mid-sagittal images and
posterior fossa coronal images.
Brain malformations, midline and
cerebellar abnormalities were stud-
ied. Results: In 27 of 30 patients,
the neuroimaging evaluation re-
vealed a relatively high incidence of
cerebral and posterior fossa abnor-
malities. The most frequent were:
dysplasia of the corpus callosum
(46%; hypoplasia, short corpus
callosum and vertical splenium),
partially opened septum pellucidum
and/or cavum vergae (33%),
ventriculomegaly (33%), cerebral
cortical dysplasia (23%), subarach-
noid space enlargement (16.6%),
vermian hypoplasia (33%), cerebel-
lar and/or vermian disorganised
folia (20%), and subarachnoid
spaces enlargement in the posterior
fossa (20%). Other anomalies were:
enlarged Virchow-Robin spaces
(10%), white matter anomalies
(10%) and cerebellar or vermian
atrophy. Conclusions: MRI has
shown a high incidence of subtle
cerebral abnormalities and unex-
pected minor forms of cerebellar
cortical dysplasia. Even if most of
these abnormalities are considered
as subtle markers of brain dysgen-
esis, their role in the pathogenesis of
mental retardation needs further
investigation.
Keywords MRI Æ Brain Æ
Cerebellum Æ Malformations Æ
Cortical dysplasia Æ Mental
retardation

Introduction syndrome or broader disorder [1, 2]. Even if a number of

Mental retardation (MR) is a human disability charac-
terised by cognitive impairment existing concurrently
with limitations in two or more adaptive skills. It is
generally accepted that MR occurs in 2–3% of the
population as an isolated finding or as a part of a
factors (single-gene disorders or chromosome abnor-
malities, congenital malformation, fetal infection, tox-
ins, metabolic disorders, prematurity) can cause MR,
the aetiology is not identified in 30–50% of cases [2, 3].
Clinical, laboratory and radiological evaluation of the
aetiology is necessary to answer questions regarding

management, prognosis and recurrence risks, and they
are also necessary to devise prevention strategies [2].
There have been few neuroimaging studies on non-
specific MR. The descriptions depend on patient selec-
tion criteria and on consideration of MR as an isolated
finding or as a part of a syndrome. MRI has shown
minimal abnormalities: mega cisterna magna, hypopla-
sia of the corpus callosum, wide cavum septum pelluci-
dum, white matter alterations, heterotopia and
cerebellar hypoplasia [2, 4, 5, 6]. Some are generally
considered as incidental findings and/or normal ana-
tomical variants. Even if MRI is usually not helpful for
understanding either the cause of these brain abnor-
malities or their relationship with MR [7], a consensus
conference on evaluation of MR recommended large
uniform MRI studies. Neuroimaging should be consid-
ered in patients with abnormal head size or shape,
craniofacial malformation, somatic anomalies, neuro-
cutaneous findings, seizures or neurological signs [1, 2].
The objective of these studies is to confirm that abnor-
malities commonly found in retarded individuals are
incriminated in the pathogenesis of this disorder.
Using currently available techniques, we could define
subtle dysgenetic abnormalities of the cerebral hemi-
spheres and cerebellar development. Our purpose was to
study the type and frequency of brain abnormalities in
children with non-specific MR in order to establish a
neuroanatomical picture of this disorder. Because these
subtle morphological changes could represent markers
of brain dysgenesis [3], the recognition of minor brain
abnormalities could probably be the first step in un-
derstanding the pathogenesis of MR.
Materials and methods
We reviewed the MRI findings of 30 patients with non-specific MR.
Table 1 documents their general clinical background and presen-
tation. They were selected from a cohort of 81 children (47 boys, 34
girls; M:F 1.4/1; mean age 5.2 years; range 1 month to 15.3 years)
referred to the university-based paediatric neurologists of our in-
stitution for evaluation of developmental delay between November
1999 and June 2000. A group of paediatric neuropsychologists
evaluated the children with impaired cognitive function as regards
their intellectual skills using neuropsychological tests and devel-
opmental assessment. MR was severe in 36 (44.5%) patients
(IQ<50) and moderate in 45 (55.5%; IQ 50–70). Further clinical,
metabolic and genetic investigations were carried out, including
infection and metabolic tests, otorhinolaryngological examination,
karyotype, and tests for fragile X, Angelman, Prader-Willi and Di
George syndromes. In patients with focal neurological deficits and/
or facial deformities (77 patients; 35 with severe MR and 42 with
moderate MR), neuroimaging was performed. Because access to
MRI was difficult compared with CT, 35 of 77 patients had a CT
scan and 42 of 77 had MRI.
Only patients with non-progressive MR were included if com-
plete clinical and MRI evaluations were available and if the aeti-
ological diagnosis before MRI remained unknown (n=29; 36%).
Patients with unavailable or incomplete MRI studies were excluded
(n=12/29 patients of unknown aetiology).
335
The cerebral MRI scans of 30 patients with cerebral malfor-
mations (n=13) and with mental retardation of unknown aeti-
ology (n=17) were reviewed by two experienced neuroradiologists
blinded to the aetiology of MR. They assessed cerebral and
cerebellar malformations, and minor brain abnormalities.
According to the descriptions of normal MRI brain anatomy
reported by Barkovich [8], we have considered as minor abnor-
malities: enlargement of subarachnoid spaces with or without
macrocephaly, minor abnormalities of the corpus callosum
including short corpus callosum or vertical splenium [8, 9], cere-
bellar atrophy defined as enlarged cerebellar sulci (>1 mm), and
enlargement of the posterior fossa subarachnoid spaces (mega
cisterna magna and supravermian cistern) with or without
enlargement of the fourth ventricle. Other abnormalities were:
prominent and diffuse enlargement of the perivascular fluid
spaces (Virchow-Robin spaces), ventricular enlargement consid-
ered according to standard linear measurements (Evan’s ratio,
Huckman’s measurement, minimal lateral ventricular width and
lateral ventricular span at the body) [10] and patchy or diffuse
white-matter hyperintensities.
MRI examinations were performed in a 1.5-T magnet. Axial,
sagittal and coronal images were acquired using turbo spin-echo
(TSE) T2-weighted (TW-2) sequence (slice thickness 5, 3 and 4 mm,
respectively). The acquisition parameters were TR/TE 5,000/120,
NEX 2, FOV 20–25 cm, matrix 300·512. An inversion recovery
sequence (TR/TI/TE 11,520/400/60, NEX 2, FOV 20–25 cm, ma-
trix 198·512) was performed in one or two orthogonal planes ac-
cording to the results of the previous sequences. The total scanning
time was about 20 min per patient. Children under 1 year of age or
10 kg body weight were sedated using chloral hydrate 50–100 mg/
kg; anaesthesia using a laryngeal mask was used for the other
patients.
Results
In our group of 30 patients, clinical, metabolic and ge-
netic investigations were positive in 2. One had dupli-
cation of chromosome 2 (case 7) and 1 patient had a
disorder of amino acids and organic acids (case 16).
According to the MRI findings, three groups could be
defined. They are summarised in Tables 2, 3, and 4,
which compare their clinical presentations and MRI
findings. Brain malformations were diagnosed in 13
patients (16%).
In the first group, the posterior fossa was normal or
demonstrated non-specific anomalies and was associated
with minimal supratentorial abnormalities (n=9; cases
1–9). MRI abnormalities were: enlarged subarachnoid
spaces, white matter hyperintensities and tonsillar
ectopia. Supratentorial anomalies were: dysgenesis of
the corpus callosum (n=4; hypoplasia or vertical
orientation of the splenium), septum pellucidum or
cavum vergae cysts (n=3), ventricular enlargement
(n=2) and one case each of white matter hyperintensi-
ties and enlargement of subarachnoid and Virchow-
Robin spaces.
A second group comprised patients with vermian or
cerebellar hypoplasia or atrophy associated with subtle
cerebral anomalies (n=9; cases 10–18). MRI abnor-
malities were: cerebellar or vermian atrophy (n=6;
Fig. 1), vermian hypoplasia (n=3), enlarged fourth
 336

Table 1 Clinical background and IQ

Case Sex/age Prenatal course Clinical background (family) Clinical background (personal) MR
(years,
months)

1 M/10 Unknown.Brazilian adopted child Unknown Absent IQ 53 moderate

2 F/8 Fever at 5th month of pregnancy Father has Glanzmann None IQ 41 severe
thrombopathy
3 F/6,7 None Cousin with MR Cryptogenic epilepsy IQ 63 moderate
4 M/0,11 None Maternal alcohol West syndrome IQ 40 severe
5 F/7,5 None None None IQ 45 severe
6 F/12,5 None Maternal epilepsy Partial complex epilepsy IQ 57 moderate
7 F/1,2 Mother-fetal infection Family history of MR Axial hypotonia at 24 h of age IQ 62 moderate
8 F/3,10 None None Febrile convulsions at 9 months IQ 45 severe
9 M/6,1 Anti-hypertensive treatment None Surgery at 3 weeks for pyloric stenosis IQ 65 moderate
10 M/6,5 Maternal hypertension Uncle mentally retarded Transient Respiratory distress IQ 45 severe
and hypocalcaemia; oral infections
and anaemia
11 F/1,7 Maternal hypertension; born at 36 weeks’ gestation None Surgery for oesophageal atresia IQ 53 moderate
12 F/5,6 None None Growth delay IQ 50 moderate
13 M/4,4 Twin pregnancy. Born at 34 weeks’ gestation None CIV Febrile convulsions at 2 years IQ 60 moderate
14 M/3 None None None IQ 72 moderate
15 M/7,10 None Parental consanguinity Previous cyanosis IQ 51 moderate
16 F/3,2 None None Partial convulsions IQ 40 severe
17 M/12,5 None MR in family members Obesity IQ 40 severe
18 M/5,2 Polyhydramnios; caesarean section MR in mother’s cousin Partial convulsions; hypocalcaemia IQ 40 severe
19 F/5,4 Antenatal haemorrhage at 6 months Parental consanguinity; 2 brothers Measles infection IQ 52 moderate
with developmental delay
and dystonia died
20 M/2,2 Absent fetal movements in last week Febrile convulsions in father None IQ 50 severe
21 M/1,3 Antenatal haemorrhage 1–4 months; caesarean section None None IQ 66 moderate
22 F/2 Apgar scores 3/7/10 MR in family members None IQ 72 moderate
23 M/6,3 Maternal alcohol; born at home at 36 weeks Alcohol Hypocal caemia; absent eye pursuit IQ 40 severe
24 M/2,10 Ventriculomegaly MR in uncle Oedema of extremities IQ 45 severe
25 M/7,2 Viral infections, lipothymia; Apgar score 3/10/10 None Cyanosis and partial epilepsy IQ 54 moderate
26 F/1,11 Poly hydramnios; caesarean section; Apgar score 8/10/10 Uncle retarded Hypotonia; ecchymoses; febrile convulsion IQ 54 moderate
27 F/4,1 Viral infection at 5 months; caesarean section MR in both parental families None IQ 45 severe
28 M/12,8 Born at 33 weeks; Apgar score 3/4 during resuscitation Uncle and cousins with MR Hyperkinesia IQ 59 moderate
29 F/15,11 None None Partial epilepsy since 6 years of age IQ 51 moderate
30 M/4,11 None Cousin with MR None IQ 53 moderate
 337

Table 2 Group 1. Clinical and MRI findings

Case Clinical Posterior fossa MRI Supratentorial MRI

1 Facial and extremity dysmorphism; Amygdalar ectopia Normal

motor disturbances; hypotonia
2 Small mandibule; hypochromic spot at left Normal Corpus callosum Hypoplasia
shoulder; left monoparesis; strabismus
3 Epilepsy Normal Corpus callosum hypoplasia and verticalised
4 Microcephaly; facial dysmorphism; White-matter Corpus callosum hypoplasia; ventricular enlargement;
West syndrome; tetrapyramidal signs; hyperintensities white-matter hyperintensities
hypertonia
5 Absent Normal Septum pellucidum cyst
6 Left pyramidal syndrome Normal Enlarged Virchow-Robin spaces
7 Ohtahara syndrome; spastic tetraparesis; Enlarged posterior fossa Enlarged subarachnoid spaces and ventricles;
axial hypotonia; swallowing difficulties subarachnoid spaces septum pellucidum cyst; corpus callosum hypoplasia
8 Craniostenosis; facial dysmorphism; Normal Enlarged subarachnoid spaces and ventricles;
minor cerebellar syndrome cavum vergae; corpus callosum hypoplasia
9 Retrognathia; minor skeletal abnormalities; Normal Moderate ventricular enlargement; cavum vergae
motor disturbances; hypotonia

Table 3 Group 2. Clinical and MRI findings

Case Clinical Posteriorfossa MRI Supratentorial MRI

10 Facial deformities; hypertelorism; Cerebellar atrophy Asymmetrical lateral ventricles

thin upper lip without philtrum;
large ears; bilateral clinodactyly
11 Tetrapyramidal syndrome
12 Facial deformities; hypertelorism;
epicanthus; triangular-shaped mouth;
diadochokinesia
13 Left pyramidal syndrome
14 Microcephaly; plagiocephaly; hypotonia;
ataxia with cerebellar syndrome
15 Microcephaly; retrognathia; cerebellar
syndrome
16 Arched palate; prominent forehead;
pyramidal syndrome; asymmetrical hypotonia mega cisterna magna
17 Retrognathia; round face; obesity; abnormal
dentition; clinodactyly; high arched palate
18 Microcephaly; nose and ear malformations;
epicanthus; hypotonia; ataxia
Superior vermis atrophy
Superior vermis atrophy
Fourth ventricle and posterior
fossa subarachnoid spaces enlarged;
vermian atrophy
Fourth ventricle and posterior fossa
subarachnoid spaces enlarged
with vermian atrophy
Inferior vermis hypoplasia;
cerebellar atrophy
Inferior vermis hypoplasia;
Vermis hypoplasia
Vermis hypoplasia
Enlarged subarachnoid spaces;
corpus callosum hypoplasia
Enlarged occipital horns of lateral
ventricles
Septum pellucidum cyst
Posterior corpus callosum
verticalized
Septum pellucidum cyst; isolated
focus of white-matter hyperintensity
Enlarged occipital horns of lateral
ventricles; corpus callosum hypoplasia;
enlarged Virchow-Robin spaces
Septum pellucidum cyst; corpus
callosum hypoplasia
Septum pellucidum cyst; frontal
white-matter hyperintensities

ventricle or subarachnoid spaces (n=2) and one case of
mega cisterna magna. Supratentorial anomalies were:
corpus callosum hypoplasia (n=2), vertically orientated
splenium of the corpus callosum (n=1; Fig. 2), septum
pellucidum cysts (n=3; Fig. 3), ventricle enlargement or
asymmetry (n=3), white matter hyperintensities (n=2)
and one case of Virchow-Robin enlargement.
The third group included patients with vermian
hypoplasia or cerebellar cortical dysplasia (CDD) asso-
ciated with severe brain malformations (n=9; cases
19–27). In this group the posterior fossa anomalies were:
CCD within the cerebellar hemispheres or vermis (n=6;
Figs. 4, 5, 6), vermian anomalies including atrophy,
hypoplasia or enlargement (n=5), and one case each of
the following: pontine hypoplasia, unilateral tentorial
agenesis, Dandy-Walker variant and cerebellar heterot-
opia. Supratentorial anomalies were: anomalies of the
corpus callosum (short corpus callosum n=2, hypopla-
sia n=3, Fig. 7), enlarged ventricles (n=4), enlargement
of subarachnoid spaces (n=1), cavum vergae (n=2),
hemimegalencephaly (n=2), pachygyria (n=2; Fig. 8),
polymicrogyria (n=1; Fig. 9), enlarged Virchow Robin
spaces (n=1), white-matter hyperintensities (n=1) and
ventricular asymmetry (n=1).
Our results revealed that MRI was normal in 10% of
cases, anomalies of the posterior fossa and supratento-
338

rial compartment were associated in 47% of cases,

infoldings, heterotopia and enlarged Virchow-Robin spaces

whereas they were isolated to the posterior fossa in 10%

Cavum vergae; parietal atrophy; ventricular asymmetry

of cases and to the supratentorial compartment in 33%

Probable right hemimegalencephaly: right hemispheric

Ventricular enlargement; corpus callosum hypoplasia;

Ventricular enlargement; corpus callosum hypoplasia;

enlargement with internal occipito-temporal cortical
of cases. In the posterior fossa the most frequent

cerebellar cortical dysplasia: cortical thinning polymicrogyria, and white-matter hyperintensities

and frontal subarachnoid spaces; cavum vergae
anomalies were: vermian hypoplasia (33.3%), enlarge-

Corpu scallosum hypoplasia; enlarged ventricles

Short corpus callosum; ventricular enlargement

ment of subarachnoid spaces (20%), CCD (20%),
enlargement of the fourth ventricle (16.6%), vermian
atrophy (16.6%) and cerebellar atrophy (6.6%). The
most frequent supratentorial anomalies were: hypopla-
sia of the corpus callosum (43.3%), ventricular

and right hemimegalencephaly

enlargement (33.3%), cavum vergae or septum pelluci-
dum cysts (33.3%), cortical dysplasias (23.3%) enlarge-
ment of subarachnoid spaces (16.6%), enlargement of
Short corpus callosum

Virchow-Robin spaces (10%) and white-matter abnor-

Supratentorial MRI

mal signal (10%).

From the 17 patients previously diagnosed with MR
pachygyria

of unknown aetiology (cases 1–7, 10–14, 19, 20, 28–30),

Pachygyria
only three had normal MRI findings (cases 28–30).
Normal

Discussion
medial vermian fissure and enlarged cortex;

Cerebellar cortical dysplasia; right cerebellar

cortex enlargement; left tentorial agenesis
Cerebellar and vermian cortical dysplasia;

Dandy-Walker variant; cerebellar cortical

Cerebellar and vermian cortical dysplasia

In accordance with the established literature, our study

Enlarged vermis; subarachnoid spaces

and heterotopia; vermian hypoplasia

white-matter arborization suggesting

showed a high frequency of brain malformations in

Inferior vermis and pons hypoplasia;
Superior vermis atrophy; abnormal

mental retardation [2, 4, 5, 6]. We found two types of

brain abnormalities in mentally retarded patients: severe
malformations, especially cortical dysplasias, and minor
cerebral or cerebellar abnormalities. In the latter, the
abnormalities were of different types and often associ-
vermian hypoplasia
Posterior fossa MRI

ated. The most frequent supratentorial findings were:

cortical dysplasia

corpus callosum hypoplasia (43.3%), ventriculomegaly

(33.3%), enlargement of subarachnoid spaces (16.6%),
dysplasia

cavum vergae or septum pellucidum cysts (33.3%) and

Normal

Strabismus; hypermetropia; retrognathia; plagiocephaly; Normal

absent

cortical dysplasias (23.3%). Compared to previous

reports on non-specific MR, we have found a higher
incidence of posterior fossa abnormalities. These
include: vermian hypoplasia (33.3%), vermian atrophy
clinodactyly; short palate; hypotonia; cerebellar signs
retrognathia; hypotonia; ataxia; pyramidal syndrome

arched palate; hypotonia; tetrapyramidal syndrome

abnormal movements; tetraparesis; axial hypotonia

(16.6%), enlargement of posterior fossa subarachnoid

Multiple minor facial abnormalities; hair fragility;
Minor facial abnormalities: forehead, nose, ears;

spaces (20%), enlarged fourth ventricle (16.6%) and

Partialepilepsy; hypotonia; cerebellar syndrome

cerebellar hemispheric atrophy (6.6%). Furthermore, we

Talipes; epicanthus; bilateral enophthalmia;

Microcephaly; absent eye pursuit; deafness;

found CCD in 20%, which to our knowledge has never

prominent forehead; thin lips; hypotonia

tetrapyramidal and cerebellar syndrome

High arched palate; prominent forehead;
Table 4 Group 3. Clinical and MRI findings

Epicanthus; minor facial abnormalities;

been reported before in MR, and also a very high inci-

clinodactyly; strabismus; hypotonia;

dence (63.3%) of craniofacial dysmorphism and/or

cerebellar signs; right-sided deficit

multiple somatic anomalies associated with MR.

Brain dysgenesis is one of the most common diag-
Microcephaly; tetrapyramidal
syndrome with dystonia and

nostic categories in MR of unknown aetiology [5].

extrapyramidal syndrome

Shaefer et al. [11] predicted that many findings, repre-

senting markers of brain dysgenesis, will be better
identified with progression in neuroimaging techniques.
Our results confirm this statement; abnormal MRI
findings were present in 90% of the patients. Some of
these findings include abnormalities that are generally
Case Clinical

accepted to be present in normal individuals or may be

the result of some other unknown underlying process.
However, some have been reported in association with
19

20

21

22

23

24

25

26

27

MR and are considered as markers of brain dysgenesis

 339

Fig. 1 a Case 15. Cerebellar

atrophy. Coronal T2-weighted
MRI shows diffuse enlargement
of vermian and cerebellar fis-
sures as compared with the
supratentorial subarachnoid
spaces. b Case 19. Cerebellar
vermian atrophy. Coronal T2-
weighted MRI shows superior
vermian atrophy with enlarged
transverse fissures

Fig. 3 Case 17. Absent closure of the septum pellucidum. Axial IR

T1-weighted MRI shows separation of the two thin plates or
’laminae’ of the interventricular septum

representing a risk for developmental delay—wide cav-

Fig. 2a, b Multiple minor posterior fossa and midline abnormal-
ities. a Sagittal T2-weighted MRI shows enlargement of the
posterior fossa cisterns and fourth ventricle associated with
vermian hypoplasia and minor posterior corpus callosum hypo-
plasia. As described by Gabrielli et al. [9], the splenium is thin and
vertically orientated. b A normal corpus callosum in another
patient with normal MRI
um septum pellucidum [12], corpus callosum hypoplasia
[4] and mega cisterna magna [3, 13].
One of the most important findings in our study is
that in patients with non-specific MR, subtle brain ab-
normalities are frequently multiple in the same patient
and are located at different sites, including cerebral
hemispheres (ventricles or cortex), the midline, the cer-
340

Fig. 4a–d Case 21. Cerebellar

cortical dysplasia. a Coronal
T2-weighted MRI shows bilat-
eral hypoplasia of the white
matter, thick cerebellar cortex
and vertically orientated folia,
compared with normal findings
(b). c Axial view shows verti-
cally orientated folia in the
cerebellar hemispheres (white
arrow) compared with normal
findings (d). Subarachnoid
spaces posterior to the amygd-
ala are difficult to distinguish
from bilateral clefts (black
arrow head)

ebellum or the vermis. Interpretation of these findings is
difficult because their significance is currently unclear
[12]. In order to investigate their pathogenic significance
in retarded individuals, a Consensus Conference rec-
ommended large uniform studies in ‘control’ subjects to
assess the incidence of these morphological findings in
the ‘normal population’ [2]. A limitation of our study is
the absence of a control group. The selection of a
paediatric ’control group’ is a difficult task. Patients
having MRI for other clinical indications may not only
be a poor representative cross-section of the general
population, but may also introduce a bias because of
their clinical symptoms. On the other hand, a group of
so-called ‘normal children’ is difficult to define. Ethical
considerations advocate against MRI screening of a
normal population, since minor abnormalities of no

Fig. 5a, b Case 23. Cerebellar
cortical dysplasia. a Coronal
T2-weighted MRI (compared
with normal findings in b)
shows defective, large or verti-
cal fissures with lack of normal
arborisation of the white matter
within the superior cerebellar
hemispheres leading to disor-
ganised foliation (cerebellar
polymicrogyria)
Fig. 6 Case 24. Vermian hypoplasia. Coronal IR T1-weighted
MRI shows vermian hypoplasia and superior vermian dysgenesis;
the transverse fissuration is absent and the cortex is thickened
(white arrow). These abnormalities are associated with supratento-
rial ventricular enlargement
specific significance or pathological findings without
clinical symptoms can be found in these children. For all
these reasons, we have compared our results to the an-
atomical and radiological descriptions of the normal
brain in children [8, 9], neuropathological literature [14,
15] and radiological studies. These studies have reported
tonsillar ectopia, ventriculomegaly, corpus callosum
hypoplasia and white matter hyperintensities [16], de-
layed myelination, white matter hyperintensities, corpus
callosum hypoplasia and migration malformations [17]
and microcephaly, cerebellar hypoplasia, corpus callo-
sum agenesis, and ’cerebral dysgenesis’ [18]. In agree-
ment with these reports, we have found minor and
multiple anomalies in 90% of patients.
In the diagnosis of non-specific MR, the role of MRI
has been clearly defined. Although the underlying cause
of brain dysgenesis remains mostly unknown, its radio-
341
logical diagnosis is often the first positive finding in the
evaluation of mentally retarded patients, excludes other
potentially more serious conditions and may avoid fur-
ther aetiological testing. In other cases, MRI may
identify specific features of a neurometabolic or degen-
erative disorder. Aetiological diagnosis not only modi-
fies the medical management of the child, but is also
needed to inform the family of prognosis, recurrence
risks and genetic counselling [1]. Thus, MRI must be
recommended if a diagnosis has not been achieved after
a detailed history and physical examination, and in
children with abnormal head size or shape, craniofacial
malformations and/or multiple somatic anomalies,
neurocutaneous findings, cerebral palsy or motor
asymmetry, seizures, loss or plateau of developmental
skills, and an intelligence quotient (IQ) below 50 [2].
According to the literature, the aetiology of severe MR
can be identified in 60–70% of affected individuals and
in 35–55% of patients with mild MR [12]. In a cohort of
60 patients, Majnemer and Shevell [5] made an aetio-
logical diagnosis in 63.3% of children, and they ex-
plained their results by the improvement of diagnostic
testing, especially neuroimaging and cytogenetic analy-
sis. They suggested that biological factors underlie the
majority of cases of MR. No single cause predominates;
cerebral dysgenesis, chromosomal anomalies (Down’s
syndrome, fragile X), toxins (fetal alcohol syndrome),
and hypoxic-ischaemic perinatal/postnatal encephalop-
athy account for two-thirds of aetiological diagnoses
[19]. In cases of unknown aetiology, a chromosomal
abnormality can be detected in as many as a quarter of
patients [20]. For this reason, even in retarded patients
with apparent well-being and a nearly normal pheno-
type, a Consensus Conference [2, 20] recommended
500-band level karyotyping to determine chromosome
aberrations.
Another limitation of our study is that the selection
of patients could be biased: the results of only 30 com-
plete MRI examinations have been analysed from a
342
Fig. 7a, b Case 4. Corpus callosum hypoplasia. a Sagittal T2-
weighted MRI shows a thin corpus callosum. Note enlargement of
the posterior fossa cisterns and fourth ventricle, and medial
vermian hypoplasia. b White-matter hyperintensities and moderate
hypoplasia of the white matter are associated with corpus callosum
hypoplasia in a 10-year, 5-month-old boy
cohort of 81 children with MR. In MR, we perform
MRI for some indications according to recommenda-
tions of the Conference of Consensus in MR [2]. Despite
this bias, our study suggests that in patients with non-
specific MR, subtle brain abnormalities are frequent and
may affect cerebral cortex or ventricles, the midline
Fig. 8 Case 27. Pachygyria. Axial T2-weighted MRI shows shallow
gyri and thickened cortex in frontal lobes
structures (corpus callosum and septum pellucidum) and
the posterior fossa (cerebellar hemispheres or vermis).
Although we were not able to define clinical phenotypes
in non-specific MR, relying on our MRI findings, we
defined three groups of patients. The first group includes
patients with normal posterior fossa and minor supra-
tentorial abnormalities. Clinical manifestations in this
group were variable, including neurological deficits
(44%), epilepsy (33%), motor disturbances (22%) and
hypotonia (22%), associated with facial and skeletal
abnormalities in 55% of cases. The second group in-
cludes patients with mild or moderate MR. Their clinical
manifestations were also variable, but they included
cerebellar signs (33.3%) and dysmorphism (77.7%). On
MRI they had subtle cerebral anomalies associated with
vermian or cerebellar hypoplasia or atrophy. Finally, we
distinguished a third group of patients who presented
frequently (77.7%) with hypotonia and congenital
ataxia associated with severe MR, neurological deficit
and dysmorphism. In these patients, MRI showed severe
brain malformations and vermian hypoplasia or CCD.
Although these morphological findings have previously
been described in MR, to our knowledge CCD has not
been previously reported in non-specific MR.
CCD has been reported in trisomy chromosomal
abnormalities [21, 22], congenital muscular dystrophies
and related syndromes [23], intrauterine infections [24,
25], gamma radiation [26], ethanol exposure [27] and in
cases with widespread brain malformations [28]. Isolated

Fig. 9a, b Case 26. Cortical dysplasia. Coronal T2-weighted MRI
show ventriculomegaly and diffuse cortical dysplasia associated
with thin superior cerebellar cortex
cases of CCD are infrequent [28, 29, 30] and the
pathogenesis has been considered a genetic disorder
affecting the migration of cerebellar cells or a patho-
logical event secondary to infection, hypoxia or toxins
such as ethanol [24, 25, 27, 31]. MRI findings in CCD
include defective, large or vertical abnormal fissures,
irregular grey/white matter junction, lack of normal
arborisation of the white matter and heterotopia within
the cerebellar hemispheres, leading to disorganised
foliation [28]. In histological studies, some cases of CCD
have shown cerebellar polymicrogyria [23]. As for other
subtle cerebral anomalies that have been found in
343
non-specific MR, the functional significance of CCD is
poorly understood. Moreover, its correlation with MR
is difficult to confirm because it is frequently associated
with other brain abnormalities. Nevertheless, neurobe-
havioral, neuroimaging and functional MRI studies
suggest that cerebellar as well as frontal regions make
distinctive contributions to cognitive performance and
that cerebellar pathology leads to some general cogni-
tive, memory and language deficits [3, 11, 32, 33, 34, 35,
36, 37, 38, 39, 40, 41, 42]. Such data inevitably lead us
to wonder whether CCD may have a role in some
particular cases as in the third group of our study in
which non-specific MR was associated with congenital
ataxia.
The recognition of subtle brain abnormalities or
CCD could probably be the first step in understanding
their role. Their study should be completed by further
functional and metabolic investigations in order to
evaluate whether they may affect brain function.
Identifying areas of abnormal metabolism by metabolic
imaging may help to increase our understanding of
pathogenesis in conditions in which morphology seems
to be normal with abnormal neurological function.
Although this information could increase our knowl-
edge about the underlying cause and effects of brain
dysgenesis, its characterisation as a dysgenetic event
involved in the pathogenesis of MR should be prob-
lematic. In this setting, molecular mechanisms of cere-
bral dysgenesis, neurotransmitters, genetic programs
and other epigenetic stimuli factors that influence the
development and differentiation of neuronal precursor
cells and synaptic dysfunctions have been described
recently [43, 44, 45, 46, 47, 48, 49, 50] and have
revealed alterations of cortical connectivity and excit-
ability, which are important in different clinical disor-
ders. These alterations may be related to disorders of
cortical organisation which could be responsible for
developmental disabilities and/or MR. Further investi-
gation of children with non-specific MR and subtle
brain dysgenesis should be undertaken to improve our
understanding of the role of brain dysmorphism in the
clinical expression of MR.
In conclusion, aetiological diagnosis in MR could
modify the medical management of the retarded child
and is also needed to inform the family with regard to
prognosis, recurrence risks and genetic counselling.
Neuroimaging and cytogenetic analysis, together with
the history and physical examination, are helpful in
determining the aetiology of MR.
Neuroimaging studies must be carried out whenever
clinical evaluation reveals abnormal head size or shape,
craniofacial malformations and/or multiple somatic
anomalies, neurocutaneous findings, cerebral palsy or
motor asymmetry, seizures, loss or plateau of develop-
mental skills and an IQ below 50. Imaging results could
reveal several subtle abnormalities within the cerebral
344
hemispheres, the brain midline or the cerebellum. Some
of these findings may be incidental and unrelated to MR.
CCD may be included in the list of minor brain
abnormalities found in non-specific MR. The increased
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