Human
malformations of the midbrain and hindbrain: review and proposed classification
scheme.
Parisi MA, Dobyns
WB.
Department of
Pediatrics, University of Washington, Seattle, WA 98195, USA. [email protected]
Although a great
deal of interest in the genetics and etiology of cerebral, particularly
forebrain, malformations has been generated in the past decade, relatively
little is known about the basis of congenital malformations of the
structures of the posterior fossa, namely the midbrain, cerebellum,
pons, and medulla. In this review, we present a classification scheme
for malformations of the midbrain and hindbrain based on their embryologic
derivation, highlight four of the conditions associated with such
abnormalities, and describe the genetics, prognosis, and recurrence
risks for each. We describe several disorders in addition to Joubert
syndrome with the distinctive radiologic sign known as the "molar
tooth sign," comprised of midbrain and hindbrain malformations.
We discuss Dandy-Walker malformation, its classical definition, and
the surprisingly good outcome in the absence of other brain malformations.
We consider the heterogeneous entity of cerebellar vermis hypoplasia
and describe the recently identified gene associated with an X-linked
form of this condition. Finally, the pontocerebellar hypoplasias are
discussed in the context of their generally progressive degenerative
and severe course, and the differential diagnosis is emphasized. We
anticipate that as imaging technologies improve, differentiation of
the various disorders should aid in efforts to identify the causative
genes.
Development
and malformations of the cerebellum in mice.
Chizhikov V,
Millen KJ.
Department of
Human Genetics, University of Chicago, 920 E 58th Street, CLSC 319,
Chicago, IL 60637, USA.
The cerebellum
is the primary motor coordination center of the CNS and is also involved
in cognitive processing and sensory discrimination. Multiple cerebellar
malformations have been described in humans, however, their developmental
and genetic etiologies currently remain largely unknown. In contrast,
there is extensive literature describing cerebellar malformations
in the mouse. During the past decade, analysis of both spontaneous
and gene-targeted neurological mutant mice has provided significant
insight into the molecular and cellular mechanisms that regulate cerebellar
development. Cerebellar development occurs in several distinct but
interconnected steps. These include the establishment of the cerebellar
territory along anterior-posterior and dorsal-ventral axes of the
embryo, initial specification of the cerebellar cell types, their
subsequent proliferation, differentiation and migration, and, finally,
the interconnection of the cerebellar circuitry. Our understanding
of the basis of these developmental processes is certain to provide
insight into the nature of human cerebellar malformations
J
Neurol. 2003 Sep;250(9):1025-36. Development and developmental disorders
of the human cerebellum.
Ten Donkelaar HJ, Lammens M, Wesseling P, Thijssen HO, Renier WO.
321 Dept. of Neurology, University Medical Centre Nijmegen, 9101, 6500
HB, Nijmegen, The Netherlands, [email protected]
The human cerebellum develops over a long time, extending from the early
embryonic period until the first postnatal years. This protracted development
makes the cerebellum vulnerable to a broad spectrum of developmental
disorders. The development of the cerebellum occurs in four basic steps:
1) characterization of the cerebellar territory at the midbrain-hindbrain
boundary; 2) formation of two compartments for cell proliferation: first,
the Purkinje cells and the deep cerebellar nuclei arise from the ventricular
zone of the metencephalic alar plate; second, granule cell precursors
are formed from a second compartment of proliferation, i. e. the upper
rhombic lip; 3) inward migration of the granule cells: granule precursor
cells form the external granular layer, from which (and continuing into
the first postnatal year), granule cells migrate inwards to their definite
position in the internal granular layer, and 4) formation of cerebellar
circuitry and further differentiation. The precerebellar nuclei, i.
e. the pontine nuclei and the inferior olive, arise from the lower rhombic
lip. Developmental disorders of the cerebellum are often accompanied
by malformations of the precerebellar nuclei. In this review the development
of the cerebellum and some of its more frequent developmental disorders,
such as the Dandy-Walker and related midline malformations, and the
pontocerebellar hypoplasias, are discussed.
Childs
Nerv Syst. 2003 Aug;19(7-8):484-9. Epub 2003 Jul 16.
Dandy-Walker malformation: prenatal
diagnosis and prognosis.
Klein O, Pierre-Kahn A, Boddaert N, Parisot D, Brunelle F.
Service de Neurochirurgie Pediatrique, Hopital Necker Enfants-Malades,
149 rue de Sevres, 75743 Paris Cedex 15, France.
INTRODUCTION: The difficulty in prognosticating the clinical and intellectual
outcome of fetuses presenting with a Dandy-Walker malformation (DWM)
comes from the great variety of cystic, median, and retrocerebellar
malformations that probably have nothing in common and the variability
of the definitions given to these lesions. In addition, many of these
lesions can mimic each other. A correct diagnosis cannot be made without
a good quality MRI including sagittal views of the vermis and T2-weighted
images. We limited the diagnosis of DWM to those malformations with
all of the following features: 1) a large median posterior fossa cyst
widely communicating with the fourth ventricle, 2) a small, rotated,
raised cerebellar vermis, 3) an upwardly displaced tentorium, 4) an
enlarged posterior fossa, 5) antero-laterally displaced but apparently
normal cerebellar hemispheres, 6) a normal brain stem. If any one
of the previous criteria were not met, the malformation was considered
distinct from DWM. MATERIALS AND METHODS: The charts of 26 patients
with DWMs (18 females and 8 males; median age 10.5 years) were reviewed
retrospectively. The diagnosis of the malformation was made prenatally
in 7 children and postnatally in the 19 others. All the patients had
both one MRI including axial and sagittal views of the posterior fossa
as well as T1- and T2-weighted sequences, and one neuro-psychological
investigation. Syndromic DWMs and Dandy Walker variants were excluded
from the study. MRIs were reviewed in a blinded manner looking for
brain malformation or damage and studying with particular attention
the anatomy of the vermis. Systemic malformations were also recorded.
Developmental quotient (DQ) and intellectual quotient (IQ) were said
to be normal when equal or greater than 85, and low when below this
value. Statistical analysis was performed using a Fisher test to analyze
the relationship between intellectual performances, vermis anatomy,
ventricular size, brain anatomy, and associated malformations. RESULTS.
On scrutiny of sagittal T2 sequences, the vermis, although constantly
small, rotated, and pushed towards the tentorium presented as two
distinct morphologies, leading us to distinguish two groups of patients.
In the first group (n=21), the vermis presented with two fissures,
three lobes, and a fastigium as in the normal situation. In this particular
group, none of the patients had associated brain malformation and
all but 2 were functioning normally. One of the 2 retarded children
had a fragile X syndrome. The other had a severe periventricular leukomalacia
due to prematurity, which, per se, was sufficient to account for mental
delay. In the second group (n=5), the vermis was highly malformed,
obviously dysplastic, presenting with only one fissure or no fissure
at all. It was constantly associated with major brain anomalies, most
often a complete corpus callosum agenesis. All the patients in this
group were more or less severely retarded. Vermis anatomy in DWMs
was statistically correlated to neurological and intellectual outcome.
Is the vermis dysplasia responsible, in itself, for this poor outcome?
No answer can be given from this series, because retardation was observed
in children who always had both a severely dysplastic vermis and other
brain malformations. No other patient-related factor was statistically
correlated to the outcome, in particular, hydrocephalus and extracerebral
malformations. CONCLUSION: We described two types of DWM. The most
frequent is characterized by an isolated and partially agenetic vermis.
This malformation is compatible with a normal life. The second type
consists of a severely abnormally lobulated vermis and associated
brain malformation. This malformation is always accompanied by mental
retardation.
Intellectual prognosis of the Dandy-Walker
malformation in children: the importance of vermian lobulation.
Boddaert N, Klein O, Ferguson N, Sonigo P, Parisot D, Hertz-Pannier
L, Baraton J, Emond S, Simon I, Chigot V, Schmit P, Pierre-Kahn A, Brunelle
F.
Paediatric Radiology Department, Hopital Necker Enfants-Malades, 149
rue de Sevres, 75015 Paris, France. [email protected]
Half of patients with the Dandy-Walker malformation (DWM) have normal
intellectual development. We aimed to identify feature on MRI associated
with good intellectual prognosis. We reviewed 20 patients with DWM diagnosed
on MRI, mean age 14.6+/-9.9 years. We assessed their intellectual development
and related it to the MRI features. We found two groups with a statistically
different intellectual outcome. All 14 patients with normal intellectual
development had a normal lobulation of the vermis, without supratentorial
anomalies. Of the six patients with mental retardation, three had an
abnormal vermis, together with dysgenesis of the corpus callosum. In
the other three, there were normal vermian anatomy with associated anomalies.
Normal lobulation of the vermis, in the absence of any supratentorial
anomaly, appears to be a good prognostic factor in DWM. Preservation
of cerebrocerebellar pathways and neonatal plasticity could explain
the normal intellectual development. These findings might be useful
in prenatal diagnosis.
Intraoperative direct neuroendoscopic
observation of the aqueduct in Dandy-Walker malformation.
Kawaguchi T, Jokura H, Kusaka Y, Shirane R, Yoshimoto T.
Department of Neurosurgery, Tohoku University Graduate School of Medicine,
Sendai, Japan.
A 3-month-old female infant with Dandy-Walker malformation manifesting
as hydrocephalus was treated successfully by only ventriculoperitoneal
shunting. A flexible neuroendoscope was used intraoperatively to confirm
the patency of the aqueduct, i.e. communication of the ventricular system
and the cyst in the posterior fossa. Direct confirmation of the patency
of the aqueduct and cyst communication is valuable to select the shunt
procedure in the treatment of Dandy-Walker malformation.
Malformations of the posterior fossa:
current perspectives.
Niesen CE.
Division of Pediatric Neurology, Cedars-Sinai Medical Center, Los Angeles,
CA 90048, USA.
Posterior fossa malformations are a special group of central nervous
system anomalies that present during infancy with hypotonia, developmental
delay, microcephaly, or hydrocephalus. Recent discoveries of the genetic
and epigenetic factors that control hindbrain ontogenesis explain some
of these disturbances in cerebellar development. A comprehensive classification
of posterior fossa malformations is proposed with particular attention
to Dandy-Walker malformation, Joubert syndrome, and other cerebellar
hypoplasias. A rare form of cerebellar hypertrophy which caused repeated
obstruction at the foramen magnum is recognized. The importance of the
cerebellum in language, cognition, and brain growth is stressed.