Congenital disorders of the brain and spine are extremely complex and are best studied by correlating with the embryological development.

Stage 1: Dorsal Induction: Formation and Closure of the Neural Tube

Weeks 3 - 4

Three phases: Neurulation, canalization, retrogressive differentiation

Failure: Anencephaly



Spinal dysraphism


Stage 2: Ventral Induction: Formation of the Brain Segments and Face

Weeks 5-10

Three vesicles (prosencephalon, mesencephalon, and rhombencephalon) form the cerebrum, mid-brain, cerebellum, and lower brain stem.

Division into two hemispheres.

Failure: Holoprosencephalies

Corpus callosum agenesis

Dandy Walker

Facial anomalies


Stage 3: Migration and Histogenesis

Neuronal migration from germinal matrix to the cortex.

Cortical organization.

Months 2-5.

Disorders: Heterotopias, agyria-pachygyria, polymicrogyria, vascular malformations, teratomas, phakomatosis.


Stage 4: Myelination

Inferior to superior; posterior to anterior.

5 - 15 months; matures by 3 years.

Failure: developmental delay, dysmyelinating disease

Comments on Embryology

Dorsal induction is the first stage in the formation and closure of the neural tube. This occurs at weeks 3 - 4 gestation. The first phase of neurulation leads to the formation of the neural tube which will be the foundation for the brain and spinal cord. The second phase and third phase of dorsal induction involving canalization and retrogressive differentiation leads to the formation of the caudal part of the neural tube. Subsequent defects with these two phases lead to such things as sacral agenesis, caudal regression syndromes, lipomas, and tethered cords.

During neurulation, the embryonic ectoderm forms dorsal to the notochord, and this thickens to form a neural plate. The neuro ectoderm invaginates along its central axis to form the neural groove with neural folds on either side. The neural folds grow upward and then close like a zipper to form the neural tube. With abnormal closure of the neural tube, problems such as cephaloceles and spinal dysraphisms can occur.

In stage of ventral induction, the brain and face develop from 3 main vesicles. These are the prosencephalon (which eventually forms the cerebral hemispheres) and the thalamus, the mesencephalon (which forms the mid-brain), and the rhombencephalon (which will form the pons, cerebellum, and medulla). During this time, the face also develops, so facial anomalies may accompany brain anomalies during ventral induction. These anomalies include the holoprosencephalies, corpus callosal agenesis, and Dandy Walker.

Stage 3 (Migration and Histogenesis)

These two processes occur about the same time between two to five months of gestation. Neuronal migration proceeds from the germinal matrix to the cortex. Disorders of migration include the heterotopias, agyria-pachygyria, and polymicrogyria. Disorders of histogenesis include the phakomatosis. It should be noted that phakomatoses may be associated with gray matter heterotopias (e.g. Tuberous sclerosis has subependymal tumors that most likely represent failure of neuronal migration). In addition, vascular malformations and teratomas may form at this time.

Stage 4 (Myelination)

This is the formation of white matter, which proceeds from more primitive areas to more advanced areas of the brain. This process occurs from an inferior to a superior direction and from a posterior to anterior direction. Myelination occurs between approximately five to fifteen months and should be mature by three years of age. Failure of myelination would lead to developmental delay as well as dysmyelinating diseases.


Stage 1 Failures: Dorsal Induction



Chiari malformations



Defect in the dura and cranium with associated extra cranial herniation felt to be related to abnormal closure of the neural tube.

Two types: meningocele (herniation of meninges with CSF) and encephalocele (herniation of brain and meninges).

Usually mid-line.

Occipital location most common in the U.S.

Frontal ethmoidal most common in Asia.

Often the herniated brain is dysgenetic and nonfunctional.


Failure of the brain and skull development.

Most severe anomaly.

Ultrasound diagnosis as early as twenty weeks.

Polyhydramnios, high alpha fetoprotein.


Chiari I

Low tonsils.

Small fourth ventricle.



Occipitalization of the atlas.

 Chiari II


Low tentorium.

Medullary kink.


Beaked tectum.

Corpus callosum agenesis.



Lacunar skull.

 Chiari III

Cervical occipital encephalocele that contains cerebellum.


Chiari IV

Severe cerebellar hypoplasia.


Stage II: Failures: Ventral Induction


Corpus callosum agenesis.

Dandy Walker.

Facial anomalies.


Failure to separate into hemispheres.

Alobar: complete failure, no falx, single mono-ventricle, fused thalami.

Semi lobar: Partial separation of the posterior occipital and temporal lobes. Frontal brain is fused, thalami partially fused.

Ace of spades configuration of the ventricles.

Lobar: fusion of only anterior inferior frontal lobes so no faux in that location. Otherwise the brain appears to be quite normal except for lack of septum pellucidum.

Septal optic dysplasia: most mild form in which there is no septum pellucidum and the optic nerves are very atrophic. Schizencephaly may be present in fifty percent of these cases. Corpus callosum agenesis may also be seen with this entity.

Agenesis of the Corpus Callosum

Growth anterior to posterior starting at the genu. Myelination from posterior to anterior.

Association with Chiari II, Dandy Walker, Holoprosencephaly and lipomas.

Splaying of the anterior horns (Bulls horn appearance) due to realignment of the Probst bundles.

High third ventricle.

Colpocephaly (splaying of the atria).

Absent cingulate sulcus.

Dandy Walker

Defective development of the roof of the fourth ventricle.

Posterior fossa cyst; hydrocephalus often.

Large posterior fossa; high torcula; absent falx in the posterior fossa.

Partial Dandy Walker lacks high torcula. Represents a form of cerebellar hypoplasia.

Mildest aspect of this spectrum would be mega cisterna magna.

DDX: arachnoid cyst, mega cisterna magna.

Facial Anomalies

Often found with alobar holoprosencephaly, corpus callosal agenesis.

Usually midline.

Hypertelorism, hypotelorism, cleft palate, pug nose.

Stage III: Failure of Histogenesis, Neuronal Migration




Gray Matter Heterotopias

Interruption of normal migration of neural blast from the general matrix to the cortex.

Various degrees range from simple nodular gray matter heterotopias to band heterotopias to schizencephaly to lissencephaly and to polymicrogyria.

Seizures, mental retardation.

Association with corpus callosum agenesis, Chiari malformations, Tuberous Sclerosis, septo-optic dysplasia.


Gray matter extension from the ventricle to the cortex.

Two types: closed lip (mild, no CSF within) and open lip (contains CSF, severe with cortical defects and large ventricles).

Association with septo-optic dysplasia and optic atrophy.

Lissencephaly (Agyria-Pachygyria)

Most severe form of neuronal migrational anomalies. Patients often have small brains, mental retardation, spasticity, seizures.

Agyria (complete lissencephaly) presents with smooth brain and is identified by figure eight configuration with clefts extending to the sylvian fissures.

Pachygyria (incomplete lissencephaly) has broad, shallow gyre. More mild form than agyria.


Neurons reach the cortex but are abnormally distributed into multiple small gyri like dimples on the surface of a basketball. The cortex of polymicrogyria has bumps of about 5-7 millimeters in size whereas those of pachygyria are over 8 millimeters in size.

Clinically less severe than lissencephaly. Seizures, developmental delays.

Focal polymicrogyria may be seen with an anomalous draining vein and gliosis.

May be associated with Chiari II, schizencephaly, and congenital infections (C.M.V.).

Unilateral Megalencephaly

Hamartomatous overgrowth of a cerebral hemisphere with associated migrational anomalies.


Neurofibromatosis Type I.

Neurofibromatosis Type II.

Tuberous Sclerosis.

Von Hippel Lindau.

Sturge Weber.



NF1 (Von Recklinghausen)

1:4000 births.

Chromosome 17.

Optic Nerve Gliomas.

Hamartomas, gliosis.

Bone dysplasias.

Vascular dysplasias.


Cafe au lait spots.

NF2 (Miss-me)

Bilateral acoustic schwannomas.



Chromosome 22.

1:40,000 births.

NF2 has less skin manifestations than NF1.

Tuberous Sclerosis (Bourneville's Disease).

Chromosome 9.

Seizures, mental retardation, adenoma sebaceum.

Ash Leaf spots.

Cortical tubers, periependymal nodules (hamartomas).

Giant cell astrocytoma.

Gray matter heterotopias.

Angiomyolipomas of the kidney.

Rhabdomyoma of the heart.

Adenoma of the liver.

Skeletal cysts.

Lymphangiomyomatosis of the lungs.

Von Hippel Lindau

Hemangioblastomas of the brain and spine.

Retinal angiomas and hemangioblastomas (? retinal hemorrhage).

Renal cell carcinoma.

Cysts in any visceral organ.


Sturge Weber

A.k.a encephalotrigeminal, angiomatosis.

Facial port wine stain (V1).

Paraplegia, hemiatrophy.

Leptomeningeal venous angiomas leading to vascular shunting and cortical infarcts.

Cortical calcifications in a tram track fashion.

Visual field defects.

Retinal telangiectasias (hemorrhage and glaucoma).

Visceral angiomas.


Mental retardation.

Possible Dyke Davidoff configuration.


Stage IV: Failures of Myelination

To recognize abnormal myelination patterns, one must be aware of normal myelination patterns.

Normal Myelination

Rules: Caudal to cranial.

Posterior to anterior.

Techniques: T1 imaging if less than approximately seven months.

T2 imaging if greater than seven months.

Note: wide variability of normal.

Myelination Milestones

Brain stem, cerebellum, posterior limb of internal capsule: term birth.

Anterior limb internal capsule: two months.

Splenium of the corpus callosum: three months.

Genu corpus callosum: six months.

Occipital white matter.

Central: five months (T1)/fourteen months (T2)

Peripheral: seven months (T1)/fifteen months (T2)

Frontal white matter.

Central: six months (T1)/sixteen months (T2)

Peripheral: eleven months (T1)/eighteen months (T2)

Failures of normal myelination results in:

Developmental delay.

Dysmyelinating diseases.

Dysmyelinating Diseases

Alexander's disease.


Metachromatic leukodystrophy.

Canavan's disease.

Krabbe's disease.


Acquired Lesions

Acquired Lesions







Hypoxic Destructive Lesions

Porencephaly: cyst in the brain that communicates with the ventricle or the subarachnoid space.

Probably due to neonatal infarct, trauma, or infection.

DDx: Porencephalic cysts are lined by gliotic white matter whereas schizencephaly is lined by grey matter.

Dyke Davidoff syndrome possible (hemiatrophy of the brain with compensatory thickening of the skull and enlargement of the ipsilateral paranasal sinuses).

Hydranencephaly: reabsorption/destruction of the cerebral hemispheres thought to be due to bilateral ICA occlusions although congenital infection may also be a cause.

There is a preservation of the more primitive areas (thalami, brain stem, and the falx is also preserved).

Differential diagnosis of water filled brain should include hydranencephaly, marked hydrocephalus (still has a mantle of brain beyond the dilated ventricles), and alobar holoprosencephaly (no falx).

Periventricular Leukomalacia

Nonspecific white matter changes due to ischemia.

In adults, this is usually seen around the centrum semiovale.

In kids, this is usually seen around the atria.

Germinal Matrix Hemorrhage (Complication of prematurity)

I. Germinal matrix


III. + IVH + hydrocephalus


Metabolic Destructive Lesions

Abnormalities usually due to enzyme deficiencies leading to errors of aerobic metabolism (defects in the Krebs cycle) lead to global abnormalities which are usually manifested by symmetrical defects in areas that have high oxygen and other metabolic requirements. These include the basal ganglia and the thalami as well as parts of the brain stem.

Common metabolic processes which are manifested by defects in enzyme deficiencies throughout the Krebs cycle would include Leigh's disease, proprionic acidemia, glutaric acidemia, and others. The MELAS (mitochondrial encephalopathy, lactic acidosis, stroke) syndrome also may be seen with defects in the basal ganglia as well as multiple cortical infarctions in a nonvascular distribution predominantly in the occipital lobes. Other metabolic misfires such as maple syrup urine disease may be seen diffuse cerebral edema.

Therefore bilaterally symmetrical abnormalities (especially if centered at the basal ganglia) should make one think very strongly of an underlying metabolic process.

Destructive Lesions: Congenital Infections

TORCH (Toxoplasmosis, rubella, CMV, herpes).



TORCH and Aids commonly have periventricular calcifications especially around the basal ganglia.

Hydrocephalus may develop from synechiae especially at the aqueduct of Sylvius.

Transmitted via placenta or at birth.

Seizures, failure to thrive, abnormal development.

Skull Abnormalities: Cranial Synostosis (early sutural closure)

Sagittal: dolichocephaly-long, thin.

Coronal: brachycephaly-round, short.

Lambdoid: turricephaly-high pointed skull.

Asymmetric: unilateral plagiocephaly.

Unilateral coronal: harlequin eye.

Metopic: trigonocephaly.


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