Approach to Brain Malformations A General Imaging Approach to Brain CSF spaces. This is the basis for development of the Dandy- Malformations Walker malformation; it requires abnormal development of the cerebellum itself and of the overlying leptomeninges. Whenever an infant or child is referred for imaging because of Looking at the midline image also gives an idea of the relative either seizures or delayed development, the possibility of a head size through assessment of the craniofacial ratio. In the brain malformation should be carefully investigated. If the normal neonate, the ratio of the cranial vault to the face on child appears dysmorphic in any way (low-set ears, abnormal midline images is 5:1 or 6:1. By 2 years, it should be 2.5:1, and facies, hypotelorism), the likelihood of an underlying brain by 10 years, it should be about 1.5:1. malformation is even higher, but a normal appearance is no guarantee of a normal brain. In all such cases, imaging should After looking at the midline, evaluate the brain from outside be geared toward showing a structural abnormality. The to inside. Start with the cerebral cortex. Is the thickness imaging sequences should maximize contrast between gray normal (2-3 mm)? If it is too thick, think of pachygyria or matter and white matter, have high spatial resolution, and be polymicrogyria. Is the cortical white matter junction smooth or acquired as volumetric data whenever possible so that images irregular? If it is irregular, think of polymicrogyria or Brain: Pathology-Based Diagnoses can be reformatted in any plane or as a surface rendering. The cobblestone cortex. Polymicrogyria is seen in many underlying high resolution and ability to reformat will aid in the diagnosis disorders, including congenital cytomegalovirus and genetic of subtle abnormalities. High-resolution T1-weighted syndromes, among others. Cobblestone cortex may be volumetric images are essential for this purpose. High- associated with congenital muscular dystrophies, such as resolution 2D coronal T2 images remain a workhorse for muscle-eye-brain disease. Pachygyria that is more severe in evaluation of midline structures, hippocampi, and optic the parietal and occipital lobes suggests a mutation of LIS1 or nerves. High-resolution 3D FLAIR images may be particularly TUBA1A (TUBA1A is also associated with microcephaly), helpful in evaluating for focal cortical dysplasia. The use of whereas pachygyria that is worst in the frontal lobes suggests diffusion tensor imaging (DTI) to acquire color fractional a mutation of DCX. Similarly, there are many different anisotropy (FA) maps and perform tractography is useful to polymicrogyria syndromes that depend upon the location of better understand the connectivity of the malformed brain, the polymicrogyria. Bilateral frontal polymicrogyria is a particularly in the brainstem, and may become clinically useful different entity than bilateral perisylvian polymicrogyria or in the near future. bilateral parasagittal parietooccipital polymicrogyria; it is important to be specific in reporting the location of the After acquisition of appropriate images, image analysis must abnormality. If the cortex is abnormally thin and associated take place in an orderly manner. The midline structures with diminished underlying white matter, one should think of (including cerebral commissures, septum pellucidum, nose a prenatal injury (infectious or ischemic), particularly if the and rhinencephalon, pituitary gland, optic chiasm, and thinning is focal or multifocal. hypothalamus), the cerebral cortex (cortical thickness, gyral pattern, and cortical gray matter-white matter junction), the After the cortex, look at the cerebral white matter. Make sure cerebral white matter (myelination, presence of nodules or myelination is appropriate for age (there are many sources of clefts), the basal ganglia, the ventricular system (all ventricles normal myelination charts, including journal articles and completely present and of normal size and shape), the textbooks). Then, look for areas of abnormal myelination interhemispheric fissure, and the midbrain hindbrain within the deep white matter. Diffuse layers of structures (brainstem and cerebellum) should all be hypomyelination or amyelination associated with overlying scrutinized in every patient. polymicrogyria should raise suspicion for congenital cytomegalovirus infection. Generalized ipsilateral ↑T1 & ↓T2 Evaluate the midline structures first, as many disease signal in the white matter of a neonate with overlying cortical processes of children take place in the midline, including malformation should prompt one to think of anomalies of the cerebral commissures (corpus callosum, hemimegalencephaly, which is often accompanied by anterior commissure, and hippocampal commissure), midline ipsilateral hemisphere & ventricular enlargement. Focal tumors (suprasellar, pineal, brainstem, and 4th ventricle), cortical dysplasias (FCDs) are often most conspicuous at birth anomalies of the cerebellar vermis, and anomalies of the with ↑T1 & ↓T2 in the subcortical white matter. After craniocervical junction. Anomalies of the cerebral myelination, FCDs are typically most conspicuous on FLAIR, commissures are the most common brain malformations; where one may see a curvilinear cone-shaped abnormality more than 130 syndromes involving them have been coursing from the cortex to the superolateral margin of a described. Many of these malformations are associated with lateral ventricle (known as the transmantle sign). Narrowing anomalies of the hypothalamus, so always look at the the window on FLAIR images increases conspicuity of FCD. hypothalamus and pituitary gland to ensure that the posterior Also, look for nodules of heterotopic gray matter in the pituitary lobe is in the sella turcica and not in the median periventricular or deep white matter. Transmantle gray eminence of the hypothalamus. The midline leptomeninges matter heterotopia typically extends from the cortex all the are important in commissural development, so be sure to look way to the lateral ventricular wall, whereas periventricular for other anomalies associated with abnormal midline nodular heterotopia is more localized to the immediate leptomeninges, such as interhemispheric lipomas and subependymal/periventricular region. Heterotopia might be interhemispheric cysts, when the commissures are absent or difficult to differentiate from unmyelinated or injured white dysmorphic. Remember that large CSF spaces in the posterior matter on T1-weighted images, so be sure to look at T2- fossa may be a sign of associated anomalies of the weighted images or FLAIR images to ensure that the lesion is cerebellum. The reason for this has only recently been isointense to gray matter on all sequences. discovered. Several cerebellar growth factors derive from the overlying leptomeninges. Therefore, abnormalities of the The basal ganglia are sometimes abnormal in neuronal- cerebellar leptomeninges may result in anomalies of the migration disorders, as they are formed from neurons cerebellum itself, as well as abnormalities of the surrounding generated in the medial and lateral ganglionic eminences, the 4 Approach to Brain Malformations Brain: Pathology-Based Diagnoses Brain Anomaly Imaging Checklist Anomaly Findings Anomalies of Cerebral Cortex Agyria/pachygyria Thick cortex, smooth inner margin, few shallow sulci Polymicrogyria Nodular cortex & gray matter-white matter junction Cobblestone cortex Thick cortex, irregular inner margin, abnormal myelin Focal cortical dysplasia Thick cortex, blurred gray-white junction, ± deep sulcus White Matter Abnormalities With Cortical Malformation Hemimegalencephaly ↑ T1, ↓T2 in neonatal white matter; dysplastic neurons Cobblestone cortex Delayed myelination, patchy hypomyelination Congenital cytomegalovirus Deep layers of hypomyelination/gliosis Focal cortical dysplasia "Tail" of signal abnormality extending toward ventricle Malformations Associated With Absent Septum Pellucidum Septo-optic dysplasia ON hypoplasia, pituitary anomaly, ± PMG/schizencephaly Holoprosencephaly Varying degrees of incomplete hemispheric separation Malformations with severe prolonged hydrocephalus Absent septum typically thought to be destructive ON = optic nerve; PMG = polymicrogyria. same germinal zones that produce GABAergic neurons that abnormal, refer to an axial or coronal image to make sure the migrate to the cerebral cortex. In particular, the basal ganglia vermis is present; if the cerebellar hemispheres are tend to be dysmorphic in appearance in patients with continuous without a vermis between them, make a diagnosis subcortical heterotopia. In addition, the hippocampi are often of rhombencephalosynapsis. Whenever aqueductal stenosis is abnormal in cortical-development malformations. In patients encountered, look carefully for rhombencephalosynapsis. If with lissencephaly, in particular, the hippocampi are the 4th ventricle has an abnormal rectangular shape (with a incompletely folded. Sometimes the only structural horizontal superior margin) with a narrow isthmus and small abnormalities in children with developmental delay are vermis, consider a molar tooth malformation. To confirm this hippocampal; always ensure that they are fully folded and not diagnosis, look on axial images for the molar tooth sign of the too round. In the case of longstanding seizures, carefully lower midbrain, consisting of large, horizontal superior inspect the hippocampi for asymmetric atrophy and increased cerebellar peduncles