24
Commissural and Cortical Maldevelopment
Section to be Named Later
Commissural and Cortical Maldevelopment
Fig. 24-1.
Sagittal graphic depicts the anterior commissure
and corpus callosum segments: Rostrum
, genu
, body
, isthmus
, splenium
.
Fig. 24-2.
Graphic depicts fibers from corona radiata converging into and crossing transversely through the corpus callosum
.
Fig. 24-3.
DTI shows the normal red "X-shape" corpus callosum formed by the genu
and forceps minor, body
, and splenium
with forceps major.
Commissural and Cortical Maldevelopment
Fig. 24-4.
Fig. 24-5.
Fig. 24-6.
Fig. 24-7.
Sagittal T1WI shows classic subcortical band heterotopia with thin outer cortex, myelinated WM, band of GM
, periventricular WM.
Fig. 24-8.
Fig. 24-9.
Axial section shows mostly the appearance of perisylvian thick cortex
although a slight "pebbly" appearance with irregular GM-WM interface can be discerned
(courtesy R Hewlett, MD).
Fig. 24-10.
CC agenesis shows "Viking helmet" appearance with high, wide 3rd ventricle
, pointed nonconverging lateral ventricles
, Probst bundles
.
Fig. 24-11.
Coronal autopsy of CC agenesis shows thin 3rd ventricle roof, Probst bundles
.
Fig. 24-12.
CC agenesis shows absent cingulate gyrus, "radiating" gyri
converging on high-riding 3rd ventricle
. (Courtesy R. Hewlett, MD.)
Normal Development and Anatomy of the Cerebral Commissures
Normal Development
Normal Gross and Imaging Anatomy
Commissural Anomalies
Callosal Dysgenesis Spectrum
Corpus callosum dysgenesis and malformations of cortical development are some of the most common congenital brain anomalies. They can occur in isolation but frequently accompany other disorders such as Dandy-Walker spectrum, Chiari II malformation, and malformations of the hypothalamus and pituitary gland.
Normal Development and Anatomy of the Cerebral Commissures
The telencephalon has three major commissural tracts: The corpus callosum (the largest and most prominent), the anterior commissure, and the hippocampal (posterior) commissure. Coordinated transfer of information between the cerebral hemispheres is essential for normal function and occurs via these three axonal commissures.
In this section we briefly review the normal development of the commissures and then delineate their gross and imaging anatomy.
Normal Development
Commissural development is a complex process in which axons from cortical neurons are actively guided across the midline to reach their targets in the contralateral hemisphere. A set of genetically-mediated guidance mechanisms are used by these axons from cortical neurons to locate and innervate their targets. Details of this process are beyond the scope of this text but are summarized briefly below. The interested reader is referred to the excellent text by Barkovich and Raybaud.
Commissural Plate
The commissural plate (CP) is a band of tissue within which all telencephalic commissures cross the midline into the contralateral hemisphere during embryonic development. The CP consists of multiple molecular domains, each of which is associated with separate genetic expressions and specific commissural projections. Correct CP development is required for normal forebrain commissural formation.
Specialized glial cells in the anterior CP (the "subcallosal glial sling") together with a second set of midline glial populations (the glial "wedge" below and the indusium griseum glia above) form the foundation for axonal ingrowth and crossing. The subcallosal sling, the two midline glial populations, and "pioneering axons" all work in unison to guide axons across the midline.
The anterior commissure (AC) is the first forebrain commissure to develop and sends a group of "pioneering axons" across the midline during the eighth fetal week. Near the end of the first trimester, axons that will eventually form the anterior segments of the corpus callosum (CC) begin navigating from the cortex towards the midline near the embryonic foramen of Monro.
The hippocampal commissure forms posteriorly around week 11 and is followed by axons that will eventually become the posterior body and splenium of the corpus callosum.
Corpus Callosum
The CC forms in two independent segments, with some axons crossing the glial sling anteriorly and others following the hippocampal commissure posteriorly. Fiber bundles in the anterior and posterior callosum are initially separated but eventually unite to form a single continuous structure, the definitive corpus callosum.
The first axons cross the midline at 13-14 fetal weeks and the last finally cross between 18-20 weeks. The genu, rostrum, and body form in rapid succession and can clearly be identified at 15 weeks while the caudal portion--the splenium--does not become prominent until 18-19 weeks.
The CC in the fetus and preterm infant is very thin and relatively uniform in gross appearance. At birth, it is still comparatively thin and quite flat. The CC continues to grow and its shape evolves for several months after birth.
Myelination of the splenium generally precedes genu maturation. As myelination proceeds, the genu and splenium thicken noticeably. Both the length and thickness of the CC gradually increase. By 10 postnatal months the overall appearance resembles that of a normal adult although some myelination continues into young adulthood.
Normal Gross and Imaging Anatomy
Corpus Callosum
The CC is the largest of the three forebrain commissures and is composed of five parts. From front to back these are the rostrum, genu, body, isthmus, and splenium. The
rostrum
is the smallest segment and connects the orbital surfaces of the frontal lobes. A prominent anterior "knee--the
genu
--connects the lateral and medial frontal lobes. White matter fibers that curve anterolaterally from the genu form the
forceps minor
.
The longest CC segment is the
body
. Its fibers pass laterally and intersect with projection fibers of the corona radiata. The body connects broad regions of each hemispheric cortex together.
The
isthmus
is a shorter, slightly more narrow area that lies between the posterior body and splenium. The isthmus connects the pre- and postcentral gyri and auditory cortex with their counterparts in the contralateral hemisphere. The
splenium
is the expanded, rounded termination of the CC. MOst of its fibers curve into the occipital lobes as the
forceps major
.
Sagittal T1- and T2WIs demonstrate the rostrum as a thin WM tract that curves posteroinferiorly from the genu. The dorsal CC surface is typically not straight, but has a slightly "wavy" with a distinct posterior narrowing--the isthmus--just before the the CC widens again into the splenium.
Coronal scans show the CC curving from side to side across the midline. Anteriorly, the genu is seen as a continuous band of WM connecting the frontal lobes. More posteriorly, the CC lies above the fornices, fanning out from the splenium into the forceps major.
Anterior Commissure
The anterior commissure (AC) is a transversely-oriented bundle of compact, heavily-myelinated fibers that crosses the midline anterior to the fornix.
The AC lies in the anterior wall of the third ventricle. From the midline, it curves laterally in the basal forebrain and splits into two bundles. The smaller more anterior bundle courses toward the orbitofrontal cortex and olfactory tract. The much larger posterior bundle fans out into the temporal lobe. The AC connects the anterior parts of the temporal lobes and lies anterosuperior to the temporal horn of the lateral ventricle.
On sagittal T1WIs the AC is seen as a hyperintense ovoid structure lying midway up the anterior wall of the third ventricle. On axial T2WIs it can be identified as a compact well-defined hypointense band of tissue lying just in front of the third ventricle. As it courses laterally, both sides of the AC curve slightly anteriorly so it resembles an archer's bow on axial MR scans.
Hippocampal Commissure
The hippocampal commissure (HC) is the smallest of the three major commissures but the earliest to develop. It is a transversely-oriented fiber bundle that crosses the midline in the posterior pineal lamina.
In contrast to the CC and AC, the HC is less easily distinguished on MR scans. In the midline sagittal plane, its myelinated fibers blend imperceptibly with those of the inferomedial WM in the corpus callosum splenium. On coronal scans through the lateral ventricle atria the HC can be seen lying below the corpus callosum where its fibers blend in with those of the fornices.
Commissural Anomalies
Anomalies of the cerebral commissures are the most common of all brain malformations and have been described in nearly 200 different syndromes! Any one or a combination of the three forebrain commissures can be affected by developmental failures. Recognizing the surprisingly broad spectrum of commissural malformations and delineating any associated abnormalities is essential for accurate, complete diagnosis.
We begin this section by discussing the spectrum of corpus callosum malformations together with a few associated lesions and some representative syndromes. Meningeal dysplasias such as interhemispheric cysts and lipomas are common. Lipomas are discussed in detail in the concluding chapter of this book. Developmental lesions of the pituitary gland and hypothalamus--both frequently associated with callosal dysgenesis--are delineated in chapter .
Callosal Dysgenesis Spectrum
Terminology
The corpus callosum can be completely absent (agenesis) or partially formed (hypogenetic or dysgenetic).
Complete CC agenesis
almost always is accompanied by absence of the hippocampal commissure (HC) although the anterior commissure (AC) is usually present and normal.
In
partial posterior agenesis
, the HC and posterior callosum (the splenium, with or without some involvement of the body) are both absent. In rare instances, the CC is completely absent but the HC is present. If all three commissures fail to develop at all, the result is termed
tricommissural agenesis
.
Etiology
When the underlying mechanisms that regulate the guidance of commissural fibers fail, pathological dysgenesis of one or more commissures ensues. To date, nearly 40 genes have been linked to human callosal dysgenesis.
CC anomalies can result from failure of axons themselves to form, failure of genetically-determined molecular guidance mechanisms, failure of the glial sling or hippocampal commissure to develop normally, or malfunction of these substrates in guiding axons to their proper destinations across the midline.
Pathology
In complete CC agenesis, no segments are present. Sagittal sections show an
absent cingulate gyrus
while the hemispheres demonstrate a radiating
"spoke-wheel" gyral pattern
extending perpendicularly to the roof of the third ventricle.
On coronal sections the
"high-riding" third ventricle
looks as if it opens directly into the interhemispheric fissure but is actually covered by a thin membranous roof that bulges into the interhemispheric fissure, displacing the fornices laterally. The lateral ventricles have upturned, pointed corners.
A prominent longitudinal WM tract called the
Probst bundle
is situated just inside the apex of each ventricle. These bundles consist of the misdirected commissural fibers that should have crossed the midline but instead course from front to back, indenting the medial walls of the lateral ventricles.
The septum pellucidum often appears to be absent but instead has widely separated leaves that course laterally--not vertically--from the fornices to the Probst bundles.
Axial sections show the lateral ventricles are parallel and nonconverging. The occipital horns are often disproportionately dilated, a condition termed colpocephaly.
Clinical Issues
Epidemiology and Demographics.
CC dysgenesis can be discovered at any age. It has a prevalence of at least 1:4,000 live births. CC dysgenesis is the most common CNS malformation and is found in 3-5% of individuals with neurodevelopmental disorders. Nonsyndromic CC dysgenesis has a slight male predominance.
Presentation.
MInor CC dysgenesis is often discovered incidentally on imaging studies or at autopsy. Major commissural malformations are associated with seizures, developmental delay, and symptoms secondary to disruptions of the hypothalamic-pituitary axis.
Imaging Findings
CT Findings.
Axial NECT scans show parallel, nonconverging, widely separated lateral ventricles. Disproportionate enlargement of the occipital horns is common.
MR Findings.
Sagittal T1- and T2WIs demonstrate partial dysgenesis or complete CC absence. With complete agenesis, the third ventricle appears continuous with the interhemispheric fissure and is surrounded dorsally by fingers of radiating gyri that "point" towards the third ventricle. In partial agenesis, the rostrum and splenium are often absent and the remaining genu and body have a "blocky" thickened appearance. The hippocampal commissure is typically absent but the AC may be preserved and often appears quite normal or even larger than usual.
A midline interhemispheric cyst may be present above the third ventricle. Such cysts can be a ventricular outpouching or separate structures that do not communicate with the ventricular system.
An azygous anterior cerebral artery (ACA) can be seen "wandering" upwards in the interhemispheric fissure. Look for associated malformations of the eyes, hindbrain, and hypothalamic-pituitary axis.
Axial scans demonstrate the parallel lateral ventricles especially well. The prominent myelinated tracts of the Probst bundles can appear quite prominent.
Coronal scans show a "Viking helmet" or "moose-head" appearance caused by the curved, upwardly pointed lateral ventricles and high-riding third ventricle that expands into the interhemispheric fissure. The Probst bundles are seen as densely myelinated tracts lying just inside the lateral ventricle bodies. The hippocampi appear abnormally rounded and vertically-oriented. Moderately enlarged temporal horns are common. Look for malformations such as heterotopic gray matter.
DTI is especially helpful in depicting CC agenesis. The normal red (right-to-left encoded) color of the corpus callosum is absent. Instead, prominent front to back (green) tracts of the Probst bundles are seen.
Angiography.
In complete CC agenesis, CTA, DSA, and MRA demonstrate an azygous ACA that courses directly upwards in the interhemispheric fissure.
Differential Diagnosis
The major differential diagnosis of CC dysgenesis is destruction caused by
trauma, surgery (callosotomy), or ischemia
. Occasionally the
hippocampal commissure
forms while the CC is absent and may mimic a remnant portion of the CC on sagittal images. Coronal views show the HC connects the fornices, not the hemispheres.
Selected References
Normal Development and Anatomy of the Cerebral Commissures
Normal Development
•
Barkovich AJ et al: Congenital malformations of the brain and skull. In X Y (et al): Pediatric Neuroimaging. 5th ed. Philadelphia: Lippincott Williams & Wilkins. 368-83, 2012; name of general editor(s) missing from this cite. I also suspect the pub date is 2011 rather than 2012, but not sure. Pretty sure the full cite for this book exists elsewhere in this book; find it and match it.
Normal Gross and Imaging Anatomy
•
Peltier J et al: Microsurgical anatomy of the anterior commissure: correlations with diffusion tensor imaging fiber tracking and clinical relevance. Neurosurgery. 69(2 Suppl Operative):241-6; discussion 246-7, 2011
•
Wang F et al: Microsurgical and tractographic anatomical study of insular and transsylvian transinsular approach. Neurol Sci. 32(5):865-74, 2011
•
Patel MD et al: Distribution and fibre field similarity mapping of the human anterior commissure fibres by diffusion tensor imaging. MAGMA. 23(5-6):399-408, 2010
Commissural Anomalies
•
Barkovich AJ: Congenital malformations overview. In Osborn AG et al: Diagnostic Imaging: Brain. 2nd ed. Salt Lake City: Amirsys. I-1-2 to I-1-5, 2010
•
Ren T et al: Imaging, anatomical, and molecular analysis of callosal formation in the developing human fetal brain. Anat Rec A Discov Mol Cell Evol Biol. 288(2):191-204, 2006
Callosal Dysgenesis Spectrum
•
Paul LK: Developmental malformation of the corpus callosum: a review of typical callosal development and examples of developmental disorders with callosal involvement. J Neurodev Disord. 3(1):3-27, 2011