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flow in the ventricular cavities is unidirectional and rostrocaudal. CSF exits the fourth ventricle into the SASs through the medial foramen (of Magendie) and the two lateral foramina (of Luschka), which form the only natural communications between the ventricles and the SAS (34-6).

In the classic model, CSF resorption was thought to occur mostly via bulk flow, driven by the hydrostatic pressure difference between the CSF and cerebral veins. Flow-sensitive MR has now demonstrated that CSF motion is actually pulsatile and is driven by pressure waves from intracranial blood vessels generated during the cardiac cycle. This results in a relatively small net flow from the ventricles toward the SAS.

Updated Model of CSF and ISF Homeostasis. New evidence suggests that the traditional model of CSF production, circulation, and function is too simplistic and much more complex than previously thought. It is now recognized that CSF plays an essential role in the maintenance of brain ISF homeostasis and that the two are intimately interrelated in maintaining normal brain function. The main sources of ISF are the blood and CSF.

In the updated CSF-ISF model, the brain perivascular spaces (PVSs) (Virchow-Robin) and paravascular spaces play a critical role in CSF homeostasis. The PVSs form a key component of the brain's "protolymphatic" or "glymphatic" system. The PVSs are lined with leptomeningeal (pial) cells that coat the PVSs as well as arteries and veins in the SAS, thus separating CSF in the SAS from the brain parenchyma and PVSs.

Human brain capillaries are formed by an endothelium that separates them from the extracellular space (ECS). Fibrous astrocytes form end-feet that completely surround the capillaries. A basement membrane separates the astrocyte end-feet from the capillary endothelium. The capillary endothelial basement membrane is fused with the layer of basement membrane adjacent to the astrocyte end-feet and is also shared with contractile pericytes. The endothelial cells, astrocytes, and pericytes are all involved in the regulation of blood-brain barrier permeability.

ISF diffuses through the ECS and then drains via bulk flow along the basement membranes of cerebral capillaries. ISF circulation likely occurs through the water-selective aquaporin (AQP) channels of the glymphatic system, key factors in regulating ECS water homeostasis. AQP4 is highly expressed in astrocytic end-feet and also appears to be crucial for fluid exchange between the CSF and ISF.

A substantial amount of ISF exits the brain via connections between the perivascular spaces and leptomeningeal arteries. Tracer experiments show that both CSF and ISF drain through the cribriform plate to lymphatics of the head and neck.

Estimates are that CSF drainage is approximately one-third via arachnoid granulations (and possibly lymphatics) in the cranial dura mater, one-third via paravascular spaces adjacent to intracerebral arteries and around leptomeningeal arteries passing through the cribriform plate to the cervical lymphatics/deep cervical lymph nodes, and one-third via spinal vessels.

Finally, in this model of CSF and ISF homeostasis, drainage of extracellular fluids in the CNS and integrity of the brain glymphatic system is important for not only volume regulation, but also clearance of waste products such as amyloid-β (Aβ) from the brain parenchyma.

Subarachnoid Spaces/Cisterns

The subarachnoid spaces (SASs) lie between the pia and arachnoid (34-3). The sulci are small, thin SASs that are interposed between the gyral folds. Focal expansions of the SASs form the brain CSF cisterns. Numerous pial-covered septa cross the SASs from the brain to the arachnoid, which is loosely attached to the inner layer of the dura.

The major cisterns are found at the base of the brain above the sella turcica, around the brainstem, at the tentorial apex, adjacent to the cerebellopontine angles, and above/below the foramen magnum. All SASs normally communicate freely with each other and the ventricular system, providing natural pathways for disease dissemination (34-5).

Normal Variants

Age-Related Changes

Morphometrical ageand sex-related studies using threedimensional volume rendering derived from standard 3-T MR scans show that an increase in lateral ventricular volume is a constant, linear function of age throughout life.

Asymmetric Lateral Ventricles

Asymmetric lateral ventricles can be identified on imaging studies in approximately 5-10% of normal patients. The asymmetry is typically mild to moderate (34-7). Bowing, deviation, or displacement of the septi pellucidi across the midline is common; by itself, it neither indicates pathology nor implicates an etiology for nonspecific headache.

Severe degrees of asymmetry, diffuse nonfocal ventricular enlargement, or evidence of transependymal CSF migration should prompt a search for possible accompanying disorders.

The major differential diagnosis for asymmetric lateral ventricles is unilateral obstructive hydrocephalus. Unilateral obstructive hydrocephalus is rare, occurring when only one arm of the foramen of Monro becomes occluded (34-8). Membranous obstruction of the foramen of Monro can be overlooked and is best differentiated from benign ventricular asymmetry using special MR techniques (see below).

Cavum Septi Pellucidi and Vergae

Terminology

A cavum septi pellucidi (CSP) is a fluid-filled cavity that lies between the frontal horns of the lateral ventricles (34-9). A cavum vergae (CV) is an elongated finger-like posterior extension from the CSP that lies between the fornices (3410).

(34-7) (L) NECT shows that the right lateral ventricle is larger than the left, septum pellucidum is displaced across the midline. (R) FLAIR shows that the ventricular asymmetry is normal without evidence for obstruction.

A CSP may occur in isolation, but a CV occurs only in combination with a CSP. When the two occur together, the correct Latin terminology is "cavum septi pellucidi et vergae." In common usage, the combination is often referred to simply as a CSP.

Etiology

The septum pellucidum consists of two paired glial membranes ("leaflets") that develop at about 12 weeks of gestation. These embryonic leaflets are initially unfused, and the cavity between them is filled with CSF. Normally the two leaflets eventually fuse, and the cavity between them is obliterated. The fused membranes then become the septum pellucidum.

If the two leaflets fail to fuse, the persisting cavity between them has two different names. Anterior to the foramen of Monro it is called a CSP. Its posterior continuation between the fornices is designated the CV.

Clinical Issues

CSP prevalence decreases with increasing age. By 3-6 months of age, the CSP is closed in 80-85% of infants. The reported prevalence of CSP and CV in adults ranges from 1-5%. A CSP is usually asymptomatic and is typically a "leave-me-alone" lesion found incidentally on imaging studies.

Imaging

CT and MR. The appearance of CSPs and CVs on CT and MR varies from an almost inapparent, slit-like cavity to a prominent collection measuring several millimeters in diameter. A CSP is isodense with CSF on NECT and follows CSF

(34-8) (L) NECT shows enlarged, blurred right lateral ventricle, normal left , displaced septum pellucidum, and fornix .

(R) Contrast ventriculogram shows obstruction is at right limb of the foramen of Monro ; unilateral obstructive hydrocephalus.

signal intensity exactly on MR. It suppresses completely on FLAIR.

In rare cases, an unusually large CSP/CV creates significant mass effect, splaying the fornices and leaves of the septi pellucidi laterally.

Ultrasound. A CSP is present in 100% of fetuses and is therefore always identified during obstetric sonography. The CSP increases in size between 19-27 gestational weeks, plateaus at 28 weeks, and then gradually closes from back to front. By term, the posterior part is usually fused, and, in 85% of cases, the CSP is completely closed by 3-6 postnatal months. A CSP may persist into adulthood as a normal variant.

Differential Diagnosis

The location and appearance of a CSP with or without a CV is virtually pathognomonic and should not be confused with a cavum velum interpositum (CVI). A CVI is a thin, triangular CSF space that overlies the thalami and third ventricle. A CVI typically occurs without a CSP.

An absent septum pellucidum lacks septal leaves, and the frontal horns appear as a single squared-off or "box-like" CSF cavity. An asymmetric lateral ventricle has a fused septi pellucidi that may be displaced across the midline. Ependymal cysts in the frontal horn are rare. When present, they focally displace the septi pellucidi rather than splaying its leaves apart.

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Cavum Velum Interpositum

Terminology

The velum interpositum (VI) is a thin translucent membrane formed by two infolded layers of pia-arachnoid. The VI is adherent to the undersurface of the fornices and extends laterally over the thalami to become continuous with the choroid plexus of the lateral ventricles. Together with the fornices, the VI forms the roof of the third ventricle (see Chapter 20).

The VI is often CSF-filled and open posteriorly, communicating directly with the quadrigeminal cistern. In such cases, it is called a cavum velum interpositum (CVI) (34-11). A CVI is considered a normal anatomic variant.

Clinical Issues

CVIs can be found at any age. They are usually asymptomatic and discovered incidentally on imaging studies. Mild nonspecific and nonfocal headache is the most common reported symptom.

Imaging

On imaging studies, a CVI appears as a triangular CSF space that curves over the thalami between the lateral ventricles. Its apex points toward the foramen of Monro (34-12).

CVI size varies from an almost inapparent slit-like cavity to a round or ovoid cyst-like mass that elevates and splays the fornices superiorly while flattening and displacing the internal cerebral veins inferiorly (34-12).

A CVI is isodense with CSF on NECT and isointense on all MR sequences. It suppresses completely on FLAIR, does not enhance, and does not restrict on DWI.

Differential Diagnosis

The major differential diagnosis of CVI is epidermoid cyst. An epidermoid cyst of the VI can occur but is rare. An epidermoid cyst shows some diffusion restriction and does not suppress completely on FLAIR. A large CVI may be impossible to distinguish from an arachnoid cyst in the VI on the basis of imaging studies alone. A CSP with CV is elongated and finger-shaped, not triangular.

Enlarged Subarachnoid Spaces

Enlarged subarachnoid spaces (SASs) occur in three conditions: communicating hydrocephalus, brain atrophy, and benign enlargement of the SASs. Communicating hydrocephalus (both the intraand extraventricular types) is discussed below. Brain atrophy—sometimes inappropriately called "hydrocephalus ex vacuo"—is discussed in Chapter 33 as a manifestation of aging and brain degeneration. In this section, we discuss benign physiologic enlargement of the SAS.

Terminology

Idiopathic enlargement of the SASs with normal to slightly increased ventricular size is common in infants. Large CSF spaces in developmentally and neurologically normal children with or without macrocephaly may be called benign SAS enlargement, benign idiopathic external hydrocephalus, benign external hydrocephalus, and benign extracerebral fluid collections of infancy. The preferred term is benign enlargement of the SASs (BESS).

Etiology

The precise etiology of benign enlarged SASs in infants is unknown but probably related to immature CSF drainage pathways. Pacchionian granulations do not fully mature until 12-18 postnatal months, by which time the benign SAS enlargement generally resolves.

There is no known genetic predisposition, although 80% of infants with benign enlarged SASs have a family history of macrocephaly.

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(34-13) Graphic depicts benign enlarged frontal SASs . Posterior SASs are normal. Note cortical veins crossing the prominent SASs .

(34-14A) CECT scan in a 7m infant shows prominent bifrontal, interhemispheric subarachnoid spaces and bridging veins .

Pathology

Grossly, the SASs appear deep and unusually prominent but otherwise normal (34-13). There are no subdural membranes present that would suggest chronic subdural hematomas or effusions.

Clinical Issues

Epidemiology and Demographics. The incidence of benign enlargement of the SASs is difficult to ascertain. It is reported on 2-65% of imaging studies for macrocrania in children under 1 year of age.

Benign enlarged SASs typically present between 3 and 8 months. There is a 4:1 M:F predominance.

Presentation. Occipitofrontal head circumference (OFC) tends to be in the high-normal range at birth and increases rapidly within the first few months. Macrocrania with OFC above the 95th percentile is typical at presentation.

There are no findings indicative of elevated intracranial pressure or nonaccidental trauma. Mildly delayed development is present in about half of all cases, but normal milestones are eventually reached.

(34-14B) More cephalad CECT in the same patient shows fluid collections , bridging veins . These are benign enlarged SASs of infancy.

(34-15A) Sagittal T1WI in a normal 7m infant with a large head shows macrocrania and enlarged frontal subarachnoid spaces .

(34-15B) Coronal T1WI in the same patient demonstrates prominent SASs and sylvian fissures .

(34-15C) Axial T2WI shows prominent frontal, interhemispheric subarachnoid spaces and bridging veins .

The frontal SASs in infants can normally appear somewhat prominent, reaching maximum size at about 7 months. The presence of prominent SASs in and of itself does not establish the diagnosis of benign enlarged SASs; head circumference should be at or above the 95th percentile.

CT Findings. Typical NECT findings in infants with benign enlarged SASs are prominent bifrontal and anterior interhemispheric SASs larger than 5 mm in diameter, enlarged suprasellar/chiasmatic cisterns, prominent sylvian fissures, and mildly enlarged lateral and third ventricles. The posterior and convexity sulci appear normal.

CECT scans demonstrate bridging veins traversing the SAS (34-14). There is no evidence of thickened enhancing membranes to suggest subdural hematoma or hygroma.

MR Findings. Fluid in the enlarged frontal SASs exactly parallels CSF because it is CSF (34-15). The fluid suppresses completely on FLAIR, and there is no evidence of "blooming" on T2* (GRE, SWI). Enhancing veins can be seen traversing the SASs on T1 C+. DWI is normal.

Ultrasound. Ultrasound shows increased craniocortical width with linear echogenic foci caused by bridging veins that can be seen coursing directly into the superior sagittal sinus. Color Doppler demonstrates venous structures traversing the prominent SASs.

Differential Diagnosis

The major differential diagnoses of benign enlarged SASs are atrophy, extraventricular obstructive hydrocephalus, and nonaccidental trauma. In atrophy, the OFC is normal to small. In extraventricular obstructive hydrocephalus secondary to infection or trauma, the fourth ventricle is frequently enlarged, and the CSF in the extraaxial spaces does not parallel that of CSF in density or signal intensity.

Occasionally, infants with benign enlarged SASs have minor superimposed hemorrhagic subdural collections, similar to those sometimes observed with arachnoid cysts. In such infants, abusive head trauma must be a consideration until careful screening discloses no substantiating evidence of inflicted injury.

CSF Flow Artifacts

Normal CSF has long T1 and T2 relaxation times, causing the familiar dark and bright signal, respectively. CSF-related artifacts in the brain and spine are common on MR scans, primarily due to the to-and-fro pulsatile nature of CSF motion. Although a complete discussion of CSF flow-related phenomena is beyond the scope of this text, we briefly describe three examples of major CSF artifacts that can mimic pathology on MR.

CSF flow-related phenomena are caused by time-of-flight (TOF) effects, turbulent flow, and patient motion.