The Ventricular System and the Cerebrospinal Fluid

CSF, cerebrospinal fluid; IgG, immunoglobulin G.

The CSF lies in the subarachnoid space, between the arachnoid and the pia mater. Within the subarachnoid space, web-like strands of arachnoid extend between the arachnoid and pia. The pia closely invests the surface of the brain and spinal cord, dipping into the fissures and sulci. The arachnoid bridges the fissures and sulci. The blood vessels that penetrate the brain go through the subarachnoid space and become invested with two layers of arachnoid; these arachnoid coats, which accompany the vessels for varying distances into the brain, are known as the perivascular (Virchow-Robin) spaces (Figure 2.3). The CSF flows into the perivascular spaces and is carried for a certain distance into the substance of the brain and spinal cord. The subarachnoid space, containing CSF, also extends outward for varying distances in periradicular and perineural spaces along exiting nerve roots and cranial nerves (CNs). In the spinal canal, a large subarachnoid space extends from the termination of the spinal cord to about the second sacral vertebra. This terminal sac contains the cauda equina and is the usual site for performing lumbar puncture (LP).

CEREBROSPINAL FLUID CIRCULATION

The CSF percolates from the lateral ventricles, through the foramen of Monro, into the third ventricle, and then down the cerebral aqueduct into the fourth ventricle. From the fourth, a small amount enters the central canal of the spinal cord while the majority is discharged through the foramina of Luschka and Magendie into the subarachnoid cisterns surrounding the brainstem and cerebellum. There is continuous circulation between these basal cisterns and the spinal subarachnoid space all the way to the lumbosacral region. Eventually, CSF migrates into the subarachnoid space over the convexities of the hemispheres alongside the superior sagittal sinus. Harvey Cushing referred to the flow of CSF as the “third circulation.”

The arachnoid villi (pacchionian granulations) are small, convoluted projections of the subarachnoid space and arachnoid that penetrate into the venous sinuses. The arachnoid villi are the site where the CSF is reabsorbed into the venous blood. The CSF in the arachnoid granulations is separated from the venous blood in the dural sinuses by only a layer of mesothelial arachnoid cells and a layer of vascular endothelium (Figure 2.2). Villi are most numerous in the superior sagittal sinus, but are also found in the other sinuses and along the spinal cord. The arachnoid villi function as one-way valves, allowing the passage of CSF into the venous blood, but no reverse flow. Some of the CSF is absorbed into the venous system from the periradicular and perineural spaces along the spinal roots and CNs, and from the perivenous spaces. There is also some absorption through gap junctions in the ventricular ependyma. The gap junctions permit the exchange of fluid between the CSF and the ISF. This route of absorption becomes more prominent when CSF flow is obstructed and the intraventricular CSF is under increased pressure.

CEREBROSPINAL FLUID FUNCTIONS

The CSF has many functions. One of its most important is mechanical, serving as a water jacket for the brain and spinal cord, bathing and protecting them. It helps support the weight of the brain, and has a cushioning effect against displacement. Suspended in CSF, the brain weighs only a fraction of what it otherwise would. The CSF serves as a lubricant between the brain and the spinal cord on one side, and the skull and spinal column on the other. It acts to dissipate the force of a blow to the head. It serves as a space-compensating mechanism for regulating the contents of the cranium and aids in keeping the intracranial pressure (ICP) relatively constant: If there is an increase in arterial pressure, blood content, or brain volume, there is a decrease in the amount of CSF, and if there is a decrease in the amount of brain tissue due to atrophy or degeneration, there is an increase in the amount of CSF.

The CSF is important in homeostasis, helping to maintain a constant external milieu for the brain. It is in equilibrium with the extracellular fluid of the brain. The CSF serves as a medium for the transfer of substances from within the brain and spinal cord to the blood stream; it receives metabolic waste products and aids in eliminating them; it is important for the removal of pathologic products in disease and for the circulation of drugs in therapy. The CSF acts as a “sink” for the extracellular fluid of the brain. Solutes and products of metabolism diffuse from the extracellular fluid and flow into the CSF sink, and then are carried away to be removed by the bulk flow resorption of the CSF into the venous system.

BLOOD-BRAIN BARRIER

Early investigators noticed that when an animal’s circulatory system was injected with various dyes, all the body organs became stained except the brain. They postulated a blood-brain barrier (BBB) to explain this finding. Later investigators amply demonstrated the accuracy of the observation. The site of the BBB is at the level of the pial-glial membranes and the cerebral capillaries. The capillaries in the brain are distinguished by having tight endothelial cell junctions, unlike those of capillaries elsewhere in the body. Tight junction proteins, occludin and claudin, glue the endothelial cells together. Such tight junctions are also a feature of the epithelial cells of the choroid plexus, creating a blood-CSF barrier. They restrict the passive movement of macromolecular substances across the cellular barrier. In addition to the tight junctions between endothelial cells, brain capillaries are also encased by foot processes of astrocytes and have a higher number of mitochondria than capillaries elsewhere in the body. Specialized transport systems that regulate selective transport of certain substances also form part of the BBB. Neurons, astrocytes and pericytes make up the neurovascular unit. Pericytes are a combination of smooth muscle and macrophage enclosed by a basal lamina. Astrocyte foot processes surround the basal lamina of the capillary and connect to the neurons, the third component of the neurovascular unit.

The ability of solutes to cross the BBB depends on their size and solubility. Small molecules enter the central nervous system (CNS) more easily than large molecules, and very large molecules are excluded. Substances that are highly lipid soluble, such as oxygen, carbon dioxide, and volatile anesthetics, enter more easily than those with low lipid solubility. Alcohol and nicotine are highly lipid soluble and easily transported into the brain. Substances highly bound to serum proteins are unable to penetrate the BBB. Some substances (e.g., glucose and amino acids) cross the BBB by active transport. Water has an anomalous structure that allows it to pass rapidly through endothelial cells. Many antibiotics cannot gain access to the CNS unless the meninges and the BBB are damaged by inflammation. Parkinson’s disease is treated with L-DOPA because the BBB excludes dopamine, the compound really needed. Some areas of the CNS lack a BBB, including the following: the chemoreceptor trigger zone in the area postrema in the floor of the fourth ventricle, subfornical organ in the anterior wall of the third ventricle, the median eminence of the hypothalamus, choroid plexus, organum vasculosum lamina terminalis, and the pineal and posterior pituitary glands. These areas are collectively known as the circumventricular organs; their capillaries have fenestrations instead of tight junctions. Many drugs produce nausea and vomiting as a prominent side effect because the lack of a BBB allows unfettered access directly from the blood stream to the area postrema and chemoreceptor trigger zone. The permeability of the BBB barrier may be altered by various disease states.

LUMBAR PUNCTURE

Although not done as often as in the past, LP remains an important part of the neurologic workup for many patients. The use of atraumatic, noncutting, pencil-point (Sprotte) needles significantly reduces the incidence of post-LP complications, particularly headache, in comparison to traditional, cutting-tip (Quincke) needles, and is increasingly becoming the standard.

There are two essential bits of information obtained from LP: the CSF pressure and the CSF composition. The opening pressure (OP) measurement is a vital part of the LP and should never be omitted. Normal is up to 180 mm of CSF, values of 180 to 200 are borderline, and pressures above 200 are abnormal unless the patient is obese, where there is evidence to suggest the normal OP may be as high as 250. Spuriously elevated pressure readings may be caused by poor relaxation. Transmitted venous pulsations cause small fluctuations in the manometric pressure; respiration causes larger fluctuations. The OP is the most reliable indicator of the ICP. In some circumstances, the only LP abnormality is an elevated OP, as in idiopathic intracranial hypertension (IIH, pseudotumor cerebri). In other conditions, an elevation of the OP may be an important clue to the presence of intracranial pathology. It may be difficult to measure the CSF pressure in children, and counting the number of drops of CSF over a specified time is a simple, rapid method for estimating CSF pressure.

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