Cerebrospinal fluid
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Cerebrospinal fluid (CSF), Liquor cerebrospinalis, is a clear bodily fluid that occupies the subarachnoid space and the ventricular system around and inside the brain. Essentially, the brain "floats" in it.
More specifically the CSF occupies the space between the arachnoid mater (the middle layer of the brain cover, meninges) and the pia mater (the layer of the meninges closest to the brain). Moreover it constitutes the content of all intra-cerebral (inside the brain, cerebrum) ventricles, cisterns and sulci (singular sulcus), as well as the central canal of the spinal cord.
It is an approximately isotonic solution and acts as a "cushion" or buffer for the cortex, providing also a basic mechanical and immunological protection to the brain inside the skull.
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[edit] Circulation
It is produced in the brain by modified ependymal cells in the choroid plexus. It circulates from the choroid plexus through the interventricular foramina (foramen of Monro) into the third ventricle, and then through the cerebral aqueduct (aqeduct of Sylvius) into the fourth ventricle, where it exits through two lateral apertures (foramina of Luschka) and one median aperture (foramen of Magendie). It then flows through the cerebromedullary cistern down the spinal cord and over the cerebral hemispheres.
Traditionally, it has been thought that CSF returns to the vascular system by entering the dural venous sinuses via the arachnoid granulations. However, some[1] have suggested that CSF flow along the cranial nerves and spinal nerve roots allow it into the lymphatic channels; this flow may play a substantial role in CSF reabsorbtion, particularly in the neonate, in which arachnoid granulations are sparsely distributed.
[edit] Amount and constitution
The cerebrospinal fluid is produced at a rate of 500 ml/day. Since the brain can only contain from 135-150 ml, large amounts are drained primarily into the blood through arachnoid granulations in the superior sagittal sinus. This continuous flow into the venous system dilutes the concentration of larger, lipoinsoluble molecules penetrating the brain and CSF. [2]
The CSF contains approximately 0.3% plasma proteins, or 15 to 40 mg/dL, depending on sampling site. [3] CSF pressure ranges from 60 - 100 mmH2O or 4.4 - 7.3 mmHg, with most variations due to coughing or internal compression of jugular veins in the neck.
[edit] Function
The cerebrospinal fluid has many putative roles including mechanical protection of the brain, distribution of neuroendocrine factors and prevention of brain ischemia. The prevention of brain ischemia is made by decreasing the amount of cerebrospinal fluid in the limited space inside the skull. This decreases total intracranial pressure and facilitates for blood perfusion.
[edit] Pathology
When CSF pressure is elevated, cerebral blood flow may be constricted. When disorders of CSF flow occur, they may therefore affect not only CSF movement, but also the intracranial blood flow, with subsequent neuronal and glial vulnerabilities. The venous system is also important in this equation. Infants and patients shunted as small children may have particularly unexpected relationships between pressure and ventricular size, possibly due in part to venous pressure dynamics. This may have significant treatment implications but the underlying pathophysiology needs to be further explored.
CSF connections with the lymphatic system have been demonstrated in several mammalian systems. Preliminary data suggest that these CSF-lymph connections form around the time that the CSF secretory capacity of the choroid plexus is developing (in utero). There may be some relationship between CSF disorders, including hydrocephalus and impaired CSF lymphatic transport.
[edit] Laboratory diagnosis
Cerebrospinal fluid can be tested for the diagnosis of a variety of neurological diseases. It is usually obtained by a procedure called lumbar puncture in an attempt to count the cells in the fluid and to detect the levels of protein and glucose. These parameters alone may be extremely beneficial in the diagnosis of subarachnoid hemorrhage and central nervous system infections (such as meningitis). Moreover, a cerebrospinal fluid culture examination may yield the microorganism that has caused the infection. By using more sophisticated methods, such as the detection of the oligoclonal bands, an ongoing inflammatory condition (for example, multiple sclerosis) can be recognized. A beta-2 transferrin assay is highly specific and sensitive for the detection for e.g. cerebrospinal fluid leakage.
[edit] Lumbar puncture
Lumbar puncture can also be performed to measure the intracranial pressure, which might be increased in certain types of hydrocephalus. However a lumbar puncture should never be performed if increased intracranial pressure is suspected because it could lead to brain herniation.
[edit] Baricity
This fluid has an importance in anethesiology. Baricity refers to the density of a substance compared to the density of human cerebral spinal fluid. Baricity is used in anesthesia to determine the manner in which a particular drug will spread in the intrathecal space.
[edit] Normal CSF flow physiology
It is now generally agreed that CSF-circulation is propelled by a pulsating flow, which causes an effective mixing. This pulsatile flow is produced by the alternating pressure gradient, which is a consequence of the systolic expansion of the intracranial arteries causing expulsion of CSF into the compliant and contractable spinal subarachnoid space . No bulk flow is necessary. It has been suggested that the main absorption of the CSF is not through the Pacchionian granulations, but a major part of the CSF transportation to the blood-stream is likely to occur via the paravascular and extracellular spaces of the central nervous system. The intracranial CSF flow dynamics may be regarded as the result of an interplay between the demands for space by the four components of the intracranial content, i.e. the arterial blood, brain volume, venous blood and the CSF. This interaction is shown to have a time offset within the cerebral hemispheres in a fronto-occipital direction during the cardiac cycle (the fronto-occipital "volume wave"). The CSF outflow from the cranial cavity to the cervical subarachnoid space is dependent in size and timing on the intracranial arterial expansion during systole. In the same manner as the outflow from the aqueduct mirrors the brain expansion. The expansion of the brain is typically very small as evident from the minute aqueductal flow observed in healthy individuals. This expansion of the brain occurs simultaneously with an inflow of CSF and will be directed inwards towards the ventricular system. The expansion of the brain is of decisive importance for the formation of the normal transcerebral pressure gradient. The instantaneous increase of flow in the superior sagittal sinus at the beginning of the systole reflects a direct pressure transmission via the subarachnoid space from the expanding arteries to the cerebral veins. It has been suggested that this early increase in venous pressure together with the volume wave is most likely an important prerequisite for sustaining normal intracranial pressure (ICP) and normal cerebral blood flow. This counter pressure should be reduced in hydrocephalus due to the decreased arterial expansion and could explain the reduced blood flow as well as an increased transmantle pressure gradient causing the ventricular dilatation. An increased pressure in the venous system is likely to be the cause of increases in ICP, including the increased pressure observed in benign intracranial hypertension (BIH) [4].
[edit] MRI of CSF flow in pathology
Normal patterns of pulsatile flow within the ventricles, cisterns and cervical subarachnoid space could be evaluated using magnetic resonance imaging of CSF flow, using cardiac gated intracranial phase-contrast technique. There is a systolic and diastolic variation in phase contrast images of the CSF pathway. Njemanze and Beck, suggested that this is as a result of a pump action referred to as the 'third ventricular, ot thalamic pump" that consisted largely of a rhythmic squeeze between the two thalami, which are driven together by arterial pulse transformation [5]. Other pulsatile movements were observed in the aqueduct, foramen of Monro, basal cisterns, and spinal subarachnoid space, especially at the cervical level. DuBoulay and colleagues had concluded that pulsation of the CSF was due to pulsation in the vascular system [6]. There is transmission of the arterial pulse pressure wave to the brain after ventricular systole has ended, about 280 msec after R wave. In the systolic phase there is downward (caudal) flow of CSF in the aqueduct of Sylvius, the foramen of Magendie, the basal cisterns and the dorsal and ventral subarachnoid spaces. Diastole flows immediately and results in a prompt drop-off in pulse pressure with the carotid arteries and brain[7]. During the diastolic phase, there is upward (cranial) flow of CSF in the aqueduct and subarachnoid space. The flow relationships between the cardiac cycle and the CSF pulsations could be seen on both magnitude reconstruction and phase reconstruction MR images. Some investigators have calculated the actual fluid velocity within CSF containing spaces can be obtained from the phase reconstruction images and holds promise for a more accurate analysis of CSF flow [8]. Some investigators have claimed that phase-contrast MR imaging, done before and after CSF drainage, is a sensitive method to support the clinical diagnosis of normal pressure hydrocephalus (NPH), selecting patients of NPH who are likely to benefit from shunt surgery, and to select patients of NPH who are not likely to benefit from shunt surgery[9];[10];[11]. However others disagree, showing that among patients who underwent ventriculoperitoneal shunting (VPS) for the treatment of NPH, measurement of CSF flow through the cerebral aqueduct did not reliably predict which patients would improve after shunting or the magnitude of improvement[12].
Interpretation of Lumbar puncture
| Cause | Appearance | Polymorphonuclear cell | Lymphocyte | Protein | Glucose |
|---|---|---|---|---|---|
| Pyogenic bacterial meningitis | Yellowish, turbid | Markedly increase | Slightly increase or Normal | Slightly increase or Normal | Decrease |
| Viral meningitis | Clear fluid | Slightly increase or Normal | Markedly increase | Markedly increase | Normal |
| Tuberculous meningitis | Yellowish and viscous | Slightly increase or Normal | Markedly increase | Slightly increase or Normal | Decrease |
| Fungal meningitis | Yellowish and viscous | Slightly increase or Normal | Markedly increase | Slightly increase or Normal | Normal or decrease |
[edit] References
- ^ Zakharov A, Papaiconomou C, Djenic J, Midha R, Johnston M (2003). "Lymphatic cerebrospinal fluid absorption pathways in neonatal sheep revealed by subarachnoid injection of Microfil". Neuropathol. Appl. Neurobiol. 29 (6): 563-73. PMID 14636163.
- ^ Saunders NR, Habgood MD, Dziegielewska KM (1999). "Barrier mechanisms in the brain, I. Adult brain". Clin. Exp. Pharmacol. Physiol. 26 (1): 11-9. PMID 10027064.
- ^ Felgenhauer K (1974). "Protein size and cerebrospinal fluid composition". Klin. Wochenschr. 52 (24): 1158-64. PMID 4456012.
- ^ Greitz, D. (1993). Cerebrospinal fluid circulation and associated intracranial dynamics. A radiologic investigation using MR imaging and radionuclide cisternography. Acta Radiologica Suppl., 386, 1-23.
- ^ Njemanze, P.C., Beck, O.J. (1989). MR-gated intracranial CSF dynamics: evaluation of CSF pulsatile flow. American Journal of Neuroradiology (AJNR), 10, 77-80.
- ^ DuBoulay, G., O'Connell, J., Currie, J., Bostic, T., Verity, P. (1972). Further investigations on pulsatile movements in the cerebrospinal fluid pathways. Acta Radiologica, 13, 496-523.
- ^ Citrin, C.M., Sherman, J.L., Ganarosa, R.E., Scanlon, D. (1986). Physiology of the CSF flow-void sign: modification by cardiac gating. American Journal of Neuroradiology, 7, 1021-1024.
- ^ Quencer, R.M., Post, M.J., Hinks, R.S. (1990). Cine MR in the evaluation of normal and abnormal CSF flow: intracranial and intraspinal studies. Neuroradiology, 32, 371-391.
- ^ Sharma, A.K., Gaikwad, S., Gupta, V., Garg, A., Mishra, N.K. (2008). Measurement of peak CSF flow velocity at cerebral aqueduct, before and after lumbar CSF drainage, by use of phase-contrast MRI: utility in the management of idiopathic normal pressure hydrocephalus. Clinical Neurology and Neurosurgery, 110, 363-368.
- ^ Mascalchi, M., Arnetoli, G., Inzitari, D., Dal Pozzo, G., Lolli, F., Caramella, D., Bartolozzi, C. (1993). Cine-MR imaging of aqueductal CSF flow in normal pressure hydrocephalus syndrome before and after CSF shunt. Acta Radiologica, 34, 586-592.
- ^ Bradley, W.G. Jr, Scalzo, D., Queralt, J., Nitz, W.N., Atkinson, D.J., Wong, P. (1996). Normal-pressure hydrocephalus: evaluation with cerebrospinal fluid flow measurements at MR imaging. Radiology. 198, 523-529.
- ^ Dixon, G.R., Friedman, J.A., Luetmer, P.H., Quast, L.M., McClelland, R.L., Petersen, R.C., Maher, C.O., Ebersold, M.J. (2002). Use of cerebrospinal fluid flow rates measured by phase-contrast MR to predict outcome of ventriculoperitoneal shunting for idiopathic normal-pressure hydrocephalus. Mayo Clinical Proceedings, 77, 509-514.
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