Cerebrospinal fluid (CSF) is considered a part of the transcellular fluids.
It is contained in the ventricles and the subarachnoid space and bathes the brain & spinal cord.
The CSF is contained within the meninges & acts as a cushion to protect the brain from injury with position or movement.
It has been estimated that this ‘water bath’ effect gives the 1400g brain an effective net weight of only 50g.The total volume of CSF is 150 mls.
The daily production is 550 mls/day so the CSF turns over about 3 to 4 times per day.The CSF is formed by the choroid plexus (50%) and directly from the walls of the ventricules (50%).
It flow through the foramens of Magendie & Luschka into the subarachnoid space of the brain and spinal cord. It is absorbed by the arachnoid villi (90%) and directly into cerebral venules (10%).The normal intracerebral pressure (ICP) is 5 to 15 mmHg.
The rate of formation of CSF is constant and is not affected by ICP.
Absorption of CSF increases linearly as pressure rises above about 7 cmsH2O pressure.At a pressure of about 11cmsH2O, the rate of secretion & absorption are equal.
The CSF has a composition identical to that of the brain ECF but this is different from plasma.
The major differences from plasma are:
2 is higher (50 mmHg) resulting in a lower CSF pH (7.33)
Turbidity - white cell count > 200.
Erythrochromia - > 30 RBC / microliter of not greater than 6 hrs presence in CSF.
Xanthochromia - Yellow discolouration due to blood present greater than 6 hrs or due increased permeability of meninges for bilirubin or carotene ( meningitis or blocked CSF circulation).
Brown discolouration - melanosarcoma
Oligoclonal - Untreated neurosyphilis, SSPE, MS, Retrobulbar neuritis, Trypanosomiasis
Monoclonal - Gamma plasmacytoma
Communicating: CSF reabsorption is impaired eg by fibrin clots after Subarachnoid haemorrhage. All ventricles are uniformly dilated.
Obstructive: CSF flow is impaired due to local blockage with resulting accumulation of CSF and ventricular dilatiation upstream of the obstruction. congenital hydrocephalus the aqueduct of Sylvius is obstructed due to stenosis or incomplete development. Tumours are also a frequent cause of obstruction.
v Total cessation of BF to brain à ↓ in O2 delivery à Shutdown of metabolic activity à Unconsciousness within 5-10 sec.
q Brain metabolism is ≈ 15% of total metabolism of body.
q Brain has limited anaerobic capability (mostly aerobic) because:
Õ ↑ Metabolic activity of neurons.
Õ ↓↓ Amount of glycogen stored in neurons (only 2-min supply).
q Therefore, most neuronal activity depends on second-by-second delivery of glucose & O2 from blood.
q Glucose transport to cell membranes of neurons is insulin-independent.
q Brain receives ≈ 15% of total resting CO.
q Cerebral BF is related to level of metabolism.
q 3 metabolic factors have potent effects on cerebral BF: CO2, H+, O2.
q Act of making a fist with hand à immediate ↑ in BF in motor cortex of opposite cerebral hemisphere.
õ ↑↑ Neuronal activity in particular area of brain.
õ à ↑ CO2:
o Vasodilator in itself.
o CO2 + H2O D H2CO3 D H+ + HCO3-
Any substance ↑ acidity in brain (e.g. pyruvic, lactic acid) à ↑ H+ (vasodilator).
õ à ↓ O2 à Local vasodilator à ↑ Cerebral BF.
Cerebral BF is autoregulated:
q Cerebral BF is nearly constant between limits of 60 & 140 mm Hg of mean arterial pressure (MAP).
õ If arterial pressure < 60 mm Hg à Cerebral BF becomes extremely compromised.
õ If arterial pressure > 140 mm Hg à Overstretching / rupture of cerebral blood vessels.
à Brain edema / Cerebral hemorrhage.
q Sympathetic NS has a role in regulation of cerebral BF:
During strenuous exercise / states of enhanced circulatory activity à Sympathetic impulses à
Vasoconstriction of large & intermediate-sized arteries à
Prevent ↑ pressure from reaching small-sized blood vessels & thus hemorrhage.
q Capillaries (hence BF) in gray matter (where neuronal cell bodies lie) are 4X greater than in white matter.
q Capillaries are surrounded by "glial feet" à Prevent overstretching of capillaries in case of ↑ pressure.
q CSF in brain ≈ 150 mL.
q This fluid is found in: ventricles of brain, cisterns around brain, subarachnoid space around both brain & spinal cord. These chambers are interconnected & pressure of CSF is regulated at constant level.
q A major function of CSF is to cushion brain.
q Brain & CSF have same specific gravity. Therefore, brain essentially floats in CSF.
A blow to the head à Entire brain moves simultaneously with skull à
No single portion of brain becomes momentarily contorted by blow.
Formation & Absorption of CSF
q ≈ 500 mL of CSF is formed each day.
q Most of this fluid originates from choroid plexuses of the four ventricles. Additional amounts of fluid are secreted by ependymal surfaces of ventricles & arachnoidal membranes.
q CSF is absorbed by multiple arachnoidal villi à Empties into venous blood.
q Proteins that leak into interstitial spaces flows through perivascular spaces à Subarachnoid space à CSF à Absorbed through arachnoidal villi à Cerebral veins.
Normally is regulated by absorption of fluid through arachnoidal villi. Arachnoidal villi function like one-way valves that allow CSF to flow into blood of venous sinuses, but prevent backward flow of blood into CSF.
§ Normal CSF pressure ≈ 10 mm Hg (120 mm H2O).
§ Blockage of villi à ↑ CSF pressure (e.g. by infectious debris, blood cells from hemorrhage, fibrosis, tumors).
· Obstruction to flow of CSF.
· Obstructive (non-communicating) hydrocephalus:
o Block of CSF before it reaches the subarachnoid space i.e. blockage within the ventricular system.
o Usually congenital defect / tumor à blockade of aqueduct of Sylvius.
o ↑ Fluid volume in the 2 lateral & 3rd ventricles à Head swells tremendously in infants (since skull bones haven’t fused) + Brain atrophy.
· Communicating hydrocephalus:
Blockage of fluid flow into subarachnoid space around basal regions of brain / blockage of arachnoid villi themselves à
Fluid collects inside ventricles & on outside brain à Head swells tremendously in infants (since skull bones haven’t fused).
Blood-CSF barrier & BBB:
◙ Exist at choroids plexus & at tissue capillary membranes in all areas of brain parenchyma except in some areas of hypothalamus & pineal gland.
◙ These barriers are:
o Highly permeable to:
· H2O, CO2, O2, Lipophilic substances (e.g. alcohol, anesthetics).
o Slightly permeable to: Electrolytes.
o Totally impermeable to:
· Plasma proteins + hydrophilic large organic molecules.
◙ The cause of low permeability is the presence of tight junctions between adjacent endothelial cells + absence of fenestrations.
Production of CSF
is formed from two main sources:
CHOROID PLEXUS TISSUE - found in four sites: left and right lateral ventricles, the third ventricle and the fourth ventricle.
The fourth ventricle produces the greatest volume of CSF.
Choroid plexus tissue consists of a group of arterioles, each coated with a layer of pia mater and a layer of non-nervous cuboidal epithelium that is the ependymal lining of the ventricular system.
Small arteries, arterioles and capillaries suspended in the filaments of the arachnoid in the sub-arachnoid space.
Fluid produced in the lateral ventricles drains via the INTERVENTRICULAR FORAMINAE into the third ventricle, where CSF flow is added to by the choroid plexus tissue of the third ventricle.
Flow continues via the aqueduct of the midbrain to the fourth ventricle, and it is from here that fluid escapes into the subarachnoid space via two lateral apertures.
In the subarachnoid space the fluid flows over the entire surface of the brain and spinal cord.
Some fluid travels down the central canal of the spinal cord. In some species there is an exit from the caudal end of this canal into the subarachnoid space at the end of the spinal cord, this space is called the LUMBAR CISTERN.
Drainage of CSF
is produced continuously and fairly rapidly, and therefore to avoid problems a system has to exist which removes it at the same rate. In the dog the volume of the ventricles and the spinal canal in only 6-7ml, while 30ml of CSF is produced each hour. Therefore CSF is removed from the subarachnoid space at a reasonably fast rate. There are two main reabsorption routes:
DIRECT ABSORPTION into venules in arachnoid filaments. Absorption rate depends on the relative osmotic pressure of the CSF to the blood.
ARACHNOID VILLI or GRANULATIONS (see diagram) formed by the arachnoid mater pushing through the dura directly into the venous sinuses, in particular the dorsal sagittal sinus. This only occurs in the cranial cavity. Electron microscopy has shown there to be valves in the wall of these arachnoid villi, effectively allowing CSF direct access to the venous system.
Functions of CSF
Nutritive and metabolic functions.
Protection of brain and spinal cord against impact to the bony surrounds. This protective function depends mainly on buoyancy, effectively making the weight of the brain 1/30th of its actual weight. CSF also ensures that there is an equal distribution of pressure on the nervous tissue.
It allows variations in blood volume in the cranial cavity. If the blood pressure increases, CSF volume decreases, thus preventing a build-up of pressure.
It acts as a diffusion medium for neurotransmitters and neuroendocrine sustances.
Collection of CSF
The CISTERNA MAGNA (cerebromedullary cistern), which lies between the cerebellum and the medulla, and is a convenient site for CSF sampling in the anaesthetised small animal.
The LUMBAR CISTERN. The dura and arachnoid continue beyond the end of the spinal cord as far as S4 in the horse and ox. The subarachnoid space is relatively large at the caudal end of the cord and forms the lumbar cistern, which is a useful site for sampling CSF in the larger species. The needle is inserted between L6 and S1 (see diagram)
Potential Clinical Problems
INTERNAL HYDROCEPHALUS - this occurs when there is a physical interruption of flow within the ventricular system, and is usually at the narrowest parts, ie at the interventricular foraminae or in the aqueduct of the midbrain, and may occur as a result of tumour growth. (Space-occupying lesion)
EXTERNAL HYDROCEPHALUS - this results from failure of the drainage mechanism leading to a build-up of pressure in the subarachnoid space that causes compression of brain tissue.
Hydrocephalus is seen in puppies, usually of the small breeds with large skulls (Chihuahuas, Yorkies etc) and among the brachiocephalic breeds (Pekes, Bulldogs).
No treatment is possible in veterinary practice.
Normal pressure hydrocephalus (NPH) is a type of hydrocephalus which normally occurs in older adults.
NPH is an accumulation of cerebrospinal fluid (CSF), which causes the ventricles of the brain to enlarge. The enlarged ventricles of an NPH patient may not cause increased intracranial pressure, as is the case with most types of hydrocephalus. The abnormal accumulation of CSF, causing enlarged ventricles, is thought to stretch the nerve tissue of the brain causing a triad of symptoms.NPH normally occurs in adults 60-years and older, and in as many as 10% of all patients with symptoms of dementia. One quarter million Americans with some of the same symptoms as dementia, Alzheimer's, or Parkinson's may actually have NPH.
Hydrocephalus is an abnormal (excessive) accumulation of fluid in the head.
The fluid is called cerebrospinal fluid, commonly referred to as
The CSF is located and produced within cavities of the brain called
The function of CSF is to cushion the delicate brain and spinal cord tissue from injuries and maintain proper balance of nutrients around the central nervous system.Normally, the bloodstream absorbs most of the CSF produced on a daily basis. Every day your body produces a certain amount of CSF and that same amount of CSF is absorbed in the brain.When an imbalance occurs, an excess of CSF fluid builds up resulting in the condition known as hydrocephalus.Left untreated, hydrocephalus will create increased pressure in the head and may result in increased symptoms or brain
For most patients the cause of NPH cannot be determined. In some cases, history of previous brain injury or surgery can result in hydrocephalus.
Examples are brain hemorrhage, aneurysm, trauma, tumors or cysts, infections or subdural hematomas.
In other cases, the imbalance in the production or absorption of CSF causes the hydrocephalus.Diagnosis of NPH is often difficult due to the symptoms being similar to other disorders. In many cases the NPH is thought to be mild dementia, Alzheimer's, Parkinson's or simply old age factors. Many cases go completely unrecognized and are never treated. Usually, NPH causes the ventricles to enlarge due to increased CSF within the skull.
If a person exhibits symptoms of hydrocephalus a physician may perform several tests to determine if shunting is an option. The most common diagnostic tools are neuro-imaging devices such as CT or MRI and a careful clinical assessment. Once the diagnosis of NPH is suspected there is no single perfect test to determine if a patient will respond to the shunt.
Characterized by three primary symptoms, NPH patients usually exhibit
gait disturbance (difficulty walking), dementia, and urinary incontinence.
However, not all symptoms are always apparent.
Because these three symptoms are often associated with the aging process in general, and a majority of the NPH population is older than 60 years, people often assume that they must live with the problems or adapt to the changes occurring within their bodies. Symptoms can be present for months or even years before a person sees a physician. The symptoms of NPH seem to progress with time. The rate of progress is variable, and it is often a critical loss of function, or disability, that brings patients to their doctors. It seems that the longer the symptoms have been present, the less likely it is that treatment will be successful. As a general rule, the earlier the diagnosis, the better the chance for successful treatment, but some people experiencing symptoms for years can improve with treatment.
Gait disturbances range in severity, from mild imbalance to the inability to stand or walk at all. For many patients, the gait is wide-based, short, slow and shuffling. People may have trouble picking up their feet, making stairs and curbs difficult and frequently resulting in falls. Gait disturbance is often the most pronounced symptom and the first to become apparent.
Mild dementia can be described as a loss of interest in daily activities, forgetfulness, difficulty dealing with routine tasks and short-term memory loss. People do not usually lose language skills, but they may deny that there are any problems. Not everyone will have an obvious mental impairment.
Impairment in bladder control is usually characterized by urinary frequency and urgency in mild cases, whereas a complete loss of bladder control (urinary incontinence) can occur in more severe cases. Urinary frequency is the need to urinate more often than usual, sometimes as often as every one to two hours. Urinary urgency is a strong, immediate sensation of the need to urinate. This urge is sometimes so strong that it cannot be held back, resulting in incontinence. In very rare cases, fecal incontinence may occur. Some patients never display signs of bladder problems
Once symptoms of gait disturbance, mild dementia or bladder control have been identified, a physician who suspects normal pressure hydrocephalus may recommend one or more additional tests. At this point in the diagnostic process, it is important that a neurologist and a neurosurgeon become part of your medical team, along with your primary care physician. Their involvement from the diagnostic stage onward is helpful not only in interpreting test results and selecting likely candidates for shunting, but also in discussing the actually surgery and follow-up care as well as expectations of surgery. The decision to order a given test may depend on the specific clinical situation, as well as the preference and experience of your medical team.
Diagnostic procedures for normal pressure hydrocephalus may include one or more of these tests: ultrasound, computerized tomography (CT), magnetic resonance imaging (MRI), lumbar puncture or tap, continuous lumbar CSF drainage, intracranial pressure (ICP) monitoring, measurement of cerebrospinal fluid outflow resistance or isotopic cisternography, and neuropsychological testing.
Ultrasound: a device that uses sound to outline the structures within the skull.
CT Scan (Computerized Tomography): creates a picture of the brain by using x-rays and a special scanner. It is safe, reliable, painless, and relatively quick (about 15 minutes).
MRI: is safe and painless, and will take approximately 30 minutes or longer.
MRI uses radio signals and a very powerful magnet to create a picture of the brain. It will be possible to detect if the ventricles are enlarged as well as evaluate the CSF flow and provide information about the surrounding brain tissues. The MRI provides more information than the CT, and is therefore the test of choice in most cases. MRI scans can also assess how fast CSF moves through a particular part of the brain called the cerebral aqueduct.Patients with cardiac pacemakers or certain other metallic implants cannot have MRI scans because of potential interference with the pacemaker.
Lumbar Puncture or spinal tap: This allows an estimation of CSF pressure and analysis of the fluid. Under local anesthetic, a thin needle is passed into the spinal fluid space of the low back. Removal of up to 50 cc of CSF is done to see if symptoms are temporarily relieved.
Lumbar catheter insertion: This is a variation of the lumbar puncture. A spinal needle is inserted in the spinal fluid space of the low back, then a thin, flexible tube (catheter) is passed into the spinal fluid and the needle is removed. The lumbar catheter allows for continuous and more accurate recording of spinal fluid pressure, or for more continuous removal of spinal fluid over several days to imitate the effect that a shunt would have. Patients who respond dramatically to such spinal fluid drainage are likely to respond to shunt surgery.
Intracranial pressure monitoring: ICP monitoring requires admission to the hospital. A small pressure monitor is inserted through the skull into the brain or ventricles to measure the ICP. The pressure is not always high, and pressure monitoring (either by lumbar catheter or the intracranial method) can detect an abnormal pattern of pressure waves.
Measuring CSF outflow resistance: This is a more involved test that requires a specialized hospital setting. In essence, this test assesses the degree of blockage to CSF absorption back into the bloodstream. It requires the simultaneous infusion of artificial spinal fluid and measurement of CSF pressure. If the calculated resistance value is abnormally high, then there is a very good chance that the patient will improve with shunt surgery.
Isotopic cisternography: This procedure involves having a radioactive isotope injected into the lumbar subarachnoid space (lower back) through a spinal tap. This allows the absorption of CSF to be evaluated over a period of time (up to 96 hours) by periodic scanning.
Neuropsychological Test: This testing involves asking a series of questions used to determine if there is a loss of brain function due to hydrocephalus.
The treatment of choice for NPH patients who show a positive response to diagnostic testing is the placement of a CSF shunt.
A shunt is an implantable device designed to drain CSF fluid away from the brain thereby allowing the enlarged ventricles to return to a normal state.
As CSF fluid builds and the pressure in the ventricle increases, a one-way valve in the shunt opens, and the excess CSF fluid drains into the abdomen where it is easily absorbed. This technique is very effective in improving the troubling symptoms of NPH.
With a traditional fixed pressure valve, choice of the correct pressure setting is very important as under-drainage will not improve symptoms, whereas over-drainage can cause symptoms in itself, or predispose to problems such as subdural hematoma.
Incorrect choice of a fixed pressure valve requires removal of the original shunt, and repositioning of a different one.
Surgical revisions such as this can be avoided if your neurosurgeon is certified in the use of programmable valve technology.
With a programmable valve, the pressure setting can be adjusted with a special magnetic programmer in your doctor's office, eliminating the need for additional surgery if the initial setting proves not to help.
catheter, the tubing that transports and diverts the CSF from the ventricles to either the abdominal cavity or right atrium, and a
valve that regulates the pressure or flow of CSF from the ventricles. Valves are manufactured to operate at a specific pressure range. A surgeon chooses a pressure range for the valve based on experience and the needs of the patient.
Many shunt systems also have a flexible flushing chamber called a
reservoir. The reservoir may be housed within the shunt system or added as a component along with the shunt system. The reservoir serves several important functions. It permits the doctor to remove samples of CSF for testing, using a needle and syringe. The doctor also may inject fluid into the shunt system to test for flow; to be sure the system is functioning.
The parts of a shunt system are named according to where they are implanted (placed) in the body. The portion of the tube which is inserted into the ventricles is called the ventricular catheter. The peritoneal catheter is the portion of the tube that drains CSF into the abdominal or peritoneal cavity. If a drainage tube is placed into the right atrium of the heart it is called the atrial catheter. To get a better understanding of what a shunt system looks like, ask your doctor or nurse to show you samples of the shunts they use. All of the components of a shunt system are made from materials which are well known to be tolerated by the body. For this reason, the entire shunt system is implanted under the skin. There are no external parts.Use of a programmable valve can significantly increase the probability of shunt implantation being a one-time procedure. If the pressure setting of a fixed pressure valve proves to be a mismatch after surgery, causing underdrainage or overdrainage complications, the patient must undergo a complete or partial shunt revision, sometimes more than once. This is a limitation of all fixed pressure valves. The new CODMAN® HAKIMTM Programmable Valve (CHPV) gives your doctor a choice of 18 different programmable pressure settings. It is the same size as traditional fixed pressure valves and is implanted in exactly the same way. Using an exclusive external programming device, the surgeon selects the initial pressure setting prior to the procedure, and can then easily adjust the setting at any time and as many times as necessary without further surgery. The large range of pressure settings allows the surgeon to make very fine adjustments in the pressure in order to get the best resolution of symptoms after the valve is implanted. The totally non-invasive adjustments take only seconds and can be done right in the office with little or no patient discomfort.
The device used to adjust the pressure setting of the valve is simply called a Programmer. The programmer includes an electrical box connected to a round transmitter head. Using the transmitter head, the valve is programmed to a certain pressure chosen by the surgeon prior to being implanted in the patient. Upon pushing a button, the valve is changed to the selected pressure in 5 to 10 seconds. No additional surgeries or hospital visits are needed in order to reprogram the valve. The surgical procedure to implant a VP (ventricular peritoneal) shunt usually requires less than an hour in the operating room. After the patient is placed under general anesthesia, their scalp is shaved and the patient is scrubbed with an antiseptic from the scalp to the abdominal area. These steps are taken in order to reduce the chances of an infection. Incisions are then made on the head and in the abdomen to allow the neurosurgeon to pass the shunt's tubing through the fatty tissue just under the skin. A small hole is made in the skull, opening the membranes between the skull and brain to allow the ventricular end of the shunt to be passed through the brain and into the lateral ventricle. The abdominal (peritoneal) end is passed into the abdominal cavity through a small opening in the lining of the abdomen where the excess CSF will eventually be absorbed. The incisions are then closed and sterile bandages are applied.
Some neurosurgeons prefer to keep the patient flat in bed until nearly all the subdural air introduced during surgery dissipates. The bandages placed on the head and abdomen, covering the incision sites, are monitored for signs of infection.The patient will generally need to stay in the hospital from three to seven days.Follow-up visits will be necessary to check post-operative status and resolution of symptoms. Additional treatment, such as physical therapy, may be advised to help the patient attain previous levels of motor skills.
Although shunt surgery is a relatively simple neurosurgical procedure, the decision to undergo insertion of a shunt should not be taken lightly.
The treatment of normal pressure hydrocephalus carries greater risks compared to the treatment of children with hydrocephalus, and therefore the operation should be undertaken only if the degree of disability or the progression of the disorder warrants. The potential complications of shunt surgery should be viewed as those related to the actual operation, plus those that may occur days to years later.
A complication can be thought of as any unwanted event related to the surgical procedure itself or the presence of the shunt. Potential complications may include the infection of the surgical wound or of the CSF (meningitis), bleeding into the brain or ventricles, or a seizure. A shunt infection may be indicated by fever, redness or swelling along the shunt track.
Fortunately, these complications are uncommon and can be managed successfully in most cases.Unlike may other operations in which the surgical risks are highest during the operation itself, most of the common and serious problems associated with shunting can occur weeks or even years after the surgery.
The most common problem with shunt systems is that they can become obstructed (clogged).
This can occur hours or years after the operation, sometimes multiple times.
The likelihood of a shunt obstruction is thought to be about 50% for most patients.
For patients with NPH, a shunt obstruction is usually discovered when the original symptoms recur. Fortunately, shunt obstructions in NPH are easily fixed and rarely result in serious problems.The most serious complication that can occur following insertion of a shunt is a subdural hematoma (blood clot).
Because most shunts drain CSF from the center of the brain (the ventricles), this may cause the surface of the brain to pull away from the skull, thus stretching and tearing blood vessels on the surface of the brain.
The symptoms of a subdural hematoma vary from increasing headache to paralysis or even coma or death.
Shunt-related subdural hematomas most commonly occur following a fall, even one involving only a minor bump to the head.
Therefore, a patient with NPH should not hesitate to seek medical attention if abnormal symptoms develop.
The risk of a subdural hematoma in a patient with NPH is approximately 10%. Given these potential complications, individuals need to assess their own situation to determine if the possible benefits of surgery outweigh the possible risks.
1) The CSF
pressure in patients with a
PDPHA tends to be _____
CSF pressure to _____
a) rise for short time
b) rise for 24 hours
c) there is no effect
d) fall slightly