Cerebrospinal Fluid and the Brain
The brain and spinal cord are commonly referred to as the “central nervous system.” The brain is housed within the skull and is surrounded by a membrane called the “dura mater,” or “dura.” The brain and spinal cord are surrounded by a clear fluid, resembling water, called cerebrospinal fluidFluid that is made by specialized cells in the ventricles of the brain. (CSFFluid that is made by specialized cells in the ventricles of the brain.). CSF is constantly being produced by the brain, travels through fluid chambers inside the brain (called the “ventricles”), and surrounds the brain and spinal cord. The brain and spinal cord “float” in CSF and protected by it. There are two large fluid chambers within the brain called the “lateral ventricles,” one on each side of the brain, and they communicate with a third chamber sitting in the middle of the brain called the “third ventricleFour cavities within the brain filled with cerebrospinal fluid (CSF). It is the area of the brain that produces and stores CSF..”
CSF travels through the lateral ventricles, the third ventricle, and then leaves the brain at the base of the skull where it then travels around and surrounds the brain and spinal cord. Fluid also travels forward and surrounds the optic nerves that attach to the back of the eye. Fluid additionally travels down into the spine where it surrounds the spinal cord and the nerves roots present in the lower (lumbar) spine. As these chambers all freely communicate with one another, fluid in the brain ventricles is continuous with the fluid surrounding the brain, in the spine, and around the optic nerves.
In most people, there is a total of somewhere around 150 ml (2/3 of a cup) of CSF fluid inside and surrounding our central nervous system at any given time. Over the course of a day, our brains produce about 3 times this volume of fluid (450 ml per day). This means that we produce the entire volume of CSF within and around our brains three times over each day. Where does the extra fluid go? Most of the CSF that is made by the brain gets reabsorbed into the blood stream outside the brain. Since fluid is continuously being made, it must be continuously reabsorbed; therefore, if we make three times the CSF we need each day, we must also reabsorb that same amount of fluid out of the brain and into the bloodstream each day.
One analogy that often helps patients understand this process is that of a bathtub or sink. In this analogy, there is a faucet that constantly produces fluid and a drain at the bottom that continuously drains fluid out of the bathtub. The faucet in our analogy represents the choroid plexus of the brain, small organelles that manufacture CSF in the ventricles. The drain in our analogy is like that of the arachnoid villi, small organelles that reabsorb CSF into the veins outside the brain. The faucet and the drain are working at the same speed: the faucet is producing fluid every second, and the drain is draining the same amount of fluid as the faucet is producing each second. This means that there is usually a relatively constant amount of standing water in the bathtub because the faucet and drain are working at the same speeds. The standing water in the sink is similar to the CSF inside the ventricles and surrounding the brain and spinal cord (150 ml at any time). In a healthy person, our brains produce CSF constantly, reabsorb CSF constantly, and have a constant volume of CSF inside and around our brains. In the presence of disease, however, the drain may not function like it is supposed to. If drain holes are blocked or if the pipes leading out of the bathtub are partially clogged, water won’t move through the drain as quickly. This will cause the water level in the tub to rise and can causing increased pressure within the brain and enlargement of the ventricles.
The reabsorption of CSF is a complex process. In our brains, the CSF that is reabsorbed from the fluid space around the brain travels through small organelles called arachnoid villi and then into the big veins outside the brain. These veins are large pipes surrounded by the membrane outside the brain (the “dura”). We call these large veins “venous sinuses” or “dural venous sinuses” (not to be confused with the large air spaces in the front of our skulls also called “sinuses”). CSF being absorbed travels through the arachnoid villi into the venous sinuses where it then mixes with the blood traveling in these veins. This blood is then carried back to the heart through the large veins in the neck and chest.
The Veins of the Brain
Blood that leaves the skull travels in large veins back to the heart. The brain is covered in small veins called “cortical veins” that collect the blood from the brain and then drain into the large veins outside the brain. These large veins are lined by dura and called the venous sinuses. The dural venous sinuses are just inside the skull but outside of the brain. Not all people have identical brain veins; in fact, the anatomy can be quite variable. In some people, part of the venous sinuses may appear to be small or “hypoplastic,” and in others they may appear to be missing or “aplastic.”
There is a long venous sinus in the center of the head, traveling from the forehead to the back of the head, called the “superior sagittal sinus.” This long vein collects blood from smaller cortical veins from both sides of the brain. The superior sagittal sinus splits at the back of the head into two separate veins called the “transverse sinuses.” These veins begin in the midline at the back of the head and then travel across the side of the head behind the ear. The anatomy of the transverse sinus may differ greatly from person to person. Most commonly, the right transverse sinus is larger (“dominant”) and the left transverse sinus is smaller. In others, the left side may be large and the right side small. In some people, the two transverse sinuses are the same size (or “co-dominant”). At a location inside the skull near the ear, the transverse sinus turns downward and becomes the “sigmoid sinusTermed for its s-shaped anatomy, the sigmoid sinus is a long vessel that runs along the inside of the skull like a long winding road.” When the sigmoid sinus leaves the skull, the vein becomes the “internal jugular vein” which then travels through the neck to the chest to bring blood back to the heart.
The pressure of the blood in the veins is very important for understanding how IIH occurs. Veins, unlike arteries, normally contain blood under low pressure. The blood circulating in the biggest veins in the body (by the heart) is called the “central venous pressure.” Normal central venous pressures are usually 3-8 mmHg (“mmHg” is a unit of pressure; short for millimeters of mercury). So while arteries often have high pressures (130 over 70 mmHg), when blood is traveling back to the heart in veins its pressure is dramatically lower. Veins, in contrast to arteries, have soft and thin walls because the blood they carry is under much lower pressure.
The pressure in the veins inside the skull is of critical importance because CSF reabsorption back into the venous sinuses occurs through a pressure-dependent mechanism. According to this mechanism, the pressure of the CSF has to be slightly higher than the pressure in the venous sinuses outside the brain for fluid to be reabsorbed. Animal studies performed decades ago showed that CSF pressure had to be roughly 3 mmHg higher than the pressure in the venous sinuses to allow fluid to move through the arachnoid villi into these veins. This means that higher pressures in the dural sinuses will cause the CSF pressure inside the brain to be higher. This is confusing, so let’s think of a hypothetical patient with our sink analogy, where the venous pressure is analogous to a bunch of hair blocking the drain in the sink. The higher the pressure in the veins, the more hair is clogging the drain pipes. Remember that the faucet is always on.
If an average person has a pressure of 10 mmHg in the venous sinuses, CSF will build up in and around the brain until the pressure reaches a value slightly higher than 10, to approximately 12 mmHg. Once this pressure is reached, CSF can get reabsorbed, so now the pressure will stabilize. In our analogy, the water level will rise to a point where enough pressure is in the sink to force water through the hair clogging the drain pipes. Once the water level rises far enough, the water level will stabilize, because the water being produced by the faucet equals the rate at which water is going through the drain.
If we take that person and then increase their venous pressure to 15 mmHg suddenly, no CSF will be reabsorbed until the CSF builds up under pressure to an even higher pressure. The faucet keeps producing CSF, the drain now allows no water to escape (pressure not high enough yet), so the water level rises. Once the CSF slowly builds up under pressure until the pressure is 17 mmHg, the fluid can now be reabsorbed again, and the CSF pressure stabilizes at 17 mmHg.
Similarly, if we now suddenly decrease the venous pressure in the sinuses to 5 mmHg, CSF is rapidly reabsorbed into the veins until the CSF pressures reaches 7 mmHg, at which point reabsorption slows considerably and eventually a new steady state is reached.
Therefore, the pressure in the CSF is dependent on the pressure in the venous sinuses outside the brain. If the pressure in the veins goes up, CSF pressure will go up. If the venous pressure goes down, CSF pressure goes down. In a normal situation, the drain in the sink has no hair clogging its pipes and is functioning at full speed. In patients with IIH, the drain pipes are clogged, and the reabsorption of CSF only occurs at high pressures, leading to a steady state where CSF pressures are constantly high.
To date there are no studies that have reported on what normal venous sinus pressures should be in normal people, but we can infer what we think they should be based on our understanding of physiology. We think that most normal people probably have venous sinus pressures that are less than 18 mmHg. But unfortunately, our brain veins are much more complex than that! In fact, the pressures in the venous sinuses are not uniform, and all studies so far suggest that the vein pressure increases as the veins get farther away from the heart. For instance, the superior sagittal sinus at the top of the head has the highest venous pressures. In people with normal venous anatomy, there is a progressive, step-wise decrease in pressures as we move from the superior sagittal sinus, to the transverse sinus, to the jugular vein, and then eventually towards the heart. Overall, in people with normal anatomy, we think the pressure in the superior sagittal sinus is usually about 4-5 mmHg more than the central venous pressure (in the large veins by the heart); or stated another way, in the absence of vein narrowing the vein pressure in the brain veins at the top of the head is about 5 mmHg higher than the vein pressure in the heart. Lastly, we think that the pressure in the “torcula” (the point where the superior sagittal sinus splits into the transverse sinuses) may provide us with the single best reference point that probably best summarizes any given patient’s intracranial venous pressures. In a recent study, torcula pressures were the most closely linked venous sinus pressure to CSF pressure, with an almost a 1-to-1 relationship. This means that a 1 point increase in torcula vein pressure is associated with a 1 point increase in CSF pressure around the brain.
High Vein Pressures Are The Cause Of High Fluid Pressures In Idiopathic Intracranial Hypertension
Over the last 10 years, a number of studies have been published that have greatly expanded our understanding of IIH. Most of these studies provide direct evidence of a link between vein pressures and fluid pressures through cerebral venogram procedures where vein pressures in the body and brain are measured with a catheter. There are now a number of scientific studies strongly suggesting that the high venous pressures are the cause of the high CSF pressures AND that lowering the venous pressures causes an immediate reduction in CSF pressures. Many patients with medically refractory IIH will now routinely undergo a venogram procedure to record venous sinus pressure measurements. Among patients with medically refractory IIH, essentially all patients have high venous sinus pressures. Superior sagittal sinus pressures range from anywhere as low as the high teens to as high as 60 or 70 mmHg in severe cases. In the majority of patients, the pressures range from the 20-40 mmHg. Keep in mind that in normal individuals, the pressure is probably somewhere around 18 mmHg or less.
Most doctors refer to the pressure inside and around the brain as “intracranial pressure,” or “ICPincreased intracranial pressure” for short. In most instances, the terms “ICP” and “CSF pressures” are synonymous and can be used interchangeably. We most frequently measure ICP by measuring CSF pressures, so most of the time they are one and the same. Importantly, however, we usually describe ICP in a unit of measure that is different than how we describe blood pressures. When measuring arterial or venous blood pressures, we use millimeters of mercury (mmHg) as the unit of measure. Intracranial pressure, on the other hand, is almost always reported in centimeters of water (cm of water) or less frequently, millimeters of water (mm of water). A single cm of water is equal to 10 mm of water (there are 10 mm in 1 cm), so mm and cm of water values can easily be converted by multiplying or dividing by a factor of 10. Converting mmHg and cm of water is not as easy: 1 mmHg = 1.36 cm of water. So if you want to convert mmHg to cm of water, you have to multiply mmHg by about 1.3.
Most “normal” people have intracranial pressures (ICP) that are 15 cm of water (or 150 mm of water) or less. However, most doctors generally identify 25 cm of water as the threshold for intracranial pressure being too high (this is core diagnostic criteria for IIH!). This is a convention that we all learn in our training, but truth be told there is actually not a lot of scientific data supporting 25 as a firm cutoff. The real truth is that a pressure in the high teens or low twenties may still be too high in certain people and cause significant symptoms, and should not be considered ‘normal.’ There are a number of patients that have intracranial pressures in the low 20’s with severe daily symptoms that have dramatic, temporary improvement after fluid removal from a spinal tapA procedure where a needle is placed in the lower part of the spine (the lumbar spine) to access cerebrospinal fluid.. While their pressures may not meet the 25 cm of water threshold, very clearly these patients are still suffering from high fluid pressure symptoms. What about the other end of the spectrum? Most ‘normal’ people have CSF pressures that exist somewhere between 8 and 15 cm of water. If pressures get too low, usually below 8 cm of water, symptoms of intracranial hypotension (“hypo” meaning ‘too low’) may occur. Sometimes these symptoms may be hard to differentiate from high pressure symptoms, but usually involve more nausea and headaches that worsen with being upright.
Like blood pressure, intracranial pressure changes from minute-to-minute. ICP is related to your head position, what you are doing, your breathing, and other factor. When we lay flat, the pressure increases in the head; when we stand or sit upright, ICP decreases. Coughing, straining or heavy lifting causes our ICP to go up temporarily. When we sleep, we don’t breathe as well which causes ICP to be higher during sleep. In addition, there are other changes in pressure that occur regardless of what we are doing or what position we are in. Think of this as a normal minute-to-minute, day-to-day variability. If we were to have our pressures measured 5 times in a single day, each pressure measurement is likely to be slightly different. Taking an average of these readings would provide a more accurate single number to describe the pressure. Practically speaking, this means that a spinal tap may not always provide a definitive answer of what your ICP is.
