General Principles of Intracranial Pressure
Intracranial Contents Contributing to Intracranial Volume and Pressure
The skull contains three components that contribute to intracranial volume: the brain, its blood supply, and the cerebrospinal fluid (CSF). The brain accounts for approximately 80% of the intracranial volume, the arterial and venous blood approximately 10%, and the CSF approximately 10%. The skull is fixed and can only accommodate small changes in intracranial volume before intracranial pressure rises. Increased intracranial pressure can arise due to increased volume of any of the three intracranial contents (brain, blood volume, or CSF).
Increased intracranial pressure due to increased brain volume—Both focal brain lesions and diffuse brain pathology can lead to increased intracranial pressure (ICP). A focal brain lesion (e.g., stroke, tumor, abscess, demyelination) can cause increased ICP either by mass effect or by obstruction of the ventricular system leading to obstruction of CSF flow. Diffuse cerebral edema (e.g., secondary to severe head trauma, hypoxic-ischemic injury, hyponatremia, meningoencephalitis) raises overall brain volume, increasing ICP.
Increased intracranial pressure due to increased blood volume—Increased blood volume can occur either due to decreased venous outflow (e.g., venous sinus thrombosis) or due to increased arterial blood flow (e.g., due to cerebral vasodilation).
Increased intracranial pressure due to increased cerebrospinal fluid volume—Increased CSF volume (hydrocephalus) can occur due to obstruction of CSF circulation or rarely due to increased CSF production (e.g., due to choroid plexus papilloma). Obstruction of CSF circulation can be caused by a blockage anywhere within the ventricular system (e.g., tumor, intraventricular hemorrhage, congenital aqueductal stenosis) or a blockage of the arachnoid granulations where CSF is absorbed into the venous circulation (e.g., due to meningitis, subarachnoid hemorrhage). Ventricular obstruction causes noncommunicating hydrocephalus: The ventricles cannot communicate with one another to allow for CSF to circulate. In noncommunicating hydrocephalus, only the ventricles proximal to the obstruction will dilate (e.g., obstruction of the third ventricle will lead to dilation of the lateral ventricles but not the fourth ventricle). Obstruction of the arachnoid granulations causes communicating hydrocephalus: The ventricles can still communicate with one another, but CSF cannot be reabsorbed. In communicating hydrocephalus, all of the ventricles will dilate.
If brain volume increases, there is the possibility of limited compensation in the other two compartments (CSF and blood) to maintain constant intracranial volume (Monro-Kellie doctrine). The compensatory mechanisms include displacing CSF into the spinal column, constriction of arterioles, and collapse of veins. However, if intracranial volume increases beyond a certain point, compensation is no longer possible, and ICP rises.
There are two main potential consequences of increased ICP: brain herniation and decreased cerebral perfusion.
Brain herniation refers to shift of brain tissue beyond its normal location (Fig. 25–1). Types of herniation include subfalcine, uncal, transtentorial (central), upward, and tonsillar.
Schematic depicting different types of brain herniation. A: Subfalcine herniation. B: Uncal herniation. C: Transtentorial (central) herniation. D: Tonsillar herniation. Reproduced with permission from Aminoff M, Greenberg D, Simon R: Clinical Neurology, 9th ed. New York: McGraw-Hill Education; 2015.
Subfalcine herniation—In this type of herniation, the cingulate gyrus herniates beneath the falx cerebri (the interhemispheric dura). This can compress the anterior cerebral arteries, leading to stroke.
Uncal herniation—In this type of herniation, the medial temporal lobe compresses the ipsilateral third nerve causing pupillary dilatation. If uncal herniation progresses to the point of compressing the contralateral midbrain against the tentorium, the contralateral cerebral peduncle can be affected, leading to motor deficits and upper motor neuron signs ipsilateral to the side of uncal herniation (Kernohan’s notch phenomenon). For example, uncal herniation on the left generally first causes left pupillary dilatation due to compression of the left cranial nerve 3. If uncal herniation progresses, the right cerebral peduncle can be compressed against the tentorium, causing hemiparesis contralateral to this peduncle (i.e., on the left) since the corticospinal tract has not yet crossed. Therefore, the hemiparesis is ipsilateral to the side of uncal herniation and the dilated pupil (on the left in this example).
Transtentorial (central) herniation—In this type of herniation, the central components of the brain (thalami, midbrain) herniate downward through the tentorium cerebelli, which can lead to bilateral pupillary dilatation, and can ultimately proceed to coma, cardiorespiratory dysfunction, and death.
Upward herniation—With a large cerebellar mass lesion (or diffuse cerebellar pathology), the cerebellum can herniate upward through the tentorium. This causes brainstem compression leading to coma and pupillary abnormalities (the pupils may be small due to pontine distortion or dilated due to midbrain distortion). Upward herniation may be precipitated by CSF drainage via placement of an extraventricular drain in patients with increased cerebellar volume (e.g., cerebellar tumor or hemorrhage): An upward pressure vector from the expanded cerebellum leads to upward displacement when pressure from above is decreased.
Tonsillar herniation—In this type of herniation, the cerebellar tonsils descend below the foramen magnum, compressing the medulla (coning). This can cause coma, cardiorespiratory dysfunction, and death.
Cerebral Perfusion Pressure
Cerebral perfusion pressure (CPP) is determined by the pressure of the blood reaching the brain (mean arterial pressure [MAP]) and the ICP acting against this blood pressure:
Therefore, if ICP rises at a constant MAP, cerebral perfusion pressure will fall, which can lead to decreased cerebral perfusion.
Symptoms and Signs of Increased Intracranial Pressure
The symptoms and signs of intracranial hypertension depend on the degree to which ICP is elevated and the rapidity with which ICP rises. Symptoms may include headache, blurred vision, nausea/vomiting, and alteration in mental status ranging from somnolence to coma. Headache due to elevated ICP is classically worse in the supine position and improves with standing. Signs of intracranial hypertension can include:
Papilledema. Papilledema may not be present acutely since it can take hours to days to develop.
Unilateral or bilateral sixth nerve palsy. This is referred to as a “false localizing sign” in this context, since it appears focal but is a sign of a generalized process (elevated ICP) causing pressure on one or both abducens nerves due to the long intracranial course of this cranial nerve (see “Cranial Nerve 6: The Abducens Nerve” in Chapter 11 for discussion of the signs of sixth nerve palsy).
Cushing’s response: hypertension, bradycardia, and irregular respiration can result from compression of the medulla.
Signs of herniation related to compression of particular structures may be present depending on the location and cause of the responsible lesion(s) (see “Brain Herniation” above).
Treatment of Acutely Increased Intracranial Pressure
Basic measures to treat elevated ICP include:
Elevating the head of the patient’s bed to 30 degrees, which allows gravity to help with venous and CSF drainage.
Hyperventilating the patient if she or he is mechanically ventilated, although this is only a temporizing measure. Hyperventilation decreases ICP by decreasing arterial CO2, leading to cerebral arterial vasoconstriction.
Treatment of any complications of the underlying illness that could lead to further increases in ICP (i.e., treating seizures, fever, agitation, and pain).
Avoidance of hypotonic IV fluids (i.e., avoiding any IV solution less concentrated than normal saline) since these can worsen cerebral edema.
More definitive treatment strategies rest on the principles discussed above: attempting to decrease the volume of one or more of the intracranial contents in the fixed “box” of the skull (i.e., brain, CSF, and blood supply) or “opening the box” (i.e., hemicraniectomy or suboccipital craniectomy). One cannot decrease blood supply since this could lead to decreased cerebral perfusion. In fact, in the setting of elevated ICP, one must work to maintain an adequate MAP to preserve CPP (see above equation). However, one can decrease the volume of the brain (using hyperosmolar therapy to pull water out of it) and/or remove CSF (diversion via an extraventricular drain or ventriculoperitoneal shunt). If hyperosmolar therapy or CSF drainage are inadequate, one can “open the box” by performing a hemicraniectomy or suboccipital craniectomy to allow room for the brain to expand out of the skull defect rather than herniate intracranially. If ICP cannot be controlled with these treatments, pentobarbitol coma and therapeutic hypothermia can be considered to reduce brain metabolism.
If there is a tumor with surrounding edema, a large demyelinating lesion, or intracranial infection, steroids can decrease inflammation related to these etiologies. However, steroids do not appear to be beneficial (and may be harmful) for other causes of elevated intracranial pressure such as stroke and head trauma.
Hyperosmolar Therapy in the Treatment of Acutely Increased Intracranial Pressure
Hypertonic solutions draw water into them. Hypertonic IV fluids increase the tonicity of the serum, pulling water out of the brain into the bloodstream to reduce brain volume. Hyperosmolar therapy is particularly effective in treating cerebral edema. However, even if ICP is elevated due to a large mass without significant edema (e.g., an intraparenchymal hermorrhage), hyperosmolar therapy can shrink the normal regions of the brain, thereby reducing overall brain volume to decrease ICP.
Hyperosmolar therapy is generally utilized to treat edema that is expected to be transient, since hyperosmolar therapy cannot be given indefinitely. Examples include malignant edema from a full-territory middle cerebral artery (MCA) infarct or large cerebellar infarct (stroke-related edema typically peaks over the course of a week and then recedes), diffuse edema from acute encephalitis or meningitis (which should resolve with effective antibiotic treatment), and severe head trauma with diffuse cerebral edema.
Two equations are important in understanding treatments that increase serum tonicity to pull water from the brain:
Calculated serum osmolarity = [2 × Na] + [Glu/18] + [BUN/2.8]
Osmolar (or osmolal) gap = measured serum osmolality (a laboratory value) minus the calculated osmolarity (as calculated by the prior equation)
The normal value for the serum osmolar gap is around 10 (since other serum osmoles beyond sodium, glucose, and BUN normally contribute). The gap can be pathologically increased by ethylene glycol, ethanol, and other alcohols.
To treat increased ICP, serum osmolarity can be increased by adding an osmole (mannitol) or increasing one of the osmoles in the above equation (sodium).
Mannitol in the treatment of acutely increased intracranial pressure—Mannitol adds an additional osmole to the serum, increasing the osmolar gap and serum tonicity. Mannitol can be given through a peripheral IV, and the lowest effective dose should be utilized (range generally 0.5–1.0 g/kg). The effect of mannitol occurs within minutes and lasts hours. Mannitol can be given every 6–8 hours, but should not be given if serum osmolarity is >320. Complications of mannitol therapy can include electrolyte abnormalities, increased intravascular volume (which may be poorly tolerated in the setting of congestive heart failure), and hypotension and/or renal dysfunction from overdiuresis.
Hypertonic saline in the treatment of acutely increased intracranial pressure—23% saline can be given by central line as a bolus (30 mL). Like mannitol, it acts rapidly, has a duration of effect on the order of hours, causes diuresis, and can cause renal and cardiac complications. A serum sodium of up to 160 is generally targeted.
When necessary, mannitol and 23% saline can be given in alternation (e.g., both every 8 hours staggered by 4-hour intervals so the patient gets one or the other every 4 hours). Hyperosmolar therapy should not be stopped abruptly, but rather weaned by progressively increasing the time interval between doses as tolerated.
A continuous infusion of 3% saline may be used to achieve eunatremia in patients with cerebral edema who are hyponatremic. Some practitioners set a sodium goal (i.e., maintain a hypernatremic state) even in patients who are not hyponatremic, whereas others prefer eunatremia, reserving the possibility of rapidly creating an osmotic gradient with a bolus of hypertonic saline if there is an acute rise in ICP.
CSF Diversion in the Treatment of Acutely Increased Intracranial Pressure
An extraventricular drain (EVD) is a temporary catheter that allows for CSF drainage directly from the ventricles. An EVD is similar to a ventriculoperitoneal shunt except that rather than shunting CSF to another location in the body, CSF is shunted directly to the outside world. An EVD serves two purposes:
CSF drainage to reduce ICP without requiring lumbar puncture (since lumbar puncture may precipitate herniation in cases of increased ICP)
Measurement of ICP to allow for targeted therapy for elevated ICP
Treatment of Chronically Increased Intracranial Pressure: Ventriculoperitoneal Shunt and Endoscopic Third Ventriculostomy
Chronic hydrocephalus may be treated by insertion of a ventriculoperitoneal (VP) shunt. VP shunts are placed in the lateral ventricle, and pass under the skin to the peritoneal cavity. Some shunts have a programmable valve so that settings for drainage can be adjusted by an external magnetic device (and so must be reprogrammed after being subjected to the magnetism of an MRI).
Complications of VP shunts include shunt failure (leading to reemergence of hydrocephalus), overshunting (leading to intracranial hypotension; see “Decreased Intracranial Pressure: Intracranial Hypotension” below), and shunt infection. Shunt infection can present with fever and/or shunt failure. Diagnosis of shunt infection is by shunt puncture (direct puncture of the shunt reservoir rather than lumbar puncture), and treatment is with antibiotics and shunt replacement. A shunt series refers to a series of radiographs of the head, neck, chest, and abdomen to look for any discontinuities in the shunt.
Endoscopic Third Ventriculostomy
An alternative to shunting in obstructive hydrocephalus is endoscopic third ventriculostomy. In this procedure, an endoscope is passed through the skull into the ventricular system and a hole is made in the third ventricle to allow CSF to pass directly into the subarachnoid space. This procedure is most commonly used to treat congenital aqueductal stenosis.
Causes of Pseudotumor Cerebri
Pseudotumor cerebri is a condition in which symptoms and signs of elevated ICP develop without a structural lesion, hydrocephalus, or other apparent etiology on neuroimaging. The syndrome is most commonly an idiopathic condition in young obese women (idiopathic intracranial hypertension), although it can also be caused by medications (e.g., tetracycline, vitamin A, and medications derived from vitamin A [e.g., retinoids]), endocrine disease, treatment of endocrine disease, or withdrawal of treatment for endocrine disease (e.g., thyroid medications, growth hormone, steroids).
Symptoms and Signs of Pseudotumor Cerebri
Symptoms and signs of pseudotumor cerebri include:
Pulsatile tinnitus (usually described as a “whooshing” in the ears)
Visual changes including:
Enlargement of the blind spot and restricted peripheral vision due to papilledema. Importantly, these visual field deficits may not be noted by the patient or on bedside visual field testing. Therefore, all patients with pseudotumor cerebri should be followed with formal visual field testing (e.g., automated perimetry).
Papilledema, most commonly bilateral.
Diagnosis of Pseudotumor Cerebri
In any patient with symptoms and signs of elevated ICP, neuroimaging must be performed to evaluate for a mass lesion, hydrocephalus, or venous sinus thrombosis. MRI features suggestive of idiopathic intracranial hypertension include flattening of one or both optic discs and/or an empty sella. Diagnosis is confirmed by elevated opening pressure on lumbar puncture, and lumbar puncture may lead to temporary symptom relief.
Treatment of Pseudotumor Cerebri
In patients with medication-induced pseudotumor cerebri, offending medications should be discontinued. In patients with an endocrine cause of pseudotumor cerebri, the underlying disease must be treated. In patients with obesity-associated idiopathic intracranial hypertension, weight loss and acetazolamide are the mainstays of treatment. Acetazolamide works by decreasing CSF production. If acetazolamide is not tolerated, topiramate or furosemide may be considered. Patients’ visual fields must be followed closely with formal testing, and any clinical worsening or worsening in visual fields may warrant surgical intervention to prevent permanent visual loss.
Surgical options for the treatment of pseudotumor cerebri include VP shunt and optic nerve sheath fenestration. Optic nerve sheath fenestration decompresses the optic nerve, which can improve vision or prevent further visual loss, but it is less effective for the treatment of headache in pseudotumor cerebri. In patients who present with a rapidly progressive course of pseudotumor cerebri, frequent lumbar punctures may be needed as a bridge to surgical intervention if surgery is not immediately available.