Cerebral edema is excess accumulation of fluid (
edema
Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's Tissue (biology), tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels t ...
) in the
intracellular
This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...
or
extracellular
This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...
spaces of the
brain
A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...
.
This typically causes impaired nerve function,
increased pressure within the skull, and can eventually lead to
direct compression of brain tissue and blood vessels.
Symptoms vary based on the location and extent of edema and generally include
headache
Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches.
Headaches can occur as a result ...
s, nausea, vomiting, seizures, drowsiness, visual disturbances, dizziness, and in severe cases,
coma
A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to respond normally to painful stimuli, light, or sound, lacks a normal wake-sleep cycle and does not initiate voluntary actions. Coma patients exhi ...
and death.
Cerebral edema is commonly seen in a variety of brain injuries including
ischemic stroke
A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...
,
subarachnoid hemorrhage, traumatic brain injury,
subdural,
epidural
Epidural administration (from Ancient Greek ἐπί, , upon" + ''dura mater'') is a method of medication administration in which a medicine is injected into the epidural space around the spinal cord. The epidural route is used by physicians an ...
, or
intracerebral hematoma,
hydrocephalus
Hydrocephalus is a condition in which an accumulation of cerebrospinal fluid (CSF) occurs within the brain. This typically causes increased intracranial pressure, pressure inside the skull. Older people may have headaches, double vision, poor ...
,
brain cancer
A brain tumor occurs when abnormal cells form within the brain. There are two main types of tumors: malignant tumors and benign (non-cancerous) tumors. These can be further classified as primary tumors, which start within the brain, and secondar ...
, brain infections,
low blood sodium levels,
high altitude
Altitude or height (also sometimes known as depth) is a distance measurement, usually in the vertical or "up" direction, between a reference datum and a point or object. The exact definition and reference datum varies according to the context ...
, and
acute liver failure
Acute liver failure is the appearance of severe complications rapidly after the first signs (such as jaundice) of liver disease, and indicates that the liver has sustained severe damage (loss of function of 80–90% of liver cells). The complicati ...
.
Diagnosis is based on symptoms and physical examination findings and confirmed by serial neuroimaging (
computed tomography scans and
magnetic resonance imaging
Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio wave ...
).
The treatment of cerebral edema depends on the cause and includes monitoring of the person's airway and
intracranial pressure
Intracranial pressure (ICP) is the pressure exerted by fluids such as cerebrospinal fluid (CSF) inside the skull and on the brain tissue. ICP is measured in millimeters of mercury (mmHg) and at rest, is normally 7–15 Millimeter of mercury, mmHg ...
, proper positioning, controlled hyperventilation, medications, fluid management, steroids.
Extensive cerebral edema can also be treated surgically with a
decompressive craniectomy
Decompressive craniectomy ('' crani-'' + '' -ectomy'') is a neurosurgical procedure in which part of the skull is removed to allow a swelling brain room to expand without being squeezed. It is performed on victims of traumatic brain injury, str ...
.
Cerebral edema is a major cause of brain damage and contributes significantly to the mortality of ischemic strokes and
traumatic brain injuries
A traumatic brain injury (TBI), also known as an intracranial injury, is an injury to the brain caused by an external force. TBI can be classified based on severity (ranging from mild traumatic brain injury TBI/concussionto severe traumatic ...
.
As cerebral edema is present with many common cerebral pathologies, the epidemiology of the disease is not easily defined.
The incidence of this disorder should be considered in terms of its potential causes and is present in most cases of traumatic brain injury,
central nervous system tumors,
brain ischemia
Brain ischemia is a condition in which there is insufficient bloodflow to the brain to meet metabolic demand. This leads to poor oxygen supply or cerebral hypoxia and thus leads to the death of brain tissue or cerebral infarction/ ischemic stroke ...
, and
intracerebral hemorrhage.
For example, malignant brain edema was present in roughly 31% of people with ischemic strokes within 30 days after onset.
Signs and symptoms
The extent and severity of the symptoms of cerebral edema depend on the exact
etiology
Etiology (pronounced ; alternatively: aetiology or ætiology) is the study of causation or origination. The word is derived from the Greek (''aitiología'') "giving a reason for" (, ''aitía'', "cause"); and ('' -logía''). More completely, e ...
but are generally related to an acute
increase of the pressure within the skull.
As the skull is a fixed and inelastic space, the accumulation of cerebral edema can displace and compress vital brain tissue,
cerebral spinal fluid
Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates.
CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the br ...
, and blood vessels, according to the
Monro-Kellie doctrine.
Increased intracranial pressure (ICP) is a life-threatening surgical emergency marked by symptoms of headache, nausea, vomiting, decreased consciousness.
Symptoms are frequently accompanied by visual disturbances such as
gaze paresis, reduced vision, and dizziness.
Increased pressures within the skull can cause a compensatory elevation of blood pressure to maintain
cerebral blood flow
Cerebral circulation is the movement of blood through a network of cerebral arteries and veins supplying the brain. The rate of cerebral blood flow in an adult human is typically 750 milliliters per minute, or about 15% of cardiac output. Art ...
, which, when associated with irregular breathing and a
decreased heart rate, is called the
Cushing reflex Cushing reflex (also referred to as the vasopressor response, the Cushing effect, the Cushing reaction, the Cushing phenomenon, the Cushing response, or Cushing's Law) is a physiological nervous system response to increased intracranial pressure (IC ...
.
The Cushing reflex often indicates
compression of the brain on brain tissue and blood vessels, leading to
decreased blood flow to the brain and eventually death.
Causes
Cerebral edema is frequently encountered in acute brain injuries from a variety of origins, including but not limited to:
*
Traumatic brain injury
A traumatic brain injury (TBI), also known as an intracranial injury, is an injury to the brain caused by an external force. TBI can be classified based on severity (ranging from mild traumatic brain injury TBI/concussionto severe traumatic b ...
*
Stroke
A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...
*
Tumors
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
* Infections (such as a brain abscess or
meningitis
Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, headache, and neck stiffness. Other symptoms include confusion or ...
)
*
Hepatic encephalopathy
Hepatic encephalopathy (HE) is an altered level of consciousness as a result of liver failure. Its onset may be gradual or sudden. Other symptoms may include movement problems, changes in mood, or changes in personality. In the advanced stages ...
*
Posterior reversible encephalopathy syndrome
Posterior reversible encephalopathy syndrome (PRES), also known as reversible posterior leukoencephalopathy syndrome (RPLS), is a rare condition in which parts of the brain are affected by swelling, usually as a result of an underlying cause. Some ...
* Radiation-induced brain edema
* Post-surgical changes
*
Amyloid-related imaging abnormalities associated with edema (ARIA-E)
*
Hyponatremia
Hyponatremia or hyponatraemia is a low concentration of sodium in the blood. It is generally defined as a sodium concentration of less than 135 mmol/L (135 mEq/L), with severe hyponatremia being below 120 mEq/L. Symptoms can be abs ...
*
High-altitude cerebral edema
High-altitude cerebral edema (HACE) is a medical condition in which the brain swells with fluid because of the physiological effects of traveling to a high altitude. It generally appears in patients who have acute mountain sickness and involves dis ...
Risk factors
Cerebral edema is present with many common cerebral pathologies and risk factors for development of cerebral edema will depend on the cause.
The following were reliable predictors for development of early cerebral edema in ischemic strokes.
* Younger age
* Higher severity of symptoms on the
National Institutes of Health Stroke Scale The National Institutes of Health Stroke Scale, or NIH Stroke Scale (NIHSS), is a tool used by healthcare providers to objectively quantify the impairment caused by a stroke. The NIHSS is composed of 11 items, each of which scores a specific ability ...
* Signs of current ischemia on clinical exam
* Decreased level of consciousness
* Hyper dense artery sign and larger affected area on CT imaging
* Higher blood glucose
Classification
Cerebral edema has been traditional classified into two major sub-types: cytotoxic and vasogenic cerebral edema.
This simple classification helps guide medical decision making and treatment of patients affected with cerebral edema.
There are, however, several more differentiated types including but not limited to interstitial, osmotic, hydrostatic, and high altitude associated edema.
Within one affected person, many individual sub-types can be present simultaneously.
The following individual sub-types have been identified:
Cytotoxic
In general, cytotoxic edema is linked to cell death in the brain through excessive cellular swelling.
During cerebral ischemia for example, the
blood–brain barrier
The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of ...
remains intact but decreased blood flow and glucose supply leads to a disruption in cellular
metabolism
Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...
and creation of energy sources, such as
adenosine triphosphate
Adenosine triphosphate (ATP) is an organic compound that provides energy to drive many processes in living cells, such as muscle contraction, nerve impulse propagation, condensate dissolution, and chemical synthesis. Found in all known forms of ...
(ATP).
Exhaustion of energy sources impairs functioning of the
sodium and potassium pump in the cell membrane, leading to cellular retention of
sodium ions
Sodium is a chemical element with the symbol Na (from Latin ''natrium'') and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 of the periodic table. Its only stable is ...
.
Accumulation of sodium in the cell causes a rapid uptake of water through
osmosis
Osmosis (, ) is the spontaneous net movement or diffusion of solvent molecules through a selectively-permeable membrane from a region of high water potential (region of lower solute concentration) to a region of low water potential (region of ...
, with subsequent swelling of the cells.
The ultimate consequence of cytotoxic edema is the
oncotic death of neurons.
The swelling of the individual cells of the brain is the main distinguishing characteristic of cytotoxic edema, as opposed to vasogenic edema, wherein the influx of fluid is typically seen in the interstitial space rather than within the cells themselves. Researchers have proposed that "cellular edema" may be more preferable to the term "cytotoxic edema" given the distinct swelling and lack of consistent "toxic" substance involved.
There are several clinical conditions in which cytotoxic edema is present:
* Commonly caused by
traumatic brain injuries
A traumatic brain injury (TBI), also known as an intracranial injury, is an injury to the brain caused by an external force. TBI can be classified based on severity (ranging from mild traumatic brain injury TBI/concussionto severe traumatic ...
,
intracerebral hemorrhage, and the early phase of
ischemic stroke
A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...
.
* Also seen in
acute liver failure
Acute liver failure is the appearance of severe complications rapidly after the first signs (such as jaundice) of liver disease, and indicates that the liver has sustained severe damage (loss of function of 80–90% of liver cells). The complicati ...
where toxic waste, most notably
ammonia
Ammonia is an inorganic compound of nitrogen and hydrogen with the formula . A stable binary hydride, and the simplest pnictogen hydride, ammonia is a colourless gas with a distinct pungent smell. Biologically, it is a common nitrogenous was ...
, accumulates in the blood stream and crosses the blood
–brain barrier.
Hyperammonemia
Hyperammonemia is a metabolic disturbance characterised by an excess of ammonia in the blood. It is a dangerous condition that may lead to brain injury and death. It may be primary or secondary.
Ammonia is a substance that contains nitrogen. It i ...
in
central nervous system
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...
(CNS) cells causes
oxidative stress
Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily Detoxification, detoxify the reactive intermediates or to repair the resulting damage. Disturbances ...
and
mitochrondrial dysfunction, leading to
astrocytic
Astrocytes (from Ancient Greek , , "star" + , , "cavity", "cell"), also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical control of endot ...
cell swelling.
Additionally, ammonia is converted to
glutamine
Glutamine (symbol Gln or Q) is an α-amino acid that is used in the biosynthesis of proteins. Its side chain is similar to that of glutamic acid, except the carboxylic acid group is replaced by an amide. It is classified as a charge-neutral ...
in CNS cells which acts as an
osmolyte
Osmolytes are low-molecular weight organic compounds that influence the properties of biological fluids. Their primary role is to maintain the integrity of cells by affecting the viscosity, melting point, and ionic strength of the aqueous solution. ...
and draws further water into the cell through osmosis.
Cerebral edema occurs most commonly in conjunction with a rapid rise in ammonia levels.
* Toxic exposures to
methionine sulfoxime, cuprizone,
isoniazid
Isoniazid, also known as isonicotinic acid hydrazide (INH), is an antibiotic used for the treatment of tuberculosis. For active tuberculosis it is often used together with rifampicin, pyrazinamide, and either streptomycin or ethambutol. For la ...
, triethyl tin,
hexachlorophene
Hexachlorophene, also known as Nabac, is an organochlorine compound that was once widely used as a disinfectant. The compound occurs as a white odorless solid, although commercial samples can be off-white and possess a slightly phenolic odor. It ...
, and
hydrogen cyanide
Hydrogen cyanide, sometimes called prussic acid, is a chemical compound with the formula HCN and structure . It is a colorless, extremely poisonous, and flammable liquid that boils slightly above room temperature, at . HCN is produced on an ...
have been associated with cytotoxic edema and swelling of
astrocytic
Astrocytes (from Ancient Greek , , "star" + , , "cavity", "cell"), also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical control of endot ...
cells.
* Hypoxia, anoxia can lead to cytotoxic edema through several mechanisms
Vasogenic
Extracellular brain edema, or vasogenic edema, is caused by an increase in the permeability of the
blood–brain barrier
The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of ...
.
The blood–brain barrier consists of
astrocyte
Astrocytes (from Ancient Greek , , "star" + , , "cavity", "cell"), also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical control of e ...
s and
pericyte
Pericytes (previously known as Rouget cells) are multi-functional mural cells of the microcirculation that wrap around the endothelial cells that line the capillaries throughout the body. Pericytes are embedded in the basement membrane of blood ca ...
s joined together with adhesion proteins producing
tight junction
Tight junctions, also known as occluding junctions or ''zonulae occludentes'' (singular, ''zonula occludens''), are multiprotein junctional complexes whose canonical function is to prevent leakage of solutes and water and seals between the epith ...
s.
Return of blood flow to theses cells after an
ischemic stroke
A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...
can cause excitotoxicity and
oxidative stress
Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily Detoxification, detoxify the reactive intermediates or to repair the resulting damage. Disturbances ...
leading to dysfunction of the endothelial cells and disruption of the blood-brain barrier.
The breakdown of the tight endothelial junctions that make up the blood–brain barrier causes
extravasation
__NOTOC__
Extravasation is the leakage of a fluid out of its container into the surrounding area, especially blood or blood cells from vessels. In the case of inflammation, it refers to the movement of white blood cells from the capillaries to th ...
of fluid, ions, and plasma proteins, such as
albumin
Albumin is a family of globular proteins, the most common of which are the serum albumins. All the proteins of the albumin family are water-soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Albumins ...
, into the brain
parenchyma.
Accumulation of extracellular fluid increases brain volume and then intracranial pressure causing the symptoms of cerebral edema.
There are several clinical conditions in which vasogenic edema is present:
*
CNS tumors, like
glioblastoma
Glioblastoma, previously known as glioblastoma multiforme (GBM), is one of the most aggressive types of cancer that begin within the brain. Initially, signs and symptoms of glioblastoma are nonspecific. They may include headaches, personality ch ...
and
meningioma
* Infections like
meningitis
Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, headache, and neck stiffness. Other symptoms include confusion or ...
, abscess, and
encephalitis
Encephalitis is inflammation of the brain. The severity can be variable with symptoms including reduction or alteration in consciousness, headache, fever, confusion, a stiff neck, and vomiting. Complications may include seizures, hallucinations, ...
* Inflammatory
central nervous system
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...
disease such as
multiple sclerosis
Multiple (cerebral) sclerosis (MS), also known as encephalomyelitis disseminata or disseminated sclerosis, is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This d ...
* Brain hemorrhage
*
Traumatic brain injuries
A traumatic brain injury (TBI), also known as an intracranial injury, is an injury to the brain caused by an external force. TBI can be classified based on severity (ranging from mild traumatic brain injury TBI/concussionto severe traumatic ...
can lead to
increased intracranial pressure
Intracranial pressure (ICP) is the pressure exerted by fluids such as cerebrospinal fluid (CSF) inside the skull and on the brain tissue. ICP is measured in millimeters of mercury (mmHg) and at rest, is normally 7–15 mmHg for a supine adult. Th ...
, local damage, reduced cerebral blood flow, and focal ischemia secondary to vasogenic edema.
* Late stage of
ischemic stroke
A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...
after rapid recovery from cytotoxic edema
*
Hypertensive encephalopathy
Hypertensive encephalopathy (HE) is general brain dysfunction due to significantly high blood pressure. Symptoms may include headache, vomiting, trouble with balance, and confusion. Onset is generally sudden. Complications can include seizures, ...
* Radiation injury
Ionic (Osmotic)
In ionic edema, the solute concentration (
osmolality
Molality is a measure of the number of moles of solute in a solution corresponding to 1 kg or 1000 g of solvent. This contrasts with the definition of molarity which is based on a specified volume of solution.
A commonly used unit for molali ...
) of the brain exceeds that of the
plasma and the abnormal pressure gradient leads to accumulation of water intake into the brain
parenchyma through the process of
osmosis
Osmosis (, ) is the spontaneous net movement or diffusion of solvent molecules through a selectively-permeable membrane from a region of high water potential (region of lower solute concentration) to a region of low water potential (region of ...
.
The blood-brain barrier is intact and maintains the osmotic gradient.
The solute concentration of the blood plasma can be diluted by several mechanisms:
* Improper administration of
intravenous fluids, isotonic or hypotonic.
* Excessive water intake,
syndrome of inappropriate antidiuretic hormone (SIADH).
* Rapid reduction of blood glucose in
diabetic ketoacidosis
Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of diabetes mellitus. Signs and symptoms may include vomiting, abdominal pain, deep gasping breathing, increased urination, weakness, confusion and occasionally loss of ...
or
hyperosmolar hyperglycemic state
Hyperosmolar hyperglycemic state (HHS) is a complication of diabetes mellitus in which high blood sugar results in high osmolarity without significant ketoacidosis. Symptoms include signs of dehydration, weakness, leg cramps, vision problems, ...
.
* Hemodialysis has been associated with ionic edema and cellular swelling.
* Cerebral edema is a potentially life threatening complication of severely decreased sodium ion concentration in the blood (
hyponatremia
Hyponatremia or hyponatraemia is a low concentration of sodium in the blood. It is generally defined as a sodium concentration of less than 135 mmol/L (135 mEq/L), with severe hyponatremia being below 120 mEq/L. Symptoms can be abs ...
).
Ionic brain edema can also occur around the sites of brain hemorrhages, infarcts, or contusions due to a local plasma osmolality pressure gradient when compared to the high osmolality in the affected tissue.
Interstitial (hydrocephalic)
Interstitial edema can be best characterized by in noncomunnicating
hydrocephalus
Hydrocephalus is a condition in which an accumulation of cerebrospinal fluid (CSF) occurs within the brain. This typically causes increased intracranial pressure, pressure inside the skull. Older people may have headaches, double vision, poor ...
where there is an obstruction to the outflow of
cerebrospinal fluid
Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates.
CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the bra ...
within the
ventricular system
The ventricular system is a set of four interconnected cavities known as cerebral ventricles in the brain. Within each ventricle is a region of choroid plexus which produces the circulating cerebrospinal fluid (CSF). The ventricular system is co ...
.
The obstruction creates a rise in the intraventricular pressure and causes CSF to flow through the wall of the ventricles into the extracellular fluid within brain.
The fluid has roughly the same composition of CSF.
Other causes of interstitial edema include but are not limited to communicating hydrocephalus, and
normal pressure hydrocephalus
Normal-pressure hydrocephalus (NPH), also called malresorptive hydrocephalus, is a form of communicating hydrocephalus in which excess cerebrospinal fluid (CSF) occurs in the ventricles, and with normal or slightly elevated cerebrospinal fluid p ...
.
Hydrostatic
Hydrostatic extracellular brain edema is typically caused by severe arterial hypertension.
A difference in the
hydrostatic
Fluid statics or hydrostatics is the branch of fluid mechanics that studies the condition of the equilibrium of a floating body and submerged body "fluids at hydrostatic equilibrium and the pressure in a fluid, or exerted by a fluid, on an imme ...
pressure within the arterial system relative to the endothelial cells allows
ultrafiltration
Ultrafiltration (UF) is a variety of membrane filtration in which forces such as pressure or concentration gradients lead to a separation through a semipermeable membrane. Suspended solids and solutes of high molecular weight are retained in the ...
of water, ions, and low molecular weight substances (such as glucose, small amino acids) into the brain
parenchyma.
The
blood-brain barrier is intact usually and the extent of the edema depends on the arterial pressure.
The regulatory processes of the brain circulation can function up to systolic arterial pressures of 150 mm Hg and will have impaired function at higher blood pressures.
Combined types of cerebral edema
Cytotoxic, osmotic, and vasogenic edema exist on a continuum.
The mechanism of the cause of cerebral edema can often overlap between these types.
In most instances, cytotoxic and vasogenic edema occur together.
When the two edema types evolve simultaneously, the damage of one type reaches a limit and will bring about the other type of injury.
For example, when cytotoxic edema occurs in the
endothelial
The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel ...
cells of the
blood–brain barrier
The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of ...
, oncotic cell death contributes to loss of integrity of the blood–brain barrier and promotes the progression to vasogenic edema.
When brain edema types are combined, there is typically a primary form and the edema type and context of the cause must be determined in order to start appropriate medical or surgical therapy.
The use of specific MRI techniques has allowed for some differentiation between the mechanisms.
Subtypes
High-altitude cerebral edema
If not properly acclimatized to high altitude, a person may be negatively affected by the lower oxygen concentration available.
These hypoxia-related illnesses include
acute mountain sickness (AMS),
high-altitude pulmonary edema
High-altitude pulmonary edema (HAPE) is a life-threatening form of non-cardiogenic pulmonary edema that occurs in otherwise healthy people at altitudes typically above . However, cases have also been reported between in more vulnerable subjects.
...
, and
high-altitude cerebral edema
High-altitude cerebral edema (HACE) is a medical condition in which the brain swells with fluid because of the physiological effects of traveling to a high altitude. It generally appears in patients who have acute mountain sickness and involves dis ...
(HACE).
High-altitude cerebral edema
High-altitude cerebral edema (HACE) is a medical condition in which the brain swells with fluid because of the physiological effects of traveling to a high altitude. It generally appears in patients who have acute mountain sickness and involves dis ...
is a severe and sometimes fatal form of
altitude sickness
Altitude sickness, the mildest form being acute mountain sickness (AMS), is the harmful effect of high altitude, caused by rapid exposure to low amounts of oxygen at high elevation. People can respond to high altitude in different ways. Sympt ...
that results from
capillary
A capillary is a small blood vessel from 5 to 10 micrometres (μm) in diameter. Capillaries are composed of only the tunica intima, consisting of a thin wall of simple squamous endothelial cells. They are the smallest blood vessels in the body: ...
fluid leakage due to the effects of
hypoxia on the
mitochondria
A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...
-rich
endothelial cell
The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel ...
s of the
blood–brain barrier
The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of ...
.
The edema can be characterized by vasogenic cerebral edema with symptoms of impaired consciousness and
truncal ataxia
Truncal ataxia (or trunk ataxia) is a wide-based "drunken sailor" gait characterised by uncertain starts and stops, lateral deviations and unequal steps. It is an instability of the trunk and often seen during sitting. It is most visible when sh ...
.
Altitude-related illnesses can be prevented most effectively with slow ascent to high altitudes, an average ascent of 300 to 500 meters per day is recommended. Pharmacological
prophylaxis
Preventive healthcare, or prophylaxis, consists of measures taken for the purposes of disease prevention.Hugh R. Leavell and E. Gurney Clark as "the science and art of preventing disease, prolonging life, and promoting physical and mental hea ...
with
acetazoloamide or
corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involv ...
s can be used in non pre-acclimatized individuals.
If symptoms of high-altitude cerebral edema do not resolve or worsen, immediate descent is necessary, and symptoms can be improved with administration of dexamethasone.
Amyloid-related imaging abnormalities – edema
Amyloid-related imaging abnormalities
Amyloid-related imaging abnormalities (ARIA) are abnormal differences seen in magnetic resonance imaging of the brain in patients with Alzheimer's disease. ARIA is associated with amyloid-modifying therapies, particularly human monoclonal antibodi ...
(ARIA) are abnormal differences seen in neuroimaging of Alzheimer's disease patients given targeted amyloid-modifying therapies.
Human monoclonal antibodies such as
aducanumab,
solanezumab
Solanezumab (proposed INN, LY2062430) is a monoclonal antibody being investigated by Eli Lilly as a neuroprotector for patients with Alzheimer's disease. The drug originally attracted extensive media coverage proclaiming it a breakthrough, but ...
, and
bapineuzumab have been associated with these neuroimaging changes and additionally, cerebral edema.
These therapies are associated with dysfunction of the tight endothelial junctions of the blood-brain barrier, leading to vasogenic edema as described above. In addition to edema, these therapies are associated with microhemorrhages in the brain known as ARIA-H. Familiarity with ARIA can aid radiologists and clinicians in determining optimal management for those affected.
Posterior reversible encephalopathy syndrome
Posterior reversible encephalopathy syndrome
Posterior reversible encephalopathy syndrome (PRES), also known as reversible posterior leukoencephalopathy syndrome (RPLS), is a rare condition in which parts of the brain are affected by swelling, usually as a result of an underlying cause. Some ...
(PRES) is a rare clinical disease characterized by cerebral edema.
The exact
pathophysiology, or cause, of the syndrome is still debated but is hypothesized to be related to the disruption of the blood-brain barrier.
The syndrome features acute neurological symptoms and reversible
subcortical vasogenic edema predominantly involving the parieto-occipital areas on
MR imaging. PRES in general has a benign course, but PRES-related intracranial hemorrhage has been associated with a poor prognosis.
Idiopathic delayed-onset edema
Deep brain stimulation
Deep brain stimulation (DBS) is a neurosurgical procedure involving the placement of a medical device called a neurostimulator, which sends electrical impulses, through implanted electrodes, to specific targets in the brain (the brain nucleu ...
(DBS) is effective treatment for several neurological and psychiatric disorders, most notably
Parkinson's disease
Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
. DBS is not without risks and although rare, idiopathic delayed-onset edema (IDE) surrounding the DBS leads have been reported.
Symptoms can be mild and nonspecific, including reduction of the stimulation effect, and can be confused for other causes of edema.
Thus, imaging is recommended to rule out other causes.
The condition is generally self-limiting and the exact mechanism of the cause is unexplained.
Early identification can help persons affected avoid unnecessary surgical procedures or antibiotic treatments.
Massive brain swelling after cranioplasty
Decompressive craniectomy
Decompressive craniectomy ('' crani-'' + '' -ectomy'') is a neurosurgical procedure in which part of the skull is removed to allow a swelling brain room to expand without being squeezed. It is performed on victims of traumatic brain injury, str ...
is frequently performed in cases of resistant
intracranial hypertension
Intracranial pressure (ICP) is the pressure exerted by fluids such as cerebrospinal fluid (CSF) inside the skull and on the brain tissue. ICP is measured in millimeters of mercury (mmHg) and at rest, is normally 7–15 mmHg for a supine adult. Th ...
secondary to several neurological conditions and is commonly followed by
cranioplasty
Cranioplasty is a surgical operation on the repairing of cranial defects caused by previous injuries or operations, such as decompressive craniectomy. It is performed by filling the defective area with a range of materials, usually a bone piece ...
.
Complications, such as infection and
hematoma
A hematoma, also spelled haematoma, or blood suffusion is a localized bleeding outside of blood vessels, due to either disease or trauma including injury or surgery and may involve blood continuing to seep from broken capillary, capillaries. A he ...
s after cranioplasty occur in roughly about a third of cases.
Massive brain swelling after cranioplasty (MSBC) is a rare and potentially fatal complication of an uneventful cranioplasty that has recently been elucidated.
Preoperative sinking skin flap (SSF) and intracranial hypotension were factors associated with the development of MSBC after cranioplasty.
Data suggests that pathologic changes are triggered immediately following the procedure, especially an acute increase in intracranial pressure.
Radiation-induced brain edema
With the rise of sophisticated treatment modalities such as
gamma knife
Radiosurgery is surgery using radiation, that is, the destruction of precisely selected areas of tissue using ionizing radiation rather than excision with a blade. Like other forms of radiation therapy (also called radiotherapy), it is usually u ...
,
Cyberknife, and
intensity-modulated radiotherapy, a large number of individuals with brain tumors are treated with radiosurgery and radiotherapy.
Radiation-induced brain edema (RIBE) is a potentially life threatening complication of brain tissue radiation and is characterized radiation necrosis, endothelial cell dysfunction, increased capillary permeability, and breakdown of the
blood–brain barrier
The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of ...
.
Symptoms include headache, seizure, psychomotor slowing, irritability, and focal neurological deficits.
Options for management of RIBE are limited and include
corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involv ...
s,
antiplatelet drug
An antiplatelet drug (antiaggregant), also known as a platelet agglutination inhibitor or platelet aggregation inhibitor, is a member of a class of pharmaceuticals that decrease platelet aggregation and inhibit thrombus formation. They are effecti ...
s,
anticoagulants,
hyperbaric oxygen therapy
Hyperbaric medicine is medical treatment in which an ambient pressure greater than sea level atmospheric pressure is a necessary component. The treatment comprises hyperbaric oxygen therapy (HBOT), the medical use of oxygen at an ambient pressure ...
, multivitamins, and
bevacizumab.
Brain tumor-associated cerebral edema
This kind of cerebral edema is a significant cause of morbidity and mortality in patients with brain tumors and characterized by a disruption of the blood brain barrier and vasogenic edema.
The exact mechanism is unclear but hypothesized that cancerous
glial cell
Glia, also called glial cells (gliocytes) or neuroglia, are non-neuronal cells in the central nervous system (brain and spinal cord) and the peripheral nervous system that do not produce electrical impulses. They maintain homeostasis, form myel ...
s (
glioma
A glioma is a type of tumor that starts in the glial cells of the brain or the spine. Gliomas comprise about 30 percent of all brain tumors and central nervous system tumours, and 80 percent of all malignant brain tumours.
Signs and symptoms
...
) of the brain can increase secretion of
vascular endothelial growth factor
Vascular endothelial growth factor (VEGF, ), originally known as vascular permeability factor (VPF), is a signal protein produced by many cells that stimulates the formation of blood vessels. To be specific, VEGF is a sub-family of growth factors, ...
(VEGF), which weakens the tight junctions of the
blood–brain barrier
The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of ...
.
Historically, corticosteroids such as
dexamethasone
Dexamethasone is a glucocorticoid medication used to treat rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive lung disease, croup, brain swelling, eye pain following eye surgery, superior vena ...
were used to reduce brain tumor-associated vascular permeability through poorly understood mechanisms and was associated with systemic side effects.
Agents that target the VEGF signaling pathways, such as
cediranib, have been promising in prolonging survival in ''rat'' models but associated with local and systemic side effects as well.
Diagnosis
Cerebral edema is commonly present in a variety of neurological injuries.
Thus, determining a definitive contribution of cerebral edema to the neurological status of an affected person can be challenging.
Close bedside monitoring of a person's level of consciousness and awareness of any new or worsening
focal neurological deficits is imperative but demanding, frequently requiring admission into the
intensive care unit
220px, Intensive care unit
An intensive care unit (ICU), also known as an intensive therapy unit or intensive treatment unit (ITU) or critical care unit (CCU), is a special department of a hospital or health care facility that provides intensiv ...
(ICU).
Cerebral edema with sustained increased
intracranial hypertension
Intracranial pressure (ICP) is the pressure exerted by fluids such as cerebrospinal fluid (CSF) inside the skull and on the brain tissue. ICP is measured in millimeters of mercury (mmHg) and at rest, is normally 7–15 mmHg for a supine adult. Th ...
and
brain herniation
Brain herniation is a potentially deadly side effect of very high pressure within the skull that occurs when a part of the brain is squeezed across structures within the skull. The brain can shift across such structures as the falx cerebri, the te ...
can signify impending catastrophic neurological events which require immediate recognition and treatment to prevent injury and even death.
Therefore, diagnosis of cerebral edema earlier with rapid intervention can improve clinical outcomes and can
mortality, or risk of death.
Diagnosis of cerebral edema relies on the following:
Imaging
Serial neuroimaging (
CT scans and
magnetic resonance imaging
Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio wave ...
) can be useful in diagnosing or excluding
intracranial hemorrhage
Intracranial hemorrhage (ICH), also known as intracranial bleed, is bleeding within the skull. Subtypes are intracerebral bleeds ( intraventricular bleeds and intraparenchymal bleeds), subarachnoid bleeds, epidural bleeds, and subdural bleeds. ...
, large masses, acute
hydrocephalus
Hydrocephalus is a condition in which an accumulation of cerebrospinal fluid (CSF) occurs within the brain. This typically causes increased intracranial pressure, pressure inside the skull. Older people may have headaches, double vision, poor ...
, or
brain herniation
Brain herniation is a potentially deadly side effect of very high pressure within the skull that occurs when a part of the brain is squeezed across structures within the skull. The brain can shift across such structures as the falx cerebri, the te ...
as well as providing information on the type of edema present and the extent of affected area.
CT scan is the imaging modality of choice as it is widely available, quick, and with minimal risks.
However, CT scan can be limited in determining the exact cause of cerebral edema in which cases,
CT angiography
Computed tomography angiography (also called CT angiography or CTA) is a computed tomography technique used for angiography—the visualization of arteries and veins—throughout the human body. Using contrast injected into the blood vessels, i ...
(CTA), MRI, or
digital subtraction angiography
Digital subtraction angiography (DSA) is a fluoroscopy technique used in interventional radiology to clearly visualize blood vessels in a bony or dense soft tissue environment. Images are produced using contrast medium by subtracting a "pre-contra ...
(DSA) may be necessary. MRI is particularly useful as it can differentiate between cytotoxic and vasogenic edema, guiding future treatment decisions.
Intracranial pressure monitoring
Intracranial pressure
Intracranial pressure (ICP) is the pressure exerted by fluids such as cerebrospinal fluid (CSF) inside the skull and on the brain tissue. ICP is measured in millimeters of mercury (mmHg) and at rest, is normally 7–15 Millimeter of mercury, mmHg ...
(ICP) and its management is a fundamental concept in
traumatic brain injury
A traumatic brain injury (TBI), also known as an intracranial injury, is an injury to the brain caused by an external force. TBI can be classified based on severity (ranging from mild traumatic brain injury TBI/concussionto severe traumatic b ...
(TBI).
The
Brain Trauma Foundation guidelines recommend
ICP monitoring in individuals with TBI that have decreased
Glasgow Coma Scale
The Glasgow Coma Scale (GCS) is a clinical scale used to reliably measure a person's level of consciousness after a brain injury.
The GCS assesses a person based on their ability to perform eye movements, speak, and move their body. These thre ...
(GCS) scores, abnormal CT scans, or additional risk factors such as older age and elevated blood pressure.
However, no such guidelines exist for ICP monitoring in other brain injuries such as
ischemic stroke
A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...
,
intracerebral hemorrhage,
cerebral neoplasm.
Clinical researches have recommended ICP and
cerebral perfusion pressure Cerebral perfusion pressure, or CPP, is the net pressure gradient causing cerebral blood flow to the brain (brain perfusion). It must be maintained within narrow limits because too little pressure could cause brain tissue to become ischemic (having ...
(CPP) monitoring in any persons with cerebral injury who are at risk of elevated intracranial pressure based on clinical and neuroimaging features.
Early monitoring can be used to guide medical and surgical decision making and to detect potentially life-threatening brain herniation.
There was however, conflicting evidence on the threshold values of ICP that indicated the need for intervention.
Researches also recommend that medical decisions should be tailored to the specific diagnosis (e.g.
subarachnoid hemorrhage, TBI,
encephalitis
Encephalitis is inflammation of the brain. The severity can be variable with symptoms including reduction or alteration in consciousness, headache, fever, confusion, a stiff neck, and vomiting. Complications may include seizures, hallucinations, ...
) and that ICP elevation should be used in conjunction with clinical and neuroimaging and not as an isolated prognostic marker.
Treatment
The primary goal in cerebral edema is to optimize and regulate
cerebral perfusion, oxygenation, and venous drainage, decrease cerebral metabolic demands, and to stabilize the
osmolality
Molality is a measure of the number of moles of solute in a solution corresponding to 1 kg or 1000 g of solvent. This contrasts with the definition of molarity which is based on a specified volume of solution.
A commonly used unit for molali ...
pressure gradient between the brain and the surrounding vasculature.
As cerebral edema is linked to increased
intracranial pressure
Intracranial pressure (ICP) is the pressure exerted by fluids such as cerebrospinal fluid (CSF) inside the skull and on the brain tissue. ICP is measured in millimeters of mercury (mmHg) and at rest, is normally 7–15 Millimeter of mercury, mmHg ...
(ICP), many of the therapies will focus on ICP.
General measures for managing cerebral edema
Positioning
Finding the optimal head position in persons with cerebral edema is necessary to avoid compression of the
jugular vein
The jugular veins are veins that take deoxygenated blood from the head back to the heart via the superior vena cava. The internal jugular vein descends next to the internal carotid artery and continues posteriorly to the sternocleidomastoid mu ...
and obstruction of venous outflow from the skull, and for decreasing
cerebrospinal fluid
Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates.
CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the bra ...
hydrostatic pressure
Fluid statics or hydrostatics is the branch of fluid mechanics that studies the condition of the equilibrium of a floating body and submerged body "fluids at hydrostatic equilibrium and the pressure in a fluid, or exerted by a fluid, on an imme ...
.
The current recommendation is to elevate the head of the bed to 30 degrees to optimize cerebral perfusion pressure and control the increase in intracranial pressure.
It is also worth noting that measures should taken to reduce restrictive neck dressings or garments as these may lead to compression of the
internal jugular vein
The internal jugular vein is a paired jugular vein that collects blood from the brain and the superficial parts of the face and neck. This vein runs in the carotid sheath with the common carotid artery and vagus nerve.
It begins in the posteri ...
s and reduce venous outflow.
Ventilation and oxygenation
Decreased oxygen concentration in the blood,
hypoxia, and increase in the carbon dioxide concentration in the blood,
hypercapnia
Hypercapnia (from the Greek ''hyper'' = "above" or "too much" and ''kapnos'' = "smoke"), also known as hypercarbia and CO2 retention, is a condition of abnormally elevated carbon dioxide (CO2) levels in the blood. Carbon dioxide is a gaseous pro ...
, are potent
vasodilators
Vasodilation is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. The process is the opposite of vasoconstriction ...
in the cerebral vasculature, and should be avoided in those with cerebral edema.
It is recommended that persons with decreased levels of consciousness be
intubated for airway protection and maintenance of oxygen and carbon dioxide levels.
However, the
laryngeal instrumentation involved in the intubation process is associated with a acute, brief rise in intracranial pressure.
Pretreatment with a sedative agent and neuromuscular blocking agent to induce unconsciousness and motor paralysis has been recommended as part of standard
Rapid Sequence Intubation
In advanced airway management, rapid sequence induction (RSI) – also referred to as rapid sequence intubation or as rapid sequence induction and intubation (RSII) or as crash induction – is a special process for endotracheal intubation that is ...
(RSI).
Intravenous lidocaine prior to RSI has been suggested to reduce the rise in ICP but there is no supporting data at this time.
Additionally, ventilation with use of positive pressure (
PEEP
Peep, Peeps, or PEEP may refer to:
People
*Peep (given name), Estonian masculine given name
*Lil Peep (1996–2017), American singer and rapper
*Helend Peep (1910–2007), Estonian actor
*Viljar Peep (born 1969), Estonian historian and civil serv ...
) can improve oxygenation with the negative effect of decreasing cerebral venous drainage and increasing intracranial pressure (ICP), and thus, must be used with caution.
Fluid management and cerebral perfusion
Maintenance of cerebral perfusion pressure using appropriate fluid management is essential in patients with brain injury.
Dehydration
In physiology, dehydration is a lack of total body water, with an accompanying disruption of metabolic processes. It occurs when free water loss exceeds free water intake, usually due to exercise, disease, or high environmental temperature. Mil ...
, or intravascular volume loss, and the use of hypotonic fluids, such as
D5W or
half normal saline, should be avoided.
Blood serum ion concentration, or
osmolality
Molality is a measure of the number of moles of solute in a solution corresponding to 1 kg or 1000 g of solvent. This contrasts with the definition of molarity which is based on a specified volume of solution.
A commonly used unit for molali ...
, should be maintained in the normo to hyperosmolar range.
Judicial use of hypertonic saline can be used to increase serum osmolality and decrease cerebral edema, as discussed below.
Blood pressure should be sufficient so as to sustain
cerebral perfusion pressure Cerebral perfusion pressure, or CPP, is the net pressure gradient causing cerebral blood flow to the brain (brain perfusion). It must be maintained within narrow limits because too little pressure could cause brain tissue to become ischemic (having ...
s greater than 60 mm Hg for optimal blood blow to the brain.
Vasopressors
An antihypotensive agent, also known as a vasopressor agent or simply vasopressor, or pressor, is any substance, whether endogenous or a medication, that tends to raise low blood pressure. Some antihypotensive drugs act as vasoconstrictors to in ...
may be used to achieve adequate blood pressures with minimal risk of increasing intracranial pressures.
However, sharp rises in blood pressure should be avoided.
Maximum blood pressures tolerated are variable and controversial depending on the clinical situation.
Seizure prophylaxis
Seizures
An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or neural oscillation, synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much o ...
, including subclinical seizure activity, can complicate clinical courses and increase progression of brain herniation in persons with cerebral edema and increased intracranial pressure.
Anticonvulsants can be used to treat seizures caused by acute brain injuries from a variety of origins.
However, there are no clear guidelines on the use of anticonvulsants for
prophylactic
Preventive healthcare, or prophylaxis, consists of measures taken for the purposes of disease prevention.Hugh R. Leavell and E. Gurney Clark as "the science and art of preventing disease, prolonging life, and promoting physical and mental hea ...
use.
Their use may be warranted on depending on the clinical scenario and studies have shown that
anticonvulsant
Anticonvulsants (also known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of b ...
s such as
phenytoin
Phenytoin (PHT), sold under the brand name Dilantin among others, is an anti-seizure medication. It is useful for the prevention of tonic-clonic seizures (also known as grand mal seizures) and focal seizures, but not absence seizures. The intr ...
can be given prophylactically without a significant increase in drug-related side effects.
Fever
Fever
Fever, also referred to as pyrexia, is defined as having a body temperature, temperature above the human body temperature, normal range due to an increase in the body's temperature Human body temperature#Fever, set point. There is not a single ...
has been demonstrated to increase metabolism and oxygen demand in the brain.
The increased metabolic demand results in an increase in cerebral blood flow and can increase the intracranial pressure within the skull.
Therefore, maintaining a stable body temperature within the normal range is strongly recommended.
This can be achieved through the use of
antipyretic
An antipyretic (, from ''anti-'' 'against' and ' 'feverish') is a substance that reduces fever. Antipyretics cause the hypothalamus to override a prostaglandin-induced increase in temperature. The body then works to lower the temperature, which r ...
s such as
acetaminophen (
paracetamol
Paracetamol, also known as acetaminophen, is a medication used to treat fever and mild to moderate pain. Common brand names include Tylenol and Panadol.
At a standard dose, paracetamol only slightly decreases body temperature; it is inferior ...
) and cooling the body, as described below.
Hyperglycemia
Elevated blood glucose levels, known as
hyperglycemia
Hyperglycemia is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a blood sugar level higher than 11.1 mmol/L (200 mg/dL), but symptoms may not start to become noticeable until even ...
, can exacerbate brain injury and cerebral edema and has been associated with worse clinical outcomes in persons affected by
traumatic brain injuries
A traumatic brain injury (TBI), also known as an intracranial injury, is an injury to the brain caused by an external force. TBI can be classified based on severity (ranging from mild traumatic brain injury TBI/concussionto severe traumatic ...
,
subarachnoid hemorrhages, and
ischemic strokes.
Sedation
Pain and agitation can worsen cerebral edema, acutely increase intracranial pressure (ICP), and should be controlled.
Careful use of pain medication such as morphine or fentanyl can be used for
analgesia
Pain management is an aspect of medicine and health care involving relief of pain (pain relief, analgesia, pain control) in various dimensions, from acute and simple to chronic and challenging. Most physicians and other health professionals ...
.
For those persons with decreased levels of consciousness, sedation is necessary for
endotracheal intubation
Tracheal intubation, usually simply referred to as intubation, is the placement of a flexible plastic tube into the trachea (windpipe) to maintain an open airway or to serve as a conduit through which to administer certain drugs. It is frequently ...
and maintenance of a secure airway.
Sedative medication used in the intubation process, specifically propofol, have been shown to control ICP, decrease cerebral metabolic demand, and have antiseizure properties.
Due to a short half-life, propofol, is a quick-acting medication whose administration and removal is well tolerated, with hypotension being the limiting factor in its continued use.
Additionally, the use of nondepolarizing Neuromuscular-blocking drug, neuromusclar blocking agents (NMBA), such as Doxacurium chloride, doxacurium or Atracurium besilate, atracurium, have been indicated to facilitate ventilation and manage brain injuries but there are no controlled studies on the use of NMBAs in the management of increased intracranial pressure.
Depolarizing neuromuscular blocking agents, most notably succinylcholine, can worsen increased ICP due to induction of muscle contraction within the body.
Nutrition
Nutritional support is necessary in all patients with acute brain injury.
Enteral feeding, or through mouth via tube, is the preferred method, unless contraindicated.
Additional attention must be placed on the solute concentration of the formulations to avoid free water intake, decreased serum osmolality, and worsening of the cerebral edema.
Elevated blood glucose, or
hyperglycemia
Hyperglycemia is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a blood sugar level higher than 11.1 mmol/L (200 mg/dL), but symptoms may not start to become noticeable until even ...
, is associated with increased edema in patients with Brain ischemia, cerebral ischemia and increases the risk of a hemorrhagic transformation of ischemic stroke.
Maintaining a normal blood glucose level of less than 180 mg/dL is suggested.
However, tight glycemic control of blood glucose under 126 mg/dL is associated with worsening of stroke size.
Specific measures
Although cerebral edema is closely related to increased
intracranial pressure
Intracranial pressure (ICP) is the pressure exerted by fluids such as cerebrospinal fluid (CSF) inside the skull and on the brain tissue. ICP is measured in millimeters of mercury (mmHg) and at rest, is normally 7–15 Millimeter of mercury, mmHg ...
(ICP) and Brain herniation, cerebral herniation and the general treatment strategies above are useful, the treatment should ultimately be tailored to the primary cause of the symptoms.
The management of individual diseases are discussed separately.
The following interventions are more specific treatments for managing cerebral edema and increased ICP:
Osmotic therapy
The goal of osmotic therapy is to create a higher concentration of ions within the vasculature at the
blood–brain barrier
The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of ...
.
This will create an osmotic pressure gradient and will cause the flow of water out of the brain and into the vasculature for drainage elsewhere.
An ideal osmotic agent produces a favorable osmotic pressure gradient, is nontoxic, and is not filtered out by the blood–brain barrier.
Hypertonic saline and mannitol are the main osmotic agents in use, while loop diuretics can aid in the removal of the excess fluid pulled out of the brain.
* Hypertonic saline is a highly concentrated solution of sodium chloride in water and is administered intravenously.
It has a rapid-onset, with reduction of pressures within 5 minutes of infusion, lasting up to 12 hours in some cases, and with negligible rebound pressure.
The exact volume and concentration of the hypertonic saline varies between clinical studies.
Bolus doses, particularly at higher concentrations, for example 23.4%, are effective at reducing ICP and improving cerebral perfusion pressure.
In
traumatic brain injuries
A traumatic brain injury (TBI), also known as an intracranial injury, is an injury to the brain caused by an external force. TBI can be classified based on severity (ranging from mild traumatic brain injury TBI/concussionto severe traumatic ...
, a responsiveness to hypertonic saline lasting greater than 2 hours was associated with decreased chance of death and improved neurologic outcomes.
The effects of hypertonic saline can be prolonged with combination to agents such as dextran or hydroxyethyl starch, although their use is currently controversial.
When compared to mannitol, hypertonic saline has been shown to be as effective as mannitol in decreased ICP in neurocritical care and is more effective in many cases.
Hypertonic saline may be preferable to mannitol in persons with hypovolemia or
hyponatremia
Hyponatremia or hyponatraemia is a low concentration of sodium in the blood. It is generally defined as a sodium concentration of less than 135 mmol/L (135 mEq/L), with severe hyponatremia being below 120 mEq/L. Symptoms can be abs ...
.
* Mannitol is an Alcohol (chemistry), alcohol derivative of simple sugar mannose, and is historically the most commonly used osmotic diuretic.
Mannitol acts as an inert solute in the blood, decreasing ICP through osmosis as discussed above.
Additionally, mannitol decreases ICP and increased cerebral perfusion pressure by increasing reabsorption of cerebrospinal fluid, dilutes and decreased the viscosity of the blood, and can cause cerebral vasoconstriction.
Furthermore, mannitol acts in a dose-dependent manner and will not lower ICP if it is not elevated.
However, the common limitation of the use of mannitol is its tendency to cause low blood pressure hypotension.
Compared to hypertonic saline, mannitol may be more effective at increasing
cerebral perfusion pressure Cerebral perfusion pressure, or CPP, is the net pressure gradient causing cerebral blood flow to the brain (brain perfusion). It must be maintained within narrow limits because too little pressure could cause brain tissue to become ischemic (having ...
s and may be preferable in those with hypoperfusion.
* Loop diuretics, commonly furosemide, act within kidney to increase excretion of water and solutes.
Combination with mannitol produces a profound diuresis and increases the risk of systemic dehydration and hypotension.
Their use remains controversial.
* Acetazolamide, a carbonic anhydrase inhibitor, acts as a weak diuretic and modulates CSF production but has not role in the management of cerebral edema from acute brain injuries.
It can be used in the outpatient management of cerebral edema caused by idiopathic intracranial hypertension (pseudotumor cerebri).
Glucocorticoids
Glucocorticoids, such as
dexamethasone
Dexamethasone is a glucocorticoid medication used to treat rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive lung disease, croup, brain swelling, eye pain following eye surgery, superior vena ...
, have been shown to decrease tight-junction permeability and stabilize the blood-brain barrier.
Their main use has been in the management of vasogenic cerebral edema associated with brain tumors, brain irradiation, and surgical manipulation.
Glucocorticoids have not been shown to have any benefit in
ischemic stroke
A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...
and have been found to be harmful in traumatic brain injury.
Due to the negative side effects (such as peptic ulcers, hyperglycemia, and impairment of wound healing), steroid use should be restricted to cases where they are absolutely indicated.
Hyperventilation
As mentioned previously,
hypoxia and
hypercapnia
Hypercapnia (from the Greek ''hyper'' = "above" or "too much" and ''kapnos'' = "smoke"), also known as hypercarbia and CO2 retention, is a condition of abnormally elevated carbon dioxide (CO2) levels in the blood. Carbon dioxide is a gaseous pro ...
are potent
vasodilators
Vasodilation is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. The process is the opposite of vasoconstriction ...
in the cerebral vasculature, leading to increased cerebral blood flow (CBF) and worsening of cerebral edema.
Conversely, therapeutic hyperventilation can be used to lower the carbon dioxide content in the blood and reduce ICP through vasoconstriction.
The effects of hyperventilation, although effective, are short-lived and once removed, can often lead to a rebound elevation of ICP.
Furthermore, overaggressive hyperventilation and vasoconstriction and lead to severe reduction in CBF and cause Brain ischemia, cerebral ischemia, or strokes.
As a result, standard practice is to slowly reverse hyperventilation while more definitive treatments aimed at the primary cause are instituted.
It is important to note that prolonged hyperventilation in those with
traumatic brain injuries
A traumatic brain injury (TBI), also known as an intracranial injury, is an injury to the brain caused by an external force. TBI can be classified based on severity (ranging from mild traumatic brain injury TBI/concussionto severe traumatic ...
has been shown to worsen outcomes.
Barbiturates
Induction of a coma via the use of barbiturates, most notably pentobarbital and thiopental, after brain injury is used for secondary treatment of refractory ICP.
Yet their use is not without controversy and it is not clear whether barbiturates are favored over surgical decompression.
In patients with traumatic brain injuries, barbiturates are effective in reducing ICP but have failed to show benefit to clinical outcomes.
Evidence is limited for their use in cerebral disease that include tumor,
intracranial hypertension
Intracranial pressure (ICP) is the pressure exerted by fluids such as cerebrospinal fluid (CSF) inside the skull and on the brain tissue. ICP is measured in millimeters of mercury (mmHg) and at rest, is normally 7–15 mmHg for a supine adult. Th ...
, and
ischemic stroke
A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...
.
There are several adverse effects of barbiturates that limit their use, such as lowering of systemic blood pressure and
cerebral perfusion pressure Cerebral perfusion pressure, or CPP, is the net pressure gradient causing cerebral blood flow to the brain (brain perfusion). It must be maintained within narrow limits because too little pressure could cause brain tissue to become ischemic (having ...
, cardiodepression, immunosuppression, and systemic hypothermia.
Hypothermia
As discussed previously in the treatment of fever, temperature control has been shown to decrease metabolic demand and reduce further ischemic injury.
In traumatic brain injury, induced hypothermia may reduce the risks of mortality, poor neurologic outcome in adults.
However, outcomes varied greatly depth and duration of hypothermia as well as rewarming procedures.
In children with traumatic brain injury, there was no benefit to therapeutic hypothermia and increased the risk of mortality and arrhythmia. The adverse effects of hypothermia are serious and require clinical monitoring including increased chance of infection, coagulopathy, and electrolyte derangement.
The current consensus is that adverse effects outweigh the benefits and its use restricted to clinical trials and refractory increased ICP to other therapies.
Surgery
The Monroe-Kellie doctrine states that the skull is a fixed and inelastic space and the accumulation of edema will compress vital brain tissue and blood vessels.
Surgical treatment of cerebral edema in the context of cerebellar or cerebral infarction is typically done by removing part of the skull to allow expansion of the Dura mater, dura.
This will help to reduce the volume constraints inside of the skull.
A decompressive hemicraniectomy is the most commonly used procedure.
Multiple randomized clinical trials have shown reduced risk of death with hemicraniectomy compared with medical management.
However, no individual study has shown an improvement in the percentage of survivors with good functional outcomes.
Timing of
decompressive craniectomy
Decompressive craniectomy ('' crani-'' + '' -ectomy'') is a neurosurgical procedure in which part of the skull is removed to allow a swelling brain room to expand without being squeezed. It is performed on victims of traumatic brain injury, str ...
remains controversial, but is generally suggested that the surgery is best performed before there are clinical signs of Brain herniation, brainstem compression.
Postoperative complications include wound dehiscence,
hydrocephalus
Hydrocephalus is a condition in which an accumulation of cerebrospinal fluid (CSF) occurs within the brain. This typically causes increased intracranial pressure, pressure inside the skull. Older people may have headaches, double vision, poor ...
, infection, and a substantial proportion of patients may also require Tracheotomy, tracheostomy and Gastrostomy, gastrotomy in the early phase after surgery.
Outcomes
Cerebral edema is a severe complication of acute brain injuries, most notably
ischemic stroke
A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...
and
traumatic brain injuries
A traumatic brain injury (TBI), also known as an intracranial injury, is an injury to the brain caused by an external force. TBI can be classified based on severity (ranging from mild traumatic brain injury TBI/concussionto severe traumatic ...
, and a significant cause of morbidity and mortality.
* Cerebral edema is the cause of death in 5% of all patients with cerebral infarction and mortality after large ischemic strokes with cerebral edema is roughly 20 to 30% despite medical and surgical interventions.
Cerebral edema usually occurs between the second and fifth day after onset of symptoms.
Large territory ischemic strokes can lead to the rapid development of malignant brain edema and increased intracranial pressure. Cerebral edema in the context of a malignant middle cerebral artery (MCA) infarct has a mortality of 50 to 80% if treated conservatively.
Individuals with cerebral edema had a worse 3-month functional outcome than those without edema.
These effects were more pronounced with increasing extent of cerebral edema and were independent of the size of the infarct.
* Mild
traumatic brain injury
A traumatic brain injury (TBI), also known as an intracranial injury, is an injury to the brain caused by an external force. TBI can be classified based on severity (ranging from mild traumatic brain injury TBI/concussionto severe traumatic b ...
(TBI) represents 70–90% of all reported head injuries.
The presence of brain edema on the initial CT scan of those with traumatic brain injuries is an independent prognostic indicator of in-hospital death.
The association of brain edema with increased in hospital risk of death was observed in TBI across all level of severity.
Edema in the acute and chronic phases were associated with a worse neurologic and clinical outcome.
Children with TBI and cerebral edema have worse clinical outcomes as well.
Epidemiology
As cerebral edema is present with many common cerebral pathologies, the epidemiology of the disease is not easily defined.
The incidence of this disorder should be considered in terms of its potential causes and is present in most cases of
traumatic brain injury
A traumatic brain injury (TBI), also known as an intracranial injury, is an injury to the brain caused by an external force. TBI can be classified based on severity (ranging from mild traumatic brain injury TBI/concussionto severe traumatic b ...
,
central nervous system tumors,
brain ischemia
Brain ischemia is a condition in which there is insufficient bloodflow to the brain to meet metabolic demand. This leads to poor oxygen supply or cerebral hypoxia and thus leads to the death of brain tissue or cerebral infarction/ ischemic stroke ...
, and
intracerebral hemorrhage.
* In one study, cerebral edema was found in 28% of those individuals with thrombolysis-treated ischemic strokes, 10% of which occurred in severe forms.
A further study detected cerebral edema in 22.7% of cerebral ischemic strokes.
A meta-analysis of current studies showed that 31% of those affected by ischemic strokes developed cerebral edema in 31% of cases.
* In traumatic brain injuries, cerebral edema occurred in greater than 60% of those with mass lesions, and in 15% of those with initial normal CT scans.
Research
The current understanding of the pathophysiology of cerebral edema after traumatic brain injury or intracerebral hemorrhage is incomplete.
Current treatment therapies aimed at cerebral edema and increased intracranial pressure are effective at reducing intracranial hypertension but have unclear impacts on functional outcomes.
Additionally, cerebral and ICP treatments have varied effects on individuals based on differing characteristics like age, gender, type of injury, and genetics.
There are innumerable molecular pathways that contribute to cerebral edema, many of which have yet to be discovered.
Researchers argue that the future treatment of cerebral edema will be based on advances in identifying the underlying pathophysiology and molecular characteristics of cerebral edema in a variety of cases.
At the same time, improvement of radiographic markers, biomarkers, and analysis of clinical monitoring data is essential in treating cerebral edema.
Many studies of the mechanical properties of brain edema were conducted in the 2010s, most of them based on Finite element method, finite element analysis (FEA), a widely used numerical method in solid mechanics. For example, Gao and Ang used the finite element method to study changes in intracranial pressure during craniotomy operations. A second line of research on the condition looks at thermal conductivity, which is related to tissue water content.
See also
*
Intracranial pressure
Intracranial pressure (ICP) is the pressure exerted by fluids such as cerebrospinal fluid (CSF) inside the skull and on the brain tissue. ICP is measured in millimeters of mercury (mmHg) and at rest, is normally 7–15 Millimeter of mercury, mmHg ...
* Edema
*
Amyloid-related imaging abnormalities
Amyloid-related imaging abnormalities (ARIA) are abnormal differences seen in magnetic resonance imaging of the brain in patients with Alzheimer's disease. ARIA is associated with amyloid-modifying therapies, particularly human monoclonal antibodi ...
References
External links
MedPixVasogenic Edema
{{DEFAULTSORT:Cerebral Edema
Cerebrum
Body water