| Cerebral edema | |
|---|---|
| Other names | Brain edema,[1] Cerebral oedema,[2] Brain swelling |
 | |
| Skull MRI (T2 flair) of abrain metastasis with accompanyingedema | |
| Symptoms | Headache, nausea, vomiting, decreased consciousness, seizures |
| Differential diagnosis | |
Cerebral edema is excess accumulation of fluid (edema) in theintracellular orextracellular spaces of thebrain.[1] This typically causes impaired nerve function,increased pressure within the skull, and can eventually lead todirect compression of brain tissue and blood vessels.[1] Symptoms vary based on the location and extent of edema and generally includeheadaches, nausea, vomiting, seizures, drowsiness, visual disturbances, dizziness, and in severe cases, death.[1]
Cerebral edema is commonly seen in a variety of brain injuries includingischemic stroke,subarachnoid hemorrhage, traumatic brain injury,subdural,epidural, orintracerebral hematoma,hydrocephalus,brain cancer, brain infections,low blood sodium levels,high altitude, andacute liver failure.[1][3][4][5][6] Diagnosis is based on symptoms and physical examination findings and confirmed by serial neuroimaging (computed tomography scans andmagnetic resonance imaging).[3]
The treatment of cerebral edema depends on the cause and includes monitoring of the person's airway andintracranial pressure, proper positioning, controlled hyperventilation, medications, fluid management, steroids.[3][7][8] Extensive cerebral edema can also be treated surgically with adecompressive craniectomy.[7] Cerebral edema is a major cause of brain damage and contributes significantly to the mortality of ischemic strokes andtraumatic brain injuries.[4][9]
As cerebral edema is present with many common cerebral pathologies, the epidemiology of the disease is not easily defined.[1] 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, andintracerebral hemorrhage.[1] For example, malignant brain edema was present in roughly 31% of people with ischemic strokes within 30 days after onset.[10]
The extent and severity of the symptoms of cerebral edema depend on the exactetiology but are generally related to an acuteincrease of the pressure within the skull.[1] As the skull is a fixed and inelastic space, the accumulation of cerebral edema can displace and compress vital brain tissue,cerebral spinal fluid, and blood vessels, according to theMonro–Kellie doctrine.[8]
Increased intracranial pressure (ICP) is a life-threatening surgical emergency marked by symptoms of headache, nausea, vomiting, decreased consciousness.[1] Symptoms are frequently accompanied by visual disturbances such asgaze paresis, reduced vision, and dizziness.[1] Increased pressures within the skull can cause a compensatory elevation of blood pressure to maintaincerebral blood flow, which, when associated with irregular breathing and adecreased heart rate, is called theCushing reflex.[1] The Cushing reflex often indicatescompression of the brain on brain tissue and blood vessels, leading todecreased blood flow to the brain and eventually death.[1]
Cerebral edema is frequently encountered in acute brain injuries from a variety of origins, including but not limited to:[7]
Cerebral edema is present with many common cerebral pathologies and risk factors for development of cerebral edema will depend on the cause.[1] The following were reliable predictors for development of early cerebral edema in ischemic strokes:[9][10]
Cerebral edema has been traditional classified into two major sub-types: cytotoxic and vasogenic cerebral edema.[1] This simple classification helps guide medical decision making and treatment of patients affected with cerebral edema.[3] There are, however, several more differentiated types including but not limited to interstitial, osmotic, hydrostatic, and high altitude associated edema.[1][3][7] Within one affected person, many individual sub-types can be present simultaneously.[18]
The following individual sub-types have been identified:
In general, cytotoxic edema is linked to cell death in the brain through excessive cellular swelling.[1] During cerebral ischemia for example, theblood–brain barrier remains intact but decreased blood flow and glucose supply leads to a disruption in cellularmetabolism and creation of energy sources, such asadenosine triphosphate (ATP).[1] Exhaustion of energy sources impairs functioning of thesodium and potassium pump in the cell membrane, leading to cellular retention ofsodium ions.[1] Accumulation of sodium in the cell causes a rapid uptake of water throughosmosis, with subsequent swelling of the cells.[19] The ultimate consequence of cytotoxic edema is theoncotic death of neurons.[1] 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.[20] 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.[18]
There are several clinical conditions in which cytotoxic edema is present:
Extracellular brain edema, or vasogenic edema, is caused by an increase in the permeability of theblood–brain barrier.[18] The blood–brain barrier consists ofastrocytes andpericytes joined with adhesion proteins producingtight junctions.[1]Return of blood flow to these cells after anischemic stroke can cause excitotoxicity andoxidative stress leading to dysfunction of the endothelial cells and disruption of the blood-brain barrier.[1] The breakdown of the tight endothelial junctions that make up the blood–brain barrier causesextravasation of fluid, ions, and plasma proteins, such asalbumin, into the brainparenchyma.[18] Accumulation of extracellular fluid increases brain volume and then intracranial pressure causing the symptoms of cerebral edema.[1]
There are several clinical conditions in which vasogenic edema is present:
In ionic edema, the solute concentration (osmolality) of the brain exceeds that of theplasma and the abnormal pressure gradient leads to accumulation of water intake into the brainparenchyma through the process ofosmosis.[1] The blood-brain barrier is intact and maintains the osmotic gradient.[21]
The solute concentration of the blood plasma can be diluted by several mechanisms:
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.[21]
Interstitial edema can be best characterized by a noncomunnicatinghydrocephalus where there is an obstruction to the outflow ofcerebrospinal fluid within theventricular system.[1][21] 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.[21] The fluid has roughly the same composition of CSF.[21]
Other causes of interstitial edema include but are not limited to communicating hydrocephalus, andnormal pressure hydrocephalus.[18]
Hydrostatic extracellular brain edema is typically caused by severe arterial hypertension.[18] A difference in thehydrostatic pressure within the arterial system relative to the endothelial cells allowsultrafiltration of water, ions, and low molecular weight substances (such as glucose, small amino acids) into the brainparenchyma.[18] Theblood-brain barrier is intact usually and the extent of the edema depends on the arterial pressure.[18] 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.[18]
Cytotoxic, osmotic, and vasogenic edema exist on a continuum.[8] The mechanism of the cause of cerebral edema can often overlap between these types.[8] In most instances, cytotoxic and vasogenic edema occur together.[18] When the two edema types evolve simultaneously, the damage of one type reaches a limit and will bring about the other type of injury.[18] For example, when cytotoxic edema occurs in theendothelial cells of theblood–brain barrier, oncotic cell death contributes to loss of integrity of the blood–brain barrier and promotes the progression to vasogenic edema.[8] 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.[18] The use of specific MRI techniques has allowed for some differentiation between the mechanisms.[24]
If not properly acclimatized to high altitude, a person may be negatively affected by the lower oxygen concentration available.[6] These hypoxia-related illnesses includeacute mountain sickness (AMS),high-altitude pulmonary edema, andhigh-altitude cerebral edema (HACE).[6]High-altitude cerebral edema is a severe and sometimes fatal form ofaltitude sickness that results fromcapillary fluid leakage due to the effects ofhypoxia on themitochondria-richendothelial cells of theblood–brain barrier.[25] The edema can be characterized by vasogenic cerebral edema with symptoms of impaired consciousness andtruncal ataxia.[6]
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. Pharmacologicalprophylaxis withacetazolamide orcorticosteroids can be used in non pre-acclimatized individuals.[6] 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.[6]
Amyloid-related imaging abnormalities (ARIA) are abnormal differences seen in neuroimaging of Alzheimer's disease patients given targeted amyloid-modifying therapies.[26] Human monoclonal antibodies such asaducanumab,solanezumab, andbapineuzumab have been associated with these neuroimaging changes and additionally, cerebral edema.[16][26] 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.[27] Familiarity with ARIA can aid radiologists and clinicians in determining optimal management for those affected.[16]
Posterior reversible encephalopathy syndrome (PRES) is a rare clinical disease characterized by cerebral edema.[12] The exactpathophysiology, or cause, of the syndrome is still debated but is hypothesized to be related to the disruption of the blood-brain barrier.[12] The syndrome features acute neurological symptoms and reversiblesubcortical vasogenic edema predominantly involving the parieto-occipital areas onMR imaging.[28] PRES in general has a benign course, but PRES-related intracranial hemorrhage has been associated with a poor prognosis.[29]
Deep brain stimulation (DBS) is effective treatment for several neurological and psychiatric disorders, most notablyParkinson's disease.[30] DBS is not without risks and although rare, idiopathic delayed-onset edema (IDE) surrounding the DBS leads have been reported.[14] Symptoms can be mild and nonspecific, including reduction of the stimulation effect, and can be confused for other causes of edema.[14] Thus, imaging is recommended to rule out other causes.[14] The condition is generally self-limiting and the exact mechanism of the cause is unexplained.[14] Early identification can help persons affected avoid unnecessary surgical procedures or antibiotic treatments.[14]
Decompressive craniectomy is frequently performed in cases of resistantintracranial hypertension secondary to several neurological conditions and is commonly followed bycranioplasty.[15] Complications, such as infection andhematomas after cranioplasty occur in roughly about a third of cases.[15] Massive brain swelling after cranioplasty (MSBC) is a rare and potentially fatal complication of an uneventful cranioplasty that has recently been elucidated.[15] Preoperative sinking skin flap (SSF) and intracranial hypotension were factors associated with the development of MSBC after cranioplasty.[15][31] Data suggests that pathologic changes are triggered immediately following the procedure, especially an acute increase in intracranial pressure.[15]
With the rise of sophisticated treatment modalities such asgamma knife,Cyberknife, andintensity-modulated radiotherapy, a large number of individuals with brain tumors are treated with radiosurgery and radiotherapy.[13] 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 theblood–brain barrier.[13] Symptoms include headache, seizure, psychomotor slowing, irritability, and focal neurological deficits.[13] Options for management of RIBE are limited and includecorticosteroids,antiplatelet drugs,anticoagulants,hyperbaric oxygen therapy, multivitamins, andbevacizumab.[13]
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.[32] The exact mechanism is unclear but hypothesized that cancerousglial cells (glioma) of the brain can increase secretion ofvascular endothelial growth factor (VEGF), which weakens the tight junctions of theblood–brain barrier.[33] Historically, corticosteroids such asdexamethasone were used to reduce brain tumor-associated vascular permeability through poorly understood mechanisms and was associated with systemic side effects.[33] Agents that target the VEGF signaling pathways, such ascediranib, have been promising in prolonging survival inrat models but associated with local and systemic side effects as well.[32]
Cerebral edema is commonly present in a variety of neurological injuries.[1][3] Thus, determining a definitive contribution of cerebral edema to the neurological status of an affected person can be challenging.[3] Close bedside monitoring of a person's level of consciousness and awareness of any new or worseningfocal neurological deficits is imperative but demanding, frequently requiring admission into theintensive care unit (ICU).[3]
Cerebral edema with sustained increasedintracranial hypertension andbrain herniation can signify impending catastrophic neurological events which require immediate recognition and treatment to prevent injury and even death.[1][9][10][34] Therefore, diagnosis of cerebral edema earlier with rapid intervention can improve clinical outcomes and canmortality, or risk of death.[34]
Diagnosis of cerebral edema relies on the following:
Serial neuroimaging (CT scans andmagnetic resonance imaging) can be useful in diagnosing or excludingintracranial hemorrhage, large masses, acutehydrocephalus, orbrain herniation as well as providing information on the type of edema present and the extent of affected area.[1][3] CT scan is the imaging modality of choice as it is widely available, quick, and with minimal risks.[1] However, CT scan can be limited in determining the exact cause of cerebral edema in which cases,CT angiography (CTA), MRI, ordigital subtraction angiography (DSA) may be necessary. MRI is particularly useful as it can differentiate between cytotoxic and vasogenic edema, guiding future treatment decisions.[1]
Intracranial pressure (ICP) and its management is a fundamental concept intraumatic brain injury (TBI).[35] TheBrain Trauma Foundation guidelines recommendICP monitoring in individuals with TBI that have decreasedGlasgow Coma Scale (GCS) scores, abnormal CT scans, or additional risk factors such as older age and elevated blood pressure.[3] However, no such guidelines exist for ICP monitoring in other brain injuries such asischemic stroke,intracerebral hemorrhage,cerebral neoplasm.[3]
Clinical researches have recommended ICP andcerebral perfusion pressure (CPP) monitoring in any persons with cerebral injury who are at risk of elevated intracranial pressure based on clinical and neuroimaging features.[35] Early monitoring can be used to guide medical and surgical decision making and to detect potentially life-threatening brain herniation.[35] There was however, conflicting evidence on the threshold values of ICP that indicated the need for intervention.[35] Researchers also recommend that medical decisions should be tailored to the specific diagnosis (e.g.subarachnoid hemorrhage, TBI,encephalitis) and that ICP elevation should be used in conjunction with clinical and neuroimaging and not as an isolated prognostic marker.[35]
The primary goal in cerebral edema is to optimize and regulatecerebral perfusion, oxygenation, and venous drainage, decrease cerebral metabolic demands, and to stabilize theosmolality pressure gradient between the brain and the surrounding vasculature.[3] As cerebral edema is linked to increasedintracranial pressure (ICP), many of the therapies will focus on ICP.[3]
Finding the optimal head position in persons with cerebral edema is necessary to avoid compression of thejugular vein and obstruction of venous outflow from the skull, and for decreasingcerebrospinal fluidhydrostatic pressure.[3] 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.[3] It is also worth noting that measures should be taken to reduce restrictive neck dressings or garments as these may lead to compression of theinternal jugular veins and reduce venous outflow.[3]
Decreased oxygen concentration in the blood,hypoxia, and increase in the carbon dioxide concentration in the blood,hypercapnia, are potentvasodilators in the cerebral vasculature, and should be avoided in those with cerebral edema.[3] It is recommended that persons with decreased levels of consciousness beintubated for airway protection and maintenance of oxygen and carbon dioxide levels.[3] However, thelaryngeal instrumentation involved in the intubation process is associated with an acute, brief rise in intracranial pressure.[36] Pretreatment with a sedative agent and neuromuscular blocking agent to induce unconsciousness and motor paralysis has been recommended as part of standardRapid Sequence Intubation (RSI).[36] Intravenous lidocaine prior to RSI has been suggested to reduce the rise in ICP but there is no supporting data at this time.[36]
Additionally, ventilation with use of positive pressure (PEEP) can improve oxygenation with the negative effect of decreasing cerebral venous drainage and increasing intracranial pressure (ICP), and thus, must be used with caution.[3]
Maintenance of cerebral perfusion pressure using appropriate fluid management is essential in patients with brain injury.[3]Dehydration, or intravascular volume loss, and the use of hypotonic fluids, such asD5W orhalf normal saline, should be avoided.[3][37] Blood serum ion concentration, orosmolality, should be maintained in the normo to hyperosmolar range.[3] Judicial use of hypertonic saline can be used to increase serum osmolality and decrease cerebral edema, as discussed below.[3]
Blood pressure should be sufficient so as to sustaincerebral perfusion pressures greater than 60 mm Hg for optimal blood blow to the brain.[3]Vasopressors may be used to achieve adequate blood pressures with minimal risk of increasing intracranial pressures.[3] However, sharp rises in blood pressure should be avoided.[3] Maximum blood pressures tolerated are variable and controversial depending on the clinical situation.[3][38]
Seizures, including subclinical seizure activity, can complicate clinical courses and increase progression of brain herniation in persons with cerebral edema and increased intracranial pressure.[3][39] Anticonvulsants can be used to treat seizures caused by acute brain injuries from a variety of origins.[3] However, there are no clear guidelines on the use of anticonvulsants forprophylactic use.[3] Their use may be warranted on depending on the clinical scenario and studies have shown thatanticonvulsants such asphenytoin can be given prophylactically without a significant increase in drug-related side effects.[3]
Fever has been demonstrated to increase metabolism and oxygen demand in the brain.[3] The increased metabolic demand results in an increase in cerebral blood flow and can increase the intracranial pressure within the skull.[40] Therefore, maintaining a stable body temperature within the normal range is strongly recommended.[3] This can be achieved through the use ofantipyretics such asacetaminophen (paracetamol) and cooling the body, as described below.[3]
Elevated blood glucose levels, known ashyperglycemia, can exacerbate brain injury and cerebral edema and has been associated with worse clinical outcomes in persons affected bytraumatic brain injuries,subarachnoid hemorrhages, andischemic strokes.[3]
Pain and agitation can worsen cerebral edema, acutely increase intracranial pressure (ICP), and should be controlled.[3] Careful use of pain medication such as morphine or fentanyl can be used foranalgesia.[3] For those persons with decreased levels of consciousness, sedation is necessary forendotracheal intubation and maintenance of a secure airway.[3] Sedative medication used in the intubation process, specificallypropofol, have been shown to control ICP, decrease cerebral metabolic demand, and have antiseizure properties.[3] Due to a shorthalf-life,propofol, is a quick-acting medication whose administration and removal is well tolerated, withhypotension being the limiting factor in its continued use.[3] Additionally, the use of nondepolarizingneuromusclar blocking agents (NMBA), such asdoxacurium oratracurium, 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.[3][41] Depolarizing neuromuscular blocking agents, most notablysuccinylcholine, can worsen increased ICP due to induction of muscle contraction within the body.[3]
Nutritional support is necessary in all patients with acute brain injury.[3]Enteral feeding, or through mouth via tube, is the preferred method, unless contraindicated.[3] 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.[3]
Elevated blood glucose, orhyperglycemia, is associated with increased edema in patients withcerebral ischemia and increases the risk of ahemorrhagic transformation of ischemic stroke.[38] Maintaining a normal blood glucose level of less than 180 mg/dL is suggested.[38] However, tight glycemic control of blood glucose under 126 mg/dL is associated with worsening of stroke size.[38]
Although cerebral edema is closely related to increasedintracranial pressure (ICP) andcerebral herniation and the general treatment strategies above are useful, the treatment should ultimately be tailored to the primary cause of the symptoms.[42] The management of individual diseases are discussed separately.
The following interventions are more specific treatments for managing cerebral edema and increased ICP:
The goal of osmotic therapy is to create a higher concentration of ions within the vasculature at theblood–brain barrier.[3] This will create anosmotic pressure gradient and will cause the flow of water out of the brain and into the vasculature for drainage elsewhere.[3] An ideal osmotic agent produces a favorable osmotic pressure gradient, is nontoxic, and is not filtered out by the blood–brain barrier.[3]Hypertonic saline andmannitol are the main osmotic agents in use, while loop diuretics can aid in the removal of the excess fluid pulled out of the brain.[1][3][7][43]
Glucocorticoids, such asdexamethasone, have been shown to decrease tight-junction permeability and stabilize the blood-brain barrier.[3] Their main use has been in the management of vasogenic cerebral edema associated with brain tumors, brain irradiation, and surgical manipulation.[1][3][11] Glucocorticoids have not been shown to have any benefit inischemic stroke and have been found to be harmful in traumatic brain injury.[3] 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.[3]
As mentioned previously,hypoxia andhypercapnia are potentvasodilators in the cerebral vasculature, leading to increased cerebral blood flow (CBF) and worsening of cerebral edema.[3] Conversely, therapeutic hyperventilation can be used to lower the carbon dioxide content in the blood and reduce ICP throughvasoconstriction.[3] The effects of hyperventilation, although effective, are short-lived and once removed, can often lead to a rebound elevation of ICP.[3] Furthermore, overaggressive hyperventilation and vasoconstriction and lead to severe reduction in CBF and causecerebral ischemia, or strokes.[3] As a result, standard practice is to slowly reverse hyperventilation while more definitive treatments aimed at the primary cause are instituted.[3]
Prolonged hyperventilation in those withtraumatic brain injuries has been shown to worsen outcomes.[3]
Induction of a coma via the use ofbarbiturates, most notablypentobarbital andthiopental, after brain injury is used for secondary treatment of refractory ICP.[44] Yet their use is not without controversy and it is not clear whether barbiturates are favored over surgical decompression.[3] In patients with traumatic brain injuries, barbiturates are effective in reducing ICP but have failed to show benefit to clinical outcomes.[3] Evidence is limited for their use in cerebral disease that include tumor,intracranial hypertension, andischemic stroke.[3] There are several adverse effects of barbiturates that limit their use, such as lowering of systemic blood pressure andcerebral perfusion pressure, cardiodepression,immunosuppression, and systemichypothermia.[3]
As discussed previously in the treatment of fever, temperature control has been shown to decrease metabolic demand and reduce further ischemic injury.[47] In traumatic brain injury, induced hypothermia may reduce the risks of mortality, poor neurologic outcome in adults.[48] However, outcomes varied greatly with depth and duration of hypothermia as well as rewarming procedures.[47][48] In children with traumatic brain injury, there was no benefit to therapeutic hypothermia and increased the risk of mortality and arrhythmia.[49] The adverse effects of hypothermia are serious and require clinical monitoring including increased chance of infection,coagulopathy, and electrolyte derangement.[3] The current consensus is that adverse effects outweigh the benefits and its use restricted to clinical trials and refractory increased ICP to other therapies.[3][38][48]
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.[8][38] Surgical treatment of cerebral edema in the context of cerebellar or cerebral infarction is typically done by removing part of theskull to allow expansion of thedura.[38] This will help to reduce the volume constraints inside of the skull.[38] A decompressivehemicraniectomy is the most commonly used procedure.[38] Multiple randomized clinical trials have shown reduced risk of death with hemicraniectomy compared with medical management.[38][50][51] However, no individual study has shown an improvement in the percentage of survivors with good functional outcomes.[38]
Timing ofdecompressive craniectomy remains controversial, but is generally suggested that the surgery is best performed before there are clinical signs ofbrainstem compression.[38] Postoperative complications includewound dehiscence,hydrocephalus, infection, and a substantial proportion of patients may also requiretracheostomy andgastrotomy in the early phase after surgery.[38]
Cerebral edema is a severe complication of acute brain injuries, most notablyischemic stroke andtraumatic brain injuries, and a significant cause of morbidity and mortality.[3][10][34]
As cerebral edema is present with many common cerebral pathologies, the epidemiology of the disease is not easily defined.[1] The incidence of this disorder should be considered in terms of its potential causes and is present in most cases oftraumatic brain injury,central nervous system tumors,brain ischemia, andintracerebral hemorrhage.[1]
The current understanding of the pathophysiology of cerebral edema after traumatic brain injury or intracerebral hemorrhage is incomplete.[8][54] Current treatment therapies aimed at cerebral edema and increased intracranial pressure are effective at reducing intracranial hypertension but have unclear impacts on functional outcomes.[53] Additionally, cerebral and ICP treatments have varied effects on individuals based on differing characteristics like age, gender, type of injury, and genetics.[53] There are innumerable molecular pathways that contribute to cerebral edema, many of which have yet to be discovered.[8][54] 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.[8][53] At the same time, improvement of radiographic markers, biomarkers, and analysis of clinical monitoring data is essential in treating cerebral edema.[53]
Many studies of the mechanical properties of brain edema were conducted in the 2010s, most of them based onfinite 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.[55] A second line of research on the condition looks atthermal conductivity, which is related to tissue water content.[56]
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