The most basic definition of cerebral edema is swelling of the brain. It is a relatively common phenomenon with numerous etiologies. Cerebral edema categorizes into either vasogenic, cellular, osmotic, and interstitial causes.  It can arise from a variety of causes, including head trauma, vascular ischemia, intracranial lesions, or obstructive hydrocephalus resulting in interstitial edema. The consequences of cerebral edema can be devastating, even fatal, if untreated.
The explanation of the mechanism of injury arising from cerebral edema comes via the Monroe-Kellie doctrine. The Monroe-Kellie doctrine states that space of the cranial cavity is fixed in volume and contains fixed proportions of brain matter (approximately1400 ml), blood (approximately 150 ml) and cerebrospinal fluid (approximately 150 ml). Because of this fixed space, an increase in the volume of one of these components must, therefore, result in the loss of another component in equal amounts. In cerebral edema, the relative volume of brain tissue increases as the brain tissues swells with edema. This increased relative brain volume decreases perfusion (blood) to the brain, and the pressure can cause further damage to both the edematous and non-edematous brain. Clinical presentation of cerebral edema is variable, ranging from asymptomatic to severe autonomic dysregulation, coma, and death. Symptoms appear as the intracranial pressure (ICP) rises above 20 cm H2O in most patients. Treatment for cerebral edema targets the underlying cause and any life-threatening complications. Treatments include hyperventilation, osmotherapy, diuretics, corticosteroids, and surgical decompression.
Cerebral edema can result from a variety of derangements. The major types include vasogenic, cellular, osmotic, and interstitial.
Through these mechanisms, cerebral edema stems from tumor, trauma, hypoxia, infection, metabolic derangements, or acute hypertension. Causes are widespread and divide into neurological and non-neurological categories. Other non-neurologic causes include hepatitis, Reye syndrome, carbon monoxide poisoning, lead poisoning, and high altitude cerebral edema.
Cerebral edema affects all age groups, genders, and ethnic groups. The actual frequency of cerebral edema may be under-reported secondary to its sometimes non-specific symptoms.
Vasogenic cerebral edema, the most common form, results from the disruption of the blood-brain-barrier. With the disrupted blood-brain-barrier ions and proteins flow more freely into the extravascular space which causes osmotic draw of fluid into the brain interstitium. For example, vascular endothelial growth factor (VEGF), glutamate, and leukotrienes produced locally increase the permeability of vessels around tumors. These factors and a lack of tight endothelial cell junctions in the vessels around the tumors cause this increased permeability, which allows for an influx of proteinaceous solute and fluid into the brain parenchyma, particularly in the white matter. Peritumor edema, for example, leads to 65% of patients developing cognitive impairment resulting from displacement and damage to white matter tracts.
Cellular or cytotoxic edema often results within minutes of the insult/injury and affects glial, neuronal, and endothelial cells within the brain. In cytotoxic edema, the cells lack hemostatic mechanisms, and primarily sodium enters the cell freely, with the failure of the export mechanism. Anions then follow, attempting to return neutrality to the cell, resulting in intracellular edema as the cells swell with increased water following the ions into the intracellular compartment. Traumatic brain injury and stroke cause this form of edema.
Interstitial cerebral edema results from the outflow of cerebrospinal fluid from the intraventricular space to the interstitial areas of the brain. Patients with hydrocephalus or meningitis are examples of those affected by this etiology. The increased pressure, against the cerebrospinal fluid (CSF) and brain, drives fluid into the brain parenchyma. The fluid accumulates in the extracellular space of mostly the white matter causing the cerebral edema.
Osmotic edema generally stems from derangements affecting osmolarity, such as hyponatremia, diabetic ketoacidosis (DKA), or similar metabolic pathologies. The cells of the brain pull water from the plasma in these instances, resulting in widespread edema.
The histopathology of cerebral edema may show both the underlying pathology (tumor, infection, anoxic changes) as well as diffuse swelling of either the cell bodies in cytotoxic edema or interstitial spaces.
Cerebral edema can be asymptomatic, merely seen on imaging, or it can cause life-threatening complications. The history can help provide insights as to the etiology of the cerebral edema. Patients may have a history of trauma, a hypoxic event, cancer, metabolic diseases or other factors which can help identify the possible etiology of the cerebral edema.
The physical exam findings of cerebral edema can vary widely depending on the location and extent of the cerebral edema. Localized cerebral edema can cause dysfunction of the edematous brain and include weakness, visual disturbances, seizures, sensory changes, diplopia, and other neurologic disturbances. For diffuse cerebral edema, the patient may have headaches, nausea, vomiting, lethargy, altered mental status, confusion, coma, seizure or other manifestations. With diffuse or focal cerebral edema the patient can develop increased intracranial pressure (ICP) which typically presents with headaches, nausea, vomiting, lethargy, cranial neuropathy, altered mental status to coma and death.
It is extremely important to identify severe cerebral edema as early as possible to prevent herniation and death. For example malignant middle cerebral artery stroke presenting with severe cerebral edema. Malignant middle cerebral artery stroke is seen more commonly in the younger population. Usually, these patients are admitted to the ICU setting. Following the Neurological exam closely is very important. Usually, there is an altered mental status and development of fixed and dilated pupil. Patients presenting with findings suggestive of cerebral insult should undergo computed tomography (CT) scan of the brain; this can show the edema, which is visible as areas of low density and loss of gray/white matter differentiation, on an unenhanced image. There can also be the obliteration of the cisterns and sulcal spaces. A CT scan can also reveal the cause in some cases. If flattened gyri or narrowed sulci, or compression of the ventricles, is seen, this suggests increased ICP. Serial CT scans are used to show the progression or improvement of the edema.
Magnetic resonance imaging (MRI) can show increased T2 and FLAIR signal changes (hyperintensity) within the brain.
If increased ICP is a concern from the cerebral edema, then an ICP monitor or ventriculostomy may be needed to monitor ICP and can provide better outcomes by helping to tailor therapy.
Treatment of cerebral edema is two-fold: prevent further injury from the cerebral edema and remediate the original insult causing the cerebral edema if able.
Remediation of the original and ongoing insult can include correcting metabolic derangements, controlling hypertension, removing intracranial lesion(s) or shunting hydrocephalus depending on the etiology of the cerebral edema.
The edema should be controlled to prevent further injury, and complications such as increased ICP should be mitigated. Glucocorticoids have shown potential benefit in cerebral edema secondary to vasogenic edema but have limited utility in other forms of edema and should be avoided altogether in the face of trauma. Avoidance of hypotonic fluids is a strong recommendation in instances of cerebral edema as they can worsen cerebral edema and cause elevations in ICP. If the cerebral edema is causing elevated ICP, various methods are available to help control ICP including positioning, hyperosmolar therapy, antipyretics, sedatives, paralytics, modulation of PcO2, and surgical intervention.
In the management of malignant middle cerebral artery stroke presenting with severe cerebral edema, osmotic agents can be used to create an osmotic gradient across blood thereby drawing fluid intravascularly and decreasing cerebral edema. Mannitol was the primary agent used at doses of 0.25 to 1 g/kg body weight and is thought to exert its greatest benefit by decreasing blood viscosity and to a lesser extent by decreasing blood volume. Side effects of mannitol use are eventual osmotic diuresis and dehydration as well as renal injury if serum osmolality exceeds 320 mOsm. Three percent hypertonic saline is also commonly used to decrease cerebral edema and can be administered as a 5 ml/kg bolus or a continuous infusion, monitoring serum sodium levels closely. It is considered relatively safe while serum sodium is < than 160mEq/dl or serum osmolality is less than 340 mOsm. A decompressive craniectomy is a neurosurgical procedure wherein a part of the skull is removed, and dura lifted, allowing the brain to sell without causing compression. It is usually considered as a last resort when all other ICP lowering measures have failed. When considered it is a good idea to do this procedure sooner rather than later. 
The differential diagnosis for cerebral edema includes shaken baby syndrome, encephalitis, toxin poisoning, stroke, metabolic derangements, seizures, and tumors.
The prognosis for cerebral edema is highly variable and depends on the amount of brain involved, the severity, and the etiology of the edema. If the patient is comatose upon discovery, the prognosis may be poor. If the edema is widespread and severe enough to cause significantly elevated intracranial pressure, and treatment is not initiated, the patient may die or develop persistent and irreversible brain injury. An example is seen in prolonged cardiac arrest causing diffuse anoxic brain injury. The basis for prognosis in milder forms is usually the diagnosis and underlying cause (i.e., tumor, stroke, traumatic brain injury, infection, etc.) and early recognition and treatment. Cerebral edema as a consequence of reversible diagnoses, such as diabetic ketoacidosis or uncontrolled hypertension or mild head trauma can be reasonably good.
Complications of cerebral edema range from mild cognitive impairment to death. Untreated, severe cerebral edema is fatal due to brain and brainstem compression and herniation. The presence of significant cerebral edema can cause diffuse brain injury, precipitate seizures in some cases, or create large areas of ischemic brain tissue. Cerebral edema, particularly when widespread, can increase ICP, and this is the most life-threatening sequelae of this condition due to the potential for herniation and brainstem injury. Permanent brain injury can occur in more severe cases. Many of the complications are related to the underlying cause(s) of the edema.
Not all cases can are preventable. Due to the causes, identifying a single preventive measure is challenging. However, in general, patients should focus on keeping their blood pressure under control through lifestyle modification and adherence to recommended medical treatment, maintain optimal control of diabetes to prevent diabetic ketoacidosis. They should also get regular preventive care from their primary care providers, and avoid high-risk behaviors concerning potential injuries, such as not wearing seat belts, or engaging in sports in which there is a high concussive risk, especially if the patient has a history of concussions or head trauma.
The clinical presentation of cerebral edema can easily be mistaken for other issues, such as intoxication, stroke, infection, or post-ictal state. It requires a high index of suspicion, particularly in milder cases. In more severe cases, close neurological monitoring and consultation with neurology and neurosurgery are important. Communication regarding indications/risks/contraindications for ICP monitoring or craniotomy needs to be ongoing, particularly with respect to goals of care. Nursing care must pay close attention to changes in neurologic status, any change in vitals such as increasingly erratic heart rate, development of bradycardia, accurate and equal intake and output when having diuresis, and maintenance of proper blood pressure. As the patient recovers, physical therapy, occupational therapy, and speech-language pathology can help the patient maximize function after the brain injury and to evaluate patient safety both before and after discharge.
Patient education regarding avoidance of future complications should come from all team members, with social work involvement to ensure home safety after discharge, and the patient's primary care provider should be updated, to the appropriate follow-up. In cases of vasogenic edema due to brain tumor, both oncology, radiation oncology and neurosurgery should be consulted to co-manage the evaluation and management of the neoplasm, determine the best treatment for the tumor (resection/radiation/palliation) based on the tumor type/stage, and follow up with the patient after discharge. And, finally, the patient and the patient's family and care providers should be educated about what to watch for that may suggest the need for re-evaluation because of recurrence, or complications from any of the interventions.
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