- MIT: Potent New Strategies Enhancing COVID-19 RNA Vaccines
- Long-COVID Found to Have Surprising Connection with Common Cold
- AI Accelerates Deep Brain Stimulation for Treatment-Resistant Depression
- Fentanyl and Stimulant Abuse Lead to the 4th Wave of Overdose Crisis
- New Gene Editing Tool Reduces Accidental Mutations by Over 70%
- What role do Macrophages play in Tumor Immunotherapy?
Research progress on detection methods and treatment methods of cerebral edema
Research progress on detection methods and treatment methods of cerebral edema. Cerebral edema is a secondary symptom of many diseases, such as ischemic stroke, cerebral hemorrhage, liver failure, and traumatic skull injury.
Brain edema can be divided into cytotoxic brain edema and vasogenic brain edema. In the early stage of cerebral edema, the patient’s symptoms are mild, and compensatory regulation can be performed in the brain, such as reducing the cerebrospinal fluid and blood volume to balance the increase in brain water.
However, due to the presence of the skull, if the water content increases sharply and the progress rate of cerebral edema exceeds the maximum level that can be compensated, it will lead to an increase in intracranial pressure, eventually forming a brain herniation, causing damage to the brain tissue and even death of the patient.
At this stage, there is no simple and effective method of detection and treatment of cerebral edema. Clinical imaging methods are commonly used for detection, but the cost is relatively expensive; biomarkers are the current research hotspot, but there is no breakthrough progress.
At present, the clinical treatment of severe cerebral edema is still based on traditional treatment methods such as hemi craniectomy and infiltration therapy. Targeted treatment of brain edema has achieved good results in preclinical studies, but it has not been effectively applied in clinical practice.
This article reviews the current commonly used detection indicators and methods for cerebral edema, as well as commonly used treatment methods, and analyzes and compares their advantages and disadvantages, and provides references for understanding and researching cerebral edema.
1. Common detection indicators and methods for cerebral edema
Cerebral edema can directly lead to the imbalance of brain water distribution, and the increase of water leads to changes in brain resistance and blood flow. This is the basis for the application of imaging methods to detect changes in the signal changes in the course of brain edema. Secondly, brain edema can also cause changes in the corresponding biomarkers. In addition, intracranial hypertension is defined as continuous intracranial pressure> 20mmHg, and cerebral edema can also be assessed indirectly by monitoring intracranial pressure.
1.1 Imaging methods
In clinical practice, it mainly relies on imaging methods, combined with clinical history, to make a more accurate identification of cerebral edema. CT is a commonly used imaging method. The signal intensity in CT is related to tissue density and attenuation coefficient. Therefore, in CT, the signal intensity of edema will be weakened compared with the surrounding normal soft tissue. Head CT is a conventional imaging method used to assess acute stroke, which has the advantages of quickness and simplicity. CT perfusion imaging has been established as a clinically practical imaging tool that can quickly deal with acute stroke.
Minnerup et al. proposed that the best indicator of CT perfusion imaging for evaluating malignant brain edema is the ratio of cerebral blood volume to cerebrospinal fluid, and a ratio higher than 0.92 can be used as a pathological indicator. Dhar et al. believe that cerebrospinal fluid volume measurement can be used to evaluate early edema and predict the degree of edema. MRI has good contrast resolution of soft tissues and can be used to evaluate the poor prognosis after cerebral edema and moderate to severe stroke.
Vascular brain edema is caused by the destruction of the blood-brain barrier. Fluid and intravascular proteins penetrate into the brain parenchyma, and the exuded fluid accumulates outside the cells, causing an increase in brain volume and intracranial pressure. At this time, the signal strength of MRIT2 is related to blood vessels. Permeability is related to the increase in water content. Can scan T2-weighted high-intensity images. Cytotoxic brain edema is the accumulation of intracellular fluid and Na+, which leads to cell swelling. At this time, MRI can show a decrease in the apparent diffusion coefficient. Diffusion weighted imaging (DWI) can be used clinically for the diagnosis of early cerebral ischemia. Acute cerebral ischemia-hypoxia can cause cytotoxic edema, which shows high signal on DWI, so DWI can detect infarction earlier Abnormal signal in the area.
Studies have pointed out that within 6 hours of onset of symptoms of cerebral infarction, DWI volume ≥ 82 cm3 is a specific indicator of malignant infarction. Optical detection is a better method to detect cerebral edema. As the water content of brain tissue increases, the near-infrared light transmittance also increases. Therefore, the optical properties of normal brain tissue and edema brain tissue may show differences.
Optical coherence tomography is a non-invasive optical imaging technique. Experimental studies by Rodriguez et al. found that in the spectral domain centered at 1300 nm, as the edema progresses, the average attenuation coefficient of the cerebral cortex decreases with time; it is inducing cerebral edema. After 20 minutes, it drops rapidly, and at the end of the experiment (the total length of the experiment is 80 minutes), the maximum decrease is 8%. Therefore, optical coherence tomography can be used to detect the progress of brain edema, and has strong spatial specificity, which can detect local brain damage more accurately and earlier, and can also observe the movement of brain water .
The application of biomarkers to predict brain edema is a hot research topic. The increase of matrix metalloproteinases, endothelin 1, inflammatory factors in the blood are all related to brain edema. At present, there are no biomarkers that can effectively and accurately diagnose cerebral edema in clinical practice, so biomarkers can only be used as an auxiliary means of neuroimaging. Inflammatory response and oxidative stress are important factors in the occurrence of ischemic cerebral infarction. Studies have shown that serum procalcitonin, an inflammatory biomarker, can be used to predict the risk of cerebral infarction.
Studies by Katan and others have shown that serum procalcitonin concentration is independently associated with ischemic stroke (HR=1.9, 95%CI: 1.0～3.8), and that serum procalcitonin can be used as a biomarker for detecting malignant brain edema after stroke . It is worth noting that decompressive craniectomy is essentially brain damage and may cause an increase in inflammatory biomarkers. However, craniectomy can reduce the higher intracranial pressure and serum procalcitonin levels caused by edema. Therefore, whether serum procalcitonin can be used as a post-cure index of decompressive craniectomy needs to be further explored.
Brain edema can be monitored by detecting intracranial pressure, but cerebral edema is not the only cause of the increase in intracranial pressure, and the intracranial pressure monitor can only detect when the intracranial pressure caused by edema has risen to a certain threshold. Moreover, the pressure sensor measures the pathological effects caused by cerebral edema, rather than the edema itself. Therefore, the intracranial pressure detection is not spatially specific and cannot accurately reflect the specific location and size of cerebral edema, and has a certain hysteresis. Used for early detection of cerebral edema.
Asuzu et al. pointed out that the neurological deficit score and the National Institutes of Health Stroke Scale can be used to predict cerebral edema, with high accuracy and simple calculation. Some researchers hope to establish a new predictive scoring system to facilitate the identification of high-risk patients. However, the scoring is subjective, and the older the patient is, the cognitive function will decline to a certain extent, which becomes an interference factor in the establishment of a scoring system for predicting cerebral edema.
2. Common treatment methods for cerebral edema
Studies have shown that certain ion channels and proteins will be pathologically expressed when brain edema occurs. However, clinically targeted treatment of brain edema for these proteins has not been reported successfully. Non-targeted treatment is still a research hotspot in clinical treatment of cerebral edema. At present, whether it is decompressive craniectomy, which provides additional compensation space for brain swelling, or osmotic therapy to reduce fluid accumulation after edema, both are methods to indirectly alleviate brain edema.
2.1 Decompressive craniectomy
Medication alone cannot reverse the occurrence and development of cerebral hernia after edema. Although decompressive craniectomy may bring complications such as bleeding and infection, it can significantly reduce the mortality of cerebral hernia from 80% of medical treatment to 58%. . Cerebral edema usually begins to form 6-12 hours after cerebral ischemia, and reaches the highest peak at 48 hours. Therefore, decompressive craniectomy within 48 hours is a better treatment option for patients with severe cerebral edema that cannot be reversed by non-surgical treatment. Studies have shown that accurate determination of the severity of early cerebral edema is beneficial for early screening of stroke patients for craniectomy.
The current international clinical treatment guidelines for cerebral edema use stroke onset time <48h as the node whether or not to perform the operation. However, recent studies have shown that in patients with edema caused by middle cerebral artery infarction, patients who underwent craniectomy within 48 hours (43 cases) and patients who underwent craniectomy decompression after 48 hours (23 cases) are not good The difference in prognosis was not statistically significant (P=0.62). The results of this study overturn the view that decompressive craniectomy is time-sensitive, but the study counts the time between admission to decompression craniectomy, the time from non-stroke onset to admission of the patient, and the sample size Less, and the results still need further research and demonstration.
In addition, age is also an important factor affecting the prognosis of decompressive craniectomy. The mortality rate of elderly patients (>60 years old) undergoing decompressive craniectomy can reach 51.3%, which is the case for younger patients (50-60 years old). 2 times. The decompressive craniectomy itself is a damage to the skull, and different side effects may occur:
(1) Postoperative bleeding and infection. Active post-treatment and targeted care can effectively reduce the risk of complications such as bleeding and infection.
(2) Long-term skull defects can cause complications such as cerebrospinal fluid dynamics disorders, abnormal brain tissue microcirculation, and skin flap subsidence syndrome, which seriously affect the patient’s recovery. Studies have shown that after decompressive craniectomy, early cranioplasty can help prevent complications and reduce symptoms of complications.
(3) Intracranial hematoma and acute encephalocele. The use of step decompression decompression (gradual cutting of the dura mater) can reduce the occurrence of complications such as delayed intracranial hematoma and acute encephalocele.
(4) After craniocerebral injury, accumulation of toxic metabolites in local tissues may occur, leading to re-injury of nerve function (including immune response disorder and inflammatory reaction). Adjuvant treatment with low temperature can be adopted to reduce the degree of injury.
(5) For the subdural effusion caused by decompressive craniectomy, external drainage and bone flap craniotomy can be used to remove the subdural effusion. If hydrocephalus and subdural effusion are complicated , Feasible ventricular-abdominal shunt.
2.2 Penetration treatment
Osmotic therapy is a non-surgical treatment for intracranial hypertension caused by cerebral edema. Its effectiveness mainly depends on whether the blood-brain barrier is intact, the reflection coefficient of penetrating drugs, and whether the penetration gradient is generated. Studies have shown that osmotic regulation only works in areas protected by the blood-brain barrier.
Osmotic therapy is one of the main methods for clinical treatment of cerebral edema. Mannitol and hypertonic saline are the most commonly used osmotic agents in osmotic therapy. Mannitol is a first-line drug for the treatment of increased intracranial pressure, but the prolonged use of mannitol, especially after repeated administration, will have serious side effects, which can partially cross the blood-brain barrier and accumulate in the injured brain tissue , Leading to further damage to the blood-brain barrier. In addition, it may also cause complications such as hyperkalemia, pulmonary edema, and congestive heart insufficiency.
Hypertonic saline can create an osmotic pressure gradient, gradually dehydrating brain tissue, thereby reducing intracranial hypertension. At present, the concentration range of hypertonic saline in clinical use is wide (2.0%～23.5%), so the determination of the optimal concentration of hypertonic saline has always been the focus of research. Zeng et al. pointed out in the study that under the same conditions, compared with the 20% mannitol treatment group, the serum Na+ concentration and plasma crystal osmotic pressure of the 10% hypertonic saline group increased significantly (P<0.01), which may be related to 10% The hypertonic saline is more likely to establish a higher osmotic gradient. Studies have also pointed out that both equimolar mannitol (20%) and hypertonic saline (7.45%) can be used to improve intracranial hypertension, and there is no statistically significant difference in the effects between the two (P>0.05). Hypertonic saline can also be used as an alternative therapy to hypertonic mannitol. Patients who are tolerant to mannitol can choose to use hypertonic saline to relieve intracranial hypertension.
2.3 Hypothermia and anesthesia
Patients with life-threatening cerebral edema after stroke have an average body temperature of slightly higher than that of normal stroke patients by 0.3°C. Forte et al. found that in 23 cases of patients undergoing decompression decompression surgery, the average temperature of the decompression area was reduced to 35 ℃ for 61.7 hours, and the intracranial pressure of all patients was significantly reduced, and the average value was reduced from 28mmHg to 13mmHg (P <0.01), the maximum decrease is from 64mmHg to 14mmHg, and the minimum is from 21mmHg to 18mmHg, which provides new clinical treatment ideas for cerebral edema caused by ischemic stroke.
Hypothermia can reduce the need for brain metabolism, reduce intracranial hypertension by reducing cerebral blood volume, reduce blood-brain barrier damage, play a role in neuroprotection, and reduce the fatality rate and long-term disability rate of adult patients with traumatic brain injury . However, hypothermia can cause a series of side effects such as chills, high blood pressure, tachycardia, and shortness of breath. Therefore, the benefits of hypothermia should be weighed against negative physiological effects when hypothermic treatment is performed.
At present, hypothermia treatment has not achieved the same good results as animal experimental research in clinical practice. Research by Cooper et al. showed that for patients with severe traumatic brain injury, combined use of preventive hypothermia treatment [When intracranial pressure increases, hypothermia (33-35°C) treatment is performed within 72h to 7d, and then the body temperature is gradually restored to normal] Compared with standard care, it cannot have a better effect of reducing intracranial pressure than standard care alone. Anesthetics can relax the brain, reduce the volume of intracranial arteries by reducing the metabolic demand of nerve cells, thereby reducing intracranial pressure, and indirectly alleviating cerebral edema. The anesthetic propofol is administered as a bolus injection at a dose of 1 to 3 mg/kg, and continues to be administered by infusion, with a drip rate of up to 200 μg/(kg·min), which can reduce the cerebral oxygen metabolism rate and the volume of cerebral blood flow. Thereby reducing intracranial pressure and alleviating cerebral edema (P<0.05).
Clinically, the detection of intracranial pressure needs to be timely and accurate. Biomarkers may be a breakthrough point, but there is no specific biomarker that has been determined as a detection indicator.
The therapeutic targets for cerebral edema, such as ion channels, aquaporins, matrix metalloproteinases, etc., have been widely recognized, and the corresponding drugs have also achieved good results in animal experiments, but they have not achieved their clinical effects.
The future research focus on cerebral edema should include two aspects. One is the improvement of detection methods, the identification of specific biomarkers and/or the improvement of the existing imaging examination methods; the second is the exploration of treatment methods, and the use of animal The targeted drugs and experimental results obtained from experimental research are used in clinical practice.
(source:internet, reference only)